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Dermatologist (skin)
7 years of experience
Video profile
Accepting new patients

Education ?

Medical School Score Rankings
Temple University Physicians (2003)
  • Currently 3 of 4 apples
Top 50%

Awards & Distinctions ?

Awards  
Patients' Choice Award (2010)
Compassionate Doctor Recognition (2010)
Associations
American Board of Dermatology
American Society for Dermatologic Surgery

Affiliations ?

Dr. Levin is affiliated with 8 hospitals.

Hospital Affilations

Score

Rankings

  • Lehigh Valley Hospital
    1200 S Cedar Crest Blvd, Allentown, PA 18103
    • Currently 4 of 4 crosses
    Top 25%
  • Hospital of the University of PA
    3400 Spruce St, Philadelphia, PA 19104
    • Currently 4 of 4 crosses
    Top 25%
  • Lehigh Valley Hospital - Muhlenberg
    2545 Schoenersville Rd, Bethlehem, PA 18017
    • Currently 4 of 4 crosses
    Top 25%
  • Sacred Heart Hospital/Allentown
    421 Chew St, Allentown, PA 18102
    • Currently 4 of 4 crosses
    Top 25%
  • Schuylkill Medical Center - East Norwegian Street
  • Schuylkill Medical Center - South Jackson Street
  • St Lukes Hospital - Allentown Campus
  • Lehigh Valley Hospital - Allentown Campuses
  • Publications & Research

    Dr. Levin has contributed to 80 publications.
    Title Lip Plumper Contact Urticaria.
    Date May 2009
    Journal Journal of the American Academy of Dermatology
    Excerpt

    Lip plumpers are relatively new topical agents on the market that are designed to increase lip volume minutes to days after application. In this report, we describe a case of lip plumper contact urticaria in a young boy. We also discuss the mechanisms of action of lip plumpers and the sociocultural reasons for their use.

    Title Differential Effects of Acute Cocaine and Placebo Administration on Visual Cortical Activation in Healthy Subjects Measured Using Bold Fmri.
    Date April 2009
    Journal Pharmacology, Biochemistry, and Behavior
    Excerpt

    Many blood oxygenation level dependent (BOLD) functional magnetic resonance imaging studies have shown a strong response due to cocaine in brain regions with high concentrations of dopamine receptors. However, cocaine also has non-specific effects, including cardiovascular changes that may cause changes in BOLD signals, raising the possibility that measured changes could be due to these non-specific effects. The following experiment was conducted to address this concern. Subjects were given either cocaine or saline infusions during a long BOLD functional magnetic resonance imaging study. A flashing uniform-field stimulus, periodically alternating between on and off, provided a strong activation of primary visual cortex. There was a significant main effect of drug between cocaine and placebo. Although we did not demonstrate a significant drug x time interaction, BOLD signal changes associated with visual stimulation appeared unchanged after cocaine administration, whereas the signal differences appeared to decrease during placebo. Explanation of the differential response between the two groups may reflect cocaine expectancy instead of a direct effect of cocaine on BOLD signal changes but will require further investigation to fully elucidate.

    Title Ultraviolet Recall Reaction After Total Body Irradiation, Etoposide, and Methotrexate Therapy.
    Date March 2007
    Journal Journal of the American Academy of Dermatology
    Excerpt

    Ultraviolet (UV) reactivation reactions are rare and can occur in areas of prior sunburn or UV light therapy after the administration of chemotherapy, antibiotics, and other medications. Reactions may occur within days, as described after methotrexate therapy, or may appear months later, as described with ampicillin. Such reactions have been variably termed "UV recall," "sunburn recall," "photo recall," and "photodermatitis reactivation," making classification difficult. We report a UV reactivation reaction in a patient with acute lymphocytic leukemia treated with total body irradiation, etoposide, and methotrexate. We propose the terms "UV recall" and "UV enhancement" be used in future reports to classify UV reactivation reactions in a scheme analogous to the terminology for cutaneous reactions after radiotherapy.

    Title Suture Granuloma Following Surgical Neck Rejuvenation Procedure.
    Date June 2006
    Journal Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]
    Title Time-resolved Three-dimensional Magnetic Resonance Velocity Mapping of Aortic Flow in Healthy Volunteers and Patients After Valve-sparing Aortic Root Replacement.
    Date October 2005
    Journal The Journal of Thoracic and Cardiovascular Surgery
    Excerpt

    OBJECTIVE: To provide more complete characterization of ascending aortic blood flow, including vortex formation behind the valve cusps, in healthy subjects and patients after valve-sparing aortic root replacement (David reimplantation). METHODS: Time-resolved 3-dimensional magnetic resonance imaging velocity mapping was performed to analyze pulsatile blood flow by using encoded 3-directional vector fields in the thoracic aortas of 10 volunteers and 12 patients after David reimplantation using a cylindrical tube graft (T. David I) and two versions of neosinus recreation (T. David-V and T. David-V-S mod ). Aortic flow was evaluated by using 3-dimensional time-resolved particle traces and velocity vector fields reformatted onto 2-dimensional planes. Semiquantitative data were derived by using a blinded grading system (0-3: 0, none; 1, minimal; 2, medium; 3, prominent) to analyze the systolic vortex formation behind the cusps, as well as retrograde and helical flow in the ascending aorta. RESULTS: Systolic vortices were seen in both coronary sinuses of all volunteers (greater in the left sinus [2.5 +/- 0.5] than the right [1.8 +/- 0.8]) but in only 4 of 10 noncoronary sinuses (0.7 +/- 0.9). Comparable coronary vortices were detected in all operated patients. Vorticity was minimal in the noncoronary cusp in T. David-I repairs (0.7 +/- 0.7) but was prominent in T. David-V noncoronary graft pseudosinuses (1.5 +/- 0.6; P = .035). Retrograde flow (P = .001) and helicity (P = .028) were found in all patients but were not distinguishable from normal values in the T. David-V-S mod patients. CONCLUSIONS: Coronary cusp vorticity was preserved after David reimplantation, regardless of neosinus creation. Increased retrograde flow and helicity were more prominent in T. David-V patients. These novel magnetic resonance imaging methods can assess the clinical implications of altered aortic flow dynamics in patients undergoing various types of valve-sparing aortic root replacement.

    Title Images in Cardiovascular Medicine. Four-dimensional Magnetic Resonance Velocity Mapping in a Healthy Volunteer with Pseudocoarctation of the Thoracic Aorta.
    Date January 2005
    Journal Circulation
    Title Computed Tomography Angiographic Demonstration of a Ventricular Septal Defect.
    Date December 2004
    Journal European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery
    Title White Matter Hyperintensities in Subjects with Cocaine and Opiate Dependence and Healthy Comparison Subjects.
    Date December 2004
    Journal Psychiatry Research
    Excerpt

    The prevalence, severity, and location of white matter signal hyperintensities (WMH) on brain magnetic resonance images were compared in patients with cocaine or opiate dependence and healthy subjects. Patients with cocaine (n=32) and opiate dependence (n=32), whose diagnoses were confirmed with the Structured Clinical Interview for DSM-IV, and age- and sex-matched healthy subjects (n=32) were scanned using a 1.5 T whole body GE magnetic resonance scanner. Axial proton-density and T2-weighted images were obtained as well as fluid-attenuated inversion recovery axial images. The severity of WMH was assessed separately for deep (and insular) and periventricular WMH, using a modified composite version of the rating scales of Fazekas and Coffey. The cocaine-dependent group had greater severity of WMH than the opiate-dependent group, which in turn had greater severity of WMH than the healthy comparison group (odds ratios=2.54 and 2.90, respectively). The cocaine-dependent group had greater lesion severity of deep and insular WMH than the opiate-dependent group and the healthy comparison group (odds ratio>3.25 for deep WMH; odds ratio>4.38 for insular WMH). For periventricular WMH, there were no significant differences between the three groups. The frontal lobes were the predominant locations of WMH in both substance-dependent groups. The greater prevalence and severity of WMH in cocaine-dependent subjects than in opiate-dependent subjects may reflect the fact that cocaine induces more ischemia via vasoconstriction than opiates. Also, there was a trend for lower WMH severity in substance-dependent women relative to the healthy comparison group, possibly due to estrogen's protective effect against cerebrovascular accidents.

