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Biomedical subjects

A Forsman

Publications and source records attributed to A Forsman.

At least 37 records · Page 2Linked to original sources

Cerebrospinal fluid catecholamine metabolites in HIV-infected patients.

Twenty-eight HIV-seropositive individuals--11 asymptomatic cases, 8 with lymphadenopathy syndrome (LAS), and 9 with AIDS--were investigated. Clinical staging of the AIDS dementia complex was done in the 9 AIDS patients. The catecholamine metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF were determined in all the HIV patients and in 20 healthy volunteers. The CSF MHPG levels did not differ significantly between healthy subjects and HIV-infected patients at any stage of the infection. The CSF concentrations of HVA differed between the groups only during the AIDS stage. The mean CSF HVA value in the AIDS patients was 42% lower than in the healthy subjects and significantly lower than in any other stage of HIV infection (P less than .01). Patients with signs of the AIDS dementia complex had reduced CSF HVA levels, but there was no clear relationship between HVA concentration and stage of the AIDS dementia complex.

AIDS Dementia Complex↗

Minimal effective dose and relapse--double-blind trial: haloperidol decanoate vs. placebo.

Fifty-six chronic schizophrenic patients were randomized into haloperidol decanoate (HD) or placebo groups for 48 weeks of double-blind treatment. The double-blind trial was preceded by a 15-week single-blind run-in period, during which all patients were treated with 60 mg of HD (approximately corresponding to 3.6 mg orally/day) every fourth week (except for the second injection, which was given after 3 weeks). Eight relapses occurred during the run-in period, and seven other patients refused further participation. The remaining 41 patients were then treated double blind, either with HD, 60 mg/4 weeks (18 patients), or with placebo (23 patients). Two patients (11%) in the HD group and 16 (69%) in the placebo group relapsed during the 48-week double-blind period. The plasma concentrations of haloperidol were measured every fourth week in both groups. Steady state was reached after 11 weeks. The mean steady-state level was 6.3 nmol/L. In the placebo group, a 50% decrease in the mean haloperidol plasma concentration was seen 8 weeks after withdrawal of haloperidol. The haloperidol plasma concentration was a predictor of relapse. There was no statistical difference between the treatment groups regarding extrapyramidal symptoms. More biperiden, however, was used in the HD group, while the placebo patients took more sedatives. The results of this study show that the relatively low and fixed dose of 60 mg of HD every fourth week was superior to placebo in preventing relapse in schizophrenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Immune activation and decreased tryptophan in patients with HIV-1 infection.

We compared tryptophan, neopterin, and interferon-gamma (IFN-gamma) concentrations in serum and cerebrospinal fluid (CSF) of 22 patients with human immunodeficiency virus type 1 (HIV-1) infection. Tryptophan levels were found to be decreased in CSF and serum of patients whereas neopterin levels in CSF and serum and serum IFN-gamma concentrations were increased compared to healthy HIV-1 seronegatives. Tryptophan concentrations correlated negatively to neopterin concentrations, and serum neopterin concentrations correlated positively to IFN-gamma concentrations. Thus, decrease of tryptophan levels is associated with chronic immune stimulation in patients with HIV-1 infection. From the data it appears that reduced tryptophan in patients may result from induction of indoleamine (2,3)-dioxygenase by IFN-gamma.

Adult↗

Indole amine deficiency in blood and cerebrospinal fluid from patients with human immunodeficiency virus infection.

Twenty-four patients with human immunodeficiency virus (HIV) infection were investigated for possible changes in certain indole amine constituents in blood and cerebrospinal fluid (CSF). Albumin in serum was determined and used as a rough nutritional marker. Six of the 24 patients had acquired immunodeficiency syndrome AIDS, four had other clinical symptoms of HIV infection, and 14 had no apparent symptoms. The HIV-seropositive patients had significantly decreased tryptophan values; their blood concentrations were 28% lower and their CSF concentrations 30% lower than corresponding values in 14 healthy controls. The blood concentrations of 5-hydroxytryptamine (5-HT) were 50% lower, and the platelet content of 5-HT was 36% lower in HIV-infected individuals than in the control group. The most pronounced changes were invariably seen in the six cases with AIDS and in patients with a low number of CD4+ cells. No significant difference between controls and HIV-seropositive patients was detected in the mean CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), although these levels were markedly reduced in four of the HIV patients. Neither was any significant difference seen between patients and controls in the serum concentrations of albumin.

