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Biomedical subjects

R Ponce

Publications and source records attributed to R Ponce.

11 recordsLinked to original sources

Influenza virus host response of C57Bl/6 mice treated with TACI-Ig.

TACI-Ig is a soluble glycoprotein comprised of a human IgG1-Fc fused with the extracellular domain of the human TACI receptor. Chronic exposure to TACI-Ig is associated with reduced circulating B cells in mouse and non-human primates, and a concomitant decrease in circulating immunoglobulin. Because of these activities, TACI-Ig is in clinical evaluation for treatment of various autoimmune diseases and B cell malignancies. In this study, the effect of TACI-Ig treatment on the ability of C57Bl/6 mice to clear influenza virus was evaluated. C57Bl/6 mice were exposed to vehicle (negative control), dexamethasone (positive control), or TACI-Ig (0.05, 0.50, or 5.0 mg/kg, SC, thrice weekly) from within one week prior to viral exposure through 21 days thereafter. Dexamethasone treatment of influenza-infected mice prolonged the infection, and decreased survival, body weight, lymphoid organ weight, influenza-specific IgM and IgG, and viral clearance relative to control animals, consistent with its expected immunosuppressive activity. Animals treated with TACI-Ig (0.05, 0.50, and 5.0 mg/kg) demonstrated a dose-dependent decrease in spleen weight and influenza-specific IgG and IgM in both lung and serum relative to control animals. In addition, flow cytometric analyses showed a decrease in B cells, but not T cells, in peripheral blood in animals treated with TACI-Ig. However, neither viral clearance nor survival was affected by TACI-Ig treatment. These data demonstrate the expected B cell-specific pharmacological effects of TACI-Ig in influenza-challenged C57Bl/6 mice without apparent effect on influenza virus clearance. It is concluded that non-B cell related antiviral competence remains intact during TACI-Ig treatment.

Adjuvants, Immunologic↗

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Animals↗

Trace metals in ancient hair from the Karluk Archaeological Site, Kodiak, Alaska.

Considerable interest exists in characterizing the extent of changes in methylmercury exposures from preindustrial to modern-day times. Hair is often preserved over centuries and has been useful in determining the extent of dietary trace metal exposures, particularly methylmercury. We examined 16 human hair samples taken from human hair bundles buried in the soil of the Karluk One Archaeological site located near the current Karluk village on the Kodiak Archipelago of Alaska. Hair samples were analyzed for total mercury, methylmercury, selenium, and cadmium. The mean total mercury level was 1.33 ppm (SD = 1.09). The mean methylmercury level, however, was considerably lower than the total mercury concentration: the mean methylmercury level was 0.03 ppm (SD = 0.02). The mean cadmium level was 0.15 ppm (SD = 0.14) and the mean selenium level was 5.22 ppm (SD = 5.73). While the concentration of total mercury in the Karluk hair samples is comparable to those observed in ancient hair from other locations, direct methylmercury quantization demonstrated that methylmercury levels were less than 2% of the total mercury in these hair samples. Because the hair was subjected to a variety of environmental influences over the centuries, the possibility of degradation of methylmercury in the hair over the last 400 to 800 years cannot be ruled out. The use of hair from remains found in more protected frozen or dry environments may provide the best evidence for the extent of preindustrial exposures to methylmercury and other trace metals.

Alaska↗

A general algorithm for assisting medical diagnosis.

An algorithm for assisting medical diagnosis is designed; this algorithm is highly reliable and can be given general use. The method is based on the comparison of the column vector of the symptoms of a given patient with each of the columns of disease symptoms which appear on a matrix. On this matrix, the symptoms have been arranged according to the hierarchic order of each of the symptoms, which facilitates the creation of a file. Moreover, this system undertakes a simultaneous comparison of all the diseases considered in the differential diagnosis, in comparison to the alternate procedures in which the patient's symptoms are compared in separate succession with each of the vectors of the disease under study.

Algorithms↗

[Elevated gastric lesions].

Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterología Boliviano Japonés and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions.

Adult↗

Megacolon at high altitude.

Megacolon occurs frequently in high altitude areas. This report describes observations made in 60 cases seen in La Paz, Bolivia (3,600 meters above sea level). Motility of both the large and small bowel was found to be increased and the feces had a low pH. No histologic abnormalities were noted in the nervous plexus or smooth muscle. It is assumed that megacolon in these circumstances is acquired and not congenital.

Altitude↗

[Digestive changes in cholecystectomized patients].

An important number of cholecystectomized patients after some years of complete well-being, begin complaining of symptoms such as periodic diarrhea or constipation, abdominal pain, regurgitation, vomiting, etc. The purpose of this study is to try to identify an alteration or lesion in the stomach or colon in cholecystectomized patients of more than five years standing, which may be causing the aforementioned condition. The forty patients under observation, free of biliary tract post-operative lesions, were subjected to: hemogram, amylasemia, either infusion cholangiograph or ERCP, fecal parasitological-tests, upper digestive and colon X Ray series, esophagus, stomach and duodenal endoscopy with biopsies. Additionally, ten underwent a colonoscopy which also included biopsy. The result of the radiological, amylasemia and hemogram studies was normal in all cases. The parasitological tests were negative. In every case, a moderate to severe superficial, chronic gastritis was found as well as minor histopathological alterations in the colon mucosa. The presence of bile in both duodenum and colon in interdigestive periods, alterations in the enterohepatic circulation as well as in the biliary composition itself, are suggested as the possible causes of the patients symptoms.

Adult↗

Pigment gallstone pathogenesis: slime production by biliary bacteria is more important than beta-glucuronidase production.

Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta-glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta-glucuronidase or slime production. Ninety-one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta-glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P <0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta-glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62% of patients with primary CBD stones, and 50% of patients with biliary tubes had one or more bacteria that produced beta-glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta-glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes.

Bacteria↗