Presence of a platelet aggregating factor in the plasma of patients with thrombotic thrombocytopenic purpura (TTP) and its inhibition by normal plasma

Three patients with thrombotic thrombocytopenic purpura (TTP) were treated by infusion of normal plasma with dramatic responses. The plasmas collected from these patients during relapse induced in vitro aggregation of washed platelets from both normal donors and the patients during remission. The platelet aggregating factor was not dialyzable or adsorbable by Al(OH)3 and was not inactivated by diisopropylfluorophosphate, hirudin, or heparin in the presence of normal amounts of antithrombin. In contrast to the platelet aggregation induced by platelet isoantibody, the platelet aggregating activity of TTP plasma diminished as a function of time when it was incubated with normal plasma at 37 degrees C. These observations suggest that at least some instances of TTP appear to be due to deficiency of a plasma inhibitor to counteract a platelet aggregating factor demonstrated to be present in the plasma of these patients.     

Treatment of Somatization Disorder with Nefazodone: A Prospective, Open-Label Study

Somatization disorder (SD) is commonly seen in medical clinics and is associated with significant impairment in functioning as well as excessive utilization of health care. While antidepressants have been studied in some functional somatic syndromes such as fibromyalgia and chronic fatigue, there are no pharmacologic treatment studies of SD itself. In this prospective, 8-week, open-label study, 15 patients diagnosed with either full SD or abridged somatization, by Escobar's criteria (four unexplained physical symptoms for men or six for women), were given nefazodone, titrated to 150 mg bid. The primary outcomes included measures of physical symptom severity (visual analogue scale), functioning (SF-36), and overall improvement (CGI). Fourteen of the 15 patients achieved the target dose of 300 mg/day and completed the trial. 73% of the patients were rated as improved on the CGI, 79% improved on the self-rated visual analogue scale and 73% of the patients improved on the SF-36. There was significant improvement for the whole group (prepost) on the SF-36, as well as on the HAM-D and the HAM-A. Of the nine patients with a categorical depression diagnosis, 55% of them were rated as improved on the CGI, and 67% improved on both the VAS and the SF-36. Of the six nondepressed patients, 67% were rated as improved on the CGI, 83% improved on the SF-36, and 50% improved on the VAS. Adverse events were generally mild and resulted in only one discontinuation. Although these data need to be confirmed in a larger, double-blind, placebo-controlled trial, they suggest that patients with SD will accept and tolerate therapy with nefazodone and that nefazodone may be a useful treatment for these patients.     

Effectiveness of a Web-Based Physical Activity Intervention in Patients With Knee and/or Hip Osteoarthritis: Randomized Controlled Trial

Background

Patients with knee and/or hip osteoarthritis (OA) are less physically active than the general population, while the benefits of physical activity (PA) have been well documented. Based on the behavioral graded activity treatment, we developed a Web-based intervention to improve PA levels in patients with knee and/or hip OA, entitled “Join2move”. The Join2move intervention is a self-paced 9-week PA program in which the patient’s favorite recreational activity is gradually increased in a time-contingent way.

Objective

The aim of the study was to investigate whether a fully automated Web-based PA intervention in patients with knee and/or hip OA would result in improved levels of PA, physical function, and self-perceived effect compared with a waiting list control group.

Methods

The study design was a two-armed randomized controlled trial which was not blinded. Volunteers were recruited via articles in newspapers and health-related websites. Eligibility criteria for participants were: (1) aged 50-75 years, (2) self-reported knee and/or hip OA, (3) self-reported inactivity (30 minutes of moderate PA, 5 times or less per week), (4) no face-to-face consultation with a health care provider other than general practitioners, for OA in the last 6 months, (5) ability to access the Internet weekly, and (6) no contra-indications to exercise without supervision. Baseline, 3-month, and 12-month follow-up data were collected through online questionnaires. Primary outcomes were PA, physical function, and self-perceived effect. In a subgroup of participants, PA was measured objectively using accelerometers. Secondary outcomes were pain, fatigue, anxiety, depression, symptoms, quality of life, self-efficacy, pain coping, and locus of control.

Results

Of the 581 interested respondents, 199 eligible participants were randomly assigned to the intervention (n=100) or waiting list control group (n=99). Response rates of questionnaires were 84.4% (168/199) after 3 months and 75.4% (150/199) after 12 months. In this study, 94.0% (94/100) of participants actually started the program, and 46.0% (46/100) reached the adherence threshold of 6 out of 9 modules completed. At 3 months, participants in the intervention group reported a significantly improved physical function status (difference=6.5 points, 95% CI 1.8-11.2) and a positive self-perceived effect (OR 10.7, 95% CI 4.3-26.4) compared with the control group. No effect was found for self-reported PA. After 12 months, the intervention group showed higher levels of subjective (difference=21.2 points, 95% CI 3.6-38.9) and objective PA (difference=24 minutes, 95% CI 0.5-46.8) compared with the control group. After 12 months, no effect was found for physical function (difference=5 points, 95% CI −1.0 to 11.0) and self-perceived effect (OR 1.2, 95% CI 0.6-2.4). For several secondary endpoints, the intervention group demonstrated improvements in favor of the intervention group.

