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Biomedical subjects

S Cohen

Publications and source records attributed to S Cohen.

At least 325 records · Page 18Linked to original sources
PubMed1994

Alkali halide-assisted penetration of neostigmine across excised human skin: a combination of structured water disruption and a Donnan-like effect.

The penetration of neostigmine across excised human skin mounted in flow-through diffusion cells, delivered from a 0.28 M aqueous solution, was below detection limits. The presence of either NaCl or LiCl in the donor solution caused significant fluxes of neostigmine, with permeability coefficients (Kp's) in the range of 10(-6) cm min-1. Paradoxically, low concentrations of NaCl or LiCl (0.25 and 0.5 M) were more effective in this respect than the 1 M solution, which was the least effective concentration in the range of 0.25-3 M. Thus, the dependence of the experimental Kp values on inorganic ion concentration followed a biphasic course, suggesting the participation of two distinctive mechanisms in the penetration-enhancement process. The early phase corresponding to 0.25 and 0.5 M NaCl or LiCl is being partly ascribed to a decrease in the viscosity of lamellar water caused by the influx of the respective hydrated ions, hydration of LiCl or NaCl being more extensive at low alkali halide concentration that at higher ones (reference cited). The late phase corresponding to 2 and 3 M LiCl and NaCl is partly ascribed to a Donnan-like effect whereby the presence of a large excess of poorly diffusible common ion (Na+ or Li+) enhances the partitioning into the skin of the more diffusible ion, in this case neostigmine cation. The presence of inorganic ions at different concentrations had no effect on the partial molal volume of neostigmine bromide (Vi infinity = 223.5 cm3 mol-1), which was practically the same for all concentrations of either LiCl and NaCl.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzalkonium Compounds↗
PubMed1994

Analysis of lymphocyte proliferation data: do different approaches yield the same results?

We addressed whether different approaches to the treatment of lymphocyte proliferation data influence the interpretation of results. We focused on two specific issues: (1) the impact of using optimal concentrations of mitogen versus a repeated measures approach using all concentrations and (2) the impact of correcting for unstimulated wells, and the method chosen for doing so. First, analysis of only the optimal concentration yields the same results as using a repeated measures approach. Second, uncorrected stimulated data, difference scores, and statistical control of unstimulated values all yield identical conclusions. The stimulation index, however, frequently yields different outcomes than the other approaches. We discuss reasons for these differences, note that the equivalence between repeated measures and optimal concentration techniques is limited to studies predicting suppression of proliferation irrespective of concentration, and suggest situations when the various approaches to analysis be used.

Adult↗
PubMed1994

Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.

In response to exposure to the inflammatory cytokines tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma), murine brain microvascular endothelial cells (MME) synthesize the cell surface molecule, vascular cell adhesion molecule-1 (VCAM-1), and the intracellular enzyme, inducible nitric oxide synthase (iNOS). However, iNOS synthesis requires the presence of both TNF and IFN-gamma, while VCAM-1 can be induced by either cytokine alone. We examined the induction of VCAM-1 and iNOS under a variety of conditions to better define the regulation of TNF and IFN-gamma signal transduction pathways in MME. We utilized the analysis of steady-state levels of iNOS mRNA as well as the measurement of MME-released NO-EDRF (nitric oxide as an endothelium-derived relaxing factor) activity and accumulation of nitrite in the culture medium to define iNOS expression and activity. VCAM-1 expression was determined by flow cytometric analysis. Our data indicate that low density lipoproteins inhibited cytokine-induced iNOS activity by affecting the steady-state levels of iNOS mRNA. Methylxanthines (caffeine and theophylline) as well as several calcium-mobilizing agents inhibited the expression/activity of both iNOS and VCAM-1 in MME. The effectiveness of these agents was dependent upon the degree of disruption in cell calcium homeostasis during cytokine treatment. Cells which had been pretreated with calcium-modulating drugs and then washed and allowed to return to normal calcium homeostasis showed little to no effect from these agents. In addition, our results suggest that NO produced by iNOS acts as a metabolic switch during inflammation by inhibiting oxidative phosphorylation and forcing vascular endothelial cells to temporarily utilize anaerobic energy metabolism.

Amino Acid Oxidoreductases↗
PubMed1994

Dilation of woven and knitted aortic prosthetic grafts: CT scan evaluation.

