Duration of neurofibrillary changes in the hippocampal pyramidal neurons

The clinical course of grave forms of leptospirosis presents with disorders in the fluid and electrolyte balance and acid-base condition (ABC) which fact necessitates taking prompt action for the condition to be corrected. Correction of disorders in the fluid and electrolyte balance involves employment of glucose and salt solutions, dextrans, and in most severe cases albumin drugs under control of hematocrit values, plasma osmolarity, and 24-h diuresis monitoring. Correction of disorders in the ABC is primarily aimed at alleviating the metabolic acidosis through detoxication by applying specific therapy together with oral and parenteral administration of sodium hydrogen carbonate.     

Evidence for photoreceptor changes in patients with diabetic retinopathy

PURPOSE: To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy. METHODS: Twelve patients with diabetes and varying levels of retinopathy and nine age-similar control observers participated in this study. Two-color (500 versus 650 nm) dark-adapted thresholds were measured as a function of retinal eccentricity. Full-field flash electroretinograms were obtained using brief, high-intensity flashes. Dark-adapted rod-isolated (Wratten 47B filter) and light-adapted cone-isolated (Wratten 26 filter) electroretinographic responses were measured as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of Rmax (the maximal response) and log S (sensitivity). Standard clinical 30-Hz flicker electroretinographic responses were also measured. RESULTS: Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. Analysis of rod and cone a-wave data showed that Rmax was normal in most of the patients, but log S was reduced. Analysis of b-wave and oscillatory potential parameters showed rod and cone postreceptoral abnormalities, including changes in the rod-isolated semisaturation constant (log k), cone-mediated 30-Hz flicker, and cone-isolated oscillatory potentials. The electrophysiological results were not significantly correlated with blood glucose or glycosylated hemoglobin level. CONCLUSIONS: The results provide evidence for rod and cone receptoral and postreceptoral deficits in patients with diabetic retinopathy. The photoreceptor changes are primarily in the log S (sensitivity) parameter and are attributed to transduction abnormalities.     

Acute cocaine effects on stereotype and defense: an ethoexperimental approach

Germinated barley foodstuff (GBF), derived from the aleurone and scutellum fractions of germinated barley, is rich in glutamine and low-lignified hemicellulose, and increases mucosal protein, RNA, and DNA content in the intestine when fed to normal rats. The aim of this study was to evaluate the effects of feeding GBF or germinated gramineous seeds on experimental ulcerative colitis. Sprague-Dawley rats that received 3% dextran sulfate sodium in their diets were used as an experimental colitis model. The effects of sulfasalazine, a drug used to treat inflammatory bowel disease, were compared with those of GBF. After rats had consumed diets containing GBF or various aleurone and scutellum fractions, mucosal damage; the content of mucosal protein, RNA, and DNA in the colo-rectum; and serum interleukin-8 and alpha1-acid glycoprotein levels were assessed. GBF and germinated seeds more effectively prevented bloody diarrhea and mucosal damage in colitis compared with controls and rats receiving sulfasalazine, but non-germinated samples did not have a protective effect. GBF increased mucosal protein and RNA content in the colitis model. The consumption of GBF appears to prevent inflammation in a colitis model, and its effect seems to be related to the germination process. GBF and germinated seeds have the potential to serve as nutritional therapy for ulcerative colitis.     

Can experimental models of rodent implantation glioma be improved? A study of pure and mixed glioma cell line tumours

Phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH) concentrations were determined in microsomes and plasma membranes prepared from 2- and 17-month-old male Sprague-Dawley rat hepatocytes, to verify the dissimilarity of age dependency of lipid peroxidation in organelle membranes. The hydroperoxides were directly measured by chemiluminescence detection-high-performance liquid chromatography (CL-HPLC), and 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylcholine (PLPC-OOH) and 1-palmitoyl-2-(13-hydroperoxy-cis-9, trans-11-octadecadienoyl) phosphatidylethanolamine (PLPE-OOH) were enzymatically synthesized and utilized as standards for the calibration. Baseline concentrations of hydroperoxides (PC-OOH + PE-OOH) of the 17-month-old rats were 46 pmol per mg protein in microsomes (2.7 times higher than the 2-month-old rats) and 306 pmol per mg protein in plasma membranes (9.9 times higher than the 2-month-old rats). Both microsomal and plasma membrane lipids were severely peroxidized and converted to phospholipid hydroperoxides by NADPH-dependent lipid peroxidation in vitro, but the age-dependency was only observed in the plasma membranes. These results demonstrate that substantial oxidative damage to membrane phospholipids occurs with ageing both in microsomes and plasma membranes, but is more prevalent in plasma membranes in rat hepatocytes.     

