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Biomedical subjects

P Grof

Publications and source records attributed to P Grof.

At least 91 records · Page 5Linked to original sources
PubMed1984

Erythrocyte lithium efflux in bipolar patients and control subjects: the question of reproducibility.

The reproducibility of in vitro erythrocyte lithium efflux and lithium efflux in the presence of selected membrane transport inhibitors (phloretin, ouabain, 4,4'-diisothiocyano-2,2'-disulphonic acid stilbene, and p-chloromercury-benzene sulphonate) was investigated in bipolar patients and age- and sex-matched control subjects. Efflux experiments were repeated three times in each patient-control pair within a period of 14 days. No differences were detected between patients and control subjects in any of the parameters measured. All components of lithium efflux showed wide day-to-day variation in the same subject in both patients and control subjects. Intersubject variability, however, was significantly greater than intrasubject variation. Since intraindividual variation of phloretin-inhibited lithium efflux was found to be considerable, and no real patient-control differences could be detected, the significance of this in vitro parameter in bipolar affective illness seems somewhat questionable and should be carefully reconsidered. The relevance of these findings to the putative cell membrane dysfunction in this disease is discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1984

Lithium effects on neuroendocrine function.

We studied growth hormone and prolactin responses to insulin hypoglycemia and TSH response to TRH in symptom-free bipolar patients and healthy controls. There were no significant differences in prolactin and growth hormone responses to hypoglycemia between stabilized bipolar patients and healthy controls, both tested medication-free. When lithium was administered to both groups, only bipolar patients showed a dramatic reduction in prolactin and growth hormone responses. Both bipolar patients in remission and healthy controls showed an increase of TSH response to TRH when treated with lithium in comparison with the testings before lithium administration. The subjects, both patients and volunteers, showed a comparable degree of hypoglycemia on and off lithium. The observed difference in responsiveness of bipolar patients warrants further systematic investigation and offers interesting possibilities for practical utilization.

Adolescent↗
PubMed1984

Dexamethasone suppression test as a predictor of drug treatment response.

The possible predictive value of cortisol non-suppression by dexamethasone for therapeutic response to antidepressants was investigated both in "endogenous" and "neurotic" depression. Seventy-four female patients who fulfilled the RDC of Major Depressive Disorder (Study 1) and 44 female patients with the diagnosis of "Neurotic Depression" of ICD-9 (Study 2) were given DST and then treated with antidepressants, their clinical response being assessed after four weeks of drug treatment. Forty-three out of the 74 patients with Primary Major Depression were non-suppressor. The DST non-suppressors showed a significantly more frequent therapeutic response to maprotiline than to amitriptyline. DST suppressors, on the other hand, responded better to amitriptyline treatment than non-suppressors. In the neurotic depression group 23 patients were subclassified as Primary Minor Depression, and 52% of them showed non-suppressor response to DST. Twenty-one patients were diagnosed as Secondary Depression, with a history of chronic neurosis. One patient only (5%) was the non-suppressor. Patients with Primary Minor Depression showed good therapeutic response to antidepressants more frequently, than patients with Secondary Depression.

Amitriptyline↗
PubMed1984

Effects of lithium, nortriptyline and dexamethasone on insulin sensitivity.

The effects of lithium, dexamethasone, nortriptyline and their combinations on insulin sensitivity, expressed as a drop of plasma glucose in response to insulin challenge, were investigated in healthy volunteers. Short-term (three weeks) lithium treatment did not appear to exert any influence on the insulin sensitivity. Dexamethasone administered alone (2 mg given 57 hours prior to the test) had no effect on the insulin sensitivity of drug-free healthy subjects. However, after three weeks of lithium treatment the dexamethasone premedication resulted in slight flattening of glucose response to insulin in the same persons. Nortriptyline administered for three weeks to healthy volunteers, pretreated with dexamethasone, increased insulin sensitivity. These findings may have clinical implications regarding the treatment of depressed diabetic patients, and may provide information about the regulation of insulin sensitivity.

