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Biomedical subjects

N Alvarez

Publications and source records attributed to N Alvarez.

At least 19 recordsLinked to original sources

Case-control study of gastric cancer screening in Venezuela.

A screening programme for early gastric cancer was introduced in the state of Tachira, Venezuela, in 1980. Screening was performed by photofluorography, using two mobile units. The efficacy of this programme in reducing mortality from stomach cancer was evaluated by means of a case-control study. Cases were 241 individuals who died from stomach cancer in the period 1985-89. Ten live controls per case were drawn from the electoral rolls, matched by sex, age and residence. Exposure to the screening examination of cases and controls was assessed through individual linkage with the programme's centralised database. After the exclusion of examinations occurring within the 6 months preceding the case's diagnosis, the odds ratio (OR) of dying from stomach cancer for those screened was 1.26 (CI 0.83-1.91) and the OR in females was lower than in males: 0.77 (CI 0.33-1.78) and 1.52 (CI 0.94-2.47) respectively. Odds ratios associated with years since last test and number of tests did not differ significantly from 1. These results show the inefficacy of the programme in reducing mortality from gastric cancer in the area. In an attempt to determine whether this result was due to selection bias, an analysis restricted to subjects who had been screened at least once was performed. When examinations occurring after an index date at various intervals before the case's diagnosis were excluded, the screening test appeared to protect from death, although confidence intervals of the odds ratios are large, for example OR = 0.47 (CI 0.24-0.98) when excluding tests within 1 month.

Age Factors

Changes in left ventricular mass and filling after renal transplantation are related to changes in blood pressure: an echocardiographic and pulsed Doppler study.

To examine changes in left ventricular (LV) mass and function (diastolic and systolic) after successful renal allograft transplantation (RT), we prospectively studied 30 patients (19 men, 11 women, aged 37 +/- 13 years) by M-mode, two-dimensional and pulsed Doppler echocardiography at the time of surgery and 10 +/- 1.8 months later. At the time of transplantation all patients had been undergoing dialysis (4 peritoneal dialysis, 26 hemodialysis) for 2.5 +/- 3.2 years. A hematocrit of < or = 30% was present in 26 patients. After RT the mean hematocrit increased from 26 +/- 4 to 40 +/- 7 (p < 0.01), whereas systolic, diastolic and mean blood pressure (BP) remained unchanged. The LV mass index (LVMI) decreased from 201 +/- 56 to 171 +/- 41 g/m2, (p < 0.01); LV diastolic diameter corrected by body surface area (LVDDI) decreased from 298 +/- 38 to 279 +/- 35 (p < 0.01) and the LV end-diastolic volume index (LVEDVI) from 72 +/- 18 to 63 +/- 15 (p < 0.01). There were no changes in LV fractional shortening or LV end systolic wall stress. Peak late transmitral velocity (A wave) decreased from 77 +/- 16 to 68 +/- 12 cm/s (p < 0.01) with no changes in other Doppler-derived indexes of diastolic function. No fistula patency influence on changes in LV mass and function was found. After RT, BP decreased in 21 patients from 150 +/- 20 to 132 +/- 15 (p < 0.001; group I) and increased in 9 patients from 130 +/- 14 to 153 +/- 16 (p < 0.05, group II). Patients in group I suffered a reduction in LVMI (p < 0.001), LV end-diastolic diameter (p < 0.05), LVDDI (p < 0.001); LV end-diastolic volume (p < 0.05); LVEDVI (p < 0.01); cardiac index (p < 0.05), and peak late transmitral velocity (p < 0.01), but no changes in group-II patients were observed. We concluded that BP is a major determining factor with regard to changes in LV hypertrophy and function following RT. LV mass and volumes can be expected to decrease after RT in patients with BP reduction.

Adult

Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum.

It is well known that helminthic infection can cause a polyclonal stimulation of the synthesis of IgE, which is dependent on interleukin-4 (IL-4) production, and it has been suggested that this can modulate the expression of allergic reactivity in tropical populations. We evaluated the effect of regular anthelmintic treatment, for a period of 22 months, on certain aspects of the allergic reactivity of children in a slum area of Caracas, Venezuela, where helminths are endemic. The treatment (Oxantel-Pyrantel; Quantrel) effectively eliminated intestinal helminthic infection and resulted in a significant decrease in the initially elevated total serum IgE levels. IL-4 was detectable in the serum, and a significant reduction in IL-4 was also observed after treatment. In contrast, both the immediate-hypersensitivity skin-test reactivity and serum levels of specific IgE antibody against environmental allergens were markedly increased in the treated children. In a group of children who were also evaluated in the same slum, but who declined treatment, a substantial increase in helminthic infection occurred, which was related to an acute deterioration of the socioeconomic conditions of Venezuela over the course of our study period. This was paralleled by a considerable increase in total IgE levels in these children and a decrease in the skin-test reactivities and specific IgE levels. The application of Prausnitz-Küstner passive transfer tests and analysis of specific IgE antibody levels indicated that the polyclonal stimulation of IgE synthesis by helminthic parasites results in mast cell Fc epsilon receptor saturation and suppression of specific IgE antibody synthesis. This inhibition of allergic reactivity is reversible by anthelmintic treatment.

