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Biomedical subjects

M Humble

Publications and source records attributed to M Humble.

16 recordsLinked to original sources

[Young woman dies of water intoxication after taking one tablet of ecstasy. Today's drug panorama calls for increased vigilance in health care].

Increasing numbers of reports demonstrate that low doses of ecstasy (3,4-methylenedioxymethamphetamine--MDMA) may induce life-threatening conditions, such as hyperthermia and water intoxication. These lethal states are rarely due to overdose, and young women seem to be at particular risk. This is a case report of a 20-year-old previously healthy Swedish girl. She died of water intoxication and cerebral edema approximately 24 hours after ingestion of one tablet of "ecstasy" at a rave club in Amsterdam. Clinical findings and laboratory data suggested a syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by MDMA in combination with excessive intake of water. This case illustrates the dire consequences of the present drug abuse panorama, if the increasing need for awareness of potentially lethal complications is not met within emergency health care services.

Adult↗

Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder. METHODS: In a randomized, double-blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients. RESULTS: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-HT reactivity, was related to season. Depression, autistic traits, and previous serotonin reuptake inhibitor treatment predicted nonresponse. CONCLUSIONS: A fast decrease of WB-5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinically useful.

Adult↗

Randomised controlled general practice trial of sertraline, exposure therapy and combined treatment in generalised social phobia.

BACKGROUND: No controlled trial of treatment of generalised social phobia has been conducted in general practice. AIMS: To examine the efficacy of sertraline or exposure therapy, administered alone or in combination in this setting. METHOD: Study was of a randomised, double-blind design. Patients (n = 387) received sertraline 50-150 mg or placebo for 24 weeks. Patients were additionally randomised to exposure therapy or general medical care. RESULTS: Sertraline-treated patients were significantly more improved than non-sertraline-treated patients (chi(2)=12.53, P<0.001; odds ratio=0.534; 95% Cl 0.347-0.835). No significant difference was observed between exposure- and non-exposure-treated patients (chi(2)=2.18, P=0.140; odds ratio=0.732; 95% Cl 0.475-1.134). In the pairwise comparisons, combined sertraline and exposure (chi(2)=12.32; P<0.001) and sertraline (chi(2)=10.13; P=0.002) were significantly superior to placebo. CONCLUSIONS: Sertraline is an effective treatment for generalised social phobia. Combined treatment with sertraline and exposure therapy, conducted by the general practitioner, may enhance the treatment efficacy in primary care.

Adolescent↗

Noradrenaline and serotonin reuptake inhibition as clinical principles: a review of antidepressant efficacy.

Imipramine and other subsequently developed antidepressants produce numerous neurochemical effects, some of which presumably represent active antidepressant principles. Numerous studies have compared the efficacy of selective serotonin reuptake inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NRIs) with variable selectivity, such as desipramine, lofepramine, viloxazine, maprotiline or oxaprotiline. Most studies have failed to show differences in response rates or subtype responsivity. However, in some studies NRIs appear to be superior to SSRIs as regards retardation and, conversely, SSRIs appear superior as regards anxiety symptoms. Furthermore, NRIs may be more effective than SSRIs in severe depression. The novel selective NRI reboxetine has been shown to be at least as effective as imipramine, desipramine and fluoxetine in the treatment of major depression. Moreover, reboxetine may also improve social functioning significantly more than fluoxetine providing a better quality of the remission.

Adrenergic Uptake Inhibitors↗

The treatment of social phobia in general practice. is exposure therapy feasible?

BACKGROUND: Exposure therapy is an effective treatment for generalized social phobia. Most patients with social phobia are treated in primary care, but family doctors are not usually trained to perform exposure therapy. We have conducted a study in primary care of the effect of exposure therapy alone or in combination with sertraline on generalized social phobia. OBJECTIVES: The purpose of this article is to describe the training of GPs and the application of the treatment programme in general practice. METHOD: Forty-five GPs were trained for approximately 30 h in assessing patients with social phobia and conducting exposure therapy. The training programme included scoring of videotaped interviews of five patients on several social phobia scales, and a videotape demonstrating different steps of an exposure therapy was used as a model for role play in group training. RESULTS: All of the GPs completed the training programme. The doctors expressed satisfaction with the programme and also found it useful in the treatment of patients with conditions other than social phobia. There was a significant difference in response between the treatment groups (P = 0.001), and the combination of exposure therapy and sertraline seemed to be particularly beneficial.

Adult↗

Social functioning in depression: a review.

OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Adaptation, Psychological↗

Social phobia: the clinical efficacy and tolerability of the monoamine oxidase -A and serotonin uptake inhibitor brofaromine. A double-blind placebo-controlled study.

Seventy-seven patients with a primary diagnosis of social phobia (DSM-III-R) were randomized to treatment with the reversible and selective monoamine oxidase type A inhibitor brofaromine (n = 37) or placebo (n = 40) for 12 weeks in a double-blind trial. A fixed dose of 150 mg/day or a matching placebo was given after a 2-week dose titration phase. Patients with additional diagnoses of simple phobia, generalized anxiety disorder, dysthymia or major depressive disorder currently in remission were accepted. Patients with other Axis I mental disorders were excluded. In the brofaromine group, 78% of the patients scored much or very much improved on the Clinical Global Impression scale compared with 23% in the placebo group. The anxiety and avoidance scores on the Liebowitz Social Anxiety Scale (LSAS) were significantly reduced in favor of brofaromine. The clinical effects were not significantly correlated with the plasma concentration of brofaromine. After 12 weeks the brofaromine group scored significantly lower than the placebo group on a core depression part of the Montgomery-Asberg Depression Rating Scale. After 12 weeks of treatment the brofaromine group had significantly higher total scores on the LSAS than an age- and gender-matched group of healthy controls. The brofaromine group improved further during 9-month follow-up treatment period, whereas 60% of the placebo responders who continued long-term treatment relapsed. The most common side effects in the brofaromine group were sleep disturbances, dry mouth and nausea.

