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Biomedical subjects

M Weintraub

Publications and source records attributed to M Weintraub.

At least 37 records · Page 2Linked to original sources
PubMed1996

Absence of germline p53 mutations in familial lymphoma.

p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset of cancer. p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy. Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances. To determine whether the predisposition to lymphoma in these families results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds. We found no germline p53 mutations in any of the individuals tested. However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases. These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.

Adolescent↗
PubMed1996

Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine.

PURPOSE: We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. PATIENTS AND METHODS: Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles. Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF. A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. RESULTS: SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients. There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and an independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. CONCLUSION: Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine -- the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose.

Adolescent↗
PubMed1996

Brachial plexopathy associated with human granulocytic ehrlichiosis.

Human granulocytic ehrlichiosis is a tick-borne disease of humans. Involvement of the peripheral nervous system is well known with Lyme disease and some rickettsioses but has yet to be described with this disease. We describe a man with bilateral brachial plexopathies associated with an acute febrile illness and clinical, laboratory, and serologic evidence diagnostic of human granulocytic ehrlichiosis. The clinical presentation suggests that the peripheral neuropathy was postinfectious. Human granulocytic ehrlichiosis should be considered in the differential diagnosis in patients with peripheral nervous system involvement, including brachial plexopathy, of individuals who live or recreate in areas known to harbor ticks.

Adult↗
PubMed1995

Escape phenomenon of low-density lipoprotein cholesterol during lovastatin treatment.

The main issue is whether briefly stopping treatment of the hypercholesterolemic patient will accelerate the atherosclerotic process. This is possible, but such a strategy is preferable only in a subgroup of patients who cannot bear the economic burden of increasing the dosage of statins. In addition, stopping and restarting the drug at different stages lessens the likelihood of more adverse effects occurring when the dosage is increased.

Adult↗
PubMed1995

A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma.

The growth arrest mediated by p53 is caused at least in part by the p53 mediated expression of p21 (p21waf1/Cip1). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gene, we examined the structural integrity of the p21 coding region by single-strand conformational polymorphism and DNA sequence analysis to determine the extent to which this gene is mutated in BL. Of 34 BLs analyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carried a change at codon 63: Phe to Leu. This mutation was heterozygous, and both the wild-type and the mutated p21 mRNA were expressed in the tumor cell line. By transfection experiments, the mutant p21 was less efficient in suppressing clonogenicity than wild-type p21. To our knowledge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21.

Base Sequence↗
PubMed1995

Hypermagnesemia. Elderly over-the-counter drug users at risk.

We present a case of magnesium toxic effects that demonstrates the wide spectrum of associated clinical signs and symptoms. As shown by the case report, the literature review, and the MEDWATCH database, physicians frequently neglect to consider hypermagnesemia in the differential diagnosis of this clinical presentation. Abnormal renal function is a well-known risk factor for the development of hypermagnesemia. This case report highlights several associated nonrenal risk factors for hypermagnesemia, which include age, gastrointestinal tract disease, and administration of concomitant medications, particularly those with anticholinergic and narcotic effects. This case report also demonstrates how consumers may misuse magnesium-containing over-the-counter drug products. In addition, physicians may not inquire about and patients may not volunteer over-the-counter medications in a complete drug history. However, the morbidity associated with hypermagnesemia as well as its reversibility make it an important diagnostic consideration for elderly patients with gastrointestinal tract disease, regardless of renal function. For easy reference for both consumers and health-care personnel, we provide a list of over-the-counter drug products that contain significant amounts of magnesium.

Age Factors↗
PubMed1994

Classification of red blood cells as normal, sickle, or other abnormal, using a single image analysis feature.

Sickle cell anemia is a disease for which there is currently no effective treatment. One method of evaluating clinical status is the counting of cell types based on morphology. There is a need for a rapid, reproducible method, superior to human inspection, for classification of these cells. Quantitative digital-image analysis is being applied to this need. Blood from 24 patients with sickle cell anemia (SS) and SC disease and ten hematologically normal volunteers (AA) was stressed by bubbling with nitrogen. One hundred fifty cells were analyzed from each sickle specimen, and 100 were analyzed from each nonsickle specimen. Expert observers classified each cell as normal (N), sickle (S), or other abnormal (A). Cells were analyzed with a custom, high-resolution image-analysis instrument. A total of 42 features including metric, optical density-derived, and textural features were extracted. The metric feature Form Factor (4 pi Area/Perimeter2) was selected by recursive partitioning analysis as the sole feature needed for segregating cells into the classes of N, A, and S. The agreement of automated classification (using cutpoints determined by recursive partitioning analysis) with a human expert for specimens from individuals with sickle cell anemia was 89% for N-, 73% for A-, and 92% for S-classified cells. For specimens from AA individuals, the agreement was 92% for N and 76% for A. For specimens from individuals with sickle cell anemia, rates of agreement between two human experts were compared and found to be 86% for N, 84% for A, and 80% for S. For specimens from AA individuals, the agreement was 90% for N and 87% for A.

Adolescent↗
PubMed1994

Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.

Adult↗
PubMed1993

Benzodiazepines and hip fracture: the New York State experience.

We assessed rates of hip fracture before and after the institution of the triplicate prescription policy for benzodiazepines in New York State. All patients 55 years of age or older who had a diagnosis of hip fracture between January 1, 1986, and June 30, 1991, were considered for the study. Patients with severe trauma, neoplasm, arthritis, or second admission were excluded. Rates of hip fracture were calculated for each quarter by age and gender. Benzodiazepine prescribing began to decline immediately after the triplicate prescription regulation went into effect on January 1, 1989. However, yearly rates of hip fracture for women (men) > or = 75 years of age per 1000 people adjusted for New York population changes remained stable at 13.8 (6.5), 12.6 (5.7), 14.7 (6.7), 14.8 (6.4), 14.4 (6.3), and 14.4 (6.7), from 1986 through the first two quarters of 1991. Regression analyses showed no before or after regulation trend in the rate of hip fracture. We conclude that no dramatic declines in the rate of hip fractures among people older than 55 years of age have been observed in association with the benzodiazepine regulations and decreased benzodiazepine prescribing.

Aged↗
PubMed1992

Cerebral oedema in congenital nephrotic syndrome.

We report an infant with congenital nephrotic syndrome who showed clinical and radiological evidence of cerebral oedema, which resolved during prolonged intravenous albumin therapy. The cerebral oedema in this case can possibly be attributed to the relative immaturity of the blood-brain barrier in early infancy.

Albumins↗