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Biomedical subjects

J F Bale

Publications and source records attributed to J F Bale.

At least 55 records · Page 3Linked to original sources

The occupational risk of cytomegalovirus infection among day-care providers.

We prospectively studied day-care providers at six day-care centers in south-eastern Iowa to determine their occupational risk for primary cytomegalovirus infection and to define epidemiologic risk factors. Ninety-six (38%) of 252 day-care providers were seropositive for cytomegalovirus by latex agglutination at entry into the study. Among 82 seronegative providers available for follow-up, seven seroconversions occurred at only two of the six participating centers, yielding an annualized seroconversion rate of 7.9%. Median time to seroconversion among these providers was 13 months. Using Kaplan-Meier estimates of risk, we determined that the overall risk of seroconversion among providers at various centers ranged from 0% to 22% by 12 months and from 0% to 40% by 16 months. Risk of cytomegalovirus acquisition by providers was independent of race, age, education, the presence of a child at home, or caring for children younger than 2 or 3 years in the day-care center. However, the risk of seroconversion among day-care providers appeared to parallel rates of cytomegalovirus excretion and acquisition among children at each center.

Adult↗

Expression of a human cytomegalovirus glycoprotein multigene family.

The short unique component of the human cytomegalovirus genome contains several multigene families, one of which encodes glycoproteins in the virion envelope glycoprotein complex gcII (4). The HXLF glycoprotein multigene family was subcloned into pSP6 or pGEM transcription vectors. Gene products were expressed from the six open reading frames (designated HXLF1 through HXLF6) via in vitro transcription and translation in rabbit reticulocyte lysates. The HXLF gene products were analyzed by immunoprecipitation using virus-specific monoclonal antibodies or human convalescent-phase antisera. One of the anti-gcII monoclonal antibodies, designated 9E10, specifically immunoprecipitated each of the HXLF gene products. Four of the HXLF gene products were immunoprecipitated by human convalescent-phase antisera, but not preimmune sera. Southern blot analysis of genomic DNAs purified from 12 different virus isolates indicated the HXLF multigene family is present in wild-type strains of human cytomegalovirus.

Blotting, Southern↗

Large postnatally acquired porencephalic cysts: unexpected developmental outcomes.

To determine the neurodevelopmental outcome for infants with posthemorrhagic intraparenchymal cysts, we reviewed retrospectively clinical, ultrasonographic, and developmental features in 16 affected children. At a mean follow-up age of 33 months, five subjects had normal cognitive outcomes (developmental quotient [DQ] or IQ greater than 83), nine had borderline to mild deficits (DQ or IQ, 52 to 83), but only three had moderate to severe deficits (DQ or IQ less than 52). Spastic cerebral palsy was present in 13 (81%); only one child (6%) had a chronic seizure disorder requiring medication. Cognitively normal children were less likely to have had neonatal seizures (P less than .05) and tended to have more localized cysts. Otherwise, we found no relationship between outcome and neonatal clinical or laboratory findings. Overall, these results suggest that although motor deficits are common in infants with severe intraventricular hemorrhage and porencephalic cysts, cognitive outcomes may be more favorable than has been suspected previously.

Brain Damage, Chronic↗

Brain tumors occurring before 1 year of age: a retrospective reviews of 22 cases in an 11-year period (1977-1987).

Congenital brain tumors have been reported infrequently and their management remains ill defined. An 11-year review (1977-1987) of all children with brain tumors with the onset of symptoms before 1 year of age was completed. Twenty-two children with the following histological diagnoses were treated: astrocytoma (7 patients), primitive neuroectodermal tumor (6 patients), papilloma or carcinoma of the choroid plexus (3 patients), malignant teratoma (2 patients), dermoid tumor (2 patients), embryonal rhabdomyosarcoma (1 patient), and chloroma (1 patient). Fifteen tumors were supratentorial in location, and 7 were infratentorial. Initial symptoms were hydrocephalus (32%), focal neurological deficit (23%), asymptomatic increase in head circumference (18%), failure to thrive (14%), and seizures (4.5%). The goal of treatment was a radical excision when possible, with primary chemotherapy in the last 6 years of the review period. Radiation therapy was the adjunct to surgery in the initial 5-year period. All patients with papillomas of the choroid plexus and dermoid lesions underwent a total resection with no recurrence. All 7 astrocytomas were supratentorial, with 6 occurring in the diencephalon. Five of the seven patients with astrocytomas survived more than 5 years. The 6 primitive neuroectodermal tumors were located equally between the supra- and infratentorial spaces. Four of the 6 infants with these tumors received chemotherapy (2 received chemotherapy alone; 2 received chemotherapy and radiation therapy) and are tumor free 2 to 9 years later. A fifth child received radiation therapy alone early in the series and survived only 4 months. The family of the other child refused adjunctive treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗

Murine cytomegalovirus ocular infection in immunocompetent and cyclophosphamide-treated mice. Potentiation of ocular infection by cyclophosphamide.

Conventional virologic and in situ nucleic acid hybridization methods were used to study immunocompetent and immunosuppressed 3-week old BALB/c mice inoculated intravitreally with 10(4) plaque-forming units (pfu) of murine cytomegalovirus (MCMV). Immunocompetent mice experienced a self-limited ocular infection with peak virus titers of 10(3.5) pfu/ml in the retina-choroid fraction on day 4 of infection. Using biotinylated MCMV DNA probes, MCMV DNA was detected in cells of the iris, ciliary body, and rarely, the retina or choroid on days 4 and 7 of infection. With few exceptions, retinal architecture was preserved. By contrast, mice immunosuppressed with cyclophosphamide (200 mg/kg on day 0 and 100 mg/kg on days 5 and 11 after MCMV inoculation) had progressive ocular infection that culminated in a necrotizing retinitis. Virus titers in the retina-choroid fraction rose progressively (nearly 10(5) pfu/ml in cyclophosphamide-treated mice on day 11 versus 10(1.5) pfu/ml in immunocompetent mice). The MCMV DNA was detected in the iris and ciliary body of the immunosuppressed mice on days 4 and 7 and in the retina, on days 7, 11, and 14. On day 14 abundant MCMV DNA was found in most retinal layers, and extensive retinal necrosis was observed. These studies indicate that immunosuppression with cyclophosphamide potentiates MCMV ocular disease in mice, a finding analogous to CMV retinitis in immunosuppressed humans.

Animals↗

The epidemiology of cytomegalovirus infection among patients with burns.

To determine the epidemiology of cytomegalovirus (CMV) infections among patients with burns, we prospectively studied 120 burn patients admitted to the University of Iowa Burn Center over a two-and-one-half year period. At the time of their admission, 44% of the patients had serologic evidence of prior CMV infection. Among 44 seropositive patients, 23 (52%) had four-fold or greater rises in CMV antibody titers. These patients had more severe burns (mean body surface area burn [BSAB] 26.8%) than those who did not exhibit titer rises (mean BSAB 16.2%, p = .04). Among 43 seronegative patients observed for at least 65 days after discharge from the center, eight (18.6%) seroconverted. Patients who seroconverted had longer hospital stays (p = .03), trends toward more severe burns (p = .08) and a younger age (p = .15) than patients who remained seronegative. Despite frequent serologic evidence of CMV infection, CMV did not contribute, either directly or indirectly, to the morbidity or mortality of burns in these patients.

Adolescent↗

Outcome in children with symptomatic congenital cytomegalovirus infection.

To determine factors that are associated with adverse developmental outcome after congenital cytomegalovirus infection, we reviewed the clinical, laboratory, and radiographic findings in 18 children with symptomatic congenital cytomegalovirus infections. When children with adverse outcomes (intelligence or developmental quotients of 50 or less, n = 10) were compared with children with mild sequelae (intelligence or developmental quotients of 70 or higher, n = 8), we found no relationship between developmental outcome and neonatal clinical features (birth weight, jaundice, hepatomegaly, splenomegaly, or petechiae). With the possible exception of intracranial calcifications, no single clinical or radiographic feature was associated with a specific developmental outcome. However, children who had postnatal microcephaly, postnatal seizures, and an abnormal central nervous system imaging study were more likely to have severe developmental sequelae.

Adolescent↗

The pathogenesis of murine cytomegalovirus ocular infection. Anterior chamber inoculation.