Acquired Immunodeficiency Syndrome↗

Cytological and immunoglobulin findings in cerebrospinal fluid of symptomatic and asymptomatic human immunodeficiency virus (HIV) seropositive patients.

Immunostimulation in the central nervous system (CNS) measured as abnormal intrathecal immunoglobulin production or activated lymphocytes in the cerebrospinal fluid (CSF), was found in 22 of 25 HIV seropositive patients. All of 11 patients with symptomatic HIV infection and nine of 14 asymptomatic patients had an increased IgG index or a Tourtellotte's production number indicating CNS infection. The amount of intrathecal immunoglobulin was not correlated to the severity of disease since five of six AIDS patients had only slightly elevated values, while some patients without AIDS had a high intrathecal immunoglobulin production. Activated lymphocytes and plasma cells in CSF were frequently found in symptomatic HIV patients without AIDS as well as in asymptomatic HIV seropositive patients. Macrophages and activated monocytes were observed in CSF from AIDS patients. The results indicate that HIV has a high neurotropicity and is spread to CNS in all stages of the infection.

AIDS-Related Complex↗

First isolations of Borrelia burgdorferi from rodents collected in northern Europe.

Spirochetes were found in 13% of Ixodes ricinus collected from an island, near Stockholm where human borreliosis is endemic. Borrelia burgdorferi was cultivated from the kidney and/or spleen of wild rodents (Clethrionomys glareolus and Apodemus flavicollis) from the same island. Spirochetes were identified as Borrelia burgdorferi by indirect immunofluorescence assays using species and genus specific monoclonal antibodies. In these tests the spirochetes could not be differentiated from strains previously cultured from Swedish patients with Ixodes-borne borreliosis. The results show that small rodents in Europe may harbour borreliae and indicate that C. glareolus and A. flavicollis may be important reservoirs for the spirochetes causing Ixodes-borne borreliosis in humans and domestic animals in Europe.

Animals↗

The acute effects of growth hormone on amino acid transport and protein synthesis are due to its insulin-like action.

GH has acute stimulatory effects on amino acid transport and protein synthesis in a variety of tissues, but it has not been established whether these effects are expressions of the growth-promoting property of GH or of its separate insulin-like action. The 20,000-dalton structural variant of human GH (20K hGH) has been shown to have a high ratio of growth-promoting to insulin-like activity compared to native hGH (22K hGH), suggesting that it could be used as a tool to address the above question. Therefore, experiments were conducted to compare the relative abilities of native 22K hGH and 20K hGH, when added in vitro, to stimulate amino acid transport and protein synthesis in the isolated diaphragm of the female hypophysectomized rat. Paired intact hemidiaphragms were preincubated for 1 h in the absence or presence of various concentrations of 22K or 20K hGH. Then, 3-O-[14C]methylglucose was added to the medium to measure sugar transport as a test of insulin-like activity, and either alpha-[3H]aminoisobutyric acid acid or [3H] phenylalanine was also added to measure amino acid transport or protein synthesis, respectively, during a final hour of incubation. When the responses to the various concentrations of 22K and 20K were compared, 20K hGH was only about 20% as effective as 22K in stimulating 3-O-methylglucose transport, reflecting its markedly attenuated insulin-like activity on the diaphragm. Similarly, 20K hGH was only 20% as effective as 22K hGH in stimulating alpha-aminoisobutyric acid transport and phenylalanine incorporation into protein in the same muscles. Therefore, these findings support the idea that the rapid stimulatory effects of GH on amino acid transport and protein synthesis are expressions of the insulin-like action of GH and are not components of the response of target cells to its growth-promoting action.

3-O-Methylglucose↗

Biological characterization of charge isomers of human growth hormone.