Adult↗
PubMed1984

Erythrocyte lithium transport in bipolar affective disorders. The effect of membrane transport inhibitors.

Erythrocyte lithium influx and efflux were investigated in vitro in patients with bipolar affective disorders and in age- and sex-matched healthy controls. To explore the components of lithium influx and efflux five selected inhibitors (ouabain, phloretin, p-chloromercury benzene sulfonate [PCMBS], 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, and lanthanium chloride) were employed. The mean values of lithium influx were similar in both populations of erythrocytes. The addition of ouabain and phloretin reduced lithium influx, but this effect was comparable in both patients and controls. PCMBS had an accelerating effect, and this was more pronounced in patients. Total erythrocyte lithium efflux from lithium-containing erythrocytes was comparable in both patients and controls. The addition of phloretin reduced RBC lithium efflux, the magnitude of this parameter, however, was similar in patients and controls. Erythrocyte lithium efflux was accelerated in the presence of PCMBS, and this effect was greater in patients. The relevance of these findings to the postulated cell membrane defect in affective disorders is evaluated.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1983

Neuroendocrine strategies in affective disorders.

Neuroendocrine strategies in affective disorders have explored both resting values of hormones and hormonal responses to stimuli such as hypoglycemia, TRH, LHRH, dexamethasone, methadone and morphine. The abnormalities established to date have involved growth hormone, cortisol and TSH responses in particular. Prolactin has not been investigated to the same extent. We therefore describe several prolactin studies exemplifying selected neuroendocrine strategies. Our studies of prolactin responses included acute cases of either primary or secondary depression, stabilized bipolar patients, and healthy controls both off and on lithium. We found prolactin response to hypoglycemia significantly reduced in primary but not secondary depressions. Lithium administration led to flattened prolactin responses to hypoglycemia in stabilized bipolar patients but not in healthy controls. The flattened response in patients was observed already after 3 weeks of lithium, and remained flattened after years of treatment. The findings suggest a greater degree of prolactin response reduction in those patients showing most pronounced stability on lithium treatment.

Adjustment Disorders↗
PubMed1983

The relationships of neuroendocrine tests in endogenous depression.

Amphetamine induced growth hormone (GH) response (Study 1) and TRH induced TSH response (Study 2) were assessed in patients with endogenous depression (n = 20 and n = 22, respectively), who underwent a dexamethasone suppression test (DST) on the following day. The GH response to the amphetamine was significantly lower in the group of depressed patients than in the healthy controls (n = 13). There was no difference between the DST nonsuppressors (n = 12) and suppressors (n = 8) in the GH peak values. This data strongly suggests that the two tests are independent from each other. There was no significant relationship between the DST and TRH-TSH results. Patients with blunted TSH response to TRH have had significantly higher cerebrospinal fluid 5-HIAA levels.

Adult↗
PubMed1983

Effect of combined haloperidol-lithium treatment on vitro RBC lithium uptake in patients with affective disorders.

Combined treatment with haloperidol and lithium is a frequently employed strategy for the treatment of acute psychoses. Although this combination regime is safe in most clinical situations, under certain circumstances it has resulted in neurotoxicity, with organic brain syndrome, and ultimately, in some patients, irreversible brain damage and death. Plasma lithium levels in these neurotoxic patients are generally within the clinically acceptable range of 0.7 - 1.5 mEq/l, but RBC-lithium levels, when reported are abnormally elevated. To account for these observations we hypothesized that in vivo haloperidol will alter the transport of lithium across the RBC membrane and thus cause an increase in RBC lithium levels. We report preliminary results from a study that tested this hypothesis by measuring RBC lithium transport in vitro, in patients treated with a) haloperidol only, b) haloperidol, followed by haloperidol and lithium, c) combined haloperidol and lithium. In eight manic depressive patients in vivo haloperidol alone, or in combination with lithium resulted in a statistically significant (p less than 0.0001) reduction of the in vitro RBC Li+ uptake values. These results are interpreted as supportive of our hypothesis, that in vivo haloperidol alters the transport of lithium across the RBC membrane, and this effect can be detected by the use of a sensitive in vitro test. Work is currently in progress to evaluate, whether the RBC Li+ transport alteration is due to a direct effect of the drug on the cell membrane or secondary to some circulating factor, and to extend these findings to a larger sample of patients.

