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Biomedical subjects

W M Dankner

Publications and source records attributed to W M Dankner.

36 records · Page 2Linked to original sources
PubMed1993

Prenatal diagnosis of congenital cytomegalovirus infection: false-negative amniocentesis at 20 weeks' gestation.

Cytomegalovirus (CMV) is the most common cause of congenital infection. Recent studies show amniocentesis to be a 100 per cent sensitive and 100 per cent specific predictor of congenital infection, and recommend that it be offered in the at-risk pregnancy. However, these publications have focused on pregnancies at or beyond 22 weeks' gestation. Here, we report a case of maternal CMV hepatitis at 7-8 weeks' gestation, in which culture and polymerase chain reaction testing for CMV in amniotic fluid at 20 weeks' gestation were negative, but the infant had a positive CMV urine culture shortly after delivery. Implications for the prenatal diagnosis of CMV infection are discussed.

Adult↗
PubMed1993

Development and significance of zidovudine resistance in children infected with human immunodeficiency virus.

Decreasing susceptibility to zidovudine (ZDV) has been described in persons infected with human immunodeficiency virus (HIV) type 1 who are receiving ZDV therapy. However, the clinical significance of decreased ZDV susceptibility remains unclear. In this study, HIV isolates obtained from children with symptomatic HIV infection treated with ZDV were monitored for their susceptibility to the antiretroviral agent and correlated with disease progression. Using a peripheral blood mononuclear cell-based assay to measure ZDV susceptibility, we evaluated HIV isolates from 19 children (mean age, 6.8 years; range, 5 months to 12 years) during ZDV therapy for susceptibility to ZDV. Of the 19 children studied, 10 continued to have susceptible HIV strains during ZDV treatment, and 9 acquired resistant viruses. All eight isolates from children without previous exposure to ZDV were initially susceptible. After a median of 11 months of ZDV therapy, three (38%) of these eight children had acquired resistant HIV strains (defined as ZDV susceptibility > or = 10 mumol/L). Children with resistant strains had worse clinical outcomes than children whose viruses remained susceptible, as determined by a 50% decline in absolute CD4+ cell counts after 1 year of treatment, failure to thrive, or death. Children with resistant viruses who were given alternative antiretroviral therapy frequently responded to the new treatment with improved growth and stabilization of their HIV-related disease. These data suggest that, in HIV-infected children, ZDV-resistant HIV strains are associated with diminished drug efficacy and more rapid disease progression.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Pathophysiology and treatment of clinically resistant cytomegalovirus retinitis.

PURPOSE: To determine the incidence, pathophysiology, clinical outcome, and survival in patients with clinically resistant retinitis. METHODS: Cytomegalovirus (CMV) retinitis was prospectively studied in 100 patients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new activity or progression, despite at least 8 consecutive weeks of induction doses of either foscarnet or ganciclovir. Fundus photography, pharmacokinetics, CMV cultures and sensitivities, and survival analyses were studied. The therapeutic interventions attempted after clinically resistant retinitis was identified included continuing a high dose (induction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir. RESULTS: Clinically resistant retinitis occurred in 11 (11%) of 100 patients with CMV retinitis and appeared to be a manifestation of acquired CMV antiviral drug resistance. Drug metabolism and pharmacokinetics in these patients were normal. The use of combination therapy with foscarnet and ganciclovir was effective in halting the progression of retinitis in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy. CONCLUSION: Clinically resistant retinitis is a manifestation of infection by CMV that has acquired drug resistance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive longer.

AIDS-Related Opportunistic Infections↗
PubMed1993

Pediatric human immunodeficiency virus infection in a low seroprevalence area.

