Diabetes: what Americans don't know can kill them.
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Diabetes Complications↗
Biomedical subjects
S Collins
Publications and source records attributed to S Collins.
Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.
PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.
Electric Stimulation Therapy↗
Potential pitfalls in the differential diagnosis of irritable bowel syndrome.
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Colonic Diseases, Functional↗
Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes.
We previously demonstrated that the expression and function of the adipocyte-specific beta3-adrenergic receptor (beta3AR) are significantly depressed in single gene and diet-induced rodent models of obesity. Furthermore, these models are relatively unresponsive to the anti-obesity effects of beta3AR agonists. Because all of these models are hyperinsulinemic, we hypothesized that hyperinsulinemia could be responsible for this abnormality in beta3AR function. The goal of this study was to determine whether lowering insulin with the K-ATP channel agonist, diazoxide (Dz) would reverse the depressed expression and function of the beta3AR found in a model of diet-induced diabetes and obesity in C57BL/6J (B6) mice. B6 male mice were placed on either high fat (HF) or low fat experimental diets. After 4 weeks, HF-fed mice were assigned to a group: HF or HF containing disodium (R,R)-5- [2-( [2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl-1,3-benzodioxole-2,2-di carboxylate (CL; 0.001%, wt/wt), Dz (0.32%, wt/wt), or their combination (CLDz). Dz animals exhibited significantly reduced plasma insulin levels as well as increased 3pAR expression and agonist-stimulated adenylyl cyclase activity in adipocytes. CLDz was more effective in reducing percent body fat, lowering nonesterified fatty acids, improving glucose tolerance, and reducing feed efficiency than either treatment alone.
Adipocytes↗
Treatment of self-mutilation with olanzapine.
BACKGROUND: Self-mutilation or dermatitis artefacta is a facet of a much broader spectrum of factitial disease. Three nonpsychotic patients with self-mutilation are presented in this article who were successfully treated with low dose olanzapine when all other modalities of therapy had failed, including trials with numerous antidepressants and antipsychotics. OBJECTIVE: The patients were simultaneously evaluated and treated by a dermatologist and a psychiatrist who run the psychodermatology or consultation-liaison clinic based at McMaster University. After dermatologic conditions had been excluded as a cause of the clinical findings, olanzapine was prescribed on a trial basis due to its low risk of parkinsonian side-effects and its antihistaminic properties. CONCLUSIONS: The excellent clinical response of the patients can be attributed to the low side-effect profile of the drug but also to the anti-impulsive effect which stems not only from antihistaminic properties but also from its antidopamine and serotonin-blocking action.
Adult↗
Activation of
Reversible C(6)F(5) transfer takes place between the boron centers in the anion formed by methide abstraction from [MeZr{N(SiMe(3))(2)}(3)] or [Cp(2)ZrMe(2)] (L(n)M-CH(3) in the reaction scheme) by the perfluorinated diborane 1. The solution chemistry of the metallocenium ion pairs formed from 1 and [Cp(2)ZrMe(2)] is correlated with the observed ethylene polymerization behavior of 1 in comparison to the monoborane B(C(6)F(5))(3), the related diborane 1,2-C(6)H(4)[B(C(6)F(5))(2)](2), and the 9,10-diboraanthracene compound 9,10-(C(6)F(5))(2)C(12)B(2)F(8).
Journal Article↗
Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob disease.
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Aged↗
The beta3-adrenergic receptor activates mitogen-activated protein kinase in adipocytes through a Gi-dependent mechanism.
Promiscuous coupling between G protein-coupled receptors and multiple species of heterotrimeric G proteins provides a potential mechanism for expanding the diversity of G protein-coupled receptor signaling. We have examined the mechanism and functional consequences of dual Gs/Gi protein coupling of the beta3-adrenergic receptor (beta3AR) in 3T3-F442A adipocytes. The beta3AR selective agonist disodium (R, R)-5-[2[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL316,243) stimulated a dose-dependent increase in cAMP production in adipocyte plasma membrane preparations, and pretreatment of cells with pertussis toxin resulted in a further 2-fold increase in cAMP production by CL316,243. CL316,243 (5 microM) stimulated the incorporation of 8-azido-[32P]GTP into Galphas (1.57 +/- 0.12; n = 3) and Galphai (1. 68 +/- 0.13; n = 4) in adipocyte plasma membranes, directly demonstrating that beta3AR stimulation results in Gi-GTP exchange. The beta3AR-stimulated increase in 8-azido-[32P]GTP labeling of Galphai was equivalent to that obtained with the A1-adenosine receptor agonist N6-cyclopentyladenosine (1.56 +/- 0.07; n = 4), whereas inclusion of unlabeled GTP (100 microM) eliminated all binding. Stimulation of the beta3AR in 3T3-F442A adipocytes led to a 2-3-fold activation of mitogen-activated protein (MAP) kinase, as measured by extracellular signal-regulated kinase-1 and -2 (ERK1/2) phosphorylation. Pretreatment of cells with pertussis toxin (PTX) eliminated MAP kinase activation by beta3AR, demonstrating that this response required receptor coupling to Gi. Expression of the human beta3AR in HEK-293 cells reconstituted the PTX-sensitive stimulation of MAP kinase, demonstrating that this phenomenon is not exclusive to adipocytes or to the rodent beta3AR. ERK1/2 activation by the beta3AR was insensitive to the cAMP-dependent protein kinase inhibitor H-89 but was abolished by genistein and AG1478. These data indicate that constitutive beta3AR coupling to Gi proteins serves both to restrain Gs-mediated activation of adenylyl cyclase and to initiate additional signal transduction pathways, including the ERK1/2 MAP kinase cascade.
