Combined occurrence of von Willebrand's disease and factor XIII deficiency: a case report

We report the case of a three year old female child with combined occurrence of von Willebrand's disease and factor XIII deficiency, an extremely rare combination. The patient presented with prolonged bleeding following cuts and wounds. Clot solubility test using 5M urea was positive. Platelet aggregation using ristocetin was reduced, which corrected on adding normal plasma. Aggregation with other agonists was normal. We discuss the clinico- hematological profile of the case. Only one such case has been reported in literature in the past to the best of our knowledge.     

Presacral neurilemoma (schwannoma) —Report of a rare case—

A rare case of presacral neurilemoma is reported herein. Despite the large size of the tumor and the extensive destruction of the sacrum, the patient was almost asymptomatic. Accurate diagnosis depends on careful rectal examination and computerized axial tomography is the most useful single investigation. Surgery is the only treatment and for large lesions, the abdominal approach is usually preferred. Recurrence is rare and patients live a long, symptom free life even after partial resection.     

Histopathologic Alterations after Endovascular Radiation and Antiproliferative Stents: Similarities and Differences

Background: Endovascular radiation and drug-eluting antiproliferative stents in experimental animals (normal pigs and rabbit arteries) show a decrease in the neointimal growth at 1 months vs. controls. However, this is accompanied by delayed healing characterized by persistence of neointimal fibrin (with or without inflammation), a decrease in smooth muscle cells, and incomplete endothelialization. Conversely, stainless steel control stents show complete healing with the neointima consisting of smooth muscle cells in a proteoglycan-collagen matrix and near complete luminal surface endothelialization. Results: Long-term (3 and 6 months) animal studies fail to show any benefit with radiation or drug-eluting stents. These experimental results are discrepant from those seen clinically in man where both therapies have shown benefit at 6 months, suggesting that animal data may not be predictive of clinical results. The main differences can be explained on the basis of preclinical studies performed in juvenile animals without underlying atherosclerosis, which leads to accelerated healing in animals vs. man such that 1 month animal data likely correspond to 6 months in man. Therefore long-term (24-30 months) angiographic and/or IVUS follow-up studies in man will be required to determine if drug-eluting stents will behave similarly to animal studies at 3 and 6 months. Hintergrund: Sowohl die endovaskuläre Bestrahlung als auch antiproliferativ beschichtete Stents führen nach 1 Monat im Vergleich zu Kontrollen an gesunden Schweine- und Kaninchenarterien zu einer Abnahme des Neointimawachstums. Dies ist allerdings von einem verzögerten Heilungsprozess begleitet, der durch die Persistenz von Fibrinablagerungen auf der Neointima (mit oder ohne Entzündungszeichen) sowie durch eine Abnahme glatter Gefäßmuskelzellen und durch eine unvollständige Endothelialisierung charakterisiert ist. Im Gegensatz hierzu zeigen die Kontrollstents aus Edelstahl einen vollständigen Heilungsprozess mit Neointimabildung, die aus glatten Gefäßmuskelzellen und nach Proteoglykankollagenmatrix besteht und zu einer nahezu kompletten Endothelialisierung des Gefäßvolumens führt. Experimentelle Langzeitstudien (3 und 6 Monate) konnten keinen Nutzen der Bestrahlung oder der antiproliferativen Stents nachweisen. Ergebnisse: Diese experimentellen Ergebnisse stehen im Widerspruch zu den klinischen Ergebnissen, die für beide Therapieformen nach 6 Monaten einen Vorteil belegten. Hieraus könnte man schließen, daß die experimentellen Daten keinen prädiktiven Wert für klinische Ergebnisse besitzen. Dieser scheinbare Widerspruch könnte damit erklärt werden, dass die experimentellen Studien an jungen Tieren ohne zugrunde liegender Atherosklerose durchgeführt wurden, bei denen der Heilungsprozess im Vergleich zum Menschen deutlich beschleunigt abläuft. Daher entsprechen möglicherweise die experimentellen 1-Monats-Daten eher den 6-Monats-Daten beim Menschen. Aus diesem Grunde werden Langzeitstudien (24-30 Monate) mit Koronarangiographie und IVUS benötigt, um eine Vergleichsmöglichkeit zu den antiproliferativ beschichteten Stents nach 3-6 Monaten im Tierexperiment zu schaffen.     

