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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 325 records · Page 18Linked to original sources
PubMed1996

Anti-HIV potential of a new interferon, interferon-tau (trophoblastin).

Antiretroviral effects of a new class of interferon (IFN), IFN-tau, were compared with those of IFN-alpha in primary peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDMs), infected in vitro by human immunodeficiency viruses type 1, HIV-1/LAI, and HIV-1/DAS isolates, respectively. Cells were treated with recombinant IFN 24 h before or after HIV infection and then continuously exposed. Viral replication was monitored twice a week by quantifying the reverse transcriptase activity in cell culture supernatants. Integrated proviral DNA was monitored 24 h after infection in IFN-tau-pretreated MDMs, using specific gag gene amplification by the polymerase chain reaction. IFN-tau inhibited HIV-1 replication in both PBLs and MDMs as well as in peripheral blood mononuclear cells (PBMCs). IFN-tau was 35-fold more potent than IFN-alpha in PBLs and 100-fold more potent in MDMs. Differences were observed in the amount of integrated proviral DNA between untreated and 10 IU/ml IFN-tau-treated HIV-infected MDMs. IFN-tau exhibits significant anti-HIV activity in comparison to IFN-alpha, and like other IFNs, it seems to interact with several steps of HIV replication cycle.

Antiviral Agents↗
PubMed1996

A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation.

Between May 1, 1993 and April 5, 1995, 154 pancreas allograft recipients at 9 institutions were given FK506 posttransplant. Three groups were studied: (1) recipients given FK506 initially for induction and maintenance therapy (n = 82), (2) recipients switched to FK506 for antirejection or rescue therapy (n = 61), and (3) recipients converted to FK506 for other reasons (n = 11). Of 82 patients in the induction group, 7 (9%) had simultaneous bone marrow (BM) and pancreas-kidney (SPK-BM) transplants, 54 (66%) had SPK transplants without BM, 14 (17%) had pancreas transplants alone (PTA), and 7 (9%) had pancreas after previous kidney transplants (PAK). All but 1 recipient was given quadruple immunosuppression (anti-T cell agents plus azathioprine and prednisone) for induction. The median FK506 starting dose was 4 mg/day p.o.; the median average FK506 blood level, 12 ng/ml. The most common side effects were neurotoxicity (16%), nephrotoxicity (13%), and gastrointestinal toxicity (9%). New-onset diabetes mellitus requiring permanent insulin therapy did not occur. Of 61 transplants in the rescue group, 44 (72%) were SPK, 11 (18%) PTA, and 6 (10%) PAK. All but 3 (95%) of the recipients had been on cyclosporine-azathioprine-prednisone triple immunosuppression before substitution of FK506 for cyclosporine; 46% of the recipients had one, and 54% > or = 2, rejection episodes preconversion. The most common side effects were nephrotoxicity (25%), neurotoxicity (23%), and gastrointestinal toxicity (21%). Two recipients were reconverted to cyclosporine because of transient hyperglycemia, and one recipient is on insulin. In the induction group, patient survival at 6 months was 90% for SPK, 100% for PTA, and 100% for PAK. According to a matched-pair analysis, pancreas graft survival for SPK recipients at 6 months was 87% for FK506 versus 70% for cyclosporine recipients (P = 0.04); for PTA recipients, 84% versus 66% (P = n.s.); and for PAK recipients, 80% versus 14% (P = 0.11). When technical failures and death with functioning grafts were censored, pancreas graft survival remained significantly better in the FK506 group. The incidence of first reversible rejection episodes by 6 months in FK506 recipients was 35% for SPK, 40% for PTA, and 20% for PAK. Of 75 pancreas grafts, 64 are currently functioning; in 5 recipients the pancreas failed (1 from rejection); 6 recipients died with a functioning pancreas graft. There were 3 posttransplant lymphomas (all EBV-positive); 2 recipients died and 1 is alive after subtotal colectomy and transplant pancreatectomy. In the antirejection rescue group, patient survival rates at 6 months were 91% for SPK, 100% for PTA, and 80% for PAK (P = n.s.). Pancreas graft survival rates at 6 months were 90% for SPK, 72% for PTA, and 40% for PAK. The incidence of first reversible rejection episodes after conversion to FK506 at 6 months was 44% in SPK, 54% in PTA, and 50% in PAK. Of 61 pancreas grafts, 51 are currently functioning; in 7 recipients the pancreas failed (5 from rejection); 3 recipients died with a functioning graft. There were no posttransplant lymphomas in the rescue group. This multicenter survey shows that FK506 in pancreas transplantation is associated with (1) a low rate of graft loss from rejection when used for induction therapy, (2) a high rate of graft salvage when used for rescue or rejection therapy, and (3) a very low rate of new-onset insulin-dependent diabetes mellitus. These encouraging results are tarnished by 3 posttransplant lymphomas in the induction group; a possible explanation is overimmunosuppression, but further (randomized) studies are necessary to analyze the long-term risk-benefit ratio of FK506 after pancreas transplantation.

