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D A Katz

Publications and source records attributed to D A Katz.

At least 19 recordsLinked to original sources
PubMed2006

Variants in Apaf-1 segregating with major depression promote apoptosome function.

APAF1, encoding the protein apoptosis protease activating factor 1 (Apaf-1), has recently been established as a chromosome 12 gene conferring predisposition to major depression in humans. The molecular phenotypes of Apaf-1 variants were determined by in vitro reconstruction of the apoptosome complex in which Apaf-1 activates caspase 9 and thus initiates a cascade of proteolytic events leading to apoptotic destruction of the cell. Cellular phenotypes were measured using a yeast heterologous expression assay in which human Apaf-1 and other proteins necessary to constitute a functional apoptotic pathway were overexpressed. Apaf-1 variants encoded by APAF1 alleles that segregate with major depression in families linked to chromosome 12 shared a common gain-of-function phenotype in both assay systems. In contrast, other Apaf-1 variants showed neutral or loss-of-function phenotypes. The depression-associated alleles thus have a common phenotype that is distinct from that of non-associated variants. This result suggests an etiologic role for enhanced apoptosis in major depression.

Alleles↗
PubMed2005

Periacetabular osteotomy in patients with Down's syndrome.

We treated eight dysplastic acetabula in six skeletally mature patients with Down's syndrome by a modified Bernese periacetabular osteotomy. The mean age at the time of surgery was 16.5 years (12.8 to 28.5). Mean length of follow-up was five years (2 to 10.4).Pre-operatively the mean (Tonnis) acetabular angle was 28 degrees, the centre-edge angle was -9 degrees, and the extrusion index was 60%; post-operatively they were 3 degrees, 37 degrees, and 17%, respectively. Two patients with post-operative (Tonnis) acetabular angles > 10 degrees developed subluxation post-operatively and required secondary varus derotation femoral osteotomies. Another patient developed a late labral tear which was treated arthroscopically. All eight hips remain clinically stable, and are either asymptomatic or symptomatically improved. These results suggest that the modified Bernese periacetabular osteotomy can be used successfully in the treatment of acetabular dysplasia in patients with Down's syndrome.

Acetabulum↗
PubMed2001

Randomised clinical trial of two bypass operations for unresectable cancer of the pancreatic head.

OBJECTIVE: To compare two different types of prophylactic gastric bypass in patients with cancer of the pancreatic head who were not suitable for curative resection. DESIGN: Prospective study. SETTING: University hospital, Turkey. SUBJECTS: 44 patients with unresectable cancer of the pancreatic head without duodenal obstruction who presented between May 1995 and June 2000 who were randomised into 2 groups. INTERVENTIONS: 22 patients had an antecolic, isoperistaltic gastrojejunostomy, jejunojejunostomy, and hepaticojejunostomy after cholecystectomy. The remaining 22 had a hepaticojejunostomy and antecolic, antiperistaltic gastrojejunostomy procedure after cholecystectomy. MAIN OUTCOME MEASURES: Mortality, morbidity, postoperative course, and survival. RESULTS: There were no significant differences between the groups in the incidence of postoperative complications, time until restoration of oral diet, relaparotomy rate, late upper gastrointestinal bleeding, mortality, duration of hospital stay, and survival. The isoperistaltic operation took significantly longer than the antiperistaltic operation (p < 0.001) and there was less delayed gastric emptying in the antiperistaltic group but not significantly so. Both operations caused a significant lengthening in the postoperative gastric emptying time (p = 0.04 and p = 0.01, respectively). CONCLUSION: Both procedures are suitable for patients with unresectable carcinoma of the pancreatic head without impending duodenal obstruction. There was a trend towards better clinical results with the isoperistaltic procedure.

Adult↗
PubMed2001

Effect of treatment on quality of life among men with clinically localized prostate cancer.

BACKGROUND: Quality-of-life outcomes are an important consideration for patients evaluating therapeutic options for localized prostate cancer. OBJECTIVES: The objective of this study was to describe the effect of treatment choice on change in health-related quality of life (HRQOL) among men with clinically localized prostate cancer. RESEARCH DESIGN: This was a prospective observational study. SUBJECTS: The study subjects were 122 men with clinically localized adenocarcinoma of the prostate. Forty-two subjects (34%) underwent radical prostatectomy, 51 (42%) underwent radiation therapy, and 29 (24%) were followed with expectant management. MEASURES: The University of California at Los Angeles Prostate Cancer Quality of Life Inde- and the Medical Outcomes Study Short Form-36 were administered before and 3 and 12 months after initial treatment. The study used an analysis of covariance model adjusted for baseline differences in clinical and demographic factors. RESULTS: Men who underwent radical prostatectomy experienced significant declines in urinary and sexual function and bother that persisted at 12 months after treatment. Men treated with radiation therapy experienced smaller but significant declines in sexual function and a decline in social function. Expectant management patients did not have a significant change in disease-targeted or generic HRQOL domains. Differential rates of change in urinary and sexual function between treatment groups persisted after adjustment for differences in pretreatment clinical and demographic factors. CONCLUSIONS: Men undergoing radical prostatectomy have substantial declines in urinary and sexual function, and men undergoing radiotherapy have declines in sexual function. Men undergoing expectant management have no change in disease-specific or general HRQOL in the first year after treatment.

