Biomedical subjects

R C Hackman

Publications and source records attributed to R C Hackman.

At least 55 records · Page 3Linked to original sources

PubMed1988

Open lung biopsy diagnosis of diffuse pulmonary infiltrates after marrow transplantation.

The results were reviewed of 111 open lung biopsies (OLB) performed on 109 marrow transplantation recipients with diffuse pulmonary infiltrates between January 1983 and July 1987. We determined the frequency and types of infections identified, and the relationship to time after transplantation. Infection was found in 70 of the 111 cases (63 percent) and cytomegalovirus (CMV) was present in 90 percent of all cases with infection. Infection was identified in only five of 26 (19 percent) cases within the first 30 days after transplant, and when present, was viral. The prevalence of infection after 30 days (over 75 percent of 85 cases) was significantly higher (chi 2 = 26.2, p = 0.00001). Bacterial or yeast infections were found in only four cases (4 percent) (two cases each), and Pneumocystis carinii in six cases (6 percent). Simultaneous infection with two or more organisms was found in four cases (4 percent). Four of 25 autopsies performed within ten days after OLB revealed fungal infections with Aspergillus not detected at OLB. Thus, the prevalence of infection detected by OLB is low within the first 30 days after marrow transplantation among patients receiving broad spectrum antibiotics. CMV infection is found in most transplantation recipients who undergo OLB with diffuse infiltrates between days 30 and 180.

Anti-Bacterial Agents↗

PubMed1988

Rapid detection of cytomegalovirus pulmonary infection by bronchoalveolar lavage and centrifugation culture.

Cytomegalovirus infection remains a major cause of morbidity and mortality in marrow transplant recipients. Results of a rapid centrifugation viral culture of bronchoalveolar lavage specimens from 33 marrow transplant recipients with pneumonia were compared with those for conventional viral culture of concurrently or subsequently obtained lung tissue. The centrifugation culture results were also compared to results of cytologic and immunochemical examination of these specimens. Centrifugation culture was positive within 16 hours of inoculation in 22 of 23 (96%) specimens from patients with positive conventional culture of lung tissue. Detection of cells positive for cytomegalovirus by immunofluorescent antibody staining or cytologic identification was less sensitive (59% and 29%, respectively). There was no evidence of cytomegalovirus in specimens from patients without evidence of cytomegalovirus pulmonary infection by any technique. The sensitivity (96%) and specificity (100%) of centrifugation culture of specimens from marrow transplant recipients approach that of viral culture of lung tissue.

Adolescent↗

PubMed1987

Rapid diagnosis of invasive cytomegalovirus infection by examination of tissue specimens in centrifugation culture.

Two hundred eight tissue specimens from 81 patients were examined by centrifugation culture for the rapid diagnosis of invasive cytomegalovirus (CMV) infection. Results were compared with those obtained by both conventional viral cultures and histologic examination. CMV was identified by centrifugation culture in 52 (25%) specimens at 16 hours after inoculation, including 39 lung specimens and 12 gastrointestinal specimens. One additional esophageal specimen was positive (53 of 208 specimens; 25.5%) at 36 hours. In contrast, CMV was recovered from only 50 of these 53 specimens by conventional cell culture at a mean of 11 days after inoculation. Forty-three of the 208 specimens (20.5%) were positive for CMV when examined by histologic methods, including light microscopy and tissue immunofluorescence. All 43 were positive by centrifugation culture. Specimens that were positive by centrifugation culture but negative by histologic methods included three lung specimens and seven gastrointestinal specimens. The technic of centrifugation culture is more sensitive for diagnosis of invasive CMV infection by the examination of affected tissue than either conventional viral culture or histologic technics, including tissue immunofluorescence, and more rapid than conventional culture or routine histologic examination.

Antibodies, Monoclonal↗

PubMed1986

Use of bronchoalveolar lavage to diagnose acute diffuse pneumonia in the immunocompromised host.

