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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 109 records · Page 6Linked to original sources
PubMed2001

Efficacy of recombinant circumsporozoite protein vaccine regimens against experimental Plasmodium falciparum malaria.

After initial successful evaluation of the circumsporozoite-based vaccine RTS,S/SBAS2, developed by SmithKline Beecham Biologicals with the Walter Reed Army Institute of Research, protective efficacy of several regimens against Plasmodium falciparum challenge was determined. A controlled phase 1/2a study evaluated 1 or 2 standard doses of RTS,S/SBAS2 in 2 groups whose members received open-label therapy and 3 immunizations in blinded groups who received standard, one-half, or one-fifth doses. RTS,S/SBAS2 was safe and immunogenic in all groups. Of the 41 vaccinees and 23 control subjects who underwent sporozoite challenge, malaria developed in 7 of 10 who received 1 dose, in 7 of 14 who received 2 doses, in 3 of 6 who received 3 standard doses, in 3 of 7 who received 3 one-half doses, in 3 of 4 who received 3 one-fifth doses, and in 22 of 23 control subjects. Overall protective efficacy of RTS,S/SBAS2 was 41% (95% confidence interval, 22%-56%; P=.0006). This and previous studies have shown that 2 or 3 doses of RTS,S/SBAS2 protect against challenge with P. falciparum sporozoites.

Adolescent↗
PubMed2001

Self assembly of the transmembrane domain promotes signal transduction through the erythropoietin receptor.

Hematopoietic cytokine receptors, such as the erythropoietin receptor (EpoR), are single membrane-spanning proteins. Signal transduction through EpoR is crucial for the formation of mature erythrocytes. Structural evidence shows that in the unliganded form EpoR exists as a preformed homodimer in an open scissor-like conformation precluding the activation of signaling. In contrast to the extracellular domain of the growth hormone receptor (GHR), the structure of the agonist-bound EpoR extracellular region shows only minimal contacts between the membrane-proximal regions. This evidence suggests that the domains facilitating receptor dimerization may differ between cytokine receptors. We show that the EpoR transmembrane domain (TM) has a strong potential to self interact in a bacterial reporter system. Abolishing self assembly of the EpoR TM by a double point mutation (Leu 240-Leu 241 mutated to Gly-Pro) impairs signal transduction by EpoR in hematopoietic cells and the formation of erythroid colonies upon reconstitution in erythroid progenitor cells from EpoR(-/-) mice. Interestingly, inhibiting TM self assembly in the constitutively active mutant EpoR R129C abrogates formation of disulfide-linked receptor homodimers and consequently results in the loss of ligand-independent signal transduction. Thus, efficient signal transduction through EpoR and possibly other preformed receptor oligomers may be determined by the dynamics of TM self assembly.

Amino Acid Sequence↗
PubMed2001

Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II.

BACKGROUND: Weight loss appears to be an effective method for primary prevention of hypertension. However, the long-term effects of weight loss on blood pressure have not been extensively studied. OBJECTIVE: To present detailed results from the weight loss arm of Trials of Hypertension Prevention (TOHP) II. DESIGN: Multicenter, randomized dinical trial testing the efficacy of lifestyle interventions for reducing blood pressure over 3 to 4 years. Participants in TOHP II were randomly assigned to one of four groups. This report focuses only on participants assigned to the weight loss (n = 595) and usual care control (n = 596) groups. PATIENTS: Men and women 30 to 54 years of age who had nonmedicated diastolic blood pressure of 83 to 89 mm Hg and systolic blood pressure less than 140 mm Hg and were 110% to 165% of their ideal body weight at baseline. INTERVENTION: The weight loss intervention included a 3-year program of group meetings and individual counseling focused on dietary change, physical activity, and social support MEASUREMENTS: Weight and blood pressure data were collected every 6 months by staff who were blinded to treatment assignment RESULTS: Mean weight change from baseline in the intervention group was -4.4 kg at 6 months, -2.0 kg at 18 months, and -0.2 kg at 36 months. Mean weight change in the control group at the same time points was 0.1, 0.7, and 1.8 kg. Blood pressure was significantly lower in the intervention group than in the control group at 6, 18, and 36 months. The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at 6 months, 0.78 (CI, 0.62 to 1.00) at 18 months, and 0.81 (CI, 0.70 to 0.95) at 36 months. In subgroup analyses, intervention participants who lost at least 4.5 kg at 6 months and maintained this weight reduction for the next 30 months had the greatest reduction in blood pressure and a relative risk for hypertension of 0.35 (CI, 0.20 to 0.59). CONCLUSIONS: Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.

