Henry G. Cramblett

THE ETIOLOGY OF INFECTIOUS DIARRHEA IN INFANCY, WITH SPECIAL REFERENCE TO ENTEROPATHOGENIC E. COLI

Bacterial pathogens including Salmonella, Shigella, and enteropathogenic Escherichia coli (EPEC) have been accepted as causative agents of gastroenteritis for many years. These pathogens, however, have not been recovered from more than 38% of infants less than two :rears of age with diarrhea in any perennial study conducted in North America and Europe since 1955 (TABLE 1 ) . The calculated mean isolation rate of pathogenic bacteria recovered from infants less than two years of age with diarrhea as reported in the above studies is 18.5% (TABLE 1) . This leaves a mean of at least 81.5% of all moderate or severe cases of gastroenteritis unexplained bacteriologically. The assumption has been that the majority of the cases of gastroenteritis in infancy and early childhood is due to viral agents. However, proof of the etiologic association of viruses with gastroenteritis has been difficult to establish and studies to date have not accounted for a large percentage of the cases of gastroenteritis on this basis. As early as 1931, McLean speculated on the viral origin of winter epidemics of vomiting and abdominal pain among children in the United States. Seven years later, an epidemic of diarrhea in California was ascribed for the first time to viral agents.’ From 1943 on, various groups of investigators 3-6 attempted to produce diarrhea in experimental animals by exposure to bacteria-free filtrates of stool suspensions from patients with diarrhea. The experiments were successful only in calves and cats. Human volunteer experiments with such filtrates carried out in the 1940’s did not yield uniform results. By the oral route, gastroenteritis was produced in 50% of Japanese Reimann * reported a gastroenteritis attack rate of 53 % among volunteers who had inhaled filtrates of garglings or stools from diarrhea patients, as compared with an incidence of 9% of naturally occurring gastroenteritis in a matched control group. In one study conducted in New York,O in spite of the absence of demonstrable pathogenic bacteria. only the ingestion of unfiltered throat wayhings and the ingestion of filtered feces from patients with gastroenteritis resulted in a similar illness in volunteers. The inoculation of bacteria-free filtrates of throat and anal specimens from infants with stomatitis and diarrhea into the corneas of rabbits was an ingenious anticipation of modern cell culture techniques.lO.

5-Iodo-2′-deoxyuridine in neonatal herpesvirus hominis encephalitis†

Neonatal encephalitis due to herpesvirus hominis is associated with a high incidence of morbidity and mortality. This report describes an infant with encephalitis due to herpesvirus hominis which was treated with 5-iodo-2′-deoxyuridine. The infant received a total dose of 410 mg. per kilogram of body weight over a 7 day period. Evidence of transient bone marrow depression was observed. Although subsequent observations revealed the infant to be improved by the chemotherapeutic regimen, it was apparent that she had suffered irreversible brain damage prior to therapy.

Behavioral sequelae of California encephalitis virus infection in children.

An extensive psychological study was made on 14 children after their hospitalisation for California Encephalitis Virus infection. The behavioral examination was made between 7 months and 2 years after the initial hospital admittance and on routine clinical examination the children appeared to be functioning normally. This is in sharp contrast with the picture they presented when in hospital, with high fever, seizures and severe headaches, and when some were comatose or semi‐comatose.

Antibody titers to polioviruses in patients ten years after immunization with sabin vaccine.

Summary Serum neutralizing antibody titers to poliovirus Types I, II, and III were performed on 45 young adults 10 years after immunization with trivalent oral poliovirus vaccine and compared to previous antibody titers. Eighty-four per cent of the participants had antibody titers to all three types of poliovirus in a dilution of 1:3 or greater 10 years after immunization.

