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Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations OBJECTIVE: To assess the incidence of human immunodeficiency virus type 1(HIV-1) transmission by antibody (anti-HIV-1)-positive blood components, and to determine the immunologic and clinical course in HIV-1-infected recipients. DESIGN AND SUBJECTS: We retrospectively tested approximately 200,000 donor blood component specimens stored in late 1984 and 1985 for anti-HIV-1, and we contacted recipients of positive specimens to determine their serologic status. They were compared with both recipients of HIV-1-negative transfusions and healthy (untransfused) controls. Subjects were seen at 3- to 6-month intervals for up to 4 years for clinical and immunologic evaluations. MEASUREMENTS AND MAIN RESULTS: Of 133 recipients, 9 had other possible exposures. Excluding these cases, 111 of 124 (89.5%) were anti-HIV-1-positive (95% CI, 84.1% to 94.5%). The recipient's sex, age, underlying condition, and type of component did not influence infection rates. The cumulative risk for developing the acquired immunodeficiency syndrome (AIDS) within 38 months after transfusion was 13% (CI, 7.5% to 21.6%). At 36 +/- 3 months after the index transfusion, seropositive recipients had lower counts of CD2+CDw26+, CD4+, CD4+CD29+, and CD4+CD45RA+subsets and more CD8+I2+ lymphocytes than did recipients of anti-HIV-1-negative transfusions. The CD4+ and CD2+CDw26+subsets changed the most rapidly. The absolute CD8+ count remained normal. CONCLUSIONS: Transfusion of anti-HIV-1-positive blood infected 90% of recipients. The rate of progression to AIDS within the first 38 months after infection was similar to that reported for homosexual men and hemophiliacs. Although most lymphocyte subset counts changed over time, CD8+ counts were constant.
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Sulfadiazine crystalluria revisited. The treatment of Toxoplasma encephalitis in patients with acquired immunodeficiency syndrome. Toxoplasma gondii encephalitis is an important opportunistic infection in the acquired immunodeficiency syndrome, estimated to occur in 20,000 to 40,000 patients with acquired immunodeficiency syndrome in the United States by 1991. The combination of sulfadiazine and pyrimethamine is regarded as the treatment of choice. Acute renal failure due to crystal deposition in the urinary tract was well described 30 to 40 years ago and is likely to resurface as a clinical entity if appropriate prophylactic measures are not taken. We describe two cases of sulfadiazine-induced crystalluria and renal failure in patients with acquired immunodeficiency syndrome, review the pertinent literature, and discuss the pathogenesis. Recommendations are made for the prophylaxis and treatment of sulfadiazine-related renal toxic reaction. Physicians using this "new" drug must be aware of the potential danger of sulfonamide-induced injury to the urinary tract.
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Implementation of preventive services in an HMO practice. Practice does not conform to guidelines unless the guidelines are specifically implemented and performance is monitored. Several examples of implementation in one health maintenance organization (HMO) are given. These include immunization for influenza and follow up of positive screening tests for colorectal and cervical cancer. Each implementation effort has required the development of systems, which in this HMO are automated. Several issues influencing implementation are discussed, including resource constraints and priorities for the allocation of new resources. Developers cannot expect that their guidelines will be incorporated into clinical practice. They must foster specific implementation plans.
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Continued need for pneumococcal prophylaxis after splenectomy Two children died from pneumococcal infection five and eight years after splenectomy. Pneumococcal vaccination had not been given to either child. When the infection developed both children were not taking prophylactic penicillin. Vaccination and daily penicillin reduce the incidence of this complication and therefore we strongly recommend that both of these measures are continued indefinitely.
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Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus-infected patients. Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure.
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Suppression of herpes simplex virus type 1 reactivation from latency by (+-)-9-([(Z)-2-(hydroxymethyl)cyclohexyl]methyl) guanine (L-653,180) in vitro. Latent herpes simplex virus type 1 (HSV-1) infection was induced in human embryonic lung cells in vitro by using a combination of viral replication inhibitors and elevated temperature. Under reactivating conditions (superinfection by human cytomegalovirus or temperature manipulation), a nonantiviral thymidine kinase inhibitor (L-653,180) was found to suppress or delay reactivation of HSV-1 from latently infected human embryonic lung cells. L-653,180 alone or in combination with interferon was ineffective as a primary or acute viral replication inhibitor and was unable to induce latent HSV-1 infection in cell culture. These data suggest that initial or acute virus replication and replication resulting from reactivation from latency are separate events.
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Silent infections with human immunodeficiency virus type 1 are highly unlikely in multitransfused seronegative hemophiliacs. We used the polymerase chain reaction (PCR) to determine the frequency of silent human immunodeficiency virus type 1 (HIV-1) infections in seronegative high-risk individuals with hemophilia who had been exposed to contaminated blood products more than 3 years previously. In a cross-sectional study of a cohort of 57 prospectively followed seronegative hemophiliacs who received multiple transfusions before 1986, HIV-1 proviral DNA was found transiently in only one patient. These data suggest that the rate of HIV infection among high-risk antibody negative individuals with hemophilia is very low to absent, in the range of 0% to 2%. These findings should provide considerable reassurance to seronegative persons with hemophilia and their sexual partners.
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Use of single fiber EMG and macro EMG in study of reinnervation. The use of single fiber EMG and macro EMG in studies of reinnervation is discussed. SFEMG gives information about changes in the topography of the motor unit and in function of transmission in terminal nerve, motor endplate and muscle fiber. Dynamics of reinnervation may be studied with this technique. The amount of reinnervation is obtained from macro EMG studies. The capacity for reinnervation is discussed for a few conditions as well as factors that limit the reinnervation process.
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Immunopathology and viral reactivation. A general theory of schizophrenia. A theory is proposed that explains a broad range of clinical manifestations in schizophrenia. It is a heuristic device for organizing research in the neuroimmunology and virology of schizophrenia. This approach is different from other immune and viral theories of schizophrenia and defines testable hypotheses for further theory refinement or rejection. Defective alpha-interferon (aIFN) regulation resulting in excessive effect is postulated to cause schizophrenia. The role of aIFN in the regulation of development and its induction within the brain by the reactivation of viruses that are commonly present in the normal central nervous system (CNS) are the primary pathophysiological mechanisms. Biological properties of aIFN include neural excitation, opiate and adrenocorticotropic hormone activity, and inhibition of cellular proliferation and differentiation. Psychosis results from in situ viral stimulation of aIFN production in the CNS of a vulnerable host having defective regulation of either sensitivity or production. Negative symptoms result from aIFN effects on CNS development and the behavioral toxicity of aIFN. Biological developmental abnormalities, gender differences in severity, and decline in psychotic symptoms with age are discussed in the context of the theory. Research strategies and specific testable hypotheses are presented.
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Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. The human T-lymphotropic virus type I (HTLV-I), the first human retrovirus to be characterized, is associated with adult T-cell leukaemia and a chronic progressive disease of the central nervous system termed tropical spastic paraparesis, or HTLV-I-associated myelopathy. Only 1% of individuals infected with HTLV-I develop clinical disease however. The various manifestations of an HTLV-I infection may be related to differences in the genetic backgrounds of individuals, infection with variant strains of HTLV-I, differences in viral tropism or host immune response to the virus. Whereas the humoral response to HTLV-I is well characterized, little is known about the human cellular immune response, such as the production of cytotoxic T lymphocytes. Here we report the presence of high levels of circulating HTLV-I-specific cytotoxic T lymphocytes in patients with HTLV-I associated neurological disease but not in HTLV-I seropositive individuals without neurological involvement. These cytotoxic T lymphocytes are CD8+, HLA class I- restricted and predominantly recognize the HTLV-I gene products encoded in the regulatory region pX. These findings suggest that HTLV-I-specific cytotoxic T lymphocytes may contribute to the pathogenesis of associated neurological disorders associated with HTLV-I.
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Cigarette smoking: a modifier of human immunodeficiency virus type 1 infection? Two hundred and two homosexual men enrolled in a prospective cohort study of AIDS risk were assessed for differences in the occurrence and progression of human immunodeficiency virus type 1 (HIV-1) infection with respect to cigarette smoking. Among subjects who were initially seronegative, smokers were more likely than nonsmokers to become HIV-1 seropositive (p = 0.03). After seroconversion, serum beta 2-microglobulin and CD4+ lymphocyte levels were elevated in cigarette smokers relative to nonsmokers (p = 0.02 for both comparisons), but both of these differences disappeared within 2 years. There was no detectable difference in the risk of AIDS or Pneumocystis carinii pneumonia with respect to smoking. Our data suggest that cigarette smoking may alter the immune response to HIV-1 infection, but it appears to have no marked effect on clinical outcome. They also suggest that cigarette smoking may be a surrogate marker for continued high-risk sexual behavior in homosexual men.
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Clinical and pathological features of bacillary peliosis hepatis in association with human immunodeficiency virus infection BACKGROUND. Peliosis hepatis is characterized by cystic, blood-filled spaces in the liver and is seen in patients with chronic infections or advanced cancer and as a consequence of therapy with anabolic steroids. Cutaneous bacillary angiomatosis is a bacterial infection that occurs in patients with human immunodeficiency virus (HIV) infection; its histologic appearance is that of a pseudoneoplastic vascular proliferation. METHODS. We studied liver tissue from eight HIV-infected patients with peliosis hepatis, two of whom also had cutaneous bacillary angiomatosis. For comparison we examined tissue from four patients who had peliosis hepatis without HIV infection. Tissues were examined histologically on routine sections and with special stains and electron microscopy. RESULTS. The histologic features seen in peliosis hepatis associated with HIV infection, but not in the four cases unrelated to HIV infection, were myxoid stroma and clumps of a granular purple material that on Warthin-Starry staining and electron microscopy proved to be bacilli. The bacilli, which could not be cultured, were morphologically identical to those found in the skin lesions of cutaneous bacillary angiomatosis. The clinical courses of two of the patients with this "bacillary peliosis hepatis" indicate that it responds to antibiotic treatment. CONCLUSIONS. HIV-associated bacillary peliosis hepatis is an unusual, treatable opportunistic infection, probably caused by the same organism that causes cutaneous bacillary angiomatosis. Our failure to find bacilli in non-HIV-associated cases implies that other pathogenetic mechanisms may also be responsible for peliosis hepatis.
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Oligoclonal T cell receptor gene rearrangements in blood lymphocytes of patients with acute Epstein-Barr virus-induced infectious mononucleosis. Gene rearrangement studies were performed on blood lymphocytes from eight patients with acute Epstein-Barr virus-induced infectious mononucleosis. The diagnosis in each case was based on characteristic clinical, hematologic, and serologic findings. The blood lymphocytes in each patient consisted predominantly of CD8+ T cells. EBV DNA was detected in seven patients by Southern blot analysis (EBV Bam HI W probe, Bam HI). A germline configuration was found for the immunoglobulin heavy and light chain genes (JH probe, Bam HI and Eco RI; C kappa probe, Bam HI; and C lambda probe, Eco RI). T cell receptor gene rearrangements were detected with J gamma and J beta 1 + 2 probes. Using a J gamma probe with two different restriction enzymes (Bgl II and Eco RI), the blood from each patient showed several bands corresponding to the polyclonal pattern previously described in the blood of normal individuals. Using J beta 1 + 2 probes with two different restriction enzymes (Bgl II and Bam HI), each case showed from 3 to about 12 extragermline bands of varying intensity and in different locations from case to case. In addition, each case showed relative deletion of the J beta 1 germline band. This oligoclonal pattern of T cell receptor gene rearrangements has not been previously reported in benign or malignant T cell populations.
