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Biomedical subjects

D Garcia

Publications and source records attributed to D Garcia.

At least 109 records · Page 6Linked to original sources

Reactions to and antigenicity of two human-rhesus rotavirus reassortant vaccine candidates of serotypes 1 and 2 in Venezuelan infants.

The reactions to and antigenicity of two human-rhesus rotavirus (RRV) reassortants (human rotavirus strain D x RRV and human rotavirus strain DS1 x RRV) with the VP7 neutralization specificity of a serotype 1 or serotype 2 rotavirus were evaluated in a placebo-controlled double-blind trial in 116 1- to 5-month-old infants in Caracas, Venezuela. The children were randomly divided into five groups to receive orally the following inocula: (i) 10(4) PFU of D x RRV reassortant; (ii) 10(4) PFU of DS1 x RRV reassortant; (iii) 10(4) PFU of RRV; (iv) 5 x 10(3) PFU of D x RRV and 5 x 10(3) PFU of RRV; and (v) placebo. The children were examined daily for 7 days following vaccine administration; 8 to 26% of the vaccinated infants developed a mild febrile reaction which in most cases lasted only 1 day. Seroresponses to rotavirus were observed in 39 to 65% of the vaccinees by plaque neutralization assay and in 57 to 88% by an immunoglobulin A enzyme-linked immunosorbent assay. Vaccine shedding was detected in 53 to 86% of the vaccinees. Analysis of neutralization antibody responses indicates that the VP4 protein represents an important component of the response induced by the vaccines.

Age Factors↗

Relative frequencies of rotavirus serotypes 1, 2, 3, and 4 in Venezuelan infants with gastroenteritis.

We have used a recently developed monoclonal antibody enzyme-linked immunosorbent assay (K. Taniguchi, T. Urasawa, Y. Morita, H. B. Greenberg, and S. Urasawa, J. Infect. Dis. 155:1159-1166, 1987) for serotyping rotaviruses recovered from 134 Venezuelan infants over a period of 15 months. One hundred and nine of the specimens were typed with the following distribution: serotype 1, 48%; serotype 2, 16%; serotype 3, 22%; and serotype 4, 14%. Three specimens reacted with two different monoclonal antibodies. In addition, 6 specimens (5%) containing enough outer capsid antigen could not be typed; partial RNA sequence analysis of the glycoprotein gene from three of these six strains failed to reveal sequence differences with prototype strains that could be serotyped with the monoclonal antibodies. Variations in the recovery rates of the different serotypes were observed. Serotypes 2, 3, and 4 predominated at the beginning of the study, and serotype 1 predominated at the end of the study. Diarrheal illness appeared to be more prolonged in infants shedding rotavirus serotypes 1 and 3 than in those shedding serotypes 2 and 4.

Base Sequence↗

Induction of bilirubin-eliminating processes by methylphenobarbital in mature newborn babies.

In order to find a drug for the prevention of metabolic hyperbilirubinemia of the newborn, which has less sedative effects than phenobarbital (PB) the effect of methylphenobarbital (MPB) on the plasma bilirubin concentration of newborns was studied in a double blind trial. MPB (3 x 10 mg/kg on the first day) reduced the plasma bilirubin level in mature newborns on day four by 33% in comparison to those on placebo. The results justify further investigations in premature babies, who frequently suffer from disturbances which may facilitate the development of bilirubin encephalopathy.

Bilirubin↗

Definitive radiation therapy in carcinoma of the prostate localized to the pelvis: experience at the Mallinckrodt Institute of Radiology.

Definitive radiation therapy was administered to 577 patients with histologically confirmed carcinoma of the prostate localized to the pelvis between January 1967 and December 1983. All patients were available for a minimal 3-year follow-up, and the median period of observation is 6.5 years. The actuarial survival without tumor in stages A2 and B at 5 years was 78% and at 10 years 60%. In stage C, the corresponding survival figures were 60% at 5 and 40% at 10 years. The overall actuarial survival in stage B patients was 76% at 5 and 56% at 10 years, which is similar to the life expectancy of a comparable cohort of normal males. In stage C, the actuarial survival was 65% at 5 and 35% at 10 years. The pelvic failure rate in stage A2 was 12% (5 of 41), 17% in stage B (31 of 185), 28% (93 of 328) in stage C, and 48% (11 of 23) in stage D1. Distant metastases were noted in 12% of the patients with stage A2, 20% stage B, 42% stage C, and 65% stage D1. In stage B, patients who had control of the pelvic tumor exhibited an 85% actuarial 5-year survival and a 60% one at 10 years. This compares with an actuarial survival of 30% at 5 and 10 years when there was evidence of pelvic recurrence alone or combined with distant metastases. In stage C patients with pelvic tumor control, actuarial survival was 81% at 5 and 50% at 10 years, in comparison with 25% at 5 and 10% at 10 years when there was development of pelvic recurrence or distant metastases or a combination of both. There was a strong correlation between the survival and appearance of distant metastases with the histologic degree of differentiation of the tumor in all stages. However, the probability of tumor control in the pelvis was not significantly correlated with this parameter. The administration of hormones concomitantly with radiation therapy did not significantly influence the probability of tumor control, appearance of distant metastases, or survival. Major sequelae of therapy were noted in 2.2% of the patients, whereas minor sequelae were observed in approximately 12% of the patients. Radiation therapy has been shown to be an effective therapeutic alternative to radical prostatectomy or hormonal manipulation in patients with carcinoma of the prostate.

