The stability of preferences for life-sustaining care among persons with AIDS in the Boston Health Study

In 1982, the World Health Organization (WHO) identified inadequate relief from cancer pain as an international health problem. WHO recommended that governments develop and implement national policies and programs for cancer pain relief. This report evaluates national health policy and the systems of health care delivery in relation to cancer pain management in the new South Africa. This field study included multiple methods of data collection: analysis of documents, field trips with participant observation in sites of care delivery, focused interviews, and in-depth interviews of key informants. The purposive sample of key informants (n = 33) represented multiple stakeholders in a variety of settings. Strengths of the developing health policy include specific recommendations related to palliative care; the shift to universal primary care; policies to support drug availability; the inclusion of morphine and codeine as essential drug at the primary health care level; and the development of a national standard related to cancer pain management. Health services are characterized by two parallel systems of care (private and public) with numerous vestiges of the inequities of apartheid. The management of pain varies by provider and setting; major problems with access exist in the rural areas. Health services in South Africa have been plagued by inequity and inadequate resources. New health policies have set a path to ensure universal access to health care including palliative care for cancer. Their successful implementation is the next necessary step toward improving health services and alleviating the suffering of increasing numbers of individuals with cancer.     

Endovascular interventions training and credentialing for vascular surgeons

This article reviews issues concerning the training and credentialing of vascular surgeons in the use of endovascular techniques in the peripheral vascular system. These guidelines update a prior document that was published in 1993. They have been rewritten to accommodate the rapid evolution that has occurred in the field and to provide the appropriate requirements that a vascular surgeon should fulfill to be competent in the basic skills needed to safely and effectively perform all presently accepted diagnostic and therapeutic endovascular procedures.     

Immunohistochemical distribution and colocalization of regulatory peptides in the carotid body

Current investigations on the immunohistochemical occurrence and co-occurrence of biogenic polypeptides in the mammalian carotid body were reviewed and extended by our own recent findings. The family of chromogranins and related peptides in glomus cells appears to have a widespread interspecies distribution, whereas other peptides investigated occur in a species-specific pattern. Immunoreactivity to antisera against opioids, which derive from the proenkephalin sequence, appears to be present in glomus cells of the rabbit, cat, dog, and a shrew. Conversely, glomus cells of pig and guinea pig predominantly are immunoreactive to cleavage products of prodynorphin, which co-occur in some cells with substance P and met-enkephalin-arg-phe, respectively. In the rat and Callithrix jacchus, opioid immunoreactivity is present in nerve fibres but not in glomus cells. Immunoreactivity to other peptides, such as neurotensin, cholecystokinin, neuropeptide Y, and galanin, is found only in one or two particular species. Neurotensin immunolabelling occurs in beagle dog glomus cells, which are known to lack substance P. Cholecystokinin immunoreactivity is present in glomus cells of dog and Callithrix, and co-exists with chromogranin A, neuropeptide Y, and substance P. Substance P appears to exist in both carotid body glomus cells and nerve fibres. Substance P immunoreactivity is present in glomus cells of all species investigated, except dog. Coexistence of substance P and calcitonin gene-related peptide (CGRP) is demonstrated in nerve fibres of the guinea pig carotid body, which originate in the petrosal and jugular ganglia. Other peptides visualized immunohistochemically in mammalian carotid body nerve fibres are vasoactive intestinal peptide and neuropeptide Y. The functional significance of the various peptides present in the carotid body is discussed.     

Local transverse arch repair for type A aortic dissection

BACKGROUND: The management of retrograde dissections originating from the transverse arch is controversial. Although replacing the ascending aorta is clearly beneficial, the appropriate approach to the management of the arch tear is not as apparent and ranges from no intervention to total arch replacement. METHODS: Three patients presented with acute (n = 2) or subacute (n = 1) aortic dissection, with tears involving the transverse arch. All underwent local transaortic pledgeted suture repair of the arch tears during hypothermic circulatory arrest, as well as graft replacement of the ascending aorta. RESULTS: Circulatory arrest times ranged from 12 to 15 minutes (transaortic arch repairs alone) to 48 minutes (transaortic arch repair and open distal graft anastomosis). Postoperatively all patients awoke within 12 hours and subsequently did well neurologically. CONCLUSIONS: In the face of a type A dissection with an entry in the transverse arch, local transaortic repair with concomitant ascending aortic replacement represents a viable middle ground between no arch intervention and lengthy arch replacement. Huge entry tears or aneurysmal arch enlargement would preclude such an approach.     

