Psychiatrists
31 years of experience

South Anchorage
1345 W 9th Ave
Ste 200
Anchorage, AK 99501
907-276-7374
Locations and availability (2)

Education ?

Medical School Score Rankings
University of California at San Diego (1979)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Board of Psychiatry and Neurology

Publications & Research

Dr. Campbell has contributed to 103 publications.
Title Avastin As an Adjunct to Vitrectomy in the Management of Severe Proliferative Diabetic Retinopathy: a Prospective Case Series.
Date December 2008
Journal Clinical & Experimental Ophthalmology
Excerpt

PURPOSE: Bevacizumab (Avastin) is a monoclonal antibody which targets all isoforms of vascular endothelial growth factor A. Its potent anti-angiogenic effects have been shown to cause regression of neovascularization in proliferative diabetic retinopathy. The aim of this study is to investigate the role of Avastin as an adjunct to vitrectomy in the management of severe diabetic eye disease. METHODS: Sixteen patients (18 eyes) with severe proliferative diabetic retinopathy were recruited into the study. All eyes underwent a single intravitreal injection of bevacizumab 1.25 mg in 0.05 mL prior to vitrectomy surgery for the management of tractional retinal detachment or vitreous haemorrhage due to severe proliferative diabetic retinopathy. RESULTS: At 3 months, seven eyes had visual acuities which were better than baseline, four were unchanged and seven were worse. At 6 months, 14 eyes had visual acuities better than baseline, one was unchanged and three were worse. Seven of the 18 eyes (38.8%) had postoperative rebleeds, six of which required surgical washout. CONCLUSION: Avastin improved the ease of the surgery in these complex eyes and the early results are encouraging. We have found it to be particularly useful in diabetic eyes with traction detachments of short duration in which there is still active neovascularization.

Title Addiction is Treated by All Domains of Our Society.
Date July 2007
Journal Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
Title Explanatory Pluralism and Patchy Reductionism.
Date February 2006
Journal The American Journal of Psychiatry
Title Addiction: a Disease of Volition Caused by a Cognitive Impairment.
Date February 2004
Journal Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie
Excerpt

The common etiology of substance and behavioural addictions is one that suggests faulty volition caused by a cognitive impairment. A cognitive impairment that minimizes the recall of the negative effects of the addictive behaviour is viewed as necessary and causal to all addictions. The proposed definition for addiction clarifies the confusion associated with addictive disorders, explains the many variable presentations, and provides an explanation of comorbidity and treatment outcomes. In addition, this paper suggests why this process has not been previously identified.

Title [an Analysis of Treatment of Intravitreal Lens Fragments Following Phacoemulsification]
Date August 2003
Journal [zhonghua Yan Ke Za Zhi] Chinese Journal of Ophthalmology
Excerpt

OBJECTIVE: To observe and evaluate the outcome of vitrectomy in the treatment of dropped lens fragments. METHOD: Retrospectively the authors reviewed and analyzed 58 cases of dropped lens fragments that were treated with vitrectomy from October 1992 to October 1995 in Royal Victoria Eye and Ear Hospital, Melbourne, Australia and followed for at least 3 months. RESULTS: At the last follow-up, the remained complications were cystoid macular edema in three cases (5.2%), retinal detachment in two cases (3.4%) and hypotony in one case (1.7%). Other complications were all resolved. The final vision was significantly better than that before vitrectomy. There were 38 eyes (65.5%) with final visual acuities of 0.5 or better, and only 6 eyes (6.9%) with < 0.05. CONCLUSION: Once the lens fragments are dropped into the vitreous during phacoemulsification, the ocular anterior segment should be properly managed, if possible intraocular lens is inserted, and then vitrectomy should be performed as soon as possible. Generally, with the above method good therapeutic effects can be obtained.

Title Endoscopic Greater Saphenous Vein Harvesting Reduces the Morbidity of Coronary Artery Bypass Surgery.
Date June 2002
Journal American Journal of Surgery
Excerpt

BACKGROUND: Most coronary artery bypass grafting (CABG) operations still involve the use of greater saphenous vein (GSV) for one or more grafts, even with the increasing use of arterial conduits for coronary revascularization. Wound complications from GSV harvesting are common, and sometimes severe. In order to reduce the morbidity of this procedure, we adopted a technique of endoscopic vein harvesting (EVH). EVH allows nearly complete harvest of the GSV, with excellent visualization, through minimal incisions. At our institution, a physician's assistant routinely performs EVH, usually while a cardiothoracic surgeon harvests an arterial conduit. In 1997, all GSV harvesting was performed by open technique. During a transition period in 1998 and 1999 we used several different endoscopic techniques. By the beginning of 2000, our technique of EVH was standardized and used routinely. METHODS: To determine whether EVH reduced the morbidity associated with conventional open vein harvesting (OVH), we reviewed the charts of all patients having primary coronary artery bypass operations utilizing GSV during the years 1997 and 2000. RESULTS: The two groups were comparable in risk factors for leg incision complications. The year 2000 EVH group had a marked reduction in the number of wound complications compared with the year 1997 OVH group (7.1% versus 26.1%, P < 0.00001). There were no significant differences between the two groups in total operative time (OVH 224 minutes, EVH 223 minutes, number of distal coronary anastomoses (OVH 3.38 +/- 0.90, EVH 3.38 +/- 0.94), or the rate of clinically apparent early graft failure. There was a significant increase in the use of sequential grafting techniques in the 2000 group (OVH 21.9%, EVH 43.6%, P < 0.00001). CONCLUSIONS: EVH reduced the morbidity associated with GSV harvesting. EVH was associated with an increased use of sequential coronary grafting techniques. EVH does not prolong operative time when performed by experienced personnel. We believe EVH should become the standard of care.

Title The Angiotensin Type 1 Receptor Antagonist, Eprosartan, Attenuates the Progression of Renal Disease in Spontaneously Hypertensive Stroke-prone Rats with Accelerated Hypertension.
Date April 2002
Journal The Journal of Pharmacology and Experimental Therapeutics
Excerpt

The effects of the angiotensin type 1 (AT(1)) receptor antagonist, eprosartan, were studied in a model of severe, chronic hypertension. Treatment of male spontaneously hypertensive stroke prone rats (SHR-SP) fed a high-fat, high-salt diet with eprosartan (60 mg/kg/day i.p.) for 12 weeks resulted in a lowering of blood pressure (250 +/- 9 versus 284 +/- 8 mm Hg), renal expression of transforming growth factor-beta mRNA (1.5 +/- 0.2 versus 5.4 +/- 1.4) and the matrix components: plasminogen activator inhibitor-1 (5.2 +/- 1.4 versus 31.4 +/- 10.7), fibronectin (2.2 +/- 0.6 versus 8.2 +/- 2.2), collagen I-alpha 1 (5.6 +/- 2.0 versus 23.8 +/- 7.3), and collagen III (2.7 +/- 0.9 versus 7.6 +/- 2.1). Data were corrected for rpL32 mRNA expression and expressed relative to Wistar Kyoto (WKY) rats [=1.0]. Expression of fibronectin protein was also lowered by eprosartan (0.8 +/- 0.1 versus 1.9 +/- 0.5), relative to WKY rats. Eprosartan provided significant renoprotection to SHR-SP rats as measured by decreased proteinuria (22 +/- 2 versus 127 +/- 13 mg/day) and histological evidence of active renal damage (5 +/- 2 versus 195 +/- 6) and renal fibrosis (5.9 +/- 0.7 versus 16.4 +/- 1.9) in vehicle- versus eprosartan-treated rats, respectively. Our results demonstrated that AT(1) receptor blockade with eprosartan can reduce blood pressure and preserve renal structure and function in this model of severe, chronic hypertension. These effects were accompanied by a decreased renal expression of transforming growth factor-beta1, plasminogen activator inhibitor-1, and several other extracellular matrix proteins compared with vehicle-treated SHR-SP.

Title Renoprotective Effects of Carvedilol in Hypertensive-stroke Prone Rats May Involve Inhibition of Tgf Beta Expression.
Date December 2001
Journal British Journal of Pharmacology
Excerpt

1. The effect of carvedilol on renal function, structure and expression of TGF beta and the matrix proteins fibronectin, collagen I and collagen III, was evaluated in spontaneously hypertensive stroke-prone (SHR-SP) rats fed a high fat, high salt diet. 2. Carvedilol treatment for 11 to 18 weeks did not alter systolic blood pressure in SHR-SP rats, however, it resulted in a significant reduction in heart rate. 3. Carvedilol treatment reduced renal fibrosis and total, active and chronic renal damage to levels approaching those of WKY rats on a normal diet. 4. Urinary protein excretion was higher in SHR-SP rats (51+/-10 mg day(-1)) than WKY rats (18+/-2 mg day(-1)) and this was further increased when SHR-SP rats were fed a high fat, high salt diet (251+/-120 mg day(-1)). Treatment with carvedilol resulted in significantly lower urinary protein excretion (37+/-15 mg day(-1)). 5. The expression of TGF beta mRNA was significantly higher in SHR-SP rats compared to WKY rats and a further increase was observed when rats were fed a high fat, high salt diet. Renal TGF beta expression was significantly reduced by treatment with carvedilol. The expression of fibronectin and collagen I and collagen III mRNA showed a pattern similar to that observed with TGF beta mRNA expression. Collagen I mRNA expression followed a pattern similar to renal fibrosis. 6. These data indicate that carvedilol can provide significant renal protection in the absence of any antihypertensive activity and that the mechanisms involved in this action may include reduced expression of profibrotic factors such as TGF beta.

Title Immunohistochemical Localization of H-k-atpase Alpha(2c)-subunit in Rabbit Kidney.
Date August 2001
Journal American Journal of Physiology. Renal Physiology
Excerpt

The rabbit kidney possesses mRNA for the H-K-ATPase alpha(1)-subunit (HKalpha(1)) and two splice variants of the H-K-ATPase alpha(2)-subunit (HKalpha(2)). The purpose of this study was to determine the specific distribution of one of these, the H-K-ATPase alpha(2c)-subunit isoform (HKalpha(2c)), in rabbit kidney by immunohistochemistry. Chicken polyclonal antibodies against a peptide based on the NH(2) terminus of HKalpha(2c) were used to detect HKalpha(2c) immunoreactivity in tissue sections. Immunohistochemical localization of HKalpha(2c) revealed intense apical immunoreactivity in a subpopulation of cells in the connecting segment, cortical collecting duct, and outer medullary collecting duct in both the outer and inner stripe. An additional population of cells exhibited a thin apical band of immunolabel. Immunohistochemical colocalization of HKalpha(2c) with carbonic anhydrase II, the Cl(-)/HCO exchanger AE1, and HKalpha(1) indicated that both type A and type B intercalated cells possessed intense apical HKalpha(2c) immunoreactivity, whereas principal cells and connecting segment cells had only a thin apical band of HKalpha(2c). Labeled cells were evident through the middle third of the inner medullary collecting duct in the majority of animals. Immunolabel was also present in papillary surface epithelial cells, cells in the cortical thick ascending limb of Henle's loop (cTAL), and the macula densa. Thus in the rabbit kidney, apical HKalpha(2c) is present and may contribute to acid secretion or potassium uptake throughout the connecting segment and collecting duct in both type A and type B intercalated cells, principal cells, and connecting segment cells, as well as in cells in papillary surface epithelium, cTAL, and macula densa.

