Biomedical subjects
Publications and source records attributed to W Thomas.
Cytotoxic necrotizing factor 1 and Pasteurella multocida toxin induced dose- and time-dependent increases in focal adhesion kinase (FAK) Tyr397 phosphorylation in Swiss 3T3 cells. FAK autophosphorylation was sensitive to inhibitors of p160/ROCK and coincided with the formation of stable complexes between FAK and Src family members.
Lignans, similar in structure to endogenous sex steroid hormones, may act in vivo to alter hormone metabolism and subsequent cancer risk. The objective of this study was to examine effects of dietary intake of a lignan-rich plant food (flaxseed) on serum concentrations of endogenous hormones and binding proteins (estrone, estrone sulfate, 17 beta-estradiol, sex hormone-binding globulin, progesterone, prolactin, dehydroepiandrosterone sulfate, dehydroepiandrosterone, androstenedione, testosterone, and free testosterone) in postmenopausal women. This randomized, crossover trial consisted of three seven-week feeding periods, during which 28 postmenopausal women, aged 52-82 yr, consumed their habitual diets plus 0, 5, or 10 g of ground flaxseed. Serum samples collected during the last week of each feeding period were analyzed for serum hormones using standard diagnostic kits. The flaxseed diets significantly reduced serum concentrations of 17 beta-estradiol by 3.26 pg/ml (12.06 pmol/l) and estrone sulfate by 0.09 ng/ml (0.42 nmol/l) and increased prolactin by 1.92 micrograms/l (0.05 IU/ml). Serum concentrations of androstenedione, estrone, sex hormone-binding globulin, progesterone, testosterone, free testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were not altered with flaxseed feeding. In this group of postmenopausal women, consuming flaxseed in addition to their habitual diets influenced their endogenous hormone metabolism by decreasing serum 17 beta-estradiol and estrone sulfate and increasing serum prolactin concentrations.
BACKGROUND: There is an increase in the incidence of type 2 diabetes in children and adolescents. Absence of known diabetes autoimmune markers is sometimes required to confirm the diagnosis. OBJECTIVE: To identify clinical and autoimmune characteristics of type 2 diabetes in a pediatric population. METHOD: We report an analysis of 48 children and adolescents with type 2 diabetes, compared with 39 randomly selected children with type 1 diabetes, diagnosed and followed at the Loma Linda University Pediatric Diabetes Center. Ethnic, familial, seasonal, and autoimmune marker characteristics are outlined. To determine the reliability of antibody testing in confirming the type of diabetes at diagnosis, we studied the incidence of positive islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADs), and insulin autoantibodies (IAAs) at diagnosis in both groups. ICA512, GADs, and IAAs were measured by radioimmunoassay. RESULTS: The cohort with type 2 diabetes had a similar gender distribution as the group with type 1 diabetes but a significantly higher age at diagnosis. Ethnic background was significantly different between the 2 groups, predominantly Hispanic in type 2 and white in type 1. Body mass index was significantly higher in type 2 diabetes (mean = 31.24 kg/m(2)). Among the patients with type 2 diabetes, 33% presented in diabetic ketoacidosis, random blood glucose at diagnosis ranged from 11.4 to 22.25 mmol/L (228-445 mg/dL), fasting C-peptide levels ranged from 0.89 to 2.7 nmol/L (2.7-8.2 ng/mL; normal: <1.36 nmol/L), and hemoglobin A(1C) was 10.8 +/- 3.5% (normal: <6.6%). None of these parameters was significantly different from the type 1 diabetes group. Although the incidence of diabetes antibody markers was significantly lower in type 2 versus type 1 diabetes, 8.1% of patients with type 2 diabetes had positive ICAs, 30.3% had positive GADs, and 34.8% had positive IAAs without ever being treated with insulin. In the type 2 diabetes group, none of the Hispanic patients had ICAs. However, there was no significant correlation between any of the diabetes antibodies and obesity, presence of acanthosis nigricans, or family history of diabetes. The frequency of thyroid antibodies was not significantly different from the group with type 1 diabetes. Daily insulin requirements 1 year after diagnosis were significantly lower in type 2 diabetes, ranging from 0 to 1.2 U/kg with a mean of 0.33. CONCLUSION: Absence of diabetes autoimmune markers is not a prerequisite for the diagnosis of type 2 diabetes in children and adolescents.