Adolescent↗
PubMed1996

Cryptococcal meningitis after liver transplantation.

We present our experience with 10 liver transplant recipients in whom cryptococcal meningitis developed after liver transplantation. Disease developed a median period of 3.5 months (range, 2-36 months) after transplantation and patients were diagnosed a median period of 9 days (range, 2-90 days) after initial symptoms. Headache, fever, and mental status changes were the most frequent clinical presentations, while meningismus was found in only 30% of patients. Cerebrospinal fluid analysis was diagnostic in all cases. All patients were treated with amphotericin B and flucytosine. Immunosuppression was either decreased or discontinued during therapy. Five patients died, four as a direct result of cryptococcal infection and one as a result of chronic rejection. Three patients had long-term survival without any sequelae. One long-term survivor suffered blindness consequent to the disease. We conclude that cryptococcal meningitis is a rare complication in liver transplant recipients (0.25%), and has a high mortality rate (50%). Early recognition, combination antifungal therapy, and decrease or discontinuation of immunosuppression are important for cure. No relapse has been seen in surviving patients.

Adult↗
PubMed1996

Inhibition of human immunodeficiency virus infection by heparin derivatives.

Heparin (Hep) and sulfated polysaccharides (SPs) have been reported to inhibit HIV infection in vitro. In vivo, anticoagulant activity and reduced bioavailability were found to limit the antiviral effects of Hep. In this investigation, three nonanticoagulant N-acylated Hep conjugates [OI1:3Hep, Pal1:5Hep, and Pal1:5Hep(SO4)] were compared to Hep for their ability to interact with HIV replication in CD4-positive cell lines and PBMCs. Resulfated palmitoyl-Hep [Pal1:5Hep(SO4)] exhibited the strongest anti-HIV effects. For instance, no provirus HIV DNA was detected in the genome of HIV-1-LAI-infected PBMCs treated with this heparin derivative. Cell-to-cell fusion and RT activity were explored to explain these differences. Hep and Pal1:5Hep(SO4) derivative exerted identical effects on cell-to-cell fusion. On the other hand, Pal1:5Hep(SO4) displayed the strongest inhibitory effects in the acellular RT inhibition assay. This suggests that RT might be a second target for N-acylated Hep, even though SP uptake and the preferential effects of SPs on RT as opposed to DNA polymerase have not yet been demonstrated. Nevertheless, considering the anticoagulant, antiviral, and antiinflammatory effects of N-acylated Hep, the N-acylated Hep derivatives might be excellent candidates as new anti-HIV pharmacological tools.

Antiviral Agents↗
PubMed1996

Advantages and limitations of the use of isolated kidney tubules in pharmacotoxicology.

Among the cellular models used in in vitro renal pharmacotoxicology, isolated kidney tubules, used as suspensions mainly of proximal tubules, offer important advantages. They can be prepared in large amounts under nonsterile conditions within 1-2 h; thus, it is possible to employ a great number of experimental conditions simultaneously and to obtain rapidly many experimental results. Kidney tubules can be prepared from the kidney of many animal species and also from the human kidney; given the very limited availability of healthy human renal tissue, it is therefore possible to choose the most appropriate species for the study of a particular problem encountered in man. Kidney tubules can be used for screening and prevention of nephrotoxic effects and to identify their mechanisms as well as to study the renal metabolism of xenobiotics. When compared with cultured renal cell, a major advantage of kidney tubules is that they remain differentiated. The main limitations of the use of kidney tubules in pharmacotoxicology are (1) the necessity to prepare them as soon as the renal tissue sample is obtained; (2) their limited viability, which is restricted to 2-3 h; (3) the inability to expose them chronically to a potential nephrotoxic drug; (4) the inability to study transepithelial transport; and (5) the uncertainty in the extrapolation to man of the results obtained using animal kidney tubules. These advantages and limitations of the use of human and animal kidney tubules in pharmacotoxicology are illustrated mainly by the results of experiments performed with valproate, an antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules, unlike cultured renal cells, retain key metabolic properties is also shown to be of the utmost importance in detecting certain nephrotoxic effects.

