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Biomedical subjects

A Conrad

Publications and source records attributed to A Conrad.

35 records · Page 2Linked to original sources

Human neuro-specimen banking 1961-1992. The National Neurological Research Specimen Bank (a donor program of pre- and post-mortem tissues and cerebrospinal fluid/blood; and a collection of cryopreserved human neurological specimens for neuroscientists).

The National Neurological Research Specimen Bank (The Bank) was established in 1961 to provide a vital service to neuroscientists. Our purpose is to support medical research which seeks the etiopathogenesis for devastating neurological disorders with no known cause, treatment or precise animal model. It serves as a bridge between the neurology clinician who diagnoses and cares for patients with incurable disease and the basic scientist who has need for specimens to find their etiopathogenesis. In the long run this service should advance neurologic diagnoses and serve as the basis for designing treatment. The Bank has grown to be the largest, most diverse neurological specimen bank of its kind in the world. It is a type of "tissue bank" where donor members "will" their central nervous system tissues to science. Then we collect, photograph, seal in air tight bags, quick freeze, cryogenically store and distribute on request the donated tissue to research scientists around the world. All tissue diagnoses are confirmed by clinical records and neuropathologic examination; further histology is conducted on request. In addition to brain and spinal cord tissues, the Bank has samples of other tissues. There are also samples of pre- and post-mortem CSF and sera from normal individuals and patients with various neurological disorders, especially serial specimens on multiple sclerosis patients and HIV-1 seropositive and at risk individuals. This paper outlines the global operations of our human brain bank, based on protocols developed and used by the authors. These operations include donor solicitation, tissue acquisition and documentation, tissue processing and storage, specimen dissemination to users, outcome assessment of banking, quality control, cost of our operation, table of organization and the future.

Blood Donors

The role of the mitochondrial creatine kinase system for myocardial function during ischemia and reperfusion.

The subcellular distribution of ATP, ADP, creatine phosphate and creatine was studied in normoxic control, isoprenaline-stimulated and potassium-arrested guinea-pig hearts as well as during ischemia and after reperfusion. The mitochondrial creatine phosphate/creatine ratio was closely correlated to the oxidative activity of the hearts. This was interpreted as an indication of a close coupling of mitochondrial creatine kinase to oxidative phosphorylation. To further investigate the functional coupling of mitochondrial creatine kinase to oxidative phosphorylation, rat or guinea-pig heart mitochondria were isolated and the mass action ratio of creatine kinase determined at active or inhibited oxidative phosphorylation or in the presence of high phosphate, conditions which are known to change the functional state of the mitochondrial enzyme. At active oxidative phosphorylation the mass action ratio was one-third of the equilibrium value whereas at inhibited oxidative phosphorylation (N2, oligomycin, carboxyatractyloside) or in the presence of high phosphate, the mass action ratio reached equilibrium values. These findings show that oxidative phosphorylation is essential for the regulation of the functional state of mitochondrial creatine kinase. The functional coupling of the mitochondrial creatine kinase and oxidative phosphorylation indicated from the correlation of mitochondrial creatine phosphate/creatine ratios with the oxidative activity of the heart in situ as well as from the deviation of the mass action ratio of the mitochondrial enzyme from creatine kinase equilibrium at active oxidative phosphorylation in isolated mitochondria is in accordance with the proposed operation of a creatine shuttle in heart tissue.

Animals

[Methanol kinetics in chronic alcoholism].

Blood tests from 39 persons, who had been admitted to a local hospital for alcoholics, were analysed. The methanolconcentrations at the reception time lay between 10 and 82 mg/kg and the BAC between 2.00 and 3.83%. In all cases, when Ethanol existed in a sufficient concentration the Methanolconcentration showed a horizontal trend. A Methanolelimination was not observed. Only after exceeding a limiting value of Ethanol, which fluctuated between 0.8 and 0.2%, in most of the cases under 0.2%, the Methanolcurves increased significantly. An Ethanolelimination was observed between 0.15 and 0.25% per hour, the average was about 0.19%.

