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Biomedical subjects

S Weitzman

Publications and source records attributed to S Weitzman.

At least 19 recordsLinked to original sources
PubMed2006

[Trends and characteristics of diabetes-related lower limb amputations in the Negev, 1996-1999].

BACKGROUND: The loss of a lower limb because of diabetic foot problems such as infections is an important complication of diabetes mellitus. The goals of this study were: (1) to examine trends in incidence of diabetic-related lower limb amputations in the Negev, (2) to describe the clinical characteristics of patients who underwent amputations in the Soroka University Medical Center and (3) to estimate in-hospital mortality and its predictors. METHODS: This study included all diabetic patients who underwent non-traumatic lower limb amputation in the Soroka Hospital during the period 1996-1999. The computerized hospitalization files and surgery logs during the study period were reviewed for ICD-9 diagnoses of diabetes and amputations. For each patient, hospitalization records were abstracted and data on socio-demographic and clinical characteristics were collected. RESULTS: During the study period 411 amputations were performed on 250 diabetic patients (1.6 amputation/person). The estimated mean annual incidence rate of lower limb amputations in the Negev was 5 per 1000 diabetic patients, 27.3 per 100,000 total population, and 45 per 100,000 adults above 18 years of age. The mean age was 68 (SD +/- 11.4) years. The most frequent types of surgery were standard below-knee amputation. Fourteen percent of patients died during hospitalization. Systolic blood pressure, white blood count and serum creatinine at admission were independent predictors of in-hospital mortality. CONCLUSIONS: The incidence of lower limb amputation in the Negev is similar to that reported in other countries. Interventions directed to early detection of diabetic foot problems may have an impact on the reduction of lower limb amputations and related mortality.

Aged↗
PubMed2004

Health status of young children during therapy for advanced neuroblastoma.

BACKGROUND: The purpose of this study was to describe the health status experienced by young children during various phases of therapy for advanced neuroblastoma. METHODS: Nineteen patients aged 2.00-4.99 years at the time of diagnosis of neuroblastoma (stages 3 or 4) who received active therapy between 1996 and 2000 were enrolled on the study. Their parents provided proxy assessments of their health status at a maximum of 10 assessment points during therapy using the Comprehensive Health Status Classification System for Pre-school Children (CHSCS-PS), which assesses level of function on 10 separate health domains. RESULTS: Eighty-six assessment questionnaires were completed. Maximum morbidity was reported immediately following diagnosis and in the 2-3 weeks following bone marrow transplantation. The greatest morbidity was observed in the pain, self-care, mobility, and emotion domains. CONCLUSIONS: In addition to facing a high risk of mortality, young children being treated for advanced neuroblastoma also experience considerable morbidity.

Child, Preschool↗
PubMed2004

Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study.

We investigated the age-, gender- and race-specific 1-year case fatality rates of diabetic and non-diabetic individuals with a myocardial infarction. Data were obtained from the Atherosclerosis Risk in Communities (ARIC) Surveillance Study, which monitors both hospitalized myocardial infarction and coronary heart disease (CHD) deaths in residents aged 35-74 years in four communities in the USA. The study population comprised 3242 hospitalized myocardial infarctions (HMIs) in diabetic subjects and 9826 HMIs in non-diabetic individuals between 1987 and 1997. Age-adjusted and gender- and race-specific odds ratios (OR) for 1-year case fatality comparing diabetic to non-diabetic patients were 2.0 (95% CI, 1.6-2.4) for white men and 1.4 (95% CI, 1.1-1.8) for white women. Further adjustment for severity of HMI, history of previous MI, stroke and hypertension, and therapy variables showed significantly higher case fatality in white diabetic men than in non-diabetic white men (OR=1.5; 95% CI, 1.2-1.9), but no significant association in the other race-gender groups. The age-adjusted odds of out of hospital death was significantly higher among white diabetic men (OR=1.7; 95% CI, 1.2-2.3), white women (OR=2.3; 95% CI, 1.4-3.8), and African-American women (OR=2.9; 95% CI, 1.5-5.9) as compared to their non-diabetic counterparts. In conclusion, diabetes is an independent factor for mortality within one year following a myocardial infarction among white men, and following out-of hospital coronary death in white men and women and in African-American women. It is possible that these differences could be explained, at least in part, by a less than optimal medical management of the high cardiovascular risk profile of these patients after hospital discharge.

