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Biomedical subjects

S White

Publications and source records attributed to S White.

At least 127 records · Page 7Linked to original sources

Cost-benefit analysis for the treatment of severe obesity.

Cost-benefit and cost-effectiveness analyses (CEAs) are only now beginning to be used by business, government, and policymakers to evaluate various medical treatments. The evolution of why CEAs are being demanded is reviewed. To date, a formal CEA of obesity treatments has not been published. This article outlines how a CEA is performed, reviews data relevant to setting up a formal CEA of medical and surgical obesity treatments, and lists published reports that demonstrate the effectiveness of surgical obesity treatments. The general level of discrimination that society allows the obese to suffer also allows medical insurance companies, businesses, and government to not provide many obese Americans with obesity treatments that have established a level of effectiveness far surpassing many other forms of medical therapy. CEAs of obesity treatments, by themselves, cannot be expected to reverse this discrimination. This type of data, however, provides individual obese patients and their physicians with evidence to challenge policymakers' decisions, especially when cost-effective obesity treatments are excluded or placed at a lower priority than treatments with less proven effectiveness.

Cost-Benefit Analysis↗

Of genes and genomes and the origin of maize.

The crop plant maize (corn) is remarkably dissimilar to its recent wild ancestor, teosinte, making it an extremely interesting model for the study of evolution. Investigations into the evolution of maize are currently being performed at the molecular and morphological levels. Three independent lines of research are poised to shed light on the molecular basis of this spectacular transformation: (1) determining the structure and origin of the maize genome; (2) understanding the role of transposable elements in maize evolution; and (3) elucidating the genetic basis for morphological differences between maize and its wild ancestor teosinte.

Biological Evolution↗

Tube caecostomy to protect rectal anastomoses.

BACKGROUND: Low rectal anastomoses are associated with a substantial risk of anastomotic leakage. Tube caecostomy offers a potentially simple method of anastomotic protection. METHODS: Some 226 patients undergoing restorative rectal resection with on-table colonic lavage and tube caecostomy over an 11-year period were reviewed. Endpoints selected included clinical anastomotic leakage, requirement for a subsequent formal stoma and complications of tube caecostomy. RESULTS: Overall, clinical anastomotic leakage occurred in 25 patients with a caecostomy (11.1 per cent). All leaks were noted among patients in whom caecostomy protection had been used after low anterior resection, giving a leak rate of 14.9 per cent (25 of 168) for this group of whom 17 (10.1 per cent) required reoperation and a formal stoma, and five (3.0 per cent) died. Complications of caecostomy or prolonged drainage after tube removal occurred in ten (4.4 per cent) and 15 (6.6 per cent) patients respectively. There were two cases of life-threatening invasive infection. CONCLUSION: Tube caecostomy provides inadequate protection of rectal anastomoses; complications are common and may be life threatening.

Anastomosis, Surgical↗

CAG repeat expansion in autosomal dominant familial spastic paraparesis: novel expansion in a subset of patients.

Autosomal dominant familial spastic paraplegia (FSP) is a genetically heterogeneous neurodegenerative disorder displaying anticipation for which three loci have been mapped to the chromosomal positions 14q11.2-q24.3 (SPG3), 2p21-p24 (SPG4) and 15q11.1 (SPG6). The repeat expansion detection (RED) method has been used to demonstrate expanded CAG repeats in some FSP families that map to SPG4. We analyzed 20 FSP families, including four for which there is evidence for linkage to SPG4, and found that in most cases the repeat expansion detected by RED is due to non-pathogenic expansions of the chromosome 18q21.1 SEF2-1 or 17q21.3 ERDA1 locus. Polymorphic expansions at SEF2-1 and ERDA1 appear frequent and may confound RED studies in the search for genes causing disorders demonstrating anticipation. In six FSP families, however, CAG repeat expansion was detected in a subset of affected and at-risk individuals that did not result from expansion of the SEF2-1 and ERDA1 loci. Overall, 11 of 37 (30%) of the FSP patients with a CAG/CTG repeat expansion are unaccounted for by the SEF2-1 and ERDA1 loci, compared with two of 23 (9%) of the unaffected at-risk individuals and none of 19 controls. In the majority of cases these novel expansions were shorter than those previously reported.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Severe acute respiratory distress syndrome secondary to acute pancreatitis successfully treated with extracorporeal membrane oxygenation in three patients.

