Diagnosis of bovine leukemia virus infection: evaluation of serologic and hematologic tests by a direct infectivity detection assay.
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The cellular response in the course of experimental infection with Salmonella typhimurium was studied in mice. T cells were detected by the presence of theta-antigen, B cells by the binding of fluorescent immunoglobulins, and cells with receptors by labeled Salmonella binding. Lymphocytes were from spleen and lymph nodes. Results have been divided into three groups: group A, including mice with slight symptomatology; group B, including those with serious infection symptomatology; and group C, including mice that died in the course of the experiment. In spleen and lymph nodes of group A mice, an increase in the percentage of T and B lymphocytes was observed. This increase reached a peak 10 days after experimental infection. In lymph nodes, the B-cell percentage was equal to the percentage of T cells, whereas in spleen lymphocytes the B-cell percentage was higher. In spleens of group B mice we observed the same response as in mice of group A, whereas in lymph nodes there was a low response of T and B lymphocytes. In group C mice, there was no significant response of T and B lymphocytes in either spleen or lymph nodes. In B lymphocytes prepared from spleens of surviving mice, a small number of Salmonella receptors was detected: 200 bacterial cells per 10(9) lymphocytes.
A prospective study of 37 men and 32 women with culture-proved genital herpes simplex virus (HSV) infection was undertaken to characterize the clinical manifestations of the disease and effects of topical therapy with Nonoxynol 9, a nonionic surfactant active in vitro against HSV. The duration of pain, lesions, and virus shedding was significantly longer in initial than in recurrent genital HSV infection. Cervical HSV shedding occurred in 11 of 13 initial infections versus two of 19 recurrences (p less than 0.001). Type 1 HSV caused seven of 29 initial and none of 40 recurrent infections (p less than 0.01). Clinical recurrences within six weeks were detected more often in men than in women and were unrelated to the menstrual cycle. The influence of coitus on recurrence is unclear. Papanicolaou smears were transiently abnormal (Class II) in four (12.5 per cent) of 32 female patients. Evidence of herpesvirus was detected cytologic smears from only 28 (41 per cent) of 69 culture-proved external lesions and three (23 per cent) of 13 culture-positive cervices. Serology was also of limited diagnostic value except in testing paired sera from initial infections. The topical therapy had no beneficial effect.
Suspensions of Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Pseudomonas aeruginosa were used to contaminate teats excised from cows. Commercially available teat dips were applied for evaluation of comparative germicidal activity. Iodophors, sodium hypochlorite, and sodium dichloro-s-triazenetrione were highly effective against all four test organisms. Quarternary ammonium, chlorhexidine, and cetylpyridinium chloride were effective against Staphylococcus aureus, and Streptococcus agalactiae but not Escherichia coli and Pseudomonas aeruginosa. Bronopol and 8-hydroxyquinoline sulfate were marginally effective on the two Gram positive organisms and ineffective on the two Gram negatives. Three of the dips were ineffective against all four pathogens; two were in nonaqueous bases, and the other was a blend of pine oil and antibodies with udder origin. In other trials, iodophor at .3% titratable iodine was highly effective against Staphylococcus aureus and Streptococcus agalactiae. Products containing .5 and 1% iodophor maintained effectiveness after each was used to dip 140 teats under conditions of commercial dairying. Logarithmic reduction in the geometric mean number of organisms recovered from teats was more meaningful for evaluating data than percent reduction.
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22 patients with various gram-negative infections were treated with tobramycin at a dose of approximately 3 mh/kg body weight/24 h for 7 to 53 (mean 16) days. Therapy was monitored with determinations of drug serum concentrations and renal and audio-vestibular function tests. In 16 patients either cure of clinical improvement were achieved. Two patients did not improve. In another 4 patients the effect of tobramycin therapy could nto be evaluated. One patient exhibited a subclinical vestibular dysfunction and one patient experienced transient tinnitus. In one patient, slight but clinically significant renal impairment occurred.
