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Biomedical subjects

C Isaacs

Publications and source records attributed to C Isaacs.

30 records · Page 2Linked to original sources
PubMed1997

Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin.

PURPOSE: Thrombocytopenia may compromise cancer treatment, causing chemotherapy dose reductions, schedule alterations, or the need for platelet transfusions. We evaluated the efficacy and safety of recombinant human interleukin-11 (rhIL-11; Neumega, Genetics Institute, Inc, Cambridge, MA), a novel thrombopoietic growth factor, in reducing the need for platelet transfusions in patients who undergo dose-intensive chemotherapy. PATIENTS AND METHODS: Women with advanced breast cancer received cyclophosphamide (3,200 mg/m2) and doxorubicin (75 mg/m2) plus granulocyte colony-stimulating factor (G-CSF; 5 microg/kg/d). Patients were randomized to blinded treatment with placebo or 50 microg/kg/d rhIL-11 subcutaneously for 10 or 17 days after the first two chemotherapy cycles. RESULTS: Seventy-seven patients were randomized and constitute the intent-to-treat (ITT) population. Sixty-seven patients (the assessable subgroup) either completed both cycles without a major protocol violation (n = 62) or received a platelet transfusion before treatment was discontinued after the first cycle. In the ITT population, rhIL-11 significantly decreased the requirement for platelet transfusions; 27 of 40 (68%) patients who received rhIL-11 did not require transfusions, compared with 15 of 37 (41%) in the placebo group (P = .04). Treatment with rhIL-11 significantly reduced the total number of platelet transfusions required in the assessable subgroup (P = .03) and the time to platelet recovery to more than 50,000/microL in the second cycle (P = .01). Most adverse events associated with rhIL-11 were reversible, mild to moderate in severity, and likely related to fluid retention. CONCLUSION: rhIL-11 is safe and effective in reducing treatment-associated thrombocytopenia and the need for platelet transfusions in patients who undergo dose-intensive chemotherapy, and thus may permit chemotherapy to be administered as planned at intended doses and thereby maximize the potential for a successful outcome.

Adult↗
PubMed1996

Prevalence rates and correlates of psychiatric disorders among preschool children.

OBJECTIVE: To determine the prevalence and correlates of psychiatric disorders among preschool children in a primary care pediatric sample. METHOD: In a two-stage design, 3,860 preschool children were screened; 510 received fuller evaluations. RESULTS: For quantitative assessment of disorder (> or = 90th percentile), prevalence of behavior problems was 8.3%. "Probable" occurrence of an Axis I DSM-III-R disorder was 21.4% (9.1%, severe). Logistic regression analyses indicated significant demographic correlates for quantitative outcomes (older age, minority status, male sex, low socio-economic status, father absence, small family size) but not for DSM-III-R diagnoses. Maternal and family characteristics were generally not significant. Child correlates included activity level, timidity, persistence, and IQ. CONCLUSIONS: Overall prevalence of disorder was consistent with rates for older children; correlates varied by approach used for classification.

Age Factors↗
PubMed1994

Age-associated risks of prophylactic anticoagulation in the setting of hip fracture.

PURPOSE: Controversy exists as to whether patient age, either independently or as a marker of concomitant illness or medication use, is associated with the dose or complication rate of warfarin prophylaxis. The aim of this study was to assess this relationship in patients receiving warfarin prophylaxis after hip fracture repair. PATIENTS AND METHODS: We undertook a retrospective cohort study of 215 patients 55 years of age or greater who underwent surgery for a fractured hip between January 1, 1990, and December 31, 1991, and received warfarin prophylaxis. The mean age was 78.9 (SD 9.5) years. The average daily warfarin dose, the decrease in hemoglobin in the postoperative period, and the rate of bleeding complications were assessed. RESULTS: Elderly patients required a significantly lower average daily warfarin dose than younger patients. This effect persisted even after controlling for the number of medical conditions, number of medications on admission, proportion of time the international normalized ration (INR) was in therapeutic range, and gender. Postoperative hemoglobin decrease was associated with patient age as well as with the use of antibiotics postoperatively. Factors associated with bleeding complications included a history of alcohol abuse and a smaller proportion of time spent in the targeted anticoagulant range. CONCLUSIONS: Older age itself and not as a marker for polypharmacy or increased number of medical conditions is associated with lower requirements for warfarin and a greater hemoglobin decrease postoperatively even when the proportion of time the INR fell within the therapeutic range is controlled. Advanced patient age, in this study, was not associated with an increased incidence of bleeding complications.

Age Factors↗
PubMed1993

Concomitant ipsilateral intertrochanteric and subcapital fracture of the hip.

A unique case of coexistent intertrochanteric and subcapital fractures of the hip is presented. A review of the literature found only one previous report of the simultaneous occurrence of these fractures. Closed reduction with in situ pinning was performed. Other treatment alternatives are reviewed and discussed.

Aged↗
PubMed1991

Spontaneous narrative-discourse performance of parents of autistic individuals.

The spontaneous narrative-discourse performance of parents of autistic individuals was compared to controls. The narratives of autism parents were similar in length to controls' narratives but were less complex and less coherent. A subgroup of autism parents produced either skeletal or rambling narratives that were not characterized by the type of simplifications that are reported to facilitate comprehension in very young or language-impaired children. The narrative-discourse deficits of this subgroup appeared to be consistent with the hypothesis of a genetic liability for autism that expresses in milder forms and may include impaired language abilities.