Arteriosclerosis↗
PubMed2004

Inter-observer agreement of a comprehensive health status classification system for pre-school children among patients with Wilms' tumor or advanced neuroblastoma.

We assessed inter-observer agreement on a new comprehensive health status classification system for preschool children (CHSCS-PS). Prospective assessments of children aged 2-4.9 years at the time of diagnosis of neuroblastoma (stages 3-4, excluding 4S) or Wilms' tumor (stages II-V) were collected independently from a parent and nurse by self-report during therapy. Responses were used to determine functional status on 10 health domains, as well as an overall disability score. Inter-observer agreement was evaluated by a kappa statistic for agreement about levels within individual domains, and by an intraclass correlation coefficient (ICC) for agreement of overall disability scores. Twenty-four parent/nurse pairs of assessments were collected. Agreement was almost perfect for mobility and self-care, substantial for emotion and pain, and slight for speech. There was high percent agreement for vision, hearing, dexterity, learning and remembering, and thinking and problem solving, but insufficient variability in responses to calculate a kappa statistic. The ICC for overall disability scores between observers was 0.86, indicating strong agreement. Given the need for, and paucity of, instruments for the measurement of health-related quality of life in very young children, these results strongly support further evaluation of the CHSCS-PS.

Child, Preschool↗
PubMed2004

Allogeneic bone marrow transplantation vs chemotherapy for children with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Allogeneic bone marrow transplant (BMT) with an MRD in complete remission (CR)1 is the preferred treatment for children with Philadelphia-positive (Ph(+)) ALL. The role of MUD BMT in CR1 is still controversial. We compared the outcomes of two treatment strategies: BMT using an MRD or MUD vs chemotherapy in children with Ph(+) ALL in CR1. In total, 21 children were treated from 1985 to 2001. In all, 10 received chemotherapy and 11 received allogeneic BMT: four MRD, seven MUD. In the MRD group, one relapsed 12 months after BMT and died; the remaining three are long-term event-free survivors (median follow-up, 6.1 years). In the MUD group four died; the remaining three are long-term event-free survivors (median follow-up, 7.2 years). The 4-year event-free survival (EFS) for the BMT group was 53+/-15%. In the chemotherapy group, seven relapsed after a median period of 12.5 months and three remain in continuous CR (median follow-up, 2.4 years). Four chemotherapy patients received CR2 transplants; all died. The 4-year EFS for the chemotherapy and MUD groups was 33+/-17 and 35.7+/-20%, respectively. This difference was not statistically significant. We continue to support treating children with Ph(+) ALL with MRD BMT in CR1. The effectiveness of MUD BMT vs chemotherapy merits further study.

Adolescent↗
PubMed2003

[Prevalence and characteristics of myocardial infarction, diabetes and hypertension in the adult Jewish population: results from the Negev Nutritional Study].

BACKGROUND: Monitoring the prevalence of chronic conditions such as chronic heart disease, diabetes and hypertension in adult populations is essential for health services planning and identification of populations at high risk. OBJECTIVES: To describe the prevalence of self-reported conditions such as myocardial infarction, diabetes mellitus and hypertension in the Jewish Negev population and the patterns of use of health services and dietary behavior of persons suffering from these conditions. METHODS: A random proportional geographic cluster sample of the adult Jewish population (n = 1159, age 35+) from the Negev area was interviewed at home between 1998 and 1999. The interview included questions regarding chronic conditions, patterns of health services use and dietary behavior. RESULTS: Men had twice the prevalence of myocardial infarction and underwent more invasive cardiac procedures than women. The highest prevalence of myocardial infarction and hypertension were found in Central- and Eastern European-born persons while the highest prevalence of diabetes was found in Western-born participants. Of the participants < 61 years of age, 19% reporting diabetes and 33% reporting hypertension did not use medication and were not adhering to an appropriate diet. Thus, one-third of those with reported hypertension and 15% of those reported as diabetics were not adhering to any treatment. The prevalence reported in this study was higher than the national data. CONCLUSIONS: The data collected showed a higher prevalence of chronic diseases among the southern Israeli population as compared with the national data. Among people with chronic diseases, high percentages are not treated. The information reported here may help in the allocation of health services for the south of Israel and in the identification of populations at risk.

