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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 127 records · Page 7Linked to original sources
PubMed1995

The prevalence of antibodies to hepatitis C virus at two haemodialysis units in South Africa.

The prevalence of antibodies against hepatitis C virus (HCV) was determined in 103 haemodialysis patients who attended two dialysis units in South Africa. With the use of a second-generation enzyme-linked immunosorbent assay (UBI HCV EIA, Organon Teknika, The Netherlands) and a 4-recombinant immunoblot assay (Chiron Corporation, USA), antibodies to HCV were found in 22 patients (21%). Statistically significant associations with anti-HCV carrier status were duration of dialysis (P = 0.0005) and number of blood transfusions received (P = 0.008). With stepwise logistic regression analysis it was not possible to separate the effects of HCV status associated with these two variables. A transient elevation in alanine aminotransferase (ALT) occurred in 8 of the 22 anti-HCV-positive patients, compared with 14 of the 81 anti-HCV-negative patients (P = 0.054). As yet, no patients have clinical evidence of ongoing liver disease or persistently elevated ALT levels. Of the 45 dialysis staff members tested, none was positive for anti-HCV.

Adolescent↗
PubMed1994

Risk of respiratory failure after repair of thoracoabdominal aortic aneurysms.

BACKGROUND: Multiple complications occur after repair of a thoracoabdominal aortic aneurysm, the most common of which is respiratory failure. METHODS: One hundred consecutive thoracoabdominal aneurysm repairs were studied retrospectively using univariate, bivariate, and multiple logarithmic regression analyses to identify factors associated with respiratory failure. RESULTS: The mean of days of intubation was 5.8 +/- 0.8 (mean +/- SEM), with a median of 2 days. Patients who developed respiratory failure (21%) had a 42% mortality compared with a 6% mortality in patients who did not develop respiratory failure (P < 0.001). Statistical analysis demonstrated a significant (P < 0.01) age difference between those with respiratory failure (71.9 +/- 1.6 years) and those without (65.5 +/- 1.3 years). Type II aneurysms occurred in 32% of patients, a 3.2-fold increase in relative risk compared with all other types of aneurysm. Seventy-nine percent of patients had a significant smoking history. Low forced vital capacity and forced expiratory volume were both significant variables in predicting respiratory failure, but neither chronic obstructive pulmonary disease nor emphysema was a predictive variable. Intraoperative blood transfusion (mean 10.5 +/- 0.8 units) was associated with respiratory failure (P = 0.05). Postoperative complications associated with respiratory failure were creatinine elevation and pneumonia. CONCLUSION: We conclude that the independent variables affecting respiratory failure after thoracoabdominal aneurysm repair are age, type of aneurysm, excessive intraoperative blood transfusions, creatinine elevation, and postoperative pneumonia.

Age Factors↗
PubMed1994

Heparin-released superoxide dismutase inhibits postischemic leukocyte adhesion to venular endothelium.

Superoxide radicals formed during reperfusion of ischemic tissues have been identified as a key mediator in the microvascular manifestations of postischemic tissue damage. This understanding is based on studies in laboratory animals in which high doses of superoxide dismutase (SOD; 2.0-25.0 mg/kg body wt iv) were found to inhibit postischemic leukocyte adhesion and the leakage of fluid and macromolecules. Using a dorsal skinfold chamber model in hamsters, we demonstrate now that protection from reperfusion-induced leukocyte adhesion to venular endothelium after 4 h of ischemia to striated muscle can be attained by pretreatment of the animals with a significantly lower dose of exogenous CuZn-SOD (0.25 mg/kg body wt) or with heparin (2,000 IU/kg body wt), which induces a comparable increase in SOD plasma activity through the release of endogenous extracellular SOD from endothelial cell binding sites. This protective effect was maintained until 24 h after reperfusion. In contrast, CuZn-SOD or heparin failed to attenuate the postischemic shutdown of nutritional capillary perfusion, a phenomenon that is due to ischemia-induced endothelial cell swelling, rather than due to reperfusion-associated events, and hence is not susceptible to strategies directed against oxygen radicals generated during the reperfusion phase. The results of this study 1) imply that postischemic leukocyte/endothelium interaction can be attenuated by a low and clinically more relevant dose of SOD, and 2) caveat the administration of heparin in laboratory animals (i.e., to keep catheters patent) in studies of experimental ischemia/reperfusion injury or other oxygen radical-dependent pathomechanisms.