Adult

The detection of HIV by in situ hybridization.

A simplified method of in situ hybridization is described for the detection of HIV targets. This standardized method can be applied to sections of formalin-fixed paraffin-embedded tissues, cell blocks, and smears of cultured cells using 3H- or 35S-labeled DNA and 35S-labeled RNA probes. In order to use elevated stringencies in the hybridization and wash steps, tissue sections and cells are covalently bonded to silanated glass slides without their subsequent loss from the slides. Routine hematoxylin and eosin or Romanovsky's stains enable the identification of the cells detected by in situ hybridization. HIV-infected neuroblastoma and lymphoid cell lines, lymph nodes, bone marrow, kidney, as well as brain tissue from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex are used to demonstrate the generality of the procedure. The standardized method described widens the ease and applicability of in situ hybridization in the investigation of pathologic tissues with the use of diverse specimens and probes.

DNA Probes

Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques.

The status of hepatitis B virus DNA was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis B virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral DNA by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature.

DNA, Viral

A randomized double blind study of a new ready-for use prostaglandin gel (Org 2436) for cervical ripening prior to first trimester pregnancy termination.

In a placebo-controlled double-blind randomized study involving 50 primigravidae scheduled for termination of first trimester pregnancy 500 micrograms PGE2 gel or placebo gel were applied intracervically 6 hours before curettage. The priming effect was verified in all patients by means of comparative examinations with a special tonometer before application of the gel and immediately before the surgical procedure. No abortion or vaginal bleeding occurred in any of the patients. After 500 micrograms PGE2 gel the mean free passability (i.e. force less than or equal to 1 Newton) was 7.8 (+/- 2.0) mm, the corresponding value for the placebo group 5.2 (+/- 1.2) mm (p less than 0.0001). The prostaglandin pretreatment led to a significant increase in dilation of 5.9 +/- 2.3 mm versus 2.0 +/- 1.2 mm in the placebo group (p less than 0.0001). 17 of the 25 PGE2-treated patients complained of lower abdominal pain, gastrointestinal side effects were observed in one of these patients. In the placebo group there were no undesired concomitant symptoms. No intra- or postoperative complications occurred in the PGE2 gel-treated group. After application of the placebo gel cervical lesions and incomplete curettages were demonstrated in 4 cases. According to this preliminary experience, the intracervical application of the new ready-for-use-PGE2 gel represents a practicable and efficient method for preoperative cervical priming. In view of the intraoperative complications in the placebo group the frequency of side effects after PG application are within tolerable limits.

Abortion, Induced

Hippocampal pyramidal cell orientation in schizophrenia. A controlled neurohistologic study of the Yakovlev collection.

The finding of marked disorganization of the hippocampal pyramidal cell layer in the brains of schizophrenic patients has recently been reported. The present study was undertaken to determine whether similar abnormalities could be found in the brains of a population of schizophrenic patients, most of whom were never exposed to neuroleptics. Though statistical analysis of 2808 pyramidal cells failed to reveal significantly greater disorganization in a group of seven alleged schizophrenic brains than in brains of age-matched, nonpsychotic controls, the data suggest a relationship between the degree of pyramidal cell disarray and the severity of behavioral impairment due to psychosis. The implications and pitfalls in interpreting these findings are discussed.

Adult

[Prevention of anuria in uretero-sigmoidostomy without catheter].

The development of anuria following catheter-less uretero-sigmoidostomy performed between 1977 and 1982 has led to a modification of the intra-operative and post-operative intensive care. During the period 1983 to 1985, the systematic intra-operative administration of furosemide immediately after performing the uretero-colonic anastomosis, the use of intra- and post-operative filling with control of filling pressures by a pulmonary arterial catheter, resulting in considerable diuresis, have been able to prevent anuria following this type of surgery.

Anuria

Electrophysiologic effects of an acute beta-blockade induced by bisoprolol in patients with supraventricular tachycardia as assessed by His-bundle electrograms.

