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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials.

OBJECTIVE: To conduct a meta-analysis of 11 randomized controlled trials comparing enteral nutritional support supplemented with key nutrients versus standard enteral nutritional support to determine effects on morbidity and mortality rates and hospital stay. BACKGROUND DATA: Recent studies have shown that malnutrition occurs in up to 30% of patients undergoing gastrointestinal surgery, resulting in an increased risk of postoperative complications and death. With the realization that key nutrients can modulate inflammatory, metabolic, and immune processes, enteral nutritional regimens (supplemented with large amounts of key nutrients) have been developed for clinical use. METHODS: Eleven prospective, randomized controlled trials evaluating 1009 patients treated with combinations of key nutrients (Impact, Immun-Aid) were evaluated. Outcome measures examined were the incidences of pneumonia, infectious complications, and death, and length of hospital stay. Meta-analyses were undertaken to obtain the odds ratio and 95% confidence interval for incidences of infectious complications, pneumonia, and death, and the weighted mean difference and 95% confidence interval for length of hospital stay. RESULTS: The provision of nutritional support supplemented with key nutrients to patients with critical illness resulted in a decrease in infectious complications when compared with patients receiving standard nutritional support and a significant reduction in overall hospital stay. Similar results were documented in patients with gastrointestinal cancer. However, there were no differences between patient groups for either pneumonia or death. CONCLUSIONS: This meta-analysis has demonstrated that nutritional support supplemented with key nutrients results in a significant reduction in the risk of developing infectious complications and reduces the overall hospital stay in patients with critical illness and in patients with gastrointestinal cancer. However, there is no effect on death. These data have important implications for the management of such patients.

Abdominal Abscess↗
PubMed1999

Increased fat availability enhances the capacity of trained individuals to perform prolonged exercise.

METHODS: After a familiarization period, six well-trained males participated in a diet and exercise regimen lasting 9 d and comprising three cycling tests to exhaustion. A work rate was selected during the familiarization period that would result in fatigue after approximately 90-100 min at an ambient temperature of 10 degrees C (i.e., approximately 75% of VO2max). The first exercise test was a depletion trial and was preceded by a period during which the subjects' normal diet was consumed. A prescribed 70% carbohydrate (CHO) diet was then consumed for 3.5 d. After this diet, a second exercise test was performed; one of two isoenergetic experimental meals was consumed 4 h before this test (70% CHO meal, CHO trial; or 90% fat meal, fat trial). The second exercise test was followed by a further 3.5-d period on the high CHO diet. Four hours before the third test, subjects consumed the other meal. Heparin was administered intravenously 30 min (1000 U), 15 min (500 U), and 0 min (500 U) before exercise on the fat trial. Subjects were assigned to the two meals in randomized order. RESULTS: Time to exhaustion increased from 118.2 (12.4) min on the CHO trial to 127.9 (12.1) min on the fat trial (P = 0.001). Although no difference in VO2, RER, HR or RPE was found between trials, there was an earlier reduction in RER and an earlier rise in RPE on the fat trial. No difference in total CHO oxidation was found between trials (383 +/- 70 g on the CHO trial and 362 +/- 59 g on the fat trial). CONCLUSIONS: These results suggest that increasing fat availability immediately before exercise by acute fat feeding and heparin infusion can improve endurance exercise in a cool environment in well-trained individuals. This study was not intended to have immediate application to the sports performance field but rather to contribute to our understanding of the factors that may limit endurance performance. Heparin injection to elevate plasma fatty acid concentration would not represent sound medical practice.

Adult↗
PubMed1999

Skin sensitization risk assessment: a comparative evaluation of 3 isothiazolinone biocides.

Many of the chemicals in common use possess, to some degree, a capacity to cause skin sensitization. Consequently, it is important to conduct a thorough and accurate risk assessment when it can be anticipated that such chemicals are likely to come into contact with human skin. Such risk assessments must consider the nature and extent of dermal exposure together with the sensitizing potency of the chemical. Whilst the exposure elements of the risk assessment process are often well understood, or can at least be reasonably predicted on the basis of the proposed usage of the chemical, the determination of skin sensitizing potency may be problematic. In this paper, we describe an approach to the determination of relative potency of 3 isothiazolinone biocides. Initially, the local lymph node assay (LLNA) provides an estimate of relative sensitizing potency. Where appropriate, this can be followed by confirmatory testing in the human repeat insult patch test (HRIPT). The data generated reveal that (chloro)methyl isothiazolinone (CMI) is a significantly stronger sensitizer than either methyl trimethylene isothiazolinone (MTI) or benzisothiazolinone (BIT). Furthermore, both the LLNA and the HRIPT data show consistently that BIT is a somewhat weaker skin sensitizer than MTI. As an important additional component of the safety evaluation, the ability of these sensitizing isothiazolinones to cross-react has been considered; the data indicate that the more weakly sensitizing isothiazolinones do not elicit allergic reactions in subjects sensitized to MCI. The implications for use of these biocides in various product types are discussed.