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Perturbation of differentiated functions during viral infection in vivo. In vivo relationship of host genes and lymphocytic choriomeningitis virus to growth hormone deficiency. Retarded growth and disordered glucose metabolism secondary to growth hormone (GH) deficiency are associated with persistent lymphocytic choriomeningitis virus (LCMV) infection of GH-producing cells in the anterior lobe of the pituitary gland. Infected C3H/ST mice, which are H-2k haplotype, become GH deficient, and LCMV replicates in most (more than 90%) of their GH-producing cells. In contrast, BALB/WEHI and SWR/J mice, which are H-2d and H-2q, respectively, do not develop this GH deficiency, and less than 20% of their GH-producing cells are infected by virus. Yet all three strains infected at birth with LCMV strain Armstrong (ARM) carry equivalent amounts of virus in their blood, brain, heart, kidney, liver, spleen, and thymus throughout life. Of five additional H-2k murine strains tested, C3H/HEJ and CBA/N mice develop this GH-like disorder, whereas neither AKR/J, B10/BR, nor BALB/KAE mice do, indicating that the H-2K haplotype does not control the GH susceptibility. Furthermore C3H/SW mice, which have the H-2b haplotype on the C3H background, develop the disease, again negating any correlation with H-2k but inferring that the C3H background is responsible. One half of the hybrid offspring produced by crossing the C3H/ST GH-deficient strain with BALB/WEHI-resistant mice develop the disease, but the trait is not sex linked. F1 hybrid backcrosses with the susceptible C3H/ST parental strain or resistant BALB/WEHI strain indicate the involvement of more than two genes. Hence the development of a GH deficiency by LCMV-infected C3H/ST mice is not linked to the MHC haplotype, is not sex linked, and is not due to a dominant gene. Multiple genes are involved and these are related to C3H background.
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Sensitivity of digoxigenin and biotin labelled probes for detection of human papillomavirus by in situ hybridisation. The sensitivity of digoxigenin and biotin labelled DNA probes for the detection of human papillomavirus (HPV) by dot blotting and in situ hybridisation was compared in tissues from cervical, laryngeal, and anogenital neoplasia. Probes were either labelled with digoxigenin by the random primer technique and detected with anti-digoxigenin antibody, or labelled with biotin by nick translation and detected with streptavidin, both methods having a common final visualisation procedure using alkaline phosphatase. Digoxigenin labelled probes proved two to 10-fold more sensitive by quantitative dot blotting and four-fold more sensitive in detecting HPV 16 DNA in a series of 31 anal carcinomas, compared with biotinylated probes. The digoxigenin method also produced less non-specific background staining of tissue sections than biotin labelled probes. It is concluded that digoxigenin DNA labelling and detection provides a simple, reliable, and efficient alternative to the use of biotin or radioactive isotopes for the detection of HPV DNA by in situ hybridisation. Digoxigenin labelled probes also offer the possibility of double labelling in situ hybridisation procedures when used with biotin labelled probes to provide simultaneous identification of different DNA sequences.
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Cumulative AIDS incidence and altered mortality from bacterial infections. To determine whether populations with high cumulative incidence of acquired immunodeficiency syndrome (AIDS) experienced increased deaths from sepsis, central nervous system abscess, or endocarditis, New Jersey AIDS patients were grouped according to their age, sex, race, and residence-specific cumulative incidence of AIDS since the onset of the AIDS epidemic. Between 1980 and 1986, among 25-44 year olds in the highest cumulative incidence group for AIDS, sepsis mortality increased from 3.3 to 15.2 deaths/100,000/year, an increase of 11.9 deaths/100,000/year (95% confidence interval (6.9, 17.0) deaths/100,000/year); mortality from central nervous system abscesses increased from zero to 1.7 (0.1, 3.2) deaths/100,000/year; and mortality from endocarditis increased from 0.8 deaths/100,000/year to 2.4 deaths/100,000/year, an increase of 1.6 (-0.5, 3.7) deaths/100,000/year. Age-matched New Jersey patient populations with low cumulative incidence of AIDS did not sustain a similar increase. The HIV disease-associated increase in sepsis mortality among young populations represents a new component of the substantial increase in U.S. sepsis mortality that occurred over the last two decades, but was previously limited to older populations.
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Adult immunizations: are they worth the trouble? There are good data to recommend routine use of vaccines against measles, rubella, tetanus, influenza, and pneumococcal infections in adults. An adolescent or an adult born after 1956 is considered to be susceptible to measles unless he or she has received two doses of live measles vaccine or has suffered a physician-diagnosed case of measles. Tetanus is largely a disease of the elderly, and there is a universal need for immunizations with tetanus toxoid. Influenza continues to be a major public health problem, and influenza vaccine should be given annually to the elderly and to those at high risk. The efficacy of pneumococcal vaccine in American adults is still being debated. Results from case-control studies show that the vaccine is about 60% effective in reducing the incidence of disease due to vaccine-related strains. Its use in the elderly and in those at higher risk for pneumococcal infection is recommended.
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Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. The gene designated gamma 134.5 maps in the inverted repeats flanking the long unique sequence of herpes simplex virus-1 (HSV-1) DNA, and therefore it is present in two copies per genome. This gene is not essential for viral growth in cell culture. Four recombinant viruses were genetically engineered to test the function of this gene. These were (i) a virus from which both copies of the gene were deleted, (ii) a virus containing a stop codon in both copies of the gene, (iii) a virus containing after the first codon an insert encoding a 16-amino acid epitope known to react with a specific monoclonal antibody, and (iv) a virus in which the deleted sequences were restored. The viruses from which the gene was deleted or which carried stop codons were avirulent on intracerebral inoculation of mice. The virus with the gene tagged by the sequence encoding the epitope was moderately virulent, whereas the restored virus reacquired the phenotype of the parent virus. Significant amounts of virus were recovered only from brains of animals inoculated with virulent viruses. Inasmuch as the product of the gamma 134.5 gene extended the host range of the virus by enabling it to replicate and destroy brain cells, it is a viral neurovirulence factor.
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Itraconazole therapy in aspergillosis: study in 49 patients. Itraconazole, 200 to 400 mg once daily, was administered to 49 patients with different types of aspergillosis: pulmonary aspergilloma (14 patients), chronic necrotizing pulmonary aspergillosis (14), and invasive aspergillosis (21). Itraconazole was prescribed alone or in combination or after treatment with amphotericin B and flucytosine. Of 14 aspergilloma patients, 2 were cured and 8 had symptomatic improvement. In chronic necrotizing pulmonary aspergillosis, 7 of 14 patients were cured and 6 improved significantly. In invasive aspergillosis treatment failed in 6 patients and 15 were cured. Itraconazole can be an alternative to amphotericin B in the treatment of invasive aspergillosis and chronic necrotizing pulmonary aspergillosis. In aspergilloma itraconazole may be useful in inoperable cases.
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Gastrointestinal motor dysfunction in acquired selective cholinergic dysautonomia associated with infectious mononucleosis. This report documents the disturbance in gastrointestinal motor function in a patient with selective cholinergic dysautonomia that occurred following acute infectious mononucleosis. Apart from the gut, other organs affected included the pupils, sweat glands, lacrimal and salivary glands, and urinary bladder. Autonomic function tests showed the preservation of sympathetic adrenergic functions in contrast to the generalized involvement of postganglionic parasympathetic and sympathetic cholinergic nerves, including denervation hypersensitivity of the pupil and urinary bladder to exogenous cholinergic agonists. Cardiac and abdominal vagal responses were abnormal. Colon myenteric plexus ganglion cells were normal by morphological and immunohistochemical studies, suggesting that the selective cholinergic dysautonomia was the most likely pathophysiologic process responsible for the observed motility disorder. This study documents the occurrence of selective cholinergic dysautonomia following a viral illness, the importance of the extrinsic neural control on the motor function of the gastrointestinal tract, and the usefulness of combined motility and autonomic function testing in the evaluation of patients with symptoms suggestive of gut dysmotility.
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Risk factors for white matter changes detected by magnetic resonance imaging in the elderly. We found increased age (p = 0.001) and history or evidence of stroke (p = 0.016) to be significant independent multivariate predictors of the presence and severity of leukoencephalopathy on magnetic resonance imaging brain scans in a mixed population of 35 elderly psychiatric patients and 25 neurologically healthy elderly volunteers. These results suggest that subcortical ischemia, as well as age-related changes that may not be vascular in origin, contribute to the emergence of periventricular and other deep white matter hyperintensities that are commonly seen on the magnetic resonance imaging brain scans of older adults.
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An HIV-1 and HIV-2 cross-reactive cytotoxic T-cell epitope. The HLA-B27-restricted HIV gag cytotoxic T-lymphocyte (CTL) epitope, 265-279, is highly conserved amongst HIV-1 isolates, only one, HIV-1ELI, having a single amino acid substitution. Over the same region HIV-2 differs by five amino acids. As a broadly cross-protective AIDS vaccine should protect against infection from all isolates of HIV-1 and HIV-2, we tested CTL specific for the HIV-1 265-279 epitope with peptide analogues from HIV-1ELI, HIV-2 and two simian immunodeficiency virus (SIV) isolates, and with recombinant vaccinia viruses expressing the respective gag genes, to determine whether there was any cross-reactivity for this CTL epitope. CTL from the HIV-1-infected donor could recognize the HIV-1ELI peptide, the HIV-2 peptide and recombinant vaccinia virus-infected target and one of the two SIV peptide-treated targets. Epitopes that exhibit such cross-reactivity may be valuable in vaccine design.
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Laser photodynamic therapy for papilloma viral lesions. Photodynamic therapy was tested for its therapeutic efficacy in eradicating rabbit papilloma warts. The wild-type viral warts suspension was used to induce treatable papilloma warts in the cutaneous tissue of Dutch Belted rabbits. The photosensitizing agents used intravenously were Photofrin II at 10 mg/kg of body weight and Chlorin e6 monoethylene diamine monohydrochloric acid (Chlorin e6 med HCl) at 1 mg/kg of body weight. The lasers used were an argon-dye laser at 628 and 655 nm and a gold vapor laser at 628 nm. The irradiances of 25 to 180 mW/cm2 were applied topically with an end-on lens optical fiber with total radiant doses of 7.5 to 54 J/cm2. Photofrin II and the argon-dye laser at the highest light dosage (54 J/cm2) and Chlorin e6 monoethylene diamine monohydrochloride administered 2 hours before argon-dye laser irradiation at 655 nm at the highest light dosage (54 J/cm2) produced wart regression. Total wart regression without recurrence was achieved with Photofrin II and the gold vapor laser at all light dosages. The difference observed between the argon-dye laser and the gold vapor laser might be explained by the pulsed nature of the gold vapor laser, with its high-peak powers, some 5000 x the average measured light dose. In this model, the smaller, less cornified lesions were more effectively treated with photodynamic therapy.
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Idiopathic sudden sensorineural hearing loss and postnatal viral labyrinthitis: a statistical comparison of temporal bone findings. Although the cause of idiopathic sudden sensorineural hearing loss remains uncertain, a viral origin has been suggested in many cases on the basis of anamnestic microbiologic and pathologic data. Twenty-two temporal bone specimens from 18 patients who during life suffered a sudden partial or complete sensorineural hearing loss were studied. On the basis of clinical data, these cases were assigned to one of three diagnostic categories, and the temporal bones were studied by light microscopy and serial section analysis. The implications of the histopathologic findings for the pathogenesis of idiopathic sudden sensorineural hearing loss are discussed.
