The effect of gender and gender match on mortality in pediatric heart transplantation.

The effect of organ-recipient gender match on pediatric heart transplant mortality is unknown. We analyzed the effects of gender and donor-recipient gender matching. Based on Organ Procurement and Transplant Network data, we performed a historical cohort study in a population of 3630 heart transplant recipients less than 18 years old. We compared unadjusted and adjusted mortality by recipient gender, donor gender and between gender-matched and gender-mismatched recipients. Female recipients had decreased survival compared to male recipients (unadjusted hazard ratio [HR] 1.16, confidence interval [CI] 1.02-1.31; p = 0.020). Organ-recipient gender mismatch did not affect mortality for either male or female recipients, though gender-mismatched females had the worst survival compared to gender-matched males, who had the best survival (unadjusted HR 1.26, CI 1.07-1.49; p = 0.005). After adjustment for other risk factors affecting transplant mortality, female recipients had decreased survival compared to male recipients (HR 1.27, CI 1.12-1.44; p = 0.020) and gender matching had no effect. In conclusion, gender mismatch alone did not increase long-term mortality for pediatric heart transplant recipients. However, there may be additive effects of gender and gender matching affecting survival. There are insufficient data at this time to support that recipient and donor gender should affect heart allocation in children.

Novel techniques in the use of bivalirudin for cardiopulmonary bypass anticoagulation in a child with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) occurs in both the pediatric and adult populations after exposure to heparin. Bivalirudin has been used as an alternative to heparin for adults undergoing cardiac surgery and cardiopulmonary bypass, but has only been used minimally in children for this purpose. We report the successful use of bivalirudin for anticoagulation during cardiopulmonary bypass in a small child with HIT, using novel techniques not previously described.

Transmission electron microscopy of intracellular particles of polyethylene from joint replacement prostheses: size distribution and cellular response.

The objectives of this transmission electron microscopy study of peri-implant tissues retrieved at revision arthroplasty were to (1) determine the size distribution of intracellular polyethylene particles, and (2) assess the cellular response to phagocytosed polyethylene particles as revealed by the condition of the cellular organelles. The frequency distributions of intracellular polyethylene particle sizes for 15 cases of total hip replacement showed that more than 75% of the particles had lengths of less than 0.5 microm. More than 90% of the particles were less than 1.0 microm in size. In comparison, the frequency distribution for the particles in cellscomprising tissue retrieved from three total knee replacement prostheses showed that only 43% of the particles were less than 0.5 microm in length and 72% were less than 1 microm in size. There was no statistically significant difference in the mean particle length between the specimens from the hip and knee patients. The majority of the cells containing polyethylene were without signs of degeneration. The cytoplasmic and nuclear membranes were intact. Several electron lucent voids which once contained polyethylene particles were seen surrounded by several healthy appearing mitochondria, which displayed sharp membranes and intact cristae. There were no signs of a cytotoxic response to polyethylene at the ultrastructural level.

Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia-reperfusion.

BACKGROUND: Adenosine-enhanced ischemic preconditioning extends the protection of ischemic preconditioning by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. METHODS: The effects of adenosine-enhanced ischemic preconditioning on necrosis and apoptosis were investigated in the sheep heart using models of stunning (15 minutes regional ischemia, 120 minutes reperfusion) and ischemia-reperfusion (30 and 60 minutes regional ischemia, 120 minutes reperfusion). Ischemic preconditioned hearts received 5 minutes regional ischemia, 5 minutes reperfusion before ischemia. Adenosine-enhanced ischemic preconditioned hearts received a 10 mmol/L adenosine bolus (10 mL) through the left atrium coincident with ischemic preconditioning. Adenosine hearts received a 10 mmol/L bolus (10 mL) of adenosine. Regional ischemic hearts received no pretreatment. RESULTS: Minimal apoptosis (< 45 per 3,000 myocytes) was observed in the stunning models but was significantly increased with ischemia-reperfusion in regional ischemic hearts after 30 minutes (p < 0.05 versus ischemic preconditioning, adenosine, or adenosine-enhanced ischemic preconditioning) and in adenosine and ischemic preconditioned hearts after 60 minutes ischemia (p < 0.05 versus adenosine-enhanced ischemic preconditioning). DNA laddering was apparent after 60 minutes ischemia in regional ischemia, adenosine, and ischemic preconditioning but not in adenosine-enhanced ischemic preconditioned hearts. CONCLUSIONS: Adenosine-enhanced ischemic preconditioning significantly ameliorates necrosis and apoptosis in the regional ischemic blood-perfused heart.

