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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 487 records · Page 27Linked to original sources
PubMed1993

Genetic polymorphism of the beta-2 adrenergic receptor in atopic and non-atopic subjects.

To investigate a possible genetic basis for reported differences in beta-2 receptor expression in atopic subjects, DNA from 42 atopic children (22 asthmatics and 22 with allergic rhinitis) and 30 non-atopic subjects was Southern blotted and Ban-1 restriction fragment polymorphisms (RFLPS) were studied using a 2.6 kb probe of the human beta-2 receptor gene. Two alleles 3.1 kb and 2.9 kb were identified. Homozygotes and heterozygotes for the two alleles were found with equal frequency in the atopic patients who had asthma and in those who had allergic rhinitis only. The gene frequencies for the upper and lower alleles were 0.45 and 0.55 respectively. Our studies do not provide evidence for an association between a particular polymorphic form of the human beta-2 receptor gene and atopy.

Adult↗
PubMed1993

Surface expression of adenosine deaminase in mitogen-stimulated lymphocytes.

Adenosine deaminase (ADA) expression on the surface of mitogen-stimulated lymphocytes was studied by flow cytometry. The gate for lymphocytes was located by cell size (forward scatter), cytoplasmic complexity (side scatter) and by expression of the markers CD2, CD4, CD8 and CD19. After mitogenic proliferation two populations appeared, one corresponding to non-stimulated cells, and the other consisting of larger cells which showed relatively high expression of adenosine deaminase on their surface. The increase was similar to that observed for CD71 expression, and paralleled the increase in 3H-thymidine incorporation. There was a correlation between ADA and CD71 expression (r = 0.92 for phytohaemagglutinin (PHA) and 0.97 for pokeweed mitogen (PWM)). These results suggest a role for ecto-adenosine deaminase in lymphocyte proliferation and/or triggering.

5'-Nucleotidase↗
PubMed1993

Human immunodeficiency viruses containing heterologous enhancer/promoters are replication competent and exhibit different lymphocyte tropisms.

The human immunodeficiency virus (HIV) type 1 long terminal repeat (LTR) contains binding sites for nuclear factor kappa B (NF-kappa B) and the constitutively expressed transcription factor Sp1, both of which are highly conserved in HIV and simian immunodeficiency virus isolates. To delineate the effects of these motifs on the replicative capacity of HIV and to explore the possibility of extending the virus host range, known heterologous enhancer/promoters were inserted into the HIV-1 LTR in place of the NF-kappa B and Sp1 binding sites. The effects of these substitutions on viral replication in transfected HeLa cells and on HIV infection of human peripheral blood lymphocytes or continuous T-leukemia cell lines were evaluated. HIVs in which the NF-kappa B/Sp1 enhancer plus the downstream TATA element were replaced with heterologous enhancer/promoters were also constructed. Viruses containing the human cytomegalovirus immediate-early enhancer exhibited infectious kinetics similar to that of wild-type HIV in activated human peripheral blood lymphocytes and AA2 cells but replicated less efficiently in H9 and CEM cells. These studies indicate that heterologous enhancer elements are capable of restoring Tat responsiveness to the HIV LTR in the context of directing reporter gene expression as well as in the production of infectious progeny virions.

Base Sequence↗
PubMed1993

Competition between baculovirus polyhedrin and p10 gene expression during infection of insect cells.

Polyhedrin and p10 genes are expressed concurrently during the late stage of infection. To determine whether any competition occurs between these two genes at a transcriptional and/or translational level, a series of Autographa californica nuclear polyhedrosis recombinant viruses with deletions of promoter and coding sequences of the p10 or polyhedrin gene was constructed. Two modified baculoviruses with only one of the very late promoters, single late-promoter viruses AcSLP10 and AcSLP33, were made. The polyhedrin gene was used as a reporter gene to allow direct comparison between p10 and polyhedrin-driven expression. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and [35S]methionine labeling experiments showed that polyhedrin synthesis is enhanced in cells infected with baculoviruses carrying only one very late promoter. However, this enhancement is more significant when the polyhedrin gene is located in its natural site. Dot blot hybridization experiments carried out with total cytoplasmic RNA showed that deletion of the p10 promoter resulted in an increase of mRNAs derived from the polyhedrin promoter. In contrast, no increase of p10-promoted mRNA was detected when the polyhedrin gene promoter was deleted.

Amino Acid Sequence↗
PubMed1993

CNS aspergillosis in organ transplantation: a clinicopathological study.