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Increased septic complications with three-drug sequential immunosuppression for cadaver renal transplants. In 152 renal transplant recipients, the results of immunosuppression with three-drug sequential (Minnesota antilymphocyte globulin, prednisone, azathioprine, and cyclosporine) immunosuppression (n = 107) were compared with those of a two-drug sequential protocol (Minnesota antilymphocyte globulin, prednisone, and cyclosporine) that excluded azathioprine (n = 45). The study groups were comparable by age, sex, etiology of renal failure, incidence of diabetes, and degree of HLA matching. Patient survival at 1 year was not significantly different in the two groups (two drug, 93% versus three drug, 86%; p = 0.19). One-year graft survival was superior in the two-drug group (two drug, 93% versus three drug, 75%; p = 0.02). Analysis of primary transplants only (n = 116) yielded the same results. During the first year, the serum creatinine level remained stable in both groups. As expected, the three-drug therapy group had significantly more bacterial and viral infections. For low-risk primary cadaveric renal transplants, two-drug sequential immunosuppression is superior.
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Bacterial tracheitis: report of eight new cases and review. Bacterial tracheitis, previously referred to as nondiphtheritic laryngitis with marked exudate, was commonly discussed in pediatric textbooks before 1940. It seemed to disappear as a clinical entity after that time, but it has been recorded with increasing frequency in the pediatric literature since 1979. We describe eight new cases and review 110 previously described cases. The clinical course consists of a prodromal upper respiratory illness with stridor, fever, and a variable degree of respiratory distress. Unlike patients with croup, patients with bacterial tracheitis do not respond to aerosolized racemic epinephrine. Most patients require endotracheal intubation; some require tracheostomy. Reported complications include pneumonia, pneumothorax, formation of pseudomembranes, toxic shock syndrome, and cardiopulmonary arrest. Bacterial tracheitis is a secondary bacterial infection following a primary viral respiratory infection. The most common preceding viral infection is parainfluenza. Staphylococcus aureus and Haemophilus influenzae are the predominant causes of bacterial tracheitis. Secondary bacterial infection may occur as a result of tracheal mucosal injury or impairment of normal phagocytic function due to viral infection.
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Widespread flat warts associated with human papillomavirus type 5: a cutaneous manifestation of human immunodeficiency virus infection. Numerous flat and tinea versicolor-like warts developed on the face, trunk, and upper extremities of a 10-year-old boy with human immunodeficiency virus infection. Nucleic acid analysis of involved skin revealed human papillomavirus type 5, which has sometimes been associated with epidermodysplasia verruciformis. This human papillomavirus type has also been described in patients with common variable immunodeficiency and dyskeratosis congenita and in renal allograft recipients. Human immunodeficiency virus infection should be added to the list of immune-related disorders that predispose to widespread flat warts.
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Association of acute colonic pseudo-obstruction (Ogilvie's syndrome) with herpes zoster. Ogilvie's syndrome, or acute pseudo-obstruction of the colon is characterized by massive distension of the colon in the absence of organic distal obstruction. The syndrome is associated with various unrelated and, most often, extra-abdominal causes. An association between Ogilvie's syndrome and herpes zoster has been reported only once, by Ceccese et al. in 1985. We present a second such case. This patient did not show evidence of any active illness other than the involvement of the T10 dermatome by herpes zoster. The patient's symptoms of colonic obstruction subsided with resolution of the zosteriform rash.
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Application of 1 nm gold probes on paraffin wax sections for in situ hybridisation histochemistry. An in situ hybridisation technique that uses 1 nm immunogold reagents and silver enhancement was devised to detect biotinylated DNA viral probes in formalin fixed, paraffin wax sections of human cervix. DNA probes labelled with biotin-11-deoxyuridine triphosphate were detected after hybridisation to nucleic acid sequences by an antibiotin antibody, followed by a gold labelled secondary antibody. Silver enhancement then permitted visualisation of the signal at the light microscopic level. The method was reliable and produced less background staining than previously described methods. The signal could be enhanced by epi polarisation microscopy. Furthermore, biotinylated DNA probes may be detected directly by a 1 nm gold labelled goat antibiotin antibody without loss of labelling intensity, and this may be preferable to the longer two layer technique, previously described.
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Chickenpox chorioretinitis. Chickenpox infection in an adult was complicated by peripheral chorioretinitis and treated with oral acyclovir. Similarities of this case to the recently proposed mild type of acute retinal necrosis syndrome are discussed.
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Efficiency of white cell filtration and a freeze-thaw procedure for removal of HIV-infected cells from blood. Strategies for diminishing the risk of blood transfusion-associated transmission of HIV-1 were evaluated. HIV-1-infected peripheral blood mononuclear cells were added to blood that was subsequently filtered by using different white cell (WBC) filters (cellulose acetate and polyester). The average log reduction of infected cells with polyester filters was at least 2.5 as measured by ID50 titration and polymerase chain reaction. In two WBC filtration experiments with blood from seropositive donors diluted 1:4 with seronegative blood, log reductions of 2.4 and greater than 2.5 were observed. No cell-free virus was retained by the filter used. A freeze-thaw procedure applied to HIV-1-contaminated blood resulted in a minimal log reduction. These results indicate that the reduction of HIV-1 infectivity as a result of filtration is mainly due to the removal of HIV-1-infected WBCs, and that complete removal of infected WBCs cannot be achieved by the current filtration or freeze-thaw procedures. However, the development of filters with enhanced ability to remove (possibly infected) WBCs may have the added benefit of improving the safety of donor blood, especially in multiply transfused patients.
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Central airway obstruction due to cytomegalovirus-induced necrotizing tracheitis in a patient with AIDS. Cytomegalovirus (CMV) infection in patients with the acquired immunodeficiency syndrome (AIDS) can present as either disseminated disease, pneumonitis, retinitis, gastroenteritis, neuropathy, or a subclinical infection. We report a patient whose initial manifestation of CMV infection was severe central airways obstruction due to necrotizing tracheitis. At bronchoscopy, the lesion appeared deeply ulcerated, distinctly different from previously described airway lesions in patients with AIDS. Mucosal biopsies showed characteristic intranuclear and intracytoplasmic inclusions and cultures yielded only CMV. The patient responded partially to ganciclovir, steroids, and antibiotics against suspected anaerobic superinfection but died as a result of central nervous system disease believed due to toxoplasmosis or lymphoma. CMV infection of the upper airway should be considered in the patient with AIDS presenting with atypical cough or stridor and ulcerated endobronchial lesions.
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Undiagnosed tuberculosis in patients with human immunodeficiency virus infection We describe the clinical features of 11 patients with human immunodeficiency virus infection in whom tuberculosis was undiagnosed and untreated prior to death. Most patients (9 of 11) had pulmonary complaints and 8 of 11 had roentgenographic findings suggestive of tuberculosis (hilar or mediastinal adenopathy, pleural effusion, apical infiltrate or miliary pattern). Despite these findings, tuberculin skin tests were not performed in any of the patients. Acid-fast smears of sputum were obtained in three cases and bronchoscopy performed in only four, reflecting the low index of suspicion for tuberculosis. Pneumocystis carinii pneumonia was the presumptive diagnosis in nine cases but was confirmed in only one case. Autopsy revealed tuberculosis as the cause of death in four patients. Of the seven patients who did not undergo autopsy, disseminated tuberculosis, manifest by mycobacteremia, was the only life-threatening illness identified and probably contributed to death. Increased awareness of the clinical and roentgenographic features of tuberculosis in HIV-infected patients, combined with more intensive use of acid-fast smears and tuberculin skin testing, are necessary in order to decrease mortality from this treatable complication of HIV-infection.
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Cytomegalovirus and Rasmussen's encephalitis In-situ hybridisation with a biotinylated cytomegalovirus (CMV) DNA probe was done on brain biopsy specimens from 10 patients with Rasmussen's encephalitis (RE) and 46 age-matched control patients with other neurological diseases. All 10 patients with RE had intractable epilepsy and focal neurological deficits, and there was perivascular cuffing, microglial nodules, astrogliosis, and neuronal loss. CMV genomic material was demonstrated in 7 of the 10 patients with RE (in neurons, astrocytes, oligodendrocytes, and endothelial cells) and in 2 of the 46 control patients. Probes for herpes simplex virus and hepatitis B virus were negative in all patients and in fibroblast controls. The results suggest that CMV is a likely cause of Rasmussen's encephalitis.
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Human immunodeficiency virus and the primary care physician. As the scope and size of the human immunodeficiency virus (HIV) epidemic grows, the primary care physician will need to assume a greater role. A knowledge of HIV risk factors and the ability to perform pretest and posttest counseling for HIV testing is essential. Counseling patients on HIV risk reduction should be part of the HIV risk interview. An understanding of the benefits and contraindications of testing, as well as a respect for the impact of testing, is important. All HIV-seropositive individuals should undergo a complete history and review of symptoms as soon as test results are known. Judicious use of laboratory testing, including monitoring of CD4 cell counts, is recommended. Pneumocystis carinii prophylaxis and zidovudine therapy should be offered to patients with appropriately low CD4 counts.
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Current report--HIV. AIDS at the crossroads: a report from the 1990 International Conference on AIDS--San Francisco. Major scientific and clinical breakthroughs in HIV disease are rarely saved for the International Conference on AIDS. Nevertheless, this conference provides an opportunity for experts, providers, and patients to gain new information, exchange ideas, and assess progress. The Conference is also a public forum for political and social discussion and serves as a barometer of scientific and social trends as well. This year's conference featured refinements in clinical care, a deeper understanding of the epidemiologic trends, and a public awareness of the many political aspects of the AIDS epidemic. Contributions from family physicians and other primary care providers about problems they face and the family aspects of HIV need still greater prominence and exposure. Hopefully family physicians will use their expertise and report at future international conferences.
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Quantitative detection of brain aberrations in human immunodeficiency virus type 1-infected individuals by magnetic resonance imaging. The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency.
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Psychological functioning in a cohort of gay men at risk for AIDS. A three-year descriptive study. This study describes the mental health of a large cohort of gay men participating in the Chicago Multicenter AIDS Cohort Study/Coping and Change Study. Six biannual questionnaires were self-administered between 1984 and 1988. General mental health was determined by the Hopkins Symptom Checklist (HSCL). An abbreviated version of the Center for Epidemiologic Study Depression Scale (CESD-5) and an adapted Diagnostic Interview Schedule (DIS) question also measured depression. Suicidal ideation was assessed by one question in the HSCL. AIDS-specific distress was determined by three subscales specifically developed for this study. While mean HSCL and CESD-5 scores were stable during the observational period, AIDS-specific distress increased over time. The HSCL scores for the cohort were somewhat elevated above general population norms but considerably below psychiatric outpatient norms. Fewer than 12% of the men reported elevated HSCL or CESD-5 scores three or more times. A self-reported episode of depression of two weeks or more, measured by the DIS screening question, was experienced by 40.1% of the sample. Suicidal ideation was reported on three or more visits by 18.8% of the men. The younger members of this cohort exhibit greater general and AIDS-specific distress. Income was inversely associated with general distress. HIV-seropositive participants had generally higher AIDS-specific distress scores than those who were seronegative, but their scores were equivalent on the HSCL and CESD-5.