Although increasing information is available regarding human immunodeficiency virus (HIV) infections of children in high seroprevalence areas, few data are available describing trends in low seroprevalence populations. In San Diego County approximately 1 in 1450 live births are to women infected with HIV as identified by nonlinked heel stick testing. Seventy-seven HIV-infected children were identified and followed in our clinics during the period 1983 to 1991, of whom 32 (42%) were infected perinatally, 32 (42%) were hemophiliacs and 13 (17%) were infected by blood transfusions. During the last 4 years of the study period (1988 to 1991), most (28 of 37, 76%), newly identified HIV-infected children less than 13 years old were perinatally infected. Of the 32 perinatally infected children 50% were Hispanic, 34% were Caucasian and 16% were African-American. The prospective vertical transmission rate was 16%. Twenty-nine (38%) of the HIV-infected children have a diagnosis of acquired immunodeficiency syndrome and 17 (22%) have died. Comparatively few of the HIV-infected hemophiliac patients (4 (12%)) have progressed to an acquired immunodeficiency syndrome diagnosis. The number of acquired immunodeficiency syndrome diagnoses declined in the last 2 years of the study as a result of fewer cases of Pneumocystis carinii pneumonia; 11 cases of P. carinii pneumonia were diagnosed in 1988 to 1989 compared with 4 cases in 1990 to 1991. Survival analysis for the perinatally infected group yielded a median survival of 9.2 years. The apparent trend in our data toward improved outcomes of children infected with HIV suggests the beneficial effects of early identification, antiretroviral treatment, and P. carinii pneumonia prophylaxis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Mycobacterium bovis infections in San Diego: a clinicoepidemiologic study of 73 patients and a historical review of a forgotten pathogen.

We have presented 73 patients (48 adults and 25 children) with microbiologically documented M. bovis infections identified over the 12-year period from 1980 through 1991. Epidemiologic investigation of these patients revealed that the majority (80%) were of Hispanic origin. The non-Hispanic patients either had traveled extensively outside the United States, were born in the United States during its endemic period or in other countries with endemic bovine tuberculosis, or were exposed to a close relative with a positive PPD and known exposure to M. bovis. For Hispanic patients, the presence of reactivation disease in adults and primary disease in children indicate that this mycobacterium remains endemic in Mexican beef and dairy herds, a position supported by United States monitoring of Mexican cattle transferred across the border. Our review of the historical and contemporary efforts to eradicate this animal and human pathogen from the livestock industry in the United States and abroad shows that the implementation of similar methods could be effective in Mexico. The detailed presentations of selected patients and summaries of the clinical manifestations in the remainder of our 73 patients reveal striking similarities to historical accounts and to more contemporary studies of reactivated disease in England. Although M. bovis infections are still expressed predominantly in extrapulmonary sites (cervical and mesenteric nodes, the peritoneum, and the GU tract), as many as 50% of adult patients will present only with pulmonary disease. Underlying immunosuppressive disorders were particularly prominent in adults with extrapulmonary disease. For example, HIV positive patients accounted for 12 of 48 adults and 1 adolescent patient in our series. Overall, M. bovis infections accounted for almost 3% of all tuberculous disease reported in San Diego County during the study period. The intrinsic resistance of M. bovis to PZA could threaten the response of patients with bovine tuberculosis to the short-course chemotherapeutic regimens now recommended by the CDC and the American Thoracic Society. We strongly recommend continued surveillance for this forgotten pathogen because the importation of Mexican cattle, the migration of Hispanic immigrants from border areas to the United States interior, and the persistence of extrapulmonary disease in immunocompetent and HIV-infected United States citizens assure its persistence in this country.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Detection of human cytomegalovirus in plasma of AIDS patients during acute visceral disease by DNA amplification.

By using the polymerase chain reaction (PCR) amplification procedure, 19 (83%) of 23 plasma specimens obtained from individuals with AIDS and human cytomegalovirus (HCMV) visceral disease were found to be positive for plasma viremia as detected by PCR (PV-PCR), whereas 78% of cultures of peripheral blood leukocytes from the same samples were found to be positive. All 11 specimens prospectively obtained from individuals with acute HCMV disease were positive by PV-PCR. Plasma specimens from patients who received ganciclovir therapy rapidly became both culture and PV-PCR negative, and there was an excellent correlation between the two procedures. DNA detected by PV-PCR was unaffected by filtering plasma through a 0.2-microns-pore-size filter, although a conserved cellular gene, HLA-DQ alpha, was undetectable by PCR following filtration. HCMV DNA in plasma could be quantitated by PV-PCR by using endpoint serial dilutions, with detectable virus being present in 10(1) to 10(-2) microliters of plasma. A low titer of infectious virus could be detected in 2 of 11 plasma samples. The detection of HCMV DNA in plasma by PV-PCR promises to be a useful procedure for monitoring patients with AIDS suspected of having impending, acute, or recurrent HCMV visceral disease and suggests an additional route by which virus may disseminate in the immunocompromised host.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Rapid antiviral DNA-DNA hybridization assay for human cytomegalovirus.

A rapid DNA-DNA hybridization technique that can be accomplished in 4 to 5 days was compared with plaque reduction assay to determine its reliability in performing antiviral assays for human cytomegalovirus (HCMV). The assay involves lysing infected cells, direct wicking of denatured DNA onto membranes and hybridization using a 125I-labeled HCMV DNA probe. Using ten ganciclovir sensitive clinical HCMV strains for comparison, the DNA hybridization technique correlated well with the plaque assay. Clinical HCMV strains previously identified as resistant to ganciclovir were also readily identified. The DNA-DNA hybridization assay is less tedious and more rapid than plaque reduction assays, and thus, provides an excellent alternative for evaluation of the antiviral activity of drugs against HCMV.

Cells, Cultured↗
PubMed1990

Localization of human cytomegalovirus in peripheral blood leukocytes by in situ hybridization.

The in vivo interaction of human cytomegalovirus (HCMV) with leukocytes from a group of immunosuppressed patients was studied using specific subgenomic DNA probes and in situ cytohybridization. Study subjects had no recognized disease due to HCMV or had HCMV retinitis or colitis. Viral nucleic acid was detected in lymphocytes, monocytes, and polymorphonuclear leukocytes (PMNL). PMNL were consistently hybridization-positive for HCMV RNA and DNA in patients with HCMV viremia. Monocytes were occasionally positive by hybridization and lymphocytes were rarely positive. These findings demonstrate that the HCMV genome is expressed in PMNL of viremic patients and that PMNL may play an important role in virus dissemination.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Treatment of bacterial meningitis with once daily ceftriaxone therapy.

Ceftriaxone, a cephalosporin with an extended half-life and excellent antibacterial activity was used to treat bacterial meningitis, given as a single daily intravenous dose of 100 mg/kg on day one, followed by 80 mg/kg daily. A total of 22 patients were treated, of whom 14 had Haemophilus influenzae type b, five had Streptococcus pneumoniae and three Neisseria meningitidis isolated from their CSF. The CSF of all patients became sterile within 24-48 h. The CSF ceftriaxone concentrations 24 h after dosing were 10 to 100-fold higher than the MIC of the pathogenic bacteria early in therapy, and five to 50-fold higher at the end of therapy. Side effects encountered included mild diarrhoea (32%), thrombocytosis (77%) and neutropenia (9%), but none caused therapy to be stopped. Ceftriaxone is a safe and effective antibiotic for the treatment of bacterial meningitis when administered once daily.

Adolescent↗
PubMed1987

Peroxidase-antiperoxidase assay for rapid detection of respiratory syncytial virus in nasal epithelial specimens from infants and children.

A peroxidase-antiperoxidase (PAP) assay for the rapid detection of respiratory syncytial virus was compared with the indirect immunofluorescence method and with viral culture. Nasal epithelial specimens from 147 infants and children with acute respiratory infections were obtained and evaluated for the presence of respiratory syncytial virus antigens. Sensitivity, specificity, and accuracy by PAP were 91.7, 84.8, and 87.1%, respectively, and 87.0, 88.5, and 88.0%, respectively, by immunofluorescence compared with viral culture. The PAP assay was found to be as accurate as the indirect immunofluorescence method and more convenient to perform, since the color reaction and cell morphology were more easily observable by light microscopy. A new specimen collection method is reported; gentle scraping of the superficial nasal mucosa by the Rhino-probe method provided sufficient numbers of epithelial cells to perform multiple assays.

Adolescent↗
PubMed1986

Rapid viral diagnostic techniques.

The application of viral diagnosis to clinical medicine is approaching a critical period in which greater emphasis will be placed on altering patient care as a result of viral identification. Although isolation of viruses in tissue culture is the "gold standard" to which all other methods of viral identification are compared, the expense in terms of cost and technical time required as well as the time necessary for specific viral isolation has severely limited the use of viral diagnosis in clinical medicine. The concomitant development of rapid viral diagnostic procedures with the increased availability of anti-viral therapy, promises to alter how patients will be managed in the future. The greatest emphasis for rapid viral diagnosis has been placed on viral detection directly from clinical specimens since these procedures eliminate the need to cultivate the virus. Methods for direct detection of viral antigens in clinical specimens include electron microscopy and a wide range of immunologic assays. The extraction of nucleic acid directly from clinical specimens and hybridization of this DNA to specific viral probes also provides for virus identification without the need to culture the virus. Currently, many of the rapid diagnostic procedures discussed are performed only in research laboratories. Over the next several years, however, methods of antigen detection using EIA procedures and detection of viral-specific nucleic acid promise to alter how we study and diagnose viral infections.

Humans↗
PubMedDate not supplied

Applications of immunogold-silver enhancement: testing of monoclonal antibodies and detection of human cytomegalovirus in histologic specimens.

Human cytomegalovirus (HCMV) is an important pathogen in neonates, transplant patients, and individuals with acquired immunodeficiency syndrome (AIDS). Reliable techniques for the detection of this virus in clinical specimens would aid in improving methods for diagnosis and increasing our understanding of viral pathogenesis. We evaluated the utility of immunogold-silver enhancement to determine the specificity of murine monoclonal antibodies directed against HCMV proteins and applied these antibodies to the detection of HCMV in histologic material. Nine antibodies were tested in a tissue-culture system to determine the location of staining. All were found to be active in frozen tissue, but only two of these antibodies were reactive in formalin-fixed tissue. We also evaluated a novel tissue fixative technique (AMeX; Fixation and dehydration with acetone) that has been used to maintain antigenicity of T-lymphocyte cell markers. All antibodies remained reactive against their respective HCMV proteins in tissue fixed by this technique. However, dehydration of tissue may limit the usefulness of AMeX fixation. Immunogold-silver enhancement is a useful and reliable histochemical technique for detection of HCMV antigens in pathologic specimens.

Antibodies, Monoclonal↗
PubMedDate not supplied

Malassezia fungemia in neonates and adults: complication of hyperalimentation.

Until recently, Malassezia furfur was thought to be a pathogen only in tinea versicolor. More recently, this lipophilic yeast has been recovered from sick neonates with catheter-related infections. Malassezia fungemia was studied in seven patients, and the salient features of this infection in patients described in the literature were reviewed. Major risk factors include prolonged hospitalization, the presence of central venous catheters, and the use of intravenous fat emulsions. It is difficult to identify specific manifestations of fungemia in these complex cases occurring in patients with severe underlying disease; however, neonates often present with the signs and symptoms of sepsis and thrombocytopenia, whereas fever may be the only manifestation in adults. Some patients are asymptomatic. When symptoms are present, they resolve upon removal of the colonized catheter. The role of the lipophilic nature of Malassezia in the pathogenesis of infection is apparent from the ability of intravenous fat emulsions to support the growth of the fungus in vitro. A special solid medium that can be used to determine the true prevalence of malassezia fungemia has been devised. M. furfur must be considered in the differential diagnosis of opportunistic infections in patients receiving central hyperalimentation and should be sought by the culture of blood on appropriate medium.

Agar↗