The clinical characteristics and neuropathological findings of 22 organ transplant recipients with CNS aspergillosis were reviewed. Thirteen patients had liver, six kidney, two heart and one had cluster transplants. The most frequent neurological symptoms were alteration of mental status (86%), seizures (41%) and focal neurological deficits (32%). Meningeal signs were less common (19%). Aspergillus spp invasion of the blood vessels with subsequent ischaemic or haemorrhagic infarcts, and solitary or multiple abscesses were the predominant neuropathological findings. The lungs were the probable portal of entry; however, isolated CNS aspergillosis was seen in two patients. Antemortem diagnosis of the infection was made in half of the patients. Concomitant diabetes mellitus was noted in 59% of the patients and bacterial or other severe infections in 86%. No specific clinical or pathological pattern could be identified among patients with different types of organ transplants. In addition CNS aspergillosis was preceded by organ rejection and the need for intense immunosuppression and retransplantation in the majority of the patients.

Adolescent↗
PubMed1993

Primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an inflammatory disease of unknown etiology. It affects the biliary system and is characterized by fibrosis and progressive obliteration of extrahepatic and intrahepatic bile ducts. Its frequent coexistence with antibody-mediated diseases, certain human leukocyte antigens, and altered lymphocyte mechanisms suggests a strong autoimmune and genetic etiology. Other conditions such as recurrent cholangitis, acquired immunodeficiency syndrome, previous bile duct surgery, bile duct anomalies, or biliary stone disease may result in similar clinical patterns and radiologic profiles. PSC can be asymptomatic and slowly progressive over years, or it may develop rapidly with an inexorable progression to cirrhosis and portal hypertension. Clinical and biochemical abnormalities may suggest PSC, but it is the characteristic radiological pattern that secures the diagnosis. Once viewed as a rare entity, the widespread use of radiological and endoscopic methods have increased physician awareness. There is no successful medical treatment for PSC. While traditional surgical approaches have been directed at the relief of cholangitis and biliary obstruction, liver transplantation has emerged as definitive therapy for patients with PSC complicated by cirrhosis or recurrent bouts of cholangitis.

Cholangitis, Sclerosing↗
PubMed1993

Paracrine control of gastric epithelial cell growth in culture by transforming growth factor-alpha.

Studying primary cultures of replicating canine oxyntic mucosal cells, we found evidence for modulation of cell growth by endogenous factors. [3H]thymidine incorporation into DNA was rapid with cells cultured in medium free of serum or added growth factors, and growth rates of these cultures were markedly dependent on plating density, indicating mitogenic control by soluble endogenous growth factors. Data indicated that endogenous transforming growth factor-alpha (TGF-alpha) exerted mitogenic control under the following conditions. 1) TGF-alpha was detected in the cultured cells by radioimmunoassay and immunohistochemistry. 2) TGF-alpha-like immunoreactivity and receptor reactivity were present in the medium in concentrations sufficient to exert mitogenic control. 3) Receptors for TGF-alpha and epidermal growth factor (EGF) were present in the cultures. 4) Immunoabsorption by a TGF-alpha-specific antisera reduced [3H]thymidine incorporation. TGF-alpha was localized to parietal cells by immunohistochemistry and cell separation. In contrast, combined [3H]thymidine autoradiography and immunohistochemistry with anti-TGF-alpha did not detect TGF-alpha in dividing cells. We conclude that parietal cell TGF-alpha exerts paracrine control of mucosal cell growth in vitro, and we speculate that this is an important paracrine mechanism in vivo.

Cell Count↗
PubMed1993

Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer.

In a prospective, randomized, multicenter study, neoadjuvant chemotherapy (CT) with carboplatin and 5-fluorouracil (5-FU) followed by locoregional treatment (LRT) was compared with locoregional treatment alone in the treatment of patients with head and neck cancer. This study, which includes 324 patients, was conducted from January 1988 to July 1991. The aim of this study was to evaluate the impact of the carboplatin/5-FU regimen both on the incidence of mutilating surgery and on the survival rate. Chemotherapy consisted of three cycles of carboplatin 400 mg/m2 day 1 and 5-FU 1 g/m2 days 1-5, repeated every 3 weeks. Patients with a complete tumor response then received radiotherapy alone, instead of the treatment planned initially. Three hundred patients were analyzed: 79 had tumors of the oral cavity, 106 oropharyngeal tumors, and 115 pharyngolaryngeal tumors. One hundred fifty patients underwent CT+LRT; 150 patients had LRT alone. Grade 3 and 4 toxicity rates were minimal in the CT+LRT group; toxicity was mainly hematologic (24% neutropenia, 19% thrombocytopenia). There were 3 toxic deaths (2%), 2 due to septicemia and 1 due to cardiac toxicity. One hundred forty-three patients were evaluable for efficacy. The tumor objective response rate was 63% and complete response rate was 31% (35% for oropharyngeal, 34% for pharyngolaryngeal tumors, 22.5% for oral cavity tumors), which led to a 29% decrease in the rate of mutilating surgery. Conservative treatment was performed in 57% of patients in the CT+LRT group vs. 24% in the LRT group (p = 0.001). There was no significant difference between survival curves in the CT+LRT and LRT groups. At 4 years, overall survival rates were 56 and 46%; disease-free survival rates were 33 and 30% in the CT+LRT and the LRT groups, respectively. The survival rates were not significantly different in the two groups. The locoregional recurrence rates were 35% in the CT+LRT arm and 25% in the LRT arm (p = 0.04), with median follow-up of 25 months. The rates of secondary localization and distant metastasis were not significantly different in the two groups.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Muscular fibrosis induced after pig skin irradiation with single doses of 192Ir gamma-rays.

