The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury

OBJECT: Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects, such as promoting angiogenesis, increasing fibrinolysis, and reducing inflammatory responses, and has shown promise in enhancing recovery in animals with traumatic brain injury (TBI) and stroke. The authors tested the effect of atorvastatin on vascular changes after TBI. METHODS: Male Wistar rats subjected to controlled cortical impact injury were perfused at different time points with fluorescein isothiocyanate (FITC)--conjugated dextran 1 minute before being killed. Spatial memory function had been measured using a Morris Water Maze test at various points before and after TBI. The temporal profile of intravascular thrombosis and vascular changes was measured on brain tissue sections by using a microcomputer imaging device and a laser confocal microscopy. The study revealed the following results. 1) Vessels in the lesion boundary zone and hippocampal CA3 region showed a variety of damage, morphological alterations, reduced perfusion, and intraluminal microthrombin formation. 2) Atorvastatin enhanced FITC-dextran perfusion of vessels and reduced intravascular coagulation. 3) Atorvastatin promoted the restoration of spatial memory function. CONCLUSIONS. These results indicated that atorvastatin warrants investigation as a potential therapeutic drug for TBI.     

Interferon gamma inhibits inter-enterocyte communication by reducing connexin 43 phosphorylation

Introduction. Restitution of the intestinal barrier requires inter-enterocyte communication via the phosphorylated gap junction protein connexin 43. Experimental necrotizing enterocolitis (NEC) is characterized by elevated interferon gamma (IFN) and impaired restitution. We therefore hypothesized that IFN impairs gap junction (GJ) function and restitution by inhibiting phosphorylation of connexin43. We further sought to determine whether connexin 43 phosphorylation was altered in human NEC. Methods. Connexin 43 expression and phosphorylation was assessed in IEC-6 cells ± IFN (1000 u/ml) by SDS--PAGE and confocal microscopy. GJ function was detected by microinjecting IEC-6 cells ± IFN with the GJ tracer lucifer yellow (LY) and impermeant rhodamine dextran. GJ function was inhibited with oleamide (10 μM). In vitro restitution was assessed using time lapsed video microscopy of IEC-6 cells ± IFN migrating across a scraped wound. Small bowel mucosal scrapings were acquired from infants undergoing bowel resection for NEC and compared to specimens taken from infants without NEC. Data are mean ± SEM. Results. IFN significantly reduced phosphorylation of connexin 43 (band density relative to actin, Ctrl: 0.86 ± 0.3 versus IFNγ 0.37 ± 0.1, P < 0.05) and decreased membrane localization of the phosphorylated gap junctions. This correlated with decreased gap junction function as detected by loss of LY transfer (levels of intercellular transfer: Ctrl: 3.2 ± 0.2, IFN 2.4 ± 0.3, oleamide 0, P < 0.05). Oleamide and IFN significantly reduced enterocyte restitution (ctrl: 5 μm/h, oleam: 1.5 μm/h, IFN: 1.6 μm/h, P < 0.05), correlating with a lack of intercellular communication. Strikingly, phosphorylation of connexin 43 in the mucosa of infants with NEC was significantly reduced as compared to control bowel, which correlated with the extent of mucosal disease. Conclusion. IFN inhibits phosphorylation of connexin 43, leading to impaired inter-enterocyte communication and reduced restitution. The finding of decreased phosphoconnexin 43 in human NEC suggests that impaired inter-enterocyte communication may underlie the barrier dysfunction in this disease.     

Biomechanical investigation into the torsional failure of immature long bone

Approximately 50% of infant and toddler long bone fractures are attributed to non-accidental trauma; however, differentiating from benign mechanisms is subjective, due to an absence of evidence-based diagnostic tools. Previous studies investigated small ranges of rotational velocities in animal long bone models, although did not report the variation in the spiral fracture angle. This study considered the fracture angle as a potential clinical measure, correlating this data with a wider range of rotational velocities. The spiral fracture angle was measured relative to the long axis, whilst noting the narrowest diaphysial diameter, location of the fracture, and the extent of comminution and periosteal disruption. Twenty-six bones failed in spiral fracture, with the potting material failing in the remaining tests. All spiral fractures centred on the narrowest diaphysial diameter. Slower rotational velocities caused fracture angles approaching 45°, whereas fractures at greater velocities caused fracture angles nearer 30°. A relatively strong trend (R² = 0.78) is reported when the normalised fracture angle (against the narrowest diaphysial dimension) was plotted against the rotational rate. A relationship has been identified between the angle of spiral fracture and the rotational velocity using the immature bovine metatarsal model. This trend forms a scientific foundation from which to explore developing a diagnostic, evidence-based tool that may ultimately serve to assist differentiating between accidental and non-accidental injury.     

Surgical management of contiguous multilevel thoracolumbar tuberculous spondylitis

Introduction

Tuberculous spondylitis (TBS) is the most common form of extra-pulmonary tuberculosis. The mainstay of TBS management is anti-tuberculous chemotherapy. Most of the patients with TBS are treated conservatively; however in some patients surgery is indicated. Most common indications for surgery include neurological deficit, deformity, instability, large abscesses and necrotic tissue mass or inadequate response to anti-tuberculous chemotherapy. The most common form of TBS involves a single motion segment of spine (two adjoining vertebrae and their intervening disc). Sometimes TBS involves more than two adjoining vertebrae, when it is called multilevel TBS. Indications for correct surgical management of multilevel TBS is not clear from literature.

Materials and methods

We have retrospectively reviewed 87 patients operated in 10 years for multilevel TBS involving the thoracolumbar spine at our spine unit. Two types of surgeries were performed on these patients. In 57 patients, modified Hong Kong operation was performed with radical debridement, strut grafting and anterior instrumentation. In 30 patients this operation was combined with pedicle screw fixation with or without correction of kyphosis by osteotomy. Patients were followed up for correction of kyphosis, improvement in neurological deficit, pain and function. Complications were noted. On long-term follow-up (average 64 months), there was 9.34 % improvement in kyphosis angle in the modified Hong Kong group and 47.58 % improvement in the group with pedicle screw fixation and osteotomy in addition to anterior surgery (p < 0.001). Seven patients had implant failures and revision surgeries in the modified Hong Kong group. Neurological improvement, pain relief and functional outcome were the same in both groups.

Conclusion

We conclude that pedicle screw fixation with or without a correcting osteotomy should be added in all patients with multilevel thoracolumbar tuberculous spondylitis undergoing radical debridement and anterior column reconstruction.

     

Inverted papilloma of ureter: a rare cause of hydronephrosis

A case of hydronephrosis with a rare underlying cause in a 35 years old male is described. He reported with pain in the left lumbar region with a past history of left ureterolithotomy. The ultrasound and IVU studies were suggestive of left hydronephroureter. CT Scan showed left hydronephroureter with narrowing at the lower end of left ureter. Ureterorenoscopy (URS) confirmed polypoidal lesions in the left lower ureter, completely obliterating the lumen and involving the whole circumferential wall of the lower ureter. The biopsy of the lesion revealed an inflammatory polyp. Accordingly open surgical intervention was planned. Excision of the lower third of left ureter with ureteric reimplantation was done with a Boari flap. The histopathology report of the lower third of ureter confirmed inverted papilloma of ureter. The patient made a smooth postoperative recovery.     

Pancreatitis after liver transplantation in children: a single-center experience

BACKGROUND AND METHOD: Posttransplantation acute pancreatitis (PTAP) is a rare but serious complication after pediatric liver transplantation (LTx). We performed a retrospective review in a large cohort of pediatric liver transplant recipients at a single institution to define the impact of this problem in children. RESULTS: Between January 1986 and December 1999, 634 pediatric LTx were performed. Twenty-six patients developed serious acute pancreatitis. The mean age at transplantation was 7.7 years (9 months to 19 years), and the indications for transplantation were biliary atresia in seven, fulminant hepatic failure in six, chronic rejection in seven, and other etiologies in six patients. PTAP was more likely to occur early after LTx (61% within the first week), was associated with the presence of an infrarenal aortic graft in 14 (54%) of 26 patients, was more likely to occur after retransplantation (11/26 patients), and was associated with blood loss and prolonged surgery in four cases. Acute renal failure occurred in 15 (58%) of 26 patients. Mortality was 42% (11/26); causes of death were sepsis or multiple organ failure in nine and hemorrhage in two patients. Management of PTAP included antibiotics, sphincterotomy, debridement with drainage, hepatic arterial revascularization, and arterial ligation. Of the 14 patients with complicated pancreatitis, 5 were treated conservatively and died. Nine patients had extensive operative interventions and four survived (45%). CONCLUSIONS: Several risk factors such as retransplantation, extensive dissection at the time of LTx, and use of infrarenal arterial graft contribute to development of PTAP in children. Early exploration and debridement in patients with complicated pancreatitis may result in a better outcome. Retransplantation in the presence of clinical pancreatitis has a high failure rate.