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Magnetic resonance imaging of lung signal intensity and dimensions in patients with advanced lung disease before and after single lung transplantation.

A retrospective analysis of lung signal intensity normalized for fat and lung cross-sectional area normalized for body surface area was obtained from cardiac gated spin-echo (echo time 40 ms) images before and after single-lung transplantation in 12 patients with pulmonary airway disease (seven emphysema, two bronchiectasis and three obliterative bronchiolitis) and 14 with interstitial lung disease (three pulmonary fibrosis, four fibrosing alveolitis and seven lymphangioleiomyomatosis). Nine healthy volunteers were studied for comparison. The native lung in pulmonary airway disease without inflammatory processes has normalised signal intensity (79 +/- 12%) similar to that of the control (100 +/- 6%) while interstitial lung disease had a higher normalised signal intensity (172 +/- 33%; P = < 0.05). The transplanted lung had a similar normalised signal intensity (103 +/- 12%) to that of the control except when there was a rejection reaction (one patient) or infection (two patients). Compared with the control, the native lung was smaller in pulmonary fibrosis (50 +/- 8%) and fibrosing alveolitis (78 +/- 8%), while larger in lymphangioleiomyomatosis (136 +/- 6%) and pulmonary airway disease (165 +/- 8%). The cross-sectional area of the transplanted lung was comparable to that of the control (100 +/- 13%). Distinctive features of lung normalised signal intensity and cross-sectional area were demonstrated in patients with pulmonary airway disease and interstitial lung disease before lung transplantation. These measurements could be useful noninvasive indices for assessment of the transplanted lung and for frequent follow-up of patients without exposure to ionizing radiation. Future developments are required to enhance lung signal sufficiently to detect less severe diseases.

Adult↗

Conduction system findings in sudden death in young adults with a history of bronchial asthma.

OBJECTIVES: This study was conducted to determine whether there are any pathologic changes in the conduction system when death occurs suddenly in young adults with a history of bronchial asthma. BACKGROUND: There is a worldwide increase in sudden death, especially in young adults with a history of bronchial asthma. METHODS: We studied the conduction system by serial section examination in six male patients (16 to 23 years old) with a history of bronchial asthma who died suddenly. RESULTS: The sinoatrial node artery was narrowed in two patients, with chronic inflammatory cells in three; it was fibrosed in one. The atrioventricular (AV) node was within the central fibrous body in three patients and isolated by fat in one. The AV bundle was markedly fragmented in five patients and fibrosed in two. The right and left bundle branches showed fat, fibrosis and disruption in five patients. Increased fibrosis on the summit of the ventricular septum with patchy fibrosis was present in five patients, and inflammatory cells in the conduction system were found in one. CONCLUSIONS: 1) There are distinct pathologic findings in the conduction system of young adults with a history of bronchial asthma who die suddenly. 2) The significant findings appear to be a markedly fragmented bundle and changes in the sinoatrial node that are not found in normal healthy young adults. 3) The changes in the conduction system may create an arrhythmic event, and sudden death may occur in some persons during an altered physiologic state. 4) We hypothesize that bronchial asthma may be associated with an alteration in immune complexes that affects the conduction system in some patients.

Adolescent↗

Quantitative analysis of growth factor production in the mechanism of fibrosis in agnogenic myeloid metaplasia.

OBJECTIVE: The current study quantified the growth factors in megakaryocytes and monocytes and correlated them to the degree of fibrosis, as there is no quantitative analysis of growth factors from megakaryocytes or monocytes reported in patients with agnogenic myeloid metaplasia (AMM). MATERIALS AND METHODS: Megakaryocytes were obtained from cultured blood CD34+ cells. CD14+ cells were sorted by magnetic cell sorting. Quantitative analyses of the growth factors were obtained by real-time reverse-transcriptase polymerase chain reaction techniques and enzyme-linked immunobsorbent assay (ELISA). RESULTS: 1) We found that mRNA levels of transforming growth factor (TGF) beta1, platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) produced by the megakaryocytes were significantly elevated in AMM compared with those in normal controls (p < 0.05). Although these growth factors were elevated severalfold in AMM compared with other myeloproliferative disorders (MPDs) including essential thrombocythemia and polycythemia vera, they were not statistically significant. 2) TGF-beta1 was more abundantly produced than PDGF or FGF. 3) The mRNA levels of these growth factors produced from CD14+ cells were not significantly elevated in AMM compared with other MPDs or controls; the AMM mRNA levels were significantly elevated only in some patients. 4) The correlation of mRNA levels of these growth factors with the degree of myelofibrosis in AMM was significant with megakaryocytes (r = 0.73) but not with monocytes (r = 0.23). 5) ELISA of the growth factors from the cultured megakaryocytes showed that in most of the patients with AMM and other MPDs, and in volunteer controls, the growth factors were undetectable, and only a few patients with AMM (three each of TGF-beta1 and PDGF and one of FGF) and other MPDs (two of TGF-beta1 and one each of PDGF and FGF) had significantly elevated protein levels of these growth factors. CONCLUSIONS: 1) In AMM, the mRNA levels of these fibrosing growth factors are significantly elevated in megakaryocytes, and they were only elevated in a few patients in the monocyte-macrophage lineages. 2) mRNA of TGF-beta1 is more abundantly produced than that of PDGF or FGF from megakaryocytes. 3) A statistically significant correlation between the growth factor mRNA levels with the degree of myelofibrosis in AMM suggests that these fibrosing growth factors produced by the megakaryocytes may be associated with the etiology of bone marrow fibrosis in AMM. 4) Failure to substantiate at the protein level that megakaryocytes are the main source of growth factors production suggests that other factors or cells initiating translation of the growth factors in the megakaryocytes may also be important in the process of bone marrow fibrosis in AMM. Further studies are necessary.

Cells, Cultured↗

Evaluation of a homeopathic complex in the clinical management of udder diseases of riverine buffaloes.

We report an uncontrolled observational study of the treatment of udder diseases of buffalo, using a homeopathic complex medicine. Mastitis is an economically important disease of buffaloes. In India economic losses due to mastitis are estimated at 526 million US dollars annually. Conventional veterinary treatment relies on costly antibiotics; cure rate is only 60% in field conditions with a problem of milk residues. The present investigation was undertaken to evaluate the effectiveness of a homeopathic complex in the management of clinical udder health problems of riverine buffaloes. Cases of subclinical mastitis were excluded from the study. A total of 102 mastitic quarters (fibrosed--40, nonfibrosed--62) and five cases each of blood in milk and udder oedema in lactating buffaloes were treated with a homeopathic complex consisting of Phytolacca 200c, Calcarea fluorica 200c, Silicea 30c, Belladona 30c, Bryonia 30c, Arnica 30c, Conium 30c and Ipecacuanha 30c. The diagnosis of udder diseases and recovery criterion was based on physical examination of udder and milk and CMT/WST score. Bacteriological analysis and somatic cell count were not performed. Treatment was 80 and 96.72% effective in cases of fibrotic mastitis and nonfibrosed mastitis respectively. Recovery period was 21-42 days (fibrosed) and 4-15 days (nonfibrosed). Udder oedema and blood in milk responded favourably in 2-5 days. Cost of treatment was 0.07 US dollars per day. The homeopathic complex medicine may be effective and economical in the management of udder health problems of buffaloes. Definitive conclusions are premature due to the limited number of observations and lack of control group.

Animals↗

A case of retroperitoneal and mediastinal fibrosis exhibiting elevated levels of IgG4 in the absence of sclerosing pancreatitis (autoimmune pancreatitis).

There is now increasing evidence that IgG4 is closely involved in idiopathic sclerosing lesions, such as sclerosing pancreatitis and sclerosing sialadenitis. In this report, we describe a case of IgG4-related retroperitoneal and mediastinal fibroses. A 52-year-old man presented with dull back pain and was found to have a continuously surrounding paraaortic mass. A biopsy specimen taken from the retroperitoneum showed a diffuse lymphoplasmacytic infiltration intermixed with fibrosis. Many IgG4-positive plasma cells were demonstrated on immunostaining. His serum IgG4 concentration was 392 mg/dL (reference range, <70). We treated this patient with a corticosteroid, which markedly diminished the paraaortic mass along with lowering of his serum IgG4 concentration. The possible involvement of IgG4 was suggested in the pathogeneses of retroperitoneal and mediastinal fibroses in this patient. IgG4 might be useful in the clinical management of retroperitoneal or mediastinal fibrosis to differentiate them from malignant tumors and predict steroid sensitivity.

Diagnosis, Differential↗

Uveal and capsular biocompatibility of a single-piece, sharp-edged hydrophilic acrylic intraocular lens with collagen (Collamer): 1-year results.

PURPOSE: To analyze uveal and capsular biocompatibility 1 year following implantation of a sharp-edged, hydrophilic, collagen-containing posterior chamber intraocular lens (IOL). SETTING: Department of Ophthalmology, University of Vienna Medical School, Vienna, Austria. METHOD: In a prospective study, a Collamer CC4204BF IOL was implanted in 30 eyes of patients with senile cataract. A standardized surgical technique and postoperative regimen were applied. To assess uveal biocompatibility, cellular inflammation on the anterior IOL surface was evaluated with a specular microscope. Capsular biocompatibility was registered semiquantitatively with a biomicroscope, based on an assessment of fibrosis on the anterior and posterior capsules. Tyndall values were measured with the Kowa FC-1000 laser flare-cell meter. Decentration of the lens was also registered. RESULTS: One year after implantation, the values of flare and cell count in the anterior chamber were lower than preoperatively. Round and spindle-shaped, epithelioid, and foreign-body giant cells were not found on the anterior surface of the IOL. The capsulorhexis rim was moderately fibrosed in 56.6% of cases. Fibrosis of the capsule over the optic was also moderate in 36.6%. The central portion of the posterior capsule was devoid of fibrosis in 43.3% and mildly fibrosed in 50%. Three lenses revealed outgrowth of lens epithelial cells to the anterior surface of the IOL. A neodymium:YAG capsulotomy had to be performed in 1 case. All lenses were well centered in the capsular bag 1 year after implantation. CONCLUSIONS: The absence of inflammatory cells on the anterior surface of the IOL indicates the high uveal biocompatibility of the lens. In terms of capsular biocompatibility, the results were satisfactory.

Biocompatible Materials↗

Radiation-induced production of PAR-1 and TGF-beta 1 mRNA in lung of C57Bl6 and C3H murine strains and influence of pharmacoprophylaxis by ACE inhibitors.

Transforming growth factor beta 1 (TGF-beta1) plays an important role in the development of radiation- and drug-induced organ diseases. Proteinases-activated receptor 1 (PAR-1) is involved in many pathophysiologic processes after its activation by serine proteases. The aim of the present study was to determine messenger RNA (mRNA) production of TGF-beta1 and PAR-1 in the lungs after local irradiation. Mice of C57BL/6 and C3H/J strains with different susceptibility to fibrosis development were exposed to a of 15Gy. Non-irradiated mice of both strains were used as negative controls. Control (irradiated) and irradiated angiotensin-converting enzyme (ACE) inhibitor-treated animals were examined simultaneously. The ACE inhibitor group was given butylaminiperindopril for 9 days after irradiation (15Gy) at a daily dose of 0.1 or 0.2mg/kg per rectum. On day 9, all mice were sacrificed, and the production of mRNA TGF-beta1 and PAR-1 in lung tissue was determined semiquantitatively using reverse transcriptase polymerase chain reaction, and immunohistochemical analysis of PAR-1 expression in pulmonary tissue was performed. In the fibrosing murine strain C57Bl/6, there was an increase in the mRNA TGF-beta1 and PAR-1 levels in lungs 9 days after irradiation as compared with non-irradiated controls and non-fibrosing murine strain C3H/J. In butylaminiperindopril-treated mice, a decrease in transcript of TGF-beta1 and PAR-1 was observed. Thus, PAR-1 is involved in radiation-induced lung fibrosis in correlation with TGF-beta1 production. Administration of ACEI influences PAR-1 and TGF-beta1 expression.

Angiotensin-Converting Enzyme Inhibitors↗

New clinical syndromes in dermatology.

Dermatologists are in the unique position to be able to diagnose serious systemic diseases through skin findings; in addition, cutaneous manifestations can be associated with internal symptoms and clarify the pathogenesis and treatment of challenging new syndromes. Calciphylaxix, now renamed Calcific Uremic Arteriolopathy, primarily affects patients with end-stage renal disease with concomitant hyperphosphatemia, increased calcium-phosphate product and hyperparathyroidism, skin biopsy and wound care are crucial parts of the diagnosis and treatment. Hyperhomocysteinemia may play a very important role in many cutaneous and systemic diseases including, chronic cutaneous wounds, systemic lupus erythematosus, Behcet's disease and psoriasis. Through a skin biopsy and biochemical analysis of the proteoglycans accumulation it may be possible to diagnose a new systemic mucinosis and prevent sudden death in patients with severe mitral valve prolapse. Nephrogenic Fibrosing Dermopathy is a newly described fibrosing disorder occurring in patients with end stage renal disease, the etiology and pathogenesis are still unknown, and the ultimate course of this disease has not been defined.

Fibrosis↗

Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes.

BACKGROUND: Information concerning long-term operative outcomes in patients with cystic fibrosis (CF) is relatively sparse in the operative literature. METHODS: A retrospective review of CF patients with operative conditions was performed (1972-2004) at a tertiary children's hospital to analyze outcomes including long-term morbidity and survival. RESULTS: A total of 226 patients with CF presented with an operative diagnosis (113 men, 113 women). A total of 422 operations were performed in 213 patients (94%). The mean age at operation was 4.1 +/- 6.2 years (range, 1 d to 26 y) and 109 were neonates. Fifteen of 42 (36%) babies with simple meconium ileus (MI) were treated nonoperatively with hypertonic enemas, 27 of 42 and all 45 patients with complicated MI required operation, including 15 with jejunoileal atresia (17%). Seventeen of 27 (63%) patients with meconium ileus equivalent had MI as neonates; 7 of 27 (26%) required operation. Eight of 9 (89%) with fibrosing colonopathy required operation. Organ transplantation was required in 21 patients. Follow-up evaluation was possible in 204 of 213 (96%) patients. The duration of follow-up evaluation was 14.9 +/- 8.5 years (range, 2 mo to 35 y). Operative morbidity was 11% at 1 year, 2% at 2 to 4 years, 1% at 5 to 10 years, and less than 1% at more than 10 years. There were 24 deaths (11%); 22 followed CF-related pulmonary complications and included 8 of 16 (50%) children with pneumothorax. CONCLUSIONS: Long-term survival in CF patients has improved significantly (89%), with many surviving into the fourth decade. MI may predispose to late complications including meconium ileus equivalent and fibrosing colonopathy. Pneumothorax in CF patients is an ominous predictor of mortality. Children with CF are living longer and are good candidates for operation, but require long-term follow-up evaluation because of ongoing exocrine dysfunction.

Abdomen↗

Adefovir treatment in posttransplant hepatitis B virus infection resistant to lamivudine plus hepatitis B virus immunoglobulin.

Failure of prophylaxis for hepatitis B virus (HBV) recurrence in liver transplant patients with HBV immunoglobulin (HBIG) or lamivudine or both can be associated with rapid development of liver failure. Some of these patients develop a devastating clinicopathological state characterized by jaundice and rapidly progressive liver failure or fibrosing cholestatic hepatitis. We present two liver transplant recipients who experienced HBV recurrence while they were under lamivudine and HBIG prophylaxis. One of them had finding of severe HBV infection; the other, fibrosing cholestatic hepatitis. After commencing adefovir dipivoxil both patients showed improvements in clinical status and laboratory data. At month 4 of treatment, HBV DNA values became negative and liver function tests almost normalized. In addition, in one case showed HBs ag/anti-HBs seroconversion. When failure of prophylaxis with lamivudine and HBIG occurs, adefovir dipivoxil should be considered to be a safe and effective choice for recurrent HBV infections in liver transplant patients.

