Higher chlorzoxazone clearance in obese children compared with nonobese peers.

AIMS: To test the in vivo activity of Cytochrome P450 (CYP) 2E1 in obese children vs. nonobese children, aged 11-18 years. Secondly, whether the activity of CYP2E1 in these patients is associated with NALFD, diabetes or hyperlipidaemia. METHODS: Seventy children were divided into groups by body mass index (BMI) standard deviation score (SDS). All children received 250 mg oral chlorzoxazone (CLZ) as probe for CYP2E1 activity. Thirteen blood samples and 20-h urine samples were collected per participant. RESULTS: Obese children had an increased oral clearance and distribution of CLZ, indicating increased CYP2E1 activity, similar to obese adults. The mean AUC0-∞ value of CLZ was decreased by 46% in obese children compared to nonobese children. The F was was increased twofold in obese children compared to nonobese children, P < 0.0001. Diabetic biomarkers were significantly increased in obese children, while fasting blood glucose and Hba1c levels were nonsignificant between groups. Liver fat content was not associated with CLZ Cl. CONCLUSION: Oral clearance of CLZ was increased two-fold in obese children vs. nonobese children aged 11-18 years. This indicates an increased CYP2E1 activity of clinical importance, and dose adjustment should be considered for CLZ.

Treatment of 5413 hypertensive patients: a cross-sectional study.

BACKGROUND: Most hypertensive patients are managed in primary care in Denmark, but previous studies have shown that only 21-43% of hypertensive patients achieve optimal blood pressure (BP) control. Antihypertensive drug treatment, risk factors and cardiovascular disease (CVD) are some of the important factors to consider when optimizing the individual treatment strategy in hypertensive patients. OBJECTIVE: To examine treatment of BP according to Danish guidelines (BP < 140/90 mmHg generally and <130/80 mmHg for diabetics) in a population from general practice in relation to risk factors, CVD and diagnosis of diabetes. METHODS: A cross-sectional study comprising 184 practices and 5413 hypertensive patients was carried out in Denmark. The general practitioners filled in information on each patient's risk factors, CVD and antihypertensive drug treatment. Patients filled in a questionnaire on risk factors. The outcome measures were optimal BP control according to Danish guidelines and antihypertensive drug treatment. RESULTS: Mean patient age was 65.9 years [95% confidence interval (CI): 65.6-66.1]. Optimal BP control was achieved in 29.1% (95% CI: 27.9-30.3) of the study population. Among 842 diabetics with or without CVD, optimal BP control was achieved in 10.9% (95% CI: 8.8-10.3), while 38.7% (35.5-41.9) of patients with CVD achieved optimal BP control. The majority of all patients were treated with 1 (32.5%, 95% CI: 32.5 (31.3-33.8)) or two antihypertensive drugs (39.0%, 95% CI: 38.2-40.8). In hypertensive diabetics, 17.7% were not treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. CONCLUSION: In general practice, the proportion of hypertensive patients achieving optimal BP control is inadequate. The majority of hypertensive patients are treated with only one or two antihypertensive drugs.

Dose-response study of probiotic bacteria Bifidobacterium animalis subsp lactis BB-12 and Lactobacillus paracasei subsp paracasei CRL-341 in healthy young adults.

OBJECTIVE: This study was performed to investigate the dose-response effects of supplementation with Bifidobacterium animalis subsp lactis (BB-12) and Lactobacillus paracasei subsp paracasei (CRL-431) on blood lipids, recovery from feces and bowel habits. Changes of the fecal microflora was analyzed in the 10(10) CFU/day probiotic and placebo group. DESIGN: The study was designed as a randomized, placebo-controlled, double-blinded, parallel dose-response study. SUBJECTS: Healthy young adults (18-40 years) were recruited by advertising in local newspapers. Of the 75 persons enrolled, 71 (46 women, 25 men, mean age 25.6 years (range 18-40 years)) completed the study. INTERVENTION: The volunteers were randomly assigned into five groups receiving either placebo or a mixture of the two probiotics in the concentration of 10(8), 10(9), 10(10) or 10(11) CFU/day in 2 weeks run-in period, 3 weeks intervention and 2 weeks wash-out. Diary reporting bowel habits and well being (abdominal bloating, flatulence and headache) was kept for all 7 weeks and blood lipids, fecal recovery of BB-12 and CRL-431, as well as fecal microflora was tested before, immediately and 2 weeks after intervention. RESULTS: The fecal recovery of BB-12 increased significantly (P < 0.001) with increasing dose. In the group receiving 10(11) CFU/day BB-12 was recovered from 13 out of 15 volunteers. CRL-431 was not recovered in any of the fecal samples. Supplementation with probiotics did not change the fecal bacterial composition. A significant linear increase in fecal consistency (looser stool) with increasing probiotic dose (P = 0.018) was observed. No overall dose-response effect was found on the blood lipids. High doses of probiotics were well tolerated. CONCLUSION: A dose-related recovery of BB-12 from feces was observed.

