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Biomedical subjects

P Grof

Publications and source records attributed to P Grof.

At least 19 recordsLinked to original sources
PubMed1992

The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness.

Clinical research centers in Aarhus, Berlin, Hamilton and Vienna collected mortality data for 827 manic-depressive and schizoaffective patients given lithium treatment for more than 6 months. The average duration of the treatment was 81 months and the total time on lithium 5600 patient-years. For each patient, the mortality risk was calculated by entering the appropriate national life tables for the general population. The number of observed deaths was 44; the number of expected deaths was 49.7. The standardized mortality ratio, 0.89, did not differ significantly from 1.0. The mortality of manic-depressive patients is 2-3 times that of the general population. Our data show that the mortality of manic-depressive and schizoaffective patients given long-term lithium treatment does not differ significantly from that of the general population.

Adult↗
PubMed1992

Lithium treatment and memory assessment: methodology.

Clinical observations have suggested that lithium may exert adverse effects on memory. The difficulty in achieving empirical consensus regarding this issue has reflected several methodological problems: diversity of research designs, heterogeneous samples, lack of control groups and the possible confounding of memory test scores by variables such as depression, other acute psychopathologies, organicity, treatment duration, and age. The diversity of memory tests in terms of the complexity and modality of the stimuli as well as the types of memory assessed (immediate, short- and long-term, logical, visuo-practic) has further complicated the comparison of results across studies. Furthermore, the administration of test batteries has been limited by patients' fatigue and the severity of their illness, and by the time required to complete testing. Hence, the use of test norms may be restricted. Suggestions are made for the selection of appropriate memory tests, patients sampling and data analysis. The authors discuss the difficulties inherent in blind studies and in matched-group designs examining the effects of lithium on memory. Conclusions point to the advantages of prospective within-subject designs with repeated testing in which patients serve as their own controls.

Analysis of Variance↗
PubMed1991

A comparative Raman spectroscopic study of cholinesterases.

We report Raman spectra of various cholinesterases: lytic tetrameric forms (G4) obtained by tryptic digestion of asymmetric acetylcholinesterase (AChE) from Torpedo californica and Electrophorus electricus, a PI-PLC-treated dimeric form (G2) of AChE from T marmorata, and the soluble tetrameric form (G4) of butyrylcholinesterase (BuChE) from human plasma. The contribution of different types of secondary structure was estimated by analyzing the amide I band, using the method of Williams. The spectra of cholinesterases in 10 mM Tris-HCl (pH 7.0) indicate the presence of both alpha-helices (about 50%) and beta-sheets (about 25%), together with 15% turns and 10% undefined structures. In 20 mM phosphate buffer (pH 7.0), the spectra indicated a smaller contribution of alpha-helical structure (about 35%) and an increased beta-sheet content (from 25 to 35%). This shows that the ionic milieu profoundly affects either the conformation of the protein (AChE activity is known to be sensitive to ionic strength), or the evaluation of secondary structure, or both. In addition, we analyzed vibrations corresponding to the side chains of aromatic and aliphatic amino acids. In particular, the analyses of the tyrosine doublet (830-850 cm-1) and of the tryptophan vibration at 880 cm-1 indicated that these residues are predominantly 'exposed' on the surface of the molecules.

Acetylcholinesterase↗
PubMed1991

Less frequent lithium administration and lower urine volume.

OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.

Depressive Disorder↗
PubMed1991

The clinical meaning of refractory depression: a review for the clinician.