Adenocarcinoma↗
PubMed2000

Palliative decompression of obstructive hilar malignancies utilizing an extrahilar biliary approach.

Hilar cancers carry a dismal prognosis. Palliation of obstructive jaundice in patients with hilar cancer can be achieved by either surgical or nonsurgical means. Selection of the appropriate palliative measures is a challenging problem. Segmental bilioenteric anastomosis procedures were performed on 19 patients with hilar cancer. Seventeen of the bypasses were done to the segment III duct, known as the ligamentum teres approach, and two bypasses were to the segment V duct. Five patients, who had already been stented percutaneously or endoscopically, were operated on after the stents were clogged and a duodenal obstruction ensued. There were two postoperative deaths (10.5%) and four postoperative complications (21%). All of the 17 surviving patients experienced improvement in the level of jaundice postoperatively and the levels of serum total and direct bilirubin decreased by 78.9% and 84.2%, respectively. Two patients developed late cholangitis before death and were treated by external biliary drainage; one developed duodenal obstruction and was treated by gastrointestinal anastomosis. The mean length of hospital stay was 15.2 days. Mean survival was 8.2 months and the mean period of well-being was 7.8 months. Median survival was 7 months and median period of well being was 7 months. Three patients are still alive at 8, 8, and 24 months. These data suggest that the ligamentum teres approach offers effective palliation for patients with unresectable hilar cancer.

Adult↗
PubMed2000

Impact of obesity on health-related quality of life in patients with chronic illness.

OBJECTIVE: To determine the association between overweight and obesity and health-related quality of life (HRQOL) in patients with chronic conditions typical of those seen in general medical practice, after accounting for the effects of depression and medical comorbidities. DESIGN: Cross-sectional analysis of data from the Medical Outcomes Study. SETTING: Offices of physicians practicing family medicine, internal medicine, endocrinology, cardiology, and psychiatry in three U.S. cities. PATIENTS: We surveyed 2,931 patients with chronic medical and psychiatric conditions. The patients completed a self-administered questionnaire at enrollment and had complete data on height and weight. MEASUREMENTS AND MAIN RESULTS: Body mass index (BMI), chronic medical conditions, and depression were obtained by structured interview. Health-related quality of life was measured by the SF-36 Health Survey. Patients who were overweight (BMI 25.0-29.9 kg/m2), patients with class I obesity (BMI 30.0-34.9 kg/m2), and patients with class II-III obesity (BMI > or = 35 kg/m2) had significantly lower adjusted physical function scores (by 3.4, 7.8, and 13.8 points, respectively) compared with nonoverweight patients. Patients with class I and class II-III obesity also had significantly lower adjusted general health perceptions scores (by 2.8 and 4.4 points, respectively) and lower adjusted vitality scores (by 4.0 and 7.1 points, respectively), compared with nonoverweight patients. No significant differences between nonoverweight, overweight, and obese patients were observed for the mental health scale. Women with elevated BMI had significantly lower HRQOL scores compared with the scores of obese men in several domains. Additionally, blacks with elevated BMI had significantly lower scores than whites in several domains of HRQOL. CONCLUSIONS: Overweight and obesity have the largest association with physical function measures. Recent national standards, which have lowered the threshold for defining overweight, identify patients who are more likely to have clinically significant reductions in HRQOL and functional impairment.

Adult↗
PubMed1999

Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss.

Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.

Adult↗
PubMed1999

Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.

Clinically similar asthma patients may develop airway obstruction by different mechanisms. Asthma treatments that specifically interfere with the 5-lipoxygenase (ALOX5) pathway provide a method to identify those patients in whom the products of the ALOX5 pathway (that is, the leukotrienes) contribute to the expression of the asthma phenotype. Failure of an asthma patient to respond to treatment with ALOX5-pathway modifiers indicates that leukotrienes are not critical to the expression of the asthmatic phenotype in that patient. We previously defined a family of DNA sequence variants in the core promoter of the gene ALOX5 (on chromosome 10q11.2) associated with diminished promoter-reporter activity in tissue culture. Because expression of ALOX5 is in part transcriptionally regulated, we reasoned that patients with these sequence variants may have diminished gene transcription, and therefore decreased ALOX5 product production and a diminished clinical response to treatment with a drug targeting this pathway. Such an effect indicates an interaction between gene promoter sequence variants and drug-treatment responses, that is, a pharmacogenetic effect of a promoter sequence on treatment responses.

