Biomedical subjects
Publications and source records attributed to S Lindgren.
Dipotassium chlorazepate (DPC) and diazepam (DZM) were given i.m. and i.v. to 6 healthy volunteers in doses of 20 mg (48.9 mumol) DPC and 15 mg (52.0 mumol) DZM. The interval between the injections was at least 1 week. Plasma samples were analyzed for DPC and DZM by HPLC. The bioavailability of DPC and DZM after i.m. administration, determined from computer calculated AUCs, was 1.04 and 0.85, respectively.
The concentrations of GABA, glutamate, serine, glutamine, threonine, glycine and taurine in the substantia nigra and in the corpus striatum of the rat were determined electrochemically following condensation with o-phthalaldehyde-beta-mercaptoethanol and reverse-phase, high performance liquid chromatography. After a frontal hemisection at the level of the caudal hypothalamus, the GABA concentration in the substantia nigra on the operated side decreased to about 20 per cent of the normal value in 4 days, in all probability caused by degeneration of the nerve terminals of the striato-nigral GABA neurons. The concentrations of taurine in the substantia nigra and of GABA in the corpus striatum were initially lowered and later elevated following this lesion. The concentration of glutamate in the substantia nigra was lower on the sectioned side and higher on the intact side at 14 days as compared to 4 hours after a hemisection. Following an acute hemisection, the GABA transaminase inhibitor gamma-acetylenic GABA increased the concentration of GABA by 36% and 79% in the substantia nigra on the sectioned and intact side, respectively. The glutamate decarboxylase inhibitors 4-deoxypyridoxine and isoniazid lowered the concentration of GABA in the substantia nigra by about 50% on both the sectioned and intact side. The results indicate that the synthesis, but not the utilization of GABA in the substantia nigra is dependent on the normal nerve impulse flow. The concentration of glutamine was changed in directions contrary to that of GABA following a chronic hemisection or treatment with gamma-acetylenic GABA, in agreement with the suggestion that glutamine is a precursor of the GABA transmitter pool.
Rainbow trout were exposed to 0.08 X 96-hr LC50 concentration of simulated unbleached (KME-Sa) and bleached (KME-Sa + CP) kraft pulp mill effluents. A sulfate soap preparation (Sa) with and without added chlorophenols (CP) was used as the toxicant mixture. The lipid content of white muscle increased in both test groups, and its protein content decreased in the KME-Sa-treated group. The ammonia excretion rate also decreased in both test groups. These results show that there was a shift from protein to lipid metabolism. On the other hand, apart from a slight hypoglycemia, only minor changes were observed in the carbohydrate metabolism. The overall effects on blood respiratory properties were functionally insignificant. However, the effects of kraft mill effluent with and without chlorophenols were qualitatively dissimilar in several respects.
Five women undergoing acute Caesarean section were given an i.v. dose of 1600 mg tinidazole preoperatively as prophylaxis against anaerobic infection. Blood and breast milk samples were collected at 8 and 4 h intervals, respectively, for 120 h. Tinidazole concentrations were measured by means of high performance liquid chromatography (h.p.l.c). The concentration of tinidazole in breast milk was highly related to the concentration in serum (r = 0.969). Tinidazole concentrations in serum declined monoexponentially with an average half-life of 11.4 h (range 8.7-13.1). The milk/serum concentration ratio varied between 0.62 and 1.39. Seventy-two hours after the Caesarean section the milk concentration exceeded 0.5 microgram/ml in only one woman. It may be calculated that at this time the maximum daily dose to the infant would be 0.1 mg/kg body weight (assuming 3.5 kg body weight and 400 ml milk consumed). We conclude that until tinidazole has been proven harmless to the neonate breast feeding following i.v. administration of 1600 mg should not be initiated earlier than 72 h after the dose.
Plasma exchange was performed weekly during 6 months in two patients with symptomatic primary biliary cirrhosis. At the end of the treatment period improvement of liver demethylating capacity was noted, along with reduced C3 activation and a decrease in serum concentrations of IgM and procollagen III aminopeptide. Serum concentrations of aminotransferases, alkaline phosphatases, and anti-mitochondrial antibodies were not affected. These data suggest that long-term plasma exchange may improve liver function and possibly retard the progression of fibrosis in primary biliary cirrhosis.
Increased concentrations of C3dg were demonstrated in plasma from patients with primary biliary cirrhosis (PBC), indicating in vivo activation of C3. Rapid spontaneous C3 cleavage by the classical pathway was observed in vitro in serum and in EDTA plasma reconstituted with Ca++ and Mg++, suggesting the presence of complement-activating substances. On incubation with fresh normal serum, purified polyclonal IgM from patients with PBC induced C1 activation, C4 cleavage, and C3dg formation. No C3 cleavage was observed when PBC-IgM was incubated with a C2-deficient serum. We suggest that the complement activation in vivo in PBC, which occurs predominantly by the classical pathway and is characterized by increased concentrations of C1 activation complexes, decreased C4 concentrations, and hypercatabolism of C3, is attributable to an abnormal IgM population.