Animals↗
PubMed1996

Systemic inflammatory response syndrome after cardiac operations.

BACKGROUND: A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. METHODS: Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. RESULTS: Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. CONCLUSIONS: Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.

Acidosis, Lactic↗
PubMed1996

Cognitive idiosyncrasies among children with the chronic fatigue syndrome: anomalies in self-reported activity levels.

The possibility that children with the chronic fatigue syndrome (CFS) and their parents tend to display idiosyncratic cognitive processing concerning levels of activity was examined by means of subjective and objective measures of current activity, together with subjective and objective measures of desired and expected future activity. The degree to which subjective reports of current activity level reflect objectively measured activity level was examined in a group of children with CFS and a healthy control group. All subjects were assessed over a 3-day period by means of ambulatory activity monitoring, and self-reports and parent-reports of current activity level were collected by means of visual analog scales. Analysis of variance revealed a significant interaction between the method of measurement (objective versus subjective) and the participant group (CFS versus Healthy) with the CFS children and their parents underestimating actual level of activity relative to the healthy group. Desired and expected levels of future activity were also assessed by means of subjective report. Child and parent expected levels of future activity were compared with their desired levels. Although expected levels of future activity were similar in the two groups, the divergence between expected levels and corresponding desired levels was significantly greater in the CFS group. These results are discussed in terms of idiosyncratic cognitive processes, which are hypothesized to be associated with CFS and which may play a role in the maintenance of the disorder.

Adolescent↗
PubMed1996

Fatigue in the chronic fatigue syndrome: a cognitive phenomenon?

What is the source of the perception of excessive fatigue in the chronic fatigue syndrome (CFS)? Studies of physiological response to aerobic activity, of muscle pathology and muscle function in CFS, are reviewed, and suggest that the subjective report of fatigue is not due to any peripheral impairment. In addition, current technological methods such as electroencephalography have failed to uncover the nature of any abnormality in the central motor unit. A physiological model which proposes that patients with CFS possess a reduced threshold for sensory fatigue signals is rejected, because it fails to account for recent findings. Instead, it is suggested that the perception of fatigue in CFS is enhanced by idiosyncrasies in cognitive processing. The implications of this view to our understanding of the perpetuation of CFS as a whole are explored.

Cognition↗
PubMed1996

Role of stromal myofibroblasts infiltrating colon cancer in tumor invasion.

In the normal colon, myofibroblasts are closely apposed to colonocytes where they deposit type IV collagen, the main basement membrane component. In colon carcinomas, this epithelial-mesenchymal association is physically disrupted, leading to the production of an abnormal, type IV collagen defective, basement membrane. Tumor-infiltrating myofibroblasts are migratory cells that accumulate at the invasive front of the colorectal carcinomas. They produce lytic enzymes able to degrade the basement membrane surrounding tumor glands. They also participate in the synthesis of the extracellular matrix components of the tumor stroma, which could subsequently alter the adhesive and migratory properties of the epithelial colon cancer cells. These results suggest that tumor-infiltrating myofibroblasts play a role in the invasion and metastasis of colorectal tumor cells.

Animals↗
PubMed1996

Serum basic fibroblast growth factor and vascular endothelial growth factor and tumour growth kinetics in advanced colorectal cancer.

BACKGROUND: The development of new microvessels in the surrounding stroma is a prerequisite for tumour progression. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are angiogenic factors expressed in a broad range of human tumours. We have measured the concentrations of both cytokines in the serum of patients with advanced colorectal cancer. We questioned whether these levels are related to the number of tumour sites, the volume of liver and/or lung involvement and the growth kinetics. PATIENTS AND METHODS: 44 untreated colorectal adenocarcinoma patients who had developed metastatic and/or recurrent disease were evaluated. Serum levels of bFGF and VEGF were repeatedly measured using ELISA. The extent of target organ involvement and the kinetics of tumour volume growth were determined on consecutive computer tomography (CT) images. RESULTS: Patients with a tumour volume doubling time of less than 6 months showed a higher bFGF and VEGF serum level than others, independent of the number of sites involved and the extent of the metastatic disease. CONCLUSIONS: The data suggest a predictive value of serum bFGF and VEGF levels for the progression of disease in patients with untreated metastatic colorectal cancer. The results corroborate the importance of angiogenesis in the process of tumour growth. The serum levels might prove a useful tool in the quantification of angiogenesis and might be of valuable information in the decision process of initiating palliative chemotherapy. It will be of considerable importance to investigate whether the serum bFGF and VEGF levels have a predictive value on the probability of response to cytotoxic therapy.

