HDL cholesterol and bone mineral density: is there a genetic link?

Overwhelming evidence has linked cardiovascular disease and osteoporosis, but the shared root cause of these two diseases of the elderly remains unknown. Low levels of high density lipoprotein cholesterol (HDL) and bone mineral density (BMD) are risk factors for cardiovascular disease and osteoporosis respectively. A number of correlation studies have attempted to determine if there is a relationship between serum HDL and BMD but these studies are confounded by a number of variables including age, diet, genetic background, gender and hormonal status. Collectively, these data suggest that there is a relationship between these two phenotypes, but that the nature of this relationship is context specific. Studies in mice plainly demonstrate that genetic loci for BMD and HDL co-map and transgenic mouse models have been used to show that a single gene can affect both serum HDL and BMD. Work completed to date has demonstrated that HDL can interact directly with both osteoblasts and osteoclasts, but no direct evidence links bone back to the regulation of HDL levels. Understanding the genetic relationship between BMD and HDL has huge implications for understanding the clinical relationship between CVD and osteoporosis and for the development of safe treatment options for both diseases.     

Inflammatory bowel disease and diabetes: Is there a link between them?

Patients with inflammatory bowel disease (IBD) are reported to have an increased risk of diabetes. IBD therapies may also modulate blood glucose substantially. These observations are indicative of mechanistic connection(s) between IBD and diabetes.     

Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease?

PURPOSE OF REVIEW: This review summarizes current knowledge on asymmetric dimethylarginine, renal function in health and disease, and renal disease progression and examines interventions that may modify the plasma concentration of this methylarginine. RECENT FINDINGS: Nitric oxide deficiency may occur in patients with chronic kidney disease and may contribute to accelerate progression of chronic kidney disease, hypertension and cardiovascular complications. An increase of endogenous nitric oxide inhibitors like asymmetric dimethylarginine seems to play a major role in this process. The kidneys are crucial in both, in re-absorbing and generating L-arginine as well as in eliminating asymmetric dimethylarginine primarily by the enzyme dimethylarginine dimethylaminohydrolase and to a minor degree by urinary excretion. Asymmetric dimethylarginine accumulation predicts both accelerated renal function loss and death in patients with chronic kidney disease and incident cardiovascular complications in patients with end stage renal disease. SUMMARY: Asymmetric dimethylarginine is a new risk factor potentially implicated in the progression of renal insufficiency and in the high rate of cardiovascular complications of patients with chronic kidney disease.     

Crohn’s disease of the esophagus: Report of a case

(Received for publication on Jan. 18, 1999; accepted on Sept. 17, 1999)     

Dermatofibrosarcoma protuberans and breast cancer: genetic link or coincidental association?

Dermatofibrosarcoma protuberans is a low-grade cutaneous neoplasm originating from the dermis with a high propensity for local recurrence. These malignancies are classified as soft tissue sarcoma although regional or distance metastatic spread is rare. Germ-line mutations of p53 have been described with a rare autosomal dominant syndrome in patients with soft tissue sarcoma and breast adenocarcinoma (Li Fraumeni's syndrome). The described case illustrates the rare occurrence of dermatofibrosarcoma protuberans (DFSP) and breast adenocarcinoma with an emphasis on the possibility of a molecular or genetic association.     

Retraction Note: Patients with ankylosing spondylitis treatment by golimumab: a systematic review and meta‑analysis

European Spine Journal -     

Ectopic and undescended testes: 2 variants of a single congenital anomaly?

PURPOSE: We compared pathological findings in ectopic and undescended testis to determine whether the pathological evidence supports the hypothesis that the 2 conditions are variants of the same congenital anomaly. MATERIALS AND METHODS: We identified 24 boys with ectopic testis not in the superficial inguinal pouch of Denis Browne. Seven boys were excluded from study due to unavailable clinical records for 3, contralateral undescended testis in 2 and inadequate biopsy specimens in 2. Pathological findings of ectopic testis in the remaining 17 patients were compared with those of age matched patients with unilateral undescended testis. Total germ cell count, testicular volume, patency of the processus vaginalis and epididymal abnormalities were compared. Data were analyzed using the Wilcoxon matched pairs signed rank and Fisher's exact tests. RESULTS: No difference was noted in total germ cell count (p = 0.33), testicular volume (p = 0.1475), processus vaginalis patency (p = 0.0854) or epididymal abnormalities (p = 1.00) in the 2 groups. Of the 24 boys (8%) with ectopic testis 2 also had a contralateral undescended testis. CONCLUSIONS: Similar pathological findings in ectopic and undescended testes as well as the association of ectopic testis with a contralateral undescended testis suggest that ectopic and undescended testes are variants of the same congenital anomaly. Thus, boys with ectopic testis may have an increased incidence of subfertility and testicular malignancy. This spectrum of abnormal testicular position, and its range of pathological conditions and complications may appropriately be called the undescended testis sequence.     

Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link?

Hypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.     

