Biomedical subjects

M Berk

Publications and source records attributed to M Berk.

At least 37 records · Page 2Linked to original sources

PubMed2000

Augmented platelet calcium uptake in response to serotonin stimulation in patients with major depression measured using Mn2+ influx and 45Ca2+ uptake.

There is an augmented platelet intracellular calcium response to serotonin stimulation in major depression. The role that calcium influx has in this process is not known. The objective of this study was to determine platelet calcium influx in response to serotonin by two methods, Mn2+ influx and 45Ca2+ uptake, in order to observe if the uptake response to serotonin was augmented in major depression by comparing the response to normal controls. The use of the two methods of calcium influx showed that serotonin stimulates calcium uptake into platelets. Furthermore, patients with major depression have significantly augmented platelet calcium uptake in response to serotonin. The interesting finding was that calcium uptake into platelets is biphasic, occurring immediately and after five minutes. These results may support the two pool model for calcium oscillations within cells whereby extracellular calcium is needed for intracellular calcium release, and for replenishment of depleted stores once intracellular calcium is released.

Adult↗

PubMed2000

Lamotrigine compared with lithium in mania: a double-blind randomized controlled trial.

BACKGROUND: Preliminary data from case reports and small open trials suggest a role for lamotrigine in the treatment of bipolar disorder, although controlled data for the manic phase are lacking. METHOD: Thirty inpatients with a DSM-IV diagnosis of bipolar I disorder, currently manic, were randomly allocated to receive either lamotrigine (25 mg once daily for 1 week, 50 mg once daily for the second week, and 100 mg once daily for the last 2 weeks) or lithium (400 mg twice daily) in a 4-week randomized, double-blind, clinical trial. RESULTS: Both treatments improved symptoms of mania, as assessed by the Mania Rating Scale, Brief Psychiatric Rating Scale, Clinical Global Impression severity and improvement scales, and the Global Assessment of Functioning scale. There were no significant differences between groups at any time point, suggesting that the dose escalation required for lamotrigine did not adversely affect its onset of action. Secondary outcome measures, including the use of lorazepam as rescue medication, did not differ between the groups. No significant adverse events were noted in either group. CONCLUSION: In this pilot study, lamotrigine was as effective as lithium in the treatment of patients with bipolar disorder hospitalised for acute mania.

Acute Disease↗

PubMed2000

Selective serotonin reuptake inhibitors in mixed anxiety-depression.

The overlap between the depressive and anxiety disorders is extremely common. The introduction of the selective serotonin reuptake inhibitors (SSRIs) has, more than any other development, bridged the gap in terms of efficacy in both sets of disorders. A substantial body of data exists suggesting that the available SSRIs have substantial efficacy in anxiety symptoms co-occurring with depression. The clear utility of the SSRIs in disorders classified apart from depression is also established. Whilst panic disorder is the best studied, evidence on the efficacy of the SSRIs in disorders that previously did not attract much pharmacotherapeutic interest, such as social anxiety disorder and post-traumatic stress disorder is accumulating.

Anxiety Disorders↗

PubMed2000

Changes in the platelet intracellular calcium response to serotonin in patients with major depression treated with electroconvulsive therapy: state or trait marker status.

Platelet serotonin type 2A receptor (5-HT2A) sensitivity changes have previously been documented in depression, although it is unclear if this represents a stable trait marker of the illness, or whether it represents an acute state marker of depression that would change with treatment. Electroconvulsive therapy (ECT) may be a useful intervention to separate out trait and state marker status avoiding the potential confounding effects of pharmacotherapy on receptor function. Using spectrofluorometry, the platelet 5HT2A, receptor sensitivity as reflected by the intracellular calcium response to serotonin stimulation, was measured every week in patients suffering from major depression and undergoing ECT. There was a significant drop in the platelet response to serotonin stimulation over a course of ECT, with an associated progressive decrease in Hamilton Rating Scale of Depression (HAM-D) scores. This may suggest either decreased sensitivity of platelet 5HT2A receptors as a mechanism of action of ECT, or changes in second messengers such as the inositide phospholipid system. This suggests that the enhanced sensitivity of platelet 5HT2A receptors may be a state marker of major depression.

Adolescent↗

PubMed2000

Serotonergic targets in the treatment of antidepressant induced sexual dysfunction: a pilot study of granisetron and sumatriptan.

