Mild hyperhomocysteinemia promotes renal hemodynamic dysfunction without histopathologic changes in adult rats

BACKGROUND: Hyperhomocysteinemia is able to promote glomerular damage and generate tubulointerstitial lesions. These findings were reported in rats with unilateral nephrectomy or in weanling rats with normal function, two experimental models that are exposed to other concomitant vascular risk factors. The aim of this work is to study whether mild hyperhomocisteinemia per se can induce renal histopathologic changes in adults rats with normal renal function at either 10 or 44 weeks of hyperhomocysteinemia. METHODS: Two months old male Wistar rats (N= 52) were randomly allocated to either a normal control (N= 26) or hyperhomocysteinemic (N= 26) group. Control and hyperhomocysteinemic groups had free access to either tap water or homocysteine thiolactone 50 mg/kg/day, during 10 or 44 weeks. Plasma homocysteine levels were determined by a high-performance liquid chromatography (HPLC) method. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were calculated from inulin and sodium para-aminohippurate (PAH) clearance determinations. Structural renal changes were investigated in kidneys fixed by perfusion. Histopathologic and morphometric analysis were carried out by standard methods. RESULTS: Plasma total homocysteine levels were 53% (10 weeks) and 56% (44 weeks) higher in hyperhomocysteinemic group compared to the control group. GFR and RPF were significantly lower in hyperhomocysteinemic than in control group. The histopathologic and morphometric studies did not show any differences between the control and hyperhomocysteinemic rats at 10 or 44 weeks. CONCLUSION: The present results show that mild hyperhomocysteinemia is able to induce renal functional and biochemical alterations in male adult rats that are not associated with renal histopathologic changes.     

Biological variability of thyroid autoantibodies (anti-TPO and anti-Tg) in clinically and biochemically stable patients with autoimmune thyroid disease

The biological variation of anti-TPO and anti-Tg autoantibodies was studied in 17 clinically and biochemically stable female patients with autoimmune thyroid disease (AITD), at regular monthly intervals over a period of 6 consecutive months. The mean and standard deviation (SD), within-subject coefficient of variation (CV), between-subject CV, index of individuality, reliability coefficient, and critical differences were as follows: for anti-TPO 238 (197) U/ml, 9.2%, 81.4%, 0.11, 0.96, and 27.6%; and for anti-Tg 1,785 (3,170) U/ml, 6.9%, 174%, 0.04, 0.99, and 22.3%. The data indicate a low within-subject CV, and a high between-subject CV that is particularly pronounced for anti-Tg. The high individuality of both autoantibodies indicates that an isolated result compared to conventional population-based reference intervals is of very little value for diagnosis. Furthermore, the near to 1 reliability coefficient for both autoantibodies correctly classifies the patient with respect to his or her homeostatic mean antibody concentration in a 6-month period of clinical and biochemical stability of thyroid disease. Imprecision goals for anti-TPO and anti-Tg antibodies are attainable with current methodology.     

Incidence of unexpected malignancies in routine tonsillectomy specimens in children

OBJECTIVES: Controversy continues to exist regarding the necessity to routinely send for histologic examination those specimens obtained after tonsillectomy with or without adenoidectomy in children. Otolaryngologists fear missing an unsuspected diagnosis, such as a tonsil malignancy. However, given the rare incidence of this event, the cost-effectiveness ratio of routine microscopic analysis is questionable. The purpose of this study was to assess the incidence of clinically relevant unexpected diagnosis among children who underwent tonsillectomy with or without adenoidectomy in our units and to review current available series on this topic. STUDY DESIGN: Retrospective study and review. METHODS: All patients aged less than 16 years who underwent routine tonsillectomy (with or without adenoidectomy) at San Gerardo Hospital, Monza, Italy from January 1994 to June 2002 were reviewed. Histologic examination is routinely performed in our units. Patients were excluded if the primary indication for surgery was to rule out a tonsil malignancy. RESULTS: One thousand one hundred twenty-three (1,123) patients were recruited. Two cases of non-Hodgkin's lymphoma were detected, corresponding to a rate of 0.18% (95% confidence interval [CI] 0.07-0.56). Three previously published series were identified. The reported incidences of unexpected clinically relevant diagnoses varied between 0.0% and 0.05%. CONCLUSIONS: The results of our study highlight that the incidence of unexpected clinically relevant diseases of the tonsil in pediatric patients is low, albeit not extremely rare. This finding could be used to perform a cost-effectiveness analysis.     