Impact of ultrafiltration on blood use for atrial septal defect closure in infants and children

BACKGROUND: Infants and children undergoing open cardiac operations have a high incidence of blood product transfusion. Ultrafiltration has been shown to reverse hemodilution and improve myocardial function and hemodynamics after cardiopulmonary bypass (CPB). METHODS: The effect of ultrafiltration on the amount of blood transfusion and hospital charge in 39 consecutive patients who underwent elective atrial septal defect repair was examined. Patients in group I (n=26) had a conventional cardiopulmonary circuit prime with blood, whereas 13 patients had bloodless prime (group II). Ultrafiltration was used immediately after weaning from CPB in group II. The patients in group I received blood products after discontinuation of CPB to achieve a hematocrit of 30%. The amount of blood product used, hematocrit immediately after CPB and on arrival in intensive care unit, postoperative hemodynamics and saturations, total operating room charge, blood charge, hospital stay, and hospital charge were compared. RESULTS: Mean body weight (15.8 kg in group I versus 17.5 kg in group II) and preoperative hematocrit values (35.6% in group I versus 34.2% in group II) were similar. Mean hematocrit immediately after CPB was 22% and 14% in group I and II, respectively (p < 0.0001). The mean hematocrit upon arrival to the intensive care unit was 34% in group I and 22% in group II (p < 0.0001). The amount of blood product transfusion was 32 mL/kg in group I and 3 mL/kg in group II patients (p < 0.0001). The patients in group II had significantly less blood bank charges; however, operating room charges and total hospital charges were similar between the two groups. CONCLUSIONS: Elective atrial septal defect repair was performed with no blood product transfusion without increased morbidity or hospital stay. Ultrafiltration can be used to reverse hemodilution resulting from a bloodless CPB prime without an increase in hospital charge.     

Experience with a cross-study endpoint review committee for AIDS clinical trials. Terry Beirn Community Programs for Clinical Research on AIDS

OBJECTIVES: To describe the methods and results of a standardized system for clinical endpoint determination for defining and reviewing endpoints in clinical trials for HIV-infected individuals. DESIGN: A system was developed utilizing standard definitions for the 24 diagnoses or clinical events that serve as trial endpoints and together define the combined endpoint 'progression of HIV disease. A common set of case report forms were used for all trials. Thus, an event of Pneumocystis carinii pneumonia (PCP), for example, for a subject co-enrolled in an antiretroviral trial and a PCP prophylaxis trial was only reported once. METHODS: A central committee was established to define clinical events and review endpoints across all studies. Events were classified according to established criteria for confirmed, probable and possible levels of certainty. RESULTS: This report describes the methods used to ascertain and review endpoints, and summarized 2299 clinical events for 8097 subjects enrolled in one or more of nine clinical trials. Data on the diagnostic certainty of events and agreement between site clinicians and the endpoint committee are presented. CONCLUSIONS: Uniform classification of endpoints across AIDS clinical trials can be accomplished by multicenter, multitrial organizations with standardized definitions and review of endpoint documentation. Our experience suggests that nurse coordinators reviewing all submitted endpoints for every trial are warranted and the need for external review by a clinical events committee may depend on the type of trial conducted.     

Electrospray ionization mass spectrometry identification of fibrinogen Banks Peninsula (gamma280Tyr-->Cys): a new variant with defective polymerization

cis-Diamminedichloroplatinum (cisplatin) is an important anticancer drug used to treat solid tumors. The nephrotoxicity of cisplatin is recognized as the most important dose-limiting factor, but high doses of cisplatin also produce hepatotoxicity. However, little is known about cisplatin-induced liver injury and the role of metallothionein, a cysteine-rich, metal-binding protein, in modulating its hepatotoxicity. This study was designed to examine cisplatin hepatotoxicity in control and metallothionein-I/II knockout (MT-null) mice. Animals were given a single injection of cisplatin (50-200 mumol/kg i.p.), and liver injury was evaluated 3-16 h later. Cisplatin produced dose- and time-dependent liver injury, as evidenced by increased serum activity of alanine aminotransferase (ALT), as well as by histopathology. Apoptosis, rather than necrosis, predominates in cisplatin-induced liver injury, as indicated by increased numbers of apoptotic cells (hematoxylin and eosin staining), in situ apoptotic DNA detection, and DNA fragmentation on agarose gel electrophoresis. MT-null mice were more sensitive than controls to cisplatin-induced hepatotoxicity. Cisplatin (200 mumol/kg) was lethal to 12% of control mice, but 60% of MT-null mice died within 16 h. At the dose of 150 mumol/kg, serum ALT activities were increased 2-fold in control mice compared to 6.5-fold in MT-null mice. Apoptotic lesions were more pronounced in MT-null than in control mice. MT-null mice were also more susceptible than controls to cisplatin-induced nephrotoxicity, as evidenced by having higher blood urea nitrogen concentrations. Furthermore, cultured MT-null hepatocytes were more sensitive than control cells to the cytotoxicity of cisplatin (50-200 microM), as indicated by lactate dehydrogenase leakage into the medium. These results demonstrate that (1) high doses of cisplatin produce hepatotoxicity, with apoptosis as the major lesion, and (2) MT protects against cisplatin-induced liver injury.     

Personal performance profiles: a useful adjunct to quality assurance in cervical cytology

The purpose of this study was to determine whether the morphology of the midface differed in subjects with a retrognathic midfacial appearance (Class III malocclusions) using a combination of morphometric and cephalometric analyses. After obtaining appropriate consent, lateral cephalographs of 133 children of European-American descent, ages 5-11 years, were compared: 73 had Class III malocclusion, 60 had normal (Class I) occlusion. The cephalographs were traced and subdivided into seven age- and sex-matched groups. Average geometries based upon seven nodes (pterygoid point, PTS; rhinion, RO; posterior nasal spine, PNS; midpalatal point, MPP; anterior nasal spine, ANS; subspinale, A; prosthion, Pr), scaled to an equivalent size, were compared using a Procrustes routine. Euclidean distance matrix analysis (EDMA) was employed to localize differences in morphology. Bivariate analyses on unscaled data utilizing nine linear and six angular measurements were also undertaken. Results from Procrustes and EDMA analyses indicated that although the overall midfacial configurations differed statistically (P < 0.05), only about half of the seven age sub-groups maintained significance. Similarly, only four of the nine linear measures (PNS-MPP, MPP-ANS, A-Pr and PTS-RO) and two of the six angular parameters (PTS-RO-ANS and ANS-A-Pr) tested were significantly different (P < 0.05). Therefore, midfacial morphometric variability and morphological diversity may mask statistical differences. It is concluded that the midface may be the defining craniofacial component in the final appearance of Class III malocclusions compared to other craniofacial components, including the cranial base and mandible.     

Long-term regulation of leptin expression is correlated with adipocyte number in obese rats

OBJECTIVE: To investigate long-term regulation of leptin expression in adipose tissues of obese JCR:LA-corpulent rats, which have been shown to overexpress leptin. DESIGN: Manipulation of adipose tissue growth in obese rats by dietary restriction. INTERVENTIONS: Weanling female obese rats were maintained on 1 of 3 diets until 8 months old. One group was allowed to feed ad libitum, the second was pair-fed with lean rats, and the third had food intake restricted to maintain weights equal to those of age-matched lean rats. OUTCOME MEASURES: Body and fat pad weights, leptin messenger RNA (mRNA) levels, and size and number of adipocytes in retroperitoneal fat pads. RESULTS: Adipose tissue mass was increased 6-fold in the obese rats compared with the lean ones, despite equal body weight and intake restriction that was sufficient to impair growth. Although leptin mRNA level was down-regulated by intake restriction, it was still twice as elevated in the obese rats as in the lean ones, and was highly correlated with specific fat pad mass and adipocyte number, but not with size. CONCLUSIONS: These data suggest that leptin expression is correlated with adipocyte number within a fat pad, and that there is inappropriate hepatic de novo synthesis and storage of triacylglycerols in obese rats. A role for leptin in nutrient partitioning is proposed.