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Adult immunization in a network of family practice residency programs. A substantial proportion of morbidity and mortality associated with vaccine-preventable diseases occurs among adults. Teaching residents about disease prevention is mandated in the curriculum guidelines for family practice programs. A cooperative study among the Kansas City family practice residency programs was begun to look at immunization behaviors in these teaching programs. A retrospective audit of medical records and a prospective survey of residents and faculty were performed. From the medical records of 400 patients seen for health maintenance examinations, the frequency of tetanus-diphtheria immunizations recorded was 4.75%. The pooled immunization rate recorded for pneumococcal vaccine was 25%, and for influenza vaccine, 24%. Although 93% of respondents knew patients need tetanus-diphtheria immunization every 10 years, on a written questionnaire giving clinical examples, they were less likely to elect to immunize older patients eligible for tetanus-diphtheria vaccine. The following immunization criteria were listed by respondents: for pneumococcal vaccine, age over 65 years (86%); for influenza vaccine, age over 65 years (85%), chronic diseases (69%), residence in a chronic care facility (7%), and being a health care worker (28%). Educational interventions stressing the appropriate criteria and involvement of the patient are planned at the separate programs.
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Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection. We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.
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Failure to detect human T-cell leukemia virus-related sequences in multiple sclerosis blood. We tested 11 patients with multiple sclerosis for the presence of human T-cell leukemia virus type I (HTLV-I)- or type II (HTLV-II)-related sequences. DNA from blood mononuclear cells was analyzed by the polymerase chain reaction utilizing three different oligonucleotide primer pairs. Two of these primer pairs detect sequences shared between HTLV-I and HTLV-II in either p24, gag protein, or in p21, env transmembrane protein. The third primer pair was synthesized based on regions in the pol gene where amino acid sequences are conserved between HTLV-I, HTLV-II, and the related bovine leukemia virus. The multiple sclerosis samples were consistently negative while appropriate control samples were positive. We conclude that viruses related to HTLV-I, HTLV-II, or bovine leukemia virus are not present in the blood of patients with multiple sclerosis and, therefore, that HTLV-bovine leukemia virus-related viruses are not likely to be involved in the pathogenesis of multiple sclerosis.
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In situ hybridisation with digoxigenin-labelled DNA probes for detection of viral genomes. The applicability of a recently developed non-radioactive DNA labelling and detection method, which uses the digoxigenin (DIG) enzyme linked immunosorbent assay (ELISA) system, for the detection of viral infections in pathology specimens by in situ hybridisation, was examined. Its efficacy was compared with that of biotin and radioisotope labelling methods. Three cases of progressive multifocal leucoencephalopathy, two of verruca vulgaris, and seven cases of laryngeal papilloma were studied. The sensitivity of the DIG labelled probe was almost the same as that of a 35S-labelled probe in the dot-blot hybridisation test. Using in situ hybridisation with 35S-labelled and DIG labelled probes, the levels of the hybridised signals detected were similar. The biotin labelled probe was less sensitive, particularly in the cases of laryngeal papilloma. The DIG labelling and detection method was highly sensitive and applicable to the detection of viral infection by ISH, and is preferable to a radiolabelled probe, especially when in situ hybridisation is done in the pathology laboratory.
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Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome Two patients, both seropositive for the human immunodeficiency virus, developed rapidly progressive retinal necrosis associated with a systemic herpes zoster infection. The retinitis in these patients was characterized by primary involvement of the outer retina, with sparing of the inner retina and retinal vasculature until late in the disease process; a rapidly progressive course; poor response to intravenous acyclovir; and development of rhegmatogenous retinal detachment. In one of the patients, the retinitis was initially multifocal. Electron microscopy of a retinal biopsy specimen from one of the patients demonstrated virus particles consistent with a herpesvirus, and polymerase chain reaction disclosed herpesvirus in a retinal biopsy specimen of the other patient. This entity may represent a distinct form of acute retinal necrosis that is seen in immunocompromised individuals.
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Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I. A retrovirus was isolated from a T-cell line that was established from lymphocytes in the cerebrospinal fluid of a patient with human T-cell leukemia virus type I-associated myelopathy (HAM), and its genome was sequenced. The nucleotide sequence of the 3' half of the total genome was identical in 99.5% of the nucleotides to that of the prototype human T-cell leukemia virus type I that was derived from a patient with adult T-cell leukemia. These results indicate that the same retrovirus human T-cell leukemia virus type I is associated with both a neurological disease, HAM, and a lymphoproliferative disease, adult T-cell leukemia.
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Interferon system and natural killer cell activity in myasthenia gravis. The autoimmune response in myasthenia gravis is well characterized, but little is known about the mechanisms initiating it. We have studied the interferon system and natural killer cell activity in 25 patients with myasthenia gravis and compared them to 68 healthy subjects and 96 patients with acute viral infections. Forty-four per cent of patients had circulating interferon (greater than 16 mu/ml), and in a similar proportion their peripheral blood mononuclear cells were in an antiviral state, i.e., showed low levels of viral replication when infected by vesicular stomatitis virus. Spontaneous in vitro interferon production by patients' peripheral blood mononuclear cells was also common (greater than 10 mu/ml, 32 per cent), while the response to the alpha-interferon inducer poly I:C was lower than expected, possibly reflecting the already high state of activation of the interferon system. These results were essentially similar to those obtained in patients with viral illnesses and differed significantly from healthy controls. In many myasthenia gravis patients (16 of 22, 73 per cent), a markedly deficient natural killer cell activity was found, with a median cytotoxicity of 6.5 per cent compared to 29 per cent in healthy subjects (p less than 0.005). Thus, many patients with myasthenia gravis have evidence of an activated interferon system and defective natural killer cell activity, suggesting an occult viral infection or reflecting nonspecific stimulation which may nevertheless contribute to the pathogenesis of the autoimmune response.
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Effect of vaccination on serotype-specific antibody responses in infants administered WC3 bovine rotavirus before or after a natural rotavirus infection. In an evaluation of WC3 bovine rotavirus (serotype 6) vaccine in infants, some subjects experienced a natural serotype 1 rotavirus infection before vaccination and others after. Therefore, the effects of both WC3 and natural rotavirus strains as either primary or boosting immunogens on serotype-specific neutralizing antibody responses could be determined. After primary natural infection (symptomatic or asymptomatic), neutralizing antibody titers were highest to serotype 1 but were consistently high to serotype 3, and low titers (greater than or equal to 20) to serotypes 2 and 4 were often detected. Previous vaccination with WC3 had little effect on the magnitude of these responses. In contrast, subjects infected with serotype 1 strains before vaccination experienced large (average, 12-fold) rises in neutralizing antibody to human serotypes 1-4 when vaccinated with WC3. Thus, although WC3 and the natural strains are distinct serotypes, their epitopes were sufficiently similar that reinfection with WC3 could boost neutralizing antibody titers to human serotypes in subjects primed by a previous natural infection.
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The agent of bacillary angiomatosis. An approach to the identification of uncultured pathogens BACKGROUND. Bacillary angiomatosis is an infectious disease causing proliferation of small blood vessels in the skin and visceral organs of patients with human immunodeficiency virus infection and other immunocompromised hosts. The agent is often visualized in tissue sections of lesions with Warthin-Starry staining, but the bacillus has not been successfully cultured or identified. This bacillus may also cause cat scratch disease. METHODS. In attempting to identify this organism, we used the polymerase chain reaction. We used oligonucleotide primers complementary to the 16S ribosomal RNA genes of eubacteria to amplify 16S ribosomal gene fragments directly from tissue samples of bacillary angiomatosis. The DNA sequence of these fragments was determined and analyzed for phylogenetic relatedness to other known organisms. Normal tissues were studied in parallel. RESULTS. Tissue from three unrelated patients with bacillary angiomatosis yielded a unique 16S gene sequence. A sequence obtained from a fourth patient with bacillary angiomatosis differed from the sequence found in the other three patients at only 4 of 241 base positions. No related 16S gene fragment was detected in the normal tissues. These 16S sequences associated with bacillary angiomatosis belong to a previously uncharacterized microorganism, most closely related to Rochalimaea quintana. CONCLUSIONS. The cause of bacillary angiomatosis is a previously uncharacterized rickettsia-like organism, closely related to R. quintana. This method for the identification of an uncultured pathogen may be applicable to other infectious diseases of unknown cause.
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An anonymous seroprevalence survey of HIV infection among pregnant women in British Columbia and the Yukon Territory We performed an anonymous seroprevalence survey of human immunodeficiency virus (HIV) type 1 infection through HIV antibody testing of blood samples from 22,512 women aged 15 to 44 years receiving prenatal care in British Columbia and the Yukon Territory from Mar. 15 to Sept. 30, 1989. Of the samples six were confirmed to be HIV positive; this yielded a crude overall seroprevalence rate of 2.7 per 10,000 pregnant women (95% confidence interval [CI] 1.0 to 5.8). All of the positive samples were from women 20 to 29 years of age; four were from Vancouver, one was from Victoria, and one was from elsewhere. The highest seroprevalence rates were among women aged 15 to 29 years in Vancouver and Victoria (7.2 and 9.4 per 10,000 pregnant women respectively). Thus, 1 in 1300 pregnant women in that age group in the metropolitan areas of British Columbia was HIV positive. Application of seroprevalence rates to the total female population in British Columbia and the Yukon Territory revealed that as many as 401 women had HIV infection in 1989. Our estimates likely represent the minimum. As a subset of women of childbearing age pregnant women are likely at lowest risk of HIV infection, and so the true number of women 15 to 44 years of age with HIV infection is probably several times higher. Our study has provided a baseline assessment and will be repeated annually to analyse trends in HIV seroprevalence among pregnant women in British Columbia and the Yukon Territory.
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Hepatic fibrin-ring granulomas in a patient with hepatitis A. Hepatic fibrin-ring granulomas were found in a 30-year-old patient with serologically confirmed hepatitis A. Other causes associated with the presence of fibrin-ring granulomas in the liver, such as Hodgkin's and non-Hodgkin's lymphoma, cytomegalovirus infection, visceral leishmaniasis, and consumption of allopurinol, were ruled out. It is suggested that hepatitis A must be included in the differential diagnosis of a patient with hepatic fibrin-ring granulomas.
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Immunology of AIDS related to psoriasis. The association of severe psoriasis with HIV infection, which dysregulates and destroys the human immune system, supports the hypothesis that psoriasis is an immunologically mediated disease. Psoriasis and Kaposi's sarcoma share angiogenesis as basic early findings and could both be caused by differential cytokine expression or responsiveness. AIDS and research models including transgenic mice offer new models in which to study the role of the immune system and specific gene products in the pathogenesis of psoriasis and other skin diseases.
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Bronchoalveolar lavage via a modified stomach tube in intubated patients with the acquired immunodeficiency syndrome and diffuse pneumonia. A simple non-bronchoscopic bronchoalveolar lavage method was used in 30 patients with the acquired immunodeficiency syndrome undergoing assisted ventilation for respiratory failure. A modified Argyle Levin stomach tube was passed via the endotracheal tube and lavage performed. The lavage was well tolerated and performed quickly and easily, required little training, and had a high degree of sensitivity (73%--a diagnosis in 22 of the 30 cases).
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High incidence of viral hepatitis among American missionaries in Africa. Protestant missionaries (n = 360) serving in sub-Saharan Africa between 1967-1984 were studied to determine the risk of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection. Personnel were serologically screened for antibody to both the hepatitis A virus (anti-HAV) and the surface antigen to the hepatitis B virus (anti-HBs) prior to departure, periodically during service abroad, and upon completion of their African tour. Rates of seroconversion were used as measures of the incidence of infection. Prior to service, 16% of the staff had anti-HAV and 3% had anti-HBs; post-service rates were 42% and 26%, respectively. Over 90% of the staff with greater than 20 years of service were seropositive for anti-HAV. For both viruses, the infection rate was highest during the first 1-2 years of service, when 28% of those susceptible to HAV and 11% of those susceptible to HBV became infected. Over the next decade, the median annual attack rate was 5.4% for HAV and 4.2% for HBV. Differences in the missionary HBV infection rate among the various African nations served tended to reflect differences in the magnitude of chronic HBV carriage among indigenous population groups. We conclude that missionaries to sub-Saharan Africa are at enhanced risk of both HAV and HBV infection, and that all should receive passive immunization with immune globulin and active immunization with hepatitis B vaccine.
