Alpha-2-adrenoceptor sensitivity in early alcohol withdrawal.

Growth hormone (GH), blood pressure, and pulse rate responses to clonidine (100 micrograms IV) were studied three times during the first week of alcohol withdrawal in 19 alcohol-dependent patients. Fifteen healthy men were used as controls. The results suggest reduced sensitivity of the alpha-2-adrenoceptors involved in GH secretion for at least 1 week after the end of alcohol intake. In contrast, very short-lasting subsensitivity was found in the alpha-2-adrenoceptors regulating blood pressure.

Cerebrospinal fluid levels of monoamine metabolites. A preliminary study of their relation to menstrual cycle phase, sex steroids, and pituitary hormones in healthy women and in women with premenstrual syndrome.

The cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the dopamine metabolite homovanillic acid (HVA) were measured in a group of drug-free non-depressed women with premenstrual syndrome (PMS) (late luteal phase dysphoric disorder) (n = 13) and in controls with no premenstrual complaints (n = 13). In six patients and eight controls, CSF samples from both the luteal and the follicular phase were obtained, whereas in the remainder of the subjects, samples from either the follicular phase (patients: 4, controls: 2) or the luteal phase (patients: 3, controls: 3) were taken. The following observations were made: (1) Neither in the follicular phase nor in the luteal phase did the mean concentrations of CSF monoamine metabolites in the PMS group differ from the corresponding values in the control group. (2) Neither in the PMS group nor in the control group did the mean concentrations of monoamine metabolites in CSF samples obtained in the luteal phase differ from the corresponding values obtained in the follicular phase. (3) The intraindividual, intersample variations of CSF HVA and 5-HIAA concentrations were significantly smaller in the PMS group than in the control group. (4) CSF HVA correlated strongly to CSF 5-HIAA in the luteal phase of both patients and controls whereas in the follicular phase, particularly in controls, this correlation was much weaker. (5) In the luteal phase, the CSF HVA/5-HIAA ratio correlated negatively to serum levels of estradiol, progesterone, and testosterone. (6) The CSF HVA/5-HIAA ratio was significantly lower in PMS patients than in controls. (7) A positive correlation between CSF MHPG and serum luteinizing hormone was observed in the follicular phase. (8) A positive correlation between CSF HVA and serum prolactin was observed in the luteal phase. Because the study was comprised of a small number of subjects, the reported findings until replicated should be interpreted with caution.

Guanfacine as an alpha-2-agonist inducer of growth hormone secretion--a comparison with clonidine.

Doses of 0.5 mg and 1.0 mg of the alpha-2-adrenoceptor agonist guanfacine (GUA) and NaCl were administered intravenously (IV) in a randomized order to 18 healthy male subjects. GUA induced growth hormone (GH) secretion in a dose-dependent manner without affecting blood pressure or heart rate or inducing sedation. The effects of GUA 1.5 mg i.v. was compared with those of another alpha-2-adrenoceptor agonist, clonidine (CLON) 150 micrograms i.v. in six other male volunteers. Both alpha-2-agonists increased GH to similar levels. CLON reduced both systolic and diastolic blood pressure levels, whereas GUA reduced only systolic levels. Sedation was significantly more pronounced after CLON. The results suggest that the GUA/GH-test (1.5 mg GUA i.v.) may be an alternative to the CLON/GH-test in neuroendocrine assessment of alpha-2-adrenoceptor sensitivity.

Treatment-resistant mania with primary hypothyroidism: a case of recovery after levothyroxine.

A manic-depressive woman was unresponsive to treatment with lithium and neuroleptics during a period of mania. Additional levothyroxine treatment of her primary hypothyroidism resulted in rapid and complete recovery from her mania.

The effect of lithium on amphetamine-induced locomotor stimulation.

A behavioural study was performed to investigate how lithium interacts with monoamine mechanisms. Acute lithium pretreatment partially antagonized amphetamine-induced locomotor stimulation in mice. A rather small dose of L-dopa, which had no stimulant effect on locomotor activity of its own, caused a dose-dependent antagonism of the lithium-induced suppression of the amphetamine-induced locomotor stimulation. Additionally, acute lithium pretreatment had no effect on the apomorphine-clonidine-induced locomotor stimulation after elimination of presynaptic activity by means of pretreatment with reserpine and alpha-MT. Our interpretation of these results is that the inhibitory effect on amphetamine-induced locomotor stimulation is likely to be mediated via presynaptic mechanisms (i.e., decreased release of catecholamines or inhibition of catecholamine synthesis or a combination of both mechanisms) and, further, lithium seems to have no effect at or beyond the catecholamine receptors. However, the possibility that lithium may increase the activity in neuronal systems antagonizing the catecholamine neurons cannot be excluded.

Long-term effects of two different treatments for dental fear and avoidance.