The main purine analogues with activity against lymphoid malignancies are fludarabine, cladribine and pentostatin, all of which are active against slowly proliferating cells through their inhibition of DNA repair and therefore have significant synergistic activity with cytotoxic agents which cause DNA damage. Combinations of purine analogues and alkylating agents or platinum compounds result in markedly increased activity but at the expense of more severe haematological toxicity, while evidence of synergy with anthracyclines/anthracenediones is apparent in the treatment of malignant lymphoma. Interaction between fludarabine or cladribine with deoxycytidine kinase results in a significant enhancement of the activity of cytarabine. Unexpected evidence of clinical synergy is also apparent in combinations of purine analogues and anti-CD20 monoclonal antibodies.
The incidence of type 1 diabetes is increasing most rapidly in children under 5 yrs of age, a group where the disease appears to be more accelerated than traditional type 1 diabetes. Little is known about demographics, and markers of diabetes autoimmunity, in infants and pre-schoolers with type 1 diabetes. We report an analysis of 47 children diagnosed with type 1 diabetes prior to 5 yrs of age compared with a representative cohort (n=49) diagnosed after 5 yrs of age, and all were followed at Loma Linda University (LLU) Children's Hospital. Ethnic, familial, seasonal, and autoimmune marker characteristics are outlined. To determine the prevalence of diabetes autoimmune markers, ICA512, GAD65 and insulin autoantibodies (IAA) antibodies were measured. Children with early-onset diabetes had a significantly higher incidence of viral illness symptoms (p=0.005) and diabetic ketoacidosis (DKA; p=0.017) at the time of diagnosis. However, hemoglobin A1C (HbA1c) levels at diagnosis were significantly higher in the later-onset group (p=0.001). A honeymoon period was reported in 14.8% of children diagnosed before 5 yrs of age compared with 42.1% in those diagnosed over 5 yrs of age (p=0.038). Islet-cell antibodies (ICAs) and glutamic acid decarboxylase (GAD) antibody titers were significantly different between early- and later-onset groups. ICA titers were positive in 35.29%, and GAD in 41.38% of the early-onset group versus 70.83 and 71.74% in children with later-onset disease, (p=0.001 and 0.009, respectively). IAA titers, drawn after instituting insulin therapy, were not significantly different between the two groups. GAD and ICA512 antibody results suggest a relative lack of diabetes immune markers in infants and toddlers with new-onset diabetes. This finding, and the apparent shorter pre-clinical phase reflected in the lower HbA1c values, may indicate age-related differences in type 1 diabetes autoimmunity or the existence of non-autoimmune diabetogenic mechanisms in younger children.
BACKGROUND: About 9% of average dietary energy intake in the United States comes from fructose. Such a high consumption raises concern about the metabolic effects of this sugar. OBJECTIVE: The objective of this study was to determine the effect of dietary fructose on plasma lipids. DESIGN: The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center. The participants were 24 healthy adult volunteers (12 men and 12 women; 6 of each sex were aged <40 y and 6 of each sex were aged >/=40 y). All subjects received 2 isoenergetic study diets assigned by using a randomized, balanced crossover design. One diet provided 17% of energy as fructose. The other diet was sweetened with glucose and was nearly devoid of fructose. Each diet was fed for 6 wk. Both diets were composed of common foods and contained nearly identical amounts of carbohydrate, protein, fat, fiber, cholesterol, and saturated, monounsaturated, and polyunsaturated fatty acids. All meals were prepared in the metabolic kitchen of the General Clinical Research Center. RESULTS: The responses to the study diets differed by sex. In men, the fructose diet produced significantly higher fasting, postprandial, and daylong plasma triacylglycerol concentrations than did the glucose diet. The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32% greater in men than the corresponding concentration during the glucose diet (P: < 0.001). The fructose diet had no significant effect on fasting or postprandial plasma triacylglycerol concentrations in women. The fructose diet also had no persistent effect on fasting plasma cholesterol, HDL cholesterol, or LDL cholesterol in either men or women. CONCLUSIONS: Dietary fructose was associated with increased fasting and postprandial plasma triacylglycerol concentrations in men. Diets high in added fructose may be undesirable, particularly for men. Glucose may be a suitable replacement sugar.
