Double-chimaerism after transplantation of two human leucocyte antigen mismatched,unrelated cord blood units

The small number of progenitor cells is the major limitation to the use of umbilical cord blood (UCB) for the transplantation of adults. We tested the hypothesis that two units transplanted simultaneously could each contribute to haematopoietic reconstitution. A patient with advanced acute lymphocytic leukaemia received a mismatched, unrelated UCB transplant using units from two donors after conditioning. The recipient achieved a complete remission without graft-versus-host disease. Double chimaerism was documented in several leucocyte subpopulations; both units contributed to haematopoiesis until relapse. Triple chimaerism was present from relapse until death due to leukaemia. This approach may potentially improve UCB transplantation outcome for adults lacking a histocompatible donor.     

Erythropoietin: biological aspects and clinical usefulness

In the eighties there has been an enormous increase in our knowledge about erythropoietin, previously defined as "an elusive hormone". In this review we summarize the structural and molecular features, the mechanisms of production and of metabolism, the more important methods of assay, the mechanism of action and the biological effects, the main pathophysiological aspects and the therapeutic usefulness of the hormone.     

Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline

OBJECTIVE: Our objective was to develop clinical practice guidelines for the evaluation and treatment of hirsutism in premenopausal women. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, two methodologists, and a medical writer. The Task Force received no corporate funding or remuneration. EVIDENCE: Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the Task Force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: We suggest testing for elevated androgen levels in women with moderate or severe hirsutism or hirsutism of any degree when it is sudden in onset, rapidly progressive, or associated with other abnormalities such as menstrual dysfunction, obesity, or clitoromegaly. For women with patient-important hirsutism despite cosmetic measures, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For women who choose hair removal therapy, we suggest laser/photoepilation.     

Intestinal Barrier Function and Secretion in Methotrexate-Induced Rat Intestinal Mucositis

Chemotherapy-induced mucositis is an important dose-limiting and costly side effect for which there is no definitive prophylaxis or treatment. This is due in part to the lack of understanding of its pathophysiology and impact on intestinal function. The objectives of this study were to investigate the small intestine barrier function and electrolyte and water transport in an experimental model of methotrexate-induced mucositis, and to correlate these alterations with histological damage. Wistar rats were treated with methotrexate (1.5-3.5 mg/kg) for 3 days to induce mucositis. Intestinal permeability was measured by the urinary excretion rate of lactulose and mannitol following administration by gavage. Intestinal perfusion was performed in vivo for evaluation of water and electrolyte transports. Methotrexate-treated rats lost a significant amount of weight and presented a marked reduction in food intake. Methotrexate induced significant and dose-dependent villous atrophy and elongation of crypts in duodenum, jejunum, and ileum. Methotrexate also induced an increase in sodium and potassium secretion and an important reduction of the mucosa absorptive surface area, shown by the decrease in the mannitol excretion ratio. In conclusion, methotrexate caused major changes in small bowel function by disrupting intestinal permeability and inducing electrolyte secretion in parallel with substantial histological damage.     

Experimental dilatation of the cecum and colon in rats. IV. Evaluation of a model produced by the use of lactose in the food of animals in the chronic phase of infection by the Colombia strain of T. cruzi

Female Wistar albino rats (30 day of age) were inoculated three times in intervals of 7 days with 1 x 10(7) epimastigote forms of T. cruzi and challenged 30 days after the last inoculation with 1 x 10(5) trypomastigote forms of the Colombia strain of T. cruzi. Rats of the same sex and age were used as controls. One-hundred-fifty days after inoculation the animals were allocated into 4 groups: Group I (control), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); Group II (inoculated), divided into subgroup L (fed lactose for 4 weeks) and subgroup S (fed saccharose for 4 weeks); Group III (control), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks); and Group IV (inoculated), divided into subgroup L-S (fed lactose for 4 weeks and saccharose for the following 4 weeks) and subgroup S (fed saccharose for 8 weeks). The disaccharide (lactose or saccharose) was added to a standard laboratory diet, 25 g/100 g of the final weight of the diet. At the end of the experimental periods the animals were sacrificed in light ether anesthesia. The volume of the large intestine was measured, and the weights of the cecum and colon were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fracture-label:O cytochemistry of freeze-fracture faces in the erythrocyte membrane

A method--"fracture label"--is described for the cytochemical labeling of the membrane faces produced by freeze-fracture. Human erythrocytes embedded in a crosslinked matrix are frozen, fractured in liquid nitrogen, thawed, labeled, and cut into thin sections. Electron microscope observation of the fracture faces shows preferential partition of concanavalin A binding sites with the inner half of the membrane. This signifies that, during freeze-fracture, binding sites are dragged from the outer surface across the outer ("exoplasmic") half of the membrane and retained on the protoplasmic fracture face (face P). The fracture process results in exposure of new anionic sites on face P. Fracture-label can be applied to the cytochemical characterization of the cellular components exposed by freeze-fracture of isolated cells and tissues.     

Pseudotumoral form of neuroschistosomiasis: report of three cases.

Central nervous system (CSN) involvement in schistosomiasis is an ectopic manifestation with a large variety of clinical forms, including pseudotumoral, which occurs in isolated cases and is rare. Three patients with epidemiological indications of this pathology were examined; the clinical picture included lower-back pain irradiating to lower limbs, associated with progressive flaccid paraparesis and sphincterial disturbances in cases in which the spinal chord was involved; while in cases with encephalitic impairment, headache, dizziness and cerebellar syndrome, characterized by dysarthria and right-side dysgraphia, were present. Magnetic resonance imaging (MRI) showed a growing process in all cases; cerebrospinal fluid (CSF) characteristics and biological markers were compatible with neuroschistosomiasis (NS). Biopsy of the lesions confirmed this diagnosis in one case. After specific treatment with schistosomicides and corticosteroids, clinical, radiological and laboratorial improvement was observed.