Comparison of efficacy of phenoxymethylpenicillin and buffered penicillin G in treatment of streptococcal pharyngitis

Summary Seventy-seven children with streptococcalpharyngitis were given a 7 day course of therapy using alternately either 375 mg. per day of phenoxymethyl penicillin or a similar dose of buffered penicillin G orally. From data collected during the study, it would appear the two preparations can be considered equally effective in the treatment of streptococcal pharyngitis. However, the combined high incidence (69 per cent) of bacteriologic recurrences and/or reinfections within a three month period indicates the inadequacy of a 7 day period of treatment for streptococcal pharyngitis.

Cephalexin: Treatment of streptococcal pharyngitis

Twenty-five children with group A streptococcal pharyngitis were treated withcephalexin, an acid stable semisynthetic derivative of cephalosporin C. All patients responded clinically. Bacteriologically, two patients had recurrence of the group A streptococci following the cessation of therapy. Cephalexin can be considered as effective alternate therapy to penicillin in individuals who are allergic to the latter.

Treatment of herpesvirus encephalitis with iododeoxyuridine

Three children developed severe, rapidly progressive encephalitis, with the clinical picture of a mass lesion in the brain. In each patient the electroencephalogram, brain scans, and carotid angiograms revealed findings consistent with focal disease. Diagnosis was proved by recovery of herpesvirus from biopsy specimens of brain tissue. The outcome of treatment with iododeoxyuridine appears to be related to the duration of illness. A 3-year-old, girl, ill for five days, recovered with permanent sequelae. A 14-year-old boy, ill for only two days, recovered completely. A 9-year-old boy, ill for nine days, remained comatose until death.

Retrospective study for possible kanamycin ototoxicity among neonatal infants

Summary Twenty children who received kanamycin therapy during the neonatal period and 7 control children who were treated with other antimicrobial agents during the first month of life had audiometric and clinical evaluation at ages ranging from 1 to 4 years. From the kanamycin study group, 14 had P.T. audiometric testing (by air and bone conduction), and 6 had clinical evaluation of hearing. There was no evidence of sensorineural hearing loss which might be attributed to kanamycin ototoxicity.

Thymidine Kinase Activity in Cerebrospinal Fluid of Rabbits with Herpesvirus hominis Encephalitis

Extract: The rabbit model of Herpesvirus hominis (HVH) encephalitis was utilized to determine whether thymidine (TdR) kinase (EC. 2.7.1.2.1), an early enzyme in the HVH replicative cycle, is present in the cerebrospinal fluid (CSF) of rabbits with HVH encephalitis. The mean TdR kinase activity in CSF from infected rabbits was 2.30 ± 1.69 pmol product/120 min/100 μl CSF, while the mean TdR kinase activity of uninfected CSF was 0.34 ± 0.25. The enzyme appeared to be cell associated since the TdR kinase activity in the sedimented cell suspension was 5.08 ± 2.93 (seven values) while the supernatant activity was 0.14 ± 0.31 (seven values). To allow a comparison of TdR kinase from infected rabbit CSF with HVH and rabbit mononuclear cell TdR kinase, the mean ratio of TdR kinase activity at pH 6.0/pH 8.0 was calculated. The mean ratio of thymidine kinase activity, pH 6.0/pH 8.0, for infected rabbit CSF is intermediate between the ratio for HVH TdR kinase (P < 0.001) and rabbit mononuclear cell TdR kinase (P < 0.05).Speculation: The presence of TdR kinase in CSF from HVH-infected rabbits with biochemical properties intermediate between HVH and mononuclear cell TdR kinase suggests that abortive HVH infection occurs in CSF mononuclear cells during the course of HVH encephalitis.

A Longitudinal Study of Children with Learning Disabilities Subsequent to Hospitalization for Viral Encephalitis—Part II:

California encephalitic virus is a known etiology underlying an unknown but possible residual cerebral pathology. The study of such a specific viral encephalitis assists us to establish a scientific data base between the clinical findings and the behavioral deficits that underlie academic achievement. More importantly, the children with behavioral difficulties appear normal (and are in language function) but they neither outgrow a developing underachievement deficit related to perceptual problems nor are the perceptual problems altered by regular classroom instruction.