Simulated dipeptide recognition by vancomycin

The antimicrobial activity of vancomycin and related glycopeptide antibiotics is due to stereospecific recognition of polypeptide components in bacterial cell walls. To better understand how these antibiotics recognize polypeptide determinants, we have developed dynamic models of the complexes formed by the vancomycin aglycon and two different dipeptide ligands, Ac-D-ala-D-ala and Ac-D-ala-gly. Molecular dynamics simulations of the two complexes, initially conditioned with distance constraints derived from two-dimensional nuclear magnetic resonance (NMR) studies, are conformationally stable and propagate in a manner consistent with the NMR-derived constraints after the constraints are removed. Free energy calculations accurately predict the relative binding affinity of these two complexes and help validate the simulation models for detailed structural analysis. Although the two ligands adopt similar conformations when bound to the antibiotic, there are clear differences in the configuration of intermolecular hydrogen bonds, the overall shape of the antibiotic, and other structural features of the two complexes. This analysis illustrates how complex structural and dynamic factors interrelate and contribute to differences in binding affinity.     

Adenosine deaminase activity in serum and pleural effusions of tuberculous and non-tuberculous patients

In a retrospective study Adenosine deaminase (ADA), was assayed in 86 serum samples and 12 pleural fluid samples of patients with pulmonary tuberculosis. Serum and pleural fluid ADA levels were also examined in a group of 38 non-tuberculous patients with pleural effusion. Highly significant increases in both serum and pleural fluid ADA levels were noted in tuberculous patients when compared to both control enzyme cut-off values and non-tuberculous pleural effusion patients. Negative Ziehl-Nielsen staining for acid fast bacilli and Purified Protein Derivative skin test results were obtained in 32.3% and 11.1% of the examined patients respectively. All these patients showed significantly elevated serum or pleural fluid ADA levels. It is hereby suggested that serum and pleural fluid ADA levels can in conjunction with other tests, serve as a marker in patients of pulmonary tuberculosis.     

Interaction of tryptamine and ergoline compounds with threonine 196 in the ligand binding site of the 5-hydroxytryptamine6 receptor

We examined the ligand-binding site of the 5-hydroxytryptamine6 (5-HT6) receptor using site-directed mutagenesis. Interactions with residues in two characteristic positions of trans-membrane region V are important for ligand binding in several bioamine receptors. In the 5-HT6 receptor, one of these residues is a threonine (Thr196), whereas in most other mammalian 5-HT receptors, the corresponding residue is alanine. After transient expression in human embryonic kidney 293 cells, we determined the effects of the mutation T196A on [3H]d-lysergic acid diethylamide (LSD) binding and adenylyl cyclase stimulation. This mutation produced a receptor with a 10-fold reduced affinity for [3H]LSD and a 6-fold reduced affinity for 5-HT. The potency of both LSD and 5-HT for stimulation of adenylyl cyclase was also reduced by 18- and 7-fold, respectively. The affinity of other N1-unsubstituted ergolines (e.g., ergotamine, lisuride) was reduced 10-30 fold, whereas the affinity of N1-methylated ergolines (e.g., metergoline, methysergide, mesulergine) and other ligands, such as methiothepine, clozapine, ritanserin, amitriptyline, and mainserin, changed very little or increased. This indicates that in wild-type 5-HT6 receptor, Thr196 interacts with the N1 of N1-unsubstituted ergolines and tryptamines, probably forming a hydrogen bond. Based on molecular modeling, a serine residue in transmembrane region IV of the 5-HT2A receptor has previously been proposed to interact with the N1-position of 5-HT. When the corresponding residue of the 5-HT6 receptor (Ala154) was converted to serine, no change in the affinity of twelve 5-HT6 receptor ligands or in the potency of 5-HT and LSD could be detected, suggesting that this position does not contribute to the ligand binding site of the 5-HT6 receptor.