Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study

OBJECTIVE: Regular physical activity is associated with decreased morbidity and mortality. Traditionally, patients with rheumatoid arthritis (RA) have been advised to limit physical exercise. We studied the prevalence of physical activity and associations with demographic and disease-related variables in patients with RA from 21 countries. METHODS: The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) is a cross-sectional study that includes a self-report questionnaire and clinical assessment of nonselected consecutive outpatients with RA who are receiving usual clinical care. Frequency of physical exercise (>or=30 minutes with at least some shortness of breath, sweating) is queried with 4 response options: >or=3 times weekly, 1-2 times weekly, 1-2 times monthly, and no exercise. RESULTS: Between January 2005 and April 2007, a total of 5,235 patients from 58 sites in 21 countries were enrolled in QUEST-RA: 79% were women, >90% were white, mean age was 57 years, and mean disease duration was 11.6 years. Only 13.8% of all patients reported physical exercise>or=3 times weekly. The majority of the patients were physically inactive with no regular weekly exercise: >80% in 7 countries, 60-80% in 12 countries, and 45% and 29% in 2 countries, respectively. Physical inactivity was associated with female sex, older age, lower education, obesity, comorbidity, low functional capacity, and higher levels of disease activity, pain, and fatigue. CONCLUSION: In many countries, a low proportion of patients with RA exercise. These data may alert rheumatologists to motivate their patients to increase physical activity levels.     

Search for intrafamilial transmission of hepatitis C virus in hemophilia patients

This study was performed to determine the risk of family members of anti-hepatitis C virus (HCV)-positive hemophilia patients (index patients) for infection with HCV compared with the risk of acquiring hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis A virus (HAV) infection. All index patients (n = 141) were found to be positive by first and second generation anti-HCV enzyme immunoassays (EIAs). Among their household contacts (n = 228), 224 were negative and 1 positive by both assays. Three contacts gave positive results in first generation anti-HCV EIA and negative results in second generation assay. This latter result was confirmed by further tests (neutralization test, synthetic peptides, and supplemental assay). Percent positivity for anti-HBc was about the same in non-sexual household contacts and sexual partners (13 of 109 [12%] and 7 of 54 [13%], respectively). Percent prevalence of anti-HBc was higher in contacts of index patients with chronic hepatitis B than in those of index patients who had recovered from that disease (6 of 20 [30%] and 14 of 133 [10%], respectively; P < .05). The HBV infection rate of contacts participating in controlled self-treatment was not higher than that of controls (3 of 57 [5%] and 10 of 98 [10%], respectively). Of 44 sexual partners, 5 (11%) were found to be positive for anti-HIV. Prevalence of anti-HAV matched with the age-related distribution in the German population. These findings suggest that intrafamilial transmission of HCV to family members of hemophilia patients is uncommon. In contacts of hemophilia patients, the risk of acquiring HBV infection seems to be as high in household contacts as in sexual contacts. Participation in controlled self-treatment does not appear to be an additional risk for HCV and HBV infection. There is no doubt that sexual transmission of HCV is less common than that of HBV and HIV.     

Laparoscopic Radical Prostatectomy Alone or With Laparoscopic Herniorrhaphy

Background and Objectives:

Prostate cancer and inguinal hernia are common health issues in men aged more than 50 years. Recently, more data are accumulating that laparoscopic radical prostatectomy (LRP) and laparoscopic inguinal hernia repair (LIHR) can be performed in the same operation. The purpose of this study was to compare patients who underwent simultaneous extraperitoneal LRP (E-LRP) and LIHR with control patients who underwent only E-LRP in a matched-pairs design.

Methods:

Medical records of 215 patients were evaluated, and 20 patients who underwent E-LRP+LIHR were compared with 40 patients who underwent only E-LRP in a matched-pairs analysis. Preoperative clinical parameters (age, body mass index, prostate-specific antigen, clinical stage, Gleason score of the prostate biopsy, and prostate volume) and operative data (operation time, duration of catheterization, length of hospital stay, estimated blood loss, time to perform the anastomosis and its quality, and the percentage of patients with bilateral lymphadenectomy) were evaluated, as well as postoperative parameters (pathological stage, Gleason score, specimen weight, follow-up duration, biochemical recurrence, complication rates, and duration of postoperative analgesic treatment).

Results:

No statistically significant differences were found in the preoperative and operative parameters between the 2 study groups. Pathological parameters and the follow-up period and complication rates were similar between the 2 groups.

Conclusion:

Performing LIHR and E-LRP during the same operation is safe and feasible in the treatment of patients with prostate cancer and inguinal hernia.     

Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia [see comments]

