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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 325 records · Page 18Linked to original sources

[Presence of virulence factors and pathovars in strains of Campylobacter jejuni isolated from patients with diarrhea and healthy children].

BACKGROUND: To study the prevalence of virulence factors (adhesion, invasion, cytotoxicity and hemolytic activity) and to establish the presence of pathovars (virulence phenotype) in C. jejuni strains isolated in pediatric patients with inflammatory and secretory diarrhea and asymptomatic carriers. METHODS: We analyzed 95 strains of 48 patients with inflammatory diarrhea (blood and mucus in feces), 30 patients with secretory diarrhea (watery) and 17 strains isolated in asymptomatic children (control group). The study of adherence capacity, invasion and cytotoxicity was made in the Hep-2 cell line, and the analysis of hemolytic activity in blood agar plates with a 5% sheep's blood. The pathovars were defined by the cellular adhesion (phenotypes A and a) and the cytotoxicity (phenotypes E and e). RESULTS: 29.1% of inflammatory strains presented adherence capacity, 66.6% were invasive, 64.5% cytotoxic and 52.1% hemolytic. In the secretory strains the values were 70, 20, 10 and 6.6% respectively; in the control group the 11.7% presented adherence capacity and 5.8% were invasive. We obtained difference statistically significative for the secretory strains in the adherence capacity, and in inflammatory strains in the adherence capacity, cytotoxicity and hemolysis. The phenotype Ae predominate in the secretory strains, and the phenotype ae in the strains belonging to the control group. No pathovar predominates in the inflammatory strains. CONCLUSIONS: The analysis of virulence markers permit us to establish the pathogenic behaviour of the C. jejuni strains isolated in patients with diarrhea. The study of the adherence capacity and cytotoxicity (pathovars) would be used as a virulence markers and to predict the inflammatory or secretory nature of the diarrhea caused by C. jejuni strains.

Bacterial Adhesion↗

Four days' continuous infusion of cisplatin-5-fluorouracil and short daily infusion of high-dose leucovorin as induction chemotherapy for locally advanced head and neck cancer.

Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Blood parameter and heart rate response to training in Andalusian horses.

A study was performed on Andalusian horses in order to assess the response of heart rate and various blood parameters to training. Two tests were performed, at two and four months of training respectively. Exercise schedules were of increasing intensity, over a distance of 1000 meters. Speed was progressively increased, from 4 m/s to 8.5 m/s, over four exercise stages. In both tests, a recovery period of 5 min followed each stage. Sample collection (by puncture of the external jugular vein) was performed with the animals at rest, within the first minute after each exercise stage, and at 10, 15, 20 and 30 min of final recovery. Samples for analysis contained plasma for measurement of lactate, glucose, ion and creatinine levels. Heart rate was measured using the Polar Sport tester. The most important parameters in both tests proved to be glucose level, heart rate and lactate concentration. Variations in electrolyte and creatinine levels were transitory, normal resting values being regained after 30 minutes' recovery. Response to daily training was most clearly reflected in altered lactate levels and heart rate; recovery improved with increased training which enhanced aerobic capacity and decreased metabolic acidosis.

Animals↗

[Evaluation of bone mass in hip fractures measuring lumbar spine and contralateral hip with bone densitometry].

Hip fracture is frequent in postmenopausal women with osteoporosis. The aim of this work was to assess bone mass in women with hip fracture and compare it with that of normal women. Bone densities of lumbar spine (considering areas with and without spondylosis), femoral neck, greater trochanter, and unfractured hip Ward's triangle were measured with a double beam isotopic densitometer. Thirty-one women aged 58-95 years old were studied and compared with normal women studied at the same laboratory. Bone densities in fractured and normal women were 0.82 +/- 0.16 and 0.85 +/- 0.05 g/cm2 in lumbar spine respectively (NS), 0.74 +/- 0.15 and 0.85 +/- 0.05 g/cm2 in lumbar spine without spondylosis respectively (p < 0.001), 0.60 +/- 0.11 and 0.65 +/- 0.08 g/cm2 in femoral neck respectively (NS), 0.49 +/- 0.09 and 0.57 +/- 0.05 g/cm2 in greater trochanter respectively (p < 0.001) and 0.48 +/- 0.12 and 0.52 +/- 0.09 g/cm2 in Ward's triangle respectively (NS). It is concluded that the larger differences in bone density between women with and without hip fracture are observed in the greater trochanter.

Absorptiometry, Photon↗

[Acquired sideroblastic anemia and cholestasis in a hyperthyroid patient treated with methimazole and atenolol].

