Long-term survival of a stage 4 neuroblastoma patient despite persistent bone marrow disease following autologous bone marrow transplantation.
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Bone Marrow Neoplasms↗
Biomedical subjects
S Weitzman
Publications and source records attributed to S Weitzman.
Prevalence of diabetes mellitus among workers in Israel: a nation-wide study.
The prevalence of diabetes mellitus in Israel has been described in various populations and ranges from 4.1% to 8.9%. However, the large immigration wave in the late 1980s and early 1990s could have affected the previous estimates. Moreover, data from the United states and other countries report a significant proportion of undiagnosed diabetes. The main purpose of this study was to estimate the prevalence and the ratio of undiagnosed/diagnosed diabetes in a large sample of workers. The study involved interviews, anthropometric measurements at the work site, and blood glucose determinations (casual capillary, fasting, and when necessary, 2 h after a 75-gram oral glucose load). Diabetes and impaired glucose tolerance (IGT) were diagnosed according to WHO criteria. Five thousand four hundred sixteen workers participated in the study. Three hundred ten reported to be known diabetics (5.7%), 35 (0.7%) were diagnosed as diabetic during the survey, and an additional 93 (1.8%) were classified as IGT. The ratio undiagnosed/diagnosed diabetes was therefore 1:10. Extrapolation of these results produced an estimate of diabetes prevalence in Israel of 10% among people over age 40 years. It seems that in the Israeli health care system, based on universal health insurance and easy access to primary care, the proportion of undiagnosed diabetes is lower than that described in other countries.
Adult↗
A cell signal pathway involving laminin-5, alpha3beta1 integrin, and mitogen-activated protein kinase can regulate epithelial cell proliferation.
Laminin-5 (LN5) is a matrix component of epithelial tissue basement membranes and plays an important role in the initiation and maintenance of epithelial cell anchorage to the underlying connective tissue. Here we show that two distinct LN5 function-inhibitory antibodies, both of which bind the globular domain of the alpha3 subunit, inhibit proliferation of epithelial cells. These same antibodies also induce a decrease in mitogen-activated protein kinase activity. Inhibition of proliferation by the function-perturbing LN5 antibodies is reversed upon removal of the antibodies and can be overcome by providing the antibody-treated cells with exogenous LN5 and rat tail collagen. Because epithelial cells use the integrin receptor alpha3beta1 to interact with both LN5 and rat tail collagen, we next investigated the possibility that integrin alpha3beta1 is involved in mediating the proliferative impact of LN5. Proliferation of human epithelial cells is significantly inhibited by a function-perturbing alpha3 integrin antibody. In addition, antibody activation of beta1 integrin restores the proliferation of epithelial cells treated with LN5 function-perturbing antibodies. These data indicate that a complex comprising LN5 and alpha3beta1 integrin is multifunctional and contributes not only to epithelial cell adhesion but also to the regulation of cell growth via a signaling pathway involving mitogen-activated protein kinase. We discuss our study in light of recent evidence that LN5 expression is up-regulated at the leading tips of tumors, where it may play a role in tumor cell proliferation.
Animals↗
Tumorigenic conversion of a rat urothelial cell line by human polymorphonuclear leukocytes activated by lipopolysaccharide.
Chronic inflammation is a significant risk factor for the development of urinary bladder cancer. We have shown that inflammation induced by killed Escherichia coli and also by its lipopolysaccharide (LPS) strikingly enhances N-methyl-N-nitrosourea (MNU)-initiated rat bladder carcinogenesis. Aspirates from the bladder lumen contained a large quantity of hydrogen peroxide (H2O2) and several cytokines. In this study, we tested the hypothesis that reactive oxygen intermediates (ROI) released from activated polymorphonuclear leukocytes (PMN) are involved in inflammation-associated bladder carcinogenesis. Using an immortalized nontumorigenic rat urothelial cell line, MYP3, we examined the effect of LPS-activated PMN on malignant transformation. MYP3 cells pretreated with or without MNU were exposed daily to LPS-activated PMN for one week and were then tested for growth in soft agar. In contrast to no colony formation by the parental cells, a varying number of colonies developed from cells treated with LPS-activated PMN. Although combined treatment with MNU and PMN was most effective (P<0.01), cells treated with LPS-activated PMN alone also formed a small number of colonies. Addition of catalase, which decomposes H2O2, and/or an antioxidant, alpha-tocopherol, reduced the number of colonies induced by LPS-activated PMN (P<0.05). Cells derived from colonies were tumorigenic in athymic nude mice. However, tumorigenicity in mice was greater with cells treated with both MNU and PMN than with cells treated with PMN alone. Our results suggest that ROI released from LPS-activated PMN may be one of the mechanisms involved in the carcinogenesis associated with active urinary tract infection.
