St. Louis encephalitis and the substantia nigra: MR imaging evaluation.

Neuroimaging findings in cases of St. Louis encephalitis (StLE) have yet to be reported despite the relatively high frequency of this entity. An epidemic permitted the documentation of isolated hyperintensity of the substantia nigra on T2-weighted images in two patients with StLE. This distribution of MR imaging abnormality in cases of StLE mirrors the reports presented in the literature that implicate the substantia nigra as peculiarly susceptible to the StLE virus. Isolated lesions of the substantia nigra revealed by T2-weighted imaging should suggest the possibility of StLE.

Adaptation of human enteric coronavirus to growth in cell lines.

BACKGROUND: The existence of human enteric coronavirus (HEC) has been debated since its first description in stool by electron microscopy (EM) in 1975. Needed to resolve the issue is its cultivation in readily available cell lines. OBJECTIVES: To grow HEC in cell lines. To describe its characteristics and to differentiate it from other human and animal coronaviruses. STUDY DESIGN: Originally grown in human fetal intestinal organ culture, HEC was passed in J774 cells (a mouse macrophage cell line) and C6/36 cells (a mosquito cell line). Its cytopathic effect (CPE) and pattern of immunofluorescence were described. Its appearance was ascertained by negative staining and transmission EM. Its structural proteins were delineated by polyacrylamide gel electrophoresis (PAGE) and Western blotting (WB). The antigenic character of the virus was determined by immunofluorescence and WB. Agglutination with mouse erythrocytes was performed. RESULTS: In J774 cells, HEC induced the formation of giant cells and small syncytia. Immunofluorescence in both J774 and C6/36 cells was limited to the cytoplasm. Studies with transmission EM revealed the virus to have the typical appearance of other coronaviruses, to be 80-120 nm in diameter, and to bud into cysternae of the endoplasmic reticulum. By PAGE and WB, its major protein has an average molecular weight (MW) of 41 kilodaltons (kDa). Two other proteins had MWs of 190 and 24 kDa. By immunofluorescence and WB, HEC is antigenically distinct from human coronaviruses 0C43 and 229E and mouse hepatitis virus (A59 strain). Preparations of HEC did not agglutinate mouse erythrocytes. CONCLUSION: We conclude that HEC is a human coronavirus that is antigenically unrelated to 0C43 and 229E viruses. Growth of HEC in readily available cell lines should aid in elucidating its role as a pathogen in human diarrheal illnesses.

Case report: transverse myelitis associated with Epstein-Barr virus infection.

Transverse myelitis is a rare complication of Epstein-Barr virus (EBV) infection. This article describes a case of a previously healthy patient with a subacute transverse myelopathy. The cerebrospinal fluid showed lymphocytic pleocytosis and protein elevation. A magnetic resonance imaging scan demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of transverse myelitis. The patient was treated with high-dose corticosteroids and had a rapid improvement. Serologic studies for other viruses were negative; antibody tests indicated acute EBV infection. It is thought this represents a case of transverse myelitis associated with acute EBV infection. Although a few similar patients have been reported previously, this case is the first where EBV serology suggested the etiology at the time of diagnosis, when EBV antibody titers and polymerase-chain reaction for EBV DNA in the cerebrospinal fluid were performed, and when a magnetic resonance imaging scan was used for diagnosis and follow-up.

Infections of the central nervous system.

Infections of the central nervous system are common, serious medical conditions. One hundred consecutive adult cases with purulent meningitis of known etiology encountered by the Medical Service at Parkland Memorial Hospital were reviewed. Streptococcus pneumoniae was the most common pathogen (56 cases), followed by Neisseria meningitidis (16 cases) and Listeria monocytogenes (seven cases). Hemophilus influenzae, Staphylococcus aureus, and streptococci each accounted for five cases. An additional 15 patients had purulent meningitis with a pathogen being isolated. Twenty five purulent meningitis cases of known etiology after trauma or neurosurgery were reviewed. Staphylococcus aureus (five cases), Staphylococcus epidermidis (four cases), and gram negative bacilli (14 cases) were the most common pathogens. Review of intracranial suppurative infections demonstrated advances in microbiology, antibiotic therapy, and imaging, leading to improvements in therapy. Subdural empyema continues to be a difficult diagnosis to make and apparently is related to the anatomic pathology of the infectious process. To illustrate salient features about granulomatous meningitis and encephalitis, cases of tuberculous meningitis, herpes simplex encephalitis, St. Louis encephalitis, and encephalitis of undetermined etiology are presented and discussed.

Relationship between cytomegalovirus and colonization of the oropharynx by gram-negative bacilli following renal transplantation.