Adult↗
PubMed2001

Antisense-mediated depletion of p300 in human cells leads to premature G1 exit and up-regulation of c-MYC.

The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In this report, we have examined the role of p300 in the control of the G(1) phase of the cell cycle in nontransformed immortalized human breast epithelial cells (MCF10A) and fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense sequences synthesized p300 at much reduced levels and exited G(1) phase without serum stimulation. These cells also showed an increase in cyclin A and cyclin A- and E-associated kinase activities characteristic of S phase induction. Further analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is required for DNA synthesis, was also found to be up-regulated, indicating that up-regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S phase induction in p300-depleted cells was reversed when antisense c-MYC was expressed in these cells, indicating that up-regulation of c-MYC may directly contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300-dependent manner. Our results suggest an important role of p300 in cell cycle regulation at G(1) and raise the possibility that p300 may negatively regulate early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis in quiescent cells.

Breast↗
PubMed2001

Mortality of patients with childhood onset (0-17 years) Type I diabetes in Israel: a population-based study.

AIMS/HYPOTHESIS: The aim of this study was to examine the mortality rate of subjects with childhood-onset Type I (insulin-dependent) diabetes mellitus in Israel. METHODS: The whole-country cohort of 1,861 children and adolescents (0-17 years) with Type I diabetes, diagnosed between January 1965 and December 1993 in Israel, was analysed for mortality up to October 1996. RESULTS: A total of 37 deaths were identified with an ascertainment rate of 100%. There was a significant (p < 0.001) excess mortality in the patients with Type I diabetes, the standard mortality ratio being three times higher than that of the general population. The causes of mortality were ketoacidosis (n = 8), infections (n = 8), chronic diabetes complications (n = 9), external causes (n = 6) and other (n = 6). Among the subjects who died, the prevalence of nephropathy, neuropathy and anaemia was higher in female than in male subjects. A total of 17 of the patients with diabetes who died had a central nervous disease (psychosis, mental retardation, epilepsy). There was a trend to lower mortality among the Arab cohort which did not reach statistical significance. CONCLUSIONS/INTERPRETATION: Our data provide additional evidence that childhood-onset Type I diabetes carries an increased mortality risk when compared with the mortality risk of the non-diabetic population.

Adolescent↗
PubMed2001

Results of a randomized phase III trial in children and adolescents with advanced stage diffuse large cell non Hodgkin's lymphoma: a Pediatric Oncology Group study.

The Pediatric Oncology Group (POG) adopted a histology-based approach to the management of pediatric non-Hodgkin's lymphomas (NHL) utilizing the National Cancer Institute Working Formulation for Clinical Usage. Patients with diffuse large cell lymphoma (DLCL) were treated on a separate protocol from small cell diffuse undifferentiated or lymphoblastic lymphomas. This study assessed the overall and event free survival of children with DLCL and determined the effects of cyclophosphamide upon these end-points in a prospective randomized trial. One hundred and twenty eligible stage III or IV NHL patients with the confirmed diagnosis of diffuse large cell or immunoblastic histology were enrolled on study between October 1986 and November 1991. Patients were randomized to receive or not receive cyclophosphamide; 58 received cyclophosphamide, doxorubicin, vincristine, 6-mercaptopurine (6-MP), and prednisone (ACOP+) and 62 were treated with doxorubicin, vincristine, 6-MP, and prednisone (APO). In both treatment programs methotrexate was substituted when the doxorubicin cumulative dose reached 450 mg/m2. Radiation was administered to bulky disease if progression or no response were observed after induction therapy. Planned duration of therapy was 12 months. The 5-year event free survival (EFS) rates of patients treated with ACOP+ versus APO were 62% +/- 7% and 72% +/- 6%, respectively. While there was no statistically significant difference between the two treatment arms (p = 0.28), we can only say that we are 95% confident that the difference in 5-year EFS falls in the wide range from 28% in favor of APO to 8% favoring ACOP+. Marrow suppression was the main toxicity with one fatal infection. There were three other deaths on study due to respiratory failure in patients with mediastinal masses. Only one patient experienced cardiotoxicity requiring discontinuation of doxorubicin. Ten patients received radiation therapy to achieve. In conclusion the efficacy of elimination of cyclophosphamide from the treatment program of children and adolescents with advanced stage diffuse large cell lymphoma was inconclusive as to its effect on EFS. Furthermore, the majority of the patients (92%) did not require any radiation therapy to bulky disease indicating that the chemotherapy regimens are quite efficient for achievement of complete remission.