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Itraconazole in opportunistic mycoses: cryptococcosis and aspergillosis. Striking results were obtained with oral itraconazole therapy in two opportunistic mycoses. Of 28 patients with cryptococcal meningitis, 18 achieved complete responses, including 16 of 24 patients with acquired immunodeficiency syndrome. Other manifestations of cryptococcosis were similarly responsive. In aspergillosis 12 of 15 patients responded, including 8 of 10 immunocompromised hosts. These patients included those with invasive pulmonary disease (4/5), skeletal disease (2/2), pleural disease (1/2), and pericardial, sinus, mastoid, hepatosplenic, or nail disease (1/1). These results with itraconazole compare favorably to conventional (parenteral) therapy, and toxicity was minimal. This suggests that comparative trials are now in order.
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Are stressful life events risk factors for herpes zoster? To determine if psychologically stressful life events are risk factors for herpes zoster, we conducted a case-control study of zoster and self-reported recent negative life events and major changes in spousal relationships. The subjects were 101 healthy community-dwelling cases of zoster and 101 healthy controls matched for age, sex, and race and generated by random digit dialing. The Geriatric Scale of Recent Life Events was administered to case and control subjects, and additional questions were asked regarding the perception of the life event. The results showed that case subjects experienced negative life events significantly more often than subjects in the control groups in the 2 months before zoster onset by analysis of discordant pairs (26 versus 10, odds ratio 2.60, 95% confidence interval [CI] 1.13, 6.27, P = .012), 3 months before (29 versus 11, odds ratio 2.64, 95% CI 1.20, 6.04, P = .007), or 6 months before (35 versus 16, odds ratio 2.00, 95% CI 1.04, 3.93, P = .012). The mean number of total life events was significantly higher in cases at 6 months before zoster (case means = 2.64, control means = 1.82, P = .008), but there were no significant differences at 2, 3, or 12 months before. There were no significant differences between case subjects and control subjects for spousal events, or any given single life event. In conclusion, we found that whereas patients with herpes zoster experienced the same kinds of life events in the year preceding the illness as did control subjects, recent events perceived as stressful were significantly more common among patients with zoster.
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Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect.
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An analysis of the economic impact of HIV infection among patients at Mama Yemo Hospital, Kinshasa, Zaire. In a prospective study of adult admissions to the Department of Internal Medicine at Mama Yemo Hospital, Kinshasa, Zaire in late 1988, 129 women and 122 men were screened for HIV infection. Fifty per cent were found to be seropositive, with half of the seropositives meeting the World Health Organization (WHO) clinical AIDS definition. The HIV seropositives had a mortality rate of 50%, which was significantly higher (P = 0.004) than the 30% mortality rate seen in the seronegative group. Direct costs during hospitalization did not differ ($60.30 for HIV seropositives, $56.50 for HIV seronegatives), but pre-hospitalization expenses were significantly higher in the HIV-seropositive group ($170 for HIV seropositives, $110 for HIV seronegatives). Years of productive life lost due to death were also significantly higher for HIV seropositives versus HIV seronegatives (30.6 versus 21.3 years; P = 0.0007), and 73% of the premature mortality in the study population was attributable to HIV infection.
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AIDS following mother-to-child transmission of HIV-2. Mother-to-child infection with HIV-2 is thought to be rare, and there have been few previous reports of transmission by this route. Reports of morbidity associated with HIV-2 infection in children are also rare. We describe eight children born to mothers who were infected with HIV-2; five developed AIDS, and three were still seropositive at 17-49 months of age. The only apparent route of HIV-2 transmission was from mother to child, except for one child who had been transfused. Three of the children with AIDS died, all having decreased CD4+ lymphocytes and mitogen responses. Further studies are needed to determine the prevalence and natural history of mother-to-child transmission of HIV-2.
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The role of human immunodeficiency virus infection in pneumococcal bacteremia in San Francisco residents. Human immunodeficiency virus (HIV) is an important risk factor for invasive pneumococcal disease, but information on clinical course and infecting serotypes is limited. To help develop strategies to reduce the morbidity due to invasive pneumococcal disease, episodes of pneumococcal bacteremia were identified by retrospective review of microbiology records (November 1983-November 1987) at 10 San Francisco hospitals and, for patients 20-55 years old living in San Francisco, HIV antibody status was determined by review of medical records. Pneumococcal isolates from one hospital were serotyped. Of 294 patients with pneumococcal bacteremia identified, 32 (11%) had AIDS at the time pneumococcal bacteremia was diagnosed and another 43 (15%) were HIV-infected but did not have AIDS; 12 HIV-infected patients developed AIDS after the episode of pneumococcal bacteremia. The rate of pneumococcal bacteremia in AIDS patients was estimated to be 9.4/1000 patient-years. Serotypes of 27 (82%) of 33 pneumococcal isolates from HIV-infected patients and 107 (90%) from 119 patients without known HIV infection were among the 23 serotypes included in the currently available polysaccharide vaccine. The rate of pneumococcal bacteremia is approximately 100-fold greater in AIDS patients in San Francisco than rates reported before the AIDS epidemic, but more than half the episodes of pneumococcal bacteremia in HIV-infected patients occurred in patients without AIDS. Data on pneumococcal serotypes causing invasive disease in HIV-infected patients suggest that the current pneumococcal vaccine, if effective in this population, could provide significant protection against pneumococcal disease.
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Measles in Israel, the West Bank, and Gaza: continuing incidence and the case for a new eradication strategy. Measles continues to occur in epidemic waves in Israel, Gaza, and the West Bank, causing morbidity and mortality. In Israel, immunization of infants against measles began in 1967, and 90% had been immunized by the mid-1980s. In Gaza and the West Bank, where immunization of infants against measles began in 1973 and 1976, respectively, the immunization rate reached 75% in the late 1970s and increased to greater than 90% in the 1980s. Measles epidemics, which previously had occurred in 5- to 7-year cycles, occurred every 2-4 years in the 1980s and affected individuals who were older than those affected in previous years. Israel's commitment to eradicating measles by 1992 will require a substantially expanded immunization program in comparison with the traditional program that requires immunization of infants alone. The benefits of several alternative immunization strategies considerably exceed their costs. A new, two-dose immunization will be needed as a minimal strategy, and a campaign for administering booster doses to school-aged children may be required as well to achieve control and eradication of measles. Measles is a serious but preventable public health problem; appropriate strategies must be devised by national and international public health officials to control the disease in developing and developed countries.
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Herpes simplex virus hepatitis in pregnancy. Two patients successfully treated with acyclovir. Two cases of herpes simplex virus hepatitis in pregnancy are presented. Each case was characterized by extremely high serum aminotransferase levels with minimal bilirubin elevation. In both cases, liver biopsy was instrumental in arriving at the diagnosis. In addition, computed tomography showed a radiographic appearance of the liver not characteristically seen in other hepatic disorders of pregnancy. A high index of suspicion in the second case led to early recognition and treatment. Despite the presence of fulminant liver failure and evidence of herpes encephalitis in the other case, institution of therapy with acyclovir was associated with complete recovery in both patients. The present cases are compared and contrasted with the literature. The incidence of two cases within a 6-month period suggests that herpes simplex virus hepatitis in pregnancy may occur more frequently than previously reported.
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Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects. Between June 26, 1985, and Feb. 24, 1989, 101 seropositive pregnant women and 129 seronegative pregnant women from the same prenatal clinics in Brooklyn and the Bronx were recruited into a prospective study of human immunodeficiency virus infection in pregnant women and their offspring. This report details the course of pregnancy and short-term neonatal outcomes of 91 seropositive women and 126 seronegative women who gave birth during the study period. Seropositive mothers were significantly more likely to have sexually transmitted diseases (17.6% vs 7.1%, p = 0.017) and medical complications (43.0% vs 25%, p = 0.006) during pregnancy. No other obstetric complications (e. g., chorioamnionitis, endometritis, toxemia, or placental problems) were associated with serologic status. After controlling for confounding variables (drug use, tobacco use, age of mother, and clinic), we found that the mother's serologic status was not significantly associated with birth weight, gestational age, head circumference, or Apgar scores among live infants. For example, after adjustment on confounders we found that children born to seropositive mothers weighed about 7 gm more than children of seronegative mothers (95% confidence interval, -180 to 194 gm). We conclude that in this population human immunodeficiency virus infection has little demonstrable impact on the status at birth of live neonates.
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HIV seroconversion in two homosexual men after receptive oral intercourse with ejaculation: implications for counseling concerning safe sexual practices. Seroconversion for HIV antibody occurred in two homosexual men who reported no anal intercourse for greater than or equal to 5 years and multiple episodes of receptive oral intercourse with ejaculation. Neither man reported intravenous drug use or receipt of blood products. The last antibody-negative specimen was also negative by the polymerase chain reaction and p24 antigen assays. All sexually active persons should be clearly counselled that receptive oral intercourse with ejaculation carries a potential risk of HIV transmission.
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A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.
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Early treatment with acyclovir for varicella pneumonia in otherwise healthy adults: retrospective controlled study and review. The effect of early acyclovir therapy on the course of varicella pneumonia in previously healthy adults was assessed. Medical records from five university-affiliated medical centers were retrospectively reviewed; included were all immunocompetent adults with a clinical diagnosis of primary varicella, a chest radiograph consistent with varicella pneumonia, and an arterial blood gas measurement indicating significant hypoxia. Of the 38 patients who met the study criteria, 11 had had a course of intravenous acyclovir initiated within the first 36 hours of hospitalization; the mean time from admission to initiation of therapy in this early-treatment group was 9.6 hours. The group that received early acyclovir treatment had a lower mean temperature beginning on the fifth day of hospitalization (37.0 degrees C vs. 37.7 degrees C; P = .011) and a lower mean respiratory rate beginning on the sixth day of hospitalization (21 vs. 28 respirations per minute; P = .004). Early acyclovir therapy also resulted in a significant improvement in oxygenation beginning on the sixth day of hospitalization in patients with follow-up arterial blood gas measurements (P = .035). Thus, early institution of acyclovir therapy is associated with reduction in fever and tachypnea and improvement in oxygenation in otherwise healthy adults with varicella pneumonia.
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American blood donors seropositive for human T-lymphotropic virus types I/II exhibit normal lymphocyte subsets. Recent reports have demonstrated that some lymphocyte subsets are abnormal in Japanese blood donors who are seropositive for human T-lymphotropic virus type I (HTLV-I). To determine if similar changes characterize American blood donors who are seropositive for HTLV-I/II, lymphocyte subsets were measured in 42 HTLV-seropositive and 42 HTLV-seronegative blood donors. The seronegative individuals were matched by age, race, and gender to the seropositive individuals. Peripheral blood mononuclear cells were treated with a panel of 12 monoclonal antibody pairs and then analyzed by two-color flow cytometry. No significant differences were observed between the seropositive and seronegative groups with respect to the absolute number of circulating lymphocytes or the percentages of lymphocytes belonging to the subsets assessed. These subsets included B, T, CD4, and CD8 cells and subpopulations of CD4 and CD8 cells defined by the coexpression of markers that appear (CD25, HLA-DR, CD38) or disappear (Leu 8, CD45RA) after activation. These findings indicate that HTLV-seropositive persons in the American blood donor pool do not exhibit the lymphocyte subset alterations reported for HTLV-I-seropositive blood donors in Japan.
