The concentration of doxycycline in human prostate gland and its role in the treatment of prostatitis.

The concentrations of doxycycline were measured in 36 enucleated, enlarged prostate glands. After administration of 200 mg of doxycycline intravenously significant tissue concentrations (mean value 1.79 mug/g) were rapidly obtained. The mean concentration of the drug 14 hours after a repeated oral dose of 100 mg was 1.56 mug/g. The ratios of tissue and serum concentrations were 0.610 and 0.568, respectively. As there are only a few antibiotics which penetrate into the prostate, the importance of these data for the treatment of bacterial or mycoplasma prostatitis is obvious.     

Acute interstitial pneumonitis and carbamazepine therapy

A 14-year-old girl with skin rash and acute interstitial pneumonitis is presented. She had been taking carbamazepine for two months. Withdrawal of carbamazepine resulted in a prompt improvement of the clinical picture and a normalization of lung function tests. A hypersensitivity reaction to carbamazepine is suggested and the importance of a skin rash as first sign of a generalized reaction is stressed. Lymphocyte-stimulation-tests with carbamazepine were strongly positive in the patient and not in healthy persons nor in patients taking carbamazepine without adverse effects.     

Growth of analytical thinking skills over time as measured with the MATCH test

Context Ber’s Comprehensive Integrative Puzzle aims to assess analytical clinical thinking in medical students. We developed a paediatric version, the MATCH test, in which we added two irrelevant options to each question in order to reduce guessing behaviour. We tested its construct validity and studied the development of integrative skills over time. Methods We administered a test (MATCH 1) to subjects from two universities, both with a 6‐year medical training course. Subjects included 30 students from university 1 who had completed a paediatric clerkship in Year 4, 23 students from university 2 who had completed a paediatric clerkship in Year 5, 13 students from both universities who had completed an advanced paediatric clerkship in Year 6, 28 paediatric residents and 17 paediatricians. We repeated this procedure using a second test with different domains in a new, comparable group of subjects (MATCH 2). Results Mean MATCH 1 scores for the respective groups were: Year 4 students: 61.2% (standard deviation [SD] 1.3); Year 5 students: 71.3% (SD 1.6); Year 6 students: 76.2% (SD 1.5); paediatric residents: 88.5% (SD 0.7), and paediatricians: 92.2% (SD 1.1) (one‐way anova F = 104.00, P < 0.0001). Students of both universities had comparable scores. MATCH 1 and 2 scores were comparable. Cronbach’s α‐values in MATCH 1 and 2 were 0.92 and 0.91, respectively, for all subjects, and 0.82 and 0.87, respectively, for all students. Conclusions Analytical clinical thinking develops over time, independently of the factual content of the course. This implies that shortened medical training programmes could produce less skilled graduates.     

Relationship of obesity with physical activity, aerobic fitness and muscle strength in Flemish adults

AIM: The aim of this study was to analyse differences in physical activity, cardiorespiratory fitness (CRF) and muscle strength between normal weight, overweight and obese adults and to investigate the role of physical activity variables in the analyses of differences in CRF and muscle strength between these groups. METHODS: A total of 807 men and 633 women (age: 18-75 years) were included in this cross-sectional study. Weight, height, waist circumference (WC) and bioelectrical impedance were measured. Different dimensions of physical activity were assessed using a validated questionnaire. CRF (VO(2peak)) was evaluated by a maximal test on a cycle ergometer. Knee strength was measured with a calibrated Biodex System Pro 3 dynamometer. Three methods were used for classification in obesity groups: body mass index (BMI), WC and combined BMI-WC classification. RESULTS: Health-related sports and physical activity level are negatively associated with obesity in men, but not in women. Television viewing is positively associated with obesity, while VO(2peak)/fat free mass (FFM) and knee strength/FFM show a negative association with obesity in both genders. Overall, subjects with normal WC seem to be more physically active and to have somewhat better values for CRF compared to those with high WC within the same BMI category. Lower values for relative CRF and knee strength in obese subjects compared to their lean counterparts remain after adjustment for physical activity. CONCLUSION: This study confirms the lower level of physical activity and the impaired CRF and knee strength in obese adults compared to their lean counterparts. This study also sustains the importance of measuring WC and CRF during clinical examinations.     

