Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The early diagnosis and effective treatment of cytomegalovirus (CMV) pneumonia remains a keystone for patient survival after lung transplantation. At present, the use of DHPG (ganciclovir sodium) opens the possibility of a potent antiviral therapy. The use of monoclonal antibodies directed to immediate early CMV antigens offers a fast method to detect the early phase of systemic or local viral replication. Five single lung and heart-lung transplant patients at high risk for CMV infection (donor, CMV-positive; recipient, CMV-negative) were monitored by cellular immunohistology for immediate early antigens. Specimens from bronchoalveolar lavage (n = 39) and bronchial biopsies (n = 17), and peripheral blood leukocytes (n = 57) were examined. In peripheral blood leukocytes and bronchial biopsy specimens no CMV-positive cells were detected. The bronchoalveolar lavage analysis of two patients showed immediate early antigen-positive cells after 1 to 3 months. At the same time the patients had clinical symptoms that could also be related to lung rejection. Serologic conversion (CMV-IgM) occurred only 6 days later in one patient with informative follow-up analysis; CMV culture (available 4 to 6 weeks later) confirmed the diagnosis retrospectively. DHPG treatment was started immediately and resulted in CMV antigen negativity in bronchoalveolar lavage fluid after one or two courses (10 mg/kg/day; 14 days). Direct antigen detection offers a fast and specific monitoring of early CMV infection. The implications to the clinical management of lung transplant patients are discussed.
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PMID:Early diagnosis and effective treatment of pulmonary CMV infection after lung transplantation. 184 89

A 46 year old AIDS-patient, who had developed CMV-retinitis was treated with the virostatic drug dihydroxypropoxymethylguanine (DHPG, Ganciclovir) over a period of 16 months until he died due to a pneumonia. After the DHPG-treatment was initiated the retinitis improved markedly, however there still was a very slow progression of the disease in the following time. The central retina of both eyes was not affected until death. Postmortal immunohistochemically CMV-antigen-staining was positive according to the former clinically active retinitis. At the eyes of the retinal necrosis calcified deposits were identified by Kossa-staining; these areas had clinically appeared as yellowish briddle deposits. The clinical course and the immunohistochemical proof of active CMV-virus-particles suggest that DHPG was able to suppress the progression of a CMV-retinitis and to preserve a good visual acuity until death; however a true cure of the CMV-infection could not be achieved.
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PMID:[Clinico-histopathologic correlation of ganciclovir-treated cytomegalovirus retinitis]. 196

Two novel antiviral pharmacologic strategies were used for therapy of life- and sight-threatening cytomegalovirus (CMV) infection; these were continuous drug infusion by portable pump and individualized patient regimen. 9-(1,3-Dihydroxy-2-propoxymethyl)-guanine (DHPG), an active and recently licensed antiviral drug against cytomegalovirus infection, was administered to five immunocompromised patients with chorioretinitis (all patients), colitis (two), and pneumonitis (three). Through dosage escalation, correlations between plasma levels, toxicity (i.e., myelosuppression), and clinical benefit were ascertained for therapy of acute disease (pneumonitis) as well as long-term therapy (chorioretinitis). Resolution of viremia, pneumonitis, colitis, and chorioretinitis was accomplished with steady-state plasma levels of DHPG approximating the mean ID50 of CMV isolates. The most notable clinical benefit was survival from CMV pneumonia and stabilization of vision. Although no adverse toxicity occurred during the DHPG continuous long-term therapy, survival was limited by the underlying disease.
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PMID:Novel pharmacological strategies in the treatment of life-threatening cytomegalovirus infections. Clinical experience with continuous infusion 9-(1,3-dihydroxy-2-propoxymethyl) guanine. 196 31

Cytomegalovirus (CMV) infection in heart and heart-lung transplant recipients represents a serious if not mortal complication. This study reviews the beneficial effects of 9-(1,3-dihydroxy-2-proproxymethyl) guanine (DHPG), an experimental antiviral agent, in patients with CMV infections. Thirteen of 76 heart and heart-lung transplant patients treated with cyclosporine have developed CMV. Nine of 13 patients developed infections since DHPG has been available. Seven patients received hearts, and two received heart and lungs. Six patients were treated, four heart and two heart-lung recipients; five of six had negative CMV serology before surgery, and all had CMV positive donors. Of the patients not treated, one died at home from disseminated CMV; two had resolution of symptoms and were discharged before the diagnosis was made. In the treated group, three patients had gastrointestinal ulcerative disease, two in the stomach and one in the cecum. The other three patients had CMV pneumonia. DHPG was effective in resolving patient symptoms in five of six patients. The patient who did not respond had a cecal ulcer, multiorgan failure, multiple infections, and died. Two patients with abdominal pain had gastric ulcers that were proved with endoscopy. CMV-induced ulcer disease was diagnosed within 2 hours by fluorescent antibody staining, and resolution was documented by endoscopy. Three patients with CMV pneumonia were treated; two were heart-lung transplant recipients. All started to respond within 72 hours. One heart-lung transplant recipient has had a 9-month course of DHPG because of recurrence of infection when the drug was stopped. The usual dosage was 10 mg/kg/day over 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:DHPG effectively treats CMV infection in heart and heart-lung transplant patients: a preliminary report. 282 80

