Re: Measurement of vaginal and minor labial oxygen tension for the evaluation of female sexual function.
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Biomedical subjects
Publications and source records attributed to R J Levin.
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BACKGROUND: This is a retrospective review of medical and financial records to test the hypothesis that the use of a critical pathway specifically designed for the management of laryngectomy patients will result in improved patient care, decreased length of hospitalization, and optimal allocation of resources. METHODS: Thirty patients undergoing laryngectomy before the implementation of the laryngectomy critical pathway were compared with 30 patients after implementation of the pathway. Clinical outcomes, length of hospitalization, and cost analyses were performed. RESULTS: Adjusting for two outliers, the average length of stay for pathway patients was 7.3 days vs 12 days for prepathway patients. A total estimated cost-savings of $204,000 was ultimately achieved. CONCLUSIONS: Our laryngectomy critical pathway has resulted in improved patient care and optimized allocation of medical resources.
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Carcinoma of the head and neck is the sixth leading cause of cancer in the world, and the third most common neoplasia in developing countries. More than 90% of head and neck cancers are squamous cell carcinomas (SCCHN). Approximately half of the patients afflicted die within 5 years of diagnosis and survival rates for cancer of the upper aero-digestive tract have not changed in 25 years. The opioid growth factor (OGF), ¿Met5-enkephalin, inhibits the growth of SCCHN in vitro and in vivo, and acts in a receptor-mediated fashion. Receptor binding assays using CAL-27 human SCCHN cells in culture and ¿3H-¿Met5-enkephalin were employed to identify and characterize the receptor responsible for the growth-regulatory effects of OGF. Specific and saturable binding was recorded, and Scatchard analysis showed that the data were consistent for a single binding site with a binding affinity (Kd) of 5.0+/-0.9 nM and maximal binding capacity (Bmax) of 47.5+/-1.7 fmol/mg protein. Subcellular fractionation studies determined that the optimal binding occurred with the nuclear fraction. Competition experiments demonstrated that cold ¿Met5-enkephalin was at least 7-fold greater than ligands selective for classical opioid receptors. Binding was detected in 4 other SCCHN cell lines. Receptor number in xenografts of CAL-27 was decreased almost 5-fold compared to the same cells grown in vitro. Binding to radiolabeled ¿Met5-enkephalin was recorded in SCCHN obtained from surgical resections. The function, pharmacological and biochemical characteristics, distribution and subcellular location of OGF binding in human SCCHN were consonant with the OGF receptor (OGFr).
The native opioid growth factor (OGF), [Met5]-enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and migration, as well as tissue organization, during development, cancer, homeostatic cellular renewal, wound healing, and angiogenesis. OGF action is mediated by the OGF receptor (OGFr). To investigate the target of OGF as to cell proliferation, the effects of excess OGF, and a deprivation of OGF-OGFr interaction by an opioid antagonist, naltrexone (NTX), were examined in 3 human cancer cell lines: pancreatic (BxPC-3), colon (HT-29), and head and neck (CAL-27). OGF exposure decreased growth, DNA synthesis, and mitosis, and increased the doubling time from control levels. FACS analysis revealed a marked increase in cells in the G0/G1 phase and compensatory reduction in cells in S and G2/M phases. Consistent with this observation, the percentage of labeled mitosis (PLM) analysis showed a notable increase in the time of the G0/G1 phase. Receptor blockade with NTX increased the rate of growth, length of DNA synthesis and mitotic phases, and decreased doubling time from control values. FACS analysis indicated an increase in the proportion of cells in S and G2/M phases, and a decrease in the number of cells in the G0/G1 phase. PLM evaluation demonstrated a shortening of the length of the S and G2 phases in the 3 cell lines, and decreases in the M and G0/G1 phases in some cancers. These results indicate that OGF action is directed at the G0/G1 phase, but interruption of OGF-OGFr interfacing has widespread repercussions on the cell cycle. The data on blockade of OGF-OGFr during log phase growth suggest a requisite escorting of the growth peptide and its receptor through the cell cycle.