8-Hydroxy-2'-Deoxyguanosine↗
Impaired fasting glucose is not a risk factor for cardiovascular mortality.
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Blood Glucose↗
[Effects of vertical banded gastroplasty on weight, quality of life and nutrition].
We examined the long term results of vertical banded gastroplasty 3-10 years after operation. They were assessed by weight lost, incidence and severity of untoward effects and improvement in diet and in quality of life in 75 of 122 who had had the operation. Average weight lost was 28.5 +/- 14.9 kg (p < 0.001) in 5 years and 58.6 +/- 30.4% of excess weight, which brought patients to within 32 +/- 25.2% of ideal weight. According to these measures, in 63-76% the operation had been successful in causing weight loss. The 2 criteria for successful weight loss were loss of more than 50% of weight in excess of ideal body weight and residual body weight less than 50% greater than ideal body weight. There was a greater risk of failure in unmarried subjects older than 45 (odds ratio for not losing weight was 6; in those weighing more than 120 kg it was 9). We saw evidence of this mostly 4 years after operation (odds ratio 11). The degree of success in weight loss was correlated with texture of food (softness) preferred and length of operation. Of those interviewed, only 65% were satisfied with their results. The greatest improvement in quality of life measurements was in physical activity, perception of health, and frequency of feeling depressed. Side-effects were vomiting, reflux and fatigue. Only 34.7% were able to digest solid foods, so that subjects are at risk for nutritional deficiencies.
Adult↗
Use of adjuvant ICE chemotherapy in the treatment of anaplastic ependymomas.
Despite the improved outcome for patients with ependymoma treated by surgery and radiotherapy, their prognosis remains relatively poor. To assess the impact of adjuvant chemotherapy, we reviewed the overall survival of consecutive patients with anaplastic ependymoma treated over a 10-year period with surgery and ICE (ifosfamide+ VP 16+carboplatin) chemotherapy with or without radiation at our institution. There were 11 patients (6 male, 5 female), with a median age of 3.4 years (range 1.2-1 1.1): 4 under 2 years and 7 were over 2 years old. Overall, 5 had gross total resections: 4 are alive, 2 in continuous complete remission and 2 in second complete remission. One patient who was less than 2 years old died. Among the 6 with subtotal resection, 2 achieved a complete remission after chemotherapy. However, 5 of the 6 patients have since died of progressive disease, with a median overall survival of 75 months. Overall survival was 24% and progression-free survival was 39%. In 2 of 6 patients with residual postoperative disease a temporary objective response was noted with adjuvant ICE chemotherapy. This regimen did not confer an overall survival advantage.
Aging↗
Comparison of survival outcomes in patients with intracranial germinomas treated with radiation alone versus reduced-dose radiation and chemotherapy.
Concern about long-term sequelae of irradiation has led to the use of adjuvant chemotherapy with lower dose irradiation in the treatment of intracranial germinomas. To assess the feasibility of this approach versus radiation only, the survival of 16 evaluable patients (13 boys, 3 girls) with biopsy-proven intracranial germinomas treated at the Hospital for Sick Children was assessed. Between 1977 and 1988, 8 patients were treated with radiation only: 7 received tumour doses between 4000 and 5100 cGy and spinal prophylaxis; 1 received 3060 cGy to the tumour with no prophylaxis. After a median follow-up of 84 months, 7 are in continuous first CR and 1 is in second CR. Between 1988 and 1996, 8 patients received adjuvant platinum- and etoposide-based chemotherapy for two or three cycles followed by local irradiation to the tumour (2500-3500 cGy). After a median follow-up of 40 months, 6 are in continuous first CR and 1 in second CR; 1 has died of progression. Survival outcomes in the two groups are similar. Prospective trials to assess event-free survivals, neurocognitive and neuroendocrine outcomes are needed before definitive treatment recommendations can be made.
