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Central retinal artery obstruction in herpes zoster ophthalmicus and cerebral vasculopathy. We present a case of acute central retinal artery obstruction in association with Herpes zoster ophthalmicus and delayed cerebral vasculopathy. Retinal vascular obstruction is rare in zoster, and its occurrence during postherpetic cerebral vasculopathy has not been reported previously to our knowledge. The syndrome of delayed cerebral vasculopathy is discussed as is its possible relationship to central retinal artery obstruction.
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Antibody-enhanced infection of monocytes as the pathogenetic mechanism for severe dengue illness. Antibody-dependent enhancement of certain virus infections can occur in cells expressing Fc receptors. This mechanism plays an important pathogenetic role in the development of complications associated with dengue virus infection, including dengue hemorrhagic infection and dengue shock syndrome. The virulence of the virus, characterized by the ability to infect Fc receptor-bearing monocytes also influences the development of these severe illnesses.
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Rectourethral fistula caused by Kaposi's sarcoma. A 35-year-old man with the acquired immunodeficiency syndrome-related complex was evaluated for a persistent urethral discharge, pneumaturia and watery diarrhea. Radiographic and endoscopic procedures established the diagnosis of a rectourethral fistula. Perineal exploration and excision of the fistula revealed the pathological diagnosis of Kaposi's sarcoma. The differential diagnosis of an acquired rectourethral fistula and the significance of Kaposi's sarcoma are discussed.
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Tracheal stenosis and failure to wean from mechanical ventilation due to herpetic tracheitis. A 64-year-old man with chronic obstructive pulmonary disease presented with pneumococcal pneumonia that progressed to respiratory failure within one week, requiring mechanical ventilation. Despite a low minute ventilation and clear chest roentgenogram, multiple weaning attempts failed. Bronchoscopy revealed significant narrowing of the distal trachea with erythema, edema, and ulceration of the mucosa. Cytology of tracheal washings was consistent with herpes simplex virus, and the patient was successfully extubated following treatment with intravenous acyclovir. Bronchoscopy following acyclovir therapy demonstrated resolution of the inflammation and narrowing. Herpetic tracheitis is a rarely recognized reversible cause of tracheal stenosis, especially in a nonimmunocompromised patient. It should be suspected in patients without an obvious cause of failure to wean from mechanical ventilation, and can be successfully treated with acyclovir.
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Coccidioidomycosis in human immunodeficiency virus-infected patients. Coccidioidomycosis is at best a complicated fungal infection; often it is life-threatening. Coccidioidomycosis is confined epidemiologically to the southwestern region of the USA, and most cases have occurred in that area, particularly in Arizona. However, we have seen several cases in San Francisco in patients with only a history of travel to endemic areas. In part because of its regional distribution, information about the clinical presentation, diagnosis, and treatment of patients with coccidioidomycosis has lagged behind information about other, more commonly encountered AIDS-associated opportunistic infections. Drs. Galgiani and Ampel have probably had the largest single experience with coccidioidomycosis in individuals infected with the human immunodeficiency virus. These specialists share their experience and make recommendations as to how these complicated conditions should be approached.
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Complications of Tenckhoff catheters post removal. Complications due to Tenckhoff catheters can occur at prolonged intervals after their removal. From January 1979 to October 1989, 431 patients at our center began continuous ambulatory peritoneal dialysis (CAPD), 278 of whom subsequently transferred to another form of renal replacement therapy. We identified 12 patients (4.3% or 12/278) with post removal catheter complications. There were 14 post removal complications, two each in two patients, and one in each of 12 others. The mean time to complication was 541 +/- 143 days (27-2,040). In 71% (10/14) of the complications, an abscess was found at the site of the previously removed Tenckhoff catheter. In 29% (4/14) of the complications, foreign body material consistent with a retained cuff was recovered. Documentation at the time of Tenckhoff catheter removal should include a statement regarding the presence of the Tenckhoff catheter cuffs, and patients with retained cuffs should be monitored closely for the development of abscesses or other complications. Immunocompromised patients are at high risk for these complications.
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The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure. We present the combined experience of three Yugoslavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a King's College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy.
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Measles antibody: reevaluation of protective titers. A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.
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Central nervous system vasculitis after chickenpox--cause or coincidence? A 7.5 year old boy, known to have a seizure disorder, presented with an infarct in the left middle cerebral artery territory, 10 weeks after severe chickenpox. Immunofluorescent antibody titre to the varicella zoster virus in the cerebrospinal fluid was 1:32. Cerebral angiography showed evidence of focal vasculitis. He presented again seven months later with an acute exacerbation of seizures. Magnetic resonance imaging of the brain showed an old posterior extension of the infarct, but a repeated angiography demonstrated an improvement in the vasculitic process. Cerebrospinal fluid antibody titre was again 1:32. Although this may have been an unfortunate coincidence, a possible association between chickenpox and vasculitis, similar to that reported with herpes zoster, and with potentially significant clinical implications, should be considered. As a definite proof can be obtained only by a brain biopsy, however, which is generally not indicated in such cases, only additional clinical reports can lead to delineation of this association as a definite entity.
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Does prematurity alter the course of respiratory syncytial virus infection? We compared previously healthy prematurely born infants with full-term infants hospitalized with respiratory syncytial virus (RSV) infection to evaluate the role of prematurity on the clinical course of the illness. During a 5-yr period (1984 to 1989), 484 previously healthy patients were admitted to the hospital with RSV infection. No differences were found in the presenting symptoms of respiratory distress, cough, fever or shock, although the premature group was more likely to present with apnea (p less than .001). Chest roentgenograms revealed that premature infants had a higher incidence of atelectasis/infiltrate and hyperinflation (p less than .05). Premature infants had longer hospital stays as well as a higher Physiologic Stability Index and Therapeutic Intervention Score (p less than .001). They were also more likely to receive supplemental oxygen, ICU admission, mechanical ventilation, and nothing by mouth status (p less than .001). We conclude that premature birth increases the risk of more severe and prolonged RSV disease.
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Primary care of women infected with the human immunodeficiency virus. AIDS is the leading cause of death among women aged 25 to 34 years in New York City. Gynecologic care should be directed toward early identification and aggressive treatment of infectious and neoplastic processes that may take a more fulminant course in immunosuppressed women. Dealing with women's contraceptive needs highlights the problem of preventing sexually transmitted diseases through contraceptive technology. Public health policies and recommendations will be of no avail without an educated and supportive medical community.
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Chronic encephalitis caused by leukoencephalopathy. As mentioned previously, both MS and PML are demyelinating conditions of the CNS and pose diagnostic difficulties in their differentiation because of similarities in their clinical findings. However, certain features unique to each of these diseases are helpful in clinical diagnosis. MS, unlike PML, is a disease of unknown cause. Polygenetic influences in combination with exposure to an environmental agent and immune-mediated factors may be operative in the pathogenesis of MS. Age of onset peaks in the third to fourth decades with a predominance in women, as contrasted with PML, which peaks in the fifth to sixth decades in most non-AIDS-associated cases with a slight predominance in men. MS is more prevalent in areas farther from the equator: North America, Europe, Australia, and New Zealand. Common initial symptoms seen in MS include bilateral limb weakness (with the legs being affected twice as often as the arms), hyperreflexia, spasticity, optic neuritis, diplopia, incoordination, and paresthesias. (Paresthesias are typically found in the lower limbs in a symmetric pattern, but may follow no obvious anatomic distribution and often do not correspond to the distribution of sensory symptoms. Vibration and position sense are more frequently disturbed than pain and temperature.) Intellectual impairment and mental deterioration are uncommon early in MS, whereas they are a more frequent initial presentation in PML. In addition, the presence of speech impairment and monoparesis or hemiparesis with homonymous hemianopsia is more suggestive of PML. Brain stem involvement is infrequent.
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Role of the monocyte-macrophage in influenza virus infection of lymphocytes: implications for HIV infection. Knowledge of the pathogenesis of viruses which are less virulent than human immunodeficiency virus (HIV) may provide valuable insights into the pathogenesis of HIV infection. Influenza virus, an enveloped RNA virus, infects monocyte-macrophages, although the infection is brief and abortive. Isolated purified lymphocytes are completely resistant to infection. In contrast, mixtures of lymphocytes and macrophages can synthesize all virus proteins. Infection requires physical association of monocyte-macrophages and lymphocytes in "clusters." These studies with influenza virus suggest that the pathogenesis of virus infections in mixed cell cultures may be very different from that observed in purified cell populations, and they suggest that similar studies should be performed with HIV.
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Urinary retention due to sacral myeloradiculitis: a clinical and neurophysiological study. We report 5 cases of sacral myeloradiculitis presenting with transient urinary retention. Neurophysiological testing, including bulbocavernosus reflex, pudendal evoked response and external anal sphincter electromyography, was performed. Parasympathetic pelvic nerves, pudendal nerves as well as the spinal cord seem to be involved to various degrees in this infrequent disorder.
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Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS. Forty-eight patients with disseminated cryptococcosis and AIDS were retrospectively studied to define the pulmonary manifestations. Cryptococcus neoformans (CN) was first isolated from a pulmonary site in 12 patients. Disseminated disease was subsequently documented in all these patients. Symptoms and roentgenographic manifestations (normal, nodular/circumscribed infiltrates, pleural effusions, lobar consolidation) were diverse. Interstitial infiltrates predicted the presence of another opportunistic lung infection besides cryptococcosis in five patients (three untreated and two treated patients). Infectious causes other than cryptococcosis were established by culture and clinical course in five of the ten patients who developed chest roentgenographic abnormalities during amphotericin B therapy. Endobronchial abnormalities were identified in four patients at bronchoscopy. Bronchoalveolar lavage (9/9) and pleural fluid (3/3) cultures were sensitive tests for detection of pulmonary involvement with CN.
