Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermal fibrosis, loss of cutaneous appendages, and loss of subcutaneous fat are the main manifestations of chronic graft-versus-host disease (cGVHD) in mice. Mast cells (MC) may have a role in cGVHD. To investigate this point we have evaluated the effect of a MC stabilizer (nedocromil sodium) and a MC activator (compound 48/80) on skin manifestations in a murine model of cGVHD (B10.D2-->BALB/c). Mice were treated with nedocromil sodium (5 mg/day) or compound 48/80 (10 micrograms/day) from day -3 until day 15. Nedocromil ameliorated the skin features of cGVHD while compound 48/80 caused skin changes reminiscent of mild cGVHD in control mice. In addition nedocromil normalized peritoneal MC numbers and skin MC numbers and their activation state in the cGVHD mice. On the other hand compound 48/80 caused a complete disappearance of toluidine blue stainable peritoneal MC from cGVHD and control mice and decreased skin MC in controls. In summary, MC activation may play a negative role in the skin changes seen in cGVHD while MC stabilization ameliorates the skin manifestations of cGVHD and therefore may have a therapeutic benefit.
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PMID:Nedocromil sodium ameliorates skin manifestations in a murine model of chronic graft-versus-host disease. 913 76

lnterleukin-2 (IL-2) is known to cause xerostomia and skin manifestations similar to graft-versus-host disease (GVHD). We therefore evaluated major salivary gland function in patients with hematological malignancies treated with IL-2 and interferon-alpha (IFN-alpha) after ABSCT. Eleven patients (seven male, four female) of median age 40 (24-47) were evaluated, seven with non-Hodgkin lymphoma (NHL); one with Hodgkin's disease (HD) and three with acute myelogenous leukemia (AML). Parotid and submandibular salivary gland function was assessed before, during and after IL-2/IFN-alpha administration by evaluation of the salivary flow rate and the composition of secreted saliva. Significant reductions in both the resting and stimulated parotid and submandibular salivary flow rates were observed during IL-2/IFN-alpha immunotherapy compared with the pre- and post-therapy values (P < 0.01), while no hyposalivation was observed in the control patients who underwent ABSCT and did not received IL-2. Sialochemical evaluation revealed a significant increase in potassium concentration (24.4+/-0.6 mEq/l to 28.9+/-1.4 mEq/l) and a significant decrease in sodium concentration (6.7+/-2.1 mEq/l to 3.3+/-1.0 mEq/l) (P < 0.05) in the stimulated parotid gland saliva secreted during IL-2/IFN-alpha administration. Salivary protein concentrations were not altered by the IL-2/IFN-alpha immunotherapy. Similar changes were previously observed in mice and humans with chronic GVHD. We conclude that IL-2 immunotherapy induces major salivary gland dysfunction in humans, similar to our previous observations in patients with chronic GVHD, which may indicate similar pathophysiologic mechanisms.
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PMID:Major salivary gland dysfunction in patients with hematological malignancies receiving interleukin-2-based immunotherapy post-autologous blood stem cell transplantation (ABSCT). 933 59

Although drug eruptions resembling graft-versus-host disease are rare, GvH-like reactions to the sulfhydryl group of drugs (penicillamine, captopril, gold sodium), phenobarbital and hepatitis vaccine have been described. Clinical reports concerning acute GvH-like drug rash are very uncommon and restricted to acetylsalicylic acid and spironolactone. We report on a patient who developed an acute GvH-like drug reaction caused by allopurinol. To our knowledge this variant of cytotoxic drug eruption has not yet been reported in literature.
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PMID:[Allopurinol as an inducer of acute graft-versus-host-like drug reaction. Case report with review of the literature]. 955 35

Patients with graft-versus-host disease (cGVHD) suffer from oral dryness and increased levels of oral infections and mucosal pathologies. The purpose of the current study was dual: 1) to investigate the salivary functional (sialometry) and compositional (sialochemistry) alterations induced by the disease during a 12-month period following the onset of the disease; and 2) to evaluate the effect of Salagen 30 mg/d on the salivary biochemical and immunological composition in cGVHD patients. Significant higher concentrations of salivary sodium (Na), magnesium (Mg), total protein (TP), albumin (Alb), epidermal growth factor (EGF), and total IgG accompanied by a concomitant increase in total IgA that did not reach significant value was observed in cGVHD patients in comparison with controls at both resting and stimulated conditions (p < 0.05) while salivary levels of potassium (K), calcium (Ca), and phosphate (P) were not altered. Two weeks of oral Salagen 30 mg/d resulted in normalization of the salivary biochemical and immunological compositional alterations in the cGVHD patients. Oral pilocarpine was able to reduce and normalize the elevated levels of Na, Mg, TP, Alb, EGF, IgG, and IgA salivary concentrations at both resting and stimulated conditions. The ability of oral pilocarpine to normalize and reverse salivary biochemical and immunological alterations induced by cGVHD is parallel to its stimulatory effect on salivary flow rates, as we previously showed. As the biochemical and immunological composition of the saliva results in its antimicrobial protective characteristics, the ability of oral pilocarpine (Salagen) to abrogate cGVHD salivary gland abnormalities may be of clinical importance.
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PMID:Sialometrical and sialochemical analysis of patients with chronic graft-versus-host disease--a prolonged study. 1264 7