OBJECTIVE: To review three patients who underwent extracorporeal membrane oxygenation (ECMO) for acute respiratory failure secondary to pancreatitis. SUMMARY BACKGROUND DATA: Severe acute pancreatitis often causes the acute respiratory distress syndrome (ARDS), and if ventilation is required, the mortality rate is more than 50%. If the ratio of PaO2/FiO2 falls below 100 mm Hg or the Murray lung injury score exceeds 3.5, the mortality rate rises to more than 80%. Three patients who have severe ARDS secondary to pancreatitis, who were hypoxic despite ventilation with 100% oxygen and high airway pressures, and who were all successfully treated with ECMO are reported here. The consensus here is that all three patients would have died without ECMO. METHODS: Retrospective chart review and discussion of the literature. RESULTS: Pre-ECMO data: mean PaO2/FiO2 59.3 mm Hg, mean Murray lung injury score 3.7, one patient administered 20 ppm inhaled nitric oxide. ECMO data: mean extracorporeal flow at initiation of ECMO 56.3 mL/kg per minute, all patients administered veno-venous ECMO, mean duration of ECMO 104.7 hours. All patients were successfully weaned from ECMO and extubated. One patient had a protracted hospital stay because of a colo-cutaneous fistula. All patients are long-term survivors. CONCLUSIONS: Extracorporeal membrane oxygenation proved an effective therapy for severe ARDS complicating acute pancreatitis. Extracorporeal membrane oxygenation was conducted without bleeding complications in these three patients.

Acute Disease↗

Smooth muscle actin and myosin expression in cultured airway smooth muscle cells.

In this study, the expression of smooth muscle actin and myosin was examined in cultures of rat tracheal smooth muscle cells. Protein and mRNA analyses demonstrated that these cells express alpha- and gamma-smooth muscle actin and smooth muscle myosin and nonmuscle myosin-B heavy chains. The expression of the smooth muscle specific actin and myosin isoforms was regulated in the same direction when growth conditions were changed. Thus, at confluency in 1 or 10% serum-containing medium as well as for low-density cells (50-60% confluent) deprived of serum, the expression of the smooth muscle forms of actin and myosin was relatively high. Conversely, in rapidly proliferating cultures at low density in 10% serum, smooth muscle contractile protein expression was low. The expression of nonmuscle myosin-B mRNA and protein was more stable and was upregulated only to a small degree in growing cells. Our results provide new insight into the molecular basis of differentiation and contractile function in airway smooth muscle cells.

Actins↗

Standards of laboratory practice: analgesic drug monitoring. National Academy of Clinical Biochemistry.

Analgesics are the most commonly consumed over-the-counter preparations in the United States. They are used in the treatment of various pain syndromes and other medical conditions. Although analgesics are generally perceived to be safe agents, serious toxicity may occur in the setting of acute overdose, chronic abuse, or overuse. The indications for therapeutic drug monitoring in patients using these medications appropriately is as yet not well defined. The emphasis of this discussion, therefore, is on recommendations for monitoring in situations where toxicity is suspected. Preanalytical, analytical, and practice issues including drug interactions, frequency of monitoring, pertinent ancillary tests, reporting, and special patient groups at risk for toxicity are reviewed. Recent information from a major manufacturer of evacuated tubes arguing against the use of gel tubes for blood collection for drug monitoring is included. Colorimetric/enzymatic/immunoassays for the routine/stat monitoring of acetaminophen and salicylate and diflunisal cross-reactivity with most of the currently used salicylate assays are presented. Achiral and chiral chromatographic assays and newly introduced columns such as restricted access media and/or automated chromatographic systems are reviewed for the analysis of ibuprofen, naproxen, and the recently introduced tramadol. Finally, concepts regarding future directions including drug chirality and chiral analysis are presented.

Alcoholism↗

APC expression in normal human tissues.

The tumour suppressor gene APC codes for a 2843-amino acid protein whose precise functions are still poorly understood. This paper describes the development of two new antisera to APC (to amino- and carboxy-terminal epitopes) which permit localization of the protein by immunohistochemistry in archival paraffin sections. The protein is expressed in a wide variety of normal epithelial tissues. Its distribution frequently coincides with the location of post-replicative cells within tissues. Staining patterns demonstrate that the APC protein, although often diffusely cytoplasmic in distribution, may also accumulate in the apical and immediately subapical regions, or along the lateral margins of certain cells. These results indicate that APC is significant in many tissues in addition to the colorectal epithelium. They are compatible with a function related to signalling at the adherens junction and possibly with other more complex roles in cells committed to terminal differentiation.

Adenomatous Polyposis Coli Protein↗

Candida albicans morphogenesis is influenced by estrogen.

Conversion of Candida albicans from yeast to mycelial growth is believed to be associated with the organism's virulence. We investigated the role of mammalian hormones in initiating this transformation. Three clinical isolates of Candida albicans were tested for their ability to produce germ tubes under various conditions. Controlled hormonal conditions were provided by stripping rabbit serum with activated charcoal. Steroid compounds under investigation were added back to the stripped serum and yeast were inoculated into the test materials. Microscopic counts of germinated versus ungerminated cells were used as an indicator of morphogenic transformation. The percent of yeast cells germinating was profoundly reduced in stripped compared to unstripped serum. The addition of 1 microM estradiol, cholesterol or testosterone only slightly increased levels of germination above that seen in controls. Estradiol at concentrations 100 times less, however, proved a strong inducer of germination. Cholesterol did not synergize germination when combined with estradiol and the alpha isomer of estradiol had almost no activity as an inducer of morphogenic change in Candida albicans. We conclude that beta estradiol was a morphogenic inducer in three clinical isolates of Candida albicans but only at concentrations typical in vivo.

Animals↗

The management of corneal abrasions in accident and emergency.

Recent debate over the use of eyepads and mydriatics for corneal abrasions in ophthalmology departments (Mindin et al., 1996, JAMA 1996; 27: 837) has prompted this review of the management of small corneal abrasions (< 60% of cornea) in a large teaching hospital accident and emergency (A&E) department. Ninety-nine patients were studied who presented to the Leicester Royal Infirmary A&E Department with a corneal abrasion; 49 were given an eye pad and 50 were not given an eye pad. All patients received chloramphenicol (1%) ointment. There was no significance difference between the two groups in terms of the duration of pain (p > 0.2). Four patients developed corneal infections (two wore an eyepad, two had no eye pad). There was only one patient who suffered a transient but significant reduction in visual acuity (6/9-6/18), following the use of an eye pad and subsequent diagnosis in eye casualty of a dendritic ulcer. It is concluded that accident and emergency treatment of small corneal abrasions is safe and effective if an eye pad is not given. Previous criticisms of A&E management of eye problems (Nayeen and Stansfield, Archs Emerg Med, 1992; 9: 257) are unfounded in this department.

Adult↗

On the pairing rules for recognition in the minor groove of DNA by pyrrole-imidazole polyamides.

BACKGROUND: Cell-permeable small molecules that target predetermined DNA sequences with high affinity and specificity have the potential to control gene expression. A binary code has been developed to correlate DNA sequence with side-by-side pairings between N-methylpyrrole (Py) and N-methylimidazole (Im) carboxamides in the DNA minor groove. We set out to determine the relative energetics of pairings of Im/Py, Py/Im, Im/Im, and Py/Py for targeting G.C and A.T base pairs. A key specificity issue, which has not been previously addressed, is whether an Im/Im pair is energetically equivalent to an Im/Py pair for targeting G.C base pairs. RESULTS: Equilibrium association constants were determined at two five-base-pair sites for a series of four six-ring hairpin polyamides, in order to test the relative energetics of the four aromatic amino-acid pairings opposite G.C and A.T base pairs in the central position. We observed that a G.C base pair was effectively targeted with Im/Py but not Py/Im, Py/Py, or Im/Im. The A.T base pair was effectively targeted with Py/Py but not Im/Py, Py/Im, or Im/Im. CONCLUSIONS: An Im/Im pairing is energetically disfavored for the recognition of both A.T and G.C. This specificity will create important limitations on undesirable slipped motifs that are available for unlinked dimers in the minor groove. Baseline energetic parameters will thus be created which, using the predictability of the current pairing rules for specific molecular recognition of double-helical DNA, will guide further second-generation polyamide design for DNA recognition.

Base Composition↗

Autonomic control of bronchial circulation in awake sheep during rest and behaviour.

1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bronchovascular dilatation induced by non-adrenergic, non-cholinergic (NANC) mechanisms observed in the dog exist in sheep. 2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prior thoracotomy. 3. Cumulative and factorial analysis of responses to randomized combinations of autonomic alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%. 4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separate alpha- and beta-adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator alpha-/beta-adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep. 5. Nitric oxide (NO) synthase inhibition in sheep using NG-nitro-L-arginine following blockade of alpha- and beta-adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects. 6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C-fibre axon reflex using substance P, calcitonin gene-related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects.