Adenine↗

A cyclosporine-based immunosuppressive regimen may be better than tacrolimus for long-term liver allograft survival in recipients transplanted for hepatitis C.

UNLABELLED: Rapid recurrence of severe hepatitis C (HCV) after liver transplantation is a major barrier to survival of the transplanted liver. While cyclosporine (CsA) in vitro has been shown to suppress HCV replication, an effect is not seen with tacrolimus (Tac). Evidence is inconsistent whether or how this translates to clinical practice. To expand the evidence on this issue, we analyzed graft survival and histological outcomes after liver transplantation for HCV hepatitis. METHODS: Using our longitudinal database (1991 onward) graft outcomes for all liver transplant recipients with HCV were evaluated (105 grafts in 97 patients). Severe activity, severe fibrosis, and graft survival were analyzed. All liver biopsies were scored (blinded) according to the Ludwig scale. Immunosuppression was based on prednisone and a calcineurin inhibitor (Tac n = 89, 85%; CsA n = 15, 14%). Comparisons of outcomes using CsA versus Tac therapy were done using survival analysis via the log-rank test. RESULTS: Graft survival was significantly better in the CsA group. Although there was no apparent difference in severe activity (grade 2), there was a statistically significant difference in graft survival without fibrosing cholestatic hepatitis (P = .01) and a trend toward a difference in fibrosis-free survival (P = 0.1). The rate of sustained response to antiviral therapy was twice as high in the CsA group, 50% versus 22% (P = 0.16; NS). CONCLUSIONS: Graft survival in liver transplant recipients with HCV may be greater with CsA-based immunosuppression. There may also be a lower rate of fibrosing cholestatic hepatitis in this group.

Biopsy↗

Superior vena cava obstruction: bypass using spiral vein graft.

BACKGROUND: Previous midterm experience with the composite spiral saphenous vein graft to bypass the obstructed superior vena cava (SVC) has been favorable. This study looks at the long-term results in patients followed for up to 23 years. METHODS: Sixteen patients aged 17 to 68 years had operation for obstruction of the SVC with SVC syndrome caused by benign disease. Eleven patients had fibrosing mediastinitis with or without caseous necrosis, 4 had thrombosis caused by a catheter or a pacemaker electrode, and 1 had spontaneous thrombosis. All operations were performed using a composite spiral vein graft constructed from the patient's own saphenous vein. Graft diameter ranged from 9.5 to 15.0 mm. Ten grafts were from the left innominate vein, and six grafts were from the right or left internal jugular vein. The grafts were placed to the right atrial appendage in all patients except 1. Follow-up extends from 1 month to 23 years 8 months (mean follow-up, 10.9 years). RESULTS: Fourteen of 16 grafts remain patent for up to 23 years, and all patients but 1 are free from SVC syndrome. One patient required revision of the graft for thrombosis 4 days after operation. Two grafts closed during the first year after operation: one because of recurrence of spontaneous venous thrombosis and the other because of aggressive fibrosing mediastinitis requiring operation for graft revision three times over a 12-year period prior to death. CONCLUSIONS: These data demonstrate that a spiral vein bypass graft for treatment of the obstructed SVC relieves SVC syndrome and has excellent long-term patency.

Adolescent↗

Technical report: Cystic air spaces in the lung: change in size on expiratory high-resolution CT in 23 patients.