Previous studies comparing the sensitivity between different radiological exams have concluded that conventional axial computed tomography (CT; nonhelical) is unsuitable in the assessment of mandibular fractures. Axial CT was shown to have a reduced sensitivity compared with plain radiographs and panoramic tomography because it missed nondisplaced fractures in the posterior portion of the mandible. Because the resolution of CT has improved from the time of these previous studies, the authors were interested in assessing whether axial CT (nonhelical) could now provide additional clinically useful information and enhance our understanding of mandibular fractures, beyond that obtained from panoramic tomography alone. In their study, 5 staff surgeons initially evaluated the panoramic tomograms and then the CT scans of 39 patients with 66 fractures. A series of four questions assessed the relative contribution of these two radiological exams in formulating an optimal operative plan for each patient. The authors found that axial CT provided supplementary information regarding missed fractures, comminution, and the exact size and degree of displacement of fracture fragments. This additional data could have changed the operative plan in a substantial proportion of patients (17 of 39). Axial CT demonstrated two missed parasymphyseal fractures (2 of 39 patients) that were not seen on these patients' panoramic tomograms. Axial CT also revealed undiscovered comminution or demonstrated fracture displacement more precisely in 39% of patients (15 of 39) and 24% of fractures (16 of 66). This study demonstrates that axial CT was clinically useful as an additional investigation to panoramic tomography. Axial CT helped elucidate further the nature of suspected mandibular fractures.
OBJECTIVE: The objective of this study was to examine whether parental assessment of a child's usual behavioral reaction to common painful events predicts the child's ratings of needle pain intensity from routine venipuncture. DESIGN: Children aged 3 to 12 years (n = 88) used the Faces Pain Scale to rate how much venipuncture hurt and also indicated whether the pain was more, less, or the same as expected. The child's parent (mother) used the same scale to predict how much the needle would hurt the child as well as to rate the child's pain as observed at the time of venipuncture. Parents also estimated their child's usual reaction to six common painful events. An independent observer used a behavioral checklist to rate the child's pain response at the time of venipuncture as well as to assign a global pain rating on the Faces Pain Scale. OUTCOME MEASURES: The Faces Pain Scale and a behavioral checklist (scoring facial, vocal, motor, and verbal reactions) were used in this study. RESULTS AND CONCLUSIONS: Those children who reported venipuncture as hurting more than expected also gave the highest mean needle pain ratings and tended to have their pain underpredicted by their parents before venipuncture. For these children, parental estimates of reactions to other painful events proved to be a useful predictor of self-reported needle pain. Parent and child ratings of pain agreed more closely for those parents who indicated having relied on what their child "did" rather than "said." Additionally, and consistent with previous studies, independent observation of children's facial responses was the most useful indicator of needle pain severity. Preparation of children for venipuncture may be enhanced by asking a parent beforehand how the child usually responds to everyday pain. Specifically, reaction to other sharp time-limited pains (e.g., finger pinch, stepping on a prickle) may provide a useful guide to identifying which children will report experiencing greater pain than expected from venipuncture.
In contrast to other commonly employed models, the cut model femoral neck prosthesis is a cementless prosthesis of comparatively small dimensions. With the aim of investigating its functional integration in the femur, radiological, densitometric and photoelastic analyses were carried out. The biomechanical reaction of the bone tissue expected on the basis of the experimental result is tested in the clinical situation.
