Smoking delays chondrogenesis in a mouse model of closed tibial fracture healing.

Smoking delays the healing process and increases morbidity associated with many common musculoskeletal disorders, including long bone fracture. In the current study, a murine model of tibial fracture healing was used to test the hypothesis that smoking delays chondrogenesis after fracture. Mice were divided into two groups, a nonsmoking control group and a group exposed to cigarette smoke for 1 month prior to surgical tibial fracture. Mice were euthanized at 7, 14, and 28 days after surgery. The outcomes measured were immunohistochemical staining for type II collagen protein expression as a marker of cartilage matrix and proliferating cell nuclear antigen (PCNA) staining to measure proliferation at the site of injury. Toluidine blue staining and histomorphometry were used to quantify areas of cartilaginous and noncartilaginous fracture callus. Radiographs were analyzed for evidence of remodeling after injury. At day 7 after injury, mice exposed to cigarette smoke had a smaller fracture callus with less cartilage matrix compared to controls. Proliferation was present at high levels in both groups at this time point, but proliferating cells had a more immature morphology in the smoking group. At day 14, chondrogenesis was more active in smokers compared to controls, while a higher percentage of bone was present in the control animals. At day 28, X-ray analysis revealed a larger fracture callus remaining in the smoking animals. Together, these findings show that the chondrogenic phase of tibial fracture healing is delayed by smoking. This study represents, to our knowledge, the first analysis of molecular and cellular mechanisms of healing in a smoking mouse fracture model.     

Comparison of dobutamine stress echocardiography and technetium-99m sestamibi single-photon emission tomography for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy

Stress echocardiography has been considered an accurate method for the diagnosis of coronary artery disease in hypertensive patients and in patients with left ventricular hypertrophy. In contrast, the specificity of myocardial perfusion scintigraphy in these patients has been questioned. The aim of this study was to compare the accuracy of these two imaging modalities in conjunction with dobutamine stress test for the diagnosis of coronary artery disease in hypertensive patients with and without left ventricular hypertrophy. Dobutamine (up to 40 μg kg^–1min^–1) stress echocardiography in conjunction with sestamibi (MIBI) single-photon emission tomography (SPET) was performed in 84 patients with the diagnosis of systemic hypertension who had been referred for evaluation of myocardial ischaemia. Ischaemia was defined as new or worsened wall motion abnormalities at echocardiography and reversible perfusion defects at SPET. Significant coronary artery disease (≥50% luminal diameter stenosis) was detected in 66 patients (79%). The sensitivity, specificity and accuracy of the ischaemic pattern at echocardiography for the diagnosis of coronary artery disease were 73% (CI 63%–82%), 83% (CI 75%–91%) and 75% (CI 66%–84%), those for MIBI were 67% (CI 57%–77%), 83% (CI 75%–91%) and 70% (CI 60%–80%) respectively (P = NS vs echocardiography). Significant stenosis was detected in 123 (49%) of the 252 analysed coronary arteries. The sensitivity, specificity and accuracy of echocardiography for the regional diagnosis of coronary artery disease were 63% (CI 56%–69%), 90% (CI 86%–94%) and 77% (CI 72%–82%). Those for MIBI were 58% (CI 51%–64%), 91% (CI 87%–94%) and 75% (CI 69%–80) respectively (P = NS vs echocardiography). Left ventricular hypertrophy was detected in 59 patients (70%) by echocardiography and did not influence the overall or regional specificity of echocardiography or MIBI SPET. It is concluded that in hypertensive patients, dobutamine stress echocardiography and MIBI SPET have a comparable accuracy for the overall and regional diagnosis of coronary artery disease. Hypertensive patients with or without left ventricular hypertrophy should not be considered unsuitable candidates for stress myocardial perfusion scintigraphy. Received 10 July and in revised form 19 September 1997     

Expression of inactive stage anti-dsDNA idiotypes on anti-ssDNA antibodies in a lupus patient during active stage of lupus cerebritis.

The possibility that idiotypes (Ids) defined on anti-double stranded DNA (dsDNA) antibodies during active and inactive stages of lupus (1/84 Id and 4/90 Id, respectively) were expressed on anti-DNA antibodies during a subsequent active period (9/90) of the disease was investigated in a lupus patient with lupus cerebritis. Using rabbit (R)-anti-Ids specific to 1/84 Id and 4/90 Id in inhibition assays, the 4/90 Id was shown to be expressed on the framework regions of anti-single stranded DNA (ssDNA) but poorly on co-existing anti-dsDNA antibodies of active (9/90) stage. The 1/84 Id was poorly expressed on both types of 9/90 anti-DNA antibodies. While the 9/90 anti-ssDNA significantly bound to immobilized ssDNA and several single-stranded polynucleotides, only ssDNA inhibited the binding of the anti-ssDNA to ssDNA, suggesting its monospecificity toward ssDNA. Western blot analysis following isoelectric focusing showed that a spectrotype pattern of 4/90 Id-positive 9/90 anti-ssDNA IgG was similar to that of the 4/90 anti-dsDNA, suggesting that they are of related clonal origin. The present study suggests the idiotypic heterogeneity of anti-DNA antibodies and the shift of antigen specificity within an idiotypically related anti-DNA population during exacerbation of the disease.     