PURPOSE: To determine the presence of change in size of air-filled cysts in the lung on expiration by comparison between inspiratory and expiratory high-resolution computed tomography (CT) scans. MATERIALS AND METHODS: Inspiratory and expiratory high-resolution (1-mm collimation) CT scans were obtained in 23 patients with lung cysts due to a variety of lung diseases. The 23 patients had a total of 27 types of cystic lesions including bullae (n=7), honeycomb cysts due to fibrosing alveolitis (n=11), lymphangioleiomyomatosis (LAM, n=2), cystic adenomatoid malformation (n=1), and bronchiectasis (n=6). An adequate expiratory effort, with at least 5% decrease in the anteroposterior or transverse thoracic diameter, was required for inclusion in the study. Inspiratory and expiratory scans at corresponding anatomic levels were compared to determine any change in size of the cysts on expiration. RESULTS: Cystic lesions due to bronchiectasis, LAM and fibrosing alveolitis decreased in size on expiratory CT. In six of seven cases bullae decreased in size, and in one patient with a single bulla it remained unchanged. In one case a single cyst due to cystic adenomatoid malformation increased in size on expiration. CONCLUSION: The majority of lung cysts decrease in size on expiration suggesting that they communicate with the airways.

Adult↗

A preS mutation isolated from a patient with chronic hepatitis B infection leads to virus retention and misassembly.

A preS mutation derived from a patient with chronic hepatitis B virus (HBV) infection who had HBV reinfection with fibrosing cholestatic hepatitis after orthotopic liver transplantation was characterized. Sequence analysis of the HBV genome revealed two deletions and a point mutation in the regulatory CCAAT element of the S promoter. To investigate the particular preS mutation for replication competence and viral assembly in functional experiments, the mutant preS region was introduced into a replication competent HBV plasmid. Functional studies were performed by transfecting this plasmid into hepatoma cells. Analysis of the mutant HBV strain revealed an inverse ratio of S-gene products in comparison to wild-type HBV that leads to intracellular viral retention. An atypical intracellular distribution of HBV proteins and an enhanced nuclear localization of HBV DNA was also detected. Additionally, a major fraction of the extracellular viral particles was malformed. The association of intracellular accumulation of viral proteins with cirrhosis and fibrosing cholestatic hepatitis has been described recently. In this study, we show that the particular preS mutation accounted for the viral retention, which may have contributed to a more progressive form of liver disease found in this HBV-positive patient after liver transplantation.

Chronic Disease↗

Impact of EUS in the evaluation of pancreaticobiliary disorders in children.

BACKGROUND: While the role of EUS in the evaluation of pancreaticobiliary (PB) disorders in adults is well established, its utility in children remains unproven. This prospective study evaluates the feasibility, the safety, and the impact of EUS in the evaluation of PB disorders in children. METHODS: All children (<18 years) referred for ERCP for evaluation of suspected PB disorders who underwent EUS before scheduled ERCP. The main outcome measure was to evaluate the impact of EUS in the evaluation of PB disorders in children. EUS was considered to have a significant impact if a new diagnosis was established or if the findings altered subsequent management. RESULTS: Fourteen patients (mean age 13 years; range 5-17 years) underwent 15 EUS procedures over a 3-year period. Main indications were the following: acute or recurrent pancreatitis (6 patients), suspected biliary obstruction (5), and abdominal pain suggestive of PB origin (3). EUS diagnosed chronic pancreatitis (3 patients), idiopathic fibrosing pancreatitis (2), carcinoid tumor (1), pancreatic pseudocyst (1), pancreas divisum (1), choledocholithiasis (1), duodenal duplication cyst (1), and normal (4). Diagnosis of idiopathic fibrosing pancreatitis and carcinoid tumor was established by EUS-guided FNA. The procedure was successful in all patients, and no complications were encountered. EUS had an impact on patient management in 93% of cases: established new diagnosis (10), precluded need for ERCP (9), and provided additional information that facilitated focused endotherapy (4). A limitation was the small number of enrolled patients and absence of long-term clinical follow-up. CONCLUSIONS: EUS and EUS-guided FNA are feasible, safe, and have significant impact that alters subsequent management in the majority of children with PB disorders. Further studies and dissemination of information is required to facilitate its increased application in children.

Abdominal Pain↗

Changes in the incidence and severity of recurrent hepatitis C after liver transplantation over 1990-1999.

