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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 145 records · Page 8Linked to original sources
PubMed2001

The safety of immediate extubation after abdominal aortic surgery: a prospective, randomized trial.

UNLABELLED: We performed this study to assess the safety of immediate extubation after elective abdominal aortic aneurysm surgery. Consecutive patients were prospectively randomized into two groups after surgery: Group 1 (n = 29) immediate extubation; and Group 2 (n = 21) delayed (at least 4 h) extubation. All patients were assessed by a senior anesthesiologist or intensivist before extubation. The following data were collected: preoperative-demographics, presence of comorbid disease, body mass index, hemoglobin level, heart rate, and blood pressure; intraoperative-duration of surgery and cross-clamping, blood loss, amount of crystalloids, colloids, and blood transfused, temperature at end of procedure, urine output, and complications; and postoperative-time to extubation, scores on the Acute Physiology and Chronic Health Evaluation-II and Therapeutic Intervention Scoring System, total fentanyl dose, and complications. Outcome variables were length of intensive care unit and hospital stay and 28-day mortality. The results showed no significant differences in preoperative or intraoperative variables between the groups, apart from a longer duration of surgery in Group 1 (P = 0.045). Group 2 patients had a significantly higher Therapeutic Intervention Scoring System score (P = 0.04) and required a significantly larger dose of fentanyl (P < 0.001). One patient in Group 2 required reintubation after a cerebrovascular accident. The overall mortality rate was 4% (2 patients in Group 2). There were no significant differences in any of the outcome variables. We conclude that immediate extubation can safely be performed after elective abdominal aortic aneurysm surgery. IMPLICATIONS: In this prospective randomized study, we compared the outcome of patients undergoing elective aortic abdominal surgery who either were extubated immediately after surgery or after 4 h of stabilization in the intensive care unit. No significant differences were found in the length of intensive care unit or hospital stay, or 28-day mortality between the 2 groups.

Aged↗
PubMed2001

New strategies for clinical trials in patients with sepsis and septic shock.

OBJECTIVE: The difficulty in identifying new treatment modalities that significantly reduce the mortality and morbidity rates associated with sepsis has highlighted the need to reevaluate the approach to clinical trial design. The United Kingdom Medical Research Council convened an International Working Party to address these issues. DATA SOURCES: The subject areas that were to be the focus of discussion were identified by the co-chairs, and group leaders were nominated. Preconference reading material was circulated to group members. STUDY SELECTION AND DATA EXTRACTION: Small-group discussion fed into an iterative process of feedback from plenary sessions, followed by the formulation of recommendations. Finally, each working group prepared a summary of its recommendations and these are reported herein. DATA SYNTHESIS: There were five key recommendations. First, investigators should no longer rely solely on the American College of Chest Physicians/Society of Critical Care Medicine definitions of sepsis or sepsis syndrome as the basis of trial entry. Entry criteria should be based on three principles: a) All patients should have infection; b) there should be evidence of a pathologic process that represents a biologically plausible target for the proposed intervention, for example, an abnormal circulating level of a biological marker pertinent to the study drug; and c) patients should fall into an appropriate category of severity (usually severe sepsis). Second, investigators should use a scoring system for organ dysfunctions that has been validated and that can be incorporated into all sepsis studies; agreement on the use of a single system would simplify comparisons between studies. Third, the primary outcome measure generally should be mortality rates, but under appropriate circumstances major morbidities could be considered as primary end points. Regardless of choice of the duration to primary end point, patients should be followed for > or =90 days. Fourth, sample size needs to be based on a realistic assessment of achievable effect size based on knowledge of the at-risk population. Fifth, subgroups should be few in number and should be defined a priori on the basis of variables present before randomization. CONCLUSIONS: Important changes in several aspects of trial design may improve the quality of clinical studies in sepsis and maximize the chance of identifying effective therapeutic agents.

Clinical Trials as Topic↗
PubMed2001

A comparative evaluation of three root-end filling materials: an in vitro leakage study using Prevotella nigrescens.

This study used Prevotella nigrescens to evaluate the sealing ability of Geristore, Super-EBA, and ProRoot when used as root-end filling materials. One hundred single-canal, extracted, human teeth were cleaned and shaped with Gates-Glidden burs and .04 Taper (ProFile Series 29) rotary instruments. The root-ends were resected, and a 3-mm deep root-end preparation was made with ultrasonic tips. After steam sterilization, the teeth were randomly divided into three groups of 30. Each group was root-end-filled with a different material. Five root-end cavities were left open and served as positive controls; another five root-end cavities filled with sticky wax and covered with two layers of nail polish acted as negative controls. The teeth were attached to presterilized snap-on plastic caps; the root-ends submerged into 12-ml vials of chopped meat carbohydrate broth and placed in an anaerobic chamber. Twice a week, a sterile micropipette was used to inoculate 0.1 ml of a broth culture of Prevotella nigrescens into the root canal of each tooth. Results after 47 days indicated there were no significant differences between the three root-end filling materials against penetration of Prevotella nigrescens.

