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Biomedical subjects

J R Smith

Publications and source records attributed to J R Smith.

At least 145 records · Page 8Linked to original sources
PubMed1997

Role of intestinal epithelial cells in the host secretory response to infection by invasive bacteria. Bacterial entry induces epithelial prostaglandin h synthase-2 expression and prostaglandin E2 and F2alpha production.

Increased intestinal fluid secretion is a protective host response after enteric infection with invasive bacteria that is initiated within hours after infection, and is mediated by prostaglandin H synthase (PGHS) products in animal models of infection. Intestinal epithelial cells are the first host cells to become infected with invasive bacteria, which enter and pass through these cells to initiate mucosal, and ultimately systemic, infection. The present studies characterized the role of intestinal epithelial cells in the host secretory response after infection with invasive bacteria. Infection of cultured human intestinal epithelial cell lines with invasive bacteria, but not noninvasive bacteria, is shown to induce the expression of one of the rate-limiting enzymes for prostaglandin formation, PGHS-2, and the production of PGE2 and PGF2alpha. Furthermore, increased PGHS-2 expression was observed in intestinal epithelial cells in vivo after infection with invasive bacteria, using a human intestinal xenograft model in SCID mice. In support of the physiologic importance of epithelial PGHS-2 expression, supernatants from bacteria-infected intestinal epithelial cells were shown to increase chloride secretion in an in vitro model using polarized epithelial cells, and this activity was accounted for by PGE2. These studies define a novel autocrine/paracrine function of mediators produced by intestinal epithelial cells in the rapid induction of increased fluid secretion in response to intestinal infection with invasive bacteria.

Animals↗
PubMed1997

A placebo-controlled, double-blind prospective study in healthy female volunteers of dextrin sulphate gel: a novel potential intravaginal virucide.

A double-blind, placebo-controlled study was designed to evaluate the safety and tolerability of intravaginal dextrin sulphate (D2S) gel to assess its preliminary suitability as a potential vaginal virucide. Tolerability was assessed by questionnaire and patient interview. Colposcopy with vaginal biopsy was performed to assess the macroscopic and microscopic evidence of inflammation. The potential impact of the gel on normal vaginal flora was examined by quantitative lactobacilli culture with assessment of the ratio of peroxide to nonperoxide-producing organisms. Colposcopy revealed mild erythema in five of 24 subjects receiving active gel and in none of the 12 placebo recipients, but histology in all subjects revealed no evidence of inflammation. No impact on vaginal lactobacilli was found. We conclude that D2S gel is safe and well tolerated intravaginally at the dosing schedule used in this study.

Administration, Intravaginal↗
PubMed1997

Correlates and consequences of harsh discipline for young children.

OBJECTIVE: To examine the incidence, predictors, and consequences of harsh discipline in a sample of low-birth-weight children at 1 and 3 years of age. DESIGN: Analysis of data from the Infant Health and Development Program, an 8-site randomized clinical trial of low-birth-weight infants. The sample for analysis consisted of 715 children who were 3 years of age. The independent measurements of primary interest were the mother's hitting and scolding of her child as disciplinary practice. Analyses were run separately for boys and girls. Bivariate and logistic analyses were used to examine the predictors of the mother's hitting and scolding behavior. Multivariate analysis of variance was used to examine the consequences of the mother's harsh discipline on a child's IQ measured at age 3 years. MAIN OUTCOME MEASURES: The mother's self-report of whether she used more than 1 physical punishment in the past week, as well as an observer's report from 2 home visits of whether the mother hit or scolded the child during the 2-hour home visit. In addition, the Stanford-Binet Intelligence Scale was used to examine the consequences of persistent harsh discipline on child well-being. RESULTS: Findings demonstrate child, maternal, and environmental factors that might aggravate a parent's use of corporal punishment. Boys received higher amounts of harsh discipline on all outcome measures. For boys, growing up in an impoverished home was predictive of the greater likelihood of receiving harsh punishment. Using IQ at age 3 years as the outcome measure, girls were found to be vulnerable to persistent harsh discipline and lack of maternal warmth. Maternal harsh discipline in a context of low maternal warmth was associated with IQ scores for girls that are 12 points lower than the IQ scores of girls who received low punishment and high warmth.

Analysis of Variance↗
PubMed1997

Role of inducible nitric oxide synthase in pharmacological "preconditioning" with monophosphoryl lipid A.

