1/3. Human equivalent of the mouse Nude/SCID phenotype: long-term evaluation of immunologic reconstitution after bone marrow transplantation.Human Nude/SCID (severe combined immunodeficiency) is the first severe combined immunodeficiency caused by mutation of the winged-helix-nude (WHN) gene, which is expressed in the thymus but not in the hematopoietic lineage. The disease is characterized by a T-cell defect, congenital alopecia, and nail dystrophy. A Nude/SCID patient who underwent bone marrow transplantation from the human leukocyte antigen-identical heterozygote brother was studied to investigate, in this unique model, the role of the thymus in immunologic reconstitution. Despite an increase in CD3( ), CD4( ), and CD8( ) cells, CD4( ) CD45 RA naive lymphocytes were not regenerated. Conversely, naive CD8( ) cells were normal. After an initial recovery, lymphocyte proliferation to mitogens progressively declined compared with controls and genotypically identical donor cells grown in the WHN( /-) environment. Analysis of the T-cell receptor (TCR) repertoire of CD4( ) cells revealed that only 3 of 18 Vbeta families had an altered CDR3 heterogeneity length profile. Conversely, CD8( ) lymphocytes showed an abnormal distribution in most Vbeta families. These data indicate that the thymus is differentially required in the reconstitution of CD4( ) and CD8( ) naive subsets and in the maintenance of their TCR repertoire complexity. Taken together, these findings suggest that bone marrow transplantation is ineffective in the long-term cure of this form of SCID.- - - - - - - - - - ranking = 1keywords = environment (Clic here for more details about this article) |
2/3. karyotyping of cryptococcus neoformans as an epidemiological tool.karyotyping of cryptococcus neoformans var. neoformans can be used as an epidemiological tool for C. neoformans infections. In this study of over 40 isolates from both clinical and environmental sources, 90% had a unique chromosome banding by pulsed-field electrophoresis. There was no conserved pattern associated with body site of infection, geographical location of the isolate, or human immunodeficiency virus status. Karyotypes of individual isolates remained stable during both in vitro passage and in vivo infections. karyotype was used to exclude the possibility of nosocomial spread of C. neoformans in one clinical situation and supported relapse in two other cases. Because of its variable sizes between isolates, karyotyping of C. neoformans is a convenient method for molecular identification of different strains.- - - - - - - - - - ranking = 1keywords = environment (Clic here for more details about this article) |
3/3. Increased risk in esophageal obstruction with slow-release medications.Although medication-induced (pill) esophagitis has been recognized for a long time, little data are available on the risk of recently introduced slow-release medications. These formulations may have an obstructive capability (undissolved medication blocking an obstructed lumen) or may cause tissue irritation (continuous leakage from a slowly disintegrating pill). We observed a patient with esophageal carcinoma who developed complete obstruction when three Procardia XL (nifedipine) extended-release tablets blocked the narrowed lumen. An intact Procardia XL tablet and a washed shell as a control were implanted subcutaneously in a rat. The intact pill produced a large inflammatory mass: in contrast, no inflammatory response was noted at the control site implanted with a washed shell. in vitro testing of seven different slow-release medications revealed a wide difference in their solubility at a neutral pH and in gastric juice of pH 1.8 (simulation of esophageal or gastric environment). Theolair-SR (anhydrous theophylline, sustained-release) tablets had the highest obstructive, but no irritating potential. Cardizem SR (diltiazem hydrochloride) sustained-release capsules dissolved promptly without obstructive potential. Adalat CC (nifedipine) extended-release tablets also dissolved early at both pH values. Cardizem CD (diltiazem hydrochloride) extended-release capsules and Calan SR (verapamil hydrochloride) sustained-release oral caplets disintegrated into granules that had a low obstructive potential, but their prolonged presence increased the risk of tissue irritation. Ecotrin (enteric-coated aspirin) tablets had a high obstructive and no irritating potential in the first 24 hours, after which they disintegrated and directly contacted the tissue. Procardia XL extended-release tablets had an insoluble shell that continued to leak a tissue-irritating content even after 48 hours, generating a prolonged obstructive and irritating condition. In conclusion, slow-release medications greatly increase the risk of esophageal injury. Their obstructive and tissue-irritating potentials differ widely. Slow-release formulations should be contraindicated in patients who have obstructive esophageal and gastric disorders.- - - - - - - - - - ranking = 1keywords = environment (Clic here for more details about this article) |