Follow-up clinical studies of treatment for dental fear and avoidance behavior are infrequent in the literature. The present investigation reports follow-up results over more than two years from 84 out of 99 patients treated for dental fear in a Swedish community-based dental fear clinic. Broad-based behavioral therapy (BT) or general anesthesia (GA), both in combination with adjusted conventional dental treatment, were used. The frequency of patients' attendance for regular dental care after two years was unchanged or even somewhat increased and was significantly higher in those who had received the BT therapy. Most patients stated that they had no problems after leaving the dental fear clinic. Among patients reporting such problems, the change of dentist was most frequently reported. The level of dental anxiety as measured by Corah's DAS was still at a low level, in spite of a slight increase over the two years since initial therapy.

Dental fear and avoidance: a comparison of two modes of treatment.

Ninety-nine individuals, all of whom had long avoided dental treatment due to severe dental fear, received therapy according to one of two treatment modalities--behavioral therapy from a psychologist (BT) and treatment under general anesthesia (GA)--both of which were followed by clinical training and dental test treatments. These treatment programs were followed by referring the individuals to community dental clinics for complete oral rehabilitation. Among BT patients, significantly more (92%) completed the treatment program, compared with the GA patients (69%). Complete oral rehabilitation in community dental clinics was achieved by 78 and 53%, respectively. BT patients also had a significantly lower frequency of cancellations. The reduction in dental anxiety according to the Corah Dental Anxiety Scale was substantial in both groups, but the anxiety was significantly more reduced for BT patients, who reached a level equivalent to that of average dental patients. Patients' self-reported tension and the dentists' ratings of patient behavior during treatment were also significantly more positive for the BT groups.

Relaxation vs. cognitively oriented therapies for dental fear.

Cognitive therapy has been reported for the treatment of dental phobia, but comparisons with other behavioral treatments are scarce. This study investigated the outcome of two modes of treatment for phobic dental fear. Relaxation and cognitively oriented therapy were compared in a sample of 112 adult fearful dental patients. The patient made questionnaire assessments of background and outcome variables, and the specialist dentist rated successful/non-successful outcome. It was shown that a higher number of patients who received cognitively oriented therapy completed the treatment program, while anxiety was more reduced among patients who received relaxation-oriented therapy. Dropout during the initial phobia therapy with a psychologist was related to lower motivation (willingness to engage in treatment), while failures during dental treatment after the completion of therapy were related to higher levels of general fear and anxiety. A multiple logistic regression model explaining 67% of the variance revealed that the risk of failure was only slightly increased by general fears, while patients with low (below median) motivation ran a 3.6-times-higher risk of dropping out. In conclusion, it was shown that the two treatment methods were both effective in reducing dental phobic reactions. However, while cognitively oriented therapy resulted in a higher number of patients completing therapy, relaxation-oriented treatment generally resulted in a more significant reduction in dental fear as well as in general anxiety and fear. Motivation was found to be a significant predictor of successful treatment outcome.

Variations in dental anxiety among middle-aged and elderly women in Sweden: a longitudinal study between 1968 and 1996.

Cross-sectional studies have shown that older individuals are significantly less dentally anxious than younger ones. However, research has not been able to show if this is a cohort effect or an effect of fear declining with age. If it is a cohort effect, dental anxiety among the elderly may pose a greater-than-expected problem for the providers of dental services. With the exception of longitudinal studies in children and a three-year follow-up on adults, no truly longitudinal epidemiological studies concerning dental anxiety have been performed. The aim of this project was to investigate how dental anxiety changes with aging. In a longitudinal population study of women in Göteborg, Sweden, starting in 1968, 1462 women aged 38 to 54 participated. A representative subsample of 778 women took part in a psychiatric examination where an investigation of dental anxiety was included. The same questions were also included when these women were re-examined in 1974, 1992, and 1996. Three hundred seventy-five women were still eligible for investigation in 1996. In 1968-69, 48 (12.8%) of the participating women assessed themselves as "very afraid" or "terrified" when visiting the dentist, and in 1996 the frequency was 21 (5.6%) among the same women. In 1968-69, 180 women (48%) reported no dental anxiety when visiting the dentist, and 28 years later the frequency was 230 (61%). In the three youngest age groups, dental anxiety decreased significantly (p < 0.001) over the 28-year period. Older compared with younger women reported significantly less dental anxiety, and this was an age effect rather than a cohort effect. Thus, this longitudinal study supported the hypothesis that dental fear, like many other general and specific phobias, declines with age.

Further neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholism.

D2 dopamine receptor function, as assessed by growth hormone (GH) responses to apomorphine (APO; 0.18-0.24 mg i.v.), was investigated in 15 male alcoholics with reported long-term abstinence. Results from only nine subjects could be evaluated. These subjects had been heavy alcohol consumers for a mean of 15 +/- 10 years and had thereafter been abstinent for a mean of 7 +/- 6 years prior to the investigation. Eight male healthy subjects, all of whom were light social drinkers, were selected as controls. The maximum GH responses to APO were significantly lower in the alcoholics (5.8 +/- 5.8 mU/l) than in the controls (22.1 +/- 19.2 mU/l). This finding gives neuroendocrine evidence for reduced D2 dopamine receptor function in alcoholics with long-term abstinence.

Relationship between central serotonergic neurotransmission and reduction in alcohol intake by citalopram.

The relationship between the effect of citalopram on alcohol intake and central serotonergic neurotransmission, as assessed by prolactin (PRL) response to fenfluramine, was investigated in 17 male heavy drinkers. A positive correlation was obtained, suggesting that the status of central serotonergic neurotransmission in individuals is associated with the treatment response to citalopram. When the group of subjects were divided into those with high and low PRL response (above and below median, respectively) to fenfluramine, those with high PRL response had a significant reduction in alcohol intake during citalopram treatment, whereas those with low PRL response had no such effect. Thus, in subjects with evidence of unimpaired or only slightly impaired central serotonergic neurotransmission (high PRL response) citalopram may have beneficial effect on alcohol consumption, whereas in those with more evidently impaired serotonergic neurotransmission (low PRL response) citalopram treatment may have no effect on or may even increase the alcohol consumption.

Subsensitive alpha-2-adrenoceptor function in male alcohol-dependent individuals during 6 months of abstinence.

Postsynaptic alpha-2-receptor function, as assessed by growth hormone (GH) response to clonidine (CLON), has been shown to be downregulated in patients investigated in acute but also in late withdrawal after heavy alcohol intake. The results are however sometimes conflicting. The question whether this changed receptor function is a trait or state marker is not fully investigated so far. A total of seven male patients with alcohol dependence according to DSM-IV were assessed for the postsynaptic alpha-2-receptor function with the CLON/GH test (2.0 microg/kg body weight; i.v.) starting immediately after a period of heavy drinking. Neuroendocrine tests were repeated after 7 days, 2 and 6 months. A total of six healthy males were used as controls. The maximum GH responses to CLON were significantly lower on all four test occasions in the patient group as compared to the controls. Furthermore, in the patient group all neuroendocrine test results showed blunted GH responses to CLON. Thus, patients with downregulated alpha-2-receptor function during acute withdrawal after heavy alcohol intake showed similar subsensitive receptor function abnormality after a prolonged period of abstinence. The findings in this study indicate that alcohol dependent individuals have a persistent subsensitive alpha-2-adrenoceptor function which may constitute a trait factor for alcohol dependence.

Six-month open trial with Zimelidine in alcohol-dependent patients: reduction in days of alcohol intake.

In an open study, 14 alcohol-dependent male patients were treated with the selective serotonin reuptake inhibitor (SSRI) Zimelidine, 200 mg daily, for six months. They were given psychosocial therapy before and during the study. The number of days of alcohol intake was statistically significantly reduced from a mean of 14 days per month before to 1-5 days during drug treatment. No effect was observed on the amount of daily alcohol intake on drinking days. No tolerance to the effect of Zimelidine was observed during the study. The findings suggest an effect of combined psychosocial support with SSRI treatment that seems to be of clinical significance.

Dexamethasone suppression test in alcohol withdrawal: relationship to depression and liver function.

The relationship between dexamethasone suppression test (DST) response, depressive symptoms and liver function tests was investigated in 15 male alcohol-dependent patients for 2 weeks during alcohol withdrawal. Six of the patients relapsed into drinking within the investigation period. There was no association between DST response and relapse, which suggests that abnormal DST response has no predictive value for relapse into drinking. About 50% of the patients had abnormal DST responses during the first week of alcohol withdrawal. There was no relationship between DST response and depression or depressive symptoms. Depression remitted within 1-2 weeks, whereas DST responses remained abnormal for at least 2 weeks in 2 of the non-relapsing 9 patients. Abnormal DST response in alcohol withdrawal is unlikely to be due to alterations in liver function but may be attributable to the effect of alcohol on the hypothalamic-pituitary-adrenocortical axis.

A cost-minimization analysis of laparoscopic cholecystectomy versus open cholecystectomy.

BACKGROUND: Earlier economic analyses have evaluated charges but not costs, and have not considered the cost of production losses associated with open and laparoscopic cholecystectomy. This study attempted to accomplish an economic evaluation of open versus laparoscopic cholecystectomy from the point of view of society. METHODS: A cost-minimization analysis, using a clinical decision model, was performed. The data used were taken from different clinical studies, Swedish national registers, local patient statistics, and hospital accounting systems. The direct and indirect costs were measured. RESULTS: Laparoscopic cholecystectomy resulted in cost savings per patient amounting to about 2,400 SEK (as of 31 August 1994, Pound = 11.90 SEK; $1 = 7.76 SEK) compared with open surgery. CONCLUSIONS: From the point of view of society, laparoscopic cholecystectomy was a cost-saving strategy if at least 68 patients were operated on yearly. However, with regard to hospital costs, open cholecystectomy was less expensive than laparoscopic cholecystectomy.