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Primary lymphoma of the central nervous system in two children with acquired immune deficiency syndrome. Postmortem examination disclosed central nervous system non-Hodgkin's lymphoma in two children who died of acquired immune deficiency syndrome (AIDS) at 6 and 14 months of age, respectively. Systemic signs of lymphoma were not present. The B-cell origin and clonality of the neoplastic cells were established by immunohistochemistry in one case and by molecular analysis of immunoglobulin gene rearrangement in the other. Moreover, in the latter case the neoplastic cells were characterized by the presence of a single episomal EBV genome. According to these data, the monoclonal B-cell proliferation occurred after EBV infection, thus suggesting a possible pathogenetic role of EBV in the early stages of lymphomagenesis.
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Predominance of polymorphonuclear leukocytes in cerebrospinal fluid of AIDS patients with cytomegalovirus polyradiculomyelitis. Cytomegalovirus (CMV) polyradiculomyelitis was diagnosed in 4 of 241 consecutive neurologically assessed human immunodeficiency virus type (HIV-1) seropositive patients. CMV-related neurologic disease was suspected on clinical grounds and was subsequently confirmed by CMV culture from cerebrospinal fluid (CSF) and/or CMV in situ hybridization on specific specimens. All four patients showed CSF pleocytosis with predominance of polymorphonuclear leukocytes (PMNs). Retrospective analysis of the results of CSF examination, performed in 143 of 241 patients with neurologic symptoms, showed pleocytosis in 58 of 143 patients. Predominance of PMNs was found in seven patients, including the four with CMV polyradiculomyelitis. It is concluded that in HIV-1 seropositive patients with a clinical diagnosis of polyradiculomyelitis, a predominance of PMNs in CSF could be an indication that the condition is CMV related. This should lead to early diagnosis and institution of specific antiviral therapy.
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CD4+ monocyte counts in persons with HIV-1 infection: an early increase is followed by a progressive decline. In this study, we asked whether there is a difference in the number of CD4+ and CD4- peripheral blood monocytes as CD4+ T cells decrease during HIV-mediated immunodeficiency. Monocytes and T cells from 90 HIV-positive and 43 HIV-negative persons were analyzed by flow cytometry. The 90 HIV-positive patients represented the entire spectrum of CD4+ T-cell counts. We report that as CD4+ T cells decrease, the number of CD4+ monocytes decrease in parallel. Moreover, significantly higher CD4+ monocyte counts were observed in persons with early stage HIV disease, i.e., greater than 800 CD4+ T cells/mm3, than in HIV-negative persons with greater than 800 CD4+ T cells/mm3. Potential implications of these findings are discussed.
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Chancroid and the role of genital ulcer disease in the spread of human retroviruses. Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease.
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Cutaneous horn of the penis: its association with squamous cell carcinoma and HPV-16 infection. Cutaneous horns of the penis are rare. Including this case, only 19 cases have been reported in the English-language literature. In 37% of the reported cases a malignant tumor was found beneath the cutaneous horn. Our case is remarkable because a stage I squamous cell carcinoma developed on the shaft of the penis of a neonatally circumcised man. Human genital carcinoma resulting from a multifactorial process in which "promoting" papillomavirus is an integral element is being increasingly reported. We review the relationship of circumcision to genital human papillomavirus infection and their synergism in the development of squamous cell carcinoma.
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Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
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Immunological studies of the basis for the apathogenicity of simian immunodeficiency virus from African green monkeys. Potential reasons for the lack of pathogenicity of the simian immunodeficiency virus SIVagm in its natural host, the African green monkey (AGM, Cercopithecus aethiops), were investigated with respect to immunological mechanisms. The functional immune response of monkeys to infection was similar (though not identical) to that of humans to infection with human immunodeficiency virus type 1 (HIV-1). In the sera of infected animals, neutralizing antibodies were found to be low or absent, and in particular there was no neutralization of the various isolates by homologous sera. There was no detectable antibody/complement cytotoxicity, though AGM sera were able to initiate antibody-dependent cellular cytolysis of infected cells in the presence of healthy effector peripheral blood lymphocytes. As in the human/HIV system, macrophages from AGMs are readily infected by SIVagm. Two possibly important differences between the AGM/SIVagm system and the human/HIV system are (i) the low immune response of the AGMs to the core protein of SIVagm and (ii) the significantly lower inhibitory effect of SIVagm proteins on the proliferation of AGM lymphocytes.
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Use of polymerase chain reaction for successful identification of asymptomatic genital infection with herpes simplex virus in pregnant women at delivery. The polymerase chain reaction was adapted to the amplification of a herpes simplex virus (HSV) DNA sequence, common to HSV types 1 and 2 (HSV-1, HSV-2). The amplified product was detectable by ethidium-bromide staining or Southern hybridization of gels and by dot hybridization. The HSV polymerase chain reaction detected HSV DNA in samples obtained from eight patients with genital lesions from which HSV-2 was isolated in tissue culture and from four patients with labial lesions from which HSV-1 was isolated. The HSV polymerase chain reaction identified HSV in clinical specimens obtained from 11 women who had asymptomatic genital HSV infections at delivery. None of 11 samples obtained at delivery from women who had antibodies to HSV-2, but whose delivery cultures were negative, were positive by polymerase chain reaction and no false-positive reactions were obtained when the reaction mixture contained human cell DNA or varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, or human papillomavirus DNA.
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Confocal microscopic detection of human immunodeficiency virus RNA-producing cells. A central anomaly in the pathogenesis of AIDS is that few actively infected CD4+ cells (1 in 10(4)-10(5) have been detected in the peripheral blood, even though dramatic depletion (often greater than 90%) of CD4+ cells is the hallmark of disease progression. A sensitive, 35S-based human immunodeficiency virus (HIV) RNA in situ hybridization technique was coupled with a new detection method, confocal laser scanning microscopy, to examine transcriptionally active HIV-infected cells from individuals at different disease stages. In 35 symptomatic HIV-infected individuals (AIDS and AIDS related complex), an average of 1 in 350 mononuclear cells produced HIV RNA. In contrast, in an asymptomatic group of 30 individuals, an average of 1 in 2000 mononuclear cells produced HIV RNA. These data, obtained using this improved detection method, suggest there are more HIV RNA-producing cells in HIV-infected individuals than previously reported. In addition, increased numbers of HIV transcribing cells were found to correlate with declining clinical condition as assessed by Karnofsky performance score. These data suggest that viremia per se may account for the pathologic consequences in HIV infection.
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Seroprevalence of human T cell leukemia viruses in selected populations of homosexual men. This study sought to define the seroprevalence of human T cell leukemia virus (HTLV) types I and II in selected populations of homosexual men. Serum specimens were screened for antibodies to HTLV and to human immunodeficiency virus (HIV) by enzyme immunoassay; successive testing of specimens with positive results was done by Western blotting and radioimmunoprecipitation assay (RIPA) and then by polymerase chain reaction (PCR) assay on available peripheral blood mononuclear cells (PBMC). Of 1290 specimens, only 4 had antibodies against HTLV confirmed by RIPA. PCR analysis of DNA from PBMC from two subjects showed one to be HTLV-I and the other to be HTLV-II; both men also had HIV antibodies. These results demonstrate a lower seroprevalence rate for HTLV than some previous studies and emphasize the need for specific confirmatory tests.
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Influenza infection and diabetes mellitus. Case for annual vaccination. Herein, epidemiological data on influenza pneumonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. During influenza epidemics, death rates among patients with diabetes mellitus may increase by 5-15%. Diabetes mellitus is also mentioned as a risk factor in most clinical studies, making up 3-14% of the patients studied. Even in recent studies, diabetes mellitus is only preceded as a risk factor by cardiovascular disease and chronic pulmonary disorders. To what extent cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in diabetic patients remains unclear. The influence of epidemic influenza on the incidence of diabetic acidosis in combination with an impaired immune response to both Staphylococcus aureus and the influenza virus suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in official recommendations, patients with diabetes mellitus should be mentioned as a separate risk group. Whole-virus vaccines are preferred over subunit vaccines.
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Syphilis, human immunodeficiency virus infection, and targeting prevention. To examine the interaction between syphilis and human immunodeficiency virus-type 1 (HIV-1) infection in Oklahoma, we conducted an unlinked HIV seroprevalence survey using serum specimens submitted to the Oklahoma State Department of Health for serologic test for syphilis. Of specimens with positive results from fluorescent treponemal antibody absorption test (FTA-ABS), 6.3% were HIV-1 seropositive compared to 0.8% of those that had negative results from FTA-ABS. Among specimens positive for syphilis, HIV-1 seropositivity was found almost exclusively among those from persons 20 to 39 years of age and more often among those from men than those from women (9.9% vs 1.3%). Of syphilis-positive specimens from 20- to 39-year-old men, 17.6% were HIV-1 seropositive. In Oklahoma, an area with a relatively low overall prevalence of HIV-1 infection, targeting prevention efforts to young adults who test positive for syphilis should be an efficient way to reach some persons at high risk for HIV-1 infection.
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Wegener's granulomatosis presenting during first trimester of pregnancy. We describe a case of Wegener's granulomatosis in a lady who presented acutely with pulmonary haemorrhage, fever and breathlessness during her early pregnancy. She responded well to aggressive medical treatment.
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Effect of delayed captopril therapy on left ventricular mass and myonecrosis during acute coxsackievirus murine myocarditis. The effect of captopril on coxsackievirus B3 murine myocarditis was investigated. Thirty-two, 3-week-old mice were infected with coxsackievirus B3 on day 0 of the study, then randomized into a placebo group or a captopril group starting on day 3 of infection. On day 9 of infection, the mice were put to death. Hearts were weighed and processed for light microscopic examination. Heart weight was 125 +/- 19 mg in the control group versus 102 +/- 14 mg in the captopril group (p less than 0.0003). Amount of necrosis as a percentage of left ventricular section was 3.5% (2.0% to 7.5%) in the placebo group versus 2.0% (0.0% to 5.0%) in the captopril group (p less than 0.01). The amount of dystrophic calcification was 5.0% (0.0% to 27.5%) in the placebo group versus 1.3% (0.0% to 20.0%) in the captopril group (p less than 0.01). The extent of the histopathologic involvement by planimetry was 10.2% in the placebo group versus 5.4% in the captopril group (p = 0.052). We conclude that captopril is beneficial in decreasing left ventricular mass and the amount of myocardial necrosis and calcification in the short term in the murine myocarditis model.