Renal failure resulting from infiltration by inflammatory myofibroblastic tumor responsive to corticosteroid therapy.

Inflammatory myofibroblastic tumor (IMT) is a rare disease of inflammatory and spindle cell proliferative lesions in multiple sites. Most frequently reported in the lungs, a variety of extrapulmonary sites have been described. We report the first case of IMT causing renal failure by massive bilateral renal infiltration. Renal function continued to deteriorate (peak serum creatinine level, 8.4 mg/dL) despite placement of a ureteral stent. The kidneys were diffusely enlarged on computed tomographic (CT) scan. Renal biopsy showed myofibroblastic proliferation and inflammatory infiltration. Renal failure responded favorably over weeks to corticosteroid therapy (serum creatinine level, 2.8 mg/dL) with a marked reduction in bilateral renal enlargement by CT scan.

Late renal allograft failure secondary to thrombotic microangiopathy associated with disseminated malignancy.

A renal transplant recipient with a remote history of end-stage renal disease due to postpartum hemolytic-uremic syndrome (HUS) presented with acute renal failure after having stable renal allograft function for 9 years. A diagnosis of thrombotic microangiopathy was made based on clinical and histologic findings at renal biopsy. She was treated conservatively, never regaining graft function and ultimately succumbing from her overwhelming tumor load approximately 6 months following diagnosis of her malignancy. To our knowledge, this is the first report of thrombotic microangiopathy associated with disseminated malignancy resulting in renal allograft failure.

Enterocytozoon bieneusi infection and diarrheal disease in patients who were not infected with human immunodeficiency virus: case report and review.

We describe the identification of the protozoan parasite Enterocytozoon bieneusi in the stool of a patient who was not infected with HIV but who presented with persistent diarrheal disease and severe abdominal complaints. The patient was not infected with HIV but had been noted to have a decreased CD4 cell count since at least 1992 and had had a prior episode of cryptococcal meningitis. The organisms were detected in stool smears with a modified trichrome stain and were identified to the species level by transmission electron microscopy of the stool. The patient responded readily and dramatically to treatment with albendazole, with resolution of symptoms and clearance of the organisms from the stool. Eight or possibly nine other cases of E. bieneusi infection associated with diarrheal disease in individuals who were not infected with HIV were identified in the English-language literature. In two individuals with intact immune function, symptoms were self-limited and diarrheal disease resolved within 2 weeks. The cases summarized herein suggest that E. bieneusi may be more commonly associated with sporadic diarrheal disease than was previously suspected and that the immune system may play a role in the control of this organism within the intestine.

Microsporidian sinusitis in patients with the acquired immunodeficiency syndrome.

Sinusitis in patients with human immunodeficiency virus (HIV) infection usually arises from the same organisms that are infective in the nonimmunosuppressed population. The authors of this article report that optimal antimicrobial treatment and functional endoscopic sinus surgery failed to eradicate sinonasal disease in three of five patients with acquired immunodeficiency syndrome (AIDS) and refractory sinusitis. The sinonasal disease was manifested by congested, edematous, and polypoid mucosa, often with a superimposed bacterial infection from ostial obstruction. After tissue was sent for electron microscopy (EM), the patients were eventually diagnosed with microsporidiosis of the sinonasal cavities. Microsporidia are obligate intracellular protozoans that have been seen in AIDS patients with diarrhea. These protozoans have only recently been identified in sinonasal tissue. Microsporidia are often missed on routine histopathology. The authors present case reports on their five AIDS patients with refractory sinusitis. The management of refractory sinusitis in the HIV-infected population, including mandatory EM of sinonasal tissue, is also discussed.

Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: optimization of cardioplegic protection and mechanism of action.

OBJECTIVE: The effect of cardioplegic solutions with high concentrations of potassium or magnesium (or both) on cytosolic calcium accumulation was investigated with fura-2 in isolated perfused mature (n = 24) and aged (n = 24) rabbit hearts. METHODS: We compared cytosolic calcium accumulation before ischemia (control), during 30 minutes of ischemia and 30 minutes of reperfusion under global ischemia, or after treatment with potassium (20 mmol/L), magnesium (20 mmol/L), or both. RESULTS: Cytosolic calcium accumulation was increased during global ischemia in the mature heart (from 178.7 +/- 24.2 in the control group to 393.6 +/- 25.5 nmol/L; p < 0.005) and in the aged heart (from 187.4 +/- 18.7 in the control group to 501.0 +/- 46.1 nmol/L; p < 0.005). Potassium reduced cytosolic calcium accumulation during ischemia in both the mature and aged hearts (300.9 +/- 23.2 and 365.2 +/- 27.7 nmol/L, respectively; p < 0.05 vs global ischemia). Magnesium and potassium/magnesium completely controlled cytosolic calcium accumulation in the mature heart (198.7 +/- 27.5 nmol/L; p < 0.01 vs global ischemia and p < 0.05 vs potassium: 182.3 +/- 22.7 nmol/L; p < 0.05 vs global ischemia and potassium, respectively). Magnesium and potassium/magnesium attenuated cytosolic calcium accumulation in the aged heart (261.3 +/- 26.7, 262.3 +/- 25.2 nmol/L, respectively; p < 0.01 vs global ischemia). These changes in cytosolic calcium accumulation correlated with improved post-ischemic ventricular function. To investigate the mechanism(s) of magnesium-supplemented cardioplegic inhibition of cytosolic calcium accumulation, we performed parallel studies (n = 43) using nifedipine, ryanodine, and dimethylthiourea. Nifedipine with or without ryanodine reduced cytosolic calcium accumulation. Dimethylthiourea did not alter cytosolic calcium accumulation during global ischemia. Our results suggest that cytosolic calcium accumulation during global ischemia was mainly increased via the sarcolemmal 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. The modulating action of potassium/magnesium cardioplegia on cytosolic calcium accumulation during ischemia would appear to act through the inhibition of the myocardial 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. CONCLUSION: Senescent cardiac dysfunction correlates with increased ischemia-induced cytosolic calcium accumulation. Magnesium-supplemented potassium cardioplegia ameliorates this age-related phenomenon at normothermia and may have important implications in myocardial protection in the elderly population.

Epstein-Barr virus-induced infectious mononucleosis complicated by acute renal failure: case report and review.

Infectious mononucleosis, most commonly caused by Epstein-Barr virus (EBV), is generally a benign, self-limited illness. Occasionally, however, more severe complications may arise such as acute renal insufficiency. While subclinical renal involvement appears to be relatively common in patients with infectious mononucleosis, patients with significant renal parenchymal dysfunction have rarely been described in the English-language literature. In this report, we review 27 previous cases ad present a case of oliguric renal failure complicating heterophil-positive infectious mononucleosis. The patient required hemodialysis but recovered promptly with treatment with the combination of corticosteroids plus acyclovir. Renal biopsy revealed interstitial nephritis, and immunoperoxidase studies demonstrated a predominance of suppressor/cytotoxic T cells, which has been described in only one previous case report. In situ hybridization done on renal biopsy tissue failed to reveal evidence of EBV-encoded RNA-1. Acute renal failure in infectious mononucleosis is rare, often self-limited, and usually caused by interstitial nephritis that is likely the result of immunopathologic injury precipitated by EBV infection.

Malabsorption and wasting in AIDS patients with microsporidia and pathogen-negative diarrhea.