Conclusions

Join2move resulted in changes in the desired direction for several primary and secondary outcomes. Given the benefits and its self-help format, Join2move could be a component in the effort to enhance PA in sedentary patients with knee and/or hip OA.

Trial Registration

The Netherlands National Trial Register: NTR2483; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2483 (Archived by WebCite at http://www.webcitation.org/67NqS6Beq).     

The role of small intestinal bacterial overgrowth in Parkinson's disease

Parkinson's disease is associated with gastrointestinal motility abnormalities favoring the occurrence of local infections. The aim of this study was to investigate whether small intestinal bacterial overgrowth contributes to the pathophysiology of motor fluctuations. Thirty‐three patients and 30 controls underwent glucose, lactulose, and urea breath tests to detect small intestinal bacterial overgrowth and Helicobacter pylori infection. Patients also underwent ultrasonography to evaluate gastric emptying. The clinical status and plasma concentration of levodopa were assessed after an acute drug challenge with a standard dose of levodopa, and motor complications were assessed by Unified Parkinson's Disease Rating Scale–IV and by 1‐week diaries of motor conditions. Patients with small intestinal bacterial overgrowth were treated with rifaximin and were clinically and instrumentally reevaluated 1 and 6 months later. The prevalence of small intestinal bacterial overgrowth was significantly higher in patients than in controls (54.5% vs. 20.0%; P = .01), whereas the prevalence of Helicobacter pylori infection was not (33.3% vs. 26.7%). Compared with patients without any infection, the prevalence of unpredictable fluctuations was significantly higher in patients with both infections (8.3% vs. 87.5%; P = .008). Gastric half‐emptying time was significantly longer in patients than in healthy controls but did not differ in patients based on their infective status. Compared with patients without isolated small intestinal bacterial overgrowth, patients with isolated small intestinal bacterial overgrowth had longer off time daily and more episodes of delayed‐on and no‐on. The eradication of small intestinal bacterial overgrowth resulted in improvement in motor fluctuations without affecting the pharmacokinetics of levodopa. The relapse rate of small intestinal bacterial overgrowth at 6 months was 43%. © 2013 Movement Disorder Society     

Vitamin D binding protein is a key determinant of 25‐hydroxyvitamin D levels in infants and toddlers

Circulating 25‐hydroxyvitamin D (25‐OHD) levels vary among human populations. Only limited information regarding determinants of these measures is available for infants and children, particularly in minority groups at greatest risk for vitamin D deficiency. We identified demographic determinants of circulating 25‐OHD in a large cohort of minority children, and now extend our studies to examine potential roles of vitamin D binding protein (DBP) as a determinant of 25‐OHD levels. Serum DBP level and common single nucleotide polymorphisms (SNPs) at positions 432 and 436 in the GC gene, encoding DBP, were examined. We confirmed self‐reported ancestry using ancestry informative markers (AIMs), and included quantitative AIMs scores in the analysis. The multivariate model incorporated previously identified demographic and nutritional determinants of 25‐OHD in this cohort, as well as GC SNPs and circulating DBP. Genetic variants in GC differed by self‐reported ancestry. The 1f allele (D432/T436) was enriched in African Americans, occurring in 71%. Homozygosity for the 1f allele (DDTT) occurred in 53% of African Americans but only 6% of Caucasians and 13% of Hispanics. Circulating DBP was significantly correlated with 25‐OHD. GC SNPs were associated with both circulating DBP and 25‐OHD. It appears that progressive substitution of lysine for threonine at the 436 position results in lower circulating 25‐OHD. Multivariate analysis revealed that genetic variance in GC significantly contributes to circulating DBP as well as 25‐OHD. Moreover, the effect of GC SNPs on 25‐OHD are evident after adjusting for their effects on circulating DBP. Thus in young children genetic variance of the common GC T436K SNP affects circulating levels of the DBP protein, which in turn affects circulating 25‐OHD. However, the GC genotype also affects circulating 25‐OHD independently of its effect on circulating DBP. These findings provide data that may be important in the interpretation of vitamin D status in children of varying ancestral backgrounds. © 2013 American Society for Bone and Mineral Research