Antitrophic properties of antihypertensive drugs may depend solely on their blood pressure-lowering capability. A comparative study of isradipine, hydralazine, and metoprolol.

The objective of this study was to examine the effect of antihypertensive treatment on the structure of intramyocardial resistance vessels in spontaneously hypertensive rats. The rats were divided into four groups: one was used as control and the other three were treated from the age of four to 24 weeks with isradipine, hydralazine, and metoprolol, respectively. Half of the animals in each group were examined at the end of active treatment and the rest were examined three weeks later. The rats were anesthetized and killed during constant flow perfusion with 1 percent glutaraldehyde. The media index was determined by point counting. The media indices of rats treated with isradipine and hydralazine were significantly smaller than those of age-matched spontaneously hypertensive rat controls, whereas the media indices of rats in the metoprolol group did not differ significantly. Three weeks after treatment withdrawal, the media index tended to increase in all three groups, but the values for the isradipine and hydralazine groups were still significantly reduced. Non-invasive blood pressure measurements taken at the same time demonstrated a significant blood pressure reduction in all groups, although differences within each treatment group were evident. All pressures had stabilized on the level of spontaneously hypertensive rats three weeks after withdrawal. Thus, it is evident that both isradipine and hydralazine were able to prevent hypertrophy of intramyocardial vascular structure and continue to do so even after treatment withdrawal. This finding is consistent with previous findings, suggesting a close relationship between the extent of blood pressure reduction and the degree of prevention of vascular hypertrophy.

Smoking related to 24-h ambulatory blood pressure and heart rate: a study in 352 normotensive Danish subjects.

This study shows the association between smoking and both office and ambulatory blood pressure. By means of stratification, a uniform number of subjects of both sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from the local community register. A total of 352 subjects participated, including 161 smokers. Smokers (both sexes and all age groups summed), as compared with nonsmokers had statistically significant lower office blood pressure as follows (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/- 2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/- 1.1). The intraperson variability of the day ambulatory blood pressure (as measured every 15 min) was identical for the smokers and the nonsmokers. Smokers were found to have a diminished "white coat" effect; this diminished white coat effect has not previously been described. The major white coat effect was seen in the older nonsmokers, whereas the diminished white coat effect was most pronounced in the older male smokers and in the younger female smokers. Smokers seem to have a diminished white coat effect, as well as a lower ambulatory blood pressure throughout the day (diastolic) and at night (systolic and diastolic). The similar intraperson variability found in the smokers' and nonsmokers' blood pressure further speaks for a consistently lower blood pressure in smokers as compared with nonsmokers.

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender.

UNLABELLED: The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION: Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

Unchanged acetylation of isoniazid by alcohol intake.

SETTING: In 10 healthy subjects, the influence of acute alcohol intake on the pharmacokinetics of isoniazid (INH) was studied. OBJECTIVE: To test the hypothesis that alcohol increases the conversion of INH by acetylation into its metabolite acetylisoniazid. DESIGN: In a crossover design, an oral dose of 300 mg INH was administered on 2 separate days, 14 days apart, with or without alcohol to a serum alcohol of about 21 mmol/l (1 g/l) maintained for 12 h. RESULTS: Neither the metabolism of INH nor that of acetylisoniazid was changed by acute alcohol intake. CONCLUSION: Acute alcohol intake has no impact on the conversion of INH to its metabolite acetylisoniazid, which is catalysed by the enzyme N-acetyltranferase. Accordingly, a metabolic effect of acute alcohol intake on INH metabolism probably contributes little to the therapeutic failure of anti-tuberculosis treatment among alcoholics.

A randomized comparison of isradipine slow release given once daily with isradipine twice daily on 24 hour blood pressure in hypertensive patients.