To investigate the pathogenesis of ocular cytomegalovirus infections, 3-week-old BALB/c mice were inoculated with 10(4) plaque-forming units of murine cytomegalovirus (MCMV) by the right anterior chamber and studied sequentially with the use of virus assays and in situ nucleic acid hybridization methods. During acute infection, MCMV was recovered from the right vitreous, lens, cornea, retina/choroid, and optic nerve. Titers of MCMV exceeded 10(3) per ml of homogenate on days 4 and 7 after inoculation. With the use of biotinylated MCMV DNA probes, MCMV nucleic acids were detected in and adjacent to cells of the iris and ciliary body and occasionally within inflammatory lesions of the cornea. During chronic infection, MCMV was recovered, with the use of co-cultivation or explant methods, from ocular tissues of occasional mice inoculated with MCMV 1 yr earlier. Infectious MCMV was also recovered from the ocular homogenates of a group of mice immunosuppressed with antilymphocyte serum and cortisone. These studies indicate that cells of the uveal tract are permissive for MCMV and suggest that intrinsic persistence or latency of cytomegalovirus in ocular tissues could contribute to the pathogenesis of ocular infections in immunosuppressed hosts.

Acute Disease↗

Detection of murine cytomegalovirus DNA in circulating leukocytes harvested during acute infection of mice.

We used virus assay and in situ hybridization with a cloned fragment of the murine cytomegalovirus (MCMV) genome to study MCMV infection of circulating leukocytes harvested from 3-week-old BALB/c, C57BL/6, and C3H mice infected with MCMV intraperitoneally. Infectious virus or MCMV DNA was detected in leukocytes on days 1 through 21 of infection in BALB/c mice and on days 3 through 7 in C57BL/6 mice. On days 5 and 7, MCMV DNA or infectious virus was detected in the leukocytes of 17 (94%) of 18 BALB/c mice and 10 (59%) of 17 C57BL/6 mice. In both strains infection peaked on days 5 and 7, when as many as 0.01 to 0.1% of the circulating leukocytes contained MCMV DNA. In C3H mice, however, infectious virus was rarely recovered from leukocyte fractions and MCMV DNA was detected in the circulating leukocytes of only one animal. Circulating leukocytes may have an important role in the dissemination of CMV infections in susceptible hosts.

Acute Disease↗

Selective nontreatment of neurologically impaired neonates.

We are convinced that a best-interests approach is the best approach to take in making decisions to treat or not to treat disabled young infants. Such an approach acknowledges that there are some medical conditions that are so severe that efforts to sustain the lives of infants having the conditions cannot be said to be in the best interests of those infants. By paying attention to the variables that compose the best-interests approach, decision makers can arrive at decisions not to sustain life that are more easily justifiable than with any other approach.

Ethics, Medical↗

The natural history of acquired cytomegalovirus infection among children in group day care.

We studied the natural history of cytomegalovirus (CMV) excretion among 79 children in a single day-care center over a 2 1/2-year period. During the study interval, 28 children (35%) excreted CMV in their urine, or saliva, or both. The CMV acquisition rate among children who were initially culture negative was 12.6% per year. In such children, CMV excretion began 11 to 59 months after entry into day care. The duration of CMV excretion varied from 3.0 to 28.4 months, with a mean of 13.0 +/- 9.1 months for urine and 7.0 +/- 2.7 months for saliva. The quantity of CMV in saliva or urine was highest during the first three months of excretion, as high as 10(5) 50% tissue culture infectious dose per milliliter. Children excreting CMV entered day care at a younger age (mean, 5.3 +/- 8.5 months for excretors vs 12.7 +/- 14.8 months for nonexcretors) and spent more hours in day care per week than the nonexcretors (mean, 41.8 +/- 9.0 h/wk for excretors vs 36.1 +/- 10.9 h/wk for nonexcretors).

Child↗

Murine cytomegalovirus genomic material in marrow cells: relation to altered leukocyte counts during sublethal infection of mice.

