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The global public health importance of mosquitoes cannot be over-emphasised. The tourist industry relies heavily on customer satisfaction and this study examined the importance of mosquitoes as a cause of dissatisfaction amongst tourists visiting Grenada. Tourists who had spent three days or more at four popular hotels were included in the study. This study also examined the species and breeding site distribution of mosquitoes in the hotels selected. Three cross sectional surveys were carried out in both the dry and wet seasons at various time intervals and ovitraps were placed in various parts of each hotel for up to a week. Eggs collected from these traps were identified. Aedes sp were more numerous than Culex sp eggs and were more numerous in the rainy season. Of the tourists interviewed by questionaire, 87 percent had been bitten by mosquitoes during their stay; 74 percent had been bitten twice, 18 percent twenty times and 8 percent more than 20 times. Seventy-seven percent (77 percent) of tourists perceived mosquitoes as a severe biting nuisance whilst 16 percent and 7 percent perceived them as moderate or mild, respectively. Biting nuisance was most severe in the wet season and the dining room was reported as the most important site where biting took place for all hotels studied. Potential breeding sites were identified and appropriate mosquito control measures have been suggested to the hotels.(AU)

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PURPOSE: A pharmacokinetic study in children to determine plasma flumazenil concentrations after the intranasal administration of 40 microg x kg(-1). METHODS: Following institutional approval and informed written consent, 11 ASA physical status I-II patients, aged two to six years, undergoing general anesthesia for dental surgery were recruited. After induction, 40 microg x kg(-1) flumazenil Anexate, Roche, 0.1 mg x mL(-1) (0.4 mL x kg(-1))) were administered via a syringe as drops, prior to nasal intubation. Venous plasma samples were drawn prior to administration of flumazenil (t = 0), and then at 2, 4, 6, 8, 10, 15, 20, 30, 40, 60, and 120 min thereafter. The plasma samples were immediately processed by the on-site laboratory and then stored at -70 degrees C, before batch analysis via high performance liquid chromatography assay. Pharmacokinetic data calculations were performed using WinNonLin software (Scientific Consulting Inc.). RESULTS: Eleven patients were studied, but data for one patient were discarded due to insufficient sampling. The median age was 4.3 yr (range 3 to 6), with a median weight of 18.9 kg (range 14.9 to 22.2). There were seven boys and three girls. Mean Cmax was 67.8 ng x mL(-1) (SD 41.9), with Tmax at two minutes. The calculated half-life was 122 min (SD 99). CONCLUSION: The mean plasma concentrations of flumazenil attained were similar to those reported after intravenous administration, and may be sufficient to antagonize the side-effects of benzodiazepines. This route of administration may be useful when the intravenous route is not readily available.

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Long-term population-based studies have identified and quantified risk factors for cardiovascular and cerebrovascular (CCV) events. In addition, a number of well-designed clinical trials have shown that various drug therapies that reduce these factors decrease the risk of some CCV events. In the practice of evidence-based medicine, data from clinical trials should inform treatment decisions. The clinician and patient, however, are faced with the difficult task of assessing the patient's particular risk and likelihood of benefit on the basis of the results of large, randomized trials. To assist clinicians and their patients in arriving at treatment decisions, the authors provide simple nomograms for estimating the risk of a CCV event for an individual patient and suggest an approach to estimating the potential benefit of drug therapy for primary prevention.