Isradipine, a new calcium channel blocker, was given to 32 patients with mild to moderate essential hypertension. After a run-in period of three weeks, 32 patients were randomized double-blindly to six weeks' treatment with either isradipine 2.5 mg twice daily or isradipine 5.0 mg once daily in a modified release formulation. Based on conventional 'clinic' BP measurements 12 or 24 hours postdose, the two treatments resulted in clinically relevant BP reduction (16/11 and 19/15 mmHg) without reflex tachycardia. No differences were seen between the groups. Efficacy increased throughout the study period. By determination of the 24 hour BP profile with a noninvasive method, the two groups were comparable during the placebo period, and no differences were seen between the two treatments. Both treatments resulted in satisfactory BP reduction during 24 hours (daily reduction of 4/6 and 12/9 mmHg twice daily and once daily dosing respectively). One third of the patients had 'white-coat' hypertension based on ambulatory daytime mean BPs, compared with conventional measurements. No relationship was found between the initial BP lowering effect and the effect after long-term treatment with isradipine in either dose.

Effect of oral calcium supplementation on blood pressure in patients with previously untreated hypertension: a randomised, double-blind, placebo-controlled, crossover study.

It has been claimed that calcium lowers BP. The present randomised, double-blind, placebo-controlled crossover study is the first to investigate the effect on BP of a high oral dose of calcium given for a long period to patients with previously untreated hypertension. Elemental calcium (2 g) was administered for 12 weeks interchanging with a period of 12 weeks of placebo. Twenty patients completed the protocol. There was no significant difference in change of BP during the period of additional calcium intake when compared with placebo (P = 0.33). The risk of not detecting a real BP-lowering effect of calcium of at least 3 mmHg was < 5%. No evidence for the existence of a subgroup of 'responders' was found. It is concluded that a high daily dose of calcium supplementation given for 12 weeks does not decrease BP in previously untreated patients with mild to moderate hypertension.

Development of a polyclonal antibody-based sensitive enzyme-linked immunosorbent assay for fumonisin B(4).

Polyclonal antibodies (PAb) against fumonisin B(4) (FmB(4)), which have good cross-reactivity with four major fumonisins, were produced by immunizing a rabbit with FmB(4)-keyhole limpet hemocyanin conjugate. A sensitive competitive direct enzyme-linked immunosorbent assay (CD-ELISA) for fumonisins was developed. Because of the limited supply of FmB(4), both FmB(1)-horseradish peroxidase conjugate (HRP) and FmB(3)-HRP were tested as the toxin-enzyme markers in the CD-ELISA. In the FmB(1)-HRP-based CD-ELISA, the concentrations of FmB(1), FmB(2), FmB(3), and FmB(4) causing 50% inhibition of binding of enzyme marker (IC(50)) were 9.0, 2.1, 9.0, and 6.5 ng/mL (or the relative cross-reactivities toward FmB(1), FmB(2), FmB(3), and FmB(4) were 58.5, 309.5, 58.5, and 100%), respectively. In the FmB(3)-HRP-based CD-ELISA, the IC(50) values for FmB(1), FmB(2), FmB(3), and FmB(4) were 7.1, 1.9, 7.6, and 5.3 ng/mL (or the relative cross-reactivities toward FmB(1), FmB(2), FmB(3), and FmB(4) were 74, 280, 70, and 100%), respectively. The FmB(3)-HRP-based CD-ELISA was then used in a series of analytical recovery experiments using Fusarium moniliforme corn culture material spiked with FmB(1) and with clean corn spiked with a FmB(3)/FmB(4)-containing extract. The overall recovery of FmB(1) from culture material in the range of 10-100 ppm was 65%. The detection limit for FmB(1) with clean corn as matrix was between 100 and 500 ppb. F. moniliforme cultures were analyzed with the developed CD-ELISA and a well-established FmB(1) antibody-based ELISA, which is not sensitive to FmB(4). Differences in the fumonisin levels found by the two assays were used as an indication of the presence of FmB(4) in the culture material and, therefore, as a method to identify FmB(4)-producing strains. Using ELISA in combination with HPLC individual B-series fumonisins were quantified. The ELISA developed in the present study would be a useful supplement to FmB(1) antibody-based ELISA for screening of Fusarium strains for the production of major fumonisins.

