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Biomedical subjects

L David

Publications and source records attributed to L David.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Chronic recurrent multifocal osteomyelitis in children: report of 17 cases].

UNLABELLED: Chronic recurrent multifocal osteitis (OCRM) is a rare condition in children, of unknown aetiology, which may be misdiagnosed as osteomyelitis, arthritis or tumour. PATIENTS AND METHODS: We present a retrospective multicentric study of 17 patients (five boys and 12 girls) with an average follow-up of 7.5 years (six months-25 years). RESULTS: A spectrum of presenting features is possible, ranging from bone lesions alone to lesions combined with arthritis, palmoplantar pustulosis or psoriasis. The diagnosis was delayed from two weeks to five years. Roentgenographic evaluation was often normal at the beginning of the disease or showed nonspecific bone reactions. Radioisotope bone scans assisted in establishing the diagnosis and in identifying lesions that were initially clinically silent. Bone biopsies were performed in seven cases. Histopathological examination showed only mild inflammatory nonspecific changes. Microbiological cultures were always negative. Treatments were different according to the evolution of the disease and the hospital. There was no response to antibiotics in seven patients. The response to nonsteroidal anti-inflammatory agents and steroids was moderate and often transient. Salazopyrine and pamidronate treatment used in two patients allowed a durable remission. We lost sight of four patients, pain persisted in three in spite of treatment, it disappeared in two with treatment, mild pain persisted in five without treatment and remission occurred in three without treatment. CONCLUSION: This study clarifies the clinical and radiologic features of chronic recurrent multifocal osteomyelitis. The recognition of this rare entity is often delayed and difficulties in patient management sometimes emerge from its usual protracted course.

Adolescent↗
PubMed2001

Ligand-receptor docking with the Mining Minima optimizer.

The optimizer developed for the Mining Minima algorithm, which uses ideas from Genetic Algorithms, the Global Underestimator Method, and Poling, has been adapted for use in ligand-receptor docking. The present study describes the resulting methodology and evaluates its accuracy and speed for 27 test systems. The performance of the new docking algorithm appears to be competitive with that of previously published methods. The energy model, an empirical force field with a distance-dependent dielectric treatment of solvation, is adequate for a number of test cases, although incorrect low-energy conformations begin to compete with the correct conformation for larger sampling volumes and for highly solvent-exposed binding sites that impose little steric constraint on the ligand.

Algorithms↗
PubMed2001

MUC1 gene polymorphism in the gastric carcinogenesis pathway.

MUC1 like most mucin genes shows extensive length polymorphism in the central core region. In a previous study it was shown that individuals with small MUC1 alleles/genotypes have an increased risk for development of gastric carcinoma. Our aim was to see if MUC1 gene polymorphism was involved in susceptibility for the development of conditions that precede gastric carcinoma: chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). We evaluated MUC1 polymorphism in a population of 174 individuals with chronic gastritis (CG) displaying (CAG) and/or intestinal metaplasia (IM). The population of patients with CG shows MUC1 allele frequencies significantly different from the gastric carcinoma patients and blood donors population. A significantly lower frequency of CAG and IM was observed in MUC1 VNTR heterozygotic patients. Within the group of patients with IM, MUC1 large VNTR homozygotes show a significantly higher frequency of complete IM while small VNTR homozygotes show a significantly higher frequency of incomplete IM. These findings show that MUC1 polymorphism may define different susceptibility backgrounds for the development of conditions that precede gastric carcinoma: chronic atrophic gastritis (CAG) and intestinal metaplasia (IM).

Adult↗
PubMed2001

Body composition in children after renal transplantation.