Title Eprosartan Reduces Cardiac Hypertrophy, Protects Heart and Kidney, and Prevents Early Mortality in Severely Hypertensive Stroke-prone Rats.
Date June 2001
Journal Cardiovascular Research
Excerpt

OBJECTIVE: Eprosartan is a selective angiotensin II type I receptor antagonist approved for the treatment of hypertension. In the present studies, eprosartan's ability to provide end-organ protection was evaluated in a model of cardiomyopathy and renal failure in stroke-prone rats (SP). METHODS: SP were fed a high fat (24.5% in food) and high salt (1% in water) diet (SFD). Eprosartan (60 mg/kg/day) or vehicle (saline control) (n = 25/group) was administered by intraperitoneally-implanted minipumps to these SP on the SFD for 12 weeks. Normal diet fed SP and WKY rats (n = 25/group) were also included for comparison (i.e. served as normal controls). Mortality, hemodynamics, and both renal and cardiac function and histopathology were monitored in all treatment groups. RESULTS: Eprosartan decreased the severely elevated arterial pressure (-12%; P < 0.05) produced by SFD but did not affect heart rate. Vehicle-treated SP-SFD control rats exhibited significant weight loss (-13%; P < 0.05) and marked mortality (50% by week 6 and 95% by week 9; P < 0.01). Eprosartan-treated SP-SFD rats maintained normal weight, and exhibited zero mortality at week 12 and beyond. Eprosartan prevented the increased urinary protein excretion (P < 0.05) that was observed in vehicle-treated SP-SFD rats. Echocardiographic (i.e. 2-D guided M-mode) evaluation indicated that SP-SFD vehicle control rats exhibited increased septal (+22.2%) and posterior left ventricular wall (+30.0%) thickness, and decreased left ventricular chamber diameter (-15.9%), chamber volume (-32.7%), stroke volume (-48.7%) and ejection fraction (-22.3%), and a remarkable decrease in cardiac output (-59.3%) compared to controls (all P < 0.05). These same parameters in eprosartan-treated SP-SFD rats were normal and differed markedly and consistently from vehicle-treated SP-SFD rats (i.e. treatment prevented pathology; all P < 0.05). Cardiac-gated MRI data confirmed the ability of eprosartan to prevent cardiac pathology/remodeling (P < 0.05). Histopathological analysis of hearts and kidneys indicated that eprosartan treatment significantly reduced end-organ damage (P < 0.01) and provided corroborative evidence that eprosartan reduced remodeling of these organs. Vehicle-treated SP-SFD rats exhibited a 40% increase in the plasma level of pro-atrial natiuretic factor that was reduced to normal by eprosartan (P < 0.05). CONCLUSION: These data demonstrate that eprosartan, at a clinically relevant dose, provides significant end-organ protection in the severely hypertensive stroke-prone rat. It preserves cardiac and renal structural integrity, reduces cardiac hypertrophy and indices of heart failure, maintains normal function of the heart and kidneys, and eliminates premature mortality due to hypertension-induced end-organ failure.

Title Differential Global Gene Expression in Red and White Skeletal Muscle.
Date April 2001
Journal American Journal of Physiology. Cell Physiology
Excerpt

The differences in gene expression among the fiber types of skeletal muscle have long fascinated scientists, but for the most part, previous experiments have only reported differences of one or two genes at a time. The evolving technology of global mRNA expression analysis was employed to determine the potential differential expression of approximately 3,000 mRNAs between the white quad (white muscle) and the red soleus muscle (mixed red muscle) of female ICR mice (30-35 g). Microarray analysis identified 49 mRNA sequences that were differentially expressed between white and mixed red skeletal muscle, including newly identified differential expressions between muscle types. For example, the current findings increase the number of known, differentially expressed mRNAs for transcription factors/coregulators by nine and signaling proteins by three. The expanding knowledge of the diversity of mRNA expression between white and mixed red muscle suggests that there could be quite a complex regulation of phenotype between muscles of different fiber types.

Title A Randomized Controlled Study of the Use of Transscleral Diode Laser and Cryotherapy in the Management of Rhegmatogenous Retinal Detachment.
Date December 2000
Journal Retina (philadelphia, Pa.)
Excerpt

PURPOSE: Cryotherapy, the most common modality used to create a chorioretinal adhesion during retinal reattachment surgery, is associated with the dispersion of viable pigment epithelial cells and breakdown of the blood-ocular barrier, which are thought to be causative in a number of postoperative events, including macular pucker, proliferative vitreoretinopathy (PVR), and cystoid macular edema. Transscleral diode laser has been used successfully to create a chorioretinal adhesion in retinal reattachment surgery (diopexy) and experimentally has been shown to cause less pigment dispersion and blood-ocular barrier breakdown than cryotherapy. The authors carried out a prospective randomized study to compare the results and complication rates of transscleral diopexy with those of cryopexy during surgery for rhegmatogenous retinal detachment (RRD). METHODS: Data from 120 patients with recent onset RRD without significant PVR who were suitable for scleral buckling surgery and randomized to treatment using diode laser or cryotherapy were analyzed. The primary outcome measure was reattachment at 6 months with one operation. Secondary outcome measures were pain and swelling on the first postoperative day, cystoid macular edema as assessed angiographically at 6 weeks, and visual acuity, macular epiretinal membrane, and pigment migration under the fovea at 3 months. RESULTS: There was no significant difference between the primary and secondary outcome measures between the two treatment groups, with a primary success rate of 83% in the diode group and 92% in the cryotherapy group. Pain and postoperative swelling on the first postoperative day were equivalent. Cystoid macular edema was angiographically present in 12% in the diode group and 14% in the cryotherapy group. Visual acuity of at least 20/40 was achieved in 54% of patients in both groups. The rate of PVR was 5% in the diode group and 3% in the cryotherapy group. CONCLUSION: In this study of patients with uncomplicated RD without significant preoperative PVR, the experimentally shown benefits of transscleral diode laser did not result in significant improvement in the results of reattachment surgery compared with cryotherapy.

Title Brain Spect Imaging and Neuropsychological Testing in Coronary Artery Bypass Patients: Single Photon Emission Computed Tomography.
Date January 2000
Journal The Annals of Thoracic Surgery
Excerpt

BACKGROUND: Cognitive deficits appear frequently after cardiac operation. While the etiology remains unclear, alterations in cerebral perfusion during cardiopulmonary bypass may be causative. Single photon emission computed tomography (SPECT) scanning utilizes a radiopharmaceutical to provide images of cerebral perfusion. We proposed to study the cerebral circulation of patients during coronary artery bypass operation employing cardiopulmonary bypass. METHODS: Thirty-five neurologically normal patients underwent preoperative SPECT brain scanning and neuropsychological testing. A second SPECT brain perfusion scan was obtained by administering the radioisotope during cardiopulmonary bypass, with subsequent scanning upon completion of the procedure. Postoperative neuropsychological testing was performed prior to discharge. RESULTS: Fourteen (40%) of patients demonstrated significant neuropsychological decline. Patients who suffered cognitive impairment were no different in demographic, general health, or surgical variables. Patients who demonstrated neuropsychological decline had significantly poorer cerebral perfusion both at baseline and during operation. CONCLUSIONS: Impaired cerebral perfusion at baseline may identify patients at risk for cognitive injury after cardiac operation. Alterations in cerebral perfusion during cardiopulmonary bypass is common, and may be a factor in neuropsychological deficits seen after cardiac operation.

Title Molecular Identification of the Renal H+,k+-atpases.
Date October 1999
Journal Seminars in Nephrology
Excerpt

The pharmacological properties of H+,K+-ATPase activity described in the kidney were not necessarily consistent with the properties of the well-characterized gastric H+,K+-ATPase. Recent molecular biology experiments suggest that renal H+,K+-ATPase activity may be the product of several closely related P-type ATPases. At least 3 different pumps containing the HKalpha1, HKalpha2a, and HKalpha2c subunits have been detected in rabbit kidney. The current view is that these HKalpha subunits arose through gene duplication early in evolution and the proteins evolved their differing activities over time. The HKbeta protein associates with HKalpha1 in gastric tissues and is the likely mate for the HKalpha1 subunit in renal tissues. Three distinct beta subunits have been implicated as possible partners for the HKalpha2 subunits, but it remains to be determined which beta subunit predominantly associates with the HKalpha2 subunits in vivo. Sequence analysis suggests the beta subunit was constrained by size and shape of the protein rather than specific amino acid content during the course of evolution. Multiple H+,K+-ATPases in the kidney may be an important adaptation providing redundancy for the essential physiological function of maintaining ionic balance.

Title H-k-atpase in the Rcct-28a Rabbit Cortical Collecting Duct Cell Line.
Date March 1999
Journal The American Journal of Physiology
Excerpt

In the present study, we demonstrate that the rabbit cortical collecting duct cell line RCCT-28A possesses three distinct H-K-ATPase catalytic subunits (HKalpha). Intracellular measurements of RCCT-28A cells using the pH-sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) indicated that the mechanism accounting for recovery from an acid load exhibited both K+ dependence and sensitivity to Sch-28080 characteristic of H-K-ATPases. Recovery rates were 0.022 +/- 0.005 pH units/min in the presence of K+, 0.004 +/- 0.002 in the absence of K+, and 0.002 +/- 0.002 in the presence of Sch-28080. The mRNAs encoding the HKalpha1 subunit and the H-K-ATPase beta-subunit (HKbeta) were detected by RT-PCR. In addition, two HKalpha2 species were found by RT-PCR and 5' rapid amplification of cDNA ends (5'-RACE) in the rabbit renal cortex. One was homologous to HKalpha2 cDNAs generated from other species, and the second was novel. The latter, referred to as HKalpha2c, encoded an apparent 61-residue amino-terminal extension that bore no homology to reported sequences. Antipeptide antibodies were designed on the basis of this extension, and these antibodies recognized a protein of the appropriate mass in both rabbit renal tissue samples and RCCT-28A cells. Such findings constitute very strong evidence for expression of the HKalpha2c subunit in vivo. The results suggest that the rabbit kidney and RCCT-28A cells express at least three distinct H-K-ATPases.

Title Use of Silicone Oil in the Treatment of Complicated Retinal Detachment: Results from 1981 to 1994.
Date February 1999
Journal Australian and New Zealand Journal of Ophthalmology
Excerpt

PURPOSE: To evaluate the advantages and disadvantages of the retention and removal of silicone oil in the treatment of complicated retinal detachments. METHODS: The records of 344 patients (348 eyes) that underwent vitrectomy and silicone oil injection for complicated retinal detachments were abstracted and analysed. The anatomical and functional results, complications and influencing factors are discussed. The outcome in eyes after removal of the silicone oil was compared with the outcome in a comparable group of eyes in which the silicone oil was retained. RESULTS: The overall retinal reattachment rate was 63% (220/348). The final vision of 5/300 or better was 52% (115/220) in those eyes with totally attached retinas. The silicone oil-related complications included keratopathy (23%) and secondary glaucoma (11%). Comparing removal of silicone oil with retention of silicone oil, we found: (i) there was no statistical difference in the redetachment rate (19 vs 17%); (ii) oil-removed eyes had a better final vision (P < 0.05); and (ii) keratopathy (13 vs 23%), secondary glaucoma (11 vs 25%) and optic nerve atrophy (4 vs 18%) were significantly lower in oil-removed eyes. CONCLUSION: Silicone oil injection is useful in the treatment of complicated retinal detachments. For reducing the incidence of complications, early removal of silicone oil is recommended in those cases in which the retina is attached, all breaks adequately closed and traction relieved.

