Neurological Surgeons
8 years of experience

Accepting new patients
East LA
Los Angeles County + University of Southern California Medical Center
1200 N State St
Los Angeles, CA 90033
323-226-2622
Locations and availability (2)

Education ?

Medical School Score Rankings
Columbia University (2002)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
Congress of Neurological Surgeons
American Association of Neurological Surgeons

Affiliations ?

Dr. Elder is affiliated with 1 hospitals.

Hospital Affilations

Score

Rankings

    • Currently 4 of 4 crosses
    Top 25%
  • Publications & Research

    Dr. Elder has contributed to 114 publications.
    Title Local Disease Control After Decompressive Surgery and Adjuvant High-dose Single-fraction Radiosurgery for Spine Metastases.
    Date August 2010
    Journal Journal of Neurosurgery. Spine
    Excerpt

    OBJECT Adjuvant radiation following epidural spinal cord decompression for tumor is a powerful tool used to achieve local disease control and preserve neurological function. To the authors' knowledge, only 1 published report addresses adjuvant stereotactic radiosurgery after this procedure, but that study used significantly lower doses than are currently prescribed. The authors review their experience using high-dose single-fraction radiosurgery as a postoperative adjuvant following surgical decompression and instrumentation to assess long-term local tumor control, morbidity, and survival. METHODS A retrospective chart review identified 21 patients treated with surgical decompression and instrumentation for high-grade, epidural, spinal cord compression from tumor, followed by single-fraction high-dose spinal radiosurgery (dose range 18-24 Gy, median 24 Gy). Spinal cord dose was limited to a cord maximal dose of 14 Gy. Tumor histologies, time between surgery and radiosurgery, time to local recurrence after radiosurgery as assessed by serial MR imaging, and time to death were determined. Competing risk analysis was used to evaluate these end points. RESULTS In this series, 20 tumors treated (95%) were considered highly radioresistant to conventional external beam radiation. The planning target volume received a high dose (24 Gy) in 16 patients (76.2%), and a low dose (18 or 21 Gy) in 5 patients (23.8%). During the study, 15 (72%) of 21 patients died, and in all cases death was due to systemic progression as opposed to local failure. The median overall survival after radiosurgery was 310 days (range 37 days to not reached). One patient (4.8%) underwent repeat surgery for local failure and 2 patients (9.5%) underwent spine surgery for other reasons. Local control was maintained after radiosurgery in 17 (81%) of 21 patients until death or most recent follow-up, with an estimated 1-year local failure risk of 9.5%. Of the failures, 3 of 4 were noted in patients receiving low-dose radiosurgery, equaling an overall failure rate of 60% (3 of 5 patients) and a 1-year local failure estimated risk of 20%. Those patients receiving adjuvant stereotactic radiosurgery with a high dose had a 93.8% overall local control rate (15 of 16 patients), with a 1-year estimated failure risk of 6.3%. Competing risk analysis showed this to be a significant difference between radiosurgical doses. One patient experienced a significant radiation-related complication; there were no wound-related issues after radiosurgery. CONCLUSIONS Spine radiosurgery after surgical decompression and instrumentation for tumor is a safe and effective technique that can achieve local tumor control until death in the vast majority of patients. In this series, those patients who received a higher radiosurgical dose had a significantly better local control rate.

    Title Postoperative Continuous Paravertebral Anesthetic Infusion for Pain Control in Posterior Cervical Spine Surgery: a Case-control Study.
    Date June 2010
    Journal Neurosurgery
    Excerpt

    Patients who undergo posterior cervical spinal fusion procedures frequently experience significant postoperative pain. Use of a local anesthetic continuous infusion pump after surgery may improve these outcome variables.

    Title Novel Use of an Endovascular Embolectomy Device for Retrograde Suction Decompression-assisted Clip Ligation of a Large Paraclinoid Aneurysm: Technical Case Report.
    Date October 2008
    Journal Neurosurgery
    Excerpt

    OBJECTIVE: Several different methodologies for proximal occlusion and retrograde suction decompression of large paraclinoid aneurysms have been reported previously. In this article, we describe the novel use of an endovascular embolectomy device (F.A.S.T. funnel catheter; Genesis Medical Interventional, Inc., Redwood City, CA) for temporary internal carotid artery occlusion and suction decompression of an intracranial aneurysm to facilitate surgical clip ligation. The combination of atraumatic occlusion technology and large lumen size makes this technique safer and easier. CLINICAL PRESENTATION: A 53-year-old woman with progressive headaches underwent computed tomographic angiography, which revealed an unruptured large left paraclinoid aneurysm. Cerebral angiography confirmed the diagnosis. The patient did not tolerate a balloon test occlusion for therapeutic Hunterian internal carotid occlusion. The patient was subsequently taken to the operating room for a craniotomy and clip ligation of the aneurysm. INTERVENTION: A standard left pterional craniotomy was performed with opening of the sylvian fissure and exposure of the left paraclinoid aneurysm. Intraoperative angiography with introduction of a new endovascular embolectomy device was performed. The device was deployed to achieve temporary occlusion of the cervical internal carotid artery, and aspiration through the central lumen allowed for retrograde suction decompression of the aneurysm. Collapse of the aneurysm through this technique permitted visualization of the aneurysmal neck with successful clip ligation. CONCLUSION: A new endovascular embolectomy device can be used to safely perform suction decompression of large paraclinoid aneurysms to facilitate clip ligation.

    Title The Future of Cerebral Surgery: a Kaleidoscope of Opportunities.
    Date October 2008
    Journal Neurosurgery
    Excerpt

    The emerging future of cerebral surgery will witness the refined evolution of current techniques, as well as the introduction of numerous novel concepts. Clinical practice and basic science research will benefit greatly from their application. The sum of these efforts will result in continued minimalism and improved accuracy and efficiency of neurosurgical diagnostic and therapeutic methodologies.Initially, the refinement of current technologies will further enhance various aspects of cerebral surgery. Advances in computing power and information technology will speed data acquisition, storage, and transfer. Miniaturization of current devices will impact diverse areas, such as modulation of endoscopy and endovascular techniques. The increased penetrance of surgical technologies such as stereotactic radiosurgery, neuronavigation, intraoperative imaging, and implantable electrodes for neurodegenerative disorders and epilepsy will enhance the knowledge and experience in these areas and facilitate refinements and advances in these technologies. Further into the future, technologies that are currently relatively remote to surgical events will fundamentally alter the complexity and scale at which a neurological disease may be treated or investigated. Seemingly futuristic concepts will become ubiquitous in the daily experience of the neurosurgeon. These include diverse fields such as nanotechnology, virtual reality, and robotics. Ultimately, combining advances in multiple fields will yield progress in diverse realms such as brain tumor therapy, neuromodulation for psychiatric diseases, and neuroprosthetics. Operating room equipment and design will benefit from each of the aforementioned advances. In this work, we discuss new developments in three parts. In Part I, concepts in minimalism important for future cerebral surgery are discussed. These include concrete and abstract ideas in miniaturization, as well as recent and future work in microelectromechanical systems and nanotechnology. Part II presents advances in computational sciences and technological fields dependent on these developments. Future breakthroughs in the components of the "computer," including data storage, electrical circuitry, and computing hardware and techniques, are discussed. Additionally, important concepts in the refinement of virtual environments and the brain-machine interface are presented, as their incorporation into cerebral surgery is closely linked to advances in computing and electronics. Finally, Part III offers insights into the future evolution of surgical and nonsurgical diagnostic and therapeutic modalities that are important for the future cerebral surgeon. A number of topics relevant to cerebral surgery are discussed, including the operative environment, imaging technologies, endoscopy, robotics, neuromodulation, stem cell therapy, radiosurgery, and technical methods of restoration of neural function. Cerebral surgery in the near and distant future will reflect the application of these emerging technologies. As this article indicates, the key to maximizing the impact of these advancements in the clinical arena is continued collaboration between scientists and neurosurgeons, as well as the emergence of a neurosurgeon whose scientific grounding and technical focus are far removed from those of his predecessors.

    Title Neurosurgery in the Realm of 10(-9), Part 2: Applications of Nanotechnology to Neurosurgery--present and Future.
    Date June 2008
    Journal Neurosurgery
    Excerpt

    Neurosurgery in the future will witness an increasing influx of novel technologies, many of which will be based on developments in the emerging science of nanotechnology. Additionally, the continued trend in medicine toward minimally invasive diagnostic and surgical techniques will be aided by incorporation of applications of nanotechnology. Neurosurgeons of the future must facilitate the development of nanotechnology and nanomedicine in their clinical practice and research efforts to optimize patient benefit and facilitate scientific advancement. The fields of nanotechnology and nanomedicine remain in their infancy. Recently, however, the literature regarding nanoscience has rapidly expanded. This article is the second of two and provides a review of recent nanotechnology research relevant to clinical neurosurgery and neurology. The first article reviewed recent developments and issues in nanotechnology with a particular focus on applications to the neurosciences. This article also discusses current developments in nanotechnology and nanomedicine that may yield applications in neurosurgery in the future. Additional attention is given to other emerging technologies that are not truly nanotechnology, such as microelectromechanical systems, which will influence the future of medicine and neurosurgery. The goal is to provide the reader with a brief outline and description of some of the new developments in nanotechnology that may affect the clinical practice or operative experience of neurosurgeons. Continued innovation in nanotechnology presents novel opportunities for translation to the clinical arena. Neuroscience, neurology, and neurosurgery will be greatly affected by the influx of nanoscience and its applications. Through continued collaboration, physicians, scientists, and engineers will shape the futures of nanomedicine and nanoneurosurgery.

    Title Neurosurgery in the Realm of 10(-9), Part 1: Stardust and Nanotechnology in Neuroscience.
    Date April 2008
    Journal Neurosurgery
    Excerpt

    Nanotechnology as a science has evolved from notions and speculation to emerge as a prominent combination of science and engineering that stands to impact innumerable aspects of technology. Medicine in general and neurosurgery in particular will benefit greatly in terms of improved diagnostic and therapeutic capabilities. The recent explosion in nanotechnology products, including diverse applications such as beauty products and medical contrast agents, has been accompanied by an ever increasing volume of literature. Recent articles from our institution provided an historical and scientific background of nanotechnology, with a purposeful focus on nanomedicine. Future applications of nanotechnology to neuroscience and neurosurgery were briefly addressed. The present article is the first of two that will further this discussion by providing specific details of current nanotechnology applications and research related to neuroscience and clinical neurosurgery. This article also provides relevant perspective in scale, history, economics, and toxicology. Topics of specific importance to developments or advances of technologies used by neuroscientists and neurosurgeons are presented. In addition, advances in the field of microelectromechanical systems technology are discussed. Although larger than nanoscale, microelectromechanical systems technologies will play an important role in the future of medicine and neurosurgery. The second article will discuss current nanotechnologies that are being, or will be in the near future, incorporated into the armamentarium of the neurosurgeon. The goal of these articles is to keep the neuroscience community abreast of current developments in nanotechnology, nanomedicine, and, in particular, nanoneurosurgery, and to present possibilities for future applications of nanotechnology. As applications of nanotechnology permeate all forms of scientific and medical research, clinical applications will continue to emerge. Physicians of the present and future must take an active role in shaping the design and research of nanotechnologies to ensure maximal clinical relevance and patient benefit.