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Neutral endopeptidase 24.11 (NEP) inhibitors are known to have vascular, diuretic, and natriuretic effects that may be helpful in the treatment of congestive heart failure (CHF). Most NEP inhibitors may act principally through intrarenal mechanisms, which are not completely understood. The purpose of this study was to determine the principal renal effects of the NEP inhibitor ecadotril in dogs with progressive CHF induced by rapid ventricular pacing. Renal function was measured before, during, and after acute i.v. infusion of normal saline in a total of six dogs during normal cardiac function, early left ventricular dysfunction, and overt CHF. During overt CHF, each dog was treated with either ecadotril or placebo orally for 1 week. Parameters measured included glomerular filtration rate, renal blood flow, urine output, sodium clearance, sodium fractional excretion, and proximal and distal sodium reabsorption. Ecadotril treatment resulted in increased urine output, sodium clearance, and renal sodium excretion relative to placebo-treated controls. The principal intrarenal effect of ecadotril was decreased distal renal tubular sodium reabsorption. Both glomerular filtration rate and renal blood flow declined during overt CHF and were unaffected by ecadotril treatment. The results of this study are consistent with the principal action of ecadotril occurring by way of intrarenal events as opposed to changes in renal hemodynamics. The principal effect of ecadotril on distal tubular sodium reabsorption suggests that inhibition of NEP activity in the proximal renal tubules may allow increased binding of filtered atrial natriuretic peptide to natriuretic peptide receptor sites in the distal renal tubules and collecting ducts.
Estrogen is metabolized along two competing pathways to form the 2-hydroxylated and the 16alpha-hydroxylated metabolites. Based on proposed differences in biological activities, the ratio of these metabolites, 2-hydroxyestrogen:16alpha-hydroxyestrone (2:16alpha-OHE1), has been used as a biomarker for breast cancer risk. Women with an elevated 2:16alpha-OHE1 ratio are hypothesized to be at a decreased risk of breast cancer. Flaxseed, the most significant source of plant lignans, and wheat bran, an excellent source of dietary fiber, have both been shown to have chemoprotective benefits. Some of these benefits may be attributable to their influence on endogenous sex hormone production and metabolism. We examined the effect of flaxseed consumption alone and in combination with wheat bran on urinary estrogen metabolites in premenopausal women. Sixteen premenopausal women were studied for four feeding treatments lasting two menstrual cycles each in a randomized cross-over design. During the four feeding treatments, subjects consumed their usual diets supplemented with baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Urinary excretion of 2-hydroxyestrogen and 16alpha-hydroxyestrone, as well as their ratio, 2:16alpha-OHE1, were measured by enzyme immunoassay. Flaxseed supplementation significantly increased the urinary 2:16alpha-OHE1 ratio (P = 0.034), but wheat bran had no effect. These results suggest that flaxseed may be chemoprotective in premenopausal women.
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Dietary estrogens, such as lignans, are similar in structure to endogenous sex steroid hormones and may act in vivo to alter hormone metabolism and subsequent cancer risk. The objective of this study was to examine the effect of dietary intake of a lignan-rich plant food (flaxseed) on urinary lignan excretion in postmenopausal women. This randomized, cross-over trial consisted of three 7-week feeding periods during which 31 healthy postmenopausal women, ages 52-82 years, consumed their habitual diets plus 0, 5, or 10 grams of ground flaxseed per day. Urine samples collected for 2 consecutive days during the last week of each feeding period were analyzed for lignan content (enterodiol, enterolactone, and matairesinol) by isotope dilution gas chromatography/mass spectrometry. Compared with the 0-gram flaxseed diet, consumption of 5 or 10 grams of flaxseed significantly increased excretion of enterodiol by 1,009 and 2,867 nmol/day, respectively; significantly increased excretion of enterolactone by 21,242 and 52,826 nmol/day, respectively; and significantly increased excretion of total lignans (enterodiol + enterolactone + matairesinol) by 24,333 and 60,640 nmol/day, respectively. Excretion of matairesinol was not significantly altered by flaxseed consumption. Consumption of flax, a significant source of dietary estrogens, in addition to their habitual diets increased excretion of enterodiol and enterolactone, but not matairesinol, in a dose-dependent manner in this group of postmenopausal women. Urinary excretion of lignan metabolites is a dose-dependent biomarker of flaxseed intake within the context of a habitual diet.
