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Biomedical subjects

W Cohen

Publications and source records attributed to W Cohen.

At least 19 recordsLinked to original sources

Intra-arterial urokinase for acute ischemic stroke: factors associated with complications.

The authors abstracted the records of 43 patients treated with intra-arterial urokinase for acute ischemic stroke to identify predictors of serious complications. Sixteen (37%) had such a complication. Higher urokinase dose (>1.5 x 10(6) U), higher mean arterial blood pressure before treatment (>130 mm Hg), basilar occlusive strokes, and severe strokes were most predictive of these complications. Although urokinase is no longer manufactured, these findings identify patients at risk for complications from other intra-arterial thrombolytics.

Acute Disease↗

Characteristics of HIV-1 Nef regions containing multiple CD8+ T cell epitopes: wealth of HLA-binding motifs and sensitivity to proteasome degradation.

First and foremost among the many factors that influence epitope presentation are the degradation of Ag, which results in peptide liberation, and the presence of HLA class I molecules able to present the peptides to T lymphocytes. To define the regions of HIV-1 Nef that can provide multiple T cell epitopes, we analyzed the Nef sequence and determined that there are 73 peptides containing 81 HLA-binding motifs. We tested the binding of these peptides to six common HLA molecules (HLA-A2, -A3, -A24, -B7, -B8, and -B35), and we showed that most of them were efficient binders (54% of motifs), especially peptides associating with HLA-A3, -B7/35, and -B8 molecules. Nef peptides most frequently recognized by T cells of HIV-1-infected individuals were 90-97, 135-143, 71-81, 77-85, 90-100, 73-82, and 128-137. The frequency of T cell recognition was not directly related to the strength of peptide-HLA binding. The generation of Nef epitopes is crucial; therefore, we investigated the digestion by the 20S proteasome of a large peptide, Nef(66-100). This fragment was efficiently cleaved, and NH(2)-terminally extended precursors of epitope 71-81 were recognized by T cells of an HIV-1-infected individual. These results suggest that a high frequency of T cell recognition may depend on proteasome cleavage.

Amino Acid Motifs↗

Electroconvulsive therapy is associated with superior symptomatic and functional change in depressed patients after psychiatric hospitalization.

BACKGROUND: Major depressive episode is associated with quality of life (QOL) deficits, and QOL improves following remission of depression. We conducted an observational study of the relationship between depressive symptoms and QOL for 1 year after psychiatric hospitalization, and compared QOL in patients who received ECT against those who did not. METHODS: We examined 88 patients with major depressive disorder (53.4+/-15.4 years old; 69 women) upon admission, with repeated measurements at discharge, 1, 3, 6, and 12 months after discharge. Depression severity was measured with the Beck Depression Inventory. QOL measurements encompassed ADLs, IADLs, performance in major roles, and satisfaction with relationships. Treatment for depression was at the discretion of the respective physicians. RESULTS: Depression severity dropped dramatically by discharge, and changed little thereafter. QOL measures showed improvement at the first month, with additional improvement at the third month. Improvement in QOL was closely tied to improvement in depression severity. ECT during the index hospitalization was associated with greater improvement in depressive symptoms and in most measures of QOL. LIMITATIONS: The results of this study may not apply to the treatment of outpatients, and the large number of statistical comparisons may have resulted in some spurious associations. CONCLUSIONS: Inpatient treatment of depression is followed by improvement in QOL. Novel findings in this study include evidence that maximum improvement in QOL does not occur until an average of 3 months after discharge, and that ECT-treated patients had superior outcomes.

Adult↗

Bypass graft to the midpopliteal artery with a combined anterior and posterior approach.

PURPOSE: The medial supragenicular and infragenicular approaches to the popliteal artery were introduced almost 50 years ago and replaced the posterior approach to the popliteal artery for distal graft implantation. We review a contemporary series of bypass grafts to the midpopliteal artery by use of a combined anterior and posterior approach to evaluate its potential clinical benefits. TECHNIQUE: After the proximal graft anastomosis is constructed, an incision is made in the popliteal fossa to access the midpopliteal artery, the graft is passed into that incision, and all but the popliteal incision is closed. The patient is turned, the midpopliteal artery dissection is completed, and the graft is anastomosed distally. METHODS: Fifty-seven bypass grafts, implanted distally on the midpopliteal artery by this technique over a 13-year period, chosen in preference to an infragenicular bypass graft in selected patients when a supragenicular bypass was not feasible, were assessed in terms of indications for surgery, conduit type, complications, length of postoperative hospitalization, and graft patency. RESULTS: Bypass grafting originated from the axillary artery in two cases, the common iliac artery in one case, and the femoral artery in 54 cases. The procedure was performed in five patients with a popliteal trifurcation anomaly, nine patients with a blind popliteal segment, 20 patients with limited length of autologous vein, and five patients with an above-knee graft infection requiring an alternate path for revascularization. Autologous vein was used in 35 and polytetrafluoroethylene (PTFE) in 19 bypass grafts. Three other patients had a composite sequential femoral-popliteal-tibial bypass graft, with PTFE and autologous vein. Postoperative (30 day) complications include one death (composite sequential), one stroke (PTFE), and one graft thrombosis (saphenous vein). The mean postoperative hospitalization for the last 31 patients was 4.2 +/- 3.7 days. In the autologous vein group, the 1-year primary patency rate was 87%, and the primary assisted patency rate was 94%. In the PTFE group, the 1-year primary patency rate was 72%. Two composite sequential grafts remained patent at 1 year. CONCLUSIONS: Bypass grafting to the midpopliteal artery with a combined anterior and posterior approach offers a safe and effective option to below-knee bypass grafting when an above-knee bypass grafting is not feasible. Compared with the medial infragenicular incision, the posterior incision results in reduced morbidity rates, rapid mobilization, and early hospital discharge.

Aged↗

Arteriovenous fistula construction in the thigh with transposed superficial femoral vein: our initial experience.

PURPOSE: The National Kidney Foundation-Dialysis Outcomes Quality Initiative guidelines favor autogenous vein for arteriovenous fistulas (AVFs). This report describes our experience constructing AVFs in the lower extremities of selected patients with the superficial femoral vein (SFV). PATIENTS AND METHODS: This is a retrospective analysis of 25 patients who had AVF construction with SFV from March 1998 to July 2000. In all patients upper extremity access had been exhausted. Eighteen (72%) patients were female, 15 (60%) had diabetes, and 14 (56%) were obese (body mass index > 30 kg/m(2)). The SFV was freed from the supragenicular popliteal level to the profunda femoris vein and divided distally. Eighteen (72%) patients had SFV transposition and distal superficial femoral artery reimplantation; 10 veins were banded to reduce the incidence of postoperative steal syndrome. In seven patients (28%) a composite loop fistula was constructed with a deeply buried 4- to 7-mm polytetrafluoroethylene (PTFE) graft proximally and with superficially transposed SFV distally. One of these seven patients had a PTFE above-knee femoral-popliteal bypass graft with banding of the vein at its takeoff from the distal PTFE graft. RESULTS: Mean follow-up was 9.1 months. One patient died before the fistula could be used. Seven patients (28%) experienced major wound complications. Mean ankle/brachial index before operation was 1.03, and after operation it was 0.81 (paired difference [n = 16] = -0.26.) Mean ankle circumference before operation was 19.5 cm, and after operation it was 20.7 cm (paired difference [n = 17] = +0.87.) Cumulative primary fistula patency at 6 and 12 months was 78% and 73%, respectively. Cumulative secondary fistula patency at 6 and 12 months was 91% and 86%, respectively. There were no fistula infections. One patient eventually had an above-knee amputation after experiencing an acute compartment syndrome. Eight patients required a second operation to alleviate a symptomatic steal syndrome. CONCLUSIONS: The SFV is an excellent conduit for vascular access, whether it is transposed or is part of a composite PTFE-SFV fistula. In this series, fistula infection was nonexistent, thrombosis rates were low, and clinical evidence of venous hypertension was minimal. The major impediment to unrestricted use of SFV in constructing AVFs is a high incidence of clinically significant postoperative ischemia requiring reoperation.

Arteriovenous Shunt, Surgical↗

Subjective measurement of insomnia and quality of life in depressed inpatients.

Insomnia and major depressive episodes (MDE) have each been associated with quality of life (QOL) deficits. In this study we examined insomnia as an independent predictor of QOL deficits during MDE, and used a secondary analysis of cross-sectional data. The study was based at the inpatient psychiatric ward and included 88 adults (mean age 53; 78% women). We assessed insomnia severity with the 21-item Hamilton Rating Scale for Depression (HRSD) and the Beck Depression Inventory (BDI). Measurements of QOL in the week prior to admission included activities of daily living (ADLs), instrumental ADLs (IADLs), daily living and role functioning, and relation to self and colleagues (the last two both subscales of the Basis 32). Linear regression models used the insomnia items as independent variables and the QOL measures as the dependent variables, after adjusting for age and nonsleep related depression severity. The results showed that 93% of patients endorsed insomnia on the observer-rated HRSD, and 97% endorsed sleep disturbance in the self-rated BDI. However, the insomnia items on the HRSD and BDI showed poor concurrent validity. Increasing severity of insomnia on the HDRS was associated with better QOL, while increasing severity of insomnia on the BDI was associated with worse QOL. We conclude that the BDI and HRSD do not produce equivalent measures of insomnia severity in depressed inpatients, and each insomnia measure has a unique relationship with QOL.

Adult↗

Dendritic cells transfected with the nef genes of HIV-1 primary isolates specifically activate cytotoxic T lymphocytes from seropositive subjects.

The HIV-1 Nef protein down-modulates surface expression of MHC class I proteins. Primary infected T lymphocytes thus escape lysis by cytotoxic T lymphocytes (CTL). In contrast, during HIV-1 infection there are strong CTL responses to several HIV proteins, and there is mounting evidence that CTL are critical for controlling the virus. The present study was carried out to assess Nef protein-cell interaction as it occurs in naturally infected antigen-presenting cells. To evaluate the presentation of peptides derived from viral antigen to CTL, we transfected nef genes obtained from peripheral blood mononuclear cells of HIV-1-seropositive subjects into dendritic cells isolated from monocytes of healthy donors. We demonstrate that expression and subsequent processing of Nef by transfected dendritic cells did not alter the presentation of an immunodominant epitope of Nef to CTL of HIV+ subjects. However, mutations in nef gene sequences from primary isolates may abolish this presentation by a mechanism that probably interferes with protein processing.

Antigen Presentation↗

Effects of mood and age on quality of life in depressed inpatients.

BACKGROUND: Prior investigations have demonstrated a link between quality of life (QOL) deficits and depression. This report elaborates on prior investigations findings by implementation of formal assignment of the diagnosis of depression and a hierarchical approach to assessment of QOL. METHODS: A masters or doctoral level mental health clinician used the SCID to confirm a diagnosis of major depression in ninety psychiatric inpatients. Function was assessed with the PSMS (a measure of ADL), the IADL scale, and the "daily living and role functioning" and the "relation to self and others" subscales of the Basis-32. RESULTS: Patient age and severity of depression were the most consistent predictors of QOL deficits, although the direction of the age-effect on QOL depended on the specific measure of QOL. Increasing severity of depression was consistently associated with worse QOL, and remained significant after adjusting for age. LIMITATIONS: The cross-sectional method of this study limits the inference of causality between depression severity and poor QOL. CONCLUSIONS: QOL deficits in acutely depressed hospitalized patients occur at multiple strata in the hierarchy of behavior and are most consistently influenced by age and severity of depression. The effect of age on QOL in depressed inpatients is complex, and age is not uniformly associated with poor QOL.

Adult↗

Bright light therapy: improved sensitivity to its effects on rest-activity rhythms in Alzheimer patients by application of nonparametric methods.

Sleep-wake rhythm disturbances in patients with Alzheimer's disease (AD) make a strong demand on caregivers and are among the most important reasons for institutionalization. Several previous studies reported that the disturbances improve with increased environmental light, which, through the retinohypothalamic tract, activates the suprachiasmatic nucleus (SCN), the biological clock of the brain. The data of recently published positive and negative reports on the effect of bright light on actigraphically assessed rest-activity rhythms in demented elderly were reanalyzed using several statistical procedures. It was demonstrated that the light-induced improvement in coupling of the rest-activity rhythm to the environmental zeitgeber of bright light is better detected using nonparametric procedures. Cosinor, complex demodulation, and Lomb-Scargle periodogram-derived variables are much less sensitive to this effect because of the highly nonsinusoidal waveform of the rest-activity rhythm. Guidelines for analyses of actigraphic data are given to improve the sensitivity to treatment effects in future studies.

Activity Cycles↗

Valproate therapy for prevention of posttraumatic seizures: a randomized trial.

