Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it.

The impact of lithium prophylaxis on mortality has been studied in 497 patients, 405 bipolars and 92 unipolars, who attended the same out-patient lithium clinic for up to 30 years. In order to avoid preselection, no minimum period of lithium treatment was required in our study. Of a total of 6014 patient-years, 4330 were spent in regular contact with the study clinic. General mortality due to natural causes was not significantly increased; among cardiovascular diseases, only pulmonary embolism showed an excess mortality. No patients died of lithium intoxication or chronic renal insufficiency. Patients were divided into three groups: Group A, 277 patients, attended the study clinic until death or the end of the study, Group B, 86 patients, left the clinic but continued to take lithium, and Group C, 134 patients, both left the clinic and stopped taking lithium. Among bipolars, the suicide rate compared to the general population was in excess in all three groups. Among unipolars, suicides occurred only after the patients had left the study clinic and stopped taking lithium. A special analytical method was used for intergroup comparisons of suicide rates. Bipolars in Group A attending the study clinic regularly had a suicide rate of 3.5 per 1000 patient-years. The rate increased to 6.3 or by 80 % if patients had left the clinic and did not take lithium any longer as in Group C. The suicide rate in Group C increased by 45% compared to Group B, patients who left the clinic but continued to take lithium. Our results support the hypothesis that lithium has a significant antisuicidal effect in bipolars as well as in unipolars. The suicide mortality can be further reduced by regular attendance in a specialised mood disorder clinic.

Glucocorticoid receptor inhibits microtubule assembly in vitro.

The effect of glucocorticoid hormones, purified glucocorticoid receptor (GR) and purified heat shock protein M(r) 90,000 (hsp90) on microtubule (MT) assembly in vitro was tested by a spectrophotometric MT assembly assay and electron microscopy. GR significantly prolonged the nucleation phase, slowed down the assembly rate and reduced the maximal amplitude of MT assembly compared with control. The effects were partially reversed by the addition of glucocorticoid hormone. GR associated with MTs. These results indicate that GR affects MT assembly in vitro, which may be a functional correlate to the structural association of GR with MTs. This implies that factors affecting GR may affect MT assembly in vivo.

A long-term cross-over pharmacokinetic study comparing perphenazine decanoate and haloperidol decanoate in schizophrenic patients.

The purpose of the study was to investigate clinical and pharmacokinetic parameters concerning perphenazine decanoate (PD) and haloperidol decanoate (HD) with an interval of 3 weeks during a study period of 51 weeks. This was done by using the available drug preparations in chronic schizophrenic patients in a randomised, double-blind, cross-over, multicentre study. In addition, an elimination phase of 6 weeks was added, when no IM injections of the depot drugs were given. Twenty-nine patients in a stable neuroleptic maintenance phase entered the study. The patients were rated during the trial according to the CPRS-SCHZ and CGI scales, the UKU side effect scale and serum concentrations of the drugs and prolactin were monitored. There was no significant difference between the drugs in antipsychotic efficacy or side effects. Thus, the doses were equipotent with regard to the CPRS-SCHZ scores. However, the patients' global improvement rating was higher for PD (52%) than for HD (39%) (P > 0.05). The elimination of both drugs was very slow. No interaction effects between PD and HD were observed. The serum levels of HD were in most patients lower than those recommended for acute-subacute treatment. The mean doses were 117 mg (0.29 mmol), range 20-313 mg PD and 120 mg (0.32 mmol), range 20-350 mg HD. The serum concentrations in nmol/L of perphenazine and haloperidol (week 24) were 0.8-15.9 and 2.3-46.7, respectively.

Local anesthesia of the genital mucosa with a lidocaine/prilocaine cream (EMLA) for laser treatment of condylomata acuminata: a placebo-controlled study.