The authors describe a 62 year-old white male who was diagnosed as autoimmune hyperthyroidism and treated with methimazole and atenolol. Ten days later he showed itching, jaundice and choluria. All drugs were discontinued. The patient was given radioactive iodine. Two months later direct serum bilirubin levels reached 35 mg%. Endoscopic retrograde cholangiogram evidenced normal extrahepatic biliary ducts. The percutaneous liver biopsy showed marked cholestasis specially in the centrolobular zone with a slight infiltrate of mononuclear cells in the portal areas. Together with the liver disease the patient presented an anemic syndrome. Bone marrow aspiration showed rich cellularity, Perls staining showed 70% sideroblasts, with 10% ringed sideroblasts and increased extracorpuscular iron. The patient's evolution was satisfactory. Twenty months after the beginning of the disease clinical and biochemical tests were normal. A new bone marrow aspiration rendered normal. Hepatic cholestasis suffered by our patient was probably due to an adverse reaction of methimazole. Physiopathology of reversible sideroblastic anemia is discussed.

Anemia, Sideroblastic↗

Isolation of genomic DNA fragments corresponding to genes modulated in vivo by a transcription factor.

A new methodology for the identification of genes modulated by transcription factors in vivo is described. Mouse genomic DNA fragments bound by the thyroid hormone receptor (T3R) were selected and amplified in vitro. Subsequent hybridisation with biotinylated cDNA allowed the selection of those DNA fragments containing binding sites for T3R that corresponded to transcribed DNA. Expression analysis of the corresponding genes showed that more than 80% are indeed modulated by thyroid hormones in vivo in the liver. Together with the presence of consensus binding sites for T3R this result suggests that the selected DNA fragments may contain T3R transcriptional regulatory elements. This method, extensive to other ligand-modulated transcription factors, might be useful to all transcription factors with slight modifications.

Animals↗

Spinothalamic projections in amphibians as revealed with anterograde tracing techniques.

Direct spinothalamic pathways were demonstrated in anurans (Rana ridibunda, Xenopus laevis) and in the ribbed newt, Pleurodeles waltl. With the powerful anterograde tracers Phaseolus vulgaris leucoagglutinin and biotinylated dextran amine, rather extensive spinothalamic projections were found, including the ventromedial thalamic nucleus, the dorsal thalamus and several posterior diencephalic nuclei (anurans), and the neuropil lateral to the pars ventralis thalami as well as to the anteroventral and posterodorsal zones (P. waltl), respectively.

Animals↗

Direct comparison of the relationship between clinical outcome and change in CD4+ lymphocytes in human immunodeficiency virus-positive homosexual men and injecting drug users.

BACKGROUND AND METHODS: To compare rates of decline of CD4+ lymphocytes among human immunodeficiency virus-positive homosexual men and injecting drug users, we followed up prevalent human immunodeficiency virus-positive homosexual men and current or former injecting drug users from February 1988 through August 1991. Subjects were free of acquired immunodeficiency syndrome at study entry and had semiannual clinical and laboratory evaluation, including measurement of T-cell subsets, under common protocols. Initial levels and rates of change of CD4+ lymphocyte counts were compared according to cohort membership and clinical progression, defined by the development of thrush or an acquired immunodeficiency syndrome--defining illness. Median follow-up was 30 months for both cohorts. RESULTS: At study entry, homosexual men had lower absolute numbers of circulating CD4+ lymphocytes than did injecting drug users (459/microL [0.46 x 10(9)/L] vs 509/microL, respectively). During follow-up, homosexual men exhibited a faster decline in CD4+ lymphocyte counts as well as more frequent development of HIV-related symptoms (thrush or acquired immunodeficiency syndrome). In both cohorts, initial levels of CD4+ lymphocytes and rates of decline in these cells were strongly associated with progression of disease, defined as remaining asymptomatic, onset of thrush, or onset of acquired immunodeficiency syndrome. Once homosexual men and injecting drug users were stratified by disease progression, their initial levels and rates of decline of CD4+ lymphocyte counts were similar. Thus, crude differences between the two study groups largely resulted from differences in development of clinical symptoms. CONCLUSIONS: In these cohorts of homosexual men and injecting drug users, clinical outcome was much more important than risk group membership in determining changes in CD4+ lymphocyte numbers. The close similarity between the groups also suggests that drug use, ethnicity, and socioeconomic status play a minor role in the progression of human immunodeficiency virus infection.

Adult↗

Characterization of the promoter region and flanking sequences of the neuron-specific gene RC3 (neurogranin).