Numerous investigators have reported an increased incidence of pneumonia caused by Gram-negative bacilli and other secondary pathogens in transplant recipients infected by cytomegalovirus (CMV). To determine if CMV infections are related to colonization of the upper respiratory tract by Gram-negative bacilli, we examined prospectively 22 renal transplant recipients with sequential bacteriological, virological and biochemical examinations performed just prior to and at various times after transplantation. Only 11% of subjects had Gram-negative bacilli isolated from gargle specimens prior to transplantation, as compared to 54% after transplantation. More importantly, after transplantation, subjects with active CMV infections were more likely to have prolonged oropharyngeal carriage of Gram-negative bacilli than subjects without CMV infections (36% v. 25%). During active CMV infections, the rate at which Gram-negative bacilli were isolated from gargle specimens rose from 28 to 47%. During culture-positive CMV infections, the isolation rate reached 57% and was significantly different from that of CMV-negative samples (P less than 0.01). The increased rate of Gram-negative bacillary isolation from gargle specimens during CMV infections was not a function of type of immunosuppressive agents used, rejection episodes, antibiotic administration, concomitant hepatitis B, Epstein-Barr (EBV) virus, or herpes simplex virus infections, or alterations in salivary fibronectin concentrations.

Pneumonia caused by Mycoplasma pneumoniae infection.

The features characterizing pneumonia due to Mycoplasma pneumoniae are described. Typical cases, along with chest radiographs of laboratory-documented cases, are presented.

Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis.

Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process.

Tuberculosis epidemic among hospital personnel.

Six employees of the emergency department at Parkland Memorial Hospital developed active tuberculosis in 1983-1984. Five of the cases occurred four to 12 months after exposure to the index case, a patient with severe cavitary tuberculosis seen in the emergency department in April 1983. One resident physician developed cavitary disease after exposure to this patient. An additional employee case may have resulted from transmission from one of the initial employee cases. One immunocompromised patient may have acquired tuberculosis as a result of exposure to the index case. In addition, the tuberculin skin tests of at least 47 employees exposed to the index case converted from negative to positive. Of 112 previously tuberculin-negative emergency department employees who were tested in October 1983, 16 developed positive skin tests, including the 5 employees with active disease. Fifteen of these new positives had worked on April 7, 1983, while the index case was in the emergency department (X2 = 20.6, P less than 0.001). Factors related to the genesis of the epidemic included the disease characteristics in the index case and the recirculation of air in the emergency department. This investigation indicates that city-county hospital emergency department employees should be screened at least twice a year for evidence of tuberculosis and that the employee health services of such hospitals should regard the surveillance of tuberculosis infection among personnel at a high-priority level.

Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections.

Thirty-seven patients with methicillin-resistant Staphylococcus aureus infections and/or colonization were treated with oral ciprofloxacin (750 mg twice a day). Clinical cure or improvement of infections occurred in 91% of the patients, and bacteriologic cure occurred in 60%. Ciprofloxacin therapy suppressed methicillin-resistant S. aureus colonization in 55% of the patients. Ciprofloxacin-resistant strains emerged in 6 of the 37 patients.

Applanation tonometer tip sterilization for adenovirus type 8.

Eighty-nine ophthalmologists in the Dallas-Fort Worth area were surveyed to find the methods used to sterilize applanation tonometer tips. Sixteen different methods were in use, with the most popular being alcohol wipes (26%) and diluted sodium hypochlorite soak (23%). Six of the most frequently used sterilization techniques were evaluated for removal of type 8 adenovirus applied to sterile tonometer tips. Adenovirus was removed or inactivated from applanation tonometer tip surfaces by using one of the following techniques: soaking inoculated tips for 15 minutes in diluted sodium hypochlorite (1:10 household bleach), 3% hydrogen peroxide, or 70% isopropyl alcohol; or wiping with alcohol "prep pads", 1:1000 merthiolate, or dry tissues.

Effect of human sex hormones on cytomegalovirus growth and Fc receptor expression.

Pretreatment of human embryonic lung cells with estradiol, progesterone, and testosterone was found to have little effect on cytomegalovirus (CMV) replication in vitro. The three hormones in combination delayed the expression of CMV-induced Fc receptors in this cell line. However, similar effects on Fc receptor expression were observed at both first trimester and third trimester concentrations of the hormones. CMV grew well in a primary cell line derived from endometrial stromal cells. However, in this female genital line, as in the (male somatic) human embryonic lung cells, estradiol, progesterone, and testosterone had little effect on CMV replication. CMV-induced Fc receptors could not be demonstrated in endometrial stromal cells. These results suggest that the variation in cervical CMV excretion during gestation is mediated by some mechanism other than a direct effect of sex hormones on viral replication or Fc receptor expression.

Pneumonias in adults due to mycoplasma, chlamydiae, and viruses.