Aluminum Compounds↗
PubMed2001

Remifentanil.

Remifentanil is an opioid with a unique pharmacokinetic profile. Its metabolism by nonspecific esterases results in rapid and uniform clearance leading to highly predictable onset and offset of action. This review will describe the features that set remifentanil apart from other opioids and outline its potential usefulness in a critical care setting. Most studies on remifentanil have been in postoperative neurosurgical and cardiothoracic ICU settings. In the former, the agent has proved especially useful because rapid predictable emergence from sedation allows regular clinical evaluation. Remifentanil also prevents procedure-associated rise in intracranial pressure. In the cardiac setting, the drug provides excellent intraoperative hemodynamic control while allowing return of spontaneous ventilation within minutes of discontinuation of the infusion. One study suggests that the use of remifentanil will reduce the need for postoperative intensive care, especially after hepatic transplantation.

Humans↗
PubMed2001

Bovine rotavirus nonstructural protein 4 produced by Lactococcus lactis is antigenic and immunogenic.

Rotavirus nonstructural protein 4 (NSP4) can induce diarrhea in mice. To get insight into the biological effects of NSP4, production of large quantities of this protein is necessary. We first tried to produce the protein in Escherichia coli, but the nsp4 gene proved to be unstable. The capacity of the generally regarded as safe organism Lactococcus lactis to produce NSP4 either intra- or extracellularly was then investigated by using the nisin-controlled expression system. Production of recombinant NSP4 (rNSP4) was observed in L. lactis for both locations. In spite of a very low secretion efficiency, the highest level of production was obtained with the fusion between a lactococcal signal peptide and rNSP4. Cultures of the rNSP4-secreting strain were injected into rabbits, and a specific immune response was elicited. The anti-rNSP4 antibodies produced in these rabbits recognized NSP4 in MA104 cells infected by rotavirus. We showed that L. lactis is able to produce antigenic and immunogenic rNSP4 and thus is a good organism for producing viral antigens.

Animals↗
PubMed2001

Rotavirus 2/6 virus-like particles administered intranasally in mice, with or without the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin, induce a Th1/Th2-like immune response.

We investigated the rotavirus-specific lymphocyte responses induced by intranasal immunization of adult BALB/c mice with rotavirus 2/6 virus-like particles (2/6-VLPs) of the bovine RF strain, by assessing the profile of cytokines produced after in vitro restimulation and serum and fecal antibody responses. The cytokines produced by splenic cells were first evaluated. Intranasal immunization with 50 microg of 2/6-VLPs induced a high serum antibody response, including immunoglobulin G1 (IgG1) and IgG2a, a weak fecal antibody response, and a mixed Th1/Th2-like profile of cytokines characterized by gamma interferon and interleukin 10 (IL-10) production and very low levels of IL-2, IL-4, and IL-5. Intranasal immunization with 10 microg of 2/6-VLPs coadministered with the mucosal adjuvants cholera toxin and Escherichia coli heat-labile toxin (LT) considerably enhanced the Th1/Th2-like response; notably, significant levels of IL-2, IL-4, and IL-5 were observed. Since rotavirus is an enteric pathogen, we next investigated the production of IL-2 and IL-5, as being representative of Th1 and Th2 responses, by Peyer's patch and mesenteric lymph node cells from mice immunized intranasally with 2/6-VLPs and LT. The results were compared to those obtained from splenic and cervical lymph node cells. We found that both cytokines were produced by cells from each of these lymphoid tissues. These results confirm the Th1/Th2-like response observed at the systemic level and show, on the assumption that T cells are the primary cells producing the cytokines after in vitro restimulation, that rotavirus-specific T lymphocytes are present in the intestine after intranasal immunization with 2/6-VLPs and LT.

Adjuvants, Immunologic↗
PubMed2001

Mechanisms of tissue injury in sepsis: contrasts between gram positive and gram negative infection.

Sepsis is the systemic response to infection, and is caused by gram positive and gram negative bacteria in approximately equal numbers. In recent years it has become increasingly clear that there are significant differences between sepsis caused by gram positive and gram negative infections, both in the microbial components that initiate the injury, and the host responses that follow it. These differences will assume greater importance in developing targeted therapeutic interventions to severe sepsis.

Bacteremia↗
PubMed2001

Diagnosis and treatment of feeding disorders in children with developmental disabilities.

