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Biomedical subjects

C Martinez

Publications and source records attributed to C Martinez.

At least 127 records · Page 7Linked to original sources
PubMed1996

The multicentre south European study 'Helios'. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

The role of sun exposure in development of basal cell and squamous cell carcinomas among different populations from south Europe was investigated. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from the other three centres. We gathered information on life-long exposure to sunlight during different activities. Results are analysed for 1549 basal cell carcinoma (BCC) cases and 228 squamous cell carcinoma (SCC) cases compared with 1795 controls. We observed a statistically significant increase of risk of SCC with increasing sun exposure beyond a threshold of 70,000 cumulated hours of exposure in a lifetime. Sun exposures during work and holidays were, however, inversely correlated. Odds ratios (ORs) of SCC were up to eight or nine times the reference for the highest exposures (200,000 cumulated hours or more). BCC exhibited a 2-fold increase of risk for lower exposure (8000-10,000 cumulated hours in a lifetime) with a plateau and a slight decrease of risk for the highest exposures (100,000 cumulated hours or more). Outdoor work showed a significantly increased risk of SCC (OR 1.6 for more than 54,000 cumulated hours of exposure in a lifetime), whereas recreational activities such as sun exposure during holidays at the beach (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) or during water sports (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) were associated with an increased risk of BCC. Risk patterns were different in poor or good tanners with a significant risk trend for good tanners, whereas poor tanners were on a plateau of increased risk at any level of exposure. Solar radiation is associated with a risk of BCC even for relatively short periods of exposure such as during holidays and sports, whereas SCC develops later if exposure continues. The skin's ability to tan modulates the risk of BCC; subjects who tan poorly have a steady risk increase, whereas people who tan easily develop cancer only after prolonged exposures.

Basal Cell Carcinoma↗
PubMed1996

Acquisition of CD40 expression during murine B-cell differentiation.

Expression of CD40 on mouse cells was investigated comparing the binding to cells of a monoclonal antibody against CD40, to that of a soluble fusion protein consisting of the extracellular domains of the mouse CD40-ligand. The analysis of a series of established cell lines failed to demonstrate expression of CD40 on pro- or pre-B cells, and indicated that CD40 expression was restricted to cells that had undergone productive heavy- and light-chain gene rearrangements, and expressed surface Ig. In cells from normal mice, CD40 first becomes detectable, although at low levels, on a subset of small pre-B-II cells in bone marrow, the levels of CD40 expression increasing thereafter during B-cell maturation. Thus, immature B cells (IgM+ IgDlo B220lo) express intermediate levels of CD40, and mature B cells (IgM+ IgDhi B220hi) express high levels of CD40. Anatomical location also seems to correlate with the levels of CD40 expression, as B cells expressing the highest levels of CD40 were found in lymph nodes and Peyer's patches.

Animals↗
PubMed1996

In vivo activation of T-cell induction into the primed phenotype and programmed cell death by staphylococcal enterotoxin B.

The authors demonstrate that SEB immunization activates V beta 8+ T cells and induces the acquisition of the primed phenotype as defined previously by low MEL-14 and high Pgp-1 expression. SEB-activated spleen CD4+ and CD8V beta 8+ T cells have different population dynamics and regulate the expression of MEL-14 and Pgp-1 differentially, suggesting that the SEB-MHC class II complex preferentially activates CD4V beta 8+ T cells. Interestingly, at day 3 after SEB immunization, V beta 8+ T cells expressing low, but not high, levels of MEL-14 undergo apoptosis, indicating that T-cell activation is a prerequisite for triggering programmed cell death. These results might help to trace antigen-reactive cells to the activated or primed pool, as well as to identify those cells which will undergo programmed cell death.

Animals↗
PubMed1996

Case report: failure of adrenal scintigraphy to exhibit 131I cholesterol uptake in a CT-demonstrated, surgically proven aldosteronoma.

This is the case of a large 2 x 1.5 cm adrenal tumor demonstrated on CT scan that was proven biochemically and surgically to be an aldosteronoma and that did not concentrate 6-beta(131I)-iodo-methyl-19-norcholesterol (NP-59). Before the publication of this case, all CT-identified aldosteronomas of greater than 1 cm have concentrated NP-59. Previously, an adrenal mass of greater than 1 cm that failed to concentrate NP-59 was excluded from being an aldosteronoma. This concept must be reevaluated with the publication of this case.