Title Carvedilol Prevents Severe Hypertensive Cardiomyopathy and Remodeling.
Date September 1998
Journal Journal of Hypertension
Excerpt

BACKGROUND: Carvedilol (Coreg/Kredex) is an unselective vasodilating beta-blocker with potent antioxidant activity used in the treatment of hypertension, angina, and congestive heart failure. In previous studies, carvedilol has been demonstrated to confer significant cardiac protection in acute ischemic paradigms and reduction of left ventricle hypertrophy in spontaneously hypertensive rats. OBJECTIVE: To examine the effects of carvedilol on discrete histopathologic changes in the heart induced by severe hypertension in stroke-prone spontaneously hypertensive rats. DESIGN: Three groups of stroke-prone spontaneously hypertensive rats were maintained on 1% NaCl drinking solution and a high-fat (24.5%) diet (salt-fat diet). Two of these groups had their salt-fat diet supplemented by 1200 or 2400 ppm carvedilol. The third group had the same diet but it was not supplemented with drug and this group served as a control. We fed a fourth group of stroke-prone spontaneously hypertensive rats a normal diet and used this group to define cardiac changes induced by salt-fat diet. METHODS: In total, 33 stroke-prone spontaneously hypertensive rats from these four groups (n = 7-9 in each group) survived for 18 weeks under these treatment regimens and were evaluated in terms of cardiovascular parameters and several quantitative and semiquantitative histopathologic indices that we developed to identify and compare cardiac muscle and vascular pathology/remodeling. RESULTS: Administration of carvedilol had no effect on systolic blood pressure (range for all salt-fat diet groups 288 +/- 8 to 294 +/- 6 mmHg compared with the value for the normal diet group of 228 +/- 12 mmHg) whereas heart rate was slightly reduced (by 10-18%; P<0.05). Administration of carvedilol produced a significant (P<0.01) dose-related decrease in total cardiac histologic damage (i.e. the sum of several histopathologic indices) induced by the salt-fat diet (i.e. it reduced damage by 54 and 82% at low and high doses, respectively). Specifically, administration of carvedilol produced dose-dependent reductions in histopathologic indices of coronary artery hypertrophy (by up to 88%), hyperplasia (by up to 89%), degeneration of myofiber (by up to 91%), myocardial inflammation (by up to 100%), cardiac fibrosis (by up to 67%), arterial microthrombosis (by up to 95%), and myocardial microinfarction (by up to 100%; all P<0.01). Salt-fat diet induced an increase in total cardiac mass and left ventricle-intraventricular septum cross-sectional area that was completely eliminated by administration of carvedilol (P<0.01). CONCLUSIONS: These data indicate that carvedilol provides remarkable cardioprotection, by suppressing severe hypertension-induced cardiac remodeling and myopathies at doses that do not reduce systemic blood pressure.

Title Evaluation of a Residential Program Using the Addiction Severity Index and Stages of Change.
Date July 1997
Journal Journal of Addictive Diseases
Excerpt

Fifty six individuals admitted to Recovery Acres (a thirty five bed male residential recovery program/half way house) were evaluated using the Addiction Severity Index (ASI) and Socrates, an instrument designed to measure stage of change. Composite scores obtained from the ASI indicated that major problems were present in the areas of employment, alcohol, family/social, and emotional functioning. Stages of Change revealed 27% to be in preparation, 67% action, and 6% in maintenance. Patients left Recovery Acres either through relapse, or to follow a non-residential program. Follow-up of 26 cases revealed that residents showed statistically significant improvement in areas of alcohol, drug, family/social and emotional problems. Employment, medical, and legal problems as identified by the ASI composite score were significant indicators of negative outcome. Employment still remained a problem three months after admission for most residents. Stage of Change did not predict outcome in terms of abstinence or residential status.

Title Infantile Myofibromatosis with Hemangiopericytoma-like Features of the Tongue: a Case Study Including Ultrastructure.
Date June 1997
Journal Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association
Excerpt

We report a case of an infantile myofibromatosis with hemangiopericytoma-like features arising in the tongue of a 5-month-old female infant. Many authors now classify neoplasms as infantile myofibromatosis that were previously called infantile hemangiopericytoma. The ultrastructural features of our tumor illustrate its biphasic nature and provide a possible explanation for its histogenesis. Infantile myofibromatosis, including those diagnosed as infantile hemangiopericytomas, rarely arise in any intraoral location. Despite the generally good prognosis associated with these neoplasms, complete surgical excision is recommended to avoid recurrences.

Title Autoimmune Hypothesis of Acquired Subglottic Stenosis: Lack of Support at Time of Surgical Repair in Children.
Date May 1997
Journal International Journal of Pediatric Otorhinolaryngology
Excerpt

Numerous mechanisms have been suggested for the development of subglottic stenosis. This study sought serum antibody and cricoid cartilage immunohistologic evidence of an autoimmune process. The autoimmune hypothesis is that subglottic inflammation may extend into the cricoid cartilage, degrade the extracellular matrix and expose normally-sequestered type II collagen to the afferent arm of the immune system. The resultant anti-collagen antibodies are hypothesized to contribute to further injury and scarring. Specimens were obtained from 10 patients. Immunofluorescent stains for antibodies in histologic specimens, and serum antibodies to type II and type IX collagen were sought. No evidence for an autoimmune process was found in these specimens with the techniques used. The negative findings may be attributable to the autoimmune process being inactive at the mature stage of the disease in the patients studied.

Title Is Self-organized Criticality Relevant to Alcoholism?
Date May 1997
Journal Journal of Addictive Diseases
Excerpt

The concept of self-organized criticality suggests that large interactive (dynamic) systems move toward a critical state. Seen throughout nature these systems follow a power law where the amount of energy involved in a change is related to the number of events that have occurred such that N is proportional to one over E to the power b (N alpha 1/Eb), where N is the number of events, E is the energy of the event and b is a constant for the system. A pilot series of 316 individuals reporting alcohol problems were studies and the number of individuals (N) reporting number of detoxifications (DN) was found to be related such that N was proportional to one over DN to the power k (N alpha 1/DNk), where k varies with the parameters of the population studies (i.e., gender, time sober). It is hypothesized that the "disease of alcoholism" can be conceptualized to be related to the energy of effort required to move from one "attractor" (drinking) to another (non-drinking) as a power law. The results suggest that alcoholics are "attracted" to the critical state of intoxication independent of clinical presentation or initial conditions.

Title Morphogenesis of Inclusion Bodies of Urothelial Carcinoma: a Case Study.
Date January 1997
Journal Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
Excerpt

The morphogenesis of inclusions of urothelial carcinoma (K. Donhuijsen et al.: Hum Pathol 23:860, 1992) is described in a case of a 51-year-old man with poorly differentiated urothelial carcinoma. Peritoneal fluid preparations contained numerous dyscohesive, large, anaplastic cells with abundant dense amphophilic cytoplasm often compartmentalized into multiple, variably sized, intracytoplasmic lumina, each containing "bull's eye"-like inclusions, with a periodic acid Schiff-positive refractile central core and an alcian blue/mucicarmine-positive rim. Ultrastructurally, the progression of osmiophilic substance from membrane-bound exocrine-type secretory granules, via exocytosis, to a presence in both intracytoplasmic lumina and extracellular space has been documented. Immunohistochemically, the periodic acid Schiff-positive refractile cores, as well as the minute periodic acid Schiff-positive granules in the cytoplasm, stained positively for secretory component and peanut agglutinins, whereas the alcian blue-positive mucinous material, which coated the refractile cores as well as the lining of the intracytoplasmic lumina, stained strongly for epithelial membrane antigen and leu M1. Ultrastructurally, protein A-gold probes, immunolabeled for peanut agglutinin and secretory component, were localized to the osmiophilic substance.

Title Chronic Carvedilol Reduces Mortality and Renal Damage in Hypertensive Stroke-prone Rats.
Date December 1996
Journal The Journal of Pharmacology and Experimental Therapeutics
Excerpt

The effects of carvedilol, a novel vasodilating beta-blocker and antioxidant, and propranolol on survival, neurobehavioral deficits, cardiovascular parameters, plasma renin, plasma aldosterone levels and renal pathology were determined in stroke-prone spontaneously hypertensive rats. Stroke-prone spontaneously hypertensive rats were allowed access to 1% NaCl as the drinking solution and a high fat diet supplemented with carvedilol (1200 or 2400 ppm) or propranolol (2400 ppm). The control group consisted of stroke-prone spontaneously hypertensive rats placed on the same diet with no drug supplement. Animals fed propranolol had a blood level of 864 +/- 68 ng/ml, whereas carvedilol-fed animals had blood levels of 24 +/- 4 ng/ml at 1200 ppm and 471 +/- 145 ng/ml at 2400 ppm. Carvedilol and propranolol treatment resulted in significant beta adrenoceptor blockade. Both compounds reduced heart rate, but had no significant effects on systolic arterial blood pressure. Carvedilol- and propranolol-treated animals also exhibited significant, prolonged protection from neurobehavioral deficits and mortality (P < .01). Elevated plasma renin activity and aldosterone levels seen in untreated controls were significantly decreased by propranolol (P < .05), and to a considerably greater extent by the same dose of carvedilol (P < .01). Carvedilol decreased renal histopathological damage and cardiac hypertrophy to a greater extent (P < .01) than propranolol (at equal doses). Both carvedilol (P < .01)- and propranolol (P < .01)-treated animals had considerably reduced renal damage at 18 weeks of treatment. Carvedilol reduced renal damage more than propranolol (P < .05). In addition, the lower (1200 ppm) dose of carvedilol, which decreased neurobehavioral deficits and mortality, had no significant effects on organ mass or renal function, but significantly (P < .01) reduced renal damage. These data indicate that both beta adrenoceptor blockers, especially carvedilol to a considerably greater degree, convey significant protection in a genetic model of severe hypertension that results in renal and cardiovascular organ pathology, neurobehavioral deficits and premature death.

Title Plasma and Renal Prorenin/renin, Renin Mrna, and Blood Pressure in Dahl Salt-sensitive and Salt-resistant Rats.
Date June 1996
Journal Hypertension
Excerpt

We measured plasma prorenin and renin levels, renal renin mRNA, renal anti-renin and anti-prorenin-prosequence immunoreactivity, and blood pressure in maturing Brookhaven Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats during 14 days of low (0%), medium (0.4%), or high 4%) NaCl diets. Blood pressure was higher in Dahl S rats and did not increase with high NaCl. Seven-week-old Dahl R rats had twofold and sixfold higher levels of plasma prorenin and renal prosequence immunoreactivity, respectively, which by 9 weeks were the same as in Dahl S rats. The anti-renin antiserum, BR1-5, was found to detect prorenin better than renin; Dahl S rats had suppressed renal anti-renin immunoreactivity relative to Dahl-R rats. Dahl R rats were unresponsive to high NaCl, whereas in Dahl S rats, plasma renin and renal prosequence immunoreactivity fell by 90% (P < .01), renal anti-renin immunoreactivity and renal renin MRNA fell by 35% (P < .05 for both), and plasma prorenin fell by 30% (P = NS). NaCl depletion increased prorenin/renin parameters similarly in both strains. There were direct relationships among all of the prorenin/renin parameters. Between low and high salt diets in Dahl S rats, plasma renin increased 20-fold, plasma total renin (renin plus prorenin) and renal renin mRNA both increased threefold, and plasma prorenin increased twofold. The results indicate that under steady-state conditions, plasma and renal renin/prorenin parameters change concordantly and that plasma total renin (renin plus prorenin) reflects changes in renal renin mRNA. The lower blood pressure of Dahl R rats is associated with later maturation-related declines in plasma and renal prorenin. Suppression of plasma renin may delay the salt-induced blood pressure rise in Dahl S rats. Finally, the renin system and blood pressure of Dahl R rats have remarkable disregard for a high salt diet.