Animals↗
PubMed1994

Ectopic ACTH syndrome and CRH-mediated Cushing's syndrome.

The ectopic ACTH syndrome accounts for a substantial number of patients with naturally occurring Cushing's syndrome. Despite the progress achieved in elucidating the pathophysiology of Cushing's syndrome, clinicians continue to experience diagnostic and therapeutic challenges. This is especially true in those patients presenting with disease mediated by ectopically produced ACTH and CRH. Patients with these disorders may be indistinguishable based on clinical grounds or simple biochemical and radiologic testing from those with Cushing's disease. However, this differentiation is critical because their therapies differ. While clinical researchers continue to develop more effective diagnostic techniques and therapies, further advances in the molecular and cell biology of ACTH and CRH-producing tumors will undoubtedly shed light on the pathogenesis of this perplexing, fascinating and still controversial entity.

ACTH Syndrome, Ectopic↗
PubMed1994

Search for the human papillomavirus in nasal polyps, using a polymerase chain reaction-method.

Viral etiology of nasal polyps was postulated as many as 40 years ago, but so far, no study has shown an association or causal relation between any specific virus and nasal polyps. By using the polymerase chain reaction (PCR) technique, nasal polyps from both 10 patients with intolerance to nonsteroidal anti-inflammatory drugs (NSAID intolerance) (e.g., Aspirin) and from 10 patients with no history of NSAID intolerance were studied for the presence of papillomavirus DNA. Nasal mucosa from 10 patients who had undergone surgery for septoplasty served as controls. The PCR test used covers approximately 30 different types of human papillomaviruses. In this test, all tissue samples studied were found negative for papillomavirus DNA.

Adult↗
PubMed1993

High affinity binding and direct antiproliferative effects of LHRH analogues in human ovarian cancer cell lines.

Recently, specific binding sites for luteinizing hormone releasing hormone (LHRH) and its analogues have been demonstrated in biopsy samples of human epithelial ovarian cancer. Their biological significance remained obscure. In this study we ascertained whether such LHRH-binding sites are also present in the human epithelial ovarian cancer cell lines EFO-21 and EFO-27 and if they could mediate antiproliferative effects of LHRH analogues. Using [125I, D-Trp6]LHRH, a high affinity/low capacity binding site was detected in both lines: EFO-21 (Kd1 = 1.5 x 10(-9) M; binding capacity (Bmax1) = 4.9 fmol/10(6) cells) and EFO-27 (Kd1 = 1.7 x 10(-9) M; Bmax1 = 3 fmol/10(6) cells). In addition, a second class of low affinity/high capacity binding sites (EFO-21: Kd2 = 7.5 x 10(-6) M; Bmax2 = 24 pmol/10(6) cells; EFO-27: Kd2 = 4.3 x 10(-6) M; Bmax2 = 14.5 pmol/10(6) cells) was demonstrated. Specific binding of [125I, D-Trp6]LHRH was displaced with nearly equal efficiency by unlabeled [D-Trp6]LHRH, the LHRH-antagonists SB-75 and Hoe-013, and by native LHRH but not by unrelated peptides such as oxytocin and somatostatin. In the presence of 10(-5) M agonist [D-Trp6]LHRH, the proliferation of both cell lines was significantly reduced to 77% of controls after 24 h and to approx. 60% after 6 days. Lower concentrations (10(-9) M) of the agonist, significantly decreased the proliferation to 87.5% for EFO-21 and 86% for EFO-27 after 6 days. These antiproliferative effects were enhanced by increasing doses of [D-Trp6]LHRH and were maximal at 10(-5) M (EFO-21: 65.5% of control, EFO-27: 68% of control). Similar dose-dependent antiproliferative effects were obtained in EFO-21 line with the LHRH-antagonists SB-75 and Hoe-013, while these analogues had no effects on the proliferation of EFO-27 cells. SB-75 partly antagonized the antiproliferative effect of [D-Trp6]LHRH in a dose dependent way in the EFO-27 line. These data suggest that LHRH analogues can directly inhibit the in vitro proliferation of human ovarian cancer cells. This effect might be mediated through the high affinity LHRH binding sites.