    Title Transplantation of Adipose Tissue-derived Stromal Cells Increases Mass and Functional Capacity of Damaged Skeletal Muscle.
    Date November 2004
    Journal Cell Transplantation
    Excerpt

    The regenerating skeletal muscle environment is capable of inducing uncommitted progenitors to terminally differentiate. The aim of this work was to determine whether adipose tissue-derived stromal cells were able to participate in muscle regeneration and to characterize the effect on muscle mass and functional capacities after transplantation of these cells. Adipose tissue stromal cells labeled with Adv cyto LacZ from 3-day-old primary cultures (SVF1) were autotransplanted into damaged tibialis anterior muscles. Fifteen days later, beta-galactosidase staining of regenerated fibers was detected, showing participation of these cells in muscle regeneration. Two months after SVF1 cell transfer, muscles were heavier, showed a significantly larger fiber section area, and developed a significantly higher maximal force compared with damaged control muscles. These results are similar to those previously obtained after satellite cell transplantation. However, SVF1 transfer also generated a small amount of adipose tissue localized along the needle course. To minimize these adipose contaminants, we transferred cells from 7-day-old secondary cultures of the SVF1, containing only a small proportion of already engaged preadipocytes (SVF2). Under these conditions, no adipose tissue was observed in regenerated muscle but there was also no effect on muscle performances compared with damaged control muscles. This result provides further evidence for the existence of progenitor cells in the stromal fraction of freshly isolated adipose tissue cells, which, under our conditions, keep some of their pluripotent properties in primary cultures.

    Title Time-resolved 3-dimensional Velocity Mapping in the Thoracic Aorta: Visualization of 3-directional Blood Flow Patterns in Healthy Volunteers and Patients.
    Date August 2004
    Journal Journal of Computer Assisted Tomography
    Excerpt

    OBJECTIVE: An analysis of thoracic aortic blood flow in normal subjects and patients with aortic pathologic findings is presented. Various visualization tools were used to analyze blood flow patterns within a single 3-component velocity volumetric acquisition of the entire thoracic aorta METHODS: Time-resolved, 3-dimensional phase-contrast magnetic resonance imaging (3D CINE PC MRI) was employed to obtain complete spatial and temporal coverage of the entire thoracic aorta combined with spatially registered 3-directional pulsatile blood flow velocities. Three-dimensional visualization tools, including time-resolved velocity vector fields reformatted to arbitrary 2-dimensional cut planes, 3D streamlines, and time-resolved 3D particle traces, were applied in a study with 10 normal volunteers. Results from 4 patient examinations with similar scan prescriptions to those of the volunteer scans are presented to illustrate flow features associated with common pathologic findings in the thoracic aorta. RESULTS: Previously reported blood flow patterns in the thoracic aorta, including right-handed helical outflow, late systolic retrograde flow, and accelerated passage through the aortic valve plane, were visualized in all volunteers. The effects of thoracic aortic disease on spatial and temporal blood flow patterns are illustrated in clinical cases, including ascending aortic aneurysms, aortic regurgitation, and aortic dissection. CONCLUSION: Time-resolved 3D velocity mapping was successfully applied in a study of 10 healthy volunteers and 4 patients with documented aortic pathologic findings and has proven to be a reliable tool for analysis and visualization of normal characteristic as well as pathologic flow features within the entire thoracic aorta.

    Title Using in Silico Biology to Facilitate Drug Development.
    Date July 2003
    Journal Novartis Foundation Symposium
    Excerpt

    G protein-coupled receptor (GPCR) mediation of cardiac excitability is often overlooked in predicting the likelihood that a compound will alter repolarization. While the areas of GPCR signal transduction and electrophysiology are rich in data, experiments combining the two are difficult. In silico modelling facilitates the integration of all relevant data in both areas to explore the hypothesis that critical associations may exist between the different GPCR signalling mechanisms and cardiac excitability and repolarization. An example of this linkage is suggested by the observation that a mutation of the gene encoding HERG, the pore-forming subunit of the rapidly activating delayed rectifier K+ current (I(Kr)), leads to a form of long QT syndrome in which affected individuals are vulnerable to stress-induced arrhythmia following beta-adrenergic stimulation. Using Physiome's In Silico Cell, we constructed a model integrating the signalling mechanisms of second messengers cAMP and protein kinase A with I(Kr) in a cardiac myocyte. We analysed the model to identify the second messengers that most strongly influence I(Kr) behaviour. Our conclusions indicate that the dynamics of regulation are multifactorial, and that Physiome's approach to in silico modelling helps elucidate the subtle control mechanisms at play.

    Title Sfrp2 Expression in Rabbit Myogenic Progenitor Cells and in Adult Skeletal Muscles.
    Date July 2002
    Journal Journal of Muscle Research and Cell Motility
    Excerpt

    Satellite cells derived from fast- and slow-twitch muscles have different properties in culture. We have used the differential display technique to retrieve genes differentially expressed in fast- and slow-twitch muscle satellite cell cultures. Amongst these genes we have identified, cloned, sequenced and studied the expression in muscle of rabbit secreted frizzled related protein 2 (SFRP2) mRNA, whose importance in cell fate determination has been well documented. It has been shown that SFRP2 is widely expressed in the developing embryo but its expression in the adult is much more restricted. We show that primary cultures of satellite cells from adult rabbit fast- and slow-twitch muscles strongly and differentially express SFRP2 mRNA. Embryonic rabbit muscle cell primary cultures also strongly express SFRP2 mRNA whereas the myoblast C2.7 cell line shows little expression. We also studied SFRP2 mRNA expression in growing, regenerating and denervated muscles. Embryonic rabbit muscles express SFRP2 mRNA but this rapidly falls off after birth. In adult rabbit muscles SFRP2 mRNA is detected within 1 day of either muscle damage or denervation. Thereafter the SFRP2 mRNA expression profiles are different for fast- and slow-twitch muscle. The function of SFRP2 in muscle is unknown but its putative activity as a Wnt antagonist and its precocious expression after muscle damage suggest a role in satellite cell activation.

    Title Influence of Baseline Hematocrit and Hemodilution on Bold Fmri Activation.
    Date January 2002
    Journal Magnetic Resonance Imaging
    Excerpt

    Current understanding of blood oxygenation level dependent (BOLD) fMRI physiology predicts a close relationship between BOLD signal and blood hematocrit level. However, neither this relationship nor its effect on BOLD percent activation (BPA) has been empirically examined in man. To that end, BPA in primary visual cortex in response to photic stimulation was determined in a group of 24 normal subjects. A positive linear relationship between BPA and hematocrit was seen, particularly in men. To evaluate the effect of change in hematocrit on BPA, 9 men were studied before and following isotonic saline hemodilution, resulting in an average 6% reduction in hematocrit and an 8-31% reduction in BPA. No significant change in the number of activated pixels was seen. A model of predicted BPA as a function of hematocrit and vessel size was developed, and results from this model closely mirrored the empiric data. These results suggest that hematocrit significantly influences the magnitude of BPA and that such baseline factors should be accounted for when comparing BOLD data across groups of subjects, particularly in the many instances in which hematocrit may vary systematically. Such instances include several disease states as well as studies involving sex differences, drug administration, stress and other factors. Finally, the robust agreement between predicted and empiric data serves to validate a semiquantitative approach to the analysis of BOLD fMRI data.

    Title Cocaine-induced Cerebral Vasoconstriction Differs As a Function of Sex and Menstrual Cycle Phase.
    Date August 2001
    Journal Biological Psychiatry
    Excerpt

    BACKGROUND: Chronic cocaine abusing women experience fewer cerebral perfusion defects and less neuronal injury than men with comparable drug use histories. This study assessed whether a basis for this discrepancy is a sex difference in cocaine's acute cerebrovascular effects. METHODS: The subjects in this study were 13 healthy and neurologically normal women, reporting occasional cocaine (mean 13, range 1-40 lifetime cocaine exposures). All subjects were administered cocaine (0.4 mg/kg) intravenously, during both the follicular (days 3-8) and luteal (days 18-24) menstrual cycle phases. Dynamic susceptibility contrast magnetic resonance imaging assessments of relative global cerebral blood volume (CBV) changes were conducted on both study days, 10 min after cocaine administration. RESULTS: Cocaine did not alter CBV in follicular phase women, but reduced luteal phase CBV by 10%, indicative of vasoconstriction (analysis of variance [ANOVA], F = 5.1, p <.05). Postcocaine CBV was lower in men administered the drug via an identical protocol relative to follicular phase women (ANOVA, F = 5.4, p <.04). Postcocaine CBV was also lower in the male referent group relative to luteal phase women, but this difference did not achieve statistical significance. No measurable sex or menstrual cycle phase differences in cocaine's cardiovascular effects were noted. CONCLUSIONS: These findings suggest both menstrual cycle phase and sex differences in cocaine's acute cerebrovascular effects, which may contribute to sex differences in the severity of brain dysfunction found in chronic cocaine abusers. These findings imply that gonadal steroids or the factors they modulate merit study as possible therapeutic agents for reducing cocaine-induced cerebrovascular disorders.

    Title A Clinical Comparison of the Safety and Efficacy of Multihance (gadobenate Dimeglumine) and Omniscan (gadodiamide) in Magnetic Resonance Imaging in Patients with Central Nervous System Pathology.
    Date April 2001
    Journal Investigative Radiology
    Excerpt

    RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

    Title Sex Differences in Response to Red and Blue Light in Human Primary Visual Cortex: a Bold Fmri Study.
    Date March 2001
    Journal Psychiatry Research
    Excerpt

    Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.

    Title Meniscal Ossification in Spontaneous Osteoarthritis in the Guinea-pig.
    Date October 2000
    Journal Osteoarthritis and Cartilage / Oars, Osteoarthritis Research Society
    Excerpt

    OBJECTIVE: The purpose of this study was to evaluate the ossification state of the meniscus in the guinea-pig stifle joint using micro-computerized tomography. DESIGN: Hind limbs from six (N=12) and 24 (N=11) month-old male Hartley guinea-pigs were removed and the joints were imaged using high resolution micro-computerized tomography. The ossified volume of the medial and lateral menisci from both groups of animals was quantified. RESULTS: Ossification of both the medial and lateral menisci of the both the 6- and 24-month-old animals was observed. In both age groups, the ossified region of the medial meniscus was significantly larger than the lateral meniscus. In addition, there is a significant increase in ossified volume of the medial meniscus between 6 and 24 months of age. CONCLUSIONS: There is a significant amount of ossification of the menisci in the male Hartley guinea-pig, with the medial compartment showing more bone than the lateral. In addition, as the animals age, there is an increase in ossification within the medial compartment. Bone remodeling and cartilage degeneration is evident in the medial compartment within these animals as they age. It is possible that the increased ossification of the medial meniscus could alter the joint biomechanics and, in part, stimulate this medial compartment joint destruction.

    Title Illicit Cocaine Use Patterns in Intravenous-naive Cocaine Users Following Investigational Intravenous Cocaine Administration.
    Date March 2000
    Journal Drug and Alcohol Dependence
    Excerpt

    This study evaluated whether cocaine use patterns changed following investigational intravenous cocaine administration to intravenous-naive cocaine users. Subjects were respondents to a follow-up survey who had participated in one to three intravenous double-blind cocaine (0.2 or 0.4 mg/kg) administration studies. The group included healthy men (n = 17) and women (n = 8) with histories of occasional cocaine use (lifetime self-reported use of 12+/-12 (mean +/- S.D.) exposures, primarily via nasal insufflation) who were recontacted an average of 39 weeks (range 7-107 weeks) after study participation. The recontacted group constituted 45% of the total eligible sample of 55 subjects. Baseline demographics for the recontacted and non-recontacted (n = 30) samples were similar, suggesting that the recontacted sample was representative of the group as a whole. Investigational cocaine exposure did not induce adverse health events in any subject. Self-reported cocaine use estimates obtained at follow-up were compared to baseline estimates obtained with identical questionnaires and were highly concordant (Spearman rank correlation p = 0.52 and 0.78, respectively; P < 0.02 and < 0.0002, respectively). This suggests that participants provided stable and reliable reports of cocaine use. No subject reported either illicit intravenous cocaine use or altered frequency of illicit cocaine use by the customary route after investigational intravenous cocaine exposure. These data suggest that illicit cocaine use frequencies and routes of administration are not altered following investigational intravenous cocaine administration to healthy, occasional cocaine users.

    Title Cocaine Pharmacokinetics in Men and in Women During the Follicular and Luteal Phases of the Menstrual Cycle.
    Date September 1999
    Journal Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
    Excerpt

    Preclinical and clinical studies suggest that females may be less vulnerable to cocaine's toxic effects than males. The pharmacokinetics of intravenous cocaine (0.2 and 0.4 mg/kg) were measured in 12 men and 22 women with a history of cocaine abuse, matched with respect to age and body mass index (BMI). Women were studied during the follicular and the luteal phases of the menstrual cycle. There were no differences between men and women in pharmacokinetic measures [peak plasma cocaine levels (Cmax), elimination half-life (T 1/2 min), area under the curve (AUC)] or cardiovascular or subjective effects "high" measures. Heart rate increases were cocaine dose-related (p < .01-.02) and also did not differ between men and women. Cocaine's pharmacokinetic and pharmacodynamic effects were similar in men and women, and in women during the follicular and mid-luteal phases of the menstrual cycle.

    Title Applications of Micro-ct and Mr Microscopy to Study Pre-clinical Models of Osteoporosis and Osteoarthritis.
    Date May 1999
    Journal Technology and Health Care : Official Journal of the European Society for Engineering and Medicine
    Excerpt

    There is a tremendous unmet therapeutic need for the treatment of osteoporosis and osteoarthritis. The ovariectomized rat and the guinea pig are widely used animal models for the evaluation of new therapeutics for osteoporosis and osteoarthritis, respectively. We have utilized X-ray micro-CT techniques to quantitatively evaluate the differences in trabecular bone in the rat proximal tibia following ovariectomy and treatment with estrogen (17-B-estradiol). Results demonstrate a loss of trabecular bone and architecture following ovariectomy (p < 0.001), and a marked inhibition of trabecular bone loss in the estrogen treated group (p < 0.001). A similar change in architecture can be visualized in images obtained by high resolution MR microscopy. In addition, a good correlation was observed between the values of trabecular bone fraction (BV/TV) in the rat tibiae as obtained from 3-dimensional micro-CT data and 2-dimensional static histomorphometry (r = 0.89, 0.73, 0.79 for sham, OVX, and treated groups, respectively). Micro-CT images were also obtained from a set of lumbar vertebrae from sham operated and ovariectomized rats. Significant bone loss can be measured as early as 8 weeks following ovariectomy (p < 0.005). Micro-CT and MR images were also obtained to study age related changes in the stifle joint of the guinea pig. Significant boney changes can be seen in the tibia and femur from the animals at various ages. Changes in cartilage and joint space can also be visualized in the images. The utility of micro-CT imaging in evaluating the mouse skeletal system is illustrated by obtaining morphological and architectural details from high resolution images of the mouse hind limb and proximal tibia, respectively. The results demonstrate the advantages that multi-dimensional imaging techniques can offer in evaluating bone and joint related changes in animal models of osteoporosis and osteoarthritis.

    Title Reduction in Bold Fmri Response to Primary Visual Stimulation Following Alcohol Ingestion.
    Date November 1998
    Journal Psychiatry Research
    Excerpt

    The physiology of alcohol's effects on brain function is poorly understood. Emission tomographic imaging has revealed both acute and chronic alterations in resting cerebral hemodynamics and metabolism following alcohol ingestion. However, cerebral functional integrity under these conditions has received less attention. Functional magnetic resonance imaging (fMRI) offers a non-invasive method for assessing brain functional activation. In order to assess its utility for studying the effect of alcohol on brain function, we performed fMRI with photic stimulation before and after administration of either 0.7 mg/kg alcohol (N = 12) or placebo (N = 5), resulting in peak breath alcohol levels averaging 0.069 g/dl. We found that the amplitude of visual cortical activation in response to photic stimulation was significantly reduced by approximately 33% following alcohol administration (4.0 +/- 1.7% vs. 2.7 +/- 1.3%, P = 0.02), but not following placebo (4.2 +/- 1.5% vs. 4.1 +/- 1.4%, P = 0.7). The results also suggest that the baseline right hemispheric predominance of activation in response to photic stimulation may be reduced following alcohol, suggesting a greater effect on the right hemisphere, consistent with previous studies and alcohol's known effects on visuospatial processing. In addition, through the course of each activation session, there was a progressive reduction in response following alcohol. These data demonstrate that the cerebral effects of alcohol intoxication can be studied with fMRI, and that the effects on brain function of even moderate alcohol intoxication may be widespread, may be lateralized, and may include the visual system.

