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Biomedical subjects

M Alvarez

Publications and source records attributed to M Alvarez.

At least 19 recordsLinked to original sources

Daily assessment of severity of illness and mortality prediction for individual patients.

OBJECTIVE: To refine the prognosis of critically ill patients using a statistical model that incorporates the daily probabilities of hospital mortality during the first week of stay in the intensive care unit (ICU). DESIGN: Prospective inception cohort. SETTING: Fifteen adult medical and surgical ICUs in Spain. PATIENTS: A total of 1,441 patients aged > or =18 yrs who were consecutively admitted from April 1, 1995, through July 31, 1995. INTERVENTIONS: Prospective data collection during the stay of the patient in the ICU. Data collected included vital status at hospital discharge as well as all variables necessary for computing the Mortality Probability Models II system at admission and during the first 7 days of stay in the ICU. MEASUREMENTS AND MAIN RESULTS: Four logistic regression models were obtained. These models contained survival status at hospital discharge as a dependent variable and the following explanatory variables: (model 1) only the probability of dying at admission; (model 2) only the probability of dying during the current day; (model 3) the probability of dying at admission and during the current day; and (model 4) the probabilities of dying at admission and during the previous and current days. Models were evaluated using the Hosmer-Lemeshow statistic and the area under the receiver operating characteristic curve. For survivor and nonsurvivor patients, mortality probabilities obtained using the aforementioned models were compared using linear regression and the paired Student's t-test. Although severity at admission was a statistically significant variable, models 2 and 3 produced almost the same probabilities of hospital mortality, as shown with the linear regression and paired Student's t-test results. CONCLUSIONS: To have an accurate measurement of the prognosis, it is necessary to update the severity measure. The best estimate of hospital mortality was the probability of death on the current day. Severity at admission and at previous days did not improve the assessment of prognosis.

Adult↗

Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses.

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.

Amlodipine↗

Cloning and functional analysis of a family of nuclear matrix transcription factors (NP/NMP4) that regulate type I collagen expression in osteoblasts.

Collagen expression is coupled to cell structure in connective tissue. We propose that nuclear matrix architectural transcription factors link cell shape with collagen promoter geometry and activity. We previously indicated that nuclear matrix proteins (NP/NMP4) interact with the rat type I collagen alpha1(I) polypeptide chain (COL1A1) promoter at two poly(dT) sequences (sites A and B) and bend the DNA. Here, our objective was to determine whether NP/NMP4-COL1A1 binding influences promoter activity and to clone NP/NMP4. Promoter-reporter constructs containing 3.5 kilobases (kb) of COL1A1 5' flanking sequence were fused to a reporter gene. Mutation of site A or site B increased promoter activity in rat UMR-106 osteoblast-like cells. Several full-length complementary DNAs (cDNAs) were isolated from an expression library using site B as a probe. These clones expressed proteins with molecular weights and COLIA1 binding activity similar to NP/NMP4. Antibodies to these proteins disrupted native NP/NMP4-COL1A1 binding activity. Overexpression of specific clones in UMR-106 cells repressed COL1A1 promoter activity. The isolated cDNAs encode isoforms of Cys2His2 zinc finger proteins that contain an AT-hook, a motif found in architectural transcription factors. Some of these isoforms recently have been identified as Cas-interacting zinc finger proteins (CIZ) that localize to fibroblast focal adhesions and enhance metalloproteinase gene expression. We observed NP/NMP4/CIZ expression in osteocytes, osteoblasts, and chondrocytes in rat bone. We conclude that NP/NMP4/CIZ is a novel family of nuclear matrix transcription factors that may be part of a general mechanical pathway that couples cell structure and function during extracellular matrix remodeling.

Alternative Splicing↗

Epidemiologic studies on Dengue in Santiago de Cuba, 1997.

