The effect of sexual hormone abnormalities on proximal femur bone mineral density in hemodialysis patients and the possible role of RANKL.

Sexual hormone concentrations are commonly affected in chronic renal failure. The contribution of sex steroids to bone turnover regulation implies that sex steroid's dysfunction may be implicated in the emergence of renal osteodystrophy. This study was conducted to evaluate sex steroids and gonadotrophins in hemodialysis (HD) patients and to investigate their role in bone homeostasis in concert with other hormones and cytokines. Bone mineral density (BMD) at the proximal femur and intact parathyroid hormone (iPTH), osteoprotegerin, soluble receptor activator of NF-kappaB ligand (sRANKL), prolactin, total testosterone, estradiol, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured in serum samples in 42 patients, 21 men and 21 women, on maintenance HD therapy. Possible associations between clinical characteristics, biochemical parameters, and BMD values were investigated. In male HD patients, the testosterone concentration declined significantly with aging, whereas the estradiol level increased with longer duration of HD. Concurrently, testosterone correlated negatively with sRANKL concentrations (r=-0.520, p=0.016). Luteinizing hormone levels in male patients demonstrated statistically significant negative correlations with BMD values of the proximal femur. In the entire cohort of patients, FSH and LH were negatively associated with absolute values of proximal femur BMD. Gonadotrophin and sexual hormone concentrations in HD patients are associated with bone mineral status and consequently their derangements appear to contribute to the development of bone composition abnormalities in different types of renal osteodystrophy. Furthermore, testosterone's association with sRANKL levels in male HD patients suggests that RANKL may mediate the effect of testosterone on bone metabolism in these patients.

Time-dependent alterations in serum NO concentration after oral administration of L-arginine, L-NAME, and allopurinol in intestinal ischemia/reperfusion.

OBJECTIVE: To study the effect of oral administration of a nitric oxide (NO) donor L-arginine (L-Arg), a NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. METHODS: Male Wistar rats receivedper os L-Arg (800 mg/kg) or L-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (L-Arg(IR1), L-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (L-Arg(IR8), L-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. RESULTS: After 1 hr of reperfusion serum NO concentration was elevated in IR1 and L-Arg(IR1) groups compared with group C but not in L-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in L-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, L-Arg(IR8), L-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. CONCLUSIONS: The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of L-Arg but not after administration of L-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os supplementation of L-Arg or Allo in intestinal I/R.

Diagnosis and treatment of intracystic breast carcinomas.

Cystic breast masses are very common in female patients attending breast clinics. Most of them are benign and managed by simple aspiration. We reviewed histology records for the last 12 years to find patients with cystic breast carcinomas and to evaluate special clinical signs that may help to identify patients with this rare entity. Eighteen patients with cystic breast carcinomas were found among 1510 new breast cancer patients (1.19%) who were seen at our Breast Unit during this period. Ten had intracystic papillary carcinoma (0.66% of all breast cancers), seven had cystic degeneration of ductal carcinoma, and one had a mucinous carcinoma. The diagnosis of intracystic papillary carcinoma was based on cyst fluid cytology and breast imaging in most patients and on open breast biopsy in two cases only. The prognosis of our cystic breast carcinoma patients was excellent regardless of the specific histologic type of the tumor. We conclude that cysts in postmenopausal women should be viewed with suspicion. Bloodstained aspirated cyst fluid should be sent for cytology and breast imaging should be carried out in all these cases. Residual mass after cyst aspiration is also an indication for open biopsy.

Regulatory effect of parathyroid hormone on sRANKL-osteoprotegerin in hemodialysis patients with renal bone disease.

Receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin are newly identified molecules that contribute to the modulation of bone remodeling. RANKL activates osteoclast function by binding to RANK in either a soluble or membrane-bound form, whereas osteoprotegerin (OPG) neutralizes its effects. The aim of this study is the evaluation of soluble RANKL (sRANKL)-OPG in cohorts of hemodialysis patients and the establishment of possible correlations between their serum levels and those of other biochemical markers. We measured intact parathyroid hormone (iPTH), osteocalcin (OC), OPG, alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and sRANKL in 104 hemodialysis patients. The patients were studied as a whole and in two subgroups according to their bone turnover state. In patients with low serum levels of bone turnover markers (intact parathyroid hormone [iPTH] < 100 pg/mL, ALP < 100 U/L, TRAP < 4 U/L; 33 patients), the following correlations were found: (i) positive correlations of iPTH with RANKL (r = 0.394, P = 0.023) and RANKL/OPG ratio (r = 0.49, P = 0.004); (ii) a negative correlation between iPTH and OPG (r = -0.365, P = 0.037). The subgroup of patients with normal or high serum levels of bone turnover markers (iPTH >or= 150 pg/mL, ALP >or= 100 U/L, OC >or= 40 ng/mL; 19 patients) exhibited the following significant correlations: (i) a positive correlation between OPG and iPTH serum level (r = 0.649, P = 0.003); and (ii) a negative correlation between RANKL/OPG ratio and iPTH (r = -0.464, P = 0.045). In conclusion, the observation that PTH favors RANKL and inhibits OPG production was only demonstrated in the serum of hemodialysis patients in a low turnover state. The positive correlation between serum OPG and iPTH in normal or high turnover rates implies a homeostatic mechanism to limit bone resorption, probably associated with skeletal resistance to PTH.

Associations between osteoprotegerin and femoral neck BMD in hemodialysis patients.