We compared the diagnostic information obtained by bronchoscopy and needle aspiration of the lung with information obtained concurrently by open-lung biopsy in 15 marrow transplant recipients. Bronchoscopy included a wash, brush, and bronchoalveolar lavage. Laboratory evaluation included standard histological and cytological methods, specific immunofluorescence with monoclonal antibodies, and DNA hybridization to detect cytomegalovirus (CMV). Bronchoscopy permitted diagnosis of five of six patients with CMV pneumonia, whereas needle aspiration alone permitted diagnosis of only one of six. Bronchoalveolar lavage alone provided the diagnosis in four of six patients. Bronchoscopy also identified the bacterial component of a combined infection and identified one case of primary lung hemorrhage. Immunofluorescent staining and hybridization studies each diagnosed one case of CMV pneumonia not identified by standard techniques. The diagnostic sensitivity of the bronchoscopy was 89%, as compared with 17% for needle aspiration, and there were no complications.

Antibodies, Monoclonal↗

PubMed1986

A prospective study of unexplained nausea and vomiting after marrow transplantation.

We prospectively studied patients with enigmatic nausea and vomiting after allogeneic marrow transplantation to define the causes of this syndrome. Fifty consecutive episodes of persistent vomiting were investigated using physical examination and laboratory tests, endoscopic biopsies and brushings, and clinical follow-up for four weeks. Potential causes of vomiting were identified in 39 of the 50 cases (78%). Fifteen cases had gastrointestinal infections (mainly herpesviruses), 13 had unsuspected acute intestinal graft-versus-host disease (GVHD), 8 had intestinal infection plus acute GVHD, and 3 had other causes (subdural hematomas, bacteremia, and encephalitis). In the remaining 11 cases, no cause of vomiting was found. Endoscopy was necessary for diagnosis in 36 cases and required a combination of methods: routine histology, cytology, viral culture, and immunohistology using monoclonal antibodies to cytomegalovirus (CMV) and herpes simplex virus type 1. Patients with unexplained vomiting or intestinal GVHD had significant improvement of nausea and vomiting over the four-week observation period, but those with CMV did not (P = .01). We conclude that most allogeneic marrow transplant patients with enigmatic nausea and vomiting have gastrointestinal herpesvirus infections, acute GVHD, or both. Untreated CMV infections and persistent GVHD are associated with protracted vomiting in these patients.

Adolescent↗

PubMed1986

Occurrence of the adult respiratory distress syndrome in neutropenic patients.

Neutrophils are believed to play an essential role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This concept is largely based on the observation that neutrophil depletion protects against altered pulmonary vascular permeability in several models of acute lung injury produced in laboratory animals. Four patients who developed ARDS during periods of profound neutropenia are presented. These patients met commonly accepted clinical and roentgenographic criteria for the syndrome, and each had the characteristic findings of diffuse alveolar damage by lung histologic examination. The failure of this degree of neutropenia to protect against ARDS in humans raises questions about whether neutrophils or neutrophil products are essential in the pathogenesis of the syndrome.

Adolescent↗

PubMed1985

Adenovirus infections in patients undergoing bone-marrow transplantation.

Viral infection is commonly observed after bone-marrow transplantation. We isolated adenovirus from 51 of 1051 patients undergoing marrow transplantation between 1976 and 1982. Of the 46 isolates available for typing, 13 (27.7 per cent) were of the closely related species 11, 34, or 35 (subgenus B). All 13 of the patients with these species had positive urine cultures. The species have previously been associated with the acquired immunodeficiency syndrome or with renal transplantation but are not commonly found in community surveys. Invasive infection was confirmed by biopsy or autopsy in 10 of 51 patients. Seven of the 10 had virus isolated from lung, and 4 died from pneumonia attributed to adenovirus. Two of the five patients with renal isolates had evidence of virally induced renal impairment, and both patients with liver isolates had adenovirus hepatitis. There was no common source that accounted for these adenovirus infections, and the most likely source of infection appeared to be endogenous viral reactivation. The only identifiable risk factor for the development of infection and for severe disease was the presence of moderate to severe graft versus host disease.

