A COMPARATIVE STUDY OF TENIDAP, A CYTOKINE-MODULATING ANTI-RHEUMATIC DRUG, AND DICLOFENAC IN RHEUMATOID ARTHRITIS: A 24-WEEK ANALYSIS OF A 1-YEAR CLINICAL TRIAL

Tenidap is a novel anti-rheumatic drug that combines cytokinemodulation with cyclo-oxygenase inhibition. This 24-week, multicentre,double-blind, randomized study compared the clinical efficacy,biochemical effects and safety of tenidap 120 mg/day (once daily)with diclofenac 150 mg/day (50 mg t.i.d.) in the treatment of384 patients with active rheumatoid arthritis. After 24 weeks,improvement with tenidap was significantly greater than withdiclofenac for all five primary efficacy parameters, two ofthe four secondary efficacy parameters and 11 of the 13 ArthritisImpact Measurement Scales assessments. The superior efficacyof tenidap was apparent after 4 weeks of treatment with furtherimprovements observed by 24 weeks. The probability of discontinuationdue to lack of efficacy was significantly greater in the diclofenacgroup. Tenidap but not diclofenac was associated with significant,rapid and sustained reductions in C-reactive protein and serumamyloid A levels and with a significant reduction in plasmainterleukin-6. The nature and frequency of side-effects weresimilar in the two groups as was the discontinuation rate fortreatment-related safety reasons. Tenidap was associated withan equal incidence of elevated transaminases, but a higher incidenceof mild (     

Anthropometric Characteristics of Mohawk Children Aged 6 to 11 Years: A Population Perspective

OBJECTIVE: Recent studies have concluded that Native North American children have higher proportions of overweight and obesity than children from the general North American population. This study presents anthropometric data on a representative sample of children from the Mohawk Nation that can be used for comparison with other Native American populations. DESIGN: This is a cross-sectional study comparing distributions of anthropometric characteristics of Mohawk children to the corresponding age and gender data from the Second National Health and Nutrition Examination Survey (NHANES II). Weight, height, triceps and subscapular skinfold thickness, and waist and hip circumferences were measured in 527 children. SUBJECTS/SETTING: All children in grades 1 to 6 (aged 6 to 11 years) in the 3 elementary schools of 2 Mohawk communities in Canada, for whom parental consent was obtained, were enrolled in the present study. There were no exclusion criteria. With a participation rate of 83%, the 527 children enrolled in this study represent an unbiased sample of the population from 2 Mohawk territories. RESULTS: Compared with children studied in NHANES II, Mohawk children were similar in height and triceps skinfolds but were generally heavier, had thicker subscapular skinfolds, and had greater waist and hip circumferences. These differences were greater in older children. Mohawk children who had extreme-high weight values compared with their population means were heavier than their NHANES II counterparts. APPLICATIONS/CONCLUSIONS: Results indicated that, on average, Mohawk children seem to be slightly heavier than children in NHANES II. Except for those with extreme overweight values, Mohawk children show less variation of weight and body mass index than children in NHANES II. Finally, overweight Mohawk children seem to be more likely to carry their excess body fat truncally, compared with overweight children from NHANES II. Health practitioners working with Native American populations should be careful when assessing childhood obesity. Simple comparisons of weight or body mass index with NHANES standards may lead to inappropriate risk assessments.     

Personal and Social Factors Influencing Age at First Sexual Intercourse

Early initiation of sexual activity is aconcern, in part because of increased risk of sexuallytransmitted diseases, including HIV, and unwantedpregnancies among young people. In this study, 241 high schoolers were administered a questionnaire toestablish the relationships between age at first sexualintercourse and personal qualities (sexual style,attractiveness, physical maturity, restraint, autonomy expectations, and attitudes to gender roles),smoking and drug use, and aspects of the social context(social activities, media impact, peer norms). Therewere few effects of sex of respondent and none in which respondents' sex impacted on age ofinitiation. Overall (and among the male sample),perceptions of greater physical maturity, greater use ofuncommon (mostly illicit) drugs, and expectations of earlier autonomy significantly differentiatedbetween early and later initiators. This group offactors tends to confirm the view that early experienceof sexual intercourse is correlated with problembehaviors and a press toward adultbehaviors. For girls, this pattern was even clearer,with use of uncommon drugs being replaced as asignificant contributor to early sexual experience byrelative lack of restraint. We conclude that the desire to achieve thetransition to adulthood at an earlier age than theirpeers constitutes a powerful incentive for young peopleto become sexually active.     