Bipolar Disorder↗
PubMed1983

Prediction of response to stabilizing lithium treatment.

As lithium has a wide range of biological effects, it is not surprising that the benefit from lithium treatment has been observed in several types of psychiatric disorders. Mood stabilization has been seen in episodic disorders; antiaggressive effect has been reported in mental retardation and other illnesses, and some endocrine and hematological effects have been utilized in internal medicine and neurology. To date, however, only the stabilizing effect on recurrent mood disorders appears to be reliably predictable. The prediction is based primarily on the diagnosis, quality of free interval and frequency of episodes; and several associated indicators can also be helpful. Results of the presented series of studies on the response to stabilizing lithium treatment suggest that such a response is predictable for most patients. The epitome of an excellent lithium responder is a patient with a good quality of remissions, a moderate frequency of recurrences, and a diagnosis of primary affective disorder. If the MMPI profile taken at the patient's optimum is abnormal, the chances of stabilization on lithium alone are greatly reduced. In addition, the responders more frequently have a family history of primary affective disorder and a positive M antigen. It appears that in the present practice the assessment of patients for stabilizing lithium treatment may frequently not be comprehensive enough. As a result, lithium is at present probably overprescribed in North America, and possibly elsewhere as well.

Bipolar Disorder↗
PubMed1982

Genealogic study of patients with admission diagnosis of functional psychosis.

The results are reported of a genealogic study of 313 patients (171 males and 142 females) consecutively admitted to the psychiatric department of the Medical School of Charles University in Prague, Czechoslovakia. Patients suffering from psychosis were selected and divided into five groups: "schizophrenia", "bipolar psychosis", "unipolar depressive psychosis", "schizoaffective psychosis" and "unspecified disorder" (the diagnosis of psychosis suspected but not yet certain at the time of investigation). A total of 1086 first degree relatives (parents and siblings) were ascertained and one or more first degree relatives of each proband were interviewed. The total morbidity risk of psychiatric disorder for parents and siblings was 12.6% for schizophrenic probands, 17.8% for bipolar probands, 10.7% for unipolar probands, 12.0% for schizoaffective probands and 12.6% for probands with unspecified psychosis. A striking increase of the frequency of affective disorders was found among secondary cases of schizoaffective probands. Heterogeneity between schizophrenia and primary affective disorders was tested and demonstrated. The pros and cons of the study design was discussed.

Adolescent↗
PubMed1982

Prolactin response to hypoglycemia in acute depression.

1. We tested a group of acutely depressed patients with a neuroendocrine battery and confirmed the alterations of growth hormone response to hypoglycemia and TSH response to TRH reported by others. 2. In addition, in the same patient sample we found markedly reduced response of prolactin to hypoglycemia. 3. Prolactin response remained low when the patients were retested during depression, however, normalization took place on recovery. 4. An attempt is made to explain these findings by underlying neurotransmitter abnormalities.

Adolescent↗
PubMed1982

Kidney function and response to lithium treatment.

1. Kidney function during long-term lithium treatment was studied in the representative sample of patients with recurrent affective disorders. Creatinine clearance, maximum urinary osmolality and 24-hour urine volume were determined. 2. Patients were divided according to their type of response to long-term lithium treatment, expressed by the effect on the frequency of recurrencies. Various indicators of kidney function were compared in excellent responders and in non-responders. 3. Long-term lithium treatment did not lead to any detectable changes of glomerular filtration in either group. 4. In comparison with responders, non-responders showed a significantly greater increase in 24-hour urine volume and a trend towards a greater reduction of maximum urinary osmolality, and thus a greater impairment of tubular function. 5. The findings stress the need for a careful selection of patients for long-term lithium stabilization.

Bipolar Disorder↗