OBJECTIVE: To define the clinical syndrome, nutritional status and malabsorptive status in patients with HIV and chronic diarrhea and either microsporidia or no identified pathogen. PATIENTS: HIV-positive patients from an urban, hospital-based infectious disease clinic with chronic diarrhea who had undergone exhaustive gastrointestinal and stool studies for enteric pathogens and were found to have either microsporidia or no pathogen. METHODS: Patients were evaluated for clinical history, physical, body composition, nutritional and malabsorptive studies including D-xylose, Schilling test, determinations of 24 h stool fat, weight and nitrogen, and 24 h urea nitrogen. RESULTS: Ten patients with microsporidia were studied, four of whom were infected with Septata intestinalis, six with Enterocytozoon bieneusi; nine patients had no identified pathogen. Patients in both groups were comparable in stage of HIV disease, and demonstrated abnormal nutritional status and malabsorptive parameters. Patients with no pathogen had significantly longer duration of symptoms prior to presentation; however, patients with microsporidia had significantly greater malabsorption of fat, D-xylose, vitamin B12, and significantly lower serum levels of zinc. Nutritional status and malabsorption were similarly depressed in patients infected with either species of microsporidia. CONCLUSION: HIV-infected patients with chronic diarrhea associated with either microsporidial infection or with no identified pathogen had abnormal parameters of absorption and malnutrition, and those infected with microsporidia demonstrated more severe malabsorption.

Osteomalacia and osteoporosis in a woman with ankylosing spondylitis.

Three months postpartum, a 33-year-old woman with ankylosing spondylitis (AS) suffered multiple vertebral fractures. Bone mineral density was 61-67% of age-matched normal values at the lumbar spine and proximal femur, and an initial iliac crest bone biopsy revealed osteoporosis and osteomalacia. Secondary causes of bone disease were excluded, and the patient was treated with calcium, vitamin D, and nasal spray calcitonin (400 u/day). Over 4 years, she has shown partial recovery of bone mass and almost complete resolution of osteomalacia. Osteoporosis and fracture occur in patients with AS, yet this case represents a rare association between AS and both osteomalacia and postpregnancy spinal osteoporosis.

Magnesium cardioplegia enhances mRNA levels and the maximal velocity of cytochrome oxidase I in the senescent myocardium during global ischemia.

BACKGROUND: The aged myocardium accumulates significantly more cytosolic calcium [Ca2+]i during ischemia, and functional recovery is more severely compromised as compared with the mature heart. Cardioplegia ameliorates these phenomena. The mechanism by which increased calcium accumulation reduces functional recovery in the senescent myocardium is unknown, but it has been suggested that futile calcium cycling in the mitochondria leading to depletion of ATP stores during normothermic global ischemia may be involved. METHODS AND RESULTS: To investigate the effect of cardioplegia on mitochondrial calcium ([Ca2+]mt) accumulation and the expression of cytochrome oxidase I (COX I) during global ischemia, mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age > 130 weeks) rabbit hearts after Langendorff perfusion. Five perfused heart groups were investigated: 30 minutes of global ischemia without treatment (control), with potassium (K, 20 mmol/L), magnesium (Mg, 20 mmol/L), or potassium and magnesium (K/Mg) cardioplegia. No significant difference in [Ca2+]mt was evident in mature hearts with any protocol. In aged hearts, [Ca2+]mt was increased in global ischemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in aged hearts were lower in both control and global ischemia but were increased with cardioplegia. Maximal velocities for COX I were significantly increased with Mg cardioplegia both in the mature and the aged myocardium. CONCLUSIONS: K and/or Mg cardioplegia ameliorates [Ca2+]mt accumulation in aged hearts during normothermic global ischemia and increases COX I mRNA levels to a level not significantly different from that found in mature hearts.

Characterization of an invasive phenotype associated with enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAggEc) strains are associated with persistent diarrhea in children in the developing world and exhibit a classic aggregative phenotype. We have demonstrated that EAggEc strains isolated from children with persistent diarrhea in Brazil, Bangladesh, and Pakistan also have the potential to be internalized by HeLa cells in the gentamicin protection assay. We have confirmed this phenomenon with transmission electron micrographs of bacteria engulfed by HeLa cells. We examined the mechanisms by which this process occurs. Staurosporine inhibited internalization of EAggEc strain 162 by 50% at a concentration of 0.1 microM. Genistein inhibited internalization of this same organism by 50% at a concentration of 50 microM. Cytochalasin D inhibited internalization by 50% at a concentration of 1 microgram/ml. Staurosporine, genistein, and cytochalasin D inhibited the internalization of EAggEc strain 162 by HeLa cells in a dose-dependent manner. These data suggest that active cell processes such as signal transduction by protein kinase and/or tyrosine kinase may be involved in the internalization of EAggEc strain 162 by HeLa cells and that actin filaments and cytoskeletal structure may be important for this process.

