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Biomedical subjects

A Erice

Publications and source records attributed to A Erice.

At least 55 records · Page 3Linked to original sources

Management of acyclovir-resistant herpes simplex and varicella-zoster virus infections.

Persons with AIDS who have CD4+ counts < or = 100 and transplant patients, especially bone marrow allograft recipients, may experience clinically significant infections with acyclovir-resistant herpes simplex virus (HSV) or varicella-zoster virus (VZV). Patients who have received prior repeated acyclovir treatment appear to be at the highest risk of harboring acyclovir-resistant strains. Algorithms for the management of these infections were developed at a recent roundtable symposium. The consensus of the panelists was that treatment with foscarnet should be initiated within 7-10 days in patients suspected to have acyclovir-resistant HSV or VZV infections. Foscarnet therapy should be continued for at least 10 days or until lesions are completely healed.

Acquired Immunodeficiency Syndrome↗

Ganciclovir susceptibilities of cytomegalovirus (CMV) isolates from solid organ transplant recipients with CMV viremia after antiviral prophylaxis.

Ganciclovir susceptibility studies were done on the last cytomegalovirus (CMV) isolate available from 42 solid organ transplant recipients with CMV viremia who were enrolled in a prospective CMV prophylactic trial. Viruses were categorized as follows: 13 isolates (group 1) from patients who received ganciclovir prophylaxis; 9 isolates (group 2) from patients who received acyclovir prophylaxis; 8 isolates (group 3) from patients who received acyclovir prophylaxis and ganciclovir treatment; and 12 isolates (group 4) from patients who received prophylaxis and treatment with ganciclovir. All CMV isolates were sensitive to ganciclovir (mean 50% inhibitory concentration [IC50] 1.7 microM; range, 0.2-5.3 microM). Mean IC50 values (in microM) were 1.7 for group 1 isolates, 1.2 for group 2 isolates, 2.2 for group 3 isolates, and 1.7 for group 4 isolates (P > .05). Thus, acyclovir or ganciclovir prophylaxis in solid organ transplant patients did not select ganciclovir-resistant isolates of CMV.

Acyclovir↗

Acyclovir susceptibilities of herpes simplex virus strains isolated from solid organ transplant recipients after acyclovir or ganciclovir prophylaxis.

We determined the acyclovir (ACV) susceptibilities of herpes simplex virus (HSV) isolates (n = 18) recovered from solid organ transplant patients after antiviral prophylaxis with ACV or ganciclovir. All isolates tested were susceptible to ACV (50% inhibitory concentration, < 1 microM). A clinical review of patients with HSV disease showed that all improved with specific anti-HSV therapy, and no recurrences were reported.

Acyclovir↗

Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein.

The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents. Mean alpha CD4-PAP IC50s were 48 x 10(-3) nM (range, 0.02 x 10(-3) to 212 x 10(-3) nM) for isolates from zidovudine-untreated individuals, and 16 x 10(-3) nM (range, 2 x 10(-3) to 28 x 10(-3) nM) for isolates from treated patients. Overall, higher concentrations of alpha CD4-PAP were necessary to inhibit HIV-1 strains from untreated individuals at more advanced stages of disease. Seventeen isolates were susceptible to zidovudine (mean IC50, 117 nM), and five were resistant to zidovudine (mean IC50, 3,724 nM). Mean alpha CD4-PAP IC50s were 43 x 10(-3) nM for zidovudine-susceptible isolates and 19 x 10(-3) nM for isolates resistant to zidovudine. All HIV-1 strains had IC50s greater than 0.5 nM for unconjugated PAP, the alpha CD19-PAP immunoconjugate, and monoclonal antibody alpha CD4. At concentrations as high as 5,000 nM, alphaCD4-PAP did not inhibit colony formation by normal bone marrow progenitor cells(BFU-E, CFU-GM , and CFU-GEMM) or myeloid cell lines (KG-1 and HL-60) and did not decrease cell viabilities of T-cell (Jurkat) or B-cell (FL-112 and Raji) precursor lines. Overall, alphaCD4-PAP demonstrated more potent anti-HIV-1 activity than zidovudine and inhibited replication of zidovudine-susceptible and zidovudine-resistant viruses at concentrations that were not toxic to lymphohematopoietic cell populations.

AIDS-Related Complex↗

Cocaine amplifies HIV-1 replication in cytomegalovirus-stimulated peripheral blood mononuclear cell cocultures.