Cell Division↗
PubMed1993

Cloning and functional expression of a Schistosoma japonicum cDNA homologous to the enolase gene family.

A cDNA encoding the complete open reading frame of Schistosoma japonicum enolase has been cloned. The 1494bp cDNA (C30) was isolated from a S. japonicum cDNA expression library immunoscreened with hyperimmune rabbit sera raised against soluble adult S. japonicum proteins. The ORF encodes a protein of 434 amino acids exhibiting 72% identity to human, murine, and rat enolases, and 62% identity to Saccharomyces cerevisiae enolase. The inferred molecular mass of the protein is 47,251 Daltons, similar to that reported for the enolases of other species. In vitro translation of C30 also generated a protein of 47kDa. After subcloning and expression, the recombinant protein was purified by affinity chromatography under non-denaturing conditions and shown to exhibit functional enolase enzymatic activity.

Amino Acid Sequence↗
PubMed1993

Low infection rate and long durability of nontunneled silastic catheters. A safe and cost-effective alternative for long-term venous access.

BACKGROUND: Tunneled central venous catheters (CVCs) and infusion ports have often been considered as the only safe alternative for long-term venous access. The objective of this study was to assess the durability, cost, and infection rate of nontunneled, noncuffed Silastic CVCs. METHODS: We studied a representative cohort of 340 consecutive cancer patients with 359 nontunneled Silastic CVCs inserted and followed up at our center. All patients were evaluated clinically and microbiologically at the time of CVC removal. RESULTS: The mean in-place duration of the catheter for the 359 nontunneled CVCs studied was 109 days (total, 39,147 days of catheter use), and the infection rate was 0.13 per 100 catheter days. When compared with the tunneled Hickman catheter, the insertion cost saving was at least $2322 per CVC. At our institution, the use of nontunneled Silastic catheters with the support of an expert infusion team has resulted in an annual cost saving of at least $7,692,000. Long peripheral CVCs (in the basilic/cephalic vein) had a 26% rate of inflammation at the insertion site compared with only 2.6% for the short subclavian CVCs (P < .01). Most of the exit-site inflammations were sterile, with negative skin and catheter cultures. Neutropenia, bone marrow transplantation, high-dose steroids, and use of vesicant chemotherapeutic agents through the CVC did not predispose the patients to catheter infection. By univariate analysis, acute leukemia was the only risk factor for catheter infection. CONCLUSIONS: Given the low infection rate and long durability of nontunneled silicone CVCs, these catheters could offer a cost-effective and safe alternative to surgically implantable tunneled catheters.

Adult↗
PubMed1993

Properties of a M(r) 110,000 tumor rejection antigen of the chemically induced BALB/c Meth A sarcoma.

A M(r) 110,000 glycoprotein, designated gp110, isolated from the concanavalin A-Sepharose-binding protein fraction of the chemically induced BALB/c Meth A sarcoma by Mono Q fast protein liquid chromatography, has been shown to: (a) increase the resistance of these mice to growth of the Meth A sarcoma, but not the antigenically unrelated BALB/c CI-4 sarcoma, and (b) induce an antitumor cellular immune response in mice, which was detectable in cell-mediated cytotoxic assays. The immunogenicity of the concanavalin A-Sepharose-binding protein fraction of Meth A cytosol had been attributed to gp96, the major component of this fraction. The evidence presented here, however, demonstrates that Meth A gp96, when sufficiently purified, is nonimmunogenic. The results of the present analysis of gp110 strongly support the concept that gp110 represents a family of proteins expressed on a variety of chemically induced tumors, in which variations in molecular fine structure account for the antigenic diversity associated with these tumors.

