Cyclooxygenase-2 expression in human soft-tissue sarcomas is related to epithelial differentation

BACKGROUND: Cyclooxygenase-2 (Cox-2) is expressed by several types of epithelial malignancies, i.e., carcinomas, and inhibition of Cox-2 may have a therapeutic role in chemoprevention and treatment of cancer. The role of Cox-2 in non-epithelial malignancies, however, is unclear. MATERIALS AND METHODS: We investigated, by immuno- histochemistry, the expression of Cox-2 in 103 human soft-tissue sarcomas. RESULTS: All 10 biphasic synovial sarcomas were positive for Cox-2, but positivity was observable only in the epithelial component of these tumours. Excluding sarcomas with epithelial differentation, uniform staining of the tumour was observed in only 2 samples. In addition, positivity for Cox-2 appeared in tumour cells in only 18 samples around necrotic areas. CONCLUSION: In human soft-tissue sarcomas, Cox-2 expression seems to be associated with epithelial differentation and, in some types of sarcomas, to be expressed in otherwise negative tumours at sites of necrosis.     

Effective blood signal suppression using double inversion-recovery and slice reordering for multislice fast spin-echo MRI and its application in simultaneous proton density and T2 weighted imaging

PURPOSE: To design a multislice double inversion-recovery fast spin-echo (FSE) sequence, with k-space reordered by inversion time at slice position (KRISP) technique, to produce black-blood vessel wall magnetic resonance imaging (MRI). MATERIALS AND METHODS: In this sequence, central k-space sampling for each slice is required at inversion time (TI) of the blood signal. To fill the entire k-space, the peripheral lines are obtained less or greater the TI and using a rotating slice order. Blood flow signal suppression was first evaluated using a phantom. Simulation studies were used to investigate FSE image quality. The final sequence was then applied to the rabbit abdominal aorta MRI at 4.7 T. RESULTS: In the flow phantom study, artifacts from slow-flowing water were substantially reduced by the KRISP technique; residual water spins were dephased by the strong phase-encoding gradient required for peripheral k-space. These dephased spins flowed into the slice plane where the center of k-space was being acquired at the TI of the flowing water signal. Multislice black-blood MR images were successfully obtained in the rabbit abdomen using the sequence with the k-trajectory optimized by the simulation study. CONCLUSION: The KRISP technique was effective both in multislice double inversion-recovery FSE and in blood signal suppression.     

Adolescent smoking and exposure to tobacco marketing under a tobacco advertising ban: findings from 2 Norwegian national samples

OBJECTIVES: We examined the extent to which adolescents in Norway have been exposed to tobacco marketing despite an existing ban, and whether exposure is related to their current smoking or expectations they will smoke in the future. METHODS: Questionnaires were administered to nationally representative systematic samples of Norwegian youths aged 13 to 15 years in 1990 (n = 4282) and 1995 (n = 4065). RESULTS: About half in each cohort reported exposure to marketing. Youths reporting exposure were significantly more likely to be current smokers and to expect to be smokers at 20 years of age, after control for important social influence predictors. CONCLUSIONS: Adolescents' current smoking and future smoking expectations are linked to marketing exposure even in limited settings, suggesting the need for comprehensive controls to eliminate the function of marketing in promoting adolescent smoking.     

High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone

BACKGROUND: When cancellous bone is impregnated with antibiotics the subsequent release of antibiotics from the bone shows a high early release. Hence, impaction of large amounts of netilmicin-impregnated bone may cause toxic netilmicin values in serum. PATIENTS AND METHODS: We studied kidney and otovestibular function after impacting 50 g of netilmicin-impregnated cancellous bone during revision hip or knee arthroplasty in 20 patients. The bone was impacted in the acetabulum (n = 8), proximal femur (n = 9) and distal femur/proximal tibia (n = 3). Serum creatinine concentration was measured and audiometry was performed before and after the operation. Netilmicin concentrations in serum, joint fluid, and in urine were recorded postoperatively at regular intervals. We analyzed pharmacokinetics in two study groups receiving bone impregnated with netilmicin (50 mL), at either 50 mg netilmicin/mL (group I) or 100 mg netilmicin/mL (group II). RESULTS: Neither netilmicin-induced renal toxicity, nor otovestibular toxicity was registered. Peak serum netilmicin values in group I and group II were 0.9 (0.5-1.3) mg/L and 1.8 (0.6-4.0) mg/L, respectively (p = 0.04). Peak netilmicin concentrations in wound drainage fluid in group I and group II were 237 (9-647) mg/L and 561 (196-1132) mg/L, respectively (p = 0.01). In both groups, netilmicin was recovered in urine samples for approximately 4 weeks. INTERPRETATION: 50 grams of cancellous bone impregnated with 100 mg/mL netilmicin solution was impacted in the hip or knee joint with no adverse effects. Extremely high local concentrations of netilmicin in joint fluid were recorded postoperatively. The use of antibioitic-impregnated cancellous could be an option when performing revision of hip and knee prostheses.     