Adult↗
PubMed2001

Measuring the incremental cost of clinical cancer research.

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

Clinical Trials as Topic↗
PubMed2001

Complementation of a speA negative Streptococcus pyogenes with speA: effects on virulence and production of streptococcal pyrogenic exotoxin A.

We have shown previously that an isogenic SPEA-negative Streptococcus pyogenes strain did not attenuate virulence in a murine model of necrotizing fasciitis. The aim of this study was to confirm that streptococcal pyrogenic exotoxin A (SPEA) is not crucial for streptococcal invasiveness in murine invasive infection. The SPEA-negative S. pyogenes (H326) was complemented with speA extra-chromosomally to create strain H361 which produced 2.2-fold more SPEA compared with the parental speA(+)wild-type (H305). The growth phase-regulated expression of SPEA in vitro was unaffected in this strain. Complementation with speA resulted in reduced virulence and bacterial counts in invasive murine infection. SPEA production was quantitated from muscle tissue of infected mice. However, H361 did not produce more SPEA than H305 in vivo. We conclude that SPEA does not play a key role in invasive murine streptococcal infection.

Animals↗
PubMed2001

Zenker's diverticulostomy with cricopharyngeal myotomy: the endoscopic approach.

BACKGROUND: The gold standard for the surgical treatment of Zenker's diverticulum is diverticulectomy and cricopharyngeal myotomy by an external approach. Unfortunately, many of the patients who present with this entity are elderly and have significant comorbidities that increase operative risk. Traditional minimally invasive approaches have not met with widespread success. However, by combining the exposure afforded by the otolaryngologist's newer bivalved operating laryngoscopes with the operative techniques made possible by the general surgeon's laparoscopic instrumentation and staplers, it is possible to achieve reliable and safe endoscopic outpatient management of this disease entity, with resumption of a normal diet on the same day. METHODS: We reviewed the physiologic basis, instrumentation, and technical considerations for this endoscopic procedure. We also documented our operative experience with 21 patients treated over an 18-month period. RESULTS: Successful minimally invasive management of Zenker's diverticulum was possible in 18 of 21 patients. In two patients, anatomic limitations of mouth and neck anatomy precluded exposure of the diverticulum; in another patient, the diverticulum was too small. Small operative perforations of the apex of the diverticulum occurred in three cases. Two of these perforations were repaired primarily with minimally invasive techniques; in the other case, treatment consisted of observation alone. In all but this last patient, oral diet was resumed on the day of the operation. Eleven of the patients were discharged from the hospital on the same day; the remaining patients went home the following morning. CONCLUSIONS: With proper patient selection, minimally invasive management of Zenker's diverticulum is a safe and effective surgical technique that allows for outpatient management of the majority of patients who present with this disease.

Cricoid Cartilage↗
PubMed2001

Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.

BACKGROUND: A 4-week-old male infant (4.9 kg) with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) underwent a laparoscopic pancreatectomy to evaluate its feasibility. Preoperative medications included diazoxide and glucagon to maintain adequate blood glucose levels. METHODS: Laparoscopic pancreatectomy was performed using a 5-mm cannula at the umbilicus, external fixation, transcutaneous suture-assisted gastric retraction to expose the lesser sac, and three additional 3.5-mm cannula sites. The pancreas was resected from the splenic hilum to the mesenteric vessels. The splenic vein was dissected from the under surface of the pancreas using electrocautery, and the spleen was easily preserved. Surgery time was 75 min, and minimal blood loss occurred. RESULTS: The child required no narcotic medication and tolerated a regular diet immediately after surgery. Serum glucose levels did decrease postoperatively, and the child required diazoxide, dextrose infusion, glucagon, and octreotide. On postoperative day 7, the child underwent an open near-total pancreatectomy, after which he remained asymptomatic. Essentially no scarring was found in the lesser sac, and the remaining pancreatic remnant was resected without difficulty. CONCLUSIONS: Laparoscopic pancreatectomy can be performed safely, even in a newborn patient, without prolonged operative time or unnecessary risk. The technique using external fixation and transcutaneous suture-assisted gastric retraction provides excellent exposure to the pancreas and lesser sac. In patients with PHHI, in whom reoperative additional pancreatectomy is very likely, this technique is the ideal initial surgical approach.

