Use of a tracer activity for health centre evaluation

The effectiveness of five Finnish health centres was assessed on the basis of a study of their physiotherapy units. This single area of activity proved to be a valid indicator of the general state of affairs in the centres.     

Late onset reactions to oral food challenge are linked to low serum interleukin-10 concentrations in patients with atopic dermatitis and food allergy

BACKGROUND: Aberrant cytokine production in vitro has been associated with atopic disease. No study has as yet been made of the circulating cytokine profiles in atopic patients with food allergy in response to oral allergen challenge. OBJECTIVE: To assess the effect of oral allergen challenge on the serum cytokine concentrations in patients with atopic dermatitis and food allergy. METHODS: Serum concentrations of interleukin (IL)-10, transforming growth factor beta 1, IL-1ra, IL-6, IL-5, IL-4 and interferon (IFN)-gamma were measured before and after double-blind, placebo-controlled food challenges (DBPCFC) (n = 73). Before DBPCFC, combined skin prick and patch testing was performed for cow milk, egg, soybean and cereals, and production of IFNgamma, IL-4, IL-10 and tumour necrosis factor alpha (TNFalpha) was determined in supernatants of cultures of peripheral blood mononuclear cells (PBMCs) stimulated by cow milk. RESULTS: The oral food challenge triggered immediate onset exanthematous reactions in 22 cases and late onset eczematous reactions in 29. The late-reacting cases had more positive skin patch test and negative skin prick test reactivities with allergenic food, and they had lower serum IL10 concentrations than immediate-reacting cases. In challenge-positive cases, IL-10 concentrations increased from 2.9 (0.1-5.04) pg/mL to 3. 9 (1.2-8.3) pg/mL in response to DBPCFC, P = 0.05, median (interquartile ranges), but not in those tolerant to cow milk. PBMCs of patients with cow milk allergy but not of those tolerant to cow milk generated TNFalpha in response to cow milk in vitro. CONCLUSION: These results indicate that oral allergen challenge in atopic patients with food allergy triggers systemic release of IL-10. Patients with late onset reactions were found to have lower serum IL-10 concentrations than their immediate-reacting counterparts. Considering that IL-10 is an inhibitory cytokine of delayed-type hypersensitivity, low IL-10 in late-reacting patients may explain the high frequency of their positive skin patch tests combined with negative skin prick tests.     

Gastric air tonometry during laparoscopic cholecystectomy: a comparison of two PaCO2 levels

PURPOSE: Pneumoperitoneum can cause disturbances in acid-base balance and splanchnic perfusion. We studied the effect of ventilation on acid-base balance and gastric mucosal tonometric values in patients undergoing laparoscopic cholecystectomy. METHODS: Twenty-four patients (ASA I-II) were randomly allocated into two groups. In the fixed ventilation group, ventilation was constant allowing free increase in PCO2, while in the constant CO2 group end-tidal PCO2 was fixed with ventilatory adjustment. Intraabdominal pressure was limited to 12 mmHg. Arterial acid-base balance, automated air tonometric variables and gastric mucosal to arterial PCO2 gap were determined frequently from anesthesia induction until three hours postoperatively. RESULTS: During pneumoperitoneum, in the fixed ventilation group arterial PCO2 changed from 5.0 +/- 0.2 to 6.6 +/- 0.4 kPa and pH from 7.43 +/- 0.03 to 7.33 +/- 0.04, tonometric PCO2 from 5.1 +/- 0.5 to 6.9 +/- 0.4 and pH from 7.44 +/- 0.04 to 7.33 +/- 0.04. In the constant CO2 group these variables remained at control levels (P < 0.01 between groups). The PCO2 gap remained unchanged without any differences between the groups. In the recovery room all measured variables were within normal range in both groups. CONCLUSION: Despite inter-group differences in arterial and tonometric PCO2 and pH values during CO2 pneumoperitoneum, the patients did not develop splanchnic hypoperfusion detectable by air tonometric method, as indicated by normal PCO2 gap in both groups throughout the study.     

Prenatal diagnosis in Pelizaeus-Merzbacher disease using RFLP analysis

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with severe psycho-motor retardation and neurological symptoms due to an inborn abnormality of proteolipid protein (PLP), the major protein component of myelin. A tight linkage between the gene of PLP and PMD locus has been suggested. We have carried out a series of RFLP studies using a cDNA probe for PLP and an anonymous DNA-fragment DXYS12 in a large Finnish family with at least three affected individuals. DNA analysis on chorionic villus specimens allowed us to exclude the disease in a male fetus of a possible carrier mother and, likewise, to demonstrate carrier status in a female fetus in another at-risk pregnancy.     

Enzymic degradation of a beta-lactam antibiotic,ampicillin, in the gut: a novel treatment modality

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant beta-lactamase (TRBL) to degrade a beta-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified beta-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and beta-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the beta-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade beta-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.     

Geographical variation in the incidence of acute myocardial infarction in eastern Finland--a Bayesian perspective

BACKGROUND: Large geographical variation in the incidence and mortality of cardiovascular disease (CHD) has been repeatedly reported in Finland with persistent difference between east and west. We undertook this study to estimate the geographical distribution of Acute Myocardial Infarction (AMI) incidence in the high-risk province of North Karelia and in the province of Kuopio. METHODS: Data on men aged 25-64 years with first event of acute myocardial infarction (AMI) were obtained from the FINMONICA AMI register, which recorded detailed information of AMI events during the period 1983 to 1992. The geographical pattern of AMI incidence was studied in two five-year periods 1983 to 1987 and 1988 to 1992 separately in 10 km x 10 km grid cells employing the Geographical Information System (GIS) and a Bayesian hierarchical approach. RESULTS: In both periods Bayesian modeling revealed a geographical pattern of AMI incidence and high risk (probability that incidence exceeds the observed mean incidence) in the remote rural areas. CONCLUSIONS: Detection of high-risk areas in both provinces showed that underlying environmental and/or genetic risk factors of AMI are not evenly distributed within the province but enriched in certain geographical non-administratively defined locations in eastern Finland.     

Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide

OBJECTIVE: Our aim was to investigate the possible effects of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide, a new short-acting meglitinide analog antidiabetic drug. METHODS: In a randomized, double-blind, crossover study with 2 phases, 10 healthy volunteers took 200 mg fluconazole (400 mg on day 1) or placebo once daily for 4 days. On day 4, they ingested a single 30-mg dose of nateglinide. Plasma nateglinide and blood glucose concentrations were measured for up to 7 hours. RESULTS: Fluconazole raised the total area under the plasma concentration-time curve from time 0 to infinity of nateglinide by 48% (range, 20%-73%; P <.00001) and prolonged its half-life from 1.6 to 1.9 hours (P <.05), but the peak plasma nateglinide concentration remained unchanged. The peak plasma concentration of the M7 metabolite of nateglinide was reduced by 34% by fluconazole (P <.001), and its half-life was prolonged from 2.2 to 3.5 hours (P <.05). No significant differences were seen in the blood glucose response to nateglinide between the phases. CONCLUSIONS: Fluconazole raised the plasma concentrations and reduced the systemic elimination of nateglinide probably by inhibiting its cytochrome P4502C9-mediated biotransformation. Concomitant use of fluconazole with nateglinide may prolong its blood glucose-lowering effect.     

Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression

BACKGROUND: In adults, pravastatin reduces the development and progression of transplant vasculopathy, the main long-term risk after cardiac transplantation. The pharmacokinetics of pravastatin is not known in children taking calcineurin inhibitors. Our aim was to determine the single-dose pharmacokinetics and short-term safety of pravastatin in children undergoing regular triple-drug immunosuppressive therapy after cardiac transplantation. METHODS: Nineteen pediatric cardiac transplant recipients (aged 4.4 to 18.9 years) receiving triple immunosuppression therapy consisting of methylprednisolone (19 patients), cyclosporine (INN, cyclosporin) (17 patients) or tacrolimus (2 patients), and azathioprine (18 patients) or mycophenolate mofetil (1 patient) ingested a single 10-mg dose of pravastatin, and plasma pravastatin concentrations were measured up to 24 hours. Subsequently, the patients took 10 mg pravastatin orally once daily for 8 weeks. The lipid-lowering effect and the safety of pravastatin therapy were studied. RESULTS: The mean peak plasma concentration (C(max)) of pravastatin was 122.2 +/- 88.2 ng/mL (range, 11.4-305.0 ng/mL), and the area under the plasma concentration-time curve of pravastatin from 0 to 10 hours [AUC(0-10)] was 264.1 +/- 192.4 ng.h/mL (range, 30.8-701.6 ng.h/mL). These C(max) and AUC(0-10) values are nearly 10-fold higher than the corresponding values reported in hypercholesterolemic children in the absence of immunosuppressive therapy. The time of peak concentration (t(max)) of pravastatin was 1.1 +/- 0.4 hours (range, 0.5-2 hours), and the mean elimination half-life (t(1/2)) was 1.2 +/- 0.3 hours (range, 0.7-2.2 hours); these parameters were similar to those in the hypercholesterolemic children. By 8 weeks of treatment, the concentration of serum total cholesterol decreased by 13% (P =.005), low-density lipoprotein cholesterol by 27% (P <.0001), and triglycerides by 6% (not significant, P =.28); the concentration of high-density lipoprotein cholesterol increased by 7% (not significant, P =.30). No clinically significant increases in serum ALT, creatine kinase, or creatinine levels were observed. CONCLUSIONS: The plasma concentrations of pravastatin in pediatric cardiac recipients receiving triple immunosuppressive medication are nearly 10-fold higher than in hypercholesterolemic children after the same pravastatin dose. However, the short-term therapy of pravastatin was well tolerated and effective in lowering serum cholesterol levels in cardiac recipients.     

Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmacokinetics and neonatal exposure

Physiological changes during pregnancy may change pharmacokinetics of compounds. Oxycodone is an increasingly used opioid agonist in acute pain management but its pharmacokinetics in labouring women has not been established. We studied the maternal pharmacokinetics and neonatal exposure of intravenous oxycodone for pain relief in the first stage of labour. The study was prospective, open‐labelled and with a control group. After informed consent, 15 nulliparous parturients and newborns, and newborns in a control group were studied. In the study group, oxycodone boluses of 1 mg i.v., up to a cumulative dose of 5 mg, was administered when labour pain score was 5/10 or higher. As the control group, 30 other newborns after uncomplicated deliveries with no systemic opioids were assessed for the neonatal outcome. In the study group, maternal pharmacokinetics of oxycodone was measured from plasma concentrations during labour, and neonatal exposure was assessed from umbilical plasma samples using population pharmacokinetic methods. Maternal plasma oxycodone concentration decreased with a median half‐life of 2.6 hr (range, 1.8–2.8). Oxycodone concentrations in the umbilical plasma 2.7 μg/l (0.3–14.5) were similar as in maternal plasma 2.4 (0.1–14.8) μg/l at the time of birth. No severe or unexpected adverse effects were noted. To conclude, firstly, maternal elimination half‐life of i.v. oxycodone was significantly shorter than that reported in non‐pregnant women, and secondly, maternal plasma oxycodone at the birth correlated well with neonatal umbilical concentrations and may, thus, be used as an estimate of neonatal exposure.