Fracture Risk in Perimenopausal Women Treated with Beta-Blockers

β2-adrenergic receptors have been identified on human osteoblastic and osteoclastic cells, raising the question of a sympathetic regulation of bone metabolism. We investigated effects of treatment with β-adrenergic receptor antagonists (β-blockers) on bone turnover, bone mineral density (BMD), and fracture risk. Within the Danish Osteoporosis Prevention Study (DOPS) a population based, comprehensive cohort study of 2016 perimenopausal women, associations between treatment with β-blockers and bone turnover and BMD were assessed in a cross-sectional design at the start of study. Moreover, in a nested case-control design, fracture risk during the subsequent 5 years was assessed in relation to treatment with β-blockers at baseline. Multiple regression- and logistic regression-analyses were performed. Treatment with β-blockers was associated with a threefold increased fracture risk (OR_adj 3.3; 95% CI: 1.1–9.4). Analyses on duration of treatment showed that women who had been treated for more than 8 years had a higher fracture risk (OR_adj 5.3; 95% CI: 1.1–26.3) than those treated for less than 8 years (OR_adj 2.4; 95% CI: 0.6–9.5). In addition, cross-sectional data showed 20% lower serum osteocalcin levels (an osteoblastic marker of bone formation) in women treated with β-blockers compared to untreated women (P < 0.001), whereas BMD at the lumbar spine and femoral neck did not differ between groups. β-blockers may decrease the activity of bone-forming cells and thereby increase fracture risk. However, confirmative studies and studies exploring mechanisms of action are needed.     

Omeprazole treatment of Korean patients: effects on gastric pH and gastrin release in relation to CYP2C19 geno- and phenotypes

This study aimed to investigate the effect of omeprazole on intragastric pH and gastrin release as well as the plasma concentration of omeprazole in relation to CYP2C19 genotypes after repeated doses in Korean patients. Twenty-six Korean patients with acid related disease were genotyped for CYP2C19 by allele specific PCR (wt/wt, CYP2C19*1/*1; wt/mut, CYP2C19*1/*2 or *1/*3; mut/mut, CYP2C19*2/*2, *2/*3 or *3/*3). Intragastric pH was monitored during 24 hr, and the plasma concentrations of omeprazole, hydroxyomeprazole, omeprazole sulfone and meal-stimulated gastrin were measured during 4 hr before and after 8 consecutive daily doses of 20 mg omeprazole. Unexpectedly the AUCs of omeprazole in the three genotypes were similarly high on Day 8. The mean 24 hr pH increased significantly in all three genotypes (paired t-test; P<0.0001), and the AUCs (4 hr) of gastrin in all patients increased markedly from 129+/-73 to 298+/-142 pMhr (P<0.0001). However, there was no statistically significant difference between the three genotypes in the mean pH and gastrin AUCs on Day 8. After 8 consecutive doses of 20 mg omeprazole, the gastric pH and the plasma gastrin were increased significantly in all three CYP2C19 genotypes, which were confirmed by high plasma concentrations of omeprazole in all three genotype groups. We suggest that the reason why the wt/wt had high concentrations of omeprazole similar to those in the other two genotype groups is that some of them were old with low CYP2C19 activity. In these patients omeprazole accumulated from the first to the eighth dose similar to that in the heterozygotes.     

Task uncertainty and rationality in medical problem solving.

QUALITY ISSUE: Medical problem-solving situations are characterized by various degrees of 'task uncertainty'--i.e. uncertainty related to the definition of a problem, the effect of a technology, the value of a solution, and so on. The need for professional discretion varies and depends on the degree of perceived task uncertainty. SUGGESTED SOLUTION: In this report it is argued that, in order to obtain rationality in problem-solving processes, differences in the degree of task uncertainty need to be met by variation in the structure of the health care organization. IMPLICATIONS: The main implications of this view are that (under norms of rationality) problem-solving processes with low task uncertainty must be organized in one way and processes with high task uncertainty in another. Furthermore, processes with high and low task uncertainty also need to be evaluated according to different standards. Some hypotheses regarding the different organizational requirements are presented.     

Psychiatric comorbidity and hostility in patients with psychogenic nonepileptic seizures compared with somatoform disorders and healthy controls

PURPOSE: To investigate the prevalence of psychiatric comorbidity and level of anxiety, depression, and aggression in patients with psychogenic nonepileptic seizures compared with those in patients with somatoform disorders and healthy controls. METHODS: Twenty-three patients with psychogenic nonepileptic seizures (PNESs) and 23 age- and sex-matched patients with somatoform disorders (SDs) underwent a clinical and a semistructured psychiatric interview (MINI) and filled in the Hospital Anxiety and Depression scale (HAD) and the Aggression Questionnaire (AQ). Twenty-three sex- and age-matched controls without psychopathology also underwent a clinical interview and completed the HAD and AQ. RESULTS: PNES reported more minor head injuries in the past than did the two comparison groups, and more unspecific EEG dysrhythmias were observed on EEG. Twenty-one PNES patients and 18 with SDs had comorbid psychiatric diagnoses. However, the mean number of comorbid psychiatric diagnoses was higher in the PNES group (1.9 +/- 0.3 compared with 1.5 +/- 0.5 in the SD group; p = 0.003). Ten PNES patients additionally had a somatoform pain disorder, and seven had an undifferentiated somatoform disorder. Both patient groups reported significantly higher levels of anxiety, depression, and anger than did the healthy controls, but the PNES patients had significantly higher level of hostility than both comparison groups. CONCLUSIONS: Increased psychiatric comorbidity is known to be associated with poorer response to regular interventions, and hostility is associated with more hostile coping patterns, often interfering with treatment compliance. Thus the increased prevalence of soft neurologic signs and comorbid psychiatric disorders and increased hostility as well in the PNES group, emphasizes that assessment and treatment of patients with PNES referred to a tertiary center requires an integrated approach involving both neurologic and psychiatric resources.