    Title Cocaine Decreases Relative Cerebral Blood Volume in Humans: a Dynamic Susceptibility Contrast Magnetic Resonance Imaging Study.
    Date October 1998
    Journal Psychopharmacology
    Excerpt

    Cocaine has substantial effects on cerebral hemodynamics which may partly underlie both its euphorigenic and toxic effects. Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) was used to determine whether a dose-effect relationship could be detected between cocaine administration and cerebral blood volume reduction in human brain. Twenty-three healthy and neurologically normal adult males with a history of recreational cocaine use (3-40 lifetime exposures) participated. Subjects underwent DSC-MRI measurements of relative cerebral blood volume (rCBV) at baseline and 10 min after i.v. double-blind placebo or cocaine (0.2 or 0.4 mg/kg) administration. Placebo administration resulted in superimposable rCBV curves with post-placebo CBV averaging 104+/-4% (mean+/-SE) of baseline, indicating no CBV change. Both cocaine doses induced CBV decreases which were statistically equivalent and post-cocaine CBV averaged 77+/-4% of baseline (P < 0.002), when measured 10 min following drug administration. These data suggest that DSC-MRI can detect cocaine-induced CBV reductions indicative of vasoconstriction, and that it may be useful for evaluating treatments designed to reduce the cerebrovascular effects of cocaine.

    Title T1 Effects in Sequential Dynamic Susceptibility Contrast Experiments.
    Date April 1998
    Journal Journal of Magnetic Resonance (san Diego, Calif. : 1997)
    Excerpt

    Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence of T1 effects is now investigated with experiments in which T1 weighting is varied as well as with serial regional T1 measurements. Little evidence for significant residual T1 effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.

    Title Concurrent Pharmacokinetic Analysis of Plasma Cocaine and Adrenocorticotropic Hormone in Men.
    Date April 1998
    Journal The Journal of Clinical Endocrinology and Metabolism
    Excerpt

    The purpose of this study was to determine the covariance between plasma cocaine and ACTH pharmacokinetics. Twelve healthy male occasional cocaine users participated in a double blind study. Intravenous cocaine (0.2 mg/kg) or placebo was infused over 1 min, and samples for cocaine, ACTH and cortisol analysis were collected at 2, 4, 8, 12, 16, 20, 30, 40, 60, 80, 120, 180, and 240 min. Peak cocaine plasma levels averaged 101.2 +/- 14.6 ng/mL. ACTH increases were significantly correlated (P < 0.0001) with increases in plasma cocaine levels (r = 0.67; r2 = 0.44). Pharmacokinetic analysis showed that the t(max) (observed time to maximum concentration) values for cocaine (6.0 +/- 1.4 min) and ACTH (7.3 +/- 1.2 min) were almost identical. The area under the curve was calculated using the trapezoidal rule. The area under the curve for plasma cocaine was 6463 +/- 1070 ng/min x mL, and the area under the curve for ACTH was 1873 +/- 188 pmol/min x L. The mean half-life for plasma cocaine was 46.7 +/- 4.0 min, and that for ACTH was 35.8 +/- 5.1 min. Cardiovascular and subjective effect measures were correlated with concurrent increases in plasma cocaine and ACTH levels.

    Title Sex Differences in Blood-oxygenation-level-dependent Functional Mri with Primary Visual Stimulation.
    Date March 1998
    Journal The American Journal of Psychiatry
    Excerpt

    OBJECTIVE: The authors evaluated the effect of sex on data derived from activation studies using blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (MRI). METHOD: Gradient echo-echo planar imaging was used to measure BOLD signal response in the primary visual cortex in response to binocular photic stimulation in 16 healthy, young subjects (eight women and eight men). RESULTS: BOLD signal response was 38% lower in women than in men, and much of the difference was lateralized to the right hemisphere. CONCLUSIONS: Lower BOLD signal response in women may reflect a sex difference in the brain's response to a primary visual stimulation or in the physiology underlying BOLD functional MRI signal changes.

    Title Cocaine-induced Cerebral Vasoconstriction Detected in Humans with Magnetic Resonance Angiography.
    Date February 1998
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    CONTEXT: Clinical observations and case reports suggest that there are important cerebrovascular complications of cocaine use, but no studies have documented a direct link. OBJECTIVE: To determine whether low-dose cocaine administration induces cerebral vasoconstriction in healthy cocaine users. DESIGN: Randomized controlled trial. SUBJECTS: Twenty-four healthy and neurologically normal men (mean age, 29 years) reporting median cocaine use of 8 lifetime exposures (range, 3 to >40). INTERVENTION: Double-blind intravenous administration of cocaine (0.4 or 0.2 mg/kg) or placebo, with cerebral magnetic resonance angiography performed at baseline and 20 minutes following infusion. MAIN OUTCOME MEASURE: Cocaine-induced angiographic change indicative of vasoconstriction, as independently and concordantly rated by 2 reviewers blind to treatment condition. RESULTS: Cocaine-induced cerebral vasoconstriction in a dose-related fashion (P=.03), with angiograms indicative of vasoconstriction found in 5 of 8 and 3 of 9 subjects receiving 0.4- and 0.2-mg/kg cocaine, respectively, compared with 1 of 7 subjects administered placebo. Outcome stratification by frequency of self-reported lifetime cocaine use (3-10 times, 11-40 times, or >40 times) revealed a statistically stronger dose-related effect (P<.001), suggesting that greater lifetime cocaine use was associated with a greater likelihood of vasoconstriction. CONCLUSIONS: Cocaine administration induced dose-related cerebral vasoconstriction on magnetic resonance angiograms. These changes occurred at low cocaine doses and in the absence of other risk factors, including polydrug abuse, hypertension, or cerebrovascular disease. Outcome stratification by prior cocaine use statistically strengthened the relationship between cocaine administration and vasoconstriction, suggesting that cocaine may have a cumulative residual effect in promoting cerebrovascular dysfunction.

    Title Dynamic Susceptibility Contrast Magnetic Resonance Imaging in Neuropsychiatry: Present Utility and Future Promise.
    Date January 1998
    Journal European Radiology
    Excerpt

    Dynamic susceptibility contrast magnetic resonance imaging (DSC MRI) provides a noninvasive means to create high resolution maps of the regional distribution of cerebral blood volume (CBV). Most DSC MRI studies conducted to date have focused on the evaluation of patients with cerebral neoplasms, ischemia or infarction, and epilepsy. However, preliminary work suggests that DSC MRI may also provide clinically important information for the evaluation of patients with neuropsychiatric disorders, especially dementia and schizophrenia. Additionally, with appropriate modification, DSC MRI may be used to reliably evaluate the effects of pharmacological challenges on cerebral hemodynamics. As pharmacotherapy is an important component in the treatment of a range of psychiatric disorders, the dynamic assessment of changes in cerebral perfusion associated with drug administration may ultimately lead to the development of "brain function tests" for a wide range of disorders.

    Title Applications of Dynamic Susceptibility Contrast Magnetic Resonance Imaging in Neuropsychiatry.
    Date December 1997
    Journal Neuroimage
    Excerpt

    Functional neuroimaging has assumed an important role in the cognitive and clinical neurosciences. Recently, substantial progress has been made toward developing functional magnetic resonance imaging techniques for the examination of cerebral hemodynamic changes that accompany brain function and toward earlier and better diagnosis of brain disease. Dynamic susceptibility contrast (DSC) MRI offers unique information about cerebral hemodynamics both at rest and in response to brain activation. We review the clinical applications of DSC MRI and present our experience with this modality in the evaluation of patients with neuropsychiatric disorders. Our experience suggests that DSC MRI may afford new insights into the diagnosis and treatment of cognitive disorders.

    Title Exploring the Limits of Nearest Neighbour Secondary Structure Prediction.
    Date November 1997
    Journal Protein Engineering
    Excerpt

    This paper presents a simple and robust secondary structure prediction scheme (SIMPA96) based on an updated version of the nearest neighbour method. Using a larger database of known structures, the Blosum 62 substitution matrix and a regularization algorithm, the three state prediction accuracy is increased by 4.7 percentage points to 67.7% for a single sequence and up to 72.8% when using multiple alignments. The increase in prediction accuracy with respect to the previous version can be almost entirely ascribed to the sevenfold increase in the size of the database. A more detailed analysis of the results shows that badly predicted regions of a protein sequence are randomly distributed throughout the database and that the goal of perfect secondary structure predictions by methods which use only local sequence information is illusory.

    Title Age-related Reduction in Functional Mri Response to Photic Stimulation.
    Date February 1997
    Journal Neurology
    Excerpt

    Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.