Urinary tract infections (UTIs) are the most common severe bacterial infections in young children, often associated with vesicoureteral reflux (VUR). To explore host genetic-microbiota interactions and their clinical implications, we analyzed the urinary microbiota (urobiota) and conducted genome-wide association studies for bacterial abundance traits in pediatric patients with UTI and VUR from the Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation cohorts. We identified 4 urobiota community types based on relative abundance, characterized by the genera Enterococcus, Prevotella, Pseudomonas, and Escherichia/Shigella, and their associations with VUR, age, and toilet training. Children with VUR exhibited decreased microbial diversity and increased abundance of genera that included opportunistic pathogens, suggesting a disrupted urobiota. We detected genome-wide significant genetic associations with urinary bacterial relative abundances, in or near candidate genes including CXCL12, ABCC1, and ROBO1, which are implicated in urinary tract development and response to infection. We showed that Cxcl12 was induced 12 hours after uropathogenic bacterial infection in mouse bladder. The association with CXCL12 suggests a genetic link between UTI, VUR, and cardiovascular phenotypes later in life. These findings provide the first characterization to our knowledge of host genetic influences on the pediatric urobiota in UTI and VUR, offering insights into the interplay between disease, host genetics, and the urobiota composition.
The etiology of 72 episodes of liver disease that developed in 62 of 162 renal-transplant recipients was evaluated. Infection with hepatitis B virus was a minor problem, and none of our patients had evidence of infection with hepatitis A. Cytomegalovirus infection was ubiquitous in the population and probably accounted for many episodes of acute liver disease. This agent's role in causing chronic hepatitis is less secure. Infections with other viruses including Epstein-Barr virus, adenovirus, and the herpes viruses were only rarely associated with hepatic disease. Azathioprine was responsible for some episodes of acute cholestasis but could not be incriminated as a direct cause of chronic disease. A cause could be identified for the majority of episodes of acute hepatic dysfunction, but the cause of most of the chronic hepatitis remains undetermined. It is likely that infection with non-A, non-B hepatitis virus accounts for much of this serious, often fatal, complication of renal transplantation.
Fifty-seven patients with ocular herpes simplex (HS) infection were studied for evaluation of existing methods for virus isolation and its application in diagnosis of HS infection. Virus was isolated in 90% of 34 cases with keratitis dendritica, when specimens were taken within eight days of onset of symptoms. The same isolation frequency was obtained in 10 cases of palpebral herpes with conjunctivitis. No isolation was possible in 11 cases of keratitis disciformis. Laboratory confirmation was obtained within four days in 70% of the positive cases. Ten strains of HS virus type 1 were examined for IDU resistance, 5 strains isolated prior to and 5 during IDU treatment. Nine of the strains had the same degree of sensitivity. One strain isolated during treatment was found to be highly resistant.
Nosocomial infections acquired in a special care nursery were surveyed longitudinally. The rates of acquired infection were determined, allowing the evaluation of specific infection control measures. A blood pressure cuff, utilized for all infants in the nursery, was associated with an increased rate of infection.
An indirect immunofluorescent antibody test was used to detect antibody to Babesia microti in human sera. Nine patients from Nantucket Island, Massachusetts infected with B. microti had serum titers greater than or equal to 1,024. Of 84 control sera from New York City residents, 246 sera from patients with possible exposure to ticks, and 36 sera from patients with suspected or confirmed tick bites, none was reactive at titers of 1:16 or above. The within-test reproducibility was within one fourfold dilution in 95% of trials. Test-to-test reproducibility was within one fourfold dilution in 33% of trials and within two fourfold dilutions in 100% of trials. Although cross-reactions among infected patients' sera and antigens of B. argentina, B. equi, B. bigemina, Plasmodium vivax, P. falciparum, and P. brasilianum were common, titers were highest to the homologous antigen.