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Doppler ultrasound was used to study the effect of the first intravenous dose of caffeine on splanchnic haemodynamics in preterm neonates. Peak systolic velocity in the superior measenteric artery and coeliac axis was significantly reduced for 6 hours after caffeine infusion. The effect of this reduction in blood flow to the neonatal gut is not known.
BACKGROUND: Escherichia coli heat stable enterotoxin (STa) is a major cause of secretory diarrhoea in humans. AIMS: To assess the effects of instilling STa into the ileum on remote fluid secretion in the jejunum and colon in rats in vivo by a gravimetric technique. METHODS AND RESULTS: Ileal STa (55 ng/ml) stimulated fluid secretion in both ileal and jejunal loops but not in the colon. The fluid secretion induced by ileal STa was inhibited by L-NAME (Nomega-nitro-L-arginine methyl ester, 40 mg/kg intraperitoneally) but not by D-NAME (Nomega-nitro-D-arginine methyl ester). Ileal carbachol (183 mg/ml) instilled into the lumen stimulated ileal secretion but not jejunal secretion, and was unaffected by L-NAME. Capsaicin (10 microM), instilled luminally with STa in the ileum, blocked both the ileal and jejunal fluid secretion. Acute bilateral vagotomy prevented luminal ileal STa from inducing jejunal fluid secretion but not from activating ileal fluid secretion. CONCLUSION: Ileal E coli STa stimulates remote secretion in the rat jejunum but not in the colon, probably by a nitrinergic, vagal reflex mediated by C fibres. This neural pathway will amplify the action of the toxin in its generation of secretory diarrhoea.
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common malignancy worldwide. Approximately half of the patients afflicted die within 5 years of diagnosis, and surviving patients may be left with severe esthetic and functional compromise. In this study, we discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the growth of human SCCHN in vitro; in view of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF was found to be a constitutively expressed, receptor-mediated growth inhibitory agent that appears to be autocrine produced and secreted. Growth regulation was dose-related, reversible, cytostatic, and independent of serum. All 6 human SCCHN cell lines examined exhibited growth modulation by OGF. Blockade of peptide-receptor interaction by opioid antagonists (naltrexone), or addition of antibody to OGF, resulted in substantial increases in cell number compared to control levels, showing the tonic nature of OGF-zeta activity. Immunocytochemical studies detected both OGF and its related receptor, zeta, in these cells, correlating with earlier findings of peptide and receptor in specimens of SCCHN obtained at surgery. These data suggest that a native opioid peptide, OGF, interacts with a novel opioid receptor, zeta, to tonically arrest the growth of human SCCHN.
BACKGROUND: Managed care reduces the demand for internal medicine subspecialists, but little empirical information is available on how increasing managed care may be affecting residents' training choices. OBJECTIVE: To determine whether increased managed care penetration into an area where residents train was associated with a decreased likelihood that residents who completed general internal medicine training pursued subspecialty training. DESIGN: Secondary logistic regression analysis of data from the 1993 cohort of general internal medicine residents. SETTING: U.S. residency training sites. PARTICIPANTS: 2263 U.S. medical school graduates who completed general internal medicine residency training in 1993. MEASUREMENTS: The outcome variable (enrollment in subspecialty training) was derived from the Graduate Medical Education Tracking Census of the Association of American Medical Colleges (AAMC). Health maintenance organization (HMO) penetration (possible range, 0.0 to 1.0; higher values indicate greater penetration) was taken from the Interstudy Competitive Edge Database. Individual and medical school covariates were taken from the AAMC's Student and Applicant Information Management System database and the National Institutes of Health Information for Management Planning, Analysis, and Coordination system. The U.S. Census division was included as a control covariate. RESULTS: 980 participants (43%) enrolled in subspecialty training. Logistic regression analyses indicated a nonlinear association between managed care penetration into a training area and the odds of subspecialization. Increasing managed care penetration was associated with decreasing odds of subspecialization when penetration exceeded 0.15. The choice of subspecialty training increased as HMO penetration increased from 0 to 0.15. CONCLUSIONS: Local market forces locally influenced the career decisions of internal medicine residents, but the influence was small compared with the effects of age and sex. These results suggest that market forces help to achieve more desirable generalist-to-specialist physician ratios in internal medicine.
BACKGROUND: Catecholamine secretion by head and neck paragangliomas is uncommon. Dopamine secretion by these tumors has not routinely been assessed. This case report describes a dopamine-secreting glomus vagale and evaluates seven other paragangliomas immunohistochemically for their ability to synthesize dopamine. METHODS: Light microscopic and immunohistochemical studies were performed on eight tumors, and biochemical testing for serum/urine catecholamines was performed on two patients. RESULTS: One patient (case report) had elevated serum dopamine which corrected following surgery. Five tumors stained strongly positive for the presence of tyrosine hydroxylase, the critical enzyme in the biosynthesis of dopamine. CONCLUSION: This case report describes the ability of a glomus vagale to secrete dopamine. Other paragangliomas express the enzymatic machinery necessary to begin catecholamine synthesis. Now that dopamine is routinely screened during catecholamine determination, other cases may be identified.
Three adenoid cystic carcinomas and two epithelial-myoepithelial carcinomas, which focally shared common histologic features, were studied to examine the common differentiation pathways manifested by these tumors and to discuss criteria for hybrid salivary gland tumors. Regions of the adenoid cystic carcinomas had cellular features ranging from simple clear cell change of basal/myoepithelial cells to combined clear cells and prominent ductal structures mimicking epithelial-myoepithelial carcinoma. Conversely, two epithelial-myoepithelial carcinomas had adenoid cystic carcinoma-like regions caused by the formation of "pseudocysts"; this resulted in a focal cribriform pattern. Electron microscopy of two additional but typical epithelial-myoepithelial carcinomas revealed both excess basal lamina at the margins of cellular nests and widened intercellular spaces containing reduplicated basal lamina and accumulations of glycosaminoglycans; these ultrastructural features were identical to those seen in adenoid cystic carcinomas. The five current cases are not examples of hybrid tumors, but they demonstrate the effects of gene expression and the resulting differentiation of synthetic products and tumor cells that are generally restricted to one or the other of these two tumor types by as-yet-unknown means. To avoid misdiagnosis and its prognostic implications, adenoid cystic carcinoma-like regions in epithelial-myoepithelial carcinoma and epithelial-myoepithelial-like regions in adenoid cystic carcinoma should be recognized simply as anomalous differentiation.
5-hydroxytryptamine (5-HT) stimulates electrogenic Cl- secretion in rat ileum stripped of its outer smooth musculature and myenteric plexus. The myenteric plexus, however, is a site of 5-HT synthesis in the gut, and the plexus mediates electrogenic ion secretion activated by luminal enterotoxin STa and taurocholate. Thus, we investigated the role of the myenteric plexus in 5-HT-induced electrogenic secretion in vitro by measuring short-circuit current (Isc, microamps) with voltage-clamp apparatus as an index of electrogenic Cl-secretion in rat ileum which was either stripped of the myenteric plexus or was left intact. Serosally added 5-HT stimulated electrogenic Cl- secretion in muscle-stripped and intact ileum in a concentration-dependent manner. Pre-treatment of stripped ileum with atropine (1 micron), hexamethonium (100 microns), tetrodotoxin (1.25 microns) and capsaicin (1 micron) for 15 min did not effect the maximum Isc induced by 5-HT which would implicate a direct action on the enterocyte. In intact ilea, however, tetrodotoxin (TTX) and capsaicin reduced significantly the maximum values of Isc stimulated by 5-HT, and the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) caused a significant decrease in the maximum response to 5-HT. These results suggest that electrogenic secretion induced by 5-HT in rat ileum in vitro occurs partly by activation of a non-neural pathway probably involving a direct interaction with the enterocyte, and partly via a nitrinergic-myenteric secretory reflex activated by sensory afferent fibres. These data highlight the danger of characterising intestinal secretory activity from in vitro experiments by using muscle-stripped tissue only.
