Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.     

Concentration of TBA-reactive substances in type II pneumocytes exposed to oxidative stress

INTRODUCTION: Oxidative lung damage may be associated with the destruction of alveolar cells. Type II alveolar epithelial cells (AECs),as progenitors of type I cells, are indispensable for the renovation of alveolar structure after lung injury. Extensive damage to type II cells could be responsible for unfavorable outcome. However, the susceptibility of type II AECs to oxidative stress is unclear. MATERIAL/METHODS: We investigated the susceptibility of freshly isolated and cultured rat type II AECs to oxidative stress (H2O2 and Fe2+). Thiobarbituric acid reactive substances (TBARS)were measured as indices of lipid peroxidation and cytotoxicity was estimated by the MTT test. Aminotriazol (ATZ), an inhibitor of intracellular catalase, was used to estimate the protective role of catalase. RESULTS: TBARS concentration increased significantly in freshly isolated, oxidant-exposed cells (4.0 +/-1.3 vs.8.3 +/-2.2 nmol/g protein, p=0.0313)and insignificantly in cultured cells (1.7 +/-0.4 vs.4.4 +/-1.7 nmol/g protein).ATZ was toxic even to cells not exposed to oxidants. Inhibition of catalase in cells exposed to oxidants resulted in an insignificant increase in TBARs:4.5 +/-1.5 vs.16.2 +/-3.9 nmol/g protein, p=0.0625,and 4.0 +/-0.8 vs.7.6 +/-4.0 for freshly isolated and cultured cells, respectively. Oxidative stress itself did not increase cytotoxicity. CONCLUSIONS: Type II AECs are not resistant to oxidative stress. We cannot, however, explain why cells with evidence of lipid peroxidation do not show increased cytotoxicity. The toxicity of ATZ is not related to oxidative cell damage. In cells exposed to oxidants, TBARS may fur-ther increase when catalase is inhibited, which suggests an important protective role for catalase.     

Cytomegalovirus Isolation from a Chimpanzee with Acute Demyelinating Disease After Inoculation of Multiple Sclerosis Brain Cells

A strain of cytomegalovirus (CMV) was isolated during the third subcultivation of explants from the left frontal lobe of a chimpanzee that developed paralysis more than 3 years after intracerebral inoculation at birth with brain cell cultures derived from a patient with multiple sclerosis. Another strain of CMV was also isolated from a lymph node culture taken from the same chimp. The isolates, designated MZM-13 and MZM-14, produced a cytopathic effect characteristic for CMV when inoculated into brain, ganglion, or fibroblast cultures of human or simian origin. Infected cells contained characteristic Cowdry A intranuclear as well as intracytoplasmic inclusion bodies, and 100-nm spherical herpes-like virus particles were detected by electron microscopy in the nucleus and cytoplasm of infected cells. Virus was further identified as CMV with convalescent human anti-CMV serum. Complement-fixing antibody to CMV was present at a titer of 1:32 when the acutely ill chimpanzee was sacrificed. No antibody was detected at birth or at 1 or 2 years of age. A newborn chimpanzee inoculated intracerebrally with MZM-13 developed clinically asymptomatic lesions in the central nervous system characterized by acute and chronic inflammation and degeneration of myelin in cranial and spinal nerve roots. Restriction endonuclease analysis of viral deoxyribonucleic acid isolated from these two viruses indicated that MZM-13 and MZM-14 are identical and are closely related to chimpanzee CMV. No similarity in restriction endonuclease fragment patterns was found between MZM virus and the Towne and Clegg strains of human CMV.     

Hepatic lysosomal enzymes activity and liver morphology after short-time omeprazole administration

The aim of the study was to establish the influence of short-time omeprazole administration on liver function and morphology. Omeprazole was administered intraperitoneally, twice daily, for 3 days to male Wistar rats in two doses: 0.571 mg/kg and 5.71 mg/kg. Control animals were treated with physiological saline. Half of the animals were sacrificed 12 hours after the last injection. The remaining rats were raised for another 6 weeks, without any xenobiotics, and sacrificed on the 47th day of the experiment. The activity of free and bound fractions of hepatic acid phosphatase, beta-galactosidase, beta-N-acetyl-glucosaminidase, cathepsin B, D and L, lipase, and sulphatase were determined spectrophotometrically in homogenates of the liver. The liver sections were examined by light microscopy with hematoxylin-eosin, azan, and periodic acid-Schiff stains. Marginally significant (p < 0.1) differences in activity of free sulphatase fraction, and free and bound fractions of beta-galactosidase were found in animals exposed to the higher dose of omeprazole and sacrificed 12 hours after the last injection. Enzymatic profiles were normalised during the next 6 weeks. Histological evaluation revealed small degenerative and adaptive changes in all examined groups. It could be concluded that observed differences of hepatic lysosomal enzyme activities were the result of accompanied chemical-induced peritonitis as previously reported, and not a direct drug-toxic effect.     

Type of isoniazid (INH) acetylation determined in tuberculosis patients treated at the Institute of Tuberculosis and Lung Diseases in Warsaw during the years 1990-1997

The researched has dealt with the type of acetylation in 237 TB patients treated with standard course of chemotherapy with a dose of 300 mg of INH in period 1990-1997 in National Research Institute of Tuberculosis and Lung Disease in Warsaw Blood samples were taken before (time 0) and 1, 3, 6 and 24 h after drug administration. Plasma concentrations of isoniazid were determined with biological methods. Two indies of acetylation rate--I3 and C6 have been used to determine an acetylation type. Majority of the treated patients (68.8%) have shown fast type of INH acetylation. After similar dose of isoniazid different profile of absorption and excretion of the drug and significant differences (p < 0.01) in INH concentrations, acetylation rate and bioavailability between 163 fast and 74 slow acetylators have been observed. In plasma of 38.6% fast acetylators drug concentration 3 h after ingestion of a dose did not achieve the concentration of 1 mcg/ml. In plasma of 29.7% slow acetylators, concentrations of INH 6 h after ingestion were higher than 2 mcg/ml.     