Adolescent

Ascaris reinfection of slum children: relation with the IgE response.

Total and Ascaris-specific serum IgE levels were measured in a group of 98 Ascaris-infected children from a slum area of Caracas, Venezuela, in whom the infections were eliminated by regular treatment for 22 months with the anthelmint Oxantel/Pyrantel ('Quantrel'). The children were re-evaluated at the end of the treatment programme, and then 8 months later, at which time reinfection was assessed. Total IgE levels at the beginning of the study were significantly higher in the children who became reinfected after treatment, compared with those who did not. The anthelmint treatment caused a significant decrease in the total IgE levels in most of the children, and after a period of 8 months without treatment these continued to decrease in the non-reinfected group, but increased again in the reinfected children. The reverse pattern was found for Ascaris-specific IgE antibody levels, and in fact an inverse correlation was found between total and anti-Ascaris IgE levels. Striking associations were found between reinfection and high pretreatment values of total IgE, but low levels of specific IgE antibody. These data support the concept that specific IgE antibody may participate in the protection against helminthic infection, and suggest that the polyclonal stimulation of IgE synthesis caused by these parasites may reduce the effectiveness of such responses. The results also indicate that different individuals have varying propensities to respond polyclonally to the helminths, and this influences their resistance to infection.

Animals

High-performance liquid chromatographic determination of N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine, the active plasma metabolite of a prodrug atriopeptidase inhibitor (SCH 42495), using a thiol selective (Au/Hg) amperometric detector.

A high-performance liquid chromatographic assay for the determination of N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methionine (SCH 42354; II), the active metabolite of the atriopeptidase inhibitor prodrug, N-[2(S)-(acetylthiomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L-methi onine ethyl ester (SCH 42495; I), in human plasma was validated for use in clinical pharmacokinetic studies. Plasma (200 microliters) was processed by protein precipitation with acetone containing the internal standard, N-[2(S)-(mercaptomethyl)-3-(2-methylphenyl)-1-oxopropyl]-L- ethionine (III). Compound II was recovered (ca. 90%) in the supernatant after centrifugation and prepared for injection by the addition of 0.15 M monochloroacetic acid containing 0.2 mM EDTA. Separation of II and III was accomplished on commercially available reversed-phase C8 columns designed for the separation of basic compounds. Both compounds were detected using amperometric detection (+0.125 V versus Ag/AgCl) on a thin-layer Au/Hg amalgam electrode. The lower limit of quantitation was 10 ng/ml, where the inter-assay precision (coefficient of variation) was +/- 11.4% and the inter-assay accuracy (bias) was +1.0%. No endogenous interferences were observed in the extracts obtained from drug-free plasma. The detector response (using either peak area or height ratios of II to III) was linear from 0.01 to 1.0 micrograms/ml. Compound II was stable in plasma supplemented with EDTA and sodium hydrogensulfite for at least 3 months when stored frozen at -78 degrees C; no significant decomposition of II was observed following three freeze-thaw cycles. The feasibility of this liquid chromatographic assay with electrochemical detection was demonstrated with plasma samples from hypertensive subjects administered 100 mg of compound I.

Chromatography, High Pressure Liquid

Bronchoconstriction in helminthic infection.

In order to determine whether infection by helminthic parasites can be associated with a state of bronchoconstriction, we evaluated the response to the inhalation of a bronchodilator before and after long-term anthelmintic treatment of children in a urban slum of Caracas, Venezuela. In untreated children, a direct association was found between the degree of helminthic infection and the increase in peak expiratory flow rates caused by the bronchodilator. The elimination of the infections was accompanied by a significant decrease in response to the bronchodilator. These results indicate that helminthic infection could contribute to the development of asthmatic conditions in areas where these parasites are endemic.

Albuterol

The relationship between enlargement of the temporal horns of the lateral ventricles and dementia in aging patients with Down syndrome.

Head CT studies of patients with Alzheimer's disease (AD) show global atrophic changes. Tissue loss is especially prominent in the temporal lobes, with widening of the temporal horns of the lateral ventricles and, usually, widening of the temporal sulci. Some recent studies have found a familial form of AD to be mapped to chromosome 21. Down syndrome (DS) results from the inheritance of three chromosomes 21, and it has been shown that after the age of 35 the brains of patients with DS commonly show neuropathological changes similar to those in patients with AD. CT studies of 25 patients with DS (ages 29-64 years) were examined for tissue loss in the temporal regions, and this was compared to the findings commonly seen in patients with AD. The widths of CSF spaces varied considerably in patients with DS, but after the age of 50 most of them showed significant widening of the temporal horns. In some patients the horns were large enough to suggest obstructive hydrocephalus. Because of a new trend toward deinstitutionalization of patients with DS, radiologists will be seeing more studies on these patients and should familiarize themselves with the unique ways in which they manifest the aging process.

Activities of Daily Living

The effects of the everyday environment on epileptic activity in three mentally retarded individuals.

Three mentally retarded epileptic subjects with frequent epileptiform EEG paroxysms were monitored with simultaneous radio-telemetered EEG and video recording while they were exposed to their everyday environmental conditions. These conditions included prompts and reinforcement for performing vocational training tasks, speech therapy, eating and drinking, and cues for resting, waiting, playing, exercising, and relaxing. Epileptiform EEG activity and the occurrence of clinical seizures varied as a function of the particular environmental conditions. Epileptiform EEG discharges were longer in duration, and clinical seizures were more frequent in all 3 subjects during conditions which produced inactive behavior than during conditions which produced active behavior. The modulation of epileptiform activity by everyday environmental conditions carries implications for (1) the optimum structuring of the environment for mentally retarded patients with frequent, subtle seizures, and (2) the analysis of the effects of epileptiform discharges on behavior.

Activities of Daily Living

Discontinuance of antiepileptic medications in patients with developmental disability and diagnosis of epilepsy.

Fifty patients with developmental disabilities and past history of epilepsy but without reported seizures fo several years underwent trial reductions of an antiepileptic drug. After an 8-year follow-up there was recurrence of seizures in 26 patients. Predictors for a seizure free state off medication were: few documented seizures in lifetime, no gross neurological abnormalities, medication below therapeutic levels at time of discontinuance, and persistently normal EEGs before and after discontinuance. Successful withdrawal of medication may have resulted from early control of seizures or early treatment; lack of actual epileptic seizures but presence of "pseudoseizures"; isolated event seizures; or seizures that could have resulted from nonepileptic, self-limiting factors.

Adolescent

Atlantoaxial instability in adults with Down syndrome: a clinical and radiological survey.

A survey of 129 adults with Down syndrome was undertaken to determine the prevalence of atlantoaxial instability (AAI) and to establish a base line for long term prospective study. Clinical and radiological evaluations were performed to determine optimal screening methods for this condition. The findings indicate that radiological evidence of AAI was found in 40% with anterior atlanto-odontoid distance (AAOD) of 3 mm or more and in 10% with 5 mm or more. These findings are similar to those reported in the pediatric age group. A preponderance of females with symptomatic AAI is noted. Clinical evaluation suggested the presence of spinal cord compression, which was confirmed by CT scan of the atlantoaxial region. There were no false negative clinical results. Among the false positive clinical findings other explanations were present in some cases. A comparison with the literature is offered along with guidelines on screening and management.

Adult

Differential diagnosis of epileptic versus pseudoepileptic seizures in developmentally disabled persons.

One-hundred and twenty-four mentally retarded persons with behaviors suggestive of epilepsy were monitored with an 8-channel radiotelemetered electroencephalograph-video recording system (TEEG-VR). Target behaviors were identified by the clinical description of the primary care providers before the TEEG-VR sessions. Whenever possible, the known antecedents of those behaviors were replicated. The target behaviors were considered epileptic when they were observed simultaneously with epileptiform EEG patterns, and pseudoepileptic when nonepileptiform patterns were observed. Twenty persons were classified as epileptic, 50 as pseudoepileptic, 11 as both epileptic and pseudoepileptic, and 43 as inconclusive. Among the pseudoepileptics there were 15 with abnormal EEGs and 4 with epileptiform EEGs. The most frequent topographies of behavior were not significantly related to diagnosis. These included myoclonus, eye blink, head drop, cessation of ongoing activity, and hand and arm automatisms. The diagnosis of epilepsy in mentally retarded persons, on the basis of clinical description, interictal EEG, and medical history, may be inaccurate. TEEG-VR is extremely useful for obtaining a definitive diagnosis of each target behavior.

Adolescent

Effect of different doses of valproic acid on the serum levels of total and free diphenylhydantoin.

In the course of a large prospective study aimed at evaluating the efficacy of Valproic Acid (VPA) in persons with intractable seizures, six patients that were on a steady dose of diphenylhydantoin (DPH) were exposed to different steady doses of VPA. The changes observed in the serum levels of total, free, and percentage of free DPH are reported here. There were no consistent changes in the serum levels of total DPH, but when serum levels of DPH, obtained before VPA was added to the therapeutic plan, were considered, it was found that the total DPH decreased in those patients with the higher baseline levels while it increased in those with the lower baseline levels. There also was an increase in the absolute total and the percentage of free DPH in most instances. The data suggested that the changes occurred soon after VPA was added and remained constant in the same patient as long as the total dose of VPA did not change. The data also suggested that VPA most probably interfered through a dual mechanism, displacement of albumin-fixed DPH, and decreased liver clearance of DPH. The interpersonal variability was such that only broad generalizations are possible. There is a need to measure free DPH in patients on VPA.

Adolescent

Physiologic analysis of the myoclonus of Alzheimer's disease.

Ten patients with clinically diagnosed Alzheimer's disease, including three cases of trisomy 21 (Down's syndrome), developed a chronic myoclonic disorder. The technique of jerk-locked averaging of EEG activity was used to analyze the myoclonus. Seven subjects demonstrated a focal, contralateral central, negative cerebral potential antecedent to the myoclonic jerks. This EEG event differs from that previously reported to be associated with the myoclonus of subacute spongiform encephalopathy (Creutzfeldt-Jakob disease).

Aged

Paroxysmal spike and wave activity in drowsiness in young children: its relationship to febrile convulsions.

Paroxysmal rhythmic theta waves appearing during early stages of sleep have long been recognized in the EEGs of normal children. A similar pattern with intermixed spikes appears to have a different correlation. We called this pattern 'hypnagogic paroxysmal spike wave activity' or 'hypnagogic PSW.' This investigation was designed to test whether there exists a relationship between hypnagogic PSW, febrile convulsions (FC) and age. We selected 3 cohorts of children: G-1 or normal control consisted of 94 children selected with the following criteria: complete normal neurodevelopmental examination and no personal or family history of FC, epilepsy, or other neurological disorder. They all had one EEG obtained without drug induction showing a clear sequence of awake-drowsy-sleep-arousal-awake states. G-2 or pathological control group consisted of 126 children selected at random, referred to the Division of Neurophysiology at the Children's Hospital Medical Center for any problem excluding FC. At least one EEG met the criteria mentioned above. G-3 or FC group consisted of 375 children in whom the very first seizure was associated with fever without evidence of other causes for the convulsion. All met the same EEG criteria of G-1 and G-2. The medical record of 169 children of this group (40 with hypnagogic PSW and 129 without hypnagogic PSW) were reviewed.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain

Vitamin K-dependent proteins and anticonvulsant medication.

Certain anticonvulsant drugs, especially phenytoin and phenobarbital, interfere with vitamin K metabolism as indicated by a raised serum osteocalcin level. This finding may be of importance in the pathogenesis of side effects of these medications.

Adolescent

Attempted rapid elbow flexion movements in patients with athetosis.

Voluntary rapid elbow flexion movements were studied in 14 patients with athetosis on the basis of cerebral palsy. When the movement was attempted with one arm, other muscles inappropriate for the task, such as muscles in the opposite limb, were also activated. EMG activity of the biceps and triceps was analysed in detail, and the patterns seen in the different patients were divided into six groups: (1) The normal "ballistic" triphasic pattern, with bursts of normal duration, alternating in biceps and triceps, but the triceps might be activated first, causing the limb to extend rather than flex, (2) The triphasic pattern, with bursts of long duration, (3) Repetitive cycles of the triphasic pattern with particularly long antagonist bursts, apparently limiting the movement in each cycle, (4) Long bursts synchronous in agonist and antagonist muscles, (5) Continuous activity of the agonist, with reduction in activity of the antagonist, (6) Failure to be able to do the task. The pathophysiology of athetosis is that voluntary movement is characterised by excessive muscular activity, most prominently in inappropriate muscles, both extraneous to the task and directly antagonistic.

Adult