Antidepressant induced sexual dysfunction is a common adverse event that is particularly evident with serotonergic antidepressants. There is a paucity of clinical trial evidence on the treatment of this problem. While there is some evidence of involvement of the serotonin (5-HT2) receptor subtype in this phenomenon, other serotonergic receptor systems are not well studied. In this trial, 35 patients on maintenance therapy with a variety of serotonergic antidepressants, who reported antidepressant induced sexual dysfunction, were enrolled. Patients were given both granisetron 1 mg, and sumatriptan 100 mg, in a crossover design, to be used 1 h before intercourse. Sexual dysfunction was measured using the Feiger scale. There was a high dropout rate in the trial, reflecting both embarrassment with the pharmacological treatment of sexual dysfunction and difficulties with planning and timing the medication. Nevertheless, there was a significant effect of granisetron in this study, with scores decreasing from 23.7 (SD 2.52) to 16.0 (SD 6.42) on the Feiger scale (n = 14, P = 0.001, Wilcoxon sign rank test). Sumatriptan failed to show a significant change from baseline at the 0.01 level of significance. While the small sample size, high dropout rates and open label design are limitations to this study, it suggests efficacy of the granisetron in antidepressant induced sexual dysfunction and the role of the 5-HT3 receptor in this phenomenon.

Adult↗

PubMed2000

An investigation into puerperal psychoses in black women admitted to Baragwanath Hospital.

OBJECTIVES: Puerperal psychosis was studied in black African women at Baragwanath Hospital in Johannesburg. DESIGN: A retrospective study analysed the clinical notes of 314 cases of puerperal psychosis seen over previous years. A prospective study researched 67 cases of puerperal psychosis referred during a full calendar year. A control group of 98 patients was matched with the prospective study patients for age, marital status, parity and month of delivery. RESULTS: The incidence (2-3 cases per 1,000 births), onset and pattern of illness are all remarkably similar to that described in the international literature. Confirmed risk factors were a primiparous patient; a family history of psychiatric illness; and a personal psychiatric history, particularly a history of mania. Additional risk factors found in this study were substance dependence; a medical illness; the season of the year; a male child; and psychosocial stress including need for intensive medical care for the baby or death of the baby. CONCLUSION: The conclusion reached is that the puerperal psychoses are undifferentiated psychoses, usually mood disorders, showing some special symptomatology, and are precipitated in constitutionally predisposed patients by the physiological factors of the involutionary period.

Adult↗

PubMed1999

Relationship between serotonin and the temperament and character inventory.

The unified biosocial theory of personality, proposed by Cloninger, conceptualises personality as a combination of heritable, neurobiologically based traits (temperament dimensions), and traits reflecting sociocultural learning (character dimensions). The temperament dimensions are thought to be related to activity in specific central neurotransmitter systems. The relationship of the dimensions of the Temperament and Character Inventory, particularly harm avoidance (HA), and platelet 5-HT2 receptor sensitivity was investigated in a sample of undergraduate student volunteers (N = 49). Serotonin-receptor binding results in Ca2+ release from intracellular stores. The concentration of serotonin required to produce half maximal Ca2+ response (EC50) is indicative of 5-HT2 receptor sensitivity such that the lower the EC50 serotonin concentration, the greater the 5-HT2 receptor sensitivity. A significant inverse correlation was found between HA and EC50 (r = -0.644, P < 0.001). Self-directedness was also significantly correlated with EC50 (r = 0.391, P = 0.005). Novelty seeking, a personality trait similar to sensation seeking, was not significantly correlated with serotonin.

Adult↗

PubMed1999

The platelet intracellular calcium response to serotonin and thrombin in patients with panic disorder.

Serotonin is implicated in both the biology of depression and anxiety. The aim of this study was to examine the platelet intracellular calcium response to serotonin and thrombin using spectrofluorometry in 14 patients with DSM-4 panic disorder compared to 14 matched controls. Patients did not show significantly higher baseline platelet intracellular calcium levels and serotonin stimulated levels of intracellular calcium than control subjects. There was a much smaller standard deviation in the control subjects than in the panic patients. The intracellular calcium response to thrombin activation was however greater in panic patients than in control subjects (P<0.001). The failure of this study to find enhanced sensitivity of 5-HT2 receptors in panic disorder is compatible with the findings of previous challenge studies that found no consistent dysregulation of serotonin in panic disorder. The enhanced thrombin sensitivity, nevertheless suggests some receptor mediated second messenger changes independent of serotonin in the disorder.

Adolescent↗

PubMed1999

Lamotrigine and the treatment of mania in bipolar disorder.

Anticonvulsants, including valproate and carbamazepine, have established efficacy in the treatment of mania. The anticonvulsant, lamotrigine. has been reported to have antimanic and antidepressant efficacy, and mood-stabilising effects in case reports and preliminary open trials. The efficacy and tolerability of lamotrigine has been compared with olanzapine and lithium in a randomised, prospective, controlled fashion over a period of 4 weeks treatment in a total of 45 hospitalised patients with DSM-IV-defined mania. Significant improvements of a similar magnitude were observed for all treatment groups and lamotrigine was well tolerated. Mechanisms of action proposed to explain the antimanic activity of lamotrigine include inhibition of voltage-sensitive and use-dependent sodium channels, inhibition of glutamate release and calcium channel blockade. Platelet studies have indicated supersensitivity of glutamate receptors and increased intracellular calcium concentrations in patients with mania. Further clinical and mechanistic studies of lamotrigine use in mania are warranted.

Adult↗

PubMed1999

Effects of enforcement of youth access laws on smoking prevalence.

Smoking is the primary preventable cause of death, and yet 3,000 adolescents become smokers each day. Most adult smokers begin this deadly habit when they are under the age of 18, which is the minimum legal age for the purchase of cigarettes. The majority of adolescent smokers are able to purchase cigarettes even though laws prohibit the sale of cigarettes to minors. In the late 1980s, Woodridge, IL, became one of the first towns in the nation to demonstrate a significant reduction in the ability of youth to purchase cigarettes. Almost 2 years after passage of this legislation, the percentage of regular smokers among 7th- and 8th-grade students had been reduced from 16 to 5%. Seven-year follow-up data in a sample of high school youths indicate that youths living in communities with regular enforcement had significantly less smoking than those living in communities without regular enforcement. In particular, rates of regular smoking were 8.1% in communities with regular enforcement versus 15.5% in communities without regular enforcement. It is possible that adolescents who had restricted access to tobacco products were less likely to become regular smokers. These findings have important public health implications, particularly in light of recent federal legislation mandating that all states develop programs to reduce access of youth to tobacco products.

Adolescent↗

PubMed1999

Evidence-based psychiatric practice: doctrine or trap?

Medical practice has rapidly shifted towards an 'evidence-based' approach. While there are acknowledged clear benefits to this, a number of pitfalls are frequently not appreciated. Perhaps the most important limitation is the extent to which the current body of data is inadequate for many common clinical decisions. Algorithms risk being developed, frequently by third parties, without acknowledgement of these limitations and with substantial implications for clinical independence and the quality of patient care. This paper discusses potential problems of the evidence-based approach and suggests possible guidelines for the management of clinical decisions given the limitations of data-based guidelines.

Evidence-Based Medicine↗

PubMed1999

Supersensitive platelet glutamate receptors as a possible peripheral marker in schizophrenia.

Hypoglutamatergic function is implicated in the pathogenesis of schizophrenia. The aim of this study was to examine the platelet intracellular calcium response to glutamate using spectroflourometry in 15 schizophrenic patients and 15 matched control individuals as an index of platelet glutamate receptor sensitivity. Patients with schizophrenia had significantly lower baseline intracellular calcium levels than matched control individuals (P = 0.03). The percentage response of the schizophrenic individuals to glutamate stimulation was significantly greater than control individuals (P < 0.001). These data suggest that platelet glutamate receptors may be supersensitive in schizophrenia. Furthermore, the platelet may be a possible peripheral marker of glutamate function in schizophrenia.

Adult↗

PubMed1999

Auto-amputation of the tongue associated with flupenthixol induced extrapyramidal symptoms.

We report a case of tongue auto-amputation in a mentally retarded patient after a flupenthixol injection. Four days after flupenthixol administration, the patient developed orolingual dyskinetic movements involving mainly tongue biting and protrusion. Self-mutilation in this case may be secondary to flupenthixol induced acute atypical orolingual dyskinesia in the face of mental retardation.

Adult↗

PubMed1999

Olanzapine compared to lithium in mania: a double-blind randomized controlled trial.

Neuroleptics are of established efficacy in mania. Controlled data on the use of olanzapine in mania is however, absent. In this study, 30 patients meeting DSM-IV criteria for mania were randomly allocated to receive either olanzapine or lithium in a 4 week double-blind randomized controlled design. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (lithium 28.2; olanzapine 28.0; P = 0.44); Clinical Global Impression (CGI) improvement scale (lithium 2.75, olanzapine 2.36; P = 0.163) or the Mania Scale (lithium 13.2, olanzapine 10.2; P = 0.315). Olanzapine was however, significantly superior to lithium on the CGI-severity scale at week 4 (lithium 2.83, olanzapine 2.29; P = 0.025). Olanzapine did not differ from lithium in terms of treatment emergent extrapyramidal side-effects as measured by the Simpson-Angus Scale. Olanzapine appears to be at least as effective as lithium in the treatment of mania.

Adult↗

PubMed1999

A double-blind placebo-controlled trial of paroxetine in the management of social phobia (social anxiety disorder) in South Africa.

BACKGROUND: Social phobia, also known as social anxiety disorder, is a highly prevalent disorder with significant morbidity. Patients with social phobia frequently develop co-morbid psychiatric disorders such as depression and substance abuse, and the disorder impacts significantly on social and occupational functioning. It has been suggested that the selective serotonin reuptake inhibitors (SSRIs) are useful in the management of this disorder, but few controlled trials have been undertaken in this regard. There are also few data on the pharmacotherapy of social phobia in South Africa. METHODS: A double-blind randomised placebo-controlled multi-site flexible-dose trial of paroxetine was undertaken over 12 weeks among patients with a primary diagnosis of social phobia. Primary response measures were the Global Improvement item on the Clinical Global Impression scale (CGI) and mean change from baseline in the patient-rated Liebowitz Social Anxiety Scale (LSAS) total score. Ninety-three patients participated at 9 South African sites; their data are reported here. RESULTS: There was a significant drug effect on both the CGI Global Improvement score and the LSAS at 12 weeks. In addition, there was no significant difference in overall rate of adverse experiences between those on paroxetine and those on placebo. CONCLUSIONS: Paroxetine is both effective and safe in the acute treatment of social phobia. The findings here are consistent with those of previous controlled studies of the SSRIs as well as with previous work done in the USA on the use of paroxetine in the treatment of this disorder. Early diagnosis and treatment of social phobia should be encouraged. However, further research on long-term pharmacotherapy of social phobia is needed.

Adult↗

PubMed1999

A comparison of olanzapine with haloperidol in cannabis-induced psychotic disorder: a double-blind randomized controlled trial.

Little controlled data exist on the treatment of substance induced psychotic disorders. In this study, 30 patients meeting DSM-IV criteria for cannabis induced psychotic disorder were randomly allocated to receive either olanzapine or haloperidol in a 4-week double-blind clinical trial. There were no significant outcome differences between the two groups on any of the primary outcome measures, the Brief Psychiatric Rating Scale (haloperidol 25.7; olanzapine 27.1; P = 0.70); Clinical Global Impression (CGI) severity scale (haloperidol 1.8, olanzapine 2.3; P = 0.21) or the CGI improvement scale (haloperidol 1.3, olanzapine 1.7; P = 0.16). The haloperidol group however, developed significantly more extrapyramidal side-effects as measured by the Simpson Angus Scale (haloperidol 11.4, olanzapine 2.5; P = 0.014). Significantly (P = 0.027) more biperidin was used for extrapyramidal side-effects in the haloperidol (7.143 mg) than in the olanzapine (0.357 mg) group. Olanzapine appears to be as effective as haloperidol in the treatment of cannabis induced psychotic disorder, but is associated with a lower rate of extrapyramidal side-effects.

Adult↗

PubMed1998

Clozapine associated neutropenia and cytomegalovirus colitis.

Both diarrhea and colitis associated with clozapine have been reported. We present a case of clozapine-associated neutropenia complicated by cytomegalovirus colitis. The definitive diagnosis was suggested on biopsy which showed eosinophilic intranuclear inclusions suggestive of cytomegalovirus infection, and confirmed on immunohistochemistry. Neutropenia or agranulocytosis in association with clozapine treatment may be complicated by colitis. In such cases, investigations for cytomegalovirus may be indicated.

Adult↗

PubMed1998

The platelet intracellular calcium response to serotonin in subsyndromal depression.

The relationship of subsyndromal depression to syndromal depression is unclear. Increased sensitivity of platelet serotonin type 2 receptor has been reported in depression using the Fura-2 technique. The sensitivity of the platelet serotonin type 2 receptor was assessed using the Fura-2 method in 16 patients with subsyndromal depression and 14 controls. The patient group had higher numerical values of both basal and serotonin-stimulated levels of platelet intracellular calcium that did not however reach statistical significance.

Adult↗