Title In Situ Hybridization of H-k-atpase Beta-subunit Mrna in Rat and Rabbit Kidney.
Date November 1995
Journal The American Journal of Physiology
Excerpt

Through a variety of techniques, several investigators have demonstrated the presence of an H-K-adenosinetriphosphatase (H-K-ATPase) enzyme in the renal collecting duct, suggesting that this enzyme serves an important physiological role in the regulation of acid-base balance and potassium excretion by the kidney. The present study was designed to localize cells expressing H-K-ATPase beta-subunit mRNA in rat and rabbit kidney by nonradioactive in situ hybridization. A 570-bp DNA fragment of rabbit renal H-K-ATPase beta-subunit was used to produce digoxigenin-labeled riboprobes by in vitro transcription. Northern blot hybridization demonstrated transcripts in rat gastric oxyntic mucosa and kidney. In situ hybridization on kidney tissue sections demonstrated H-K-ATPase beta-subunit mRNA localization in epithelial cells, including intercalated cells in the connecting segment and cortical and medullary collecting duct, principal cells in the inner stripe of the outer medullary collecting duct, and inner medullary collecting duct cells in both the rat and the rabbit. These observations provide evidence that H-K-ATPase beta-subunit mRNA is present throughout the collecting duct of the kidney. The distribution of this message is consistent with a role for H-K-ATPase in bicarbonate absorption in both the outer and inner medullary collecting duct.

Title Renal Expression of the Gene Encoding the Gastric H(+)-k(+)-atpase Beta-subunit.
Date April 1995
Journal The American Journal of Physiology
Excerpt

The gastric mucosal parietal cells and cells of the renal collecting duct both possess H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) activities. In the stomach, the H(+)-K(+)-ATPase (EC 3.6.1.3) is responsible for acidification of luminal contents. The kidney H(+)-K(+)-ATPase protein(s) contribute to potassium reabsorption and secretion of hydrogen ions to maintain potassium and acid-base homeostasis. The stomach H(+)-K(+)-ATPase is well defined and consists of an alpha-catalytic subunit of apparent molecular mass of 95 kDa and a highly glycosylated beta-subunit of 60-90 kDa. The molecular identity of the protein that mediates the H(+)-K(+)-ATPase activity in the kidney has been addressed in this paper. A combination of RNA hybridizations, polymerase chain reaction analysis of kidney RNA, and sequence analysis of cDNAs indicated that gastric H(+)-K(+)-ATPase beta-subunit mRNA is present in kidney. Immunoblotting with antibodies specific for the gastric H(+)-K(+)-ATPase beta-subunit detected proteins, which, after deglycosylation, had the same molecular mass as the gastric beta-subunit in membrane protein preparations from rabbit, pig, rat, and mouse kidneys. Furthermore, we have used transgenic mice to demonstrate that the gastric H(+)-K(+)-ATPase beta-subunit gene contains cis-acting regulatory sequences that are active in both gastric parietal cells and the renal collecting ducts. Overall, these data indicate that the gastric H(+)-K(+)-ATPase beta-subunit is found in the kidney and probably associates with the gastric H(+)-K(+)-ATPase alpha-subunit and/or other P-type ATPase alpha-subunits, thus contributing to acid-base and potassium homeostasis.

Title Concurrent Malakoplakia and Primary Squamous Cell Carcinoma Arising in Long-standing Chronic Cystitis.
Date February 1995
Journal British Journal of Urology
Title Pituitary-specific Transcription Factor (pit-1) Binding Site in the Human Renin Gene 5'-flanking Dna Stimulates Promoter Activity in Placental Cell Primary Cultures and Pituitary Lactosomatotropic Cell Lines.
Date October 1994
Journal Circulation Research
Excerpt

Renin gene expression is limited to a number of specific tissues, including the kidney, adrenal glands, reproductive organs (of particular relevance to this study, the placenta), and the pituitary gland. In the present study, we investigated the human renin (hRen) 5'-flanking DNA sequences required to drive the expression of a luciferase reporter gene in placental and pituitary cells and in two cell lines, 293 and JEG-3, which have been proposed as model systems with which to study transcriptional regulation of renin genes. The activities of specific sequences in the hRen 5'-flanking DNA sequences in human placental cell primary cultures were very similar to those that we previously reported in pituitary cells, suggesting the involvement of common promoter elements and related transcription factors. Accordingly, the binding site for the pituitary-specific transcription factor (Pit-1) was the major determinant of renin promoter activity in both pituitary and placental cells. Gel mobility shift analysis showed a placental nuclear factor with a gel mobility different from that of Pit-1. However, Northern blot analysis failed to demonstrate abundant Pit-1-related mRNAs in renin-expressing cultures of chorionic and decidual cells, suggesting that the placental factor is not closely related to Pit-1. Although a factor from 293 cells also bound to the Pit-1 site, it had gel mobility shift characteristics different from Pit-1 and the placental factor. Moreover, the low promoter activity in 293 cells was independent of this site or, indeed, of sequences upstream from the TATA box. In JEG-3 cells, renin 5'-flanking DNA sequences showed virtually no transcriptional activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Title The Concurrence of Duodenal Epithelioid Stromal Sarcoma, Pulmonary Chondromatous Hamartoma, and Nonfunctioning Pancreatic Islet Cell Tumor. A Possible Analogue of Carney's Triad?
Date September 1994
Journal Archives of Pathology & Laboratory Medicine
Excerpt

A 63-year-old man with non-insulin-dependent diabetes mellitus and peripheral vascular disease presented with acute pulmonary edema and ascites. He died after a brief illness. Coincidence of duodenal epithelioid stromal sarcoma, pulmonary chondromatous hamartoma, and pancreatic islet cell tumor was found at autopsy. This rare concurrence of three uncommon neoplasms may be a pathogenetic variant or an analogue of Carney's triad in an elderly individual. Since all three tumors expressed markers for neural differentiation, the coincidence of tumors with these features may represent a form of neurocristopathy.

Title Alcohol-related Blackouts in a Medical Practice.
Date November 1993
Journal The American Journal of Drug and Alcohol Abuse
Excerpt

One hundred thirty-five individuals seeking help for an alcohol or drug problem from a family physician completed a self-report questionnaire. Eighty-six percent of respondents reported having experienced alcohol-related blackouts. Blackouts were found to be most strongly related to severity of alcohol problems. They were not clearly early-stage nor middle-stage indicators of alcohol problems and were not associated with a variety of neuropsychological indicators.

Title Needle Drainage of Subretinal Fluid. A Randomized Clinical Trial.
Date April 1993
Journal Retina (philadelphia, Pa.)
Excerpt

Needle drainage of subretinal fluid with simultaneous observation using the indirect ophthalmoscope has been reported to have a very low complication rate. The technique was evaluated by a prospective clinical trial. The study group consisted of 100 patients undergoing scleral buckling for rhegmatogenous retinal detachment who were randomly assigned to groups treated with needle drainage or conventional two-stage drainage. At 1 month, the retina was anatomically flat in 88% of all cases. Subretinal hemorrhage occurred in 10 of 45 patients (22.2%) after needle drainage and in 7 of 55 patients (12.7%) after conventional drainage. The difference was not statistically significant. Retinal puncture occurred during conventional drainage in one case and in no cases during needle drainage. There were no cases of retinal incarceration. The results showed that subretinal hemorrhage was more common after needle drainage, but a larger study would be required to show whether this difference was statistically significant. The fear that the retina would be damaged by placement of a needle in the subretinal space throughout the drainage procedure was unfounded.

Title Comparison of Fine-needle Aspiration Biopsy, Doppler Ultrasound, and Radionuclide Scintigraphy in the Diagnosis of Acute Allograft Dysfunction in Renal Transplant Recipients: Sensitivity, Specificity, and Cost Analysis.
Date April 1993
Journal Nephron
Excerpt

150 episodes of allograft dysfunction in 128 renal transplant recipients, 77 due to acute rejection, 32 secondary to acute-on-chronic rejection, 33 due to either prerenal factors, acute tubular necrosis, or ciclosporin A nephrotoxicity, and 8 secondary to multiple causes, were evaluated by fine-needle aspiration biopsy (FNAB), Doppler ultrasound (DUS), and radionuclide scintigraphy (RS), each performed within a 24-hour period and prior to any specific therapeutic intervention. Tests were interpreted by appropriate specialists in a large transplant center without access to clinical information. The final diagnosis was based primarily upon response to therapeutic maneuvers with histological (core biopsy) confirmation in 123 episodes. RS was the most sensitive (70%) test for the diagnosis of acute rejection during the early posttransplant period, exceeding both FNAB (52%) and DUS (43%). The predictive accuracy of either FNAB, DUS, RS, or core biopsy in the detection of a steroid-responsive component to acute rejection when superimposed upon chronic rejection was low at approximately 50%. When the underlying cause of renal dysfunction was either prerenal, acute tubular necrosis, or ciclosporin A nephrotoxicity, FNAB, DUS, and RS each gave an erroneous diagnosis of acute rejection in about 50% of the episodes. Cost analysis revealed that core biopsy was the most expensive test, but only 9% more than RS, with FNAB the least costly. In conclusion, the lack of ideal sensitivity and specificity combined with the expense of present-day FNAB, DUS, RS, and core biopsy in the diagnosis of a therapeutically reversible component to acute-on-chronic rejection and of FNAB, DUS, and RS in the diagnosis of acute rejection during the early posttransplant period should prompt research into ways to improve their diagnostic yield or alternate modalities.

Title Control of Blood Pressure and End-organ Damage in Maturing Salt-loaded Stroke-prone Spontaneously Hypertensive Rats by Oral Angiotensin Ii Receptor Blockade.
Date March 1993
Journal Journal of Hypertension
Excerpt

OBJECTIVE: To study the effects of renin-angiotensin system blockade by a novel non-peptide angiotensin II receptor antagonist, losartan, on development of hypertension and acceleration of end-organ damage in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). DESIGN AND METHODS: One hundred and eighty-one male SHRSP were fed a 4% sodium diet from 6 to 18 weeks of age. Seventy-eight SHRSP were treated orally with losartan, 30 mg/kg per day. One hundred and three rats constituted untreated controls. Blood pressure, plasma renin activity (PRA), renal function and end-organ damage were monitored during the transition to malignant hypertension. RESULTS: Losartan prevented a blood pressure rise during the first 4 weeks of salt loading. Thereafter, blood pressure rose slowly in losartan-treated rats; however, at each time-point studied blood pressure was significantly lower in losartan-treated rats than in control rats. Losartan treatment increased PRA during the first 4 weeks, but this effect was not sustained. Thereafter, PRA decreased to control (week 0) levels. In contrast, 2 weeks after high-sodium feeding started, untreated SHRSP failed to suppress PRA appropriately; thereafter, PRA rose significantly. Losartan affected renal pathophysiology by blunting the decline in glomerular filtration rate, controlling proteinuria and preventing or delaying the appearance of malignant nephrosclerosis. Losartan treatment significantly increased survival and completely prevented cerebrovascular infarcts. CONCLUSIONS: The results indicate that angiotensin II blockade markedly reduces both hypertension and end-organ damage in chronically salt-loaded SHRSP and that the renin-angiotensin system may play an important role in the development of hypertensive cardiovascular disease in SHRSP.

Title Angiotensin Ii Receptor Antagonist Delays Renal Damage and Stroke in Salt-loaded Dahl Salt-sensitive Rats.
Date November 1992
Journal Journal of Hypertension
Excerpt

OBJECTIVE: To study the effects of blockade of the renin-angiotensin system upon the development of hypertension, end-organ damage and mortality in Dahl salt-sensitive (DSS) rats using an angiotensin II receptor antagonist, losartan. DESIGN AND METHODS: DSS rats (n = 186) were fed 8% NaCl from 6 to 16 weeks of age. One group received losartan whilst the control group was untreated. Changes in blood pressure and plasma renin activity (PRA), as well as renal and cerebrovascular damage and survival were assessed during the study. RESULTS: Losartan blunted the blood pressure rise only transiently. Salt loading suppressed PRA in both groups until week 4 and thereafter it rose more markedly in the treated group. With no treatment renal lesions were first detected at 2 weeks, and strokes at 6 weeks. However, losartan transiently decreased the incidence and delayed the progression of renal damage and cerebrovascular lesions (strokes) and increased survival. PRA correlated with renal damage and the incidence of strokes in both groups. Blood pressure only partially affected survival, but did not correlate with stroke incidence. CONCLUSIONS: These results indicate that whereas the rise in blood pressure is dependent upon sodium loading, morbidity and mortality in salt-loaded DSS rats are associated with activation of the renin-angiotensin system and are only partially related to blood pressure.

