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Biomedical subjects

M C Jordan

Publications and source records attributed to M C Jordan.

At least 55 records · Page 3Linked to original sources

Development of a Crohn's index for survey research.

Current Crohn's disease activity indices are not suitable for survey research because they rely on information from the laboratory or physical examination. We used data from a multicenter controlled trial of adjuvant sulfasalazine to develop an index of Crohn's disease activity based on information which could be obtained exclusively by interview. The study population consisted of 89 actively symptomatic patients seen on 1082 occasions in eight medical centers. Multiple regression analyses identified three variables which predicted the ratings of physicians: stool frequency, abdominal pain and sense of well-being. The new index correlated very well (r = 0.87, p less than 0.001) with the Crohn's Disease Activity Index from which it was derived. The index may be used in epidemiologic studies to accurately place patients into quartiles of disease severity which correspond to similar quartiles of the CDAI.

Abdomen↗

Nosocomial adenovirus infections: molecular epidemiology of an outbreak due to adenovirus 3a.

An immunocompromised woman died of disseminated infection due to adenovirus type 3. During her hospitalization and after her death, 38 hospital personnel developed an acute respiratory illness. Adenovirus type 3 infection was documented by culture in 18 of the 38 individuals and by seroconversion in one additional employee. Four of 34 asymptomatic hospital personnel exposed to the index case also seroconverted. Thus, 23 personnel were considered to have confirmed infections, and 22 of these 23 reported direct contact with the index case. Acquisition of infection was associated with the number and type of contacts. Protection against infection was associated with detectable serum-neutralizing antibody in the early serological sample. Restriction enzyme analysis using six different endonucleases indicated that all isolates of virus were type 3a and had identical genetic composition. This study underscores the importance of adenovirus as a cause of nosocomial infection and indicates that genetic analysis of viral DNA is a powerful tool for studying common-source outbreaks.

Adenoviridae Infections↗

Disseminated cytomegalovirus infection. Molecular analysis of virus and leukocyte interactions in viremia.

Viremia is a hallmark of disseminated cytomegalovirus (CMV) infection and disease. Using conventional virus culture and a subgenomic cloned CMV DNA probe to detect viral DNA within leukocytes, we studied the virus-cell interactions involved in immunocompromised patients with viremic CMV infection. CMV was recovered by culture in 17/17 samples enriched for polymorphonuclear leukocytes. Viral DNA was detected by dot-blot hybridization in 16/17 (94%). In contrast, samples enriched for mononuclear cells yielded infectious CMV in culture in only 7/15 (47%) instances; nonetheless, viral DNA was present in 16/17 samples probed. The quantity of CMV DNA in polymorphonuclear cells was significantly greater than in mononuclear leukocytes (mean 13.1 vs. 9.1 estimated viral genome equivalents per 100 cells, respectively), and CMV was always recovered from these cells regardless of the amount of viral DNA present. Yet, when the amounts of CMV DNA were virtually identical in granulocytes and mononuclear cells (6.3 and 7.1 genomic equivalents, respectively) collected simultaneously, infectious CMV could not be recovered from mononuclear cells. Although several interpretations are possible, these data are consistent with the view that CMV exists within granulocytes in a mature infectious form during viremia. The virus interactions with mononuclear cells appear to be more complex, particularly in those cells that contain CMV DNA but do not yield infectious virus.

Autoradiography↗

Diagnosis of viral pneumonia.

The diagnosis of viral pneumonia has changed during the past decade from a purely clinical diagnosis to one that is both clinical and laboratory in nature. Viral pneumonias can be divided into two clinical groups: the so-called "atypical" pneumonias in otherwise normal hosts, and viral pneumonitis in the immunocompromised host. Clinical factors such as patient age, immune status, time of year, illness in other family members, community outbreaks, onset, severity, duration of symptoms, and the presence of a rash remain important aids in diagnosing viral causes of both atypical pneumonia and pneumonia in the immunocompromised patient. However, advances in virus culture methodologies and the use of monoclonal antibodies coupled with immunofluorescence and ELISA techniques have markedly enhanced both the sensitivity, specificity, and rapidity of the diagnosis of viral pneumonias. Further advances are expected in the future as nucleic acid hybridization techniques are increasingly applied to both viral cultures and direct analysis of clinical specimens.

Adenovirus Infections, Human↗

Ganciclovir treatment of cytomegalovirus disease in transplant recipients and other immunocompromised hosts.

Thirty-one immunocompromised patients with severe cytomegalovirus (CMV) disease were treated with intravenous ganciclovir. Twenty-one patients had received transplants--15 bone marrow recipients, five renal allograft recipients, and one liver transplant recipient--while the other ten were immunocompromised due to acquired immunodeficiency syndrome (six), hematologic malignancies (three), and systemic lupus erythematosus (one). They presented with one or more of the following syndromes: CMV pneumonitis (19), CMV of the gastrointestinal tract (six), CMV retinitis (seven), and CMV hepatitis (three). Seventeen (55%) of 31 patients demonstrated clinical improvement during ganciclovir therapy, with the best response seen in the transplant recipients. Viremia ceased in 14 (93.3%) of 15 patients after a mean of 4.7 days of therapy; viruria ceased in eight (53.3%) of 15 patients after a mean of 11 days of therapy. Ganciclovir plasma concentrations at a dosage of 2.5 mg/kg/three times a day were as follows: mean peak, 16.04 mumol/L; mean trough, 2.38 mumol/L. Neutropenia occurred in 11 (35%) of 31 patients and in nine (60%) of 15 bone marrow transplant recipients. We conclude that ganciclovir exerted an antiviral effect against CMV and may play a role in the treatment of CMV disease in patients with depressed immunity, especially bone marrow and organ transplant recipients.

Acyclovir↗

Interactions of human cytomegalovirus with leukocytes in vivo: analysis by in situ hybridization.

Reactivation of human cytomegalovirus (HCMV) from latency occurs in immunosuppressed individuals and infection is itself immunosuppressive. To better understand the basis for this virally induced impairment of immune function, we have analyzed virus-leukocyte interactions by in situ hybridization. We detected viral DNA in 12 viremic patients in the mononuclear cell population, predominantly in cells identified as monocytes by their morphology and by labelling the cells with a monocyte specific monoclonal antibody prior to in situ hybridization. We detected immediate early RNA in infected cells at frequencies comparable to DNA (10(-3) to 10(-5)). By contrast, no viral transcripts were detected in polymorphonuclear cells and viral DNA was inclusively cytoplasmic in accord with the interpretation that this cell type harbors HCMV in phagosomes. These findings in vivo continue to suggest that infection of monocytes plays an important part in the immunosuppressive effects of HCMV infections.

Autoradiography↗

Successful treatment of murine cytomegalovirus disease does not prevent latent virus infection.

9-(1,3-Dihydroxy-2-propoxymethyl)guanine (DHPG), a nucleoside analogue, inhibits the replication of human and murine cytomegalovirus (MCMV) in cell culture. We studied the effects of treatment with DHPG on acute MCMV infection in mice and assessed the impact of drug therapy on the eventual development of latent viral infection. In virus-susceptible Balb/c mice, DHPG treatment limited dissemination of virus infection and prevented death. In sublethal infection of both Balb/c and virus-resistant C3H/St mice, DHPG prevented recovery of infectious virus from visceral organs, including the spleen. Despite these effects of drug treatment on virus replication during acute infection, latent MCMV could be reactivated in vivo by immunosuppression and in vitro by spleen explantation in virtually all mice. These results indicate that successful treatment of MCMV infection and marked suppression of viral replication do not prevent establishment of viral latency.

Acute Disease↗

Inhibition of murine cytomegalovirus lung infection and interstitial pneumonitis by acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine.

We compared the effects of acyclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) on murine cytomegalovirus (MCMV) replication in lung and salivary gland tissues, the evolution of interstitial pneumonitis in vivo, and MCMV replication in mouse embryo cells in vitro. As measured by plaque reduction, ACV was more active than DHPG in vitro. In vivo, whether administered orally by gastric intubation or in the drinking water, or subcutaneously, DHPG was more effective than ACV in reducing MCMV titers in lung or salivary gland tissues. This was true in both normal and cyclophosphamide-treated mice. Neither drug was able to prevent MCMV interstitial pneumonitis, despite substantial reductions in virus titer, but both drugs reduced the severity of the pneumonitis.

Acyclovir↗

Cytomegalovirus viremia detected by molecular hybridization and electron microscopy.

Fatal cytomegalovirus interstitial pneumonitis developed in a patient with chronic leukemia. The diagnosis was suspected on the basis of cytologic examination of bronchial washings. The virus was subsequently recovered from saliva, urine, and blood leukocytes after 8, 9, and 18 days in culture respectively. Premortem cytomegalovirus DNA was found by molecular hybridization methods using a complete viral genome probe in blood leukocytes after 4 hours' reaction time. Electron microscopic examination showed herpes-like virions consistent with cytomegalovirus in 3% of the patient's granulocytes. Thus, DNA:DNA hybridization and ultrastructural methods can be used for rapid diagnosis of disseminated cytomegalovirus infection.

Aged↗

Latent herpesviruses of humans.