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Cytomegalovirus-induced osteomyelitis in a patient with the acquired immunodeficiency syndrome. A 43-year-old man with AIDS had a periodontal abscess, no fever, and normal findings on funduscopic examination. Three months later, the abscess area was debrided, and histologic examination of the tissue revealed osteomyelitis of the mandible. Within the area of osteomyelitis were numerous cells with inclusions typical of cytomegalovirus (CMV) infected cells. Funduscopic examination at that time revealed extensive CMV retinitis. Osteomyelitis should be added to the list of infections caused by CMV in patients with AIDS.
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Measles incidence, vaccine efficacy, and mortality in two urban African areas with high vaccination coverage. Measles incidence, vaccine efficacy, and mortality were examined prospectively in two districts in Bissau where vaccine coverage for children aged 12-23 months was 81% (Bandim 1) and 61% (Bandim 2). There was little difference in cumulative measles incidence before 9 months of age (6.1% and 7.6%, respectively). Between 9 months and 2 years of age, however, 6.1% contracted measles in Bandim 1 and 13.7% in Bandim 2. Even adjusting for vaccination status, incidence was significantly higher in Bandim 2 (relative risk 1.6, P = .04). Even though 95% of the children had measles antibodies after vaccination, vaccine efficacy was not more than 68% (95% confidence interval [CI] 39%-84%) and was unrelated to age at vaccination. Unvaccinated children had a mortality hazard ratio of 3.0 compared with vaccinated children (P = .002), indicating a protective efficacy against death of 66% (CI 32%-83%) of measles vaccination. These data suggest that it will be necessary to vaccinate before age 9 months to control measles in hyperendemic urban African areas.
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HIV disease: a review for the family physician. Part II. Secondary infections, malignancy and experimental therapy. The first part of this two-part article included recommendations for the initial evaluation of patients suspected of having HIV infection, the Centers for Disease Control's classification scheme for HIV disease and current recommendations for the use of zidovudine. In this second part, secondary infections and malignancy are reviewed, and various experimental therapies are briefly discussed.
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Clinical features of adenovirus enteritis: a review of 127 cases. We retrospectively analyzed the clinical features of 127 hospitalized pediatric patients whose fecal samples were positive for adenovirus (Ad) by electron microscopy during an 18-month period. Serotyping results obtained by microneutralization tests and restriction endonuclease analysis were available for 105 of 127 cases. There were 69 males and 58 females and 94% of patients were less than 4 years of age. The average body temperature was 38 degrees C rectal (range, 36.2-40.8 degrees C) with an average duration of fever of 1.6 days. The average duration of clinical illness was 8.8 days (range, 1 to 32 days). Although Ad 40 and Ad 41 were isolated in the majority of cases (59 of 105 (56%], Ad 31 was associated with 18 of 105 cases (17%). Of the 18 cases associated with Ad 31, 14 were nosocomial and associated with diarrhea. Our survey confirms the importance of fastidious enteric Ad in infantile diarrhea (Ad 40, Ad 41) and suggests that Ad 31 produces a clinical syndrome indistinguishable from that caused by Ad 40 and Ad 41. The occurrence of Ad enteritis in patients admitted for unrelated illnesses well after initial hospitalization suggests that Ad is also an important cause of nosocomial enteritis in our hospital.
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Infection of mice with lactate dehydrogenase-elevating virus destroys the subpopulation of Kupffer cells involved in receptor-mediated endocytosis of lactate dehydrogenase and other enzymes. In previous experiments in rats, we have shown that the rapid plasma clearance of a number of clinically important enzymes is due to receptor-mediated endocytosis by Kupffer cells and other resident macrophages. Others have shown that infection of mice with lactate dehydrogenase-elevating virus, a virus that proliferates in macrophages, leads to reduced plasma elimination of these enzymes. This paper integrates these two sets of experiments. Plasma elimination of intravenously injected, radioactively labeled lactate dehydrogenase M4 and mitochondrial malate dehydrogenase in mice was shown to be caused in part by uptake in liver, spleen and bone. Uptake of lactate dehydrogenase M4 by these tissues was, to a large extent, saturable and the two dehydrogenases competitively inhibited each other's clearance. These results suggest that, also in mice, these enzymes are partly cleared from plasma by endocytosis by way of a common receptor on cells (probably macrophages) from liver, spleen and bone marrow. Morphometrical data showed that normal mouse liver contains 23 x 10(6) Kupffer cells/cm3. This number was reduced to about 30% of that of controls 24 hr after infection of mice with lactate dehydrogenase-elevating virus but returned to normal within the next 9 days. The saturable component of uptake of lactate dehydrogenase M4 by liver, spleen and bone had disappeared 24 hr after infection with the virus, and did not return after the Kupffer cell population had recovered. Our findings suggest that lactate dehydrogenase M4 is, to a large extent, removed from the circulation by way of a receptor on a subpopulation of macrophages that is permissive for replication of lactate dehydrogenase-elevating virus.
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Extensive vulvar and vaginal varicella necessitating abdominal delivery. Maternal varicella occurs in fewer than five per 10,000 pregnancies in the United States. A case is reported in which markedly painful, extensive vulvar and vaginal ulcers prevented cervical examination, and cesarean section was performed with the patient under general anesthesia.
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Isolation of human T-cell lymphotropic virus type 2 from Guaymi Indians in Panama. Human T-lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukemia/lymphoma and with a chronic degenerative myelopathy. However, another major type of HTLV, HTLV-II, has been isolated only sporadically, and little is known of disease associations, transmission routes, and risk factors for HTLV-II infection. Recent studies indicate that a high percentage of certain groups of i.v. drug users and blood donors are infected with HTLV-II. Seroepidemiologic studies have found an elevated rate of seroreactivity to HTLV among Guaymi Indians from Bocas del Toro Province, Panama. To identify the cause of seroreactivity among this unique population we used HTLV-II-specific polymerase chain reaction techniques to detect HTLV genetic sequences from blood leukocytes of three seropositive Guaymi Indians. The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions. A CD4+ T-lymphocyte line established from one of these same subjects produced HTLV-II-specific proteins when tested in antigen-capture and immunoblot assays, as well as mature HTLV particles. The demonstration of HTLV-II infection in this geographically and culturally isolated Central American Indian population without typical risk factors for HTLV infection suggests that HTLV-II infection is endemic in this population and provides an important clue to potential natural reservoir for this virus.
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HIV-1 infection of lung alveolar fibroblasts and macrophages in humans. We have studied the infected cell populations in the lungs of four human immunodeficiency virus type 1 (HIV-1) seropositive patients suffering from lymphocytic alveolitis or lymphocytic interstitial pneumonitis. Adherent cells were obtained by bronchoalveolar lavage (BAL) and were analyzed by various technical approaches. The cells considered here were alveolar macrophages and fibroblasts, and could be clearly identified morphologically and by the expression of specific cell-surface markers using monoclonal antibodies. The presence of HIV-1 in both of these cell types was established by serological, virological, and molecular procedures. Our results show that alveolar macrophages and fibroblasts are naturally infected in the lungs of HIV+ patients. Both cell types express the CD4 receptor molecule, in contrast to skin fibroblasts which are negative. Alveolar macrophages and fibroblasts thus may act as eventual HIV-1 reservoirs in vivo, and are probably involved in the induction of inflammatory reactions because they are targets for CD8 cytotoxic T lymphocytes (CTL).
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Infectious mononucleosis in older adults. Infectious mononucleosis as a manifestation of primary Epstein-Barr virus infection occurs uncommonly in adults over age 40. While fever is almost universal, older patients with the disease often present without lymphadenopathy, pharyngitis, splenomegaly, lymphocytosis or atypical lymphocytes. Jaundice and hepatomegaly occur more commonly in older patients than in adolescents and create diagnostic confusion. Often, infectious mononucleosis in this age group is confused with lymphoma, leukemia or biliary obstruction, or is classified as "fever of unknown origin.".
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Disseminated strongyloidiasis with central nervous system involvement diagnosed antemortem in a patient with acquired immunodeficiency syndrome and Burkitts lymphoma. A 45-year-old man presented with central nervous system involvement as the initial manifestation of disseminated infection with Strongyloides stercoralis. Several concurrent clinical factors contributed to this event, all related to the patient's immunosuppression, including high-grade lymphoma, corticosteroid therapy, and acquired immunodeficiency syndrome. This is only the third case of CNS involvement in disseminated strongyloidiasis diagnosed antemortem.
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Comparison of Southern transfer hybridization and dot filter hybridization for detection of cervical human papillomavirus infection with types 6, 11, 16, 18, 31, 33, and 35. A commercial dot filter hybridization kit (Virapap Kit) was compared with Southern transfer hybridization for the detection of seven types of human papillomavirus (HPV) in cervical specimens from 450 consecutive females attending a sexually transmitted diseases clinic. In comparison with Southern transfer hybridization, performed with the same probes used in the dot filter kit, the sensitivity, specificity, and positive and negative predictive values of dot filter hybridization were 90%, 94%, 74%, and 98%, respectively. Among patients with cervical cytologic dysplasia, HPV DNA was detected in 44% by dot filter hybridization and in 35% by Southern transfer hybridization. Although 26% of specimens positive by dot filter hybridization were not confirmed by Southern transfer hybridization, cervical dysplasia was detected in 5 (25%) of 20 with HPV DNA detected by dot filter hybridization alone, compared with 25 (8%) of those with no definitive evidence of HPV by either method (P = 0.009) and with 16 (30%) of 53 with HPV DNA detected by both methods (P = 0.7). The kappa statistic for interobserver and intraobserver reproducibility for interpretation of blots was similar for the two methods. The dot filter hybridization method evaluated appears to be a satisfactory alternative to Southern transfer hybridization for detection of HPV DNA.
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A rhesus monkey model for sexual transmission of a papillomavirus isolated from a squamous cell carcinoma. Recently we molecularly cloned and characterized a papillomavirus from a lymph node metastasis of a primary penile carcinoma found in a rhesus monkey; this virus species, rhesus papillomavirus type 1 (RhPV-1), is similar to oncogenic human papillomaviruses (HPVs), such as HPV-16 or HPV-18, in that the RhPV-1 DNA was found to be integrated in the tumor cell DNA. To compare the sexual transmission and oncogenic nature of RhPV-1 with these HPVs, we undertook an extensive retrospective study of a group of rhesus monkeys whose sexual mating and offspring histories were known. These animals had mated directly with the index male mentioned above or were secondarily exposed to this virus through intermediate sexual partners. This study combines cytological, histopathological, and several complementary hybridization and DNA amplification techniques on multiple tissue samples to demonstrate the sexually transmitted nature of RhPV-1. The oncogenic potential of RhPV-1 is suggested in several of the infected animals by the presence of various degrees of neoplasia including squamous cell cancer of the cervix.
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Transbronchial biopsies in children after heart-lung transplantation. Sixty transbronchial biopsies have been performed in eight children after heart-lung transplantation. The selection of fiber-optic bronchoscope or a small (4 mm; 30 cm) rigid bronchoscope was made according to the size of endotracheal tube required at surgery. If the endotracheal tube was size 7.5 or greater, a fiber-optic bronchoscope was used, whereas if the endotracheal tube size was below 7, a rigid bronchoscope was used. For the diagnosis of lung rejection, the histology of biopsies revealed a sensitivity of 91% and specificity of 69% (similar to the result in adults). The histology also distinguished lung infection from rejection. Complications included three pneumothoraces and two clinically significant episodes of hemorrhage, one of which led to a cardiorespiratory arrest, which may have been caused by hypoxia. As a result, arterial oxygen saturation is now monitored during the procedure using a pulse oximeter.
