Determinants of bone mass in end-stage renal failure patients at the time of kidney transplantation

Abstract: Background:  Patients with chronic renal failure (CRF) are at high risk of renal osteodystrophy. Our study aimed to identify predictors of bone mass and cumulative fracture rate at the time of renal transplantation (RTx). This is important since the patients experience further substantial bone loss the first month post-transplant.
Material and methods:  Altogether 133 renal transplant patients were examined for bone mineral density (BMD) using dual-energy X-ray absorptiometry shortly after RTx.
Results:  The patients' Z -scores were significantly lower at the time of RTx compared to the reference population (p < 0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical activity (p = 0.027) were associated with high BMD. Cumulative fracture rate (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and osteopenia (p < 0.001) at the time of RTx.
Conclusion:  In a representative CRF population, BMD was reduced. Independent predictors of BMD were as for the general population, and uremia associated predictors were time on HD, previous transplantation and serum iPTH level. Fracture rate was high, and physical inactivity had the strongest association with fractures.     

Impaired Fas-induced apoptosis of T lymphocytes in patients with abdominal aortic aneurysms

OBJECTIVE: Homeostasis of the immune system is maintained by apoptotic elimination of potentially pathogenic autoreactive lymphocytes. Emerging evidence shows that Fas-mediated apoptosis is impaired in activated lymphocytes from patients with autoimmune disease. The aim of this work was to assess apoptosis mediated by the cell death receptor Fas in peripheral T lymphocytes from patients with abdominal aortic aneurysms (AAA). METHODS: The apoptotic pathway was triggered by anti-Fas monoclonal antibodies in cultured and activated peripheral T-cell lines from 20 AAA patients with control groups of 15 patients with aortic atherosclerotic occlusive disease (AOD) and 25 healthy individuals. Cell survival and death (apoptosis) rate were assessed. RESULTS: Cross-linkage of Fas receptor exerted a strong apoptotic response on T cells from AOD patients and healthy controls, but a much less pronounced effect on T cells from AAA patients. The evaluation of cell survival rate showed a significantly higher percentage in AAA group (98.9% +/- 10.3%) than in the AOD subjects (58.9% +/- 15.2%) or the healthy group (59.4% +/- 12.9%; P < .001). Apoptosis assessment by annexin V and propidium iodide staining and flow cytometry showed similar results. The defect in AAA group was not due to decreased Fas expression, since Fas was expressed at normal levels. Moreover, it specifically involved the Fas system because cell death was induced in the normal way by methylprednisolone. Complementary DNA sequencing identified no causal Fas gene mutation, but two silent single nucleotide polymorphisms with higher frequency were found in the AAA group. CONCLUSIONS: Fas-induced apoptosis in activated T cells from AAA patients is impaired. This may disturb the normal down-regulation of the immune response and thus provide a new insight into possible mechanisms and routes in the pathogenesis of AAA.     

Minimally invasive treatment of ureteropelvic junction obstruction: long-term experience with an algorithm for laser endopyelotomy and laparoscopic retroperitoneal pyeloplasty

PURPOSE: First line treatment of ureteropelvic junction obstruction is still open dismembered pyeloplasty. The development of videoendoscopic techniques like endopyelotomy and laparoscopy offers less invasive alternatives. The long-term outcome of an algorithm selectively using these techniques is presented. MATERIALS AND METHODS: From February 1995 to March 2006, 256 patients with ureteropelvic junction obstruction were treated with 113 laser endopyelotomies and 143 laparoscopic retroperitoneal pyeloplasties. According to changing selection criteria, an early group (92 in 1995 to 1999) treated with laser endopyelotomy for extrinsic as well as intrinsic stenoses, and a late group (164 in 2000 to 2006) treated with laser endopyelotomy for intrinsic stenosis, were evaluated. In the late group extrinsic ureteropelvic junction obstruction was treated with nondismembered pyeloplasty in cases of anteriorly and by dismembered pyeloplasty in cases of posteriorly crossing vessels or a redundant renal pelvis. RESULTS: Operating time of laser endopyelotomy averaged 34 (range 10 to 90) minutes with a complication rate of 5.3% and a success rate of 72.6% (intrinsic 85.7% vs extrinsic 51.4%). Operating time of laparoscopic retroperitoneal pyeloplasty averaged 124 (range 37 to 368) minutes with a 6.3% complication rate and an overall success rate of 94.4% (intrinsic 100% vs extrinsic 93.8%). In the late group the LAP success rate was 98.3% with no significant differences related to the cause of ureteropelvic junction obstruction (intrinsic 100% vs extrinsic 98.1%) or the type of pyeloplasty (YV plasty 97.0% vs Anderson-Hynes 97.7%). CONCLUSIONS: Laparoscopic retroperitoneal pyeloplasty yields an efficacy similar to that of open surgery. The inferior success of laser endopyelotomy even in optimally selected cases and the increasing expertise with endoscopic suturing may favor laparoscopic pyeloplasty with or without robotic assistance in the future.     

