Showing papers by "Jewish Hospital published in 2000"

BRCA1 and BRCA2 Mutation Analysis of 208 Ashkenazi Jewish Women with Ovarian Cancer

Abstract: Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in ∼2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 41.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5–6.8; P=.002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4–3.0; P=.0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.

Fluconazole vs low-dose amphotericin B for the prevention of fungal infections in patients undergoing bone marrow transplantation: a study of the North American Marrow Transplant Group.

Abstract: Systemic fungal infections are a major problem in bone marrow transplant recipients who have prolonged neutropenia or who receive high-dose corticosteroids. Prophylaxis with Fluconazole or low-dose amphotericin B reduces, but does not eliminate these infections. To determine which prophylactic agent is better, we performed a prospective randomized study. Patients undergoing allogeneic (related or unrelated) or autologous marrow or peripheral stem cell transplantation were randomized to receive Fluconazole (400 mg/day p. o. or i.v.) or amphotericin B (0.2 mg/kg/day i.v.) beginning 1 day prior to stem cell transplantation and continuing until recovery of neutrophils to >500/microl. Patients were removed from their study drug for drug-associated toxicity, invasive fungal infection or suspected fungal infection (defined as the presence of fever >38 degrees C without positive culture while on broad-spectrum anti-bacterial antibiotics). Proven or suspected fungal infections were treated with high-dose amphotericin B (0.5-0.7 mg/kg/day). Patients were randomized at each institution and stratified for the type of transplant. The primary end-point of the study was prevention of documented fungal infection; secondary endpoints included fungal colonization, drug toxicity, duration of hospitalization, duration of fever, duration of neutropenia, duration and total dose of high-dose amphotericin B and overall survival to hospital discharge. From July 1992 to October 1994, a total of 355 patients entered into the trial with 159 patients randomized to amphotericin B and 196 to Fluconazole. Patient groups were comparable for diagnosis, age, sex, prior antibiotic or antifungal therapy, use of corticosteroids prior to transplantation and total duration of neutropenia. Amphotericin B was significantly more toxic than Fluconazole especially in related allogeneic transplantation where 19% of patients developed toxicity vs 0% of Fluconazole recipients (p 0.05). In this prospective trial, low-dose amphotericin B prophylaxis was as effective as Fluconazole prophylaxis, but Fluconazole was significantly better tolerated.

The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor type 1 gene: An independent risk factor for serious pregnancy complications

Abstract: The specific aim of the current study of 133 women with at least 1 pregnancy and measures of hypofibrinolytic and thrombophilic gene mutations was to determine retrospectively whether the mutations were associated with adverse pregnancy outcomes including prematurity, miscarriage, stillbirth, intrauterine growth retardation (IUGR), eclampsia, and abruptio placentae. Four gene mutations (factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], prothrombin, and 4G/5G polymorphism of the plasminogen activator inhibitor type 1 [PAI-1] gene) were assessed by polymerase chain reaction (PCR). One hundred twenty-two women were genotyped for all 4 genes and divided into gene mutation (n = 68) and non-gene (n = 54) groups. The gene mutation group included those with at least 1 thrombophilic mutation (heterozygous for factor V Leiden, heterozygous for prothrombin, and homozygous for MTHFR), or hypofibrinolysis with homozygosity for the 4G polymorphism of the PAI-1 gene. The non-gene mutation group included those with no mutation for all 4 genes (wild-type normal) or who were wild-type normal for the prothrombin and factor V Leiden mutations and heterozygous for MTHFR and/or 4G/5G for the PAI-1 gene, neither heterozygosity associated with coagulation abnormalities. The 68 women with gene mutations, versus 54 in the non-gene mutation group, has more prematurity (10% v 4%, chi2 = 5.4, P = .021), more IUGR (3% v 0%, P = .035), and more total complications of pregnancy (37% v 21%, chi2 = 11.6, P = .001). The number of pregnancies (P = .0001) and 4G/4G polymorphism of the PAI-1 gene (P = .029) were positively associated with complications of pregnancy by stepwise logistic regression when the age, number of pregnancies, and all 4 gene mutations were the explanatory variables. Heritable hypofibrinolysis, mediated by 4G/4G homozygosity for the PAI-1 gene, is an independent significant, potentially reversible risk factor for pregnancy complications, probably acting through thrombotic induction of placental insufficiency.

