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Biomedical subjects

M B Rennels

Publications and source records attributed to M B Rennels.

At least 55 records · Page 3Linked to original sources

Immunogenicity and reactogenicity of lowered doses of rhesus rotavirus vaccine strain MMU 18006 in young children.

Rhesus rotavirus oral vaccine strain MMU 18006 at a dose of 10(5) plaque-forming units (PFU), a 1:10 dilution of the original undiluted vaccine, is highly immunogenic in young children. Fevers have occurred, however, on Days 3 and 4 following vaccination. This study was conducted to determine whether febrile reactions could be eliminated and immunogenicity maintained by (1) giving smaller doses of vaccine or (2) vaccinating younger infants. Thirty-one children between 3 and 11 months of age received, in a randomized, double blind manner, either 10(4) PFU of vaccine virus, 10(3) PFU of vaccine virus or placebo. All recipients of the 10(4) PFU dose had a seroresponse; however, some degree of immunogenicity was lost with the smaller dose (10(3) PFU). Fevers were observed in recipients of both of the lowered doses of vaccine but the febrile reactions were related to the age of the vaccinee. No infant younger than 5 months of age experienced a temperature elevation, whereas the majority of children older than 5 months had fevers. Our data suggest that the lack of reaction in the younger infants correlates with the presence of prevaccination neutralizing antibody, presumably transplacentally acquired. We conclude that the rhesus rotavirus oral vaccine at a dose of 10(4) PFU is immunogenic and appears to be safe in young infants.

Antibodies, Viral↗

Streptococcal sepsis presenting as acute abdomen in a child with transient hypogammaglobulinemia of infancy.

Group A streptococcal sepsis was documented in a child who presented with an acute abdomen. Massive retroperitoneal edema was observed at laparotomy with no focus of infection. Immunologic evaluation revealed low serum immunoglobulins and deficient in vitro IgG synthesis consistent with transient hypogammaglobulinemia of infancy. Unusual or severe infections in infancy should be evaluated for congenital immunologic disease.

Abdomen, Acute↗

Intestinal Salmonella carriage in patients with major sickle cell hemoglobinopathies.

The increased incidence of Salmonella osteomyelitis in patients with sickle cell disease has never been entirely explained. Problems such as cholelithiasis, intestinal infarction, and frequent antibiotic use in this population could possibly result in prolonged or chronic intestinal carriage of Salmonella after acute gastroenteritis. If prolonged carriage were a factor in the pathogenesis of osteomyelitis, attempts to eliminate the Salmonella with antibiotics would be indicated. We did a stool culture survey of 71 patients attending our pediatric sickle cell clinic to determine the incidence of asymptomatic Salmonella carriage. At least two rectal swab cultures were obtained from each patient; 69% of patients also mailed in a stool sample for culture. No Salmonella was isolated. It therefore appears unlikely that prolonged intestinal Salmonella carriage is an important mechanism in the development of Salmonella osteomyelitis in patients with major sickle hemoglobinopathies.

Adolescent↗

Cholelithiasis in patients with major sickle hemoglobinopathies.

Cholelithiasis is a common complication of homozygous sickle cell disease. The frequency of gallstones appearing in patients with heterozygous sickle hemoglobinopathies is unknown. We performed sonographic tests on 65 unselected patients with major sickle hemoglobinopathies. Cholelithiasis was found in 11 (26%) of the 42 patients with hemoglobin SS, in three (20%) of the 15 with Hb SC, and in one (12.5%) of the eight with Hb S-beta-thalassemia. There was a correlation between the presence of gallstones and increasing age. All patients with major sickle hemoglobinopathies are at risk for the development of biliary tract disease.

Adolescent↗

Arthropod-borne virus infections of the central nervous system.

Arthropod-borne viruses (arboviruses) are an important cause of meningoencephalitis in North America. This article considers the common features of the four major CNS arbovirus infections in this country and gives detailed descriptions of the individual virus infections.

Arbovirus Infections↗

Medical cure of apparent brain abscesses.

Two children with apparent brain abscesses were cured with antibiotic therapy. Review of the literature reveals clinical and experimental evidence that both cerebritis and an encapsulated abscess may appear as an enhancing ring lesion on cranial computed tomography. Patients reported to have had brain abscesses cured without surgery actually may have had cerebritis. There are only preliminary hints as to how to differentiate patients with cerebritis from those with an abscess. More experience is necessary to develop criteria to determine which patients may be appropriately treated with antibiotic therapy alone.

Anti-Bacterial Agents↗

Bronchial reactivity in experimental infections with influenza virus.

In an attempt to develop an objective, quantitative test to assess the reactogenicity of candidates for attenuated influenza virus vaccines, the clinical responses and bronchial reactivity to methacholine were assessed in 36 normal volunteers lacking antibody to both hemagglutinin and neuraminidase (doubly seronegative) who were inoculated with either wild-type or temperature-sensitive attenuated influenza A (H1N1) virus by intranasal droplets. Five of six volunteers infected with wild-type virus developed systemic and/or febrile illness that lasted for a mean of five days. Nineteen of 30 persons who received attenuated virus developed infection without febrile or systemic illness. In the six recipients of wild-type virus, bronchial reactivity appeared to increase after inoculation and persist for four weeks. This trend was not observed in infected or noninfected vaccinees. Analysis of variance provided suggestive (but not significant) evidence that the different trends in bronchial reactivity manifested by the wild-type virus and vaccine groups were distinct (P = 0.075).

Airway Resistance↗

Evaluation of A/Alaska/6/77 (H3N2) cold-adapted recombinant viruses derived from A/Ann Arbor/6/60 cold-adapted donor virus in adult seronegative volunteers.