    Title Abnormal Cerebral Metabolism in Polydrug Abusers During Early Withdrawal: a 31p Mr Spectroscopy Study.
    Date October 1996
    Journal Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
    Excerpt

    Phosphorus magnetic resonance spectroscopy (31P MRS) at 1.5 T was performed on nine polysubstance abusing men. All nine patients met DSM-III-R criteria for concurrent cocaine and heroin dependence, were neurologically normal, were negative for the human immunodeficiency virus, and had normal clinical brain MRI scans. Patients were scanned 2-7 days after admission to a drug treatment unit. Eleven age-matched control subjects also were studied. The ISIS localized phosphorus spectra were obtained from a 5-cm thick axial brain slice and a 100-cc white matter volume. In the brain slice, the phosphorus metabolite signal expressed as a percentage of total phosphorus signal was 15% higher for phosphomonoesters, 10% lower for nucleotide triphosphates (beta-NTP), and 7% lower for total nucleotide phosphates in polydrug abusers compared with those in controls. Phosphodiesters, inorganic phosphate, phosphocreatine, total phosphorus, pH, and free magnesium concentration were unchanged. None of these parameters correlated with the methadone dose or the number of days abstinence. Single photon emission computed tomographic imaging of a subgroup of the patients revealed abnormal cerebral perfusion in 80% of the patients scanned. These data suggest that cerebral high energy phosphate and phospholipid metabolite changes result from long term drug abuse and/or withdrawal and that these changes can be detected and studied by 31P MRS.

    Title Clinical Applications of Functional Mri in Neuropsychiatry.
    Date February 1996
    Journal The Journal of Neuropsychiatry and Clinical Neurosciences
    Excerpt

    Clinical neuroimaging is due for yet another sea change as functional neuroimaging becomes increasingly powerful and available. Functional magnetic resonance imaging (fMRI) is perhaps the most promising of the emerging techniques. The following review helps us understand the physics, strengths, limitations, and promise of fMRI. The authors are all affiliated with the Brain Imaging Center at McLean Hospital and with the Departments of Neurology (Dr. Levin) and Psychiatry (Dr. Renshaw) at Harvard Medical School.

    Title Sequential Dynamic Susceptibility Contrast Mr Experiments in Human Brain: Residual Contrast Agent Effect, Steady State, and Hemodynamic Perturbation.
    Date February 1996
    Journal Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
    Excerpt

    The stability and reproducibility of the dynamic susceptibility contrast (DSC) MRI method for sequential relative cerebral blood volume (relCBV) measurements was evaluated to validate the method for use in quantitative studies of cerebral hemodynamics in humans. A spin echo echo planar imaging protocol was used in conjunction with multiple bolus injections of the susceptibility contrast agent gadoteridol (GD). The effects of variation in interbolus interval (10 min to 4 h), the number of injections (two to four), and the effect of the cerebral vasodilating agent acetazolamide (ACZ) were evaluated in 44 experiments performed with 22 normal subjects. Two fundamental observations were made. First, with multiple injections of GD, the change in MR signal over time was not consistent from first to subsequent boluses. A second bolus administered 10 min to 2 h after an initial bolus resulted in signal change of greater amplitude and duration, resulting in artifactually elevated estimates of relCBV, consistent with a residual effect of GD. Second, a relative steady state could be reached with serial injections of GD, such that the profile of subsequent boluses closely paralleled those of previous ones. This facilitates the reliable measurement of relCBV during activation, as demonstrated by use of ACZ.

    Title Improved Regional Cerebral Blood Flow in Chronic Cocaine Polydrug Users Treated with Buprenorphine.
    Date July 1995
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Excerpt

    Chronic cocaine and polydrug abuse have been associated with regional abnormalities in cerebral perfusion. The authors have previously demonstrated that these abnormalities are partially reversible after drug addiction treatment with buprenorphine. This study was designed to separate the effect on cerebral perfusion of abstinence from drug use from that of buprenorphine directly. METHODS: Fifteen cocaine- and heroin-dependent men were studied with 99mTc-hexamethylpropyleneamine oxime (HMPAO) brain SPECT. The men, all part of an inpatient drug abuse treatment research program, were randomly assigned after detoxification to receive placebo or either 6 or 12 mg daily buprenorphine treatment. SPECT studies were performed at baseline, after maximum dosage was reached and after tapering off the study drug. Studies were compared visually with regard to the number and location of perfusion defects by reviewers blinded to treatment assignment. RESULTS: Subjects receiving buprenorphine had a significant reduction in the number of defects per study between baseline and maximum buprenorphine dose as compared with those receiving placebo (decrease of 4 +/- 5.4 versus increase of 4.8 +/- 4.7, p = 0.006). These differences were dose-related. Improvement with buprenorphine was temporary, with return to baseline after tapering off. CONCLUSION: Buprenorphine treatment, and not abstinence from drug use alone, leads to improvement in regional cerebral perfusion abnormalities in chronic cocaine- and heroin-dependent men.

    Title Functional Studies in Substance Abuse: Imaging and Beyond.
    Date July 1995
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Title Gender Differences in Cerebral Perfusion in Cocaine Abuse: Technetium-99m-hmpao Spect Study of Drug-abusing Women.
    Date January 1995
    Journal Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
    Excerpt

    Cocaine abuse continues to be a major public health concern, with a variety of medical and neurologic sequelae. Previous studies have demonstrated abnormalities in cerebral perfusion in chronic cocaine abusers and after acute administration of cocaine. Although women are becoming increasingly represented among drug abusers, few studies have included women. To the authors' knowledge, none has compared cerebral perfusion in asymptomatic women with that in men. METHODS: The cerebral perfusion of 13 cocaine-dependent women, 4 of whom were also heroin dependent, was studied with 99mTc hexamethylpropyleneamine oxime (HMPAO) SPECT. These women were compared with 13 cocaine-dependent men and 26 healthy control subjects. Structural brain lesions and neurologic abnormalities were excluded by MRI and neurologic evaluation. Perfusion studies were interpreted in a standardized fashion by reviewers blinded to clinical information. RESULTS: It was found that cocaine-dependent women were much less likely to have abnormal study findings than cocaine-dependent men (p = 0.003) and were indistinguishable from normal women (p = 1.0). However, the results in both women and men who concurrently used heroin plus cocaine were all abnormal. Perfusion abnormalities tended to be located in anterior brain structures, such as the frontal and temporal cortex and the basal ganglia. CONCLUSION: These data suggest that cocaine-dependent women have fewer abnormalities in cerebral perfusion than cocaine-dependent men, but that concurrent abuse of heroin and cocaine is associated with more perfusion abnormalities in both sexes.

    Title Hyperperfusion of Ictal Seizure Focus Demonstrated by Mr Perfusion Imaging.
    Date September 1994
    Journal Ajnr. American Journal of Neuroradiology
    Excerpt

    MR using a susceptibility-weighted sequence and dynamic contrast enhancement with gadolinium demonstrated relative hyperperfusion of the right temporoparietal cortex in a patient in focal status epilepticus. A single-photon emission CT (SPECT) scan also demonstrated hyperperfusion of the right temporoparietal cortex. Perfusion MR, SPECT, and electroencephalogram normalized when the seizures ended.

    Title Long Term Results of Stereotactic Brachytherapy Used in the Initial Treatment of Patients with Glioblastomas.
    Date July 1994
    Journal Cancer
    Excerpt

    BACKGROUND. Despite optimal therapy with surgery and radiotherapy, the prognosis of patients with glioblastomas remains poor. Stereotactic brachytherapy involves the accurate placement of radioactive isotopes within brain tumors, significantly increasing the dose of radiation that can be delivered to the tumor bed without substantial risk to surrounding normal tissue, potentially improving local tumor control and patient survival. METHODS. Between February 1987 and July 1993, the authors treated 56 patients with glioblastomas with stereotactic brachytherapy as part of their initial therapy. Patients underwent surgery, limited field external beam radiotherapy, and brachytherapy with temporary high-activity iodine 125 sources, giving an additional 50 Gy to the tumor bed. RESULTS. Median survival for patients undergoing brachytherapy was 18 months compared with 11 months for a matched brachytherapy control group with similar clinical and radiologic features (P < 0.0007). Survival rates at 1, 2, and 3 years after diagnosis of 83%, 34%, and 27%, respectively, for patients receiving brachytherapy were significantly increased compared with survival rates of 40%, 12.5%, and 9%, respectively, for control subjects. Thirty-six patients (64%) underwent reoperation for symptomatic radiation necrosis from 3 to 42 months (median, 11 months) after brachytherapy. The median survival of patients undergoing reoperation was 22 months compared with 13 months for those who did not have further surgery (P < 0.02). Thirty-five percent of patients relapsed locally within the brachytherapy target volume, whereas 65% had marginal or distant relapses. CONCLUSIONS. Brachytherapy may improve local tumor control and prolong survival when used in the initial treatment of selected patients with glioblastomas.