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Although the recommended dose of rectal acetaminophen (25-30 mg.kg-1) is twice that for oral administration (10-15 mg.kg-1), the literature justifies the use of a higher dose when acetaminophen is administered via the rectal route. We measured venous plasma acetaminophen concentrations resulting from 45 mg.kg-1 of rectal acetaminophen in ten ASA 1, 15 kg paediatric patients undergoing minor surgery with a standardized anaesthetic. After induction of anaesthesia, a single 650 mg suppository (Abenol, SmithKline Beecham Pharma Inc.) was administered rectally. Plasma was sampled at t = 0, 15, 30, 45, 60, 90, 120, 180, 240 min in the first five patients and at t = 0, 30, 60, 90, 120, 180, 240, 300, 420 min in the subsequent five. Acetaminophen plasma concentrations were determined using a TDxFLx fluorescence polarization immunoassay (Abbott Laboratories, Toronto, Ontario). The maximum plasma concentration was 88 +/- 39 mumol.L-1 (13 +/- 6 micrograms.ml-1) and the time of peak plasma concentration was 198 +/- 70 min (mean +/- SD). At 420 min, the mean plasma concentration was 46 +/- 18 mumol.L-1 (7.0 +/- 0.9 micrograms.ml-1). No plasma concentrations associated with toxicity (> 800 mumol.L-1) were identified. A 45 mg.kg-1 rectal dose of acetaminophen resulted in peak plasma concentrations comparable with those resulting from 10-15 mg.kg-1 of oral acetaminophen at three hours after suppository insertion. It is concluded that the delayed and erratic absorption of acetaminophen after rectal administration leads to unpredictable plasma concentrations. Rectal acetaminophen will not be consistently effective for providing rapid onset of analgesia in children.

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Previous studies have shown that the injection of IgG-coated erythrocytes (EIgG) increased the mortality rate caused by bacterial lipopolysaccharide (LPS) and that animals made tolerant to LPS show a decrease in the mortality rate caused by LPS. The present study determined the effect of the injection of EIgG and of LPS tolerance on the depression of vascular reactivity caused by LPS in vivo or in vitro. For in vivo studies, LPS was injected intravenously into rats 2 h after the injection of E or EIgG. Aortae were removed 90 min after the injection of LPS, and cumulative concentration-response curves to phenylephrine were performed in helically cut aortic strips. LPS (.1 mg/kg) caused a 21% decrease in the maximum tension developed in response to phenylephrine in aortae from animals given erythrocytes. In contrast, animals given EIgG showed a 63% decrease in maximum tension following the injection of this dose of LPS. For in vitro studies, the depression of vascular reactivity caused by incubation with LPS of aortae from rats injected with EIgG was determined. As with the in vivo studies, there was a greater depression of vascular reactivity caused by incubation with LPS of aortae taken from animals injected with EIgG. Similar studies were carried out with rats made tolerant to LPS. Tolerance was induced by giving a regimen of five daily injections of LPS. Following the injection of LPS (1 mg/kg), the maximum tension of aortae from sham tolerant animals was depressed 63%, while aortae from LPS tolerant animals were depressed only 16%.(ABSTRACT TRUNCATED AT 250 WORDS)

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OBJECTIVE: To evaluate the prevalence of pain, how pain affects patients' lives, what treatments are being used, and the effectiveness of these pain treatments in ambulatory patients with human immunodeficiency virus (HIV) disease. DESIGN: A self-administered pain survey (modified version of the Wisconsin Brief Pain Questionnaire). SETTING: An ambulatory infectious disease clinic that deals mainly with ambulatory HIV patients. PATIENTS: Ambulatory HIV patients. OUTCOME MEASURES: Results of the response to the questionnaire. RESULTS: Eighty-two of 148 patients surveyed had pain due to their disease in the month prior to completing the survey. Of those reporting pain, 60-70% reported that their pain interfered with aspects of their daily lives from a moderate to severe degree. In patients with pain, 40% reported that they were not receiving any pain treatment. Those patients who were receiving treatment only obtained a mean pain relief of 65%. CONCLUSIONS: Pain is an important problem in terms of its prevalence and impact on patients with HIV disease. Pain control in this patient population is inadequate. Clinicians should realize that pain can be present regardless of the duration of the disease and its severity. Patients need to be educated about the proper use of pain medications and helped to understand that pain medications will not "worsen their disease."