In two previous studies, we observed that recombinant human interleukin- 3 (IL-3) induced an increase in marrow burst-forming unit-erythroid- derived colonies in vitro in some patients with Diamond-Blackfan anemia (DBA). To determine whether a similar erythropoietic response could be induced in vivo, we treated 13 patients with DBA (aged 4 to 19 years) with two preparations of IL-3. All patients had absent absolute reticulocyte counts and markedly reduced to absent recognizable bone marrow erythroid elements; patients with circulating reticulocytes in the previous 12 months were excluded from study. All patients except 1 had failed steroid therapy and had been transfusion-dependent since infancy; 1 patient was maintained on high-dose prednisone at the time of enrollment. On the first arm of the study, IL-3 (Immunex Corp, Seattle, WA) was administered subcutaneously using a dose escalation regimen of 125 to 500 micrograms/m2/day in divided dosage at 12-hour intervals, coadministered with 1.5 mg/kg/d of oral ferrous sulphate. Of the 13 patients that entered the trial, 4 stopped prematurely because of adverse side effects. In the other 9 evaluable cases, reticulocytes increased transiently in 1 patient from 0 to 65 x 10(9)/L after 35 days of IL-3 therapy at 250 micrograms/m2, but transfusion dependency persisted. One transient peak in absolute reticulocyte count was noted in 6 other patients, but no erythroid response was observed after completion of a full course of IL-3. Oral prednisone at 0.5 mg/kg/d was then coadministered with IL-3 at 500 micrograms/m2 to 5 of the patients without effect, and treatment was stopped. In 2 patients, a second preparation of IL-3 (Sandoz Canada Inc, Dorval, Quebec, Canada) was initiated in a dose escalation regimen of 2.5 to 10 micrograms/kg and was coadministered with ferrous sulphate. No erythroid response was observed in either patient, and in one of the two, alternate-day subcutaneous recombinant erythropoietin at 300 U/kg was administered for 3 weeks in combination with daily IL-3 at 10 micrograms/kg, but no increased erythropoiesis was seen. Significant increases in white blood cell and eosinophil counts during administration of both preparations of IL-3 were observed in all patients. These data show that the response of DBA patients to IL-3 in vivo is heterogeneous and cannot be predicted from in vitro studies. The absence of a corrective effect of IL-3 in these patients with DBA indicates that a deficiency of the cytokine is not central in the pathogenesis of the disorder.     

Locus assignment of two alpha-globin structural mutants from the Caribbean basin: alpha Fort de France (alpha 45 Arg) and alpha Spanish Town (alpha 27 Val)

Two alpha-globin structural mutants were mapped to their encoding loci by in vitro translation of hybrid-selected alpha 1- and alpha 2-globin mRNA. The more highly expressed mutant, alpha Spanish Town (alpha 27Val), is encoded at the alpha 2 locus and the less expressed mutant, alpha Fort de France (alpha 45Arg), is encoded at the alpha 1 locus. These results further define the distribution of alpha-globin structural mutations within the alpha-globin gene cluster and substantiate the dominant role of the alpha 2-globin locus in alpha- globin expression.     

C-Reactive protein as a risk factor for left ventricular thrombus in patients with acute myocardial infarction

BACKGROUND: Elevated C-reactive protein (CRP) has been found to correlate with higher risk for cardiac events in patients with acute myocardial infarction (AMI). It has been suggested that CRP may be involved in initiation process of coagulation; however, the role of CRP level in the formation of left ventricular (LV) thrombus has not been studied. HYPOTHESIS: This study investigated whether CRP is a risk factor for LV thrombus in patients with AMI. METHODS: Clinical, echocardiographic, and biochemical data were analyzed in 141 consecutive patients (aged 57 +/- 13 years; 33 women) with first anterior AMI. Two-dimensional and Doppler echocardiographic examinations were performed on Days 1, 3, 7, 15, and 30. Blood samples were obtained every day during hospitalization. Serum CRP concentrations were measured by an ultrasensitive immunonephelometry method. RESULTS: Left ventricular thrombus was detected in 33 (23.4%) patients. Univariate analysis showed that patients with LV thrombus had a higher peak creatine kinase (CK) level (2,879 +/- 742 vs. 1,693 +/- 1,210 I/U, p = 0.001), higher peak CRP level (14.9 +/- 7.1 vs. 9.2 +/- 6.8 mg/dl, p = 0.001), higher wall motion score index (1.8 +/- 0.2 vs. 1.5 +/- 0.3, p = 0.002), higher apical wall motion score index (2.35 +/- 0.72 vs. 2.07 +/- 0.70, p = 0.001), larger end-diastolic volume (145.2 +/- 43.7 vs. 116.5 +/- 44.2 ml, p = 0.002), larger end-systolic volume (85.4 +/- 37.2 vs. 62.9 +/- 31.6 ml, p = 0.003), and lower ejection fraction (42.1 +/- 12 vs. 47.3 +/- 13, p = 0.04). In multivariate analyses, only peak CK level (p = 0.0001), LV apical wall motion score index (p = 0.001), and CRP levels (p = 0.001) were independent predictors of LV thrombus formation. CONCLUSIONS: These results suggest that CRP is a risk factor for LV thrombus in patients with AMI.     

Frequent methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene in pancreatic endocrine tumors

Molecular mechanisms contributing to the tumorigenesis of pancreatic endocrine tumors (PETs) are still not well understood. Allelic deletions at chromosome 22q12.3 were detected in about 30-60% of PETs, suggesting that inactivation of one or more tumor suppressor genes on this chromosomal arm is important for their pathogenesis. Because the putative tumor suppressor gene tissue inhibitor of metalloproteinase-3 (TIMP-3) has been located at 22q12.3, we undertook a genetic analysis of TIMP-3 to determine its role in the tumorigenesis of PETs. Single-strand conformational polymorphism analysis, methylation-specific PCR, RNA expression analysis, and immunohistochemistry of TIMP-3 were performed in 21 sporadic PETs. Thirteen of 21 PETs (62%) revealed TIMP-3 alterations, including promoter hypermethylation and homozygous deletion. The predominant TIMP-3 alteration was promoter hypermethylation, identified in 8 of 18 (44%) PETs. It was tumor-specific and corresponded to loss or strong reduction of TIMP-3 protein expression. Notably, 11 of 14 (79%) PETs with metastases had TIMP-3 alterations, compared with only 1 of 7 (14%) PETs without metastases (P < 0.02). These data suggest a possibly important role of TIMP-3 in the tumorigenesis of human PETs, especially in the development of metastases, which has to be further evaluated in large-scale studies.