Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility

We conducted a 12-month trial of cisapride (10 mg three times a day) in 21 patients with gastric stasis due to clinically and manometrically diagnosed gastroparesis (N=9; seven due to diabetes) or chronic intestinal pseudo-obstruction (N=12). Radionuclide solid-liquid gastric emptying tests were performed at baseline and at the end of the 12-month period. Symptoms were assessed monthly by diary and every three months by the investigators; frequency and severity of symptoms were scored in a standardized manner. For the whole group of 21 patients, gastric emptying of both solids and liquids improved significantly after one year of cisapride (P<0.05). Among chronic intestinal pseudoobstruction patients, there was predominantly an improvement in gastric emptying of solids; in contrast, patients with gastroparesis had a greater improvement in liquid emptying. Total symptom score improved significantly in the gastroparesis group (median score: 8 at baseline vs 6 at one year,P<0.05) but not in the chronic intestinal pseudoobstruction patients (median score at baseline 10 vs 9 at one year). Similarly, body weight showed a trend towards improvement in the gastroparesis group. No significant side effects were noted. We conclude that during a 12-month open trial, cisapride was effective in improving gastric emptying in patients with gastric stasis and consistently improved symptoms in those with gastroparesis.     

Effect of transforming growth factor-beta 1 on proliferation and induction of hemoglobin accumulation in K-562 cells

The effects of transforming growth factor-beta 1 (TGF-beta 1) on proliferation and hemoglobinization in K-562 cells, a human multipotential hematopoietic cell line, were studied. We found that TGF- beta 1 could induce hemoglobin accumulation in K-562 cells. Various clones were selected on the basis of the inducibility of hemoglobinization by TGF-beta 1. One high response clone (no. 1) and one low response clone (no. 8) were studied in detail. Hemoglobin accumulation peaked on day 5 of culture in the presence of TGF-beta 1 (0.5 ng/mL, 20 pmol/L), when 90% of clone 1 cells, 55% of parent line cells, and less than 10% of clone 8 cells contained hemoglobin. There was a concomitant reduction in proliferation of 60% for clone 1, 40% for the parent line, and 30% for the clone 8 on day 5 of culture. Quantitative analysis showed that the hemoglobin contents in clone 1 after 5-day induction by TGF-beta 1 and hemin were 1.0 pg/cell and 2.9 pg/cell, respectively. The hemoglobin induced by TGF-beta 1 showed the same electrophoretic characteristics as the hemoglobin induced by hemin. The expression of epsilon-globin mRNA was minimally detectable in control cells and was induced in both TGF-beta 1 and hemin treated cells. Other cytokines with potential effects on K-562 cell proliferation and differentiation were also studied. Interleukin-1, interleukin-3, interferon alpha, interferon gamma, and inhibin, tested as single agents, showed minimal effects on proliferation. None of these agents could induce hemoglobinization or inhibit the hemoglobinization induced by TGF-beta 1.     

The effect of solvent/detergent-treated plasma on red cells stored in vitro

BACKGROUND: The potential use of solvent/detergent-treated plasma (S/D plasma) in transfusion practice raises concerns about the cytolytic effects that any residual solvent and detergent in the virally inactivated blood component might have on units of red cells in vitro, if the two components are mixed during preparation. STUDY DESIGN AND METHODS: S/D plasma was mixed with variously processed units of stored red cells, in vitro, to evaluate the effect the residual solvent and detergent would have on cell membrane integrity. A paired protocol design was used in which half-units of red cells were exposed to S/D plasma (test), and the matched half-units were exposed to either the supernatant additive solution from the original red cell unit or standard fresh-frozen plasma (FFP) (control). After incubation for up to 5 days, the units were evaluated for evidence of hemolysis or changes in other red cell storage assays. RESULTS: This study showed that, for fresh additive solution red cells (AS-1), the 5-day storage plasma hemoglobin levels were comparable in the red cells exposed to S/D plasma (21 mg/dL) and in the paired half-units stored in the original AS-1 supernatant (31 mg/dL) (p > 0.05). Similar findings were recorded for stored AS-1 red cells (S/D plasma; 111 mg/dL vs. AS-1 supernatant, 147 mg/dL; p > 0.05); stored CPDA-1 red cells (S/D plasma, 133 mg/dL vs. FFP, 103 mg/dL; p > 0.05); frozen red cells (S/D plasma, 28 mg/dL vs. FFP, 18 mg/dL; p > 0.017); and stored irradiated AS-1 red cells (S/D plasma, 608 mg/dL vs. AS-1 supernatant, 726 mg/dL; p > 0.05). Comparable results were found for other assays, including levels of plasma potassium, osmotic fragility, and red cell antigen titer. CONCLUSION: These data show that S/D plasma does not induce red cell lysis even after 5 days of in vitro storage. These results are consistent with previous findings by this laboratory that platelets are not harmed by storage in S/D plasma. Red cells resuspended in S/D plasma and stored for up to 5 days maintain in vitro storage characteristics that are acceptable for the use of the cells in clinical transfusion practice.     

Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patients with non-Hodgkin's lymphoma

A prospective comparative trial of allogeneic versus autologous bone marrow transplant (BMT) was conducted. Sixty-six consecutive patients (median age, 41; range, 15 to 60; female:male ratio = 21:45) entered this clinical trial. Priority for allogeneic BMT was given to patients who were 55 or younger and had a major histocompatibility complex- matched or 1-antigen-disparate sibling donor. Autologous BMT was offered to all other patients whose age was 60 or younger. Patients who had no sibling donor and who had BM involvement at the time of evaluation were not eligible. Thirty-one patients received an allograft, and 35 patients received an autograft. Thirteen patients received a BM graft purged with 4-hydroperoxycyclophosphamide because of previous BM involvement. Patients who had previous radiation to the thoracic and/or abdominal areas of more than 20 Gy received a preparative regimen consisting of cyclophosphamide (1,800 mg/m2/d for 4 days), VP-16 (200 mg/m2 every 12 hours for 8 doses), and 1,3-bis(2- chloroethyl)-1-nitrosourea (600 mg/m2 as 1 dose). Other patients received cyclophosphamide 1,800 mg/m2/d for 4 days followed by total body irradiation of 12 Gy administered as a single daily fraction over 4 days. With a median follow-up of 14 months, the progression-free survival (PFS) for autograft and allograft recipients was 24% +/- 8% (+/- SE) and 47% +/- 9%, respectively, (P = .21). However, the probability of disease progression was significantly higher in the autologous group (69% +/- 9%) than in the allogeneic group (20% +/- 10%; P = .001). When other confounding prognostic factors were adjusted in the multivariate analysis, chemosensitive disease and allograft were found to have a significant favorable influence on probability of disease progression (P = .03 and .003), but only chemosensitive disease had a significant influence on the PFS (P < .002). Our results suggest the existence of graft-versus-lymphoma effect and also support the rationale of using immunotherapy after autologous BMT. Allogeneic BMT should be preferable to autologous BMT in younger patients with lymphoma.     

Invited review: Prion‐like transmission and spreading of tau pathology

Filaments made of hyperphosphorylated tau protein are encountered in a number of neurodegenerative diseases referred to as ‘tauopathies’. In the most prevalent tauopathy, Alzheimer's disease, tau pathology progresses in a stereotypical manner with the first lesions appearing in the locus coeruleus and the entorhinal cortex from where they appear to spread to the hippocampus and neocortex. Propagation of tau pathology is also characteristic of argyrophilic grain disease, where the tau lesions appear to spread throughout distinct regions of the limbic system. These findings strongly implicate neurone‐to‐neurone propagation of tau aggregates. Isoform composition and morphology of tau filaments can differ between tauopathies suggesting the existence of conformationally diverse tau strains. Altogether, this points to prion‐like mechanisms in the pathogenesis of tauopathies.     

Panniculitis–an unusual cutaneous manifestation of systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by small vessel involvement that leads to tissue ischemia and fibroblast stimulation resulting in accumulation of collagen (fibrosis) in the skin and internal organs. Lipomembranous panniculitis is a peculiar type of fat necrosis and has been reported with clinical conditions, commonly with peripheral vascular diseases. We describe a case of a 43‐year‐old woman with SSc manifestations, who presented with black scaly skin plaques, associated with thickening of the subcutaneous fat tissue, on the lateral surface of her thighs, her calves, gluteal area and lower abdomen. Biopsy revealed lipomembranous panniculitis. Lipomembranous changes have been seen in connective tissue disorders such as lupus profundus, morphea, systemic sclerosis and panniculitis associated with dermatomyositis, but rarely in thighs, calves, gluteal area and lower abdomen. Almeida MSTM, Lima SCB, Carvalho LL, Almeida JVM, Santos LG, Rolim JRA, Rocha TE. Panniculitis–An unusual cutaneous manifestation of systemic sclerosis.