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Biomedical subjects

H Cramer

Publications and source records attributed to H Cramer.

At least 55 records · Page 3Linked to original sources

Somatostatin-like immunoreactivity in cerebroventricular fluid of patients with basal midline tumours.

The concentration of somatostatin-like immunoreactivity (SLI) was determined by specific radioimmunoassay in the cerebroventricular fluid of patients with tumours of the basal midline and compared to findings in patients with multiple sclerosis. Mean SLI levels of the two groups were not significantly different. In patients with basal tumours (astrocytoma, craniopharyngioma, etc.) SLI levels varied widely and tended to increase with increased intracranial pressure. Lateral ventricular SLI levels decreased in patients with blockade of foramen Monro and in patients with communicating hydrocephalus or post-radiation encephalopathy. There was no apparent correlation with dysfunction of the hypothalamohypophyseal axis.

Adolescent

Effects of somatostatin on dopamine sensitive adenylate cyclase activity in the caudate-putamen of the rat.

The effect of somatostatin-14 (SRIF) on dopamine-sensitive adenylate cyclase in caudate-putamen pellets was studied in naive female rats, and in rats with chemical lesions of the nigrostriatal dopaminergic tract produced by injection of 6-hydroxydopamine, or of the caudate-putamen itself produced by injection of kainic acid 3 week earlier. In unlesioned rats somatostatin at a concentration of 10(-7) moles/l inhibited adenylate cyclase activation by submaximal concentrations of dopamine, increasing the apparent Km but not altering Emax. In 6-hydroxydopamine lesioned rats somatostatin no longer influenced adenylate cyclase activity, whereas in kainic acid lesioned rats somatostatin still increased the apparent Km for dopamine activation. The effect of somatostatin in untreated and lesioned rats is compatible with a partial competitive antagonism to dopamine. Although the data from the lesioned rats present preliminary results, the dose response characteristics and the effects in lesioned animals suggest a more complex interaction, possibly by binding of somatostatin to an inhibitory subunit of regulatory adenylate cyclase components.

Adenylyl Cyclases

Effects of haloperidol on somatostatin-like immunoreactivity in the CSF of Schizophrenic patients.

The levels of somatostatin-like immunoreactivity (SLI) were determined in the cerebrospinal fluid (CSF) of 14 schizophrenic patients before and after 3 weeks on haloperidol treatment. Baseline levels of SLI correlated negatively with psychopathological items on the Brief Psychiatric Rating Scale related to psychotic productivity. SLI levels increased after haloperidol treatment, but this increase did not correlate with psychopathological improvement. A difference in the ratio of larger and smaller molecular forms of the peptide was found before and after treatment. The drug-free samples showed a preponderance of the larger molecular forms, resulting in a ratio of 4:1, whereas the haloperidol-treated samples showed an equal distribution of both species.

Adult

Permeability of epidural somatostatin and morphine into the intrathecal space of dogs.

In an in vivo saline perfusate of the intrathecal space of 6 dogs, the concentration of somatostatin was determined by radioimmunoassay before and over 2 h after epidural administration of 3 mg somatostatin. The total recovered amount of somatostatin was negligible, about 0.02%. However, within 50 min after the bolus epidural injection of somatostatin, the concentration per ml perfusate increased from 0.1 +/- 0.02 ng/ml to 138 +/- 102 ng/ml (P less than 0.001) and declined to 4 +/- 1.7 ng/ml after 120 min. This increase of the somatostatin concentration by 3 orders of magnitude might explain why epidurally administered somatostatin is effective in treatment of acute and chronic pain. In a control investigation with epidural morphine in another 6 dogs to prove the feasibility of the method, the total recovered amount of morphine in the intrathecal perfusate over 2 h was about 12%.

Animals

Molecular size distribution of somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with degenerative brain disease.

