PubMed Health⌕ Search

Biomedical subjects

R C Hackman

Publications and source records attributed to R C Hackman.

At least 37 records · Page 2Linked to original sources

Legionellosis in a bone marrow transplant center.

We reviewed 10 cases of culture proven legionellosis that occurred at a marrow transplant center (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) over a 6-year period ending in 1993. Infections were caused by four species of Legionella with no apparent clustering of cases. Detection of Legionella using direct fluorescent antibody assays proved unreliable due to the high proportion of rare Legionella species isolated. The clinical presentation, course and outcome of patients varied and did not correlate with underlying disease, type of transplant, transplant day or engraftment status. However, five of the seven patients infected with non-pneumophila species recovered from their pneumonia compared to none of the three patients infected with L. pneumophila. Persistent or relapsed infection after 3 weeks of appropriate therapy was documented in one case suggesting that prolonged antibiotic treatment is indicated in these patients.

Adolescent↗

Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features.

To determine the prevalence of fungal liver infection at autopsy in marrow transplant recipients, we reviewed autopsy results for the period 1980-1989. Cases were compared to randomly chosen autopsied controls without fungal infection. Fungal liver infection was found in 67 (9%) of 731 patients. Fungal cultures of liver lesions were positive for 34 of 67 patients, most of whom had been culture-positive for the same fungal species (largely Candida) during life. Multivariate analysis revealed that independent predictors of fungal liver infection were deep fungal infection after transplantation (RR, 35), colonization or superficial infection after transplantation (RR, 13), and severe liver dysfunction caused by veno-occlusive disease of the liver and/or graft-versus-host disease (RR, 7). Clinical and laboratory findings during the last month of life revealed no differences between cases and controls. Liver imaging studies performed during the last 15 days of life had a sensitivity of only 18% for detecting fungal liver lesions.

Adult↗

Early pulmonary recurrence of non-Hodgkin's lymphoma after autologous marrow transplantation: evidence for reinfusion of lymphoma cells?

Disease recurrence is a major cause of failure after autologous bone marrow transplantation for Hodgkin's disease or non-Hodgkin's lymphoma. Relapse usually occurs at sites of previous involvement. The patient described here died of massive pulmonary involvement with Ki-1 antigen (CD30)-positive immunoblastic lymphoma 2 months after transplantation with unpurged autologous marrow. This relapse in a previously uninvolved organ prompted resectioning of the pre-storage marrow biopsy and resulted in identification of one small aggregation of malignant cells. A review of open lung biopsies and necropsies of autologous marrow recipients treated in Seattle identified no other patients with pulmonary malignancy who lacking previous lung tumor or evidence of contiguous pulmonary and mediastinal involvement. These observations raise questions about the assessment of pre-harvest marrow involvement and the need for marrow purging. This case also suggests that organ and tissue localization of malignant cells may be determined by abnormally expressed 'homing' ligands.

Adolescent↗

Etiology and outcome of diarrhea after marrow transplantation: a prospective study.

BACKGROUND/AIMS: Acute diarrhea after marrow transplant is usually ascribed to acute graft-vs.-host disease (GVHD) or infection, with a reported 40%-50% incidence of infection. The aim of this study was to determine the incidence of acute diarrhea after transplantation, its causes, and its outcome. METHODS: Two hundred ninety-six patients were followed up; patients with diarrhea were studied using standard evaluation of stool plus immunoelectron microscopy; assays for astrovirus, picobirnavirus, and Norwalk virus; and gene-probe methods for toxin-producing Escherichia coli. In 38 patients with diarrhea, intestinal biopsy specimens and duodenal fluid were also analyzed. RESULTS: One hundred fifty acute diarrheal episodes developed in 126 patients (an incidence of 43%). Intestinal infection was found in 20 of 150 episodes: viruses (astrovirus, adenovirus, cytomegalovirus, and rotavirus) in 12 patients, nosocomially acquired bacteria (Clostridium difficile and Aeromonas) in 7 patients, and mixed infection in 1 patient. Acute GVHD was responsible for 72 of 150 episodes (48%). Clinical signs and symptoms of infection and GVHD were similar. In 58 of 150 episodes (39%), no clear etiology could be found for self-limited diarrhea. CONCLUSIONS: Intestinal infection accounted for 13% and acute GVHD for 48% of diarrheal episodes. The most common infecting organisms were astrovirus, C. difficile, and adenovirus. Most cases of diarrhea after marrow transplant are not caused by infection.

