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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 217 records · Page 12Linked to original sources
PubMed1997

Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein.

BACKGROUND: Tumor necrosis factor (TNF) is a proinflammatory cytokine involved in the pathogenesis of rheumatoid arthritis, and antagonism of TNF may reduce the activity of the disease. This study evaluated the safety and efficacy of a novel TNF antagonist - a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1 (TNFR:Fc). METHODS: In this multicenter, double-blind trial, we randomly assigned 180 patients with refractory rheumatoid arthritis to receive subcutaneous injections of placebo or one of three doses of TNFR:Fc (0.25, 2, or 16 mg per square meter of body-surface area) twice weekly for three months. The clinical response was measured by changes in composite symptoms of arthritis defined according to American College of Rheumatology criteria. RESULTS: Treatment with TNFR:Fc led to significant reductions in disease activity, and the therapeutic effects of TNFR:Fc were dose-related. At three months, 75 percent of the patients in the group assigned to 16 mg of TNFR:Fc per square meter had improvement of 20 percent or more in symptoms, as compared with 14 percent in the placebo group (P<0.001). In the group assigned to 16 mg per square meter, the mean percent reduction in the number of tender or swollen joints at three months was 61 percent, as compared with 25 percent in the placebo group (P<0.001). The most common adverse events were mild injection-site reactions and mild upper respiratory tract symptoms. There were no dose-limiting toxic effects, and no antibodies to TNFR:Fc were detected in serum samples. CONCLUSIONS: In this three-month trial TNFR:Fc was safe, well tolerated, and associated with improvement in the inflammatory symptoms of rheumatoid arthritis.

Antibodies↗
PubMed1997

Social ties and susceptibility to the common cold.

OBJECTIVE: To examine the hypothesis that diverse ties to friends, family, work, and community are associated with increased host resistance to infection. DESIGN: After reporting the extent of participation in 12 types of social ties (eg, spouse, parent, friend, workmate, member of social group), subjects were given nasal drops containing 1 of 2 rhinoviruses and monitored for the development of a common cold. SETTING: Quarantine. PARTICIPANTS: A total of 276 healthy volunteers, aged 18 to 55 years, neither seropositive for human immunodeficiency virus nor pregnant. OUTCOME MEASURES: Colds (illness in the presence of a verified infection), mucus production, mucociliary clearance function, and amount of viral replication. RESULTS: In response to both viruses, those with more types of social ties were less susceptible to common colds, produced less mucus, were more effective in ciliary clearance of their nasal passages, and shed less virus. These relationships were unaltered by statistical controls for prechallenge virus-specific antibody, virus type, age, sex, season, body mass index, education, and race. Susceptibility to colds decreased in a dose-response manner with increased diversity of the social network. There was an adjusted relative risk of 4.2 comparing persons with fewest (1 to 3) to those with most (6 or more) types of social ties. Although smoking, poor sleep quality, alcohol abstinence, low dietary intake of vitamin C, elevated catecholamine levels, and being introverted were all associated with greater susceptibility to colds, they could only partially account for the relation between social network diversity and incidence of colds. CONCLUSIONS: More diverse social networks were associated with greater resistance to upper respiratory illness.

Adolescent↗
PubMed1997

No association of the Ser/Cys311 DRD2 molecular variant with schizophrenia using a classical case control study and the haplotype relative risk.

Arinami et al. (1994) reported an association between the Ser311/Cys311 variant of the DRD2 gene and schizophrenia in a Japanese population. We did not find statistically significant differences in the distribution of the allele frequencies between schizophrenics (103) and controls (97) in a case-control sample (chi 2 = 2.07; p = 0.150) or in 64 nuclear families with the haplotype relative risk (HRR) design (chi 2 = 0.13; p = 0.718). Our results seem to exclude a main involvement of this variant of the dopamine D2 receptor gene in the etiopathogenesis of schizophrenia.

Age of Onset↗
PubMed1997

Small polydispersed circular DNA (spcDNA) in human cells: association with genomic instability.

Small Polydispersed Circular DNA (spcDNA) was suggested to be associated with genetically unstable cells. However, until now, qualitative and quantitative research has been limited due to the lack of efficient methods for detection and analysis. We developed a two-dimensional (2-D) neutral-neutral gel electrophoresis assay for the identification, characterisation and quantitation of spcDNA. Using this method, we established the relation of spcDNA to genetic and induced genomic instability in human cells, both in vitro and in vivo. Enhanced amounts of spcDNA were found in genetically unstable cells and tissues. spcDNA was detected in a tumor cell-line (HeLa) and in tumor tissue (colon carcinoma) as well as in fibroblasts derived from patients suffering from the genomic instability disease, Fanconi's Anemia. We failed to detect spcDNA in the genetically stable normal human fibroblasts. However, following treatment with the initiating carcinogen MNNG, an induction of spcDNA was observed. The level of spcDNA was quantified according to mitochondrial DNA (mtDNA) standards. In light of these findings, we discuss the possible role of spcDNA as a marker and an enhancer of genomic instability.

Carcinogens↗
PubMed1997

No association between schizophrenia and the serotonin receptor 5HTR2a in an Italian population.

A major role of the serotonergic system has been hypothesized in the pathogenesis of schizophrenia, mostly based on the evidence of action of new and atypical neuroleptics such as Risperidone or Clozapine. We evaluated the genotypes and alleles of the 5HT2a receptor gene in 67 nuclear families following the Haplotype Relative Risk (HRR) strategy and in a second sample of 100 schizophrenics and 103 controls. The 5HT2a receptor gene polymorphism, following PCR amplification and subsequent Hpa II digestion, reveals a two-alleles system in the coding region of the gene. We did not find statistically significant differences between patients and controls for genotypes, nor for alleles, both in the HRR and in the case-control groups. These results do not confirm the positive association obtained by Inayama et al.: [Neuropsychopharmacology 1(35): 145-219, 1994] and by Williams et al. [Lancet, 397:1294-1296, 1996] in our population.

Alleles↗
PubMed1997

Peroxovanadate induces tyrosine phosphorylation of multiple signaling proteins in mouse liver and kidney.

The intraperitoneal injection of a vanadate/H2O2 mixture (peroxovanadate) into mice resulted within minutes in the appearance of numerous tyrosine-phosphorylated proteins in the liver and kidney. These effects are presumably due to the inhibition of phosphotyrosine phosphatase activity. Three of the tyrosine-phosphorylated proteins have been identified as the receptors for epidermal growth factor, insulin, and hepatocyte growth factor. The injection of peroxovanadate also enhanced the tyrosine phosphorylation of many of the proteins known to function downstream of these receptors, including SHC, signal transducer and activator of transcription (Stat) 1alpha,beta, Stat 3, Stat 5, phospholipase C-gamma, insulin receptor substrate 1, GTPase-activating protein, beta-catenin, gamma-catenin, p120cas, SHP-1, and SHP-2. The administration of peroxovanadate also induced nuclear translocation of a number of tyrosine-phosphorylated Stat proteins. In addition, the global effects on tyrosine phosphorylation permitted the detection of a number of novel intracellular protein interactions, including an association of Tyk2 with beta-catenin. The in situ administration of peroxovanadate may prove useful in the search for novel tyrosine-phosphorylated proteins and the identification of new interactions between previously identified tyrosine-phosphorylated substrates.

Animals↗
PubMed1997

Morphogens and pattern formation.