BACKGROUND/AIM: Changes in immunosuppression and other factors may have changed the severity of recurrent hepatitis C during recent years. This study sought to establish the changes in incidence and severity of recurrent hepatitis C, and its association with the changes in acute rejection and induction immunosuppressive therapy between 1990 and 1999. PATIENTS AND METHODS: Among 213 liver transplants in HCV-infected recipients, 129 grafts were selected for this study: all grafts with severe recurrent hepatitis C (fibrosis 3-4 in Scheuer's score or fibrosing cholestatic hepatitis), and those grafts without severe recurrence with at least 2 years of follow up. Grafts were divided in 5 groups depending on the year of transplantation to compare recurrent hepatitis C-related variables, AR incidence and induction immunosuppression. RESULTS: Hepatitis-free survival decreased in recent years (p=0.015). The incidence of fibrosing cholestatic hepatitis was higher among 1996-1997 and the 1998-1999 periods (p=0.019). Survival free of severe hepatitis at 1 year follow up was 95% in 1990-1991 and 80% in 1998-1999; however, in the long-term the survival was similar between groups (p=0.933). HCV-related graft survival at 5 years was 93.5% in the 1990-95 period and 82.5% in 1996-99 (p=0.068). Neither AR nor any regimen of induction immunosuppression was associated with changes in the occurrence of recurrent hepatitis C related survival. CONCLUSIONS: Severity of recurrent hepatitis C and HCV-related graft loss after liver transplantation were higher in the second half of the 1990s; however, there was no association with AR or induction immunosuppression.

Disease-Free Survival↗

Lipid peroxidation, stellate cell activation and hepatic fibrogenesis in a rat model of chronic steatohepatitis.

BACKGROUND/AIMS: We explored the involvement of cell types, cytokines and lipid peroxidation in a rat dietary model of fibrosing steatohepatitis. METHODS: Male rats were fed a high fat diet deficient in methionine and choline (MCD) for up to 17 weeks. Whole liver, hepatocytes and non-parenchymal cells were analysed for reduced glutathione (GSH) levels, products of lipid peroxidation (thiobarbituric acid reactive substances, TBARS), liver injury, and fibrosis. RESULTS: MCD diet-fed rats developed hepatic steatosis at week 2 and focal necroinflammatory change by week 5, while pericellular fibrosis evolved and progressed between weeks 12 and 17. Collagen alpha(1)(1) gene expression was upregulated by week 5 and increased fivefold by week 17. Stellate cells were the unique source of collagen gene expression. TIMP-1 and -2 were increased at week 12. Livers of MCD diet-fed rats exhibited lowered levels of GSH and elevated TBARS. Hepatocytes were the source of lipid peroxidation, and mRNA levels for TGFbeta1 were increased only in this cell type. CONCLUSIONS: The MCD model of 'fibrosing steatohepatitis' replicates the histologic features of human steatohepatitis, and the sequence of steatosis, inflammatory cell injury and fibrogenesis. The temporal sequence is consistent with a concept for involvement of oxidative injury in inflammatory recruitment and pathogenesis of hepatic fibrogenesis.

Animals↗

Dermatomyositis and pulmonary fibrosis associated with anti-Jo-1 antibody.

Although fibrosing alveolitis is a rare complication of dermatomyositis, early detection and treatment are important in preventing pulmonary fibrosis. Anti-Jo-1 antibody, an antibody to the cellular enzyme histidyl-t-RNA synthetase, has been found to correlate closely with the subset of dermatomyositis/polymyositis associated with fibrosing alveolitis. This association is well known to rheumatologists but has received little attention in the dermatologic literature. We wish to alert dermatologists to the importance of the association of anti-Jo-1 antibody in patients with dermatomyositis and present a patient with anti-Jo-1 antibody who had Raynaud's phenomenon and mild arthritis in association with dermatomyositis and pulmonary fibrosis. We suggest screening patients with polymyositis/dermatomyositis for this antibody, to detect the population at high risk of developing pulmonary complications.

Antibodies, Antinuclear↗