Acute Disease↗

Recognition and rapid diagnosis of upper gastrointestinal cytomegalovirus infection in marrow transplant recipients. A comparison of seven virologic methods.

This is a retrospective study of 54 consecutive upper gastrointestinal endoscopies in marrow graft recipients performed to determine the incidence and distribution of CMV infection in symptomatic patients and to compare the sensitivities of 7 CMV detection techniques. At each endoscopy, 3 biopsies were obtained from the esophagus, stomach, and duodenum. Each of the 3 biopsies was assayed for CMV by different techniques. Enteric CMV was identified by one or more techniques in 52 of 486 (11%) biopsies from 14 infected patients. All patients infected with CMV initially had nausea and vomiting. In 13 of these patients, there was esophageal CMV, often associated with stomach (10 patients) and duodenal (7 patients) involvement. CMV infection of the esophagus was never identified cytologically in esophageal imprints or histologically, immunohistologically, or by DNA hybridization in esophageal epithelial cells. The most sensitive diagnostic methods were conventional and centrifugation cultures, which each identified CMV in 17 of the 30 (57%) organs positive by any technique. Indirect fluorescent antibody (IFA) staining for a late CMV antigen detected 53%, followed by in situ DNA hybridization (40%), IFA and immunoperoxidase (IP) staining for an early CMV antigen (37% and 43%), and routine histology (30%). Although no single detection technique is completely adequate for the rapid identification of CMV in small endoscopic biopsies, centrifugation culture is the method of choice, with supplementary immunohistology and in situ hybridization of archival tissue if needed.

Adult↗

Human herpesvirus 6 and pneumonia.

Studies of lung tissues and bronchoalveolar lavage specimens from patients with pneumonia have led some investigators to propose that human herpesvirus 6 (HHV-6) can cause pneumonia. As the etiologic role of HHV-6 in pneumonia remains poorly defined, cases of pneumonia that are associated with pulmonary HHV-6 infection are best described as HHV-6-associated pneumonias. The clinical spectrum of HHV-6-associated pneumonia encompasses both mild and severe cases. Most cases reported so far occurred in immunosuppressed individuals following bone marrow transplantation or HIV infection. Some studies have identified coinfections with HHV-6 and other viruses in a surprising number of HHV-6-associated pneumonias. Although no systematic evaluation of treatment regimens is available at this time, coincidental administration of antiviral drugs did not generally result in clinical improvement. Controlled, prospective studies are needed to understand the clinical presentation, clinical course, etiology, diagnosis and treatment of HHV-6-associated pneumonias.

Adult↗

Cytomegalovirus infection of the tongue following marrow transplantation.

Tongue ulcerations in seven patients who had undergone allogeneic BMT for hematologic or lymphoid malignancies were examined for the presence of CMV. The clinical presentation of these tongue lesions was nonspecific and showed ulcerations similar to those associated with severe preparative conditioning regimen-related mucositis, HSV infection and oral acute GVHD. Tissue biopsies were studied by routine histology, immunocytochemistry for CMV and HSV antigens, in situ hybridization for CMV nucleic acid and standard as well as centrifugation viral cultures. Five of the 7 patients had lesions which were positive for CMV. While CMV oral lesions are known to occur in patients with the acquired immune deficiency syndrome (AIDS), these findings will improve our ability to recognize and diagnose tongue lesions in BMT patients and indicate that CMV should be considered in the differential diagnosis for similar ulcerations in other immunocompromised patients.

Adult↗

Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience.

Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.

Adolescent↗

Human herpesvirus 6 in lung tissue from patients with pneumonitis after bone marrow transplantation.