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OBJECTIVE: To illustrate the concepts of relative and absolute risk reduction, and by example, present and discuss the results of prevention trials that have evaluated the impact of drug therapy on cardiovascular disease. Additional approaches to evaluating the results of prevention trials are also presented. DATA SOURCES: Data were gathered from eight frequently quoted major cardiovascular intervention trials. CONCLUSIONS: Reference to large reductions in relative risk in review papers, newspapers, and at professional meetings can lead to false expectations among clinicians and patients regarding the potential impact of the treatment in individual patients. When making decisions about preventive drug therapy, clinicians are encouraged to examine measures other than relative risk reduction and to include the patient in the decision process. Educators should emphasize these other measures of outcome and not rely solely on relative risk reduction in discussing particular areas of therapeutics.

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A randomized, placebo-controlled, double-blind clinical trial was conducted to compare the use of regularly dosed po morphine and on-demand in morphine in 47 patients undergoing total hip arthroplasty. Patients were randomized to receive either 20 mg (initial dose) of regularly dosed morphine (every four hours po) plus breakthrough pain medication on-demand consisting of both 10 mg morphine po and placebo im, or an equivalent regularly dosed oral placebo (every four hours) with breakthrough pain medication consisting of oral placebo and 5-10 mg morphine im. Subsequent to each request for breakthrough pain medication, the next regularly dosed oral solution was increased by 5 mg (or equivalent volume of placebo) to a maximum of 40 mg po Q4H. Time-averaged pain scores were lower on both postoperative day 1 and 2 in the group receiving regularly dosed morphine po (P < 0.05). Fewer patients requested breakthrough pain medication on both days in the oral morphine group. The incidence of nausea and vomiting, and of decreased respiratory rates were similar in both groups. Regularly dosed oral morphine is inexpensive and should be compared to other methods of opioid delivery.

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The manufacturers of thiopentone recommend that after reconstitution, it should be kept only for 24 hr to reduce the risk of contamination. However, there are no studies to support this practice and compliance with this recommendation has economic implications. The reasons for discarding a reconstituted bottle of thiopentone are related to concerns about chemical and physical (pH) stability, contamination with infectious agents, and contamination with cellular material. We studied the incidence of bacterial contamination and pH stability of thiopentone in clinical use, as well as the pH stability of thiopentone not in clinical use, and surveyed the eight hospitals affiliated with the University of British Columbia to determine their protocols for thiopental preparation and storage. Cost comparisons were made between our current practice of discarding thiopentone when depleted and the practice of routinely discarding it 24 hr after reconstitution. Samples of thiopentone in clinical use were cultured daily and the pH was measured. The bottles had been in clinical use from 1 to 25 days (mean 4.23 +/- 4.32 SD). Of 106 samples there were no positive bacteriological cultures and there were only minor changes in pH. The telephone survey of the eight hospitals revealed that only one had a policy to discard thiopentone after 24 hr. Cost comparisons indicate that discarding thiopentone 24 hr after reconstitution would result in increased cost. In conclusion, reconstituted thiopentone retains its alkalinity for up to four weeks, and has an acceptably low risk of bacterial contamination for periods beyond 24 hr, therefore thiopentone need not be discarded after 24 hr.

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Routine pharmacokinetic drug monitoring has become an inherent component of aminoglycoside therapy over the last 10-15 years. The intent of this monitoring is to improve the outcome of treatment and to decrease the incidence of toxicity through the attainment and maintenance of serum aminoglycoside concentrations within a normal therapeutic range. The primary objective of this review was to critically analyze the scientific support for the following premises: (1) there is a causal relation between peak serum aminoglycoside concentrations in serum and the outcome of treatment; (2) there is a causal relation between trough serum aminoglycoside concentrations in serum and the outcome of treatment; (3) outcome is improved by monitoring and maintenance of serum aminoglycoside concentrations in the normal therapeutic range; (4) there is a causal relation between serum aminoglycoside concentrations and toxicity; and (5) monitoring and maintenance of serum aminoglycoside concentrations within a normal therapeutic range decrease the risk of toxicity. After a critical review of the literature, it was concluded that the evidence was insufficient to support the presently accepted normal therapeutic range. Recommendations for the monitoring of aminoglycoside therapy were drawn up.

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