Alleles↗
PubMed1999

Extrapituitary parasellar microadenoma in Cushing's disease.

Negative sellar exploration (despite the results of endocrine evaluation indicating Cushing's disease), the high incidence of failure of total hypophysectomy, and remission of Cushing's syndrome after unsuccessful hypophysectomy and sellar irradiation suggest that the etiology of refractory Cushing's disease, in some patients, lies near the sella but not in the pituitary gland. We present 5 patients, out of 626 who received surgery for Cushing's disease, in whom an ACTH-secreting extrapituitary parasellar adenoma was identified: 2 after unsuccessful total hypophysectomy for the treatment of refractory Cushing's disease, 2 after unsuccessful hemihypophysectomy (the first, 2 yr before treatment at the NIH for Nelson's syndrome; and the second, with recurrent Cushing's disease 5 yr after negative transsphenoidal exploration), and 1 with a preoperative diagnosis of an intraclival microadenoma, which was cured by resection of the tumor. In all cases, an extrapituitary parasellar microadenoma was confirmed unequivocally as the cause of the disease, by negative pathology of the resected pituitary gland (patients 1, 2, 3, and 5), and/or the remission of the disease after selective resection of the extrasellar adenoma (patients 3, 4, and 5). Three of 5 patients had a partial empty sella. These patients support the thesis that ACTH-secreting tumors can arise exclusively from remnants of Rathke's pouch, rather than from the adenohypophysis (anterior lobe or pars tuberalis of the pituitary gland) and can be a cause of Cushing's disease. In the sixth presented case, an extrapituitary tumor was suspected at surgery after negative pituitary exploration, but serial sections of the hemihypophysectomy specimen revealed a microscopic focus of tumor at the margin of the resected gland. This case demonstrates the importance of negative pituitary histology to establish the presence of an extrapituitary parasellar tumor as an exclusive source of ACTH, and it supports the value of clinical outcome to establish the diagnosis with selective adenomectomy of an extrapituitary parasellar tumor. In patients with negative pituitary magnetic resonance imaging, especially in the presence of a partial empty sella, the diagnostic and surgical approach in Cushing's disease should consider the identification and resection of extrapituitary parasellar adenoma, which can avoid total hypophysectomy, as was possible in 3 of our 5 patients.

Adenoma↗
PubMed1999

Barriers between guidelines and improved patient care: an analysis of AHCPR's Unstable Angina Clinical Practice Guideline. Agency for Health Care Policy and Research.

OBJECTIVES: To describe common barriers that limit the effect of guidelines on patient care, with emphasis on recommendations for triage in the Agency for Health Care Policy and Research (AHCPR) Unstable Angina Clinical Practice Guideline. DATA SOURCES: Previously reported results from a prospective clinical study of 10,785 patients presenting to the emergency department (ED) with symptoms suggestive of acute cardiac ischemia. STUDY DESIGN: Design is an analysis of the AHCPR guideline with regard to recognized barriers in guideline implementation. Presentation of hypothetical scenarios to ED physicians was used to determine interrater reliability in applying the guideline to assess risk and to make triage decisions. PRINCIPAL FINDINGS: The AHCPR guideline's triage recommendations demonstrate (1) poor interobserver reliability in interpretation by ED physicians; (2) limited applicability of recommendations for outpatient management (applies to 6 percent of patients presenting to the ED with unstable angina); (3) incomplete specifications of exceptions that may require deviation from guideline recommendations; (4) unexpected effects on medical care by significantly increasing the demand for limited intensive care beds; and (5) unknown effects on patient outcomes. In addition, analysis of the guideline highlights the need to address organizational barriers, such as administrative policies that conflict with guideline recommendations and the need to adapt the guideline to conform to local systems of care. CONCLUSIONS: Careful analysis of guideline attributes, projected effect on medical care, and organizational factors reveal several barriers to successful guideline implementation that should be addressed in the design of future guideline-based interventions.

Angina, Unstable↗
PubMed1998

Clinical correlates of insomnia in patients with chronic illness.

