Wakefulness impairs selective consolidation of relevant trauma-associated memories resulting in more frequent intrusions.

Recent studies show that sleep reduces intrusive memories after analog trauma. This effect is assumed to be caused by sleep's impact on memory consolidation. However, the underlying processes of this phenomenon have not been uncovered. Thus, the current study investigates the hypothesis that sleep reduces intrusive memories by supporting the selective consolidation of relevant memories. Seventy-five participants were exposed to traumatic picture stories before nocturnal sleep or wakefulness during daytime. Memory for relevant and irrelevant trauma-associated stimuli was assessed prior to and after the retention period. Consistent with the hypothesis, results demonstrate reduced memory loss for relevant as opposed to irrelevant trauma-associated stimuli after sleep but not after wakefulness. Moreover, an incremental retention benefit for relevant trauma-associated stimuli was negatively correlated with the number of intrusive trauma memories after wakefulness. These results suggest that lack of sleep impairs selective gating of relevant trauma-associated memories, thereby enhancing intrusion development after trauma.

Determinants of success and failure of EMLA.

Although EMLA is known to be an effective topical anesthetic, its rate of success is unknown. Indeed, researchers have suggested that EMLA may fail with young and apprehensive children. Therefore, the objectives of this study were to assess EMLA's rate of success as well as factors which predict success. A double-blind, placebo-controlled design was utilized. The sample included 258 children and adolescents aged 5-18 years who were having venipuncture or intravenous (i.v.) cannulation. After having their anxiety assessed, subjects were randomly assigned to have EMLA or placebo applied over the procedure site for 90 min. The visual analogue scale was used to assess pain caused by removal of the semi-permeable dressing and by the procedure. Other information that was collected included: duration of drug application, interval between drug removal and procedure, skin changes at bandage and drug sites and rated difficulty of the procedure. EMLA was successful 84% of the time for venipuncture and 51% of the time for i.v. cannulation. Factors which predicted success of EMLA included type of procedure, duration of drug application and anxiety. EMLA was less successful for i.v. cannulation compared to venipuncture even with duration of drug application controlled. Those who had a poor outcome were more anxious than those with a good outcome. Age of child was not a factor. Strategies for improving efficient use of EMLA were recommended.

Serum theophylline profile with once-daily theophylline (Uniphyl) following conversion from intravenous theophylline in adult asthmatic patients.

Although guidelines are available for conversion from intravenous (IV) theophylline to twice-daily, oral, controlled-release theophylline, the optimal method for conversion to Uniphyl, a chronotherapeutically formulated, once-daily theophylline preparation, has not been previously evaluated. The present study was designed to prospectively evaluate a method for converting patients from IV theophylline to Uniphyl, to formulate simple, practical dosage recommendations for use in clinical practice. Ten patients with acute exacerbation of asthma receiving IV theophylline for > or = 48 hours and with steady state serum theophylline concentrations (STCs) between 4.5 and 15.5 mg/L (25 and 86 mumol/L) were enrolled into the study. Patients with STCs > or = 4.5 and < 12 mg/L (> or = 25 and < 66 mumol/L) and those with STCs > or = 12 and < or = 15.5 mg/L (> or = 66 and < or = 86 mumol/L) received their first Uniphyl dose immediately following termination of IV theophylline (No Time Lapse [NTL] group) and after a 4-hour delay (Time Lapse [TL] group), respectively. The differences in the area under the curve values between Uniphyl dosing and IV theophylline were 11% in the NTL group (1214.6 +/- 247.9 mumol/h.L-1 vs 1370.4 +/- 148.1 mumol/h.L-1, 95% confidence interval, 74% to 103%; P = 0.068) and 10% in the TL group (1959.4 +/- 165.1 mumol/h.L-1 vs 1784.6 +/- 119.4 mumol/h.L-1, 95% confidence interval, 103% to 117%; P = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)

Containing cefoxitin costs through a program to curtail use in surgical prophylaxis.

