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H M Shulman

Publications and source records attributed to H M Shulman.

86 records · Page 5Linked to original sources
PubMed1981

Esophageal abnormalities in chronic graft-versus-host disease in humans.

Disabling esophageal symptoms ((dysphagia, painful swallowing, and severe restrosternal pain) developed in 8 of 63 patients with chronic graft-versus-host disease after allogeneic bone marrow transplantation. At endoscopy 7 patients had characteristic desquamation of the upper esophagus; 2 of these also had distal esophagitis; and 3 had distinctive upper esophageal webs. No infectious pathogens were detected in esophageal biopsies or brushings. Abnormalities of esophageal motility were seen in 5 of 7 patients studied including 3 with aperistalsis. Retrosternal pain in 3 patients resulted from acid reflux. Esophageal histology from 5 autopsied patients showed no muscle or neuronal abnormalities by silver stain or conventional light microscopy. There was increased submucosal fibrosis associated with mucosal esophagitis and ulceration. Blind microscopic review of histology clearly distinguished the esophagus of chronic graft-versus-host disease from that of progressive systemic sclerosis. We conclude that esophageal epithelium, like skin and mucous membranes, is a target organ in chronic graft-versus-host disease. This immunologic disease results in desquamative esophagitis with web formation. Peptic esophagitis, a cause of severe pain and perhaps distal esophageal strictures in these patients, may be related to poor acid clearing from the esophagus. Diagnostic endoscopy and disruption of webs should be performed carefully to avoid perforation. Treatment should be directed toward suppressing the underlying immunologic disorder and at preventing acid-peptic reflux.

Adolescent↗
PubMed1980

Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.

This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.

Adolescent↗
PubMed1980

The diagnostic accuracy of the rectal biopsy in acute graft-versus-host disease: a prospective study of thirteen patients.

We carried out a coded, prospective analysis of sequential rectal biopsies from 13 patients undergoing allogeneic bone marrow transplantation in order to study the accuracy of these biopsies in the diagnosis of acute graft-versus-host disease (GVHD). We also tested the hypothesis that individual crypt cell degeneration is the initial lesion of intestinal GVHD. Pretransplant biopsies were normal. All biopsies taken 7--10 days after transplantation were diffusely abnormal with nuclear atypia and crypt cell degeneration. These changes were due to the conditioning regimen of total body irradiation and chemotherapy and had resolved by day 20 after transplantation. When acute GVHD was present, rectal biopsies were focally abnormal with crypt cell degeneration, crypt dilation, and crypt abscess. Rectal biopsies were normal after day 20 in those patients who did not have clinical evidence of GVHD. The location of cell degeneration at the base of crypts suggests that an immunologic mechanism is responsible for damage to rectal mucosa in GVHD. The rectal biopsy is an accurate way of detecting intestinal involvement with acute GVHD if done after resolution of radiation/chemotherapy effects.

Adolescent↗
PubMed1980

An analysis of hepatic venocclusive disease and centrilobular hepatic degeneration following bone marrow transplantation.

In order to assess the prevalence of venocclusive disease in autopsied recipients of bone marrow transplantation, we reviewed coded liver histology from 204 consecutive autopsied recipients transplanted for leukemia (142), other malignancies (5), or aplastic anemia (57). Twenty-seven patients with leukemia, 2 with carcinoma, and 3 with aplasia had venocclusive disease and survived 2-86 days post-transplant. Early lesions showed subintimal edema and hemorrhage within small central venules and centrilobular congestion with hepatocyte degeneration. Later lesions showed subtotal to complete fibrous obliteration of the central venule lumina and centrilobular sinusoidal fibrosis. Thirteen patients had a subclinical course, and 19 were symptomatic. Venocclusive disease was life-threatening or lethal in 13. Typical symptoms developed 1-3 wk post-transplant and consisted of sudden weight gain, hepatic enlargement, ascites, high bilirubin, and encephalopathy. Statistical analyses showed a significantly higher prevalence of venocclusive disease associated with transplantation for leukemia (P = 0.014), pretransplant conditioning with more rigorous chemoradiotherapy regimens (P < 0.001) and three- to fourfold increase of venocclusive disease in patients whose conditioning included dimethyl busulfan (P < 0.005). Abnormal liver tests before transplant were also more prevalent among patients with venocclusive disease. No factors predicted the clinical outcome of established venocclusive disease. Venocclusive disease showed no association with hepatic graft-versus-host disease even among prolonged cases with severe periportal hepatitis and cholestasis. Other centrilobular lesions (hepatocyte degeneration, sinusoidal fibrosis, and phlebosclerosis) were identified in 23 patients. These non-specific changes may occur with viral hepatitis, graft-versus-host disease or chemoradiotherapy effects.

Anemia, Aplastic↗
PubMed1979

Gastrointestinal graft-versus-host disease in man. A clinicopathologic study of the rectal biopsy.

Evaluation of the diagnostic utility of the rectal biopsy in graft-versus-host disease (GVHD), using the crypt abscess as a major diagnostic criterion, was based on 52 patients who had received marrow allografts for leukemia or aplastic anemia. Thirty-six of these patients had acute GVHD by skin biopsy criteria. These 36 patients demonstrated a strong association of the rectal crypt abscess with severity of clinical GVHD. High stool volume also correlated strongly with the crypt abscess. Patients without clear evidence of GVHD usually had normal rectal histology. Serial studies showed a good correlation of rectal biopsy results with the clinical course of acute GVHD. Patients with chronic GVHD had rectal mucosal damage only during the acute phase. Rectal ileal and cecal disease accurately. The rectal biopsy is a useful adjunct to serial skin biopsies in the diagnosis of GVHD in man.