Title The Greater Renin System. Its Prorenin-directed Vasodilator Limb. Relevance to Diabetes Mellitus, Pregnancy, and Hypertension.
Date June 1992
Journal American Journal of Hypertension
Excerpt

A greater renin system is proposed. Evidence is presented that a greater renin system exists that has both vasodilator and vasoconstrictor properties. Vasodilator activity is induced by prorenin, vasoconstrictor activity by renin. Our model is based on evidence that both prorenin and renin have the capacity to generate angiotensin and that angiotensin causes vasodilation at high concentrations and vasoconstriction at low concentrations. In our model, prorenin acts only at particular target sites while renin of renal origin acts via the general circulation. Prorenin's designation as a biosynthetic precursor implies lack of intrinsic catalytic activity whereas in fact it can become reversibly active. Activation may occur in vivo at binding sites without cleavage of the prosequence. In this framework, prorenin should be more aptly called renin I and circulating active renin, renin II. In our model, the role of renin I (prorenin) is to generate localized high concentrations of angiotensin II, eg, in the afferent arteriole of the kidney and in other vital organs, causing regional dilation by rendering tissues insensitive (tachyphylactic) to the vasoconstrictor effect of circulating angiotensin II or by releasing vasodilator substances. The role of renin II (active renin) is to constrict resistance vessels and the efferent arteriole of the kidney, thereby raising blood pressure, maintaining glomerular filtration rate, and enabling more blood flow to those organs that selectively bind prorenin. This twin control system is ideally designed to maintain blood flow to vital organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Estrogen Receptor Status in Malignant Melanoma.
Date February 1991
Journal The American Journal of Dermatopathology
Excerpt

Estrogen receptor (ER) positivity demonstrated in malignant melanomas by histochemical and biochemical assays suggested the possibility of hormonal management and improved prognosis as for breast carcinoma patients. We studied the ER status of 5 primary and 28 metastatic malignant melanomas with a commercial immunohistochemical kit (ER-ICA monoclonal), that utilizes monoclonal anti-ER and a peroxidase-antiperoxidase technique, and by a histochemical method using fluorescein-conjugated estradiol (Fluoro-Cep Estrogen assay), on frozen sections. In addition, we conducted a biochemical assay [dextran-coated charcoal cytosolic assay (DCC)] in 16 cases. All 33 cases were ER negative by ER-ICA and Fluoro-Cep: 11 biochemical assays were negative (less than 3 fmol ER/mg protein), four were in the borderline range (3 to 10 fmol ER/mg protein), and one was positive (greater than 10 fmol ER/mg protein) at 11 fmol. The melanomas in 97% of the cases we studied were ER negative by two or three different assays. Low-level estrogen binding of MM tissues may be the result of interactions other than with Type I true ER. The low frequency of ER positivity of malignant melanomas appears to preclude the clinical use of ER status as an indicator for response to hormonal manipulation in patients with malignant melanoma.

Title Arterial Disease of the Iris Predicts Visceral Arterial Necrosis in Rabbits with Acute One-kidney, One Clip Hypertension: Comparisons with Acute One-kidney, One Wrapped Hypertension.
Date January 1991
Journal Journal of Hypertension
Excerpt

Tortuosity, dilations, aneurysms and satellite hemorrhages consistently develop in the circular arteries of the iris of rabbits with acute one-kidney, one clip (1K1C) malignant hypertension. These lesions are easily visualized, quantitated and monitored during life. Graded iridoarteriopathy correlates directly with visceral arterial necrosis (r15 = 0.843; P less than 0.001), final indirect blood pressure (r15 = 0.591; P less than 0.02) and cardiac hypertrophy (r15 = 0.565; P less than 0.02). Arterial necrosis in the irises and other viscera in acute 1K1C hypertension in rabbits is qualitatively similar to that occurring in rabbits with acute one-kidney, one wrapped (1K1W) hypertension with regard to both the histological features and organ distribution. However, over three times as many arterial lesions occur in rabbits with acute 1K1W hypertension as occur in those with acute 1K1C hypertension (P less than 0.001). Since blood pressure elevation does not correlate with graded iridoarteriopathy or with visceral arterial necrosis in 1K1W rabbits, factors other than blood pressure elevation appear to be especially important in the pathogenesis of arterial necrosis in the 1K1W model. On the other hand, the present study indicates that high grade iridoarteriopathy appears to be indicative of a high risk of cerebral hemorrhage in 1K1C rabbits, as earlier studies have shown for 1K1W rabbits.

Title Vaginitis Emphysematosa. A Report of Four Cases.
Date January 1991
Journal The Journal of Reproductive Medicine
Excerpt

It has been hypothesized that vaginitis emphysematosa is a manifestation of trichomonal or Gardnerella infection. In support of this etiologic concept, four cases of the disorder are described showing the apparent curative effect of treating the associated infection. The linkage of these and other reported cases with conditions of impaired immunity suggests that immunologic factors are involved in the pathogenesis.

Title Transthoracic Needle Aspiration Biopsy in Wegener's Granulomatosis. Morphologic Findings in Five Cases.
Date May 1990
Journal Acta Cytologica
Excerpt

Percutaneous needle aspiration biopsies of the lung from five patients with Wegener's granulomatosis were reviewed. Three of the patients presented with the generalized form of the disease while two presented with the limited pulmonary form; one of the latter subsequently developed disseminated disease. The morphologic findings in the pulmonary aspirates were similar in all cases. The cytologic preparations contained neutrophils entrapped within necrotic debris plus scattered but prominent histiocytic giant cells, which often had nuclei arranged in rings or horseshoes, in a background of lymphocytes, epithelioid histiocytes and reactive pneumocytes. Cell block preparations showed discrete areas of necrosis containing a neutrophilic infiltrate and focally palisaded by epithelioid histiocytes. The intervening viable tissue contained prominent histiocytic giant cells and chronic inflammatory cells enmeshed in a fibrous matrix. One cell block contained a small artery with a small focus of possible granulomatous arteritis. While an open lung biopsy is generally required for a definitive diagnosis, the pathologist may encounter unsuspected Wegener's granulomatosis in a needle aspirate. Recognition of the findings observed in these cases should alert the pathologist to the possibility of Wegener's granulomatosis so that an open lung biopsy can be performed if clinically indicated and cytotoxic therapy can be promptly instituted if the diagnosis of this entity is confirmed.

Title Naproxen-induced Nephropathy in Systemic Lupus Erythematosus.
Date April 1990
Journal Nephron
Excerpt

A 34-year-old female with an 8-month history of systemic lupus erythematosus and intermittent naproxen use presented with acute oliguric renal failure, hypoalbuminemia, 4+ proteinuria, and an active urinary sediment. The clinical picture suggested a rapidly progressive lupus glomerulonephritis. Renal biopsy, however, demonstrated chronic, active interstitial nephritis without evidence of immune deposits by immunofluorescence or electron microscopy. Nonsclerotic glomeruli revealed diffuse foot process fusion without cellular proliferation. These findings were consistent with nonsteroidal anti-inflammatory drug induced nephropathy. Discontinuation of naproxen and institution of corticosteroid therapy was followed by improvement in renal function and remission of nephrotic syndrome. This case represents the first report of nonsteroidal antiinflammatory drug nephropathy associated with systemic lupus erythematosus.

Title Relation of Plasma Renin to End Organ Damage and to Protection of K+ Feeding in Stroke-prone Hypertensive Rats.
Date March 1990
Journal Hypertension
Excerpt

We studied the effects of regular diet (0.35% NaCl/1.1% potassium), high sodium diet (4% NaCl/0.75% potassium), or high sodium and high potassium diet (4% NaCl/2.11% potassium) on blood pressure, plasma renin activity, renal and cerebrovascular lesions, and incidence of stroke and mortality in male stroke-prone spontaneously hypertensive rats (SHRSP). In the first 4 weeks, the rise in blood pressure was higher in high NaCl than in high NaCl/high potassium or regular diet groups. However, by 8 and 12 weeks, the blood pressure in all three groups was similar. After 4 weeks of diet, plasma renin activity was similar in the three groups (3.4 +/- 0.8, 4.1 +/- 0.9, and 5.2 +/- 1.6 ng/ml/hr, in high NaCl, high NaCl/high potassium, and regular diet groups, respectively) and were not related to sodium excretion. After 8 weeks, plasma renin activity was significantly increased only in the high NaCl group (13.7 +/- 3.7 ng/ml/hr), and by 12 weeks plasma renin activity was significantly higher in the high NaCl group (25.3 +/- 3.6 ng/ml/hr) than in the high NaCl/high potassium (11.1 +/- 2.9 ng/ml/hr) or in the regular diet (7.8 +/- 4.6 ng/ml/hr) groups. Moderate to severe renal vascular lesions were first detected in the high NaCl group by 8 weeks of diet. At 12 weeks, renal vascular damage index (RVDI), estimated histologically, was significantly higher in the high NaCl group (RVDI = 79 +/- 14) than in the high NaCl/high potassium (RVDI = 40 +/- 11) and regular diet (RVDI = 7.8 +/- 4.6) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Hypocomplementemic Proliferative Glomerulonephritis with C3 Nephritic-factor-like Activity in Multiple Myeloma.
Date July 1989
Journal Nephron
Excerpt

Advanced renal failure, nephrotic-range proteinuria due to proliferative glomerulonephritis and multiple myeloma with circulating IgG2 lambda and free lambda light-chain paraproteins occurred in a 31-year-old male. Commonly established causes of renal failure in multiple myeloma were excluded. Immunofluorescence revealed heavy granular glomerular deposition of C3. Serum C3 was decreased, and C3c was increased. C3 nephritic-factor (C3 NeF)-like activity was demonstrated in the serum. Plasmapheresis and chemotherapy resulted in a decrease in paraprotein concentration up to 90%, a decrease in C3 NeF-like activity to negligible, normal serum complement levels and a marked improvement in both renal function and proteinuria. With reference to the literature, the possibility of a syndrome of paraproteinemia, C3 NeF-like activity and glomerulonephritis is forwarded.

Title Acute Renal Failure Due to Bilateral Renal Parenchymal Malacoplakia.
Date June 1989
Journal American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
Title Atypical Monoclonal Plasma Cell Hyperplasia of the Central Nervous System: Precursor of Plasmacytoma with Evolutionary Considerations.
Date April 1989
Journal Neurosurgery
Excerpt

Hematopoietic proliferations rich in plasma cells rarely occur within the central nervous system without the involvement of other organ systems. Depending on their histological pattern and cellular composition, several different terms, including plasmacytoma, plasma cell granuloma, hyalinizing plasmacytic granulomatosis, and inflammatory meningioma, are used for these lesions. We report a left temporal dural lesion composed of plasma cells, lymphocytes, histiocytes, and rare eosinophils with hyaline changes and a suggestion of follicle formation, which stained predominantly for IgG and kappa light chains. This lesion arose in an otherwise healthy 52-year-old woman. Free kappa light chains without a monoclonal peak were found in the urine. We are aware of only two other heterogeneous, predominantly plasmacytic, solitary dural lesions that were found to be monoclonal on immunohistochemical examination. The label atypical monoclonal plasma cell hyperplasia appears to suit the morphological characteristics of our lesion. We suggest that a spectrum of solitary plasmacytic lesions may occur within the central nervous system and that atypical plasma cell hyperplasias have the potential to evolve into plasmacytoma. The preneoplastic nature of this lesion and its potential for evolution to malignant myeloma should be considered when planning treatment and lifelong follow-up for patients.