Adolescent↗
PubMed1999

Human opsonins induced during meningococcal disease recognize transferrin binding protein complexes.

Patient serum opsonins against transferrin binding protein A+B (TbpA+B) complexes from two Neisseria meningitidis strains (K454 and B16B6, with 85- and 68-kDa TbpB, respectively) were quantified by a functional phagocytosis and oxidative burst assay. TbpA+B complexes adsorbed to fluorescent beads were opsonized with individual acute and convalescent sera from 40 patients infected by a variety of meningococcal strains. Flow cytometric quantitation of leukocyte phagocytosis products (PP) demonstrated that disease-induced serum opsonins recognized TbpA+B, and the highest anti-TbpA+B serum opsonic activities were found between admission to hospital and 6 weeks later. The PP values obtained with TbpA+B from strain B16B6 (PP(B16B6)) were higher than those obtained with TbpA+B from strain K454 (PP(K454)), with both acute and convalescent sera (P < 0.0001), and correlated positively with higher immunoglobulin G enzyme-linked immunosorbent assay titers against TbpA+B from strain B16B6 than from strain K454 (P < 0.001). In spite of considerable variations between individuals, significant correlations were found between the PP(B16B6) and PP(K454) values, and the PP values did not depend on the variability of the TbpB proteins of the disease-causing strains. Simultaneously measured oxidative burst activity correlated closely with the PP values. We conclude that highly cross-reactive anti-TbpA+B serum opsonins are produced during meningococcal disease. The anti-TbpA+B opsonic activities were not affected by the variability of the TbpB proteins of the disease-causing strains, which further adds to the evidence for the vaccine potential of meningococcal TbpA+B complexes.

Adolescent↗
PubMed1999

Transcriptional control of the iron-responsive fxbA gene by the mycobacterial regulator IdeR.

Exochelin is the primary extracellular siderophore of Mycobacterium smegmatis, and the iron-regulated fxbA gene encodes a putative formyltransferase, an essential enzyme in the exochelin biosynthetic pathway (E. H. Fiss, Y. Yu, and W. R. Jacobs, Jr., Mol. Microbiol. 14:557-569, 1994). We investigated the regulation of fxbA by the mycobacterial IdeR, a homolog of the Corynebacterium diphtheriae iron regulator DtxR (M. P. Schmitt, M. Predich, L. Doukhan, I. Smith, and R. K. Holmes, Infect. Immun. 63:4284-4289, 1995). Gel mobility shift experiments showed that IdeR binds to the fxbA regulatory region in the presence of divalent metals. DNase I footprinting assays indicated that IdeR binding protects a 28-bp region containing a palindromic sequence of the fxbA promoter that was identified in primer extension assays. fxbA regulation was measured in M. smegmatis wild-type and ideR mutant strains containing fxbA promoter-lacZ fusions. These experiments confirmed that fxbA expression is negatively regulated by iron and showed that inactivation of ideR results in iron-independent expression of fxbA. However, the levels of its expression in the ideR mutant were approximately 50% lower than those in the wild-type strain under iron limitation, indicating an undefined positive role of IdeR in the regulation of fxbA.

Bacterial Proteins↗
PubMed1999

Pacifier use and sudden infant death syndrome: results from the CESDI/SUDI case control study. CESDI SUDI Research Team.

