Biomedical subjects
Publications and source records attributed to D Arnold.
Twenty-five Tunisian families were analyzed for their complement alleles in order to detect duplications at the C4 loci. In this population, the most characteristic duplications are C4A2, B1.12 or C4A1, B1,12 always associated with BFS07 and C2C. This previously undescribed C4B1,12 duplication was found in seven families, five times in association with HLA-A2, B50.
Thirty samples contributed by seven laboratories to the VIth Complement Genetics Workshop were analyzed by isoelectric focusing and immunoblotting with a specific antihuman C2 antibody for the study of the polymorphism of native, activated and desialated C2. This study allowed to compare almost all the C2 variants so far described and also several 'new variants'. According to our results, the C2 system consists of nine structural variants at the protein level which include the common C2 C, the less common C2 B (in Caucasoids), four rare acidic and three rare basic variants. The polymorphic site for the basic variants is carried by the C2a fragment. Typing of desialated C2 is necessary to identify rare acidic or basic variants, especially the C2 BH and C2 BJ variants which seem difficult to be recognized in the native protein.
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Models for the statistical determination of withdrawal times have been compared using computer-generated kinetic residue data. Estimates of withdrawal times obtained by direct evaluation of the 'known' frequency distributions of residue contents of very large samples have been compared to results obtained by regression analysis of the data on very small samples of the same populations. In this context, the hypothesis was tested that the natural logarithms of the residue contents were normally distributed and that the decrease of the natural logarithms was linear with time. Withdrawal times were then determined as the times when the upper limit of the (statistical) tolerance interval in a given percentile was below the acceptable daily intake. From the results obtained with computer-generated small data bases, it was concluded that adequate, but not necessarily precise, withdrawal times could be determined on a limited base of suitable kinetic residue data.
Spontaneous field potential oscillations were recorded from the CA3 distal apical dendritic region of guinea pig hippocampal slices maintained in 'normal' artificial cerebrospinal fluid in vitro. Power spectral analysis revealed a mixture of frequencies mainly under 20 Hz without distinct peaks. High concentrations of extracellular Mg2+ blocked the activity. These findings suggest that the intrinsic spontaneous activity of the hippocampus is produced by partially synchronized synaptic potentials. This in vitro system may provide a suitable model for studying the mechanisms underlying the generation of EEG rhythms.
Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.
The role of insulin-like growth factor-II (IGF-II) in the hypoglycemia associated with nonislet cell tumors is controversial. In this study we have addressed this question by measuring the IGF-II mRNA levels in extracts of these tumors. Hybridization of a 32P-labeled IGF-II cDNA to a Northern blot of RNA from three nonislet cell tumors associated with hypoglycemia (a hemangiopericytoma, fibrosarcoma, and malignant mesenchymal tumor) demonstrated six hybridizing bands, 6.8, 5.6, 4.7, 3.6, 2.6, and 2.1 kilobases in length. These bands were similar to those described by others in a range of tumors and normal tissues. Tissue IGF-II mRNA levels were quantitated using a solution hybridization/RNase protection assay. IGF-II mRNA levels in the tumors were similar to the level present in one line of human hepatoblastoma-derived Hep G2 cells, 5- to 6-fold higher than that in another line of Hep G2 cells, and 2- to 3-fold higher than that in term placenta. In contrast, little or no IGF-II mRNA was detected in a nonfunctioning islet cell adenoma or normal spleen. There was no evidence for amplification of the IGF-II gene in the one tumor in which it was sought. These data suggest that nonislet cell tumors associated with hypoglycemia produce large amounts of IGF-II mRNA and that this IGF-II mRNA appears to be the product of an IGF-II gene, which is apparently normal in the region encoding mature IGF-II peptide.
Two cases of posterior fossa hemorrhage in full-term newborns are presented. Because of possible sonographic misinterpretations computer tomographic (CT) scans are advocated for a reliable diagnosis. Regarding the management of the primary hemorrhage as well as the posthemorrhagic hydrocephalus a conservative approach is recommended.
The concentration of phosphate-containing metabolites in the resting gastrocnemius muscle of three patients in chronic renal insufficiency was monitored by NMR spectroscopy before and during their regular hemodialysis using a conventional acetate bath. During dialysis, the muscle ATP concentration did not change, and no significant pyrophosphate accumulation was seen. The intracellular and extracellular inorganic phosphate concentration fell as expected. It is concluded that the rapid metabolism of acetate induced by dialysis does not affect the concentration of high energy phosphate-metabolites in the resting muscle of acetate-tolerant patients.