Humans↗
PubMed2001

Protecting the child's abdomen: a retractable bicycle handlebar.

A surveillance system in the Emergency Department of a level 1 pediatric trauma center previously identified minor bicycle crashes as a cause of serious child abdominal injury. A discordancy exists between the apparently minor circumstances and serious injuries sustained by child bicyclists who impact bicycle handlebars. The objective of this work was to redesign the bicycle handlebar to reduce the forces transmitted to the child's abdomen during an impact with the handlebars. A retractable handlebar consisting of a spring-mass-damper system was designed to retract and absorb the majority of energy at impact (Patent pending). Because the child remains in contact with the bar after impact, the retracting system also includes a mechanism to damp the outward motion of the handlebar. This prototype will reduce the forces at impact by approximately 50% in a collision similar to those discussed above. A unique methodology of translating research findings into product design produced a novel handlebar that absorbs significant energy that otherwise would be transferred to the child's abdomen when impacting the handlebar.

Abdominal Injuries↗
PubMed2001

Paramecium genome survey: a pilot project.

A consortium of laboratories undertook a pilot sequencing project to gain insight into the genome of Paramecium. Plasmid-end sequencing of DNA fragments from the somatic nucleus together with similarity searches identified 722 potential protein-coding genes. High gene density and uniform small intron size make random sequencing of somatic chromosomes a cost-effective strategy for gene discovery in this organism.

Animals↗
PubMed2001

Severe traumatic brain injury.

In western countries, injuries remain the leading cause of death in young adults (Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry 1996; 60: 362-369). Worldwide, injuries are estimated to account for 15% of the burden of death and disability, and are projected to account for 20% in 2020 (Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and Development (Document TDR/Gen/96.1). Geneva: World Health Organisation, 1996). In developing countries road traffic injuries in particular are increasing in incidence and injuries are projected to be the third leading cause of death and disability worldwide by 2020 (Ad Hoc Committee on Health Research Relating to Future Intervention Options. Investing in Health Research and Development (Document TDR/Gen/96.1). Geneva: World Health Organisation, 1996). Head injury accounts for up to half of all deaths from trauma (Kraus J. Epidemiology of head injury. In: Cooper PR, Ed. Head Injury, 3rd ed. Baltimore, MD: William Wilkins, 1993), and in addition to causing death often causes severe and long-lasting functional impairment in survivors.

Accidental Falls↗
PubMed2001

Immunocytochemical characterization of viruses and antigenic macromolecules in viral vaccines.

Gold immunolabeling combined with negative staining (GINS) provides a valuable immunocytochemical approach that allows a direct ultrastructural definition of all viral vaccine constituents that share common antigenic features with pathogenic viral particles. These results have implications for the development of viral vaccines since it has been demonstrated that incomplete viral particles such as natural empty capsides and Rotavirus-like particles lacking the infective genome are potential candidates for the production of neutralizing antibodies. Furthermore comparative results of the application of GINS to either inactivated vaccines or unfixed samples provide direct evidence that even after inactivation specific antigenic sites are still available for gold immunolabeling.

Animals↗
PubMed2001

Infectious diarrhea in human immunodeficiency virus.

Chronic HIV-associated diarrhea is currently a field in flux. Improved noninvasive diagnostic tests, improved pathogen-specific regimens, and better empiric therapies may change some of the assumptions used to select algorithms for diagnostic evaluation and management. Any shift in the cause of diarrhea from pathogen-associated to idiopathic or a reduction in the overall incidence of diarrhea would have considerable impact. It is unclear how significant the problem of pathogen relapse in previous responders will become. Existing studies reviewed in this article show that the high diagnostic yield of endoscopy when stool tests are negative, coupled with significantly better outcomes when pathogens are identified, support the current practice of routine endoscopic evaluation. There currently are scant data on the economic impact of HIV-associated diarrhea as it relates to pathogen-specific and empiric therapy in the era of protease inhibitors. Such data would be integral to future evaluation of the impact of diagnostic and therapeutic strategies.

AIDS-Related Opportunistic Infections↗