Title Vitrectomy Techniques in the Treatment of Giant Retinal Tears: a Flexible Approach.
Date December 1988
Journal Australian and New Zealand Journal of Ophthalmology
Excerpt

We describe a flexible approach employing vitrectomy, scleral buckling and intraocular tamponading agents in the treatment of giant retinal tears. Intraocular gas without a buckle was used in the 10 least complicated cases. In five eyes we considered a scleral buckle to be necessary in addition to gas tamponade. Silicone oil was selected as the primary tamponading agent in the six most complex cases with PVR and in five re-operations. The overall anatomical success rate was 71% of which 73% had a final visual acuity of at least 6/60 and 60% achieved 6/18 or better.

Title Adrenal and Vascular Tyrosine Hydroxylase Activity in Goldblatt Hypertension.
Date November 1988
Journal Hypertension
Excerpt

To examine the role of the sympathetic nervous system in hypertension, the in vitro activity of tyrosine hydroxylase was examined in one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) hypertensive rabbits and their respective controls 2 weeks after surgical procedures. The in vitro activity of tyrosine hydroxylase provides a measure of catecholamine synthesis and serves as a biochemical index of activity of noradrenergic neurons and the adrenal medulla. Mean atrial pressure rose from 91.5 +/- 1.0 to 128.5 +/- 5.6 mm Hg (p less than 0.01) in the 1K1C group and from 91.8 +/- 1.3 to 106.5 +/- 5.0 mm Hg (p less than 0.02) in the 2K1C group, whereas no change in blood pressure was found in their respective controls. Adrenal tyrosine hydroxylase activity was increased 85% in the 1K1C group, as compared with values in one-kidney controls (from 11.8 +/- 1.5 to 21.8 +/- 1.1 pmol CO2/min/mg; p less than 0.0002), and was increased 49% in the 2K1C group, as compared with values in two-kidney controls (from 8.01 +/- 1.2 to 11.9 +/- 1.1 pmol CO2/min/mg; p less than 0.02). In the 1K1C group, proximal mesenteric tyrosine hydroxylase activity was decreased 46% compared with values in one-kidney controls (from 23.5 +/- 5.0 to 12.8 +/- 2.5 pmol CO2/min/mg; p less than 0.03) and distal mesenteric tyrosine hydroxylase activity was decreased 42% (from 7.73 +/- 1.2 to 4.46 +/- 0.8 pmol CO2/min/mg; p less than 0.03). In the 2K1C group, neither proximal nor distal mesenteric tyrosine hydroxylase activity was altered. Tyrosine hydroxylase activity was not detectable in the femoral arteries, or in the thoracic and abdominal aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Synthesis of Catecholamines in the Hypothalamus and Brainstem in One-kidney, One Clip and Two-kidney, One Clip Hypertension in Rabbits.
Date November 1988
Journal Journal of Hypertension
Excerpt

In order to examine the role of central catecholaminergic neurons in hypertension, the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, was studied in the hypothalamus, midbrain, pons-upper medulla, mid-medulla and lower medulla of one-kidney, one clip (1-K,1C) and two-kidney, one clip (2-K,1C) hypertensive rabbits and their respective operated controls (1-K,1 Cc and 2-K,1 Cc). Comparing the 1-K,1 C group to the 1-K, 1 Cc group, the activity of TH was increased by 79% in the hypothalamus (P less than 0.02), 37% in the mid-medulla region (P less than 0.02) and was unchanged in the midbrain, pons-upper medulla and the lower medulla. Comparing the 2-K,1 C group to the 2-K,1 Cc group, the activity of TH was increased by 89% in the mid-medulla (P less than 0.01), decreased by 36% in the pons-upper medulla (P less than 0.01) and unchanged in the hypothalamus, midbrain and lower medulla. These results indicate that similarities and differences exist in the contribution of central catecholaminergic neurons to the pathophysiology of 1-K,1 C and 2-K,1 C hypertension in rabbits.

Title Minimal Change Glomerulonephropathy and Interstitial Infiltration with Mycosis Fungoides.
Date August 1988
Journal The American Journal of Medicine
Excerpt

The nephrotic syndrome developed in a patient with mycosis fungoides shortly after systemic involvement by his tumor occurred. Renal biopsy examination revealed atypical lymphocytic interstitial infiltration and changes consistent with minimal change glomerulonephropathy. The patient's proteinuria decreased following steroid therapy. This is the first report of an association between minimal change glomerulonephropathy and a proven T-cell malignant lymphoma. The implications are discussed with reference to the literature.

Title Nephrectomy-induced Alterations in the Synthesis of Catecholamines in the Sympathetic Nervous System and Central Nervous System.
Date July 1988
Journal American Journal of Hypertension
Excerpt

Reduction in renal function is a key factor to the development of salt-dependent hypertension; however, the mechanism is obscure. To examine the role of the sympathetic nervous system (SNS) and central catecholaminergic neurons in this predisposition to the development of hypertension, the activity of tyrosine hydroxylase (TH) was determined in SNS and in several brain regions. In another group of unilaterally nephrectomized rabbits, cardiovascular responsiveness to norepinephrine was determined. A unilateral nephrectomy increased the activity of TH in the midmedulla, a brain region important in the baroreflex regulation of blood pressure, and in the adrenal gland, the major source of circulating catecholamines. The activity of TH was decreased in the pons-upper medulla region. No alterations were found in the proximal and distal mesenteric arteries, lower medulla, midbrain or hypothalamus. No alteration in blood pressure or cardiovascular responsiveness to norepinephrine was found. This study indicates that a unilateral nephrectomy produces long-lasting effects on central catecholaminergic neurons and the sympathetic nervous system without an effect on blood pressure or cardiovascular responsiveness.

Title Efficacy of Okt3 Monoclonal Antibody Therapy in Steroid-resistant, Predominantly Vascular Acute Rejection. A Report of Three Cases with Morphologic and Immunophenotypic Evaluation.
Date May 1988
Journal Transplantation
Excerpt

We describe three patients who became oliguric and uremic in the early posttransplantation period. Following treatment with pulse methylprednisolone, all had biopsy evidence of severe residual rejection that was predominantly vascular. T cells formed the bulk of the infiltrates. Subsequent treatment with the monoclonal antibody OKT3 was associated with an immediate diuresis and improvement in serum creatinine. Repeat renal biopsy, obtained in clinical remission, in two of the three patients, showed marked improvement in the vascular lesions. All three patients maintain normal renal function 9, 13, and 18 months later. We conclude that OKT3 was effective in reversing steroid-resistant rejection despite a predominantly vascular pattern of cellular infiltration not usually considered amenable to any antirejection therapy.

Title Plasma Inhibitors of Na,k-atpase: Relation to Salt Balance and Hypertension.
Date July 1987
Journal Klinische Wochenschrift
Title Light Chain Cast Nephropathy and Acute Renal Failure Associated with Rifampin Therapy. Renal Disease Akin to Myeloma Kidney.
Date June 1987
Journal The American Journal of Medicine
Excerpt

Acute renal failure developed in a patient with a normal serum creatinine level, after treatment with rifampin was begun for tuberculosis. Renal biopsy revealed an obstructive nephropathy due to tubular casts. Immunoperoxidase and immunofluorescence studies demonstrated the presence of heterogeneous light chains within these casts. This unique drug-induced renal disease is discussed with reference to the literature and to possible analogies with myeloma kidney.

Title Plasma Levels of an Ouabain-like Factor Associated with an Increased Incidence of Cerebral Haemorrhage in One-kidney, One Wrap Hypertension in Rabbits.
Date June 1987
Journal Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension
Excerpt

To examine the role of an ouabain-like factor (OLF) in the pathogenesis of cardiovascular disease in hypertension, we examined plasma levels of OLF in a malignant form of one-kidney, one wrap (1K,1W) hypertension. Two weeks after the induction of hypertension plasma OLF increased to 282% compared to control animals. Additionally, blood pressure, the cardiac index, incidence of cerebral haemorrhage and vascular aneurysms were increased. Blood pressure was found to be inversely correlated with cardiac hypertrophy. No correlations between plasma OLF and blood pressure, cardiac hypertrophy or vascular aneurysms were found. However, hypertensive animals with cerebral haemorrhage had significantly higher plasma OLF than animals without cerebral haemorrhage. These results suggest that high plasma OLF in hypertensive subject may increase the risk of cerebral haemorrhage.

Title Cystitis Cystica: an Electron and Immunofluorescence Microscopic Study.
Date April 1987
Journal The Journal of Urology
Excerpt

Cystitis cystica was studied with the aid of electron and immunofluorescence microscopy. By electron microscopy, the epithelium demonstrated morphologic features suggestive of an active metabolism. Secretory-type granules were seen in the cytoplasm just beneath the luminal membrane of surface columnar cells. Microvilli of the plasma membrane also were seen at the luminal surface. Rough endoplasmic reticulum and Golgi apparatuses were present. The cells were rich in mitochondria. By immunofluorescence microscopy, IgA, secretory piece and IgM were localized in the epithelial cells, especially at the luminal surfaces. IgG was occasionally found. These findings contrast markedly with the transitional cells and their relatively scanty content of secretory-type organelles. In addition, they may explain the large amounts of IgA in the urine of patients with cystitis cystica.

Title Vertebral Malacoplakia. A Case Report.
Date April 1987
Journal The Journal of Bone and Joint Surgery. American Volume
Title Thyroid Indices in Arterial and Venous Cord Blood: Significantly Greater Levels of Reverse Triidothyronine in Venous Blood Than in Arterial Blood.
Date August 1986
Journal Metabolism: Clinical and Experimental
Excerpt

Paired arterial and venous cord blood samples were obtained from 42 normal newborns (24 males and 18 females). T4 was determined in all paired samples. In addition, other indices were determined: T3 in 40, RT3 in 29, TBG in 29, thyroglobulin (Tg) in 14, and TSH in 11. Gender difference in any of the thyroid indices was not found. Arterial and venous cord serum thyroid indices correlated positively (T4, r = 0.743; T3, r = .907, rT3, r = .920; TBG, r = .752; Tg, r = .934, and TSH, r = .989; P less than 0.005). The difference between the means +/- SD of arterial and venous levels was significant (P less than 0.01) only for rT3 (191 +/- 43.2 v 224 +/- 55.8 ng/dL). Arterial (T4 v T3, r = .453, P less than .005; T4 v RT3, r = .660, P less than 0.005) and venous (T4 v T3, r = .620, P less than 0.005; T4 v rT3, r = .612, P less than 0.005); T3 and rT3 levels correlated positively with T4 levels. In contrast, T3 and rT3 levels for arterial (r = .216, P greater than 0.1) and venous (r = .216, P greater than 0.1) samples did not show a significant correlation. These data are in keeping with earlier reports for animal placental models studied in vitro, suggesting that placental inner ring deiodination of maternal thyroxine is a source of fetal RT3.

Title Mesangial Glomerulonephropathy with Decreased Circulating C4 and Predominant Mesangial C4 Deposition in Association with One Null Gene at the C4b Locus.
Date July 1986
Journal Nephron
Excerpt

We report a case of mesangial glomerulonephropathy associated with decreased circulating C4 in a young man with recurrent microscopic hematuria and one null gene at the C4B locus. Mesangial deposits moderately reactive with anti-C4 and weakly reactive with anti-C3 and anti-IgA were found on renal biopsy. No evidence was found to support a diagnosis of IgA nephropathy or any other of the recently described mesangial glomerulonephropathies with immunoglobulin and complement deposition. This case apparently represents a unique, heretofore undescribed variant of mesangial glomerulonephropathy associated with mesangial C4 deposition and C4 hypocomplementemia.

