Expression of a novel PDGF isoform, PDGF-C, in normal and diseased rat kidney

Platelet-derived growth factor-C (PDGF-C) is a new member of the PDGF family. Its expression in normal and diseased kidney is unknown. Rabbit antisera were generated against human full-length, core domain, and mouse PDGF-C, and their specificity was confirmed by Western blot analyses. Renal PDGF-C expression was analyzed by immunohistochemistry in normal rats (n = 8), mesangioproliferative anti-Thy 1.1 nephritis (n = 4 each at days 1, 4, 6, and 85), passive Heymann nephritis (PHN, n = 4), puromycin nephrosis (PAN, n = 2), Milan normotensive rats (MN, n = 2), and obese Zucker rats (n = 3). PDGF-C expression was also studied in anti-Thy 1.1 rats treated with PDGF-B aptamer antagonists (n = 5) or irrelevant control aptamers (n = 5). PDGF-C was constitutively expressed in arterial smooth muscle cells and collecting duct epithelial cells. Mesangial PDGF-C was markedly upregulated in anti-Thy 1.1 nephritis in parallel with the peak mesangial cell proliferation. Furthermore, PDGF-CC acted as a potent growth factor for mesangial cells in vitro. Inhibition of PDGF-B via specific aptamers reduced the injury in anti-Thy 1.1 nephritis but did not affect the glomerular PDGF-C overexpression or the mitogenicity of PDGF-CC in vitro. In PHN, PAN, and obese Zucker rats, glomeruli remained negative for PDGF-C despite severe glomerular injury. PDGF-C localized to podocytes at sites of focal and segmental sclerosis in MN. Interstitial PDGF-C expression was increased at sites of fibrosing injury in obese Zucker rats. The use of the different antisera resulted in virtually identical findings. It is concluded that PDGF-C is a novel mesangial cell mitogen that is constitutively expressed in the kidney and specifically upregulated in mesangial, visceral epithelial, and interstitial cells after predominant injury to these cells. PDGF-C may therefore be involved in the pathogenesis of renal scarring.     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.     

Endoluminal stent graft repair for acute and chronic type B aortic dissection and atherosclerotic aneurysm of the thoracic aorta: an interdisciplinary task

Objective: Endoluminal thoracic aortic stenting is a new therapeutic tool in reducing the operative trauma of the patient. However, the inherent risks of aortic stent grafting are perivascular leakage, stent dislocation, blunt rupture of the aorta, side branch occlusion and neurological sequelae. To reduce these risks, in our institution all stent implantations were performed in close collaboration with our fellow cardiologists under biplane X-ray control supported by simultaneous intravascular and transoesophageal ultrasound imaging. Methods: Between August 1999 and August 2001, endovascular stent graft repair was performed in 34 patients (27 male, seven female) with a mean age of 68.6±7 years (range 58–84). Indication for treatment was an acute Type B aortic dissection in six patients (18%), a symptomatic chronic Type B dissection in 12 patients (35%), a true aneurysm of the descending aorta in seven patients (21%) and an atherosclerotic contained rupture of the descending aorta in nine (26%) patients. Out of six acute type B dissections three patients (8.8%) and one patient (2.9%) out of the chronic dissection group were in severe haemorrhagic shock, ventilated and required high-dose adrenergic support. The others (30 patients, 88.3%) remained symptomatic despite maximum medical treatment. In a special case a combined surgical and endoluminal stent graft repair was performed. Individually manufactured Talent, Medtronic AVE (33), and Gore (1) stents were used. Follow-up examination was performed 1 week after implantation and repeated every 3 months (mean follow-up 8 months, range 1–24). Results: In all patients the aneurysm or the entry of the dissection could be excluded. The observed hospital mortality was 2.9% (one patient). No perivascular leakage, no stent dislocation, no neurological deficit or perfusion impairment was observed. All patients except four were extubated immediately after the procedure and discharged from hospital on postoperative day 2–3. The late procedure-related mortality was 5.8% (two patients) resulting in an overall mortality of 8.8% (three patients). Conclusion: Stent graft repair is a safe and feasible treatment option for selected patients, especially in emergency situations, if the aortic lesions can be clearly identified and localized. The use of biplane X-ray control combined with simultaneous intravascular and transoesophageal ultrasound imaging in an interdisciplinary approach enables a more precise targeting of the stent landing zone, resulting in low morbidity and mortality rates.     

