Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.     

Peripheral glucose metabolism in human hyperprolactinaemia

OBJECTIVE Prolactin has important biological actions in several species which include metabolic control and waterlelectrolyte balance. However, human PRL has generally been characterized as a mammotrophic hormone and it is unknown whether PRL has any important metabolic actions. This study was thus conducted to evaluate the effect of hyperprolactinaemia on peripheral muscle glucose metabolism. DESIGN The study was designed to determine forearm muscle glucose uptake and utilization (oxidative and non-oxidative metabolism) in normal and hyperprolactinaemic subjects in the post-absorptive state and lor 3 hours after the ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrates combined with local indirect calorimetry. PATIENTS Eight hyperprolactinaemic patients (HP group, 6 females and 2 males) and ten normal sublects (N group, 7 females and 3 males) were studied. The hyperprolactinaemic patients showed no clinical or laboratory evidence of acromegaly or hypothyroidism and were not using any PRL releasing drugs. MEASUREMENTS Forearm blood flow was measured by capacitance plethysmography and arterial and venous blood samples were drawn simultaneously to determine plasma glucose, serum FFA, total blood CO₂ and O₂ and serum insulin in the post-absorptive state (0 time) and at 30, 60, 120 and 180 minutes after glucose Ingestion. RESULTS No significant difference in glucose uptake by the forearm muscle tissue was observed between the N and HP groups (823 plusmn; 103 vs 828 ± 110 μmol/100 ml forearm 3h, respectively), nor were any significant differences observed in the intracellular utilization of glucose (oxidative and non-oxidative metabolism). However, the serum insulin levels after glucose ingestion were significantly higher in hyperprolactinaemic patients than in normal subjects, especially at 30 (N 283 ± 46 vs HP 581 ± 133 pmol/l) and 60 minutes (N 291 ± 37 vs HP 544 ± 61 pmol/l). Furthermore, after glucose ingestion the suppression of serum FFA levels was smaller in the hyperprolactinaemic patients than in normal subjects. CONCLUSIONS This study demonstrated that insulin resistance is associated with the presence of spontaneous human hyperprolactinaemia. The hyperinsulinaemia detected in the hyperprolactinaemic patients after the oral glucose stimulus did not determine a proportional Increase in forearm glucose uptake and utilization, which were similar to the normal levels. The suppression of serum free fatty acid concentrations was also smaller in hyperprolactlnaemlc patients during the oral glucose challenge, suggesting an impaired antilipolytic effect of Insulin.     

Colon perforation following percutaneous nephrostomy and renal calculus removal

Two patients had colonic perforation as a result of percutaneous nephrostomy placement followed by track dilatation and renal calculus removal. We present the technical aspects of nephrostomy placement and stone removal, as well as the clinical diagnosis and management of these cases. Both patients recovered well with conservative therapy and required no surgical intervention. This report reviews the anatomic considerations for percutaneous nephrostomy in patients undergoing renal stone removal.     

Effect of curriculum reform on graduating student performance

With the aim of evaluating the efficacy of a new curriculum implemented in the Faculty of Medicine of Ribeir?o Preto (University of S?o Paulo, Brazil), a yearly objective assessment of both cognitive and practical skills of undergraduate (sixth year) students was performed. All graduating student underwent a multiple-choice questions (MCQs) test and groups of 18-20 students were randomly assigned to OSCEs for either clinical (real and standardized patients) or procedure (manikins) skills. The average MCQs score for the students graduating in the new curriculum (63.1, SD = 8.9, n = 261) was significantly higher (p < 0.001) than for the previous curriculum (55.3, SD = 8.1, n = 222). Results for practical exams showed that the new curriculum was associated with significantly improved performance in five out of the six stations for procedure skills, but in only two of the 10 clinical skills stations. Final evaluation of graduating students revealed deficiencies in the local curriculum and may serve as a guide to take measures to correct them.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.     

Hypoaldosteronism in three sibs due to 18-dehydrogenase deficiency

Three sibs all presented in the early neonatal period with a salt-losing syndrome. The salt-losing form of congenital adrenal hyperplasia was diagnosed and appropriate treatment with glucocorticosteroids, mineralocorticosteroids, and additional dietary salt started. Although early life was maintained with difficulty, with age all 3 children required decreasing amounts of replacement steroids to maintain normal plasma electrolyte balance. They were reinvestigated at the ages of 15 years and 8 years (twins), when cortisol synthesis and metabolism proved normal, but aldosterone synthesis was blocked by deficiency of 18-dehydrogenase. Rational treatment of these cases of a salt-losing syndrome in which aldosterone synthesis alone is blocked due to lack of the enzyme 18-dehydrogenase requires the administration of a mineralocorticosteroid drug only. Since deoxycorticosterone (acetate or pivalate) requires intramuscular administration, as life-long therapy oral fludrocortisone is preferable. Although fludrocortisone has glucocorticoid activity, the "hydrocortisone equivalent" effect of the small dosage used was unlikely to inhibit either pituitary corticotrophin or growth hormone production.     

Centrilobular emphysema: CT-pathologic correlation

Over a 5-year period, 25 patients who had undergone chest computed tomography (CT) died and were autopsied. Their lungs were fixed in the inflated state and were assessed for the presence and severity of centrilobular emphysema (CLE). Three radiologists independently evaluated the CT scans for nonperipheral low-attenuation areas, peripheral low-attenuation areas, pulmonary vascular pruning, pulmonary vascular distortion, and pulmonary density gradient. The CT criterion that best correlated with the presence and severity of CLE was the nonperipheral low-attenuation area. With this CT criterion, lung destruction was correctly identified in 13 of 15 cases. The absence of this criterion resulted in correct identification of eight of ten normal lungs. These preliminary data suggest that CLE can be reliably identified and quantified with current CT scanners.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.