Cytomegalovirus (CMV) infection is a frequent cause of serious illness in heart transplant patients and may cause life-threatening pneumonia, with a reported mortality of greater than 50%. We investigated the clinical efficacy of a new antiviral agent, 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG) in the treatment of CMV pneumonia in heart transplant patients. Four of these patients with biopsy-proved CMV pneumonia were treated with DHPG, with resolution of pneumonia and no relapse at a mean follow-up period of 21 weeks. DHPG may be useful in the treatment of CMV pneumonia in heart transplant patients.
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PMID:Treatment of cytomegalovirus pneumonia in heart transplant recipients with 9(1,3-dihydroxy-2-proproxymethyl)-guanine (DHPG). 283 68

Ganciclovir, also called DHPG, was administered intravenously to eight renal transplant recipients with life-threatening cytomegalovirus (CMV) pneumonitis. One patient died of pulmonary failure; a favorable clinical response was observed in the seven others. In one patient, CMV pneumonitis recurred but responded well to a second course of the drug. At no time was the immunosuppressive regimen completely stopped in the seven surviving patients. Six of them maintained a good renal function 1-11 months after treatment with ganciclovir. No toxic effect was detected during therapy. We conclude that ganciclovir appears to be a promising and effective treatment for CMV pneumonitis after renal transplantation.
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PMID:Treatment of cytomegalovirus pneumonitis with ganciclovir in renal transplantation. 285 5

The drug 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (DHPG) was used to treat serious cytomegalovirus infections in 26 patients with underlying immunodeficiency (including 22 with the acquired immunodeficiency syndrome). In 17 of 22 patients in whom cytomegalovirus was virologically confirmed, clinical status improved or stabilized, although in 4 of them the status of some affected organs deteriorated or did not improve. Fourteen of 18 patients with adequate viral-culture data had clearing of cytomegalovirus from all cultured sites. Patients with cytomegalovirus pneumonia often responded poorly; four of seven died before completing 14 days of DHPG therapy. The condition of 11 of 13 patients with cytomegalovirus retinitis and 5 of 8 with gastrointestinal disease stabilized or improved. However, clinical and virologic relapses occurred in 11 of 14 patients (79 percent) when DHPG was discontinued. Neutropenia was the most frequent adverse reaction. We conclude that DHPG offers promise for the therapy of severe cytomegalovirus infections in some immunodeficient patients, but further study will be necessary to establish its efficacy and safety.
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PMID:Treatment of serious cytomegalovirus infections with 9-(1,3-dihydroxy-2-propoxymethyl)guanine in patients with AIDS and other immunodeficiencies. 300 61

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.
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PMID:Inhibition of murine cytomegalovirus lung infection and interstitial pneumonitis by acyclovir and 9-(1,3-dihydroxy-2-propoxymethyl)guanine. 301 Aug 35

The pharmacokinetics of the antiviral drug 9-[2-hydroxy-1-(hydroxymethyl) ethoxymethyl]guanine (DHPG) were examined in six patients receiving 2.5 or 5.0 mg/kg every 8 or 12 hours for human cytomegalovirus (HCMV) pneumonitis or retinitis. Biexponential decay with a mean distribution t1/2 of 0.23 hours and terminal t1/2 of 2.53 hours was observed. Total clearance correlated well with and exceeded creatinine clearance by a factor of 2.4. Mean volume of the central compartment was 15.26 L/1.73 m2 and the volume of distribution at steady state was 32.8 L/1.73 m2. Peak (model predicted) and trough plasma concentrations were 4.75 to 6.20 micrograms/ml and less than 0.25 to 0.63 microgram/ml, respectively, in patients receiving 2.5 mg/kg. Peak concentrations are well above those needed to inhibit HCMV at the 50% level (ID50) and troughs are near this ID50. Cerebrospinal fluid concentrations of DHPG indicate a penetration of 24% to 67%. No accumulation of DHPG was apparent in these patients. However, dosage reduction is necessary in renal insufficiency. Neutropenia occurred in one patient. The plasma concentration profile of DHPG suggests potential beneficial activity against HCMV.
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PMID:Human pharmacokinetics of the antiviral drug DHPG. 301 30

Cytomegalovirus (CMV) infection is the most frequent cause of lethal infection after bone marrow transplantation. Viremia occurs in 50% of patients seropositive for CMV before transplantation. Interstitial pneumonitis due to CMV occurs in 10% to 20% of patients with 85% mortality. It is known that CMV infection is due to host reactivation of latent CMV infection or to the transmission of the virus by the marrow donor or by blood transfusions. Treatment of CMV infection has been disappointing in the past. All attempts to treat CMV pneumonia with available agents have failed. Recent studies have indicated the usefulness of prophylactic measures and the early treatment of CMV infections. The use of hyperimmune gammaglobulins has given contradictory results. The selection of seronegative marrow donors or blood donors is useful only if the recipient is seronegative. New antiviral drugs have been used recently in preliminary clinical trials. In preliminary studies a guanosine analogue similar to Acyclovir (DHPG Synthex or BWB 759 U Wellcome) has given reasonable hope of disease cure if it is used early before the occurrence of pneumonia. Phosphonoformate (Foscarnet) has also been shown to be active against CMV infection. Both drugs have good antiviral and clinical action in immunosuppressed patients but the results have been disappointing in cases of pneumonia. Relapse occurs frequently after cessation of the treatment and attempts are being made to use maintenance therapy.
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PMID:[Prevention and treatment of cytomegalovirus infections after graft of allogenic bone marrow]. 303 85


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