Title Keratoplasty for Pseudophakic Keratopathy.
Date June 1986
Journal Australian and New Zealand Journal of Ophthalmology
Excerpt

Penetrating corneal grafts were performed on 15 eyes with keratopathy due to implantation of iris-supported intraocular lenses, on one eye with keratopathy due to an anterior chamber lens, and one eye with keratopathy due to a posterior chamber lens. A systematic meticulous surgical technique, with a softened eye, the use of a Flieringa ring, anterior vitrectomy and sodium hyaluronate (Healon) have resulted in clear grafts in all except in four eyes. Although most grafts have remained clear, the visual results are poor mainly due to glaucoma and/or maculopathy. Every effort was made to retain the implants and some were repositioned and sutured to the iris. Long-term postoperative follow-up, with good patient compliance and the judicious use of topical corticosteroids and timolol, is essential to maintain clear grafts.

Title Malignant Melanoma. Inflammatory Mononuclear Cell Infiltrates in Cerebral Metastases During Concurrent Therapy with Viral Oncolysate.
Date April 1986
Journal Cancer
Excerpt

Five patients with advanced malignant melanoma, treated with viral oncolysate, had solitary central nervous system metastases that were removed surgically. Histologic examination revealed striking and significant mononuclear inflammatory cell infiltrates, consisting of a mean of 60% plasma cells and a lesser proportion of lymphocytes at the edges of the lesions, within their supporting fibrovascular trabeculae, and among the tumor cells. Comparable inflammatory changes were not found in solitary metastatic malignant melanomas removed surgically from the brains of 19 patients not treated with viral oncolysate. Similarly, multiple metastatic malignant melanomas obtained postmortem from the brains of 12 patients not treated with viral oncolysate showed minimal inflammatory responses. Ultrastructural examination of material from a single treated patient revealed morphologic abnormalities of the blood-brain barrier, changes that were perhaps conducive to infiltration of the neoplasm by inflammatory cells. The authors suggest that administration of viral oncolysate enhances the inflammatory cell response to metastatic malignant melanoma in the brain.

Title Perineural Cell Tumor. Immunocytochemical and Ultrastructural Characterization. Relationship to Other Peripheral Nerve Tumors with a Review of the Literature.
Date March 1986
Journal Virchows Archiv. A, Pathological Anatomy and Histopathology
Excerpt

A perineurial cell tumor occurred in the shoulder girdle of a 47 year old woman. Light microscopy demonstrated a well-differentiated spindle-cell neoplasm of uncertain histogenesis. Immunocytochemical staining for S-100 protein was negative. Ultrastructural study revealed tumor cells with characteristics of perineurium, e.g. large numbers of micropinocytotic vesicles, numerous intercellular junctions, and elongated cell processes surrounded by basal lamina. Tumors of perineurial cells should be distinguished from the commonly recognized schwannomas as well as from various soft tissue lesions so that their biologic behavior can be better defined. A review of three other reported cases of perineurial cell tumors suggested that these tumors are benign and are usually located in the extremities and shoulder girdle. In addition, perineurial cell proliferation has been identified in other lesions of peripheral nerves, such as neurofibromas and localized hypertrophic neuropathy. Immunocytochemical and ultrastructural study of spindle-cell lesions with unusual histologic features may reveal that perineurial cell proliferation occurs more frequently than currently recognized.

Title Moderate Drinking: an Alternative Treatment Goal.
Date April 1985
Journal Canadian Medical Association Journal
Title Iron Pigment in the Brain of a Man with Tardive Dyskinesia.
Date March 1985
Journal The American Journal of Psychiatry
Excerpt

A 64-year-old man with bipolar affective disorder developed persistent tardive dyskinesia following an overdose of lithium and haloperidol. Two years later he died of unknown causes. Neuropathologic examination revealed extensive deposition of iron in basal ganglia and substantia nigra.

Title Characterization of Two Types of Crystalloids in Pleomorphic Adenomas of Minor Salivary Glands. A Light-microscopic, Electron-microscopic, and Histochemical Study.
Date March 1985
Journal The American Journal of Pathology
Excerpt

Crystalloids have been previously described in salivary gland tumors. In order to ascertain the incidence of these structures, the authors reviewed a series of 294 minor salivary gland tumors. One hundred thirty pleomorphic adenomas were identified, and 6 of these contained crystalloids. No crystalloids were found in other benign or malignant salivary gland tumors. These six file cases and a recent seventh case containing crystalloids were studied by light and electron microscopy and with histochemistry. Two types of crystalloids were found. One case contained previously described tyrosine-rich crystalloids, and the other six contained crystalloids composed of radially arranged collagen fibers. Both types of crystalloids are further characterized and discussed.

Title Intraoral Multifocal Adult Rhabdomyoma. Report of a Case and Review of the Literature.
Date December 1983
Journal Archives of Pathology & Laboratory Medicine
Excerpt

Adult rhabdomyomas are uncommon, benign neoplasms of the head and neck region. They are usually solitary, but may rarely be multifocal. We report the clinical and morphologic features of a multifocal adult rhabdomyoma apparently present in the floor of the mouth of an elderly woman for 20 years. At the time of exploratory surgery, the surgeon believed there was diffuse multinodular enlargement of both sublingual glands. The differential diagnosis of a biopsy specimen that was taken for frozen section included salivary gland oncocytosis, a reactive process. On examination of permanent sections, however, the lesion was found to be a multifocal rhabdomyoma. No evidence of salivary gland tissue was found. Ultrastructural study demonstrated the characteristic attempts by this tumor to recapitulate its origin from skeletal muscle by the formation of abnormal contractile elements.

Title Hyperinsulinemic Hypoglycemia in Adults with Islet-cell Hyperplasia and Degranulation of Exocrine Cells of the Pancreas.
Date February 1983
Journal American Journal of Clinical Pathology
Excerpt

Five adults with pancreatic islet-cell hyperplasia presenting as hyperinsulinemic hypoglycemia are reported. Additional insular lesions including nesidioblastosis, adenomatosis, and insulinoma were variably present. This apparent spectrum of islet-cell lesions has been rarely noticed in hypoglycemic adults, although it is a recognized cause of a similar clinical syndrome in children. B-cell hyperplasia was confirmed in all five cases by histochemistry, immunochemistry, and electron microscopy. In addition, nodules of eosinophilic exocrine cells, another recently recognized finding in similar cases, were present in all cases studied. Ultrastructural study revealed that these nodules were composed of degranulated acinar cells. These acinar changes may provide a diagnostic aid in cases of pancreatic endocrine hyperplasia. Consideration of the embryologic development of the pancreas suggests that this spectrum of islet-cell hyperplasia and acinar cell change is due to neoformation of islets from ducts. The etiologic factors of such proliferation are still unknown.

Title Light and Electron Microscopic Studies of the Pathogenesis of Vaccinia Virus Infection in Mouse Brain.
Date January 1983
Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
Title The Syndrome of Prolapse of the Mitral Valve: an Etiologic and Pathogenic Enigma.
Date September 1982
Journal Archives of Pathology & Laboratory Medicine
Excerpt

Prolapse of the mitral valve has superseded rheumatic heart disease in recent years as the most common cause of isolated mitral insufficiency in Europe and North America. This condition is recognized with increasing frequency, and its prevalence increases with age, apparently afflicting more than 5% of all persons older than 50 years of age. Consequently, mitral valve prolapse has acquired considerable medical and economic importance. Familial and nonfamilial forms are recognized. Nonfamilial forms can be further classified into cases that occur in statistically significant association with other diseases, and sporadic cases that include those possibly secondary to other conditions.

Title Hypnosis for Urinary Retention.
Date August 1982
Journal The American Journal of Psychiatry
Title Relationship of Sodium Retention and Induction of Hypertensive Arterial Necrosis in Rabbits.
Date May 1982
Journal Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (new York, N.y.)
Title Aggressive Fibromatosis Involving the Paramandibular Soft Tissues. A Study with the Aid of Electron Microscopy.
Date January 1982
Journal Oral Surgery, Oral Medicine, and Oral Pathology
Excerpt

The distinction at the level of light microscopy between aggressive fibromatosis and low-grade malignancies with fibroblastic features may be difficult. An electron microscopic study of four cases of aggressive fibromatosis of the mandibular soft tissue was undertaken to determine whether any ultrastructural characteristics could be identified that would aid in a more uniform distinction between these lesions. The pertinent findings include the identification of cells of fibroblastic derivation showing a range of organelle-poor to organelle-rich features, cytoplasmic microfibrils, and dilated rough endoplasmic reticulum profiles. These features are discussed in the light of previously published findings of other forms of aggressive fibromatosis and closely related lesions. The study reaffirms that although electron microscopy may be useful in confirming the cell of origin in these lesions, the accurate diagnosis of fibrous tumors still rests with the proper correlation of clinical and light microscopic features. Clinical follow-up of the cases supports both the diagnosis of aggressive fibromatosis and the recommended treatment of adequate local excision.

Title Subepithelial Argyrophilic Spicular Structures in Renal Amyloidosis--an Aid in Diagnosis. Pathogenic Considerations.
Date December 1981
Journal Human Pathology
Excerpt

Eighteen cases of amyloidosis with renal involvement were classified utilizing clinical and laboratory data as to the most likely major amyloid fibril protein type and studied as to their histological, tinctorial, immunofluorescence, and electron microscopic features. No differences could be appreciated between the AA and AL types of amyloidosis. Immunofluorescence did not aid in the diagnosis of amyloidosis and was confusing in some cases owing to apparent absorption of serum proteins. Subepithelial spicular structures were noted in the glomerular capillary loops in 14 of 18 cases (78 per cent), and similar structures were found related to tubular epithelial cells in six of these cases and were related to the parietal epithelium of Bowman's membrane in one case. These spicular structures were a valuable aid in the diagnosis of early amyloidosis by light microscopy, but electron microscopy was essential for confirmation. We postulate that because of the intense staining quality of spicular structures using argyrophilic techniques, these spicules result from a unique interaction between amyloid fibrils and locally produced substances, most probably renal epithelial basement membrane glycoprotein.

Title Nasal 'glioma' with Prominent Neuronal Component: Report of a Case.
Date November 1981
Journal Archives of Pathology & Laboratory Medicine
Title The Papillary and Solid Neoplasm of the Pancreas: a Report of Two Cases with Electron Microscopy, One Containing Neurosecretory Granules.
Date October 1981
Journal Cancer
Excerpt

Two pancreatic tumors occurred in young women without detected functional symptoms. They had similar gross and histologic features and appeared to be of low grade malignancy. Case 1 was a typical example of the recently described entity referred to as papillary and solid neoplasm of the pancreas. Electron microscopic findings in this case indicated a duct cell origin, similar to previously reported cases. Case 2, also ultrastructurally similar, is unique in that it contained neurosecretory granules. Since considerable evidence indicated that cells of small pancreatic ducts give rise to islet cells, case 2 suggests that some tumors of ductal origin recapitulate the embryogenesis of the pancreatic islets and, therefore, may contain neurosecretory granules without showing the classic morphology of the more common pancreatic endocrine tumors.

Title Clinicopathologic Conference. Grady Memorial Hospital--emory University. Progressive Systemic Sclerosis with Terminal Neurologic Manifestations.
Date August 1981
Journal Southern Medical Journal
Title Epidermoid Splenic Cyst Occurring in an Intrapancreatic Accessory Spleen.
Date March 1981
Journal Digestive Diseases and Sciences
Excerpt

This case describes a 40-year-old man with abdominal pain, nausea, and vomiting, who was found to have a cystic lesion in the tail of the pancreas. Distal pancreatectomy and splenectomy revealed a primary epidermoid cyst of the spleen lying in the substance of the tail of the pancreas. This represents the only report of a splenic cyst in an ectopic spleen that could be found in a search of the world literature.