Animals↗
PubMed1993

A novel approach to the characterization of cumulative exposure for the study of chronic occupational disease.

Inappropriate parameterization of an exposure metric for the study of occupational and environmental hazards may lead to significant misclassification and biased results. A model for identification of an optimal expression for cumulative exposure that includes exponentiated terms for concentration and time was developed. When the values of the exponents are allowed to vary, an optimal expression for cumulative exposure may be identified. The approach has advantages for the study of chronic hazards, in that it is flexible, limits the number of assumptions, and incorporates many of the models generally suggested in the literature. In addition, the model results may be interpreted to suggest particular pathophysiologic mechanisms. The model was implemented with data from a previously studied cohort of underground coal miners, and the associations between the exposure metric and measures of obstructive lung disease were identified. The results demonstrated that the exposure metric can improve the association of dust exposure histories with various outcomes over the usual measure of cumulative exposure. However, in the particular data set used, the overall predictive power of alternative models was similar and the interpretability of the results was limited.

Adult↗
PubMed1993

Preservation of peripheral nerve grafts with Schwann cell culture medium.

Preservation of peripheral nerves may, in the near future, play an important role in reconstructive surgery, especially if recent advances in immunosuppressive therapy are taken into account. Therefore, it has to be investigated whether peripheral nerves can be stored for some time after harvesting without diminishing their regenerative potential. Previous experiments of our group could demonstrate only little benefit of organ storage solution (HTK) or normal saline (NaCl 0.9%) to peripheral nerves when kept at cold ischaemia of 4 degrees C for 32 and 72 hours. In this presentation, we are reporting the results of peripheral nerve storage in Dulbecco's Modified Eagle Medium which has been used for Schwann cell culture. In 30 adult Sprague-Dawley rats, a 2.5 cm segment of the right sciatic nerve was harvested and kept at 4 degrees C for 14, 32, 72, and 120 hours. It was then reimplanted into the donor animal; regeneration quality was assessed clinically, histologically and morphometrically after 6 weeks. Best regeneration results were obtained in the 32 and 72 hour groups; regeneration here was comparable to the normal controls. These results are explained with the positive effect of nerve predegeneration.

Animals↗
PubMed1993

Cytokine enhancement of peripheral blood stem cells.

The use of cytokines to improve peripheral blood stem cell enhancement and recruitment has recently received close attention. Three main cytokines have been, or are still being, investigated in this way in human clinical trials so far: recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF), granulocyte CSF (rhG-CSF) and interleukin 3 (IL-3). While cytokines used alone appear undoubtedly capable of a marked peripheral blood stem cell (PBSC) enhancement, their combination with a chemotherapy priming often increases this phenomenon. This is particularly evident with rhIL-3, which is an earlier acting cytokine than rhGM-CSF and rhG-CSF. rhIL-3 priming alone leads to only a minor elevation of circulating progenitor cells, while its combination with chemotherapy and/or a late acting cytokine may allow enhancement and recruitment of large amounts of PBSC. The effect of cytokines on PBSC enhancement may also be at least partially thwarted by various factors. Additionally, their adequate dosage often remains uncertain. So it is presently too early to determine what is actually the most appropriate cytokine or cytokine combination to improve PBSC enhancement. Also the risk of stimulation of tumor clonogenic cells in some malignant diseases remains, and the experimenters should be as cautious as possible to not jeopardize the patients' safety.

Antineoplastic Agents↗
PubMed1993

Difficulties in collecting peripheral blood stem cells in chronic myeloid leukemia related to persistence of the leukemic cell clone.