Since deamidation of the human GH molecule may alter the manner and extent to which the hormone is cleaved by proteases, and since it has been repeatedly suggested that proteolytic processing is required for the expression of certain of the activities of GH, the present study was conducted to determine whether the biological activity profiles of more acidic forms of human GH are altered. Three charge isomers, GH-b, GH-c and GH-d, representing primarily deamidated forms, were isolated from a native human GH preparation (Crescormon) in amounts adequate for characterization of their biological activities. All three were essentially equipotent in a radioimmunoassay for human GH. When assessed for growth-promoting activity in the hypophysectomized rat, the isomers were again equipotent with each other and with the GH preparation from which they were derived. The charge isomers also had significant in vitro insulin-like activity on isolated rat adipose tissue and diabetogenic activity in the ob/ob mouse. Thus, the biological activity profiles of these charge isomers of human GH do not differ greatly from one another.

Adipose Tissue↗

HPLC assays of 5-HIAA and tryptophan in cerebrospinal fluid and 5-HT and tryptophan in blood: a methodological study with clinical applications.

HPLC methods were developed for the assay of 5-hydroxy-tryptamine (5-HT) and tryptophan in blood after a simple precipitation step, and 5-hydroxy-indolamine acetic acid (5-HIAA) and tryptophan in CSF by direct injection of CSF. Using these methods, CSF and blood contents were studied in drug-free volunteers and patients treated with tricyclic antidepressant (TCA) drugs. Previously reported variations in the CSF concentrations of 5-HIAA with sex and age were confirmed. No significant difference between patients and healthy subjects were seen in the concentrations of tryptophan in blood or CSF, which were significantly positively intercorrelated. There was no intercorrelation between the concentrations of tryptophan and 5-HIAA in CSF. Highly significant differences between patients and healthy subjects in the platelet-content of 5-HT could be ascribed to the TCA medication. Three TCA drugs, amitriptyline, clomipramine, and imipramine, were compared regarding influence on the platelet-content of 5-HT. Patients treated with clomipramine were found to have considerably lower 5-HT values than imipramine- and amitriptyline-treated patients. A logarithmic model indicated a positive correlation between the two serotonin markers studied, i.e., the amount of platelet-bound 5-HT and the CSF concentrations of 5-HIAA.

Adult↗

Biological characterization of purified native 20-kDa human growth hormone.

Because of the propensity of the 20-kDa variant of human growth hormone (GH) to aggregate with itself and with 22-kDa human GH, it has been difficult to prepare monomeric 20-kDa GH in highly purified form. This has been a major complicating factor in determining whether 20-kDa GH has a biological activity profile distinct from that of 22-kDa GH. In the present study, native 20-kDa GH was isolated from a human GH dimer concentrate and purified by a procedure that included column electrophoresis in agarose suspension as a final separation step. This procedure yielded highly purified monomeric 20-kDa GH, which was contaminated to an extent of less than 1% with 22-kDa GH, and which exhibited only a small degree of dimerization upon storage. The native 20-kDa GH was quite active in stimulating growth in hypophysectomized rats, when growth was assessed by body weight gain, longitudinal bone growth, the stimulation of sulfation of cartilage, and the elevation of serum IGF-1 level. However, in all of these growth assays, the 20-kDa GH was somewhat less active than the native 22-kDa GH to which it was compared; e.g., in the body weight gain and longitudinal bone growth assays, it had an estimated potency of 0.6 relative to the 22-kDa GH. The 20-kDa GH exhibited substantial diabetogenic activity when tested for the ability to raise fasting blood glucose concentration and to impair glucose tolerance in ob/ob mice. Also, the native 20-kDa GH had significant in vitro insulin-like activity, although its potency was approximately 20% that of the native 22-kDa GH to which it was compared. Thus, the biological activity profile of native 20-kDa GH differs from that of 22-kDa GH primarily in that insulin-like activity is markedly attenuated.

Animals↗

Ritanserin assessments in plasma and CSF by means of HPLC technique with fluorescence detection.