Is size-reducing ascending aortoplasty with external reinforcement an option in modern aortic surgery?

OBJECTIVE: Enlargement of the ascending aorta is often combined with valvular, coronary, or other cardiac diseases. Reduction aortoplasty can be an optional therapy; however, indications regarding the diameter of aorta, the history of dilatation (poststenosis, bicuspid aortic valve), or the intraoperative management (wall excision, reduction suture, external reinforcement) are not established. METHODS: In a retrospective study between 1997 and 2005, we investigated 531 patients operated for aneurysm or ectasia of the ascending aorta (diameter: 45-76mm). Of these, in 50 patients, size-reducing ascending aortoplasty was performed. External reinforcement with a non-coated dacron prosthesis was added in order to stabilize the aortic wall. RESULTS: Aortoplasty was associated with aortic valve replacement in 47 cases (35 mechanical vs 12 biological), subvalvular myectomy in 29 cases, and CABG in 13 cases. The procedure was performed with low hospital mortality (2%) and a low postoperative morbidity. Computertomographic and echocardiographic diameters were significantly smaller after reduction (55.8+/-9mm down to 40.51+/-6.2mm (CT), p<0.002; 54.1+/-6.7mm preoperatively down to 38.7+/-7.1mm (echocardiography), p<0.002), with stable performance in long-term follow-up (mean follow-up time: 70 months). CONCLUSIONS: As demonstrated in this study, size reduction of the ascending aorta using aortoplasty with external reinforcement is a safe procedure with excellent long-term results. It is a therapeutic option in modern aortic surgery in patients with poststenotic dilatation of the aorta without impairment of the sinotubular junction of the aortic valve and root.     

Kinematics of the ligamentous unstable elbow joint after application of a hinged external fixation device: a cadaveric study

We studied the kinematics of 8 ligamentous unstable elbow joint preparations after application of the Orthofix elbow external fixation device. Valgus, varus, external rotatory, and internal rotatory load tests were performed in lateral collateral ligament (LCL)-deficient and LCL/medial collateral ligament (MCL)-deficient joints. After placement of the fixator, the mean extension decreased significantly to 19.5 degrees +/- 7.2 degrees in the LCL-deficient joint and to 19.1 degrees +/- 6.6 degrees in the LCL/MCL-deficient joint compared with the mean extension of the intact joint, which was 10.5 degrees +/- 4.2 degrees. After application of the fixator, valgus displacement was significantly decreased by 4.0 degrees +/- 3.4 degrees in the LCL-deficient joint and by 3.6 degrees +/- 3.3 degrees in the LCL/MCL-deficient joint compared with the intact joint. External rotatory displacement was significantly decreased in the LCL-deficient joint by 4.9 degrees +/- 3.7 degrees and in the LCL/MCL-deficient joint by 5.0 degrees +/- 4.7 degrees. Internal rotatory displacement was significantly decreased by 3.3 degrees +/- 2.7 degrees in the LCL-deficient joint, but it was not significantly changed in the LCL/MCL-deficient joint. The Orthofix elbow external fixator guided elbow motion to a more varus position compared with the intact elbow and decreased the range of motion of the joint, constraining mainly extension. We conclude that the fixator stabilized the ligamentous unstable elbow joint efficiently but at the expense of changes in the normal motion pattern.     

Sulfonylurea compounds uncouple the glucose dependence of the insulinotropic effect of glucagon-like peptide 1

Glucagon-like peptide (GLP)-1 mimetics have been reported to cause hypoglycemia when combined with sulfonylureas. This study investigated the impact of tolbutamide on the glucose dependence of the GLP-1-mediated effects on insulin, glucagon, and somatostatin secretion in the in situ perfused rat pancreas. At 3 mmol/l glucose, GLP-1 alone did not augment insulin secretion, whereas tolbutamide alone caused a rapid increase in insulin secretion. However, when GLP-1 and tolbutamide were administered simultaneously, insulin secretion increased significantly to 43.7 +/- 6.2 pmol/min (means +/- SE), exceeding the sum of the responses to GLP-1 (2.0 +/- 0.6 pmol/min; P = 0.019) and tolbutamide (11.3 +/- 3.8; P = 0.005) alone by a factor of 3.3. At 11 mmol/l glucose, co-infusion of GLP-1 and tolbutamide augmented insulin secretion to 141.7 +/- 10.3 vs. 115.36 +/- 14.1 (GLP-1) and 42.5 +/- 7.3 pmol/min (tolbutamide). Interestingly, increases in somatostatin secretion, both by glucose and GLP-1, were consistently paralleled by suppression of glucagon release. In conclusion, we demonstrate uncoupling of GLP-1 from its glucose dependence by tolbutamide. This uncoupling probably explains the tendency of GLP-1 to provoke hypoglycemia in combination with sulfonylureas. The results suggest that closure of ATP-sensitive K(+) channels by glucose might be involved in the glucose dependence of GLP-1's insulinotropic effect and that somatostatin acts as a paracrine regulator of glucagon release.     

Management in patients with liver cirrhosis and an umbilical hernia

BACKGROUND: Optimal management in patients with umbilical hernias and liver cirrhosis with ascites is still under debate. The objective of this study was to compare the outcome in our series of operative versus conservative treatment of these patients. METHODS: In the period between 1990 and 2004, 34 patients with an umbilical hernia combined with liver cirrhosis and ascites were identified from our hospital database. In 17 patients, treatment consisted of elective hernia repair, and 13 were managed conservatively. Four patients underwent hernia repair during liver transplantation. RESULTS: Elective hernia repair was successful without complications and recurrence in 12 out of 17 patients. Complications occurred in 3 of these 17 patients, consisting of wound-related problems and recurrence in 4 out 17. Success rate of the initial conservative management was only 23%; hospital admittance for incarcerations occurred in 10 of 13 patients, of which 6 required hernia repair in an emergency setting. Two patients of the initially conservative managed group died from complications of the umbilical hernia. In the 4 patients that underwent hernia correction during liver transplantation, no complications occurred and 1 patient had a recurrence. CONCLUSIONS: Conservative management of umbilical hernias in patients with liver cirrhosis and ascites leads to a high rate of incarcerations with subsequent hernia repair in an emergency setting, whereas elective repair can be performed with less morbidity and is therefore advocated.     

Effect of induction therapy on kinetic of procalcitonin following uncomplicated heart transplantation

BACKGROUND: The aim of the study was to determine the early postoperative kinetics of serum procalcitonin (PCT) levels in uncomplicated heart transplant patients under induction therapy using antithymocyte globulin (ATG). METHODS: PCT serum concentrations were measured for 7 days in 30 adult patients (26 males, 4 females, mean age 54.5 +/- 7.7 years) undergoing uncomplicated orthotopic heart transplantation. Of the 30 patients, 28 received ATG and 2 with the same immunosuppression regimen had no induction therapy. The induction therapy consisted of 100 mg/day ATG and was started 6 hours postoperatively. RESULTS: Mean PCT levels immediately before HTX were <0.3 ng/mL in both groups. After the first ATG infusion patients developed a significant (p < 0.05) elevation in PCT plasma levels without any incidence of infectious disease with peak levels up to 11.7 +/- 19.7 ng/mL on postoperative day (POD) 1. Thereafter values continuously decreased independently of further ATG administration in all patients (6.7 +/- 10.5 ng/mL on POD 3, 3.2 +/- 7.4 ng/mL on POD 5 and 1.2 +/- 3.0 ng/mL on POD 7). In the non-ATG group a mild postoperative rise in the serum PCT was observed. The values peaked on POD 2 with 2.0 +/- 1.6 ng/mL and normalized within four days. CONCLUSIONS: Perioperative administration of ATG is associated with significantly increased PCT levels even in uncomplicated heart transplant recipients. This phenomenon should not be misinterpreted as systemic infection, as systemic inflammatory reaction that seems to be induced by ATG therapy is responsible for increased PCT production.     

Minimally invasive anterolateral approach to the hip: risk to the superior gluteal nerve

BACKGROUND: Minimally invasive approaches to the hip show promise of less muscle trauma compared to conventional approaches. What is the risk of damage to the superior gluteal nerve? We studied the course of the superior gluteal nerve. METHOD: 20 legs of 11 formalin-fixed Caucasian cadavers were dissected and the course and the distances of the superior gluteal nerve branches from the tip of the greater trochanter were documented. RESULTS: The branch of the gluteal superior nerve leading to the gluteal minimus muscle was 33 (20-50) mm from the tip of the greater trochanter, within a deeper layer. The nearest point of the superior gluteal nerve branches from the tip of the greater trochanter in the posterior region was 19 (10-30) mm, in the middle region 20 (20-30) mm and in the anterior region 20 (10-35) mm. In half of the cases, a distal intermuscular branch between gluteal medius and tensor fasciae latae muscle could be found, mean 27 (10-40) mm caudal and 38 (25-60) mm ventral to the tip of the greater trochanter. This distal branch is considered to create a loop with upper branches of the superior gluteal nerve within the tensor fasciae muscle. INTERPRETATION: The safe zone for the superior gluteal nerve was smaller than previously reported. Use of a minimal direct lateral approach puts the inferior branches within the gluteal medius at risk; however, a minimal anterolateral approach to the hip may compromise branches of the superior gluteal nerve to the tensor fasciae latae muscle.