Eight chronic myeloid leukemia (CML) patients ineligible for allogeneic bone marrow transplantation (BMT) were intensively treated by a myeloablative chemotherapy identical to the treatment that we use in acute myeloid leukemia (AML). The objectives of such an intensive treatment were both to reduce the size of the leukemia stem cell mass as much as possible and subsequently to allow a better mobilization of the residual Ph-negative (Ph-) stem cells. Cytogenetic analyses were systematically performed on blood-derived stem cells collected at the hematopoietic recovery phase following post-chemotherapy aplasia. The length of aplasia did not correlate with the evolutive stage of the disease, but was negatively correlated with the total colony forming units-granulocyte macrophage (CFU-GM) amounts collected. The cytogenetic abnormality remained present in most cases in all metaphases counted in leukapheresis products. Three patients were transplanted with these leukapheresis products. One died due to sepsis before engraftment; the two others engrafted very slowly, while Ph-positive (Ph+) cells were found at post-transplant controls. These disappointing results suggest that the myeloablative chemotherapy used in this study has not resulted in satisfactory advantages for the proliferation of residual normal stem cells over the expansion of the Ph+ clone.

Adolescent↗
PubMed1993

A new patient focused index for measuring quality of life in persons with severe and persistent mental illness.

The quality of life in persons with severe and persistent mental illness is often poor. Most treatment programmes have the goal of increasing quality of life. Unfortunately, existing methods to assess quality of life are cumbersome and oriented towards research rather than clinical settings. This study describes preliminary steps in the development, testing and application of a new patient focused index for measuring quality of life in persons with severe mental illness. The Quality of Life Index for Mental Health (QLI-MH) differs from existing instruments in that it is based on an easy to use, self-administered questionnaire that assesses nine separate domains that together encompass quality of life. Each domain can be individually weighted depending on its relative importance to the patient. Different parts of the instrument solicit information from the patient, the primary clinician, and, when available, the family. The instrument and its scoring system address limitations of previous approaches to quality of life measurement.

Activities of Daily Living↗
PubMed1993

Treatment of severe familial hypercholesterolemia in childhood with sitosterol and sitostanol.

This study was undertaken to compare the ability of two plant sterols to reduce serum levels of lipids and to compare their mechanism of action in nine children with severe familial hypercholesterolemia (total and low-density lipoprotein cholesterol concentrations averaged 9.57 mmol/L (370 mg/dl) and 7.87 mmol/L (301 mg/dl)). After a 3-month strict diet, the children were given sitosterol pastils (2 gm three times a day) for 3 months, followed by a 7-month course of sitostanol (0.5 gm three times a day). Serum lipoprotein levels and serum concentrations of campesterol and sitosterol were determined in all nine children, and the fecal excretion of neutral and acidic sterols were determined in seven children at the end of each therapeutic regimen. Sitosterol reduced low-density lipoprotein cholesterol levels by 20% (p < 0.01); sitostanol reduced low-density lipoprotein cholesterol levels by 33% after 3 months and 29% after 7 months (p < 0.01 compared with diet; p < 0.05 compared with sitosterol). Although sitosterol did not alter serum concentrations of campesterol and sitosterol, a significant reduction did occur during sitostanol therapy (-47% and -51%, respectively; p < 0.01). Fecal excretion of neutral sterols increased from 6.7 mg/kg per day during the control period to 9.7 mg/kg per day during sitosterol administration (p < 0.05), and to 12.6 mg/kg per day during sitostanol administration (p < 0.05 compared with diet and sitosterol periods), indicating an increase in the inhibition of intestinal cholesterol absorption. All children completed the study and no obvious side effects occurred. The data indicate that sitostanol, even with a dose four-fold lower than that of sitosterol, was significantly more effective in reducing elevated levels of low-density lipoprotein cholesterol, and the reduction in serum lipid levels was of the same magnitude as that observed with systemic lipid-lowering drugs. These results suggest that sitostanol, a nonabsorbable plant sterol, could be the drug of choice for treating familial hypercholesterolemia in childhood.

Adolescent↗