Abscess↗
PubMed1979

The ultrastructure of the human epidermis in chronic graft-versus-host disease.

The epidermal ultrastructure of 11 allogeneic bone marrow recipients with chronic graft-versus-host disease (GVHD) was compared with that of 4 recipients without chronic GVHD. This electron microscope study revealed three patterns of epidermal injury typical of chronic GVHD. The first type was a nonacantholytic (nondissecting) injury with a prominent cellular infiltrate consisting primarily of lymphocytes accompanied by a few macrophages. The second type was an acantholytic (dissecting) injury with a prominent infiltrate, while the third was a nondissecting injury with a sparse infiltrate. Broad-zone contact was observed between lymphocytes and all epidermal cell types as well as between other lymphocytes and macrophages. Point contact was only observed between lymphocytes and epidermal cells. Lymphocytes appeared to detach desmosomes from adjacent keratinocytes by isolating them with cytoplasmic projections, a phenomenon not previously described. Typical damage to the epidermal cells in the basal and spinous layers consisted of either swelling of the organelles or condensation of the cytoplasm and nucleus. In the keratinocyte, the condensation reaction resulted in the formation of colloid bodies, some of which were phagocytized by macrophages. Besides the cytolytic events, a concurrent stimulatory reaction occurred in the epidermal cells. The number of melanosomes in melanocytes and of Langerhans cell granules and dense bodies in the Langerhans cells all increased. Extensive areas of replication and disruption of the basal lamina were subjacent to areas of necrosis in the basal layer.

Chronic Disease↗
PubMed1978

Chronic cutaneous graft-versus-host disease in man.

This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.

Adolescent↗
PubMed1977

The skin biopsy in the diagnosis of acute graft-versus-host disease in man.

Criteria for diagnosis of acute graft-versus-host disease (GVHD) using skin biopsies were derived from a) general experience with more than 300 human marrow grafts and b) the results of "blind" studies of skin biopsy specimens of patients grafted with either allogeneic or syngeneic marrow. Large doses of cytotoxic drugs and irradiation given before grafting can produce transient skin changes interfering significantly with the diagnosis of GVHD. Artifacts can also cause difficulty. Epidermal cytologic atypia, dyskeratosis, and satellitosis were present both in allografted patients with acute clinical GVHD of multiple systems and in patients given autologous or syngeneic marrow. Due to the marked overlap in histopathologic findings between these two types of skin injury, frequent serial skin biopsies must be combined with all other available clinical and biopsy data to provide reliable diagnosis of acute GVHD in man.

Acute Disease↗
PubMedDate not supplied

Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors.

Venocclusive disease (VOD) of the liver, a fibrous obliteration of small hepatic venules, can be caused by chemoradiation therapy. We reviewed 255 consecutive patients undergoing bone marrow transplantation for malignancy during 1978 to 1980 in order to determine the incidence of VOD and the predisposing factors. Fifty-three of 255 patients met our criteria for VOD, for an incidence of 21%. Multivariate analysis showed that the most significant risk factors for VOD were age over 15, an underlying malignancy other than acute lymphocytic leukemia and hepatitis prior to transplantation. Patients with hepatitis had a 3.4-fold risk of developing VOD, as compared to patients with normal SGOT values (p = 0.0004). Hepatitis in this setting is probably of non-A, non-B viral etiology and represents a relative contraindication to marrow transplantation because of enhanced toxicity from conditioning chemoradiotherapy.

Adolescent↗
PubMedDate not supplied

A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation.

We tested the hypothesis that liver histology from patients with graft-versus-host disease could be distinguished from other common liver diseases. Liver biopsies from 33 allogeneic marrow transplant recipients with acute and chronic graft-versus-host disease and 37 nontransplant liver disease patients without graft-versus-host disease were recut, restained and coded for blind review. Analysis of individual histologic features showed significantly more cytologic aberration of bile duct epithelium and more cholestasis among biopsies with graft-versus-host disease when compared to biopsies without graft-versus-host disease (p less than or equal to 0.05). The duration of graft-versus-host preceding the biopsy influenced the histologic features. Biopsies before Day 35 showed frequent acidophilic bodies but infrequent bile duct changes. Biopsies from Days 35 to 90 posttransplant had more frequent bile duct exocytosis and disruption, and biopsies from patients with chronic graft-versus-host disease (beyond Day 90) showed more frequent portal fibrosis and bile duct dropout. Pattern assessment of coded biopsies showed that a histologic diagnosis of graft-versus-host disease had a positive predictive value of 86%, a sensitivity of 66% and a specificity of 91%. False-negative diagnoses occurred most frequently in biopsies obtained less than 4 weeks posttransplant, usually because bile duct abnormalities were not present. False-positive diagnoses of graft-versus-host disease occurred in nongraft-versus-host disease biopsies with periportal inflammation and proliferated bile ducts. However, biopsies of chronic graft-versus-host disease had more frequent dropout and disruption of bile duct epithelium than did biopsies of acute or chronic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