Flerobuterol: a potential antidepressant drug related to β-adrenergic agonists. Experimental profile in mice

The potential antidepressant effect of flerobuterol (dl-(fluoro-2 phenyl)-1 t-butylamino-2 ethanol), a new drug related to beta-adrenoceptor agonists, was evaluated and compared with imipramine and salbutamol using classical psychopharmacological tests in mice. Like imipramine and salbutamol, flerobuterol (0.5-32 mg kg-1, ip) fully prevented apomorphine (16 mg kg-1, sc)- and partly reversed reserpine- and oxotremorine-induced hypothermia. At higher doses (16-32 mg kg-1), flerobuterol enhanced the toxic effects of yohimbine. Unlike imipramine, flerobuterol and salbutamol did not reduce immobility duration in the behavioural despair test. Salbutamol and flerobuterol decreased locomotor activity. Flerobuterol did not induce mydriasis, did not prevent oxotremorine-induced tremors or salivary and lacrimal gland secretion and did not reduce reserpine-induced palpebral ptosis. Propranolol (8 mg kg-1, ip) but not alpha-methyl-paratyrosine (75 mg kg-1, ip) prevented the flerobuterol-induced antagonism of apomorphine-induced hypothermia. Our results suggest that flerobuterol demonstrates potential antidepressant activity, which could be related to beta-adrenoceptor activation in mice.     

Cavernous sinus involvement in recurrent Nelson's syndrome

Summary Two cases of meningiomas, which are considered to have been caused by the preceding irradiation, are reported. In both cases, the cytokinetic study of the tumour using bromodeoxyuridine (BrdU) was performed. The percent of the tumour cells in the S phase of the cell cycle was less than 1% in both cases. The low labelling indices might suggest a relatively slow growing potential of these tumours, though the radiation-induced meningiomas were reported as being rapidly growing and malignant.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Gastrointestinal dysfunction among intensive care unit patients

This study used the Acute Physiological and Chronic Health Evaluation (APACHE II) system to select two groups of ICU patients with comparable risk of hospital death to evaluate the importance of GI dysfunction, defined as failure to tolerate enteral nutrition (EN), as a prognostic factor. In our ICU, patients who have not undergone recent bowel surgery are treated by EN. Those patients who cannot tolerate EN are treated by total parenteral nutrition (TPN). One hundred and eleven patients who tolerated EN (functioning gut) and 97 TPN patients who failed to tolerate EN (GI dysfunction) were studied. The mean APACHE II scores of the two groups were 17.7 +/- 6.5 (SD) and 17.7 +/- 5.1, respectively. The observed mortality of patients with GI dysfunction (51%) was significantly higher (p less than .0005) than that of patients with a functioning gut (25%). This was associated with significantly poorer APACHE II mean BP, oxygenation, and creatinine scores among the GI dysfunction patients. Our results suggest that shock, ischemia, and hypoxemia, in addition to causing impairment of renal function, may bring about changes in the GI tract, evident clinically only as a failure to tolerate EN, which have an adverse effect on the prognosis of ICU patients so affected.     

Not Geropharmacotherapy 101

Critical to survival is the geriatric concept, allostasis, defined as the ability to achieve stability through change. It is appropriate that allostasis is an introduction to this commentary, which may partially apply to the medical and pharmacy profession as currently constituted.