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Biomedical subjects

O Hetmar

Publications and source records attributed to O Hetmar.

At least 19 recordsLinked to original sources

[HIV-positive drug addicts treated at the Copenhagen City Drug Dependency Clinic 1986-1992].

The Copenhagen City Drug Dependency Clinic at the former Rudolph Bergh's Hospital was established in 1986 as part of the measures taken by the municipality of Copenhagen to control the spread of HIV/AIDS among the intravenous drug addicts in the City of Copenhagen. The aim was to attract those HIV-positive drug addicts who were in no formal treatment for their drug addiction at other treatment centres and to retain them in treatment for a longer period acknowledging the fact that no causal cure exists for either the drug addiction or for AIDS. The goal of the treatment was to reduce HIV-risk behaviour i.e. sharing needles and syringes and unprotected sex with multiple partners and to reduce the adverse medical and social consequences of continued drug abuse. The treatment was supported by methadone treatment. During the five year period of 1986-92 a total of 196 HIV-positive drug addicts were referred to the clinic. A little more than half of those referred for the first through the third time and five out of six referred for the fourth time were admitted to treatment at the clinic. Half of the 126 first-time treated patients were retained in treatment for up to one year, while the rest were retained in treatment from one to five years. The mean time spent in treatment at the clinic was shorter for the relatively few patients who were admitted for the second time than for those admitted for the first time. At the end of the study 39 patients (20%) had died, most of them for non-AIDS related reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Kidney functioning during lithium treatment: a prospective study of patients treated with lithium for up to ten years.

A cohort of 53 patients with affective disorders who originally carried through renal functional tests before start of prophylactic lithium treatment were followed up prospectively after an average period of 8.5 years (range 7-10 years). Ten patients who had continued lithium treatment were re-examined. In this subgroup, the glomerular function was unaffected by the treatment, whereas the average urine volume increased during lithium treatment (NS). Polyuria and low renal concentrating abilities were also found before start of treatment and these findings underline the importance of access to renal baseline information prior to lithium treatment.

Adult↗

Lithium: long-term effects on the kidney. A prospective follow-up study ten years after kidney biopsy.

Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy.

Adult↗

Long-term effects of lithium on the kidney: functional-morphological correlations.

Correlations between quantitative kidney biopsy findings and clinical renal function in 46 unselected patients treated with lithium for an average of eight years were studied. A significant relationship between maximum renal concentrating capacity and degree of tubular atrophy was found. GFR correlated significantly with sclerotic glomeruli as well as atrophic tubules in patients on a multiple dosage schedule, whereas no relationship was seen in patients receiving lithium in a single daily dose. Thus, renal dysfunction may have a structural basis in a subgroup of lithium-treated patients on a multiple dosage schedule.

Adult↗

The impact of long-term lithium treatment on renal function and structure.

The effects of long-term lithium treatment on kidney function have been intensively studied. Both retrospective and prospective functional studies have shown that prolonged lithium treatment has a profound influence on renal tubular function, and may result in reduced renal concentrating capacity and increased urine volumes. More important, long-term lithium administration at non-toxic serum levels has little demonstrable or no effect at all on glomerular function. Prospective studies found no evidence of a progressive impairment of renal clearance. Renal biopsy studies have shown significant histopathological changes in patients with acute lithium intoxication, but only a slight degree of morphological injury in patients with no episodes of lithium poisoning. Other factors than lithium may contribute (e.g. analgesic abuse) or predispose (e.g. pyelonephritis) to similar changes. The lithium dosage schedule may represent an important factor.

Bipolar Disorder↗

Chronic treatment with lithium chloride: reduced number of GABA receptors in frontal cortex of rat brain.

Chronic consumption of lithium leads to a significant decrease in GABA receptor binding in frontal cortex of rat brain with no change in the binding characteristics in the remaining part of the cortex and in the hippocampus. In conclusion, the effect of lithium on the muscimol receptor is brain region-specific and due to a change in the number of receptors rather than in the affinity constant.

Animals↗

Lithium: long-term effects on the kidney--II. Structural changes.

Forty-six patients treated with lithium for an average of 8 yr participated in a follow-up study involving a kidney biopsy. The results were compared with renal biopsy specimens from an age-matched group of controls never treated with lithium. The average number of totally scelerotic glomeruli and atrophic tubuli was higher in lithium-treated patients. The histopathological changes showed significant correlations with lithium dosage schedule. Both the proportions of sclerotic glomeruli, atrophic tubuli and focally distributed interstitial fibrosis were higher in patients receiving their lithium two or three times a day than when lithium was given in a single daily dose.

Adult↗

Lithium: long-term effects on the kidney. III. Prospective study.

Renal function in 32 patients treated with lithium for an average period of 10 years was reexamined 2 years after the first examination. A markedly influenced tubular function leading to increased urine volume (average 3 litres/24 h) and decreased renal concentrating capacity was still found, whereas glomerular function remained unimpaired in nearly all of the patients. No statistically significant changes in renal functions were observed at the follow-up examination. The results were compared with the same renal functional tests obtained from a control group consisting of 53 patients with affective disorders never treated with lithium. The control group had a significantly lower urine output (average 2 litres/24 h), but lithium-treated patients on a one-dose schedule had an average urine volume of only 500 ml/24 h more than the controls. In conclusion, this prospective study found no evidence of a progressive impairment of glomerular or tubular function in lithium-treated patients reexamined after 2 years. Patients with affective disorders never treated with lithium had normal renal concentrating capacity.

Adult↗

Lithium: long-term effects on the kidney. IV. Renal lithium clearance.

Renal lithium clearance was investigated in 44 patients treated with lithium for an average of 8 years as part of a functional-morphological follow-up study including a kidney biopsy. The average renal lithium clearance was 0.36 ml/s (= 21.6 ml/min). A significant correlation with age, sex and glomerular filtration rate was seen, whereas no significant relationship with urine volume, lithium treatment regimen and histopathological biopsy variables was found. The results were compared with the same renal functional tests obtained from a control group consisting of 26 patients with affective disorders never treated with lithium. The control group had a lower urine output, but no significant difference in lithium clearance was observed. In conclusion, renal lithium clearance is a specific investigation, which may provide valuable baseline information on glomerulo-tubular function in patients before and during prophylactic lithium treatment.

Adult↗

Lithium: long-term effects on the kidney. I. Renal function in retrospect.

46 patients treated with lithium for an average of 8 years participated in a functional-morphological follow-up study based on a 12-day hospitalization and involving a kidney biopsy. The functional part of the study showed that tubular function was markedly influenced, leading to increased urine volume (average 3 1/24 h) and a decreased renal concentration capacity in 85% of the patients. Glomerular function was generally not influenced, and only 10% of the patients had glomerular filtration rates below their age-corrected normal ranges. Both urine volume and glomerular filtration rates showed significant correlations with dosage schedule. Urine volume was lower and glomerular filtration rate higher on a one-dose schedule than when lithium was given in divided doses during the day. It is concluded that discontinuity in lithium treatment minimizes lithium effects on kidney function.

Adult↗

Decreased number of benzodiazepine receptors in frontal cortex of rat brain following long-term lithium treatment.

Chronic administration of lithium led to a decreased number of benzodiazepine receptors (ca. 20%) in frontal cortex of rat brain, whereas no change was observed in the binding characteristics in the remaining part of the cortex and in the hippocampus and the cerebellum. Long-term lithium treatment did not change the binding of [3H]lysergic acid diethylamide and [3H]quinuclidinyl benzilate to membranes of various brain regions in the rat. We concluded that the effect of lithium on the benzodiazepine receptor is brain region specific and cannot be explained as a consequence of a reduced gamma-aminobutyric acid-ergic stimulation of benzodiazepine receptor, as the change in receptor binding was due to a change in the number of receptors rather than in the affinity constant.

Animals↗

The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia: a new gamma-aminobutyric acid agonist.

gamma-Aminobutyric acid (GABA) agonists have been proposed for the treatment of tardive dyskinesia, but their therapeutic potential has been limited by side effects and toxicity. To elucidate further the role of GABA in neuroleptic-induced dyskinesias, we evaluated tetrahydroisoxazolopyridinol (THIP), a new, less toxic GABA analog and GABA receptor agonist, in both a dose-finding (single-dose) pilot study with five patients and a longer (four-week) placebo-controlled study with 13 patients. The patients were videotaped during a standardized examination; tardive dyskinesia, parkinsonian symptoms, and eye-blinking rates were rated blindly and randomly. The maximal short-term dose of THIP was 10 to 25 mg, whereas in the longer-term study the highest daily dose ranged from 20 to 120 mg. Tardive dyskinesia was unchanged during THIP treatment, but preexisting parkinsonism increased significantly and eye-blinking rates decreased. Psychiatric symptoms showed no significant changes, although tension and depression lessened. Side effects included sedation, confusion, dizziness, vomiting, and myoclonic jerks. Although THIP is not an effective new treatment for tardive dyskinesia, more specific GABA agonists should be evaluated in future studies of this syndrome.

Adult↗

Lithium treatment regimen and renal water handling: the significance of dosage pattern and tablet type examined through comparison of results from two clinics with different treatment regimens.

For many year two Danish psychiatric hospitals having used different lithium treatment regimens. In one, slow-release tablets were given in two daily doses and, in the other conventional tablets were given in a single daily dose. In both hospitals many patients developed polyuria. Multiple regression analyses with sex, age, treatment duration, serum lithium concentration, and treatment regimen as predictor variables showed that the two treatment regimens did not affect the glomerular filtration rate or the proximal reabsorption differently, but that distal water reabsorption was significantly less affected and polyuria less pronounced in the patients given conventional tablets once daily than in those give slow-release tablets twice daily. The authors are divided among themselves as regards the implications of these findings.

Adult↗

Lithium treatment: does the kidney prefer one daily dose instead of two?

Renal structure and function were investigated in two groups of long-term lithium treated patients. Lithium was administered in two different ways either in a one-dose per day schedule where the whole dose of lithium was given between 8 and 10 p.m. or in a schedule where the lithium dose was given, divided into two or three doses, during the day. Kidney biopsy was performed, and structural changes in the kidney tissue were determined together with 24-h urine volume in the individual patients. The functional as well as the structural changes were most pronounced in patients given their lithium in divided doses during the day. Lithium may be more harmful to the kidney when the lithium administration gives a relatively constant serum lithium level than when the administration causes greater variations including peak values and low minimum levels in serum lithium. The reason for this might be that a number of regenerative processes only occur in periods with low lithium concentrations.

Adult↗