The time of onset and duration of local anesthesia of a lidocaine/prilocaine cream (EMLA) applied to the genital mucosa were assessed in a double-blind study. Eighty women with condylomata on their genital mucosa were randomly allocated to either EMLA (N = 60) or placebo cream (N = 20) between 1-75 minutes before CO2 laser treatment. The pain was evaluated by the patient on a visual analogue scale. The most effective degree of anesthesia was achieved after 5-15 minutes' application of EMLA. The patients given EMLA, regardless of application time, felt significantly less pain than the patients given placebo. EMLA could provide an alternative to general anesthesia in patients with extensive condylomata on the genital mucosa.

Intra- and intersubject variation of erythromycin absorption from single-unit and multiple-unit enteric-coated products.

Based on the in vitro dissolution test for erythromycin capsules introduced in USP XX, Suppl. 3, there are no reasons to expect any difference in bioavailability after administration of two enteric-coated products, tablets and pellets in hard capsules. The present results in vivo are contradictory and, following duplicate administrations of the two preparations to 12 volunteers after a standardized breakfast, it is apparent that the multiple-unit, pellets, produce a better reproducibility in absorption both within and between subjects than the single-unit tablets. All subjects attained measurable levels of erythromycin on all occasions after administration of pellets, while levels were below the detectable limit on six out of the 24 occasions tested after administration of tablets. The better reproducibility of serum levels after pellets than after tablets was also shown in a descriptive way and is given as a low median discrepancy value of 23.5 per cent (moderate) compared to 73.2 per cent (large).

Topical anaesthesia with EMLA, a new lidocaine-prilocaine cream and the Cusum technique for detection of minimal application time.

The minimal effective onset time of the new topical anaesthetic formulation EMLA (a eutectic mixture of lidocaine and prilocaine), was evaluated by the double-blind technique in 53 female and 66 male patients (median age 40 and 36 years, respectively) subjected to intravenous cannulation. Conventional plotting and regression analysis failed to answer the question. The Cusum technique, originally designed for industrial production control, could successfully be applied to solve the problem. It demonstrated a minimal effective EMLA application time of 45 min in adults.

Chlormethiazole (Heminevrin), pethidine and nitrous oxide as compared to halothane for general anesthesia.

The anaesthetic and postanaesthetic course in a group of gynaecological patients anaesthetized with chlormethiazole (Heminevrin) was investigated and the results compared to a similar group of patients anaesthetized with halothane. Both drugs were used as the main anaesthetic agent in the respective regimes, supplemented by nitrous oxide/oxygen and muscle relaxants. Because chlormethiazole is devoid of analgetic effects, the importance of using pethidine in combination with chlormethiazole is emphasized. An advantage of using chlormethiazole is that it can serve as both an induction and maintenance agent. The plasma concentrations of chlormethiazole were studied in seven patients. For induction, the mean concentration was 4.5 micrograms/ml. The mean concentration on waking at the termination of operation was 1.3 micrograms/ml. No serious side effects were encountered in either treatment. The results suggested that chlormethiazole in combination with an analgetic drug and nitrous oxide could be suitable in elderly patients, although occasionally less effective in the young.

Mild analgesics as an alternative to ergotamine in migraine. A comparative trial with acetylsalicylic acid, ergotamine tartrate, and a dextropropoxyphene compound.

The effect of ergotamine tartrate was compared with that of acetylsalicylic acid and a dextropropoxyphene compound (Doleron novum) on 525 acute migraine attacks in a double-blind crossover study of 25 adult female patients. Ergotamine tartrate and the dextropropoxyphene compound were equally effective and significantly superior to acetylsalicylic acid in preventing the attacks entirely. If the attacks were only partially prevented, the dextropropoxyphene compound was significantly superior to acetylsalicylic acid in making the attacks shorter and milder, while ergotamine tartrate did not differ significantly from acetylsalicylic acid or the dextropropoxyphene compound. The incidence of nausea and vomiting was lowest during treatment with the dextropropoxyphene compound. In the patients' overall preference, the dextropropoxyphene compound and ergotamine tartrate were significantly superior to acetyl-salicylic acid. In acute migraine the combination of dextropropoxyphene, a centrally acting analgesic, with acetylsalicylic acid and phenazone gives an alternative to ergotamine tartrate that is equally effective and causes less nausea and vomiting.