3T3 Cells↗
Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene.
Protein tyrosine phosphatase-1B (PTP-1B) has been implicated in the negative regulation of insulin signaling. Disruption of the mouse homolog of the gene encoding PTP-1B yielded healthy mice that, in the fed state, had blood glucose concentrations that were slightly lower and concentrations of circulating insulin that were one-half those of their PTP-1B+/+ littermates. The enhanced insulin sensitivity of the PTP-1B-/- mice was also evident in glucose and insulin tolerance tests. The PTP-1B-/- mice showed increased phosphorylation of the insulin receptor in liver and muscle tissue after insulin injection in comparison to PTP-1B+/+ mice. On a high-fat diet, the PTP-1B-/- and PTP-1B+/- mice were resistant to weight gain and remained insulin sensitive, whereas the PTP-1B+/+ mice rapidly gained weight and became insulin resistant. These results demonstrate that PTP-1B has a major role in modulating both insulin sensitivity and fuel metabolism, thereby establishing it as a potential therapeutic target in the treatment of type 2 diabetes and obesity.
Animals↗
Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study.
BACKGROUND: Apart from the small number of iatrogenic and familial cases, the cause of most cases of Creutzfeldt-Jakob disease (CJD) is not known. We aimed to identify risk factors for sporadic CJD. METHODS: In a case-control study, we compared the medical history and selected demographic characteristics of 241 definite (neuropathologically confirmed) and probable (clinically likely) patients with CJD, ascertained from the Australian National Creutzfeldt-Jakob Disease Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls, recruited from the community by random telephone interview in August, 1997. Standard logistic regression was used for the comparisons. FINDINGS: Surgical procedures were significantly associated with the development of sporadic CJD. This risk progressively increased with the number of surgical treatments to a maximum for three procedures (odds ratio 2.13 [95% Cl 1.34-3.41], p=0.002). There was also a significant association between risk of CJD and residence or employment on a farm (p<0.001) or market garden (p=0.002) for longer than 10 years. We found no significant risk associated with a history of blood transfusion, organ transplantation, major dental work, or occupation. INTERPRETATION: Our findings accord with the hypothesis that a range of surgical treatments may serve as unrecognised contamination events and account for a proportion of cases of sporadic CJD. Possible biases in different methods and times for the acquisition of data on cases and controls suggest our findings need to be replicated in independent studies with community controls.
Adolescent↗
Failure of cricopharyngeal myotomy to improve dysphagia following head and neck cancer surgery.
OBJECTIVE: To determine whether cricopharyngeal myotomy can improve dysphagia associated with head and neck cancer surgery. DESIGN: Prospective, randomized, multicenter trial. SETTING: Twelve clinical sites across the United States. PATIENTS: Between 1989 and 1994, 125 patients undergoing combined modality therapy for head and neck cancer, including resection of the tongue base or supraglottic larynx, were prospectively entered into the trial. INTERVENTION: Cricopharyngeal myotomy on a randomized basis. MAIN OUTCOME MEASURES: Videofluoroscopic examination to determine oropharyngeal swallowing efficiency, which is defined as the ratio of percentage of the bolus swallowed to total swallowing time using 3 different bolus consistencies. RESULTS: No significant difference in oropharyngeal swallowing efficiency between myotomy vs no myotomy was seen at 6 months of follow-up regardless of bolus consistency. CONCLUSIONS: In this prospective test of cricopharyngeal myotomy, the procedure fails to significantly improve dysphagia associated with head and neck cancer surgery. The efficacy of this surgical procedure in other disease entities should also be rigorously explored.
Adult↗
3D coronary artery imaging with phase reordering for improved scan efficiency.