Cocaine and CMV each have been suggested to promote the progression of HIV-1 infection. In the present study, the interaction of cocaine and CMV was investigated in a PBMC coculture assay in which release of HIV-1 p24 Ag into coculture supernatants was used as an index of HIV-1 replication. CMV was an effective activation signal for HIV-1 replication when PBMC from CMV-seropositive donors were used in the coculture assay, and cocaine markedly increased replication of HIV-1 in these cocultures. The synergistic activity of cocaine was reduced by neutralizing antibodies to TNF-alpha and by pentoxifylline, an inhibitor of TNF-alpha mRNA production. Also, antibodies to transforming growth factor-beta (TGF-beta) eliminated the amplifying effect of cocaine on HIV-1 replication, whereas antibodies to IL-6 were inactive. The potentiating effect of cocaine could be reproduced by addition of rTNF-alpha or rTGF-beta to the cocultures of CMV-activated PBMC, although TGF-beta was substantially more potent than TNF-alpha. The possibility that TNF-alpha may act indirectly through stimulation of TGF-beta was suggested by the finding of reduced TGF-beta levels in culture supernatants of PBMC that were treated with CMV and cocaine in the presence of antibodies to TNF-alpha. Thus, cocaine amplifies HIV-1 replication in cocultures containing CMV-activated PBMC via a mechanism that appears to involve both TNF-alpha and TGF-beta. The results of this study support the possibility that cocaine and CMV could enhance HIV-1 replication and, thus, aggravate HIV-1-related disease.

Cells, Cultured↗

Quantitative assay for testing susceptibility of HIV isolates to zidovudine and sCD4 (178)-PE40.

A quantitative coculture assay is described for determining susceptibility of HIV-1 isolates to zidovudine and sCD4 (178)-PE40 (a 60 kDa hybrid protein consisting of the gp120 binding region of CD4 linked to the translocation and ADP-ribosylation regions of Pseudomonas aeruginosa exotoxin). The assay was relatively simple to perform and gave highly reproducible results often within three to five days. IC50 values of zidovudine for HIV-1 strains isolated from two AIDS patients and an asymptomatic seropositive individual were in the range 0.001-0.002 mumol. Isolates obtained after six months of zidovudine treatment had zidovudine IC50 values of 0.01-0.5 mumol. All isolates were equally sensitive to sCD4 (178)-PE40 (IC50 1-5 micrograms/ml). HIV-1 activation in the chronically infected cell line U-1 was inhibited by sCD4 (178)-PE40 but not by zidovudine.

Antiviral Agents↗

Adenovirus in the gastrointestinal tracts of immunosuppressed patients.

Adenovirus was cultured from various gastrointestinal sites and one lung specimen from seven immunosuppressed patients, four of whom were bone marrow transplant recipients. Histologic examination and in situ hybridization studies of the lung demonstrated adenovirus in the bronchial epithelium and alveolar lining cells. In contrast, none of the 34 gastrointestinal biopsies performed within 30 days of the positive adenovirus culture showed histologic or molecular evidence of invasive adenovirus in the gastrointestinal mucosa. These results suggest that isolation of adenovirus from gastrointestinal biopsy specimens taken from immunosuppressed patients probably does not indicate an invasive adenoviral infection.

Adenovirus Infections, Human↗

Cytomegalovirus (CMV) antigenemia assay is more sensitive than shell vial cultures for rapid detection of CMV in polymorphonuclear blood leukocytes.

We compared the cytomegalovirus (CMV) antigenemia assay with shell vial cultures of polymorphonuclear leukocyte (PMNL)-enriched blood fractions for rapid diagnosis of CMV viremia. PMNL fractions of 280 blood specimens from 171 patients (170 solid-organ transplant recipients and 1 patient undergoing pretransplant evaluation) were inoculated in shell vial and conventional CMV cultures. A commercially available kit (CMV-vue kit; INCSTAR Corp.) was used for the CMV antigenemia assay, in which PMNL preparations were stained with monoclonal antibodies directed against the CMV protein pp65. Mixed-leukocyte blood fractions from the same blood specimens were inoculated in parallel shell vial and conventional cultures. CMV viremia (defined by the isolation of CMV in conventional cultures) was detected in 32 (13%) of 245 PMNL fractions included in the final analysis. Twenty-eight (87.5%) were also positive in the CMV antigenemia assay, whereas 22 (69%) were positive in shell vial cultures. Ten (4%) additional PMNL fractions positive only in the CMV antigenemia assay were from eight patients with active CMV infections (six patients), who had previous or subsequent episodes of CMV viremia (seven patients), or in whom CMV was isolated in cultures of simultaneously obtained mixed-leukocyte fractions (three patients). Overall, the CMV antigenemia assay was significantly more sensitive than shell vial cultures for detection of CMV in the PMNL fraction of blood leukocytes (P < 0.01, McNemar's test), and we recommend it as the method of choice for rapid diagnosis of CMV viremia.

Antigens, Viral↗

Sensitive microculture method for isolation of human immunodeficiency virus type 1 from blood leukocytes.

A study was conducted to compare our standard culture with a new microculture procedure for isolation of human immunodeficiency virus type 1 (HIV-1) from blood leukocytes. A total of 137 blood specimens from 102 HIV-1 antibody-positive individuals (52 were asymptomatic, 31 were symptomatic, and 19 had AIDS) were cultured in a microculture system in which 10(6) of the patients' peripheral blood mononuclear cells (PBMC) were cocultured with 10(6) phytohemagglutinin (PHA)-stimulated PBMC from an HIV-1 antibody-negative blood donor in 1.2 ml of culture medium. Results were compared with those of a historical control group of 139 standard HIV-1 cultures from 108 HIV-1 antibody-positive subjects (58 were asymptomatic, 36 were symptomatic, and 14 had AIDS). For standard cultures, 10 x 10(6) of the patients' PBMC were cocultured with 5 x 10(6) PHA-stimulated PBMC from an HIV-1 antibody-negative blood donor in 15 ml of culture medium. HIV-1 was isolated in 128 (93%) microcultures and 133 (96%) standard cultures. Both methods identified more than 75% of the positive cultures within 7 days and 100% of the positive cultures within 14 days. The isolation rates for HIV-1 in microcultures compared with standard cultures were 91 versus 93% (specimens from asymptomatic individuals), 93 versus 96% (specimens from symptomatic individuals), and 97 versus 100% (specimens from patients with AIDS). The median time to positivity for both culture methods was 7 days, and this correlated significantly with symptoms and CD4+ cell counts. The microculture method is a sensitive and less expensive system for isolation of HIV-1 from PBMC of HIV-1 antibody-positive individuals, and we recommend it as the culture method of choice, especially for children and patients with AIDS and severe anemia or leukopenia whose blood volume is an important consideration.

Evaluation Studies as Topic↗

An outbreak of herpes gladiatorum at a high-school wrestling camp.

BACKGROUND AND METHODS: Herpes simplex virus type 1 (HSV-1) has been identified as a cause of cutaneous or ocular infection among athletes involved in contact sports; in this context it is known as herpes gladiatorum. In July 1989, we investigated an outbreak among 175 high-school wrestlers attending a four-week intensive-training camp. Cases of infection were identified by review of medical records, interview and examination of the wrestlers, and culture of skin lesions. Oropharyngeal swabs were obtained for HSV-1 culture, and serum samples for HSV-1 serologic studies. HSV-1 isolates were compared by restriction-endonuclease analysis. RESULTS: HSV-1 infection was diagnosed in 60 wrestlers (34 percent). The lesions were on the head in 73 percent of the wrestlers, the extremities in 42 percent, and the trunk in 28 percent. HSV-1 was isolated from 21 wrestlers (35 percent), and in 39 (65 percent) infection was identified by clinical criteria. Five had conjunctivitis or blepharitis; none had keratitis. Constitutional symptoms were common, including fever (25 percent), chills (27 percent), sore throat (40 percent), and headache (22 percent). The attack rate varied significantly among the three practice groups, ranging from 25 percent for practice group 1 (lightweights) to 67 percent for group 3 (heavyweights). Restriction-endonuclease analysis identified four strains of HSV-1 among the 21 isolates. All 10 isolates from practice group 3 were identical (strain A), and 5 of 7 isolates from practice group 2 (middleweights) were identical (strain B), which suggested concurrent transmission of different strains within different groups. HSV-1 was not isolated from any oropharyngeal swabs. CONCLUSIONS: Herpes gladiatorum may cause substantial morbidity among wrestlers, and it is primarily transmitted by direct skin-to-skin contact. Prompt identification and exclusion of wrestlers with skin lesions may reduce transmission.

Adolescent↗

Treatment of invasive cytomegalovirus disease in solid organ transplant patients with ganciclovir.