    Title Complications of Therapy for Venous Thromboembolic Disease in Patients with Brain Tumors.
    Date June 1994
    Journal Neurology
    Excerpt

    Venous thromboembolic disease is a frequent complication in patients with intracranial malignancies. Because these patients are often perceived to be at increased risk of intracranial hemorrhage with anticoagulation, inferior vena cava (IVC) filters are frequently used in their treatment. We reviewed the records of 49 patients with intracranial malignancies and venous thromboembolic disease to determine the effectiveness of, and the complications resulting from, treatment. Of the 42 patients receiving IVC filters, a strikingly high percentage (62%) developed complications. Twelve percent developed recurrent pulmonary embolism, while 57% developed either IVC or filter thrombosis, recurrent deep venous thrombosis, or post-phlebitic syndrome. These complications severely reduced the quality of life of the affected patients. Only 15 of our patients were treated with anticoagulation, and seven of these received it because of continued thromboembolic disease. None of these 15 patients had proven hemorrhagic complications. This study suggests that the complication rate of IVC filters in patients with brain tumors is higher than commonly perceived and may outweigh the risk of anticoagulation.

    Title Quantification of Secondary Structure Prediction Improvement Using Multiple Alignments.
    Date March 1994
    Journal Protein Engineering
    Excerpt

    The use of multiple sequence alignments for secondary structure predictions is analysed. Seven different protein families, containing only sequences of known structure, were considered to provide a range of alignment and prediction conditions. Using alignments obtained by spatial superposition of main chain atoms in known tertiary protein structures allowed a mean of 8% in secondary structure prediction accuracy, when compared to those obtained from the individual sequences. Substitution of these alignments by those determined directly from an automated sequence alignment algorithm showed variations in the prediction accuracy which correlated with the quality of the multiple alignments and distance of the primary sequence. Secondary structure predictions can be reliably improved using alignments from an automatic alignment procedure with a mean increase of 6.8%, giving an overall prediction accuracy of 68.5%, if there is a minimum of 25% sequence identity between all sequences in a family.

    Title Hiv-specific T-helper Activity in Seronegative Health Care Workers Exposed to Contaminated Blood.
    Date January 1994
    Journal Jama : the Journal of the American Medical Association
    Excerpt

    OBJECTIVE--To evaluate human immunodeficiency virus (HIV) type 1-specific cellular immune responses in HIV-seronegative health care workers with occupational high-risk exposures to HIV-infected (HIV-positive) patients. DESIGN--Peripheral blood mononuclear cells (PBMCs) were obtained after occupational exposures to HIV, and PBMCs from health care workers exposed to HIV-negative patients served as controls. The PBMCs were stimulated in vitro with HIV envelope synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay. The HIV antibody status was determined by standard enzyme-linked immunosorbent assays. Exposed individuals were also evaluated for HIV proviral DNA by polymerase chain reaction techniques. PARTICIPANTS--The PBMCs from eight health care workers with high-risk exposures and nine control health care workers were studied. RESULTS--The PBMCs from all individuals showed strong IL-2 production to control antigens, indicating intact T-helper function. Interleukin 2 production to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals, but in only one of the nine health care workers exposed to HIV-negative body fluids (P < .008). None of the HIV-exposed health care workers became infected as determined by negative HIV antibody and polymerase chain reaction analysis after follow-up evaluation that ranged from 8 to 64 weeks. CONCLUSION--Human immunodeficiency virus-specific T-helper activity was detected in six (75%) of eight HIV-negative health care workers with exposure to HIV-positive body fluids. Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the exposure and was lost in individuals followed up for 8 to 64 weeks. Three health care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without evidence of subsequent infection appears to result in activation of cellular immunity without activation of antibody production.

    Title In Vitro Susceptibility of Borrelia Burgdorferi to 11 Antimicrobial Agents.
    Date September 1993
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    The in vitro susceptibility of Borrelia burgdorferi to 11 antimicrobial agents was investigated. The antimicrobial agents evaluated included ceftizoxime, FK037, cefotaxime, dirithromycin, clarithromycin and its metabolite 14-hydroxy-clarithromycin, erythromycin, doxycycline, amoxicillin, ciprofloxacin, and ofloxacin. Isolates of B. burgdorferi tested included two reference strains (B31 and ATCC 53899), six isolates from the midwestern United States, and three from Europe. A broth macrodilution method was used to determine MICs and MBCs. B. burgdorferi was inhibited by < or = 0.5 micrograms of each of the agents except the quinolones per ml. The MBCs for 90% of strains tested of ceftizoxime, FK037, clarithromycin, 14-OH clarithromycin, and dirithromycin (< or = 1.0 microgram of each per ml) were superior to those of amoxicillin (2.0 micrograms/ml) and doxycycline (4.0 micrograms/ml). Further in vivo studies are warranted to determine whether these agents may be efficacious in the treatment of Lyme borreliosis.

    Title Mutational and Structural Analysis of the Nitrate Reductase Heme Domain of Nicotiana Plumbaginifolia.
    Date December 1991
    Journal The Journal of Biological Chemistry
    Excerpt

    We have analyzed four Nicotiana plumbaginifolia null mutants presumably affected in the heme domain of nitrate reductase. The DNA sequence of this domain has been determined for each mutant and for the wild type. Two mutations were identified as single base changes leading to, respectively, the substitution of a histidine residue by an asparagine (mutant E56) and to the appearance of an ochre stop codon (mutant E64). Based on the amino acid sequence homology between the nitrate reductase heme domain and mammalian cytochrome b5, we have predicted the three-dimensional structure of this domain. This showed that the nitrate reductase heme domain is structurally very similar to cytochrome b5 and it also confirmed that the residue involved in E56 mutation is one of the two heme-binding histidines. The two other mutations (mutants A1 and K21) were found to be, respectively, -1 and +1 frameshift mutations resulting in the appearance of an opal stop codon. These sequence data confirmed previous genetic and biochemical hypotheses on nitrate reductase-deficient mutants. Northern blot analysis of these mutants indicated that mutant E56 overexpressed the nitrate reductase mRNA, whereas the nonsense mutations present in the other mutants led to reduced levels of nitrate reductase mRNA.

    Title Secondary Structure Prediction and Protein Design.
    Date August 1991
    Journal Biochemical Society Symposium
    Excerpt

    For non-homologous proteins, and after cross-validation, the methods reviewed in this article exhibit a probability index (percentage of correctly predicted residues per predicted residues) of 59-65.5% according to the methods employed with a standard deviation of 7% for three conformational states: alpha-helix, beta-strand and coil. These present limitations in the accuracy of prediction are related both to the limited number of known structures and to the effect of long-range interactions. The methods based on sequence similarity can improve the accuracy of prediction by expressing the homology of the protein to be predicted explicitly with proteins in the database. Under these circumstances, the probability index can reach 87% with a standard deviation of 6.6%. This property was used for modelling homologous proteins by assisting in amino acid sequence alignments. Examples will be given for the alignment of serine proteinases.

    Title The Protein Structure Code: What is Its Present Status?
    Date August 1991
    Journal Computer Applications in the Biosciences : Cabios
    Excerpt

    Current methods of prediction of protein conformation are reviewed and the algorithms on which they rely are presented. For non-homologous proteins and after cross-validation the reported methods exhibit a probability index, i.e. the per cent of correctly predicted residues per predicted residues, of 63-65% with a standard deviation of the order of 7% for three conformational states--helix, beta-strand and coil. This present limitation in the accuracy of predictions that use only the information of the local sequence can be related essentially to the effect of long-range interactions specific for each protein family. The methods based on sequence similarity can improve the accuracy of prediction by expressing explicitly the homology of the protein to be predicted with proteins in the database. In these circumstances the probability index can reach 87% with a standard deviation of 6.6%. This property can be used for modeling homologous proteins by aiding in amino acid sequence alignments. The prediction of the tertiary structure of a protein is still limited to the case of modeling a structure based on the known three-dimensional structure of a homologous protein.