The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.

Antibodies, Viral↗

Chlamydia trachomatis infection in infant delivered by cesarean section.

Neonatal Chlamydia trachomatis infection is thought to be acquired as a result of contact with infected cervical secretions during vaginal delivery. An infant, delivered by cesarean section, who was infected with C trachomatis has been described. At 31 days of age he had conjunctivitis and respiratory distress. Nasopharyngeal aspirate grew C trachomatis and serum IgM antibody titer was 1:32 for serotype J. The patient's mother had serum IgG antibody against C trachomatis serotype J. Her cervical culture was negative for Chlamydia; however, cultures were not taken until two months after delivery and she had received antibiotics for postpartum fever and abdominal pain. The literature has been reviewed and possible modes of transmission have been discussed.

Antibodies, Bacterial↗

Hemagglutination and colonization factors in enterotoxigenic and enteropathogenic Escherichia coli that cause diarrhea.

Controversy exists as to whether all strains of enterotoxigenic Escherichia coli must possess colonization factor antigen pili I or II (CFA/I, CFA/II) in order to be virulent for humans. Failure to detect CFA/I or CFA/II in enterotoxigenic strains from human diarrhea has been explained by some as due to plasmid loss and by others as evidence that CFA/I and CFA/II pili are not prerequisites for human virulence in all enterotoxigenic strains of E. coli. Seven enterotoxigenic and three enteropathogenic strains of E. coli that have been used in volunteer challenge studies were tested for CFA/I, CFA/II, and type 1 somatic pili after culture on solid agar and in broth. Six of the seven enterotoxigenic and two of the three enteropathogenic strains caused diarrhea in humans. Of these eight virulent strains, one produced CFA/I, and one had CFA/II. Threre remained four enterotoxigenic and two enteropathogenic strains that unequivocally caused diarrhea while lacking CFA/I or CFA/II. In such strains other organelles or surface properties must be operative to promote adhesion to and colonization of small intestinal mucosa. CFA/I and CFA/II are not prerequisites of virulence for all E. coli strains that cause diarrhea in humans.

Adult↗

Selective vs. nonselective media and direct plating vs. enrichment technique in isolation of Vibrio cholerae: recommendations for clinical laboratories.

The occurrence of human cholera along the Gulf of Mexico and the isolation of Vibrio cholerae O1 from the Gulf and Chesapeake Bay make it imperative that microbiology laboratories along estuaries develop the capabilities to culture for these pathogens. In attempts to devise a simplified but efficient culture procedure, a selective medium, thiosulfate-citrate-bile salts-sucrose (TCBS) agar, was compared with a nonselective medium, gelatin agar (GA), and the utility of enrichment was examined. TCBS agar detected 99% of the stools found to be positive by all techniques combined, whereas GA identified only 80%. Of acute diarrheal stools, 96% were positive on direct plating, whereas only 66% of formed stools containing V. cholerae were detected by direct plating. Stools from patients with acute diarrhea can be plated directly into TCBS agar alone; stools from persons shedding low numbers of organisms (such as contacts, carriers, or patients receiving antibiotics) should be incubated first in an enrichment broth and then on TCBS agar.

Bacteriological Techniques↗

Lack of person-to-person transmission of enterotoxigenic Escherichia coli despite close contact.

The scanty epidemiologic evidence available suggests that enterotoxigenic Escherichia coli (ETEC) are usually spread by contaminated food and water vehicles; little is known of the risk of secondary spread by contact transmission. Studies carried out in a 22-bed isolation Ward at the U. of Maryland Hospital gave the opportunity to determine whether individuals excreting ETEC, with and without diarrhea, would transmit the pathogen to controls living in close contact. In one combined study, seven volunteers who had ingested 10(8) virulent ETEC (strain H10407), were housed day and night for two weeks with eight other volunterrs participating in an intranasal attenuated influenza vaccine study. In a second study, four persons ingesting 10(8) ETEC (strain 214-4) lived with 13 who were inoculated with intranasal influenza vaccine. The individuals in the E. coli and influenza groups were randomly mixed in bedrooms and shared bathrooms, dining and recreation areas of the ward. Seven persons who ingested ETEC developed diarrhea; all 11 excreted the pathogen (10(7)-10(9) organisms/gm or ml of stool), and 10 had significant rises in anti-O or antitoxin antibody. In contrast, no influenza vaccinees, despite close sharing of facilities, developed diarrhea, excreted ETEC or had rises in antibody to E. coli antigens. These data suggest that ETEC are not readily transmitted to healthy adults by direct person-to-person contact. Precautions to prevent contamination of shared food sources would appear to be the most rational intervention to avoid secondary cases of ETEC diarrhea.

Adolescent↗

Evaluation of influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

Adult↗

Genetic susceptibility to cholera.

In the course of studies of immunity to experimental cholera in man, 10(5) or 10(6) Vibrio cholerae were given to 66 college students and other community volunteers under quarantine in an isolation ward. HLA antigen and blood group determinations were carried out to test the hypothesis that severity of clinical cholera is dependent in part upon genetically-determined host susceptibility. Fifty-five volunteers developed diarrhoea; 38 had mild illness and 17 had severe cholera (stool volume greater than or equal to 5.0 litres). HLA antigens were found in similar frequency in volunteers with severe, mild or no diarrhoea; antigen A1, A2, A3 and B7 were most common. Blood group O, however, was found in 64% of persons with severe cholera versus 36-38% of volunteers with mild or absent illness. Thus, while no correlation was found between HLA type and severity of cholera, these results do support the claims of other investigators that blood group O is found more frequently in patients with severe cholera than in the normal population.

ABO Blood-Group System↗