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Biomedical subjects

M Becker

Publications and source records attributed to M Becker.

At least 199 records · Page 11Linked to original sources

Comparative survival, quality of life and cost-effectiveness of intensive therapy with autologous blood cell transplantation or conventional chemotherapy in multiple myeloma.

We retrospectively compared survival time, quality of life, and the therapy costs in 37 patients suffering from newly diagnosed multiple myeloma (MM), divided into 3 groups. Twelve patients with grade III MM, according to the classification of Durie-Salmon, all with widespread lytic lesions (group I), underwent a two-phase intensive therapy. They first received high-dose melphalan (HDM), both as tumor-reducing and blood cell (BC)-mobilizing chemotherapy, subsequently followed by BC transplantation. Group II comprising 10 patients, also with grade III MM and with characteristics similar to those of group I, were treated with conventional polychemotherapy. Finally, group III enrolled 15 patients with lower grade disease (grade II) who were also treated with conventional chemotherapy. The median overall survival time and the quality of life index were significantly lower in group II than in group I (P = 0.0013 and < 0.001 respectively). Although the overall survival time of group III (43 months) was similar to that of group I, its quality of life index was also significantly lower (P < 0.05). However, the total therapy costs of group I were globally higher than those of the 2 other groups, but when absolute cost-effectiveness as well as qualitative cost-effectiveness (corrected for quality of life) were analyzed, the costs per week of life gained of group I compared extremely favorably with those of group II and, to a lower degree, of group III. Intensive therapy therefore seems capable of substantially improving the survival time for high-risk MM patients with satisfactory quality of life and at a reasonable cost.

Adult↗

Focal inflammation of the corpus cavernosum in a diabetic man due to acute occlusion of the cavernous artery.

Inflammation of the penile corpus cavernosum is an unusual condition most often associated with an infectious process. We report on a diabetic man with localized inflammation of the corpus cavernosum resulting from acute occlusion of the cavernous artery. Diagnosis was made by exclusion and ultimately confirmed by penile angiography. Conservative measures led to resolution of this process.

Acute Disease↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