Whole genome association study of rheumatoid arthritis using 27 039 microsatellites

A major goal of current human genome-wide studies is to identify the genetic basis of complex disorders. However, the availability of an unbiased, reliable, cost efficient and comprehensive methodology to analyze the entire genome for complex disease association is still largely lacking or problematic. Therefore, we have developed a practical and efficient strategy for whole genome association studies of complex diseases by charting the human genome at 100 kb intervals using a collection of 27,039 microsatellites and the DNA pooling method in three successive genomic screens of independent case-control populations. The final step in our methodology consists of fine mapping of the candidate susceptible DNA regions by single nucleotide polymorphisms (SNPs) analysis. This approach was validated upon application to rheumatoid arthritis, a destructive joint disease affecting up to 1% of the population. A total of 47 candidate regions were identified. The top seven loci, withstanding the most stringent statistical tests, were dissected down to individual genes and/or SNPs on four chromosomes, including the previously known 6p21.3-encoded Major Histocompatibility Complex gene, HLA-DRB1. Hence, microsatellite-based genome-wide association analysis complemented by end stage SNP typing provides a new tool for genetic dissection of multifactorial pathologies including common diseases.     

Minimal incision transinguinal repair for incarcerated obturator hernia

Background

Patients with incarcerated obturator hernia are usually elderly, frail, and physically inactive women with serious comorbidities. Although a laparotomy is standard surgical intervention for emergency incarcerated or strangulated obturator hernia, it is invasive particularly for these high-risk patients. The aim of this study is to show the feasibility of minimum open inguinal approach to reduce surgical risk for preoperatively diagnosed incarcerated obturator hernia.

Methods

Between April 2008 and July 2012, 3 consecutive incarcerated obturator hernia patients at Kamitsuga General Hospital who were diagnosed preoperatively by computed tomography underwent the following procedure. First a 4 cm inguinal hernia incision and preperitoneal dissection through the opening of the deep inguinal ring are made. The obturator hernia can be easily found 2 cm dorsally from the Cooper’s ligament extraperitoneally. A small incision is made at medial sharp edge of the hernia defect. The hernia sac and its content can then be reduced. If the incarcerated bowel is viable, a prosthetic mesh is placed as a patch. If the bowel is necrotic, the damaged bowel loop is withdrawn through the wound and easily reconstructed extra-abdominally.

Results

All operations were successfully completed with this procedure. All patients recovered without incident.

Conclusions

Minimal incision transinguinal repair for diagnosed incarcerated obturator hernia is feasible and provides an improved option to more invasive procedures.     

Simple way to improve accuracy in diagnosis of quadrant inflammatory disease: how to avoid adverse laparotomy by using plain CT

BACKGROUND/AIMS: It has been reported that contrast computed tomography (CT) provides a rapid and accurate diagnosis of acute appendicitis, and could potentially prevent adverse appendectomy. In the present study, we evaluated the diagnostic value of precontrast CT combined with that of serum C reactive protein (CRP) concentration for right lower quadrant inflammatory diseases. METHODOLOGY: One hundred consecutive patients who had rebound tenderness and muscular rigidity or guarding on right lower quadrant underwent an emergency abdominal CT without contrast medium and laboratory tests. Based on the CT findings, 10 patients with peritonitis and 41 patients with definite acute appendicitis underwent emergency operations. Of 19 patients with negative CT findings, 11 patients who had positive CRP levels also underwent emergency appendectomies. The remaining patients, of whom 8 had negative CRP levels and 30 had CT findings of other inflammatory diseases, underwent conservative therapy and were examined again later on. RESULTS: The final diagnosis was acute appendicitis in 58 cases, other intestinal diseases in 21, gynecological disease in 6, urolithiasis in 1, and unknown in 14. Among 86 patients who underwent emergency operations and had a pathological diagnosis, CT had a sensitivity of 81% for the diagnosis of appendicitis, with a specificity of 89%, and an accuracy of 84%. CT combined with serum CRP concentration yielded a sensitivity of 100%, an accuracy of 97%, and a specificity of 89%. The adverse appendectomy rate was 3%. None of the patients underwent a delayed appendectomy. CT differentiated other inflammatory diseases from acute appendicitis in 23 patients. CONCLUSIONS: It may be concluded that precontrast CT scan combined with serum CRP can provide a rapid and accurate diagnosis of acute appendicitis and other right lower quadrant inflammatory diseases.     

Evaluation of coronary flow velocity and coronary flow reserve before and after coronary angioplasty using transthoracic Doppler echocardiography and Doppler guide wire

Evaluation of left anterior descending coronary (LAD) blood flow before and after coronary angioplasty was carried out non-invasively by ultrasonic Doppler echocardiography with a newly developed digital, high-frequency, high-resolution transthoracic ultrasonic Doppler flowmeter and a 7.5 MHz probe. The results were compared with those obtained using an intracoronary Doppler guide wire. Sixteen patients, 12 males and 4 females (mean age 57 +/- 14 years) with old myocardial infarction (8 patients) and angina pectoris (8 patients) were studied. Coronary flow reserve was compared following intravenous administration of adenosine triphosphate in 12 patients. The LAD blood flow was detected in 15 of 16 patients. There was a significant increase in the diastolic peak velocity from 22.2 +/- 10.6 to 29.4 +/- 14.6 cm/sec (mean +/- SD) and the coronary flow reserve from 1.8 +/- 0.3 to 2.8 +/- 0.6 (mean +/- SD). There was a good correlation between the data obtained using transthoracic flow measurement and intracoronary flow measurement (r = 0.61, p < 0.05). LAD blood flow can be easily detected parasternally using a digital, high frequency, high-resolution ultrasonic Doppler flowmeter. This method may be applicable for judging the efficacy of coronary angioplasty by measuring coronary flow reserve and for observing the clinical course of the patient non-invasively.     

Detection of coronary artery disease by free-breathing, whole heart coronary magnetic resonance angiography: our initial experience

Free-breathing, whole heart coronary magnetic resonance angiography (MRA) has gained great attention as a totally noninvasive diagnostic modality for the detection of coronary artery disease. We examined the accuracy of coronary MRA to identify the presence or absence of coronary artery stenosis in comparison with conventional coronary angiography. Free-breathing, whole heart coronary MRA was performed in 43 consecutive patients undergoing conventional coronary angiography. A total of 172 coronary arteries and 344 coronary artery segments were analyzed. In the coronary artery segment-based analysis, the sensitivity to detect coronary stenosis ≥50% was 82% and specificity was 100%. The accuracy, positive predictive value, and negative predictive value was 97%, 98%, and 96%, respectively. In the vessel-based analysis the sensitivity was 86%, specificity 99%, accuracy 95%, positive predictive value 98%, and negative predictive value 94%. In the patient-based analysis, the sensitivity to detect coronary stenosis <50% was 97% and the specificity to define luminal narrowing <50% was 90%. The accuracy, positive predictive value, and negative predictive value was 95%, 97%, and 90%, respectively. Free-breathing, whole heart coronary MRA yields excellent diagnostic accuracy to detect significant coronary artery disease and has the potential to become the routine diagnostic modality for patients with suspected coronary artery disease.