Nitric oxide synthase-immunoreactive neurons in human and porcine respiratory tract

The presence of nitric oxide synthase (NO-synthase), the enzyme responsible for the production of nitric oxide (NO) from L-arginine, is shown immunocytochemically in the intrinsic neurons of the human and porcine respiratory tract. NO-synthase immunoreactivity is demonstrated in a subpopulation of neurons of the microganglia present in the wall of the extra- and intrapulmonary bronchi as well as in the hilar region of the lung in relation to blood vessels. The immunostaining was also found in some nerve fibers of the respiratory nervous system. Human and porcine lung gave similar results. The possible involvement of NO in the nonadrenergic noncholinergic (NANC) nervous regulation of the lung is discussed.     

Eruption times of third molars in young rural Nigerians

The mechanical stability of proximal femoral osteotomies fixed by the tension band wire technique was studied in flexion-compression and torsion tests. The fixation consisted in crossing the section with two Kirschner wires and with a wire cerclage applied to the tension surface. The study was conducted in three steps. First, cyclinders of wood were cut either transversely or at 30 degrees of inclination in relation to the long axis of the specimen, and fixed with two Kirschner wires and a wire cerclage. We concluded that the inclination of the plane of section significantly increased the stability of fixation. No significant difference was observed when oblique sections were made in the reverse orientation. Second, 30 degrees subtrochanteric varus osteotomies were performed in dog femurs, so that the section plane was transverse in one group and oblique in another, after closing the osteotomy. In both groups the fixation was achieved by two Kirschner wires that crossed the osteotomy and a wire cerclage placed on the lateral cortex (tension surface). We concluded that inclination of the osteotomy plane increased the stability of osteosynthesis in bone specimens, as already seen with the wood pieces. Third, the stability of tension band wire fixation was compared with that provided by the AO/ASIF paediatric angled plate. Varus osteotomies (30 degrees) were created at the subtrochanteric level of paired dog femurs. On one side, the femur was fixed with Kirschner wires and a wire cerclage as described previously. For the other femur, the osteotomy was fixed with the angled plate. We found that both types of fixation presented the same stability in flexion-compression tests. However, under torsion the tension band wire fixation was 30%-50% less stable than the plate fixation.     

Attenuated hematopoietic response to granulocyte-macrophage colony-stimulating factor in patients with acquired pulmonary alveolar proteinosis

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment.     

Role of relaxin and estrogen in the control of eosinophilic invasion and collagen remodeling in rat cervical tissue at term

The modified fluorescence method was used to determine the accumulation of norfloxacin by Mycobacterium aurum A+ and Mycobacterium smegmatis mc(2)155. By using an exogenous norfloxacin concentration of 10 microg/ml, a steady-state concentration (SSC) of 160 to 180 ng of norfloxacin/mg of cells was obtained for M. aurum, and an SSC of 120 to 140 ng of norfloxacin/mg of cells obtained for M. smegmatis. For both species of mycobacteria, the SSC was achieved within 5 min. The silicon oil method was investigated and gave higher SSCs than the modified fluorescence method. Further studies on the mechanism of norfloxacin accumulation by M. aurum were performed. An increase in the pH of the wash buffer from 7.0 to 9.0 did not significantly affect the final SSC obtained. Accumulation was nonsaturated over a norfloxacin concentration range of 0 to 100 microg/ml, and the proton motive force inhibitor 2,4-dinitrophenol (1 and 2 mM), whether it was added before or after norfloxacin was added, had no effect on the final SSC obtained. 2,4-Dinitrophenol also had no effect on norfloxacin accumulation by M. smegmatis. Furthermore, norfloxacin accumulation by M. aurum was unaffected by the presence of either Tween 80 or subinhibitory concentrations of ethambutol in the growth medium. Therefore, it is proposed that norfloxacin accumulation by mycobacteria occurs by simple, energy-independent diffusion.     

Chronic HCV hepatitis with normal level of alanine transaminase: interferon therapy of active observation?

AIM: This study of trimetasidine effects on plasmic hemostasis and blood biochemistry in patients with chronic heart failure (CCF) of NYHA functional class II-III. MATERIALS AND METHODS: This study enrolled 30 patients (24 males and 6 females) aged 40-72 years with class II-III CCF, postinfarction cardiosclerosis and ejection fraction under 40%. Previously the patients received perindopril (the inhibitor of angiotensin converting enzyme) in daily dose 2-4 mg, on-demand digoxin and diuretics. Trimetasidine was given in a daily dose 60 mg for 6 months. Before and after the treatment the patients' blood was examined for: levels of factors VII and X of antithrombin III coagulation, soluble fibrinomonomeric complexes (SFMC), fibrinogen, glucose, uric acid, creatinines, total cholesterol, high density lipoprotein, triglycerides, AST, ALT, LDH, acid phosphotase, gamma-GT, sodium, potassium, activated partial thrombin time. RESULTS: Initially, the patients had a 23.9% increase in the levels of factors VII and X, a 14.3% decrease of antithrombin III, 29.8 and 227.6% rise in concentrations of fibrinogen and SFMC, respectively, compared to controls. Aftertreatment values of fibrinogen, factors VII and X, SFMC fell by 21.1, 17 and 35.5%, respectively. The thrombin time arose by 17.9% (p > 0.05). Insignificant inhibition was registered in the activity of acid phosphotase and gamma-GT. Glucose, AST, ALT, LDH levels remained unchanged. Plasma creatinine tended to lowering. Total cholesterol insignificantly increased at high levels of HDL cholesterol (p > 0.05) and reduced levels of triglycerides (p > 0.05). CONCLUSIONS: Trimetasidine therapy, given after conventional treatment with diuretics, digoxin, inhibitor of angiotensin-converting enzyme, aspirin has a beneficial effect in patients with circulatory deficiency through improving hemostatic and biochemical parameters.     