    Title Postoperative Continuous Paravertebral Anesthetic Infusion for Pain Control in Lumbar Spinal Fusion Surgery.
    Date February 2008
    Journal Spine
    Excerpt

    STUDY DESIGN: A retrospective, case-control study was conducted to analyze postoperative outcomes in patients who received local anesthetic infusion pumps after lumbar spinal fusion procedures. Data were collected prospectively via nursing protocol and third party assessment, and analyzed retrospectively. OBJECTIVE: To review the safety and efficacy of continuous infusion of local anesthetic into the subfascial aspects of the wound after lumbar fusion surgery for treatment of postoperative pain, and to determine whether other outcome measures such as postoperative nausea and vomiting, ambulation and length of hospitalization were affected by the presence of the device. SUMMARY OF BACKGROUND DATA: Patients who undergo lumbar spine fusion procedures frequently experience significant, debilitating pain related to their surgery. This pain may delay postoperative mobilization, increase length of hospitalization, and require prolonged use of high doses of narcotics. Use of a local anesthetic continuous-infusion pump after surgery may lead to improvements in these outcome variables. METHODS: After posterior lumbar spine fusion procedures, 26 consecutive patients received the ON-Q PainBuster, which infused 0.5% marcaine via an elastomeric pump into the subfascial aspects of the wound. Retrospective analysis compared each of these patients with a case-matched control patient. Data included pain scores and opiate use during the first 5 postoperative days (PODs), length of hospital stay, and complications. Variables such as age, American Society of Anesthesiologists (ASA) physical status, and surgical procedure were similar between matched cases. One patient was excluded because of active heroine abuse. RESULTS: Patients with the ON-Q PainBuster used 41.2% less narcotics on POD 1, 50.1% less on day 2, and 47.1% less on day 3 compared with the control patients. Differences in opiate usage were not statistically significant on POD 4 (45.5% less) and 5 (50.3% less). A lower average pain score was observed among patients with the ON-Q PainBuster on each POD: 39.1% less pain on POD 1, 34.0% on day 2, 45.1% on day 3, 29.5% on day 4, and 43.6% on day 5. No differences were observed in length of hospital stay or complication rate. CONCLUSION: Patients who received the ON-Q PainBuster used less narcotic medications than case-matched patients during the first 3 PODs, and reported lower pain scores during the first 5 PODs. No complications attributable to the device were noted. These results suggest that continuous infusion of local anesthetic into the wound during the immediate postoperative period is a safe and effective technique that results in lower pain scores and narcotic use. Further data may reveal additional benefits such as lower incidence of nausea and vomiting and decreased times to mobility and functional independence.

    Title Primary Intraosseous Meningioma.
    Date December 2007
    Journal Neurosurgical Focus
    Excerpt

    Primary intraosseous meningiomas are a subtype of primary extradural meningiomas and constitute fewer than 2% of meningiomas overall, but they represent approximately two thirds of all extradural meningiomas. These types of meningiomas originate within the bones of the skull and thus can have a clinical presentation and radiographic differential diagnosis that is different from those for intradural meningiomas. Primary intraosseous meningiomas are classified based on their location and histopathological characteristics. Treatment primarily involves resection with wide margins if possible. Very little literature exists regarding the use of adjuvant therapies such as radiation and chemotherapy for these tumors. In fact, the literature regarding primary intra-osseous meningiomas consists mostly of clinical case reports and case series. This literature is reviewed and summarized in this article.

    Title Primary Colorectal Tumors Fail to Express the Proapoptotic Mediator Ptag and Its Reexpression Augments Drug-induced Apoptosis.
    Date October 2007
    Journal Genes, Chromosomes & Cancer
    Excerpt

    Genes implicated in tumor evolution and progression, including those in apoptotic pathways, are associated with methylation-associated gene silencing in different tumor types. By exploiting differential methylation we recently isolated a novel pituitary tumor derived apoptosis gene (PTAG) that augments drug-induced apoptosis. The importance of PTAG was determined in other tumor types, and these studies show that the majority of primary colorectal tumors fail to express the PTAG gene, indicating an important role for PTAG in colorectal tumorigenesis. The effects of expression of PTAG were examined through stable transfection of the colorectal cell lines HCT116 and SW480. Expression of PTAG, per se, had no discernible effects on cell viability or cell kinetics. In contrast to these findings, in cells subject to drug challenges that engaged either a death-receptor mediated or mitochondrial pathway, all of the experiments indicated a role for PTAG in the intrinsic pathway of apoptosis. Loss of PTAG therefore contributes to a blunted apoptotic response and is likely to predispose cells toward malignant transformation and resistance to chemotherapeutic interventions.

    Title Giant Cell Tumor of the Skull in Pediatric Patients. Report of Two Cases.
    Date August 2007
    Journal Journal of Neurosurgery
    Excerpt

    Giant cell tumors of the bone are rare, locally aggressive lesions that primarily affect the epiphyses of long bones. These tumors can occur in the skull, principally in the sphenoid and temporal bones. Symptoms of these tumors depend on their site of origin but typically include headache, pain, visual field defects, and conductive hearing loss. Histologically, these tumors consist of three cell types: osteoclast-like multinucleated giant cells; round mononuclear cells resembling monocytes; and spindle-shaped, fibroblast-like stromal cells. Radiographically, the tumors appear osteolytic and radiolucent without a sclerotic border. These tumors typically present in the third to fourth decades of life and rarely occur in patients under 20 years of age. The small number of studies of giant cell tumors of the skull has focused on the adolescent and adult populations. The authors report two cases of giant cell tumors of the skull in pediatric patients. In the first case, a 2-year-old girl presented with swelling behind the right ear. In the second case, a 7-week-old girl presented with a mass within the external auditory canal. Both patients underwent metastatic workup and biopsy procedures before resection of the tumor. Both case reports contribute to the literature of giant cell tumors of the skull by describing this condition in pediatric patients. To the authors' knowledge, these cases represent the youngest two patients with giant cell tumors of the skull yet described.

    Title Lack of B7 Expression, Not Human Leukocyte Antigen Expression, Facilitates Immune Evasion by Human Malignant Gliomas.
    Date July 2007
    Journal Neurosurgery
    Excerpt

    OBJECTIVE: Lack of human leukocyte antigens and costimulatory molecules have been suggested as mechanisms by which human malignant gliomas avoid immune recognition and elimination. METHODS: Using quantitative multiparameter flow cytometric analysis, tumor cells from patients with glioblastoma multiforme (n = 18) were examined ex vivo for the expression of human leukocyte antigen Class I and II molecules and the costimulatory molecules B7-1 and B7-2. They were compared with reactive astrocytes from peritumoral brain metastases (n = 7), and astrocytes removed during nontumor surgery (n = 5). RESULTS: In contrast to the vast majority of solid peripheral human tumors, these results demonstrate that glioblastoma multiforme frequently express both human leukocyte antigen Class I and II molecules. Like most solid peripheral tumors, glioblastoma multiforme tumor cells express few or no B7 costimulatory molecules. Functional assays using heterogeneous ex vivo tumor preparations or pure populations of ex vivo tumor cells and microglia obtained using fluorescence-activated cell sorting indicate that CD4+ T-cells are activated by tumor cells only in the presence of exogenous B7 costimulation (provided by addition of soluble agonist anti-CD28 monoclonal antibody). CONCLUSION: Thus, in contrast to many solid peripheral tumors, failure to present tumor antigens is not a likely impediment to immunotherapeutic strategies against malignant gliomas. Rather, immunotherapeutic strategies need to overcome low levels of B7 costimulation.

    Title Surgical Interventions for Primary Central Nervous System Lymphoma.
    Date January 2007
    Journal Neurosurgical Focus
    Excerpt

    Early diagnosis is central to proper management of primary central nervous system lymphomas (PCNSLs). Surgical intervention hinges on initial entertainment of a diagnosis of a PCNSL, based on acute neurological presentation and neuroimaging findings. Unless there is an urgent need for surgical decompression, a biopsy to obtain a diagnosis of PCNSL is the first step in surgical management. Repeated biopsy may be necessary in patients who have received preoperative steroid therapy. Patients with PCNSL may also present with leptomeningeal involvement, resulting in the need for an Ommaya reservoir for intrathecal chemotherapy. In cases in which hydrocephalus develops, placement of a ventriculoperitoneal shunt may be necessary. Two case studies are presented to highlight the role of surgical intervention in PCNSL.

    Title Polymorphisms in the Glutathione S-transferase Mu Cluster Are Associated with Tumour Progression and Patient Outcome in Colorectal Cancer.
    Date January 2006
    Journal International Journal of Oncology
    Excerpt

    Glutathione S-transferase (GST) enzymes catalyse the detoxification of by-products of reactive oxygen species and are thus important in cellular defence mechanisms. The GSTs are polymorphic with allelic variants encoding isoforms with functional differences. GST polymorphism has been associated with susceptibility and clinical outcome in patients with cancer. In this retrospective cohort, we have investigated associations between common GSTM1, GSTM3 and GSTP1 polymorphisms with factors known to influence clinical out-come and patient survival in colorectal cancer. Significant linkage disequilibrium was demonstrated between GSTM1 and GSTM3 alleles (P< or =0.001). We identified no significant associations between the GSTP1(Ile105Val105) polymorphism and any clinical outcome parameters or patient survival. However significant associations were demonstrated with mu class GSTs. Those patients who were GSTM1 null presented less frequently with poorly-differentiated tumours (P=0.038). Furthermore, patients who were GSTM3 AA were less likely to present with advanced stage tumours (T-stage, P=0.036 and Dukes' classifications, P=0.012) or distant metastases (P=0.017) when examined alone. Upon further examination of the effect of linkage disequilibrium, we found that, in GSTM1 null individuals, GSTM3 AA (compared with other GSTM3 genotypes combined) had longer disease-free survival (HR=0.54, 95% CI 0.30-0.98, P=0.044). Thus, the GSTM3 AA genotype is associated with improved prognosis especially in those with GSTM1 null. Our findings suggest that the GST mu gene cluster mediates tumour characteristics and survival in patients with colorectal cancer.

