Acquired haemoglobin H disease

Acquired haemoglobin H disease has been described in various premalignant haematological conditions and is most commonly associated with myelodysplastic and myeloproliferative syndromes. The condition is not restricted to any specific population group or geography. Affected individuals have no family or past history of alpha thalassaemia and these subjects usually suffer from severe uncompensated haemolysis. Extensive mapping and sequence analysis of the alpha globin gene cluster have demonstrated intact alpha globin genes, leading workers to conclude that an acquired in trans mechanism is responsible for the disorder. ATRX gene mutations on the X chromosome have been shown to be instrumental in the suppression of alpha globin gene expression. Despite recent advances in the understanding of its pathogenesis, the precise mechanism of acquired haemoglobin H disease remains a mystery.     

Involvement of NKR‐P2/NKG2D in DC‐mediated killing of tumor targets: indicative of a common,innate, target‐recognition paradigm?

DC are the most efficient antigen-presenting cells that regulate the immune response. Here, we demonstrate the expression of NK cell receptor protein-2 (NKR-P2) on rat and mouse DC, and we show that NKR-P2 gets reorganized upon antigen contact. DC activated with anti-NKR-P2 mAb exhibit enhanced apoptotic killing of tumor targets, whereas blocking the interaction between NKR-P2 and its ligand with rNKR-P2 abrogated apoptotic killing, suggesting NKR-P2 to function as an activating molecule on DC. In vivo injection of anti-NKR-P2 mAb augmented DC activity and delayed tumor progression. NKR-P2 signaling involved Ca(2+ )influx, culminating in the expression of the apoptosis-inducing molecule, TNF-alpha. Taken together, these observations suggest that NKR-P2 (the rat orthologue of human NKG2D) acts as a target-recognition molecule on DC.     

Prospective evaluation of combined suprapubic and urethral catheterization to urethral drainage alone for intraperitoneal bladder injuries

BACKGROUND: The role of suprapubic catheterization after repair of intraperitoneal bladder injury is controversial and has been found to be superfluous in retrospective studies. We sought to evaluate bladder drainage prospectively. METHODS: Patients were prospectively enrolled and were assigned to suprapubic catheter drain after bladder repair or urethral catheter alone determined by the unit admitting the patient. Factors that were evaluated were associated injuries, hospital stay, duration of catheterization, and catheter-related complications. RESULTS: There were 42 patients: there were 39 male patients, and the mean age was 29.6 years. The patients were matched for age and associated injuries. The morbidity (p = 0.004) and hospital stay (p = 0.028) were significantly higher in the suprapubic drainage group. CONCLUSION: Urethral catheterization is adequate to effect bladder drainage after intraperitoneal bladder injury. In addition, it is associated with a shorter hospital stay and lower morbidity.     

Low urine pH is associated with reduced indinavir crystalluria in indinavir-treated HIV-infected individuals

Indinavir is a potent HIV-1 protease inhibitor included in current antiretroviral therapeutic regimens. It is associated with renal and urological complications ascribed to indinavir crystalluria. We have previously reported that indinavir crystalluria is frequently observed soon after initiation of therapy. In a cohort of 54 asymptomatic indinavir-naive HIV-1-infected individuals during their first year of treatment with indinavir, approximately 25% of urinalyses (U/A) contained indinavir crystals. Because the determinants of the crystalluria are unknown, we examined the relationship between urine specific gravity (SG) and pH, singly and in combination, and indinavir crystalluria in these subjects. A total of 579 U/A were obtained from the study subjects at their scheduled monthly outpatient medical assessments. The frequency of indinavir crystalluria was lower in U/A with lower pH, irrespective of the SG. Conversely, U/A with high pH (> or = 6.0) had a higher frequency of indinavir crystalluria, which was further influenced by the urine SG. As a result, nearly half of the U/A (46.7%) with high pH (> or = 6.0) and intermediate-high SG (> or = 1.015) contained indinavir crystals. In conclusion, the frequency of indinavir crystalluria in asymptomatic HIV-1 infected individuals during their first year of treatment with indinavir was markedly influenced by the urine pH and SG. Our findings suggest that low urine pH may have a protective effect against indinavir crystalluria across the entire range of urine SG.     

The radial intercepts method for measuring bronchial mucous gland volume.

A new linear method, the radial intercepts method, has been introduced for quantitating the components of the bronchial wall. The method is an adaptation of Rosiwal's (1898) original linear measurement technique, but unlike Rosiwal's the radial intercepts method takes measurements along radii at regular sectoral intervals. The method is reproducible and, from its high correlation with the standard planimetric, cut-weigh, and point-count techniques for quantifying bronchial wall components (Bedrossian, Anderson and Foraker, 1971), it is concluded that the method is reliable.     

Kinetics of adventitial repair in the rat carotid model.

BACKGROUND: Discrepancies between success in experimental animals with a variety of pharmacologic strategies and failure with such agents in clinical trials have raised questions concerning the mechanism of restenosis. Recent observations suggest a potential implication for the adventitial (Adv) layer in neointimal formation. METHODS: The purpose of this study was to examine the Adv changes in the rat carotid artery subjected to balloon injury. These changes were characterized by morphometric, immunohistochemical, and electron microscopy analyses, with special attention devoted to early time-points post-injury. RESULTS: We report that the most important adventitial changes occurred in the first 48 h post-injury. Within 2 h there was extensive cell-loss by apoptosis and oncosis in the Adv and in the media; this was followed by the rapid onset of proliferation and a parallel slow increase in Adv thickening, reaching a maximum at 7 days. We further demonstrate an early migration of these Adv cells to the media and neointima. Moreover, we characterize the Adv cell phenotype with a panel of antibodies. Within 48 h after injury, a population of Adv cells expressed alpha-actin and vinculin with a maximum expression 7 days post-injury. At that time, these Adv cells started to express smooth muscle myosin heavy chain, a specific marker of smooth muscle cells. In parallel, we report an impaired production of elastic fibres in the Adv and medial layer. CONCLUSIONS: We reported a detailed time-course of adventitial changes after rat carotid injury (cell death, proliferation, migration and differentiation) that supports an important role of adventitia in neointima formation.     

Phenytoin hypersensitivity syndrome

Phenytoin hypersensitivity syndrome (PHS) is a rare, and important entity characterized by rash, fever, lymphadenopathy, leukocytosis with atypical lymphocytes, eosinophilia and associated hepatitis. In this article, we present the clinical, laboratory and histopathologic results of 5 cases of PHS. In therapy, pheyntoin was stopped and sodium valproate (10–20 mg/kg day) was started. Additionally, prednisolone was given in two patients who had not resolved eruption with conservative therapy. Received: 2 January 2001 / Accepted in revised form: 24 May 2001