Adult↗

Serotonin, panic disorder and agoraphobia: short-term and long-term efficacy of citalopram in panic disorders.

A serotonin-anxiety connection has been widely recognized. In panic disorder (PD), however, most researchers have emphasized noradrenergic mechanisms. Serotonin related findings in PD, e.g. the documented antipanic potential of selective serotonin reuptake inhibitors (SSRIs), are reviewed, lending support for a serotonergic deficit contributing to the pathophysiology of PD. Since citalopram is the most selective SSRI described, it was chosen as a tool for testing whether the serotonin reuptake inhibition per se is responsible for this antipanic effect. Twenty patients with PD with or without agoraphobia (DSM-III-R criteria) were treated openly with citalopram and assessed with CAS, MADRS, SCL-90 the Agoraphobia Scale, other self-ratings, and a panic diary. Thirteen of the 17 patients completing 8 weeks of treatment were judged as responders. The response seemed similar to or better than that seen with other antidepressants. The response covered broad aspects of morbidity, e.g. anticipatory anxiety, agoraphobia and somatization. In the first week, a transient increase of panic-related symptoms was observed. Sixteen of the patients were enrolled in a 15 months' study of long-term maintenance treatment; 11 patients completed this phase. The gains were maintained during this follow-up, and further improvement was observed. Side-effects were similar to those of other SSRIs and mostly mild. For instance, weight-gain was not associated with citalopram treatment. The results support the hypothesis that serotonin reuptake inhibition is essential for the antipanic effect of antidepressants as well as for the initial paradoxical increase of anxiety often seen with these drugs. Thus, an initial deterioration, possibly due to transient decrease of serotonin transmission, turns to improvement when serotonergic potentiation has occurred.

Adult↗

Netilmicin in the treatment of clinical peritonitis in chronic renal failure patients managed by continuous ambulatory peritoneal dialysis.

The efficacy and systemic absorption of netilmicin following intraperitoneal instillation were studied during ten episodes of clinical peritonitis in chronic renal failure patients managed by CAPD. Episodes were unselected for sensitivity of microorganism in vitro to netilmicin. Five subjects studied as inpatients had sequential dialysate and frequent plasma samples assayed for netilimicin up to 110 hours of therapy. Five patients who managed their peritonitis at home had dialysate and plasma netilmicin levels estimated at two and six days. In a dose of 10 mg/l, netilmicin was curative in the majority of patients (70%). Toxic blood levels were not found. Experience with netilmicin compared favourably with that observed in eight consecutive episodes of outpatient peritonitis managed with intraperitoneal cefamandole, the first line treatment for CAPD peritonitis in our unit (75% cure). No side effects were recorded with either agent. We conclude that netilmicin can be used effectively in the majority of microbiologically undifferentiated episodes of CAPD peritonitis, including in the home setting.

Absorption↗

Aetiology and mechanisms of anxiety disorders.

Theories on the aetiology of pathological anxiety abound. A critical review is given of the most influential approaches (e.g. psychoanalytical, "somatogenic", behavioural, psychophysiological and "biological" theories), with emphasis on panic and agoraphobic disorders. Evidence is presented from epidemiological and genetic research and from observations on the course of illness. A surprisingly constant prevalence of anxiety syndromes, and a familial distribution suggesting a pivotal importance of genetic factors, speak in favour of a biological model. The course of illness, however, points to the importance of environmental influences as triggering factors, and to cognitive and behavioural mechanisms for the perpetuation of the symptoms. Treatment responses hitherto documented support the biological and behavioural concepts, but the cognitive and psychophysiological theories are also supported to some extent. An attempt is made to combine these findings with biochemical and pharmacological findings in an integrated model of panic and agoraphobia. This model takes the form of a vicious circle, and is compatible with biological and neuropharmacological as well as evolutionary and psychological concepts.

Agoraphobia↗

Low prevalence of smoking among patients with obsessive-compulsive disorder.

Tobacco smoking is common among psychiatric patients, especially among those with schizophrenia, where the prevalence is extremely high, 74% to 88%, compared with 45% to 70% in patients with other psychiatric diagnoses. Patients with anxiety disorders are less well investigated in this respect, particularly obsessive-compulsive disorder (OCD) patients. Eighty-three psychiatric outpatients with OCD and 110 members of the Swedish OCD Association responded to questions concerning their smoking habits. Among OCD patients, 14% were current smokers (compared with 25% in the general population of Sweden), 72% had never smoked, and 11 previous smokers had stopped, mostly without any difficulties. Since a decreased smoking rate among OCD subjects was confirmed, the smoking prevalences in schizophrenia and OCD, respectively, seem to represent either end of a continuum, and OCD may also differ significantly from other anxiety disorders in this respect. Possible implications of this finding for the purported frontal lobe dysregulation in OCD are discussed.

Adolescent↗