The therapeutic effect of absorbing plasma from tumour patients with immobilized staphylococcal protein A was tested. Plasma prepared by centrifugation was passed over protein A-Sepharose and then reinfused into the patient. Five patients were thus treated. One with malignant melanoma and one with renal adenocarcinoma showed measurable regression of metastatic lesions. In another with malignant melanoma a subcutaneous metastasis showed histopathological changes compatible with a therapeutic effect. In two patients, one with malignant melanoma and one with renal adenocarcinoma, no signs of regression were found. No severe adverse effects of the treatment were observed.
A 7-year-old boy with recurrent pneumonia of the right lower lobe is described. At bronchoscopy a small tumour almost totally obliterating the right lower lobe was detected. Surgical treatment was undertaken. Histopathologic studies showed findings consistent with those of a muco-epidermoid tumour. The case emphasizes bronchoscopy as an important investigation in children with recurrent pneumonia. It also shows the importance of performing the bronchoscopy during a prolonged course of antibiotic prophylaxis in order to ensure a minimum of infected mucus within the bronchi. This report is completed with a short review of the literature on muco-epidermoid tumours of the bronchus in children. Their favourable prognosis and very low malignant potential is underlined.
The influence of different kinds of industrial solvents on the vestibular function of rats has been studied by recording nystagmus, induced by accelerated rotation. The effect was related to the blood levels of the solvents. One group of solvents, including halogenated saturated hydrocarbons like dichloromethane, caused depression of the vestibulo-oculomotor reflex (VOR). Another group, including benzene compounds like xylene, toluene, styrene and cumene and halogenated unsaturated hydrocarbons like trichloroethylene caused an excitation of the VOR. The most striking chemical similarity between the different solvents in the last group is the occurrence of double-bonds. If the animals were exposed simultaneously to solvents from both groups the excitatory effect prevailed and was even potentiated. It is suggested that solvents cause depression or excitation of the VOR by interaction with central pathways in the reticular formation and the cerebellum.
Changes in the GABA concentration in different parts of the rat brain were studied following inhibition of the glutamic acid decarboxylase or the GABA-alpha-ketoglutaric acid aminotransferase. The GABA concentration was reduced by the decarboxylase inhibitors 4-deoxypyridoxine and isoniazid, but not by 3-mercaptopropionic acid and DL-allylglycine. The aminotransferase inhibitor gamma-acetylenic GABA increased the concentration of GABA and this effect was markedly inhibited by 3-mercaptopropionic acid and partly by 4-deoxypyridoxine and isoniazid. The 4-deoxypyridoxine-induced decrease in GABA concentration was approximately maximal after 400 mg/kg intraperitoneally and 90 min. The brain DOPA decarboxylase activity in vivo was not inhibited by 4-deoxypyridoxine. The GABA concentration in the substantia nigra was reduced by 75 per cent 4 days after section of the striato-nigral GABA neurones. In the denervated substantia nigra, 4-deoxypyridoxine did not change the concentration of GABA whereas the effect of gamma-acetylenic GABA was reduced by 70 per cent.
Direct immunofluorescence showed intense extracellular granular deposition of IgM and C3 in liver and small-intestinal biopsy specimens from patients with primary biliary cirrhosis. In contrast, IgM deposits were not observed in liver tissue from patients with other liver diseases, whereas small-intestinal IgM deposits were seen also in 2 of 17 patients with various intestinal disorders. The tissue deposition of IgM did not vary with plasma IgM levels, degree of cholestasis, or histological stage of the disease but seemed to reflect an abnormal property of the IgM molecule. The number of IgM-positive mononuclear cells in intestinal mucosa from patients with primary biliary cirrhosis was markedly increased, suggesting increased local synthesis of IgM. Deposition of IgM with complement-activating ability might contribute to the development of tissue damage in primary biliary cirrhosis. In addition, the apparent specificity of these IgM deposits in liver for primary biliary cirrhosis might be of diagnostic value when histological classification is difficult.
We studied 33 patients with primary biliary cirrhosis representative of a well-defined population (240,000) during the decade 1973-82. Mean annual incidence was 13.7 per 10(6) and point prevalence, 92 per 10(6) inhabitants in 1982. An accumulation of asymptomatic cases, constituting 45% of all patients, with a normal life expectancy accounted for this high prevalence. During the study period no disease progress was seen in asymptomatic patients, in contrast to a 50% mortality in the symptomatic group. Disease progress in the latter group was reflected by deterioration of N-demethylating capacity and increasing bilirubin levels. Although our data confirm an increasing prevalence of primary biliary cirrhosis, the mortality rate during the study period was almost identical to that in an earlier period, 1951-60.