Neuroendocrine evidence for decreased function of alpha 2-adrenergic receptor after electroconvulsive therapy.

Growth hormone (GH) and hypotensive responses to clonidine (150 micrograms, i.v.) were investigated before and after electroconvulsive therapy (ECT) in 16 depressed patients. Because of high baseline serum GH concentrations, results from only 10 patients could be evaluated. The level of GH secretion induced by clonidine was significantly reduced after ECT, but the hypotensive responses to clonidine remained unchanged. The results indicate downward regulation of the sensitivity of alpha 2-adrenergic receptors in the hypothalamus after ECT.

General and specific fears in referred and self-referred adult patients with extreme dental anxiety.

The levels of, and relationships between, dental fear and general fears and phobias were studied in 109 adult patients at a specialized dental fear clinic using two dental fear scales (the Dental Anxiety Scale and the Dental Fear Survey) together with the Fear Survey Schedule II (FSS-II) and some additional fear items. Referred and self-referred fearful dental patients answered mailed questionnaires in conjunction to being put on a 1 yr waiting list for treatment. Among feared objects and situations the separate item 'pain' revealed the highest mean scores for both men and women, followed by fear of suffocating, death of a loved one and sharp objects among women, and death of a loved one, suffocating and hypodermic needles among men. With few exceptions, women scored higher than men. The frequencies of extreme fears (6 and 7 on a 7-point scale) were high and 92.7% of the patients reported at least one extreme fear. Half of the subjects (49.5%) reported five fears or more. It was also shown that a number of FSS-II items correlated to dental fear indicating a relationship between general and dental fear. These results indicated that a large proportion of these dentally fearful individuals were prone to fear-associated reactions and behaviors, which has previously been shown to negatively influence the prognosis of treatment.

Cardiovascular responses to clonidine in alcohol withdrawal: are they related to psychopathology and mental well-being?

The possible relationships between alpha-2-adrenoceptor function, as assessed by blood pressure, heart rate, and sedative responses to clonidine (CLON; 1.5 microg/kg, i.v.), and psychopathology and mental well-being were investigated in 19 patients with alcohol-dependence in the early withdrawal period (days 1 and 7). An age-matched control group was used (n=17). CLON-induced maximum reduction of systolic blood pressure was less day 1 in the alcohol-dependent patients compared to controls. CLON was found to induce less sedation at day 7 compared to day 1 and to controls. No relationships were seen between the parameters for alpha-2-adrenoceptor function and psychopathology and mental well-being. These findings suggest that CLON-induced changes in blood pressures and heart rate reflect the cardiovascular situation in alcohol withdrawal and not aspects of behavior.

No effect of the cortisol-synthesis inhibitor metyrapone on alcohol drinking: a pilot study.

Two bases for this study were the theory of stress as a provoking factor for high alcohol consumption in human being and findings that the stress hormones stimulate ethanol intake in rats. We therefore investigated whether the cortisol-synthesis inhibitor metyrapone could reduce high alcohol consumption in socially stable subjects who reported drinking mainly for relaxation purposes. Most of the investigated subjects were found to be alcohol dependent (81%), with moderately high levels of intake, yet they had not reported more severe life problems. All subjects reported their daily alcohol consumption during 2-week baseline, medication, and postmedication periods. Sixteen subjects were given 1 g of metyrapone orally daily for 14 days, and 15 subjects received placebo. Morning serum cortisol concentration was assessed four times in the course of the study period. Metyrapone treatment was not found to reduce alcohol consumption more than placebo. Serum cortisol concentrations remained within the laboratory reference interval during the study and did not differ between the study groups. In this study, we found that a cortisol-synthesis inhibitor had no effect on alcohol consumption. One reason may be that cortisol secretion has no role in the maintenance of high alcohol consumption. On the other hand, because this study is the first of its kind, further studies using other doses of treatment and treatment schedules are suggested.

Usefulness of two psychometric scales in Swedish patients with severe dental fear.

Dental fears and other fears were assessed in 67 patients with dental fear with the Corah Dental Anxiety Scale (CDAS), the Geer Fear Scale (GFS), and a behavioral dentist's rating scale (DR). Patients were selected because of extreme initial dental fear (n = 20), favorable response to treatment for dental fear (n = 23). CDAS change paralleled behavioral change (DR), supporting the usefulness of CDAS in assessing dental fear. GFS scores did not change in either group but were higher among patients who did not respond to treatment for dental fear; these findings are discussed in terms of treatment outcome prediction and treatment specificity.