Pretreatment with monophosphoryl lipid A (MLA) can pharmacologically mimic the second window of ischemic preconditioning (SWOP) to protect the heart from prolonged ischemia and reperfusion injury. Based on the delayed time course for development of MLA associated cardioprotection, this study was designed to test if MLA's cardioprotective effect is mediated by signalling through production of inducible nitric oxide synthase (iNOS), a proposed effector of SWOP. Rabbits were assigned to one of four groups: (1) vehicle control; (2) MLA: (3) vehicle+aminoguanidine (AMG) control; or (4) MLA+AMG. Monophosphoryl lipid A (35 micrograms/kg) or vehicle was given intravenously 24 h before ischemia. The selective iNOS inhibitor AMG (300 mg/ kg) was injected subcutaneously 1 h before ischemia. All rabbits experienced 30 min coronary artery occlusion followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. followed by 3 h of reperfusion. Infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Myeloperoxidase activity, an index of neutrophil infiltration, was also quantified in heart tissue collected from the post-ischemic viable border zone surrounding the infarct area. MLA pretreatment significantly reduced infarct size and neutrophil infiltration in rabbit hearts compared to control (P < 0.05). Inhibition of iNOS activity by AMG abolished the infarct size reductive effect of MLA. Aminoguanidine also blocked the ability of MLA to significantly reduce neutrophil infiltration. Although measurement of iNOS activity did not show induction of the enzyme in normal myocardial tissue 24 h after MLA pretreatment, an increase in iNOS activity in ischemic tissue relative to non-ischemic tissue was found after either 15 or 30 min of coronary occlusion in MLA treated rabbits. These results suggest that MLA pretreatment may enhance iNOS enzyme activity by MLA during ischemia which may be responsible for the observed cardioprotection.

Adjuvants, Immunologic↗
PubMed1997

Lead-induced hypertension is not associated with altered vascular reactivity in vitro.

In confirmation of a previous study (Am J Hypertens 1993;6:723), mean arterial blood pressure (MBP), as determined by tail cuff plethysmography, was found to be significantly elevated in Sprague-Dawley rats after 3 months of feeding 0.48 mmol/L (100 ppm) lead acetate/day (144 +/- 3.3 [SEM], in lead-treated [L] v 107 +/- 3.3 mm Hg in controls [C], P < .001). Thoracic aorta was excised from L and C animals (n = 6). Segments were suspended in tissue baths with Krebs' bicarbonate solution, then tested sequentially for vasoreactivity to 68 mmol/L K+, followed by graded concentrations of phenylephrine (PE), 0.01 to 0.3 micromol/L, acetylcholine (Ach), 0.001 to 3 micromol/L, nitroprusside (SNP), 0.0001 to 0.1 micromol/L, norepinephrine (NE), 0.001 to 300 micromol/L. There were no differences between L and C animals with respect to either vasoconstrictors (PE and NE) or vasodilators (Ach and SNP). The tissue levels of cGMP measured with and without phosphodiesterase inhibition, and in the absence and presence of either Ach or SNP, were comparable in the two groups. We conclude that the intrinsic vascular responsiveness is unchanged in lead-treated animals. The elevation of MBP is due to the presence of circulating factor(s) and hemodynamic changes.

Acetylcholine↗
PubMed1997

Wada memory and timing of stimulus presentation.

We compared Wada memory performance for stimuli presented at two timing intervals following amobarbital injection in 47 non-lesional patients with complex partial seizures (L = 26; R = 21). A significant interaction between seizure focus and timing of presentation was present (P < 0.03). Memory performance for objects whose presentation began approximately 50-55 s following amobarbital administration differed as a function of ipsilateral vs. contralateral injection at a very high level of statistical significance (P < 0.00001). Items presented approximately 4 min, 30 s post injection were also related to seizure onset literality, but at a lower statistical level (P < 0.01). Presentation of Wada memory stimuli earlier during hemispheric anaesthesia yields results that are more sensitive to lateralized temporal lobe seizure onset than does presentation of items later during the procedure.

Adult↗
PubMed1997

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

Alleles↗
PubMed1997

Abdominal radical trachelectomy: a new surgical technique for the conservative management of cervical carcinoma.

Traditionally radical hysterectomy has formed the mainstay of treatment for early stage cervical carcinoma. More recently radical trachelectomy and laparoscopic lymphadenectomy have been introduced to allow preservation of fertility. We present a new approach to fertility-sparing surgery, namely abdominal radical trachelectomy. The technique is similar to a standard radical hysterectomy and lymphadenectomy. In our technique the ovarian vessels are not ligated and, following lymphadenectomy and skeletonisation of the uterine arteries, the cervix, parametrium and vaginal cuff are excised. The residuum of the cervix is then sutured to the vagina and the uterine ateries re-anastomosed.

Anastomosis, Surgical↗
PubMed1997

Antenatal serum screening for genital herpes: a study of knowledge and attitudes of women at a central London hospital.

OBJECTIVE: To evaluate the knowledge and attitudes of women regarding genital herpes and specifically serum screening for prevention of vertical transmission. SETTING: Antenatal clinic at the Chelsea and Westminster Hospital, London. POPULATION: Randomly selected women at their first antenatal visit. METHODS: A questionnaire focussing on the women's knowledge of, and their attitudes about, genital herpes was completed. The results were analysed using the Statistical Package for Social Sciences (SPSS). RESULTS: One hundred women were surveyed over six weeks. The majority (80%) were aware that genital herpes was a sexually transmitted disease and 60% were aware that it can be transmitted to the baby in pregnancy. Only 34% thought that genital herpes is always symptomatic and 56% believed that they would know for certain if they had herpes. Sixty percent thought they would know whether their partners had ever been infected. Eighty percent of our sample population were prepared to be screened, and 76% would also encourage their sexual partner to have a blood test. CONCLUSION: This study shows that the study population had a good knowledge about genital herpes and that there would be acceptance of antenatal testing. Whether serum screening is cost-effective must still be evaluated. The impact of such a screening on a couple's relationship is potentially deleterious and needs to be assessed carefully before a screening programme for genital herpes is actually introduced. The next phase of our study will address this issue.

Attitude to Health↗
PubMed1997

Adenosine induced polymorphic ventricular tachycardia in adults without structural heart disease.

Adenosine has been reported to cause polymorphic VT in patients with congenital or acquired prolonged QT intervals and to cause pause dependent VT in a patient with a normal QT interval. There have been no previous reports of adenosine causing nonpause dependent polymorphic VT in patients without structural heart disease. We report two patients, with normal hearts and normal QT intervals, who developed nonsustained polymorphic VT that was not pause dependent. Adenosine induced polymorphic VT does not appear to be a marker of the long QT syndrome, but may be an uncommon yet not unexpected pharmacological response to drug administration.

Adenosine↗
PubMed1997

Results of lesional vs. nonlesional frontal lobe epilepsy surgery.

Fifty-three seizure focus resections limited to the frontal lobe were performed. Forty-nine had adequate follow-up. Five of 17 (29%) nonlesional (NL) cases and 21 of 32 (66%) lesional (L) cases were seizure free (SF) at 1 year postoperatively. Eight of 9 (89%) L cases < or = 18 years old vs. 13 of 23 (57%) > 18 years old were SF. Eight of 10 (80%) tumor vs. 13 of 22 (59%) nontumor L cases were SF. Sixteen NL cases were localized by invasive recording. Five (31%) were SF. Ictal localization was obtained in 4 of 32 L cases. Three of 4 (75%) were SF. Eighteen of 24 (64%) L cases without ictal localization were SF. Nine of 12 (75%) lateral resections, 7 of 12 (58%) lobectomies, and 2 of 13 (15%) mesial resections were SF. Three of 20 cases with at least 90% reduction in seizures became SD > or = 2 years postresection. No case with < 90% seizure reduction at one year showed improvement with longer follow-up.

Adolescent↗
PubMed1997

A computerized business simulation for dental practice management.

Computerized simulations have been used for many years for teaching principles of management in business schools. This paper describes the development of a computerized business simulation for use in dental school practice management courses. The simulation is in a competitive game format. It requires students to formulate strategies and to implement management decisions that reinforce and fulfill that strategy. Participants use the outcomes of these decisions to formulate new management decisions for the upcoming period. Student response to participation in the simulation has been positive, with students indicating that participation is valuable for developing better understanding of analytical business management techniques and interpersonal techniques such as group process and leadership skills.

Commerce↗
PubMed1997

A pilot study comparing ketoprofen and acetaminophen with hydrocodone for the relief of postoperative periodontal discomfort.

The aim of this study was to compare ketoprofen to acetaminophen with hydrocodone (A/H) in a postoperative periodontal pain model. A double-blind protocol was used. Thirty minutes prior to each procedure, subjects were given orally either 100 mg ketoprofen or a placebo tablet. Four hours later, the subjects took either 50 mg ketoprofen (ketoprofen group) or 1000 mg acetaminophen with 10 mg hydrocodone (placebo group). Subjects reported levels of overall discomfort and pain using visual analog scales at eight hourly intervals following the first dose of ketoprofen or placebo. Information about adverse side effects was requested from the patients in the form of a checklist. The results revealed only small differences between the two drug regimens with respect to levels of pain or overall discomfort. A/H provided significantly better pain relief at Hours 5 and 6, while overall discomfort levels were significantly higher with ketoprofen than with placebo at Hours 3 and 4. Pain levels were low for both groups. It is recommended that additional analgesics for mild to moderate pain should be tested.

Acetaminophen↗
PubMed1996

Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search.

Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families with markers in this region resulted in significant evidence of linkage in the combined set of 91 families. The data provide strong evidence of a major prostate cancer susceptibility locus on chromosome 1.

Adult↗