Adenoviridae Infections↗

PubMed1985

Esophageal infections in immunosuppressed patients after marrow transplantation.

We reviewed all cases of infectious esophagitis diagnosed after marrow transplantation during a 2-yr period. Twenty-one infections were found during 46 fiberoptic endoscopic examinations; most infections were viral, with equal numbers due to cytomegalovirus and herpes simplex virus. These infections presented with nonspecific esophageal symptoms weeks to months after transplantation. Diagnoses depended on histology and viral cultures. During the same time span, autopsies revealed 25 cases of infective esophagitis among 59 patients; most were again viral, with equal numbers of herpes simplex virus and cytomegalovirus infections. Mixed infections due to viral, fungal, and bacterial pathogens were found in both endoscopy and autopsy series. The prevalence of esophageal infection in marrow transplant patients with esophageal symptoms is high, but the organisms could not be predicted on the basis of symptoms, oropharyngeal surveillance cultures, or esophageal x-ray. Accurate diagnosis requires that endoscopic biopsy specimens and brushings be examined by both histologic and virologic methods.

Bacterial Infections↗

PubMed1985

Rapid diagnosis of cytomegaloviral pneumonia by tissue immunofluorescence with a murine monoclonal antibody.

A murine monoclonal antibody to cytomegalovirus (CMV) was used to identify virus-infected cells in coded frozen tissue sections from 52 consecutive open-lung biopsies obtained from marrow transplant recipients with pneumonia. The diagnostic sensitivity of immunofluorescence (IF) using this antibody exceeded that of standard histology performed on touch imprints and frozen and permanent lung sections and was equal to viral culture and in situ CMV nucleic acid hybridization. In comparison with patients with CMV pneumonia demonstrated histologically and by IF, those with negative histology and positive IF were more likely to have seroconverted before biopsy. Despite this evidence of an immune response to CMV pneumonia, the two groups did not differ in CMV positivity by culture or by hybridization, and their long-term survival was equally poor. The findings demonstrate that this antibody can play an important role in both the rapid diagnosis of CMV infection and the elucidation of CMV pathophysiology.

Antibodies, Monoclonal↗

PubMed1985

Toxoplasma gondii reactivation identified by detection of parasitemia in tissue culture.

Three patients developed acute toxoplasmosis after allogeneic marrow transplantation for treatment of leukemia. In each case, Toxoplasma gondii was isolated from peripheral blood buffy-coat cells inoculated into fibroblast tissue culture after 10 to 39 days of incubation. Serologic studies did not suggest acute toxoplasmosis, but complete autopsies done in two patients showed active invasive disease. Serologic tests done before the transplants showed that these cases resulted from reactivation of latent infection rather than primary disease. Parasitemia is a feature of reactivation toxoplasmosis in immunosuppressed patients that may be identified by recovery of T. gondii from peripheral blood buffy-coat cells in tissue culture.

Adult↗

PubMed1985

Autologous marrow transplantation as consolidation therapy for canine lymphoma: efficacy and toxicity of various regimens of total body irradiation.

Dogs with malignant lymphoma were given chemotherapy consisting of nitrogen mustard, vincristine sulfate, prednisone, L-asparaginase, and 6-mercaptopurine (MOPA-6) for 14 days. Among 62 dogs that completed treatment with MOPA-6, 47 (76%) had complete remission, and 13 (21%) had partial remission and 2 had no response to chemotherapy. Twenty-two of the 62 dogs were not returned by their owners for additional therapy and died 15 to 391 (median 21) days after MOPA-6 from infections or recurrent disease. A median of 1 month after starting MOPA-6 therapy, 40 dogs (35 in complete remission, 5 in partial remission) were given total body irradiation (TBI), followed by infusion of fresh autologous marrow. Twenty dogs were given 13.5 Gray (Gy) of TBI at 4 centi-Gray (cGy)/min. Among 16 evaluable dogs, 7 had recurrence of lymphoma at a median of 169 days. Two dogs died with veno-occlusive disease of the liver, 3 with pneumonia, 3 with hemorrhage, and 1 was killed. Twenty dogs were given 11.8 to 14.7 Gy of TBI at 2 cGy/min. Among 14 evaluable dogs, 9 had recurrence of lymphoma at a median of 117 days. The remaining 5 dogs were killed at 110 to 680 days; lymphoma was not present at necropsy. The results indicated that doses of TBI of 11.8 to 14.7 Gy did not reduce the recurrence of lymphoma, compared with results obtained in a previous study with 8.4 Gy of TBI. Furthermore, increased doses of TBI increased acute and delayed toxicities. Alternatively, recurrent disease may have been due to lymphoma cells contained in the infused remission marrow.