Because there are few reports in the literature concerning short- and medium-term outcome of woven and knitted aortic prosthetic grafts, we conducted CT evaluations in 58 asymptomatic patients (53 males and five females with a mean age of 63.5 years) undergoing infrarenal aortic reconstruction between June 1988 and June 1991. Joined CT slices after contrast enhancement, centered on the proximal anastomoses, prosthetic bodies, and prosthetic limbs, were obtained in the early (mean 19 days) and late (mean 19 months, range 6 to 40 months) postoperative periods. In end-to-side aortoprosthetic anastomoses (n = 28), early and late CT examinations revealed that the anteroposterior diameter increased 1.9% (p = NS) and 8.8% (p < 0.0001) for woven and knitted grafts, respectively. In end-to-end aortoprosthetic anastomoses, the diameter of the prosthetic body on early CT scans increased 12.6% (p < 0.0001) and 28% (p < 0.0001) for woven and knitted prosthetic grafts, respectively, as compared with diameter values provided by the manufacturer. Dilation continued to progress 2.2% (p < 0.04) for woven and 6.2% (p < 0.0002) for knitted prosthetic grafts on late CT scans. The mean diameter of the prosthetic graft limbs (n = 96) increased 22.3% (p < 0.0001) and 34.6% (p < 0.0001) for woven and knitted prosthetic grafts, respectively, on early CT scans as compared with manufacturers' values. Secondary increases were 3.2% (p < 0.002) and 7.7% (p < 0.007) for woven and knitted prosthetic grafts, respectively. These data show that dilation of aortic prostheses occurs early in most cases, most likely soon after declamping of the graft, as shown by recent intraoperative measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Nonoperative management of esophageal strictures following esophagomyotomy for achalasia.

The optimal management of reflux-induced esophageal strictures that occur after esophagomytomy for achalasia is uncertain. This paper presents our experience with the nonsurgical treatment of postesophagomyotomy strictures in achalasia patients using endoscopic dilation and gastric acid suppression. Six patients with achalasia who had undergone prior esophagomyotomy subsequently developed recurrent dysphagia and were found to have an esophageal stricture. Esophagrams typically showed a markedly dilated esophagus with a narrowed, sharply angulated gastroesophageal junction. Esophageal manometry confirmed esophageal aperistalsis and, when measured, the LES pressure was < 5 mm Hg. Endoscopy showed esophageal inflammation and a fixed stricture at the gastroesophageal junction. Strictures were dilated under direct visualization using through-the-scope balloon dilators. Patients began gastric acid suppressive treatment at the same time. Five patients who remained symptomatic underwent repeat endoscopy, which demonstrated improvement in esophagitis. Dilation was then repeated with a larger balloon dilator. Over a mean follow-up period of 3.8 years, the average number of repeat dilations per patient was 3.6 (range: 0-12). All patients had symptomatic improvement and weight gain. No patient required surgery. We conclude that esophageal strictures after esophagomyotomy for achalasia can be safely treated using endoscopic dilation and gastric acid suppression, thus avoiding the need for reoperation.

Aged↗
PubMed1994

Gastroesophageal reflux during gastrostomy feeding.

BACKGROUND/AIMS: Aspiration pneumonia is one of the most serious complications of gastrostomy tube feeding, with a reported incidence of 10%-20% in nursing home patients. The aims of this prospective study were to examine lower esophageal sphincter (LES) pressure before and after placement of gastrostomy tubes and to examine the effects of rapid intragastric bolus and slow, continuous feeding on LES pressure. METHODS: Ten subjects were enrolled in the study. Basal LES pressure was measured before and after placement of gastrostomy tubes. Thereafter, LES pressure was measured for 15 minutes during rapid intragastric infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous infusion of the enteral feeding formula at 80 mL/h. Scintigrams evaluating gastroesophageal reflux were obtained during each method of feeding. RESULTS: Placement of gastrostomy tubes had no effect on basal LES pressure. Rapid intragastric bolus infusion led to a reduction in LES pressure to incompetent levels at 2.1 +/- 2.0 mm Hg (P < 0.001). Free gastroesophageal reflux to the sternal notch was shown by scintigraphy. Slow, continuous gastrostomy feedings did not alter LES pressure (P > 0.05) or show free gastroesophageal reflux by scintigraphy. CONCLUSIONS: Gastroesophageal reflux and aspiration in patients fed via the gastrostomy tube may be caused by LES relaxation secondary to gastric distention caused by distention of the stomach.

Aged↗
PubMed1994

Novel approaches to controlled-release antigen delivery.

Two strategies for vaccine-delivery systems, both relying on concepts of controlled-release technology, are described in this review. The first strategy involves using biodegradable polymer microspheres for parenteral and oral delivery of antigens. The other strategy combines two technologies, the encapsulation of antigen within liposomes and liposome encapsulation in hydrogels, to protect them from a rapid degradation in vivo. Both strategies have shown promise in terms of increasing the immunogenicity of poorly immunogenic peptides and protein vaccines. The microencapsulation process, antigen stability, mechanism of antigen release, and optimal release kinetics for vaccine delivery are reviewed, and the strengths and weaknesses of each approach are discussed.