RC3 encodes a thyroid hormone-dependent, calmodulin-binding, protein kinase C substrate (neurogranin, p17) present in the dendritic spines of discrete neuronal populations in the forebrain. Its physiological role could be related to synaptic plasticity, memory, and other processes. In the present work we have isolated and sequenced 2.4 kbp of genomic DNA upstream from the origin of transcription and determined its nucleotide sequence. The major features of the RC3 promoter are the absence of TATA and CAAT boxes and the presence of an Initiator sequence surrounding the cap site. By sequence analysis we identified several cis-acting regulatory elements, among them response elements for retinoic acid and steroid (glucocorticoids/progesterone) hormone receptors. An oligonucleotide containing the retinoic acid responsive element bound to retinoic acid receptors specifically in vitro and conferred retinoic acid regulation to a heterologous promoter after transfection in COS-7 cells. Retinoic acid and dexamethasone, respectively, increased activity of the RC3 promoter in neuroblastoma cells when a deletion construct containing the retinoic acid and the glucocorticoid responsive elements was cotransfected with retinoic acid receptor or glucocorticoid receptor expression vectors. When added together all-trans retinoic acid and dexamethasone had additive effects. Despite the fact that RC3 expression in vivo is thyroid hormone-dependent, no evidence for the presence of a thyroid hormone responsive element was found within the 2.4 kbp flanking region analyzed and thyroid hormone did not increase reporter activity after cotransfection of suitable constructs with thyroid hormone receptor expression vectors. Our results suggest that the expression of RC3 in vivo could be subject to complex physiological signals, including retinoids and steroid hormones in addition to thyroid hormones.

Amino Acid Sequence↗

Expression of neurotrophins and the trk family of neurotrophin receptors in normal and hypothyroid rat brain.

Thyroid hormone deficiency has dramatic effects on rat brain maturation. The expression of genes encoding neurotrophins and the trk family of neurotrophin receptors has been evaluated in several brain regions of normal and of neonatal or adult hypothyroid rats to analyze whether they are subject to thyroid hormone action. We found that hypothyroidism decreased trk mRNA levels in its major site of expression, the striatum, on postnatal days 5 (P5; 45%) and 15 (P15; 25%) and also in adults (35%). In contrast, no differences in trkB or trkC mRNAs levels were observed in any brain region at studied ages. According to previous reports, p75LNGFR mRNA was elevated in hypothyroid cerebellum as compared to age-matched controls on P5 and P15. We have also observed a distinct pattern for neurotrophin genes. The level of NGF mRNA was 20-50% lower in the cortex, hippocampus, and cerebellum of hypothyroid rats on neonatal hypothyroid rats on P15 and also after adult-onset hypothyroidism. Treatment of neonatally-induced hypothyroid rats with a single injection of triiodothyronine led to the recovery of hippocampal but not cortex NGF mRNA levels to that of control animals. On the contrary, no differences in the relatively high expression of the two mRNAs encoding BDNF were observed in any brain area. In contrast to a recent report, we did not find a reduction in brain NT-3 mRNA levels in hypothyroid animals. If any, the effect of thyroid deficiency in the hippocampus and cortex seems to be an early upregulation of NT-3 expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sample size estimation using repeated measurements on biomarkers as outcomes.

The objectives of this paper are to (1) examine methods of using longitudinal data in designing comparative trials and calculating sample sizes or power and (2) show the effect of autocorrelation of repeated measures on the assessment of sample sizes. A statistical model with a simple regression structure for the mean trajectory of the longitudinal data and a two-parameter model for the correlations of within-individual observations given by corr(yt,yt+s) = gamma s theta is used. The methods are illustrated by considering a two-group trial and investigating the effect of different values of the correlation parameters, gamma and theta on the sample size. The results show that taking account of the autocorrelation structure of longitudinal data may lead to more efficient designs. Specifically, the stronger the autocorrelation is, the smaller the sample size that is required.

AIDS Vaccines↗

Influence of calorie source on the physiological response to parenteral nutrition in malnourished rabbits.