    Title Towards Understanding the Glycoprotein Hormone Receptors.
    Date June 1991
    Journal Biochimie
    Excerpt

    Lutropin (LH), follitropin (FSH) and thyrotropin (TSH), as well as choriogonadotropin (CG, which binds to the LH receptor) constitute the glycoprotein hormone family. Their 3 receptors have been cloned during the last few months. They belong to the large group of G-protein coupled membrane proteins, with their specific N-terminal domain likely to bind the hormone and the characteristic 7 membrane-spanning segments in their C-terminal moiety. The present review discusses the main results of amino acid sequence analysis performed on the glycoprotein hormone receptors. The putative extracellular head exhibits less than 45% homology over the 3 receptors, while approximately 70% residue conservation is found in the transmembrane moiety. Here only, limited sequence homologies (approximately 20%) can be found with other G-protein coupled receptors. The secondary structure predictions performed on the 3 receptors revealed that the polypeptide sequence predicted as ordered (either alpha-helix or beta-strand) were repeated evenly throughout the extracellular head with a period of approximately 25 amino acids. This analysis helped to define the intervening loops between this ordered stretches as potential candidates for bearing at least part of the binding site of the hormones. Some of the perspectives opened by the cloning of the receptors are described, like the production of the extracellular head of the porcine LH receptor in baculovirus-infected insect cells, and the exploration of the LH receptor's mechanism of functioning as a dimer.

    Title Erythromycin Failure with Subsequent Pasteurella Multocida Meningitis and Septic Arthritis in a Cat-bite Victim.
    Date December 1990
    Journal Annals of Emergency Medicine
    Excerpt

    We report the case of a 75-year-old woman who developed Pasteurella multocida meningitis and septic arthritis while being treated for a cat-bite wound infection with erythromycin. Review of the literature revealed that erythromycin has poor in vitro activity against this bacterium and has been associated with serious clinical failures. We recommend that erythromycin not be prescribed for empiric therapy of established animal-bite infections. Suggestions for optimal empiric therapy of animal-bite infections and the differential diagnosis of severe cat-bite-associated sepsis are discussed.

    Title A Highly Charged Sequence of Chick Hsp90: a Good Candidate for Interaction with Steroid Receptors.
    Date March 1990
    Journal Journal of Steroid Biochemistry
    Excerpt

    The sequence of the entire chick 90 kDa heat shock protein (hsp90), the non hormone binding component of the heterooligomeric form of steroid receptors, is reported. A comparison of the amino acid sequence of the chick hsp90 to that of the homologous hsp90 from yeast to man, reveals 64-96% identity respectively, and even with E. coli hsp90 an identity of 44% is observed. Analysis of the sequence and a secondary structure prediction of chick hsp90 suggest that two hydrophilic regions A and B, predicted in alpha-helix may play a role in the interaction of hsp90 with other proteins such as steroid hormone receptors. While there are regions of the sequences completely conserved in all hsps90, the most negatively charged hydrophilic region (A) is absent in the E. coli protein.

    Title Secondary Structure Prediction: Combination of Three Different Methods.
    Date May 1989
    Journal Protein Engineering
    Excerpt

    A combination of three complementary secondary structure prediction methods is presented. The methods used are the GOR III method, the Homologue method and a new method, the bit pattern method, which is based on hydrophilic/hydrophobic residue patterns. For this purpose a hydropathy scale was developed and is presented here. The combination algorithm (Combine method) was designed to take the best results of each method and use their differences in order to improve the prediction. The combination yields 65.5% correctly predicted residues in three states: alpha-helix (H), beta-strand (E) and aperiodic structure (C) which is an improvement ranging from 2.5 to 6.5% compared with the individual methods when tested with a 67-polypeptide chain database. Seventy-five per cent of the regular secondary structure (H and E) runs are correctly located and beta-sheet runs are much better located by the Combine method in comparison to the other methods.

    Title The Cdna-derived Amino Acid Sequence of Chick Heat Shock Protein Mr 90,000 (hsp 90) Reveals a "dna Like" Structure: Potential Site of Interaction with Steroid Receptors.
    Date April 1989
    Journal Biochemical and Biophysical Research Communications
    Excerpt

    We report cDNA sequence, the complete derived aa sequence, and a predicted secondary structure of the chick hsp 90, a protein which has been found to form complexes with steroid hormone receptors. The modelling of the most negatively charged "region A" indicates that the alpha-helices of this portion of hsp 90 mimick DNA configuration. We propose that this region can, in absence of hormone, interact with and cap the positively charged DNA-binding domain of steroid receptors.

    Title Ketoprofen Versus Indomethacin in Patients with Acute Gouty Arthritis: a Multicenter, Double Blind Comparative Study.
    Date January 1989
    Journal The Journal of Rheumatology
    Excerpt

    Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter, double blind trial of ketoprofen versus indomethacin. Patients were randomly assigned to receive 100 mg of ketoprofen (n = 29 patients) or 50 mg of indomethacin (n = 30 patients) 3 times a day. More than 90% of the patients in each group reported pain relief within the 1st day of treatment. By Day 5, 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief. At the end of the study, most patients in both groups were rated as having marked improvement both by the investigators and by self-assessment. Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders. Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis.

    Title Improvements in a Secondary Structure Prediction Method Based on a Search for Local Sequence Homologies and Its Use As a Model Building Tool.
    Date September 1988
    Journal Biochimica Et Biophysica Acta
    Excerpt

    This report describes an optimised version of a secondary structure prediction method based on local homologies, using a new data base. A 63% prediction accuracy, for three states, was obtained after elimination of the protein to be predicted and all proteins with a percentage identity greater than 22% from the data base. This corresponds to a 5% increase in accuracy on the original method (Levin et al. FEBS Lett. 205 (1986) 303-308). The flexibility of the method to the incorporation of information extraneous to the prediction was demonstrated by the prediction of the homologous proteins in the data base. Using the percentage identity with the protein to be predicted, to weight the relative importance of each protein, for all proteins with a percentage identity greater than 30%, the mean correct prediction per chain was 87%. As a result this algorithm can be used during the molecular modelling process, both to give an idea of the structural similarity between two proteins and as an aid in the determination of the best alignment. Incorporation of the result of a protein folding type assignment based on the global amino-acid composition increased the overall prediction to 66%.

    Title A Technique for Reimplantation of the Visceral Artery During Repair of Thoracoabdominal Aneurysm.
    Date November 1987
    Journal Surgery, Gynecology & Obstetrics
    Title Hemifacial Spasm Due to Cerebellopontine Angle Lipoma: Case Report.
    Date March 1987
    Journal Neurology
    Excerpt

    We report the unique case of a patient with hemifacial spasm caused by a lipoma of the cerebellopontine angle, which was identified preoperatively by CT and MRI. Surgery resulted in complete resolution of facial spasm.

    Title An Algorithm for Secondary Structure Determination in Proteins Based on Sequence Similarity.
    Date October 1986
    Journal Febs Letters
    Excerpt

    A secondary structure prediction algorithm is proposed on the hypothesis that short homologous sequences of amino acids have the same secondary structure tendencies. Comparisons are made with the secondary structure assignments of Kabsch and Sander from X-ray data [(1983) Biopolymers 22, 2577-2637] and an empirically determined similarity matrix which assigns a sequence similarity score between any two sequences of 7 residues in length. This similarity matrix differs in many respects from that of the Dayhoff substitution matrix [(1978) in: Atlas of Protein Sequence and Structure, (Dayhoff, M.O. ed). vol. 5. suppl. 3, pp. 353-358, National Biochemical Research Foundation, Washington, DC]. This homologue method had a prediction accuracy of 62.2% over 3 states for 61 proteins and 63.6% for a new set of 7 proteins not in the original data base.

    Title Effect of Utilization Review on Surgical Training with Reference to the Increasing Importance of the Ward Service in This Changing Environment.
    Date March 1983
    Journal American Journal of Surgery
    Title Life Threatening Trauma and Serious Hand Injuries.
    Date September 1982
    Journal The Journal of Trauma
    Title Reconstruction of Complexes of Histone and Superhelical Nuclear Dna.
    Date March 1982
    Journal Journal of Cell Science
    Excerpt

    When HeLa cells are lysed in solutions containing a non-ionic detergent and 2 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear RNA and DNA but few of the proteins characteristic of chromatin. Their DNA is supercoiled and so intact. Using a simple and rapid procedure we have reconstructed nucleohistone complexes from nucleoids and the 'core' histones without breaking the DNA. We have probed the integrity and structure of the reconstructed complexes using a non-destructive fluorometric approach, which provides a general method for detecting agents that bind to DNA and alter its supercoiling. The superhelical status of the DNA in the reconstructed complexes is indistinguishable from that found in control nucleoids containing core histones. Experiments with micrococcal nuclease confirm that the DNA in the reconstructed complexes is organized into nucleosome-like structures. These, however, are spaced 145 base-pairs apart and not 200 base-pairs apart as is found in native chromatin.