Antigens↗
PubMed1994

Socioeconomic status and health. The challenge of the gradient.

Socioeconomic status (SES) is consistently associated with health outcomes, yet little is known about the psychosocial and behavioral mechanisms that might explain this association. Researchers usually control for SES rather than examine it. When it is studied, only effects of lower, poverty-level SES are generally examined. However, there is evidence of a graded association with health at all levels of SES, an observation that requires new thought about domains through which SES may exert its health effects. Variables are highlighted that show a graded relationship with both SES and health to provide examples of possible pathways between SES and health end points. Examples are also given of new analytic approaches that can better illuminate the complexities of the SES-health gradient.

Health Behavior↗
PubMed1994

Analysis of epidemic and endemic isolates of Xanthomonas maltophilia by contour-clamped homogeneous electric field gel electrophoresis.

BACKGROUND: Xanthomonas maltophilia is increasingly a cause of nosocomial infections. The mode of transmission of this organism is not well known. OBJECTIVE: To investigate clonality of X maltophilia isolates in epidemic and endemic settings. METHODS: An outbreak of X maltophilia was noted in the Intensive Care Nursery (ICN). Over the ensuing 9 months, hospital wide isolates of X maltophilia were analyzed using contour-clamped homogeneous electric field (CHEF) gel electrophoresis of chromosomal DNA. This method was compared with the antibiogram for detecting differences and similarities among strains. RESULTS: X maltophilia was recovered from 76 sites in 72 patients; 65 isolates from 61 patients and the hands of one nurse were available for analysis. CHEF demonstrated differences between most epidemiologically unrelated strains and similarity between most epidemiologically related strains. Several strains, initially presumed to be related because of temporal and spatial proximity of the patients involved, were determined by CHEF analysis to be independent infections. One pair of isolates whose XbaI CHEF patterns differed by a single band were differentiated clearly by SspI. There was enough variation in the minimum inhibitory concentrations of selected antibiotics to allow typing of some strains. The antibiogram, however, did not group all of the ICN outbreak isolates with others found to be genetically identical by CHEF, and it grouped 39 of 56 isolates with others not genetically the same. CONCLUSIONS: Although it is a convenient and economical tool, the antibiogram has limitations. Analysis by CHEF should help to elucidate the epidemiological spread of X maltophilia in the hospital.

Adult↗
PubMed1994

Benign melanocytic nevus cells in axillary lymph nodes. A prospective incidence and immunohistochemical study with literature review.

Benign nevus cell aggregates (NCAs) in lymph nodes usually present as intracapsular or trabecular collections of small, uniform melanocytes that resemble those seen in intradermal melanocytic nevi. The surgical pathologist must be aware of nodal NCAs because they can mimic micrometastasis of carcinoma. Although not uncommon, the frequency with which NCAs occur is controversial. Two previous studies attempted to determine the case incidence of NCAs in axillary lymphadenectomies; widely different results were reported, ranging from .33% to 6.2%. In this study, the authors examined prospectively 300 axillary lymph node dissections containing 5186 lymph nodes, using S-100 protein immunohistochemistry as a supplemental evaluation measure, to determine the incidence of NCAs. Twenty-eight NCA-positive lymph nodes from 22 cases were found, for a 7.3% case incidence and a .54% nodal incidence; these figures were higher than those previously reported. The possible pathogenesis of this phenomenon is discussed, with a review of the literature.

Adult↗
PubMed1994

Decreased incidence of headache after accidental dural puncture in caesarean delivery patients receiving continuous postoperative intrathecal analgesia.

To examine the effects of prolonged (> 24 h) intrathecal catheterization with the use of postoperative analgesia on the incidence of post-dural puncture headache (PDPH), charts of 45 obstetric patients who had accidental dural puncture following attempts at epidural block were reviewed retrospectively. Three groups were identified: Group I (n = 15) patients had a dural puncture on the first attempt at epidural block, but successful epidural block on a repeated attempt; Group II (n = 17) patients had a dural puncture with immediate conversion to continuous spinal anaesthesia with catheterization lasting only for the duration of caesarean delivery; Group III (n = 13) patients had an immediate conversion to spinal anaesthesia and received post-caesarean section continuous intrathecal patient-controlled analgesia consisting of fentanyl 5 micrograms.ml-1 with bupivacaine 0.25 mg.ml-1 and epinephrine 2 micrograms.ml-1 with catheterization lasting > 24 h. No parturient in group III developed a PDPH. This was substantially lower (P < 0.009) than the 33% incidence for group I and the 47% incidence for group II. The incidence of a PDPH did not differ between group I and II. Similarly, there was no difference between group I and II with regard to requests for a blood patch. Patients receiving continuous intrathecal analgesia had excellent pain relief, could easily ambulate and none complained of pruritus, nausea, vomiting, sensory loss or weakness. In conclusion, indwelling spinal catheterization > 24 h with continuous intrathecal analgesia following accidental dural puncture in parturients may for some patients be a suitable method for providing PDPH prophylaxis and postoperative analgesia.

