Biomedical subjects
Publications and source records attributed to K Schmidt.
The case of a 2-year-old boy with associated anomalies of the limbs and the urinary system is reported. Similar to cases reported earlier he presented a split hand and foot syndrome, but differed from previously reported cases by the presence of bilateral renal hypoplasia leading to end stage renal failure. Renal histology disclosed oligomeganephronia.
[14,15-3H]14,15-Dihydroforskolin [( 3H]DHF) has been used as a radioactive ligand to identify forskolin binding sites in rat brain membranes. The binding was saturable and reversible. The binding sites showed positive cooperative properties as evident from an upward convex Scatchard plot and a Hill coefficient of 1.6. The equilibrium dissociation constants (KD) were in the range between 10 microM and 10 nM as estimated from the limiting slopes of the curved Scatchard plot. Half-maximal saturation of the binding sites was observed at a ligand concentration of 225 nM. The binding kinetics were very rapid: Binding equilibrium was reached in less than 2 min and a large excess of cold forskolin displaced 80% of the radioligand within 2 min. The dissociation reaction was not first order, characterized by a decreasing dissociation rate constant. Bound [3H]DHF could be displaced with forskolin (IC50 0.3 microM), 14,15-dihydroforskolin (IC50 0.8 microM) and 7-desacetylforskolin (IC50 3 microM). However, nucleotides (ATP, GTP) and other receptor ligands (adenosine, isoproterenol) had no effect on the binding. Although the density of the forskolin binding sites (3.2 pmole/mg protein) is similar to those of other adenylate cyclase linked receptors, discrepancies between the KD and the ED50 obtained in adenylate cyclase studies and the finding that activation of the enzyme by forskolin is negative cooperative makes it difficult to clearly relate the binding sites to adenylate cyclase.
Data from a previously published single dose study of d-propoxyphene 65 mg given i.v. to 8 healthy subjects have been subjected to non linear regression analysis by a curve-fitting program to test the applicability of a 2- and a 3-compartment open model. Analysis of residuals (difference between observed and computed concentrations) revealed similar systematic deviations in all 8 subjects when the 2-compartment model was used (5-10 h negative residuals, after 13 h positive residuals). In contrast, curve-fit by a 3-compartment model (with two parallel peripheral compartments) was good with no systematic deviations. The data show that a terminal monoexponential decline in d-propoxyphene concentrations cannot be expected until 15-30 h after single dose administration, and that the determination of the corresponding half-life is rather inaccurate. Accordingly, precise steady state level predictions may be difficult to obtain from conventional single dose studies with d-propoxyphene.
Tyrosine methyl esters of 2'-O-succinyl cyclic AMP and 2'-O-succinyl cyclic GMP were radioiodinated, and the products were purified by anion-exchange chromatography on polyethyleneimine-cellulose thin layers. Using 1.0 M LiCl for development, two major, immunologically active fractions (presumably the mono and diiodo products) were separated from unreacted iodide, ScAMP-TME, or ScGMP-TME, and immunologically inactive radiolabeled fractions. When used in a radioimmunoassay, both major fractions from each nucleotide showed essentially identical binding affinities; however, assays were more sensitive with the presumed diiodo product because of its higher content of 125I. Compared with other purification methods, this technique is faster and permits separation of defined, radioactive iodine-containing products from unreacted starting materials.
Twenty pancreatic endocrine tumors and one duodenal somatostatinoma were stained with polyclonal antisera against eight hormones, neuron-specific (NSE), and with a monoclonal antibody against the endocrine granule protein chromogranin. Silver staining was performed on all tumors with the Grimelius method. All the tumors and all cells in the normal pancreatic islet showed NSE immunoreactivity. Chromogranin immunoreactivity was found predominantly in the glucagon cells of normal islets, in one glucagonoma, four gastrinomas and in 10 tumors associated with multiple hormonal production, but not in five insulinomas or in one somatostatinoma. Grimelius reactivity was identical to chromogranin immunoreactivity in all cases except that more cells in the tumors and in the normal islets were positive for chromogranin. Both chromogranin and NSE were detected in a metastasized pancreatic endocrine tumor which had metastasized to a peripancreatic lymph node. The metastatic tumor failed to stain with antisera to all eight hormones. These results indicate that chromogranin and NSE are excellent general markers for pancreatic endocrine tumors and that the Grimelius stain and other related argyrophilic reactions may involve binding to chromogranin.
Stimulant medications enhance performance on attentional, memory, and perceptual laboratory tasks and improve behavior in the majority of children with attention deficit disorder with hyperactivity. Most investigators, however, fail to find academic improvement. This report presents two cases in which stimulant medication in the context of multimodal treatment led to considerable gain in academic performance. One case was diagnosed as a combination of attention deficit disorder with hyperactivity and overanxious disorder of childhood. In the other case, disordered conduct was the complicating factor. The necessity of using a multimodal approach in children who suffer from multiple behavioral impairments is emphasized.
The mortality rate, risk of rebleeding, relevant subjective and objective symptoms, and daily functional capacity after a verified subarachnoid hemorrhage (SAH) of unknown etiology were evaluated in 44 patients treated during a 5-year period (1978 to 1983). A vascular basis for the SAH had been excluded by bilateral carotid and vertebral angiography and computerized tomography. The patients were interviewed at a follow-up examination from 3 to 64 months (median 36 months) after the bleed. The results revealed a 5% mortality rate and a 7% risk of rebleeding. Persisting headache and fatigue were found in 40% of patients, 29% had mild demential symptoms, and 5% had persisting and severe objective neurological symptoms. None had developed epilepsy. A normal daily functional capacity was enjoyed by 84%, while 14% had a moderate reduction in these functions, but were independent of help from other persons. One patient (2%) was not fully assessed.