The present study was designed to investigate whether calorie source influences sodium and water metabolism and sympathetic activity during parenteral nutrition (PN). 20 New Zealand rabbits were starved until a mean weight loss of 18% was achieved and then re-fed for 6 days with 2 formulae of PN with different glucose-fat proportions. In the Glucose group (n = 9), 70% of non-protein calories were given as glucose while in the Lipid group (n = 11), 70% of non-protein calories were administered as lipids. Rabbits with a high glucose intake showed significantly higher weight gain (151 +/- 87 vs. 52 +/- 7 g, P = 0.01), water cumulative balance (542 +/- 132 vs. 411 +/- 87 ml; P = 0.02) and urinary metanephrine excretion (0.42 +/- 0.12 vs. 0.30 +/- 0.1 mumol/d, P = .03). Only in this group, urinary metanephrines correlated positively with water and sodium balances (r2 = 0.6; P = 0.02 and r2 = 0.7; P = 0.009 respectively). The Glucose group showed 2 different responses and in a second experiment 10 additional rabbits were added to this group to allow a statistical analysis of the response pattern: half of the animals increased their extracellular water (ECW) compartment while the remaining animals did not. The former group had higher sodium balance (13.9 +/- 8 vs. 4.3 +/- 5; P = 0.004) and wet lung weight (8.9 +/- 0.9 vs. 7.9 +/- 0.8; P < 0.05) after re-feeding and, at the beginning of PN, their serum aldosterone concentration were also higher (221 +/- 11 vs. 130 +/- 47 pmol/l; P < 0.05). In conclusion, glucose based PN appears to increase sympathetic activity and induce spurious weight gain due to markedly positive wate and sodium balances. Plasma aldosterone concentration at the end of starvation period influences sodium retention and ECW expansion during high glucose re-feeding.

Journal Article↗

Low power? Use two-dimensional confidence regions as a graphical method for depicting uncertainty.

Prospective studies of rare outcomes, such as HIV seroconversion or obsessive-compulsive disorder, can often result in small sample sizes with limited power for detecting associations. For this reason, it is useful to develop graphical procedures that enable researchers to depict uncertainty around parameter estimates and examine the direction of association when statistical power is low. Classical procedures include the reporting of confidence intervals, which typically are derived from asymptotic normality of parameters estimated using large samples. In this paper, we present a likelihood-based procedure for the estimation of the confidence region of two parameters from a conditional logistic regression of a nested case-control study with a relatively small number of cases. Graphical depiction of the confidence regions provides an easily comprehensible procedure to quantify the uncertainty of the estimation based on small samples.

Adult↗

Maturity of human immunodeficiency virus infection and incubation period of acquired immunodeficiency syndrome in injecting drug users.

This study was aimed at estimating the maturity of the human immunodeficiency virus (HIV) epidemic in cohorts of injecting drug users with existing HIV infection at the time of first observation, and using this information to estimate the incubation period of acquired immunodeficiency syndrome (AIDS) in this population group. The method imputed the "missing" time from seroconversion to first observation for seroprevalent subjects in a combined cohort including injecting drug users from New York (n = 246) and Baltimore (n = 621). Imputation relied on a probability model predicting time since seroconversion on the basis of two markers of maturity of HIV infection: percent of CD4+ lymphocytes and platelet count. The model was developed from data observed in a combined cohort of subjects from New York (n = 24) and Baltimore (n = 112) who had incident HIV infections. The estimates of median time since seroconversion for the Baltimore and Bronx seroprevalent subcohorts were 28 and 39 months, respectively. The total time from seroconversion to AIDS was then estimated for the incident plus completed-prevalent cohorts using a modified version of the nonparametric product-limit method. The results showed that approximately 95% (95% confidence interval: 90 to 98%) of drug users remained AIDS-free 2 years after seroconversion; 83% (74-91%), 4 years after seroconversion; and 72% (61-82%), 6 years after seroconversion. Median time to AIDS was 10.2 years, with an estimated 95% confidence interval of 7.9 to 12.3 years. Consistency of these results with those derived from large cohorts of homosexual men indicate that the HIV incubation distributions for drug users and homosexual men are similar.

Acquired Immunodeficiency Syndrome↗

Incidence of clinical AIDS conditions in a cohort of homosexual men with CD4+ cell counts < 100/mm3. Multicenter AIDS Cohort Study.

Incidence rates of AIDS illnesses are described among patients with < or = 100 CD4 cells/mm3 grouped by use of antiretrovirals and chemoprophylaxis. Data were obtained from 2646 homosexual men infected with human immunodeficiency virus type 1. Participants were in the Multicenter AIDS Cohort Study during 1985-1993. The incidence rates per 100 person-years for Pneumocystis carinii pneumonia were 47.4 without treatment, 21.5 with antiretrovirals alone, and 12.8 with antiretrovirals combined with chemoprophylaxis. For Kaposi's sarcoma these rates were 23.2, 11.3, and 15.1, respectively. The incidence of some opportunistic infections, including Mycobacterium avium complex, nonretinitis cytomegalovirus disease, and cytomegalovirus retinitis, increased among persons receiving P. carinii pneumonia prophylaxis, because of reduction of this pneumonia and extension of life span. The incidence pattern of AIDS-defining illnesses in patients receiving treatment points to the changing AIDS epidemic and the need for new therapies. The data are particularly relevant to the development and planning of clinical trials and to health care providers.