Morphogen gradient theories have enjoyed considerable popularity since the beginning of this century, but conclusive evidence for a role of morphogens in controlling multicellular development have been elusive. Recently, work on three secreted signalling proteins. Activin in Xenopus, and Wingless and Dpp in Drosophila, has strongly suggested that these proteins function as morphogens. In order to define a factor as a morphogen, it is necessary to show firstly, that it has a direct effect on target cells and secondly, that it affects the development of target cells in a concentration-dependent manner. With these criteria in mind, the evidence available for a variety of proposed morphogens is discussed. While the evidence is not conclusive in most of the cases considered, there is a strong case in favour of the three proteins mentioned above, which suggests that morphogens are potentially of general importance in controlling the development of multicellular organisms.

Activins↗
PubMed1997

Measurement variability in upper extremity posture among VDT users.

Hand and arm posture while keying is frequently mentioned as a risk factor for upper extremity musculoskeletal disorders (UEMSDs) among video display terminal (VDT) operators. However, many epidemiologic studies have not included measures of posture of VDT operators, in part, because of the difficulty of assessing posture rapidly and reliably among large numbers of subjects. For a single measure of posture to be useful for estimating dose-response relationships between posture and risk of UEMSDs, the within-subject variability of the postural measure must be smaller than the between-subject variability of the postural measure. In addition, the measure must be stable over time. We estimate the ratio of between- to within-subject variability for manual goniometry by measuring six postural angles on six occasions among 19 subjects using VDTs. For each postural angle, between-subject variability was substantially and statistically significantly larger than within-subject variability. Stability of postural measures over time was sufficient to justify a single postural measurement in epidemiologic studies. We conclude that manual goniometry can provide useful information about upper extremity posture among VDT users for use in epidemiologic studies of UEMSDs.

Adult↗
PubMed1997

Histamine-evoked acetylcholine release in sensitized tracheal preparation.

The contractile response to histamine of tracheal muscle was studied in preparations from BSA-sensitized and non-sensitized guinea-pigs. Sensitization did not enhance the overall response to histamine. However, this response showed evidence of acetylcholine participation. In sensitized preparations, atropine (0.1 microM) caused a significant depression of the dose response to histamine (n = 11, p = 0.028), especially in the range 2-8 microM. Physostigmine (0.1 microM) significantly potentiated the effect of histamine (n = 8, p = 0.003), especially at greater than 4 microM histamine. The response to histamine of non-sensitized preparations was not altered by atropine (n = 11) or physostigmine (n = 8). The following agents did not discriminate between sensitized and non-sensitized preparations: Famotidine, an H2 antagonist; dimaprit, an H2 agonist; thioperamide, an H3 antagonist; alpha-methylhistamine, an H3 agonist; gallamine, an M2 antagonist, suggesting that muscarinic M2 receptor dysfunction alone is not sufficient to cause bronchial hyper-responsiveness. The results show that sensitization causes a change in the components of the contractile response to histamine rather than bronchial hyper-responsiveness to this agent.

Acetylcholine↗
PubMed1997

Novel alginate sponges for cell culture and transplantation.

This paper describes the preparation and characterization of a three-dimensional, porous sponge made from the marine polysaccharide alginate for creating a cell-matrix transplant to replace damaged organs or tissues. The sponge is prepared by a three-step procedure: first gelation of the alginate with bivalent cations, followed by freezing of the hydrogel and finally lyophilization to produce a porous sponge. The pattern and the extent of sponge porosity, as well as its mechanical properties, were influenced by the concentration and the type of alginate (guluronic to mannuronic ratio and viscosity), the type and concentration of the cross-linkers and the freezing regime. By controlling these variables, macroporous sponges (pore size of 70-300 microns) that are suitable for cell culture and neovascularization were achieved. Fibroblasts seeded within the sponges preferred the pores, where they maintained a spherical shape. The alginate sponges conserved their initial volume for at least 3 months. It appears that alginate sponges may provide an excellent support for cell transplantation.

Alginates↗
PubMed1997

Pediatric cataract management with variations in surgical technique and aphakic optical correction.