OBJECTIVES: To determine the results of diagnostic evaluation and the effects of nutritional intervention on energy consumption, weight gain, growth, and clinical status of children with neurodevelopmental disabilities and suspected feeding disorders. METHODS: We studied 79 children with moderate to severe motor or cognitive dysfunction (male:female, 38:41; age, 5.8 +/- 3.7 years) who were referred for diagnosis and treatment of feeding or nutritional problems. Initial assessments included a 3-day calorie intake record, videofluoroscopic swallowing study (VFSS), 24-hour intraesophageal pH monitoring, milk scintigraphy, and esophagogastroduodenoscopy. RESULTS: These studies demonstrated gastroesophageal reflux (GER) with or without aspiration in 44 of 79 patients (56%), oropharyngeal dysphagia in 21 (27%), and aversive feeding behaviors in 14 (18%). Diagnosis-specific approaches included medical GER therapy in 20 patients (25%), fundoplication plus gastrostomy tube (GT) in 18 (23%), oral supplements in 17 (22%), feeding therapy only in 14 (18%), and GT only in 10 (13%). After 24.6 +/- 3.0 months, relative calorie intake, expressed as intake (kcal/d)/recommended daily allowance (RDA, kcal/d), improved significantly (initial:final = 0.78 +/- 0.36:1.23 +/- 0.27). The z scores increased significantly for both weight (initial:final = -2.80 +/- 1.33:-0.81 +/- 0.69) and height (-3.14 +/- 0.98:-2.00 +/- 0.67). Improved subcutaneous tissue stores were demonstrated by increased thickness of both subscapular skinfolds (change = 71% +/- 26%) and triceps skinfolds (38% +/- 17%). After nutritional intervention, the acute care hospitalization rate, compared with the 2-year period before intervention, decreased from 0.4 +/- 0.18 to 0.15 +/- 0.06 admissions per patient-year and included only 3 admissions (0.02 per patient-year) related to feeding problems. CONCLUSIONS: In children with developmental disabilities, diagnosis-specific treatment of feeding disorders results in significantly improved energy consumption and nutritional status. These data also indicate that decreased morbidity (reflected by a lower acute care hospitalization rate) may be related, at least in part, to successful management of feeding problems. Our results emphasize the importance of a structured approach to these problems, and we propose a diagnostic and treatment algorithm for children with developmental disabilities and suspected feeding disorders.children, developmental disabilities, fundoplication, gastroesophageal reflux, gastrostomy, hospitalization, nutrition.

Adolescent↗
PubMed2001

Fine-mapping, mutation analyses, and structural mapping of cerebrotendinous xanthomatosis in U.S. pedigrees.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder of bile acid biosynthesis. Clinically, CTX patients present with tendon xanthomas, juvenile cataracts, and progressive neurological dysfunction and can be diagnosed by the detection of elevated plasma cholestanol levels. CTX is caused by mutations affecting the sterol 27-hydroxylase gene (CYP27 ). CTX has been identified in a number of populations, but seems to have a higher prevalence in the Japanese, Sephardic Jewish, and Italian populations. We have assembled 12 previously unreported pedigrees from the United States. The CYP27 locus had been previously mapped to chromosome 2q33-qter. We performed linkage analyses and found no evidence of genetic heterogeneity. All CTX patients showed segregation with the CYP27 locus, and haplotype analysis and recombinant events allowed us to precisely map CYP27 to chromosome 2q35, between markers D2S1371 and D2S424. Twenty-three mutations were identified from 13 probands analyzed thus far; 11 were compound heterozygotes and 2 had homozygous mutations. Of these, five are novel mutations [Trp100Stop, Pro408Ser, Gln428Stop, a 10-base pair (bp) deletion in exon 1, and a 2-bp deletion in exon 6 of the CYP27 gene]. Three-dimensional structural modeling of sterol 27-hydroxylase showed that, while the majority of the missense mutations disrupt the heme-binding and adrenodoxin-binding domains critical for enzyme activity, two missense mutations (Arg94Trp/Gln and Lys226Arg) are clearly located outside these sites and may identify a potential substrate-binding or other protein contact site.

Adolescent↗
PubMed2001

IRB/FDA requirements relevant to HIV/AIDS clinical trials in correctional settings.

Federally funded research involving inmates in US correctional facilities requires the approval of the Office for Protection from Research Risks (now called the Office for Human Research Protections [OHRP] and located in the Office of the Secretary of the Department of Health and Human Services). Trials that are carried out by pharmaceutical companies (not federally funded) fall under the jurisdiction of the FDA. This article reviews OHRP and FDA guidelines relevant to the conduct of HIV/AIDS clinical trials in correctional settings.

Acquired Immunodeficiency Syndrome↗