Prevalence and determinants of histological abnormalities of the gastric cardia in volunteers

Objective. The findings of studies examining the prevalence and major risk factors of histological abnormalities of the gastric cardia have been inconsistent. Selection bias was possible in these studies depending on whether patients were referred for ulcer or gastroesophageal reflux disease (GERD). There have been no studies on non-patient populations. The aim of this study was to mitigate the potential effects of selection bias. Material and methods. In a study comprising health-care workers, we distributed symptom questionnaires and invitations to undergo upper endoscopy. A single endoscopist performed standard endoscopy and biopsy examinations (2 antral, 2 corporal, and 2 cardiac biopsies). Staining was done using triple stain. Two pathologists, who were blinded to the results of the questionnaires and endoscopy, interpreted and recorded the histological findings. Results. A total of 226 participants underwent endoscopy. Gastric cardia, as defined by the presence of mucous glands, was identified in 191 subjects; mean age of the subjects was 45 years, 117 (61%) were women, and 49% were black. Active gastritis of the cardia was present in 58 (30.4%), chronic gastritis in 133 (69.6%), intestinal metaplasia (IM) in 29 (15.2%), and pancreatic metaplasia in 25 (13%). Direct (organisms) or indirect evidence (active anywhere or chronic gastritis in antrum or corpus) for Helicobacter pylori was present in all participants with active gastritis, 60% of subjects with chronic gastritis, and approximately half of those with IM of the cardia. Approximately 15% with chronic carditis had neither H.pylori nor GERD symptoms. There were also no significant differences in the prevalence of heartburn or acid regurgitation, or the use of histamine-2-receptor antagonists (H₂RAs) or proton-pump inhibitors (PPIs) between groups with and without active or chronic gastritis, IM, or pancreatic metaplasia, whereas active or chronic gastritis in the antrum or corpus and H. pylori infection were more frequent (1.5- to 2-fold) among those with histological abnormalities of the cardia. Conclusions. Active and chronic gastritis as well as intestinal metaplasia of the gastric cardia are relatively common in health-care worker volunteers. Although GERD symptoms are not significantly associated with these abnormalities, H. pylori infection is a strong risk factor. However, a considerable number of participants with chronic gastritis of the cardia have neither H. pylori nor GERD.     

Is Helicobacter pylori infection associated with alopecia areata?

Background  Alopecia areata (AA) is an immune-mediated form of hair loss that occurs in all ethnic groups, ages, and both sexes. Helicobacter pylori has been associated with certain extra-digestive dermatological conditions, including chronic urticaria, rosacea, Schönlein-Henoch purpura, Sweet syndrome, systemic sclerosis, and atopic dermatitis.
Objective  The causal relation between alopecia areata and H. pylori is discussed. We have screened for the presence of H. pylori in patients with AA in order to determine any potential role in its pathophysiology.
Patients and methods  We have prospectively studied 31 patients with AA and 24 healthy volunteers of similar gender for the presence of H. pylori surface antigen (HpSag) in stool.
Results  Optical density values for H. pylori infection were positive in 18 of all 31 patients evaluated (58.1%), while in 13 patients, values did not support H. pylori infection (41.9%). While in the control group, 10 of 24 (41.7%) had positive results. Within the group of AA, there was no significant difference between HpSag-positive and HpSag-negative patients.
Conclusions  Based on these results, the relation between H. pylori and AA is not supported. We advise that H. pylori detection should not be included in the laboratory workup of AA.     

FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

Recognition of regional hypertrophy in hypertrophic cardiomyopathy using thallium-201 emission-computed tomography: Comparison with two-dimensional echocardiography

The configuration of the hypertrophied myocardium was evaluated by thallium-201 emission-computed tomography and 2-dimensional (2-D) sector scan in 10 patients with obstructive hypertrophic cardiomyopathy (HC), 10 with nonobstructive HC with giant negative T waves and 10 with concentric left ventricular (LV) hypertrophy. Thallium-201 myocardial imaging was reconstructed into multiple 12-mm-thick slices in 3 planes. The thickness ratio of the ventricular septum and the LV posterior wall in the short-axis plane and the ratio of the ventricular septum and the apical wall in the long-axis plane were analyzed. In the patients with obstructive HC the ventricular septal wall thickness index was increased, and the ratio of septal to posterior wall thickness index (1.45 ± 0.23) was greater than that in the patients with nonobstructive HC with giant negative T waves or in those with concentric LV hypertrophy (1.03 ± 0.20 and 0.98 ± 0.11, respectively; p <0.01 for each). In the patients with nonobstructive HC with giant negative T waves, increased apical wall thickness with apical cavity obliteration was characteristic, and the ratio of ventricular septal to apical wall thickness index (0.66 ± 0.14) was less than that in the patients with obstructive HC or in those with concentric LV hypertrophy (1.46 ± 0.38 and 1.04 ± 0.09, respectively; p <0.001 for each). In contrast, technically satisfactory 2-D sector scanning (83%) demonstrated various configurations of the hypertrophied ventricularseptum, but could not detect apical hypertrophy in 4 of the 10 patients with nonobstructive HC with giant negative T waves whose LV cineangiograms demonstrated apical hypertrophy. Thus, thallium-201 emission-computed tomography is useful in evaluating the characteristics of LV hypertrophy and assists 2-D sector scan, especially in patients with apical hypertrophy in HC.     

Mobilization of early hematopoietic progenitor cells with BB-10010: a genetically engineered variant of human macrophage inflammatory protein- 1 alpha

BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha with improved solution properties. We show here that it mobilizes stem cells into the peripheral blood. We investigated the mobilizing effects of BB-10010 on the numbers of circulating 8-day spleen colony-forming units (CFU-S8), CFU-S12, and progenitors with marrow repopulating ability (MRA). A single subcutaneous dose of BB-10010 caused a twofold increase in circulating numbers of CFU-S8, CFU-S12, and MRA 30 minutes after dosing. We also investigated the effects of granulocyte colony-stimulating factor (G- CSF) and the combination of G-CSF with BB-10010 on progenitor mobilization. Two days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA progenitors by 25.7-, 19.8-, and 27.7-fold. A single administration of BB-10010 after 2 days of G-CSF treatment increased circulating CFU-S8, CFU-S12, and MRA even further to 38-, 33-, and 100- fold. Splenectomy resulted in increased circulating progenitor numbers but did not change the pattern of mobilization. Two days of treatment with G-CSF then increased circulating CFU-S8, CFU-S12, and MRA by 64-, 69-, and 32-fold. A single BB-10010 administration after G-CSF treatment further increased them to 85-, 117-, and 140-fold, respectively, compared with control. We conclude that BB-10010 causes a rapid increase in the number of circulating hematopoietic progenitors and further enhances the numbers induced by pretreatment with G-CSF. BB- 10010 preferentially mobilized the more primitive progenitors with marrow repopulating activity, releasing four times the number achieved with G-CSF alone. Translated into a clinical setting, this improvement in progenitor cell mobilization may enhance the efficiency of harvest and the quality of grafts for peripheral blood stem cell transplantation.