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Ocular disease associated with Epstein-Barr virus infection. Epstein-Barr virus (EBV) is a ubiquitous DNA virus of the herpesvirus genus with a high prevalence rate for antibody (about 90%) in the adult population. It is the most common causative agent of infectious mononucleosis syndrome. During recent years an increasing number of ocular disease entities have been reported to be linked to EBV infection. These entities include oculoglandular syndrome, conjunctivitis, dry eye, keratitis, uveitis, choroiditis, retinitis, papillitis and ophthalmoplegia. While EBV-specific serologic tests can now document recent and past primary infection with EBV and also identify patients manifesting atypical immunologic reactions to EBV, the lack of an animal model, the absence of clear-cut response to therapy and the paucity of documentation by culture render the pathogenesis uncertain or the association questionable in many of these cases.
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A routine tool for detection and assessment of epidemics of influenza-like syndromes in France. A regression model for the nonepidemic level of influenza-like syndrome has been estimated from the 55,200 cases collected between October 1984 and August 1988 using the French Communicable Diseases Computer Network. The start of a major epidemic in 1988-89 was detected early. The size of the epidemic, for the entire country, was estimated at approximately 4.3 million cases. The excess cost of sick-leave, among those of working age, was estimated at $86 million.
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The role of antihistamines in otitis. Chronic and recurrent otitis media can manifest as otitis media with effusion. Both infection and eustachian tube obstruction (ETO) have been found to play an important role in its pathogenesis. ETO can be demonstrated during both early- and late-phase reactions in patients with allergic rhinitis after intranasal challenge with an allergen. Intranasal challenge with either histamine or prostaglandin D2 also provokes ETO, with the latter mediator perhaps more potent than the former. Middle ear effusions from patients with chronic or recurrent otitis media have been found to contain dramatically increased concentrations of histamine relative to the concentrations in their plasma. The development of nasal and eustachian tube obstruction in allergic rhinitis patients has been prevented by pretreatment with an antihistamine plus decongestant before intranasal challenge with pollen allergen. Investigations are currently under way to assess the effect of antihistamine pretreatment on nasal and eustachian tube obstruction in patients undergoing intranasal histamine challenge.
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Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection. Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.
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Treatment of adult chickenpox with oral acyclovir. Thirty-one late adolescents and adults with varicella were studied. Patients identified within 72 hours of varicella exanthem were offered open treatment with acyclovir (4 g/d), and those patients identified after 72 hours of exanthem were followed up but not treated. Twenty-two patients were treated with acyclovir. Nine patients were not treated. No severe complications occurred in any of the 31 patients. Minor complications, including prolonged fever, localized secondary infections, persistent cough, and prolonged fatigue were more frequent in the untreated group. If the acyclovir therapy was begun within the first 24 hours of varicella exanthem, then the rash and clinical illness were dramatically lessened. Treatment with oral acyclovir should be considered for varicella in adults who are identified within the first 24 hours of exanthem.
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Response of mononuclear cells from HIV-infected patients to B-cell mitogens: correlation with immunological and clinical features of disease progression. Proliferation of mononuclear cells from HIV-seropositive patients to B-cell mitogens was studied in the absence and presence of mixed lymphocyte culture supernatants (MLC-sup). The results show: (1) patients' responses to B-cell mitogens overlap with normal responses but are, on average, consistently lower than normal; (2) the addition of MLC-sup increases the proliferative responses to T-cell-independent mitogens, but does not bring patient's responses up to control levels; (3) HIV-positive patients in all clinical categories have decreased responses to B-cell mitogens. Although some patients with AIDS Centers for Disease Control (CDC) group IVC and IVD have the lowest responses, asymptomatic (CDC group II) and AIDS-related complex (ARC; CDC groups III/IVA and IVB) patients also show significant defects. (4) The same patients were recategorized using an immunological staging system. Those patients with more normal immunohematological parameters have significantly greater responses to mitogens compared with patients with more abnormal immunological parameters. The data suggest that immunological staging could provide more information than clinical classification with respect to the underlying immunopathogenic events occurring in HIV infection.
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Isolation of measles virus in primary rhesus monkey cells from a child with acute interstitial pneumonia who cytologically had giant-cell pneumonia without a rash. The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy.
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Measles update. The incidence of measles in the United States dramatically increased in the 1980s, from a low of 1,497 cases in 1983 to over 17,000 cases in 1989. Family physicians can help reverse this trend by following the revised immunization schedule, which includes a measles-mumps-rubella (MMR) booster for preschool-age children. New guidelines also recommend that either the two-dose MMR schedule or serologic evidence of immunity be required for all persons entering college or employed in the medical field. Immunization policies for physician's offices should ensure that all office staff have acquired measles immunity and that a triage policy separating patients with rash from those with other illnesses is utilized. Mild upper respiratory illness, a history of seizures, nonanaphylactic egg allergy and asymptomatic human immunodeficiency virus infection are not contraindications to measles vaccine. All cases of measles should be reported to the local health department.
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Tropical neuromyelopathies and retroviruses: a review. Debilitating disorders of the nervous system have a relatively high prevalence in the tropics, a geographic region that is often deficient in specialists in the fields of neurology and epidemiology. During World War II, attention was called to a possible nutritional origin for most of these diseases. Recently, however, human T lymphotropic virus type I (HTLV-I), formerly linked only to a rare form of leukemia (adult T cell leukemia), has been associated with a spastic paraplegia observed mostly in tropical areas and referred to as tropical spastic paraparesis. This entity is also observed in nontropical areas endemic for HTLV-I, including Japan, South America, and the southern United States. Viruses of the HTLV family are being associated increasingly with pathology in humans. The pathogenesis of HTLV-I-associated tropical spastic paraparesis remains to be understood. However, future research is expected to favor a multidisciplinary approach, with exciting potential insights derived from the fields of neurology, immunology, and infectious diseases. The aim of this review is to summarize contemporary research related to the viral etiology of this clinical entity.
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Spontaneous splenic rupture following infectious mononucleosis. Four cases of spontaneous splenic rupture after infectious mononucleosis (IM) have been treated at this institution since 1978. The condition is rare, occurring in 0.1-0.5 per cent of patients with proven infectious mononucleosis. Splenectomy is considered the treatment of choice for these patients. However, because recent trends in the management of traumatic splenic rupture are moving towards nonoperative treatment with selected patients, a similar approach has been considered for the patient with spontaneous splenic rupture following IM. The major reason for avoiding splenectomy is the increased incidence of sepsis in splenectomized patients. Yet, splenic rupture is accompanied by hemorrhage and the risks associated with blood transfusion for ongoing hemorrhage are of similar magnitude as those of sepsis following splenectomy. In addition, the grossly abnormal spleens seen at operation tend to include large, contained hematomas that may also be prone to rupture. Therefore, operative management still appears to be the preferred treatment for spontaneous splenic rupture following IM. Splenectomy is curative, safe, and obviates the need for transfusion, extended hospitalization, and activity restriction.
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Disseminated cutaneous herpes zoster following cardiac surgery. Our case report describes disseminated cutaneous Herpes Zoster in the early post-operative period following cardiac surgery with cardiopulmonary bypass. This has not been reported previously in the absence of immunosuppressive therapy. Despite associated neurologic and respiratory impairment, our patient was treated successfully with intravenous Acyclovir and subsequently discharged.
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A semiquantitative microassay for measurement of relative number of blood mononuclear cells infected with human immunodeficiency virus. A simple semiquantitative microassay was developed for the measurement of relative number of infected peripheral blood mononuclear cells (PBMC) from individuals infected with human immunodeficiency virus (HIV). The assay is based on cocultivation of serially diluted PBMC of a seropositive person with phytohemagglutinin-stimulated normal PBMC. The microassay has comparable sensitivity with the standard virus culture method in detecting positive HIV cultures. Since the microassay uses only 2-3 x 10(5) patients' PBMC, the assay is also most suitable for HIV isolation from HIV-infected infants or from AIDS patients with extremely low T-cell counts. The microassay can also be used to measure antiviral effects of a drug on persistent HIV infection in vitro. Because the microassay measures the relative number of infected PBMC, it can be readily used for following the quantitative antiviral effect of a drug in a clinical trial.
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Rotavirus-specific antibody response in saliva of infants with rotavirus diarrhea. The reliability of saliva as an indicator of rotavirus infection was assessed among 15 infants (3-12 months) with rotaviral and 15 with nonrotaviral diarrhea. Paired salivary samples collected during acute and convalescent phases were tested for rotavirus-specific IgA and IgM by an ELISA. The sensitivity of IgA or IgM alone to predict infection was 53.3% and 46.6%, respectively; used in conjunction, the sensitivity rose to 80%. It seems that infants with rotaviral diarrhea mount mucosal antibody responses as reflected in their saliva; possibly salivary antibodies could be used to evaluate vaccine "take" in rotavirus vaccine trials.
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Human T cell lymphotropic virus infection in Guaymi Indians from Panama. Preliminary studies found that 9% of Guaymi Indians from Bocas del Toro province have antibody to human T cell lymphotropic virus (HTLV-I/II). The present study enrolled 317 (21% of the population) Guaymi Indians from Changuinola, the capital of Bocas del Toro province and 333 (70% of the population) from Canquintu, an isolated rural village. Demographic information and family relationships were ascertained and subjects were screened for neurologic diseases. Serum specimens were screened by an enzyme-linked immunosorbent assay for HTLV-I/II antibody and positives were confirmed according to U.S. Public Health Service criteria. Twenty-five (8%) Guaymi residing in Changuinola and 7 (2.1%) from Canquintu were confirmed seropositive. In Changuinola, antibody was virtually limited to residents greater than or equal to 15 years of age (24 [16%] of 153) and rates were slightly higher in males than in females; in Canquintu, antibody rates did not increase significantly with age and appeared higher in females than in males. In Changuinola, there was no evidence for household clustering of infection. In contrast, HTLV antibody among Canquintu residents clustered significantly by household. HTLV-associated neurologic disease was not detected in either population. The atypical seroepidemiology observed in both locations might be explained if the virus endemic to the Guaymi differed from HTLV-I previously described in the Caribbean basin and Japan.
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Delayed endolymphatic hydrops and its relationship to Meniere's disease. Delayed endolymphatic hydrops (EH) can be characterized as having ipsilateral and contralateral types. They are similar in that both have early and late phases of otologic symptoms and that the early phase is a profound hearing loss in one ear. The late phases differ, however, in that the ipsilateral type develops the symptoms of EH (episodic vertigo) in the deaf ear and the contralateral type develops the symptoms of EH (fluctuating hearing loss and/or episodic vertigo) in the hearing ear. In more than half the cases of both types of delayed EH, the profound hearing losses in the early phase are simply discovered to be present in early childhood without a known time of onset. The temporal bones of two patients with contralateral delayed EH show pathologic changes in the deaf ears that are similar to those known to occur in mumps and measles labyrinthitis, whereas the pathologic changes in the hearing ears are similar to those known to occur in Meniere's disease. These observations support the proposition that Meniere's disease may occur as a delayed sequela of inner ear damage sustained during an attack of subclinical viral labyrinthitis occurring in childhood.
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Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.
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Use of immunoelectron microscopy to show Ebola virus during the 1989 United States epizootic. A filovirus, serologically related to Ebola virus, was detected by "post-embedment" immunoelectron microscopical examination of MA-104 cells. These had been infected by inoculation with serum samples obtained during the 1989 epizootic in cynomolgus monkeys (Macaca fascicularis), imported from the Philippines and maintained at Reston, Virginia, USA, a primate holding facility. The immunoelectron microscopy method, when used in conjunction with standard transmission electron microscopy (TEM) of infected cells, provided consistent results and was simple to perform in this epizootic. It is concluded that immunoelectron microscopy is potentially useful in the direct immunological diagnosis of Ebola and related filoviral infections (such as Marburg) in clinical samples obtained from those with acute infection.
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Characterization of the dermal infiltrate in human immunodeficiency virus-infected patients with psoriasis. We investigated the dermal inflammatory cell infiltrates of psoriatic lesions from nine human immunodeficiency virus-infected patients and nine age-, sex-, and site-matched control specimens. The study was retrospective and observer blinded. T lymphocytes were quantitated using UCHL-1, a pan-T-cell monoclonal antibody, and plasma cell number was estimated in hematoxylin-eosin-stained sections. Differences in both variables reached statistical significance. There were fewer T cells and the number of plasma cells was significantly higher in specimens from the human immunodeficiency virus-positive individuals in comparison with control specimens. As plasma cells are readily identified on hematoxylin-eosin-stained sections, their presence in skin biopsy specimens from psoriatic leisons should arouse suspicion of human immunodeficiency virus infection. The depletion of helper/inducer T lymphocytes by the human immunodeficiency virus may promote the presence of plasma cells in cutaneous inflammatory infiltrates.
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Modeling the impact of breast-feeding by HIV-infected women on child survival [published erratum appears in Am J Public Health 1991 May;81(5):658-9] This study models the survival outcomes of children born to HIV-infected (human immunodeficiency virus) women who are breast-fed, bottle-fed, and wet-nursed. It is estimated that, given the relative risk of alternatives to maternal milk in developing countries, the probability of HIV transmission via breast milk would need to be at least .12 in a community with an under five child mortality rate from non-HIV causes of 100/1000 live births and at least .27 in a community with a rate of 200/1000 before alternative feeding practices should be recommended even to the known HIV-infected mother who has an available feeding alternative with a relative risk of 2:1. While such a low relative risk may be achievable with wet nursing, most studies report a relative risk of at least 3:1 for bottle feeding. A sensitivity analysis is conducted around the relative risk of child mortality from non-HIV causes associated with different feeding practices. While the critical transmission rate does not vary significantly with a rate of false positives as high as 20 percent on the HIV screening test, the critical transmission rate is very sensitive to the availability of HIV screening. In communities where the HIV prevalence rate among mothers reaches 40 percent, breast-feeding should still be recommended in the absence of HIV screening unless HIV transmission via breast milk surpasses 30 percent.
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The myelodysplastic syndromes. Case report and review. The myelodysplastic syndromes are a heterogenous group of hematologic disorders of myeloid progenitor cells. Oral manifestations may be among the first signs and often reflect degrees of neutropenia or neutrophil dysfunction. A patient with persistent herpes labialis and severe oral mucosal ulceration in myelodysplastic syndrome is reported. The features of myelodysplasia are reviewed and their oral manifestations and significance to dental management outlined.
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Transfusion risks. Hepatitis remains the most serious transfusion risk, in terms of incidence and severity. Transfusion-associated AIDS, hemolytic reactions, TRALI, and anaphylaxis are severe problems that occur relatively rarely, while febrile reactions and mild allergic reactions are common but not serious. The key to avoiding all these complications is autotransfusion (see the article "Autologous Transfusion" in this issue). Although intraoperative scavenging became available in many centers in the United States in the 1980s, it is hoped that pre-deposit autotransfusion will also become widely utilized in the next decade.
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Outbreak of spontaneous staphylococcal arthritis and osteitis in mice. Staphylococcus aureus is the most common bacterial species found in association with nongonococcal bacterial arthritis in humans. We present here the first description of spontaneous bacterial arthritis and osteitis in mice. Clinically, the most obvious findings were swelling and/or ankylosis of hindpaws and nodose changes of the tail. The prevalence of arthritis and osteitis ranged from 0% to greater than 50% of the mice studied, depending on the mouse strain. The most prominent histopathologic feature of the arthritis was hypertrophy of the synovial tissue and destruction of cartilage and underlying bone. Most of the S aureus-infected mice displayed an identical phage type, which was also the only S aureus phage type found in skin isolates from clinically healthy mice. However, a few S aureus isolates were not typeable, indicating that an additional strain(s) might cause bacterial arthritis in mice.
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Comparison of species distribution and antimicrobial susceptibility of aerobic actinomycetes from clinical specimens. To compare the species distribution and antimicrobial susceptibility of aerobic actinomycetes, we evaluated 366 isolates referred to the Centers for Disease Control from October 1985 through February 1988. We used conventional biochemical tests to identify the various species. Four species accounted for 191 (52%) of aerobic actinomycete isolates: Nocardia asteroides (98 isolates), Actinomadura madurae (42 isolates), Streptomyces griseus (28 isolates), and Nocardia brasiliensis (23 isolates). Sputum and wounds were the most common sources. No isolate was resistant to amikacin, no N. brasiliensis isolate was resistant to sulfamethoxazole or trimethoprim-sulfamethoxazole, and no A. madurae isolate was resistant to ceftriaxone or imipenem. In summary, our findings show that unusual species of aerobic actinomycetes can cause infection, colonization, or both and that antimicrobial resistance varies markedly by species.
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The role of mucous glycoproteins in the rheologic properties of cystic fibrosis sputum. Cystic fibrosis (CF) is characterized by excessive amounts of thick and tenacious mucous secretions that obstruct organ ducts and passages. In the respiratory tract this is associated with chronic infection resulting in the hypersecretion of purulent sputum, which the patient finds difficult to clear. We have studied the rheologic properties of purulent sputum from six patients with CF and five patients with chronic bronchitis to assess whether CF is associated with increased sputum viscoelasticity. In addition, we have isolated the major rheologic determinants, mucous glycoproteins, from CF and chronic bronchitis sputa and, using a magnetic microrheometer, investigated the possibility that the altered properties of mucus in CF are associated with abnormalities in these glycoproteins. Creep compliance analysis indicated that the CF sputa possessed raised levels of both elasticity (p less than 0.01) and viscosity (p less than 0.01). These increases in both rheologic parameters were found to be associated with increases in the DNA content (p less than 0.01) and dry weight (p less than 0.05). Mucous glycoproteins were isolated from CF and chronic bronchitis sputum samples by gel filtration on Sepharose CL4B, followed by concentration to form 8% wt/wt gels. In the absence of other sputum components, no abnormality in the rheologic properties of CF mucin gels could be detected. However, when DNA was added, the CF gels responded with increases in both elasticity and viscosity of as much as 30% (p less than 0.05), an effect not observed in the chronic bronchitis gels. These results suggest that a subtle abnormality may exist in CF mucous glycoproteins and that this could have a role in the altered physical properties of mucous secretions in CF.
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Causes, diagnosis, and treatment of pharyngitis. Pharyngitis is a common disease of the respiratory tract that can be caused by several different viruses and bacterial organisms. Clinically speaking, the most important causative agent is group A streptococcus (Streptococcus pyogenes). Although rare, postpharyngitis complications arise as a result of disease caused almost exclusively by group A streptococcus. Because group A streptococcal pharyngitis usually responds well to antimicrobial treatment, it is important to diagnose it. Penicillin, erythromycin, and peroral first-generation cephalosporins have been documented to be effective. In addition to group A streptococcus, C. pneumoniae and M. pneumoniae have also been detected in patients with pharyngitis. The possibility of diagnosing these organisms is limited at the present. Clinical surveys are still needed, moreover, to evaluate the effect of antimicrobial treatment on the disease caused by these organisms. Although routine viral diagnostic methods do not help primary care physicians in treating patients with pharyngitis, information on bacteria and viruses in the immediate environment could prove to be of great help in daily clinical work.
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Assessing the risk of occupational acquisition of the human immunodeficiency virus: implications for hospital policy. In determining infection control policy, it is essential to quantitatively assess the risk of transmission of human immunodeficiency virus (HIV) to health care workers and their families. The risk should be placed in perspective by comparing it with other occupational hazards. The risk of seroconversion from a needlestick injury can be calculated from the probability of a needlestick occurrence, the probability that the source patient is infected, and the probability of seroconversion, given an exposure. The risk of seroconversion due to drawing 1000 blood specimens from seropositive patients is between 86 and 470 in 100,000. The risk to surgeons from performing 25 operations on infected patients is approximately 272 in 100,000. The risk of fatal injury in the course of one year's work on a Louisiana oil rig is between 188 and 283 per 100,000.
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Broad spectrum penicillin as an adequate therapy for acute cholangitis. In a previous study of patients with acute cholecystitis, we demonstrated equal efficacy with a broad spectrum penicillin (piperacillin) and a penicillin plus amino-glycoside combination. Whether a single agent broad spectrum penicillin is adequate treatment for more severe infections, such as acute cholangitis, however, is still unclear. We, therefore, conducted a three center, prospective, randomized trial to determine whether or not a broad spectrum penicillin alone is adequate therapy for patients with acute cholangitis. During a 36 month period, 96 patients with sepsis and biliary obstruction were randomly assigned to receive either piperacillin (n = 49) or ampicillin plus tobramycin (n = 47). The two groups receiving antibiotics were similar with respect to all clinical and laboratory parameters. The incidence of blood cultures with positive results (20 versus 21 per cent) and underlying malignant lesions (51 versus 62 per cent) was also similar between the two groups. The percentage of patients with a clinical cure or significant improvement was the same in the two groups (69 versus 70 per cent). However, there was a significant difference in the cure rate between patients with benign and malignant biliary obstructions (83 versus 59 per cent, p less than 0.01). No significant differences were noted between the two antibiotic groups with respect to drug toxicity, but patients with malignant conditions were more prone to antibiotic related toxicities (2 versus 19 per cent, p less than 0.05). These data suggest that outcome of treatment in patients with acute cholangitis is similar with either a broad spectrum penicillin or a penicillin plus aminoglycoside combination and is dependent upon the nature of the biliary obstruction.
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Spectrum of invasive Haemophilus influenzae type b disease in adults. A prospective nationwide surveillance of invasive Haemophilus influenzae type b disease among adults (greater than or equal to 16 years old) was conducted in Finland during 1985 through 1988. Thirty-one cases were identified (annual incidence, 0.22/100,000). Of these infections, 71% occurred in patients with severe underlying conditions. The overall case fatality rate was 26%. Septicemia (13 patients) and pneumonia (seven patients) were the most common clinical manifestations of H influenzae type b infection; the others were epiglottitis (six patients), meningitis (three patients), and arthritis (two patients). Epiglottitis occurred in significantly younger patients, all of whom were women and four of whom were previously healthy. Subtyping of the H influenzae type b isolates according to the major outer membrane protein subtype, biotype, and lipopolysaccharide serotype showed that patterns that were uncommon (14%) among children were more common (27%) in the adults.
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Occurrence of secondary attenuating mutations in avirulent Salmonella typhimurium vaccine strains. The attenuating delta aroA554 mutation in Salmonella typhimurium strain SL3261 was complemented in vitro by selecting for AroA+ recombinant DNA clones. SL3261 containing cloned aroA+ genes did not require exogenous phenylalanine, tryptophan, tryosine, p-aminobenzoic acid, or dihydroxybenzoic acid for growth in defined media. Cloned aroA+ genes did not restore wild-type virulence to SL3261, however, in a murine typhoid model. The delta aroA554 mutation was transduced into S. typhimurium strain SR-11, a mouse-virulent strain recently passaged in mice. The SR-11 delta aroA554 mutant was highly attenuated for mice challenged parenterally. The same cloned aroA+ genes isolated in SL3261 restored the virulence of the SR-11 delta aroA554 mutant to that of wild-type SR-11. These results suggest that while the delta aroA554 allele remains effective in reducing S. typhimurium virulence, laboratory passage of attenuated vaccine strains may lead to the accumulation of additional attenuating defects.
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Antibiotic therapy for Bacillus species infections. We reviewed 36 cases of culture-proven Bacillus species ocular infections occurring between September 1974 and December 1989. Kirby-Bauer disk sensitivities were available in 34 of the 36 cases (95%). All Bacillus species isolates were sensitive to the aminoglycoside antibiotics (N = 34) and to vancomycin hydrochloride (N = 32); resistance to clindamycin was found in four of 18 (22%) of tested isolates. Although B. cereus was uniformly sensitive to these antibiotics, resistance to clindamycin occurred in four cases in the non-B. cereus group. The microbroth dilution technique confirmed the Kirby-Bauer data. The aminoglycosides were uniformly effective, but the cephalosporins (first, second, and third generation drugs) were consistently ineffective against B. cereus and varied from sensitive to moderately sensitive for the non-B. cereus isolates. Our microbiologic laboratory findings suggest that vancomycin hydrochloride in combination with an aminoglycoside ensures more consistent antibiotic coverage of Bacillus species ocular infections.
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Activity of compound G2 isolated from alfalfa roots in experimental dermatophyte infection. Compound G2 isolated from alfalfa roots was applied topically to skin lesions of guinea pigs experimentally infected with the dermatophyte Trichophyton mentagrophytes var. granulare. After 12 to 15 applications, 80% of the infected lesions were cured, as judged by clinical and microbial criteria, compared with 20% of the untreated lesions which healed spontaneously (P less than 0.01).
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A case of group B streptococcal pyomyositis The group B streptococcus is an opportunistic pathogen that causes a variety of serious infections including bacteremias, puerperal sepsis, and neonatal meningitis. Group B streptococcal infections of muscle are rare. We report here an unusual case of group B streptococcal pyomyositis. Pyomyositis arises predominantly from infections caused by Staphylococcus aureus and, occasionally, Streptococcus pyogenes. Because of the rarity of pyomyositis in temperate climates, the common lack of localizing signs or symptoms, and the frequently negative blood cultures, considerable delay often precedes the diagnosis of pyomyositis; in fact, the infection has been initially misdiagnosed as muscle hematoma, cellulitis, thrombophlebitis, osteomyelitis, or neoplasm. Diagnosis may be greatly aided by radiologic techniques that can demonstrate the sites of muscle enlargement and the presence of fluid collections. The response to antibiotics is usually rapid, but resolution of the infection may require aspiration of deeply situated muscle abscesses. This report describes a diabetic patient with an unusual presentation of pyomyositis that mimicked an acute abdomen.
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Splenic septic emboli in endocarditis. The significance of septic emboli to the spleen is inferred by the frequency of septic emboli in general seen in patients with left-sided infective endocarditis who are referred for valve replacement. To determine the proper management of splenic infarcts and abscess due to septic emboli, we retrospectively reviewed the records of 108 patients with left-sided endocarditis who underwent valvular surgery at the University of Illinois Hospital from 1980 through 1988. Intravenous drug abuse was the etiology in 68% (n = 73). The incidence of splenic infarcts and abscess was 19% (n = 20), but an incidental finding of splenic infarcts was found in 38% (n = 11) of 29 asymptomatic patients who had computed tomograms. Streptococci and staphylococci were the causative organisms in 85% (n = 17). Localized findings were absent in 90% of splenic infarcts and abscesses. Abdominal computed tomograms were diagnostic of the sequelae of splenic septic emboli in 100%. No patient had intra-abdominal bleeding complications associated with cardiopulmonary bypass. Splenectomy was performed in 50% (n = 10) of patients 3-24 days (mean, 11.2 days) after valve replacement. Indications for splenectomy included persistent sepsis in 60% (n = 6), large (greater than 2 cm) and peripheral lesions in 30% (n = 3), and splenic rupture in 10% (n = 1). Perioperative mortality of patients who underwent splenectomy was 30% (n = 3). The following conclusions can be drawn: 1) Splenic septic embolus is common in endocarditis. 2) Abdominal computed tomography should be performed for all patients.
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Day care characteristics associated with Haemophilus influenzae disease. Haemophilus influenzae Study Group. To identify characteristics of day care facilities associated with H. influenzae disease, we compared 92 licensed facilities in which a case of H. influenzae disease had occurred with randomly selected facilities at which no cases occurred. Matched univariate analysis showed that personnel at facilities where H. influenzae disease occurred were more likely than those at control facilities to use towels or handkerchiefs to wipe children's noses, admit children who were not toilet trained or had diarrhea ("liberal fecal policy"), had a narrower age range, were more likely than control facilities to be for-profit and less likely to use volunteers. In a multivariate model that adjusted for age range, profit status and liberal fecal policy, towel or handkerchief use (OR 5.5, 95% CI: 1.1, 30) was the only variable independently associated with case facilities. This is the first association of a specific day care practice with H. influenzae disease.
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Duplex Doppler examination of a perinephric abscess in a renal transplant. Perinephric abscess has no characteristic ultrasonic appearance or location. Differentiation from urinoma, lymphocele, or hematoma depends on clinical and laboratory findings. Therapy consists of percutaneous catheter drainage, surgical drainage, and antibiotic therapy. Acute rejection is the most common cause of decreased diastolic flow during the immediate postoperative period. Acute tubular necrosis does not usually alter blood flow unless it is severe. Duplex doppler ultrasonic assessment of the renal transplant during the immediate postoperative period may provide a valuable baseline for comparison if complications develop. Baseline and follow-up ultrasonography to evaluate diastolic flow can help determine whether a posttransplant patient should receive emergency or conservative therapy for complications.
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Effect of short-term intermittent antibiotic treatment on growth of Burmese (Myanmar) village children. To test the hypothesis that subclinical enteric infection (such as bacterial overgrowth), rice malabsorption, and growth faltering are causally linked, a field trial of low-dose, short-term, intermittent antibiotic treatment was carried out in 142 hydrogen-producing (by lactulose breath hydrogen test) Burmese village children aged 6-59 months. The children were randomly allocated treatment with metronidazole (20 mg/kg or 5 mg/kg daily), amoxycillin (25 mg/kg daily), or placebo given 1 week per month for 6 months. A cooked rice meal breath hydrogen test was done to classify the children as rice absorbers (RA) or rice malabsorbers (RM) before treatment and monthly on the day before each cycle of treatment. There were no differences between the treatment groups, so they were considered together. Factorial analysis showed that antibiotic treatment did not significantly affect the proportion of RM children. The only significant difference between antibiotic-treated and placebo-treated children's growth was in the subgroup of RM children aged 36-47 months; the antibiotic-treated children had significantly greater linear growth. In other age groups antibiotic treatment had no effect on growth.
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Bacterial infections in patients with visceral leishmaniasis. Bacterial infections are often seen in patients with visceral leishmaniasis. To determine the incidence of such infection and the more common infectious agents, 30 consecutive patients with visceral leishmaniasis were followed throughout hospitalization. There were 24 episodes of bacterial infection in 18 patients (60%). The incidence of bacterial infections in these patients was 22.2/1000 days of admission. The proportion of patients becoming infected by time was significantly greater in the visceral leishmaniasis group than in controls (P less than .01). The skin, respiratory tract, and middle ear were the most common sites of infection, and Pseudomonas aeruginosa and Staphylococcus aureus were the most common agents. Low-grade-virulence bacteria (e.g., Serratia and Providencia species) were also isolated from some cases. Bacterial infections (mainly nosocomial) in patients with visceral leishmaniasis tend to be severe and can cause death. When bacterial infection is suspected in these patients, empiric antibiotic therapy should be started immediately, including coverage for P. aeruginosa and S. aureus, after appropriate diagnostic procedures are taken.
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The prevalence of Helicobacter pylori in nonulcer dyspepsia. Importance of stratification according to age Helicobacter pylori (formerly Campylobacter pylori) is causally related to active antral gastritis and is highly associated with duodenal and gastric ulcers. However, the relationship of H pylori to nonulcer dyspepsia is less clear. We determined the presence of H pylori in unselected patients who were undergoing upper gastrointestinal tract endoscopy, and we found a prevalence of 37% in 110 patients with nonulcer dyspepsia that was similar to previous data. Patients with nonulcer dyspepsia who had H pylori were found to be significantly older than patients with nonulcer dyspepsia who did not have H pylori. In addition, when stratified according to age, we detected an increased prevalence of H pylori in patients with nonulcer dyspepsia with increasing age, similar to that reported for asymptomatic control populations. This finding casts doubt as to the causal role of H pylori for most patients with nonulcer dyspepsia and stresses the importance of considering epidemiologic factors, such as age, when evaluating the role of H pylori in specific disease states.
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Perinatal mortality in Victoria, Australia: role of group B Streptococcus. Group B beta-hemolytic streptococcus is the most common infective cause of neonatal morbidity and mortality. It is therefore surprising that no agreement exists for an approach to its prevention. There is also increasing evidence that occult infection may play an etiologic role in premature rupture of the membranes and preterm labor. In this report we review the role of group B beta-hemolytic streptococcal sepsis as a cause of perinatal wastage in the state of Victoria, Australia during the period 1982 to 1987. Group B beta-hemolytic streptococcus accounted for 1.7% of overall perinatal deaths, and for 30.3% (77 of 254) perinatal deaths directly attributable to infection. By comparison, over the same 6-year period, erythroblastosis accounted for 0.5% of perinatal wastage and there were only two deaths as a result of congenital syphilis. The true incidence of lethal group B beta-hemolytic streptococcal infection is probably greater because of the absence of histologic and bacteriologic studies in many perinatal deaths. We believe that intrapartum chemoprophylaxis with penicillin of all group B beta-hemolytic streptococcus-positive carrier mothers would significantly reduce neonatal morbidity and mortality from this cause.
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The many faces and phases of borreliosis. I. Lyme disease [published erratum appears in J Am Acad Dermatol 1991 Apr;24(4):663] Lyme disease is increasingly being reported throughout the United States and many parts of the world. Borrelia burgdorferi, the etiologic agent of Lyme disease, is a spirochete that, not unlike the treponema of syphilis, can cause a spectrum of disease from the initial skin lesion, through widely varied symptoms and signs, to chronic neurologic and arthritic disability. The borrelial spirochete and Lyme disease are the subject of this review. A subsequent article will review other definite and possible cutaneous manifestations of borreliosis.
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Fatal disseminated mycobacterial infection following intravesical bacillus Calmette-Guerin. We describe a fatal case of disseminated mycobacteriosis after intravesical bacillus Calmette-Guerin immunotherapy. We summarize the prior safety record of this therapeutic modality, discuss local and systemic pathophysiological mechanisms by which dissemination might have occurred, and review the reported clinical experience with antituberculous chemotherapy for significant bacillus Calmette-Guerin infection. Finally, we offer suggestions for prophylaxis of certain patients with a history of exposure to intravesical bacillus Calmette-Guerin.
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Controversies in the treatment of streptococcal pharyngitis An increasing number of cases of sore throat caused by group A beta-hemolytic streptococci occur with concomitant colonization by organisms that may "protect" the streptococci through beta-lactamase inactivation of penicillin at the site of infection. The failure of penicillin to eradicate many of these bacteria, which include Staphylococcus aureus, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis and a multitude of pharyngeal anaerobes, may help to explain why penicillin is sometimes ineffective for acute and recurrent group A streptococcal infections. Therapeutic alternatives currently include cephalosporins, erythromycin, rifampin combined with penicillin, amoxicillin/clavulanate potassium and others.
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Antibiotic compared with antiseptic prophylaxis for prostatic surgery. Two different regimens of cephalosporin antibiotic prophylaxis were compared with antiseptic lubricating jelly to try to prevent infection and complications in 196 men after prostatic surgery. Pre-operative urine was cultured and prostatic chips (170 cases) were also cultured to define the source of any infection. The use of antibiotics was associated with a reduced risk of postoperative bacteriuria. No serious complications occurred, although 1 patient in the antiseptic treated group developed rigors; 79 of 170 patients (46%) had positive prostatic chip cultures, of whom 74 had sterile pre-operative urine. There was no association between the result of chip culture and the presence of a pre-operative catheter. Culture positive patients had an increased risk of post-operative urine infection, although the same organism was found in the prostate and urine in only 36% of cases of post-operative bacteriuria and in 43 (54%) the organism cultured from the prostate was Staphylococcus albus. This study provides further evidence of the benefit of true prophylactic antibiotic therapy for transurethral prostatic surgery and the prostatic chip data suggest that some of the risk is due to pre-operative contamination of the prostate in the absence of per-operative urinary infection or catheterisation.
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Acute syphilitic posterior placoid chorioretinitis. Six patients with evidence of secondary syphilis presented with visual loss in both eyes caused by large, placoid, yellowish lesions with faded centers at the level of the pigment epithelium in the macula and juxtapapillary areas. All eyes had vitreitis. All of the lesions showed a similar fluorescein angiographic pattern of early hypofluorescence and late staining. Five patients had mucocutaneous lesions typical of secondary syphilis. All five patients treated with antibiotics had prompt improvement in visual function and resolution of the fundus lesions. The ophthalmoscopic and angiographic appearance of these posterior fundus lesions was sufficiently characteristic to suggest a diagnosis of secondary syphilis. Modification of the host response to syphilis by human immune deficiency virus (HIV) infection may be partly responsible for this peculiar fundus picture. Three of the four patients tested positive for HIV.
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Value of antigen detection in predicting invasive pulmonary aspergillosis Two ELISAs were used to detect serum and urinary aspergillus antigen in 121 patients who were profoundly neutropenic after leukaemia therapy or bone marrow transplantation. The presence of antigen correctly predicted development of invasive pulmonary aspergillosis (IPA) in 16 patients. In 2 other cases antigen appeared after the clinical diagnosis had been made, while in only 1 case was antigen not detected. In 11 of 13 episodes of clinically suspected fungal infection antigen was detected before clinical diagnosis was made. By contrast, antigen was detected in only 1 of 90 patients who had no evidence of IPA. Both ELISAs gave positive and negative predictive values for IPA of greater than 95%, demonstrating the value of antigen detection in early diagnosis of aspergillus infection and the assay's ability to predict subsequent development of IPA. We conclude that neutropenic patients should be screened for aspergillus antigen, and propose that initial detection of fungal antigen justifies commencement of empirical antifungal therapy. Such an approach should improve the survival of patients who are at risk of developing this usually fatal infection.
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Drug therapy for Helicobacter pylori infection: problems and pitfalls. Antibacterial chemotherapy against Helicobacter pylori is currently being assessed by open or randomized controlled clinical studies for its efficacy in eradicating this bacterium from the stomach of patients with gastritis or gastroduodenal ulcer. Whereas there is presently no "optimal" agent and treatment scheme, the combination of some antibiotics (metronidazole, tinidazole, amoxicillin) with bismuth salts proves definitely superior in vivo to either of these agents administered alone. Several reasons have been proposed, to explain the clinical failure after treatment: insufficient concentration of active drugs in gastric mucus, instability of some agents at an acidic pH, inappropriate formulation of drug, insufficient duration of treatment, and variable compliance of patients. Recently, it has appeared from several clinical trials that H. pylori may rapidly acquire resistance to some antibiotics, and that this event might also account for clinical failure. A critical review of the literature on H. pylori treatment indicates that association of bismuth and antibiotics or of antibiotics alone both may efficiently reduce the risk of emergence of resistance and improve the therapeutic outcome. Guidelines of treatment are suggested in order to avoid the future misuse of antibiotics that would increase selection of antibiotic-resistant H. pylori and negatively affect the ecology of the gastric microflora. Likewise, an accurate definition of a subset of patients with H. pylori who really will require treatment needs to be rapidly established.
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The process of microbial translocation. The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.
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Antibodies in human tears during and after infection. The tear content of antibodies specific for various infectious agents has recently begun to be investigated. Important parameters of tear analysis with respect to antibody content are the method of tear collection and the laboratory techniques used to detect specific antibodies in the lacrimal fluid. Normal tears contain antibodies directed against both bacteria and viruses, and the antibody response in lacrimal fluid during immunization of animals and humans has been studied to some extent. This response has also been analyzed in humans during and after natural infection with certain viral and bacterial pathogens. It has become clear that local antibody synthesis takes place in the lacrimal gland, but at least some of these antibodies appear in tears because of lymphocyte sensitization in the common mucosal immune system. A certain degree of transudation of serum antibodies to tears is also often encountered, especially in severely inflamed eyes. Much of the data currently available needs to be confirmed, and more extensive studies need to be carried out for many pathogens. Potential benefits of such studies include development of new diagnostic techniques as well as a better understanding of when and how antibodies confer protection or may be potentially damaging.