Title Observations on the Small Kidney Associated with Vesicoureteral Reflux.
Date July 1980
Journal Transactions of the American Association of Genito-urinary Surgeons
Excerpt

Of 63 patients with reflux and renal atrophy renal dysplasia was found in 9.5%. Pyelonephritis was apparent in 81% of the atrophic lesions. Urinary obstruction or ectasia was apparent in each case with dysplasia and only 2 were associated with histologic evidence of pyelonephritis. Pyelonephritis appears to be a major causal factor in atrophy occurring in renal units with reflux. Early urinary tract obstruction or distension may predispose to renal dysplasia.

Title Observations on the Small Kidney Associated with Vesicoureteral Reflux.
Date May 1980
Journal The Journal of Urology
Excerpt

Of 63 patients with reflux and renal atrophy renal dysplasia was found in 9.5 per cent. Pyelonephritis was apparent in 81 per cent of the atrophic lesions. Urinary obstruction or ectasia was apparent in each case with dysplasia and only 2 were associated with histologic evidence of pyelonephritis. Pyelonephritis appears to be a major causal factor in atrophy occurring in renal units with reflux. Early urinary tract obstruction or distension may predispose to renal dysplasia.

Title Alterations in Responses to Bradykinin, Angiotensin I, and Angiotensin Ii During the Induction Phase of One-kidney, One-wrapped Hypertension and Associated Arterial Disease in Rabbits.
Date April 1980
Journal The American Journal of Pathology
Title Pneumocystis Pneumonia. Animal Model: Pneumocystis Cartinii Pneumonia in the Immunosuppressed Rat.
Date August 1979
Journal The American Journal of Pathology
Title Serum Angiotensin Converting Enzyme Activity and the Capacity to Develop Hypertention-associated Arterial Disease. Studies During the Induction Phase of One-kidney Perinephritis Hypertension in Rabbits.
Date January 1979
Journal The American Journal of Pathology
Excerpt

Serum angiotensin converting enzyme (ACE) activity and plasma renin activity (PRA) were studied during the development of the widespread necrotic arterial disease that occurs in the induction phase of one-kidney perinephritis hypertension. Control serum ACE activity was significantly higher in rabbits developing many arterial lesions than it was in rabbits developing relatively few arterial lesions. Serum ACE decreased 7 days after the production of unilateral perinephritis in all rabbits. Following contralateral nephrectomy, serum ACE decreased further in rabbits devloping many arterial lesions but returned toward control values in rabbits developing relatively few arterial lesions. Significant inverse correlations were demonstrated for the total number of arterial lesions that developed relative to a) the decrease in serum ACE activity 7 days after the production of unilateral perinephritis, b) the lowest or the average serum ACE activity during the period of development of the arterial lesions after contralateral nephrectomy, and c) the change in serum ACE activity during the period of development of the arterial lesions. Chronic treatment with SQ 20,881, a synthetic nonapeptide inhibitor of ACE activity, during the period of development of the hypertension and the arterial lesions significantly reduced the serum ACE activity and the hypertension but did not change interrelationships between serum ACE activity and the number of arterial lesions that developed. PRA significantly decreased after the production of perinephritis and decreased somewhat further during the induction period of the hypertension after contralateral nephrectomy. No relationships were demonstrated between PRA, or changes in PRA, and the development of arterial lesions. The increase in blood pressure during the incubation period of the hypertension did not correlate with the number of arterial lesions that developed. These finding indicate that serum ACE activity reflects importantly on the capacity to develop necrotic arterial lesions during the induction phase of one-kidney perinephritis hypertention and on functional events relating to their pathogenesis.

Title Hepatoblastoma in Infant Sister and Brother.
Date August 1977
Journal Cancer
Excerpt

Two infants, a sister with motor retardation and brother with slight microcephaly and an undescended testis, died of hepatoblastoma. Only another documented familial occurrence of this tumor, affecting siblings of the same sex, can be found in the literature. The two patients described in this paper exhibited high platelet counts prior to liver resection. Although iron deficiency may have contributed to the thrombocytosis, the finding of many megakariocytes within the hepatoblastomas suggests an intra-tumoral production of platelets. An epidemiological investigation of the family under study failed to yield conclusive data. Hepatoblastoma is a rare tumor, but it may affect more than one sibling. Therefore, periodic clinical and laboratory evaluations of the siblings at risk appear to be justified.

Title Pulmonary Pneumocystosis in Nonhuman Primates.
Date April 1976
Journal Archives of Pathology & Laboratory Medicine
Excerpt

Pulmonary infection with Pneumocystis carinii was detected in two aged owl monkeys (Aotus trivirgatus) and two young chimpanzees (Pan troglodytes). The clinical histories of the owl monkeys were similar and included progressive weight loss, anorexia, failure to thrive, and death. One of the owl monkeys had no concurrent disease, whereas the other had been experimentally inoculated with Treponema pallidum 44 months before death. In both chimpanzees, an underlying myeloproliferative malignant neoplasm was associated with Pneumocystis infection. Pneumocystis organisms were found in alveolar spaces and alveolar lining cells by light and electron microscopy. Pathologic features of these untreated cases and a case in a chimpanzee treated with pentamidine isethionate were similar to those described in humans. To our knowledge, this is the first report of pulmonary pneumocystosis associated with death in nonhuman primates.

Title The Pathogenesis of Vaccinia Virus Toxicity. I. The Role of Virus-platelet Interaction.
Date February 1976
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Excerpt

When mice are injected intravenously with a large dose of vaccinia virus, prepared in the Ehrlich ascites carcinoma of the mouse, there is a precipitous loss of plasma fibrinogen and blood platelets. Death occurs usually within 24 hours. A specific role of the virus in this toxic syndrome can be demonstrated when heparin is employed to circumvent intravascular coagulation and fibrinogen loss. Heparin does not prevent a profound thrombocytopenia from occurring, but it modifies the rate of platelet loss. Toxicity is prevented when heparinized virus preparations are pretreated with beta-propiolactone or specific antibody, although a mild thrombocytopenia occurs. Thrombocytopenia does not occur in mice injected with heparinized material prepared from uninfected tumors. These studies indicate that the basic mechanism of vaccinia virus toxicity is an early interaction between infectious virus and blood platelets, with marked thrombocytopenia and consequential pathophysiologic changes.

Title The Pathogenesis of Vaccinia Virus Toxicity. Ii. An Electron Microscopic Study.
Date February 1976
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Excerpt

The intravenous injection of mice with toxic doses of vaccinia virus, prepared in the Ehrlich ascites carcinoma, usually produces fatal intravascular coagulation, within 24 hours. Light and electron microscope studies demonstrate occlusion of the microcirculation of lungs and livers by fibrin. Fibrin deposition appears to be prevented in mice injected with heparinized virus preparations. However, in lieu of fibrin deposition, within the microcirculation widespread intravascular platelet aggregation occurs. Platelets within these aggregates are in various stages of degranulation, and some platelets have phagocytosed vaccinia virus. Platelet aggregation was not observed in mice receiving injections of heparinized material prepared from uninfected tumors. In mice surviving longer than 12 hours, hepatocytes and endothelial cells of pulmonary capillaries are the sites of viral replication. Although many hepatocytes are infected in mice surviving longer than 12 hours, it is postulated that hepatocyte necrosis is in part due to the congestive effects resulting from obstruction of liver and pulmonary capillaries. These studies suggest that vaccinia virus may trigger in vivo platelet aggregation, and that obstruction of the lung and liver microcirculation by these aggregates is the initial lesion of vaccinia virus toxicity.

Title Fatal Infectious Mononucleosis. Association with Liver Necrosis and Herpes-like Virus Particles.
Date May 1975
Journal Archives of Pathology
Excerpt

A 20-year-old woman died of infectious mononucleosis associated with extensive hepatic necrosis with herpes-type inclusions within nuclei of remaining liver cells. Electron microscopical examination of these liver cells showed intranuclear and occasional intracytoplasmic herpes-like virus. This case supports the concept that a herpes-like virus, or a structurally closely related agent, is the etiological agent of infectious mononucleosis.

Title Ultrastructure of the Giant-cell Fibroma of the Oral Mucosa.
Date December 1974
Journal Oral Surgery, Oral Medicine, and Oral Pathology
Title Exudative Peritonitis Induced in Mice by Bovine Serum Albumin.
Date January 1974
Journal Archives of Pathology
Title Ultrastructure of Pneumocystis in Human Lung. Life Cycle in Human Pneumocystosis.
Date June 1972
Journal Archives of Pathology
Title Diabetes Insipidus As a Complication of Leukemia. A Case Report with a Literature Reviews.
Date December 1971
Journal Cancer
Title Effects of Dietary Copper Loading on Livers of Rats. I. Changes in Subcellular Acid Phosphatases and Detection of an Additional Acid P-nitrophenylphosphatase in the Cellular Supernatant During Copper Loading.
Date September 1971
Journal The American Journal of Pathology
Title Regeneration of Synovium of Rabbit Knees After Total Chemical Synovectomy by Ingrowth of Connective Tissue-forming Elements from Adjacent Bone. A Light and Electron Microscopic Study.
Date August 1971
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Title Infection of Rabbit Knee Joints After Intra-articular Injection of Staphylococcus Aureus. Comparison with Joints Injected with Staphylococcus Albus.
Date October 1970
Journal The American Journal of Pathology
Title Pneumocystis Carinii in Lungs of Rats Treated with Cortisone Acetate. Ultrastructural Observations Relating to the Life Cycle.
Date April 1969
Journal The American Journal of Pathology
Title Posterior Prostatectomy.
Date February 1969
Journal International Surgery
Title Synovial Fine Structure and Permeability After Intra-articular Nitrogen Mustard.
Date February 1968
Journal Archives of Pathology
Title Further Observations on the Ultrastructure of Pneumocystis.
Date July 1967
Journal Archives of Pathology
Title Widely Distributed Necrotic Arterial Lesions Induced in Rabbits by Experimental Renal Alterations. Vi. Demonstration of Antigenic Determinants of Gamma-globulin and of Thrombin-clottable Plasma Protein in Arterial Lesions: Uptake of Guinea Pig Complement in Vitro.
Date April 1967
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Title Widely Distributed Necrotic Arterial Lesions Induced in Rabbits by Experimental Renal Alterations. V. Light Microscopic Studies of Early Lesions of Arterial, Cardiac, and Skeletal Muscle.
Date April 1967
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Title Experimental Induction of Athero-arteriosclerosis by the Synergy of Allergic Injury to Arteries and Lipid-rich Diet. I. Effect of Repeated Injections of Horse Serum in Rabbits Fed a Dietary Cholesterol Supplement.
Date January 1967
Journal The Journal of Experimental Medicine
Title Evidence of a Causative Role of Adrenocortical Activity in the Genesis of Disseminated Arterial Lesions Induced in Rabbits by Renal Alterations.
Date January 1967
Journal Laboratory Investigation; a Journal of Technical Methods and Pathology
Title A Comparison of Two Methods of Assessing Alcoholism.
Date
Journal Canadian Family Physician Médecin De Famille Canadien
Excerpt

The author examined Michigan Alcohol Screening Test (MAST) scores and selected laboratory results of 50 patients encountered in a family physician's office. The severity of alcohol-related problems (as reflected by the MAST) was compared to the toxic effects of alcohol (as measured by the SGOT, γ-glutamyltransferase levels, and the mean cell volume). No association was found between the MAST scores and the cellular toxic effect of alcohol. Patients with extensive alcohol-related problems were more likely to report prolonged sobriety. These results suggest that testing with both MAST and laboratory tests is required to discover the effects of alcohol abuse in ambulatory patients.


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