Expression of cell cycle regulatory proteins and analysis of apoptosis in normal nasal mucosa and in nasal polyps

BACKGROUND: The etiopathogenesis of nasal polyps still is to be clarified. Although hyperplasia is a typical feature of these pathological processes, little attention has been paid to specific aspects of cellular growth in polyps. We have evaluated the expression and localization of some of the regulatory proteins that direct the cell through the specific sequence of events culminating in mitosis or apoptosis in nasal polyps. METHODS: Twenty samples of nasal polyps and 20 samples of normal nasal mucosa have been analyzed for apoptotic index by detecting the DNA 3'OH ends deriving from DNA fragmentation. Moreover, they have been evaluated by immunohistochemical staining for expression of Ki-67, cyclins A and B1, p53, p21, p27, murine double minute clone 2, and Bcl-2. RESULTS: We have identified a greater proportion of proliferating cells in the lining epithelial cells of the polyps when compared with the normal mucosa as stained with anti-Ki-67 antibodies. An overexpression of p53, MDM2, and Bcl-2 and an increased apoptosis were observed in nasal polyps compared with the normal mucosa, whereas no variation of p27 expression was observed. The p21 and cyclins A and B1 were rarely expressed in both pathological and normal tissue. CONCLUSION: The p53-based control system of cell cycle progression appears to be altered in nasal polyps, potentially leading to an abrogation of the DNA damage checkpoint. Evaluation of the expression of the regulatory proteins that direct the cells throughout their cycle in nasal polyps may allow a better understanding of the biological behavior and clinical outcome of these benign pathological entities.     

Amplified-fragment length polymorphism as a complement to IS6110-based restriction fragment length polymorphism analysis for molecular typing of Mycobacterium tuberculosis

The amplified-fragment length polymorphism (AFLP) technique was applied to clusters of Mycobacterium tuberculosis clinical isolates obtained by using IS6110-based restriction fragment length polymorphism (RFLP). Ten of the RFLP clusters showed identical AFLP patterns also, but the other 13 could be resolved into subclusters by AFLP. Our results suggest that some RFLP clusters may not be due to recent transmission and that AFLP may be a useful complementary technique.     

Evaluation of enzyme-linked immunosorbent assays and a PCR test for detection of shiga toxins for shiga toxin-producing Escherichia coli in cattle herds

Antigen capture enzyme-linked immunosorbent assays (ELISAs) for the detection of Stx1 and/or Stx2 in cattle feces were validated in comparison to the Vero cell cytotoxicity neutralization test (as a "gold standard") applied in the course of a monitoring program for Shiga toxin-producing Escherichia coli in German cattle herds as a prescreening test and compared to MK1/MK2 PCR as an alternative prescreening test.     

Small vessel disease (SVD) in patients with unexplained ventricular arrhythmia and dilated congestive cardiomyopathy

Small vessel coronary disease is not commonly found in endomyocardial biopsies (EMB) of nondiabetic patients with clinical evidence of ischemic heart disease, congestive heart failure, or ventricular arrhythmia (VA). In 166 patients studied by heart catheterization and multiple right ventricle EMB, we identified 4 patients with histologic evidence of small vessel disease and normal coronary arteriograms. Two patients were suffering from VA without an obvious cardiac cause. Of the other two, one initially showed frequent ventricular tachycardia attacks followed by congestive heart failure alone. In both patients, the cardiac chambers were dilated and the left ventricular function seriously impaired. In all four patients, the histologic examination of right EMB revealed a wall thickening of the precapillary arterioles and capillary vessels. At ultrastructural examination, an increased thickening (four or five times normal) of the subendothelial lamina and of the basement membrane of capillary pericytes was found. Degenerative changes of cardiac myocells were found in all cases.