Localized irradiation of the skin and subcutaneous tissues with large single doses of gamma-rays can induce delayed effects characterized by fibrosis which invades the irradiated tissues. In this study the depth of penetration of muscle fibrosis was measured in the pig 30 weeks after irradiation of the skin surface with single doses of 192Ir gamma-rays of 16-256 Gy. Irradiation was directed either to the outer side of the thigh or to the back, close to the mid-dorsal line. Fibrosis only developed in irradiated muscle after doses that induced moist desquamation of the skin in the acute phase of the reaction, i.e. after skin surface doses of 48-64 Gy. In skeletal muscles, the limit of fibrotic expansion was reached at a depth dose of 14 +/- 4 Gy (+/- SD) for skin surface doses exceeding 48 Gy.

Animals↗
PubMed1993

Survey for secondary dapsone and rifampicin resistance in Cuba.

A total of 1211 Cuban multibacillary leprosy patients treated for at least 5 years were clinically and bacteriologically examined. They were being treated according to a 2-phase monotherapy regimen with RMP first and DADDS afterwards. On skin-smear examination 50 patients were found positive, of which 9 showed a BI of 3+ or higher at any site. With regard to the clinical status the only cases found with clinical signs of relapse were 5 out of 7 long-standing patients with BI of 4+ and 5+. A 6th patient of this high BI group who showed a good clinical condition, except for a heavy infiltration of both earlobes, was receiving a second RMP course when examined and biopsied for this research. These 9 patients were biopsied and susceptibility tests to RMP and DDS performed. The results showed that in 1 case the Mycobacterium leprae were resistant to both drugs; the organisms from 2 other patients were susceptible to RMP but low-grade resistant to DDS. Those from another patient were susceptible to RMP and fully resistant to DDS. In 3 other cases the bacilli did not multiply in any of the mice but 1 of these strains was from the patient taking a second RMP course, therefore this strain might also be susceptible to RMP and resistant to DDS. In the last 2 cases multiplication was only observed in 2 of the controls and in 1 of the 0.0001% DDS treated mice; therefore, these experiments were not conclusive, and the AFB recovered were inoculated into fresh mice to repeat the tests but these failed to multiply.

Animals↗
PubMed1993

The safety and efficacy of outpatient midazolam intravenous sedation for oral surgery with and without fentanyl.

This study examined midazolam and midazolam plus fentanyl in a placebo-controlled, double-blind clinical trial. It tested the hypothesis that combined drug therapy results in significantly poorer safety but no difference in efficacy compared to the single drug approach. Subjects were among 207 mildly anxious young adults having their third molars removed. Fentanyl had a significant depressant effect on respiration. Fifty of 79 (63%) subjects who received a midazolam-fentanyl combination became apneic, while only two of 78 (3%) who received midazolam alone were apneic (Fisher's Exact Test, P < 0.001). Two subjects (2.5%) in the combination group and none in the midazolam alone group had oxygen saturations drop below 90%. About twice as many subjects in the combination group had end-tidal carbon dioxide (EtCO2) levels greater than 25% above baseline. While these results are consistent with those for apnea, contingency analyses of the oxygen saturation and EtCO2 results were not statistically significant. Subjects in the combination group were more than four times as likely to have excellent versus good, fair, or poor sedation at a given level of intraoperative pain, and behavioral (movement and verbalization) but not cognitive measures of anxiety were attenuated.

Adolescent↗
PubMed1993

Providing clinicians with problem-based access to knowledge: troubleshooting pulmonary artery catheter waveforms.