Children undergoing hematopoietic stem cell transplantation (HSCT) may develop toxicity-related neurological complications (NC). Known risk factors include total body irradiation (TBI) and the use of busulfan or cyclosporine A, but other risk factors might also be of importance. The medical records of 144 children (0-18 yr) who underwent their first HSCT at Karolinska University Hospital (Huddinge) between 1995 and 2002 were reviewed retrospectively concerning pretransplantation parameters and clinical course during the first 3 months after HSCT. Sibling donors were used in 49 transplantations, unrelated donors in 88 and haploidentical donors in seven cases. Nineteen patients (13%) developed NC within the first 3 months after HSCT. A significant association was seen between pretransplant viral status, defined as a higher number of positive herpes group viral serologies in the recipient before transplantation, and NC (p = 0.04). A significant association was also seen for CMV-positive recipients and NC (p = 0.01) as well as for disturbances in serum levels of sodium, potassium and calcium and NC. No association was found between sex, age at HSCT, underlying disease, previous neurological symptoms, the conditioning regimen, GVHD, donor type and NC. Number of positive herpes group viral serologies in the recipient before transplantation and certain electrolyte disturbances may contribute to neurological complications after HSCT.
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PMID:Acute neurological complications after hematopoietic stem cell transplantation in children. 1566 14

Intradermal inoculation of cloned self-reactive alphabeta T cells into the footpads of mice induced cutaneous graft-versus-host disease (GVHD), and after recovery from GVHD, the epidermis became resistant to subsequent attempts to induce GVHD. Resistance to GVHD was not induced in the epidermis of T-cell receptor delta-deficient (TCRdelta(-/-)) mice that lacked gammadelta T cells bearing canonical Vgamma5/Vdelta1(+)gammadeltaTCRs, known as dendritic epidermal T cells (DETCs), and resistance was restored by reconstitution of these mutant mice with precursors of Vgamma5(+) DETCs. Pulmonary infection by Cryptococcus neoformans induced an increase of gammadelta T cells in the lung, and in comparison with wildtype mice, TCRdelta(-/-) mice eliminated C. neoformans more rapidly and synthesized more interferon-gamma in the lung. In the mouse small intestine, the absence of gammadelta T cells is associated with a reduction in epithelial cell turnover and downregulation of the expression of major histocompatibility complex class II molecules. The protective role of gammadelta T cells was verified in a dextran sodium sulfate-induced inflammatory bowel disease (IBD) model, whereas in a spontaneous model of IBD, gammadelta T cells were involved in the exacerbation of colitis in TCRalpha(-/-) mice. Taken together, in addition to the homeostatic regulation of epithelial tissues, gammadelta T cells appear to play a pivotal role in the modification of inflammatory responses induced in many organs containing epithelia.
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PMID:gammadelta T cells: firefighters or fire boosters in the front lines of inflammatory responses. 1729 Dec 82

A double-blind, placebo-controlled study was conducted to evaluate the effect of orally administered pilocarpine on unstimulated whole-saliva flow and composition in 28 patients with chronic graft-versus-host disease (cGVHD). Thirteen patients were treated with pilocarpine of 20 mg/day orally for 7 days, and 15 patients with placebo. Unstimulated whole saliva was collected in the morning on four occasions (30 min before pilocarpine or placebo intake, and 1 h, 1 day and 7 days after the first intake). Significantly, higher salivary flow rates, and sodium and total protein outputs were observed in the second samples of pilocarpine-treated patients compared with controls, whereas calcium and IgA outputs were not altered. Changes in these parameters were not significant in the third and fourth samples, although they were higher in the pilocarpine group. Patients who had received pilocarpine expressed satisfaction with their treatment. These data suggest that pilocarpine may improve salivary flow rate and the feeling of xerostomia in patients with cGVHD.
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PMID:Effect of pilocarpine hydrochloride on unstimulated whole saliva flow rate and composition in patients with chronic graft-versus-host disease (cGVHD). 1731 Jan 30