Effect of Surgery on the Outcome of Midgut Carcinoid Disease with Lymph Node and Liver Metastases

We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.     

Urinary tract infection caused by <Emphasis Type="Italic">Haemophilus influenzae</Emphasis> and <Emphasis Type="Italic">Haemophilus parainfluenzae</Emphasis> in children

There are few reports on urinary tract infections caused by Haemophilus influenzae or Haemophilus parainfluenzae in children. The true incidence is not known, since bacteria of Haemophilus species do not grow in standard urine culture media. With the objective of investigating the occurrence and character of urinary tract infections (UTIs) caused by Haemophilus bacteria in children, we searched the files of our UTI clinic. Over a 24-year period 36 children with Haemophilus spp. bacteriuria were identified out of a total of more than 5,000 UTI episodes. There was a significant gender difference in that Haemophilus influenzae dominated in girls and Haemophilus parainfluenzae in boys. With one exception, all children had important urinary tract abnormalities, such as malformation, gross reflux or bladder dysfunction. Permanent renal damage was seen in 25. We conclude that growth of Haemophilus bacteria in urine is associated with serious urinary tract abnormalities. The inability of bacteria of the Haemophilus species to grow in standard media commonly used for culture of uropathogens suggests that the true frequency of these strains as a cause of urinary tract infections is underestimated.     

Trans-catheter aortic valve implantation--early recovery of left and preservation of right ventricular function

This study aimed to assess the early effect of trans-catheter aortic valve implantation (TAVI) on right (RV) and left ventricular (LV) function in severe aortic stenosis (AS) patients. Twenty AS patients (age 79±6 years) were examined before, one week and six weeks after TAVI using Doppler echocardiography. LV ejection fraction (EF), long-axis [mitral annular plane systolic excursion (MAPSE)] and RV long-axis [tricuspid annular plane systolic excursion (TAPSE)] function, septal radial motion were studied. Results were compared with 30 AS patients before and one week after aortic valve replacement (AVR) as well as 30 normals (reference group). Before TAVI, LVEF was reduced and E/A was higher than the reference and AVR groups (P<0.05 for all). MAPSE, TAPSE and septal motion were equally reduced in TAVI and AVR patients (P<0.05 for all). One week after the TAVI, EF increased in patients with values <50% before the procedure. In contrast, AVR resulted in reversed septal motion (P<0.001) and depressed TAPSE (P<0.001). The extent of reversed septal motion correlated with that of TAPSE in the patients group as a whole after procedures (r=0.78, P<0.001). Six weeks after TAVI, RV function remained unchanged, but LVEF increased and E/A decreased (P<0.05 for both). Thus, TAVI procedure results in significant early improvement of LV systolic and diastolic function particularly in patients with reduced EF and preserves RV systolic function.     

Survival trends and predictors of mortality in severe pelvic trauma: estimates from the German Pelvic Trauma Registry Initiative

Study objective

To determine longitudinal trends in mortality, and the contribution of specific injury characteristics and treatment modalities to the risk of a fatal outcome after severe and complex pelvic trauma.

Methods

We studied 5048 patients with pelvic ring fractures enrolled in the German Pelvic Trauma Registry Initiative between 1991 and 1993, 1998 and 2000, and 2004 and 2006. Complete datasets were available for 5014 cases, including 508 complex injuries, defined as unstable fractures with severe peri-pelvic soft tissue and organ laceration. Multivariable mixed-effects logistic regression analysis was employed to evaluate the impact of demographic, injury- and treatment-associated variables on all-cause in-hospital mortality.

Results

All-cause in-hospital mortality declined from 8% (39/466) in 1991 to 5% (33/638) in 2006. Controlling for age, Injury Severity Score, pelvic vessel injury, the need for emergency laparotomy, and application of a pelvic clamp, the odds ratio (OR) per annum was 0.94 (95% confidence interval [CI] 0.91–0.96). However, the risk of death did not decrease significantly in patients with complex injuries (OR 0.98, 95% CI 0.93–1.03). Raw mortality associated with this type of injury was 18% (95% CI 9–32%) in 2006.

Conclusion

In contrast to an overall decline in trauma mortality, complex pelvic ring injuries remain associated with a significant risk of death. Awareness of this potentially life-threatening condition should be increased amongst trauma care professionals, and early management protocols need to be implemented to improve the survival prognosis.     