HIV-associated tuberculosis in Africa exemplified by Zimbabwe

In Africa, a rapid increase of human immunodeficiency virus (HIV)-associated tuberculosis cases has been observed; 80% of a worldwide 6 million dually infected persons live in this part of the world. The annual risk of progression to clinically overt tuberculosis in dually infected persons approaches the lifetime risk in persons with tuberculosis but no HIV infection. Zimbabwe is an example which illustrates the rapid increase in notified tuberculosis cases since 1985, accounted for primarily by HIV-associated tuberculosis cases. In sputum-smear positive HIV-associated tuberculosis, classical symptoms are reported with the same frequency as in HIV negative cases. Thus, case-finding activities need not be altered. In sputum-smear negative patients, reliable diagnostic tests are not available. Therapeutic trials are widely used and this causes overdiagnosis of tuberculosis. Extrapulmonary manifestations are common in HIV-associated tuberculosis. A majority of lymph node enlargements, pleurisy and pericarditis in Africa are now due to tuberculosis. If compliance is ensured, response to chemotherapy is excellent, but overall case fatality and relapse rates are increased. The cost-effectiveness of tuberculosis control programmes using directly observed therapy for at least the first 2 months of treatment is well established. With the prominent global significance of tuberculosis and the possibility of cost-effective interventions, a commitment to the fight against the worldwide epidemic is more important than ever before.     

Bronchopulmonary dysplasia and oxidative stress: are we closer to an understanding of the pathogenesis of BPD?

OBJECTIVES: To determine if induction of heat shock protein 70 (HSP 70), a stress protein that plays a cytoprotective role and inhibits cell death in response to various stimuli, will protect thymocytes and T-cell clones from radiation-induced apoptosis, and to define the mechanism of such protection. DESIGN: Thymocytes from BALB/c mice or T-lymphocyte clones were incubated at 43 degrees C for 1 hour to induce HSP 70, then irradiated. Control cells were irradiated but not heated. Fragmentation of DNA was quantitated, and p53, bax, and bcl-2 expression was analyzed at various times by the Western blot method. RESULTS: Only heated cells expressed HSP 70. The induction of HSP 70 increased basal apoptosis but significantly decreased radiation-induced apoptosis. Furthermore, introduction of an HSP 70 antisense oligomer prior to heating reversed the protective effect of HSP 70. Induction of HSP 70 in T-cell clones with sodium arsenite had a similar protective effect against radiation-induced apoptosis. Irradiation induced p53 and markedly up-regulated bax. The expression of p53 peaked at 4 hours and preceded maximal bax induction. Induction of HSP 70 prior to irradiation suppressed p53 and significantly decreased bax levels. Levels of bcl-2 were unaffected. CONCLUSIONS: Our data show that HSP 70 induction protects thymocytes from radiation-induced apoptosis by down-regulating p53 and bax expression. The induction of HSP 70 may represent a novel mechanism by which the immunosuppressive effects and the associated infectious complications of radiation therapy can be minimized.     

Treatment of complications in primary cementless total hip arthroplasty

Five hundred eight consecutive cases (481 patients) treated with the extensively porous coated Anatomic Medullary Locking prosthesis were followed for an average of 9 years (range, 5-14 years). Thirty-one (6%) hips were lost to followup and 33 (7%) hips had complications that required revision surgery. The indications for revision were symptomatic stem loosening (six cases), symptomatic cup loosening (five cases), asymptomatic periarticular osteolysis (seven cases); trochanteric fracture through an osteolytic cyst (four cases), polyethylene fracture (five cases), sepsis (one case), and heterotopic ossification (one case). The surgical treatment of these complications is described. After these revisions, 11 (33%) cases had additional complications, most commonly a dislocation. Four required a second revision. Questionnaires and physical examinations were used to compare the outcome of the cases requiring revision with the outcome of those that did not. There were no differences in patient satisfaction between cases requiring revision surgery and those that did not (97% and 95% patient satisfaction, respectively). Function was also similar between the two groups, with 93% reporting increased function in each group.     

Racial differences in lens opacities: the Salisbury Eye Evaluation (SEE) project

Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders.