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Biomedical subjects

S Bernstein

Publications and source records attributed to S Bernstein.

At least 19 recordsLinked to original sources

The utilization of intraluminal formalin for intractable rectal haemorrhage in advanced rectal cancer: a case report.

A patient with a metastatic fixed low rectal carcinoma presented severe rectal bleeding requiring massive transfusion over with a 36-hour period. Bleeding was controlled with the instillation of a 4% intrarectal formalin solution permitting the completion of a course of neoadjuvant chemoradiotherapy. This technique has been reserved for intractable transfusion-dependent radiation proctitis and is presented as a primary alternative in severe rectal bleeding from inoperable rectal cancer.

Administration, Rectal↗

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

Cost-Benefit Analysis↗

Cloning, modeling, and chromosomal localization for a small leucine-rich repeat proteoglycan (SLRP) family member expressed in human eye.

PURPOSE: To examine a highly abundant novel transcript from human iris. METHODS: Expressed sequence tag (EST) analysis of an adult human iris cDNA library revealed an abundant (>0.7%) transcript for a novel member of the small leucine-rich proteoglycan (SLRP) family. Other 3' ESTs from retina were also detected in dbEST. The structure of the leucine-rich repeat (LRR) domain was investigated by molecular modeling. Antisera were raised against a specific peptide and used in western blots of human and rat eye tissues. RESULTS: From its prevalence in the eye and its superfamily relationships, this SLRP protein has been given the names oculoglycan or opticin (Optc). Sequence analysis suggests that Optc has a signal peptide and two structural domains, the larger of which is the LRR domain. Modeling of the LRR domain reveals structural variability in the repeat motifs, forming potential interaction sites for binding partners. Antiserum to a specific peptide detected a protein of approximately 48 kDa, in human iris, ciliary body and retina while the major protein detected in rat ocular tissues was 37 kDa in size. This may reflect a species difference in post-translational modification. Radiation hybrid mapping shows that the gene for OPTC is located on chromosome 1q31, close to the inherited eye diseases ARMD1 and AXPC1. CONCLUSIONS: Optc is a newly identified SLRP family member, which appears to have eye-preferred expression. Molecular modeling reveals local deviations from the familiar LRR structure, which are candidates for specific interaction sites. Western blotting with a specific peptide antibody detects Optc in iris, ciliary body and retina in the human eye and suggests that the protein is post-translationally modified. In rat, the antibody detects Optc in several eye tissues and in brain but the protein appears to have undergone much less modification, suggesting that this is not essential for all aspects of function. Considering its eye-preferred expression, the OPTC gene has the potential for involvement in inherited eye disease. Indeed, it maps close to at least two disease loci for which no gene has so far been identified.

Adolescent↗

The implementation of reproductive health programs: experiences, achievements and challenges.

As a fundamental element of population strategies for international development, reproductive health has received much recognition since the International Conference on Population and Development held in Cairo in 1994. Nevertheless, much remains to be done to improve the understanding of the concept of reproductive health, support reproductive rights, operationalize reproductive healthcare within basic health services and promote a more conducive social, cultural and economic environment, especially for women and girls, to enable the attainment of reproductive health. Collaboration between governments and non-governmental organizations will be crucial and obstetrician-gynecologists have a unique role, through service provision, review of regulatory frameworks, education and advocacy, for the promotion of reproductive health.

Delivery of Health Care↗

Effects of nicotine and chlorisondamine on cerebral glucose utilization in immobilized and freely-moving rats.