Reproductive performance and productive traits of beef bulls selected for different levels of testosterone response to GnRH.

In two separate studies, one with four Hereford-Shorthorn and one with three Zebu x British crossbred bulls, the efficacy of using the testosterone response to gonadotrophin-releasing hormone (GnRH; Lutal, Hoechst) to predict differences in reproductive performance was assessed. Young bulls (17 or 29 months of age) selected for low to high (3.1 to 10.3 ng/ml) peak plasma testosterone 2 to 2.5 hours after the intramuscular injection of GnRH (62.5 to 2000 ng/kg LWT) were each later individually joined with groups of 19 to 30 cows in which estrus had been synchronized. In both studies, the rankings of bulls for overall fertility (capable cows pregnant), for libido (estrous cows mounted), and for fertilizing ability (mounted cows pregnant) were in close agreement with rankings for testosterone responses to GnRH. In the Bos indicus bulls rankings for both reproductive performance and testosterone response to GnRH were repeatable when measured at two and four years of age. Other reproductive measurements (semen quality, scrotal circumference, pen-type serving capacity tests) were less reliable predictors of reproductive performance. Measurements of liveweight gains and parasite resistance indicated that bulls superior for these characteristics do not always have satisfactory reproductive performance. These studies suggest that the testosterone response to GnRH could be a useful test to ensure that bulls selected for productive traits have adequate reproductive potential.

Incidence of Tritrichomonas foetus in young replacement bulls following introduction into an infected herd.

Three hundred 8-year-old Shorthorn and Santa Gertrudis bulls, with a 47% incidence of Tritrichomonas foetus infection in the 30 surveyed, were removed from a herd of approximately 6000 cows and replaced by 325 two-year-old Brahman bulls. A sample of 50 of the replacement bulls was examined at introduction and found to be uninfected. After 2 years, the incidence of infection in a sample of 80 of the replacement bulls was 4%. The results suggests that a major reduction in incidence of infection in extensively managed herds might be achieved by the exclusive use of young bulls for mating.

[Gamma-hydroxybutyrate--an endogenous substance and a new central nervous system stimulant. Clinical aspects of acute poisoning]. / Gammahydroxybutyrat--en endogen substans og et nyt rusmiddel. Kliniske aspekter hos den akut forgiftede patient.

During the last six months, the Poison Control Centre at Bispebjerg Hospital, Copenhagen, Denmark, has observed an increasing number of patients intoxicated with GHB, a drug of abuse. The patients are often admitted to the emergency ward shortly after having taken the drug, unconscious or comatose. If younger patients present with these symptoms, intoxication with GHB should be seriously considered. The effects are seen within 15 to 30 minutes after oral ingestion of the drug. Spontaneous recovery usually occurs within three to five hours. The most common effects are mild euphoria, sedation, vomiting, somnolence, bradycardia, aggressive behaviour, apnoea, respiratory depression, and coma. Normally the patient breathes adequately, but insufficient respiration may occur and deaths have been described. The drug is often consumed together with alcohol and other drugs of abuse, which strengthens the effect of GHB. Treatment is symptomatic. A review of the literature with special emphasis on clinical effects included toxicology and treatment is given.

[Amphetamine, ecstasy and cocaine. Clinical aspects of acute poisoning]. / Amphetamin, ecstasy og cocain. Kliniske aspekter hos den akut forgiftede patient.

Consumption of the illicit drugs amphetamine, ecstasy and cocaine is increasing in Denmark and Europe leading to an increasing number of intoxications with these drugs. Abroad, several deaths after ingestion of a few doses of the drugs have been reported. Amphetamine, ecstasy and cocaine increase the amount of dopamine, norephedrine and serotonine in the nervous system, resulting in CNS stimulation and a general sympathomimetic stimulation. Symptoms to be treated originate mainly from the CNS and the cardiovascular system, and present as tachycardia, hypertension and seizures, later hypotension and coma. Hyperpyrexia, rhabdomyolysis and affections of the kidneys, lung and liver function are also often seen. Hyperpyrexia is an important marker of poor prognosis, and must be handled aggressively. A review of the literature concerning the optimal treatment based on pharmacological and diagnostic considerations is given in the article.

[Physical therapy and mask treatment of chronic bronchitis and chronic obstructive lung disease (COPD)]. / Fysioterapi og maskebehandling af kronisk bronchitis og kronisk obstruktiv lungesygdom (COPD).