Adrenergic alpha-Antagonists↗

Computer-based surgical audit programs: a review of three current options.

BACKGROUND: In order to find the most useful computerized auditing system for the needs of the QE II Hospital surgical department three surgical auditing software programs were assessed. METHODS: The Otago University Surgical Auditing Program, the Australian Surgical Auditing Program, and RACS-Audit were trialled for a period of 1 month each. The software programs were evaluated to find the time requirements for data entry, the level of surgical knowledge needed for effective audit information entry, and the perceived usefulness of the generated reports. RESULTS: It was found that the Otago University program best suited the needs of the department. This system was designed for use in a hospital environment with multiple users. The method of data collection was simple and rapid. Entry of data into the program was logical, well structured and able to be performed by both junior medical staff and clerical staff. Reports generated by this system included information in an appropriate format for the departments' morbidity and mortality meetings. CONCLUSION: Personal computers are an ideal tool for the undertaking of surgical audit. Software programs are designed for different uses and should be critically assessed to ensure that the method of data entry, the time involved, and the reports generated enable an efficient and effective audit to be carried out.

General Surgery↗

Genetic Diversity through the Looking Glass: Effect of Enrichment Bias.

The effect of enrichment bias on the diversity of 2,4-dichlorophenoxyacetate (2,4-D)-degrading (2,4-D(sup+)) bacteria recovered from soil was evaluated by comparing the diversity of isolates obtained by direct plating to the diversity of isolates obtained from 85 liquid batch cultures. By the two methods, a total of 159 isolates were purified from 1 g of soil and divided into populations based on repeated extragenic palindromic sequence PCR (rep-PCR) genomic fingerprints. Approximately 42% of the direct-plating isolates hybridized with the tfdA and tfdB genes from Alcaligenes eutrophus JMP134(pJP4), 27% hybridized with the tfdA and tfdB genes from Burkholderia sp. strain RASC, and 30% hybridized with none of the probes. In contrast, the enrichment isolates not only represented fewer populations than the isolates obtained by direct plating but also exhibited, almost exclusively, a single hybridization pattern with 2,4-D catabolic gene probes. Approximately 98% of the enrichment isolates possessed pJP4-type tfdA and tfdB genes, whereas isolates containing RASC-type tfdA and tfdB genes were obtained from only 2 of the 85 enrichment cultures. The skewed occurrence of the pJP4-type genes among the isolates obtained by enrichment suggests that the competitive fitness of 2,4-D(sup+) populations during growth with 2,4-D may be influenced either by specific tfd alleles or by genetic factors linked to these alleles. Moreover, the results indicate that evaluation of the diversity and distribution of catabolic pathways in nature can be highly distorted by the use of enrichment culture techniques.

Journal Article↗

Contact lens use after corneal trauma.

BACKGROUND: This study was performed to explore the epidemiology and visual outcomes of major anterior segment trauma cases referred to the Contact Lens Service (CLS) in a large, urban, eye trauma center at a university hospital. METHODS: All eye trauma patients seen on the CLS at The University of Illinois in Chicago for a 2-year period were identified (n = 122). A search of all eye trauma cases seen at UIC (n = 2279) during the same period yielded 757 cases with the same diagnostic codes. RESULTS: CLS cases represent 16.1% of cases with similar diagnoses and 5.35% of all cases seen during the period of study. Cases were predominantly young men (mean age, 28 years). The mean age for CLS cases (mean age, 17 years) was significantly younger. Best-corrected visual acuity was 20/100 or better in 75% of cases with a contact lens and in 68% of cases with a spectacle lens; 82% of CLS cases had iris damage versus 14.5% of non-CLS cases; 73% of CLS cases were aphakic; 105 CLS cases were given contact lenses. Mean follow-up time was 24 months. Mean wearing time was 11 hours/day. On interview, 35 of 79 cases (44%) continued to wear lenses. CONCLUSIONS: Cases referred to the CLS tended to be young men with unilateral injuries-predominantly open globes-with resultant aphakia and iris damage. Good visual acuity was achieved in most cases. Long-term success wearing contact lenses for this population was poor, suggesting that alternatives to contact lens wear should be more actively considered.

Adolescent↗