Multiorgan microsporidiosis: report of five cases and review.

We describe five cases and review 34 reported cases of multiorgan microsporidiosis. Most of the patients with multiorgan involvement have been adults with AIDS. Organs most commonly infected include the small intestine, urinary tract, biliary tree, and eye; involvement of the respiratory tract, nasal sinuses, and central nervous system is also described but appears to be less frequent. Although patients with multiorgan disease may be asymptomatic, clinical presentation usually relates to the involved organs. Enterocytozoon bieneusi and Septata intestinalis are the most frequently identified species of pathogens. An affinity for certain tissues is observed among different microsporidial species. In all but one case of E. bieneusi infection, infection was limited to intestinal and hepatobiliary tracts, a finding suggestive of local extension. In contrast, the patients infected with S. intestinalis had widespread involvement, suggesting true hematogenous or lymphatic dissemination. Treatment may have to be based on findings regarding which organs and specific microsporidial species are involved. Further investigation of the pathogenic tendencies and route of acquisition of these organisms and the therapeutic agents active against them is needed.

Diagnosis of intestinal microsporidiosis by examination of stool and duodenal aspirate with Weber's modified trichrome and Uvitex 2B strains.

Severe, chronic diarrhea is a frequent complication of human immunodeficiency virus disease, and intestinal microsporidiosis is being recognized with increasing frequency in patients with AIDS. Noninvasive, cost-effective techniques are needed to optimize its diagnosis. Weber's modified trichrome stain (MTS) and the fluorochrome Uvitex 2B stain were used to detect microsporidial spores in smears of stool and duodenal aspirate (DA) samples received from human immunodeficiency virus-infected patients for examination for ova and parasites. Of 305 samples (292 stool and 13 DA samples) from 140 patients examined by MTS, 83 samples from 26 (18.6%) of the patients were positive for microsporidia (23 patients diagnosed initially and 3 diagnosed upon review). A subset of the samples studied by MTS consisting of 108 smears of stool and DA specimens from 60 patients was examined by Uvitex 2B. All 44 samples positive by MTS were also positive by Uvitex 2B. In addition, seven specimens and three patients were initially detected as positive by Uvitex 2B only (all three patients were positive also by MTS upon review). Confirmation of the diagnosis was obtained for 24 of 26 smear-positive patients by duodenal biopsy and/or stool transmission electron microscopy. Of 114 patients with stained smears negative for microsporidia, 23 had duodenal biopsies which showed no microsporidia. For the 43 patients who underwent duodenal biopsy, the sensitivity of both the MTS and the Uvitex 2B methods compared with biopsy results was 100%. Of six patients with negative duodenal biopsies and positive stained smears, four had microsporidia demonstrated by stool transmission electron microscopy. The examination of stool and DA smears stained by Uvitex 2B and/or MTS is a sensitive, noninvasive test for diagnosis of intestinal microsporidiosis which can be successfully implemented in a clinical laboratory. Strict adherence to precise diagnostic criteria is necessary to avoid incorrect results. The simultaneous use of both staining methods enhances performance and may provide greater accuracy, especially for patients with light infections.

Triggering of plaque disruption and arterial thrombosis in an atherosclerotic rabbit model.