AIDS-Related Opportunistic Infections↗

Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil, both in continuous 96-hour infusion, in the treatment of locally advanced head and neck cancer.

In this study, 79 patients with locally advanced head and neck cancer were treated with induction chemotherapy. Cisplatin, 25 mg/m2, and 5-fluorouracil (5-FU), 1000 mg/m2, were employed, both of them in 24-hour continuous infusion over 96 hours, four cycles. The patients later underwent surgery and/or radiation therapy. The response to chemotherapy was 49%: of the complete responses (CR), 56% were histological; 29% were partial responses (PR). With the administration of the fourth cycle, CR increased from 30% to 49%. Once the complete treatment had been finished, 75% of CR and 5% PR were achieved. With a maximum follow-up period of 44 months, overall survival stands at 50%.

Antineoplastic Combined Chemotherapy Protocols↗

Comparison of clinical manifestations of HIV infection between male and female injecting drug users.

OBJECTIVE: To compare occurrence of clinical symptoms, physical examination findings and hematologic variables in male and female HIV-seropositive injecting drug users (IDU) with similar CD4+ lymphocyte counts. METHOD: We interviewed and examined 118 female and 444 male AIDS-free HIV-seropositive IDU for clinical signs and symptoms. HIV serology and T-lymphocyte subset evaluations were performed. Comparisons were analyzed by Mantel-Haenszel procedures. RESULTS: In this population, median age for men was 35 years versus 33 years for women; median CD4 cell count was 490 x 10(6)/l for men versus 480 x 10(6)/l for women. The overall frequency of oral candidiasis increased as CD4 cell count decreased, but did not vary by sex. Recent history of genital herpes was more frequent (P < 0.05) in women than men, but this difference was not significant on physical examination. Symptoms of diarrhea, fatigue, weight loss, shortness of breath, presence of enlarged posterior cervical lymph nodes did not vary by CD4 cell count or sex, and no strong interactions were evident. Although absolute values of hematocrit were higher (P < 0.001) and platelet count lower (P < 0.001) in HIV-seropositive men than women, distributions of hematocrit and platelet count by sex were similar for HIV-seropositive participants and HIV-seronegative controls. CONCLUSION: Our data on IDU prior to a diagnosis of AIDS suggest that constitutional signs and symptoms are generally similar among men and women early in HIV infection. Additional follow-up is needed to determine whether differential rates of signs and symptoms by sex appear with progression of HIV infection.

AIDS-Related Opportunistic Infections↗

Validation of the proposed World Health Organization staging system for disease and infection in a cohort of intravenous drug users.

OBJECTIVE: To assess the prognostic utility of the clinical criteria of the World Health Organization's (WHO) proposed staging system for HIV disease and infection in a cohort of intravenous drug users (IVDU) from the ALIVE study. METHODS: All study subjects known to be HIV-seropositive were included in this analysis. Subjects were classified as WHO clinical stage 1, 2, or 3 at their initial seropositive evaluation. Product-limit estimates and Cox proportional hazard models were used to compare time of progression to AIDS (stage 4) for the first three clinical stages. RESULTS: Of the original cohort of 2921 IVDU in the ALIVE study, 694 were known to be HIV-positive by January 1992. At the time of their index visit, 49% of the cohort were WHO clinical stage 1, 10% stage 2 and 41% were stage 3. Demographic characteristics of the three groups were similar. Product-limit estimates for progression to AIDS over a 3-year period were 6.5% (SE, 1.5%), 10.4% (SE, 4.1%) and 17.1% (SE, 2.5%) for clinical stages 1, 2, and 3, respectively (log-rank P = 0.003). In a proportional hazards model adjusting for race, age, sex and injection status within 6 months prior to enrollment, the hazard for progression to AIDS was 1.51 [95% confidence interval (CI), 0.60-3.77] and 2.39 (95% CI, 1.40-4.08) for stages 2 and 3, respectively, relative to stage 1. CONCLUSION: This study, in a population of IVDU, supports the utility of the WHO staging system in predicting progression from HIV seropositivity to AIDS on the basis of clinical signs and symptoms.

Acquired Immunodeficiency Syndrome↗