Pneumonias in adults due to mycoplasma, chlamydiae, and viruses are a common clinical problem. These microorganisms contribute to the etiologies in 6-35% of all cases of pneumonia and are the sole pathogens in 1-17% of hospitalized cases. Important trends and developments in the field include the emergence of a Chlamydia psittaci strain (TWAR) that is passaged from human to human, causes a mycoplasma-like illness, and that is relatively resistant to erythromycin, the recognition of respiratory syncytial virus as a pathogen in nursing home outbreaks and in immunosuppressed adults, the continuing high lethality of fully developed influenza pneumonia, the efficacy of acyclovir and adenine arabinoside in limiting the complications of varicella-zoster virus infections, and the increasing frequency of pneumonia caused by cytomegalovirus and the severity of this disorder in highly immunosuppressed patients. Developments in the rapid diagnosis and therapy of respiratory syncytial virus infections with an aerosolized antiviral drug in children may pave the way for comparable advances in difficult pneumonias in adult patients.

Possible association of mycoplasma and viral respiratory infections with bacterial meningitis.

The presence of viral infection was evaluated in 160 children older than three months with bacterial meningitis who were admitted to Children's Medical Center or Parkland Memorial Hospital, Dallas, TX, between October 1979 and March 1982. Results were compared with a single serologic specimen in 138 children without meningitis. A recent history of upper respiratory infection was obtained from 60% of patients, including 10/13 with pneumococcal, 9/16 with meningococcal, and 77/131 with Haemophilus influenzae meningitis. Viral infection was documented by serologic response (23.8%) or viral isolation (13.2%) in 63/160 (40%) of patients with meningitis. There were 23 positive cultures (one patient with both adenovirus and respiratory syncytial virus). Picornaviruses, including two rhinoviruses, were isolated from six of the 24 subjects without meningitis who had viral cultures. There were 69 serologic conversions in meningitis patients, with 12 patients converting to two organisms and four patients converting to three organisms. Viral diagnoses included: adenovirus, 32 children; respiratory syncytial virus, 14; influenza A, 8; influenza B, 4; parainfluenza (1, 2, and 3), 12; picornaviruses, 9; herpes simplex virus, 1; and cytomegalovirus, 1. Additionally, 6/15 seroconverted to Mycoplasma pneumoniae. The acute geometric mean serum antibody titers of meningitis patients were lower than those of the comparison group for adenovirus (3.5 vs. 6.6, p less than or equal to 0.001) and influenza B (1.2 vs. 1.6, p less than or equal to 0.05). Twenty nine of 131 patients with H. influenzae had evidence of recent adenovirus infection. Primary infection with adenoviruses and possibly influenza B or mycoplasma precedes development of bacterial meningitis in some patients and may be a predisposing factor.

Factors indicative of outcome in a comparative trial of acyclovir and vidarabine for biopsy-proven herpes simplex encephalitis.

A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.

Vidarabine versus acyclovir therapy in herpes simplex encephalitis.

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.

Isolation and propagation of a human enteric coronavirus.

Coronavirus-like particles were found by electron microscopy in stools from infants with necrotizing enterocolitis. Stool samples from these infants as well as control specimens were passaged in cultures of human fetal intestinal organs. Two samples yielded virus-like particles and these have now been passaged 14 times (HEC 14). Gradient-purified HEC 14 strains had typical coronavirus morphology on electron microscopy and contained five major proteins with molecular sizes ranging from 190 to 23 kilodaltons. Infants with necrotizing enterocolitis developed specific antibody to the viral antigens between the acute and convalescent stages of the disease, as shown by examining serum specimens by single radial hemolysis, immunoenzymatic assay, and Western immunoblotting. No cross-reactivity was shown with other coronavirus strains tested, or with the newly isolated viruses of the Breda-Berne group, responsible for calf or horse diarrhea.

Bactericidal activity of antiseptics against methicillin-resistant Staphylococcus aureus.

Various commonly used antiseptics were tested against three strains of methicillin-resistant Staphylococcus aureus (MRSA) at stock strength and in serial 10-fold dilutions. The stock solutions of 4% chlorhexidine gluconate-alcohol (Hibiclens), 1% p-chloro-m-xylenol (Acute-Kare), and 3% hexachlorophene (Phisohex) produced 2-log reductions of MRSA after a 15-s exposure, but even after 240 s, these solutions failed to kill all the MRSA. Povidone-iodine (Betadine) solution was maximally effective at the 1:100 dilution, killing all the MRSA within 15 s; other dilutions were less effective, though each killed the MRSA within 120 s. Similar results were obtained with three different strains of methicillin-susceptible S. aureus. Thus, of the four most commonly used antiseptics, povidone-iodine, when diluted 1:100, was the most rapidly bactericidal against both MRSA and methicillin-susceptible S. aureus.