OBJECTIVE: The authors' goal is to address the complex issue of treatment-refractory depression from a clinical perspective. DATA COLLECTION: They review the literature on the major clinical and methodological issues involved in the treatment and study of treatment-refractory depression as well as primary and tertiary care surveys of patients whose depression has not responded to treatment. FINDINGS: There are methodological problems in defining treatment-refractory depression and in the tertiary care surveys of treatment-refractory depression. The authors define treatment-refractory depression as primarily involving diagnostic-treatment variables rather than patient variables. They articulate these variable as a series of questions the clinician may consider when confronted with patients who are considered refractory: 1) Is the diagnosis correct? 2) Has the patient received adequate treatment? 3) Was a rational stepped-care approach used? 4) How was outcome measured? 5) Is there a coexisting medical or psychiatric disorder that interferes with response to treatment? and 6) Are there factors in the clinical setting that are interfering with treatment? CONCLUSIONS: The problem of treatment-refractory depression has to do primarily with the diagnostic-treatment process than with patient variables. This has a number of implications in the areas of training, education, research, and public health. The evidence indicates that improvements in the recognition and treatment of depression are needed.

Antidepressive Agents↗
PubMed1990

Varieties of lithium benefit.

Over the years much effort has gone into clarifying lithium's mechanism of action. It has been well-documented, and reviewed in the present symposium, that the effects of lithium on the human body are widespread, however it remains unclear which of the many effects is the one which mediates clinical benefit. One of the obstacles to progress has probably been an incomplete integration of clinical and laboratory approaches to the problem. In this paper we briefly summarize the main observations in the clinical dimension. The best-documented clinical effects of lithium have been mood stabilization, antimanic effects and antiaggressive action. Several other effects have, however, been observed and reported, some still controversial but all deserving our attention. We conclude that one can observe not one but several distinct, qualitatively separable benefits, with different clinical characteristics. It appears important that in any future laboratory search for the relevant mechanisms of action of lithium, we keep this clinical multiplicity in mind.

Affect↗
PubMed1990

[Canadian geriatric psychiatry and psychopharmacology 1987-1988].

The paper offers a brief outline of the current state of geriatric psychiatry and psychopharmacology in Canada and partially in the USA. Major trends are described in clinical care, in organization and education, along with some basic historical comments. The important role of self-help groups is sketched. The contents of recent major scientific meetings illustrate the increasing emphasis in research in ageing, geriatric psychiatry and geriatric psychopharmacology. The developments are characterized by intimate connections between basic and applied research, and between clinical observations and experimental neurobiology. The analysis of developments in the current practice and research offers some insight into upcoming treatment strategies. The next decade in geriatric psychiatry will probably belong in particular to molecular biology, genetic, psycho-immunology and psychopharmacology.

Aged↗
PubMed1989

Effect of chronic lithium on sensitivity to light in male and female bipolar patients.

1. Sensitivity to white light was quantified in euthymic bipolar male and female patients maintained on long term lithium therapy and age and sex matched unmedicated controls. 2. The Dark Adaptation Threshold procedure was used to assess sensitivity of both the cone and rod photoreceptors to short pulses of light. 3. Male and female controls did not differ in sensitivity to light. 4. Male patients in comparison to both controls and female patients evidenced reduced sensitivity to light during the cone and rod portion of the dark adaptation procedure. 5. Female patients did not differ from controls on sensitivity to light. 6. Using these and other published data the results were interpreted as suggesting that lithium reduces sensitivity to light during adaptation to dark.

Adaptation, Ocular↗
PubMed1989

Genotoxicity testing: phage T7 inactivation test of various furan and arenofuran derivatives.

The genotoxic activities of 28 furan and arenofuran derivatives were tested by the phage T7-inactivation test. The genotoxic activity of the compounds was characterized quantitatively. All the compounds studied have pronounced genotoxic activities in our system. Empirical rules relating structure to genotoxic activity were found. Data obtained with our system were compared with the results of other biological systems (Salmonella assay, SOS Chromotest, CHO/HGPRT, gene amplification) in the case of some compounds included as references.

Animals↗
PubMed1988

The effect of lithium administration on LH response in healthy volunteers.