BACKGROUND: It is now recognized that plaque disruption and thrombosis, a process often triggered by activities of the patient, is generally the cause of the onset of acute coronary syndromes. Understanding of disease onset could be greatly enhanced by the availability of a suitable animal model of plaque disruption and thrombosis. The aim of this study was to replicate and further characterize an atherosclerotic rabbit model of triggering of arterial thrombosis that was introduced by Constantinides and Chakravarti more than 30 years ago but not subsequently used. Aortic plaques were induced by a high-cholesterol diet, by mechanical balloon injury of the artery, or by a combination of the two. Triggering was attempted by injection of Russell's viper venom (RVV), which is a proteolytic procoagulant, and histamine. METHODS AND RESULTS: A total of 53 New Zealand White rabbits were exposed to one of four preparatory regimens: rabbits in group I (n = 9) were fed a regular diet for 8 months; rabbits in group II (n = 13) were fed a diet of 1% cholesterol for 2 months alternated with 2 months of a regular diet for a total of 8 months; rabbits in group III (n = 5) underwent balloon-induced arterial wall injury, then were given a regular diet for 8 months; and rabbits in group IV (n = 14) underwent balloon-induced arterial wall injury, then were given a diet of 1% cholesterol for 2 months followed by a regular diet for 2 months for a total of 4 months. After completion of the preparatory regimen, triggering of plaque disruption and thrombosis was attempted by injection of RVV (0.15 mg/kg IP) and histamine (0.02 mg/kg IV). In group I, normal control rabbits without atherosclerosis, only one small thrombus was noted in 1 of 9 rabbits. In group II, cholesterol-fed rabbits, thrombosis occurred in 3 of 13 rabbits. Thrombus occurred in all rabbits in group III (5 of 5) and in 10 of 14 rabbits in group IV. Although the frequency of thrombosis was not significantly different between groups I and II, possibly due to a small sample size, it was significantly different among all four groups (P < .001). Also, the frequency and amount of thrombus formation were significantly different among all four groups (P < .001; P < .0001) but not between groups I and II. Rabbits with atherosclerosis (those in groups II and IV) demonstrated plaque disruption and overlying platelet-rich thrombus formation similar to that observed in patients with acute coronary syndromes. The surface area covered by thrombus was 2 mm2 in group I, 15.3 +/- 19.2 mm2 in group II, 223 +/- 119 mm2 in group III, and 263 +/- 222 mm2 in group IV. Rabbits in groups III and IV had the greatest amount of thrombus, and this amount was significantly greater than in rabbits in groups I and II (P < .001 and P < .03, respectively). CONCLUSIONS: A suitable animal model is available for the study of plaque disruption and arterial thrombosis. Hypercholesterolemia and mechanical arterial wall injury seemed to produce plaques vulnerable to triggering of disruption and thrombosis, whereas normal arteries were relatively resistant to triggering. This model provides a method to evaluate agents that might decrease the occurrence of vulnerable plaques or the amount of thrombus formed after triggering. Most important, the model can be used to identify the features of vulnerable plaques and the pharmacological stressors that trigger plaque disruption and thrombus formation.

Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium.

Previous reports have indicated that the senescent myocardium is less tolerant to surgically induced ischemia and that diminished functional recovery is associated with alterations in cytosolic calcium ([Ca2+]i) accumulation. Recently, increased [Ca2+]i has been suggested to alter nuclear calcium ([Ca2+]n) accumulation. To investigate the relation between [Ca2+]i and [Ca2+]n, we subjected mature and aged rabbit hearts to normothermic global ischemia, either without treatment or after treatment with potassium cardioplegia, magnesium cardioplegia, or a combination of potassium and magnesium cardioplegia. The relation between altered [Ca2+]n and DNA fragmentation was also investigated. Our results indicate that [Ca2+]i was increased during 30 minutes of normothermic global ischemia without treatment in both the mature and aged hearts (p < 0.05). Accumulation of [Ca2+]i during global ischemia was reduced with the use of potassium, magnesium, and a combination of potassium and magnesium cardioplegia (p < 0.05 versus untreated ischemia) in both the mature and aged hearts. Levels of [Ca2+]n were unaffected by global ischemia or cardioplegia in the mature myocardium; however, in the aged myocardium, [Ca2+]n was increased during global ischemia and with potassium cardioplegia and was associated with increased nuclear DNA fragmentation (p < 0.05). The use of magnesium and a combination of potassium and magnesium cardioplegia attenuated [Ca2+]n accumulation and nuclear DNA fragmentation (p < 0.05). Control of [Ca2+]i and [Ca2+]n was associated with enhanced functional recovery during reperfusion. These results indicate that during normothermic ischemia, there is increased [Ca2+]i and [Ca2+]n in the aged myocardium, and increased [Ca2+]n is associated with increased nuclear DNA fragmentation.(ABSTRACT TRUNCATED AT 250 WORDS)