19-Iodocholesterol↗
PubMed1996

First pass Tc-99m MIBI ventriculography in the assessment of left ventricular diastolic function. A comparison with Doppler echocardiography.

Tc-99m MIBI is used for myocardial imaging and first-pass studies. However, little is known about its utility in the assessment of left ventricular diastolic function. The authors retrospectively compared first pass studies of Tc-99m MIBI at rest with Doppler flow velocity measurements to assess left ventricular diastolic performance. Thirty-nine patients who had both studies performed within 48 hours of each other were evaluated. Three indices of diastolic function were measured by first pass Tc-99m MIBI ventriculography and Doppler echocardiography: 1) Time to peak early diastolic velocity; 2) normalized peak filling rate; and 3) half filling fraction. The results demonstrated a correlation of 0.82 (P < 0.001), 0.82 (P < 0.001), and 0.53 (P = 0.001) for the above indices, respectively. This study indicates that the indices of left ventricular diastolic function by first pass Tc-99m MIBI compare favorably with those derived from Doppler flow velocity measurements in which the diagnostic value has been previously established. Both methods accurately reflect diastolic flow and may facilitate clinical evaluation of diastolic function.

Adult↗
PubMed1996

High-dose paclitaxel, cyclophosphamide, and cisplatin with autologous hematopoietic progenitor-cell support: a phase I trial.

PURPOSE: To determine the maximal-tolerated dose (MTD) of paclitaxel in combination with high-dose cyclophosphamide (CPA) and cisplatin (cDDP) followed by autologous hematopoietic progenitor-cell support (AHPCS). PATIENTS AND METHODS: Forty-nine patients with poor-prognosis breast cancer, non-Hodgkin's lymphoma (NHL), or ovarian cancer were treated with escalating doses of paclitaxel infused over 24 hours, followed by CPA (5,625 mg/m2 intravenously over 1 hour in three divided doses) and cDDP (165 mg/m2 intravenously as a continuous infusion over 72 hours) and AHPCS. Pharmacokinetic measurements for each drug were performed. RESULTS: Dose-limiting toxicities were encountered in two patients at 825 mg/m2 of paclitaxel; one patient died of multiorgan failure that involved the lung, CNS, and kidneys, and the other developed grade 3 respiratory, CNS, and renal toxicity, which resolved. The MTD of this combination was determined to be paclitaxel 775 mg/m2, CPA 5,625 mg/m2, and cDDP 165 mg/m2 followed by AHPCS. Sensory polyneuropathy and mucositis were prominent toxicities, but both were reversible and tolerable. The pharmacokinetics of paclitaxel correlated significantly with the severity of mucositis (P < .001) and peripheral neuropathy (P < .00004). Eighteen of 33 patients (54%) with measurable, heavily pretreated metastatic breast cancer achieved a partial response (PR). Responses were also observed in patients with NHL (four of five patients) and ovarian cancer (two of two). CONCLUSION: It is possible to escalate the dose of paclitaxel to 775 mg/m2 in combination with 5,625 mg/m2 of CPA, 165 mg/m2 of cDDP, and AHPCS. An encouraging response rate in poor-prognosis patients with breast cancer, NHL, and ovarian cancer warrants further study.

Adult↗
PubMed1996

Concepts in risk-benefit assessment. A simple merit analysis of a medicine?

The term 'benefit-risk ratio' is often used as a general term linked to the use of a medicine. To balance risk and benefit is, however, a very complex exercise. For most medicines the benefits are limited to a few indications and for an individual patient there is usually only a single benefit sought but the potential risks are multiple. Perceptions of risks versus benefits are influenced to a great extent by the context in which they occur. Thus, perception of risk may be different to actual risk. In the end in any given situation, the acceptable risk-to-benefit balance is an individual judgement on the part of the patient or the prescriber. For newer medicines, where there is likely to be limited experience, conservative estimates of the overall merit seem preferable so that the prescriber will use the drug critically. Subsequently, re-evaluation of the risk-to-benefit balance is necessary as greater knowledge of efficacy and adverse effects is acquired. It is possible to provide a general 'principle of threes' structure for a merit assessment based upon the concepts of seriousness, duration and incidence as related to disease indication, disease amelioration by a medicine, and the adverse effects ascribed to the medicine. This allows a rapid first comparison of medicines for a given indication. In using this general conceptual model in a transparent fashion for a given hypothesis and context, it is possible to identify the essential data used and assumptions involved that make up a merit statement. The quality and value, particularly of risk data, is problematic. Risk perception is an issue that needs to be clearly identified alongside a merit analysis. A simple merit assessment should pave the way for more focused studies.

