Biomedical subjects
Publications and source records attributed to M Velez.
Abdominal manifestations of cardiac disease may result in misleading and erroneous diagnoses. We present a case of congestive heart failure secondary to rheumatic valvular disease resulting in the appearance of an acute surgical abdomen.
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A variation of fluorescence photobleaching recovery (FPR) suitable for measuring the rate of rotational molecular diffusion in solution and cell membranes is presented in theory and experimental practice for epi-illumination microscopy. In this technique, a brief flash of polarized laser light creates an anisotropic distribution of unbleached fluorophores which relaxes by rotational diffusion, leading to a time-dependent postbleach fluorescence. Polarized FPR (PFPR) is applicable to any time scales from seconds to microseconds. However, at fast (microsecond) time scales, a partial recovery independent of molecular orientation tends to obscure rotational effects. The theory here presents a method for overcoming this reversible photobleaching, and includes explicit results for practical geometries, fast wobble of fluorophores, and arbitrary bleaching depth. This variation of a polarized luminescence "pump-and-probe" technique is compared with prior ones and with "pump-only" time-resolved luminescence anisotropy decay methods. The technique is experimentally verified on small latex beads with a variety of diameters, common fluorophore labels, and solvent viscosities. Preliminary measurements on a protein (acetylcholine receptor) in the membrane of nondeoxygenated cells in live culture (rat myotubes) show a difference in rotational diffusion between clustered and nonclustered receptors. In most experiments, signal averaging, high laser power, and automated sample translation must be employed to achieve adequate statistical accuracy.
Seventeen severe chronic alcoholic patients with and without Wernicke-Korsakoff syndrome (WKS) were examined prospectively after being treated by withdrawal from alcohol. The WKS patients also received thiamine supplements. Three-dimensional measurements of local cerebral blood flow (LCBF) and local partition coefficients (L lambda) were made utilizing xenon contrast computed tomography (Xe CT-CBF). Results were displayed as color-coded brain maps before and after treatment and these were correlated with neurological and cognitive examinations. Before treatment chronic alcoholics without WKS (n = 10) showed diffuse reductions of LCBF values throughout all gray matter including hypothalamus, vicinity of nucleus basalis of Meynert, thalamus, and basal ganglia. Similar, but more severe, reductions were seen in patients with WKS (n = 7), however, white matter perfusion was also reduced. In WKS, most prominent reductions of LCBF were also seen in hypothalamus and basal forebrain nuclei but thalamus, basal ganglia, and limbic systems were severely reduced. After treatment, both groups with alcoholic encephalopathy showed marked clinical improvement and cerebral perfusion was restored toward normal. Chronic alcohol abuse, in the absence of thiamine deficiency, reduces CBF by direct neurotoxic effects. If thiamine deficiency is also present, more severe and localized hemodynamic reductions are superimposed.
Twenty severe chronic alcoholic patients with signs of neurotoxicity but without Wernicke-Korsakoff syndrome were treated by abstinence from alcohol and examined prospectively at intervals thereafter. Serial examinations included detailed medical histories, neurological examinations, cognitive capacity screening examinations, computed tomography scans with measurements of sulcal and ventricular volume, and measurements of regional CBF. All sedatives were withdrawn before CBF measurements were made. Before treatment, gray matter blood flow values were significantly reduced compared with those of age-matched normal volunteers, but white matter blood flow values were normal and the ventricles were enlarged. After abstinence from alcohol, mean gray matter blood flow values and brain volume both increased significantly.
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The activity of rat heart succinate dehydrogenase (SDH) increases 1.7-fold in old animals (Vitorica, J., Cano, J., Satrústegui, J. and Machado, A., Mech. Ageing Dev., 16 (1981) 105-116). This increase is due to an increase in enzyme protein itself because: (a) the activation state of the enzyme does not vary with age; and (b) the increase of activity is paralleled by an increase in immunoprecipitable SDH in old rat heart mitochondria. SDH from old rat heart mitochondria differs in a number of ways from that of young animals: (a) The km value for succinate increases with age. (b) The thermostability decreases, and the activation energy in the 20-40 degrees C interval is higher in old animals. (c) The breaking points of the Arrhenius plots of SDH are shifted to higher values. (d) Reactivity towards N-ethylmaleimide in succinate protected mitochondria decreases with age.
Nineteen patients with sudden onset of impaired recent memory, cerebellar ataxia, peripheral neuropathy, and other signs of Wernicke-Korsakoff syndrome (WKS) were treated and examined prospectively for 3 months. Serial studies included histories, neurological examinations, cognitive capacity screening examinations (CCSE), computed tomography (CT) scans, and measurements of regional CBF. Patients were detoxified and withdrawn from sedatives before CBF measurements were examined. Treatment included alcohol withdrawal, nutritious diet, and 300 mg thiamine daily. Before treatment CCSE scores and blood flow values of both white and gray matter were reduced, particularly within both temporoparietal regions. After treatment of compliant patients (n = 10), white and gray matter blood flow increased concurrently with improved CCSE scores. Abnormal eye signs, ataxia, peripheral neuropathy, and performance of activities of daily living also improved. Cerebral atrophy and ventricular enlargement measured by CT decreased. Early recognition and treatment of WKS in compliant patients permit rapid reversals of cognitive and neurological impairments associated with increased blood flow of gray and white matter and improvements of brain atrophy measured by CT scanning.