Adolescent↗
PubMed2001

[Prevalence of fibromyalgia in type 2 diabetes mellitus].

This study aimed to assess the prevalence of fibromyalgia and other pain characteristics among patients with type 2 diabetes mellitus. We assessed 137 patients with type 2 diabetes mellitus and a control group of 139 patients matched for age and sex that do not suffer from diabetes mellitus. We examined 9 of 18 typical tender points and 4 control points with a dolorimeter. There was no difference in the prevalence of fibromyalgia among men in both groups. However, diabetic men had more tender points than men in the control group and their threshold for pain at the corresponding tender points was significantly lower compared to that of the men in the control group. The diabetic men also reported more pain than patients in the control group. Diabetic women, on the other hand, had a significantly higher prevalence of fibromyalgia than women in the control group: 23.3% versus 10.6% respectively (p = 0.043). There was no significant difference in the number of tender points and the pain threshold in the two groups of women. Diabetic women reported more pain than the women in the control group. In both diabetic men and women the number of tender points and dolorimeter count directly correlated with the duration of diabetes.

Diabetes Mellitus, Type 2↗
PubMed2000

Health-related quality of life in survivors of Wilms' tumor and advanced neuroblastoma: aA cross-sectional study.

PURPOSE: In pediatric oncology, Wilms' tumor and advanced neuroblastoma represent opposite ends of the spectra of survival probability and therapeutic intensity. Consequently, it was envisaged that survivors of Wilms' tumor would enjoy better health status and health-related quality of life (HRQL) than survivors of advanced neuroblastoma. PATIENTS AND METHODS: Health status questionnaires were sent to the parents of all eligible children and to the children themselves if they were > or = 8 years of age. Responses were received from 84% of 93 eligible families. Responses were converted by established algorithms into levels of two multiattribute health status classification systems known as Health Utilities Index Mark 2 and Mark 3. These systems are linked to measures of preference, in the form of multiattribute utility functions, which provide scores of morbidity for single-attribute levels and of global HRQL for comprehensive health states. RESULTS: A greater burden of morbidity was identified in the survivors of advanced neuroblastoma than in survivors of Wilms' tumor based on the assessments of the parents of these children. In particular, survivors of advanced neuroblastoma exhibited deficits in hearing and speech. It is possible that this morbidity burden reflects the prevalent use of platinum compounds (causing ototoxicity) in this group. Within parent-child dyads there was a high level of percentage agreement on responses in all attributes except cognition. CONCLUSION: Extension of this study to a larger sample size of patients will provide clarification of these observations.

Adolescent↗
PubMed2000

Sex differentials in predictors of mortality for patients with adult-onset diabetes: a population-based follow-up study in Beer-Sheva, Israel.

OBJECTIVE: To test the hypothesis that factors predicting mortality differ between diabetic men and women. RESEARCH DESIGN AND METHODS: A total of 498 known patients with diabetes residing in a well-defined geographical area and receiving primary health care in 3 primary care community clinics were interviewed and examined between 1988 and 1990. RESULTS: By 31 July 1998, after a mean follow-up period of 7.8 years, 148 patients (68 men and 80 women) had died (29.7%). No statistical differences in survival rate or in the specific causes of death were found between men and women. In the univariate analysis of factors examined at baseline, GHb levels were significantly higher among women who died compared with women who survived, but this was not the case for men. Conversely, a trend of higher triglyceride and uric acid levels was found for men who died compared with men who survived, but this was not the case for women. Multivariate Poisson regression analysis showed significantly higher risk ratios for mortality in men > or = 63 years of age, men with microalbumin excretion > or = 30 mg/l, and men with higher triglyceride levels. In contrast, the analysis in women showed that higher GHb and creatinine levels and a reported history of heart disease were the only factors at the baseline examination significantly and independently associated with an increased risk ratio of mortality. CONCLUSIONS: The results suggest the existence of sex-specific interactions with various metabolic factors associated with diabetes that may have a different effect on mortality for each sex.

Age Factors↗
PubMed1999

p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.

Binding Sites↗
PubMed1999

Lymphoproliferative disorders after organ transplantation in children.

BACKGROUND: After organ transplant, patients are at risk of posttransplant lymphoproliferative disorders (PTLD). The purpose of this study was to analyze 26 pediatric cases of PTLD observed at our institution between 1988 and 1996, and to evaluate the validity of the Society for Hematopathology Workshop (SHPW) 1997 classification in our patient population. METHODS: Charts were reviewed for analysis of incidence, clinical course, and outcome. Tissue samples were classified by a pathologist according to SHPW recommendations. RESULTS: By morphology, 20 were monomorphic, 5 polymorphic, and 1 hyperplastic. Assessment of lineage by morphology, molecular studies, and immunophenotyping did not correlate in six cases. By immunophenotyping, 12 were B cell, 4 T cell, 8 mixed B/T cells, and 2 undetermined. The 20 patients evaluable for treatment efficacy were treated with various therapeutic combinations, including immunosuppressive drug reduction, acyclovir/ganciclovir, interferon-alpha, immunoglobulins, surgery, and local irradiation. No patient received systemic chemotherapy. Thirteen patients achieved complete remission and 3, partial; 1 died 5 days after starting therapy, and 3 of progressive disease. Adverse prognostic factors included low platelet or neutrophil counts; stage III-IV and SHPW morphology were marginally significant. CONCLUSIONS: The majority of patients eligible for treatment can be cured with immunosuppressive drug reduction and antiviral drugs, along with surgery and irradiation when indicated. Systemic chemotherapy or innovative approaches may have a role in unresponsive cases. Morphologic SHPW grouping is feasible and seems to have clinical relevance. However, correlation with clonality and immunophenotyping is not always possible, necessitating modifications including segregation of descriptive morphology from clonality and cell origin.

Adolescent↗
PubMed1999

Nucleoside analogues in the therapy of Langerhans cell histiocytosis: a survey of members of the histiocyte society and review of the literature.

BACKGROUND: Previous reports have suggested activity of the nucleoside analogues 2-chlorodeoxyadenosine (2-CdA) and 2'-deoxycoformycin (2'-DCF) in Langerhans cell histiocytosis (LCH). PROCEDURE: To assess the efficacy of 2-CdA and 2'-DCF as salvage therapy for LCH, a survey of members of the Histiocyte Society and a literature review were undertaken. Twenty-three patients treated with 2-CdA and 4 treated with 2'-DCF were found, age range 2 months to 49 years. RESULTS: All 15 survey patients had multiorgan involvement, and 14 were heavily pretreated. Doses of 2-CdA ranged from 0.1 mg/kg/day continuous infusion for 5-7 days (majority of patients) to 13 mg/m(2)/day for 5 days, for 1-6 courses. One of the 15 patients had an early death, 5 had no response (NR), 3 had partial response (PR), and 6 achieved complete response (CR). Among 8 published patients, 7 achieved stable CR and 1 NR. Among 4 patients treated with 2'-DCF (4 mg/m(2)/week for 8 weeks then q 2 weekly), 2 achieved CR for 16+ and 18+ months and 2 PR for 2 and 5 months. Toxicity consisted mainly of combined myelo- and immunosuppression but no significant infections occurred and there were no toxic deaths. A cumulative thrombocytopenia was noted, which in 1 case took up to 6 months to resolve. Transient gastrointestinal toxicity and elevation of liver enzymes was seen, and 2 patients developed renal tubular acidosis. The peripheral neuropathy reported in adult patients receiving high doses was not seen. CONCLUSIONS: 2-CdA and 2'-DCF appear to have a useful role in LCH and are worthy of prospective trial in patients unresponsive to routine therapy.

Adolescent↗