Drug Therapy↗
PubMed1996

Clinical results of a stringent policy on prophylactic platelet transfusion: non-randomized comparative analysis in 190 bone marrow transplant patients from a single institution.

The threshold for prophylactic platelet transfusion remains controversial. Usually the decision is based on arbitrary numerical criteria. The classical 20 x 10(9)/l trigger could be safely reduced with considerable benefits. Few studies have evaluated the clinical impact of stringent policies. We have performed a retrospective analysis comparing major haemorrhages during hospitalization in 190 patients undergoing BMT in two different periods. In 87 patients transplanted from 1990 to 1991, the 20 x 10(9)/l trigger was used for prophylactic platelet transfusion. In 103 other patients transplanted from 1993 to 1994, we adopted a stringent prophylactic policy: < 10 x 10(9)/l for stable patients and < 20 x 10(9)/l when higher platelet consumption factors were present. In the stringent group, 12 patients presented 13 major haemorrhages and four died from haemorrhage. In the classical group 12 patients presented 14 major haemorrhages and three died from haemorrhage. Platelet consumption factors were present in 12 of 13 haemorrhages in the stringent group and in 12 of 14 in the classical group. By contrast, stable patients presented less haemorrhages (2/14 and 1/13, respectively). A statistically significant reduction in the use of platelet units was observed when comparing both groups: the median of platelet units administered in the first 100 days of transplant was 73 (3-943) and 54 (0-647) in the classical and in the stringent group, respectively (P < 0.01); and the median of platelet units received per day was 0.8 (0.03-30) and 0.5 (0-6.94) (P < 0.01). Our results emphasize the safety of a stringent prophylactic platelet transfusion policy after BMT, reducing the overall use of platelet transfusions. Further studies are necessary to confirm these results and to define optimal transfusion strategies.

Adolescent↗
PubMed1995

Impairment of the liver insulin receptor autoactivation cascade at full-term pregnancy in the rat.

Partially purified liver insulin receptors from full-term pregnant rats show decreased autophosphorylation rates if compared with receptors from virgins. We studied the molecular mechanism of this phenomenon, looking at possible structural and functional changes of several domains. The ATP-binding domain seems to be unaltered in receptors from pregnant rats since Km for ATP was similar to that observed in virgins. In contrast, the Vmax. is decreased some 45%, suggesting changes in the kinase domain. Truncation of a fragment of 10 kDa from the C-terminal tail does not normalize the kinase activity in receptors from pregnant rats, suggesting that this domain is not involved in the inhibitory regulation. Treatment with alkaline phosphatase increases the [32P]Pi incorporation into receptors from pregnant rats; however, the autophosphorylation remains lower than that observed in virgin rats. Tryptic phosphopeptide maps of phosphorylated receptors show that the same phosphopeptides are present in receptors from virgin and pregnant rats. However, the progression through the autoactivation cascade in the kinase domain is impaired in receptors from pregnant rats. Differences in the cleavage by trypsin at the two alternative sites in the kinase domain were observed, indicating possible structural changes in receptors from pregnant rats that could be related to the impairment of the autoactivation cascade. Integrity of the alpha- and beta-subunits, as well as differential expression of the two receptor isotypes, were shown to be unaltered. We conclude that (1) the decreased autophosphorylation rate of the liver insulin receptor from pregnant rats is associated with the impairment of its autoactivation cascade, probably as a consequence of the basal Ser/Thr phosphorylation; and (2) the inhibition of the autoactivation cascade does not account for the overall inhibition of autophosphorylation observed in receptors from pregnant rats.

Adenosine Triphosphate↗
PubMed1995

Role of the autophosphorylation site on the biological function of pp56lck.