Mycobacterium terrae: Case Reports, Literature Review, and In Vitro Antibiotic Susceptibility Testing

Abstract: Mycobacterium terrae infection can cause debilitating disease that is relatively resistant to antibiotic therapy. Two cases are presented, and data from an additional 52 reports from the literature are reviewed. Tenosynovitis of the upper extremity, often following trauma, was the most commonly reported presentation (59% of cases), with pulmonary disease occurring in an additional 26% of cases. Underlying medical problems were absent (44%) or not reported (28%) in 72% of the cases. One-half of the patients with upper extremity tenosynovitis were treated with local or systemic corticosteroids, before microbiological identification. Only one-half of the patients with tenosynovitis who were followed up for 6 months had clinical improvement or were cured. The other one-half of the patients required repeated debridement, tendon extirpation, or amputation. The best antimicrobial therapy for M. terrae infection is unknown but might include a macrolide antibiotic plus ethambutol and one other effective drug for at least 12 months after clinical response. Parenteral treatment with an aminoglycoside and surgery may be useful in selected cases.

Clinical and genetic variables associated with acute arousal and nonarousal-related cardiac events among subjects with the long QT syndrome

Abstract: In patients with the long QT syndrome (LQTS), the occurrence of cardiac events (syncope or cardiac arrest) is frequently associated with acute arousal caused by exercise, swimming, emotion, or noise. However, cardiac events may also occur during sleep or with ordinary daily activities. The purpose of this study was to determine whether there are differential clinical, electrocardiographic, and genetic features among LQTS patients who experienced cardiac events with and without acute arousal. We identified 1,325 patients with cardiac events from the International LQTS Registry. Based on the precipitating conditions of the first event, 427 patients were classified as arousal, 345 as nonarousal, and the remaining 553 were unknown (not classifiable). Gene linkage was known in 78 of the 772 patients with classifiable first events. The age at first cardiac event was significantly younger in the arousal than the nonarousal group (11.7 vs 15.5 years, respectively; p

Psychiatric assessment of candidates for hand transplantation.

Abstract: An important part of the pretransplant evaluation of candidates for hand transplantation is a psychiatric assessment to formulate psychological benefits and risks of transplantation and determine any appropriate psychosocial interventions to optimize the patient's candidacy for the procedure and prevent psychiatric morbidity. Screening data are presented from 213 individuals who contacted a national referral center for hand surgery regarding hand transplantation, and from the subsequent detailed psychiatric assessments of 9 individuals considering the procedure. Most of the nine patients undergoing intensive psychiatric assessment were assessed as demonstrating an overall favorable profile of psychological benefits and risks. In addition to providing information regarding the psychological experience of patients with amputations and their motivation for hand transplantation, it is hoped this information, as compared with posttransplant outcome data, will help further refine the assessment of candidates for this procedure and possibly other forms of composite tissue allotransplantation. © 2000 Wiley-Liss, Inc. Microsurgery 20:453–457 2000

Initial experience with the AbioCor implantable replacement heart at the University of Louisville.

Abstract: Potential benefits of heart transplantation are limited by the severe donor organ shortage. The AbioCor implantable replacement heart has been developed as a potential alternative to heart transplantation. We report our initial experience with the AbioCor in a bovine model. A right thoracotomy was performed for access to the heart and great vessels. After initiation of cardiopulmonary bypass, excision of the native ventricles was followed by orthotopic placement of the IRH and complete implantation of the transcutaneous energy transfer coil, controller, and battery pack. Invasive monitoring of IVC, SVC, carotid artery, pulmonary artery, and left atrial (LA) pressures was performed in all animals. Twelve calves have undergone implantation of the AbioCor. There were three early deaths, one from bleeding, one from respiratory failure, and one from neurodysfunction from low flow during CPB. Nine animals have had a normal recovery and survived a mean of 24.5 days (range, 4-48 days). All the animals have demonstrated excellent hemodynamics with the maintenance of normal pressures in the LA, SVC, IVC, pulmonary artery, and aorta. Adjustment of the right-sided internal hydraulic fluid shunt has allowed for control of right-left balance and, thereby, manipulation of left and right side filling pressures. Late morbidity has consisted of neck wound infection and sepsis, pneumonia, and bleeding. Successful orthotopic implantation of all components of the AbioCor has been achieved in a bovine model. This device has demonstrated restoration of normal hemodynamics and excellent function of the atrial hydraulic shunt to achieve right-left balance.

Comparison of the effectiveness of two pressure-relieving surfaces: low-air-loss versus static fluid.

Abstract: Limited research has been done to determine the effectiveness of the multitude of pressure reduction devices currently available for patient care. The purpose of this investigation was to examine the relative effectiveness of a dynamic low-air-loss (LAL) mattress and a static fluid mattress in reducing the risk of pressure ulcer development. The investigation consisted of two components: a comparative laboratory study and a retrospective clinical study. In the laboratory study, tissue interface pressures were measured on the two surfaces at three interface sites in a sample of six healthy adult volunteers. In the clinical study, a retrospective chart review was conducted to compare the actual incidence of pressure ulcer formation in a sample of 73 postoperative transplant patients who were placed on either the static fluid or LAL product. The instruments used were the Xsensor Pressure Mapping System (laboratory) and chart review tool (clinical). The main outcome measures included tissue interface pressures and incidence of pressure ulcer formation. The results were as follows: the laboratory study revealed significantly lower sacral pressures (t = -5.30, P = .003) on the low-air-loss mattress than on the static fluid mattress. Pressures did not differ significantly at the heel or trochanter sites. In the clinical study, the overall incidence of skin breakdown was 8.2%, with 5 occurrences (13.8%) in the LAL group and 1 occurrence (2.7%) in the static fluid group. However, this difference was not significant (Fisher's exact test = 0.107, P = .09). When considered jointly, the results of the two studies suggest that the static fluid and LAL products may be comparable in efficacy. Although the relatively small sample sizes used in the investigation limit generalizability, the results provide some initial direction for further clinical research in this area.

Take the wind out of asthma.

Abstract: Learn how to take a team approach to managing your patient's asthma. Strategies focus on preventing acute attacks, relieving acute attacks when they occur, and preventing complications.

Adaptation of a weight management program for a potential lung transplant candidate.

Abstract: Obesity is a relative contraindication for heart and lung transplantation at most transplant centers. Surgical risks are higher for obese patients, and 1 study suggests that obesity is significantly correlated with higher posttransplant death rates in cardiac transplantation. Obesity is a restrictive disease that contributes to exercise intolerance in patients with lung disease. A weight management group was formed at a transplant center to help obese patients with heart and/or lung disease lose weight and maintain their goal weight, with the hope of decreasing their waiting time to be listed for transplantation and their incidence of weight-related complications. Some patients experienced symptomatic improvment, which delayed their need for heart or lung transplantation.

Psychiatric Clinical Nurse Specialist as Chemical Dependence Consultant

Abstract: A significant number of hospitalized individuals have alcohol- and drug-related health problems that are often unrecognized or untreated. A psychiatric clinical nurse specialist (CNS) in chemical dependence is in an excellent position to serve as a consultant to access those in need of services. This article describes how the CNS role was marketed and implemented in an acute care setting. The role is described, and some associated rewards and challenges are discussed.

Chemoreflexes: an experimental study.

Abstract: Hypothesis Transmyocardial laser revascularization (TMLR) will not denervate the heart, because it does not destroy all of the afferents. This study was designed to determine if stimulation of cardiac sympathetic and vagal afferents from an area of the left ventricle treated with TMLR could evoke reflex effects, and thus whether TMLR would denervate the heart. Methods The effect of TMLR on reflexes evoked by chemically stimulating cardiac afferents was examined in 9 dogs. Bradykinin and capsaicin were applied topically or injected into the left anterior descending coronary artery before and after TMLR and after bilateral vagotomy and sympathectomy. Aortic (AoP) and left ventricular pressures (LVP) and electrocardiography were monitored. The first derivatives of LVP (dP/dt) were calculated. Results Topical bradykinin elicited variable hemodynamic responses. Topical capsaicin evoked pressor responses, increasing mean (± SEM) AoP (105±9 to 115±9 mm Hg; P P P P P Conclusion Since activation of cardiac afferent nerves and reflex responses remained intact after TMLR, but changed after vagotomy or sympathectomy, TMLR does not denervate the heart sufficiently to be the cause of improved angina after TMLR.

Directional coronary atherectomy in intermediate sized vessels: final results of the intermediate vessel atherectomy trial (IVAT).

Abstract: Revascularization options for intermediate sized vessels (2.5-2.9 mm) have historically been limited. IVAT is a pilot study to assess the efficacy and safety of debulking intermediate sized vessels using directional coronary atherectomy (DCA). Between March 1996 and June 1997, 50 patients were enrolled at seven hospitals in the United States. Of those patients, 70% presented with unstable angina and 52% had single vessel disease. Of the lesions treated, 96% were de novo. Adjunctive PTCA after DCA was performed in 90% of cases at the discretion of the investigator to maximize luminal diameter. The GTO DCA device was used in 90% of cases. Procedural success (residual stenosis <50% without major complications) was 94%. Stents were placed in 12% of patients. The only complications were three non-Q wave MIs. Mean reference vessel diameter increased from 2.49 mm pre-procedure to 2.57 mm after DCA and 2.61 post-procedure; mean MLD increased from 0.76 mm to 2.03 mm to 2.31 mm; and mean stenosis decreased from 70% to 21% post DCA and to 11% post procedure. At six months follow-up, 18.0% of target lesions required revascularization. Total revascularization, including non-target vessels, was 32%. These results suggest that DCA has a high procedural success rate and a low target lesion revascularization rate in intermediate sized vessels.