Dichlorazepate (DPC) was given to eight healthy volunteers aged 22-38 years (five males and three females). The dose was 20 mg (48.9 mumol) given either as an IV or an IM injection. The interval between the injections was at least 1 week. Plasma samples were analysed for desmethyldiazepam (DMD) by HPLC before and after acid hydrolysis. The kinetics after both IV and IM administration could be explained by a one or two compartment open model. By comparing values before and after hydrolysis an estimate of di- and/or monopotassiumchlorazepate (MPC) could be made. The bioavailability was almost 100% after IM administration. The plasma half lives of DPC and DMD were independent of the form of administration (2.42 and 46.0 h respectively after IV and 2.29 and 45.1 h respectively after IM injection).
The synthesis rate of dopamine and noradrenaline in different parts of the rat brain was estimated by measuring the accumulation of DOPA following decarboxylase inhibition. Although the synthesis of dopamine was enhanced in all regions by haloperidol and gammabutyrolactone, it was increased to almost 400% of the control in the corpus striatum but to only somewhat more than 200% in the olfactory tubercle and some other limbic regions. The dopamine autoreceptor agonist B-HT 920 was more potent and effective in lowering the synthesis of dopamine in the limbic regions than in the corpus striatum. These differences between the extrastriatal and striatal brain areas in the pharmacological responses might be explained by a 50% higher norma synthesis rate constant of the dopamine in the limbic system than in the corpus striatum. The lower dopamine synthesis rate in the latter region may be due to a negative neuronal feedback from the corpus striatum to the substantia nigra. Functional studies support this proposal. Indeed, B-HT 920 was less effective than haloperidol in changing the direction of head turning of rats with a diencephalic hemisection at doses equieffective in reducing the motor activity. The findings indicate that B-HT 920 is relatively more potent than haloperidol in inhibiting the dopamine neurotransmission in the limbic system than in the corpus striatum.
The effects of the glutamic acid decarboxylase inhibitor 3-mercaptopropionic acid (MPA) on the concentration of GABA in the mouse brain were studied. MPA completely inhibited the postmortem increase in GABA. This effect was used in order to achieve a maximal inhibition of the GABA synthesis in vivo during 67.5 minutes before killing by giving the drug repeatedly (50 mg/kg + 6 X 10 mg/kg i.p.) to mice pretreated with chloral hydrate (100 mg/kg i.p., 65 min before killing). Such a treatment with MPA markedly reduced the accumulation of GABA following inhibition of the GABA transaminase by aminooxyacetic acid but it did not change the endogenous concentration of GABA. This discrepancy might be due to inhibition of the impulse--evoked release of GABA following MPA.
Extracerebral non-haemorrhagic collections of fluid and air causing significant impairment in the early period after intracranial surgery have received very little attention in the literature. Twenty-five fluid collections have been encountered, of which 17 appeared after intracerebral operations and were often in communication with the ventricular system. After extracerebral explorations supratentorial fluid collections accumulated in the Sylvian fissure or between the brain surface and the falx or tentorium in 5 cases, while a collection of fluid occurred infratentorially in the cerebellopontine angle in three cases. Intracranial air collections have been described more often after craniotomies, particularly after drainage of chronic subdural haematomas, but have not been recognized after intracerebral removal of tumours or in cases where exploration has been performed beyond the limits of the craniotomy in the presence of high intracranial pressure. Improvement after reoperation occurred most promptly in the cases with fluid collections, while additional factors often seem to play a more significant role in the cases with postoperative intracranial air.
Physiological effects of a high sublethal DHAA exposure on respiration, ammonia excretion and haematology of rainbow trout were studied in July at 15 degrees C and in December at 10 degrees C. In the control fish plasma glucose concentration was higher (P less than 0.001) in December than in July, but plasma protein (P less than 0.02) and Na+ (P less than 0.001) concentrations were lower. Due to DHAA exposure the oxygen consumption (P less than 0.01) and ammonia excretion rates (P less than 0.001) increased significantly in July but not in December. In December a significant decrease in plasma Cl- and increase in plasma protein concentration occurred with a slight haemoconcentration. Microscopic examination of the gills, performed on the trout in December only, revealed a 25% hypertrophy of secondary lamellar structures due to the exposure.
Vitamin D2 was administered orally as a single dose (2 mg) to 19 elderly subjects and 17 young adults. The maximum elevation of serum 25-hydroxyvitamin D was significantly greater in young than in elderly subjects. To evaluate intestinal absorption we also measured serum levels of vitamin D2 5 h after the given dose. A vitamin A absorption test was also performed simultaneously. Small differences between young and old subjects were seen with respect to serum vitamin D2 or vitamin A increments. In both groups the serum level of 25-hydroxyvitamin D was still elevated above initial level 60 days after a dose was given. No side effects, nor any change in serum calcium ion activity were noted during this period. These results speak in favour of the use of intermittent large doses of vitamin D2 as a prophylaxis against vitamin D deficiency in the elderly.