Chlorisondamine blocks central nicotinic receptors for many weeks via an unknown mechanism. Intracerebroventricular administration of [(3)H]-chlorisondamine in rats results in an anatomically restricted and persistent intracellular accumulation of radioactivity. The initial aim of the present study was to test whether nicotinic receptor antagonism by chlorisondamine is also anatomically restricted. Male adult rats were pretreated several times with nicotine to avoid the disruptive effects of the drug seen in drug-naïve animals. They then received chlorisondamine (10 microg i. c.v.) or saline, and local cerebral glucose utilization (LCGU) was measured 4 weeks later after acute nicotine (0.4 mg kg(-1) s.c.) or saline administration. During testing, rats were partially immobilized. Nicotine significantly increased LCGU in the anteroventral thalamus and in superior colliculus. Chlorisondamine completely blocked the first of these effects. Chlorisondamine significantly reduced LCGU in the lateral habenula, substantia nigra pars compacta, ventral tegmental area, and cerebellar granular layer. The second experiment was of similar design, but the rats were not pre-exposed to nicotine, and were tested whilst freely-moving. Acute nicotine significantly increased LCGU in anteroventral thalamus, superior colliculus, medial habenula and dorsal lateral geniculate. Overall, however, nicotine significantly decreased LCGU. Most or all of the central effects of nicotine on LCGU were reversed by chlorisondamine given 4 weeks beforehand. These findings suggest that chlorisondamine blocks nicotinic effects widely within the brain. They also indicate that in freely-moving rats, nicotine can reduce or stimulate cerebral glucose utilization, depending on the brain area. British Journal of Pharmacology (2000) 129, 147 - 155

Animals↗

Severe respiratory depression after dimethylsulphoxide-containing autologous stem cell infusion in a patient with AL amyloidosis.

Adverse reactions with DMSO-cryopreserved stem cell infusion are well-recognized. However, severe, life-threatening anaphylactic reactions with DMSO are very rarely described in the literature. We report here a 58-year-old female with AL amyloidosis who developed an unexpected episode of respiratory arrest a few seconds after the beginning of thawed stem cell product infusion. Fortunately, the patient was resuscitated successfully without the need for intubation. The prompt development of the reaction just a few seconds after the stem cell infusion convincingly implicates DMSO as the potential suspect. The presence of amyloid cardiomyopathy might have also contributed to this adverse event. Bone Marrow Transplantation (2000) 25, 1299-1301.

Amyloidosis↗

Use of PEG-rHuMGDF in platelet engraftment after autologous stem cell transplantation.

This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) microg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to > or = 20 x 10(9)/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred.

Adult↗

Microbial quality of water in rural communities of Trinidad.

A cross-sectional study was conducted in four rural communities of northeastern Trinidad to determine the microbial quality of water supply to households and that quality's relationship to source and storage device. Of the 167 household water samples tested, total coliforms were detected in 132 of the samples (79.0%), fecal coliforms in 102 (61.1%), and E. coli in 111 (66.5%). There were significant differences among the towns in the proportion of the samples contaminated with coliforms (P < 0.001) and E. coli (P < 0.001). Of 253 strains of E. coli studied, 4 (1.6%) were mucoid, 9 (3.6%) were hemolytic, and 37 (14.6%) were nonsorbitol fermenters. Of 69 isolates of E. coli tested, 10 (14.5%) were verocytotoxigenic. Twenty-eight (14.0%) of 200 E. coli isolates tested belonged to enteropathogenic serogroups. Standpipe, the most common water source, was utilized by 57 (34.1%) of the 167 households. Treated water (pipeborne in homes, standpipes, or truckborne) was supplied to 119 households (71.3%), while 48 households (28.7%) used water from untreated sources (rain, river/stream, or well) as their primary water supply. The type of household storage device was associated with coliform contamination. Water stored in drums, barrels, or buckets was more likely to harbor fecal coliforms (74.2% of samples) than was water stored in tanks (53.3% of samples), even after controlling for water source (P = 0.04). Compared with water from other sources, water piped into homes was significantly less likely to be contaminated with total coliforms (56.9% versus 88.8%, P < 0.001) and fecal coliforms (41.2% versus 69.8%, P < 0.01), even when the type of storage device was taken into account. However, fecal contamination was not associated with whether the water came from a treated or untreated source. We concluded that the drinking water in rural communities in Trinidad was grossly unfit for human consumption, due both to contamination of various water sources and during household water storage.

Humans↗

A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors.

Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x3 subcutaneously with the specific Ras peptide along with Detox adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 micrograms). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy.

Adult↗

A time-saving technique for the treatment of simple phobias.