Adult↗
PubMed1990

No evidence for human T-cell leukemia virus type I or human T-cell leukemia virus type II infection in patients with multiple sclerosis.

The involvement of human T-cell leukemia viruses (HTLVs) in the pathogenesis of 18 Hungarian patients with multiple sclerosis was investigated. No antibody to HTLVs could be detected in any of the patients. Furthermore, using polymerase chain reaction under highly sensitive conditions, neither HTLV-I DNA nor HTLV-II DNA could be noted in peripheral blood lymphocytes of the patients. Our data do not support a causal association of HTLV-I or HTLV-II with multiple sclerosis.

Adult↗
PubMed1985

Substrate binding properties of the human liver hexosaminidase A activator protein.

The human liver hexosaminidase A activator protein has been shown to bind to the substrate GM2 ganglioside by cosedimentation in sucrose density gradients. Among other proteins tested only serum albumin forms a GM2 ganglioside - protein complex. Both activator protein and albumin bind to the monomeric form of GM2 ganglioside and not to the micellar form of the substrate. The GM2 ganglioside - activator protein complex can be recovered in a stable form. Storage at various temperatures or incubation with monosaccharides or with detergent does not result in dissociation of the complex. GM2 ganglioside in the activator-substrate complex is exchangeable with exogenous GM2 ganglioside. Hexosaminidase A, prepared from human liver, hydrolyzes GM2 ganglioside in the activator-substrate complex as efficiently as GM2 ganglioside supplied exogenously. The activator - GM2 ganglioside complex forms at pH 3.0 and exhibits an optimum similar to the pH optimum of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside in the presence of the activator; however, the ability of the activator to stimulate enzymic hydrolysis of substrate is rapidly lost after heating at 75 degrees C, whereas its ability to bind substrate is increased. The sphingolipids cerebroside sulfate and sphingomyelin show little or no binding to the hexosaminidase A activator protein nor do they inhibit activation of hexosaminidase A catalyzed hydrolysis of GM2 ganglioside. By contrast GM1 ganglioside inhibits both substrate binding and enzyme activation.

Enzyme Activation↗
PubMed1983

A new form of residual hexosaminidase activity in infantile Tay Sachs disease fibroblasts.

Fibroblast cell lines obtained from five patients with the early onset form of Tay Sachs disease (TSD) possess a species of beta-N-acetylhexosaminidase (Hex) which is more anionic than Hex B but which is stable to heating under conditions which completely inactivate Hex A. This species, which comprised between 3 and 20% of the total hexosaminidase activity in homozygous TSD fibroblasts, appeared to be unstable and upon isoelectric focussing produced a mixture of Hex B (pI = 7.2) and an isozyme with a pI of 6.2. This intermediate form of hexosaminidase was not seen in two normal fibroblast cell lines but was observed following anion exchange chromatography of extracts of fibroblast cell lines obtained from two obligate heterozygotes. A species of hexosaminidase with the same chromatographic properties, thermostability and isoelectric point as the intermediate form found in fibroblasts with the TSD genotypes can be recovered after anion exchange chromatography of a partially purified preparation of human liver Hex A that had been treated with merthiolate. We hypothesize that in TSD cells a form of the beta subunit which is usually incorporated into Hex A accumulates due to the absence of alpha subunits. This form of the beta subunit is more anionic than the beta subunit found in Hex B. In the absence of alpha subunits these anionic beta subunits form tetramers with a pI = 6.2. This form of the enzyme is unstable in the presence of cellular proteases and may be modified to Hexosaminidase B.

Cell Line↗
PubMed1978

Translation of mRNA from calf thymus in the wheat germ system: evidence for a precursor of thymosin alpha1.

When translated in the wheat germ system, mRNA from fresh calf thymus stimulates incorporation of radioactive amino acids into an acid-insoluble product, and 10--20% of the total radioactivity incorporated is precipitated with antisera to active thymosin fractions. In sodium dodecyl sulfate disc gel electrophoresis, radioactivity was recovered mainly in two peptides, corresponding to 16,000 and 11,000 daltons; the latter probably represents incomplete chains. Tryptic digests of each of these peptides yielded fragments corresponding to the sequence of residues 15--19 of thymosin alpha1; these peptides were characterized by cochromatography with digests of synthetic thymosin alpha1 and by Edman degradation. Thus, the 16,000-dalton peptide synthesized in the cell-free system appears to be q precursor of thymosin alpha1 and possibly of other peptides in the fractions isolated from calf thymus. The results support the conclusion that this peptide is synthesized in the thymus gland.

Cell-Free System↗
PubMedDate not supplied

Ethnic differences in knowledge and attitudes about BRCA1 testing in women at increased risk.

Informed consent for BRCA1 mutation testing will require adequate knowledge of patterns of inheritance of cancer and the benefits, limitations, and risks of DNA testing. This study examined knowledge about the inheritance of breast cancer and attitudes about genetic testing for breast-ovarian cancer susceptibility in women at increased risk. Knowledge and attitudes were measured in 407 African American and Caucasian women aged 18-75 who had at least one first-degree relative (FDR) with breast and/or ovarian cancer. The average knowledge score was 6.0 out of a total of 11 (S.D. = 2.15). Compared to Caucasian women, African American women had lower levels of knowledge and had more positive attitudes about the benefits of genetic testing. There were no significant ethnic differences in attitudes about the limitations and risks of testing, however, income was negatively associated with this outcome. Ethnic differences in knowledge and attitudes about genetic testing for breast-ovarian cancer risk may be attributable to differences in exposure to genetic information and referral by health care providers.

Adolescent↗