A small, isolated outbreak of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) due to dengue virus type 2 (DEN-2) was documented in Santiago de Cuba on the island of Cuba beginning in January 1997. There were 205 DHF/DSS cases, all in persons older than age 15 years. All but three had evidence of a prior dengue infection, with the only known opportunity being the islandwide dengue virus type 1 (DEN-1) epidemic of 1977-1979. Virtually complete clinical and laboratory surveillance of overt disease was achieved. From December 1997 to January 1998, a random, age-stratified serum sample was obtained from 1,151 persons in 40 residential clusters in Santiago. Sera were tested for DEN-1 and DEN-2 neutralizing antibodies. The prevalence of DEN-2 antibodies in children age 15 years and under, born after the 1981 DEN-2 epidemic, was taken as the 1997 DEN-2 infection rate. This was adjusted slightly to accommodate observed cases, resulting in an estimated infection rate of 4.3%. Dengue fever and DHF/DSS attack rates were calculated from estimated total primary and secondary DEN-2 infections. Only 3% of 13,116 primary infections were overt. The DHF/DSS attack rate for adults of all ages was 420 per 10,000 secondary DEN-2 infections.

Adolescent↗

The relationship between glycogen synthesis, biofilm formation and virulence in salmonella enteritidis.

Salmonella enteritidis accumulated large quantities of intracellular polysaccharide when grown in unrestricted nutrient conditions. Dense, abundant cytoplasmic granules were observed by electron microscopy in sections stained by the periodic acid-chlorite technique, indicating that the polysaccharide was of the glycogen type. When biofilm-producing S. enteritidis was pre-incubated in media containing increasing levels of glucose concentration, the levels of both cytoplasmic glycogen and biofilm rose correlatively to a point where a ceiling effect was observed. Studies carried out with activators and inhibitors of glycogen biosynthesis confirmed that biofilm was formed from glycogen cell stores. On the other hand, the virulence of the biofilm-producing strain in infected chickens increased proportionally to the amount of stored glycogen, suggesting a possible role of the glycogen depot in the virulence of S. enteritidis.

Animals↗

Persistence of well-defined collective excitations in a molten transition metal

Well-defined microscopic collective excitations are found in liquid Ni at 1763 K by means of inelastic neutron scattering. Such excitations are supported by the liquid despite an anharmonic character of its thermodynamic functions. Consideration of the detailed shape of the interionic pair potential provides a way to understand why atomic motions at microscopic scales behave in a way much closer to the alkali metals than to the liquefied rare gases.

Journal Article↗

Long-term evolution of local, proximal and remote astrocyte responses after diverse nucleus basalis lesioning (an experimental Alzheimer model): GFAP immunocytochemical study.

A study on long-term astrocytic responses (from 1 day to 20 months after lesioning in 4-month-old rats, and from 1 day to 6 months in 20-month-old rats) to diverse unilateral damage of the nucleus basalis (nbM) by injection of 40 nmol of ibotenic acid, or 50 or 100 nmols of quisqualic acid was performed using a histochemical method (immunoreactivity against the glial fibrillary acidic protein GFAP). Glial reactivity (i.e., isolated or clustered hypertrophic and/or hyper-reactive astrocytes) was evaluated in several ipsilateral and contralateral brain regions: the 'local response' within the damaged nbM region; the 'proximal response' (a new concept proposed by us) in the non-damaged structures neighbouring the nbM; and the 'remote response' in the ipsilateral brain cortex and in the contralateral cortex and nbM. In 4-month-old animals, the remote cortical glial responses, independent of the involution of cortical cholinergic activity and randomly located in layers I-V of motor and somatosensory cortical regions, were similar in appearance over a long period (13-20 months), with the highest reactivity 45 days after lesioning. The proximal response lasted from 1 day to 13 months and afterwards tended to disappear. Contralateral reactivity and ipsilateral cortical scars were observed. The local (nbM) glial response was maintained throughout the period studied. Subsets of astrocytes of different reactivities were observed, most of their elements being highly intermeshed. In 20-month-old animals, nbM lesions produced less positive, but similar, glial reactive patterns. This glial reactivity was superposed onto the glial reactivity of old age. All these results are discussed. The maintenance of reactive astrocytes many months after lesioning suggests the existence of cellular factors other than those produced by damaged nbM neurons. Taking into account the role of glial cells under pathological conditions, it is possible that these reactive astrocytes in humans could promote neurodegenerative processes, such as amyloid plaque formation and neurodegeneration (Alzheimer's disease). Along this line, nbM cholinergic involution could then originate cortical involution through induced reactive astrocytosis.

