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Biomedical subjects

C Franklin

Publications and source records attributed to C Franklin.

At least 19 recordsLinked to original sources

Clinically relevant differences between the statins: implications for therapeutic selection.

Although the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, share a common lipid-lowering effect, there are differences within this class of drugs. The low-density lipoprotein (LDL) cholesterol-lowering efficacy, pharmacokinetic properties, drug-food interactions, and cost can vary widely, thus influencing the selection of a particular statin as a treatment option. The statins that produce the greatest percentage change in LDL cholesterol levels are atorvastatin and simvastatin. Atorvastatin and fluvastatin are least affected by alterations in renal function. Fewer pharmacokinetic drug interactions are likely to occur with pravastatin and fluvastatin, because they are not metabolized through the cytochrome P450 (3A4) system. The most cost-effective statins, based on cost per percentage change in LDL cholesterol levels, are fluvastatin, cerivastatin, and atorvastatin. Awareness of these differences may assist in the selection or substitution of an appropriate statin for a particular patient.

Decision Making↗

'Round-table' ethical debate: is a suicide note an authoritative 'living will'?

Living wills are often considered by physicians who are faced with a dying patient. Although popular with the general public, they remain problems of authenticity and authority. It is difficult for the examining physician to know whether the patient understood the terms of the advance directive when they signed it, and whether they still consider it authoritative at the time that it is produced. Also, there is little consensus on what spectrum of instruments constitutes a binding advance directive in real life. Does a 'suicide note' constitute an authentic and authoritative 'living will'? Our panel of authorities considers this problem in a round-table discussion.

Critical Care↗

The pulmonary artery catheter: uses and controversies.

The pulmonary artery catheter is an invasive hemodynamic monitor that can provide diagnostic information in situations where history and physical examination are inconclusive. Assisting the physician in therapeutic decisions has added to its clinical value. Understanding the information it provides and making thoughtful therapeutic decisions lie at the core of its use. Despite its use, the PA catheter has been the center of great controversy. Clearly the paucity of prospective randomized trials proving its efficacy is alarming. The inability of physicians to interpret the provided data properly is also unacceptable. Although instituting a moratorium on its use may be extreme, limiting its use to approved indications seems more appropriate. In the future, ready availability of other less invasive methods such as echocardiography may allow clinicians to become less reliant on the PA catheter. Until then, clinicians would be served best by comprehending the intricacies and the limitations of this sophisticated instrument.

Blood Pressure↗

Educating students with TBI: themes and recommendations.

Ten educational consultants and researchers, each with extensive experience working with children with traumatic brain injury (TBI) in school settings, identified seven themes related to serving this population in public schools. These themes are discussed under the headings (1) incidence of TBI and prevalence of persistent educational disability, (2) diversity and central tendencies within the population, (3) assessment, (4) intervention and support in school settings, (5) training and support for educators, (6) intervention and support for families, and (7) systems change and flexibility. For each theme, a set of recommendations is provided, forming an educational research and policy agenda for pediatric TBI.

Adolescent↗

Identification of a cDNA encoding an active asparaginyl endopeptidase of Schistosoma mansoni and its expression in Pichia pastoris.

Asparaginyl endopeptidases, or legumains, are a recently identified family of cysteine-class endopeptidases. A single gene encoding a Schistosoma mansoni asparaginyl endopeptidase (a.k.a. Sm32 or schistosome legumain) has been reported, but by sequence homology it would be expected to yield an inactive product as the active site C197 had been replaced by N. We now describe a new S. mansoni gene in which C197 is present. Both gene products were expressed in Pichia pastoris. Autocatalytic processing to fully active C197 Sm32 occurred at acid pH. In contrast, N197 Sm32 was not processed and this is consistent with the hypothesis that C197 is essential for catalysis. This was confirmed by mutation of N197 to C and re-expression in Pichia. The availability of recombinant active Sm32 allows detailed analysis of its catalytic mechanism and its function(s) in the biology of this important human parasite.

Amino Acid Sequence↗

Preventing adolescent pregnancy: a review of programs and practices.

This article reviews literature on the programs and practices available for the primary prevention of adolescent pregnancy. Using the outcomes from research studies, the review defines some of the "best practices" available for the purpose of guiding practitioners in their selection of programs and interventions. Prevention programs, their major components, and curricula are discussed. Best practices discussed include community-based and school-based clinics, programs offering contraceptive knowledge-building along with comprehensive sex education and skills training, and sex education curricula based on social learning theory and skills training.

Adolescent↗

Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise.

To examine the effect of caffeine ingestion on muscle glycogen utilization and the neuroendocrine axis during exercise, we studied 20 muscle glycogen-loaded subjects who were given placebo or caffeine (6 mg/kg) in a double blinded fashion 90 min before cycling for 2 h at 65% of their maximal oxygen consumption. Exercise-induced glycogen depletion in the thigh muscle was noninvasively measured by means of 13C nuclear magnetic resonance spectroscopy (NMR) spectroscopy, and plasma concentrations of substrates and neuroendocrine hormones, including beta-endorphins, were also assessed. Muscle glycogen content was increased 140% above normal values on the caffeine trial day (P < 0.001). After cycling for 2 h, caffeine ingestion was associated with a greater increase in plasma lactate (caffeine: +1.0 +/- 0.2 mmol/L; placebo, +0.1 +/- 0.2 mmol/L; P < 0.005), epinephrine (caffeine, +223 +/- 82 pg/mL; placebo, +56 +/- 26 pg/mL; P < 0.05), and cortisol (caffeine, +12 +/- 3 mg/mL; placebo, +2 +/- 2 mg/mL; P < 0.001) levels. However, plasma free fatty acid concentrations increased (caffeine, +814 +/- 133 mmol/L; placebo, +785 +/- 85 mmol/L; P = NS), and muscle glycogen content decreased (caffeine, -57 +/- 6 mmol/L muscle; placebo, -53 +/- 5 mmol/L muscle; P = NS) to the same extent in both groups. At the same time, plasma beta-endorphin levels almost doubled (from 30 +/- 5 to 53 +/- 13 pg/mL; P < 0.05) in the caffeine-treated group, whereas no change occurred in the placebo group. We conclude that caffeine ingestion 90 min before prolonged exercise does not exert a muscle glycogen-sparing effect in athletes with high muscle glycogen content. However, these data suggest that caffeine lowers the threshold for exercise-induced beta-endorphin and cortisol release, which may contribute to the reported benefits of caffeine on exercise endurance.

Adult↗

The emetic reflex in a reptile (Crocodylus porosus).

The emetic (vomiting) reflex in a crocodilian, Crocodylus porosus, was characterised for the first time using the plant alkaloid veratrine (5 mg kg(-)(1) i.v. or i.p.) as an emetic stimulus. The latency to the onset of vomiting was 8.0+/-0.9 min (mean +/- s.e.m., N=5 animals). Vomiting was preceded by a clearly defined set of prodromal behaviours including, in temporal sequence, rhythmic contraction of the pharynx, sneezing and jaw snapping. Expulsion of vomitus was not particularly forceful and was accompanied by lateral shaking of the head. Physiological studies revealed that vomiting was accompanied by oscillatory (9.1+/-0.7 oscillations over 29.7+/-3. 6 s, N=9 episodes in three animals) increases in intraperitoneal pressure (7.0+/-0.9 kPa, cf. 0.7+/-0.1 kPa during respiration). The significance of these results is discussed in the context of the role(s) of vomiting as a protective reflex and as a mechanism for removal of indigestible food residues (e.g. fur, claws) from the gut.

Abdomen↗

Structural features that modulate the transmembrane migration of a hydrophobic peptide in lipid vesicles.

Two approaches employing nuclear magnetic resonance (NMR) were used to investigate the transmembrane migration rate of the C-terminal end of native alamethicin and a more hydrophobic analog called L1. Native alamethicin exhibits a very slow transmembrane migration rate when bound to phosphatidylcholine vesicles, which is no greater than 1 x 10(-4) min(-1). This rate is much slower than expected, based on the hydrophobic partition energies of the amino acid side chains and the backbone of the exposed C-terminal end of alamethicin. The alamethicin analog L1 exhibits crossing rates that are at least 1000 times faster than that of native alamethicin. A comparison of the equilibrium positions of these two peptides shows that L1 sits approximately 3-4 A deeper in the membrane than does native alamethicin (Barranger-Mathys and Cafiso. 1996. Biochemistry. 35:489). The slow rate of alamethicin crossing can be explained if the peptide helix is irregular at its C-terminus and hydrogen bonded to solvent or lipid. We postulate that L1 does not experience as large a barrier to transport because its C-terminus is already buried within the membrane interface. This difference is most easily explained by conformational differences between L1 and alamethicin rather than differences in hydrophobicity. The results obtained here demonstrate that side-chain hydrophobicity alone cannot account for the energy barriers to peptide and protein transport across membranes.

Alamethicin↗

A comparison of intraoral Candida carriage in Sjögren's syndrome patients with healthy xerostomic controls.

OBJECTIVE: Determination of the incidence of Candida carriage in patients with Sjögren's syndrome (SS) and xerostomic controls to assess the influence of immunologic disturbances in SS on carriage. STUDY DESIGN: A total of 16 primary SS patients, 12 secondary SS patients, and 14 xerostomic controls were included in the study. Sampling was performed using an oral rinse method. Aliquots (100 microliters) were spread onto CHROMagar* and incubated for 48 hours. Species identification was confirmed by the germ tube test and API ID32C. Total colony-forming units per milliliter (CFU/ml) were counted and statistical analyses performed by the Kruskal-Wallis test. RESULTS: Candida carriage in primary SS, secondary SS, and xerostomic patients was 81.25%, 66.7%, and 71.4%, respectively. There were no statistically significant differences in total CFU/ml. A wide range of species was isolated in each group. CONCLUSION: The immunologic disturbances seen in SS do not significantly influence the intraoral Candida carriage in patients with a dry mouth.

Adult↗

A primitive enzyme for a primitive cell: the protease required for excystation of Giardia.

Protozoan parasites of the genus Giardia are one of the earliest lineages of eukaryotic cells. To initiate infection, trophozoites emerge from a cyst in the host. Excystation is blocked by specific cysteine protease inhibitors. Using a biotinylated inhibitor, the target protease was identified and its corresponding gene cloned. The protease was localized to vesicles that release their contents just prior to excystation. The Giardia protease is the earliest known branch of the cathepsin B family. Its phylogeny confirms that the cathepsin B lineage evolved in primitive eukaryotic cells, prior to the divergence of plant and animal kingdoms, and underscores the diversity of cellular functions that this enzyme family facilitates.

Animals↗