Animals↗

PubMed1984

Widespread presence of histologically occult cytomegalovirus.

Disseminated cytomegalovirus (CMV) has been investigated by in situ hybridization in formalin-fixed paraffin-embedded tissue sections with biotinylated DNA probes. Two cases of disseminated CMV infection were studied at autopsy by this highly specific technique. The presence of CMV in cytomegalic cells is readily shown. In addition, CMV has been detected and localized in many normal-appearing cells. This occult infection occurs in cardiac myocytes, hepatocytes, spleen and lymph node reticular cells, endometrial stromal and glandular cells, and breast stromal cells, as well as in cells in the renal glomerulus, tubule, and interstitium, adrenal cortex and medulla, fallopian tube submucosa, myometrium, and anterior pituitary. Cytomegalovirus infection of endothelial cells has been further documented by immunohistochemical methods utilizing antibody to Factor VIII. These findings suggest that CMV disseminates hematogenously throughout the body, initiating necrotizing foci of infection. The appearance of many diffuse foci suggests that local viral spread occurs via endothelial cell infection. Surprisingly , lymphocyte involvement was not observed.

Adult↗

PubMed1984

Diagnosis of cytomegaloviral pneumonia by in situ hybridization.

Cytomegalovirus was assayed by in situ hybridization in 29 consecutive specimens obtained by open-lung biopsy. Biotin-labeled cytomegaloviral DNA was hybridized to formalin-fixed, paraffin-embedded tissue sections and was detected by an immunoperoxidase procedure. The sensitivity of this technique was similar to that of both viral culture and viral antigen detection in frozen sections by monoclonal antibody. Cytomegaloviral infection was diagnosed within 24 hr by study of the formalin-fixed, paraffin-embedded sections of lung tissue. The assay was specific, reproducible, and readily applicable both to the study of multiple tissue sections for diagnostic purposes and to retrospective studies. Hybridization studies of multiple sections from two patients with fatal cases of pneumonia showed that cytomegaloviral infection is not homogeneous in all cases.

Antibodies, Monoclonal↗

PubMed1984

Lymphocytic bronchitis unrelated to acute graft-versus-host disease in canine marrow graft recipients.

We reviewed coded autopsy material from 71 dogs, 46 receiving allogeneic and 25 receiving autologous bone marrow transplants, to evaluate the hypothesis that lymphocytic bronchitis is associated with severe acute graft-versus-host disease (GVHD). We found no significant correlation between the presence of lymphocytic bronchitis and severe acute GVHD (P greater than 0.16). Using a binary regression model that corrected for possible confounding relationships, we failed to show a correlation between lymphocytic bronchitis and acute GVHD of each of the 3 classically affected organ systems. Also, no correlation was found between lymphocytic bronchitis and acute bacterial pneumonia (P greater than 0.32). Finally, lymphocytic bronchitis was present in autografted dogs with a prevalence at autopsy not significantly different from that of allografted dogs (P greater than 0.32). We conclude that lymphocytic bronchitis in this canine model represents nonspecific inflammation rather than acute pulmonary GVHD.

Acute Disease↗

PubMed1984

Rapidly progressive air-flow obstruction in marrow transplant recipients. Possible association between obliterative bronchiolitis and chronic graft-versus-host disease.