The acute electrophysiologic effects of 10 mg bisoprolol (B, given intravenously) were evaluated during an electrophysiological study in 10 patients with a history of paroxysmal tachycardia. Drug administration resulted in a significant decrease of sinus rate (Control [C]; 70.8/min; B: 59.4), and in an increase in sinus node recovery time (+20%). AV-nodal depression was marked at high heart rates during incremental atrial pacing. A second-degree AV-block occurred at a pacing cycle length (CL) of 329 ms (182/min) before and at a CL of 378 ms (158/min) after drug administration. Depression of AV-nodal conduction was negligible at low heart rates; the AH-interval at sinus rhythm was not affected (C: 84 ms, B: 86 ms); and functional and effective refractory periods of the AV-node were only slightly prolonged. Conduction intervals and refractory periods on atrial and ventricular level did not change. In 5 of 6 patients with accessory AV-pathways, circus movement tachycardia (CMT) could be elicited prior to as well as after B. Due to AV-nodal delay, CMT CL was slightly prolonged after B. Echozone and refractoriness of accessory pathways were not affected. In 1 of 2 patients with ectopic atrial tachycardia, B prevented the induction of paroxysms. In one patient with paroxysmal atrial fibrillation, the ventricular response decreased from 128/min to 94/min. The findings suggest that the electrophysiologic effects of B are due to a selective beta-adrenergic antagonism. Therapeutic efficacy is only to be expected if an increased adrenergic drive is a prerequisite for induction and continuation of a tachycardia.

Adrenergic beta-Antagonists

[Immediate renal function after kidney transplantation (author's transl)].

The postoperative course management of kidney transplant patients appears to be easier when a large efficient diuresis resumes without delay. A decreased hemodialysis rate is observed and diagnosis of rejection is easier. Immediate diuresis resumed in 180 out of 186 (97%) recipients who received a large fluid load, given under mean pulmonary arterial pressure (PAP) monitoring. The purpose of fluid load is to provide the graft with an optimal blood flow immediately after vascular clamp release. The optimal filling pressure required varies according to initial PAP value. Fluid load aims to raise PAP to reach 25 mm Hg when the initial value is below this figure whereas it merely maintains the initial value when PAP is at 25 mm Hg or above. Mean peroperative fluid load reaches 3860 ml of water with 33 g of sodium chloride, 600 ml of 20% albumin and 3 units of packed red blood cells. During the immediate postoperative course a minimal 400 ml/h urine output is aimed at. Good hemodynamic tolerance is maintained through deliberate controlled ventilation during the first six postoperative hours. Application of this protocol was associated with general improvement of kidney transplantation outcome.

Adolescent

[Morphology of cavernous transformation of the portal vein (author's transl)].

Morphology of cavernous transformation of the portal vein is discussed on the basis of 5 case reports. On histological examination it can be shown, that in these cases a combination is present of chronic recanalized portal vein thrombosis and formation of paraportal hepatopetal collaterals. Formation of collaterals starts with new growth of primitive sinusoidal vessels originating from the portal vein and protruding into the paraportal tissue. Later on these vessels exhibit increasing venous differentiation up to the point of formation of varices very late in the development. The meaning of the veins of Sappey is discussed in regard to collateral circulation and to the formation of the new vessels mentioned.

Adult

Prevention by specific perceptual remediation for vulnerable first-graders. Controlled study and follow-up of lasting effects.

In a pretest-posttest design with two matched control groups, 86 first-graders screened as vulnerable to academic failure and behavioral decompensation were each assigned to one of three groups: (1) channel-specific perceptual stimulation, (2) regular academic tutoring (contact controls), or (3) no contact. On most measures, including perceptual and achievement tests and behavior ratings by teachers, group 1 showed more improvement than either of the control groups. Several of these differences were significant (P less than .05, two-tailed). In general, the two control groups came closer to each other than to group 1. With no further intervention, follow-up one year later showed more dramatic significance. On every measure, group 1's improvement surpassed that of the control groups, and diverged from them even more than at posttest; this divergence was significant on most measures. Group 1 improved significantly (P less than .05 to P less than .01) in reading, IQ, and three behavior scales, while both control groups showed only deterioration on these measures. Group 1 gained five IQ points on the Wechsler Intelligence Scale for Children, while the controls lost five. On the Davids Scale, group 1 improved significantly (P less than .01) to "probably not hyperkinetic," while both control groups deteriorated to "probably hyperkinetic." The hypothesized mechanism of group 1's behavioral superiority at follow-up was its significant (P less than 0.1) reading improvement, with secondary emotional benefits.

Adolescent

Influence of mitochondrial creatine kinase on the mitochondrial/extramitochondrial distribution of high energy phosphates in muscle tissue: evidence for a leak in the creatine shuttle.

The influence of mitochondrial creatine kinase on subcellular high energy systems has been investigated using isolated rat heart mitochondria, mitoplasts and intact heart and skeletal muscle tissue. In isolated mitochondria, the creatine kinase is functionally coupled to oxidative phosphorylation at active respiratory chain, so that it catalyses the formation of creatine phosphate against its thermodynamic equilibrium. Therefore the mass action ratio is shifted from the equilibrium ratio to lower values. At inhibited respiration, it is close to the equilibrium value, irrespective of the mechanism of the inhibition. The same results were obtained for mitoplasts under conditions where the mitochondrial creatine kinase is still associated with the inner membrane. In intact tissue increasing amounts of creatine phosphate are found in the mitochondrial compartment when respiration and/or muscle work are increased. It is suggested that at high rates of oxidative phosphorylation creatine phosphate is accumulated in the intermembrane space due to the high activity of mitochondrial creatine kinase and the restricted permeability of reactants into the extramitochondrial space. A certain amount of this creatine phosphate 'leaks' into the mitochondrial matrix. This leak is confirmed in isolated rat heart mitochondria where creatine phosphate is taken up when it is generated by the mitochondrial creatine kinase reaction. At inhibited creatine kinase, external creatine phosphate is not taken up. Likewise, mitoplasts only take up creatine phosphate when creatine kinase is still associated with the inner membrane. Both findings indicate that uptake is dependent on the functional active creatine kinase coupled to oxidative phosphorylation. Creatine phosphate uptake into mitochondria is inhibited with carboxyatractyloside.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

Correlation of serum HCV RNA and alanine aminotransferase levels in chronic hepatitis C patients during treatment with ribavirin.

To evaluate the effect of ribavirin on serum hepatitis C virus (HCV) RNA and alanine aminotransferase (ALT) levels, 22 patients with chronic HCV infection were treated with oral ribavirin 1200 mg daily in three divided doses for 4 weeks. At the end of 4 weeks treatment, the serum ALT decreased in all but one patient and became normal in three individuals. The mean pretreatment serum ALT was reduced significantly from 193 +/- 45 i.u./L to 95 +/- 16 i.u./L after 4 weeks therapy (P = 0.009). However, 8 weeks after cessation of treatment, the serum ALT rose to a mean value of 154 +/- 21 i.u./L. The mean pretreatment serum HCV RNA was not significantly decreased at the end of 4 weeks treatment (7.0 x 10(5) vs. 4.1 x 10(5) copies/mL, P > 0.05). However, serum HCV RNA levels were decreased in 12 and increased in 10 patients at the end of 4 weeks therapy. Eight weeks after cessation of therapy, the serum HCV RNA of 22 patients rose to a mean value of 4.9 +/- 10(5) copies/mL. Six patients who continued to have elevated serum ALT and positive HCV RNA after the initial 4 weeks treatment received oral ribavirin at the same dosage for an additional 24 weeks. The serum ALT again decreased in all six patients during therapy, but rose to pretreatment values by 8 weeks after cessation of the treatment. In addition, no significant changes were noted in the mean serum HCV RNA levels during and after 24 weeks of ribavirin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral