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Biomedical subjects

R C Smith

Publications and source records attributed to R C Smith.

At least 55 records · Page 3Linked to original sources

Applications of developmental biology to medicine and animal agriculture.

With the complete sequence of the human genome expected by winter 2001, genomic-based drug discovery efforts of the pharmaceutical industry are focusing on finding the relatively few therapeutically useful genes from among the total gene set. Methods to rapidly elucidate gene function will have increasing value in these investigations. The use of model organisms in functional genomics has begun to be recognized and exploited and is one example of the emerging use of the tools of developmental biology in recent drug discovery efforts. The use of protein products expressed during embryo-genesis and the use of certain pluripotent cell populations (stem cells) as candidate therapeutics are other applications of developmental biology to the treatment of human diseases. These agents may be used to repair damaged or diseased tissues by inducing or directing developmental programs that recapitulate embryonic processes to replace specialized cells. The activation or silencing of embryonic genes in the disease state, particularly those encoding transcription factors, is another avenue of exploitation. Finally, the direct drug-induced manipulation of embryonic development is a unique application of developmental biology in animal agriculture.

Agriculture↗

Gene therapy for restenosis.

This review provides an overview of candidate genes that are currently being evaluated for genetic strategies in vascular gene therapy. We discuss treatment strategies that have proven efficacious in limiting postinterventional restenosis through evaluation with in vivo model systems. The candidate strategies utilize genes that are either cytotoxic, regulate vascular smooth muscle cell differentiation or proliferation. In addition, we review oligonuclotide and ribozyme strategies that function by suppressing the expression of cell cycle regulators.

Animals↗

Evidence-based guidelines for teaching patient-centered interviewing.

In a rare study of effectiveness of an interviewing method, we previously reported a randomized controlled trial demonstrating that training in a step-by-step patient-centered interviewing method improved residents' knowledge, attitudes, and skills and had a consistently positive effect on trained residents' patients. For those who wish to use this evidence-based patient-centered method as a template for their own teaching, we describe here for the first time our training program--and propose that the training can be adapted for students, physicians, nurse practitioners, physician assistants, and other new learners as well. Training was skills-oriented and experiential, fostered positive attitudes towards patient-centered interviewing, and used a learner-centered approach which paid special attention to the teacher-resident relationship and to the resident's self-awareness. Skills training was guided by a newly identified patient-centered interviewing method that described the step-by-step use of specific behaviors.

Attitude of Health Personnel↗

Addition of tyrosyl-arginine to parenteral nutrition is anabolic in unstressed rats.

To determine whether the addition of tyrosine and arginine (Arg), as tyrosyl-arginine (TyrArg), to parenteral nutrition (PN) can promote anabolism, rats were assigned to: 1) PN (1.20 MJ. kg body weight [BW](-1) x d(-1) and 1.22 gN x kgBW(-1) x d(-1); PN control group, n = 5), 2) PN plus TyrArg (2.6 mmol. kgBW(-1) x d(-1); TyrArg group, n = 6), or 3) PN plus Arg (2.6 mmol. kgBW(-1). d(-1); Arg group, n = 5). Results from these three groups were compared with an unoperated chow-fed reference group (chow control group, n = 5). The BW gain during PN and the proportion of lipid in the total body after 14 d of PN was greater for the TyrArg group than for the PN group (P<0.01). Although the differences in weight gain, body water, lipid, and protein between the TyrArg and Arg groups were not significant, the mean weight gain throughout PN was greater in the TyrArg group than in the Arg group. The proportion of protein in the small intestine, colon, and gastrocnemius muscle was greater in the TyrArg and Arg groups than in the PN group (P<0.01). A distinct requirement for tyrosine has not been demonstrated in this model, and additional studies in stressed animals are required. In contrast, arginine had tissue-specific anabolic activity.

Animals↗

Analysis and comparison of four anhysteretic polarization models for lead magnesium niobate.

Four anhysteretic polarization models that have been used in the literature to evaluate data acquired from lead magnesium niobate (PMN) are analyzed and compared. Derivations of two of the models from assumed spatial distributions of dipole energy states, using first physical principles, are presented. A third model is derived from a suitable integral averaging calculation. These derivations are used as the basis for developing an integral equation for determining an energy-state distribution that produces a fourth model, which was not originally formulated in terms of an assumed distribution. A new polarization function is also presented. Excellent approximations to each of the four polarization functions of interest can be deduced from this new polarization function by adjusting the numerical value of just a single parameter. An application of two of the models to data is presented. It is shown that it can be necessary to consider a sample to be an admixture of two distinct species of poles, in the sense that two polarization functions must be added together in order to accommodate the data.

Acoustics↗

Aorto caval fistula--the "bursting heart syndrome".

Aorto caval fistula is one of the less well recognised complications of abdominal aortic aneurysm seen in accident and emergency departments. It presents in a number of different ways the commonest of which is high output congestive cardiac failure with warm peripheries. Initial diagnosis is based on the index of suspicion of the clinician. However, early diagnosis by the emergency physician and early surgery can markedly improve the patients prognosis.

Aged↗

Effectiveness of sealant treatment over five years in an insured population.

BACKGROUND: The authors analyzed an insurance claim database to evaluate the use and effectiveness of placing sealants on first and second permanent molars of children in private dental practices. METHODS: A retrospective study was conducted using an insured population with sealant coverage at 70 percent of the usual fee in a preferred provider organization than that limited reapplication to once every three years. Children were selected who were eligible for sealant benefits from July 1, 1990, to June 30, 1991. Two groups were selected for analysis, based on age, as determined by permanent molar eruption dates. Children who received sealants were compared with those who did not to determine post-sealant restorative outcomes after five years. RESULTS: During the full year of coverage, sealants were used in only 16.3 percent of first permanent molars and 11.6 percent of second permanent molars. The five-year incidence of an occlusal restoration having been placed was 13.7 percent and 20.8 percent, respectively, on nonsealed first and second molars and 6.5 percent and 10.4 percent, respectively, on sealed first and second molars. From years three to five, sealant placement provided only nominal additional preventive effect. CONCLUSIONS: In the population selected, both the incidence of occlusal caries and the use of sealants were lower than expected for both age groups. However, within these groups, molar occlusal surfaces were only half as likely to have been restored in sealed teeth than in nonsealed teeth after five years. CLINICAL IMPLICATIONS: Based on the five-year data from a population with a low incidence of caries, the authors found that 15 sealed first permanent molars or 10 sealed second permanent molars prevented placement of one occlusal restoration. Therefore, sealants are more effective when placed in patients with risk factors for occlusal caries.

Adolescent↗

Superior mesenteric artery bypass for chronic mesenteric ischaemia: a DGH experience.

This article evaluates the results of single vessel bypass surgery for symptomatic chronic mesenteric ischaemia (CMI) in 6 patients undergoing a total of 8 superior mesenteric artery (SMA) bypass operations, all with good post-operative symptom relief. Post-prandial pain and weight loss was present in 5 out of 6 patients. Epigastric bruit was present in only two patients and 4 out of 6 patients had diarrhoea. The patients had varying degrees of peripheral vascular disease, ischaemic heart disease and hypertension. All patients had occlusion of the SMA on angiography and bypassing the occluded segment resulted in disappearance of the symptoms and weight gain. The vascular graft was sutured end to side to the front of the infra-renal aorta and end to side to the SMA, distal to the origin of the middle colic artery. Two patients had recurrence of symptoms due to graft occlusion at 3 and 4 years, respectively; they were successfully treated with repeat SMA bypass. There were no major complications or deaths related to the procedure in this study; one patient developed an incisional hernia requiring elective repair. Thus, early restoration of SMA circulation by bypass grafting in patients with CMI is sufficient to alleviate symptoms and prevent intestinal infarction with its high mortality rate.

Adult↗

Plasma sample preparation by ultrafiltration for FTIR analysis.

Total body water (TBW) may be significantly altered with disease. Isotope dilution techniques, considered to be the "gold standard" methods for measuring TBW, are expensive, time consuming and require considerable expertise, especially during the sample preparatory phase. In this study, a new method, ultrafiltration (UF), was hypothesised to be an efficient alternative to vacuum sublimation (VS) in the preparation of plasma samples for Fourier Transform Infra Red (FTIR) determination of TBW. Deuterium Oxide (D2O) concentrations were prepared in human plasma and subjected to both techniques. FTIR analysis was carried out on the resulting VS and UF solutions and on D2O concentrations in distilled water. The resulting absorbance values were then statistically compared. Urea concentrations prepared in D2O-containing plasma were also compared to "blank" plasma to investigate the effect of high plasma urea concentration on the resulting H2O/D2O mixture obtained during UF Paired t-tests showed that the VS plasma samples (p=0.003), but not the UF samples (p=0.9), were significantly different to D2O standards prepared in distilled water. While there was no evidence of an effect of urea on UF at low (0.4 g/L) D2O concentration, a marginal (p=0.04) effect occurred at a higher (1.6 g/L) D2O level. Throughput of samples was much more efficient with the UF technique. These findings indicate that the new UF method is an accurate, more efficient method of plasma sample preparation than the VS method in the FTIR determination of TBW.

Blood Chemical Analysis↗

Comparison of outcomes following transhiatal or Ivor Lewis esophagectomy for esophageal carcinoma.

Transhiatal esophagectomy (THO) may be a valid alternative to the traditional Ivor Lewis (ILO) procedure, but there have been reservations about procedure mortality, nodal clearance, and survival. ILO is preferred for bulky midesophageal lesions and THO in frail patients, making randomization difficult. This retrospective study compares results of a 10-year period from January 1985 with a minimum follow-up period of 12 months. Four patients were lost to follow-up. Preoperative nutritional markers were similar in the two groups, as were the age and sex distribution. Altogether 33 ILOs and 65 THOs were performed. TNM staging was similar between groups, there being 43% stage II and 45% stage III lesions among the ILO patients and 53% stage II and 32% stage III disease in the THO group. Operating time was shorter for THO (256 +/- 58 minutes vs. 279 +/- 50 minutes) (p = 0.05); if two surgeons operated concurrently, THO could be performed 40 minutes quicker than THO or ILO performed by a single surgeon (p = 0.018). The mean initial intensive care unit stay was 2.9 days for ILO versus 1.7 days for THO (p = 0.014). The 30-day mortality was 5.1%; total in-hospital mortality was 7.1% with no difference for operation type. There were similar morbidity rates for the procedures. Kaplan-Meier survival analysis indicated no significant effect of surgical technique; there were no apparent advantages for either operation when patients were compared by tumor type or matched for stage. Hence THO is a valid alternative to ILO, particularly for stage II and III cancer.

Aged↗

Helical CT of urinary tract stones. Epidemiology, origin, pathophysiology, diagnosis, and management.

Urolithiasis is a common medical problem. The diagnosis of this entity in the setting of acute flank pain presents an interesting challenge to the radiologist. Unenhanced helical CT has recently entered the fray and has quickly become the imaging study of choice when evaluating patients with acute flank pain and suspected ureterolithiasis. The nature and origin of ureteral stones and the pathophysiology of ureteral obstruction provide a basis for understanding the imaging findings in these patients.

Acute Disease↗

Acute flank pain: a modern approach to diagnosis and management.

Acute flank pain is a common and complex clinical problem. In addition to flank pain caused by ureterolithiasis, other urinary and extraurinary abnormalities can result in a similar clinical picture. Unenhanced CT can rapidly, accurately, and safely determine the presence or absence of ureteral obstruction. When obstruction is caused by ureterolithiasis, CT allows precise determination of stone size and location. These are the two most important factors used for patient management. In addition to direct stone visualization, there are many secondary CT signs of ureteral obstruction that are direct manifestations of the underlying pathophysiology. On the other hand, when obstruction is absent, CT can diagnose or exclude most other abnormalities that result in flank pain. As a result of its many advantages, unenhanced helical CT should become the dominant imaging modality for evaluation of all patients with acute flank pain in whom a clinical diagnosis is uncertain.

Acute Disease↗

Changes in body composition during breast cancer chemotherapy with the CMF-regimen.