BACKGROUND: Patients with chronic insomnia are more likely to develop affective disorders, cardiac morbidity, and other adverse health outcomes, yet many clinicians tend to trivialize the complaint of insomnia or to attribute it only to psychiatric causes. OBJECTIVES: To estimate the prevalence and longitudinal course of insomnia in patients with documented chronic medical illness and/or depression and to quantify the associations between specific chronic conditions and insomnia. METHODS: The presence of mild or severe insomnia was based on responses to a sleep questionnaire completed by 3445 patients with at least 1 of 5 physician-identified chronic conditions (hypertension, diabetes, congestive heart failure, myocardial infarction, or depression) at baseline; a subsample of 1814 patients completed follow-up questionnaires at 2 years. Using multivariate techniques, we evaluated the relationship between chronic conditions, patient-reported comorbidities, and insomnia (complaints of initiating and maintaining sleep), adjusting for sociodemographics and health habits. RESULTS: Sixteen percent of study patients had severe and 34% had mild insomnia at baseline. At 2-year follow-up, 59% (95% confidence interval, 55%-63%) of patients with mild insomnia and 83% (95% confidence interval, 78%-88%) of patients with severe insomnia at baseline still had sleep problems. Odds ratios corresponding to mild and severe insomnia for key risk factors were as follows: current depressive disorder, 2.6 and 8.2; subthreshold depression, 2.2 and 3.4; congestive heart failure, 1.6 and 2.5; obstructive airway disease, 1.6 and 1.5; back problems, 1.4 and 1.5; hip impairment, 2.2 and 2.7; and prostate problems, 1.6 and 1.4. The majority of insomnia-comorbidity associations observed at baseline persisted at 2-year follow-up. CONCLUSIONS: Patients with insomnia require follow-up, as the majority continue to be bothered by difficulty initiating and maintaining sleep. In addition to detecting affective disorders in patients with insomnia, clinicians should focus on medical conditions that disturb sleep, especially cardiopulmonary disease, painful musculoskeletal conditions, and prostate problems.

Airway Obstruction↗
PubMed1997

MR and conventional angiography: work in progress toward assessing utility in radiology.

RATIONALE AND OBJECTIVES: The authors assessed health-related quality of life changes associated with peripheral x-ray angiography and magnetic resonance (MR) angiography. MATERIALS AND METHODS: Utility (the desirability or preference that individuals exhibit for a particular health state) was assessed in 30 patients with peripheral vascular disease referred for angiography by using a rating scale, additional categoric scaling questions to separate preference from experience, a willingness-to-pay technique, functional and cognitive status questions, and a time trade-off technique. All patients underwent both MR angiography and x-ray angiography. RESULTS: Patients reported significantly (P < .05) less anxiety after the test, less pain after the test, fewer new physical limitations, and less effect on performance of daily activities with MR angiography. Findings from the overall rating scale and categoric scaling questions also significantly (P < .05) favored MR angiography. Patients were willing to pay a mean of 2.12% of annual income to avoid MR angiography and a mean of 7.41% to avoid x-ray angiography. The median quality-adjusted life gain required by patients to undergo the procedures was 52.5-60 days for x-ray angiography and 10.5 days for MR angiography, without discounting. CONCLUSION: X-ray angiography has more profound short-term adverse effects on life than does MR angiography. Preference-based measures can be adapted to elicit patient values for short-term health states as seen in radiology.

Angiography↗
PubMed1997

Predicting Clostridium difficile stool cytotoxin results in hospitalized patients with diarrhea.

OBJECTIVE: To validate a model for the prediction of Clostridium difficile cytotoxin assay results, and to identify a subgroup of patients with a very low likelihood of C. difficile-associated disease in whom the yield of routine cytotoxin testing is low. DESIGN: Prospective cohort study. Relevant clinical symptoms, signs, and antibiotic exposure were recorded before reporting of assay results. Each predictor was assigned a score based on regression coefficients, and patients were stratified according to their total score. SETTING: Two urban, tertiary care, university hospitals. PATIENTS: A total of 609 consecutive adult inpatients who received testing for C. difficile cytotoxin during a 3-month period in 1994. MEASUREMENTS AND MAIN RESULTS: The prevalence of positive cytotoxin assays was 8% in the validation set, compared with 14% in the derivation set. Defining patients without both prior antibiotic use and at least one symptom predictor (significant diarrhea or abdominal pain) as a low-risk subgroup, the misclassification rate was 2.8% (5/177) for assay results; of the five misclassified cases patients, only one was judged to have C. difficile-associated disease. Use of this rule to identify low-risk patients could have potentially averted 29% of all cytotoxin assays. CONCLUSIONS: Patients without a history of antibiotic use and either significant diarrhea or abdominal pain are unlikely to have positive C. difficile cytotoxin assays and may not require cytotoxin testing.

Adult↗
PubMed1997

The profile of HIV infection in women: a challenge to the profession.

Human Immunodeficiency Virus (HIV) has become a leading cause of morbidity and mortality among women and children in the United States. As advances are made in the area of diagnosis and treatment of HIV infection, strategies must be developed to support the psychosocial needs of women with HIV disease. The diagnosis of HIV infection in women and their children presents a unique array of complicated social, emotional and medical consequences. Care must be provided in a holistic manner with special emphasis on the needs of women within a systemic context.

Female↗