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Biomedical subjects

J Cohen

Publications and source records attributed to J Cohen.

At least 271 records · Page 15Linked to original sources
PubMed2000

Course and outcome of obstetric patients in a general intensive care unit.

BACKGROUND: To characterize the course, interventions required to achieve predetermined end-points and outcome of obstetric patients admitted to a general intensive care unit. METHODS: A retrospective case series study was performed including all pregnant patients admitted to an 8-bed general intensive care unit at a tertiary care university-affiliated hospital over a 4-year period. All patients referred by the obstetricians were admitted. Patients were divided into two groups: group 1, (n = 19) those requiring mechanical ventilatory support and group 2, (n = 27) those requiring intensive monitoring. Data collected included demographics, reason for admission, admission diagnosis, Acute Physiology and Chronic Health Evaluation (APACHE II) and Therapeutic Intervention Scoring System (TISS) scores, intensive care unit course, types of interventions used and outcome. End-points of therapy included systolic blood pressure 110-150 mmHg, urine output > or = 1 cc/kg/h and oxygen saturation > 95%. RESULTS: Over the study period, 46 obstetric patients were admitted to the intensive care unit, representing 0.2% of all deliveries and an intensive care unit utilization rate of 2.3%. Commonest admission diagnoses were pregnancy-induced hypertension and hemorrhage. Reason for admission was mechanical ventilation in 41% while 59% were admitted for monitoring. Median length of stay was 25 +/- 80.9 (mean 48.8) hours. The median APACHE II score was 6 +/- 3.9 (mean 7.24) and the TISS score was > 20 in both groups. Only one patient died (mortality rate 2.3%). CONCLUSION: Despite a short length of stay and low APACHE score, the high TISS score in obstetric patients admitted for both ventilation and monitoring suggests that these patients require a level of intervention and care typically provided by a general intensive care unit.

Adult↗
PubMed2000

Quality of life and locus of control of migraineurs.

Advanced practice nurses (APNs) are essential primary healthcare providers actively engaged in health promotion, illness prevention, and the management of acute and chronic diseases. The purpose of this study was to measure the quality of life and locus of control (LOC) among three different groups of migraineurs. A retrospective quantitative study was conducted using Ferrans and Powers' (1985) Quality of Life Index and Martin, Holroyd, and Penzien's (1990) Headache Specific Locus of Control questionnaire. The analysis of 79 adult migraineurs indicated that those who received headache education had a higher quality of life and higher external LOC scores than those without the intervention. This study's findings reinforce the notion that disease-specific education is an effective practice intervention. APNs can positively affect the quality of life for migraineurs by providing an educational intervention as part of high-quality, accessible, and cost-effective primary care.

Adolescent↗
PubMed1999

Discovery of a series of cyclohexylethylamine-containing protein farnesyltransferase inhibitors exhibiting potent cellular activity.

Synthesis of a library of secondary benzylic amines based on the Sebti-Hamilton type peptidomimetic farnesyltransferase (FTase) inhibitor FTI-276 (1) led to the identification of 6 as a potent enzyme inhibitor (IC(50) of 8 nM) which lacked the problematic thiol residue which had been a common theme in many of the more important FTase inhibitors reported to date. It has previously been disclosed that addition of o-tolyl substitution to FTase inhibitors of the general description 2 had a salutary effect on both FTase inhibition and inhibition of Ras prenylation in whole cells. Combination of these two observations led us to synthesize 7, a potent FTase inhibitor which displayed an IC(50) of 0.16 nM for in vitro inhibition of FTase and an EC(50) of 190 nM for inhibition of whole cell Ras prenylation. Modification of 7 by classical medicinal chemistry led to the discovery of a series of potent FTase inhibitors, culminating in the identification of 25 which exhibited an IC(50) of 0.20 nM and an EC(50) of 4.4 nM. In vivo tests in a nude mouse xenograft model of human pancreatic cancer (MiaPaCa cells) showed that oral dosing of 25 gave rise to impressive attenuation of the growth of this aggressive tumor cell line.

Alkyl and Aryl Transferases↗
PubMed1999

Role of locus coeruleus in attention and behavioral flexibility.

Previous findings have implicated the noradrenergic locus coeruleus (LC) system in functions along the dimension of arousal or attention. It has remained uncertain what role this system has in attention, or what mechanisms may be involved. We review our recent work examining activity of LC neurons in monkeys performing a visual discrimination task that requires focused attention. Results indicate that LC cells exhibit phasic or tonic modes of activity, that closely correspond to good or poor performance on this task, respectively. A computational model was used to simulate these results. This model predicts that alterations in electrotonic coupling among LC cells may produce the different modes of activity and corresponding differences in performance. This model also indicates that the phasic mode of LC activity may promote focused or selective attention, whereas the tonic mode may produce a state of high behavioral flexibility or scanning attentiveness. The implications of these results for clinical disorders such as attention-deficit hyperactivity disorder, stress disorders, and emotional and affective disorders are discussed.

Animals↗
PubMed1999

The epithelial cell response to rotavirus infection.

Rotavirus is the most important worldwide cause of severe gastroenteritis in infants and young children. Intestinal epithelial cells are the principal targets of rotavirus infection, but the response of enterocytes to rotavirus infection is largely unknown. We determined that rotavirus infection of HT-29 intestinal epithelial cells results in prompt activation of NF-kappaB (<2 h), STAT1, and ISG F3 (3 h). Genetically inactivated rotavirus and virus-like particles assembled from baculovirus-expressed viral proteins also activated NF-kappaB. Rotavirus infection of HT-29 cells induced mRNA for several C-C and C-X-C chemokines as well as IFNs and GM-CSF. Mice infected with simian rotavirus or murine rotavirus responded similarly with the enhanced expression of a profile of C-C and C-X-C chemokines. The rotavirus-stimulated increase in chemokine mRNA was undiminished in mice lacking mast cells or lymphocytes. Rotavirus induced chemokines only in mice <15 days of age despite documented infection in older mice. Macrophage inflammatory protein-1beta and IFN-stimulated protein 10 mRNA responses occurred, but were reduced in p50-/- mice. Macrophage inflammatory protein-1beta expression during rotavirus infection localized to the intestinal epithelial cell in murine intestine. These results show that the intestinal epithelial cell is an active component of the host response to rotavirus infection.

Aging↗
PubMed1999

Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial.

OBJECTIVE: To evaluate the effectiveness of a population based, multifaceted shared care intervention for late life depression in residential care. DESIGN: Randomised controlled trial, with control and intervention groups studied one after the other and blind follow up after 9.5 months. SETTING: Population of residential facility in Sydney living in self care units and hostels. PARTICIPANTS: 220 depressed residents aged >/=65 without severe cognitive impairment. INTERVENTION: The shared care intervention included: (a) multidisciplinary consultation and collaboration, (b) training of general practitioners and carers in detection and management of depression, and (c) depression related health education and activity programmes for residents. The control group received routine care. MAIN OUTCOME MEASURE: Geriatric depression scale. RESULTS: Intention to treat analysis was used. There was significantly more movement to "less depressed" levels of depression at follow up in the intervention than control group (Mantel-Haenszel stratification test, P=0.0125). Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders, with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group (95% confidence interval 0.76 to 2.97, P=0.0011). CONCLUSIONS: The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration, by enhancing the clinical skills of general practitioners and care staff, and by providing depression related health education and activity programmes for residents.

Aged↗
PubMed1999

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.

Alkyl and Aryl Transferases↗
PubMed1999

Potent and orally bioavailable noncysteine-containing inhibitors of protein farnesyltransferase.

Potent and orally bioavailable nonthiol-containing inhibitors of protein farnesyltransferase are described. Oral bioavailability was achieved by replacement of the pyridyl ether moiety of 1 with a 2-substituted furan ether to give 4. Potency was regained with 2,5-disubstituted furan ethers while maintaining the bioavailability inherent in 4. p-Chlorophenylfuran ether 24 is 0.7 nM in vitro (FTase) and is 32% bioavailable in the mouse, 30% bioavailable in rats, and 21% bioavailable in dogs.

Alkyl and Aryl Transferases↗