OBJECTIVE: To reduce drug costs attributable to anti-anaerobic cephalosporins - specifically to reduce cefoxitin use in surgical prophylaxis. DESIGN: Before and after intervention cefoxitin use comparison. SETTING: Tertiary care hospital. PARTICIPANTS: Hospitalized patients. INTERVENTIONS: Chart review of patients identified through pharmacy records as cefoxitin recipients was carried out to determine which physicians were the principal users of cefoxitin and the purpose for such use. These data were used to direct cost containment strategies. MAIN OUTCOME MEASURES: Hospital quarterly pharmacy acquisition costs and grams of cefoxitin used. RESULTS: The departments of surgery (49%) and obstetrics/gynecology (37%) were the principal users of cefoxitin, and surgical prophylaxis was found to be the principal indication for use (63%). These departments were invited by the Antibiotic Utilization Subcommittee of the hospital's Pharmacy and Therapeutics Committee to draft surgical prophylaxis guidelines in keeping with published recommendations. Such guidelines were written and distributed to medical staff and substituted cefazolin for most forms of prophylaxis, gentamicin/metronidazole for colorectal prophylaxis and cefoxitin only for appendectomies. Over the following 21 months, hospital-wide cefoxitin use fell from 6093 g, $70,076 per quarter, to 1316 g, $11,515 per quarter (partially offset by a 2595 g, $9,131 per quarter increase in cefazolin use). CONCLUSION: As a first step in reducing hospital costs of anti-anaerobic cephalosporins, rationalization of cefoxitin use may be preferable to formulary interchange with alternatives such as ceftizoxime or cefotetan.

Clinical presentation and management of acute 2,4-D oral ingestion.

2,4-D, an extensively used herbicide, was intentionally ingested by a 61-year-old woman. An initial serum 2,4-D concentration of 392 mg/L was measured. The prominent clinical feature was marked central nervous system depression; primary laboratory abnormalities were extreme elevation of creatine kinase activity, and transitory elevation of AST and lactate dehydrogenase enzyme activities. Alkaline diuresis was initiated early and decreased the half-life of the drug from an initial 39.5 to 2.7h. It is concluded that alkaline diuresis to produce urine pH in the range of 7.5 to 8.5 should be considered in the management of an overdose patient with central nervous system depression and a history of 2,4-D ingestion.

Isoflurane therapy for status asthmaticus in children and adults.

Two adults and two children with life-threatening asthma refractory to maximal standard therapy were treated with the inhalational anesthetic agent isoflurane. In each case, the temporal response to the initiation of therapy was striking. All patients survived and none experienced adverse reactions attributable to the drug. Rapid therapeutic benefit, minimal side effects, absence of cumulative toxicity, and ease of administration are factors supporting the use of isoflurane for patients with severe asthma.

In vitro recovery of carbamazepine from ensure.

The in vitro recovery of three different dosage forms of carbamazepine (CBZ) when dispersed in gastric or intestinal fluids, in the presence or absence of Ensure was determined. An equivalent of 1 mg of pure CBZ from Tegretol 200 mg of conventional tablets, chewtablets of Tegretol 200-mg and Apo-carbamazepine (200-mg tablets) were dispersed in five dissolution mediums (0.5 ml of Ensure; 0.5 ml of Ensure and 1.0 ml of gastric fluid; 1.0 ml of gastric fluid; 0.5 ml of Ensure and 1.0 ml of intestinal fluid; and 1.0 ml intestinal fluid) and mixed for 1 hr and filtered. The filtrates were then assayed for CBZ using a UV spectrophotometer. The mean recoveries of CBZ for all dosage forms in the various dissolution mediums were: Ensure/gastric fluid, 85%; gastric fluid, 75%, Ensure/intestinal fluid, 59%; intestinal fluid, 79%; and Ensure, 58%. The differences in CBZ recovery from gastric or intestinal fluid, in the presence or absence of Ensure were found to be statistically significant (p less than 0.05). The difference in dosage forms were statistically not discernible. The significant differences observed in recoveries of CBZ due to Ensure warrants an in vivo study to realize the clinical implication of administering CBZ with Ensure.

A survey of parenteral nutrition programs.

A questionnaire on parenteral nutrition (PN) programs was sent to Canadian hospital pharmacy directors in a random sample of 100 hospitals. The intent was to obtain information about the existing status of PN committees, PN teams, PN pharmacists, and the environment in which they function. Sixty-seven of the 74 respondents had PN programs. PN protocols were approved in 85 percent of the hospitals; and PN committees existed in 60 percent of the hospitals. Ten hospitals had multidisciplinary PN teams, with pharmacists on each team. Most of the hospitals required routine standardized laboratory tests for PN patients; but only 34 percent of the hospitals had developed monitoring forms. Canadian pharmacists have made progress in the area of PN, however, there are still opportunities for pharmacist involvement in the clinical areas of PN therapy.

Spironolactone-induced agranulocytosis.

