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Biomedical subjects

S Collins

Publications and source records attributed to S Collins.

At least 91 records · Page 5Linked to original sources

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↗

Interaction between impaired and unimpaired speakers: inter-subjectivity and the interplay of culturally shared and situation specific knowledge.

The part played by culturally shared knowledge in interaction is generally recognised. However, the details of how it may be manifested in interaction are largely undocumented. This study explores this issue in the context of interactions between impaired and unimpaired speakers, using a conversation analytic approach in combination with a communication task commonly employed in experimental social psychology. Three exemplary cases are analysed. Results show that when the task interaction is co-constructed, the interaction is collaboratively enacted, participants' actions are in alignment, and the task outcome is relatively accurate. When the unimpaired speaker proceeds on the basis of culturally shared knowledge, and thereby 'unilaterally' manages the interaction, two courses of action are available to the impaired speaker. The impaired speaker may make attempts to provide situation specific details. In this case, because each participant is drawing on different resources to construct the interaction, their actions are out of alignment, and the task outcome is less accurate. Alternatively, the impaired speaker may concur with the culturally shared knowledge drawn on by the unimpaired speaker, in which case the participants' actions are in alignment, but the task outcome is highly inaccurate. The authors conclude that by combining a conversation analytic approach with a communication task which reflects participants' everyday experiences, orientations to different interaction resources can be drawn out. This can have relevance for, and help to elicit, practices in everyday interaction.

Adult↗

The Texarkana mercury incident.

In November 1997, 2 teenagers allegedly removed a large amount of metallic mercury from an abandoned sign plant and distributed the material among friends. One teenager developed symptoms and admitted playing with mercury to his physician. His blood mercury was elevated. In February 1998, faculty from the University of Texas Health Center at Tyler conducted an investigation that included in-depth evaluations on 10 patients with urine mercury concentrations up to 100 micrograms/L. Exposure pathways and timelines were reconstructed from records assembled by the Arkansas State Health Department epidemiologist. Mercury contamination was found among teenagers, children, and adults who came in contact with the metal. Biomarkers of exposure documented reduction in mercury concentrations after these persons were removed from their homes and sources of mercury. Neurobehavioral assessment, including assessment of tremor, failed to establish a relationship between mercury exposure and performance.

Adolescent↗

BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast.

We report here the cloning and functional analysis of a novel homologue of the mitochondrial carriers predominantly expressed in the central nervous system and referred to as BMCP1 (brain mitochondrial carrier protein-1). The predicted amino acid sequence of this novel mitochondrial carrier indicates a level of identity of 39, 31, or 30%, toward the mitochondrial oxoglutarate carrier, phosphate carrier, or adenine nucleotide translocator, respectively, and a level of identity of 34, 38, or 39% with the mitochondrial uncoupling proteins UCP1, UCP2, or UCP3, respectively. Northern analysis of mouse, rat, or human tissues demonstrated that mRNA of this novel gene is mainly expressed in brain, although it is 10-30-fold less expressed in other tissues. In situ hybridization analysis of brain showed it is particularly abundant in cortex, hippocampus, thalamus, amygdala, and hypothalamus. Chromosomal mapping indicates that BMCP1 is located on chromosome X of mice and at Xq24 in man. Expression of the protein in yeast strongly impaired growth rate. Analysis of respiration of total recombinant yeast or yeast spheroplasts and in particular of the relationship between respiratory rate and membrane potential of yeast spheroplasts revealed a marked uncoupling activity of respiration, suggesting that although BMCP1 sequence is more distant from the uncoupling proteins (UCPs), this protein could be a fourth member of the UCP family.

Amino Acid Sequence↗

Diet-induced changes in uncoupling proteins in obesity-prone and obesity-resistant strains of mice.

Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased by high fat feeding in adipose tissue of the A/J strain of mice, which is resistant to the development of dietary obesity. More recently, a third UCP (UCP3) was identified, which is expressed largely in skeletal muscle and brown adipose tissue. The UCP2 and UCP3 genes are located adjacent to one another on mouse chromosome 7. Thus, the roles of these UCPs in both metabolic efficiency and the linkage to obesity and diabetes syndromes is unclear. For this reason, we examined the expression of UCP2 and UCP3 in white adipose tissue and interscapular brown adipose tissue and in gastrocnemius/soleus muscle preparations from the obesity-resistant A/J and C57BL/KsJ (KsJ) strains and the obesity-prone C57BL/6J (B6) mouse strain. In both KsJ and A/J mice, UCP2 expression in white fat was increased approximately 2-fold in response to 2 weeks of a high fat diet, but there was no effect of diet on UCP2 levels in B6 mice. In skeletal muscle and in brown fat, neither UCP2 nor UCP3 expression was affected by diet in A/J, B6, or KsJ mice. However, in brown fat, we observed a 2-3-fold increase in the expression of UCP1 in response to dietary fat challenge, which may be related to diet-induced elevations in plasma leptin levels. Together, these results indicate that the consumption of a high fat diet selectively regulates UCP2 expression in white fat and UCP1 expression in brown fat and that resistance to obesity is correlated with this early, selective induction of UCP1 and UCP2 and is not associated with changes in expression of UCP3.

Adipose Tissue↗

Overexpression of the nonpancreatic secretory group II PLA2 messenger RNA and protein in colorectal adenomas from familial adenomatous polyposis patients.

The synovial fluid or group II secretory phospholipase A2 (sPLA2) has been implicated in various inflammatory processes and has been shown to release arachidonic acid for prostaglandin biosynthesis. In human colorectal cancer, both arachidonic acid and eicosanoid levels are elevated. Recently, sPLA2 has been identified as a candidate gene that modifies the Apc gene in the Min mouse, a murine model for familial adenomatous polyposis (FAP). Loss of sPLA2 gene function results in susceptibility to the Min phenotype and the formation of multiple intestinal polyps, whereas mice expressing an active sPLA2 gene are resistant to polyp formation. Therefore, there are two potentially contrasting roles for sPLA2 in colon cancer; one is protection against polyp formation, and the other, the release of arachidonic acid for prostaglandin production and subsequent tumor promotion. To investigate these contrasting dual roles of sPLA2, we have examined the expression and sequence of the sPLA2 mRNA in normal mucosa and duodenal and colorectal polyps from FAP patients. In 11 of 14 patients, there was a significant increase in sPLA2 mRNA levels in the adenoma over the normal tissue. In some cases, there was over 100-fold increase in mRNA levels in the adenoma compared with normal tissue. Analysis of multiple adenomatous polyps from individual patients revealed that not all polyps contained elevated levels of sPLA2 mRNA. Immunoblot analysis also showed that sPLA2 protein expression was elevated in adenoma over normal tissue in five of six FAP patients analyzed. Furthermore, sequence analysis of sPLA2 mRNA present in these samples did not reveal mutations in the coding region. The implications of the up-regulation of sPLA2 in FAP is not clear, but unlike the Min mouse model, it does not seem to have a significant effect on polyp formation. In contrast, the high level of sPLA2 expression is more likely contributing to the elevated levels of arachidonic acid found in colorectal cancer and, in conjunction with the elevated expression of cyclooxygenase-2, could be another factor in tumor formation.

Adenoma↗

International differences in survival from colon cancer: more effective care versus less complete cancer registration.

BACKGROUND: Reporting of a recent international comparison of cancer survival rates has left an impression of inadequate treatment of patients in the UK but failed to address adequately the extent to which differences in survival may reflect variation in the completeness and accuracy of cancer registration. The aim of this study was to quantify the extent to which differences in registration practice may confound comparisons of survival from cancer of the colon. METHODS: A cohort of incident cases of colon cancer identified from records held by the North Western Regional Cancer Registry was used to simulate the effects on survival of changes in clinical and registration factors. The survival curve produced after each simulation was compared with that for aggregated data from 21 European registries. RESULTS: The observed survival differences were not explained by more effective primary treatment or by misclassification of in situ cases as malignant disease, whereas the exclusion of cases with only a clinical diagnosis produced estimates close to those of the European cohort. CONCLUSION: The observed survival differentials may not be due to differences in the quality of care but may reflect the failure of some European registries to register all patients with advanced disease.

Cohort Studies↗