Biomedical subjects
Publications and source records attributed to M Roth.
The pathological-anatomical and histological examinations of different organs from a calf that died at the age of 9 weeks indicated a disseminated candidiasis. Candida albicans was isolated from brain, lung, liver, spleen, kidney, intestinal lymph nodes and small intestinal contents. The antibiotics administered to the calf by the owner probably initiated the disseminated candidiasis.
This review discusses the knowledge on the transformation of bilirubin into urobilinoids before its elimination from the organism. The following aspects are presented: mechanism of bilirubin reduction by anaerobic intestinal bacteria, structure of the resulting urobilinoids, and enterohepatic circulation of the latter. Investigations on the reduction of bilirubin by intestinal bacteria in vitro are described, and the diagnostic value of urobilinoids determination is discussed.
Pseudodelphis oligocotti n. gen., n. sp. (Dracunculoidea; Guyanemidae) is described from the tidepool sculpin, Oligocottus maculosus (Scorpaeniformes; Cottidae), from various localities in coastal British Columbia. The species is placed in Guyanemidae because of its reduced buccal capsule, divided esophagus, functional vulva, and single ovary. It is distinguished from Guyanema, the only other genus in the family, by the absence of caudal alae and the arrangement of caudal papillae in the male. Females of the new genus are distinguished from those of Guyanema by the presence of a blind uterine diverticulum, without associated oviduct and ovary, extending anteriorly from the junction of the posterior uterus and vagina, and a more posteriorly positioned vulva. Fish were sampled every 2 wk throughout 1988. Worms were overdispersed in the host population. Prevalence and mean intensity of infection were highest from February to March.
Acute intestinal ischemia is a severe condition for which no early biochemical index exists at present. We have investigated the effect of experimental intestinal infarction in the rat on the serum concentration of total creatine kinase, creatine kinase BB and total lactate dehydrogenase. Suppression of blood supply from the superior mesenteric artery resulted in marked increases of total creatine kinase, of its BB isoenzyme, and of total lactate dehydrogenase. Whereas total creatine kinase and total lactate dehydrogenase cannot be regarded as specific markers of the intestine, creatine kinase BB could prove to be more specific in view of its limited tissue distribution.
Biotinylation of human C8 with the water-soluble biotin derivative biotinylamidohexanoic acid, N-hydroxysulfosuccinimide ester is an excellent method for labelling this terminal complement component with preservation of its functional activity. The biotinylated product can be detected both in native form and also following its incorporation into the terminal complement complexes. Detection assays include Western blotting, crossed immunoblotting, ELISA, and immunocytochemistry. Biotinylation is an attractive alternative method for labelling C8 and may be used for detecting and quantifying C8 and C5b-9 complexes in their soluble and membrane-bound forms.
Penetrating injuries of the anterior cranial fossa may result in permanent neurologic changes or even death if injuries are unrecognized and remain untreated. The diverse etiologies of such injuries are reviewed, as well as their diagnosis, treatment and prognosis.
The effects of recombinant human interleukin-1 beta (rhIL-1 beta) on various serum constituents were studied following subcutaneous injection (12.5 or 125 micrograms/kg) in female Wistar rats. Protein electrophoresis and the determination of the serum concentrations of carboxypeptidase N (CPN), aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, aldolase, total proteins, iron, urea, creatinine, and several amino acids were performed 12, 24, and 72 hr after injection. With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration. Iron and CPN were still low after 24 hr but returned to normal levels after 72 hr. With the higher dose of rhIL-1 beta, only alanine and phenylalanine levels were increased after 12 and 72 hr, taurine after 12 hr, and methionine after 24 hr. There were no biochemical or histological signs of hepatotoxicity. The findings indicate that rhIL-1 beta produces a reversible alteration of various biochemical plasma constituents without any apparent signs of cytotoxicity. Moreover, the decrease in CPN observed may influence the degradation of inflammatory peptides.
A monoclonal antibody-based immunoassay has been used to detect age-related changes in the rate of loss of photoproduct antigenicity from the DNA of peripheral blood lymphocytes irradiated with 10 J m-2 uv-C. Lymphocytes were obtained from 75 healthy volunteers whose ages ranged from 14 months to 82 years. The samples were divided by age decades into groups of 10 individuals, except the first decade which contained only 5 individuals. The mean loss of antigenicity +/- 1 standard deviation was determined for each group at 10, 30, and 60 min after irradiation. The data were analyzed by Mann-Whitney U test and by the Kruskal-Wallis test. After a recovery period of 10 min the loss of antigenicity was most rapid in group I (0-9 years), less rapid in group II (10-19 years), and least rapid in all other groups. The differences between groups became less at 30 min and were not significant at 60 min incubation. These data obtained from normal cells concur with our previous conclusions, that reductions in the rate of loss of antigenicity in nondiseased cells isolated from patients with melanoma and dysplastic naevus syndrome reflect genetic abnormalities in these patients.
An insertion mutation in the pol gene of Moloney murine leukemia virus (M-MuLV) was found to render the virus temperature-sensitive for replication. A provirus containing a 12-bp insertion at the boundary between the reverse transcriptase (RT) and integrase (IN) domains induced the formation of mutant virions containing a partially processed RT-IN fusion protein. Some proteolytic processing to form mature RT and IN was observed at 32 degrees, but only aberrantly processed proteins were detected at 39 degrees. The uncleaved precursor was found to exhibit DNA polymerase activity, even though it could not support replication of the virus in vivo at 39 degrees.
Tacrine (1,2,3,4-tetrahydro-9-acridinamine) has been employed in diverse clinical situations but has recently been of considerable interest for the treatment of cognitive deficits associated with senile dementia (Alzheimer's disease). The present studies examined tissue distribution of radiolabeled tacrine by quantitative whole-body autoradiography. Tacrine radioequivalents were widely distributed to tissue following iv or peroral dose, with an apparently prolonged absorption phase following po dose. The presence of high levels of activity in kidneys and ureters indicates a major role for urinary excretion, but there is also evidence for biliary excretion and direct secretion of compound or metabolites into the intestinal lumen. Tacrine was rapidly taken up into the brain and demonstrated regional localization to cortex, hippocampus, thalamus, and striatum. Although the inhibition of acetylcholinesterase by tacrine is well documented, regional uptake in brain did not correlate consistently with distribution of the enzyme, supporting suggestions by others that the alleged action of tacrine in treatment of senile dementia may be by mechanisms other than cholinesterase inhibition.
Zero-order release of oxprenolol hydrochloride was obtained by controlling the swelling and erosion of the matrix. This formulation involves only mixing of drug, hydroxypropylmethylcellulose (HPMC), and sodium carboxymethylcellulose (Na CMC) at the ratio of 1:0.4:1.6, respectively, and compressing the mixture directly into tablets. The in vitro release pattern from this optimized matrix tablet was reproducible. Accelerated stability studies revealed that the optimized formulation remains stable for an approximately 2-year shelf life. This sustained-release (SR) tablet was evaluated in dogs, and for comparison a conventional (CV) formulation was also given at the same dose level. Plasma oxprenolol levels were monitored by a sensitive and specific high-performance liquid chromatographic (HPLC) method. Significant differences in the pharmacokinetic parameters, i.e., lower Cmax, higher values of tmax, MRT, AUC, and plasma concentration at 24 hr, and nearly constant plasma levels over 12 hr, indicated that the SR matrix tablet is superior to the CV rapid-releasing formulation. The in vitro release parameters and in vivo pharmacokinetics correlated well.
General practice patients aged 75 years and over were screened for cognitive impairment using the Mini-Mental State Examination. Those scoring 23 or below and a sample of those scoring 24 or 25 were assessed using the Cambridge Mental Disorders of the Elderly Examination (CAMDEX), a structured interview schedule specifically designed to detect mild dementia. The CAMDEX includes a mental state examination, a psychiatric history, detailed cognitive testing and an information interview. The prevalence of dementia in 2311 patients was found to be 10.5%, about half that found in most earlier studies. Possible reasons for this low rate are discussed.
The effects of dose, route, regimen, and the presence or absence of a repository vehicle [benzopurpurine (BPP)] were determined for a human relaxin (hRlx) in the mouse pubic symphysis bioassay. Administration of 88 micrograms/kg hRlx sc in 1% BPP resulted in delayed, prolonged absorption. Although peak hRlx concentrations were lower, serum concentrations remained elevated longer in the presence of BPP compared to a single sc administration of hRlx in saline at the same dose. The bioavailabilities with and without BPP were similar (109 and 96%, respectively). While the pharmacodynamic effect (i.e. lengthening of the pubic ligament in estrogen-primed mice) was approximately maximum at 88 micrograms/kg hRlx sc with BPP, single sc administration of hRlx without BPP up to 264 micrograms/kg had no effect on pubic ligament length. In the absence of the BPP vehicle, manipulation of the regimen (e.g. multiple sc doses) showed that emulation of the serum concentration-time profile observed for hRlx in the presence of BPP resulted in similar pharmacodynamic effects. It appears that BPP delays the absorption of hRlx after sc administration, resulting in prolonged, elevated hRlx serum concentrations. hRlx has been shown to be effective in this model without BPP if it is administered by a multidose sc schedule. As has been observed with other protein therapeutics, the dosage regimen employed for hRlx delivery appears to be an important determinant of the expression of its pharmacodynamic effects.
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Avoidance behaviour and secondary major depression are both frequent in clinical samples of patients with panic disorder. Their status is unclear: indicators of severity of panic disorder or indicators of separate psychiatric disorders. Among the data of the Cross-National Collaborative Panic Study (n = 1,168) we found that especially avoidance behaviour defines more severe states of panic disorder (earlier age at onset, higher frequency of panic attacks and higher level of psychopathology); co-occurrence of major depression is less clearly associated with more severe panic disorder. The results are compatible with the DSM-III-R concepts of comorbidity of panic disorder and major depression and of subtyping panic disorder by avoidance behaviour.
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Phenomenological data are presented for panic attacks and non-panic anxiety in 159 patients. Anxiety episodes of sudden onset tend to have greater severity, more symptoms, and shorter duration and some distinctive cognitive features. This cluster of features emerged from the analysis as characteristic of the panic attack. There were no differences between situational and spontaneous attacks nor are attacks occurring in depressed patients different from those in-patients who suffered from anxiety disorders. The ideas characteristic of normal anxiety are directed towards ordeals in the future. It is the immediacy of the anxious cognitions of imminent death, collapse or becoming insane that are characteristic of panic attacks. A definition of panic attacks is suggested.