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Congenital insensitivity to pain with neuroparalytic keratitis. Congenital insensitivity to pain is a well-defined entity in the group of sensory deficiency syndromes. To the best of our knowledge, unilateral neuroparalytic keratitis associated with congenital insensitivity to pain has not been reported. We report such a case to alert clinicians to this potentially blinding problem.
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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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Development and potential use of antibody directed against lipopolysaccharide for the treatment of gram-negative bacterial sepsis. Gram-negative bacterial sepsis remains a major cause of lethality in hospitalized patients, despite routine therapy consisting of antimicrobial agents, hemodynamic monitoring and fluid resuscitation, and metabolic support. Because a large body of evidence supports the concept that Gram-negative bacterial lipopolysaccharide (endotoxin, LPS) is responsible for many of the direct and host mediator-induced deleterious effects, recent work has been centered on the development and use of anti-LPS antibody preparations in order to ameliorate lethality. Both polyclonal and monoclonal antibody preparations directed against the common deep core/lipid A region of LPS are cross-reactive in vitro and cross-protective in vivo against a wide range of challenge organisms and LPS, and preliminary clinical trials indicate that a reduction in lethality may be possible. The precise endotoxin epitope against which antibody should be directed in order to maximize protection, however, has not been established. This modality most probably will become a standard form of adjunctive therapy within the next several years for the treatment of Gram-negative bacterial sepsis.
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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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A randomized, double-blind trial of nystatin therapy for the candidiasis hypersensitivity syndrome BACKGROUND. Candida albicans infection has been proposed to cause a chronic hypersensitivity syndrome characterized by fatigue, premenstrual tension, gastrointestinal symptoms, and depression. Long-term antifungal therapy has been advocated as treatment for the syndrome, which is most often diagnosed in women with persistent or recurrent candida vaginitis. METHODS. To determine the efficacy of nystatin therapy for presumed candidiasis hypersensitivity syndrome, we conducted a 32-week randomized, double-blind, cross-over study using four different combinations of nystatin or placebo given orally or vaginally in 42 premenopausal women who met present criteria for the syndrome and had a history of candida vaginitis. The outcomes studied were the changes from base line in scores for vaginal, systemic, and overall symptoms and in the results of standardized psychological tests. RESULTS. The three active-treatment regimens (oral and vaginal nystatin, oral nystatin and vaginal placebo, and oral placebo and vaginal nystatin) and the all-placebo regimen significantly reduced both vaginal and systemic symptoms (P less than 0.001), but nystatin did not reduce the systemic symptoms significantly more than placebo. On average, the scores for systemic symptoms improved 25 percent with the three active-treatment regimens and 23 percent with the all-placebo regimen, a difference of only 2 percent (95 percent confidence interval, -3 to 7 percent). As expected, the three active-treatment regimens were more effective than placebo in relieving vaginal symptoms (P less than 0.001). All four regimens reduced psychological symptoms and global indexes of distress; there were no significant differences among the treatment regimens. CONCLUSIONS. In women with presumed candidiasis hypersensitivity syndrome, nystatin does not reduce systemic or psychological symptoms significantly more than placebo. Consequently, the empirical recommendation of long-term nystatin therapy for such women appears to be unwarranted.
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In vitro evaluation of nicotinamide riboside analogs against Haemophilus influenzae. Exogenous NAD, nicotinamide mononucleotide, or nicotinamide riboside is required for the growth of Haemophilus influenzae. These compounds have been defined as the V-factor growth requirement. We have previously shown that the internalization of nicotinamide riboside is energy dependent and carrier mediated with saturation kinetics. Thionicotinamide riboside, 3-pyridinealdehyde riboside, 3-acetylpyridine riboside, and 3-aminopyridine riboside were prepared from their corresponding NAD analogs. These compounds and several other nicotinamide riboside analogs were evaluated for their ability to support the growth of H. influenzae and for their ability to block the uptake of [carbonyl-14C]nicotinamide riboside by H. influenzae. 3-Aminopyridine riboside blocked the uptake of [carbonyl-14C]nicotinamide riboside and inhibited the growth of H. influenzae when NAD, nicotinamide mononucleotide, or nicotinamide riboside served as the V factor. The antibacterial activity of 3-aminopyridine riboside was found to be specific for H. influenzae but had no effect on the growth of Staphylococcus aureus or Escherichia coli. In additional experiments by reversed-phase high-performance liquid chromatography, it was determined that whole cells of H. influenzae degrade 3-aminopyridine adenine dinucleotide to 3-aminopyridine riboside, which is then internalized. Inside the cell, 3-aminopyridine riboside has the ability to interfere with the growth of H. influenzae by an undetermined mechanism.
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Whither short-course chemotherapy for tuberculous meningitis? Short-course chemotherapy is well established for the treatment of pulmonary tuberculosis but not for extrapulmonary disease. We present a series of 35 cases in which chemotherapy for tuberculous meningitis was given for a period of less than 2 years. Short-term therapy was associated with recrudescence of tuberculous meningitis and, in some cases, with the development of deep cerebral infarcts and permanent neurological deficits. We think short-term chemotherapy for tuberculosis of the central nervous system is inadequate.
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Sexually transmitted arthritis syndromes. Sexually transmitted infections may provoke a wide variety of rheumatic lesions. Disseminated N. gonorrhoeae infection leads to septic arthritis, which may be rapidly destructive but which responds promptly to appropriate antibiotic therapy. In contrast, both gonococcal and nongonococcal infections may lead to aseptic "reactive" arthritis or Reiter's syndrome. Inheritance of HLA B27 confers a relative risk of 30 to 50 times for the development of this condition. The demonstration of C. trachomatis antigen in joint material from a minority of patients suggests that direct interaction between microbial components and class I HLA antigens in the joint may be central to the pathogenesis of this disease. Arthralgia and arthritis occur in up to 50% of individuals in the prodrome of hepatitis B infection. Joint symptoms may be accompanied by urticarial or cutaneous vasculitic lesions, especially on the legs; both features resolve with the onset of jaundice. Hepatitis B infection is also a major cause of necrotizing vasculitis, which may or may not be associated with overt hepatitis. Seronegative arthritis, including Reiter's syndrome, psoriatic arthritis, and undifferentiated arthritis, a Sjogren's-like syndrome, vasculitis, and myopathies have been described in association with HIV infection. It is clear that synovitis occurs in those patients despite the fact that HIV is present in immune cells within the joint during inflammatory arthritis and that both antigen presentation and lymphocyte responsiveness within the joint are impaired. Nevertheless, synovitis may occur in the presence of marked CD4-positive lymphocyte depletion. Rheumatic syndromes, including arthralgia, inflammatory arthritis, and neuropathic arthritis, may occur during any stage of congenital or acquired syphilis. Syphilitic synovitis responds well to antibiotic therapy, but neuropathic lesions cannot be treated effectively. Septic arthritis has rarely been described as a complication of disseminated Mycoplasma or Urea-plasma infections, and joint lesions sometimes associated with erythema nodosum have also been reported in lymphogranuloma venereum and granuloma inguinale.
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Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. About five out of 1,000 patients admitted to hospital develop bacterial sepsis leading to shock, the mortality rate for which is high despite antibiotic therapy. The infection results in hypotension and poor tissue perfusion, and eventually leads to the failure of several organ systems. Bacterial endotoxin is thought to be the direct cause of shock in Gram-negative sepsis, because it can cause shock in animals, and antibodies against endotoxin prevent Gram-negative shock in animals and in humans. But, the symptoms of septic shock are the result of the actions of host cytokines induced by the endotoxin. The cytokine interleukin-1 has been implicated as an important mediator of septic shock because it can induce tachycardia and hypotension and act synergistically with tumour necrosis factor to cause tissue damage and death. We now report that a specific interleukin-1 receptor antagonist reduces the lethality of endotoxin-induced shock in rabbits, indicating that interleukin-1 does indeed play an important part in endotoxin shock.
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The efficacy of pediatric blood culture sets in the determination of burn bacteremia. A blood culture is an essential laboratory procedure necessary to confirm a septic episode. However, it is important to collect the blood sample at the appropriate time with an acceptable technique. The standard method is to collect at least 5 to 10 ml blood per culture bottle from patients with fevers. However, this volume of blood is an unrealistic amount to take from the frequently febrile pediatric patient. Alternatively, the pediatric blood culture bottle allows the collection of 1 ml blood per bottle to perform the same evaluation. We evaluated the two techniques of blood-culture collection over a 9-month period and compared the results between adult and pediatric blood culture bottles. Seventy-six patients, from November 1988 through February 1989, had blood cultures performed with the adult culture bottles, which produced a total of 1314 samples. A total of 113 patients, from March through July 1989, had blood cultures performed with the pediatric culture bottles, which produced a total of 758 samples. Percent recovery for the adult bottles versus the pediatric bottles was 13.95% versus 22.8% (p less than 0.0001). Since the amount of blood necessary to isolate an infectious agent is critical not only for laboratory identification but also for the volume of blood of pediatric patients, these data clearly establish the efficacy of pediatric blood culture bottles and the utilization of smaller amounts of blood. Not only did this approach significantly enhance organism recovery rate, but it may well be more cost-effective because fewer cultures need to be performed to isolate the infectious organism.