Agranulocytosis associated with spironolactone administration is described in a 57-year-old man. Four days after initiation of spironolactone, leukocyte counts decreased from 8.2 to 2.3 X 10(9)/L with 6% neutrophils. Spironolactone, domperidone, and prochlorperazine were discontinued. Domperidone and prochlorperazine were reintroduced and there was concomitant improvement of the leukocyte and neutrophil counts. Substitution of triamterene for spironolactone was not associated with recurrent leukopenia. The potential association of spironolactone with granulocytopenia warrants increased awareness of this rare but serious adverse drug reaction.

Attitudes and hiring patterns of residency graduates by Alberta pharmacy directors.

Pharmacy directors of 126 Alberta Hospitals were sent a survey requesting information on their attitudes and hiring practices of residency graduates. Sixty completed surveys were returned for a response rate of 48 percent. Seventy percent of the directors indicated that completion of a residency program was a favourable prerequisite prior to hiring. However, pharmacists with previous hospital experience were ranked with a higher preference for hiring than pharmacists with only a residency certificate. The main reason for directors hiring residency graduates was their comprehensive hospital pharmacy background. The initial starting salary for residents was equivalent to a starting salary for a pharmacist with one to two years of previous hospital experience. A residency certificate was not seen as a requisite for the director's position by the majority of the directors.

Vitamin K1 increases sister chromatid exchange in vitro in human leukocytes and in vivo in fetal sheep cells: a possible role for "vitamin K deficiency" in the fetus.

The levels of the vitamin K-dependent clotting factors are markedly lower in the human fetus and newborn than in older infants and adults. Direct measurement of vitamin K1 in cord plasma records low or undetectable levels. This phenomenon, although the norm, is referred to as vitamin K deficiency and is a significant risk factor for hemorrhage in the fetus and newborn. Sister chromatid exchange (SCE), which may be used as an index of mutagenic activity, was assayed in cultured leukocytes of placental and adult blood following phytohemagglutinin stimulation. The mean number of SCEs per metaphase in human placental blood was 3.32 +/- SE 0.219 as compared with levels of 5.13 +/- SE 0.273 in young adults (p less than 0.01), and in the presence of added vitamin K1 at a concentration of 1 X 10(-6) M the SCE increased significantly in both adult and placental cells. In vitro SCE dose response curves to K1 in the blood of fetal and maternal sheep were obtained. When five fetal sheep were given 1 mg of K1 by catheter into the femoral vein the SCE increased from 3.94 +/- SE 0.15 preinjection to 5.38 +/- SE 0.23 at 24 h postinjection (p less than 0.01). In the pretreatment fetal sheep, serum vitamin K1 was below detectable levels in all seven animals in which it was assayed and reached levels as high as 0.3 X 10(-6) M 1 h post-K1 injection. The low level of K1 in the fetus may in fact confer some biological advantage by reducing the risk of mutagenic events during a period of rapid cell proliferation.

Vitamin K as a regulator of benzo(a)pyrene metabolism, mutagenesis, and carcinogenesis. Studies with rat microsomes and tumorigenesis in mice.

Vitamin K3 inhibits the conversion of benzo(a)pyrene to its more polar metabolites in an in vitro rat liver microsomal system. Vitamin K3 also inhibits benzo(a)pyrene metabolism in rat liver fragments and reduces its mutagenicity in the Ames test. Higher concentrations of vitamin K3 are required to comparably reduce benzo(a)pyrene metabolism when the microsomal system has been induced with 3-methylcholanthrene. High pressure liquid chromatography analysis of the products of benzo(a)pyrene metabolism shows a uniform reduction of all the metabolic products. When tumors were induced in ICR/Ha female mice by the intraperitoneal injection of benzo(a)pyrene, those mice given vitamin K3 before or both before and after benzo(a)pyrene had a slower rate of tumor appearance and tumor death rate as compared with those receiving benzo(a)pyrene alone. However, vitamin K1 increased the rate of tumor death while vitamin K deprivation and warfarin decreased the rate of tumor appearance and death in benzo(a)pyrene-injected mice. These studies indicate that vitamin K3 is an inhibitor of aryl hydrocarbon hydroxylase and reduces the carcinogenic and mutagenic metabolites in vitro, and inhibits benzo(a)pyrene tumorigenesis in vivo. That vitamin K1 enhances the benzo(a)pyrene effect while warfarin and vitamin K deficiency inhibit benzo(a)pyrene tumorigenesis indicates that vitamin K1, vitamin K deprivation, or possibly blockade of its metabolic cycle also modulates benzo(a)pyrene metabolism in vivo but by a mechanism or at a site different from the vitamin K3 effect. The vitamin K series should be considered as capable of serving a regulatory function in the metabolism of benzo(a)pyrene and possibly other compounds metabolized through the mixed function oxidase system.