Research shutdown roils Los Angeles VA.
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Biomedical subjects
Publications and source records attributed to J Cohen.
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Atypical circular dichroism intensity enhancements previously associated with Psi-DNA condensates are reported for poly(dG-dC):poly(dG-dC) and poly(dA-dT):poly(dA-dT) upon addition to them of a polycationic string salt. Polycationic strings are organic species incorporating several cationic sites in a linear array through the molecule. The effect observed herein with a small molecule model system holds promise for elucidation of the structural details associated with Psi-DNA condensate formation.
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Synthesis and biological evaluation of heteroarenes as reduced cysteine replacements are described. Of the heteroaryl groups examined with respect to FT inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective. Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity. Compound 9a was found to have moderate in vivo bioavailability.
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OBJECTIVE: To analyze the initial experience at Oregon Health Sciences University, Portland, with the use of long-term indwelling tracheoesophageal voice prostheses. DESIGN: Retrospective case series. SETTING: Tertiary referral academic medical center. PATIENTS: Thirty patients undergoing speech rehabilitation after laryngectomy during a period of 18 months. INTERVENTION: Insertion of a long-term indwelling tracheoesophageal voice prosthesis. MAIN OUTCOME MEASURES: Duration of use, complications. RESULTS: The mean duration of placement for a single prosthesis was 4.9 months (148 days), with a range of 14 to 330 days. Sixteen of the 30 patients encountered problems with leakage because of fungal colonization, the majority of which (15 of 16 cases) were solved with either oral or topical application of nystatin. Size matching in terms of prosthesis length and tract length was critical, and problems of this nature were encountered in 11 of 30 patients. The incorporation of a second system of prostheses that offered an increased number of size options solved these problems in all of these patients. Ultimately, 27 of 30 patients were able to successfully wear these prostheses. CONCLUSIONS: The indwelling tracheoesophageal voice prosthesis offers patients all the advantages of tracheoesophageal speech rehabilitation after laryngectomy without the inconvenience of frequent prosthesis changes. With careful attention to the details of fitting and care, it can be worn by the majority of patients successfully.
OBJECTIVE: To determine the epidemiology of fever on the intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Nine-bed general ICU in a 500-bed tertiary care inner city institution. PATIENTS: 100 consecutive admissions of 93 patients over a 4-month period between July and October 1996. INTERVENTIONS: All patients were seen and examined by one investigator within 24 h of ICU admission. Patients were followed up on a daily basis throughout their ICU stay, and all clinical and laboratory data were recorded during the admission. MEASUREMENTS AND RESULTS: Fever (core temperature > or = 38.4 degrees C) was present in 70% of admissions, and it was caused by infective and non-infective processes in approximately equal number. Most fevers occurred early in the course of the admission, within the first 1-2 days, and most lasted less than 5 days. The median Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15 (+/- 0.6). The 70 episodes associated with fever at any time were associated with a significantly higher APACHE II score on admission than the afebrile episodes (15.8 +/- 6.1 vs 12.1 +/- 6.7, p = 0.04). The most common cause of non-infective fever was in the group designated post-operative fever (n = 34). All the patients in the post-operative fever group were febrile on day 0 or day 1; their mean admission APACHE score was 12.4 (+/- 4.4) compared to 15.9 (+/- 7.1) for the remaining patients (p = 0.01). Fever alone was not associated with a higher mortality: 26/70 (37%) of febrile patients died, compared to 8/30 (27%) of afebrile patients, (chi 2 = 1.23, p = 0.38). Prolonged fever (> 5 days) occurred in 16 patients. In 13 cases, fever was due to infection, and in the remaining 3 both infective and non-infective processes occurred concurrently. The mortality in the group with prolonged fever was 62.5% (10/16) compared to 29.6% (16/54) in patients with fever of less than 5 days' duration, a highly significant difference (p < 0.0001). CONCLUSIONS: Fever is a common event on the intensive care unit. It usually occurs early in the course, is frequently non-infective and is often benign. Prolonged fever is associated with a poor outcome. Post-operative fever is a well-recognised but poorly defined syndrome which requires further study.
OBJECTIVE: To evaluate the effects of fragmentation and fragment removal in day 3 human embryos on implantation and pregnancy. DESIGN: Retrospective analysis of ETs homogeneous with respect to embryo fragmentation. SETTING: A program of IVF-ET. PATIENT(S): The study population consisted of 2,410 patients. INTERVENTION(S): The degree and pattern of fragmentation were evaluated on days 2 and 3; microsurgical fragment removal was performed after assisted hatching on day 3. MAIN OUTCOME MEASURE(S): Clinical pregnancy and implantation rates. RESULT(S): The degree and pattern of fragmentation significantly impact pregnancy and implantation. With the application of microsurgical fragment removal before ET, embryos with 6%-35% fragmentation implant with similar frequency. The presence of large fragments (type IV) is detrimental to the developing embryo, whereas localized or small and scattered fragments do not significantly affect implantation. CONCLUSION(S): The potential of fragmented embryos for implantation is determined partly by the distribution of fragments. Adoption of an embryo classification system reflecting types of fragmentation is advisable. The use of microsurgical fragment removal significantly alters the course of development for some embryos and improves their implanting potential.
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This article has reviewed the mechanisms by which gram-positive bacteria lead to septic shock, with regard to bacterial structure and toxicology and the host responses elicited both in animal models and in the clinical setting. Gram-positive organisms are better suited to invade host tissues and elicit, in general, a brisker phagocytic response than gram-negative organisms. The lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of other toxic secreted products. It appears that cell wall components of gram-positive bacteria may signal via the same receptor as gram-negative endotoxin, although the type of signal and coreceptor may differ. Both animal and clinical data suggest that, unlike endotoxin-mediated shock, gram-positive infection produces a modest TNF response only and does not respond well to anti-TNF therapies. This leads one to conclude that the mechanisms leading to shock in gram-positive infection may be multifactorial and perhaps more difficult to treat. A thorough review of gram-positive mechanisms of sepsis is hampered by a lack of basic research in this field. Understanding of gram-negative bacterial structure and the regulation of virulence genes is at an advanced stage, yet the molecular tools to analyse virulence factors in the gram-positive genome have only recently become available. There is a paucity of good animal models of gram-positive infection and a lack of microbiologic data from some of the major trials in sepsis that might have given greater insight into the mechanisms leading to shock in various infections.
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