The molecular size distribution of somatostatin-like immunoreactivity (SLI) in the cerebrospinal fluid (CSF) of patients with brain disease was investigated by separation with a Sephadex G-25 superfine column and subsequent radioimmunoassay of the eluate. Marked heterogeneity of SLI in the CSF of control subjects as well as in demented patients, was observed. Controls and schizophrenics exhibited an SLI distribution pattern consisting mainly of two pronounced peaks: the first eluting with the void volume of the column; the second being compatible with a peptide of N-terminally extended somatostatin-14. SLI from the CSF of patients with senile dementia of the Alzheimer type (SDAT), multi-infarct dementia (MID) and normal pressure hydrocephalus (NPH) showed the same two peaks found in controls and schizophrenics; and in addition, a third peak co-eluting with somatostatin-14. However, this peak was more pronounced in patients with SDAT and MID than in patients with NPH. Re-chromatography of G-25 sf void volume immunoreactivity afforded two fractions of an apparent molecular weight of about 10,000 daltons and 15,500 daltons, respectively.

Adult

Endocrine profile of a long-acting somatostatin derivative SMS 201-995. Study in normal volunteers following subcutaneous administration.

The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201-995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 micrograms. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 micrograms of SMS 201-995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P less than 0.001 and P less than 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P less than 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P less than 0.001) inhibited by previous sc injection of 50 micrograms of SMS 202-995. Pretreatment with 50 and 100 micrograms of SMS 202-995 sc (n = 9) inhibited (P less than 0.001) the stimulatory effect of TRH (200 micrograms iv) on TSH without modifying basal levels. The injection of 100 micrograms/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials. Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease.

The concentrations of somatostatin-like immunoreactivity (SLI) in lateral ventricular fluid of patients with extrapyramidal motor disease were determined by specific radio-immunoassay. Mean SLI levels were significantly lower in patients with Parkinson's disease (mean +/- SEM); 42.9 +/- 2.9 fmol/ml) and in patients with dystonic syndromes (39.4 +/- 3.2) than in patients with benign essential tremor (65.3 +/- 9.7). The lowest levels were found in patients with athetosis (34.7 +/- 5.4). In parkinsonian patients somatostatin levels correlated with the degree of akinesia, rigidity and autonomic disturbances.

Adult

Somatostatin-like immunoreactivity and substance-P-like immunoreactivity in the CSF of patients with senile dementia of Alzheimer type, multi-infarct syndrome and communicating hydrocephalus.

The concentrations of somatostatin-like immunoreactivity (SLI) and substance-P-like immunoreactivity (SPLI) in lumbar spinal fluid of patients with senile dementia of the Alzheimer type (SDAT), multi-infarct syndrome, communicating hydrocephalus and control patients were determined by specific radio-immunoassay. Mean SLI and SPLI levels were significantly lower in an aged control patient group (mean age 83.5 +/- 5.6 years) than in an adult control patient group (mean age 30.8 +/- 10 years). In the latter group SPLI levels correlated negatively with age. Mean SLI levels decreased with deterioration in SDAT patients by up to 33% in late dementia. SPLI correlated with SLI in SDAT patients but was decreased significantly only in late dementia patients. Moderate and insignificant decreases of SLI were observed in patients with multi-infarct syndrome or communicating hydrocephalus. Analysis of SLI by gel-permeation chromatography revealed molecular heterogeneity of SLI. At least four peaks of SLI were eluted, two of which had apparent molecular weights of about 10,000 and 15,500, possibly representing somatostatin precursors. The ratio of SRIF to SLI of higher molecular weight was increased in patients with dementia compared to control patients.

Aged

Haloperidol increases the cerebrospinal fluid concentrations of cyclic GMP in schizophrenic patients.

The concentration of cyclic guanosine 3',5' monophosphate (cGMP) in cerebrospinal fluid (CSF) is supposed to reflect central cholinergic activity. Earlier findings in the literature of decreased CSF concentrations of cGMP in drug-free schizophrenic patients accorded with the hypothesis of a cholinergic-dopaminergic imbalance in schizophrenia, with a relative dominance of dopaminergic activity. In the present study, treatment with haloperidol for 3 weeks significantly increased the CSF concentration of cGMP in 14 of 18 schizophrenics. This finding suggests that haloperidol and possibly other antipsychotic drugs might restore the cholinergic-dopaminergic balance in schizophrenia through central cholinergic stimulation in addition to the blockade of dopaminergic receptors.

