Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia

Esophageal atresia (EA) is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO). Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA), and DOXO with EA (DOXO+EA). Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh). The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P<0.05). The maximum effect values (Emax) for DOXO+EA and DOXO-EA were significantly lower than control (P<0.05), but the half-maximal effective concentration (EC50) values were not significantly different when the three groups were compared (P>0.05). In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05). No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05). In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

Contractile profile of esophageal and gastric fundus strips in experimental doxorubicin-induced esophageal atresia.

Esophageal atresia (EA) is characterized by esophageal and gastric motility changes secondary to developmental and postsurgical damage. This study evaluated the in vitro contractile profile of the distal esophagus and gastric fundus in an experimental model of EA induced by doxorubicin (DOXO). Wistar pregnant rats received DOXO 2.2 mg/kg on the 8th and 9th gestational days. On day 21.5, fetuses were collected, sacrificed, and divided into groups: control, DOXO without EA (DOXO-EA), and DOXO with EA (DOXO+EA). Strips from the distal esophagus and gastric fundus were mounted on a wire myograph and isolated organ-bath system, respectively, and subjected to increasing concentrations of carbamylcholine chloride (carbachol, CCh). The isolated esophagus was also stimulated with increasing concentrations of KCl. In esophagus, the concentration-effect curves were reduced in response to CCh in the DOXO+EA and DOXO-EA groups compared to the control group (P<0.05). The maximum effect values (Emax) for DOXO+EA and DOXO-EA were significantly lower than control (P<0.05), but the half-maximal effective concentration (EC50) values were not significantly different when the three groups were compared (P>0.05). In response to KCl, the distal esophagus samples in the three groups were not statistically different with regard to Emax or EC50 values (P>0.05). No significant difference was noted for EC50 or Emax values in fundic strips stimulated with CCh (P>0.05). In conclusion, exposure of dams to DOXO during gestation inhibited the contractile behavior of esophageal strips from offspring in response to CCh but not KCl, regardless of EA induction. The gastric fundus of DOXO-exposed offspring did not have altered contractile responsiveness to cholinergic stimulation.

Rotavirus subgroups, G serotypes, and electrophoretypes in cases of nosocomial infantile diarrhoea in Belém, Brazil.

From November 1992 to November 1994 stool samples were obtained from 237 children admitted to a public hospital in Belém. Rotaviruses were detected in 19.3 per cent (60/310) of faecal samples. Of these, 32.1 per cent (18/56), 20.9 per cent (38/181), and 5.4 per cent (4/73) were recorded in cases of nosocomial diarrhoea, community-acquired diarrhoea, and controls, respectively. Fifty-two (86.7 per cent) of the 60 rotavirus-positive specimens were subgrouped and the G serotypes of 55 (91.7 per cent) of them were determined. Subgroups I and II were detected in 50 per cent each of the 52 subgrouped strains. G type 2 was present in 46 (83.6 per cent) of the 55 serotyped samples; serotypes G1 and (mixed) G1 and G4 were found in 14.5 per cent and 1.8 per cent, respectively, of these specimens. Viral RNA electrophoresis showed 14 distinct patterns, including 56.7 per cent (34/60) and 43.3 per cent (26/60) of long and short profiles, respectively. In 40 (66.6 per cent) of the 60 rotavirus-positive faecal samples no enteropathogens other than rotavirus were detected. There was an increased incidence of rotavirus infection from July 1993 to February 1994. The rotavirus-related episodes of diarrhoea were more severe than those of other aetiology and greater clinical severity was not related to a specific G type, subgroup, or electrophoretype.

[Congenital syphilis: incidence among newborns] / Sífilis congênita: incidência em recém-nascidos.

OBJECTIVE: To determine the incidence of congenital syphilis among newborns at the maternity of a public hospital. METHODS: The study was conducted at the maternity of Fundação Santa Casa de Misericórdia do Pará, from May to September 1996; 361 mothers were interviewed, and physical examination was performed in their newborns. Serum samples from both, mothers and neonates, were tested using three methods: VDRL, FTA - Abs, ELISA IgM. The diagnosis of congenital syphilis was established according to the criteria defined by Ministério da Saúde in 1993. RESULTS: The rate of congenital syphilis was of 9.1% (33); in 14 cases, there were one or more signs of the disease: prematurity, hepatomegaly, stillbirth, splenomegaly, perinatal death, abdominal distention, nasal stuffiness, jaundice, newborn small for gestational age. The majority of the infected mothers belonged to the age group of 20-35 years (81.8%); 60.6% were married; 63.6% received prenatal care; 48.5% reported previous spontaneous abortion, and 12.1% previous stillbirth. The rate of bisexuality among fathers was of 9.1%. CONCLUSION: The syphilis control measures and the prenatal care, have not been sufficient to prevent the high rate of the disease.

Inmunogenicidad, inocuidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos en Belém, Brasil / Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil

Se evaluó la inocuidad, inmunogenicidad y eficacia de una vacuna tetravalente obtenida por recombinación genética de rotavirus aislados de monos rhesus y seres humanos (RRV-TV) (4 x 104 unidades formadoras de placas por dosis) en un ensayo prospectivo, aleatorio, a doble ciego y controlado con placebo que se efectuó con 540 lactantes brasileños. Se administraron dosis de vacuna o de placebo a la edad de 1, 3 y 5 meses. No se observaron diferencias significativas en la frecuencia de diarrea o vómito en los bebés de ninguno de los dos grupos después de administrar la dosis correspondiente. De 2 a 3% de los vacunados tuvieron fiebre baja los días tercero a quinto después de recibir la primera dosis, pero no después de las dosis segunda o tercera. Se observó una respuesta de anticuerpos del tipo IgA al rotavirus aislado de monos rhesus (RRV) en 58% de los vacunados y en 33% de quienes recibieron placebo. La respuesta de anticuerpos neutralizantes a cada serotipo no pasó de 20% cuando se determinó con la prueba de reducción de focos de fluorescencia, pero fue superior a 40% al medirse con la prueba de neutralización a base de reducción de placas. Se presentaron 91 casos de diarrea causada por rotavirus entre los niños que recibieron las tres dosis (de vacuna o de placebo) durante un seguimiento de 2 años, 36 de ellos en los niños vacunados. La eficacia general de la vacuna fue de 8% (P = 0,005) contra toda clase de diarrea y de 35% (P = 0,03) contra la diarrea causada por rotavirus. La protección durante el primer año de seguimiento, cuando predominó el rotavirus G del serotipo 1, fue de 57% (P = 0,008), pero se redujo a 12% en el segundo año. Se obtuvieron resultados similares al restringir el análisis a episodios en que el rotavirus fue el único agente patógeno identificado. Se observó en la vacuna una mayor tendencia a proteger contra casos de enfermedad con un promedio de seis o más deposiciones diarias. Estos resultados son lo suficientemente...

A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 104 plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages, 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3­5 in 2­3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.

Cholera in north Brazil: on the occurrence of strains of Vibrio cholerae O1 which fail to ferment sucrose during routine plating on thiosulphate-citrate-bile salt-sucrose agar (TCBS). A new problem in diagnosis and control?

The occurrence is recorded from a biochemical strain variant of Vibrio cholerae O1 originating from the municipality of Oiapoque, Amapá State, north Brazil and responsible for an epidemic outbreak of cholera in that region in August, 1994. The principal characteristic of the strain is its incapacity of break down sucrose on T.C.B.S. agar plates, and its delayed utilization of that sugar only after 48 hs. when cultivated in liquid medium. The strain spread rapidly in north Brazil, becoming responsible for most of the cases of cholera reported in Amazonian Brazil. The importance of this observation in laboratory diagnosis and the control of cholera is discussed.

Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.

A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy.

Rotaviruses as a cause of nosocomial, infantile diarrhoea in northern Brazil: pilot study.

Faecal samples were obtained from 190 children, aged 0 to 5 years, admitted to a public hospital in Belém, Pará, Brazil. These patients were placed in a pediatric ward with 40 beds distributed in six rooms. Cases were classified into three groups: (a) nosocomial: children who developed gastroenteritis 72 hr or later after admission; (b) community-acquired: patients admitted either with diarrhoea or who had diarrhoea within 72 hr following admission; (c) non-diarrhoeic: those children who had no diarrhoea three days before and three days after collection of formed faecal sample. Specimens were routinely processed for the presence of rotaviruses, bacteria and parasites. Rotaviruses were detected through enzyme-linked immunosorbent assay (ELISA) and subsequently serotyped/electrophoretyped. Rotaviruses were the most prevalent enteropathogens among nosocomial cases, accounting for 39% (9/23) of diarrhoeal episodes; on the other hand, rotaviruses occurred in 8.3% (11/133) and 9% (3/34) of community-acquired and non-diarrhoeic categories, respectively. Mixed infections involving rotavirus and Giardia intestinalis and rotavirus plus G. intestinalis and Entamoeba histolytica were detected in frequencies of 8.6 and 4.3%, respectively, in the nosocomial group. The absence of bacterial pathogens in this category, and the unusual low prevalence of these agents in the other two groups may reflect the early and routine administration of antibiotics following admission to this hospital. Rotavirus serotype 2 prevailed over the other types, accounting for 77.8% of isolates from nosocomial diarrhoeal episodes. In addition, at least five different genomic profiles could be observed, of which one displayed an unusual five-segment first RNA cluster. Dehydration was recorded in all cases of hospital-acquired, rotavirus-associated diarrhoea, whereas in only 57% of nosocomial cases of other aetiology. It was also noted that nosocomial, rotavirus-associated diarrhoeal episodes occur earlier (7 days), following admission, if compared with those hospital-acquired cases of other aetiology (14 days).

[Prospective study of rotavirus infections in Belém, Pará, Brazil: clinical and epidemiological features]. / Estudo prospectivo das infecções por rotavírus em Belém, Pará, Brasil: uma abordagem clínico-epidemiológica.

A prospective study of acute diarrhoeal diseases was carried out from April 1990 to September 1992 with the purpose of assessing the immunogenicity, safety and efficacy of a Rhesus-human reassortant rotavirus ("RRV-TV") vaccine, involving 540 children living in Belém, Pará, Brazil. As half of the children received placebo, this trial provided the opportunity of broadening the knowledge on both clinical and epidemiological aspects of rotavirus infection in the Amazon region. There were 2,789 diarrhoeal episodes during the above mentioned period, of which 86 (3.1%) associated with rotavirus; serotype 1 was the more prevalent, accounting for 67.9% of serotyped strains. Rates of 5.9 and 0.2 episodes of diarrhoea per child/year were noted for all cases and the rotavirus-related ones, respectively. This agent was the only pathogen found in 70.9% of the 86 rotavirus-related episodes of acute diarrhoea, whereas the most frequent associations involved Giardia intestinalis and enteropathogenic Escherichia coli, accounting for 7.0% and 11.6% of mixed infections,respectively. The monthly rates of rotavirus-related episodes of diarrhoea ranged from 0.8% to 9.6%, reaching the highest peaks during the dry months of the year. Means of clinical severity scores of 9.4 and 5.3 were recorded for the rotavirus-related episodes of diarrhoea and those of other aetiology, respectively.