Src-family tyrosine kinases act as signaling molecules in a wide array of cellular activation processes. The existence of the various src-family members reflects the requirement for different cell-surface receptors to transmit cell-type specific intracellular signals. The structural basis for the functional specificity of src-kinases is being actively investigated. In the present report we have analysed the contribution of the area surrounding the autophosphorylation site (located at subdomain VII of the catalytic domain) in determining src-kinases activity and functional specificity. To this end we analysed the kinase activities of the lymphoid src-kinase pp56lck and a mutant of pp56lck in which this region has been exchanged for the corresponding area of the serine/threonine kinase c-Raf. Our studies indicate that the change at subdomain VII affected the ability of pp56lck to phosphorylate physiological substrates. Furthermore, when analysed in T cells, the mutant at subdomain VII failed to induce interleukin-2 production, a specific biological function of pp56lck. Thus, the area surrounding the autophosphorylation site of pp56lck plays a critical role in mediating its specific biological function.

Base Sequence↗
PubMed1995

Lck unique domain influences Lck specificity and biological function.

Src-family tyrosine kinases share structural and amino acid sequence homology, particularly in the catalytic domain as well as in the SH2 and SH3 domains of the regulatory region. However, each src-family member also contains a unique domain which is specific to and characteristic of each individual tyrosine kinase. These unique or specific domains may contribute to the functional specificity of each src-family kinase. To address this possibility, we analyzed the kinase activities and substrate specificities of the lymphoid src-kinase, pp56lck, and a mutant of pp56lck lacking its specific domain. Our data show that both the wild type enzyme and the specific domain-deleted mutant displayed similar affinities for ATP and the non-physiological substrate denatured enolase. However, the specific domain-deleted mutant failed to phosphorylate a number of physiological substrates of pp56lck. In addition, the ability of pp56lck to mediate induction of the interleukin-2 promoter was strongly impaired upon deletion of its specific domain. Thus, the unique domain is not required for the intrinsic kinase activity of pp56lck, however, it influences substrate preference and contributes to the unique physiological function of this src-family tyrosine kinase.

Base Sequence↗
PubMed1995

Balloon-expandable stent repair of severe coarctation of aorta.

Experimental studies have shown that stents implanted at the aorta become incorporated within the aortic wall and can be further expanded in growing animals. This study evaluates the feasibility and immediate results of balloon-expandable stent implantation in 10 patients with severe coarctation of aorta. The ages of the patients ranged from 1 month to 43 years; 1 was an infant, 8 were children (mean age 5.3 +/- 4 years), and 1 was an adult. All had an unfavorable anatomy for balloon angioplasty; 9 had isthmus hypoplasia. Balloon predilation was first performed and its immediate effect evaluated. Then a balloon-expandable stent that was 30 mm long and covered the isthmus and coarctation levels was deployed, and it was further expanded to the preselected final diameter (12 +/- 4 mm). A final hemodynamic and angiographic evaluation was then obtained. Full deployment of an incompletely expanded and distally displaced stent in the infant led to aortic disruption that was controlled by a second stent covering the disrupted zone and the isthmus. After balloon angioplasty alone was done, the mean gradient (43 +/- 12 vs 31 +/- 10 mm Hg) and the percentage stenosis (72% +/- 11% vs 54% +/- 11%) had an insufficient decrease. However, after stent implantation was done, the gradient almost disappeared (mean 2 +/- 3 mm Hg). The angiographic stenosis disappeared in 7 patients and was markedly reduced in 3. The ratio of isthmus/descending aorta changed from 0.65 +/- 0.14 to 1 +/- 0.08 (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1995

ICAM-1 is required for T cell proliferation but not for anergy or apoptosis induced by Staphylococcus aureus enterotoxin B in vivo.

The response of T lymphocytes to superantigens requires expression of the appropriate TCR V beta gene products as well as the establishment of cellular interactions mediated by adhesion molecules. To study the role of intercellular adhesion molecule (ICAM)-1 in the response in vivo to superantigens, we have analyzed the effects induced by the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) in mice which have been made genetically deficient in ICAM-1. SEB treatment of wild-type mice causes proliferation, deletion and anergy of the SEB-reactive V beta 8+ T cell population. Here we show that cellular interactions mediated by ICAM-1 are not essential for the induction of anergy or for the deletion of CD4+ V beta 8+ or CD8+ V beta 8+ T cells, but are required for the proliferation of these peripheral T lymphocytes. This is the first demonstration in vivo that the absence of the co-stimulatory signals provided by the interaction of ICAM-1 with its specific ligands impairs the proliferation of SEB-reactive T cells. Interestingly, our study showed that SEB-induced proliferation of CD8+ V beta 8+ T cells from lymph nodes (not from spleen) is independent of the interactions mediated by ICAM-1.