A 2 months old girl was given a tenfold increased dosage of Beta-Methyldigoxin for 2 weeks and subsequently developed severe symptoms of glycoside intoxication. In hospital she was treated by digoxin-specific Fab antibody fragments. 18 hours later the symptoms had totally disappeared. However, 48 hours from the beginning of the treatment free digoxin levels rose again to toxic ranges. In chronic intoxications the rediffusion of glycosides from tissues and interstitial space seems to be much more pronounced than in acute intoxications, and there is a higher risk of reintoxication.
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In the present study we systematically investigated the synthesis of prostaglandins in the mucosa and the muscle layer along the length of the rabbit gut. Homogenates of mucosa and muscle layer were incubated with (14C)-labelled arachidonic acid, and prostaglandin formation was determined using thin-layer chromatography. With respect to total prostaglandin synthesis the highest values in the mucosa were measured in fundus, antrum and colon, whereas the prostaglandin synthesis in the muscle layer was maximal in the small bowel, particularly the ileum. In the mucosa, the prostaglandins E2 and F2a predominated, and there were minor differences along the gastrointestinal tract. In the muscle layer of the stomach, high amounts of 6-keto prostaglandin F1a, the stable degradation product of prostacyclin were produced, while small and large bowel homogenates synthesized mostly F2a. Consistently the prostaglandins A2/B2 were a major product in most locations. In addition, PG E2 catabolism to 15-keto PG E2 and 13,14-dihydro-15-keto PG E2 in the absence of NAD was slow. No significant changes in total prostaglandin synthesis and prostaglandin profile were detected between 24 hrs fasted and normally fed rabbits at any part of the gastrointestinal tract.
ECMO is a therapeutic alternative for newborns with respiratory insufficiency unmanageable by artificial ventilation. A modified heart-lung machine well suited for long-term application is used both to support life and to take over organ function, allowing this organ to rest and to recover. The ECMO-technique as practised in our group is equivalent to the venous-arterial bypass initiated by the Bartlett-team. Venous blood is drained from the right atrium via the right internal jugular vein. After passage through a membrane oxygenator and a heat exchanger it is returned in an arterialized state to the ascending aorta via the right carotid artery. Cannulation is followed by systemic heparinization. With a roller pump extracorporeal circulation is installed for 3-6 days with flow-rates of 80-120 ml/kg/min. The operation is performed under local anesthesia in the neonatal intensive care unit. The typical course of ECMO is stabilization for the first 24-48 hours on high bypass flow rates keeping paO2 at 50-60 mmHg with minimal ventilator settings (Pmax 20 mmHg. FiO2 0.3-0.4). Bypass flow rates can be reduced for the next 24 h and the patient is taken off and decanulated while on similar ventilator settings. Because of systemic heparinization intracranial bleeding is the main complication for a newborn child on ECMO. The incidence is about 10%. Premature infants per se have a high risk of major intracranial bleeding without ECMO. Therefore contraindications are infants under 35-weeks gestation, and a hemorrhage diagnosed by ultrasound prior to ECMO. Prediction of mortality is estimated by the alveoloarterial oxygen gradient (D [Aa] O2).(ABSTRACT TRUNCATED AT 250 WORDS)
The evolution of the organization of long-term care services in the United States has resulted in a fragmented non-system of long-term care for the elderly. The proposed solution to the crises in long-term care is to coordinate services through a pure brokerage model of service organization. The author argues that such a model cannot meet the criteria for a fully coordinated system because it does not restructure or reform the current organization of services. It is suggested that a consolidated model will restructure and reform the system.
Extracorporeal Membrane Oxygenation (ECMO) is a promising alternative for newborns with critical respiratory disease, where conservative management is no longer sufficient. - Indications for ECMO include mainly the diagnoses Persisting Pulmonary Hypertension (PPHN), Meconium-Aspiration and Congenital Diaphragmatic Hernia. In patients with a mortality-prognosis of 80-100% ECMO will raise survival rates to about 80% with a good general developmental prognosis. Conditions, trainee programs, and experiences up to the first clinical application of ECMO are reported.
Guinea pig embryonic fibroblasts were more sensitive and McCoy and Hep-2 cells were less sensitive than human foreskin fibroblasts in parallel titrations of herpes simplex virus. No difference in sensitivity was found for five lines of human fetal lung fibroblasts (including WI-38 cells), two lines of human embryo fibroblasts, one line of human foreskin fibroblasts, cells from a human fetal kidney, amnion cells from a human placenta, the Chang liver cell, the HeLa cell, and a line of mink cells. The cell doubling level of human or guinea pig fibroblast lines did not affect their sensitivity. One hundred ninety-five clinical specimens submitted for herpes simplex virus isolations were tested in parallel in primary rabbit kidney, guinea pig embryo, and human fetal lung fibroblast cultures. The percentages of positive or false-negative cultures were essentially the same for the three types of cells.
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