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We evaluated a semiquantitative culture technic for identifying infection due to intravenous catheters: rolling the catheter segment across blood agar. This method was compared to broth culture. Of 250 catheters studied, 225 (90%) had low-density colonization on semiquantitative culture (less than 15 colonies on the plate) although 49 (19.6%) of these grew some organisms in broth or on the plate. None of these catheters led to septicemia. Twenty-five catheters (10%) grew greater than or equal to 15 colonies by the semiquantitative technic; most gave confluent growth. Septicemia originated from four of these catheters (P = 0.008). Of 37 catheters exposed to bacteremias from distant foci of infection, four yielded matching growth in broth, whereas none were concordant with the blood isolate on semiquantitative culture. Local inflammation was associated with high-density colonization semiquantitative culture (P less than 0.001). The semiquantitative technic distinguishes infection (greater than or equal to 15 colonies) from contamination and is more specific in diagnosis of catheter-related septicemia than culture of the catheter in broth.
Renal uptake of 99mTechnetium sulphur colloid (99mTcSC) was investigated in 99 animals with experimentally induced unilateral pyelonephritis and in 60 animals with a thermally induced renal injury. The degree of localization of 99mTcSC in the kidney was determined by direct counting of retained isotope after bilateral nephrectomy at autopsy. Phagocytosis of 99mTcSC by inflammatory tissue has been reported and it was anticipated that renal infection would lead to an increase in 99mTcSC uptake by the kidney. In fact it was found that renal infection with pathologic changes resulted in a significant decrease in the localization of 99mTcSC in the pyelonephritic kidney. A similar decrease was found in the thermally injured kidney but renal infection without pathologic changes did not give rise to any changes in radionuclide uptake. These findings suggested that phagocytosis by the proximal convoluted tubular cells is the normal mechanism for 99mTcSC accumulation in the kidney and that renal infection reduced the phagocytic capability of these cells.
ObjectiveTo evaluate the diagnostic efficacy of computed tomography-guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy.MethodsThis single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography-guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (α = 0.05, β = 0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled.ResultsComputed tomography-guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p < 0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9-98.5), specificity of 100.0% (95% confidence interval: 29.2-100.0), positive predictive value of 100.0% (95% confidence interval: 94.9-100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9-81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients.ConclusionsThe integration of computed tomography-guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.
Patient-derived xenografts are crucial for drug development but their use is challenged by issues such as murine viral infection. We evaluate the scope of viral infection and its impact on patient-derived xenografts by taking an unbiased data-driven approach to analyze unmapped RNA-Seq reads from 184 experiments. We find and experimentally validate the extensive presence of murine viral sequence reads covering entire viral genomes in patient-derived xenografts. The existence of viral sequences inside tumor cells is further confirmed by single cell sequencing data. Extensive chimeric reads containing both viral and human sequences are also observed. Furthermore, we find significantly changed expression levels of many cancer-, immune-, and drug metabolism-related genes in samples with high virus load. Our analyses indicate a need to carefully evaluate the impact of viral infection on patient-derived xenografts for drug development. They also point to a need for attention to quality control of patient-derived xenograft experiments.
An indirect fluorescent antibody (IFA) test for the diagnosis of Babesia equi infections was evaluated. Antigen prepared by conventional methods was of high quality in one instance and of lesser quality in a second when possible autofluorescence of the horse blood caused inconvenience in reading tests. Tests on 14 horses shown by parasitological means to be either infected (9) or uninfected (5) produced reactions at dilutions of 1/270 to 1/7290 for infected and at 1/10 to 1/90 for uninfected animals. The accuracy of the test was further demonstrated during investigations of 701 horses in 3 states of Australia. The 30 horses reacting at 1/270 to 1/2430 were from 33 imported to 3 different farms in Australia from a common source. Investigations of crossreactivity between B. equi and B. bovis of cattle suggested that B. bovis would not interfere with the test for B. equi, but that the reverse was possible.