Three-dimensional (3D) coronary imaging has the potential to overcome problems resulting from vessel tortuosity and to reduce partial volume effects. With these techniques, however, acquisition times are long and respiratory motion artifacts problematical. This work describes the development of a method that applies phase encode reordering to 3D acquisitions, allowing larger navigator acceptance windows to be used, with a consequent reduction in acquisition time. This method is compared with navigator acceptance window methods (the acceptance-rejection algorithm and the diminishing variance algorithm) and the retrospective respiratory gating technique, both in vitro and in vivo. The use of phase reordering with a 10 mm acceptance window provided a significant increase in scan efficiency over a non-reordered 5 mm method (P<0.001) with no significant change in image quality, and a significant increase in image quality compared with a non-reordered image acquired in the same time (P<0.05). A significant improvement in both image quality and scan efficiency was demonstrated over the retrospective respiratory gating method (P<0.05).
Adult↗
Use of a handheld, battery-operated chemistry analyzer for evaluation of heat-related symptoms in the backcountry of Grand Canyon National Park: a brief report.
STUDY OBJECTIVES: To test the feasibility of using handheld, battery-operated chemical analyzers by EMS personnel in a wilderness environment to aid in the diagnosis and management of heat illness. METHODS: During the summer of 1996, 3 portable clinical analyzers (i-STAT Corp, Princeton, NJ) were kept at different locations along the main hiking trail into the Grand Canyon. An operational protocol was designed for field use, and Park Service EMS personnel used the instruments at their discretion, primarily to determine serum sodium concentration and identify cases of hyponatremia. Data were collected on all EMS encounters. This study reviews our experience with the instruments. RESULTS: The i-STAT analyzer was used for 64 patients in the backcountry; of these uses, at least 22 were in the field and the remainder in backcountry ranger stations. Eight error messages were recorded in 6 patients. Subsequently, all but 1 had a successful determination. Among patients evacuated for further evaluation and care, serum sodium values were highly consistent with later analysis using standard laboratory equipment. The instrument was used in 31 (48%) of 64 of patients evaluated and released for self-treatment and self-evacuation, and 31 (36%) of 87 of patients evacuated by EMS personnel from the canyon. Nine cases of hyponatremia were confirmed in the field, allowing appropriate intervention. CONCLUSION: Portable clinical analyzers can reliably be used in a hot wilderness environment. In our application, it allowed identification of exercise-associated hyponatremia, an important cause of serious heat illness during endurance exercise in a hot environment. The results helped make treatment and disposition decisions.
Arizona↗
A population-based survey of the management of women with cancer of the cervix.
The aim of this study was to investigate the influence of diagnostic throughput on survival outcome for women with cancer of the cervix. We conducted a case note review of 359 women in Lancashire and Greater Manchester diagnosed with cancer of the cervix during 1990, identified from records held by the North Western Regional Cancer Registry. Univariate and multivariate survival analyses were undertaken to investigate the influence on survival of woman, disease and treatment related factors. Following adjustment for woman- and disease-related factors there was no evidence of a statistically significant association between diagnostic throughput and survival. The findings of this study do not support the need for any change in the referral patterns to gynaecologists of women with symptoms suggestive of cancer of the cervix.
Adenocarcinoma↗
Depressed expression of adipocyte beta-adrenergic receptors is a common feature of congenital and diet-induced obesity in rodents.
OBJECTIVE: To determine whether the dramatic reduction in expression and functional activity of the beta3-adrenergic receptor (AR) and beta1AR subtypes originally observed in adipose tissue of the C57BL/6J Lep(ob)/Lep(ob) ('obese') mouse are general features of all models of obesity, and whether obesity-related differences in betaAR subtype expression occur between adipose depots. DESIGN: Survey of adipose tissue betaAR expression from four mouse models of congenital obesity: the 'obese' mouse (C57BL/6J Lep(ob)/Lep(ob)), the 'diabetic' mouse (C57BL/KsJ LepRdb/LepRdb), the 'tubby' mouse (C57BL/6J tub/tub) and the 'fat' mouse (C57BL/KsJ Cpe(fat)/Cpe(fat)), and in a model of high-fat diet-induced obesity in C57BL/6J mice. MEASUREMENTS: Expression of the betaAR subtypes was measured by Northern blot hybridization in white and brown adipose depots. RESULTS: In the severely obese Lep(ob) and LepRdb mice, mRNA concentrations of beta3AR and beta1AR in white adipose tissue (WAT) were decreased by > 99% and by > 70%, respectively. More modest effects on beta3AR expression were observed in brown adipose tissue (BAT, decreased by 20 - 30%). In less severe forms of obesity, as found in the tubby and carboxypeptidase (Cpe)fat mice, and in diet-induced obese B6 mice, beta3AR expression was decreased in WAT by up to 90%, with more modest decreases in interscapular BAT (IBAT). Changes in beta1AR mRNA concentrations were more variable. Beta2AR mRNA levels did not differ in most cases, with the exception that there was a 3-5-fold increase in BAT for both Lep(ob) and LepRdb mice. CONCLUSIONS: Impaired expression of adipocyte betaAR subtypes is a general feature of both genetic and dietary obesity in mice. The degree of obesity is correlated with the extent of loss of beta3AR and beta1AR expression in WAT. The distinct endocrine abnormalities associated with these obesity models may be responsible for the degree of impaired adipocyte betaAR expression.