Age Factors↗

[Prevalence of anti-HAV antibodies and efficacy of pre-vaccine detection at institutions for mentally retarded of the city of Alicante].

OBJECTIVE: The aim of this study was to investigate the prevalence and efficacy of the anti-HAV antibodies detection in institucions for mentally retarded people in the city of Alicante. DESIGN: Prevalence study. SETTING: Two institucions for mentally retarded people in the city of Alicante. PARTICIPANTS: One hundred and seven residents and seventy seven in care of them. MEASUREMENTS AND MAIN RESULTS: We have investigated the anti-HAV antibodies prevalence by enzymeinmunoanalysis of microparticle test. The efficacy of the anti-HAV antibodies detection before the vaccination has been studied by calculating the threshold of prevalence with the following formula: unit cost of detection + (1 - X) x unit cost vaccination anti-HAV negative subjects = unit cost vaccination. RESULTS: The global prevalence of anti-HAV antibodies was 56.5% (95% CI, 49-63.7). The prevalence of the residents was 55.1% (95% CI, 45.2-64.7) and 58.4% in care of them (95% CI, 46.6-69.5). Among the sociodemographic variables evaluated only the age was associated with the prevalence of anti-HAV antibodies (p < 0.001). The unit cost of prevaccination detection of anti-HAV antibodies was calculated as 998 pesetas and the unit cost of the vaccination as 3595, obtaining a prevalence anti-HAV threshold of 27.8%. CONCLUSIONS: The prevalence of anti-HAV antibodies in this collective studied is similar to the prevalence of anti-HAV antibodies of the spaniard population. The direct vaccination without a previous marker study is recommended to people under the age of 31 in this population group.

Adolescent↗

Determination of beta-globin gene cluster haplotypes and prevalence of alpha-thalassemia in sickle cell anemia patients in Venezuela.

Sickle cell anemia and alpha-thalassemia have a heterogeneous distribution in Venezuela with a high frequency in the coastal area (sea level) and few cases in the mountains. Most of our population is an ethnic admixture of Europeans (Spaniards colonists), Africans (slaves), and Amerindians. The purpose of our study was to determine the origin of the beta(s) globin haplotype, age and survival dependency, and the admixture among the different African groups in our population. The alpha(3.7) globin gene deletion status was also studied and found in a very high frequency. DNA from peripheral blood of 191 non-related patients (81 with HbS homozygous and 15 patients compound heterozygous for HbS, HbC, HbD with beta-thalassemia, and 95 with sickle cell trait) were studied. The beta(s) chromosome was linked 51% to the Benin Haplotype, 29.5% with the CAR, 12.5% to the Senegal, and 2.5% to the Cameroon. We did not find any significant difference between the haplotype distribution among adults and children and among sickle cell patients and traits. Only 8.6% of the patients have homozygosity for the Benin haplotype. These results show a very high frequency of admixture in our African origin population.

Age Distribution↗

Interobserver variability of the measurement of the mortality probability models (MPM II) in the assessment of severity of illness.