The literature concerning traditional chest physiotherapy (postural drainage, percussion, vibration, breathing exercises), treatments with masks (CPAP, IPPB, RMT, PEP, PEEP) and general physical training in the treatment of chronic bronchitis is reviewed. The mucociliary clearance is increased after postural drainage, cough, forced expiratory manoeuvres and general physical training, but the influence of this upon the course of the disease is unknown. Chest physiotherapy in the treatment of patients admitted on account of acute exacerbation of chronic bronchitis does not appear to help. The use of face masks in this population has only been subject to limited investigation, but results from controlled trials do not indicate any favourable effect. In contrast, general physical training seems to increase physical endurance and decrease dyspnoea. Specific rehabilitation programmes comprising psychological assistance, cessation of smoking and general physical training seem promising.

[Diurnal blood pressure. Practical, prognostic and therapeutic aspects]. / Døgnblodtryk. Praktiske, prognostiske og terapeutiske aspekter.

Outpatient blood pressure monitoring is now feasible employing good equipment which is easy to handle. However, some major problems must be solved before outpatient measurement of blood pressure (AMBP) can be employed routinely in the treatment of hypertension. Normal measurements, a satisfactory description of the AMBP curve and more prognostic studies with and without treatment are necessary.

[Fatal intracerebral hemorrhage after amphetamine intake]. / Letal intracerebral blødning efter indtagelse af amphetamin.

A fatal case of massive intracerebral hemorrhage in a 20-year-old woman after first-time amphetamine abuse is described along with a review of the literature.

[Discrepancies between medical records and dispensing records in two large hospital departments in Copenhagen]. / Uoverensstemmelse mellem journal og medicinkardex på to store afdelinger i København.

This study was performed to investigate the possible differences between prescribed medicine, as entered in the hospital record, and the medicine dispensed to the patients according to the nurse's dispensing records (NDR's) in two clinical departments at a Copenhagen University Hospital. Discrepancies were defined as either dosage differences or drugs only present in one file, and were divided into major and minor discrepancies, according to clinical significance. In the first department, discrepancies were found in 61.4% of the records, and major discrepancies were found in 35.1%. In the second department, discrepancies were found in 70.5% of the cases, and major discrepancies in 42.5%. No correlation was found between the number of drugs per patient and the number of discrepancies. A significant difference exists between what is prescribed, and what is dispensed. This can have clinical as well as legal consequences.

[Clinical pharmacological drug information. Well over one year's experience]. / Klinisk farmakologisk laegemiddelrådgivning. Godt et års erfaring.

Clinical pharmacology was established quite recently in Denmark as a medical specialty. It comprises--among other items--clinical pharmacological drug information service, the primary aim of which is to provide service to health personnel with clinical responsibility involving drugs and specific patient-related questions. Questions forwarded to the clinical pharmacological drug information service at two Copenhagen hospitals have been summarized. The questions were categorized according to the profession and the affiliation to the health care system of the inquirer as well as the nature of the question. At the two hospitals, 118 and 77 questions were answered from January 1st 1997 to June 1st 1998, respectively. Physicians employed at hospitals were responsible for the majority of the questions. Most questions concerned adverse drug reactions, choice of therapy/drug, and therapy during pregnancy or breast feeding.

[Peroral terbutaline in the treatment of patients with severe irreversible obstructive pulmonary disease]. / Peroral terbutalinbehandling af patienter med svaer irreversibel obstruktiv lungefunktionsnedsaettelse.

This investigation assesses the effect of oral terbutaline in doses of 7.5 mg twice daily as compared with placebo in patients with moderate to severe chronic airflow limitation (CAL) without reversibility. Seventeen patients completed this double-blind randomised cross-over trial. Diaries with reports of dyspnoea during activities of daily living and peak-flow measurements, were obtained. Measurement of pulmonary function, walking distance and various scorings of function after treatment for three and five weeks were assessed. The investigation demonstrates that in patients with CAL treatment with terbutaline tablets may lead to improvement of several subjective effect variables although no real improvement in the majority of objective effect variables is observed. In patients with irreversible obstructive reduction of pulmonary function, in whom no other form of treatment can be considered, oral treatment with beta-2-agonists may be attempted. If no effect is obtained, the treatment should be withdrawn after one to two months.