Sagittal balance of thoracic lordoscoliosis: anterior dual rod instrumentation versus posterior pedicle screw fixation

Posterior pedicle screw fixation is now the standard treatment for surgical correction of idiopathic scoliosis and has largely replaced anterior techniques, but there have been reports describing a lordogenic effect of segmental pedicle screw instrumentation in the thoracic spine. This clinical study compared anterior dual rod instrumentation with posterior pedicle screw fixation for idiopathic thoracic lordoscoliosis, including 42 patients (7 male, 35 female; average age 16 years, range 12–34) who underwent posterior pedicle screw fixation (n = 20) or anterior dual rod instrumentation (n = 22) at two centers. The average follow-up period was 33 months (24–108 months). Inclusion criteria were a diagnosis of adolescent idiopathic scoliosis with a structural thoracic curve (Lenke 1–3) and thoracic hypokyphosis (T4–T12 < 20°). The main thoracic curve magnitude and sagittal profile on standing radiographs were evaluated. Thoracic kyphosis was significantly restored from preoperatively 10.2° to 23.4° postoperatively in the anterior group and from 7.6° to 12.9° in the posterior group (P < 0.005). Kyphosis improved significantly better in the anterior group than in the posterior group (P < 0.005). The preoperative and postoperative main thoracic curve values were 63° (48–80°) and 25.2° in the anterior group and 60.6° (50–88°) and 23.6° in the posterior group, with no significant differences between the groups. No neurological or other severe complications were observed. Anterior dual rod instrumentation in patients with thoracic lordoscoliosis allows significantly better restoration of thoracic kyphosis than posterior pedicle screw instrumentation.     

Second-Look Operation for Unresectable Pancreatic Ductal Adenocarcinoma at a High-Volume Center

Background The value of re-exploration for pancreatic ductal adenocarcinoma after the initial diagnosis of unresectability is unclear. Methods In this study, we analyzed 33 patients who were re-explored after an initial diagnosis of unresectability. Results At the time of reoperation, a resectable tumor was found in 18 patients: therefore, 15 pancreaticoduodenectomies, two total pancreatectomies and one left resection were performed with three vascular resections. Morbidity and mortality rates for the cohort were 6/33 and 1/33, without significant differences between resectable and nonresectable patients. Length of stay, duration of operation, and blood loss were significantly increased in the resection group. Kaplan–Meier survival analysis demonstrated increased median survival for resected patients (1078 days after the initial operation versus 547 days in the group of unresectable patients; p = 0.018). Analysis of the reasons against initial resection showed that, if the patients had been sent to a tertiary referral center for pancreatic surgery, a different decision in favor of resection would probably have been made in 14 out of 33 patients. A review of 10 published reports on reoperation for pancreatic cancer revealed results comparable to our study in terms of low morbidity and mortality as well as a survival benefit. Conclusions Reoperation for pancreatic ductal adenocarcinoma that is initially deemed unresectable can be safely performed in a selected group of patients by experienced surgeons, supporting the concept of patient centralization in pancreatic surgery. Resection at the second operation may confer a survival benefit even when the initial findings preclude a potentially curative approach.     

Factors influencing survival after bypass procedures in patients with advanced pancreatic adenocarcinomas

BACKGROUND: Patients with occult metastasis or locally nonresectable pancreatic cancer found during surgical exploration have a limited life expectancy. We sought to define markers in these patients that could predict survival and thus aid decision making for selection of the most appropriate therapeutic palliative option. METHODS: In a prospective 4-year single-center study, 136 consecutive patients with obstructive pancreatic cancer and intraoperative diagnosis of nonresectable or disseminated pancreatic cancer underwent a palliative surgical bypass procedure. Potential factors predicting survival were evaluated. RESULTS: Ninety-eight patients had metastatic disease and 38 locally advanced disease. Surgical morbidity rate was 16 %, re-operation rate 1%, and overall in-hospital mortality 4%. Univariate analysis showed American Society of Anesthesiologists (ASA) score, pain, operation time, presence of metastasis, and levels of leukocytes, albumin, C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were associated significantly with survival. The multivariate analysis identified ASA score, presence of liver metastasis, pain, CA 19-9, and CEA levels as independent indicators for poor survival. Patients with none or 1 of these risk factors had a median survival of 13.5 months, whereas patients with 4 or 5 risk factors had a median survival of 3.5 months. CONCLUSIONS: The clinical markers identified predict poor outcome for patients with palliative bypass surgery and therefore aid the appropriate selection of either surgical bypass or endoscopic stenting in these patients.