This study examines changes in body composition after renal transplantation (Tx) in 16 children who underwent dual-energy X-ray absorptiometry examination within 6 months preceding Tx; the examination was then repeated every 6 to 12 months after Tx. Body composition was analyzed with regard to whole-body bone mineral content (BMC), lean body mass (LBM), and fat body mass (FBM). Median BMC decreased from the initial value of +0.98 standard deviation scores (SDS) to -0.55 SDS during the first 3 months after Tx, and a further decrease was noted at the end of month 6 (M6; -1.34 SDS) and M12 after Tx (-1.32 SDS). Improvement was observed during the second year after Tx (P for global changes < 0.0001). LBM and FBM also changed significantly during the 2 years after Tx (P = 0.006 and P = 0.0001, respectively). LBM decreased during the first 3 months after Tx (median change, 0.71 SDS) and remained less than 0 SDS in all but 4 patients. Median LBM did not decrease to less than -1 SDS during the entire study period. Conversely, median FBM increased by a median of 3.73 SDS during the first 3 months and remained elevated during the first 12 months after Tx, with a subsequent decrease at 2 years after Tx. No significant correlation was found between cumulative doses of prednisone and BMC, FBM, or LBM at any interval if absolute values were considered. However, relative changes in FBM correlated significantly with relative changes in prednisone cumulative doses.

Absorptiometry, Photon↗
PubMed2001

Long-term follow-up of dynamic cranioplasty for brachycephaly--non-syndromal bicoronal synostosis.

We followed up 10 patients whose non-syndromal bicoronal synostosis had been operated on with a dynamic cranioplasty technique developed by this craniofacial unit in 1992. With this technique, the growth of the brain is redirected in an anteroposterior direction as wire-mediated compression and restraint are exerted on the transverse and vertical dimensions of the skull. The mean operating time was 160 minutes (range 120-275) and mean stay in the intensive care unit was 36 hours (range 23-58). There was no operative mortality and few complications. The surgical results were assessed objectively by analysis of cephalometric tracings. The mean (SD) cephalic index was 87.6 (4.9) preoperatively and 77.7 (1.8) postoperatively (p = 0.001). The modified Whitaker scale was used as a subjective outcome measurement, and nine patients were classified as Whitaker grade 1 (no additional surgery). One patient required additional intracranial surgery. A questionnaire was sent to all families to obtain an additional subjective measurement of outcome. Parents' satisfaction was high. We conclude that dynamic cranioplasty is a safe and efficient operation for treatment of brachycephaly.

Cephalometry↗
PubMed2001

Clinical outcome of the modified pi-plasty procedure for sagittal synostosis.

The aim of the study was to evaluate the modified pi-plasty procedure for the treatment of sagittal synostosis, assessing the issues of safety, complications, morphological outcome, and degree of parental satisfaction. A retrospective evaluation of 110 patients with nonsyndromal single suture sagittal synostosis operated on with the modified pi-plasty procedure was undertaken. Cephalometric radiographs were obtained preoperatively and postoperatively at ages 3 and 5 years in three standardized projections. The Cephalic Index and the Axial Width Ratio were determined and used as objective outcome measures. An evaluation of the radiographic digital markings was carried out using a Beaten Copper Score. A parental questionnaire was used to obtain a subjective esthetical outcome assessment. The patient population consisted of 76% boys and 24% girls with a 20% incidence of a positive familial history of craniosynostosis. The mean age at surgery was 7.73 months. Morbidity from the procedure was minimal and there were no mortalities. The Cephalic Index changed from a mean preoperative value of 65% to a postoperative mean value of 72% (P = 0.00004). The mean Axial Width Ratio changed from a preoperative 80% to 72% at the 3-year evaluation (P = 0.00029). The Beaten Copper score changed from a mean preoperative value of 2.35 to 5.42 postoperatively at 3 years (P = 0.00001). The response rate to the questionnaire was 86%, and there were significant postoperative improvements in all studied aspects of the skull shape. The modified pi-plasty is a safe technique, and it induces significant objective changes in skull morphology toward normality. It also yields a high degree of parental satisfaction with regard to aesthetic outcome, as evaluated by a written questionnaire.

Attitude to Health↗
PubMed2001

Clinicopathologic profiles and prognosis of gastric carcinomas from the cardia, fundus/body and antrum.

BACKGROUND/AIMS: The putative influence of tumor location on the biologic behavior of gastric carcinomas remains controversial. The aim of this study was to investigate if carcinomas arising in the three types of gastric mucosa (cardia, fundus/body and antrum) have different clinical and pathologic profiles and carry a different prognosis. METHODS: Three hundred and two patients with cardia or gastric carcinoma resected between 1984 and 1996 were retrospectively studied. Cases were divided in three groups according to tumor location: cardia (n = 80); fundus/body (n = 60); antrum (n = 162). The three groups were crosstabulated with clinic and pathologic parameters, such as age, sex, macroscopy, histology, desmoplasia, tumor size, depth of tumor wall penetration, nodal status, venous invasion and stage. Survival rates were calculated for the three locations according to the aforementioned parameters. Univariate survival analysis and Cox regression were performed for each location. RESULTS: Cases from the cardia and fundus/body were similar and distinct from antrum cases according to macroscopy, tumor size, depth of wall penetration, venous invasion, nodal status and stage. Cases from fundus/body were similar to antrum cases and distinct from cardia cases according to gender and Laurén's classification. An overall difference in survival between the three locations was observed (p = 0.006). Cumulative survival was better for patients with carcinomas in the antrum than in the cardia (p = 0.04) and in the fundus/body (p = 0.003); no significant differences were observed in survival between cardia and fundus/body carcinoma cases. Cox regression identified stage and venous invasion as prognostic factors for patients with carcinomas in the three locations. In the group of cardia tumors, older patients had a worse outcome and in the group of fundus/body carcinomas, large tumors were associated with a poorer survival. CONCLUSIONS: Our results show that cardia carcinoma and antrum carcinoma are distinct gastric carcinoma entities whereas fundus/body carcinoma shares some characteristics from both entities.

Adult↗
PubMed2000

Simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, T and sialosyl-T) and gp 230 mucin-like glycoprotein are candidate markers for neoplastic transformation of the human cervix.

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed2000

Evolution of secondary hyperparathyroidism after renal transplantation.

Renal osteodystrophy is an important problem in children with chronic renal failure, leading to skeletal deformities. The most-frequent type of renal osteodystrophy is secondary hyperparathyroidism, and the main factors contributing to the pathogenesis of this condition are completely or partially corrected after successful renal transplantation. The present paper reviews data on the evolution of secondary hyperparathyroidism after transplantation. Studies in both adults and children suggest that secondary hyperparathyroidism and increased bone remodelling activity may persist months after transplantation. The severity of secondary hyperparathyroidism prior to transplantation, the duration of dialysis, and the development of nodular and/or monoclonal hyperplasia of parathyroid glands are the most-important factors that determine the phenomenon. Important issues, which still need to be answered, are the possible roles of growth factors, cytokines, VDR gene polymorphism (B/b allele), and type of immunosuppressive regimen in the skeletal abnormalities observed.

Adult↗
PubMed2000

Immunohistochemical study of the expression of MUC6 mucin and co-expression of other secreted mucins (MUC5AC and MUC2) in human gastric carcinomas.

To investigate the expression of MUC6 mucin in gastric carcinomas, we generated a novel monoclonal antibody (MAb CLH5) using an MUC6 synthetic peptide. MAb CLH5 reacted exclusively with the MUC6 peptide and with native and deglycosylated mucin extracts from gastric tissues. MAb CLH5 immunoreactivity was observed in normal gastric mucosa restricted to pyloric glands of the antrum and mucopeptic cells of the neck zone of the body region. In a series of 104 gastric carcinomas, 31 (29.8%) were immunoreactive for MUC6. The expression of MUC6 was not associated with histomorphological type or with clinicopathological features of the carcinomas. Analysis of the co-expression of MUC6 with other secreted mucins (MUC5AC and MUC2) in 20 gastric carcinomas revealed that different mucin core proteins are co-expressed in 55% of the cases. MUC6 was co-expressed and co-localized with MUC5AC in 45% and with MUC2 in 5% of the cases. Expression of MUC2 alone was observed in 25% of the cases. All carcinomas expressing MUC2 mucin in more than 50% of the cells were of the mucinous type according to the WHO classification. The co-expression of mucins was independent of the histomorphological type and stage of the tumors. In conclusion, we observed, using a novel well-characterized MAb, that MUC6 is a good marker of mucopeptic cell differentiation and is expressed in 30% of gastric carcinomas, independent of the clinicopathological features of the cases. Furthermore, we found that co-expression and co-localization of mucins in gastric carcinomas is independent of histomorphology and staging. Finally, we observed that intestinal mucin MUC2 is expressed as the most prominent mucin of the mucins tested in mucinous-type gastric carcinomas.

Animals↗
PubMed2000

High-dose albuterol by metered-dose inhaler plus a spacer device versus nebulization in preschool children with recurrent wheezing: A double-blind, randomized equivalence trial.

UNLABELLED: Inhaled albuterol is the most frequently used bronchodilator for acute wheezing, and nebulization is the standard mode of delivery in hospital setting. However, recent guidelines consider spacer devices as an easier to use, and cost-saving alternative and recommend the high-dose metered-dose inhaler bronchodilator. OBJECTIVE: To demonstrate clinical equivalence between a spacer device and a nebulizer for albuterol administration. DESIGN: Randomized, double-blind, parallel group equivalence trial. SETTING: Pediatric emergency wards at 2 tertiary teaching hospitals. PATIENTS: Sixty-four 12- to 60-month-old children with acute recurrent wheezing (32 per group). INTERVENTIONS: Albuterol was administered through the spacer device (50 microg/kg) or through the nebulizer (150 microg/kg) and repeated 3 times at 20-minute intervals. Parents completed a questionnaire. OUTCOME MEASURES: Pulmonary index, hospitalization, ease of use, acceptability, and pulse oximetry saturation. RESULTS: The 90% confidence interval of the difference between treatment groups for the median absolute changes in pulmonary index values between T0 and T60 was [-1; +1] and was included in the equivalence interval [-1.5; +1.5]. Clinical improvement increased with time. Less than 10% of the children (3 in each group) required hospitalization (2 in each group attributable to treatment failure). Parents considered administration of albuterol using the spacer device easier (94%) and better accepted by their children (62%). CONCLUSIONS: The efficacy of albuterol administered using the spacer device was equivalent to that of the nebulizer. Given its high tolerance, repeated 50-microg/kg doses of albuterol administered through the spacer device should be considered in hospital emergency departments as first-line therapy for wheezing.

Acute Disease↗
PubMed1999

Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression.

Intestinal metaplasia is a well-established premalignant condition of the stomach that is characterized by mucin carbohydrate modifications defined by histochemical methods. The purpose of the present study was to see whether the expression of mucin core proteins was modified in the different types of intestinal metaplasia and to evaluate the putative usefulness of mucins as "molecular markers" in this setting. We used a panel of monoclonal antibodies with well-defined specificities to MUC1, MUC2, MUC5AC, and MUC6 to characterize the expression pattern of mucins. In contrast to normal gastric mucosa, the complete form or type I intestinal metaplasia (n = 20) displayed little or no expression of MUC1, MUC5AC, or MUC6 in the metaplastic cells and strong expression of the intestinal mucin MUC2 in the goblet cells of all cases. The incomplete forms of intestinal metaplasia, type II (n = 25) and type III (n = 16), expressed MUC1 and MUC5AC in every case, both in goblet and in columnar cells. MUC6 was also expressed in 16 cases of type II intestinal metaplasia and in 11 cases of type III intestinal metaplasia. The intestinal mucin MUC2 was expressed in every case of incomplete intestinal metaplasia, mostly in goblet cells. The mucin expression profile in the different types of intestinal metaplasia allows the identification of two patterns: one defined by decreased levels of expression of "gastric" mucins (MUC1, MUC5AC, and MUC6) and expression of MUC2 intestinal mucin, which corresponds to type I intestinal metaplasia, and the other defined by coexpression of "gastric mucins" (MUC1, MUC5AC, and MUC6) together with the MUC2 mucin, encompassing types II and III intestinal metaplasia. Our results challenge the classical sequential pathway of intestinal metaplasia (from type I to type III via a type II intermediate step).

Antibodies, Monoclonal↗
PubMed1999

Mucins and mucin-associated carbohydrate antigens expression in gastric carcinoma cell lines.

Mucins are high-molecular-mass glycoproteins with high carbohydrate content and marked heterogeneity both in the apoprotein and in the oligosaccharide side chains. Mucin genes are expressed in a regulated manner, namely in the human stomach. The first aim of the present study was to characterise the expression of mucins and mucin-associated carbohydrate antigens in seven gastric carcinoma cell lines, and to compare their expression profiles with those of normal gastric tissues and human gastric carcinomas. Secondly, we aimed to see whether or not there is an association between the expression of mucins and mucin-associated carbohydrate antigens. Our results show that mucin expression in gastric carcinoma cell lines: (a) follows in part the mucin expression profile of normal gastric mucosa and gastric carcinomas with wide expression of MUC1 and MUC5AC; (b) parallels the aberrant pattern of mucin expression observed in human gastric carcinomas with occasional expression of MUC2, MUC3, MUC4 and MUC5B; (c) does not include, at least in our series, the expression of MUC6 mucin; and (d) follows in part the differentiation pattern of the carcinomas from which the cell lines originated, keeping S-Tn expression in cell lines derived from glandular carcinomas. Our results further demonstrate that there is no apparent relationship between the mucin core proteins and the simple mucin-type or Lewis carbohydrate antigens.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1999

MUC1 gene polymorphism does not explain the different incidence of gastric cancer in Portugal and Denmark.

MUC1 is a highly polymorphic mucin type glycoprotein expressed on the surface of many epithelia, including gastric mucosa, and is present in several body fluids and mucous secretions. A genetic polymorphism due to variation in length of a 60 bp tandemly repeated sequence domain constitutes more than half of the coding region of the glycoprotein. We demonstrated previously in a Portuguese population sample that the frequency of small MUC1 alleles is increased in patients with gastric carcinoma, suggesting that the possession of small MUC1 alleles confers increased risk for gastric carcinoma development. This finding raised the possibility that the very high prevalence of gastric carcinoma in Portugal could be partly due to a high frequency of small MUC1 alleles in the Portuguese population. In the present study we compared the MUC1 allele distribution in a population of Danish blood donors with the distribution in a population of Portuguese blood donors. The frequency of small MUC1 alleles was significantly higher in the Danish than in the Portuguese sample, thus failing to lend support to the hypothesis that a relatively higher frequency of the small MUC1 alleles might account for the high prevalence of gastric carcinoma in Portugal when compared to Denmark.

Adult↗
PubMed1999

Modifications to rat lens major intrinsic protein in selenite-induced cataract.

PURPOSE: To identify modifications to rat lens major intrinsic protein (MIP) isolated from selenite-induced cataract and to determine whether m-calpain (EC 3.4.22.17) is responsible for cleavage of MIP during cataractogenesis. METHODS: Cataracts were induced in rats by a single injection of sodium selenite. Control and cataract lenses were harvested on day 16 and dissected into cortical and nuclear regions. Membranes were washed with urea buffer followed by NaOH. The protein was reduced/alkylated, delipidated, and cleaved with cyanogen bromide (CNBr). Cleavage products were fractionated by high-performance liquid chromatography (HPLC), and peptides were characterized by mass spectrometry and tandem mass spectrometry. MIP cleavage by m-calpain was carried out by incubation with purified enzyme, and peptides released from the membrane were analyzed by Edman sequencing. RESULTS: The intact C terminus, observed in the control nuclear and cataractous cortical membranes, was not observed in the cataractous nuclear membranes. Mass spectrometric analysis revealed heterogeneous cleavage of the C terminus of MIP in control and cataract nuclear regions. The major site of cleavage was between residues 238 and 239, corresponding to the major site of in vitro cleavage by m-calpain. However, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analysis indicated that in vivo proteolysis during cataract formation also included sites closer to the C terminus not produced by m-calpain in vitro. Evidence for heterogeneous N-terminal cleavage was also observed at low levels with no differences between control and cataractous lenses. The major site of phosphorylation was determined to be at serine 235. CONCLUSIONS: Specific sites of MIP N- and C-terminal cleavage in selenite-induced cataractous lenses were identified. The heterogeneous cleavage pattern observed suggests that m-calpain is not the sole enzyme involved in MIP C-terminal processing in rat lens nuclei.

Animals↗