Adolescent↗
Lack of cisplatin-ranitidine kinetic interactions: in vivo study in children, and in vitro study using dog renal brush border membrane vesicles.
The interactions between cisplatin and organic ions have been extensively investigated in animal models for the potential to reduce cisplatin cellular uptake and resultant nephrotoxicity. To further investigate the beneficial interaction clinically, we studied the effects of the organic cation, ranitidine, on the renal handling of cisplatin in children. In parallel, we examined the effects of cisplatin on the uptake kinetics of organic cations and anions by brush border membrane vesicles (BBMV) prepared from dog renal cortex. The results indicate that: 1) there is no measurable effect of ranitidine on renal clearance of cisplatin in children; and 2) BBMV uptake of anionic p-aminohippurate, but not cationic N-methylnicotinamide, is inhibited by cisplatin at concentrations of <1 mM. These findings suggest that cisplatin may not share transport systems with organic cations to a clinically significant degree. Assuming that renal tubular transport is a prerequisite for cisplatin nephrotoxicity, the lack of apparent kinetic interactions between cisplatin and organic cations may preclude clinical use of organic cations as a modality to prevent cisplatin nephrotoxicity.
Adolescent↗
Alternative nutritional cancer therapies.
Increasing attention is being paid to the role of nutrition in cancer. Dietary measures, such as decreased consumption of calories, fat, alcohol and smoked or pickled foods have been shown to reduce the incidence of specific "adult" cancers, while increased dietary fiber appears to have a protective role. However, no clear scientific evidence exists that dietary manipulation is a successful primary therapy for established cancer. A significant percentage of adult and child cancer patients take unproven therapies during their illness. Alternative nutritional therapies, of which there is a wide variety, are the commonest of these reflecting current public interest in "natural" remedies. The efficacy and potential toxicity of commonly utilized dietary therapies are here reviewed, in particular the macrobiotic philosophy, the Gerson diet, the Livingstone diet, and the use of vitamin and mineral therapy. While details may differ, most alternative approaches involve fresh whole foods, with strong emphasis on low-fat vegetarian diet. Most are nutritionally adequate, at least for adults. No anti-cancer diet has been shown to cure established cancers, even those whose incidence is decreased by dietary changes. Careful dietary manipulation may at least improve quality of life for adult cancer patients, and, together with conventional therapy, may prolong survival in selected cancer patients. Assessment by carefully controlled prospective clinical trials is essential; those in pediatric patients must be controlled very strictly, since tumors in children have not been shown to be influenced by diet, and the diets described may be inadequate for children with malignant disease.
Adult↗
[Penetrating ocular injuries: an epidemiologic and retrospective study].
Penetrating injuries of the eye are an important cause of unilateral visual loss. We studied a series of 82 cases of penetrating injuries treated here from 1987 through 1993. The injuries were caused by sharp objects in 66% and blunt trauma in 6%. The prognosis after a penetrating injury is greatly influenced by the nature of the injury and the extent of the initial drainage. Among factors associated with an unfavorable visual outcome were diminished preoperative visual acuity and scleral wounds with dense vitreous hemorrhage.
Adolescent↗
Mind over matter about keeping warm.
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Cold Climate↗
Gender, racial, and geographic differences in the performance of cardiac diagnostic and therapeutic procedures for hospitalized acute myocardial infarction in four states.
This study compared rates of performance of cardiac procedures in relation to gender, race, and geographic location in patients hospitalized for myocardial infarction. The Atherosclerosis Risk in Communities (ARIC) study provides population data and standardized data collection methods. Hospital records of eligible people aged 35 to 74 years were abstracted in communities of 4 states in the United States: North Carolina, Mississippi, Maryland, and Minnesota. Between January 1987 and December 1991, 5,462 "definite" hospitalized patients with myocardial infarctions were identified. Women treated in nonteaching hospitals were less likely than men to have coronary angiography (odds ratio [OR] 0.7, 95% confidence interval [CI] 0.5 to 1.0), coronary artery bypass graft surgery (CABG) (OR 0.6, 95% CI 0.4 to 0.8), and thrombolytic therapy (OR 0.8, 95% CI 0.6 to 1.0), after controlling for age, race, severity of myocardial infarction, co-morbidity, and geographic area. Findings were similar in teaching hospitals. Blacks in the biracial communities were significantly less likely than whites to have coronary angiography, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery, and thrombolytic therapy. After controlling for age, race, severity of myocardial infarction and co-morbidity, no consistent geographic differences were observed, except for Forsyth whites having the highest and Washington County the lowest odds for coronary angiography. Appropriate outcome measures would serve to evaluate the effect, if any, of the differences described on the ARIC population.
Adult↗
Association of diabetic retinopathy, ischemic heart disease, and albuminuria with diabetic treatment in type 2 diabetic patients. A population-based study.
The management of type 2 diabetes has been a controversial issue. The objective of the present study was to estimate patients' characteristics, particularly diabetes treatment, associated with retinopathy, coronary heart disease, and microalbuminuria in an unselected population of 532 type 2 diabetic individuals from three communities. Questionnaires, clinic record review, and physical examination were used for the assessment of the three conditions. Fasting C-peptide was measured in all insulin-treated participants to establish type 2 diabetes. Patients with and without each of the studied complications were matched for age at diagnosis of diabetes and duration of diabetes. Univariate matched and multivariate conditional logistic regression analyses were used to estimate the independent association between each of the various factors studied and the three complications. Insulin treatment was the only factor independently associated with all three complications (odds ratios 3.3, 3.4, and 5.3 for diabetic retinopathy, coronary heart disease, and albuminuria, respectively). Glycosylated hemoglobin, uric acid, systolic blood pressure levels, and body mass index were also independently associated with at least one of the complications but not with all of them. Although no cause-effect relationship can be established from this cross-sectional design, insulin therapy seems to be a marker of severer diabetes from the time of diagnosis.
Aged↗
Lymphadenopathy and pulmonary infiltrates in a 12-year-old girl.
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Child↗
Neonatal oncology: diagnostic and therapeutic dilemmas.
Tumors are a rare but important cause of mortality and morbidity in the neonate. There is a wide spectrum of benign and malignant tumors that can occur, some of which have a unique presentation and behavior in this age group. It is important to recognize that tumors such as stage IVS neuroblastoma, which have a good prognosis in older children, may be rapidly fatal in the newborn and constitute an oncological emergency. Other tumors behave in a less aggressive fashion at this age than in the older child, and should not be overtreated. An increasing number of tumors are being detected by prenatal screening, and understanding of their natural history and management is important. Management of neonatal cancer requires knowledge also of the developmental biology of the neonate, of the way in which they handle drugs, and the increased potential for acute toxicity and long-term morbidity from chemotherapy and radiation therapy.
Abdominal Neoplasms↗
Screening for neuroblastoma is ineffective in reducing the incidence of unfavourable advanced stage disease in older children.
Neuroblastoma exhibits many characteristics which would suggest that preclinical detection may improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. All 476,603 children born in the province of Quebec during a 5-year period of time (1 May 1989 to 30 April 1994) were eligible for determinations of urinary catecholamine metabolites at 3 weeks and 6 months of age. Children with positive screening were referred to one of four paediatric cancer centres in Quebec for uniform evaluation and treatment. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in Quebec and two comparable population-based controls during the same period of time using similar ascertainment procedures. Compliance with screening in Quebec was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Up to 31 July 1995 with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically prior to screening at 3 weeks of age and 55 detected clinically after 3 weeks of age having normal screens (n = 52) or never screened (n = 3). Based on data from concurrent control populations, 54.5 cases of neuroblastoma would have been expected in Quebec during the study period for an SIR of 2.17 (95% CI 1.79-2.57, P < 0.0001). For the two control groups, the overall SIR was 1.00 (NS). SIRs for Quebec by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR = 2.85, 95% CI 2.26-3.50), with no reduction in incidence in subsequent years. We conclude that screening for neuroblastoma markedly increases the incidence in infants without decreasing the incidence of unfavourable advanced stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce the mortality of this disease.
Canada↗
The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis.
In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin 'backbone', play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.
Antibodies↗