Two cases are presented in detail and two in summary fashion to illustrate a technique that can frequently be used instead of systematic desensitization to reduce the time needed to treat simple phobias. This method combines techniques developed by Strategic Therapy and Critical Incident Debriefing. Symptoms that the patient experiences as out of control are prescribed by the therapist and then normalized. For example, a 26-year-old woman with a fear of social situations learns that it is not unusual for people to feel somewhat awkward and anxious as they try to reestablish themselves with friends after being away from them for a long period of time. Therapy taught her to accept rather than fight her initial anxiety in these situation. Another client with claustrophobia was taught to imagine himself getting anxious and telling himself, "yes, this is exactly what I expect. I am going to get anxious, and my anxiety will increase, but it isn't going to get higher than a '5' (on a 1-10 scale), and I can handle that." When these interventions are successful, the anxiety initially experienced in a phobic situation as a signal for panic is reinterpreted in new situations as expectable. This reframing renders the anxiety manageable. The treatment of two additional patients is briefly presented to further illustrate the application of this approach. Their phobias included a fear of sweating in public and a fear of sleep.

Adaptation, Psychological↗

Approaching the management of the neonatal intensive care unit graduate through history and physical assessment.

NICU graduates, often ex-premature infants, offer unusual challenges to the primary care provider. History and physical assessment require an organized approach with meticulous attention to detail. These infants are at high risk for multiple problems including growth delays, nutrition and feeding problems, pulmonary sequelae, neurological sequelae and developmental delays, vision and hearing disturbances, as well as abnormalities in parent-infant bonding. This article emphasizes particular aspects of the history and physical examination that signify pathophysiology and sequelae common to the NICU graduate.

Bronchopulmonary Dysplasia↗

Effect of melatonin on activated macrophage TNF, IL-6, and reactive oxygen intermediates.

Melatonin has recently been investigated as a biological response modifier in sepsis and hypovolemic shock. Although melatonin is reported to influence a variety of inflammatory and immune responses, evidence supporting its effects on important macrophage-derived mediators is incomplete. This study was designed to determine whether melatonin alters the release TNF, IL-6, and reactive oxygen intermediates by activated macrophages. TNF and IL-6 bioactivity in LPS-stimulated Wistar rat alveolar macrophage and RAW 264.7 cell culture supernatants were unchanged by pretreatment with melatonin. Similarly, macrophage production of reactive oxygen intermediates, including H2O2 and superoxide anion, were unaffected by melatonin pretreatment. PMA-stimulated H2O2 production was determined in rat alveolar macrophages and RAW 264.7 cells. Superoxide anion generation was determined in the rat alveolar macrophage NR8383 cell line. Melatonin, at concentrations ranging from 10(-7) to 10(-4) M, does not alter LPS-stimulated TNF and IL-6, or PMA-stimulated H2O2 and superoxide anion production by the macrophage populations studied. These observations are in contrast to previous reports. Further studies are necessary to determine whether melatonin indirectly influences macrophage function by actions on nonmacrophage cell populations.

Animals↗

Alkaline phosphatase activity in Penicillium roqueforti and in blue-veined cheeses.

The Penicillium roqueforti mold exhibits alkaline phosphatase activity. Therefore, blue mold-ripened cheeses made from properly pasteurized milk test positive for phosphatase. Because microbial phosphatases are considered to be more resistant to heat than is milk phosphatase, a statutory control test recommends the repasteurization of cheese at 66 degrees C for 30 min to inactivate selectively the native milk enzyme. However, because of thermal lability of Penicillium roqueforti phosphatase, this control test leads to confusion of the fungal enzyme with native milk alkaline phosphatase and does not confirm whether the milk used to make cheese has been pasteurized.

Alkaline Phosphatase↗

Hospital information system and patterns of cancer screening.

Relative ease, implied accuracy, and unprecedented possibilities of computerized health care information systems, is very tempting for researchers. Attempts at determining the referral patterns for cancer screening at a large county hospital through the use of computerized administrative and clinical files, and some of the problems encountered is reported here. Only 17% of women over 18, and 16% of women over 50 who visited this hospital were referred and received screening for cervical and breast cancer, respectively. Pap testing was concentrated at clinics dealing with reproductive health, and women with higher visit frequencies had a higher referral rate. Major problems encountered were lack of uniformity in capturing information for similar variables in different files, inconsistency in capturing data elements, and partial coverage. To enhance capabilities of computerized health information system, following principles must be incorporated in the designs: complete coverage, uniform collection of data across time and files, and inclusion of linking capabilities.

Adolescent↗