Stevens-Johnson syndrome (SJS) is a mucocutaneous disorder induced by an immune-complex-mediated hypersensitivity reaction. Nearly half of cases are caused by a reaction to drugs or appear during viral infections and malignancies. A very few cases are caused by a bacterial infection (Streptococcus) or Mycoplasma pneumoniae. Graft versus host disease is another well-established cause, independent of drugs. No specific etiology has been identified in up to half of cases. We report a 54-year-old man with SJS induced by carbamazepine. Reported patient had prodromal symptoms like fever, headache and polyarthralgia, which preceded mucocutaneous lesions by 3 days. Physical examination on admission, revealed asthenic male with a temperature of 37.2 degrees C and generalized dermatitis with positive Nikolsky sign, large erosions of the palms and soles, onychomadesis, numerous oral and vermilion border of the lips erosions. The patient was administered systemic steroidotherapy and carbamazepine dose was gradually decreased and finally replaced with valproic acid and valproate sodium. During the hospitalization, temperature normalized and the skin lesions disappeared after 3 weeks of treatment.
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PMID:Stevens-Johnson syndrome induced by carbamazepine. 1766 56

Characteristics of the goose hepatitis virus strain SHM 319 were studied in goose embryos and tissue cultures of avian origin. The virus was found to be resistant to both ether and sodium deoxycholate (0.25%). The growth of the virus was inhibited by 5-iodo-2-deoxyuridine. Virus infectivity was not affected by heating at 56 degrees C for 3 hours, exposure to pH 3.0, formalin (1:1000), and other inactivating chemicals. Cell culture systems of three avian species were inoculated with GVH-SHM 319. Extensive cytopathic effect was produced only in goose cell cultures. No virus replication was observed in chicken or White Pekin duck cells. Fluorescent antibody staining revealed granular nuclear staining in infected susceptible tissue cultures. May-Grunwald-Giemsa-staining of infected tissue culture cells showed formation of mainly intranuclear inclusion bodies. Millipore filtration procedures revealed a particle size less than 50 nm. Hemagglutination was not observed. Precipitating antibodies could not be detected in GHV hyperimmunized birds. Neutralization tests could not demonstrate a relationship to known viruses of waterfowl, including duck virus enteritis and duck virus hepatitis. A certain discrepancy in the neutralization test with Hungarian goose sera is discussed.
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PMID:Virus hepatitis of geese. 3. Properties of the causal agent. 1877 96

The aim of this study was to investigate the incidence, risk factors of acute renal failure (ARF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and evaluate its effect on the prognosis of patients after allo-HSCT. A retrospective analysis was performed in 86 patients undergoing allo-HSCT at Peking University First Hospital from June 2003 to April 2007. ARF is defined as a doubling of baseline serum creatinine at any time during the first 100 days post-transplant. The risks of ARF and mortality after ARF were examined using univariate analysis and multivariate unconditional logistic regression. The correlation of ARF and survival was examined using Cox regression. The results indicated that 27 patients (31.40%) developed ARF at a median of 59.5 days after transplant (range 1 to 93 days). The univariate analysis showed that elevated risks were severe acute GVHD (OR 6.196; 95% CI 1.121 - 34.249, p = 0.033), sepsis or septic shock (OR 4.184; 95% CI 1.314 - 13.325, p = 0.018) and hyperbilirubinemia (OR 3.709; 95% CI 1.428 - 9.635, p = 0.006). Renal disease before transplant (OR 6.711; 95% CI 1.199 - 37.564, p = 0.027), hypertension (OR 2.067; 95% CI 0.739 - 5.782, p = 0.165), the use of vancomycin (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) or foscarnet sodium (OR 2.133; 95% CI 0.844 - 5.392, p = 0.106) may be potential risks. Multivariate logistic regression analysis showed that renal disease before transplant (OR 6.288; 95% CI 1.218 - 32.455, p = 0.028), sepsis or septic shock (OR 3.614; 95% CI 1.040 - 12.544, p = 0.043) and hyperbilirubinemia (OR 4.448; 95% CI 1.563 - 12.665, p = 0.005) appear to be independently associated with an increased risk of ARF. Age, gender, baseline serum creatinine level, advanced malignant disease, unrelated-donor, total body irradiation (TBI) and cyclosporine levels were not associated with the development of ARF. Cox regression showed that ARF (RR 2.124; 95% CI 1.016 - 4.441, p = 0.045) was independently associated with survival of patients after allo-HSCT. The mortality of patients with ARF within 6 months post-transplant was significantly higher than that of those without ARF (44.4% vs 8.47%, p < 0.001). It is concluded that the cumulative incidence of ARF after allo-HSCT remains high. Renal disease before transplant, hyperbilirubinemia and sepsis or septic shock are all related factors which can increase the risk of ARF. ARF appears to be independent factor influencing survival of patients after allo-HSCT.
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PMID:[Clinical analysis of acute renal failure after allogeneic hematopoietic stem cell transplantation]. 1954 95


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