The occurrence of cytomegalovirus infection after solid organ transplantation has been correlated with decrease patient and allograft survival. The disease has not been conquered for two majors reasons: the length of time to establish the diagnosis of CMV has been excessive, and suitable, nontoxic antiviral agents have not been available for use. The purpose of this study was to examine the current incidence and impact of tissue-invasive cytomegalovirus (TI-CMV) disease that developed in 93 patients who underwent solid organ transplantation at University of Minnesota Hospitals (3/1/87 and 6/30/89) and who were treated with antiviral agent ganciclovir ( [9-(1,3-dihydroxy-2-2-propoxymethyl)-guanine [DHPG]). During this same period of time 323 patients received kidney transplants and 71 received kidney-pancreas transplants. Three patient groups were defined: (1) no CMV; (2) CMV infection (cultural or serologic evidence of noninvasive CMV infection); and (3) evidence of TI-CMV disease based upon initial complaints of fever, malaise, dyspnea, or abdominal pain, leukopenia (WBC less than 3000/ml), and evidence of a positive CMV rapid antigen test, CMV culture, or the presence of characteristic CMV inclusion bodies upon examination of material obtained by means of bronchoscopy, upper-gastrointestinal endoscopy, colonoscopy, or liver or renal biopsy. Patients with solely fever, leukopenia, but without a rising CMV serum titer, or positive CMV urine or blood cultures were excluded from the study. A multivariate analysis revealed that rejection therapy, age greater than 50 years, and receiving an organ from a seropositive donor were all significant variables that predisposed to TI-CMV. Analysis of patient and kidney allograft survival indicated that asymptomatic CMV infection had little current impact upon patient or allograft survival, while patients who developed TI-CMV exhibited higher rates of allograft loss and mortality, despite DHPG therapy. Comparison with historical group of patients indicated that TI-CMV DHPG-treated patients exhibited a trend toward improved allograft survival that may be relevant because the historical group of patients included patients with mild CMV infection. DHPG therapy was well tolerated and produced minimal toxicity, and excellent 30-day cure rates (89.2%), although 21.2% of patients required retreatment subsequently. We are currently conducting a trial to compare the ability of DHPG administered plus an anti-CMV immune globulin preparation with acyclovir to prevent posttransplant TI-CMV disease.

Acyclovir↗

Ganciclovir-resistant cytomegalovirus clinical isolates: mode of resistance to ganciclovir.

Cytomegalovirus strains with reduced in vitro susceptibilities to ganciclovir have been recovered from patients who failed long-term ganciclovir therapy. The ganciclovir-resistant clinical isolates in this study were unable to induce ganciclovir phosphorylation in virus-infected cells. The viral DNA polymerase function appeared unaltered in one genetically pure ganciclovir-resistant strain, compared with that of its wild-type ganciclovir-sensitive counterpart. All nine of the ganciclovir-resistant strains were susceptible to foscarnet. Moreover, these strains were sensitive to inhibition both by vidarabine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine (FIAC), antiviral agents that are activated by cellular enzymes, and by (S)-1(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), which is a monophosphate nucleoside analog. The in vitro resistance to ganciclovir of the ganciclovir-resistant clinical isolates studied was attributed to the inability of the cells infected with these isolates to phosphorylate ganciclovir; the virally encoded DNA polymerase did not appear to play a role in this ganciclovir resistance.

Acquired Immunodeficiency Syndrome↗

Visceral leishmaniasis in patients infected with human immunodeficiency virus. Co-operative Group for the Study of Leishmaniasis in AIDS.

We describe 40 HIV-seropositive patients who developed visceral leishmaniasis. All the patients lived in areas endemic for visceral leishmaniasis and belonged to groups at risk for AIDS. Twenty-three patients (57.2%) had definitive AIDS before or after diagnosis of leishmaniasis and 77.5% were classified as belonging to CDC group IV. Fever was present in 95% patients and enlargement of the liver and/or spleen in 92.5%. Lymphopenia was found in 78.3%, depression of the absolute number of CD4 lymphocytes in 90% and depression of the CD4 to CD8 ratio in all evaluated cases but leishmania antibodies were found in only 35.2%. Parasites were demonstrated in the bone marrow or liver in every case. Thirty patients (75%) showed an initial good response to antimonial drugs, although the leishmaniasis followed a chronic or relapsing course in 17 (42.5%). HIV-related mortality was 40%. A significant correlation was found only between the relapsing course of the disease and mortality. In a multivariate linear regression model, the relapsing course was the only variable that influenced mortality. Visceral leishmaniasis is an opportunistic disease that should be suspected in HIV-infected patients. We suggest that it should be included in the CDC group IV C-1 and considered as a disease indicative of AIDS.

Acquired Immunodeficiency Syndrome↗

[Lymphoma of the rectum associated with lymphoid nodular hyperplasia in a common variable immunodeficiency].

A patient with common variable immunodeficiency developed lymphoid nodular hyperplasia and, subsequently, a follicular non-Hodgkin lymphoma with excellent response to chemotherapy. The patient remained in remission after 4 years. The very unusual type of this lymphoma and its localization are discussed, and the possible relations between these different conditions as a single spectrum of B lymphocyte are analyzed.

Adult↗