To investigate infection of hematopoietic cells by murine cytomegalovirus (MCMV), we used in situ hybridization to detect MCMV genomic material in marrow cells during sublethal infection of three-week-old mice. MCMV genomic material was present in femoral marrow cells on days 3, 5, 7, and 14, and detection of MCMV genomes correlated strongly with recovery of infectious virus. Peak infection occurred on day 5, when 0.003%-0.185% of the marrow cells contained MCMV genomic material. At peak infection, MCMV genomic material was observed predominantly in marrow mononuclear cells. Coincident with marrow infection, mice experienced significant leukopenia, whereas cessation of MCMV replication in marrow cells was associated with leukocytosis and restoration of normal peripheral blood leukocyte counts.

Animals↗

Murine cytomegalovirus infection of reaggregate cultures of fetal mouse brain.

We used cultures of reaggregate embryonic mouse brain cells to study murine cytomegalovirus (MCMV) infection of neural tissues. After 21 to 28 days in culture, aggregates were infected with MCMV and studied sequentially for 14 days using virus assay, electron microscopy and indirect immunofluorescence. Infectious virus could be recovered from aggregate cultures beginning three days after infection, and peak virus titers were observed on day 7 in aggregate tissues and on day 14 in culture fluids. By transmission electron microscopy, intranuclear viral nucleocapsids were identified in neural cells at the periphery of the aggregates on day 3. Infection then spread centripetally into aggregate tissues so that by day 14 the majority of neural cells contained intranuclear inclusions, numerous nucleocapsids, and mature virus particles. Virion production in neural cells was the result of a sequence of events that included budding of nucleocapsids from the nucleus and envelopment of cytoplasmic virus particles by membranes of the Golgi apparatus. These studies indicate that MCMV infection of murine brain aggregate cultures is a potentially useful in vitro system for the study of CMV infections of neural tissue.

Animals↗

Magnetic resonance imaging of the brain in childhood herpesvirus infections.

We used magnetic resonance imaging (MRI) to evaluate nine children with neurologic disorders caused by infections with members of the herpesvirus family. MRI studies were abnormal in eight children and demonstrated a wide range of central nervous system lesions, including cystic encephalomalacia, ventricular enlargement, cerebral atrophy and focal parenchymal lesions. When compared with conventional computed tomographic scanning, MRI was more sensitive in detecting abnormalities of white matter and in defining the extent of parenchymal lesions. These studies indicate that MRI scans are highly useful in children with herpesvirus infections involving the central nervous system.

Brain↗

Risk of cytomegalovirus infection among educators and health care personnel serving disabled children.

To determine the risk of cytomegalovirus (CMV) infection for personnel who provide services to young disabled children, we studied the prevalence of CMV infection among such children and determined the seroconversion rate among exposed personnel. The prevalence of CMV excretion was 9.8% among children aged 0 to 5 years in a University-based outpatient program vs. 3.3% in 3- to 5-year-old children attending community-based preschools. Initial serologic studies of personnel demonstrated no differences in CMV seropositivity rates among staff with occupational child contact vs. staff without such contact (40% (40 of 99) vs. 34% (26 of 77] (P = 0.37). However, 21 of the 31 personnel 40 years and older who had occupational child contact were seropositive vs. 10 of 26 personnel of comparable age who had no occupational child contact (P = 0.026). During a 1-year follow-up, 2 of 86 (2.3%) susceptible personnel seroconverted. Rates were 4.4% (2 of 45) among staff with occupational child contact vs. no seroconversions (0 of 41) for those without (P = 0.27). These results indicate that the risk of CMV infection for personnel who work with disabled children is low. However, we cannot exclude the possibility that there may be a small cumulative risk of CMV infection that may exceed that of adults who do not have occupational contact with children.

Adult↗

Cytomegalovirus infection in a healthy adult associated with recurrent branch retinal artery occlusion.

The authors report a 16-year-old healthy male who developed branch retinal artery occlusions sequentially in both eyes. A few vitreous cells and retinal vasculitis were associated findings. A complete work-up of the patient for an etiology for the occlusions failed to show any possible embolic source. Spinal fluid studies showed increased protein content and lymphocytic pleocytosis. Serologic studies showed a tenfold rise in the cytomegalovirus (CMV) titer. Other viral titers did not rise. CMV could not be cultured from the patient's body. The case represents a possible cause of the so-called idiopathic recurrent branch retinal artery occlusion syndrome.

Acute Disease↗