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Impact of cytomegalovirus infection on organ transplant recipients. Cytomegalovirus (CMV) is the single most important infectious agent affecting recipients of organ transplants, with at least two-thirds of these patients having CMV infection 1-4 months after transplantation. Latently infected allografts are the major exogenous source of CMV infection in transplant recipients, although leukocyte-containing blood products can also transmit the virus. Three patterns of CMV infection are recognized: primary infection, reactivation infection, and superinfection. Primary infection has the greatest clinical impact. The clinical effects of CMV infection include infectious disease syndromes such as pneumonia and chorioretinitis; an immunosuppressed state that predisposes to potentially lethal opportunistic infection; and the initiation of a process that can result in allograft injury. Progress has been made in controlling CMV infection; hyperimmune anti-CMV globulin and certain antiviral drugs appear promising for prophylaxis, and the combination of hyperimmunoglobulin and ganciclovir appears promising for therapy.
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Lymphomatoid granulomatosis presenting as ulcerodestructive gastrointestinal tract lesions in patients with human immunodeficiency virus infection. A new association. We describe cases of severe odynophagia, extensive oral ulcerations, and bowel perforation in patients with human immunodeficiency virus infection that were caused by lymphomatoid granulomatosis. Such presentations in human immunodeficiency virus-infected individuals are usually ascribed to other causes and may be incorrectly treated on an empiric basis. In addition, deep tissue specimens obtained at the margin of ulcerative lesions are often necessary for definitive diagnosis. We review our limited treatment experience with zidovudine, interferon alfa, and H2 blockers in our patients. Based on the markedly increased frequency in which lymphomatoid granulomatosis is being diagnosed at our institution in the post-human immunodeficiency virus era, we postulated an association between these two entities.
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Epidemiology of human immunodeficiency virus infection in women in the United States. From 1981 to 1989, the number of women with HIV infection and acquired immunodeficiency syndrome (AIDS) increased rapidly. Most women were infected through intravenous drug use or sexual contact with an infected man. Most children were infected through mother-to-infant transmission during pregnancy or delivery. Available data suggest that the rapid increase in the number of women with AIDS will continue for at least the next few years.
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High infectious morbidity in pregnant women with insulin-dependent diabetes: an understated complication. Patients with insulin-dependent diabetes are prone to infection, possibly related to poor metabolic control. Relative immune deficiency exists in pregnancy. We hypothesized that pregnant patients with insulin-dependent diabetes are at an increased risk for infection and that infection is related to poor glycemic control. We matched 65 pregnant women with insulin-dependent diabetes to 65 nondiabetic pregnant controls. At least one episode of infection before delivery occurred in 83% of the women with insulin-dependent diabetes (26% in control group). The rate of postpartum infection was five times higher in the group with insulin-dependent diabetes and they were susceptible to more kinds of infections. Although there was no overall difference among the indices of glycemic control, hemoglobin A1 obtained before the infection was higher than during infection. We conclude that a high rate of infection exists in pregnant women with diabetes; infection and poor glycemic control may be associated, but it is unclear whether improvement in metabolic control will reduce this high infection rate.
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Human papillomavirus infections of the genital tract. Infection of the genital tract by HPV is a sexually transmitted disease of increasing prevalence. The association of HPV infection with genital tract malignancies is of great concern, and further studies are needed to clarify this association. Few investigators believe at this time that proof of a direct causative role exists for HPV in these cancers, but indirect evidence of such a role is abundant. There are many clinical forms of HPV infection of the genital tract, and few clinicians can easily recognize them all. Treatment of condyloma acuminatum is difficult and frustrating. Cryotherapy with liquid nitrogen is the safest and most effective therapy for most forms of condyloma acuminatum. Recurrence of condyloma acuminatum is common with all presently used forms of therapy, probably owing to latent HPV infection in normal-appearing skin. No form of treatment is ideal for all forms of condyloma acuminatum, but without continued efforts to find better therapeutic modalities and preventative measures, the epidemic of genital HPV infection will continue unchecked.
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The use of in situ hybridization to show human papillomavirus deoxyribonucleic acid in metastatic cancer cells within lymph nodes. Southern blot hybridization has been used to identify human papillomavirus types in both primary tumors and lymph node metastases. However, this technique requires fresh-frozen tissue and is incapable of localizing deoxyribonucleic acid sequences to specific cell types in the tumor sample. In contrast, in situ hybridization precisely locates viral sequences within tumor cells while preserving cellular architecture. Further, in situ hybridization requires only small samples of formalin-fixed, paraffin-embedded tissues. Five lymph nodes (from four patients) containing metastatic cervical squamous tumor cells (identified with hematoxylin and eosinophil staining) were analyzed with in situ hybridization techniques with human papillomavirus type 16 deoxyribonucleic acid probes labeled with sulfur 35. The primary cervical cancer from all four patients had been shown to contain human papillomavirus type 16 sequences by Southern blot. Three specimens from two patients clearly showed the presence of human papillomavirus type 16 sequences within the nuclei of metastatic tumor cells, whereas two specimens were nondiagnostic most likely as a result of the small volume of cancer relative to the size of the lymph node. This information indicates that it is the tumor cells themselves that contain viral deoxyribonucleic acid and provides additional evidence linking human papillomavirus with cervical carcinogenesis.
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Increasing incidence of varicella hospitalizations in United States Army and Navy personnel: are today's teenagers more susceptible? Should recruits be vaccinated? Hospital records for 10,687 United States Army and Navy adult varicella (chickenpox) admissions were reviewed. Annual hospital admission rates for varicella increased more than fourfold in the active-duty army during 1980 to 1988 and more than 18-fold among active-duty navy enlisted personnel during 1975 to 1988. Fifty-seven percent of varicella admissions occurred in the most junior military members, aged 17 to 20. More than half of the total varicella admissions occurred in personnel with less than a year of military service. Multivariate analysis of the navy data confirmed increasing time-related trends of risk, suggesting a national temporal trend of increased varicella susceptibility in US teenagers and young adults. Administering a safe and effective varicella vaccine to army and navy recruits could prevent more than 7260 hospital-bed days during the first year of use.
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Sensitivity and specificity of various morphological features of cervical condylomas. An in situ hybridization study. Fifty-seven cervical biopsy specimens or endocervical curettings showing condyloma, changes suggestive of condyloma, or no changes of condyloma were analyzed for presence of nuclear atypia (nuclear enlargement and irregularity in superficial epithelium), presence of multinucleated cells, and presence of perinuclear cytoplasmic clearing in superficial squamous epithelium. The findings were correlated with results of in situ hybridization with biotin-labeled human papillomavirus DNA probes. Moderate nuclear atypia was significantly more specific than perinuclear cytoplasmic clearing and 100% sensitive for predicting cases positive for human papillomavirus. Of the various morphological features analyzed, perinuclear cytoplasmic clearing had the lowest specificity for predicting positive results on in situ hybridization.
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No evidence for human T-cell leukemia virus type I or human T-cell leukemia virus type II infection in patients with multiple sclerosis. The involvement of human T-cell leukemia viruses (HTLVs) in the pathogenesis of 18 Hungarian patients with multiple sclerosis was investigated. No antibody to HTLVs could be detected in any of the patients. Furthermore, using polymerase chain reaction under highly sensitive conditions, neither HTLV-I DNA nor HTLV-II DNA could be noted in peripheral blood lymphocytes of the patients. Our data do not support a causal association of HTLV-I or HTLV-II with multiple sclerosis.
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Sexually transmitted diseases and human immunodeficiency virus infection among women with pelvic inflammatory disease. Both human immunodeficiency virus infections and pelvic inflammatory diseases are sexually acquired illnesses of great consequence to women. This study was undertaken to determine if women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, were at high risk to be infected with human immunodeficiency virus and if human immunodeficiency virus infections altered their hospital course. One hundred ten women hospitalized with pelvic inflammatory disease in Brooklyn (in a hospital in which 2% of parturients are human immunodeficiency virus seropositive) agreed to human immunodeficiency virus testing; 15 (13.6%) were found to be seropositive. Seropositive women were significantly more likely to have an admission white blood cell count less than 10,000/mm3 (p = 0.001). Human immunodeficiency virus seropositivity was not associated with a higher frequency of other sexually transmitted diseases although there was a trend toward more cases of syphilis among human immunodeficiency virus-infected women. Similarly, although there was no significant difference in rates of operative intervention (26.6% among seropositive and 8.4% among seronegative; p = 0.058), there was a trend toward more surgery among those who were human immunodeficiency virus infected. Women hospitalized with pelvic inflammatory disease, in a community endemic for human immunodeficiency virus, are at high risk for human immunodeficiency virus infection. More research is needed to verify a trend toward more refractory infections among human immunodeficiency virus-infected women.
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Occurrence of groups A and B of respiratory syncytial virus over 15 years: associated epidemiologic and clinical characteristics in hospitalized and ambulatory children. Over 15 years respiratory syncytial virus (RSV) isolates from 1209 hospitalized and ambulatory children were examined for strain group and in a subset for subgroup to determine the associated epidemiologic and clinical characteristics. Three patterns of yearly outbreaks existed: (1) strong predominance of group A strains (9 years with 83%-100% A strains), (2) relatively equal proportions of group A and B strains (4 years), and (3) strong predominance of group B strains (78%-85%) in 2 years, separated by a decade. The first pattern of highly dominant A strains occurred in cycles of 1 or 2 consecutive years with a single intervening year in which B strains were greater than or equal to 40% of the isolates. Subgroups A1 and A2 predominated, while B2, 3, and 4 occurred almost equally. A greater clinical severity for Group A strains was suggested by children with group A infections requiring intensive care significantly more often (15.4 vs. 8.3%, P = .008). Further, strongly dominant A strain years were associated with higher proportions of RSV admissions requiring intensive care (16.6% vs. 5.5%, P less than .01). Strains of subgroups A2 and B4 were more frequently found in hospitalized patients and A1 in outpatients, and the 2 years with the highest rates of intensive care admissions were those in which subgroup A2 dominated.
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Evaluation of WC3 rotavirus vaccine and correlates of protection in healthy infants. The safety, immunogenicity, and efficacy of WC3 rotavirus vaccine was evaluated in a double-blind, placebo-controlled trial of healthy infants 2-12 months of age; 103 received one dose of vaccine and 103 received placebo. Vaccination appeared to be safe and induced an antibody response (WC3 neutralizing antibody) in 97% of vaccinees. Only 9 (9%) of these, however, produced antibody to human rotavirus serotypes; at least 7 of the 9 were naturally infected before vaccination. Neither the number of symptomatic episodes of rotavirus diarrhea (21 vs 25) nor the number of moderate to severe rotavirus illnesses (9 vs. 15) was significantly different in vaccine or placebo recipients, respectively, during a predominantly serotype 1 rotavirus season. A slight but significant decrease in mean symptom score was detected in vaccine recipients. Despite an overall lack of efficacy, protection could be correlated to previous rotavirus infection, high levels of WC3 neutralizing antibody, and preexisting (maternal) serotype 1 neutralizing antibody with a titer greater than or equal to 30.