Comparison of laparoscopic and open ileocecal resection for Crohn’s disease: a metaanalysis

Background The role of laparoscopic surgery for patients with ileocecal Crohn’s disease is a contentious issue. This metaanalysis aimed to compare open resection with laparoscopically assisted resection for ileocecal Crohn’s disease. Methods A literature search of the Medline, Ovid, Embase, and Cochrane databases was performed to identify comparative studies reporting outcomes for both laparoscopic and open ileocecal resection. Metaanalytical techniques were applied to identify differences in outcomes between the two groups. Sensitivity analysis was undertaken to evaluate the heterogeneity of the study. Results Of 20 studies identified by literature review, 15 satisfied the criteria for inclusion in the study. These included outcomes for 783 patients, 338 (43.2%) of whom had undergone laparoscopic resection, with an overall conversion rate to open surgery of 6.8%. The operative time was significantly longer in the laparoscopic group, by 29.6 min (p = 0.002), although the blood loss and complications in the two groups were similar. In terms of postoperative recovery, the laparoscopic patients had a significantly shorter time for recovery of their enteric function and a shorter hospital stay, by 2.7 days (p < 0.001). Conclusions For selected patients with noncomplicated ileocecal Crohn’s disease, laparoscopic resection offered substantial advantages in terms of more rapid resolution of postoperative ileus and shortened hospital stay. There was no increase in complications, as compared with open surgery. The contraindications to laparoscopic approaches for Crohn’s disease remain undefined.     

Discordant Hirschsprung's disease in monozygotic twins: a clue to pathogenesis?

Presented is a case of discordant aganglionosis in monozygous twins that supports the "post migration" destruction mechanism in Hirschsprung's disease.     

Psoas abscess complicating Crohn’s disease: Report of a case

We describe herein the case of a psoas abscess complicating Crohn's disease, and present a review of the literature on this unusual disease entity. A 22-year-old Japanese man with a 5-year history of Crohn's ileocolitis presented with right lower abdominal and hip pain, and a diagnosis of right psoas abscess was subsequently made by abdominal computed tomography (CT). Following the administration of antibiotics and CT-guided percutaneous drainage of the abscess, the patient's symptoms temporarily improved; however, 2 weeks later, the abscess cavity was found to have extended around the periarticular tissue of the right hip joint. To prevent the development of septic arthritis of the hip joint, surgical drainage of the abscess cavity and ileocecal resection were immediately performed, after which the patient's condition greatly improved. The resected specimen showed Crohn's ileocolitis with an external fistula in the terminal ileum which was considered to have caused the psoas abscess. Since psoas abscess in Crohn's disease can result in serious complications such as septic arthritis of the hip joint if left untreated, aggressive treatment should be initiated without delay. Received: June 17, 1999 / Accepted: March 24, 2000     

Serum calcitonin and endothelial dysfunction in chronic kidney disease: a novel risk factor?

Background

Endothelial dysfunction (ED) is highly prevalent in patients with CKD. The relationship between ED and calcitonin has not been demonstrated before in CKD patients.

Methods

The study included non-diabetic CKD patients not on dialysis. Demographic data (age, gender, comorbidities, current drug therapy, smoking status, weight, and height) were collected from the individual charts in the hospital’s electronic database. After overnight fasting, laboratory measurements including serum calcitonin levels were performed in all patients. A single observer who was blinded to the results of the study assessed ED by measurement of flow-mediated dilatation (FMD).

Results

In total, 84 CKD patients (41 men, age 45.1 ± 13.3 years) were included. Thirty-seven patients had stage 3 and 47 patients had stage 4 CKD. Patients with calcitonin levels above the median had lower FMD (6.87 ± 0.58 vs. 7.23 ± 0.66, P = 0.008) when compared with patients with calcitonin levels below the median. None of the other demographic, laboratory and clinical parameters was different between the two groups. In multivariate regression analysis, serum calcitonin (P = 0.01), fetuin-A (P < 0.001), high-sensitive C-reactive protein (P < 0.001), and hemoglobin (P = 0.004) were independently associated with FMD.

Conclusion

Our present study demonstrated for the first time that serum calcitonin is independently related with ED. This finding deserves further experimental and clinical exploration, in order to elucidate whether calcitonin is an innocent bystander or has a pathophysiologic relationship with ED in patients with CKD.     

Rising PSA in patients with minor LUTS without evidence of prostatic carcinoma: a missing link?

Objectives To determine the role of pressure flowmetry in patients without bothersome lower urinary tract symptoms (LUTS), rising prostate-specific antigen (PSA) levels and diagnosed as having clinical benign prostatic hyperplasia (BPH) after negative (multiple) extended multi-site biopsy. Methods The study enrolled patients with minor LUTS who were referred to our urological practice by their general practitioner because of a rising PSA level (≥4 ng/ml). After exclusion of clinical prostatic carcinoma by digital rectal examination and transrectal ultrasound, all patients underwent at least one set of extended multi-site biopsies to exclude T1c prostate cancer. Patients with negative biopsies (clinical BPH) were subjected to pressure flowmetry whereafter those with bladder outlet obstruction underwent TURP. Results The study included 82 patients, with a mean age of 64.8 years (50.2–78.2 years), satisfying the inclusion criteria. Urodynamic analysis showed that all patients had bladder outlet obstruction. After TURP, eight patients (9.8%) were diagnosed as having histologically proven prostate cancer; 74 patients (90.2%) were diagnosed as having BPH. Patients of the BPH group had a mean preoperative PSA level of 8.8 ng/ml (4.3–25.8 ng/ml) and a mean international prostate symptom score of 8.8 (2–18). The mean detrusor pressure at maximum flow in BPH patients was 89.5 cmH₂O (20–200 cmH₂O). Conclusions An increased PSA in patients with minor or no LUTS, clinical BPH and negative extended multi-site prostate biopsy is strongly correlated to bladder outlet obstruction. Therefore, patients with these characteristics should be treated with TURP.