PURPOSE: The purpose of the study was to compare the results of three techniques of cataract surgery in children. Two methods included intraocular lens (IOL) implantation and one used contact lens correction of aphakia. DESIGN: Nonrandomized clinical trial. PARTICIPANTS: Seventy-seven eyes of 50 children between the ages of 2 1/2 and 16 years who had cataract surgery for the treatment of uncomplicated cataract. INTERVENTION: Thirty-one eyes underwent a "conventional" style of implantation, and a "phaco-style" of surgery was used in 24 eyes. A contact lens was used as the primary means of aphakic correction in 22 eyes. MAIN OUTCOME MEASURES: The visual results and complications of each type of surgery were compared. RESULTS: Corrected visual acuities did not differ significantly between the three groups 6 months after surgery. The incidence and type of complications were significantly different. Better lens centration, less long-term iris changes, or wound-related problems were observed with "phaco-style" modification of the technique of IOL insertion. CONCLUSIONS: Pediatric IOL insertion eliminated the need for contact lens wear and did not lead to a significantly different corrected visual acuity 6 months after surgery compared with lensectomy with contact lens correction. Adoption of some of the techniques of modern small-incision cataract surgery for pediatric IOL procedures produces a significant reduction in postoperative anterior segment complications compared with a standard limbal approach. Such modifications allow pediatric IOL insertion to be a safe alternative for the correction of pediatric aphakia.

Adolescent↗
PubMed1997

Management of congenital atresia of the external auditory canal.

The management of a unilateral congenital atresia of the external auditory canal is nonuniform and debated. Various surgical approaches, timing, coordination with microtia repair, and variable hearing improvements all contribute to the debate regarding management of this entity. This paper outlines our craniofacial team approach to the congenital unilateral atresia and microtia in children. Selection criteria, timing of repair, coordination with microtia repair, surgical results, and pitfalls will be discussed. The results of surgery in 16 patients with unilateral congenital atresia of the external auditory canal and 2 children with bilateral atresia will be presented. Repair of the atresia was undertaken in children 5 years or older who had pneumatized mastoids and middle ears. Replacement of the malleus/incus complex with a partial ossicular reconstruction prosthesis improved closure of the air-bone gap. Drawbacks included meatal stenosis and deepithelization of the split thickness skin graft lining the external auditory canal. Repair of the unilateral congenital atresia is a demanding and challenging problem but one in which excellent results are achievable.

Adolescent↗
PubMed1997

Adrenosensitivity of injured afferent neurons does not require the presence of postganglionic sympathetic terminals.

Nerve injury sometimes triggers neuropathic pain states that are exacerbated by sympathetic efferent activity. A classic example is causalgia. The mechanism of coupling between sympathetic efferent activity and the afferent discharge responsible for pain sensation is a subject of controversy. Some authors hold to the 'direct coupling hypothesis' which proposes that noradrenaline (NA), released from sympathetic varicosities, acts directly on alpha-adrenoreceptors located in the membrane of injured primary afferents. Others believe that coupling is indirect; that the effects of NA are mediated by additional, non-adrenergic, chemical substances and their receptors (the 'indirect coupling hypothesis'). For example, it has been proposed that in inflamed skin NA acts back on the sympathetic endings which, secondarily, release a prostanoid mediator which sensitizes afferent endings. We report that the responsiveness of injured afferent axons to systemically applied NA persists, and in fact increases in prevalence, in rats that underwent prior chemical or surgical sympathectomy. The observation of adrenosensitivity in injured afferents in the absence of sympathetic postganglionic endings is consistent with the direct coupling hypothesis, which associates adrenosensitivity with the injured afferent axon. It is not consistent with the indirect coupling hypothesis which requires the presence of sympathetic endings as a source for NA-evoked prostanoid release.

Adrenergic alpha-Agonists↗
PubMed1997

Susceptibility of beta-hemolytic streptococci to nine antimicrobial agents among four medical centers in Salt Lake City, Utah, USA.

