Biomedical subjects
C Allen
Publications and source records attributed to C Allen.
Increasing the reach of flexible sigmoidoscopy.
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Sporadic medulloblastomas contain oncogenic beta-catenin mutations.
The beta-catenin, glycogen synthase kinase 3beta (GSK-3beta), and adenomatous polyposis coli (APC) gene products interact to form a network that influences the rate of cell proliferation. Medulloblastoma occurs as part of Turcot's syndrome, and patients with Turcot's who develop medulloblastomas have been shown to harbor germ-line APC mutations. Although APC mutations have been investigated and not identified in sporadic medulloblastomas, the status of the beta-catenin and GSK-3beta genes has not been evaluated in this tumor. Here we show that 3 of 67 medulloblastomas harbor beta-catenin mutations, each of which converts a GSK-3beta phosphorylation site from serine to cysteine. The beta-catenin mutation seen in the tumors was not present in matched constitutional DNA in the two cases where matched DNA was available. A loss of heterozygosity analysis of 32 medulloblastomas with paired normal DNA samples was performed with four microsatellite markers flanking the GSK-3beta locus; loss of heterozygosity with at least one marker was identified in 7 tumors. Sequencing of the remaining GSK-3beta allele in these cases failed to identify any mutations. Taken together, these data suggest that activating mutations in the beta-catenin gene may be involved in the development of a subset of medulloblastomas. The GSK-3beta gene does not appear to be a target for inactivation in this tumor.
The relationship between staff burnout/distress and interactions with residents in two residential homes for older people.
OBJECTIVE: The main hypothesis was that staff burnout/distress would be negatively associated with the quantity and quality of social interactions between staff and residents. The subsidiary hypothesis hypothesis was that 'perceived involvement in decision-making' among staff would be positively associated with the quantity and quality of staff-resident interactions. DESIGN: Cross-sectional and within-group. Standardized self-report questionnaires completed by staff; and non-participant, time-sampling observation and coding of staff-resident interactions. SETTING. Two independent (not-for-profit) residential care homes for older people in the UK. PARTICIPANTS: 18 out of 24 residential workers completed questionnaires. MEASURES: The 12-item General Health Questionnaire (GHQ-12); the Maslach Burnout Inventory (MBI); the Perceived Involvement Personal Questionnaire (PIPQ); and the Quality of Interactions Schedule (QUIS). RESULTS: Staff who reported higher levels of personal accomplishment (ie lower levels of burnout on the personal accomplishment subscale) exhibited significantly more staff-resident interactions; and staff who perceived more involvement in decisions relating to their work showed significantly fewer negative staff-resident interactions. Staff distress, emotional exhaustion and depersonalization were not found to be significantly related to the quantity or quality of staff resident interactions. CONCLUSIONS: The results provide some support for the hypotheses. It appears that levels of personal accomplishment and perceived involvement in decision-making among staff may significantly influence the quantity and quality of staff-resident interactions in residential settings. However, the causal relationships are uncertain, and replication of these findings is required in other contexts.
Effect of combined axial compressive and anterior tibial loads on in situ forces in the anterior cruciate ligament: a porcine study.
This study investigated the impact of a combination of axial compressive and anterior-posterior tibial loads on the in situ forces in the anterior cruciate ligament. An axial compressive load is believed to contribute to increased stability of the knee joint; however, its effect on in situ forces in the anterior cruciate ligament has not been clearly defined, to our knowledge. It was hypothesized that the application of an axial compressive load, when combined with an anterior tibial load, would result in larger in situ forces in the anterior cruciate ligament than those caused by an isolated anterior tibial load. With use of a porcine knee model, the results confirmed this hypothesis; the addition of a 200 N axial compressive load to a 100 N anterior tibial load increased knee stability by reducing anterior-posterior tibial translation and internal-external tibial rotation and also caused a significant increase in in situ forces in the anterior cruciate ligament (p < 0.05). Specifically, there was a 34% increase in the in situ force at 30 degrees of flexion, a 68% increase at 60 degrees of flexion, and an 84% increase at 90 degrees of flexion compared with those for an isolated anterior tibial load of 100 N. Additionally, there was a statistically significant increase of the in situ forces in the anterior cruciate ligament at 60 and 90 degrees as compared with those at 30 degrees. These results suggest that axial compressive loads on the knee may play a role in injury of the anterior cruciate ligament when the knee is flexed.
Esophageal and lower esophageal sphincter pressure profiles 6 and 24 months after laparoscopic fundoplication and their association with postoperative dysphagia.
BACKGROUND: It has been suggested that antireflux surgery may cause an improvement in esophageal motor function (EMF) and lead to reduced postoperative dysphagia. METHODS: We evaluated the changes in dysphagia symptom scores and esophageal and lower esophageal sphincter (LES) pressures in patients before (n = 381), at 6 months (n = 260), and at 24 months (n = 97) after laparoscopic fundoplication. RESULTS: There was a significant increase in LES basal and nadir pressure following surgery in all patients and an improvement in EMF only in patients with poor preoperative esophageal motor function. A total of 76% of the patients reported no dysphagia or an improved dysphagia score 6 and 24 months after surgery. This improvement was more marked in patients with poor EMF. An improvement in EMF did not correlate with the improvement in dysphagia score reported by other patients. Patients with increased dysphagia scores 2 years after surgery had significantly higher LES basal and nadir pressures as compared to other patients. CONCLUSIONS: Laparoscopic Nissen fundoplication is associated with an overall reduction in dysphagia scores and leads to an improvement in esophageal motor function in patients with poor preoperative esophageal motility. Tightness and inadequate relaxation of the wrap during swallowing may be a determinant of long-term dysphagia.