OBJECTIVE: To assess the interobserver variability of the measurement of the MPM II system. DESIGN: Random sample of an inception cohort. SETTING: Fifteen adult medical and surgical intensive care units (ICUs) in Spain. PATIENTS: A 5% random sample (n = 119) of 2332 patients consecutively admitted in the ICU, aged 18 years or older. INTERVENTIONS: Prospective data collection during the stay of the patient in the ICU. Repeated data collection, after the patient's hospital discharge. MEASUREMENTS AND MAIN RESULTS: Demographic information, length-of-stay and vital status at both ICU and hospital discharge, as well as all variables necessary for computing the MPM II system were measured. Interobserver variability for categorical variables was measured computing the kappa index. For interval variables the interobserver variability was assessed by the intraclass correlation coefficient, the paired t-test, and linear regression. In the MPM II0 index, the variables coma, heart rate, systolic blood pressure, chronic renal insufficiency, metastatic neoplasm, acute renal failure, cardiac dysrhythmia and cardiopulmonary resuscitation, showed moderate or low levels of agreement. In the MPM II24 index, the variables coma or deep stupor, PaO2 and prothrombin time showed low or moderate interobserver agreement. Agreement for the MPM II probability of death was high, although the external observer obtained a lower estimation than the hospital observer. CONCLUSIONS: The MPM II severity system showed a high level of stability when used in groups of patients. Nevertheless, the observed variability in some variables means that it should be used with caution for individual patients.

Adult↗

Prevalence and viral persistence of TT virus in patients on hemodialysis.

The aim of this study was toevaluate the prevalence of TT virus (TTV) in 107 hemodialysis patients and 100 healthy individuals. Sixteen percent of hemodialysis patients and 2% of the control population were TTV positive (P<0.001). Sex, time on dialysis, transfusions, and alanine aminotransferase levels were not related to the presence of TTV DNA. TTV was more frequent in patients 50 to 70 (12/51) years of age and persisted in the serum of six of nine patients 8 months later. TTV was found in peripheral blood mononuclear cells of all patients with chronic infection, and sequence variation was noted in the peripheral blood mononuclear cells of two patients. No relationship between TTV infection and hepatitis was observed. Viral persistence and nonparenteral transmission may be possible in patients on hemodialysis.

Aged↗

Oral iron cutaneous adverse reaction and successful desensitization.

BACKGROUND: The oral administering of iron preparations sometimes produces adverse gastrointestinal effects. In contrast, cutaneous reactions are extremely rare. OBJECTIVE: We report a patient with several episodes of generalized pruritus and erythematous maculopapular eruption after receiving oral compounds of iron and on whom desensitization with oral iron was attempted. METHODS: We studied a female with microcytic anemia due to gynecologic blood loss who presented several episodes of cutaneous eruption after receiving oral compounds of iron. Skin prick-test and two simple-blind, placebo-controlled oral challenges were performed with various iron compounds, and finally desensitization with oral iron was carried out. RESULTS: Skin prick-test and patch-test with iron preparations were negative. Two simple-blind, placebo-controlled oral challenges were performed and the patient began experiencing similar cutaneous symptoms. We started a slow desensitization protocol using increasing doses until the target amount of the drug was tolerated without adverse effects. The chronic administration of oral iron therapy once a day for 9 months sustained the desensitized state and the anemia disappeared. CONCLUSION: We present methods to effectively manage iron supply for a microcytic anemia patient with cutaneous reactions due to oral iron compounds, to avoid repeated transfusions, slow desensitization with oral iron was successfully attempted.

Administration, Oral↗

Serological prevalence to six leptospiral serovars in cattle in Asturias (Northern Spain).

The prevalence of antibody to six serovars of Leptospira interrogans in cattle in Asturias (Northern Spain) was determined by the microscopic agglutination test (MAT). Using 50% agglutination or lysis at a dilution of 1:10 or more as the criteria for seropositivity, 371 of 3578 (10.36%) animals were found to react with one serovar. The most commonly detected serovars were pomona (5.59%) and grippotyphosa (2.37%), whilst serovar hardjo (0.75%), icterohaemorrhagiae (0.64%), poi (0.64%) and autumnalis (0.36%) were found at lower frequencies.

Agglutination Tests↗