Cardiomyopathy in a child with hypereosinophilic syndrome

Summary A 9-year-old boy presented with increasing fatigue, anorexia, weight loss, fever, and absolute eosinophilia (48,000/μL). Pulmonary infiltrates occurred 3 months later. A murmur of mitral regurgitation was heard 5 months after onset of illness, and heart failure soon followed. Despite corticosteroid therapy the eosinophilia persisted intermittently until 1 month before death. The patient died within 9 months of the onset of illness. At necropsy there was cardiomegaly with subendocardial fibrosis in the right and left ventricles. Thrombi were present in the left ventricular apex and behind the posterior mitral leaflet. The findings in 12 previously reported pediatric cases are reviewed. The etiopathogenesis of the hypereosinophilic syndrome is discussed: half of the cases in children are associated with leukemia. Supported in part by the Clinical Research Service, Walter Reed Army Medical Center The opinions expressed herein are those of the authors and do not necessarily represent the views of the Department of the Army or the Department of Defense     

Complications of the intraaortic balloon counterpulsation device: Clinical and morphologic observations in 45 necropsy patients

Of 45 patients who died after insertion of an intraaortic balloon assist device and who were studied at necropsy, 16 (36 percent) were found to have one or more complications (total 20) related to use of the device. The 20 complications consisted of dissection of the aorta or its distal branches, or both (9), arterial perforation (3), arterial thrombi (3), arterial emboli (3), limb ischemia (1) and local wound infection (1). Of the nine cases of arterial dissection, none were diagnosed or suspected before necropsy. Of the entire 20 complications, only 4 (20 percent) were suspected before death. Although the operating team frequently encountered no difficulty at the time of insertion of the device, 12 of the 20 complications were a direct result of insertion of the intraaortic balloon assist device. In two patients in whom insertion of the balloon caused dissection of the aorta, hemodynamic improvement occurred for 2 and 3 days, respectively, even though the “intraaortic” balloon (as well as the catheter) was not located in the true lumen of the aorta. Thus, clinical evaluation of complications related to use of the intraaortic balloon assist device underestimates their frequency. Most complications are consequences of insertion of the device, not consequences of its being in place.     

Some characteristics of the adrenergic neurone blocking action of dehydroemetine

The uptake of dehydroemetine by adrenergic neurones was studied indirectly by testing the ability of various procedures to prevent or reverse adrenergic neurone blockade in the periarterially stimulated rabbit isolated ileum. Adrenergic neurone blockade was prevented but not reversed by equilibration with dehydroemetine at low temperature (0 degrees C), in the absence of sodium or in the presence of tetrodotoxin. Noradrenaline, cocaine, potassium deprivation and potassium excess did not modify the adrenergic neurone blocking action of dehydroemetine.     

Spectrum of inherited bleeding disorders in Indians.

The incidence of hereditary hemorrhagic disorders may vary according to the country and ethnic origin. Von Willebrand disease has emerged as the most common hereditary hemorrhagic disease in the industrialized world. In this series of 966 patients diagnosed to have inherited bleeding disorders, hemophilia A was the most common and was seen in 410 (42.4%) of the patients followed by platelet function defects seen in 380 (39.4%) of the patients. It is thus concluded that, similar to the white population, hemophilia A remains the most common bleeding disorder in the Indian population, although this is closely followed by platelet function defects in India, which are quite rare in whites. Von Willebrand disease is relatively rare in the Indian population.     