Adult

Cerebral gigantism associated with jaw cyst basal cell naevoid syndrome in two families.

We report 9 subjects from 2 families with the syndrome of cerebral gigantism, seven of the patients also had jaw cyst basal cell naevoid syndrome. Neurological, radiological, somatic and biochemical features of this hitherto unreported association are described. Neurological symptoms included mild hydrocephalus, ventricular malformation, cerebellar syndrome, intracranial calcification, oculomotor disturbances, EEG abnormalities and rarely, mild peripheral nervous disorders. A disturbance of calcium metabolism appears to be a prominent feature of the genetically determined nonprogressive syndrome.

Adolescent

The effects of probenecid on cyclic adenosine 3',5'-monophosphate levels in cerebrospinal fluid and on brain phosphodiesterase activity in the rat.

In rats, probenecid exhibits a dose-dependent increase in the concentration of cyclic adenosine 3',5'-monophosphate (cAMP) in cisternal cerebrospinal fluid (CSF). Maximal accumulation is reached 2 h after IP administration at a dosage of 150 mg/kg body weight. Serum levels of cAMP are unchanged after 200 mg/kg probenecid. In vitro investigations show an inhibitory effect of probenecid on the uptake of cAMP into the isolated choroid plexus of the rabbit. A non-competitive inhibition of probenecid on a high affinity fraction of cyclic nucleotide phosphodiesterase from rat brain homogenates is demonstrated with an inhibitor constant of 3.4 X 10(-3M. The results appear to validate the "probenecid test" for cAMP in clinical diagnostics.

Animals

Low CSF concentrations of cyclic GMP in schizophrenia.

Increasing evidence suggests that the concentrations of cyclic guanosine 3'5'-monophosphate (cGMP) in the cerebrospinal fluid (CSF) may reflect central cholinergic activity. When the concentrations of this nucleotide in the CSF from 28 schizophrenic patients (13 without and 15 with neuroleptic treatment) and 16 psychiatrically healthy controls was determined the schizophrenics showed significantly lower CSF levels of cGMP as compared to controls. As dopamine and homovanillic acid concentrations were not altered in these CSF samples, this finding of reduced cGMP suggests a cholinergic-dopaminergic imbalance in schizophrenia, with a reduction of the former and consequently a relative dominance of the latter.

Adult

Huntington's disease - imbalance of free amino acids in the cerebrospinal fluid of patients and offspring at-risk.

A total of 27 different amino acids were determined in the fasting, morning lumbar CSF of 12 patients with Huntington's Disease (HD), 8 at-risk offspring and 16 non-choreic control patients. A significant (P less than 0.001) decrease was observed for asparagine, isoleucine, leucine, phenylalanine, histidine, arginine, alpha-aminoadipic acid and homocarnosine in patients with HD compared to the non-choreic controls. Only tyrosine was increased in HD. These alterations were to an extent more pronounced in 5 neurophysiologically conspicuous offspring. The alterations suggest that amino acid imbalance is an early metabolic disturbance in HD.

Amino Acids

Somatostatin-like immunoreactivity in the cerebrospinal fluid of neurological patients.

Using a specific radioimmunoassay we have measured somatostatin-like immunoreactivity (SLIR) of CSF in patients with brain atrophy, spinal spasticity, seizures, brain tumors and inflammatory disorders. Patients with marked brain atrophy had significantly decreased somatostatin levels in CSF. In patients with spinal spasticity significantly higher levels were observed. Seizure patients had reduced levels but the difference was not significant. In patients with inflammatory disorders and malignant brain tumors SLIR levels were significantly elevated but not in patients with benign brain tumors. A possible pathophysiologic meaning of SLIR in spasticity and seizures is discussed. The altered levels in brain atrophy, tumors and inflammatory disorders are probably indirect signs of altered somatostatin turnover or increased somatostatin leakage from damaged CNS.

Adolescent