OBJECT: Seizures frequently accompany moderate to severe traumatic brain injury. Phenytoin and carbamazepine are effective in preventing early, but not late, posttraumatic seizures. In this study the authors compare the safety and effectiveness of valproate with those of short-term phenytoin for prevention of seizures following traumatic brain injury. METHODS: The study was a randomized, double-blind, single-center, parallel-group clinical trial. Treatment began within 24 hours of injury. One hundred thirty-two patients at high risk for seizures were assigned to receive a 1-week course of phenytoin, 120 were assigned to receive a 1-month course of valproate, and 127 were assigned to receive a 6-month course of valproate. The cases were followed for up to 2 years. The rates of early seizures were low and similar when using either valproate or phenytoin (1.5% in the phenytoin treatment group and 4.5% in the valproate arms of the study; p = 0.14, relative risk [RR] = 2.9, 95% confidence interval [CI] 0.7-13.3). The rates of late seizures did not differ among treatment groups (15% in patients receiving the 1-week course of phenytoin, 16% in patients receiving the 1-month course of valproate, and 24% in those receiving the 6-month course of valproate; p = 0.19, RR = 1.4, 95% CI 0.8-2.4). The rates of mortality were not significantly different between treatment groups, but there was a trend toward a higher mortality rate in patients treated with valproate (7.2% in patients receiving phenytoin and 13.4% in those receiving valproate; p = 0.07, RR = 2.0, 95% CI 0.9-4.1). The incidence of serious adverse events, including coagulation problems and liver abnormalities, was similar in phenytoin- and valproate-treated patients. CONCLUSIONS: Valproate therapy shows no benefit over short-term phenytoin therapy for prevention of early seizures and neither treatment prevents late seizures. There was a trend toward a higher mortality rate among valproate-treated patients. The lack of additional benefit and the potentially higher mortality rate suggest that valproate should not be routinely used for the prevention of posttraumatic seizures.

Adult↗

Pretreatment differences in specific symptoms and quality of life among depressed inpatients who do and do not receive electroconvulsive therapy: a hypothesis regarding why the elderly are more likely to receive ECT.

Electroconvulsive therapy (ECT) is among the most commonly performed medical procedures requiring general anesthesia in the United States. Nevertheless, very little is known about the characteristics of depressed patients who receive ECT and how they differ from depressed patients receiving psychotropic medication. We conducted a detailed examination of demographic, clinical, and quality-of-life (QOL) measurements in a group of 90 depressed inpatients, and we then used these measurements to contrast the 31 patients who received ECT with the 59 who received alternative therapies. The ECT group did not differ from the non-ECT group in gender composition, marital status, race, education, employment status, overall severity of depression, chronicity of depression, adequacy of prehospitalization antidepressant treatment, extent of physical illness, or extent of social support. The ECT group was older. Furthermore, the ECT group had greater weight loss, worse functioning in activities of daily living (ADLs), and worse functioning in instrumental activities of daily living (IADLs). The differences in weight loss, ADL, and IADL scores disappeared after age adjustment. However, statistical adjustment for age revealed that the ECT group reported worse capacity in their daily living and role functioning than did the non-ECT group. We conclude that the decision to pursue ECT is based in part on the perceived effect of the depression on QOL, as well as the severity of specific symptoms such as weight loss. The elderly seem particularly vulnerable to depression-related functional deficits and weight loss, and this may explain why prior studies showed a differential use of ECT in the elderly.

Adult↗

Practice of geriatric psychiatry and mental health services for the elderly: results of an international survey.

The authors conducted a survey of members of the International Psychogeriatric Association (IPA) to determine the state of development of both the profession of geriatric psychiatry and services for mentally ill elderly. Ratings for both issues were based on a scale of 1 to 4, with 1 being little to no development and 4 being the highest. A rating of 2 was set as the desired minimum, and 12 countries met this goal in both categories, with 6 more countries reaching this goal in service development only. We conclude that although the field of geriatric psychiatry and services for mentally ill elderly are still underdeveloped in much of the world, in many countries they are developed sufficiently enough that the IPA is in an excellent position to provide both information and technical assistance to nations wishing to advance.

Aged↗

Risks and benefits of diagnostic angiography after aneurysm surgery: a retrospective analysis of 597 studies.

INTRODUCTION: Cerebral angiography performed after aneurysm surgery can identify causes of morbidity and mortality that may be corrected. The risks and benefits of angiography that is performed after aneurysm surgery, however, have not been clearly defined. We therefore reviewed our experience with postoperative angiography to determine its dangers and benefits. METHODS: During 10 years, 543 consecutive patients received treatment for cerebral aneurysms. A retrospective analysis of 597 diagnostic angiograms obtained after aneurysm surgery for 494 of these patients was performed. RESULTS: Catheter-induced vessel spasm and dissection, occurring most frequently in the internal carotid artery, were observed in seven (1.2%) and six (1%) studies, respectively. No angiography-associated strokes were identified. No association between age, smoking, hypertension, blood pressure, atherosclerosis, or severe vasospasm and angiographic complications was observed. Aneurysm remnants were identified in 36 (5.7%) of the 637 aneurysms that were surgically treated. Atherosclerosis (P < 0.01) or multiple clip applications (P < 0.01) were significantly associated with aneurysm remnants. Angiographic vessel occlusion was observed in 28 (5.7%) patients and resulted in stroke in 14 of these patients. Vessel occlusion was significantly associated with increasing aneurysm size (P < 0.001), atherosclerosis (P < 0.001), temporary clips (P < 0.001), multiple clips (P=0.03), multiple clip applications (P=0.001), and a new postoperative neurological deficit (P=0.002). Severe vasospasm and newly identified aneurysms were observed in 51 and 16 patients, respectively. CONCLUSION: Angiography after aneurysm surgery is safe and can be routinely performed. Angiography after aneurysm surgery should be particularly considered for patients with large aneurysms or cerebrovascular atherosclerosis and for those who develop new postoperative neurological deficits.

Adolescent↗

DDK rates in the paediatric clinic: a methodological minefield.

There are substantial differences in the norms reported for speech diadochokinetic (DDK) rates among several published studies. These may well be due to differences in type of data used, methods of data collection and DDK rate calculation. Such differences doubtless also exist in the calculation of DDK rate in routine clinical assessment. Methodological problems in DDK rate measurement are identified and discussed and a detailed protocol for DDK measurement is described.

Adolescent↗

Assessing HCFA's Health Care Quality Improvement Program.

BACKGROUND: In 1992 the Health Care Financing Administration introduced the Health Care Quality Improvement Program (HCQIP), through which quality improvement projects are conducted in partnership with quality improvement organizations (QIOs), hospitals, health plans, or physicians. An evaluation of HCQIP began in May 1996 in response to the QIOs' request for an independent assessment of their activities. METHODOLOGY: The methodology and objectives of the evaluation were determined by an independent panel. The QIOs' full cohort of 970 HQIP projects could not be reviewed in the 10-month time frame available, but two topics were chosen: the management of warfarin or aspirin in patients with atrial fibrillation and the management of community-acquired pneumonia. FINDINGS: Analyses were limited to the 49 of the 68 projects that had progressed to the "improvement plan implemented" stage. However, only 39 of these 49 projects had information on outcomes, organization changes, and/or changes in process of care--and only 20 of the 49 had moved beyond the "improvement plan implemented" phase. Feedback of data led hospitals collaborating on improvement projects to revise or create processes of care. DISCUSSION: Although the assessment is the most comprehensive of its type to date, it should be viewed as a pilot study of some of the methods that could be incorporated in a more extensive and rigorous future evaluation of the impact of the HCQIP projects. Specific recommendations include random sampling of HCQIP projects across all clinical areas, conducting both prospective and retrospective assessments, developing uniform process and outcome program impact measures, and developing sustainable, ongoing automated data abstraction and analysis systems.

Atrial Fibrillation↗

Phototherapy for patients with Alzheimer disease with disturbed sleep patterns: results of a community-based pilot study.

We examined the entraining effects of phototherapy delivered by light visors on disturbed sleep patterns of community-dwelling research subjects with Alzheimer disease (AD). The pilot project used a single subject design and activity monitoring as the primary outcome measures. The protocol consisted of a 5-day baseline monitoring period, followed by 10 consecutive days of phototherapy (2,000 lux of full spectrum bright light) delivered by light visors for 2 hours each morning; this was followed by an additional 14 days of activity monitoring. Cosinor analyses found no consistent changes in acrophase, mesor, or amplitude. Observed changes in acrophase were consistent with phase advancement of the rest-activity cycle and consistent with the biological intervention. Changes in the number of nighttime awakenings were not found. One subject had a significant increase in total sleep time, whereas another had a significant decrease in total sleep time. Failure to find a consistent biological effect of light on AD subjects may be secondary to: (1) insufficient duration of light exposure; (2) timing of light administration (given at a time when circadian rhythm is refractory to the effects of light); (3) advanced stages of AD making the Y circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus insensitive to the biological effects of light; and (4) inadequacy of light visors as a means of providing light.

Activities of Daily Living↗