Proinflammatory and anti-inflammatory cytokine balance in gasoline exhaust induced pulmonary injury in mice

Proinflammatory and anti-inflammatory cytokine balance and associated changes in pulmonary bronchoalveolar lavage fluid (BALF) of unleaded gasoline exhaust (GE) exposed mice were investigated. Animals were exposed to GE (1 L/min of GE mixed with 14 L/min of compressed air) using a flow-past, nose-only, dynamic inhalation exposure chamber for different durations (7, 14, and 21 days). The particulate content of the GE was found to be 0.635, +/-0.10 mg PM/m3. Elevated levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were observed in BALF of GE-exposed mice, but interleukin 1beta(IL-1beta) and the anti-inflammatory cytokine interleukin-10 (IL-10) remained unaffected. GE induced higher activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (gammaGT), and lactate dehydrogenase (LDH) in the BALF, indicating Type II alveolar epithelial cell injury, Clara-cell injury, and general toxicity, respectively. Total protein in the BALF increased after 14 and 21 days of exposure, indicating enhanced alveolar-capillary permeability. However, the difference in the mean was found statistically insignificant in comparison to the compressed air control. Total cell count in the BALF of GE-exposed mice ranged between 0.898 and 0.813x10(6) cells/ml, whereas the compressed air control showed 0.65x10(6) cells/mL. The histopathological changes in GE-exposed lung includes perivascular, and peribronchiolar cuffing of mononuclear cells, migration of polymorphonuclear cells in the alveolar septa, alveolar thickening, and mild alveolar edematous changes indicating inflammation. The shift in pro- and anti-inflammatory cytokine balance and elevation of the pulmonary marker enzymes indicate toxic insult of GE. This study will help in our understanding of the mechanism of pulmonary injury by GE in the light of cytokine profiles, pulmonary marker enzymes, and lung architecture.     

Cell migration and metastasis as targets of small RNA-based molecular genetic analyses

Metastatic tumor cells can migrate from one place to another in the body. This involves their adherence to host cell layers and subsequent transcellular movements by a complex process, molecular basis of which are yet to be clarified. Elucidation of genes functionally involved in metastasis may lead to deeper understanding of the mechanism of cell migration, and identification and designing of metastasis-modulating strategies for cancer therapeutics. We review here cell migration in tumor metastasis and the use of small RNA-based approaches to identify functional genes. We then describe our promising novel approach that uses randomized ribozyme libraries for identification of genes involved in cell migration, a consistent feature of metastatic cells. This revised version was published online in July 2006 with corrections to the Cover Date.     

Polymorphism of Fc receptor IIa for IgG in infants is associated with susceptibility to perinatal HIV-1 infection

OBJECTIVE: To evaluate the effect of polymorphism of the Fc gamma receptor IIa, which is associated with differential human IgG subclass binding, on perinatal HIV-1 transmission. METHODS: Fc gamma RIIa genotype was tested in 448 HIV-seropositive mothers and their infants from a cohort study designed to assess the effect of placental malaria on HIV vertical transmission conducted from 1996 to 2001 in western Kenya. Fc gamma RIIa polymorphism was analyzed for associations with susceptibility to perinatal HIV infection and all-cause child mortality in HIV-positive children. RESULTS: Overall, 20% of infants were perinatally infected with HIV. There was no statistically significant association between maternal genotype and perinatal HIV-1 transmission. However, frequency of the infant Fc gamma RIIa His/His131 genotype was higher in HIV-positive compared with HIV-negative infants (35% and 21%, respectively), whereas the distribution was reversed (15% and 28%, respectively) for infants with the Fc gamma RIIa Arg/Arg131 genotype. Multivariate logistic regression controlling for maternal and infant confounding factors demonstrated that the odds of perinatal HIV infection in infants with the Fc gamma RIIa His/His131 versus Fc gamma RIIa His/Arg131 genotypes were significantly higher (adjusted odds ratio, 2.22; 95% confidence interval, 1.23-4.02; P = 0.009). There was no evidence for an association between HIV-positive child all-cause mortality and Fc gamma RIIa genotype. CONCLUSIONS: This study provides the first evidence that the infant Fc gamma RIIa His/His131 genotype is associated with susceptibility to perinatal HIV-1 transmission and further suggests that there is a dose-response relationship for the effect of the Fc gamma RIIa His131 gene on transmission.