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Primary central nervous system lymphoma in patients with and without the acquired immune deficiency syndrome. A retrospective analysis and review of the literature. Twenty-two cases of PCL were reviewed, in which 9 patients had AIDS and 13 did not. A review of the literature identified 247 cases of AIDS-related PCL. Differences between patients with AIDS and immunocompetent PCL were noted in our series. AIDS-related PCL when compared to non-AIDS PCL in our series has the following notable clinical features: 1) significantly younger age at presentation, median age 34 versus 59 years; 2) significantly higher incidence of B symptoms, 44% versus 8%; 3) worse median performance status at presentation, 3 versus 1; and, 4) shorter median survival, 3 versus 10 months. Differences in performance status and survival, however, were not significant. AIDS-related PCL is further characterized by frequent (44%) ring-enhancing mass lesions on head CT scan, a finding that makes it clinically difficult to distinguish from toxoplasmosis. Median survival appears to be improved in the absence of opportunistic infection at time of diagnosis of PCL, 6 versus 2 months. The therapeutic approach to patients with PCL, with and without AIDS, is variable. Combined modality therapy may improve the survival in patients with non-AIDS PCL. Therapy for patients with AIDS-related PCL is tailored to the status of the individual and it is, therefore, difficult to make comparisons to non-AIDS PCL patients. AIDS patients are often too ill to tolerate aggressive surgery or systemic treatment and in this instance, radiotherapy alone may be an acceptable alternative. Nonetheless, overall survival for patients with AIDS-related and non-AIDS PCL remains poor.
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Infectious mononucleosis complicated by lingual tonsillitis. Although upper airway obstruction and superimposed infection are well-known complications of infectious mononucleosis, lingual tonsillitis in this context has not been mentioned in the literature. We describe a case of acute bacterial lingual tonsillitis with airway obstruction complicating infectious mononucleosis. The role of the base of tongue region in the pathophysiology of infectious mononucleosis is discussed.
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Five year prospective study of HIV infection in the Edinburgh haemophiliac cohort OBJECTIVE--To identify measures of immune state that reflect the course of HIV related disease in order to predict deterioration of symptoms and assess response to treatment. DESIGN--Five year longitudinal clinical and laboratory study. SETTING--Regional haemophilia centre, university virology laboratory, and Medical Research Council laboratory. PATIENTS--32 Patients with haemophilia A exposed to a single batch of HIV contaminated factor VIII concentrate from the Scottish National Blood Transfusion Service in 1984 who were followed up regularly in Edinburgh (31) or abroad (one). MAIN OUTCOME MEASURES--Counts of circulating T cell subsets (CD4 and CD8); plasma beta 2 microglobulin, neopterin, and IgA concentrations; and delayed type hypersensitivity to multiple skin test antigens. RESULTS--18 Patients who seroconverted after exposure had received significantly more contaminated factor VIII than the 14 who did not (mean 43 (range 9-109) v 15 (3-30) phials, p less than 0.01). The two groups were not distinguishable by other criteria before exposure. The group that seroconverted subsequently showed a progressive fall in mean circulating CD4 lymphocytes and an increase in plasma beta 2 microglobulin and neopterin concentrations. From 1987 patients in this group also showed an increase in mean circulating CD8 lymphocytes and in plasma IgA concentration, neither of which was seen in patients who did not seroconvert. Patients with HIV antibody who developed Centers for Disease Control category IV symptoms within five years after infection showed more extreme changes in all measures, except CD8 lymphocyte count, than those whose symptoms remained in categories II and III. Skin test reactivity declined to barely detectable levels in all patients positive for HIV antibody. CONCLUSIONS--Serial estimates of circulating CD4 lymphocytes and of plasma beta 2 microglobulin concentration are the most reliable measures of disease progression; of these, beta 2 microglobulin concentration seems to be the better predictor of impending serious symptoms. High IgA concentrations reflect rather than predict disease state. Individual variation in most measures is such that a wide range of measurements should be used in assessing the effects of trial treatment in HIV infected patients without symptoms.
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Early ribavirin treatment of respiratory syncytial viral infection in high-risk children. A 3-year prospective, blinded, multicenter study was done to assess the efficacy of early ribavirin intervention in mild respiratory syncytial virus illness in children with bronchopulmonary dysplasia or with congenital heart disease. A cohort of 178 children younger than 36 months of age with bronchopulmonary dysplasia or congenital heart disease were followed. Forty-seven infants whose respiratory syncytial virus infection resulted in mild symptoms of less than or equal to 72 hours' duration received ribavirin (n = 20) or water placebo aerosol (n = 27) either in a hospital or at home. Outcome measures included respiratory and analog score, room air oxygen, saturation, and oxygen flow needed to maintain saturation at greater than or equal to 91%. No difference in age, gender, family size, passive smoking, baseline oxygen saturations in room air, or duration of symptoms before treatment was found between groups. After 3 days of therapy, ribavirin produced a greater rate of improvement of analog scores (p = less than or equal to 0.001), lower oxygen requirements (p = 0.01), and higher oxygen saturation (p = 0.01). Respiratory scores and total hospital days did not differ significantly between the groups. Treatment failure occurred in 2 of 20 children (10%) in the ribavirin group versus 5 of 27 children (18%) in the placebo group, a nonsignificant difference. No child required assisted ventilation or had an adverse reaction. We conclude that early ribavirin therapy may help to reduce morbidity from respiratory syncytial virus infection in high-risk young children.
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Study design considerations for ribavirin: efficacy studies. Five placebo-controlled double-blind studies, each including approximately 30 subjects, have addressed the question of the effect of aerosolized ribavirin on the course of RSV lower respiratory infection in infancy. The fact that each was able to establish a beneficial effect despite the small number of subjects studied is convincing evidence that such an effect exists. The studies from Rochester using oximetry and an analog illness severity scale indicate that this effect is both statistically significant and clinically relevant. These tools are reliable and easily applicable measures for multicenter studies when illness severity is selected as an outcome measure. Characteristics that should be taken into consideration when assigning experimental groups include age, sex, a history of prematurity or underlying conditions and arterial oxygen saturation. Future studies will address additional questions about the efficacy of ribavirin, such as its role in critically ill children, the economic benefits of its use in terms of duration of hospitalization, the usefulness of early treatment of RSV disease in high risk infants, and the impact of treatment on long-term consequences of RSV infection. These studies may require outcome variables and subject selection strategies different from those used in earlier studies.
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A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia BACKGROUND. We identified a motile, curved, gram-negative bacillus as the cause of persistent fever and bacteremia in two patients with symptomatic human immunodeficiency virus infection. The same organism was subsequently recovered from a bone marrow-transplant recipient with septicemia and from two immunocompetent persons with week-long febrile illnesses. All the patients recovered after antimicrobial therapy. METHODS AND RESULTS. Primary cultures of blood processed by centrifugation after blood-cell lysis yielded adherent, white, iridescent, morphologically heterogeneous colonies in 5 to 15 days. Subcultures grew in four days on chocolate, charcoal-yeast extract, or blood agar. The organisms stained weakly with safranin and were not acid-fast. Fluorescent-antibody tests for legionella and francisella were negative. Biochemical reactivity was minimal and difficult to ascertain. Agar-dilution testing revealed in vitro susceptibility to most antimicrobial agents tested. The cellular fatty acid composition of the isolates was similar, resembling that of Rochalimaea quintana or brucella species, but not Helicobacter pylori or species of campylobacter or legionella. As resolved by gel electrophoresis, cell-membrane preparations of all isolates contained similar proteins, with patterns that differed from that of R. quintana. Patterns of digestion of DNA from all isolates by EcoRV restriction endonuclease were virtually identical and also differed from that of R. quintana. On immunodiffusion, serum from one convalescent patient produced a line of identity with sonicates of all five isolates. CONCLUSIONS. This pathogen may have been unidentified until now because of its slow growth, broad susceptibility to antimicrobial agents, and possible requirement of blood-cell lysis for recovery in culture. It should be sought as a cause of unexplained fever, especially in persons with defective cell-mediated immunity.
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Type-specific antigens for serological discrimination of HTLV-I and HTLV-II infection. 55 HTLV-I (human T-cell lymphotropic virus) and 45 HTLV-II carriers, confirmed by HTLV-type specific polymerase chain reaction (PCR), were distinguished by western blot assays with recombinant HTLV I or II envelope glycoproteins. Recombinant protein (RP) B1 contains aminoacids 166-201 from HTLV-I exterior glycoprotein gp46 and was reactive with HTLV-I samples only. RP-IIB, which contains aminoacids 96-235 from HTLV-II exterior glycoprotein gp52, was reactive with all HTLV-II samples. 39 patients (86.6%) had high reactivity by densitometry. Of 55 HTLV-I samples, 35 (65.5%) had antibody reactivity to RP-IIB, but only 1 (1.8%) had high reactivity by densitometry. RP B1 and IIB western blot assays may replace the PCR test in diagnosis of HTLV infection.
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Pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody in murine experimental viral myocarditis. The pharmacokinetics of indium-111-labeled antimyosin monoclonal antibody Fab were investigated with use of murine experimental viral myocarditis as a model. The biodistribution of indium-111-labeled antimyosin antibody Fab on days 3, 5, 7, 14, 21 and 28 after encephalomyocarditis virus inoculation demonstrated that myocardial uptake increased significantly on days 5, 7 and 14 (maximum on day 7) in infected versus uninfected mice (p less than 0.001). In vivo kinetics in infected mice on day 7 demonstrated that the heart to blood ratio reached a maximum 48 h after the intravenous administration of indium-111-labeled antimyosin Fab, which was considered to be the optimal time for scintigraphy. The scintigraphic images obtained with indium-111-labeled antimyosin Fab demonstrated positive uptake in the cardiac lesion in infected mice. The pathologic study demonstrated that myocardial uptake correlated well with pathologic grades of myocardial necrosis. High performance liquid chromatography revealed the presence of an antigen-antibody complex in the circulation of infected mice after the injection of indium-111-labeled antimyosin Fab. This antigen bound to indium-111-labeled antimyosin Fab in the circulation might be whole myosin and this complex may decrease myocardial uptake and increase liver uptake. It is concluded that indium-111-labeled antimyosin monoclonal antibody Fab accumulates selectively in damaged heart tissue in mice with acute myocarditis and that indium-111-labeled antimyosin Fab scintigraphy may be a useful method for the visualization of acute myocarditis.
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Nosocomial bacteremias in measles. The purpose of this study was to determine whether nosocomial bacteremias occurred more frequently in patients admitted with severe measles compared with general pediatric admissions. In a retrospective survey of 977 blood culture reports during a 4-year period, 1985 to 1988, the incidence of nosocomial bacteremias in patients with measles was found to be on the average of 3.37/100 admissions/year, approximately 6 times that of general pediatric patients (0.57). Gram-negative organisms (predominantly Klebsiella and Salmonella species) accounted for 86.5% of all isolates from measles patients, with 23% of these being multiply antibiotic-resistant. All the isolates from the general patients were fully susceptible to antibiotics. The duration of hospitalization was more than doubled in both groups of affected patients. The onset of hospital-acquired bacteremias occurred on an average of 11.2 days after admission in the patients with measles and 20.5 days in the general patients. Our findings revealed that nosocomial bacteremias occurred with greater frequency in patients with measles and contributed to the morbidity of these patients.
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Disseminated, nonmeningeal gastrointestinal cryptococcal infection in an HIV-negative patient. Gastrointestinal cryptococcosis is extremely rare, especially in patients with no involvement of the central nervous system. We describe a 63-yr-old man undergoing prednisone therapy for chronic hepatitis and cirrhosis who presented with peritonitis, colitis, and skin lesions. Pathological studies revealed necrosis and numerous cryptococcal organisms in the colon, omentum, and skin, and cultures yielded Cryptococcus neoformans. The patient died of multisystem organ failure following emergency exploratory surgery performed when he had onset of symptoms of a bowel perforation after an endoscopic biopsy. Clinicians should be aware that gastrointestinal cryptococcosis can occur in the absence of infection of the central nervous system or lungs, and that it may affect relatively healthy patients who are immunocompromised because of splenectomy, chronic liver disease, or steroid therapy.
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