The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.     

A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys

The purpose of this study was to determine whether disruption of early social attachment alters the activity of brain biogenic amine systems in rhesus monkeys (Macaca mulatta). Male rhesus monkey infants were deprived of maternal interaction, peer interaction, or both, during the first 22 months of life. Cerebrospinal fluid (CSF) was collected under rigorously controlled conditions approximately every month and assayed for levels of norepinephrine (NE), its major metabolite, and the metabolites of dopamine and serotonin. Mother-Deprived infants had lower levels of CSF NE than Mother-Reared infants. Mother-Deprived infants also failed to develop the same pattern of intercorrelations between compounds and month-to-month stability in levels of neurotransmitter and metabolites in CSF as the Mother-Reared infants. Finally, there were changes in CSF NE levels associated with social separation and social group formation. The brain NE system appears to be sensitive to changes in the social environment. Its level of activity, as reflected in levels of NE in CSF, appears to depend on both the prevailing social environment and the prior rearing environment.     

The preadministration of activated charcoal and aspirin absorption.

There is little information describing the effects of activated charcoal preadministration on drug absorption. This study was undertaken to determine the effect of activated charcoal preadministration at two different times on aspirin absorption. Fifteen volunteer subjects completed three study phases: 1) 975 mg aspirin alone, 2) 975 mg aspirin 30 min after 10 g activated charcoal, and 3) 975 mg aspirin 60 min after 10 g activated charcoal. Urine was collected for 48 h after the initiation of each study phase, and total aspirin recovery determined by HPLC. The aspirin recovery was 88.8% +/- 4.5% for the control phase, and 84.8% +/- 9.4% (Phase 1) and 85.8% +/- 12.6% (Phase 2) for the activated charcoal treatments (p > 0.05). These results suggest that activated charcoal administered 30 and 60 min prior to drug ingestion has little effect on drug absorption. Further studies of the effect of charcoal preadministration on the absorption of other drugs may provide useful information regarding factors important in determining activated charcoal efficacy.     

Achieving compliance with influenza immunization of medical house staff and students. A randomized controlled trial.

OBJECTIVE--To determine the optimal method to increase influenza immunization rates of medical house staff and students. DESIGN--Prospective randomized trial and cross-sectional survey. STUDY GROUP--Four hundred forty-two internal medicine, obstetrics-gynecology, and general surgery residents and junior medical students. MEASUREMENTS--The four interventions employed were (1) an educational memorandum outlining vaccine indications sent to all study group members, (2) a personal letter mailed to a random sample of half of the remaining unimmunized persons, (3) a telephone call to half of the unimmunized letter recipients, and (4) vaccine offered directly to the remaining unimmunized persons in clinics and conferences. In addition, a questionnaire was administered to all persons requesting or offered vaccine. MAIN RESULTS--During the 3 weeks after the memorandum, 87 (20%) of 442 persons were immunized. Five weeks after the letter, 61 (34%) of persons receiving a letter and 30 (17%) of the no-letter controls (P = .0005) had been immunized. After the telephone call, there was a statistically insignificant trend toward increased compliance. In clinics and conferences, 90% of persons reached were immunized and 10% refused, largely extinguishing the effect of prior interventions. At completion of the study, 275 (62%) of 442 participants were immunized, 29 (7%) refused, and 138 (31%) were not reached. Questionnaire results revealed that only 32% had ever been previously immunized against influenza, yet 70% stated that they had worked despite having influenzalike symptoms. CONCLUSION--A high rate of immunization of house staff and medical students can be achieved most effectively by offering vaccine in clinics and conferences. Continued education about influenza immunization is necessary for physicians and medical students.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.