Weight gain is a reported problem associated with adjuvant chemotherapy for breast cancer and often generates psychosocial stress in women [1]. It also may affect prognosis and survival. Changes in body composition and weight during chemotherapy, particularly adjuvant treatment of breast carcinoma, have been previously reported [1-3]. Multiple reasons for this weight gain have been suggested though few theories have been scientifically validated [4]. The aim of this study was to investigate body composition and its relationship to weight change associated with the CMF-based breast cancer chemotherapy protocols. Total body nitrogen (TBN), body fat, total body water (TBW), and anthropometric measurements were conducted on 25 female out-patients (median age 47, range 26-70 years) receiving adjuvant CMF-based chemotherapy for breast cancer. Total body nitrogen was measured using the In Vivo Neutron Capture Analysis (IVNCA) technique (on day 1 of cycles 2-6) and TBP was calculated by multiplying TBN by 6.25 [5]. Nitrogen Index (NI) was calculated by expressing TBN as a percentage of normal. There was a significant increase in mean body weight during chemotherapy of 2.35 kg (p < 0.0001). Serial measurements showed no significant change in mean TBN, NI, or percentage body fat. Break down of body weight showed a significant increase in mean TBW of 0.79 kg (p = 0.003) and mean fat mass of 1.49 kg (p = 0.008). We conclude that weight gain observed during adjuvant chemotherapy for breast carcinoma is primarily due to an increase in fat and TBW.

Adult↗

Adenovirus-mediated delivery of the Gax transcription factor to rat carotid arteries inhibits smooth muscle proliferation and induces apoptosis.

Adenovirus-mediated gene delivery in animal models of vascular injury has provided insights into the mechanisms underlying vessel wall pathologies. We have previously demonstrated that overexpression of the Gax transcription factor inhibits neointimal formation in rat and rabbit models of arterial injury. Here, we evaluate potential mechanisms for the reduction in stenotic lesion size due to Gax overexpression. At 3, 7 and 14 days after injury the Ad-Gax-infected arteries displayed a marked decrease in medial vascular smooth muscle cell number (3 days, 54% reduction P < 0.01; 7 days, 41% reduction P < 0.003; 14 days, 49% reduction P < 0.02). At 3 days after injury, PCNA expression was attenuated in the Ad-Gax-treated vessels compared with control vessels (65% reduction P < 0.02), indicating a reduction in cellular proliferation. At 7 days and 14 days after injury Ad-Gax-infected arteries exhibited elevated number of TUNEL-positive medial VSMCs compared with control-treated arteries (7 days, 9.2-fold increase P < 0.03; 14 days, 17.2-fold increase P < 0.03), indicating an induction of apoptotic cell death. These data suggest that deregulated Gax expression induces first cell cycle arrest and then apoptosis in the vascular smooth muscle cells that contribute to the neointimal layer. Therefore, the efficacy of this therapeutic strategy appears to result from the ability of the Gax transcriptional regulator to modulate multiple cellular responses.

Adenoviridae↗

Predictors of breast cancer in women recalled following screening.

BACKGROUND: Established risk factors are associated with between 25 and 56% of breast cancer cases, but the relative importance and relevance to different age groups is unclear. METHODS: This case-control study examines established risk factors in 298 women with breast cancer and 1926 women without breast cancer aged 40-87 who were recalled for assessment following routine mammography. RESULTS: The cancer group were significantly older than the non-cancer group (F1,222 = 107.6; P < 0.0001). Postmenopausal obesity increased the odds of developing breast cancer (OR: 2.35; CI: 1.33-4.16). The breast cancer group were more likely to have used oral contraceptives (OR: 1.50; CI: 1.09-2.05), and women who used contraceptives for more than 10 years in total were at the highest risk (OR: 1.73; CI: 1.13-2.65). Daily consumption of alcohol was also associated with increased risk of developing breast cancer (OR: 1.62; CI: 1.13-2.33). Reproductive factors and a family history of breast cancer did not affect the odds of developing breast cancer and the reasons for these findings are explored. CONCLUSIONS: Results suggest that the effects of weight reduction in reducing postmenopausal breast cancer risk should be assessed.

Adult↗