BACKGROUND: We report novel techniques of performing bidirectional Glenn shunt (BDG) without cardiopulmonary bypass (CPB). METHODS: Five cases of single ventricle and pulmonary stenosis (PS) complex were taken up for BDG without CPB. The criteria for case selection were an unrestrictive atrial septal defect (ASD), no atrioventricular (AV) valve regurgitation, and no other intracardiac defects requiring correction. A temporary shunt was established between the superior vena cava (SVC) and contralateral branch pulmonary artery (PA) for venous drainage during SVC clamping for BDG anastomosis in four cases. In case 5, a shunt was put between the SVC and right atrium (RA) for venous drainage, and modified Blalock Taussig shunt and patent ductus arteriosus (PDA) were left open until the completion of the BDG. RESULTS: Central venous pressure (CVP) increased to a mean of 22.4 mm Hg during SVC clamping, with improvement of oxygen (O2) saturation from 62.4% to 82.4%. After Glenn shunt, CVP and O2 saturation maintained at 13.2 mm Hg and 87.4%, respectively. Postoperatively, there were no neurological abnormalities and no hospital mortality. CONCLUSIONS: Our technique provides an excellent venous drainage with improvement of O2 saturation during SVC clamping. It avoids problems related to CPB and economy. It is easily reproducible, with excellent results in a selected group of patients without compromising the completeness of repair.
Age and sex differences were investigated in children's self-report of venipuncture pain. Equal numbers of boys and girls aged 3-15 years (n = 110) made separate ratings of the intensity and unpleasantness of their needle pain, using a paired Visual Analogue Scale (VAS) technique. The parents of these children used the same method to give ratings of predicted pain and unpleasantness before the needle, as well as ratings based on observing their child during the needle. Results showed that, across age, children's intensity and unpleasantness scores were highly correlated (r = 0.78), and that both of these ratings decreased with increasing age. Analyses of covariance showed that, with the variance in the unpleasantness ratings accounted for, a significant age main effect persisted for the intensity ratings (scores decreasing with increasing age), with no effect of sex. In the corollary analysis, with intensity scores entered as a covariate, unpleasantness ratings showed no main effect of age, but a significant main effect of sex emerged: girls' ratings of pain unpleasantness, when averaged across age, were significantly higher than boys'. The interaction between age and sex was explored in analysis of the relative difference between intensity and unpleasantness ratings. The results indicated that, from approximately 8-years of age, children (especially girls) gave significantly higher ratings of unpleasantness than sensory intensity of needle pain. Prior to the age of 8 years, children tended to give equivalent ratings of intensity and unpleasantness, with no evidence of a sex difference. The agreement between parental and children's ratings was higher for parents' observed, as opposed to predicted, scores, especially for pain intensity, with no systematic influence of the child's age and sex. In conclusion, it is suggested that age effects in children's self-report of needle pain are predominantly manifest in ratings of sensory intensity, whilst sex effects are predominantly manifest in ratings of an affective (unpleasantness) dimension. It is argued that both age and sex differences are largely the function of pain reporting variables, rather than reflecting fundamental age or sex based variance in nociceptive processing.
BACKGROUND: There is increasing evidence that the house dust mite Euroglyphus maynei may be a significant source of allergic sensitization. The structural information for the E. maynei allergens is largely restricted to a single partial genomic sequence of Eur m 1. METHODS: A cDNA library was constructed from a culture of E. maynei. Clones encoding the major group 1 and 2 allergens were isolated by DNA hybridization and sequenced. RESULTS: The sequence of several full length clones of Eur m 1 and Eur m 2 were obtained. The full pre-proenzyme sequence of the cysteine protease Eur m 1 was determined. The translated amino acid sequence of Eur m 1 and Eur m 2 had 84-86% sequence identity with the corresponding allergens from Dermatophagoides pteronyssinus and Dermatophagoides farinae mites. This is the same as the degree of sequence identity found between D. pteronyssinus and D. farinae despite Euroglyphus being a member of the Pyroglyphinae subfamily rather than the Dermatophagoidinae subfamily. CONCLUSION: The sequences of the major Eur m 1 and Eur m 2 allergens are described. Their degree of divergence from the Dermatophagoides spp. is similar to that observed between D. pteronyssinus and D. farinae group 1 and group 2 allergens.