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Acute and chronic bacterial prostatitis: a review of treatment approaches. Some authors describe acute bacterial prostatitis as a self-limiting disease, and as with any other acute septic condition, parenteral broad-spectrum antibiotic therapy is indicated. Chronic bacterial prostatitis, however, is associated with a causative organism persisting unaltered in prostatic fluid and leading to relapsing urinary tract infections. In the 1970s, several workers produced a classification system and bacteriologic localization cultures for establishing the diagnosis of prostatitis. Krieger and Crawford point to an important factor that is omitted in many clinical trials with episodes of chronic bacterial prostatitis in men. If localization studies of the prostate infection are attempted in the presence of bacteriuria, the urine must be sterilized with nitrofurantoin or penicillin G. Urine cultures obtained from first-voided urine, bladder urine, and urine voided after prostatic massage should show no growth, and the expressed prostatic secretion can then be examined for evidence of prostatic infection. This procedure reduces the contamination of the expressed prostatic secretion by the organism from the urinary tract infection. This is important, because antibiotic treatment is determined by the sensitivity of the organism isolated from the prostate as well as by the ability of the antibiotics to penetrate the prostate. Meares outlines the pharmacokinetic features needed for drug diffusion into prostatic fluid and provides detailed information on the physical characteristics of the prostate during acute and chronic bacterial prostatitis. Unfortunately, the choice of an ideal drug cannot be extrapolated from this information because pharmacodynamic principles cannot predict clinical efficacy. Some authors find that sulfamethoxazole-trimethoprim has the best cure rate in the treatment of chronic bacterial prostatitis.
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Ocular syphilis. The ability of syphilis to mimic different ocular disorders can lead to misdiagnosis and delay in appropriate antimicrobial therapy. The authors describe their experience over the past 5 years with the ocular manifestations of syphilis in 25 patients who comprised 2.45% of 1020 new patients. Uveitis was the most common ocular manifestation seen. All patients had positive results from FTA-ABS tests, whereas only 68% had reactive serum VDRLs. Two of five patients tested for human immunodeficiency virus (HIV) antibody were reactive. The authors recommend routine FTA-ABS and VDRL screening in patients with uveitis or unexplained ocular inflammation. They also recommend testing for HIV antibody in luetics and aggressive treatment with high-dose aqueous penicillin for syphilis.
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Tuberculous meningitis. Short course of chemotherapy. In March 1986, we began a 6-month short course trial of therapy for tuberculous meningitis, in which 28 patients were analyzed. The diagnosis was based on the following cerebrospinal fluid test results: in 53.5% of the cases, Mycobacterium tuberculosis was identified by direct smear; in 57%, culture in Lowenstein-Jensen medium was positive; in 83.3%, the detection of anti-bacille Calmette-Guerin (BCG) antibodies by enzyme-linked immunosorbent assay was positive; and in 74%, the dosification of adenosine deaminase activity was positive. In addition, in 21.4% of the cases, the diagnosis was established by means of autopsy findings. Moreover, the diagnosis was supported by bacteriological analyses from another tissue or body fluids. Despite the administration of an antituberculous therapy, 32.4% of the patients died: all of the decreased had reached the last stage of the disease by the beginning of treatment. Sixteen percent of the patients who survived after more than 18 months of follow-up after therapy had ended suffered neurological sequelae. With the 6-month therapeutic regimen, the morbidity/mortality is similar to that found in the longer-course therapies. The latter regimen is therefore thought to be a good and acceptable therapeutic option for the treatment of tuberculous meningitis.
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Relapse of infant botulism. We report on 3 infants who had relapse of infant botulism after apparent resolution of clinical symptoms. This group represented 5% of the infants with confirmed infant botulism who were treated at our institution since 1976. The exact cause for these relapses was unclear, but three potential mechanisms are examined. There were no historical, clinical, or electrophysiological predictors of relapse. Although at the time of writing recovery from relapse appeared complete, close follow-up of patients recovering from a bout of infant botulism is necessary.
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Use of intrapleural streptokinase in the treatment of thoracic empyema. The incidence of pleural effusions in bacterial pneumonia may exceed 40%, a factor that may be related to increased morbidity and mortality. Options in the treatment of complicated pleural effusions or empyema, when unresponsive to closed tube drainage, include repositioning of the indwelling tube thoracostomy or insertion of additional chest tubes, instillation of intrapleural streptokinase, and surgical intervention. The authors describe the course of three patients wherein the use of intrapleural streptokinase was efficacious in effecting prompt drainage of previously inadequately evacuated empyema, thus eliminating the necessity for further invasive intervention.
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Itraconazole in common dermatophyte infections of the skin: fixed treatment schedules. Itraconazole is an effective medication against the most common dermatophytoses. It has been shown to be more active than griseofulvin and ketoconazole. Ease of use, affinity for keratinized tissues, lack of toxicity, continued activity after discontinuation, and the possibility of using fixed schedules are advantages of itraconazole. The fixed schedules indicated by pharmacokinetics and clinical studies are one 100 mg capsule daily for 15 days in cases of tinea corporis and tinea cruris and the same dosage for 30 days in cases of tinea pedis and tinea manuum. These fixed treatments have some limitations, and they are not recommended for treating tinea capitis and tinea unguium. The drug is well tolerated.
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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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Recombinant capsular antigen (fraction 1) from Yersinia pestis induces a protective antibody response in BALB/c mice. Yersinia pestis produces a glycoprotein capsule, the biosynthesis of which appears to be temperature dependent. The fraction I (F1) component of this capsule is specific to Y. pestis and the detection of F1 antibodies is the basis for several serological tests. We report the cloning of the F1 gene and its expression in Escherichia coli using the phagemid vector lambda ZAPII and a F1-specific monoclonal antibody. The recombinant F1 antigen had a molecular weight of 17 kDa, which proved to be identical to that of the F1 antigen produced by Y. pestis. The recombinant cells produced F1 antigen at 37 degrees C but only minimal amounts at 27 degrees C, suggesting that the genetic features affected by temperature in Y. pestis may be operating in the E. coli clone. It is not known if their similar molecular weights reflect the glycosylated nature of both proteins. F1 antigen purified from the E. coli recombinant induced a protective immune response in BALB/c mice challenged with up to 10(5) virulent Y. pestis. The resistance of immunized mice to plague infection correlated with high titers of F1 antibody. The cloned gene expresses an immunogenically competent F1 antigen suitable for use in plague serodiagnostics and vaccine development.
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Itraconazole therapy for nonmeningeal coccidioidomycosis: clinical and laboratory observations. Itraconazole, a new oral triazole antifungal agent, was administered in 75 courses to patients with chronic coccidioidomycosis at dosages of 50 to 400 mg/day for a median duration of 10 months. Assessment of efficacy was made with a standardized scoring system. Responses were seen in 42 of 58 assessable courses (72%). Nonresponse occurred exclusively in patients who had failed previous therapy and was most common in pulmonary disease. Toxicity was minimal at the doses studied. Pharmacokinetic analysis of itraconazole in serum at steady state showed negligible circadian variation; differences in serum concentrations among patients were large. Clinical isolates of Coccidioides immitis showed uniform in vitro susceptibility to itraconazole. Itraconazole shows impressive activity in this series of patients with refractory coccidioidomycosis. Further evaluation of itraconazole in this and in other systemic mycoses is in order.
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Accuracy in early prediction of prognosis of patients with septic shock by analysis of simple indices: prospective study. In 26 consecutive septic shock patients, we analyzed the clinical, hemodynamic, and metabolic data before and during volume infusion to test their circulatory reserve in response to fluid repletion. These patients were investigated to identify early variables that could predict outcome. There were 15 survivors (group A) and 11 nonsurvivors (group B). As a mean, group A patients were hemodynamically evaluated 2.3 h after onset of the sepsis syndrome, whereas group B patients underwent cardiac catheterization after a 12-h interval. At the initial evaluation, both groups demonstrated similarly decreased mean arterial pressure, mean heart rate, and mean cardiac filling pressure. Only group A patients evidenced elevated cardiac index (CI) (greater than 4 L/min.m2) associated with low systemic vascular resistance index (less than 7400 dyne.sec/cm5.m2), which is generally recognized as hyperdynamic cardiac state. However, none of the initial cardiovascular variables could serve as a predictor for survival. Fluid challenge increased left ventricular preload from 6 to 12.4 and from 7.8 to 12.7 mm Hg in group A and group B, respectively. The increases were associated with significant increases in CI from 4.4 to 6.9 and from 3 to 3.8 L/min.m2. However, at the end of fluid challenge, only group A patients exhibited normal cardiac response, as evidenced by the change in left ventricular stroke work index (LVSWI) for a given increase in the pulmonary capillary wedge pressure (WP) that was referred to as left cardiac preload.
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Diagnosis and treatment of prostatic infections. The diagnosis and management of prostatitis and pelviperineal pain is a challenge to the clinician. Careful examination of the prostatic fluid and bacteriologic cultures to differentiate bacterial from nonbacterial prostatitis are essential. Antimicrobial therapy is effective in the majority of men with acute or chronic bacterial prostatitis. Nonbacterial prostatitis is the most common type of prostatitis. The etiology is unknown and treatment with repeated antimicrobial therapy is ineffective. Alpha-blocking agents may relieve symptomatology. Pelviperineal pain may be of prostatic origin but other nonprostatic causes should be sought.
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Blood contamination of anaesthetic and related staff The incidence of skin contamination of anaesthetic and related staff by patient's blood and saliva was studied during 270 anaesthetics in Cardiff hospitals over seven continuous days in October 1989. A survey was also made of current Hepatitis B immunisation status and glove-wearing habits of 75 anaesthetists. Blood from 35 (14%) patients caused skin contamination of 65 staff during 46 incidents. Twenty-eight (61%) of the contamination incidents occurred during vessel cannulation. Five (8%) of the 65 staff contaminated by blood already had cuts on their hands. There were nine incidents (4%) of skin contamination by saliva. Fifty-three (71%) anaesthetists were immunised against Hepatitis B. Only seven (9%) anaesthetists wear gloves for oral or nasal intubation, six (8%) for insertion of peripheral venous cannulae, 47 (63%) for insertion of arterial lines and 67 (89%) for insertion of central lines. All anaesthetic and associated staff should wear gloves on a routine basis.
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Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori. Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment.
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