    Title Conformational Changes Induced by Salt in Complexes of Histones and Superhelical Nuclear Dna.
    Date March 1982
    Journal Journal of Cell Science
    Excerpt

    When HeLa cells are lysed in solutions containing a non-ionic detergent and 0.75 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear DNA, RNA and the 'core' histones, but few other proteins characteristic of chromatin. Their DNA is intact. The core histones dissociate on raising the salt concentration. We have probed the structure of nucleoid-histone complexes using the intercalating dye, ethidium, or the RNA polymerase of Escherichia coli. Both have a higher affinity for superhelical DNA than they do for relaxed DNA. The binding of ethidium is measured fluorometrically, and using this probe we find that the DNA of nucleoids containing all the core histones behaves as if it were supercoiled slightly positively. As the salt concentration is increased, free energy characteristic of negative supercoiling appears between 0.92 M and 0.95 M-NaCl. This transition, which is reversible in the presence of the arginine-rich histones, occurs without dissociation of these histones from the DNA and so must reflect a conformational change in the complex. In contrast to the results with ethidium, we find that RNA polymerase can detect the presence of some negative free energy of supercoiling in nucleoids containing the core histones. The transformations of the free energy that can assist the binding of ethidium and RNA polymerase are discussed.

    Title Pelger-huet Anomaly and D-penicillamine.
    Date October 1980
    Journal The Journal of Rheumatology
    Title The Contralateral Diseased but Asymptomatic Carotid Artery: to Operate or Not? An Update.
    Date October 1980
    Journal American Journal of Surgery
    Excerpt

    Bilaterally diseased carotid arteries were demonstrated in 147 patients in a personal series of 535 carotid reconstructions. A general policy of operating only on symptomatic patients was followed. Although stenotic and ulcerated plaques were known to be present in the contralateral artery, they were not repaired unless new symptoms occurred. No strokes were observed in these patients in a 20 year follow-up period. Twelve percent of the patients became symptomatic, leading to new arteriograms and a second artery repair. The patients at risk and their families were carefully instructed to report any symptoms of cerebrovascular insufficiency. If meticulous follow-up is carried out, the prophylactic repair of a truly asymptomatic diseased carotid artery is not believed necessary to prevent stroke.

    Title Autosensitization to Dna.
    Date May 1980
    Journal The Journal of Investigative Dermatology
    Title The Dissociation of Nuclear Proteins from Superhelical Dna.
    Date April 1978
    Journal Journal of Cell Science
    Excerpt

    Structures retaining many of the morphological features of nuclei may be released by gently lysing human cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids contain superhelical DNA. Using a double-labelling procedure we have compared, at different salt concentrations, the amounts and types of protein associated with human nucleoides containings superhelical or relaxed DNA. We find that the slightly lysine-rich histones (H2A and H2B) but not the arginine-rich histones (H3 and H4) dissociate more slowly from nucleoids containing superhelical DNA than from those containing relaxed DNA. A protein of apparent molecular weight of 22000 also binds more tightly to superhelical DNA. We conclude that this protein and the slightly lysine-rich histones transmute free energy of supercoiling into binding energy when they bind to superhelical DNA.

    Title Decreased Serum Complement in the Gardner-diamond Syndrome: Immunofluorescent Findings and Association with Angioimmunoblastic Lymphadenopathy.
    Date April 1978
    Journal Cutis; Cutaneous Medicine for the Practitioner
    Excerpt

    Immunologic and immunofluorescent profiles of two patients with the Gardner-Diamond syndrome are described. During the time ecchymoses were present, both patients had decreased serum complement levels; when the lesions healed, the serum complement level returned to normal. One patient had associated angioimmunoblastic lymphadenopathy and subepidermal deposits of immunoglobulin IgM at the basement membrane of ecchymotic skin. The other patient had a normal immunofluorescent pattern. Both patients had increased B-cell counts. The association of immunologic and immunofluorescent findings in patients with the Gardner-Diamond syndrome is suggestive and deserves further study.

    Title Therapy of Dimethylbenzanthracene-induced Mammary Carcinomas in the Rat by Selective Inhibition of Steroidogenesis.
    Date September 1976
    Journal Cancer
    Excerpt

    The effects of cyanoketone, a specific inhibitor of steroidogenesis at the levels of 3beta-hydroxysteroid oxidoreductase-dealta54-3-ketosteroid isomerase, the combination of cyanoketone with corticosterone, and corticosterone alone on the growth of dimethylbenzanthracene-induced hormone-dependent breast cancers in rats were compared with that produced by ovariectomy. Cyanoketone produces about as many regresssions of these cancers as does ovariectomy. However, cyanoketone with corticosterone results in a significant regression of tumors in all animals tested. This therapy also causes regression of significantly more tumors that are large at the beginning of treatment than does ovariectomy. These findings suggest that this kind of reversible blockade of steroidogenesis may be useful as a diagnostic tool in assessing the hormone dependence of breast tumors and as a possible therapeutic approach in the treatment of such tumors.

    Title A Simple Method for Applying and Changing a Bolus Dressing.
    Date June 1975
    Journal Plastic and Reconstructive Surgery
    Title Acinic Cell Carcinoma: Collective Review, Including Bilateral Cases.
    Date May 1975
    Journal Archives of Surgery (chicago, Ill. : 1960)
    Excerpt

    Bilateral acinic cell carcinoma of the parotid gland is rare. On the basis of one case and a review of 486 parotid acinic carcinomas, unilateral as well as bilateral, total parotidectomy seems to be the treatment of choice for this low-grade malignant neoplasm that recurs commonly following inadequate excision. If involved by tumor, the facial nerve must be taken. Metastases are more likely to lung and bone than to regional nodes. For this reason, radical neck dissection is not routinely indicated.

    Title The Treatment of Burns in the Recent Middle East Conflict.
    Date December 1974
    Journal Plastic and Reconstructive Surgery
    Title Thrombotic-hemorrhagic Diathesis of Polycythemia Vera Treated with Aspirin.
    Date August 1974
    Journal Jama : the Journal of the American Medical Association
    Title Myopia and Dental Caries.
    Date October 1973
    Journal American Journal of Optometry and Archives of American Academy of Optometry
    Title [absorbability of Some Contrast Media from the Pericardium]
    Date June 1973
    Journal Radiologia Diagnostica
    Title Relationship Between Biliary Tract Distention and the Blood Flow in the Aorta and Right Coronary and Renal Arteries.
    Date August 1970
    Journal American Journal of Surgery
    Title Auto-immunity and the Central Nervous System.
    Date August 1969
    Journal The Proceedings of the Institute of Medicine of Chicago
    Title Traumatic Rupture of the Aortic Arch Between Left Common Carotid and Left Subclavian Arteries and Avulsion of the Left Subclavian Artery.
    Date August 1969
    Journal Annals of Surgery
    Title Auto-immunity and the Central Nervous System.
    Date August 1969
    Journal Diseases of the Nervous System
    Title A Study on Autotransfusion from Hemothorax.
    Date August 1969
    Journal Southern Medical Journal
    Title The Thymus Gland and Immunity.
    Date June 1969
    Journal The American Surgeon
    Title Muscle Changes of the Anterior Chest Wall Secondary to Electrical Countershock.
    Date April 1969
    Journal American Journal of Clinical Pathology
    Title The Afferent Loop Syndrome.
    Date July 1968
    Journal The American Surgeon
    Title Magnetic Resonance Studies of Substance Abuse.
    Date
    Journal Seminars in Clinical Neuropsychiatry
    Excerpt

    Magnetic resonance imaging and spectroscopy provide numerous ways to examine the effects of substance abuse on living tissues, ranging from high resolution anatomic imaging to dynamic imaging of tissue biochemical and functional changes. This review focuses on the role magnetic resonance studies have had in detecting brain anatomic changes associated with alcohol, stimulant, and narcotic abuse. Additionally, we focus on the increasing use of spectroscopy and functional magnetic resonance imaging, which can reveal subtle brain changes associated with substance abuse and which offer great promise to help elucidate drug reinforcement mechanisms.

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