1. As part of a systematic investigation of the effects of lithium administration on neuroendocrine function we investigated the luteinizing hormone (LH) response to luteinizing hormone releasing hormone (LHRH) of healthy males. 2. In healthy volunteers after 3 weeks of therapeutic doses of lithium the LH response to LHRH was significantly increased in comparison with the responses prior to lithium administration. 3. An attempt is made to explain these findings by underlying neurotransmitter changes.

Adult↗
PubMed1988

Bipolar patients taking lithium have increased dark adaptation threshold compared with controls.

Recent epidemiological studies of mania suggest that admissions correlate with length of day and sunlight. As well, seasonal affective disorder--a depression occurring in winter, is reported to respond to light therapy and it has been proposed that supersensitivity to light is a trait-marker of manic-depressive illness. Dark adaptation threshold (D.A.T.)--a measure of night vision--was assessed in 19 euthymic manic-depressive patients stabilized on lithium, and in 19 drug-free healthy controls. The D.A.T. was significantly raised in the patients taking lithium. It is concluded that lithium induces subsensitivity to light.

Adult↗
PubMed1988

Drugs and the DST: need for a reappraisal.

It has generally been assumed that psychotropic drugs do not influence results on the dexamethasone suppression test (DST), except in some specific situations. Yet they directly affect the activity of many neurotransmitter systems, which in turn regulate hypothalamic-pituitary-adrenal (HPA) axis functioning. Several reports have shown correlations between the intake of or recent withdrawal from psychoactive substances and changes in DST results. A review of the DST literature reveals that these effects have not been controlled in most DST studies. It is therefore possible that the consequences of intake of psychotropic agents may have contributed to the debate surrounding the DST by producing unappreciated spurious DST results.

Corticotropin-Releasing Hormone↗
PubMed1987

Lithium response and the sequence of episode polarities: preliminary report on a Hamilton sample.

This is a preliminary report on a study which replicated the finding of a significant relationship between the response to long-term lithium stabilization and the sequence of episode polarities (depressive/manic) in bipolar and schizoaffective (bipolar) patients. The lithium response and the clinical course data were assessed independently, in a blind manner, utilizing a data collection which has been gathered in earlier studies. There was a significant association between lithium response (stability achieved on long-term lithium treatment) and the sequence of episode polarities. The main determinant of this association was a close link between lithium response and the MDI sequence of episode polarities. The observed association may be explained in several ways: as an artifact; due to the exclusively antimanic effect of lithium; due to true psychobiological differences between mania and depression; as a result of the differences between bipolar type one and type two patients; and finally due to bipolar heterogeneity. Considering the data available to date the explanation via bipolar heterogeneity appears to be the most likely one.

Bipolar Disorder↗
PubMed1987

Psychotropic drug withdrawal and the dexamethasone suppression test.

In a prospective study of 25 patients from the time of hospitalization, seven had recently discontinued psychotropic agents (including antidepressants, neuroleptics, and benzodiazepines). All seven had positive dexamethasone suppression test results after 1 week of hospitalization. This phenomenon did not occur in any of the other subjects who had not discontinued such medications. Some of the subjects with postdexamethasone cortisol increases reported drug discontinuation in the drug histories they gave at admission, but in three, drug screening provided the only evidence of prior drug use. Medication withdrawal may be an underappreciated confounding variable in DST studies.

Adult↗
PubMed1987

Methylene blue: a reliable and practical marker for validating compliance on the DST.

Assurance of compliance (ingestion of dexamethasone) is crucial for interpreting plasma cortisol results on the DST. In this double-blind study of 13 subjects, methylene blue (MB) 50 mg was combined with dexamethasone 1 mg in single capsules, and the resulting blue-green urinary color after ingestion was found to reliably validate compliance in 100% of patients and controls. The addition of MB did not influence DST results (i.e., plasma cortisol, plasma dexamethasone). Adding MB to dexamethasone as a marker is a reliable and safe means of validating compliance on the DST and is considerably more practical than plasma dexamethasone level determinations.

Adult↗