Numerous humoral factors are involved in the development of renal osteodystrophy, causing perturbations in bone mineral density (BMD) in patients with end-stage renal disease (ESRD). The RANKL/OPG cytokine system appears to mediate the effects of many of these factors on bone turnover, contributing to the pathogenesis of renal bone disease. The aim of this study was to evaluate the clinical and biochemical correlations of BMD measurements in patients on chronic hemodialysis. Fifty-four hemodialysis patients underwent measurement of BMD at the proximal femur and the lumbar spine (L2-L4). Intact parathyroid hormone (PTH), osteoprotegerin (OPG), sRANKL, and main bone biochemical markers were also measured in serum samples of all patients. BMD of the femoral neck was negatively correlated with OPG levels (r = 0.333, P = 0.014). OPG levels were significantly different among normal, osteopenic, and osteoporotic tertiles defined according to BMD of the femoral neck. The highest OPG levels were measured in the lowest T-score (osteoporotic) tertile and were higher than in the osteopenic and normal tertiles (P < 0.05). A threshold level for OPG at 21.5 pmol/l enabled the detection of osteoporotic patients with 76.5% sensitivity and 62.2% specificity. BMD values of trabecular bone-rich sites of the skeleton such as lumbar spine (L2-L4), trochanter, and Ward' s triangle were inversely correlated with total ALP levels (P < 0.05). Hemodialysis patients with low BMD of the femoral neck demonstrated higher OPG levels than patients with normal BMD. Those with lumbar spine (L2-L4), trochanteric, and Ward's triangle BMDs below the normal range presented higher total ALP levels. These results suggest that OPG and total ALP may be clinically useful markers in the detection of significant femoral neck and trabecular bone mineral deficit in hemodialysis patients, warranting further investigations.

Myoplasty versus omentoplasty in the surgical treatment of hydatidosis of the liver dome.

BACKGROUND AND AIMS: Even though surgery is the mainstay in the management of hydatid disease of the liver, controversies still exist about the preferred operating technique. This study was conducted to evaluate myoplasty versus omentoplasty for the surgical treatment of hepatic dome hydatidosis. PATIENTS AND METHODS: Sixty-two patients with a hydatid cyst located over the right superior-posterior part of the liver or a cyst adherent to the right hemidiaphragm were classified into two groups according to the type of surgical approach. Group A comprised 50 patients who had undergone thoracoabdominal, right subcostal, or right paramedian incision. Group B comprised 12 patients who had undergone posterior-lateral thoracotomy. Twenty-four patients with a right thoracoabdominal incision underwent partial excision of the cyst with omentoplasty (18 patients), external drainage (four patients), and marsupialization (two patients). RESULTS: Twenty-six patients with a right subcostal or paramedian incision underwent partial resection of the cyst with omentoplasty (15 patients), external drainage (eight patients), and combination of procedures (three patients). Twelve patients that had undergone a right thoracotomy underwent partial excision of the cyst wall with myoplasty of the right hemidiaphragm. Surgical approaches such as thoracoabdominal, right subcostal, or paramedian incision were associated with higher morbidity rate than thoracotomy alone (P < 0.03). In addition, patients with myoplasty of the right hemidiaphragm were associated with a lower morbidity rate than those with omentoplasty (P < 0.02). Five patients had recurrent disease and were reoperated upon. Partial cystectomy and myoplasty of the right hemidiaphragm was performed with excellent results. CONCLUSIONS: These results suggest that a thoracic approach, with myoplasty of the right hemidiaphragm and high-vacuum drainage, might produce low complication and recurrence rates and the best clinical results. Consequently, it is a promising procedure that requires more application and evaluation.

Use of short PTFE segments (<6 cm) compares favorably with pure autologous repair in failing or thrombosed native arteriovenous fistulas.

OBJECTIVE: The re-establishment of patency in a stenosed or thrombosed native arteriovenous fistula (AVF) is fundamental to regaining adequate hemodialysis through the same cannulable vein. Many surgeons have been reluctant to use even small segments of synthetic grafts in AVF revisions because of a perception that these would lead to poor results; however, studies comparing various treatment options are scarce. This study compared the use of short (<6 cm) polytetrafluoroethylene (PTFE) segments with pure autologous repair in stenosed or thrombosed native fistulas. METHODS: The cumulative postintervention primary patency rates of two groups of hemodialysis patients receiving different surgical revision operations of their vascular accesses were prospectively compared. Group I (n = 30) comprised patients who presented with stenosed or thrombosed native fistulas and received short (2 to 6 cm) interposition PTFE grafts placed after the stenosed or thrombosed outflow vein segment was resected. These short PTFE grafts were not used for cannulation. Group II (n = 29) comprised patients who presented with dysfunctional or failed AVFs and underwent various types of pure autogenous corrections. AVF dysfunction or thrombosis was detected with clinical examination and color duplex ultrasound scanning. In all cases, on-table arteriography-fistulography was performed before surgical repair. Access adequacy was assessed in all patients postoperatively after the first puncture and every month thereafter (mean follow up 16.7 months). RESULTS: No statistically significant difference in patency was observed between the two groups. Postintervention cumulative patencies were 100%, 88%, and 82% for group I and 90%, 82%, and 71% for group II at 6, 12, and 18 months, respectively ( P = .8). CONCLUSIONS: Short (<6 cm) interposition PTFE segments used for the revision of failing or failed AVFs compare favorably to purely native repair and do not alter the autologous behavior of the initial access. These short PTFE revisions resulted in satisfactory midterm primary patency without further consumption of the venous capital by harvesting segments of vein from other locations and without compromising more proximal access sites. This practice is recommended and is justified as part of an aggressive access salvage policy addressed by many authors so far.