    Title Glutathione S-transferase T1 Polymorphisms Are Associated with Outcome in Colorectal Cancer.
    Date January 2006
    Journal Carcinogenesis
    Excerpt

    Colorectal cancer (CRC) remains a significant cause of mortality accounting for approximately 10% of all deaths from malignancy in the western world. Polymorphism in the glutathione S-transferase GSTT1 gene has been associated with CRC risk in some but not all studies. In this study, we examined associations between GSTT1 genotypes and CRC risk, and prognosis in 361 cases and 881 unrelated controls. GSTT1 null was associated with a small but significant increase in risk (P = 0.0006, odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.22-2.24). GSTT1 null was also associated with a significantly younger age at diagnosis (mean 65.2 years) compared with GSTT1 A (mean 67.6 years, P = 0.031). There were no significant associations between GSTT1 genotypes and clinical factors (e.g. Dukes stage, differentiation and tumour node metastasis classification) in the total case group. However, following stratification by age (<70 versus > or =70 years at diagnosis), in the patients diagnosed <70 years of age, GSTT1 null was more common in Dukes grade A/B tumours (P = 0.046), stage T1/T2 tumours (P = 0.053) and those with a pushing margin (P = 0.066). We also identified associations between GSTT1 null and increased prevalence of host lymphocyte response, particularly in the younger patients (P = 0.036). Furthermore, GSTT1 null was associated with improved survival in younger patients (P = 0.017, hazards ratio (HR) = 0.52, 95% CI = 0.31-0.89) but poorer survival in older patients (P = 0.017, HR = 1.89, 95% CI = 1.12-3.20). We proposed a model based on the dual functionality of GSTT1 to explain these contrasting results. We suggest that the null genotype is associated with improved immune response in younger patients, but poorer detoxification in older patients. These findings may also provide an explanation for the contrasting finding of other studies on the role of this gene in CRC.

    Title P16ink4a Polymorphism: Associations with Tumour Progression in Patients with Sporadic Colorectal Cancer.
    Date March 2005
    Journal International Journal of Oncology
    Excerpt

    Deregulated tumour expression of p16INK4a has previously been described in association with clinical progression in sporadic colorectal cancer patients (CRC). Furthermore, p16INK4a promoter hypermethylation leading to gene silencing has been shown to occur in advanced colorectal tumours and has been associated with patient survival. p16INK4a is polymorphic, with variant alleles being associated with tumour progression in melanoma. In this study we have examined p16INK4a polymorphism as a marker of tumour progression in sporadic CRC. Polymorphic sites G/A(442), C/G(500), and C/T(540), were studied, these alleles obeyed Hardy Weinberg equilibrium in a control group, but not in the CRC cases. G/A(442) and CG(500) alleles were in linkage disequilibrium in both cases and controls. In controls the C/T(540) alleles demonstrated no linkage with either other site, whilst an association was demonstrated between C/G(500) and C/T(540) alleles in the cases (p=0.011). Furthermore, the distribution of C/T(540) genotypes was different between the groups (p=0.002). Within the CRC cases, patients with the GG(442) genotype were more commonly associated with decreased tumour differentiation (p=0.018), advancing Dukes' stage (p=0.006) and T-stage (p=0.007) than patients with the GA(442) and AA(442) genotypes. Patients with the CC(500) genotype were more commonly associated with decreased tumour differentiation (p=0.012), advancing Dukes' stage (p=0.015), and N-stage (p=0.031). No associations between patient C/T(540) genotype and clinical prognostic parameters were found. An analysis of patient tumour expression with p16INK4a genotype revealed patients with the CC(500) genotype were more commonly associated with reduced tumour p16 expression (p=0.046). In summary our data indicate that p16INK4a polymorphism is associated with tumour progression in patients with sporadic CRC.

    Title Effect of Dextran-induced Changes in Refractive Index and Aggregation on Optical Properties of Whole Blood.
    Date January 2004
    Journal Physics in Medicine and Biology
    Excerpt

    The purpose of the present study is to investigate systematically the mechanisms of alterations in the optical properties of whole blood immersed in the biocompatible agent dextran, and to define the optimal concentration of dextrans required for blood optical clearing in order to enhance the capability of light penetration depth for optical imaging applications. In the experiments, dextrans with different molecular weights and various concentrations were employed and investigated by the use of the optical coherence tomography technique. Changes in light attenuation, refractive index and aggregation properties of blood immersed in dextrans were studied. It was concluded from the results that the mechanisms for blood optical clearing are characteristic of the types of dextrans employed, their concentrations and the application stages. Among the substances applied, Dx500 at a concentration at 0.5 g dl(-1) gives the best result in improving light penetration depth through the blood. The increase of light transmission at the beginning of the addition of dextrans is mainly attributed to refractive index matching between the scattering centres and the ground matter. Thereafter, the transmission change is probably due to a dextran-induced aggregation-disaggregation effect. Overall, light scattering in the blood could be effectively reduced by the application of dextrans. It represents a promising approach to increasing the imaging depth for in vivo optical imaging of biological tissue, for example optical coherence tomography.

    Title Theoretical Model of Optical Coherence Tomography for System Optimization and Characterization.
    Date November 2003
    Journal Journal of the Optical Society of America. A, Optics, Image Science, and Vision
    Excerpt

    We present a detailed analytical model to describe optical coherence tomography (OCT) systems, which considers the propagation of the optical field within a scattering medium in the framework of the extended Huygens-Fresnel principle. The model includes use of the discrete-particle model and the fractal approach in treating biological tissue as being packed with scattering particles with a power-law distribution. In contrast to previous models, an imaginary lens proximal to the tissue surface is introduced that approximates the real focusing lens in the sample arm of the OCT system. This treatment avoids the consideration of backscattering light as traveling in the free space between the focusing lens and the tissue surface before mixing with the reference beam. Experiments on tissue phantoms were carried out to verify the validity of this model.

    Title Propylene Glycol As a Contrasting Agent for Optical Coherence Tomography to Image Gastrointestinal Tissues.
    Date October 2002
    Journal Lasers in Surgery and Medicine
    Excerpt

    BACKGROUND AND OBJECTIVE: Optical coherence tomography (OCT) is a recently developed imaging technique that has the potential to advance the early diagnosis of diseases in the human gastrointestinal (GI) tract. How ever, the high scattering nature of GI tissue limits its imaging depth and contrast. For more effective diagnosis using OCT, a concurrent improvement of imaging depth and contrast is, therefore, needed. In this work, we investigate the administration of chemical agents to the tissue as a means of improving the capability of OCT imaging of clinically relevant microstructures of the GI tract. STUDY DESIGN/MATERIALS AND METHODS: Normal human GI tissues, including stomach and oesophagus were obtained from patients in hospital, and were imaged with OCT within 0.5-2 hours of removal. Immediately after the first imaging of the specimens with OCT, about 0.5 ml of 80% propylene glycol solution was applied onto the tissue surface and the tissue allowed to absorb the chemical compounds for 20 minutes. Another image was then taken at the same position. The specimens were then embedded and stained in preparation for histologic evaluation. Co-registration of the images obtained using OCT before and after the topical application of the propylene glycol solution, and standard histopathologic processing provided basis for comparison. RESULTS: More detailed micro-structures, including the basal layer position and the cellular composition of the mucosal layer of GI tract tissues were observed after the topical application of propylene glycol solution, while these structures were not resolvable in the conventional OCT images. CONCLUSIONS: Propylene glycol could be used as a contrasting agent for OCT imaging of human GI tract tissues, allowing an increased capability of OCT for rapid clinical diagnosis in vivo.

    Title Epidermal Growth Factor Receptor and Transformation.
    Date October 2002
    Journal Surgery Today
    Excerpt

    The action of transforming growth factor peptides is mediated by distinct membrane receptors, which in turn activate a postreceptor signaling mechanism, eventually resulting in a mitogenic response. Such a signaling pathway may be modified by oncogene expression at the receptor or postreceptor levels, as well as by alterations in the levels of expression of the growth factor itself. One of the most extensively studied group of receptors is the type I epidermal growth factor receptor family. Activation of this receptor triggers the induction of receptor dimerization, which enables cross-phosphorylation to occur between two receptor molecules. This dimerization model provides a universal mechanism to activate the type I receptor family for growth factors and subsequent transformation.

    Title Loss of Heterozygosity on Chromosome 10q is Associated with Earlier Onset Sporadic Colorectal Adenocarcinoma.
    Date August 2002
    Journal International Journal of Cancer. Journal International Du Cancer
    Excerpt

    Recent studies have shown that loss of heterozygosity (LOH) on chromosome 10q is a frequent event in a number of tumour types including colorectal cancers. Because previous studies have used markers located mainly distally on chromosome 10, we have examined 114 sporadic colorectal adenocarcinomas for LOH using a panel of 9 highly polymorphic microsatellite markers spanning the long arm of chromosome 10. Using microdissected tumour material, LOH of one or more chromosome 10q markers was a frequent event (75 of 114; 66%). The highest frequency of loss (42 of 96; 44%) was observed at the marker D10S1790 located at 10q21.1. The mean age of presentation, of patients with LOH of D10S1790 was significantly (p = 0.0006) lower (67.1 years) compared to patients with retention of this marker (73.5 years). When we compared frequency of loss at this marker in patients presenting before 70 years of age (68%) to those above 70 years (23%) we observed a significant difference (p < 0.0001). Statistical analysis between loss, or instability at other markers and clinicopathological features did not show any significant associations. In addition LOH at D10S1790 was infrequent in adenomas (2 of 20; 10%) compared to adenocarcinomas (42 of 96; 44%) (p = 0.0047), suggesting that loss within this region is a late event in colorectal tumorigenesis. The association of loss at D10S1790 and an earlier age of presentation in adenocarcinomas suggests that this locus may harbor a tumour suppressor gene(s), which affects the rate of colorectal tumour progression. Identification of this region of genetic loss further refines our understanding of the paradigm in this tumour type of multiple-steps responsible for initiation and progression.

    Title Changes in the Immunologic Phenotype of Human Malignant Glioma Cells After Passaging in Vitro.
    Date February 2002
    Journal Clinical Immunology (orlando, Fla.)
    Excerpt

    Although immunotherapeutic strategies against glioblastomas have been promising both in vitro and in animal models, similar successes have not been realized in human clinical trials. One reason may be that immunotherapeutic strategies are based on prior studies that primarily have used human glioblastoma cell lines passaged in vitro, which may not accurately reflect the in vivo properties of glioblastoma cells. In this report, we used flow cytometry to quantify the expression of immunological cell surface molecules on human glioblastomas directly ex vivo (prior to any in vitro culturing) and after varying passages in vitro. Furthermore, we used ELISA to quantitate cytokine secretion after various passages in vitro. We demonstrate that in vitro culturing of established cell lines led to increases in the cell surface expression of MHC class I and ICAM-1 and secretion of IL-6 and TGF-beta(2). Furthermore, there were significant changes in the expression of MHC class I, MHC class II, B7-2, ICAM-1, and FasL when comparing ex vivo tumor cells to those after a single passage in vitro. After passaging once in vitro, there were also significant changes in the secretion of TGF-beta(2) and IL-10. This report indicates that in vitro culturing leads to significant changes in both cell surface molecules and secreted cytokines, which are known to affect the ability of immune cells to initiate an anti-tumor immune response. These changes in the immunological phenotype of glioblastomas after in vitro culturing may in part explain the limited success of immunotherapeutic strategies against glioblastomas in human clinical trials.

    Title Phenol Sulphotransferase Sult1a1*1 Genotype is Associated with Reduced Risk of Colorectal Cancer.
    Date January 2002
    Journal Pharmacogenetics
    Excerpt

    Sulphation is an important detoxification pathway for numerous xenobiotics; however, it also plays an important role in the metabolism and bioactivation of many dietary and environmental mutagens, including heterocyclic amines implicated in the pathogenesis of colorectal and other cancers. A major sulphotransferase (SULT) enzyme in humans, SULT1A1, is polymorphic with the most common variant allele, SULT1A1*2, occurring at a frequency of about 32% in the Caucasian population. This allele codes for an allozyme with low enzyme activity and stability compared to the wild-type (SULT1A1*1) enzyme, and therefore SULT1A1 genotype may influence susceptibility to mutagenicity following exposure to heterocyclic amines and other environmental toxins. Previously, a significant association of SULT1A1*1 genotype with old age has been observed, suggesting a 'chemoprotective' role for the high-activity phenotype. Here we have compared the frequencies of the most common SULT1A1 alleles in 226 colorectal cancer patients and 293 previously described control patients. We also assessed whether SULT1A1 genotype was related to various clinical parameters in the patient group, including Duke's classification, differentiation, site, nodal involvement and survival. There was no significant difference in allele frequency between the control and cancer patient populations, nor was there a significant association with any of the clinical parameters studied. However, when the age-related difference in allele frequency was considered, a significantly reduced risk of colorectal cancer (odds ratio = 0.47; 95% confidence interval = 0.27-0.83; P = 0.009), was associated with homozygosity for SULT1A1*1 in subjects under the age of 80 years. These results suggest that the high activity SULT1A1*1 allozyme protects against dietary and/or environmental chemicals involved in the pathogenesis of colorectal cancer.

    Title Radiosurgery for the Treatment of Recurrent Central Neurocytomas.
    Date October 2001
    Journal Neurosurgery
    Excerpt

    OBJECTIVE: Central neurocytomas are benign neoplasms with neuronal differentiation typically located in the lateral ventricles of young adults. Although the treatment of choice is complete surgical excision, patients may experience local recurrence. Adjuvant therapy for patients with residual or recurrent tumor has included reoperation, radiotherapy, or chemotherapy. To avoid the side effects of conventional radiotherapy in young patients, we present a series of patients with clear evidence of tumor progression who were treated with gamma knife radiosurgery. METHODS: Four patients (ages 20-49 yr; mean, 28 yr) who presented with an intraventricular mass on magnetic resonance imaging scans and underwent craniotomy for tumor resection were reviewed retrospectively. Histopathological analysis confirmed central neurocytoma in all cases. Each patient was followed up clinically and radiographically with serial magnetic resonance imaging. When radiographic signs of tumor progression were evident, patients were treated with radiosurgery. RESULTS: Complete radiographic tumor resection was achieved in all patients. There were no major postoperative complications. Local tumor progression was detected on magnetic resonance imaging scans 9 to 25 months after surgery (median, 17.5 mo). All patients achieved complete response to radiosurgery with reduction in tumor size. There have been no complications from radiosurgery. Follow-up ranged from 12 to 28 months (mean, 16.5 mo) after radiosurgery, and from 24 to 84 months (mean, 54.5 mo) after initial presentation. CONCLUSION: Radiosurgery with the gamma knife unit provides safe and effective adjuvant therapy after surgical resection of central neurocytomas. Radiosurgery may eliminate the need for reoperation and avoid the possible long-term side effects from conventional radiotherapy in young patients.

    Title Subcellular Localisation of Cyclin D1 Protein in Colorectal Tumours is Associated with P21(waf1/cip1) Expression and Correlates with Patient Survival.
    Date September 2001
    Journal International Journal of Cancer. Journal International Du Cancer
    Excerpt

    We investigated the expression of the cell cycle regulatory proteins cyclin D1 and p21(WAF1/CIP1) (p21) in human colorectal carcinomas using immunohistochemistry. Cyclin D1 was not detected in normal colonic epithelium; however, expression was observed in 74/126 (58.7%) of the tumour samples studied. Protein was detected in the nucleus in 22/126 (17.4%) and exclusively in the cytoplasm in 52/126 (41.3%) tumours. Nuclear expression of cyclin D1 was associated with poorly differentiated tumours (p = 0.035) and was more common in right- than in left-sided tumours (p = 0.005). Tumours displaying either, expression of cytoplasmic, (p = 0.05, HR 0.56, 95% CI 0.31-1.0) or nuclear (p = 0.021, HR 0.24, 95% CI 0.07-0.81) cyclin D1 were associated with improved patient survival compared with tumours negative for cyclin D1. p21 protein was strongly expressed mainly in the upper crypts of normal colonic epithelial cells, but in 63/126 (50%) of the tumour samples studied p21 expression was absent. Patients with tumours in which >50% of cells expressed p21 had improved survival compared to patients whose tumours were negative or had < or =50% of cells expressing p21 (p = 0.06, HR 0.33, 95% CI 0.1-1.0). We also observed a significant association between cyclin D1 subcellular localisation and p21 expression: 21/22 (95.5%) tumours expressing cyclin D1 in the nucleus also expressed p21, whereas only 17/52 (32.7%) of the tumours displaying exclusive cytoplasmic cyclin D1 staining were positive for p21 (p < 0.001). These data highlight the significance of exclusive cytoplasmic expression of cyclin D1 in colorectal cancer and lend support to recent in vitro studies suggesting that p21 protein may modulate the subcellular localisation of the cyclin D1 protein. Thus, deregulated expression of the cyclin D1 and p21 proteins are important in colorectal tumourigenesis and have implications for patient prognosis.

    Title Development of an off Bypass Mitral Valve Repair.
    Date August 2001
    Journal The Heart Surgery Forum
    Excerpt

    BACKGROUND: The Bow Tie Repair (BTR), a single edge-to-edge suture opposing the anterior and posterior leaflets of the mitral valve (MV), has led to satisfactory reduction of mitral regurgitation (MR) with few re-operations and excellent hemodynamic results. The simplicity of the repair lends itself to minimally invasive approaches. A MV grasper has been developed that will coapt both leaflets and fasten the structures with a graduated spiral screw. METHODS: Eleven explanted adult human MVs were mounted in a mock circulatory loop created for simulating a variety of hemodynamic conditions. The MV grasper was used to place a screw in each valve, which was then continuously run for 300,000 to 1,000,000 cycles with a fixed transvalvular pressure gradient. At the completion of these studies, the valves were stressed to a maximal transvalvular gradient for ten minutes. In seven cases, MR was induced and subsequently repaired using the MV screw. In vivo, the MV screw was tested in nine male canines. Through a subcostal incision, the MV grasper entered the left ventricle, approximated the mitral leaflets and deployed the MV screw under direct visualization via an atriotomy. Follow-up transthoracic echocardiograms were done at postoperative week 1, 6, and 12 to identify screw migration, MV regurgitation/stenosis or clot formation. Dogs were sacrificed up to postoperative week 12 to allow gross and histologic assessment. RESULTS: In vitro, no MV screw detached from the valve leaflets or migrated during the durability testing period of 6.8 million cycles, including periods of stress load testing up to 350 mm Hg. The percent regurgitant flow used to assess MR statistically decreased with the placement of the screw from 72 +/- 7% to 34 +/- 17%; p = 0.0025. In vivo, seven dogs whose valves were examined within the first 48 hours revealed leaflet coaptation with an intact MV screw and no evidence of MR. Two dogs, followed for a prolonged period, had serial postoperative echocardiograms demonstrating consistent coaptation, no screw migration, no clot, and no regurgitation or stenosis. In the animal sacrificed at 12 weeks, the MV screw was integrated into the tissue of both leaflets. CONCLUSIONS: The MV screw has provided durable leaflet coaptation and has reduced regurgitation in human MVs. Initial data on the MV screw's biocompatibility and interactions with living valve tissue is promising. Our early success supports further efforts towards the maturation of this prototype into off bypass mitral valve repair technology.

    Title Hereditary Non-polyposis Colorectal Cancer: an Updated Review.
    Date December 2000
    Journal European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
    Excerpt

    INTRODUCTION: Colorectal cancer is the commonest cause of death due to malignancy in non-smokers in the western countries. The two main hereditary types of colorectal cancer are familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), constituting approximately 10% of all cases of colorectal cancer. The main aim of this review is to reappraise the current advances in the genetics and diagnosis of HNPCC. METHODS: A Medline search was carried out to identify papers published from 1970 to 1999 on HNPCC. Embase and Cochrane databases were also searched. Reference lists of retrieved articles were carefully searched for additional articles. RESULTS AND CONCLUSIONS: Recent technological advances in the genetics of HNPCC have refined the criteria for diagnosis and management of HNPCC, however current policies regarding the testing of pedigrees are not clearly established. We believe that with the rapid development in this area definitive clinical guidelines will need to be available in future for the management of HNPCC.

    Title Analysis of Formaldehyde in the Headspace of Urine from Bladder and Prostate Cancer Patients Using Selected Ion Flow Tube Mass Spectrometry.
    Date September 1999
    Journal Rapid Communications in Mass Spectrometry : Rcm
    Excerpt

    We have used selected ion flow tube mass spectrometry (SIFT-MS) to determine the concentration of formaldehyde in the headspace of urine from patients suffering from bladder and prostate cancer and from several healthy subjects as controls. We address the potential problems associated with the use of ion chemistry to quantify formaldehyde in the presence of the relatively large number densities of water molecules and show that formaldehyde can be quantified in urine headspace using analysis by SIFT-MS. These studies show that formaldehyde is clearly elevated in the headspace of the urine from the cancer patients as compared with urine from the healthy controls. Thus, with further improvements in the methodology and the sensitivity of our SIFT-MS technique, formaldehyde quantification in urine headspace using this new analytical method could be a valuable non-invasive indicator of the presence of early-stage tumours in the body.