The effects of X irradiation and/or hyperthermia on both the intrinsic and total poly(ADPR)synthetase activity in permeabilized human melanoma cells were determined. All treatments were given in the early phase of exponential growth (early log phase). The intrinsic and total enzyme activities were significantly decreased immediately after heat treatment at either 42 degrees or 44 degrees C for 3 hr. These activities remained below the respective control levels over the whole period of culture, and some recovery was observed after 48 hr in both cases. X-ray doses of 3.76 to 11.28 Gy produced an increase in intrinsic activity 30 min postradiation (p.r.) but had no significant effect on the total activity. The increase may thus be associated with DNA repair. At later times after irradiation with 3.76 Gy no significant changes were observed. Combined treatment of X irradiation (3.76 Gy) followed by hyperthermia (42 degrees C for 3 hr) produced an enhanced decrease in intrinsic activity, equivalent to that after hyperthermia at 44 degrees C. The effects on cell proliferation were similar in both cases. However, the total activity was not modified to the same extent after combined treatment. The long-term decrease in total activity at 42 degrees C hyperthermia may be due to inhibitors produced during heat treatment since the enzyme activity was partially restored by changes of fresh medium. These results suggest that heat, X irradiation, and combined treatment act in a different manner on the chromatin-associated enzyme or at different sites on the enzyme complex.
Gastrin/CCK immunoreactivity appears to be widely distributed throughout the mammalian CNS, being most abundant in the cerebral cortex [Vanderhaeghen et al. 1975; Straus et al. 1977; Beinfeld et al. 1981]. Besides its putative role as a co-transmitter in dopaminergic neurotransmission [Hökfelt et al. 1980], cholecystokinin is apparently involved in the central regulation of appetite and satiety [Gibbs et al. 1973; Antin et al. 1975; Parret and Batt 1980; Smith 1980; Smith and Gibbs 1981] Furthermore, it has been shown that the brain concentration of the peptide is decreased in genetically obese mice as compared to non-obese animals [Strauss and Yalow 1979]. The sand rat (Psammomys obesus) is a desert rodent which tends to become diabetic when it is fed with normocaloric diet and restricted in movement [Haines et al. 1965; Hahn et al. 1971]. However, the usefulness of this animal as a paradigm of diabetes is now being revised, since because in its typical expression this metabolic dysfunction appears to be an obesity syndrome [Rice and Robertson 1980]. Therefore, it seems to be necessary to study the distribution of gastrin/CCK-immunoreactive nerve cells in the brain of normal and diabetic (obese) sand rats to get further information about mechanism underlying the development of this form of diabetes.
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A metacercarial infestation is reported in Canadian Umbra limi and a mass infestation by trematodes in Physa sp. from the same locality. Trials made by using parasitised snails showed that both parasites are not of the same species.
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A descriptive investigation of the frequency of discharges and the frequency of complications for patients with ulcer disease on the basis of the National Patient Registry in Denmark covering the years 1978, 1979, and 1980 for the diagnoses gastric ulcer, duodenal ulcer, gastrojejunal ulcer, peptic ulcer, site unspecified, and gastritis-duodenitis is presented. The number of discharges was constant--12,000-13,000 annually, or 250 per 100,000 inhabitants--with a 4% increase for gastric ulcer and an 11% decrease for duodenal ulcer during the period. The frequency of discharges was of the same size as for comparable groups of diseases in Denmark in 1970-1977 but greater than in the United Kingdom. The number of patients discharged was 10,000 annually. The consumption of bed days fell from 126,000 to 106,000, implying a reduction in the average length of stay from 9.6 to 8.3 days. The total number of surgical operations and the number of elective operations was constant, around 2000 and 1400 annually, respectively. Of the patients discharged 20% had had a bleeding and 8% a perforation from their ulcer. During the period of examination cimetidine was introduced in the treatment, and this may have influenced the decrease in the consumption of bed days and the frequency of discharges for duodenal ulcer.
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Two siblings with classic transferase deficiency galactosemia that was detected at birth have been treated with lactose restriction since the neonatal period. Both patients developed a unique and progressive neurologic syndrome of mental retardation, tremor, and ataxia. Careful review of the family history and medical records, the absence of metabolic disturbances other than those related to galactosemia, and the aggregate physical findings and neurodiagnostic studies ruled out other neurologic disorders in these siblings. It is therefore proposed that these patients represent a subgroup of transferase-deficient galactosemic patients, who develop characteristic neurologic sequelae with conventional dietary management. The existence of this subgroup should be considered in evaluations of therapeutic responses in cohorts of patients with galactosemia. Further, galactosemia should be included in the differential diagnosis of tremor and ataxia in the setting of mental retardation.
Using [3H]14,15-dihydroforskolin as a radioactive ligand, forskolin binding sites in rat liver and rat brain membranes were identified. Scatchard analysis of binding data revealed equilibrium dissociation constants of 1.6 microM in liver and 0.79 microM in brain membranes. The ligand could be displaced by either forskolin or dihydroforskolin. The maximal number of binding sites in liver and brain was 179 and 3.2 pmol/mg protein, respectively. The question whether these forskolin binding sites are related to the adenylate cyclase stimulating action of the diterpene remains open.
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