This paper describes a microcomputer system for providing computer-based access to expert knowledge in the area of troubleshooting pulmonary artery (PA) catheter waveforms. The system is used by both nurses and physicians in an 18-bed medical intensive care unit. Its dominant features are 1) problem-focused access to knowledge, and 2) heavy use of graphics and images to explicate knowledge. The system is used by both nurses and physicians in an 18-bed medical intensive care unit. An evaluation protocol is in place to examine the impact of the system on clinicians' knowledge, their decision-making skills, their satisfaction with the system, and costs of orientation related to PA waveform troubleshooting.

Catheterization, Swan-Ganz↗
PubMed1993

[Iatrogenic fibrosis in cancerology (1): descriptive and physiopathological aspects].

Tissue fibrosis is a non specific proliferation of connective tissue, overriding the limits of normal wound healing and essentially encountered in oncological practice as an iatrogenic pathology. This study reviews the data pertaining to the cellular and extracellular components of fibrosis and their regulation. Regulation of the fibrotic process is studied in several steps: chemotaxis and proliferation of fibroblasts, collagen metabolism, and interactions between inflammatory cells and the extracellular matrix.

Collagen↗
PubMed1993

[Radiation-induced cutaneo-muscular fibrosis (III): major therapeutic efficacy of liposomal Cu/Zn superoxide dismutase].

Sub-cutaneous and muscular fibrosis are common and irreversible late effect of radiation on normal tissues. An experiment was designed to test the effectiveness of superoxide dismutase in reducing late radiation injury. This study was performed in an experimental porcine model of acute localized gamma irradiation simulating human accidental overexposure: 12 Large White pigs were irradiated on the thigh with a collimated gamma 192Ir source, so that the dose was 160 Gy/skin (100%) and 40 Gy/2 cm depth (25%). In this model, fibrosis appears in 4 to 5 months. The heterogeneous sclerotic tissue is composed of stable fibrotic areas poorly cellularized and active areas with a high density of myofibroblasts and inflammatory perifibrotic part. Lipsod administration modalities were six intramuscular injections during 3 weeks (twice weekly) either 10 mg/inj (five pigs) or of 100 mg/inj (five pigs). A methodic evaluation by two examiners consisted of measurements being taken before and after treatment: sum of the two largest perpendicular measurable dimensions, cutaneous projected surface of palpated fibrotic block, ultrasound fibrosis deepness and extrapolated volume. We conclude that Lipsod is the first drug ever described that reduces radiation-induced fibrosis. Its efficacy in this model was highly significant, with a regression higher than 40% in size and 70% in surface and volume, 12 weeks after the end of treatment. This response was rapid, reproducible without dose-effect or toxicity in the limits studied. This work confirms previously published results in humans.

Animals↗
PubMed1993

Transjugular intrahepatic portosystemic shunt in the management of variceal bleeding: indications and clinical results.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has proved to be a successful bridge to liver transplantation in the management of variceal bleeding. The safety and ease of this technique has now challenged standard surgical approaches to portal hypertension. To define the role of TIPS, we prospectively studied patients undergoing this procedure for variceal bleeding and/or ascites. METHODS: From September 1991 to September 1992, 45 patients entered a protocol that included assessment of liver chemistries, ammonia levels, coagulation profiles, liver synthetic function by caffeine-antipyrine clearance, ultrasonographic evaluation of hepatic and portal veins, portogram and direct measurement of portal vein pressures, upper endoscopy, computed tomography for liver volume and ascites, and formal neuropsychiatric evaluation. These studies were repeated at 3-month intervals or more frequently if bleeding or complications occurred. RESULTS: Technical success and control of bleeding were achieved in all patients with only three (7%) variceal rebleeds from recurrent portal hypertension. Complete and permanent control of clinical ascites was noted in all patients with this complication. Five of six deaths occurred from sepsis and multiorgan failure in intensive care unit-bound patients with Child class C liver disease. No serial changes were noted in liver chemistries; however, progressive loss of liver volume and prolongation of caffeine-antipyrine clearance was observed in most patients. In addition, hepatic vein stricture or shunt stenosis seen in nine patients (20%) required TIPS revision, whereas the frequent appearance of symptomatic encephalopathy was a main indication for transplantation in 11 of 14 patients. CONCLUSIONS: TIPS successfully controls variceal bleeding and may serve as a novel approach to control of diuretic resistant ascites. The uncertain long-term patency and progressive decline in synthetic function emphasize the importance of initiating proper trials comparing TIPS with other management strategies before indiscriminant use of this technique is seen.

Ascites↗