Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation

Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre- BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential.     

Gastrointestinal effects of modified guar gum and soy polysaccharide as part of an enteral formula diet.

Dietary fiber supplementation may improve gastrointestinal tolerance and decrease diarrhea in patients receiving enteral formula diets. To compare the effects of two dietary fibers on bowel function parameters and short-chain fatty acid excretion we fed 11 healthy men three defined enteral formula diets in random order for 18 days each. The test diets consisted of a fiber-free formula and daily intakes of maltodextrin (0 g of fiber), 15 g of total dietary fiber as an enzymatically modified guar gum, and 15 g of total dietary fiber as soy polysaccharide. Data were also collected while subjects consumed self-selected diets for 5 days. Mean transit time was longer and fecal moisture content was lower on 0 g of fiber and modified guar than on the self-selected and soy diets. Furthermore, mean transit time was slightly longer and fecal nitrogen excretion greater on modified guar compared with 0 g of fiber. Daily fecal output and frequency of defecation were greater, fecal pH was lower, and fecal butyrate concentrations were higher on the self-selected diet compared with the enteral formula diets. However, there was no difference in these parameters among the three liquid diets. Thus, despite significant differences in mean transit time, few differences in other parameters of bowel function were observed when healthy subjects consumed enteral formula diets containing 0 g of fiber and 15 g of total dietary fiber as modified guar and soy.     

Transcranial cerebral oximetry and carotid cavernous fistula occlusion

Summary Different methods have been used in the evaluation and monitoring of the cerebral oxygen supply during neuro-interventional therapies. Attenuation of near-infrared light by the chromophores oxyhemoglobin and deoxyhemoglobin have shown to be useful in the study of the cellular oxygen metabolism and oxygen delivery to the brain. Transcranial cerebral oximetry (TCCO) has the advantage of providing real-time information regarding regional brain oxygen saturation (rSO₂) by using wavelengths in the near-infrared range.We present a patient with a carotid cavernous fistula who underwent balloon occulusion and concurrent continuous TCCO monitoring. TCCO was found to be a useful tool providing immediate rSO₂ values during the angiographic and interventional procedures. Initial balloon occlusion of a carotid cavernous fistula resulted in partial occlusion of the internal carotid artery lumen causing an immediate decrease in rSO₂ which correlated with angiographic findings. Subsequent reocclusion of the fistula produced a slower and smaller degree of decrease in rSO₂ with clinical improvement in the patient. Changes in rSO₂ were detected before any adverse clinical event was observed. TCCO was reliable, safe, sensitive, and provided a real-time assessment tool for the monitoring of brain oxygen supply in a patient undergoing a neuroendovascular procedure.