BACKGROUND: Human herpesvirus 6 (HHV-6) is a recently described herpesvirus that is epidemiologically and biologically similar to cytomegalovirus. It is the cause of exanthem subitum (roseola) in children. METHODS: To evaluate the possible role of HHV-6 infection in pneumonitis in immunocompromised patients, we used quantitative HHV-6 polymerase chain reactions to study lung-biopsy specimens from 15 patients with pneumonitis after bone marrow transplantation and lung tissue from 15 immunocompetent subjects without pneumonitis and 6 fetuses. RESULTS: HHV-6 DNA was detected in lung tissue from all 15 patients, from 14 seropositive control subjects, and from none of the 7 seronegative control subjects. Six patients had levels of HHV-6 DNA in lung tissue that were 10 to 500 times higher than those in any of the other patients or control subjects. Increased levels of HHV-6 DNA correlated with a decreased risk of death from pneumonitis (P = 0.015), an increased severity of graft-versus-host disease (P = 0.023), and the presence of idiopathic pneumonitis (P = 0.037). Levels of HHV-6 DNA correlated directly with the changes in HHV-6 antibody titers in the interval between the pretransplantation period and the open-lung biopsy (P = 0.002). Low levels of HHV-6 antibody at the time of the open-lung biopsy were also associated with the diagnosis of idiopathic pneumonitis (P = 0.002). CONCLUSIONS: The concentrations of HHV-6 genome in lung tissue and their relation to changes in serologic titers support an association between HHV-6 infection and idiopathic pneumonitis in immunocompromised hosts.

Adolescent↗

Clinical course of idiopathic pneumonia after bone marrow transplantation.

We describe the clinical course of idiopathic pneumonia diagnosed by lung biopsy after allogeneic marrow transplantation and the associations of clinical presentation with outcome. All allogeneic marrow transplant recipients with an open-lung biopsy at a single marrow transplantation research center between January 1983 and December 1988 who were without infection were reviewed as a case series (n = 41). Data were retrieved from clinical information routinely collected at the time of transplantation on all patients. The onset of pneumonia was 11 to 143 days after transplant (mean 35), and 93% of cases displayed diffuse pulmonary infiltrates. Overall in-hospital mortality was 71% (n = 29). The case fatality rate was 59% (n = 24): 13 patients (32%) died with progressive respiratory failure, and the other 11 fatalities (27%) died either with recurrent respiratory failure after initial improvement (n = 7) or from nonpulmonary causes without resolution of pneumonia (n = 4). Infection was a major complication and was present at autopsy in 11 of 16 cases (69%). Of 12 patients discharged from the hospital 6 died within 1 yr, most commonly with relapse of malignancy. Both receipt of total-body irradiation > 1,200 cGy and presence of acute graft-versus-host disease were associated with an increased rate of resolution of pneumonia. The overall mortality of idiopathic pneumonia after allogeneic marrow transplantation is high, but less than one-third of patients die of progressive respiratory failure related to idiopathic pneumonia. Infection is commonly associated with death in marrow recipients previously diagnosed with idiopathic pneumonia by lung biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Severe adenoviral nephritis following bone marrow transplantation: successful treatment with intravenous ribavirin.

Invasive adenovirus infection is recognized as an unusual cause of serious end-organ sequelae following BMT. Because symptomatic therapy may be inadequate for more serious infections, the use of investigational agents is justified. We describe a case of severe, progressive nephritis secondary to adenovirus serotype 11 following BMT. Treatment with i.v. ribavirin led to prompt clinical improvement and resolution of adenovirus excretion.

Adenoviridae Infections↗

An outbreak of respiratory syncytial virus in a bone marrow transplant center.

An outbreak of respiratory syncytial virus (RSV) infection occurred among 31 patients in a marrow transplant center over a 13-week period beginning in January 1990. RSV infection was also documented in 35 family members and employees. Of 18 patients with pneumonia, 14 (78%) died. None of 13 with upper respiratory infection died. Preengraftment patients tended to develop pneumonia more frequently than did engrafted patients. Early administration of ribavirin may have had a beneficial effect in patients with pneumonia. Antigenic and genomic analysis of 14 available isolates suggested that at least four different viral strains were responsible for the outbreak. One group of patients and 1 employee in spatial proximity were infected with the same strain and likely acquired their infections nosocomially. RSV infection in marrow transplant patients is a serious and life-threatening infection with a high mortality rate once pneumonia develops.

Adolescent↗

Secondary T-cell lymphoproliferation after marrow transplantation.

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.

Adolescent↗

Acyclovir-resistant herpes simplex virus causing pneumonia after marrow transplantation.

Three marrow transplant patients developed pneumonia due to acyclovir-resistant thymidine-kinase-deficient herpes simplex virus (HSV) type 1. In all three, pneumonia was evident at autopsy by both standard and immunohistology, and virus was recovered from culture of lung tissue. Two patients also had other pulmonary infections at death; one had only HSV pneumonia. All had received prophylaxis and repeated treatment courses with acyclovir, and all initially had acyclovir-sensitive virus. The acyclovir-resistant HSV strains were sensitive to foscarnet, and in at least one case to vidarabine, but as expected were resistant to ganciclovir. These cases represent potentially severe visceral infection in which acyclovir-resistant virus strains were primary or important copathogens. Although acyclovir-resistant HSV is generally considered less virulent, these cases illustrate the potential importance of infection due to acyclovir-resistant HSV in severely immunocompromised patients. They also highlight the need to test HSV strains for antiviral sensitivity and to consider alternative therapies to acyclovir in appropriate clinical situations.

Acyclovir↗

Pulmonary venoocclusive disease following bone marrow transplantation.

We report two cases of pulmonary venoocclusive disease (PVOD) in children with acute lymphoblastic leukemia treated by marrow allograft transplantation following conditioning with high-dose 1-3 bis chloroethyl-1 nitrosourea (BCNU), etoposide (VP-16), and cyclophosphamide (Cy). Both patients developed symptomatic pulmonary hypertension documented by right heart catheterization. Open-lung biopsy of one patient demonstrated PVOD evident even on frozen sections stained with hematoxylin and eosin. High-dose methylprednisolone was associated with significant clinical improvement in both patients. Pulmonary symptoms resolved in one patient who subsequently died in leukemic relapse. PVOD resolved in the other patient, only to recur when steroids were discontinued and then again respond to reinstitution of therapy. More aggressive therapy for malignant diseases may increase the incidence of PVOD. Prompt recognition of its subtle clinical and histological manifestations allows early institution of steroid therapy, which may be beneficial.

Bone Marrow Transplantation↗

Biopsy diagnosis and clinical outcome of persistent focal pulmonary lesions after marrow transplantation.

We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984-1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions. Infection was documented in 78% (18/23) of all lesions and was fungal in each case. FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10). Complications occurred in 15% of FNA. OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5. Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy. This study demonstrates that focal lung lesions that develop or persist despite antibiotics after BMT are most often fungal. FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved.

Biopsy, Needle↗

Direct detection of cytomegalovirus from bronchoalveolar lavage samples by using a rapid in situ DNA hybridization assay.

An in situ DNA hybridization assay was compared with centrifugation culture for rapid detection of cytomegalovirus (CMV) from bronchoalveolar lavage (BAL) samples. Eighty BAL samples were inoculated into both centrifugation culture and standard culture. Cytospin preparations of the BAL samples were studied in a 75-min in situ DNA hybridization assay using the PathoGene CMV kit (Enzo Biochem, Inc., New York, N.Y.). Of the 80 samples, 39 (49%) were positive for CMV; 37 of 39 (95%) were positive by centrifugation culture, 34 of 39 (87%) were positive in standard culture, 24 of 39 (62%) were positive by in situ hybridization, and 20 of 39 (56%) were positive by histologic and/or immunofluorescence techniques. The in situ hybridization assay detected 23 of the 37 samples positive in centrifugation culture, for a sensitivity of 62% and a specificity of 98%. We conclude that the in situ hybridization assay is a specific and more rapid test than centrifugation culture and standard culture for diagnosis of CMV pulmonary infection. For the clinical laboratory, however, current hybridization methods are not sufficiently sensitive to replace centrifugation culture for detection of CMV in BAL specimens.

Bronchoalveolar Lavage Fluid↗