    Title Sporadic Colorectal Polyps: Management Options and Guidelines.
    Date July 1999
    Journal Scandinavian Journal of Gastroenterology
    Title Selected Ion Flow Tube Mass Spectrometry of Urine Headspace.
    Date June 1999
    Journal Rapid Communications in Mass Spectrometry : Rcm
    Excerpt

    We describe the use of our selected ion flow tube mass spectrometric technique (SIFT-MS) for the analysis of the headspace above urine. Ammonia, nitric oxide, acetone, ethanol and methanol are identified as the dominant species. As expected, the ammonia is increased in the headspace by making the urine alkaline and the nitric oxide is increased by making the urine acidic. Nitric oxide is abnormally high in the headspace of acidified bacterially infected urine and nitrous acid is also detected. The potential clinical implications of analyses of urine by SIFT-MS are alluded to.

    Title Screening for Colorectal Cancer: Present, Past and Future.
    Date January 1999
    Journal European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
    Excerpt

    Colorectal cancer results in 18,000 deaths annually in England and Wales, with 24,000 new cases diagnosed each year. Despite a better understanding of the genetics, and advancement in surgical and anaesthetic techniques, there has been little reduction in mortality and morbidity from this disease over the past 25 years. Colorectal cancer fits recognized criteria for a disease that should be screened in asymptomatic individuals. The putative duration of the adenoma to carcinoma sequence gives an ample window of opportunity to detect and treat colorectal cancer. In this article we have reviewed the strategies involved in screening for colorectal cancer in an asymptomatic population. We have presented trials and arguments for and against the different screening methods and discussed cost effectiveness of screening. In the USA and Canada, major professional organizations and societies now endorse screening; in the UK it is still far from being accepted. We feel that the available evidence shows that colorectal cancer screening has the potential to reduce the morbidity and mortality from this disease and that funding for a mass screening and public education programme should be sought.

    Title A Histopathological Assessment of the Response of Rectal Adenocarcinoma to Combination Chemo-radiotherapy: Relationship to Apoptotic Activity, P53 and Bcl-2 Expression.
    Date July 1998
    Journal European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
    Excerpt

    AIMS: To investigate the use of pre-operative chemo-irradiation in downstaging advanced rectal cancer prior to surgical resection. METHODS: We examined the pathological effects of chemo-irradiation on 24 rectal tumours and correlated the efficacy of treatment with the level of apoptosis, mitosis, P53 and bcl-2 protein expression on pre-treatment biopsies. RESULTS: All tumours were resectable following chemo-irradiation. Six cancers showed complete regression with no viable tumour in the resection specimen. A significant correlation was found between spontaneous tumour apoptosis and tumour regression. CONCLUSIONS: Our results suggest that in rectal cancer the apoptotic rate in untreated tumour tissue may predict sensitivity to radiation and cytotoxic agents. No relationship was found between regression and mitotic rate, p53 or bcl-2 expression.

    Title Changes to Mucins in Uninvolved Mucosa and at the Tumour Site in Gastric Adenocarcinoma of Intestinal Type.
    Date March 1998
    Journal Clinical Science (london, England : 1979)
    Excerpt

    1. Mucin histochemistry is markedly altered in the stomach in intestinal-type adenocarcinoma. To increase understanding of these changes we have examined the content and distribution of carbohydrate in mucus glycopolypeptides isolated from non-malignant antrum, and from the uninvolved gastric mucosa and tumour site of patients with this disease. 2. The content of carbohydrate declined by 12.6% (P = 0.02) in mucus glycopolypeptides from uninvolved gastric mucosa when compared with those from non-malignant antrum, and by a further 25.4% (P < 0.001) in mucus glycopolypeptides from the tumour site. The first of these changes was accompanied by a significant decrease in the number of carbohydrate chains/1000 amino acid residues, and a significant increase in the number of monosaccharide units in each carbohydrate chain. The second of these changes was accompanied by significant decreases in both the number of carbohydrate chains/1000 amino acid residues, and in the number of monosaccharide units in each carbohydrate chain. 3. The number of sulphated monosaccharide units/100 carbohydrate chains increased from a mean of 7.2 in mucus glycopolypeptides from non-malignant antrum to a mean of 27.2 (P < 0.001) in preparations from uninvolved gastric mucosa and 22.7 (P < 0.001) in preparations from the tumour site. 4. Evidence is presented that these structural changes to mucus glycopolypeptides from the malignant stomach are due to an abnormal mucin biosynthesis by metaplastic goblet cells and/or immature gastric-type mucous cells within the uninvolved mucosa, and immature mucous cells at the tumour site.

    Title Is Helicobacter Pylori Transmitted from Cats to Humans?
    Date January 1998
    Journal Helicobacter
    Excerpt

    BACKGROUND: Subsequent to the isolation of Helicobacter pylori from domestic cats, it has been suggested that the organism might be transmitted from cats to humans. This hypothesis has already gained considerable media attention. MATERIALS AND METHODS: In a previous study of risk factors for H. pylori infection, 447 factory workers from Stoke on Trent in the UK had provided blood samples for H. pylori serological workup. They had also completed a detailed questionnaire concerning their living conditions, including the possession of any household pets, in childhood. Logistic regression was used to assess the association between cat ownership in childhood and H. pylori seropositivity. RESULTS: After adjustment for potential confounders, it was found that subjects who had owned a pet as a child were slightly more likely to be H. pylori seropositive than subjects who had not. There was, however, no difference between subjects who had owned a cat and those with other pets. CONCLUSIONS: These data do not support the hypothesis that H. pylori infection might be transmitted from cats to humans.

    Title Helicobacter Pylori Transmission: Evidence from a Comparison with Hepatitis A Virus.
    Date January 1997
    Journal European Journal of Gastroenterology & Hepatology
    Excerpt

    OBJECTIVE: To assess the possibility that faecal-oral contact might play a role in the transmission of Helicobacter pylori. DESIGN: A cross-sectional comparison of the patterns of hepatitis A and H. pylori seropositivity. METHODS: At interview, blood samples and questionnaire data were collected from a group of 467 male volunteers, aged 18-65, from Stoke-on-Trent, UK. Serum samples from each subject were then analysed for anti-H. pylori and anti-hepatitis A antibodies. RESULTS: Overall, 100 of 175 H. pylori seropositive subjects (57.1%) and 113 of 292 H. pylori seronegative subjects (38.7%) were hepatitis A seropositive (chi 2 = 15.0, P < 0.001). This difference was not statistically significant after adjustment for age group and father's occupation, as a surrogate for socioeconomic status in childhood (P = 0.15). The seroprevalence of hepatitis A increased with age at a rate of 2.3% per year, compared to only 1.0% per year for H. pylori (P = 0.015). CONCLUSION: These data suggest that the case for faecal-oral transmission of H. pylori, in a manner similar to the spread of hepatitis A, is not proven and that other modes of transmission, for instance through oral-oral contact, should also be considered.

    Title Effect of Gonadectomy on Epidermal Growth Factor Values in the Gastrointestinal Tract of Male and Female Cd-1 Mice.
    Date June 1995
    Journal Gut
    Excerpt

    The effects of gonadectomy on the epidermal growth factor (EGF) concentrations in the gastrointestinal tract of CD-1 mice were studied. The EGF concentrations in the gastrointestinal tissues were always higher in males than in females. Gonadectomy led to a decrease in the EGF concentration in males, and an increase in females. Gonadectomy with sialoadenectomy led to a decrease in the EGF concentrations in the gastrointestinal tract of both sexes; the most significant effect being observed in the stomach. Orchidectomy led to a decrease in total body weight, and to a significant decrease in the weight and the protein concentration (ng.g-1 wet weight of tissue) of the submandibular gland, but had no significant effect on the other tissues of the gastrointestinal tract of male mice. Body, tissue weights, and protein concentrations did not change with oophorectomy. This study shows that male and female gonads have a profound effect on the EGF content of the tissues of the gastrointestinal tract and suggests that the submandibular gland also influences the EGF concentration in gastrointestinal tissues in mice.

    Title The Epidemiology of Low Serum Pepsinogen A Levels and an International Association with Gastric Cancer Rates. Eurogast Study Group.
    Date November 1994
    Journal Gastroenterology
    Excerpt

    BACKGROUND/AIMS: Low serum levels of pepsinogen A are indicative of chronic atrophy, a risk factor for gastric cancer. This study investigated the relationships between low pepsinogen A levels, Helicobacter pylori seropositivity, and gastric cancer rates in 17 populations worldwide. METHODS: In each center, about 200 randomly selected subjects (50 male and 50 female, aged 25-34 and 55-64 years) provided serum samples for pepsinogen analysis and H. pylori serology. RESULTS: Cumulative gastric cancer rates were associated with the prevalence of low pepsinogen A levels in men (coefficient, 0.15 [P = 0.06] for mortality; coefficient, 0.36 [P = 0.01] for incidence) but not women. The prevalence of low pepsinogen A levels was also correlated with H. pylori seropositivity in the older age group (r = 0.55; P = 0.02). Low pepsinogen A levels were significantly more common in the older group (7.5% vs. 2.1% in the younger group; P < 0.001), among women (5.5% vs. 4.1% in men; P = 0.04), and among nonsmokers (5.8% vs. 2.9% in current smokers; P = 0.001). CONCLUSIONS: Low pepsinogen A levels are more common in areas with a high seroprevalence of H. pylori and in men in areas with high rates of gastric cancer. The prevalence of low pepsinogen A levels increases with age, but the excess in women and nonsmokers could reflect factors other than gastric pathology.

    Title Life Quality and Psychological Morbidity with an Ileostomy.
    Date April 1993
    Journal The British Journal of Surgery
    Excerpt

    The recent introduction of restorative proctocolectomy for the treatment of ulcerative colitis has reopened the debate about the effects of ileostomy on quality of life. This study analysed life quality and psychological morbidity in 113 patients with an ileostomy using a postal questionnaire which included questions about their opinion of the pouch operation. Of the questionnaires, 73 per cent were suitable for analysis. A total of 93 per cent of those responding were happy with the ileostomy and appeared to have adapted to a normal life with it. Some 87 per cent stated that they would keep the ileostomy in preference to an ileoanal pouch. In addition, psychological morbidity as assessed by the General Health Questionnaire occurred in only 5 per cent of patients.

    Title Surgical Suppression of Gastric Acid Secretion. Lessons from Long-term Follow-up Studies.
    Date March 1992
    Journal Scandinavian Journal of Gastroenterology. Supplement
    Excerpt

    This paper reviews data from case controls studies, cohort studies, and long-term follow-up papers of over 30,000 patients following surgical reduction of gastric acid secretion 20-40 years postoperatively. There is an increase in gastric cancer which becomes highly significant 20 years after Billroth II resection and rises thereafter, many studies showing a three- or four-fold increase compared with a non-operative control or contrast population. There is little doubt that surgical depression of gastric acid secretion is associated with the development of carcinoma of the stomach. The mechanisms by which this development may occur are discussed.