Intravenous high-dose methylprednisolone efficacy for treatment of idiopathic thrombocytopenic purpura in adults

OBJECTIVE: To determine the efficacy of a short intravenous course of high-dose methylprednisolone compared with the standard treatment with prednisone for adult patients with idiopathic thrombocytopenic purpura (ITP). DESIGN: Retrospective. METHODS: For all patients diagnosed with ITP between January 1st 1988 and January 1st 1998 in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands, data were obtained until June 1st 1998. These patients had received a brief course of treatment with methylprednisolone i.v. (1 g per day on three successive days in the outpatient department) or the standard treatment (protracted oral treatment with prednisone). A response was defined as a rise in platelet count of > 50 x 10(9)/l. When a remission lasted more than a year a patient was defined as longterm responder. RESULTS: The results concerned 41 patients. The prednisone group comprised 7 males and 20 females, mean age 39 years, the methylprednisolone group comprised 2 males and 12 females, mean age 43 years. Initial treatment with prednisone or methylprednisolone resulted in equal response rates of, respectively, 63% (17/27 patients) and 64% (9/14 patients). The number of longterm responders was 8 of 27 patients in the prednisone group and 2 of 14 patients in the methylprednisolone group. At time of relapse 22 patients were treated with the other treatment modality. The response rate in the group of patients treated with prednisone after first-line treatment with methylprednisolone, was 67% (6/9), for methylprednisolone after first-line treatment with prednisone the response rate was 23% (3/13). CONCLUSION: A short intravenous course of high-dose methylprednisolone is effective as initial treatment of adults with ITP. Toxicity of longterm treatment with prednisone can be avoided in a number of patients with ITP. In patients refractory to treatment with methylprednisolone, the response rate to second-line treatment with prednisone was not negatively influenced, since two thirds of these relapsing patients subsequently responded to prednisone.     

Intra-osseus gas formation in osteomyelitis of vertebrae and pelvis by Klebsiella pneumoniae]

A 59-year-old woman had persistent sepsis after abdominal operations because of a volvulus and subsequently a retroperitoneal abscess, in spite of antibiotic treatment against Klebsiella pneumoniae, which grew in blood cultures. During abscess drainage, a haemorrhage from the infrarenal part of the aorta had occurred; in view of a presumed aortitis this part had been replaced by a bifemoral bypass. Computer tomography revealed intraosseous formation of gas in vertebrae and pelvis. At operation, abscesses were drained and necrotomy and sequestrotomy of the bone were performed. Cultures of the pus from the iliac crests showed K. pneumoniae. The antibiotic management was changed; the wounds were flushed regularly. After exposure of the wounds still draining after 6 months and vascular surgery because of occlusion of the bypass after 7 months, the patient recovered well. She died 2 years later from a cerebral haemorrhage.     

Dosimetric verification of intensity modulated beams produced with dynamic multileaf collimation using an electronic portal imaging device

Dose distributions can often be significantly improved by modulating the two-dimensional intensity profile of the individual x-ray beams. One technique for delivering intensity modulated beams is dynamic multileaf collimation (DMLC). However, DMLC is complex and requires extensive quality assurance. In this paper a new method is presented for a pretreatment dosimetric verification of these intensity modulated beams utilizing a charge-coupled device camera based fluoroscopic electronic portal imaging device (EPID). In the absence of the patient, EPID images are acquired for all beams produced with DMLC. These images are then converted into two-dimensional dose distributions and compared with the calculated dose distributions. The calculations are performed with a pencil beam algorithm as implemented in a commercially available treatment planning system using the same absolute beam fluence profiles as used for calculation of the patient dose distribution. The method allows an overall verification of (i) the leaf trajectory calculation (including the models to incorporate collimator scatter and leaf transmission), (ii) the correct transfer of the leaf sequencing file to the treatment machine, and (iii) the mechanical and dosimetrical performance of the treatment unit. The method was tested for intensity modulated 10 and 25 MV photon beams; both model cases and real clinical cases were studied. Dose profiles measured with the EPID were also compared with ionization chamber measurements. In all cases both predictions and EPID measurements and EPID and ionization chamber measurements agreed within 2% (1 sigma). The study has demonstrated that the proposed method allows fast and accurate pretreatment verification of DMLC.     

Diffuse and localized pigmented villonodular synovitis: evaluation of treatment of 38 patients

We performed a retrospective study of 38 patients with pigmented villonodular synovitis (PVNS) to evaluate the treatment and functional results. The mean age of the patients was 32 (range 12-72) years at the time of treatment. Three types of PVNS have been identified: localized nodules in 9 patients, diffuse PVNS of the entire synovial membrane in 26, a combination of a diffuse involvement of the synovial membrane and an extra-articular presentation in 1, and extra-articular lesions in 2. The location of the lesions was knee (n = 31), hip (n = 3), ankle (n = 2), femoral triangle (n = 1), and gluteal region (n = 1). The procedures performed were surgery alone, surgery combined with radiosynovectomy and radiosynovectomy only. A follow-up was done after a mean of 4 (range 1-19) years in 34 patients. A functional evaluation according to the Musculoskeletal Tumor Society was performed in 31 patients. The mean functional evaluation score of 34 patients was 24 (range 15-30). Most of the ratings were excellent or good, in 6 cases fair, and in 2 cases poor. This study demonstrates that the functional results are good despite residual or recurrent disease; in addition, we showed that functional evaluation after treatment gives an optimal view of the impact and results of the operation.     

Cell type-specific acquired protection from crystal adherence by renal tubule cells in culture

BACKGROUND: Adherence of crystals to the surface of renal tubule epithelial cells is considered an important step in the development of nephrolithiasis. Previously, we demonstrated that functional monolayers formed by the renal tubule cell line, Madin-Darby canine kidney (MDCK), acquire protection against the adherence of calcium oxalate monohydrate crystals. We now examined whether this property is cell type specific. The susceptibility of the cells to crystal binding was further studied under different culture conditions. METHODS: Cell-type specificity and the influence of the growth substrate was tested by comparing calcium oxalate monohydrate crystal binding to LLC-PK1 cells and to two MDCK strains cultured on either permeable or impermeable supports. These cell lines are representative for the renal proximal tubule (LLC-PK1) and distal tubule/collecting duct (MDCK) segments of the nephron, in which crystals are expected to be absent and present, respectively. RESULTS: Whereas relatively large amounts of crystals adhered to subconfluent MDCK cultures, the level of crystal binding to confluent monolayers was reduced for both MDCK strains. On permeable supports, MDCK cells not only obtained a higher level of morphological differentiation, but also acquired a higher degree of protection than on impermeable surfaces. Crystals avidly adhered to LLC-PK1 cells, irrespective of their developmental stage or growth substrate used. CONCLUSIONS: These results show that the prevention of crystal binding is cell type specific and expressed only by differentiated MDCK cells. The anti-adherence properties acquired by MDCK cells may mirror a specific functional characteristic of its in situ equivalent, the renal distal tubule/collecting ducts.     

Correlation of heterogeneous blood flow and fatty acid uptake in the normal dog heart

Summary Blood flow heterogeneity in normal myocardium may be caused by heterogeneous metabolic demand. We studied, from 80 tissue samples of the left ventricle (LV) of eight anesthetised, open-chest dogs (with prior -blockade (metoprolol) in four dogs), the radioactivity of²⁰¹Thalliumchloride (²⁰¹Tl), an indicator of blood flow, and of the fatty acid¹³¹-Iodine-heptadecanoic acid (¹³¹I-HDA), an indicator of metabolic demand, 3 min after intravenous injection. Global LV uptake (in percent of injected dose ×10^–2, per g tissue; mean ±SD) was 4.94±0.71 for²⁰¹Tl and 4.48±0.58 for¹³¹I-HDA in the dogs without -blockade, and 2.08±0.26 and 1.69±0.20, respectively, in dogs with -blockade (p<0.05). Beta-blockade thus decreased the fraction of cardiac output delivered to the LV, concurrently with a decreased heart rate and arterial blood pressure (p<0.05) and, thus, global metabolic demand and fatty acid uptake. Regional radioactivities per gram were normalized for mean LV radioactivities and heterogeneity was expressed as the coefficient of variation (CV). For pooled data (n=320) in dogs without -blockade, regional²⁰¹Tl and¹³¹I-HDA radioactivities varied from a factor of 0.1 to 1.6 and 0.3 to 1.8 of mean radioactivities, with a CV of 22.9 and 19.4%, respectively, and correlated (r=0.77, p<0.005). For pooled data (n=320) in dogs with -blockade, regional²⁰¹Tl and¹³¹I-HDA radioactivities varied from a factor of 0.2 to 1.5 and 0.2 to 1.6 of mean radioactivity and CV was 23.6% and 24.8%, respectively: r=0.92 (p<0.005). The endo/epi ratio for both radioactivities exceeded unity in each dog. In normal myocardium, blood flow and fatty acid uptake are thus heterogeneous, both transmurally and circumferentially, and matched, concomitantly with coupling of global blood flow to global metabolic demand and fatty acid uptake. This supports the idea that heterogeneous myocardial O₂ supply reflects heterogeneous metabolic demand.