Phase I clinical study of the recombinant oncotoxin TP40 in superficial bladder cancer

Many previous studies evaluating various hormone levels in males with subnormal semen analyses were performed when the normal semen parameters were considerably higher than now. This study evaluated sera levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TET), free TET, and prolactin (PRL) in 60 males with oligospermia and decreased motility according to recent World Health Organization standards. Three separate groups were evaluated: group 1, motile density (MD) < 5 x 10(6)/mL (but not azoospermia); group 2, 5 < or = MD < 10 x 10(6)/mL; group 3, MD > 10 x 10(6)/mL, but % motility < 30%. There were no significant differences in mean FSH levels between groups. Overall FSH was increased in 47.1% of the cases. In contrast, mean LH levels were normal in all three groups. Only 17.3% of the entire group had elevated LH levels. The TET level was below normal in 32.3% of the entire group, with a fairly equal distribution between the three groups. Overall, only 7.8% had elevated PRL levels, with the highest percentage found in group 3 (22.2%). Only a small minority of patients with increased FSH had low TET levels compared to 48.0% of those with normal FSH. These data demonstrate that when using the lower semen parameters, the most common serum hormone abnormality is increased FSH; men with MD < 5 x 10(6)/mL do not have a higher incidence of elevated FSH than those with higher MDs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sonoclot analysis

Assessment of perioperative bleeding disorders, especially those related to platelet dysfunction, remains a clinical challenge. The management of the bleeding patient in the operating theatre or on the postoperative ward is often empirical with little scientific basis. Much of the reason for this is that conventional clotting studies are not immediately available and there is a perceived urgency, particularly among trainee doctors, to treat bleeding disorders without first establishing the exact nature of the coagulopathy. SCT provides useful information on platelet function, particularly in patients after cardiopulmonary bypass, and has enabled practitioners to rationalize the management of bleeding disorders and not expose their patients to the risks of unnecessary transfusion of blood products. Undoubtedly further studies are required before this instrument can be used reliably in the clinical setting but it may prove to be a useful addition to the available techniques for monitoring perioperative bleeding disorders.     

Prophylactic and therapeutic efficacy of an avian antitoxin in ricin intoxication

This study was designed to demonstrate the efficacy in animals of a ricin antitoxin consisting of purified avian antibodies. Antitoxins consisting of avian antibodies have significant advantages when compared to conventional mammalian (e.g. horse) antibodies; (a) avian antibodies do not fix human complement, eliminating associated inflammatory reactions, and, (b) avian antibodies can be manufactured more economically. Ricin toxoid was injected into laying hens followed by collection of eggs bearing hyperimmune immunoglobulin. Immunoglobulin was extracted from yolks and purified by immunoaffinity chromatography. In a mouse model for toxin neutralization it was shown that immunoaffinity purified ricin antibodies could prevent ricin lethality. Furthermore, it was shown that passive antibody treatment leads to active ricin immunization in animals given lethal ricin doses. Highly purified avian antibodies, as developed in this study, should offer enhanced clinical effectiveness, greater safety, and reduced manufacturing costs when compared to other technologies.     

Acute vision loss resulting from complications of ethanol abuse

A dynamic digital brain phantom was created from the MRI to evaluate visually the relationship between the noise and the error in the parameter estimates in the PET kinetic analysis. This phantom incorporates the noise level depending on administration dose, camera efficiency and the data acquisition schedule. We simulated a serial dynamic scan with 18F-FDG or 11C-flumazenil, assuming 2-tissue 3-parameter model and 1-tissue 2-parameter model, respectively, and the sampling schedule was determined according to the clinical examination. The noise in the tissue time activity curve in FDG had a peak in the first minute and decreased thereafter, whereas the noise increased gradually in the flumazenil study after the initial peak due to radioactivity decay. We examined the relationship between the noise level and the error in the parameter estimates. Both mean absolute differences between true and estimated values and standard deviation became large, and the quality of the parametric images became poor with increasing noise level. This simulation was compared with human tissue time activity curves and parametric images, which were obtained with 100 MBq administration dose in FDG study and 430 MBq in flumazenil study. We inferred that the noise level in the human study was 10-20% in FDG, and 20-40% in flumazenil, and the error in the estimated parameter of K-complex in FDG study was about 20%, that of DV in flumazenil study was 2%.     

Immunoassay of human Neisseria meningitidis serogroup A antibody

An enzyme immunoassay is described which quantitates antibodies to Neisseria meningitidis serogroup A capsular polysaccharide in human sera. Modifications of a previously developed two-day assay by Carlone et al. were made to permit analysis in one day and to be compatible with automation. The allowable variations in assay conditions and the areas in which stringent control must be maintained for consistent assay performance are described. Antigen-coating parameters, the kinetics of primary and secondary antibody incubation steps, the buffer compositions, including detergents, serum requirements, and the need for blocking steps were examined. Our modified one-day assay showed excellent agreement with the standardized method of Carlone, with a correlation coefficient between the two methods of 0.989. This assay is adaptable within a permissible range of parameters thus facilitating the implementation of the standardized assay. This will maximize the consistency of results from serum analysis for conjugate vaccine trials related to serotype A Neisseria meningitidis.     

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.