Amisulpride: a review of its use in the management of schizophrenia.

UNLABELLED: Amisulpride, a substituted benzamide derivative, is a second-generation (atypical) antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In patients with acute exacerbations of schizophrenia, the recommended dosage of amisulpride is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. In comparative trials, amisulpride administered within this range (400 to 1200 mg/day) was as effective as haloperidol 5 to 40 mg/day, flupenthixol 25 mg/day and risperidone 8 mg/day in patients with acute exacerbations of schizophrenia with predominantly positive symptoms. Amisulpride was more effective than haloperidol but equally effective as risperidone in controlling negative symptoms. Amisulpride 400 to 800 mg/day was more effective than haloperidol, risperidone and flupenthixol in controlling affective symptoms in these patients. In randomised, double-blind trials involving patients with predominantly negative symptoms of schizophrenia, amisulpride 50 to 300 mg/day was more effective than placebo. Amisulpride is effective as maintenance therapy in patients with chronic schizophrenia. Long-term treatment with amisulpride was associated with improvements in quality of life and social functioning. Amisulpride is generally well tolerated. In well-controlled trials, the neurological tolerability profile (including ratings on extrapyramidal symptom scales) of amisulpride 400 to 1200 mg/day was superior to that of the conventional antipsychotics (haloperidol or flupenthixol), but was similar to that of the atypical antipsychotic risperidone. At low dosages of amisulpride (< or =300 mg/day), the incidence of adverse events (including extrapyramidal symptoms) reported with amisulpride was similar to that with placebo. CONCLUSION: In comparative trials, amisulpride 400 to 1200 mg/day showed efficacy in reducing overall symptomatology and positive symptoms similar to that of conventional antipsychotics and newer atypical antipsychotics in patients with acute exacerbations of schizophrenia. Moreover, its effective alleviation of negative and affective symptoms, its lower association with extrapyramidal symptoms and loss of cognitive function than conventional antipsychotics and its long-term efficacy justifies consideration of the use of higher dosages of amisulpride in this group of patients. Consequently, the dosage of amisulpride that is recommended in patients with acute exacerbations of schizophrenia is 400 to 800 mg/day, although dosages < or =1200 mg/day may be administered. Lower dosages of amisulpride (50 to 300 mg/day) should be considered for the management of patients with negative symptoms of schizophrenia. Amisulpride is a first-line treatment option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.

Estradiol and norgestimate: a review of their combined use as hormone replacement therapy in postmenopausal women.

The focus of this review is hormone replacement therapy (HRT) with continuous administration of micronised, oral 17beta-estradiol 1 mg/day (herein referred to as continuous estradiol) plus micronised, oral norgestimate 90 microg/day administered for 3 days then withdrawn for 3 days in a 6-day repeating sequence (herein referred to as intermittent norgestimate). According to data from randomised, comparative trials of 1 year's duration, continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day relieves climacteric symptoms (vasomotor symptoms and vulvovaginal atrophy) in postmenopausal women. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day appeared as effective as estradiol 1 mg/day alone or continuous estradiol 2 mg/day plus continuous norethisterone acetate 1 mg/day in the treatment of postmenopausal women with vasomotor symptoms. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was as effective as continuous estradiol 1 mg/day in causing the maturation of vaginal epithelial cells. In a randomised, double-blind study, bone mineral density (BMD) increased to a significantly greater extent and the rate of bone turnover was slower in postmenopausal women treated with continuous oral estradiol 1 mg/day plus intermittent norgestimate 90 microg/day than in placebo-treated patients. Two randomised, double-blind studies indicated that the addition of norgestimate 90 microg/day to continuous estradiol 1 mg/day did not attenuate the beneficial effects of estradiol on lipid parameters. Continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day was associated with increases in mean serum high density lipoprotein (HDL)-cholesterol levels and decreases in total cholesterol, low density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels, compared with baseline. There was no statistically significant increase in triglyceride levels. In comparative trials, continuous oral estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was well tolerated. Headache, breast pain or discomfort, abdominal pain or discomfort, uterine bleeding, dysmenorrhoea, oedema, nausea and depression were the most commonly reported adverse events. Continuous estradiol 1 mg/day plus intermittent oral norgestimate 90 microg/day was associated with a favourable uterine bleeding profile that improved over time. In a randomised trial, 80% of women were free from bleeding (irrespective of spotting) during month 12 of treatment. Norgestimate 90 microg/day was effective in protecting postmenopausal women against induction of endometrial hyperplasia by continuous estradiol 1 mg/day. In conclusion, data from a limited number of randomised studies indicate that HRT with continuous estradiol 1 mg/day plus intermittent norgestimate 90 microg/day is effective in relieving climacteric symptoms, increasing BMD and slowing the rate of bone turnover in postmenopausal women. This HRT regimen is well tolerated and is associated with a similar incidence of adverse events to that reported in recipients of continuous estradiol 1 mg/day. The norgestimate component of the regimen provides good endometrial protection and is associated with a favourable bleeding profile. Long-term studies investigating the associated risk of breast cancer and thromboembolic events in recipients of continuous estradiol plus intermittent norgestimate are needed. In the meantime, continuous oral estradiol plus intermittent oral norgestimate can be regarded as an effective new option for HRT in postmenopausal women.

Torulopsis glabrata spinal osteomyelitis involving two contiguous vertebrae. A case report.

STUDY DESIGN: A case report and literature review of the five previous case reports. OBJECTIVES: To outline the features of Torulopsis glabrata spinal osteomyelitis, including its risk factors, diagnosis, and recommended treatments. SUMMARY OF BACKGROUND DATA: Fungal infections in general and Torulopsis glabrata in particular are becoming increasingly prevalent. Involvement of the spine will likely be more common in the future. METHODS: The literature was exhaustively reviewed and the five previous reported cases of Torulopsis glabrata identified and evaluated. This case report is analyzed in the context of the previous five cases. RESULTS: All patients responded to treatment, which varied from medical alone to medical with operative debridement and spinal fusion. CONCLUSION: Various risk factors that predisposed patients to Torulopsis glabrata osteomyelitis were present in all known cases. Diagnosis should rely on examination, history, and radiographic and laboratory evaluations. Medical therapy should be the initial treatment in most cases; however, operative intervention may be needed in patients who do not respond appropriately.

A specific L-asparaginase from Thermus aquaticus.

The L-asparaginase from an extreme thermophile, Thermus aquaticus strain T351, was highly substrate- and stereospecific, with no activity against glutamine or D-asparagine. It had a high Km of 8.6 mM. In these aspects it closely resembled the corresponding enzymes from thermophilic bacteria. The enzyme had a molecular weight of 80,000, an isoelectric point of 4.6, and a pH optimum of 9.5. It showed some substrate inhibition above 20 mM asparagine and was also inhibited by L-aspartic acid, D- and L-lysine (Ki of 5.2 and 1.25 mM, respectively), and D- and L-serine. The half-life of the enzyme at 85 degrees C was 40 min. The Arrhenius plot showed a change in slope at 55 degrees C.

A correlation between protein thermostability and resistance to proteolysis.

The loss of activity due to proteolysis of purified L-asparaginase and beta-galactosidase from different sources correlates with the thermal instability of the enzymes. A similar correlation is found when populations of soluble proteins from micro-organisms grown at different temperatures are compared for proteolytic susceptibility and thermal stability. It is proposed that there is a general correlation between the thermostability of proteins and their resistance to proteolysis.

A method for the determination of nitrate reductase.

A procedure for the assay of nitrate reductase based on Szekely's diaminodiphenylsulphone method of nitrate determination (Szekely, E. (1967) Talanta 14, 941-950) is described. The method is simple and sensitive, allowing determination of 1 microgram of nitrate in a volume of 1 ml or less. It is particularly suited to the determination of nitrate reductase.