Outcome of lateral pelvic lymph node dissection with total mesorectal excision in treatment of rectal cancer: A systematic review and meta-analysis

BackgroundTotal mesorectal excision is the gold standard treatment of mid- and low-lying rectal cancer. Lateral pelvic lymph node dissection has been suggested as an approach to decrease recurrence and improve survival. Our meta-analysis presented here aimed to review the current outcomes of lateral pelvic lymph node dissection and total mesorectal excision in comparison with total mesorectal excision alone.MethodsA systematic literature search querying electronic databases was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We reviewed articles that reported the outcomes of lateral pelvic lymph node dissection combined with total mesorectal excision in comparison with total mesorectal excision alone. The main outcome measures were local recurrence, distant metastasis, overall and disease free-survival, and complications.ResultsThis systematic review included 29 studies of 10,646 patients. Of those patients, 39.4% underwent total mesorectal excision with lateral pelvic lymph node dissection. The median operation time for the lateral pelvic lymph node dissection + total mesorectal excision was significantly longer than total mesorectal excision alone (360 minutes versus 294.7 minutes, P = .02). Lateral pelvic lymph node dissection + total mesorectal excision was associated with higher odds of overall complications (odds ratio = 1.48, 95% confidence interval: 1.18–1.87, P < .001) and urinary dysfunction (odds ratio = 2.1, 95% confidence interval: 1.21–3.67, P = .008) than total mesorectal excision alone. Both groups had similar rates of male sexual dysfunction (odds ratio = 1.62, 95% confidence interval: 0.94–2.79, P = .08), anastomotic leakage (odds ratio = 1.15, 95% confidence interval: 0.69–1.93, P = .59), local recurrence (hazard ratio = 0.96, 95% confidence interval: 0.75–1.25, P = .79), distant metastasis (hazard ratio = 0.96, 95% confidence interval: 0.76–1.2, P = .72), overall survival (hazard ratio = 1.056, 95% confidence interval: 0.98–1.13, P = .13), and disease-free survival (hazard ratio = 1.02, 95% confidence interval: 0.97–1.07, P = .37).ConclusionLateral pelvic lymph node dissection was not associated with a significant reduction of recurrence rates or improvement in survival as compared with total mesorectal excision alone; however, LPLND was associated with longer operation time and increased complication rate.     

Adult depression in Alexandria, Egypt, 1998

The objectives of this population based study were to quantify the prevalence of depression among adults in Alexandria, to identify some of its determinants as well as to reveal gender differences in its presentation. 300 adults were surveyed in their households (10 from each of 30 clusters of the governorate). The self administered Beck's inventory for usage in primary care settings was used for identifying the depression state. The prevalence rate was 11% with a non significant higher proportion among males. Mean age of depressed subjects was higher than the free Age interval with highest percentage of cases was 50-60 years Epidemiologic variables that were found to be significantly associated with a higher rate of the condition were being divorced or widowed, a positive recent history of stressful life events and having a positive personal history of psychological troubles. On the other hand, examined factors like financial state, working status and whether the person is a bread earner or dependent in the family had no association with the state of depression. Male cases were younger than female ones, they also had a higher mean score on the depression scale. The genders differed significantly in scores of psychopathological parameters related to hopelessness, low self esteem, loss of sexual interest, loss of pleasure, guilt, self reproach and suicidal ideation. The authors recommend active case finding for depression at the primary care level, instituting counseling services for marriage and family relations, intensifying mass media health education directed to mechanisms of coping with life stresses and restudying the gender differences in epidemiology of depression in a large scale community research.     

Allograft loss in renal transplant recipients with Fabry's disease and activated protein C resistance

INTRODUCTION: Fabry's disease is associated with an increased incidence of thrombotic events and rejection. Spontaneous thrombosis of a functioning cadaveric renal allograft in a recipient with Fabry's disease prompted prospective evaluation of all transplant candidates with Fabry's disease for hypercoagulability. MATERIALS AND METHODS: Transplant candidates with Fabry's disease were tested for hypercoagulability, analyzed for HLA-type and ABO group, and comorbid conditions suggestive of hypercoagulability. RESULTS: A unique association of Fabry's disease with activated protein C Resistance was documented in a cohort of Caucasian male renal transplant recipients with Fabry's disease. Four of five patients were blood group A and had no significant comorbid conditions suggestive of hypercoagulability. The resistance to activation of protein C (APCR)(+) patients shared HLA loci-B8 and Dr3, although the APCR(-) patients shared HLA loci-B27 and -B38. CONCLUSIONS: Due to the observed increase in the incidence of APCR in our Fabry's cohort, we suggest screening all patients with Fabry's disease for APCR. Because factor V and factor Va receptors are found on vascular endothelium and peripheral blood monocytes, APCR in the presence of Fabry's disease may be a nonimmunological stimulus for rejection. Analysis of HLA typing in patients with Fabry's disease may further elucidate HLA-based association of Fabry's disease and resistance to activated protein C with the risk of thrombosis and rejection.     

Short bowel syndrome: clinical guidelines for nutrition management.

Intestinal failure is a condition in which inadequate digestion or absorption of fluid, electrolytes, and nutrients leads to dehydration or malnutrition. The most common cause of intestinal failure is short bowel syndrome (SBS) defined as <200 cm of functional small intestine. SBS may result from congenital abnormalities or from surgical resection. For the past 3 decades, patients with severe SBS were managed with home parenteral nutrition (HPN). With the emergence of new therapies, the clinician now has multiple options to treat these patients. These include intestinal rehabilitation regimens whereby patients are treated with specialized oral diets, soluble fiber, oral rehydration solutions (ORS), and trophic factors to enhance absorption. There are also a variety of surgical techniques available to preserve intestinal length. Small bowel and multivisceral transplantation has evolved during the last decade to be a valid therapeutic option for those patients who cannot be rehabilitated or who fail HPN. These are interrelated services designed to offer the patient the best therapeutic options to meet their individual needs. This article reviews the principles associated with the nutrition management of this very complex and diverse group of patients.