A specific HPLC-technique based on fluorescence detection was developed for assay of ritanserin, a serotonin receptor-blocking agent, in plasma and CSF. In 5 ml sample volumes, the limit of detection was 0.5 ng/ml, the recovery of ritanserin was 83 +/- 5%, and the inter-assay variability, expressed as the coefficient of variation, was 9.5% in the 2-788 ng/ml concentration range. When the values determined by this technique were compared with the results obtained by means of an independent HPLC-method with UV-detection, the coefficient of correlation was 0.995 (p less than 0.001). However, our technique proved to be more specific and less complicated.

Chromatography, High Pressure Liquid↗

HPLC assays of noradrenaline and dopamine in CSF samples from drug-free subjects.

An analytical technique based on HPLC and electrochemical detection was developed for assay of free catecholamines in CSF. The mean CSF concentrations of noradrenaline and dopamine were found to be 123 +/- 48 pg/ml and 10 +/- 6 pg/ml, respectively, in 14 drug-free subjects. The monoamine concentrations did not vary with sex or age. No correlation was seen between the noradrenaline and dopamine values. As a preliminary investigation, signs of seasonal variation in the CSF concentration of noradrenaline and dopamine were registered in 4 female subjects.

Adult↗

Alterations in cerebrospinal fluid concentrations of somatostatinlike immunoreactivity in neuropsychiatric disorders.

The concentration of somatostatinlike immunoreactivity in cerebrospinal fluid (CSF) from normal, healthy volunteers (n = 10) and patients with DSM-III diagnoses of major depression (n = 17), schizophrenia (n = 11), or dementia (n = 29) was measured by a sensitive and specific radioimmunoassay. Statistically significant decreases in CSF concentrations of somatostatinlike immunoreactivity were seen in all three patient populations when compared with controls. These findings confirm previous reports of decreased concentrations of somatostatinlike immunoreactivity in the CSF of patients with depression and dementia and extend this observation to patients with schizophrenia as well. These findings are concordant with the view that reductions in somatostatinlike immunoreactivity concentrations are associated with diseases in which cognitive function is disturbed.

Adult↗

Teenage psychoses--epidemiology, classification and reduced optimality in the pre-, peri- and neonatal periods.

This is a population-based survey from Göteborg, Sweden, of all youngsters treated as in-patients for operationally defined 'psychotic disorders' during their teens. It was shown that 0.54% of all teenagers in Göteborg had been treated for such disorders at least once during the 13- to 19-year-old age period. Boys and girls were about equally affected, but schizophreniform disorders tended to be much more common among the boys and affective disorders more common among the girls. Child psychiatric services had been consulted much less frequently than adult ones, in spite of the many developmental aspects of the psychotic disorders. Scores for reduced optimality in the pre- and perinatal periods were marginally, though significantly, more common in the psychosis groups than in an age-, sex- and maternity clinic-matched control group.

Adolescent↗

Comparison of methionyl human growth hormone and pituitary growth hormone on somatic growth of hypophysectomized rats.

In hypophysectomized male rats the biological effects of two batches of methionyl human growth hormone, Somatonorm, (met-hGH), have been compared to those of human pituitary growth hormone, Crescormon (hGH). The rats were treated with doses ranging from 10 mIU per day to 145 mIU per day for 10 days. The parameters studied were total weight gain, longitudinal bone growth, measured by the tetracycline method and indirect cartilage growth, measured by uptake of radioactive sulphate. The results obtained demonstrated that Somatonorm stimulated weight increase in a linear and dose-dependent way, similar to that seen with the native hormone. Longitudinal bone growth, measured by the tetracycline method and the growth of different cartilages, measured as uptake of radioactive sulphate, were also similar between the two hormones.

Animals↗

A high-performance liquid chromatographic method for the assay of perphenazine and its dealkylated metabolite in serum after therapeutic doses.

A new high-performance liquid chromatographic method for the assay of perphenazine and its dealkylated metabolite is presented. The procedure is based on the use of thiethylperazine maleate as internal standard. Concentrations of perphenazine and its dealkylated metabolite could be analysed simultaneously in serum from patients being treated with the drug. The intraassay variability was 6.5% and 8.5% and the interassay variability 8.9% and 11.1% for drug and metabolite, respectively.

Chromatography, Gas↗