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D Lauro

Publications and source records attributed to D Lauro.

40 records · Page 3Linked to original sources

Molecular mechanism of insulin resistance in type 2 diabetes mellitus: role of the insulin receptor variant forms.

Type 2 diabetes is a heterogeneous and polygenic disorder resulting from interaction of genetic factors with environmental influences. Numerous candidate genes for insulin signaling proteins have been screened, but no single major susceptibility gene for type 2 diabetes has been identified. Due to its pivotal role in insulin action, the insulin receptor was considered a plausible candidate gene. The insulin receptor exists in two isoforms differing by the absence (Ex11(-)) or presence (Ex11(+)) of a 12 amino acid sequence in the COOH-terminus of the alpha-subunit, as a consequence of alternative splicing of exon 11. The Ex11(-) binds insulin with two-fold higher affinity than the Ex11(+). This difference is paralleled by a decreased sensitivity for metabolic actions of insulin. Some, but not all, studies have reported that expression of the low-affinity Ex11(+) is increased in target tissues from type 2 diabetic patients, thus suggesting that alterations in abundance of the two isoforms might contribute to insulin resistance. Insulin and type 1 IGF receptors have been shown to form hybrid receptors in tissues co-expressing both molecules. Hybrid receptors bind IGF-I, but not insulin, with high affinity, and behave as IGF-I holoreceptors, rather than insulin receptors, in terms of receptor autophosphorylation, and hormone internalization. It has been shown that the abundance of hybrid receptors is increased in skeletal muscle and adipose tissue from type 2 diabetic patients, and is negatively correlated with in vivo insulin sensitivity. Mutations in the insulin receptor gene have been identified in studies which examined an appropriately sized population of patients with type 2 diabetes. The prevalence of mutations in the insulin receptor gene ranged from 0.4%-7.8%. This review will focus on the structural and functional heterogeneity of the insulin receptor, and will discuss the pathogenetic role of insulin receptor variant forms and polymorphisms in the development of the common form of type 2 diabetes.

Alternative Splicing↗

Sentinel node detection in breast carcinoma.

AIMS AND BACKGROUND: The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. METHODS AND STUDY DESIGN: In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors > 2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. RESULTS: We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patient showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. CONCLUSIONS: At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.

Aged↗

Family planning operations research in Africa: reviewing a decade of experience.

Between 1979 and 1990, Columbia University conducted 26 family planning operations research (OR) projects in 13 sub-Saharan African countries. Most of these projects were implemented in settings where family planning service delivery had not yet been initiated or was new and poorly developed. In keeping with program needs in the early stages of development, the majority of the OR projects were based on demonstration or diagnostic designs. Only four of the 23 projects were comparative or quasi-experimental in design. Projects demonstrated the growing demand for family planning, and the feasibility and acceptability of a range of service delivery models. Sixteen of the projects have been sustained or replicated by national or local governments and institutions following the initial OR phase, replication of two others is planned, and another four resulted in policy formulation or improvements in existing national programs. OR in Africa played an important role in generating political and medical support for contraceptive services, and served to improve project management. OR proved more useful in the implementation and strengthening of individual programs than in generating universal lessons regarding service delivery. In order to maximize OR's utility in Africa, simple research designs and methods should be adopted.

Africa↗

Quality of care in family planning services in Morocco.

This study was conducted to heighten awareness of quality of care as a programmatic issue in the Moroccan governmental family planning program and to test modified Situation Analysis instruments for measuring quality of care. Data were collected from 50 service-delivery points in five provinces to measure six elements of quality in accordance with the Bruce/Jain framework. A procedure for calculating quality-indicator scores is presented. Although facilities varied by province and within provinces, most had the equipment and supplies needed to deliver services; service personnel were trained and regularly supervised; the service-delivery points scored well on mechanisms to ensure continuity of use. Notable shortcomings included a dearth of materials for counseling and a widespread unavailability of the Ovrette pill. This study raises issues regarding the complexity of measuring quality, the ownership of results, and the appropriateness of a centralized study of quality in a decentralized program.

Adult↗