During the fall of 1981, a new method for the routine isolation and identification of dengue viruses in Puerto Rico was implemented utilizing C6/36 cell cultures and serotype specific antidengue monoclonal antibodies. A blind comparison of the monoclonal antibody indirect fluorescent antibody test (IFAT) and the complement fixation (CF) test for identification of 89 newly isolated dengue viruses of all four serotypes from the Caribbean, Asia and Africa showed 100% agreement. Although virus isolation rates were slightly lower than with the mosquito inoculation technique, use of the C6/36 cell culture system was much less time-consuming and allowed the processing of larger numbers of sera. Beginning in November 1981, a new virologic surveillance system was begun in Puerto Rico. Acute sera from persons with suspected dengue were selected for virus isolation attempts on the basis of geographic area of residence on the island, day after onset the blood was taken and clinical signs and symptoms. These sera were processed for virus isolation in C6/36 cell cultures, and virus isolates were identified by the IFAT using the monoclonal antibodies. Using this system, 2,702 sera were tested from November 1981 through August 1982. Dengue virus was isolated from 518, for an isolation rate of 19.2%. Dengue 1 was the predominant virus until December 1981, when dengue 4 became dominant. The changing patterns of dengue 1 and 4 distribution by time and geographic location on Puerto Rico were followed. This system allows the dengue viruses being transmitted in an area to be monitored with a minimal amount of effort and provides the early warning capability necessary to predict epidemic dengue.
Superior vena cava (SVC) syndrome is a well-recognized clinical entity seen with mediastinal malignancies and intraluminal venous thrombosis. The role of recombinant tissue plasminogen activator (rt-PA) in the resolution of SVC syndrome caused by thrombosis in the bone marrow transplant settings has not been described. The authors report a case of SVC syndrome with good clinical response in a 16-year-old female with sickle cell disease undergoing an allogeneic bone marrow transplant (BMT) from her HLA identical sibling. Shortly after her transplant, she was found to have significant facial edema and swelling above the neck. Concomitantly, her renal function deteriorated with progressive elevation of serum urea nitrogen and creatinine levels, requiring the use of continuous veno-venous hemofiltration. An upper extremity venogram showed complete SVC obstruction (type III) with apparent inferior reflux into the azygos system. rt-PA was started at a dose of (0.5 mg/kg/day) for 2 days. There was a dramatic resolution of her symptoms, including significant improvement in renal function with increase in urine output. A repeat venogram showed free flow from the distal tip of the central line consistent with a patent superior vena cava. There was no evidence of any bleeding manifestations with rt-PA. This report highlights the usefulness of rt-PA as a treatment modality for SVC syndrome in the BMT settings.
Procollagen type I carboxyterminal and type III aminoterminal peptide concentrations were measured in sera of 60 patients with alcoholic and 14 with nonalcoholic liver disease to study whether these assays are useful as clinical tests to differentiate various stages of alcoholic liver injury. Both propeptides were markedly elevated in alcoholic hepatitis and cirrhosis: procollagen type III peptide in 90% and type I peptide in 60-80% of these patients. Moderately increased values were found less frequently in patients with fatty liver. These tests did not differentiate patients with simple fatty liver from those with fatty liver and early fibrosis. There was a significant difference in serum procollagen type III peptide between fatty liver and both alcoholic hepatitis and cirrhosis (p less than 0.001), and in type I peptide between fatty liver and alcoholic hepatitis (p less than 0.005). Although serum peptide values correlated with the degree of liver fibrosis, appreciable overlap of values was found between the various groups. The peptide concentrations also seemed to be related to the degree of hepatic inflammation, and the highest values were observed in a subgroup of patients with alcoholic hepatitis in whom numerous Mallory bodies were found. The data suggest that in alcoholic liver diseases, serum collagen propeptide determination may be useful in diagnosing severe alcoholic hepatitis.
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Coronary artery spasm is the most frequent cause of ischemic heart disease without coronary atherosclerosis once other causes such as cardiomyopathy, arteritis, coronary ectasia, valvular heart disease or hypertensive heart disease are eliminated. We report 23 patients, 15 males and 8 females, whose ages ranged from 34 to 63 years, with a mean age of 47 years, with demonstrated angina pectoris and myocardial ischemia, whose cardiac cineangiography showed no signs of atherosclerosis. Nevertheless, a significant retardation in the progression speed of the contrast medium was observed, as indirect evidence of the increment in coronary resistance at the arteriole level. Coronary spasm was ruled out by administration of intracoronary ergonovine, and other causes of myocardial ischemia, such as muscular bridges, were also discarded. The clinical presentation of the ischemic heart disease was unstable angina (UA) in 21 patients and myocardial infarction (MI) in 2. In the UA group, 14 patients showed ischemic changes in the ECG while the pain lasted, and in 8 patients the changes were present during the stress test. In all of them, the stress test perfusion scan with thallium 201 showed myocardial ischemia. In the IM group, the diagnosis was based on the clinical findings, the ECG, the enzyme curve, and the technetium 99 cardiac scintigram. In the two-year follow-up the prognosis has been favorable with treatment based on calcium antagonists. Nowadays 18 patients are asymptomatic, four have stable angina and only one has unstable angina.
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