Animals↗
PubMed1995

Risk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli.

From January 1990 to December 1992, ciprofloxacin resistant Escherichia coli was isolated in 125 of 1,946 urine cultures (6.4%) with more than 10(5) colony-forming units per ml. To determine the risk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant E. coli a retrospective chart review was done. Data from 54 patients with urinary tract infections caused by ciprofloxacin resistant E. coli were compared with 51 controls matched by temporal occurrence and randomly selected among 540 patients with urinary tract infections caused by ciprofloxacin susceptible E. coli. Patients had greater proportions of asymptomatic bacteriuria or lower urinary tract symptoms (85% versus 61%, p = 0.01) and of relapse (22% versus 0%, p = 0.001) than controls. Urinary tract abnormalities (odds ratio 7.98, 95% confidence interval 2.7 to 3.1, p < 0.001), patient age 65 years or older (odds ratio 6.48, 95% confidence interval 2.2 to 19.1, p < 0.001), previous treatment with quinolones (odds ratio 19.09, 95% confidence interval 2.2 to 166.5, p = 0.008) and urinary catheterization (odds ratio 2.92, 95% confidence interval 1.1 to 8.5, p = 0.048) were independently associated with infections caused by ciprofloxacin resistant strains. Our results suggest that patients with urological abnormalities previously treated with quinolones are especially prone to urinary tract infection caused by ciprofloxacin resistant strains.

Age Factors↗
PubMed1995

Multiple myeloma following essential thrombocythemia.

The association of essential thrombocythemia (ET) and multiple myeloma (MM) is exceedingly rare, with only four such cases reported in the literature until now. In this paper, a patient is reported who developed IgA-lambda MM more than five years after the diagnosis of ET, for which she had received alpha interferon and radioactive phosphor (32P). She died shortly afterwards despite melphalan and prednisone therapy. In four of the five patients in whom the above association has been reported, including the present one, MM appeared some time after ET was initially recognized, with three of them having received alkylating drugs as their treatment for ET. MM was heterogeneous with respect to the M--component type and the clinical course. The possible etiological & pathogenetic link between both these entities is discussed.

Aged↗
PubMed1995

Energy expenditure and body fat distribution in Mohawk children.

OBJECTIVE: Epidemiologic studies suggest that Native Americans, including the Mohawk people, have a high prevalence of obesity, diabetes, and cardiovascular risk. However, current information on alterations in related variables such as energy metabolism and body composition in Native Americans is almost exclusively limited to already obese Pima adults living in the Southwest. The aim of this study was to characterize energy metabolism and body composition in young Mohawk children (17 girls, 11 boys; aged 4 to 7 years) as compared to Caucasian children (36 girls, 34 boys; aged 4 to 7 years). Total energy expenditure was measured by doubly labeled water, postprandial resting energy expenditure by indirect calorimetry, and activity energy expenditure was derived from the difference between total and resting energy expenditure. Fat and fat free mass were estimated from bioelectrical resistance, and body fat distribution was estimated from skinfolds and circumferences. RESULTS: There were no significant effects of ethnic background or sex on body weight, height, or body mass index. Fat free mass was significantly higher in boys and fat mass was significantly higher in girls, with no effect of ethnic background. Chest skinfold thickness, the ratio of trunk skinfolds:extremity skinfolds, and the waist:hip ratio were significantly higher in Mohawk children by 2.5 mm, 0.09 units, and 0.03 units, respectively, independent of sex and fat mass. Total energy expenditure was significantly higher in Mohawk children compared to Caucasian (100 kcal/day in girls, 150 kcal/day in boys), independent of fat free mass and sex, due to a significantly higher physical activity-related energy expenditure. CONCLUSION: These data suggest that: 1) body fat is more centrally distributed in Mohawk relative to Caucasian children, and this effect is independent of sex and body fat content; 2) Mohawk children have a greater total energy expenditure than Caucasian children, independent of fat free mass, due to greater physical activity-related energy expenditure.

Adipose Tissue↗