The herpesviruses that infect humans characteristically establish a latent infection that may be reactivated later. The consequences of reactivation range from asymptomatic shedding to severe disseminated infection. Varicella-zoster and herpes simplex viruses are both highly neurotropic, establishing nonreplicating infections in sensory ganglia. Latent herpes simplex virus is known to reside in neurons, and the virus-cell interactions involved have been defined to an extent. Cytomegalovirus and Epstein-Barr virus interact with peripheral blood leukocytes. Latent cytomegalovirus infection of human leukocytes has not been proved, although studies in a murine model have implicated B lymphocytes as a repository of latent virus. Epstein-Barr virus is known to persist in a non-replicating state as extrachromosomal DNA in B lymphocytes and to cause "immortalization" of the infected cell; persistence of the viral genome in epithelial cells may also result in malignant transformation, such as nasopharyngeal carcinoma.

Animals↗

Bullous chickenpox.

We report a 70-year-old man with the bullous variant of chickenpox. Physicians should be aware of this uncommon manifestation of this common disease, which may clinically suggest other bullous disorders such as pemphigus and bullous pemphigoid. A 24-year-old hospital worker developed typical chickenpox 2 weeks after the first patient's onset of bullous chickenpox.

Adult↗

Lethal infection with murine cytomegalovirus after early viral replication in the spleen.

In acute lethal murine cytomegalovirus (MCMV) infection the spleen and liver are the principal sites of early viral replication. MCMV titers increase rapidly in the spleen and liver, exceeding 10(6) and 10(5) plaque-forming units (pfu)/g of tissue, respectively, within 96 hr of viral inoculation. Experiments were performed to determine the impact of early splenic viral replication on disease pathogenesis. Splenectomized mice survived acute infection in significantly greater numbers (25 of 34 vs 14 of 33, respectively) than controls and had lower hepatic viral titers (1.9 X 10(4) vs 2.4 X 10(5) pfu/g, respectively). Examination of the spleen by electron microscopy after administration of phagocytic markers demonstrated that macrophages were the predominant site of viral replication. It is concluded that early replication of MCMV in splenic macrophages augments virus-induced hepatic injury and thus contributes to the pathogenesis of lethal MCMV infection.

Animals↗

Virulence characteristics of murine cytomegalovirus in cell and organ cultures.

Murine cytomegalovirus infection was studied in cell and organ cultures. Regardless of the virulence characteristics of input virus, all cultures produced attenuated murine cytomegalovirus. Virulent murine cytomegalovirus has been recovered only from salivary glands of infected mice. In vivo the maintenance of murine cytomegalovirus in a virulent state is apparently due to factors other than virus replication in epithelial cells.

Animals↗

Activation of latent murine cytomegalovirus in vivo and in vitro: a pathogenetic role for acute infection.

Many cytomegalovirus (CMV) infections result from activation of virus previously latent in the host. Murine models of latent CMV infection have been developed in which latent virus can be activated in vivo by immunosuppression or by coculture of splenic lymphocytes in vitro. In the present study, latent murine CMV (MCMV) could be activated from lymphocytes of mice regardless of genetic strain, age at time of virus inoculation, or use of syngeneic or allogeneic fibroblasts for coculture. After intraperitoneal inoculation, virulent virus was activated from lymphocytes more often than attenuated MCMV (69% vs. 20% of lymphocyte cocultures were positive, respectively). Latent MCMV was not detected in lymphocytes after subcutaneous inoculation of weanling mice but could be activated from mice infected subcutaneously as newborns. The absence of latent infection in the lymphocytes of the mice that had been inoculated as weanlings was due to lack of virus replication in the spleen during acute infection.

Animals↗

Spontaneous activation of latent cytomegalovirus from murine spleen explants. Role of lymphocytes and macrophages in release and replication of virus.

Cytomegalovirus (CMV) is a major pathogen in the compromised host where many infections result from activation of latent virus. Because latent CMV infection has been difficult to study in humans, murine models have been developed and investigated. Here, we describe the events involved in activation of latent murine CMV (MCMV) from spleen explants in vitro. Infectious virus was no longer detectable in murine organs 4 mo after inoculatioN of 10(5) plaque-forming units of MCMV. 8-10 d after establishment of spleen explants, phagocytic macrophages covered 70-80% of the surface of tissue culture dishes, and lymphocytes were continuously released, reaching titers of 10(6) cells/ml. MCMV was produced spontaneously after 12-18 d from spleen explant cultures of 33 of 34 mice. Virus replicated to titers above 10(4) plaque-forming units/ml, remained at that level for 4-5 wk, and gradually disappeared as macrophages were lysed. Although MCMV was shown to be replicating in macrophages, these cells were never found to be the source of latent virus. Cell separation studies indicated that latent virus was initially released from 70% of lymphocyte cultures and was associated with the B cell enriched fraction. We conclude that MCMV establishes nonreplicating dormant infection in B lymphocytes, activates from these cells in spleen explant cultures, and is augmented in titer by replication in permissive macrophages.

Animals↗