A multicenter study was performed to evaluate the susceptibility of beta-hemolytic streptococci to nine antimicrobial agents. MICs were performed in cation-supplemented Mueller-Hinton broth with 3.5% lysed sheep red blood cells according to NCCLS guidelines. A total of 646 isolates were tested: 300 (46%) group A; 170 (26%) group B; 38 (6%) group C, 35 (5%) group F; 83 (17%) group G; and 20 (3%) nongroupable. Six percent of the total isolates were resistant to one or more of the antibiotics tested. Approximately 7% of 387 strains from the University of Utah Hospital and Clinics were resistant to erythromycin. Four isolates were resistant to clindamycin. Six strains (3%) from Primary Children's Medical Center (207 tested) were resistant to one or more of the macrolides. Resistance was rare at the LDS Hospital and the Salt Lake Veteran's Affairs Hospital. Overall, resistance among beta-hemolytic streptococci in this geographic location does not seem to be a significant problem, except at the tertiary care university hospital.

Anti-Bacterial Agents↗
PubMed1997

[Interviews with families of organ donors: analysis of motivation for acceptance or refusal of donation].

OBJECTIVE: The reasons for organ donation acceptance or refusal are still unclear. This study analysed the influence of the circumstances of the conversations with the relatives of brain dead patients on their consent for organ donation. STUDY DESIGN: Prospective study. MATERIAL: The analysis included 41 questionnaires collected over nine months in one organ harvesting centre and focusing on the circumstances of death, the conditions of the conversations and the reasons for acceptance or refusal. METHODS: Questionnaire filled in by the physicians after the interviews of the relatives of brain dead patients. RESULTS: The refusal rate was higher (54 vs 21%) when only one physician participated in the conversation, when more than two relatives had to decide (42 vs 24%), when conversations took place during night or when the request for organ donation followed immediately the announcement of death (43 vs 20%). Most often the relatives gave their decision within minutes following the request. CONCLUSION: The circumstances of conversation with families play an essential role in their decision-making. A written guideline implementation for these conversations would probably be beneficial for the decisions of families in favour of organ donation.

Adolescent↗
PubMed1997

Epidural block for obstetrics: comparison of bolus injection of local anesthetic with gravity flow technique.

STUDY OBJECTIVE: To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection. DESIGN: Prospective, randomized study. SETTING: Teaching hospital. PATIENTS: 600 ASA physical status l and II parturients scheduled for labor and delivery or elective cesarean section. INTERVENTIONS: After identification of the epidural space with pulsations of an air-fluid column, parturients for vaginal delivery (n = 380) were randomized to receive a test dose of 3 ml 3% 2-chloroprocaine with epinephrine 20 micrograms, two doses of 7 ml bupivacaine 0.03% with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow (Group 1) given over 30 seconds or by bolus injection (Group 2) given over 5 seconds through the epidural needle; parturients for Cesarean delivery (n = 220) were randomized to receive a test dose and two doses of 6 ml lidocaine 2% with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow or by bolus injection through the epidural needle. Changes in maternal heart rate (HR) and blood pressure, signs of intravascular injection, and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose. MEASUREMENTS AND MAIN RESULTS: Gravity flow administration (Group 1) was associated with a smaller increase in mean maternal HR (p < 0.001), less hypotension (p < 0.01), sedation (p < 0.01), nausea (p = 0.01), and segmental spread (p < 0.0001) than were corresponding doses given by traditional bolus injection (Group 1) for vaginal or Cesarean deliveries. The incidence of systemic toxicity was zero of 300 (0%) with gravity flow and 4 of 300 (1.3%) by bolus injection, p = 0.12, Fisher's exact test. No patient in either group had an accidental intrathecal injection. CONCLUSION: Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection. This study supports the current opinion that slow administration of local anesthetic during epidural block contributes to fewer adverse events.

Anesthesia, Epidural↗