Propylene Glycol Monomethyl Ether: A 13-Week Inhalation Toxicity Study in Rats and Rabbits

Propylene Glycol Monomethyl Ether: A 13-Week Inhalation ToxicityStudy in Rats and Rabbits. Landry, T.D., Gushow, T.S. and Yano,B.L. (1983). Fundam. Appl. Toxicol. 3:627–630. Fischer344 rats (10/sex/exposure concentration) and New Zealand Whiterabbits (7/sex/exposure concentration) were exposed to 0, 300,1000, or 3000 ppm (0, 1.09, 3.62, or 10.9 mg/L) of propyleneglycol monomethyl ether (PGME) for 6 hr/da, 5 da/wk, for 13weeks. Minimal effects were observed in animals exposed to 3000ppm. Indications of a transient central nervous system depressionwere observed in rats and rabbits exposed to 3000 ppm. Therewere also small increases (6 to 8%) in mean relative liver weightsof 3000 ppm exposed male and female rats relative to controls.Minimal histologic effects were observed in the livers of 3000ppm exposed female rats. These were suggestive of hepatocellularhypertrophy but were without evidence of degenerative changes.There was an increase in the urinary pH of male rats exposedto 3000 ppm PGME for 4 weeks, but this was not evident after12 weeks of exposure. There was no indication of histopathologicaleffects in the kidneys of either species, and there were nohematological effects. No treatment-related effects were foundin either rats or rabbits exposed to 300 or 1000 ppm.     

Oral midazolam premedication and postoperative behaviour in children

We examined the effect of oral midazolam premedication on postoperative behaviour. Seventy children (ASA Physical Status 1 and 2; aged 1–10 yrs) were assigned randomly in a prospective, blinded fashion to receive either midazolam 0.5 mg·kg⁻¹ (maximum 10 mg) or placebo. Behaviour assessments were made prior to medication, during induction of anaesthesia and 15 min following arrival to recovery room. The baseline behavioural evaluation scores were not significantly different. The children receiving midazolam cried significantly less during induction (P≤0.02). At one week follow-up, eight of 35 subjects receiving placebo had experienced adverse behaviour changes (nightmares, night terrors, food rejection, anxiety, negativism); 19 of 35 of the midazolam group experienced these changes (P≤0.02). At four week follow-up, most behaviour changes had resolved. Children given preoperative oral midazolam were less likely to cry and fight while being anaesthetized, and preoperative sedation was associated with increased incidence of adverse postoperative behaviour changes.     

THE CAUSES OF PATIENT DROPOUT FROM PENILE SELF-INJECTION THERAPY FOR IMPOTENCE

PURPOSE: Penile self-injection therapy, a second line treatment for erectile dysfunction, is the most efficacious means of reestablishing functional erections when first line therapies fail and the patient wants to avoid penile prosthesis implantation. Despite high efficacy rates, injection therapy has high dropout rates. To our knowledge studies to date analyzing patient attrition have reviewed small numbers of patients followed for only short periods. We elucidate the main reasons for patient dropout in a large penile self-injection program with long-term followup. MATERIALS AND METHODS: A questionnaire was mailed to 1,424 patients who completed the office training and home use phases of a penile self-injection program. RESULTS: The overall attrition rate was 31% of the 720 men who completed the questionnaire, with a mean followup of 38 months. The main reasons for dropout were cost of therapy, patient and partner problems with the concept of penile injection, lack of partner availability and spontaneous improvement in erections. Lack of efficacy of therapy was the primary reason for only 1 of 7 dropouts. Furthermore, adverse effects of penile injections (priapism, penile nodules, pain) appeared to be only minor contributors to dropout. CONCLUSIONS: To our knowledge this study is the largest published, single center cohort of patients treated with injection and followed for an analysis of dropout rates. Based on study data a reduction in dropout rates may be achieved by keeping the cost of therapy low, and ensuring patient and partner education as well as continued support throughout treatment.     

Diltiazem does not always increase blood cyclosporin concentration

The pharmacokinetic interaction between the calcium channel blocking drug, diltiazem (DTZ), the antifungal agent itraconazole (ICZ) and the immunosuppressive drug cyclosporin (CsA) was studied in a patient with a single lung transplant. The CsA area under curve estimations demonstrated a significant increase when ICZ was co-prescribed (5836 μg l^-1 h vs 8159 μg l^-1 h) but no increase when DTZ was co-prescribed with CsA (5836 μg l^-1 h vs 5069 μg l^-1 h). Despite widespread use as a CsA-sparing agent, DTZ does not always increase CsA concentrations.     

Complications of cone biopsy related to the dimensions of the cone and the influence of prior colposcopic assessment

Summary. A retrospective study of the complications of cone biopsy showed that among 9 15 women examined between the years 1976 and 1982, 121 (13%) had primary or secondary haemorrhage, 153 (17%) cervical stenosis and 39 (4%) subsequent infertility or an abnormal pregnancy. Cervical stenosis was commonest among women who had had long cones removed. Stenosis occurred more often in the group of women who had been assessed by colposcopy before operation but this was due to the fact that prior colposcopy selected a favourable group of patients with lesions of limited extent that were susceptible to treatment by local destructive therapy, so that prior colposcopic assessment resulted in the removal of longer cones.