Use of likelihood ratios improves clinical interpretation of IgA anti-tTG antibody testing for celiac disease

BackgroundWe investigated whether taking into account IgA anti-tissue transglutaminase antibody concentration (IgA anti-tTG) and total IgA concentration could improve clinical interpretation of serologic testing for celiac disease (CD).MethodsWe retrospectively identified 43 consecutive newly diagnosed CD patients and 545 consecutive disease control patients who had an IgA anti-tTG request during the 42-month study period and for whom intestinal biopsy results were available.ResultsSensitivity and specificity of the IgA anti-tTG assay from Genesis was 95.3% and 92.7%, respectively, with a likelihood ratio (LR) of 12.4. The LR for CD markedly increased with increasing IgA anti-tTG concentration (from 2.0 for results between 7 and 20 U/ml up to 319 for results > 100 U/ml). The LR for CD was also higher in patients with a normal IgA concentration (0.82–4.53 g/L) compared to patients with an increased IgA concentration (15.3 vs. 3.1, respectively). These observations were confirmed with a second IgA anti-tTG assay from BioRad.ConclusionSensitivity of IgA anti-tTG was good. Specificity, however, was reduced when IgA anti-tTG was weak positive or when the IgA concentration was increased. Taking into account IgA anti-tTG concentration and IgA concentration improves clinical interpretation of serologic testing for CD.     

Mutational spectrum of ATRX aberrations in neuroblastoma and associated patient and tumor characteristics

Neuroblastoma is the most common extracranial solid tumor in children. The chromatin remodeler ATRX is frequently mutated in high‐risk patients with a poor prognosis. Although many studies have reported ATRX aberrations and the associated clinical characteristics in neuroblastoma, a comprehensive overview is currently lacking. In this study, we extensively characterize the mutational spectrum of ATRX aberrations in neuroblastoma tumors reported in previous studies and present an overview of patient and tumor characteristics. We collected the data of a total of 127 neuroblastoma patients and three cell lines with ATRX aberrations originating from 20 papers. We subdivide the ATRX aberrations into nonsense, missense, and multiexon deletions (MEDs) and show that 68% of them are MEDs. Of these MEDs, 75% are predicted to be in‐frame. Furthermore, we identify a missense mutational hotspot region in the helicase domain. We also confirm that all three ATRX mutation types are more often identified in patients diagnosed at an older age, but still approximately 40% of the patients are aged 5 years or younger at diagnosis. Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together, our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.     

Serum proteins in the haemolytic uraemic syndrome

In 122 patients with the haemolytic uraemic syndrome (HUS), serum proteins were analysed in the acute phase of the disease (n = 122) and 6 weeks (n = 57) and 6 months (n = 84) later. Total serum protein levels were significantly lower on admission than 6 weeks and 6 months later (P < 0.0001). The same was true for median values of serum albumin (P < 0.0001), ₂-globulins (P < 0.0001) and -globulins (P < 0.001). There was no difference in -globulins, whereas the ₁-globulins were significantly higher in the acute phase (P < 0.0001). There was a significant positive correlation between age and total protein and -globulin levels. Serum total protein and albumin levels displayed a significant positive correlation with serum sodium levels and a significant negative correlation with urinary protein excretion. Patients with oligoanuria had significantly lower serum albumin and significantly higher ₁-globulin levels than those with preserved urine production. Marked differences were observed between patients with (D+) and patients without (D–) prodromal diarrhoea. In D(–) HUS, only albumin and total protein levels were lower on admission, but to a lesser degree than in D(+) HUS. Serum at-globulin levels were significantly higher and (₂-globulin levels significantly lower in D(+) HUS than D(–) HUS. In the D(+) subgroup of patients, by far the largest, there was a significant positive correlation between serum albumin and total protein on the one hand and the duration of the prodrome on the other. Patients with bloody stools had significantly lower serum albumin and total protein levels than those without. Faecal al-antitrypsin concentration measured in 12 HUS patients on admission was found to be significantly increased compared with age-matched controls. This study confirms the existence of hypoproteinaemia in childhood HUS and indicates that intestinal protein loss is an important, albeit not the only, physiopathological mechanism.     

Pancreatic autoantibodies in inflammatory bowel disease

BACKGROUND: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory bowel disease (IBD), unaffected family members, and control subjects. METHODS: A Belgian study cohort of 575 subjects, including 289 IBD patients (CD, 169 patients; ulcerative colitis [UC], 120 patients), 108 unaffected first-degree relatives, 78 subjects with non-IBD gastrointestinal disorders (gastrointestinal control subjects [GIcos]), and 100 healthy control subjects (Hcos), were tested for PAB by a standardized indirect immunofluorescence method. RESULTS: The prevalence of PABs in this study cohort was 32% for CD, 23.3% for UC, and 22.2% for their unaffected family members (all P < 0.001), compared with 1.3% for GIcos and 0% for Hcos. Two staining patterns could be observed: an intracellular pattern (IC); and an extracellular pattern (EC). The EC was significantly more prevalent in CD patients compared with UC patients (P = 0.014), and higher titers of this pattern were found in CD patients (P = 0.01). Both PAB patterns were negatively associated with stricturing disease behavior of CD (P = 0.021). The IC was associated with familial CD (P = 0.0009) and familial UC (P = 0.0003). CONCLUSIONS: The prevalence of PAB found in CD patients in this study was similar to that cited in previous reports. In contrast to these reports, we also found an increased prevalence of PABs in patients with UC and in unaffected first-degree relatives of IBD patients. We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease.