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Biomedical subjects

J H Welsh

Publications and source records attributed to J H Welsh.

14 recordsLinked to original sources

Granuloma faciale in a child successfully treated with the pulsed dye laser.

Granuloma faciale, a rare, chronic, cutaneous disorder, is uncommon in children. Numerous treatment modalities have been used to treat granuloma faciale but none are consistently effective. In addition, many of the previously used therapies have unwanted side effects or are not well tolerated by children. We report a case of granuloma faciale in an 11-year-old child successfully treated with the pulsed dye laser. To our knowledge, this is the first report of this treatment modality for granuloma faciale.

Child↗

Tracheobronchial mucoepidermoid carcinoma in childhood and adolescence: case report and review of the literature.

In children and adolescents, primary neoplasms of the tracheobronchial tree and lungs are rare, with most tumors involving the respiratory system being metastatic, small, blue cell tumors of childhood. Of the primary pulmonary neoplasms, most are malignant with mucoepidermoid carcinoma representing about 10% of these malignant tumors. We present an 8-year-old Hispanic male with hemoptysis and several episodes of pneumonia which initially was thought to be infectious upon biopsy during bronchoscopy, but proved to be mucoepidermoid carcinoma of the tracheobronchial tree by microscopic examination during an open lung biopsy. This rare tumor is more common in adults than in children, and infrequently presents with hemoptysis. Mucoepidermoid tumors of the tracheobronchial tree carry a more favorable prognosis in children than adults. In the adult population, the overall mortality is slightly less than 30%. In contrast, of the 31 reported cases of tracheobronchial mucoepidermoid carcinoma in pediatrics, all children are free of tumor involvement with a mean follow-up period of 5.8 years (range, 0.7-21 years). Based upon the available clinical outcome and survival data, it would appear that tracheobronchial mucoepidermoid carcinoma may be successfully managed by surgical intervention alone in children and adolescents.

Adolescent↗

Subacute care: evolution in search of value.

The postacute continuum of nonhospital-based services has experienced rapid growth over the past decade because of a variety of economic factors. Medicare's prospective payment system for inpatient hospital stays combined with the diagnostic requirements of patients in acute medical rehabilitation and the growth of managed care have all reinforced the development of alternative levels and venues of care. Market forces are leading to consolidation and integrated health delivery systems offering both acute and postacute service options. The cost-effectiveness of these new models indicates promise for increased value measured by comparing resource utilization with outcomes. Reimbursement of the developing continuum, however, offers little incentive for efficiency. This article discusses the present dynamics of postacute growth and examines the issues that should be evaluated to determine its relevance in the spectrum of care.

Cost Control↗

Beta-turns induced in bradykinin by (S)-alpha-methylproline.

The ability of (S)-alpha-methylproline (alpha-MePro) to stabilise reverse-turn conformations in the peptide hormone bradykinin (BK = Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) has been investigated. Two BK analogues containing alpha-MePro at position 3 or position 7 were synthesised and their conformations in aqueous solution investigated by NMR spectroscopy. Whereas BK is largely disordered on the NMR time scale both analogues showed ROE connectivities in 2D-ROESY spectra indicative of reverse-turn conformations at both Pro2-Phe5 and Ser6-Arg9, whose formation appears to be cooperative. Some potential applications of alpha-MePro as a reverse-turn mimetic in the construction of synthetic peptide libraries is discussed.

Amino Acid Sequence↗

Synthesis, conformational properties, and antibody recognition of peptides containing beta-turn mimetics based on alpha-alkylproline derivatives.

Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.

Amino Acid Sequence↗