Adipocytes↗
Influence of volume of work on the outcome of treatment for patients with colorectal cancer.
BACKGROUND: Recent recommendations for the reorganization of cancer services emphasize the importance of a 'minimal acceptable volume of work'. The influence of both hospital and surgical workload has been examined using a population-based series of patients with colorectal cancer. METHODS: Nine hundred and twenty-seven patients with primary colorectal cancer diagnosed during the period 1 January to 30 June 1993 were identified from the North Western Regional Cancer Registry. Case notes were reviewed for information on patient age and sex, histological diagnosis, disease stage, degree of tumour differentiation, mode of admission, identity of operating surgeon, timing of operative procedure, and use of radiotherapy and/or chemotherapy. A multivariate Cox proportional hazards model was then constructed to examine, simultaneously, the effects of patient-, disease- and health service-related variables on survival. RESULTS: Age, tumour stage and differentiation, and mode of admission were revealed as significant independent prognostic variables. After adjusting for these variables, neither operator grade (consultant versus junior), consultant workload nor hospital throughput were identified as independently influencing patient survival. CONCLUSION: The results of this study do not support an association between volume of work and patient outcome.
Adult↗
Science education partnership between the University of Colorado and a Denver High School.
The authors describe a partnership, begun in 1997, between Manual High School, a school in which about 85% of the students are African, American or Hispanic, and the University of Colorado Health Sciences Center in Denver. There are three partnership goals: help teachers transform a lecture-based curriculum into an inquiry-based curriculum, help students build their science knowledge, and give students opportunities to learn--and become excited--about careers in medicine. The current emphasis of the partnership is at the ninth-grade level. The first unique aspect of the partnership is the Medical Explorers program. One portion of the program begins when a hypothetical teenage car-crash victim arrives at the emergency room; over the next six weeks, practicing health care professionals dramatize their medical responsibilities to this patient and discuss the academic training necessary to fulfill those responsibilities. In addition, the Medical Explorers students travel to the Health Sciences Center, where they tour laboratories and clinics, help conduct experiments, and explore computer-based surgical simulations. The second unique program is a service learning project in which ninth-grade students assist with an activity that gives elementary school students a chance to participate in the process of scientific inquiry and to discover the wonder of real hearts and lungs; the ninth-graders assist with logistics (e.g., they distribute newspapers), and, more important, interact with the younger students by asking thoughtful questions of them. The partnership plans to incorporate the elementary and middle schools that graduate their students to Manual High School in order to encourage the implementation of inquiry-based science curricula and to provide sustained support to teachers throughout the entire K-12 educational pathway. If medical colleges can help teachers provide a consistent classroom draw for student fascination in science and medicine, then the colleges are more likely to help create a rich diversity of students who pursue careers in medicine.
Adolescent↗
Lipid infusion lowers sympathetic nervous activity and leads to increased beta-cell responsiveness to glucose.
We investigated the possible involvement of the autonomic nervous system in the effect of a long-term elevation of plasma free fatty acid (FFA) concentration on glucose-induced insulin secretion (GIIS) in rats. Rats were infused with an emulsion of triglycerides (Intralipid) for 48 hours (IL rats). This resulted in a twofold increase in plasma FFA concentration. At the end of infusion, GIIS as reflected in the insulinogenic index (DeltaI/DeltaG) was 2.5-fold greater in IL rats compared with control saline-infused rats. The ratio of sympathetic to parasympathetic nervous activities was sharply decreased in IL rats relative to controls. GIIS was studied in the presence of increasing amounts of alpha- and beta-adrenoreceptor agonists and antagonists. The lowest concentrations of the alpha2A-adrenoreceptor agonist oxymetazoline, which were ineffective in control rats, reduced GIIS in IL rats. At the dose of 0.3 pmol/kg, GIIS became similar in IL and control rats. The use of beta-adrenoreceptor agonist (isoproterenol) or antagonist (propranolol) did not result in a significant alteration in GIIS in both groups. GIIS remained as high in IL vagotomized rats as in intact IL rats, indicating that changes in parasympathetic tone were of minor importance. Altogether, the data show that lipid infusion provokes beta-cell hyperresponsiveness in vivo, at least in part through changes in alpha2-adrenergic innervation.
Animals↗