Atypical phenylketonuria due to tetrahydrobiopterin deficiency. Diagnosis and treatment with tetrahydrobiopterin, dihydrobiopterin and sepiapterin.
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Biomedical subjects
Publications and source records attributed to H Schmidt.
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Pyriformis muscles of Rana temporaria were completely or partially denervated by cutting the sciatic nerve or some of the small nerve branches entering the muscle. One stimulating and one to three recording microelectrodes were inserted along the fibres in order to compare the electrical activity at these points. In an early period following denervation action potentials of variable size and shape could be observed; these action potentials were often composed of two, sometimes of three or four, components. The size of individual components depended on the position of the recording microelectrode. Individual components could occasionally be triggered separately by adjusting the strength of the stimulating current pulse; propagation of these "all or none" responses was absent. In other fibres one component of the action potential could trigger another one several millimetres apart, thus indicating propagation. Conduction velocities were approximately 0.4 m/s. In partially denervated slow fibres, endplate potentials were confined to one lateral segment of the fibres, while the action potential occupied the denervated part of the membrane. The amplitudes of endplate and action potentials varied inversely with distance. Rough estimates of the length constant of the slow fibre membrane were calculated from the spatial decay of action potentials, endplate potentials and hyperpolarizing electrotonic potentials; mean values obtained were 2.5, 4.8 and 7.7 mm respectively. The results suggest that following denervation Na channels are built into discrete areas of the slow fibre membrane and that this process depends on the amount of denervation in individual fibres.
1. The contractile responses of single slow muscle fibres were investigated under isometric conditions. The fibres were isolated from normal and denervated iliofibularis muscle of Rana temporaria. Direct stimulation was achieved by external application of electrical pulses of depolarizing solutions (40 mM K and acetylcholine 10(-6) g/ml). 2. Upon electrical stimulation normal slow fibres developed contractions whose amplitude increased steadily with the strength of the pulses. These contractions did not exceed 0.22 kg/cm2, and their rates of rise and fall were approximately 1/6 of those observed in twitch fibres. During pulses of several 100 ms duration the tension continued to rise slowly until the end of the pulses. Application of 40 mM K or acetylcholine resulted in contractures which reached maximum values of 1.71 and 1.87 kg/cm2, respectively, after less than 1 min; little relaxation occurred during the following minutes. 3. The responses of slow fibres denervated for 9--76 days differed in several respects from those of normal slow fibres. a) The contractions elicited by electrical stimulation became faster but their amplitude decreased; the relationship between tension and pulse strength remained, however, essentially unchanged. b) Small and short contractions could be observed during and at the end of stimulating current pulses. Their amplitude was independent of the amplitude and duration of the stimuli; they were blocked by tetrodotoxin and must be attributed to action potentials. c) The ability to develop and maintain tension was reduced. Maximum values of K- and acetylcholine contractures were generally only 50% of those observed in normal slow fibres. Maintenance of tension was markedly reduced in some fibres, less so in others. 4. It is concluded that incorporation of Na channels into its membrane does not transform the slow fibre into a type of fibre which resembles a twitch fibre.
A partially purified calf spleen extract, which exhibits the properties of a lymphocyte chalone (tissue-specific, species non-specific, non-toxic and reversible acting, endogenous inhibitor of cell proliferation) as concerning biological activities, has been described earlier. This fraction has been further purified by ion exchange chromatography with DEAE-Sephacel to a 10,000-fold purification. The most active fraction inhibited 3H-thymidine incorporation into phytohemagglutinin- or pokeweed-mitogen-stimulated lymphocytes by 86% resp. 70%, when given in a concentration of 100 ng/ml. Ehrlich-ascites-cells were not inhibited by the same concentration. The inhibiting activity is compared to other published lymphocyte inhibitors.
Continuous peritoneal dialysis significantly prolonged mean length of survival and reduced lethality rate of taurocholate-induced pancreatitis in the rat. The effect was improved by compensating protein loss due to pancreatitis and dialysis treatment. The beneficial effect of intravenous albumin treatment was enhanced when combined with dialysis treatment. Using hypothermic dialysate or adding aprotinin intraperitoneally had no additional effect.
In acute sodium-taurocholate-induced pancreatitis in the rat, peritoneal dialysis reduced serum amylase levels and the amount of fat necrosis, but did not influence the damage to the pancreas itself. Pancreatic ascites obtained in the early course of the disease was found to have a hypotensive effect when given intraperitoneally to healthy rats. This effect vanished in the later course of acute experimental pancreatitis and was reduced by acidification of the ascites or by administration of an antihistaminic drug. Thus the beneficial effect of continuous peritoneal dialysis on survival time and mortality rate seems to be of systemic origin.
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Amount of water ingested, total laps, duration of drinking, amount per lap, laps per minute, and running velocity were investigated as a function of phenobarbital dosage (0 to 60 mg/kg). Twenty-three and a half (23 1/2) hour water deprived females rats served in the experiment. Amount of water ingested, total laps, and duration of drinking all responded similarly to phenobarbital all rose and subsequently fell as a function of phenobarbital dose on the day of drug treatment, rose as a linear function of dose a day later, and had no significant relation with dose 2 days after drug administration. These measures significantly intercorrelate with each other on the day of drug treatment and the day thereafter though not 2 days thereafter. Running velocity largely declines as a function of drug dosage on the day of treatment but is unaffected by the drug thereafter. The other measures show no definite trend. However these measures, running velocity and amount/lap and laps/minute, intercorrelate significantly with each other on the day of treatment and not thereafter. The first group of response measures and the latter group do not consistently correlate with each other. It was concluded that there are two identifiable classes of variables: one motor, which is largely a decremental function of dose, the other uncharacterized, initially rising, then falling as a function of phenobarbital dose on the day of drug treatment.
Rats were given cued and uncued inescapable shock; their voluntary alcohol intake was compared to a group given a yoked cue but no shock. Results suggested that, unlike uncued inescapable shock, cued inescapable shock caused an increase in voluntary alcohol intake, although the increase was insufficient to produce overt inebriation. It was suggested that the increase which occurred was due to a combination of adjunctive drinking and a gustatory and olfactory discrimination breakdown, both occurring in direct response to shock.
In 44 patients with stimulated goitre the trapping kinetics of 131I-iodide and 99mTc-pertechnetate are analyzed having corrected for different size of the thyroid and different physical properties of the tracers under use. Unidirectional iodide clearance (UDCL) is chosen as reliable estimator of thyroidal stimulation. UDCL shows strong correlation to iodide uptake tests and the correlation to pertechnetate uptake tests is sufficiently strong for semiquantitative evaluation of thyroidal stimulation. Under the conditions of clinical routine work the reproducibility of pertechnetate uptake tests exceeds that of iodide, thus, pertechnetate uptakes are more suitable for evaluation of regulation tests, i.e. suppression test and stimulation test with TSH. 99mTc-thyroid-uptake (TcTU) 20 min after injection is a useful parameter of thyroidal stimulation for clinical routine work as it combines excellent reproducibility with strong correlation to unidirectional iodide clearance as the relevant parameter of thyroidal stimulation.
36 patients from 19 families with erythropoietic protoporphyria were treated for about 5 years during the summer months with beta-carotene alone or beta-carotene plus canthaxanthin in daily doses of 50-200 mg. The effect of the treatment was evaluated clinically on the basis of information provided by the patients regarding the period of time they could stay in the sun. 18 patients became completely free of symptoms, 16 patients improved to some extent, and 2 patients noted a slight effect. Apart from the carotenaemia, no side-effects were recorded.
A more recently isolated strain of T.b. rhodesiense (eatro 1989) induced a chronic infection in most of 180 intraperitoneally infected NMRI-mice, surviving 6 to 9 weeks on an average. A meningoencephalitis beginning with a meningitis one week after infection and being fully developed after 4 weeks was demonstrable by investigating 22 animals killed at random between 7 and 42 days after infection. The inflammatory reactions observed correspond to those known from the late stage of human trypanosomiasis in their nature and way of spreading. Hence, this infection seems to offer a suitable model for studying a human like meningoencephalitis and for screening of compounds for activity during the late stage of human sleeping sickness.
In a double-blind randomized comparative multicenter trial, consisting of 29 patients with acne vulgaris who were unable to tolerate daily applications of retinoic acid, the retinoic acid derivative Ro 11--1430 (0.1% vanishing cream) was compared in a 6--8 weeks topical treatment with vanishing cream alone (placebo). Regarding efficacy, for most criteria measured the response was always better with Ro 11--1430 than with placebo, although the differences were not always statistically significant for several reasons, one probably being the small number of patients in the trial. Regarding tolerance, both treatments were satisfactory. Ro 11---1430 and placebo did not differ significantly regarding frequency and severity of erythema, desquamation and burning. These results suggest that treatment with Ro 11--1430 should be considered in acne patients who are unable to use retinoic acid due to severe local reactions.
Small gut of the white rat was sectioned by the cryostat in slides of 10 microns and following effectors were investigated: KCN, sodium-diethyl-dithiocarbamate (DDC), NaF, sodium acetate, sodium pyruvate, 0.1 N HCl, 0.1 N NaOH, NaN3, and copper sulfate. Phenoloxidase is completely inhibited by DDC and HCl, incompletely by pyruvate and NaN3. Peroxidase also is completely inactivated by HCl and incompletely by NaN3. DDC has no effect on peroxidase, because a precipitate is formed. Neither of both enzyme activities is inhibited by KCN. In presence of KCN and copper sulfate an unspezific colouring of the tissue resulted in the phenoloxidase proof. Non of the investigated effectors is suitable to differentiate between phenoloxidase and peroxidase in histochemical investigations.
297 materials from 446 patients with pyogenic infections were microbiologically evaluated. It was stated that Staphylococcus aureus is still the main causative organism (in spite of a downward tendency) and that its penicillin resistance is again increasing. The other gram-positive cocci occurred less frequently as pure cultures and more often as mixed cultures. The gram-negative germs increased with the increase in sensitivity to chemotherapeutical agents. 159 materials remained sterile. It must be assumed that this is in part attributable to anaerobes so far not determined. These results permit to draw the following practice-relevant conclusions: The territorial resistogram determines the use of chemotherapeutical agents; and it seems advisable not to employ penicillin in outpatient practice. Where the use of an antibiotic is indicated, treatment with oxytetracycline or gentamycin should be started.
A 3-year-old boy during a picnic collected caterpillars of Macrothylasia rubi. He developed dermatitis and was generally ill during some days. Edema developed on the affected hand and reduced the mobility. Osteitis developed corresponding to all falangeal bones on his right hand. The changes disappeared following immobilisation of the severely affected hand.
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