Efficacy of Bupivacaine Delivered by Wound Catheter for Post-Caesarean Section Analgesia

Summary: A prospective, randomized, double-blind trial was conducted to assess contribution to postoperative analgesia of intermittent instillation of 0.25% bupivacaine beneath the rectus sheath in 70 women delivered by lower uterine segment Caesarean section. The operations were performed via a Pfannenstiel incision under spinal anaesthesia. Background intravenous narcotic analgesia was provided with a patient controlled analgesia system (PCAS) using a standard morphine regimen.
Overall (44 hr) mean morphine consumption was significantly greater in the placebo (saline) group compared to the treatment group (84.2 mg versus 63.3 mg. Two tailed t test p<0.001). The most significant intergroup differences in narcotic use were found in the first 4 hours and between 24 and 36 hours after commencing PCAS (Two tailed t test p=0.014 and 0.003 respectively).
Subjective pain scores were assessed with a 10 cm visual analogue scale (VAS). The mean peak VAS score was greater in controls (5.37) than the treatment group (4.25) between 18 and 24 hours postoperatively (Mann-Whitney U=424, p=0.027). There were no intergroup differences in pain scores for any other time period. The overall incidence of nausea was lower in the treatment group compared to the control group (Chi squared with Yates' correction p=0.046) and a lower degree of sedation was seen in those receiving bupivacaine between 4 and 8 hours after commencing PCAS (Mann-Whitney U=427, p=0.028). No differences in other narcotic related side-effects (vomiting and pruritus) were shown between groups.
Regular instillation of 0.25% bupivacaine beneath the rectus sheath of women delivered by Caesarean section reduces their morphine requirements by 25% in the 44 hours after operation, with an associated reduction in both nausea and early sedation.     

Blood alcohol levels of patrons leaving licensed premises in Perth,Western Australia

Abstract: We aimed to determine the alcohol consumption, blood alcohol levels (BALs) and subsequent driving of patrons leaving 15 hotels and taverns in Perth, Western Australia. Of the 414 patrons approached by interviewers on Friday and Saturday evenings, 307 (74 per cent) consented to take part. Self-reported alcohol consumption, driving intentions, perceived levels of fitness to drive and demographic information were collected using an interviewer-administered questionnaire. Observations of subsequent driving were recorded and BALs were measured by breath-alcohol meter. The patrons surveyed were predominantly male (76 per cent) and aged between 18 and 35 (87 per cent). Average reported alcohol consumption was 7.6 standard drinks for males and 4.9 drinks for females, around double the daily amount recommended by the National Health and Medical Research Council. Further, 23 per cent of the sample had consumed more than 10 drinks (male) and 6 drinks (female). With respect to BALs, 37 per cent of patrons exceeded the drink-drive limit then in force of 0.087 and 56 per cent exceeded 0.05. Of greater concern, 23 per cent who were over the 0.08 legal limit were subsequently observed to drive even though they had been informed of their BAL and legal status with respect to driving. The results suggest that most young patrons drinking in Perth metropolitan hotels and taverns consume alcohol on such occasions in excess of limits currently recommended by health authorities and attain blood alcohol levels dangerous for driving. This is likely to remain unchanged without public debate as to the responsibility of licensees in serving a potentially harmful psychotropic drug and effective enforcement of liquor licensing laws.     

Melatonin reduces nitric oxide synthase activity in rat hypothalamus

Abstract: In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.     

Eight Days of Cyclosporine Overdose: A Case Report

A 25–year-old woman was admitted to the hospital because of rising trough cyclosporine concentrations thought to be due to self-administration of 4 times the normal dosage of the drug for 8 days. Her symptoms included colicky central abdominal pains and urinary retention; her serum creatinine concentrations were elevated. Whole blood cyclosporine and metabolite concentrations were measured by high-performance liquid chromatography and monoclonal radioimmunoassays. The highest reported trough cyclosporine concentration was 5877 ng/ml, and AM1 (M17) concentration was 3425 ng/ml. A cyclosporine half-life of 91 hours was calculated. Nine days after the agent was discontinued the patient's serum creatinine concentration had returned to normal and her symptoms resolved. Due to the availability of three sizes of cyclosporine capsules, and the need for frequent dosage changes, continued vigilance is necessary to ensure that patients understand their drug regimen.     

Self-administration of GBR 12909 on a fixed ratio and progressive ratio schedule in rats

Intravenous self-administration of GBR 12909, an indirect dopamine agonist, was examined on a Fixed Ratio (FR 1) and a Progressive Ratio (PR) schedule of reinforcement in rats. Subjects were first trained to self-administer cocaine (1.5 mg/kg/inj) during daily 5 h sessions, after which GBR 12909 (0.187–1.5 mg/kg/inj) was substituted. On the FR 1 schedule, the inter-infusion interval for GBR 12909 self-administration was directly related to dose and was approximately three times longer than that established for equivalent doses of cocaine. Breaking points on the PR schedule were comparable for GBR 12909 and cocaine self-administration. The data indicate that, compared to cocaine, GBR 12909 has a longer duration of action and a similar reinforcing efficacy.     

Induction of MHC class II expression in recipient tissues caused by allograft rejection

MHC class II antigens (DR) are not commonly expressed on parenchymal cells of kidney and liver except when they are allografts undergoing rejection. The objective of this study was to determine whether allograft rejection can also induce DR upregulation in parenchymal cells of autologous recipient organs. Dogs had unilateral renal autografts to facilitate kidney sampling. All kidneys were tubular cell DR-negative. After 8-14 days each dog received a tubular cell DR-negative allograft. Tubular cell DR became positive in both allograft and autograft simultaneously, its onset and intensity correlating with blast cell infiltration and rejection in the allograft. Blast cells were first detected in the autograft after allograft nephrectomy, and then disappeared as autograft tubular cell DR diminished over the next 6-8 days. This was reproduced on repeat allografting. In 2 untreated dogs hepatocytes became positive on day 4, with no hepatic blast infiltrate. Four other dogs received cyclosporine immunosuppression. Allograft and autograft tubular cell DR, and hepatocyte DR, increased in all dogs, but were delayed while on CsA until onset of rejection despite transient earlier allograft blast infiltration. Downregulation in autograft and liver occurred together after allograft nephrectomy. An interferon-like substance appeared in plasma after allografting in association with the DR changes in native kidney and liver. Renal allorejection therefore induces upregulation of parenchymal DR expression in autologous liver and kidney of the recipient. It is probably mediated by an interferon-like substance derived from cells infiltrating the allograft. The effect is modified by CsA.     

Phase II study of 10-ethyl-10-deaza-aminopterin (10-EdAM; CGP 30 694) for stage IIIB or IV non-small cell lung cancer

Summary Thirty-one patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with intravenous 10-EdAM on a weekly basis. The starting dose was 80 mg/m², with subsequent doses adjusted depending on evidence of toxicity. There were 20 men and 11 women with a median age of 58 years (range, 33–75). Response was evaluated in 30 patients, 5 with evaluable but not measurable tumors and 25 with measurable indicator lesions. There were no complete remissions; 3 patients achieved partial remission. Nine patients had a minor response, 6 showed no change, and 12 had progressive disease. Median survival for all 31 patients was 43 weeks (range, 12–65&#x002B;). During the first 3-week period, the 10-EdAM dose was reduced or withheld in 19 patients (because of stomatitis in 12, SGPT elevation in 3, skin rash in 2, and granulocytopenia in 2), escalated in 11 patients, and unchanged in 1 patient. A mean of 34–88 mg/m²of 10-EdAM (median, 50) was given per week during the first 5-week period. Myelotoxicity was infrequent and there was no significant nephrotoxicity. Considering the modest side effects of this treatment and the conservative dose-modification schedule which mandated substantial dose reductions, we conclude that 10-EdAM is a promising antitumor agent for NSCLC.     

The Results of Water Fluoridation in Ireland

The visit of Dr. Trendley Dean to Dublin in the mid-1950s helped accelerate the decision to introduce water fluoridation as a public health measure in the prevention of caries in the Republic of Ireland. A challenge to the constitutional validity of the Health (Fluoridation of Water Supplies) Act 1960 failed and in 1964 the water supplies of Dublin city were fluoridated. Over the next seven to eight years all the major urban communities in the Republic of Ireland were fluoridated. Currently, 67 percent of the 3.5 million people in the country reside in fluoridated communities. Studies conducted over the last 20 years show that residents of fluoridated communities have better dental health than those in nonfluoridated communities—the mean dmft is lower in children and the number of natural teeth present in adults is higher.