P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism

Precise localization of parathyroid glands using 99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy could be affected by various biological factors. There is increasing evidence that radiotracer retention could be controlled by members of multidrug resistance (MDR) system, especially P-glycoprotein (P-gp). Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH). P-HPTH (n = 19) and T-HPTH (n = 18) patients were subjected to 99mTc-MIBI scintigraphy followed by surgical treatment. The parathyroid glands were assessed in routine hematoxylin-eosin staining and P-gp expression was analyzed using immunohistochemistry. Parathyroids collected during cadaver donor multi-organ harvesting were used as a control. It has been found that P-HPTH-derived parathyroid glands with predominating adenoma morphology expressed less P-gp, as compared to P-gp-rich T-HPTH glands, mainly displaying nodular or diffused hyperplasia phenotype. This finding reversely correlated with results of 99mTc-MIBI scintigraphy. However, we did not observe any difference in P-gp expression nor scintigraphy result between nodular or diffused hyperplasia. Altogether, these data suggest that P-gp overexpression in T-HPTH could be responsible for decreased sensitivity of 99mTc-MIBI scintigraphy in those patients. Therefore, the recently proposed reduced neck exploration or limited parathyroid resection on the basis of scintigraphy could create the risk of persisted/recurrent hyperparathyroidism. However, this problem requires further study.     

Primary and acquired drug resistance of tuberculosis bacilli in Poland

Information about resistant pattern of Mycobacterium tuberculosis isolates against antituberculon drugs is a very important part of tuberculosis control and indicates the directions of TB policy in each country. Poland joined WHO/IUATLD global project on drug resistance surveillance, and carried out the first prospective survey, simultaneously on primary and acquired drug resistance of tuberculosis patients according WHO/IUATLD recommendations. The programme covered the whole country, basing on cooperation between the National Reference Laboratory (NRL) with regional TB laboratories. Questionnaires and cultures were obtained from patients who excreted TB bacilli during the period from 1 November 1996 to 1 November 1997 (12 months). Drug susceptibility testing to INH, SM, EMB and RMP were performed on Lowenstein-Jensen medium according to the proportion method or/and radiometric Bactec 460 TB system. 3970 TB patients bacteriologically confirmed by culture were included in a one-year study. The male to female ratio was 2.6:1. Patients were at the age of 6 to 83 years. Majority of patients (86% males and 77% of females) was older than 35 years. Primary resistance to any drug was found in 3.6% of new cases and 2.4% of those patients who excreted monoresistant strains. No monoresistance to EMB was found. 18 patients (0.6%) were infected by MDR strains. Total resistance in new cases was for INH--2.6%, for SM--1.8%, for RMP--0.7% and for EMB--0.1%. Acquired resistance to any drug was found in 17.0% of treated. Majority of patients--7.7% excreted monoresistant strains. 7.0% were infected by MDR strains. Total resistance to INH was 14.8%, to SM--9.2%, to RMP--7.8%, and to EBM--2.5%. No correlation was found between sex and primary resistance rates. Among new cases, 3.7% of males and 3.3% of females were infected with resistant strains. However, among treated patients, males (20%) excreted resistant strains twice as much as females (9.1%). Mean age of women and men infected with primary and acquired resistant strains was similar.     

Corneal biomechanical changes and intraocular pressure in patients with thyroid orbitopathy

AIM: To determine the relevance of the objective parameters addressing the altered biomechanical properties of cornea for glaucoma monitoring in patients with mild or moderate thyroid associated orbitopathy (TAO), and in healthy individuals. METHODS: Twenty-five patients with TAO (group 1) and 25 healthy adults (group 2) were included to the study. Both groups were of a similar age and the ratio women:man. For each patient, the following parameters of both eyes were measured with ocular response analyzer (ORA): corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular pressure (IOPg) and corneal compensated intraocular pressure (IOPcc). In both groups participating in our study, all measurements were performed within minutes to reduce the diurnal effects. RESULTS: The mean age in group 1 was 56±11y and 76% were women, 24% were men. The mean age in group 2 was 64±11y and 68% were women, 32% were men. CH correlated negatively with IOPg in group 1 (r2=0.10, P<0.05). IOPg strongly correlated with IOPcc in both groups (group 1: r2=0.79, P<0.0001; group 2: r2=0.85, P<0.0001). There was positive correlation between CRF and IOPg in group 1 (r2=0.12, P<0.05) and in group 2 (r2=0.31, P<0.0001). Statistical analysis revealed no significant correlation between CRF and IOPcc in group 1 (r2=0.009, P>0.05) and also no significant correlation in group 2 (r2=0.04, P>0.05). CRF mean value in group 2 (11.51±1.72 mm Hg) was higher than in group 1 (10.85±1.45 mm Hg) (P<0.05). IOPg strongly correlated with IOPcc in both groups (group 1: r2=0.79, P<0.0001; group 2: r2=0.85, P<0.0001). There was also strong correlation between CRF and CH in both populations: group 1: (r2=0.58, P<0.0001), group 2: (r2=0.41, P<0.0001). CONCLUSION: Biomechanical parameters of cornea, as quantified by CH and CRF, and measured together with IOPcc, precisely reveal glaucoma staging in TAO and thus are reliable for diagnosing and follow-up in clinical practice.