Humans↗

Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants.

The efficacy of the rhesus rotavirus vaccine candidate MMU-18006 was evaluated in a longitudinal double-blind field trial in Caracas, Venezuela. 247 infants aged 1-10 months were studied and followed for up to 1 year (201 completed the 1-year surveillance): 123 received a dose of 10(4) plaque-forming units of the vaccine orally and 124 received placebo. 21 episodes of rotavirus diarrhoea were detected, 16 in the controls and 5 in the vaccines: vaccine efficacy against any rotavirus diarrhoea was thus 68%. In the 1-5-month-old group the vaccine efficacy was 93%; only 1 episode of rotavirus diarrhoea was detected in 68 vaccinees and 15 such illnesses were observed in 65 controls (p less than 0.0001). For the entire study group vaccine efficacy was 100% against the most severe rotavirus diarrhoeal episodes.

Antibodies, Viral↗

Effect of intragastric pH, prostaglandins and prostaglandin synthesis inhibitors on the release of gastrin and somatostatin into the gastric lumen of anaesthetized rats.

The object of the present work was to study the influence of antral pH, of aspirin and indomethacin, and of prostaglandins A2, E1 and E2 on the intragastric output of somatostatin and gastrin induced by electrical vagal stimulation (5 V, 2 ms, 2, 5 and 10 Hz). Experiments were performed on anaesthetized rats in which the stomach was perfused with a dextran solution (pH approximately 1.5 to approximately 6). To assess the effect of vagal stimulations on gastric acid secretion and on gastrin and somatostatin release, pH as well as somatostatin and gastrin levels was recorded in the perfusate effluent. During perfusion of the stomach with dextran solution, pH approximately 6, vagal stimulation at 10 Hz decreased perfusate pH to 1.3 and gastrin and somatostatin were released at a ratio of 2:1. Less gastrin and more somatostatin (ratio 0.1:1) was released by the same stimulation when the stomach was pre-perfused with acid solution (pH approximately 1.5), although also in these experiments the pH of the perfusate fell to 1.3. When vagal stimulations were performed after the rats had been pretreated with aspirin or indomethacin, more somatostatin than gastrin was detected in the perfusate independently of the perfusate pH. The vagally induced intraluminal release of somatostatin occurring in aspirin-treated animals was abolished by a low dose of atropine (0.05 mg kg-1) or by a simultaneous infusion of prostaglandin E1 (30 micrograms kg-1 h-1).

Alprostadil↗

Prostaglandin synthesis inhibition reverses the gastric antisecretory activity of somatostatin in anaesthetized rats.

The inhibitory action on somatostatin (ST) on the spontaneous and stimulated (pentagastrin 18 micrograms/kg/h i.v. and histamine 5 mg/kg/h i.v.) gastric acid secretion and its modification after pretreatment with an inhibitor of endogenous prostaglandins biosynthesis (indomethacin 5 mg/kg i.v.) has been studied in the anaesthetized rat. ST 30 micrograms/kg/h i.v. inhibits basal and stimulated gastric acid secretion. In the presence of indomethacin the inhibition elicited by ST on basal and pentagastrin induced gastric acid secretion was partially attenuated, whereas in the histamine group the inhibitory action was totally abolished. The antagonism elicited by indomethacin was not surmounted by increasing (X 3.3) the dose of ST. These findings suggest that endogenous prostaglandins may be involved in the mechanism by which ST exerts its antisecretory effect in this model.

Anesthesia↗

Comparative molecular pharmacology in leukemic L1210 cells of the anthracene anticancer drugs mitoxantrone and bisantrene.

1,4-Dihydroxy-5,8-bis(2-[(2-hydroxyethyl)aminoethyl]amino)-9, 10-anthracenedione (mitoxantrone) and 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1H-imidazol-2y)hydrazone] dihydrochloride (bisantrene) were evaluated for their abilities to cause cytotoxicity and interact with cellular DNA using leukemic L1210 cells. On a molar basis mitoxantrone has been found to be 7-fold more toxic than bisantrene. Using a nucleoid sedimentation technique, bisantrene caused changes in DNA supercoiling which were characteristic of an intercalating drug, but mitoxantrone did not induce these changes. Both drugs were found to interact with cellular DNA with tight but noncovalent binding. Both drugs also induced protein-associated double- and single-strand DNA breaks, but with mitoxantrone only some of the DNA single-strand breaks were protein associated, whereas with bisantrene all the DNA single-strand breaks were protein associated. The cytotoxicity produced by bisantrene at a given frequency of protein-associated DNA strand breaks was low. However, with mitoxantrone at an equivalent DNA strand break frequency, the cytotoxicity was high. Treatment of isolated L1210 nuclei with either drug did not result in DNA single-strand breaks. It can be concluded that bisantrene binds DNA in whole cells by an intercalative mechanism, whereas mitoxantrone binds DNA by a nonintercalative, electrostatic interaction and induces non-protein-associated DNA strand breaks.

Animals↗

Multiple cerebral hydatid cysts.

A 39-year-old woman was admitted to hospital with headaches, vomiting, psychic impairment and diplopia. Three hydatid cysts of the lung had been previously removed. An avascular mass in the left hemisphere with left-to-right displacement of the anterior cerebral arteries was noted during a brain angioscintigraphy. A computed tomography (CT) brain scan showed two cystic lesions situated in the left-frontal and occipital regions. A CT abdominal scan showed multiple cysts in the liver, spleen and both kidneys. At operation, two brain cysts were totally extirpated without rupture. The definite pathological diagnosis was secondary hydatid cysts. The headaches, vomiting and diplopia were persistent in the post-operative period. Seven days after the operation, a CT brain scan showed an infratentorial cyst. The patient rejected any surgical intervention.

Adult↗

Clinical use of the arterial/alveolar oxygen tension ratio.

A prospective study to verify the behavior of the arterial/alveolar oxygen tension ratio (PaO2/PAO2) at different fractions of inspired oxygen (FIO2), was performed in 15 adult hypoxemic patients. This index was useful not only for predicting the arterial oxygen tension but also for choosing the necessary oxygen supplementary levels. PaO2/PAO2 was a less reliable index in patients with mild intrapulmonary shunts, probably because of changes in the distribution of alveolar ventilation/perfusion ratios.

Adult↗

The Psychological Screening Inventory as a predictor of predisposition to suicide among patients at the Oregon State Hospital.

Examined all closed patient files for the inclusion of scores from the Psychological Screening Inventory (PSI) at the Oregon State Hospital between 1977-1979. Subsequently, the patient files (N = 123) were assessed for suicidal inclination employing five categories, which ranged from "no suicidal ideation" to "serious attempt." t-tests were completed between Ss placed in category 1 (no suicidal ideation) and remaining categories. Results yielded a significant value for "discomfort," with lower discomfort scores related to higher suicide risks. Subsequent extreme group analysis yielded significant but opposite results for males and females, which suggests the importance of evaluating the results of the PSI separately for sex.

Adult↗

Identification and typing of herpes simplex viruses with monoclonal antibodies.

Monoclonal antibodies which reacted with type-specific antigens of herpes simplex virus type 2 or with antigens shared by herpes simplex virus types 1 and 2 were used in an indirect immunofluorescence assay to type virus isolates and to detect viral antigens in cells obtained from herpetic lesions. Complete concordance was obtained for 42 isolates typed by endonuclease restriction analysis of viral DNA and by indirect immunofluorescence with monoclonal antibodies. Examination of a limited number of ulcerative lesions revealed that indirect immunofluorescence and virus isolation were comparable in detecting herpes simplex virus. The results indicate that monoclonal antibodies can be used to accurately identify and type isolates of herpes simplex virus.

Animals↗

Molecular pharmacology of the anthracycline drug 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (Cl 216,942).

9,10-Anthracenedicarboxyaldehyde bis[(4,5-dihydro-1H-imidazol-2yl)hydrazone] dihydrochloride (Cl 216,942) is a new anthracene bishydrazone derivative which has shown antitumor activity in Phase I trials against both hematological cancers and solid tumors. The effects of Cl 216,942 on L1210 mouse leukemia cells were studied with the nucleoid sedimentation and alkaline elution assays. Evidence for Cl 216,942 intercalation into cellular DNA was obtained in exponentially growing cells by comparing the L1210 nucleoid sedimentation behavior in neutral sucrose gradients of ethidium bromide with nucleoids from Cl 216,942-treated cells. A 1-hr treatment of exponentially growing L1210 cells with Cl 216,942 induced both protein-associated DNA single-strand breaks and DNA-protein crosslinks as detected by the alkaline elution assay. The DNA strand break and DNA-protein cross-link frequencies were found to be within a factor of 2 of each other over a range of Cl 216,942 concentrations. The dose response for the induction of DNA damage showed a linear decrease up to 10 micrograms/ml, but this was followed by a decrease in damage at dose levels greater than 10 micrograms/ml. The biphasic dose response could not be explained by changes in the cellular uptake of Cl 216,942. The kinetics of Cl 216,942 induction of DNA damage after a 1-hr treatment showed that at the dose which gave maximum damage the degree of damage (10 micrograms/ml) decreased with further incubation, but at a higher dose (20 micrograms/ml) DNA damage increased with postincubation at 37 degrees. The cytotoxicity produced by Cl 216,942 at a given frequency of protein-associated strand breaks was low. Cl 216,942 thus appeared to belong to a low-toxicity group of DNA intercalators.

Animals↗