A biomechanical model utilizing polystyrene mandibles was devised to evaluate the fixation efficacy of various plating techniques for repair of mandibular angle fractures. A simple angle fracture was created in the mandible models at a standardized location and was repaired using five different plating techniques. Each experimental group consisted of 15 mandibles, with fracture site, plate placement, load application, and fracture displacement measurement standardized to ensure consistency among experimental groups. Measurement of fracture distraction under load application generated a load deformation curve and corresponding slope for each technique. Comparison of load deformation slopes allowed assessment of fixation stability. When applied with a subapical, medially placed monocortical tension band, bicortical compression plating demonstrated the most stable fracture fixation. The data show that biplanar plate placement in both monocortical noncompression and bicortical compression techniques yields a stronger fixation than monoplanar placement.
AIM: To study the effect of enteral feeding on splanchnic blood flow velocity in preterm infants. METHOD: Coeliac axis and superior mesenteric artery (SMA) blood flow velocity were measured longitudinally in a cohort of 61 babies using Doppler ultrasound. RESULTS: Babies fed 1 hourly had significantly higher preprandial SMA peak systolic velocity (PSV) than those fed 3 hourly (70 vs 53 cm/s). Those fed 1 hourly showed no postprandial change whereas those fed 3 hourly showed significant postprandial hyperaemia. This hyperaemia had longer latency (42 vs 27 mins) and smaller amplitude (31 vs 25 mins) after expressed breast milk compared with preterm formula. The addition of long chain polyunsaturated fatty acids to the formulas had no effect on the postprandial response. CONCLUSION: Hourly bolus feeding leads to a persistent hyperaemic state in the SMA. The composition of feeds is an important determinant of the postprandial response of the SMA to 3 hourly feeding.
The scientific study of the interaction of human genitals during coitus and after ejaculation with and without female orgasm has always been difficult and controversial with ethical, technical and social problems. The present brief review examines critically the results from these studies. Early observations utilised changes induced in sexually self-aroused subjects or by coitus with artificial (transparent) penes with few objective measurements. These culminated in the synthesis of the useful unitary descriptive, EPOR (excitation, plateau, orgasm, resolution)-model by Masters and Johnson (1966). Later investigations by other workers developed or employed instrumentation to record objectively the changes induced in the motility and pressures of genital muscles, in genital blood flow, in the ion and fluid movements creating the neurogenic transudate of vaginal lubrication, in its pH and pO2 and in the disposition of the ordered spurting ejaculate with subsequent sperm transport. More recently, studies have begun to use endoscopy and ultrasound imaging to picture what really happens especially during penile thrusting. While the newer techniques have often confirmed selected features of the original EPOR model they have also shown that the characterisation of the coital changes just by a unitary model is inappropriate. New observations suggest a plurality in the changes that can occur. Coital mechanisms are dynamic and our investigations and descriptions of them should match their dynamism. The knowledge gained will be more than helpful in the treatment of infertility, genital dysfunctions and disease transmission.
CONTEXT: Medical research conducted in academic medical centers is often dependent on support from clinical revenues generated in these institutions. Anecdotal evidence suggests that managed care has the potential to affect research conducted in academic medical centers by challenging these clinical revenues. OBJECTIVE: To examine whether empirical evidence supports a relationship between managed care and the ability of US medical schools to sustain biomedical research. DESIGN: Data on annual extramural research grants awarded to US medical schools by the National Institutes of Health (NIH) from fiscal years 1986 to 1995 were obtained, and each medical school was matched to a market for which information about health maintenance organization (HMO) penetration in 1995 was available. MAIN OUTCOME MEASURES: Growth in total NIH awards, traditional research project (R01) awards, R01 awards to clinical and basic science departments, and changes in institutional ranking by NIH awards were compared among schools located in markets with low, medium, and high managed care penetration. RESULTS: Medical schools in all markets had comparable rates of growth in NIH awards from 1986 to 1990. Thereafter, medical schools in markets with high managed care penetration had slower growth in the dollar amounts and numbers of NIH awards compared with schools in markets with low or medium managed care penetration. This slower growth for schools in high managed care markets was associated with loss of share of NIH awards, equal to $98 million in 1995, and lower institutional ranking by NIH awards. Much of this revenue loss can be explained by the slower growth of R01 awards to clinical departments in medical schools in high managed care markets. CONCLUSIONS: These findings provide evidence of an inverse relationship between growth in NIH awards during the past decade and managed care penetration among US medical schools. Whether this association is causal remains to be determined.