Biomedical subjects

A Broocks

Publications and source records attributed to A Broocks.

At least 37 records · Page 2Linked to original sources

PubMed1998

The use of the Panic and Agoraphobia Scale in a clinical trial.

A new scale for assessing severity in PDA (Panic Disorder with/without Agoraphobia) has recently been developed: the Panic and Agoraphobia Scale [P & A (Bandelow, 1995)]. The objective of this study was to test whether the scale is sensitive to changes during a treatment trial. Thirty-seven patients (mean age, 32.7; S.D., 6.3) with PDA were treated with imipramine (75-150 mg/day) for 8 weeks in an open prospective trial. Patients with concurrent agoraphobia were instructed in practising self-exposure to agoraphobic situations. The total scores on the P & A, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy criteria. Treatment results were excellent, as could be shown by a decrease in the average severity scores of the P & A observer-rated version from 28.9 (S.D., 8.1) to 13.3 (S.D., 11.8; rank statistic T(N) = 6.7; P < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the P & A, although closely followed by the CGI and the HAMA. Among the self-rated scales, the P & A (self-rated version) also showed the largest effect size. All five subscores of the P & A showed significant improvements. The highest treatment effect sizes could be seen in the 'panic attacks' subscore, followed by the 'anticipatory anxiety' subscore. The new Panic and Agoraphobia Scale (P & A) is a useful tool for measuring treatment efficacy in panic disorder trials.

Adult↗

PubMed1998

Rebound insomnia after hypnotic withdrawal in insomniac outpatients.

The effect of abrupt medication withdrawal (no-pill discontinuation) was investigated in 1507 insomniacs using the patients' self-ratings on visual analogue scales. Drug discontinuation followed a 28-day treatment period with either 7.5 mg zopiclone, 0.25 mg triazolam, 1.0 mg flunitrazepam, or placebo in a randomized, double-blind, parallel group, multicenter study in private practice. Deterioration below individual pretreatment values (no-pill baseline) in at least one of three subjective parameters of sleep quality (sleep latency, total sleep time, nocturnal awakenings) and three parameters of daytime well-being (morning freshness, daytime tiredness, anxiety) were defined as rebound. The number of patients with rebound (rebound rate) was analyzed for every day of a 2-week posttreatment period. The overall rebound rate was higher in the placebo group (p < or = 0.001) than in each group treated with active drugs. Rebound rates affecting sleep quality were higher for placebo than for zopiclone (p < or = 0.001) and for flunitrazepam (p < or = 0.05). Rebound rates were smaller for zopiclone (p < or = 0.001) and flunitrazepam (p < or = 0.01) than for triazolam. Rebound in at least one item per day appeared in 21.5% (sleep quality) and 25.5% (daytime well-being) of the patients. Rebound decreased with increasing numbers of items of sleep quality or daytime well-being. Patients who did not respond to treatment showed higher rebound rates than those who were treatment responders (p < or = 0.001). Concerning treatment nonresponders, highest rebound was seen in the placebo group, whereas rebound was lowest in placebo responders. These results show that pill discontinuation itself may worsen sleep and daytime well-being in the sense of a rebound phenomenon. Furthermore, the number of patients with rebound remained at a high and varying level during the whole posttreatment period. This result indicates that a deterioration of sleep after drug withdrawal is not apparent during a few days but may last for longer periods in some patients and is modified by marked night-to-night variations.

Adolescent↗

PubMed1998

Endurance training in panic patients: spiroergometric and clinical effects.

Endurance capacity was determined by bicycle spiroergometry in patients with panic disorder before (n = 38) and after (n = 10) a 10 week running program and compared to untrained healthy control subjects carrying out the same training (n = 11) and patients receiving clomipramine drug therapy (n = 7) or placebo (n = 7). Before the running program maximal oxygen uptake (VO2peak) and the workload corresponding to a lactate concentration of 4 mmol/l (PLAC4) were significantly reduced in panic patients compared to controls. Patients in the running program and healthy controls improved PLaC4 significantly by running. No significant differences in endurance gains were found between these groups, showing that patients and controls improved equally. At study termination (week 10) running was more efficient than placebo in improving panic symptoms (Bandelow PanicAgoraphobia Scale, Hamilton Anxiety Scale, Clinical Global Impression Scale). Clomipramine treatment was better than placebo (all scales) and running (only Clinical Global Impression). Endurance capacity did not correlate with anxiety scores at baseline, nor did improvement in fitness substantially correlate with changes in psychopathology measures during the study. Panic patients were shown to have a decreased endurance capacity which can be raised by training. Endurance training based on spiroergometric results gives rise to clinical improvement.

Adult↗

PubMed1998

Higher prevalence of obsessive-compulsive symptoms in patients with blepharospasm than in patients with hemifacial spasm.

OBJECTIVE: The prevalences of obsessive-compulsive symptoms in patients suffering from blepharospasm and in those with hemifacial spasm were determined. The two conditions have similar symptoms, but only blepharospasm is etiologically linked to basal ganglia dysfunction. METHOD: After being interviewed with the Structured Clinical Interview for DSM-III-R, 13 patients with blepharospasm and 13 with hemifacial spasm completed the SCL-90-R and the Hamburg Obsession/Compulsion Inventory-Short Form. RESULTS: Patients in the blepharospasm group had significantly more obsessive-compulsive symptoms, as indicated by higher scores on the Hamburg Obsession/Compulsion Inventory-Short Form, than the patients with hemifacial spasm. SCL-90-R scores were in the normal range for nine and eight categories, respectively (out of nine). CONCLUSIONS: The findings provide additional support for the hypothesis that obsessive-compulsive symptoms are related to basal ganglia dysfunction.

Aged↗

PubMed1998

Comparison of aerobic exercise, clomipramine, and placebo in the treatment of panic disorder.

OBJECTIVE: The purpose of this study was to compare the therapeutic effect of exercise for patients with panic disorder to a drug treatment of proven efficacy and to placebo. METHOD: Forty-six outpatients suffering from moderate to severe panic disorder with or without agoraphobia (DSM-III-R criteria) were randomly assigned to a 10-week treatment protocol of regular aerobic exercise (running), clomipramine (112.5 mg/day), or placebo pills. RESULTS: The dropout rate was 31% for the exercise group, 27% for the placebo group, and 0% for the clomipramine group. In comparison with placebo, both exercise and clomipramine led to a significant decrease in symptoms according to all main efficacy measures (analysis of variance, last-observation-carried-forward method and completer analysis). A direct comparison of exercise and clomipramine revealed that the drug treatment improved anxiety symptoms significantly earlier and more effectively. Depressive symptoms were also significantly improved by exercise and clomipramine treatment. CONCLUSIONS: These results suggest that regular aerobic exercise alone, in comparison with placebo, is associated with significant clinical improvement in patients suffering from panic disorder, but that it is less effective than treatment with clomipramine.

Adult↗

PubMed1997

Behavioral, physiological and neuroendocrine responses in healthy volunteers to m-chlorophenylpiperazine (m-CPP) with and without ondansetron pretreatment.

Several serotonin3 (5-HT3) antagonists have been shown to attenuate the anxiogenic effects of the serotonergic agent, m-chlorophenylpiperazine (m-CPP), in animal models, but little data regarding possible effects of 5-HT3 antagonists on responses to m-CPP are available from studies in humans. Therefore, we studied the behavioral, physiological and neuroendocrine responses of 12 healthy volunteers to i.v. administered placebo and m-CPP (0.08 mg/kg), with and without i.v. pretreatment with the selective 5-HT3 antagonist, ondansetron (0.15 mg/kg). Compared to placebo, m-CPP given alone significantly increased ratings of anxiety and several other behavioral measures. m-CPP also produced statistically significant increases in temperature, systolic and diastolic blood pressure, heart rate, and in plasma concentrations of adrenocorticotropic hormone, cortisol, prolactin and norepinephrine. Responses to ondansetron given alone were no different from those of placebo. Pretreatment with ondansetron did not affect peak behavioral responses to m-CPP, but was associated with a significantly earlier return to baseline levels of ratings of anxiety and functional deficit as well as a summary measure of overall behavioral effects. Following ondansetron pretreatment, the increases produced by m-CPP in systolic and diastolic blood pressure and heart rate were no longer significantly different from placebo. Ondansetron pretreatment significantly reduced their plasma cortisol response to m-CPP without affecting the other plasma hormone responses. Plasma concentrations of m-CPP were unaffected by ondansetron pretreatment. These findings suggest that in normal human subjects some behavioral, cardiovascular and neuroendocrine effects of m-CPP may be partially modulated by 5-HT3 receptor-mediated mechanisms.

Adult↗

PubMed1997

Urinary excretion of cortisol, norepinephrine, testosterone, and melatonin in panic disorder.

Nocturnal urinary cortisol, norepinephrine, epinephrine, testosterone, and melatonin secretion patterns were studied in male patients with DSM IV/ICD-10 panic disorder (n = 16) over two series of 5 consecutive nights each. Night-time urinary excretion of cortisol, norepinephrine, and epinephrine was significantly elevated in drug-free patients compared to normal individuals (n = 13). Measurements were repeated after 4 weeks, and the same differences were found again. There were high correlations between the first and the second series of measurements. Testosterone and melatonin levels did not differ between panic patients and controls.

Adult↗

PubMed1997

Exercise avoidance and impaired endurance capacity in patients with panic disorder.

Exercise habits and indices of aerobic fitness as measured by spiroergometric testing were examined in 38 patients with panic disorder and/or agoraphobia and 24 untrained healthy controls. Maximal oxygen consumption, maximal power output and the power output at a lactate concentration of 4 mmol/l were significantly reduced in the patient group when compared to untrained controls. Other parameters like physical work capacity at a heart rate of 150/min, maximal lactate concentration, vital capacity, subjective exertion at maximal work load, and maximal heart rate did not differ between patients and controls. Patient interviews revealed that aerobic exercise is avoided by the vast majority of patients. Reduced aerobic fitness might contribute to the pathophysiology of panic disorder and/or agoraphobia.

Adolescent↗

PubMed1997

[Value of sports in treatment of psychiatric illness].

Several studies in healthy volunteers have shown a positive effect of endurance training on anxiety, depressive symptoms, self-esteem, concentration and stress tolerance. There are only a few controlled studies examining the therapeutic potential of exercise in psychiatric disorders. However, there is good evidence that exercise is effective in mild to moderate depression and in anxiety disorders. The therapeutic effect did not correlate with changes in cardiopulmonary fitness in the majority of studies. Therefore, other neurobiological and psychological mechanisms are discussed which might explain the effectiveness of regular physical training. The authors offer a variety of suggestions, how exercise could be integrated and evaluated in the treatment of psychiatric disorders.

Anxiety Disorders↗

PubMed1996

Biological and behavioral responses to D-amphetamine, alone and in combination with the serotonin3 receptor antagonist ondansetron, in healthy volunteers.

Evidence that serotonin3 (5-hydroxytryptamine3, 5-HT3) antagonists attenuate behavioral responses to D-amphetamine and cocaine suggests that 5-HT3 receptors modulate brain dopamine in animals. This study examined the potential interactions of the 5-HT3 antagonist ondansetron and D-amphetamine in 10 healthy human volunteers. After the subjects were pretreated with placebo or ondansetron (0.15 mg/kg, i.v.), 5-h challenge tests with oral D-amphetamine (0.5 mg/kg) were performed. As animal studies and early clinical studies with ondansetron have suggested nonlinear dose-response relationships, three subjects also underwent pilot studies with three doses of ondansetron (0.15, 0.05, and 0.015 mg/kg) before they received D-amphetamine. Administration of D-amphetamine increased plasma levels of cortisol, prolactin, growth hormone; elevated blood pressure, pulse, and temperature; and tended to increase self-ratings of activation/euphoria and anxiety. Amphetamine-induced increases in plasma prolactin were significantly reduced by ondansetron pretreatment, but the other neuroendocrine responses were unchanged. Diastolic blood pressure elevations were also significantly attenuated after administration of the lower ondansetron doses, but the other physiologic responses were unchanged. In subjects with minimal or moderate activation/euphoria responses, ondansetron pretreatment only minimally affected these effects of D-amphetamine. Preliminary data, however, indicate that those subjects with robust activation-euphoria responses to D-amphetamine had attenuated responses after ondansetron pretreatment. Taken together, these results suggest that some but not most of D-amphetamine's biological and behavioral effects may be modified by a 5-HT3 antagonist in healthy human volunteers.

Administration, Oral↗

PubMed1996

Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis.

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.

Autoimmune Diseases↗

PubMed1995

Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity.

We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing-remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2-weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor-beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor-alpha were also observed in 6 patients with stable disease who had active magnetic resonance scans on follow-up. No correlation of disease activity was observed with interleukin-1 beta, -4, or -6, inferferon gamma or endothelin-1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing-remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.

Adult↗

PubMed1995

Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans.

Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonist m-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT3 receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine+ondansetron, and scopolamine+m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.

Aged↗

PubMed1995

[Panic disorder and agoraphobia: what is effective?].

The present survey of controlled studies on the treatment of panic disorder and agoraphobia (PDA) reveals that treatment with tricyclic antidepressants (e.g., imipramine and clomipramine), benzodiazepines (e.g., alprazolam), serotonin reuptake inhibitors (e.g., fluvoxamine) and the monoamine oxidase inhibitor phenelzine has been proven effective. Among psychological therapies, cognitive therapy and exposure therapy in agoraphobia have been shown to be effective. There is an insufficient number of comparisons between pharmacological and psychological treatments. From the existing studies it can be assumed that none of these treatment modalities is superior to the other. The few existing follow-up studies do not suffice to prove a longer lasting effect for the psychological therapies, compared with drug therapies. Because of the low number of investigations, it cannot be clearly stated whether it is useful or harmful do treat patients with psychopharmacological drugs during psychological therapy. It is more likely that this combination is advantageous.

Agoraphobia↗

PubMed1995

Obsessive-compulsive disorder among patients with anorexia nervosa and bulimia nervosa.

OBJECTIVE: The present study sought to determine the prevalence of obsessive-compulsive disorder among patients with eating disorders. METHOD: Ninety-three women who met DSM-III-R criteria for anorexia nervosa or bulimia nervosa were investigated by using a semistructured diagnostic interview, the Yale-Brown Obsessive Compulsive Scale, and the Eating Disorder Inventory. RESULTS: Thirty-four patients (37%) met the DSM-III-R criteria for obsessive-compulsive disorder and also had a clinically significant score of 16 or higher on the Yale-Brown scale. These patients also had significantly higher, and hence pathological, mean scores on five of eight Eating Disorder Inventory scales than patients with eating disorders without concomitant obsessive-compulsive disorder. CONCLUSIONS: These results suggest that there is a high prevalence of obsessive-compulsive disorder among patients with anorexia and bulimia nervosa and that this prevalence may be correlated with the severity of the eating disorder.

Adolescent↗

PubMed1994

Serial analysis of circulating adhesion molecules and TNF receptor in serum from patients with multiple sclerosis: cICAM-1 is an indicator for relapse.

We determined the serum levels for circulating adhesion molecules (circulating intercellular adhesion molecule-1 [cICAM-1], circulating endothelial leukocyte adhesion molecule-1 [cELAM-1], and circulating L-selectin [cL-selectin]) and circulating tumor necrosis factor receptor (cTNF-R) p60 in 29 patients with relapsing-remitting MS serially over a period of 12 months. During this period there were 27 relapses in 14 patients (48%). There was progression of disease activity in 12/25 patients (48%), as assessed by the occurrence of new lesions on nonenhancing, T2-weighted MRIs of the head. Clinically active patients with relapse or disease progression on MRI (n = 18) had frequent fluctuations in their serum levels for cICAM-1 if compared to patients with stable MS (n = 11). There were significant differences in the cumulative cICAM-1 production between the two groups (502 +/- 218 ng/ml in active versus 225 +/- 82 ng/ml in stable MS patients; p < 0.001). cTNF-R p60 serum levels were higher in patients with stable compared to active disease (2.3 +/- 0.5 ng/ml versus 1.5 +/- 0.6 ng/ml; p < 0.005). A significant increase in cICAM-1 levels was present at the time of a relapse (799 +/- 263 ng/ml versus 449 +/- 95 ng/ml; p < 0.001), whereas the highest serum levels for cTNF-R p60 occurred 4 weeks after the onset of a relapse (1.8 +/- 0.5 ng/ml at relapse versus 2.3 +/- 0.6 ng/ml 4 weeks after a relapse; p < 0.01). Interestingly, the cL-selectin serum levels in all MS patients were significantly higher than in healthy donors, whereas there were no differences for cELAM-1. These results reflect distinct changes of inflammatory variables in serum of patients with MS and revealed that cICAM-1 is an indicator for disease activity and that high serum levels for cTNF-R p60 are associated with remission.

Adult↗

PubMed1994

Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis.

We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 45 patients with the relapsing-remitting form of MS and 32 patients with other neurologic diseases. Using a semiquantitative polymerase chain reaction method, we detected significantly higher levels of tumor necrosis factor-alpha and lymphotoxin mRNA in patients with relapsing compared to those with stable disease (p < 0.001), but transforming growth factor-beta and interleukin-10 mRNA expressions were higher in patients with stable disease.

Cytokines↗

PubMed1993

Starvation-induced hyperactivity in the rat: the role of endocrine and neurotransmitter changes.

Semistarved rats develop high running wheel activity. This running activity induces increased norepinephrine, dopamine, and serotonin turnover in the hypothalamus. Corticosterone in plasma becomes increased while luteinizing hormone and testosterone are suppressed. In female rats cyclic gonadal function is suppressed. Running activity in the semistarved rats can be suppressed specifically by serotonin 1-c-agonists and by alpha 2-adrenoceptor agonists. This animal model is helpful in the understanding of the combined effects of starvation and hyperactivity, which are observed in many patients with anorexia nervosa. The observation of the serotonergic system might help to develop a pharmacological treatment of hyperactivity in anorectic patients.

Animals↗