Adenocarcinoma↗
PubMed1996

Effectiveness of a physician education program in reducing consumption of hospital resources in elective total hip replacement.

A physician education program altered the consumption of hospital resources by orthopedic surgeons doing total hip replacement. They were presented with verbal and written physician-specific materials during a 7-week period. Xbar and R charts were used to display measurements of resource consumption before and after the educational program. Physicians were provided with surgeon-specific data profiling their own practice and that of their peers. Inferential statistics were used to validate the effects of education. Length of hospital stay for patients receiving total hip replacement dropped from 13.7 days to 9.9 days. Adjusted total charges dropped from $22,103 to $18,607. The variance for length of stay and total charges dropped by one half or more. Physician education programs are effective in reducing consumption of hospital resources. Statistical process control data formatting appears to make the data more usable to these physicians.

Education, Medical, Continuing↗
PubMed1996

AP1 enhances polyomavirus DNA replication by promoting T-antigen-mediated unwinding of DNA.

An early step in the initiation of polyomavirus DNA replication is viral large-T-antigen-mediated unwinding of the origin. We report that components of the AP1 transcription factor, Fos and Jun, interact with T antigen in vitro to enhance unwinding of the viral origin. This provides a biochemical basis for the capacity of AP1 to activate viral DNA replication in vivo.

Antigens, Viral, Tumor↗
PubMed1996

[1-13C]glucose metabolism in brain cells: isotopomer analysis of glutamine from cerebellar astrocytes and glutamate from granule cells.

We analyzed the glutamine isotopomers released into the extracellular medium by cerebellar astrocytes incubated with [1-13C]glucose. We developed a mathematical model of the tricarboxylic acid (TCA) cycle to determine the relative flux of molecules through the anaplerotic versus oxidative pathways and the relative pyruvate carboxylase versus pyruvate dehydrogenase activities. As glutamine C2 and C3 exhibited unequivalent enrichments, we examined the possibility of: (1) both the entry of the label into the TCA cycle from pyruvate and the conversion of the oxaloacetate into citrate before equilibration with fumarate, and (2) the occurrence of an orientation-conserved transfer of the symmetrical 4-carbon intermediates. The best fit required partial cycling between oxaloacetate and fumarate, whereas the occurrence of any orientation-conserved transfer was rejected. On the other hand, the analysis of glutamate isotopomers from perchloric acid extracts of granule cells incubated with [1-13C]glucose indicated that total cycling of oxaloacetate into fumarate occurred in these cells.

Animals↗
PubMed1996

The severity and pattern of emesis following different cytotoxic agents.

Different cytotoxic drugs induce different patterns of emesis. This is relevant to clinical practice since we often see in the medical literature oversimplifications in the recommendation for management of chemotherapy-induced emesis, so that the same guidelines are given for cisplatin and non-cisplatin-containing chemotherapy. In particular, cisplatin induces a biphasic pattern of emesis which is characterized by an acute immediate phase and a delayed phase. These two phases are clearly different, especially when cisplatin is given in short i.v. administration (e.g. over 20 min to 1 h) and in high doses (1000-120 mg/m2). On the other hand, cyclophosphamide and carboplatin induce a quite different pattern of emesis, characterized by a monophasic curve which although more intense in the first 24 h, may continue for a number of days. The antiemetic response to 5-HT3 receptor antagonists on days 2-5 is good in the case of carboplatin and cyclophosphamide and poor in the case of cisplatin (delayed emesis after cisplatin). This firmly suggests that the pathogenesis of cisplatin-induced emesis may differ from that induced by other cytotoxic drugs, especially in the delayed phase of emesis. We think that we should reserve the term 'delayed emesis' for the late emesis induced by cisplatin, while 'prolonged emesis' could be a better denomination for the late emesis induced by cyclophosphamide and carboplatin. The main clinical implication of these observations is that 5-HT3 receptor antagonists should be administered over 3-5 days in the case of carboplatin and cyclophosphamide, while a short treatment during the first day could be sufficient to control the acute phase of cisplatin-induced emesis.

Antiemetics↗
PubMed1996

Understanding socially inhibited behaviors in managers.

The authors' purpose in this study is to define and highlight socially inhibited behaviors among managers, explore the implications of these behaviors for the workplace, identify ways to assist inordinately shy managers, and help staff to understand and relate more effectively when subjected to an inhibited manager. The authors search for the origins of shyness, surveying the various perspectives in personality theory and within the concept of situational causality.

Administrative Personnel↗