OBJECTIVES: To investigate the relation between pacifier use and sudden infant death syndrome (SIDS). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population > 17 million). SUBJECTS: 325 infants who had died from SIDS and 1300 control infants. RESULTS: Significantly fewer SIDS infants (40%) than controls (51%) used a pacifier for the last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence interval (CI), 0.46 to 0.83) and the difference increased when controlled for other factors (multivariate OR, 0.41; 95% CI, 0. 22 to 0.77). However, the proportion of infants who had ever used a pacifier for day (66% SIDS v 66% controls) or night sleeps (61% SIDS v 61% controls) was identical. The association of a risk for SIDS infants who routinely used a pacifier but did not do so for the last sleep became non-significant when controlled for socioeconomic status (bivariate OR, 1.39 (0.93 to 2.07)). CONCLUSIONS: Further epidemiological evidence and physiological studies are needed before pacifier use can be recommended as a measure to reduce the risk of SIDS.

Breast Feeding↗
PubMed1999

Effects of lasalocid on performance of lactating dairy cows.

Sixty lactating dairy cows (30 multiparous and 30 primiparous) were used in a completely randomized block design to determine the effect of lasalocid supplementation on dairy cow performance. Starting wk 2 prepartum and lasting through wk 17 of lactation, cows received one of three experimental diets. The experimental total mixed rations were control (CD), control + 10 mg/kg of lasalocid (CD + 10) and control + 20 mg/kg of lasalocid (CD + 20). The alfalfa-based control diet (40:60; forage:concentrate) was formulated to contain 18% crude protein, 35% nonstructural carbohydrates, 31% neutral detergent fiber, and 6.6% ether extract. Lasalocid supplementation linearly decreased dry matter intake (DMI) without affecting milk production or milk composition. Mean milk production and percentages of fat and protein were 30.0, 30.8, and 28.6; 3.56, 3.51, and 3.63; 3.06, 3.05, and 3.09; respectively for treatments CD, CD + 10, and CD + 20. Lasalocid supplementation decreased milk urea N (MUN) when compared to control cows, and increasing supplementation caused a significant linear decrease in MUN. For the primiparous cows, lasalocid supplementation decreased DMI and MUN while increasing body condition score and feed efficiency. Results from this study indicate that lactating dairy cows and, in particular, primiparous cows may benefit from lasalocid supplementation in terms of more efficient utilization of nutrients for milk production, reduced MUN levels, reduced body condition loss, and higher margin over feed cost.

Animal Feed↗
PubMed1999

New anaesthetics & techniques for day case surgery.

A variety of drugs and techniques have been introduced into day surgery over recent years and, although the tide of development appears to have slowed, may of these will still be relatively new to many. Experience with the laryngeal mask continues to grow and it is now a firmly-established airway management tool in a wide variety of procedures. The cuffed oropharyngeal airway is an interesting recent arrival, but produces inferior airway control and is not a true alternative to the laryngeal mask. Desflurane and sevoflurane offer faster recovery through low solubility although the differences are small. Sevoflurane offers the interesting prospect of inhalation induction opening up the possibility of a radical change in technique and philosophy. In the intravenous arena remifentanil offers short-lived opioid side effects, but also short-lived analgesia, while propofol has a new, computer-assisted delivery system. In combination, these developments offer another opportunity for a dramatically altered technique. The long-awaited "depth of anaesthesia" monitor may have arrived, offering the possibility of more finely titrated anaesthesia with earlier (but not intraoperative!) awakening. Reliability is as yet uncertain and a simple technique with spontaneous ventilation may achieve similar results at substantially lower cost. The relative place of all these developments will take several years to become apparent and the future remains interesting.

Ambulatory Surgical Procedures↗
PubMed1999

Review of national tuberculosis programmes: the experience in Bangladesh.

Tuberculosis control efforts should be evaluated periodically to assess progress made by national programmes and to plan for the future. Simple and reliable tools are required for such assessments. This paper summarises the methodology and results of the review of the national tuberculosis programme in Bangladesh conducted in 1997. The authors conclude that similar reviews would not only help to verify the reports from the routine recording system, but would also assist policy development and future planning.

Bangladesh↗
PubMed1998

An evolutionary link between sporulation and prophage induction in the structure of a repressor:anti-repressor complex.