Severe obstructive airways disease developed in 4 young nonsmoking adults after marrow transplantation. They were free of respiratory disease until symptoms developed 277 to 600 days after transplant. Pulmonary function testing showed that the mean forced expiratory volume in one second was 35% of predicted (range, 23 to 49%). All patients had active or inactive extensive chronic graft-versus-host disease that included oral mucositis, esophagitis, sinusitis, and oral and ocular sicca. Three patients had subnormal serum IgA levels. Bronchitis was apparent during fiberoptic bronchoscopy in 3 patients. An open-lung biopsy specimen from 1 patient showed obliterative bronchiolitis. Treatment has included bronchodilators and corticosteroids without objective benefit. The disorder stabilized in all 4 patients, but a severe reduction in air flow persisted. Awareness of this complication may lead to earlier diagnosis and more effective treatment.

Adolescent↗

PubMed1983

Chlamydia trachomatis infection as a cause of pneumonia after human marrow transplantation.

Seventy-two marrow transplant patients were studied to assess the role of Chlamydia trachomatis infection in the etiology of pneumonia in the compromised host. Sixty-four patients had pneumonia from various causes and eight died of causes other than pneumonia. Chlamydial serologies and cultures of lung tissue, or other sites, or both, were obtained from all patients. C trachomatis was recovered from a single sputum specimen obtained at the onset of pneumonia in one patient, and three patients developed sustained IgG and IgM antibody responses to chlamydiae during their pneumonia. Two of the four patients died of pneumonia. These data further confirm that C trachomatis infection occurs in immunosuppressed patients in association with pneumonia. The source of the organism and the frequency of infection remain to be determined.

Adolescent↗

PubMed1982

Rapid cytologic diagnosis of cytomegalovirus interstitial pneumonia on touch imprints from open-lung biopsy.

The diagnostic utility of Wright-Giemsa-stained touch imprints for identifying cytomegalovirus (CMV) in open-lung biopsies from marrow transplant recipients was studied. Of 41 consecutive biopsy specimens, 18 had culturally proven CMV, and 15 had typical intranuclear and intracytoplasmic inclusion bodies on permanent histologic sections. Wright-Giemsa-stained touch imprints from ten of the 15 biopsy specimens with CMV had characteristically enlarged cells containing 20-75 round to oval intracytoplasmic inclusions while only rarely containing intranuclear inclusions. The diagnosis of CMV from Wright-Giemsa-staining imprints (10/15) was superior to hematoxylin and eosin (H & E)-stained touch imprints (5/15) and H & E-stained frozen sections (2/15). Two cases of CMV had Papanicolaou-stained imprints that also demonstrated both intranuclear and intracytoplasmic inclusions. This simple technic of examining cytologic imprints from open-lung biopsy specimens will rapidly identify more than 50% of all confirmed cases of CMV, allowing earlier and possibly more successful antiviral therapy.

Biopsy↗

PubMed1982

Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients.

Herpes simplex virus (herpesvirus) was isolated from autopsy lung specimens of 20 patients with clinical, roentgenographic, and histologic evidence of pneumonia. Mucocutaneous herpesvirus infection preceded the onset of pneumonia in 17. Twelve patients had focal pneumonia, 10 of whom had concomitant herpetic tracheitis, esophagitis, or both. Eight patients had diffuse interstitial pneumonia, six of whom had dissemination of herpesvirus to the other organs. Of the eight lung isolates available for typing, seven were herpesvirus-1 and one, herpesvirus-2. A high prevalence of herpesvirus antibody in serum samples obtained before pneumonia and identical restriction endonuclease patterns between mucosal and lung isolates in individual patients indicated that, in most cases, herpesvirus pneumonia was due to endogenous reactivation of virus. Focal herpesvirus pneumonia appeared to result from contiguous spread of herpesvirus to lung parenchyma, whereas diffuse interstitial pneumonia appeared to be a manifestation of hematogenous dissemination of virus.

Adolescent↗