Platelets in Early Antibody-Mediated Rejection of Renal Transplants

Antibody-mediated rejection is a major complication in renal transplantation. The pathologic manifestations of acute antibody-mediated rejection that has progressed to functional impairment of a renal transplant have been defined in clinical biopsy specimens. However, the initial stages of the process are difficult to resolve with the unavoidable variables of clinical studies. We devised a model of renal transplantation to elucidate the initial stages of humoral rejection. Kidneys were orthotopically allografted to immunodeficient mice. After perioperative inflammation subsided, donor-specific alloantibodies were passively transferred to the recipient. Within 1 hour after a single transfer of antibodies, C4d was deposited diffusely on capillaries, and von Willebrand factor released from endothelial cells coated intravascular platelet aggregates. Platelet-transported inflammatory mediators platelet factor 4 and serotonin accumulated in the graft at 100- to 1000-fold higher concentrations compared with other platelet-transported chemokines. Activated platelets that expressed P-selectin attached to vascular endothelium and macrophages. These intragraft inflammatory changes were accompanied by evidence of acute endothelial injury. Repeated transfers of alloantibodies over 1 week sustained high levels of platelet factor 4 and serotonin. Platelet depletion decreased platelet mediators and altered the accumulation of macrophages. These data indicate that platelets augment early inflammation in response to donor-specific antibodies and that platelet-derived mediators may be markers of evolving alloantibody responses.     

Hailey–Hailey disease improved by fractional CO2 laser

Hailey–Hailey disease (HHD), also known as benign familial pemphigus, is an autosomal dominant skin condition that affects the adhesion of epidermal keratinocytes. Although the initial manifestation of flaccid vesicles on erythematous or normal skin in flexure sites frequently goes unnoticed, large, macerated, exudative plaques of superficial erosions with crusting are observed at the time of diagnosis. There is no specific treatment for HHD, and most cases are symptomatically supported. However, infrared laser ablation has been somewhat helpful. We present a case successfully treated with fractional CO₂ laser showing a long-term favourable outcome and no adverse effects. Thus, this modality could be an alternative to full ablation for this condition.     

Lack of efficacy of thickened feeding as treatment for gastroesophageal reflux

The efficacy of thickened feedings for the treatment of gastroesophageal reflux in infancy was evaluated. Fifty-two infants were examined with prolonged pH monitoring of the distal esophagus after feedings of apple juice or apple juice thickened with rice cereal. All infants had a minimum of three feedings of both thickened and unthickened juice. The recordings of distal esophageal pH were analyzed for the percent of time the pH was less than 4 in the first 2 hours after each feeding. The infants were maintained in the following positions after feeding: prone (n = 29), prone-board with the head elevated 30 degrees from horizontal (n = 29), supine (n = 7), and unrestricted (n = 21). We found no significant difference in the percent of time with reflux with thickened versus unthickened feedings except in those infants maintained in the 30-degree prone position. In the first 2 hours after eating thickened juice, infants maintained in this position had increased esophageal reflux time (P less than 0.006). Further analysis revealed that 33% of the infants had a greater than 30% increase in esophageal reflux time after thickened feedings. Our study suggests that the immediate effect of thickened feedings on gastroesophageal reflux in infants is unpredictable.     

Radioimmunoassay for amatoxins by use of a rapid, 125I-tracer-based system

In this new radioimmunoassay system for determination of amatoxins in urine and plasma, a novel chemical approach is used for antigen and 125I-tracer production, based on a detoxified alpha-amanitin derivative (aldoamanitin). Total assay time, including data processing, is less than 100 min. The lowest detectable concentration is 1 microgram/L for urine, 0.1 microgram/L for plasma. In the clinically significant range, within-run CVs are less than 8%. This new 125I-based assay is a significant improvement over existing 3H technology in terms of speed, precision, and freedom from interference.     

Herpes simplex virus hepatitis: an analysis of the published literature and institutional cases.

Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovir-treated patients as compared to 88% in the untreated subjects (P=0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age>40 yr, immunocompromised state, ALT>5,000 U/L, platelet count<75x10(3)/L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded.     

Sick sinus syndrome: strategies for reducing mortality.

The evolution of sick sinus syndrome is slow, and its clinical and electrocardiographic manifestations are intermittent. A-V and I-V conduction disturbances often arise, but incidence of defects with clinical consequences is too low. Death rate, when large groups are considered, is slightly higher than that of the general population of the same age and with similar pathologies. Mortality depends on concomitant pathologies, on the development of congestive heart failure, on the arterial thromboembolism and on the type of sinus disease. The use of ventricular pacemakers (VVI) did not reduce mortality. Atrial pacing (AAI) gives the auricles electrical stability preventing fibrillation and systemic embolism. The hemodynamic role of the auricles is also preserved. As a consequence, death rate is reduced when AAI is used. In cases with a-v conduction disturbances or with paroxysmal atrial fibrillation, dual chamber pacing (DDD) is preferable because it permits ventricular pacing to be continued even if a-v block or paroxysmal or chronic atrial fibrillation appears. When using ventricular pacing and in cases in which pacing is not considered, warfarin or aspirin can prevent strokes and systemic embolism. In bradycardia-tachycardia syndrome requiring treatment of arrhythmias dual chamber pacemaker must be implanted.