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.     

Giant intracranial germinoma

Journal of Neuro-Oncology -     

Obsessive-compulsive disorder in callers to the Anxiety Disorders Association of America.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic, impairing and often comorbid disorder. METHODS: 1000 subjects who called the Anxiety Disorders Association of America (ADAA) were surveyed and divided in three groups: (a) callers with OCD (OCD) and two overlapping control groups: (b) callers with no axis I disorder (NAC) and (c) with no-OCD (NOC) using a 97-item questionnaire. RESULTS: The rate of OCD was 14.5% (N = 145). Relative to the NOC group, OCD subjects were more likely to be female, White, younger and not married. Relative to the NAC group, subjects with OCD were more likely to be White, not married and younger. OCD was accompanied by significant comorbidity and was associated with an increased number of visits to health professionals than NAC subjects. There was no significant difference regarding unemployment rates among the three groups. However, OCD callers were more likely than both control groups to have missed work or have decreased productivity due to their mental condition. OCD subjects took an average of 1 psychotropic medication in the past year and were statistically more likely than the control groups to experience sleepiness and nervousness as side effects. CONCLUSIONS: OCD was fairly prevalent among ADAA callers and presented high levels of comorbidity, impairment, health care utilization and sensitivity to psychotropic side effects.     

Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

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.