Adult↗
PubMed1994

Rates and correlates of suicide attempts in first-admission psychotic patients.

The relationship of attempted suicide to demographic characteristics, current and lifetime psychiatric diagnoses, clinical history, and current symptoms was assessed in a sample of 184 recently hospitalized psychotic patients. Forty-three patients (23%) had an attempt history, and 28 (15% of sample; 65% of attempters) made an attempt during the episode for which they were hospitalized. Demographic characteristics did not distinguish attempters from nonattempters. Variables significantly associated with having ever attempted suicide were current diagnosis of unipolar major depressive disorder but not bipolar; lifetime major depressive episode; a history characterized by a less acute onset, lower pre-admission psychosocial functioning, and episodes of physical violence; and a symptom picture characterized by greater depression, hopelessness, negative symptoms, hallucinations and less thought disorder. Those with a current attempt had significantly higher rates of lifetime history of major depression and less physical violence than those with past attempts only. The potential importance of the data for predicting future suicidal acts is discussed.

Adolescent↗
PubMed1994

Antibacterial synergism of polymyxin B nonapeptide and hydrophobic antibiotics in experimental gram-negative infections in mice.

Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 polymyxin-susceptible strains tested more susceptible to novobiocin, lowering the MIC of novobiocin eightfold or more. The combination of polymyxin B nonapeptide with novobiocin or with erythromycin administered intraperitoneally in multiple doses synergistically protected mice infected with gram-negative bacteria. This combination may be clinically useful because of the apparent rarity of the acquisition of resistance.

Animals↗
PubMed1994

Hairpin structures are the primary amplification products: a novel mechanism for generation of inverted repeats during gene amplification.

Early events of DNA amplification which occur during perturbed replication were studied by using simian virus 40 (SV40)-transformed Chinese hamster cells (CO60) as a model system. The amplification is observed shortly after carcinogen treatment, and the amplified sequences contain molecules organized as inverted repeats (IRs). SV40 amplification in vitro was studied by using extracts from carcinogen-treated CO60 cells. In the amplified DNA the SV40 origin region was rereplicated, while more distal sequences were not replicated even once. Using several experimental procedures such as sucrose gradients, "snap-back" assay, and two-dimensional gel electrophoresis, we show that the overreplicated DNA contains IRs which are synthesized de novo as hairpins or stem-loop structures which were detached from the template molecules. The fully replicated SV40 molecules synthesized by the HeLa extracts do not contain such IRs. We propose "U-turn replication" as a novel mechanism for gene amplification, accounting for the generation of extrachromosomal inverted duplications as a result of perturbed replication and template switching of the DNA polymerases.

Animals↗
PubMed1994

Immunization of monkeys with baculovirus-dengue type-4 recombinants containing envelope and nonstructural proteins: evidence of priming and partial protection.

Groups of rhesus monkeys were immunized with baculovirus-dengue type-4 (DEN-4) recombinant-infected cell extracts. One recombinant contained all of the DEN-4 structural proteins and two nonstructural (NS) proteins (C-M-E-NS1-NS2a), while the other was a fusion protein containing a portion of the respiratory syncytial virus G glycoprotein and DEN-4 envelope glycoprotein (RSVG-E). Both preparations were immunogenic; all monkeys receiving either immunogen responded with the production of antivirion antibodies in enzyme immunoassays. All except one monkey receiving the recombinant b(C-M-E-NS1-NS2a) made antibodies to NS1. One monkey that received b(RSVG-E) showed the production of low levels of neutralizing antibodies. Following challenge with unmodified DEN-4 virus, seven of nine monkeys in the immunized group became infected and were viremic for a mean of 4.1 days. The control, sham-inoculated monkeys were also viremic; the mean number of days of viremia in this group was 4.7 days. The remaining monkeys in the immunized group (n = 7), although not protected, had evidence of priming. Hemagglutination inhibition antibody responses following challenge indicated an anamnestic response in this group of animals. Based on these results, it was concluded that future immunization schedules should be altered to optimize immune responses and that immunization with more potent and purified immunogens would probably result in higher seroconversion rates and antibody levels in monkeys.

Animals↗