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Biomedical subjects

M Fishman

Publications and source records attributed to M Fishman.

At least 19 recordsLinked to original sources
PubMed2001

HIV risk behaviors and their relationship to posttraumatic stress disorder among women prisoners.

OBJECTIVE: This study assessed HIV risk behaviors and their association with psychiatric disorders among women prisoners. METHODS: HIV risk behaviors practiced in the five years before incarceration were ascertained with the Risk Behavior Assessment interview for 177 inmates at the Maryland Correctional Institution for Women. The Structured Clinical Interview for the DSM-IV was used to determine the occurrence of posttraumatic stress disorder (PTSD), major depression, and dysthymic disorder among the women. Regression models were used to determine the association between HIV risk behavior and psychiatric disorders. RESULTS: HIV risk behaviors in the five years before incarceration included never or rarely having used condoms (56 percent of the women), injection drug use (42 percent), sexual intercourse with a partner who used injection drugs (42 percent), prostitution (30 percent), needle sharing (30 percent), receptive anal sex (19 percent), and having more than 100 sex partners (7 percent). After the analysis adjusted for age, education, race, HIV status, and addictive disorders, a lifetime occurrence of PTSD was associated with the practice of anal sex (odds ratio=1.7; 95 percent confidence interval=1.26 to 2.16; p<.02) and prostitution (OR=1.56; 95% CI=1.17 to 1.95; p<.03). CONCLUSIONS: HIV risk behaviors before incarceration were highly prevalent among the women in this study. Rates of PTSD, depression, and dysthymic disorder were also high. PTSD was associated with prostitution and receptive anal sex, and the disorder may contribute to high rates of risky sexual behavior. Targeted HIV risk reduction efforts among women prisoners should include evaluation for PTSD; conversely, women prisoners with a diagnosis of PTSD should be evaluated for prior HIV sexual risk behaviors.

Adult↗
PubMed2001

Novel therapies for renal cell carcinoma.

Metastatic renal cell cancer remains a disease which is difficult to treat medically. Prognosis often depends more on intrinsic disease features than on treatment choices. In this review, we examine novel therapies and scientific directions surrounding the RCC treatment problem. Reports relating chromosomal aberrations and of comparative gene expression analyses relating to RCC, are reviewed briefly. The central role of the von Hippel Lindau protein in clear cell RCC pathogenesis is evident. The limited contribution of conventional cytotoxic chemotherapy is mentioned. Some clinically applied agents whose clinical results are highlighted include 5-FU, retinoids, thalidomide, razoxane and IL-12. Features of the pathophysiology of von Hippel Lindau protein are described, with attention to potential novel therapies targeting HIF-1alpha, VEGF, TGF-beta1 and TGF-alpha pathways. Immunotherapy is being explored in many angles. Most basic are cytokine therapies incorporating new IL-2 and IFN-alpha schedules. Newer cytokine-based drugs include pegylated forms and IL-12. Allogeneic mini-transplantation has generated much interest. Tumour-associated antigens are being used to direct therapy using both identified and non-identified epitopes. A variety of tumour-cell vaccine and dendritic-cell vaccine clinical approaches are discussed. Finally, nephrectomy for known metastatic disease has been demonstrated to be helpful in retrospective and now prospective trials. Resection of metastases is also discussed. We are optimistic that the further clinical development among these novel therapies will improve the outlook for metastatic RCC.

Antineoplastic Agents↗
PubMed2000

Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA.

Two small RNAs regulate the timing of Caenorhabditis elegans development. Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA, and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences in the 3' untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs. Here we have detected let-7 RNAs of approximately 21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila, at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny.

Adult↗
PubMed2000

Characterization of a zebrafish/mouse somatic cell hybrid panel.

We have characterized a collection of zebrafish/mouse somatic cell hybrids with 211 genes and markers chosen from the 25 zebrafish linkage groups. Most of the zebrafish genome is represented in this collection with 88% of genes/markers present in at least one hybrid cell line. Although most hybrids contain chromosomal fragments, there are a few instances where a complete or nearly complete zebrafish chromosome has been maintained in a mouse background, based on multiple markers covering the entire chromosome. In addition to their use in mapping studies, this collection of somatic cell hybrids should constitute an important tool as a source of specific chromosome fragments and for assessing the function of genome regions.

Animals↗
PubMed1999

Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.

OBJECTIVE: To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). METHODS: Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. RESULTS: HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. CONCLUSION: In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.

Adult↗
PubMed1999

Medical records contaminated with dried blood: A quality issue.

A routine chart review over 23 months in a 256-bed community hospital revealed 246 medical records contaminated with apparent blood. Sixty percent of the records were nursing and anesthesiology records. Analysis of systematically selected records confirmed blood as the visible contaminant in 27% of the cases (8/30). Total quality improvement methodology reduced the incidents by 75%. Actions included policy development, in-service education, and changes in work practices. Although bloodborne pathogen transmission is statistically improbable, we should improve work practices to eliminate blood contamination of charts.

Blood↗
PubMed1999

Stem cell component therapy: supplementation of unmanipulated marrow with CD34 enriched peripheral blood stem cells.

Eleven patients with hematologic malignancies and two with aplastic anemia were treated using unmanipulated marrow and immunoselected CD34+ blood cells. Donors began G-CSF (10 microg/kg) injections 1 day after undergoing bone marrow harvest. Blood stem cells were collected on day 5 of G-CSF. Peripheral blood lymphocytes were depleted via CD34-positive selection. If, after marrow and blood harvest, less than 2.0 x 10(6) CD34 cells/kg were mobilized, leukapheresis was repeated on day 6. Median time to an absolute neutrophil count greater than 500 microl was day 10; transfusion-independent platelet count greater than 20,000/microl was day 13; average hospital discharge was day 14; and average inpatient hospital charges were 101,870 US dollars. Acute GVHD grade II occurred in five of 13 patients. No patient developed grade III or IV acute GVHD. At a median follow-up of 10 months, no patient has developed extensive chronic GVHD. Allografts of unmanipulated bone marrow supplemented with G-CSF-mobilized and CD34 immunoselected blood cells may prevent an increased risk of GVHD while preserving the rapid engraftment kinetics of peripheral blood. Supplementation of marrow with CD34 enriched blood cells appears to result in rapid engraftment, early hospital discharge, lower inpatient charges, decreased regimen-related toxicity, and no apparent increase in GVHD.

Adult↗
PubMed1999

Activation of chick tendon lysyl oxidase in response to dietary copper.

Lysyl oxidase (EC 1.4.3.13), a cuproenzyme, can account for 10-30% of the copper present in connective tissue. Herein, we assess the extent to which tissue copper concentrations and lysyl oxidase activity are related because the functional activity of lysyl oxidase and the copper content of chick tendon are both related to dietary copper intake. Chicks (1-d old) were fed diets (basal copper concentration, 0.4 microg/g diet) to which copper was added from 0 to 16 microg/g diet. Liver and plasma copper levels tended to normalize in chickens that consumed from 1 to 4 microg copper/g of diet, whereas tendon copper concentrations suggested an unusual accumulation of copper in chickens that consumed 16 microg copper/g diet. The molecular weight of lysyl oxidase was also estimated using matrix-assisted laser desorption ionization/time-of-flight/mass spectrometry (MALDI/TOF/MS). A novel aspect of these measurements was estimation of protein mass directly from the surface of chick tendons and aortae. Whether copper deficiency (0 added copper) or copper supplementation (16 microg copper/g of diet) caused changes in the molecular weight of protein(s) in tendon corresponding to lysyl oxidase was addressed. The average molecular weight of the peak corresponding to lysyl oxidase in tendon and aorta from copper-deficient birds was 28,386 Da +/- 86, whereas the average molecular weight of corresponding protein in tendon from copper-supplemented birds was 28,639 Da +/- 122. We propose that the shift in molecular weight is due in part to copper binding and the formation of lysyl tyrosyl quinone, the cofactor at the active site of lysyl oxidase.

Animals↗
PubMed1998

Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation.

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Activities of Daily Living↗
PubMed1998

Necrotizing fasciitis caused by Staphylococcus aureus.

Two patients with rapidly progressive necrotizing fasciitis of a lower extremity due to Staphylococcus aureus as a single pathogen are described. In both patients the portal of entry was attributed to needle puncture (intra-articular injection and intravenous catheter, respectively), followed by bacteremia. Necrotizing fasciitis occurred in a site remote from the needle puncture, suggesting metastatic infection. One patient developed toxic shock syndrome and the other a sunburn-like rash and erythematous mucosae with strawberry tongue. One patient died, and the other required above-knee amputation due to secondary infectious complications. Staphylococcus aureus may mimic the presentation of invasive group A streptococcal infections. A history of needle puncture should alert the physician to the possibility of Staphylococcus aureus infection.

Aged↗
PubMed1998

T cell-depleted autologous hematopoietic stem cell transplantation for multiple sclerosis: report on the first three patients.

Multiple sclerosis (MS) is a disease of the central nervous system characterized by immune-mediated destruction of myelin. In patients with progressive deterioration, we have intensified immunosuppression to the point of myeloablation. Subsequently, a new hematopoietic and immune system is generated by infusion of CD34-positive hematopoietic stem cells (HSC). Three patients with clinical MS and a decline of their Kurtzke extended disability status scale (EDSS) by 1.5 points over the 12 months preceding enrollment and a Kurtzke EDSS of 8.0 at the time of enrollment were treated with hematopoietic stem cell (HSC) transplantation using a myeloablative conditioning regimen of cyclophosphamide (120 mg/kg), methylprednisolone (4 g) and total body irradiation (1200 cGy). Reconstitution of hematopoiesis was achieved with CD34-enriched stem cells. The average time of follow-up is 8 months (range 6-10 months). Despite withdrawal of all immunosuppressive medications, functional improvements have occurred in all three patients. We conclude that T cell-depleted hematopoietic stem cell transplantation can be performed safely in patients with severe and debilitating multiple sclerosis. Stem cell transplantation has resulted in modest neurologic improvements for the first time since onset of progressive disease although no significant changes in EDSS or NRS scales are evident at this time.

Adult↗