    Title The Human Glutathione S-transferases: a Case-control Study of the Incidence of the Gst1 0 Phenotype in Patients with Adenocarcinoma.
    Date February 1991
    Journal Carcinogenesis
    Excerpt

    The suggestion that individuals with the GST1 0 phenotype have a greater susceptibility to carcinogens than those with other GST1 phenotypes has been examined by using a starch gel zymogram approach to compare the frequency of this phenotype in control subjects and a group of patients with adenocarcinoma of stomach and colon. A significantly greater proportion of the patients with adenocarcinoma demonstrated the null phenotype, odds ratio analysis indicating that individuals with this polymorphic variant have an approximately 3-fold greater risk of developing these cancers.

    Title Transforming Growth Factor Alpha and Epidermal Growth Factor Levels in Normal Human Gastrointestinal Mucosa.
    Date December 1989
    Journal British Journal of Cancer
    Excerpt

    Acid soluble proteins from 23 samples of normal human gastrointestinal mucosa derived from four normal adult organ donors were extracted and subjected to specific radiommunoassays for transforming growth factor alpha (TGF alpha) and urogastrone epidermal growth factor (URO-EGF). All tissues were found to contain immunoreactive TGF alpha and levels ranged from 57 to 4,776 pg-1 wet weight of tissue. Although levels varied between tissue donors, the distribution of TGF alpha throughout the gastrointestinal tract appeared similar in all cases. URO-EGF levels were much lower (0-216 pg g-1 wet weight). TGF alpha levels in extracts of gastrointestinal mucosa from a 7-year-old female donor were higher and the observed distribution was markedly different from adult levels. URO-EGF was not detected in mucosal or submucosal tissue extracts from this patient. Further studies in juveniles are indicated.

    Title Effects of Gastric Fundic Stimulation on Glucose Absorption and Water and Electrolyte Fluxes from Rabbit Small Bowel.
    Date April 1989
    Journal Digestive Diseases and Sciences
    Excerpt

    A single-pass perfusion model was developed to measure net fluxes of glucose, water, sodium, and potassium across upper jejunal and duodenal mucosa in vivo in the anaesthetised rabbit. Irrigation of the gastric fundic mucosa with Michaelis' buffer (pH 8) reduced jejunal mean glucose absorption by 21.3% (P less than 0.04) and duodenal glucose absorption by 27.2%. Irrigation of gastric fundic mucosa with 0.1 M glycine at pH 2 increased mean jejunal glucose absorption by 25%. Jejunal net secretion of water and sodium were reduced by gastric fundic alkali. Potassium net fluxes in jejunum and duodenum were not significantly affected. These results support the hypothesis that the gastric fundic mucosa is sensitive to chemical stimulation, responding by a humoral mechanism that modified the rate of glucose absorption from the small bowel mucosa.

    Title Surgical Treatment of Duodenal Ulcer.
    Date October 1988
    Journal Postgraduate Medical Journal
    Excerpt

    This paper reviews the pathophysiology of peptic ulcer disease, the role of the vagus and gastrin in the control of gastric acid secretion and motility and the rationale for modern operations for peptic ulcer. The importance of arriving at a balanced decision before recommending surgery for a peptic ulcer is discussed. The indications for surgery in elective and emergency cases are defined and the results reviewed critically and compared with medical treatment. Novel operative procedures are mentioned but still await validation follow-up studies before their final assessment. Well tried operations should not be dismissed lightly and the importance of prospective randomized trials to evaluate new procedures is emphasized.

    Title Recent Experimental and Clinical Studies on the Pharmacology of Colloidal Bismuth Subcitrate.
    Date December 1986
    Journal Scandinavian Journal of Gastroenterology. Supplement
    Excerpt

    Recent experimental and clinical pharmacological studies on colloidal bismuth subcitrate (CBS) are reviewed. CBS combines with mucus to produce a marked retardation of the movement of hydrogen ions. CBS has potent anti-ulcer and anti-erosive action in various experimental models in animals, and is able to stimulate the generation of gastric mucosal prostaglandins. CBS is thought to be a cytoprotective agent. The type of mucosal cell repair in the vicinity of the ulcer is favourably affected in man. CBS also exhibits anti-pepsin and bile acid-binding properties. Pyloric campylobacter are inhibited in vitro and in vivo. The recent pharmacological findings are discussed in the light of the clinical efficacy of CBS and new indications.

    Title Inhibition of Acid and Gastric Carcinoids.
    Date March 1986
    Journal Gut
    Title Effect of H2 Blockers on Intragastric Nitrosation As Measured by 24-hour Urinary Secretion of N-nitrosoproline.
    Date June 1985
    Journal Iarc Scientific Publications
    Excerpt

    Intragastric nitrosation of proline (500 mg daily) was studied in eight volunteers and three duodenal ulcer patients. Daily urine outputs of N-nitrosoproline (NPRO) and N-nitrosothiazolidine-4-carboxylic acid (NTCA) were measured for two days before, two days during and two days after ingestion of H2 blocker (ranitidine). No increase in NPRO output was found with ranitidine, the trend being clearly towards decreased intragastric nitrosation of this amine. A significant (p less than 0.05) increase in NTCA occurred during H2 blockade, due to increased concentration of NTCA in urine. The biological significance of the presence of NTCA in urine is uncertain.

    Title A Prospective Randomized Trial of Vagotomy in Chronic Duodenal Ulceration: 4-year Follow-up.
    Date August 1983
    Journal The British Journal of Surgery
    Excerpt

    A total of 153 patients (124 male and 29 female) with uncomplicated chronic duodenal ulceration were studied in a prospective, randomized trial of proximal gastric vagotomy (PGV) and truncal vagotomy and pyloroplasty (TVP), conducted in four Manchester hospitals. Of these, 137 patients have now been followed up for 2.5 to 5.5 (mean 4.1) yr. There have been 15 (21 per cent) recurrent ulcers following PGV compared with 5 (7.5 per cent) after TVP (P less than 0.05). A satisfactory functional result was obtained in 82 per cent of patients after TVP compared with 73 per cent following PGV and there was little difference between the groups with regard to the incidence of dumping, heartburn and vomiting. There was significantly more diarrhoea following TVP (13 per cent) compared to PGV (1.4 per cent) but this represented only a minor clinical problem.

    Title Effects of Porcine Gastric Fundic Factor, Somatostatin, Substance P, Glucagon, Neurotensin, Bombesin, Vip, Motilin, and Pentagastrin on Jejunal Glucose Absorption in the Rat.
    Date May 1983
    Journal Gut
    Excerpt

    The effects of a porcine gastric fundic mucosal extract (molecular weight less than 10 000) has been compared with the effects of eight candidate gastrointestinal peptides on glucose absorption from the jejunum in a rat model. Bolus injection of the extract produced immediate and marked depression of glucose absorption. None of the candidate peptides tested produced this response, although somatostatin and substance P depressed absorption as a late phenomenon after 30 minutes. We conclude that the effects of the fundic extract are not reproduced by any of these candidate peptides. This strengthens the evidence for a novel gastrointestinal peptide, resident in fundic mucosa, which affects absorption from upper small bowel.

    Title Randomized Trial of Elective Highly Selective or Truncal Vagotomy in Chronic Duodenal Ulceration.
    Date April 1983
    Journal Canadian Journal of Surgery. Journal Canadien De Chirurgie
    Excerpt

    Between 1973 and 1976, 153 patients (124 men, 29 women) with uncomplicated, chronic, duodenal ulcer were entered into a prospective randomized trial of highly selective vagotomy (HSV) or truncal vagotomy and pyloroplasty (TVP). The study was conducted in four Manchester hospitals and the operations were performed by consultants or chief registrars. The follow-up was conducted by personal interview using a standardized questionnaire. The medical gastroenterologist did not know which type of operation the patient had had. The patients who had symptoms were referred back to the surgeon who performed the operation. The clinical laboratory and follow-up data were analysed by computer. There were no operative deaths. Three patients died from unrelated causes, 13 were lost to follow-up; 137 (89.5%) were followed up for a mean of 4.1 years (range from 2.5 to 5.5 years). A modified Visick grading was used to assess the results of surgery. The outcome was good in 82% after TVP and 73% after HSV. This difference and those in the incidences of early or late postprandial dumping, bilious vomiting, weight loss, anemia and heartburn were not significant. Diarrhea was more frequent after TVP (13.4%) than after HSV (1.4%); although the difference was significant (p less than 0.025), this complaint did not present a serious clinical problem. Ulcers recurred in 15 (21.4%) patients following HSV and in 5 (7.5%) after TVP; this difference was statistically significant (p less than 0.05).

    Title Effect of Urogastrone on Gastric Secretion and Serum Gastrin Concentration in Patients with Duodenal Ulceration.
    Date December 1982
    Journal Gut
    Excerpt

    A one-hour infusion of 0.25 micrograms/kg urogastrone administered to seven patients with duodenal ulceration resulted in significant reduction of basal acid secretion (p less than 0.05) but was without significant effect on basal pepsin and intrinsic factor secretion or on serum gastrin concentration. In another group of five patients with duodenal ulceration a one-hour infusion of urogastrone was given on five successive days. On day 1 and 5 urogastrone was administered after establishing a plateau response to intravenous pentagastrin 1.2 micrograms/kg/h. A mean reduction of 65% in acid output during the urogastrtone infusion was seen on day 1 and this was maintained during the next hour. On day 5 the pentagastrin-stimulated acid output was less than on day 1 and a further significant decrease was noted after urogastrone. Pepsin and intrinsic factor output were also significantly inhibited. There was no change in fasting serum gastrin or urogastrone concentration.

    Title Mucus and Gastric Acid-bicarbonate Interaction.
    Date July 1982
    Journal Advances in Experimental Medicine and Biology
    Title Studies of a Gastric Fundic Mucosal Factor Which Affects Absorption from the Antrum and Jejunum in the Rat.
    Date February 1982
    Journal The Journal of Physiology
    Excerpt

    1. A rat bio-assay has been developed in which the tracer ion technetium 99 m (99mTc) was used to monitor absorption from both the antrum and the jejunum of the rat. 2. Evidence has been obtained for the release of a humoral substance from the rat gastric fundus after alkalinization of the mucosa at pH 8, and this fundic factor has been shown to reduce the absorption of the tracer ion 99mTc from both the lumen of the antrum and of the jejunum in the rat. 3. Intravenous infusion of a neutral extract of porcine fundic mucosa, distension of the rat fundus with air or exposure of the fundic mucosa to alkaline buffer all decreased absorption of the tracer ion virtually to the same extent from the lumen of the antrum (P less than 0.001) and to a lesser extent from the lumen of the jejunum (P less than 0.05). This effect does not appear to be due to histamine. 4. Preliminary biochemical data have indicted that the biological activity in the mucosal extract is protein in nature and has a molecular weight of less than 10,000.

    Title Intragastric Pco2 in Man and Calculated Gastric Bicarbonate Concentrations: Effect of Carbenoxolone Sodium.
    Date May 1981
    Journal Scandinavian Journal of Gastroenterology. Supplement
    Excerpt

    In six normal subjects, ten patients with either gastric or duodenal ulcer or combined duodenal and gastric ulcers and in one with gastric carcinoma, the fasting intragastric PCO2 was measured using a new silicon-coated teflon intragastric catheter connected to a mass spectrometer. PCO2 values ranged from 9 to 38 mm Hg in normal subjects and from 23 to 75 mm Hg in patients. In some patients sharp peaks up to 170 mm Hg were obtained. The pH of the resting juice was measured and the intragastric HCO-3 concentration calculated using the Henderson-Hasselbach equation. Intragastric HCO-3 concentration was 5--136 nmol per litre in normals and 12 nmol-960 mumol per litre in those with dyspepsia, and 6.05 mmol per litre in the patient with gastric carcinoma. Five dyspeptic patients and the one with stomach cancer were given 100 mg carbenoxolone t.d.s. for 72 hours. The fasting PCO2 decreased from a mean of 34.6 +/- 4.89 to 26.6 +/- 2.24 Se mmHg (p less than 0.05) with corresponding changes in HCO-3 concentration. These results suggest that carbenoxolone increased the thickness of the unstirred layer of mucus, making it more resistant to H+ penetration and thus reducing H+ and HCO-3 interaction with consequent lowering of PCO2.

    Title Intra-arterial Hyaluronidase in Severe Peripheral Arterial Disease.
    Date June 1980
    Journal Lancet
    Title Organochlorine Residues in Young Herons from the Upper Mississippi River-1976.
    Date May 1980
    Journal Pesticides Monitoring Journal
    Excerpt

    Chicks of great blue herons (Ardea herodias) from four heronaries located near South St. Paul, Royalton, and Wabasha, Minnesota, and La Crosse, Wisconsin, were analyzed for organochlorines, Highest mean wet-weight concentrations, 6.43 ppm PCBs. 1.31 ppm DDE, and 1.90 ppm sigma DDT, were found in the South St. Paul chicks. Among chicks from the other three heronries, most levels were similar, but were significantly lower than levels in South St. Paul chicks. Lowest mean organochlorine levels, 0.37 ppm DDE, 0.38 ppm sigma DDT, and 0.22 ppm PCBs, were found in chicks from Royalton. All birds from South St. Paul and La Crosse contained residues of DDT and TDE whereas only one of the 10 birds from Royalton contained DDT and one contained TDE residues. Five of the 12 birds from Wabasha contained DDT; eight contained TDE. Except for PCB residues in La Crosse heron chicks, the rate of organochlorine residue accumulation in the birds was generally less than the rate of dilution caused by growth.

    Title Leucocyte Ascorbate Levels and Postoperative Deep Venous Thrombosis.
    Date December 1979
    Journal The British Journal of Surgery
    Excerpt

    Forty-four general surgical patients were included in a prospective, randomized double-blind controlled trial of ascorbic acid (500 mg b.d.) or placebo for 7 days before operation. This was to test the hypothesis that vitamin C may reduce the instance of deep venous thrombosis postoperatively. Venous blood samples were taken before entering the trial, just immediately before surgery, on the day of operation and on three further occasions at 3-day intervals postoperatively for leucocyte ascorbic acid concentration (LAC). Venous thrombosis was diagnosed using the 125I-fibrinogen test and the leg scans interpreted by Roberts' criteria. There was no significant difference in the incidence of DVT between the treatment and placebo groups. In those with DVT (n = 23) the mean LAC on the day of operation was not significantly different from that in those without DVT. However, on the sixth and ninth postoperative days LAC levels were significantly lower in the DVT group. These results suggest that the administration of ascorbic acid preoperatively does not reduce the incidence of DVT, but a striking decrease in the LAC levels in the DVT patients is in keeping with the hypothesis that the initial event in the pathogenesis of DVT is adherence of leucocytes to the venous endothelium.

    Title Gastric Cancer in Patients Who Have Taken Cimetidine.
    Date October 1979
    Journal Lancet
    Title Cimetidine and Gastric Cancer.
    Date July 1979
    Journal Lancet
    Excerpt

    Three patients with dyspeptic symptoms who were being treated with the H2-receptor blocking drug, cimetidine, were later found to have gastric carcinoma. It was not possible to determine whether the association was fortuitous, whether the drug had masked the neoplastic change, or whether it was involved in some other way. Repeated clinical and endoscopic evaluation is essential in patients on this treatment for any length of time.

    Title A Prospective Randomized Trial of Vagotomy in Chronic Duodenal Ulceration.
    Date June 1979
    Journal The British Journal of Surgery
    Excerpt

    In a prospective, randomized trial, 76 patients with duodenal ulceration treated by truncal vagotomy and pyloroplasty were compared with 77 patients who underwent highly selective vagotomy. A total of 149 patients was followed up for from 1 to 4 years, the average follow-up period being 2.6 years. There was no operative mortality and no significant difference in postoperative morbidity between the two groups. The incidence of recurrent ulceration was greater after highly selective vagotomy, but this difference was not statistically significant. The clinical results were comparable in each group, and although the incidence of diarrhoea and dumping was greater after vagotomy and pyloroplasty, this difference was not statistically significant.

    Title Vascular Prostacyclin May Be Reduced in Diabetes in Man.
    Date May 1979
    Journal Lancet
    Title Comparison of an Intragastric Method of Estimating Acid Output with the Pentagastrin Test in Normal and Duodenal Ulcer Subjects.
    Date January 1979
    Journal Gut
    Excerpt

    Using Fordtran's technique but substituting the meat extract Oxo for the steak meal we investigated gastric acid secretion in eight control subjects and nine patients with chronic duodenal ulcer. Intragastric titration was performed using a double lumen tube measuring the pH in the stomach every three minutes and adjusting it to 5.5 throughout the test by infusing 0.3-M sodium bicarbonate. On a separate day a pentagastrin test was performed using a conventional gastric aspiration technique. In the eight control subjects the mean acid output after pentagastrin was 13.7 +/- 2.1 (SEM) mmol/h, whereas the mean hourly acid output measured by intragastric titration was 20.1 +/- 3.1. The greater response to Oxo than to pentagastrin in the controls (deltaAO = + 46%) was significant (P less than 0.01). This is in contrast with our duodenal ulcer patients whose mean hourly acid outputs were 22.7 +/- 4.4 and 23.0 +/- 4.4 mmol/h in response to pentagastrin and Oxo respectively (r = 0.95). The findings, while clearly at variance with those of Fordtran and Walsh (1973), are more in keeping with the concept of increased endogenous secretory drive in duodenal ulcer patients compared to normal subjects.

    Title Cellular Localisation of Human Urogastrone/epidermal Growth Factor.
    Date April 1978
    Journal Nature
    Title Proceedings: Cellular Localization Urogastrone by an Immunofluorescent Technique.
    Date October 1976
    Journal The British Journal of Surgery
    Title Proceedings: Evidence for the Existence of a Fundic Factor Affecting Antral Permeability.
    Date October 1976
    Journal The British Journal of Surgery
    Title Proceedings: Comparison of Gastric Acid Outputs Measured by an Intragastric Titration Method(oxo Stimulation) with the Response to Exogenous Gastrin Pentapeptide in Normal Human Subjects.
    Date September 1976
    Journal The Journal of Physiology
    Title Mercury in Eggs of Aquatic Birds, Lake St. Clair--1973.
    Date September 1976
    Journal Pesticides Monitoring Journal
    Excerpt

    Eggs from four species of aquatic birds inhabiting waterways of the Lake St. Clair region were collected in 1973 and analyzed for mercury. Species analyzed were mallard ducks (Anas platyrhynchos), common terns (Sterna hirundo), black-crowned night herons (Nycticorax nycticorax), and great egrets (Casmerodius albus). Mallard eggs contained relatively low residue levels, less than 0.05-0.26 ppm, and common tern eggs contained the highest residues, ranging up to 1.31 ppm. Mercury levels in the eggs were appreciably lower than those in the same species in 1970. The declines are attributed to the 1970 restrictions placed on industrial discharges of mercury into the St. Clair and Detroit Rivers.

    Title Proceeding: Gastric Mucosal Permeability--a Relationship Between Ischaemia and Cellular Damage.
    Date August 1976
    Journal Gut
    Title Proceedings: A Comparison of an Intragastric Method of Estimating Acid Output with the Pentagastrin Test in Normal and Duodenal Ulcer Subjects.
    Date June 1976
    Journal The British Journal of Surgery
    Title Proceedings: The Relationship Between Antro-fundic Permeability and Gastric Mucosal Blood Flow Using Tracer Techniques.
    Date March 1976
    Journal Gut
    Title Proceedings: The Oxo Test in the Diagnosis of Gastrinomas, Antral Gastrin Cell Hyperplasia, and Recurrent Peptic Ulceration.
    Date March 1976
    Journal Gut
    Title Effect of Urogastrone on Gastric Secretion and Plasma Gastrin Levels in Normal Subjects.
    Date February 1976
    Journal Gut
    Excerpt

    Purified human urogastrone was given by intravenous infusion to 12 normal volunteer subjects and measurements made of gastric acid, pepsin and intrinsic factor secretion, and of plasma gastrin concentration. Clinical, haematological, and biochemical screening tests were made throughout the period of study. Urogastrone inhibited acid and intrinsic factor secretion whether stimulated by pentagastrin, histamine, or insulin, but had a much less marked effect on gastric pepsin output. Plasma gastrin levels did not alter significantly. Limited dose-response studies showed that 0-25 mug urogastrone kg--1 hr--1 resulted in inhibition of acid output of 80% and was not associated with clinical side-effects. No significant alteration in any of the haematological or biochemical measurements was observed in any of the subjects.

    Title Observations of Gastric Mucosal Blood Flow Using 99tcm in Rat and Man.
    Date February 1976
    Journal The British Journal of Surgery
    Excerpt

    The 99Tcm clearance technique is shown to be a useful method of assessing gastric function. It is easily carried out and is relatively non-toxic--the dose of isotope could be reduced to 100 muCi or less without sacrificing the accuracy of the investigation. Although the results are preliminary and the number of cases investigated so far is small, they suggest that the measurement of pertechnetate clearance is directly related to gastric mucosal blood flow; it is a useful parameter of gastric function and may well prove to be a more accurate discriminant in cases of peptic ulceration than the conventional measurement of gastric acid secretion.

    Title The G Cell Population of the Pyloric Antrum of the Cat.
    Date December 1975
    Journal Digestion
    Excerpt

    The method used in this study to quantify the G cell population of the cat is similar to the technique used for measuring the parietal cell mass in the stomach of rats and man. The method may be used on the human antrum. Mucosal sampling technique and immunofluorescence methods are described. The method is reproducible. G cell distribution in the antrum was not uniform and the highest concentrations were found along the lesser curvature. The G cell population was 10.27, 12.66, 12.87, 12.88 and 15.42 million cells (mean 12.8 x 10(6)) per antrum in each of the five cats studied.

    Title Treatment of Haemorrhoids by Rubber Band Ligation.
    Date November 1975
    Journal Digestion
    Excerpt

    Outpatient treatment of haemorrhoids by elastic band ligation without anaesthetic was performed in 75 patients. Clinical review showed that 65 returned to work within 24 h of ligation, 8 in 48 h and 2 after 48 h. No patient required hospitalisation for either rectal bleeding or pain after ligation. In the first week after treatment 36 were completely symptom-free, 26 had minimal discomfort and 13 had moderate pain with a sense of imcomplete evacuation in the rectum, and some frequency of call to stool lasting up to 7 days in 1. Follow-up at 8-26 months (mean 10 months) showed that 59 were symptom free, only occasional rectal bleeding occurred in 7 and more frequent irregular bleeding in 2. Religation of residual haemorrhoids was performed in 7 and 2 and a haemorrhoidectomy. For the majority of patients hospitalisation and loss of work were avoided.

    Title Effect of Urogastrone in the Zollinger-ellison Syndrome.
    Date November 1975
    Journal Lancet
    Excerpt

    The effects of human urogastrone (0-25 mug. per kg. per hour intravenously) in four male patients with proven Zollinger-Ellison syndrome (z.e.s.) and in four healthy control subjects have been studied. After urogastrone in z.e.s. patients gastric acid volume and concentration decreased and basal acid output was reduced by 50-82%; the concentrations of intrinsic factor and pepsin in gastric juice increased by 60-300%; and peak plasma-gastrin concentration increased by 127-164% of basal concentration. A significant negative correlation between increase in plasma-gastrin concentration and decrease in acid output was observed (r=-0-72, P less than 0-01). Ulcer pain was relieved 30-60 minutes after the beginning of urogastrone infusion. These results suggest that urogastrone can inhibit the endogenously stimulated acid hypersecretion in z.e.s.

    Title Gastric-acid Output, Pepsin Output, and Lean Body Mass in Normal and Duodenal-ulcer Subjects.
    Date August 1975
    Journal Lancet
    Excerpt

    Gastric-acid output bears a significant relationship to parietal cell mass and to lean body mass. The relationships of pepsin output to gastric-acid output and to lean body mass have been investigated in 13 normal subjects and 40 duodenal-ulcer patients. Peak pepsin output (P.P.O[I]) was stimulated by insulin-induced hypoglycaemia and the enzyme was assayed by Piper's method. Peak acid output to pentagastrin (P.A.O.[Pg] was obtained at a separate test. P.P.O.(I) correlated significantly with P.A.O.(Pg) in normal subjects (r equals 0-889, P less than 0-0001). P.P.O.(I) also showed good correlation with lean body mass (L.B.M.) (r equals 0-714, P less than 0-01), suggesting that P.P.O.(I) reflects peptic cell mass in normal subjects. In 40 duodenal-ulcer subjects there was no significant overall correlation of P.P.O.(I) with P.A.O(Pg) or with L.B.M. However, expressing the results as output of pepsin per milliequivalent of acid per kilogramme of lean body mass allowed separation of the ulcer patients into two groups whose ratios appeared to correlate with their symptomatic state at the time of testing: thus mean P.P.O(I) per meq. acid per kg. L.B.M. for duodenal-ulcer patients in relapse was significantly greater than the ratios for the patients in remission and for the normal group (P less than 0-001), suggesting either the presence of an increased sensitivity to insulin stimulation or a lack of pepsin inhibitor substance during a relapse of ulcer symptoms.

    Title Proceedings: Observation of Gastric Mucosal Blood Flow Using 99tc in Rat and Man.
    Date June 1975
    Journal The British Journal of Surgery
    Title Proceedings: Effect of Urogastrone in the Zollinger-ellison Syndrome.
    Date February 1975
    Journal Gut
    Title Reproducibility of Plasma Gastrin Concentration and Gastric Pepsin Output After Insulin-induced Hypoglycaemia.
    Date February 1975
    Journal Scandinavian Journal of Gastroenterology
    Title Proceedings: Initial Observations on the Inhibitory Action of Urogastrone on Gastric Secretory Responses in Man.
    Date August 1974
    Journal Gut
    Title Proceedings: The Results of Outpatient Treatment of Haemorrhoids by Rubber Band Ligation.
    Date August 1974
    Journal Gut
    Title Letter: Antral-gastrin-cell Hyperplasia in Peptic-ulcer Disease.
    Date August 1974
    Journal Lancet
    Title Exocrine Secretory Responses of the Pancreas to Pentagastrin and to a Meat Meal in Dogs.
    Date June 1974
    Journal Digestion
    Title Antral-gastrin-cell Hyperplasia in Peptic-ulcer Disease.
    Date June 1974
    Journal Lancet
    Title Proceedings: Antral 'g' Cell Hyperplasia with Peptic Ulcer Disease: a New Clinical Entity.
    Date January 1974
    Journal Gut
    Title Proceedings: Reproducibility of Pepsin Output and Plasma Gastrin Concentration After Insulin in Peptic Ulcer Patients.
    Date January 1974
    Journal The British Journal of Surgery
    Title Proceedings: the Evaluation of Gastric Pepsin Output to Insulin in Patients with Recurrent Ulcer.
    Date January 1974
    Journal The British Journal of Surgery
    Title The Effect of Carbenoxolone on Ion Fluxes in Denervated Fundic Pouches.
    Date September 1973
    Journal Gut
    Title The Effect of Vagotomy on the Exocrine Pancreatic Secretory Response to Pentagastrin and to a 400-g. Meat Meal in Dogs.
    Date June 1973
    Journal The British Journal of Surgery
    Title Exocrine Secretory Responses of the Pancreas to Insulin and to a Meat Meal in Dogs.
    Date May 1973
    Journal Gut
    Excerpt

    Studies in five dogs with chronic pancreatic and gastric fistulae have shown that insulin-induced vagal stimulation of the pancreas (gastric fistula open) resulted in protein and bicarbonate outputs very much smaller than those obtained with a 400-g meat meal. However, when the insulin-activated gastric acid secretion was allowed access to the duodenum (gastric fistula closed) peak outputs of both bicarbonate and protein were observed which were closely similar to the response to the meal. These findings suggest that insulin-induced hypoglycaemia results in stimulation of the pancreas within the physiological range when gastric acid is allowed access to the duodenum with consequent release of secretin.

    Title Relationships Between Acid Output to Pentagastrin, Gastric Pepsin Output to Insulin and Lean Body Mass.
    Date January 1973
    Journal The British Journal of Surgery
    Title A Study of the Acid Dose-response Curve to Small Doses of Pentagastrin in Duodenal Ulcer Patients.
    Date September 1972
    Journal Clinical Science
    Title The Effect of Vagotomy on the Lower Part of the Acid Dose-response Curve to Pentagastrin in Man.
    Date September 1972
    Journal Clinical Science
    Title The Effect of Sub-threshold Doses of Pentagastrin on the Acid Response to Insulin in Duodenal Ulcer Subjects Before and After Truncal Vagotomy.
    Date September 1972
    Journal Clinical Science
    Title Analysis of Basal Acid Secretion and Its Relation to the Insulin Response in Normal and Duodenal Ulcer Subjects. New Criterion for the Insulin Test.
    Date July 1972
    Journal Gastroenterology
    Title Time of Conversion of Insulin Response After Vagotomy.
    Date July 1972
    Journal Gastroenterology
    Title Exocrine Secretory Responses of the Pancreas to Pentagastrin and to a Standard Meal in Dogs.
    Date June 1972
    Journal The British Journal of Surgery
    Title Exocrine Secretory Responses of the Pancreas to Insulin and to a Standard Meal in Dogs.
    Date February 1972
    Journal The British Journal of Surgery
    Title Effect of Insulin Hypoglycaemia on Plasma Gastrin Concentration and Gastric Acid Secretion in Normal Subjects.
    Date February 1972
    Journal Gut
    Title The Half-life (t and One-half) of Synthetic Human Gastrin I in Human Subjects.
    Date May 1971
    Journal Clinical Science
    Title Low-dose, Pentagastrin Infusion Studies.
    Date January 1971
    Journal The British Journal of Surgery
    Title Recovery of Vagal Nerve Function After Vagotomy.
    Date January 1971
    Journal The British Journal of Surgery
    Title An Analysis of Spontaneous Acid Secretion and Its Relation to the Insulin Response in Normal and Duodenal Ulcer Subjects: New Criteria for Insulin Test.
    Date January 1971
    Journal The British Journal of Surgery
    Title The Half Life (t and One-half) of Synthetic Human Gastrin I in Man.
    Date December 1970
    Journal The British Journal of Surgery
    Title The Short Term Reproducibility of the Insulin Test in Peptic Ulcer Patients.
    Date September 1970
    Journal Gastroenterology
    Title The Short-term Reproducibility of the Insulin Response.
    Date August 1970
    Journal The British Journal of Surgery
    Title Achalasia of the Cardia in Childhood.
    Date August 1970
    Journal Digestion
    Title The Long Term Stability of the Insulin Test.
    Date June 1970
    Journal Gastroenterology
    Title The Vagus and Achalasia.
    Date March 1970
    Journal Gut
    Title The Long-term Stability of the Insulin Response After Vagotomy.
    Date March 1970
    Journal Gut
    Title The Vagus and Achalasia.
    Date October 1969
    Journal The British Journal of Surgery
    Title The Long-term Stability of the Insulin Response After Vagotomy.
    Date October 1969
    Journal The British Journal of Surgery
    Title Principles of Growth Modulation in the Treatment of Scoliotic Deformities.
    Date
    Journal Neurosurgery
    Excerpt

    Intraoperative manipulation to correct scoliotic deformities relies upon spinal instrumentation for stabilization and fusion. However, novel strategies and innovative implant biotechnologies have emerged, applying natural growth and elongation of the immature spine for the treatment of scoliosis in young patients. In this work, we review the principles of growth modulation and the Hueter-Volkmann law as it applies to experimental models of scoliosis formation and correction. Current implant technologies, including shape memory alloy vertebral staples, growing rods, and vertical expandable titanium prosthetic ribs, are explored, with regards to implant design, surgical techniques, and clinical investigations. An exciting area of spinal implant technology is now becoming available to expand the surgical armamentarium for treating severe scoliotic deformity in young patients.

    Title Toward the Emergence of Nanoneurosurgery: Part Iii-nanomedicine: Targeted Nanotherapy, Nanosurgery and Progress Toward the Realization of Nanoneurosurgery.
    Date
    Journal Neurosurgery
    Title Neural Connectivity Maps: then and Now.
    Date
    Journal Neurosurgery

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