Spore formation is an extreme response of some bacteria to adversity. In Bacillus subtilis the proteins of the sin, sporulation inhibition, region form a component of an elaborate molecular circuitry that regulates the commitment to sporulation. SinR is a tetrameric repressor protein that binds to the promoters of genes essential for entry into sporulation and prevents their transcription. This repression is overcome through the activity of SinI, which disrupts the SinR tetramer through the formation of a SinI-SinR heterodimer. The interactions governing this curious quaternary transition are revealed in the crystal structure of the SinI-SinR complex. The most striking, and unexpected, finding is that the tertiary structure of the DNA-binding domain of SinR is identical with that of the corresponding domains of the repressor proteins, CI and Cro, of bacteriophage 434 that regulate lysis/lysogeny. This structural similarity greatly exceeds that between SinR and any bacterial protein or between the 434 repressor proteins and their homologues in the closely related bacteriophage lambda. The close evolutionary relationship implied by the structures of SinR and the 434 repressors provokes both comparison of their functions and a speculative consideration of the intriguing possibility of an evolutionary link between the two adaptive responses, sporulation and prophage induction.

Amino Acid Sequence↗
PubMed1998

Treatment of large and locally advanced breast cancers using neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant (primary) chemotherapy is being used increasingly in the treatment of patients with large and locally advanced breast cancer with the aim of reducing the size of the primary tumor and eliminating micrometastatic disease. Response rates to, compliance with, and survival of patients following neoadjuvant chemotherapy have been variable. We report the results of a consecutive series of 77 patients with breast cancer who received neoadjuvant chemotherapy. METHODS: Seventy-seven patients with locally advanced breast cancers were treated with multimodality therapy comprising up to six cycles of chemotherapy (cyclophosphamide, vincristine, doxorubicin, and prednisolone), radiotherapy, and then surgery. The median follow-up was 54 months. Clinical response rates to therapy and overall survival have been documented. In addition, prognostic factors for survival were identified using the Cox proportional hazards model. RESULTS: The overall objective response rate of the primary tumor to chemotherapy alone was 87% (25% complete and 62% partial responses, UICC criteria). Following radiotherapy the response rate was 90% (52% complete and 38% partial responses). The overall 5-year survival for all patients was 0.48. However, the probability of survival at 5 years was 0.74 in those with a complete response, and 0.36 if there was a partial clinical response, but no patients who had either stasis of disease or progression survived for 5 years. Independent predictors of better survival that were identified were a complete histopathological response after chemotherapy and radiotherapy, a complete clinical response to chemotherapy, and five or six cycles of chemotherapy versus four or less. CONCLUSIONS: Neoadjuvant chemotherapy in patients with large and locally advanced breast cancers can result in satisfactory local control and overall survival rates, especially in patients with a complete clinical or histopathological response after treatment.

Adult↗
PubMed1998

A rare combined fracture and ligamentous injury of the thumb.

Bennett's fracture of the base of the metacarpal of the thumb and avulsion of the ulnar collateral ligament of the thumb are both relatively common injuries. It is, however, rare for the two lesions to occur simultaneously and we report such a case.

Adult↗
PubMed1998

Interdependence of mycobacterial iron regulation, oxidative-stress response and isoniazid resistance.

Iron is an essential cofactor for vital functions in microorganisms. Bacterial pathogens have developed efficient iron-acquisition systems to counteract the defensive sequestration of iron by their hosts. In mycobacteria, the recently described protein, IdeR, negatively controls iron-uptake systems. This protein also has a role in the oxidative-stress response, as well as in resistance to the frontline antimycobacterial drug isoniazid.

Antitubercular Agents↗
PubMed1998

sigA is an essential gene in Mycobacterium smegmatis.

sigA encodes a sigma factor of the sigma70 family, sigmaA, that is found in all mycobacterial species. As sigmaA shows high similarity to the primary sigma factor in Streptomyces coelicolor, it was postulated that sigmaA has the same role in mycobacteria. However, a point mutation in sigA, resulting in the replacement of arginine 522 by histidine, was found responsible for the attenuated virulence of the Mycobacterium bovis strain ATCC 35721. This raised the possibility that sigmaA was an alternative sigma factor specifically required for virulence gene expression. In this work, we show that sigA can not be disrupted in Mycobacterium smegmatis unless an extra copy of the gene is provided at another chromosomal site, which demonstrates that sigA is essential. To characterize the pattern of sigA expression during exponential and stationary phase in M. smegmatis, we measured the beta-galactosidase activity in a strain carrying a sigA-lacZ transcriptional fusion and monitored sigmaA levels using Western blotting. Our results indicate that sigA is expressed throughout the growth of the culture. The essential character of sigA and its pattern of expression corroborate the hypothesis that sigA codes for the primary sigma factor in M. smegmatis and, most likely, in all mycobacteria.

Base Sequence↗