Differential rhodopsin regeneration in photoreceptor membranes is correlated with variations in membrane properties.
Rhodopsin, the major transmembrane protein in both the plasma membrane and the disk membranes of photoreceptor rod outer segments (ROS) forms the apo-protein opsin upon the absorption of light. In vivo the regeneration of rhodopsin is necessary for subsequent receptor activation and for adaptation, in vitro this regeneration can be followed after the addition of 11-cis retinal. In this study we investigated the ability of bleached rhodopsin to regenerate in the compositionally different membrane environments found in photoreceptor rod cells. When 11-cis retinal was added to bleached ROS plasma membrane preparations, rhodopsin did not regenerate within the same time course or to the same extent as bleached rhodopsin in disk membranes. Over 80% of the rhodopsin in newly formed disks regenerated within 90 minutes while only 40% regenerated in older disks. Since disk membrane cholesterol content increases as disks are displaced from the base to the apical tip of the outer segment, we looked at the affect of membrane cholesterol content on the regeneration process. Enrichment or depletion of disk membrane cholesterol did not alter the % rhodopsin that regenerated. Bulk membrane properties measured with a sterol analog, cholestatrienol and a fatty acid analog, cis parinaric acid, showed a more ordered, less "fluid", lipid environment within plasma membrane relative to the disks. Collectively these results show that the same membrane receptor, rhodopsin, functions differently as monitored by regeneration in the different lipid environments within photoreceptor rod cells. These differences may be due to the bulk properties of the various membranes.
Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD34+ cell yields.
The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.
Laparoscopic Nissen fundoplication: two-year comprehensive follow-up of a technique of minimal paraesophageal dissection.
OBJECTIVE: To provide a comprehensive follow-up of 381 patients after laparoscopic Nissen fundoplication (LNF) using a technique of minimal paraesophageal dissection. METHODS: Patients underwent a 24-hour pH recording, esophageal manometry, and symptom score assessment for six symptoms of gastroesophageal reflux disease preoperatively. To date, 260 patients have undergone repeat studies at 6 months and 108 patients at 2 years. RESULTS: LNF was associated with a significant (p < 0.0001) increase in the lower esophageal sphincter (LES) pressure and a significant (p < 0.0001) drop in duration of acid reflux in 24 hours and symptom score 6 and 24 months after surgery when compared to preoperative values. Twelve patients (3%) have experienced recurrence of reflux symptoms, 8 presenting in the first 6 months and 4 by the second year after surgery, but only 1 has required repeat surgery. The incidence of clinical dysphagia was found to be 1.3% of the patient group. CONCLUSIONS: LNF remains an effective antireflux procedure at 2 years. Most recurrences occur early, and there is no significant deterioration in the high-pressure zone at the LES, the percentage reflux in 24 hours, or symptom control between 6 months and 2 years after surgery, suggesting that the long-term results should be satisfactory.
Ralstonia solanacearum pectin methylesterase is required for growth on methylated pectin but not for bacterial wilt virulence
Ralstonia (Pseudomonas) solanacearum causes bacterial wilt, a serious disease of many crop plants. The pathogen produces several extracellular plant cell wall-degrading enzymes, including polygalacturonases (PGs) and pectin methylesterase (Pme). Pme removes methyl groups from pectin, thereby facilitating subsequent breakdown of this cell wall component by PGs, which are known bacterial wilt virulence factors. R. solanacearum PGs could not degrade 93% methylated pectin unless the substrate was first demethylated by Pme, but as the degree of methylation of the pectin substrate decreased, PG activity increased. Primers derived from a published pme sequence generated an 800-bp DNA probe fragment, which identified Pme-encoding plasmids from a R. solanacearum genomic library. A pme chromosomal mutant had no detectable Pme activity in vitro and no longer grew on 93% methylated pectin as a carbon source. Curiously, the pme mutant, which had no detectable PG activity on highly methylated pectin, was just as virulent as the wild-type strain on tomato, eggplant (aubergine), and tobacco. Since PG activity is required for full virulence, this result suggests that the pectin in these particular hosts may not be highly methylated, or that the breakdown of highly methylated pectin is not a significant factor in the disease process in general. A positive response regulator of PG production called PehR was not required for wild-type Pme production. However, a mutant strain lacking PhcA, which is a global regulator of several virulence genes, produced no detectable Pme activity. Thus, pme expression is directly or indirectly regulated by PhcA but not by PehR.
Systemic multifocal fibrosclerosis.
We describe a case of hydronephrosis as a result of retroperitoneal fibrosis in a patient who had previous sclerosing lobulitis of the breast. To the best of our knowledge this is the first reported association between these two conditions in the english literature. We presume these conditions are linked and unify them under the general heading of systemic multifocal fibrosclerosis.
Assessing animal cognition: ethological and philosophical perspectives.
Developments in the scientific and philosophical study of animal cognition and mentality are of great importance to animal scientists who face continued public scrutiny of the treatment of animals in research and agriculture. Because beliefs about animal minds, animal cognition, and animal consciousness underlie many people's views about the ethical treatment of nonhuman animals, it has become increasingly difficult for animal scientists to avoid these issues. Animal scientists may learn from ethologists who study animal cognition and mentality from an evolutionary and comparative perspective and who are at the forefront of the development of naturalistic and laboratory techniques of observation and experimentation that are capable of revealing the cognitive and mental properties of nonhuman animals. Despite growing acceptance of the ethological study of animal cognition, there are critics who dispute the scientific validity of the field, especially when the topic is animal consciousness. Here, a proper understanding of developments in the philosophy of mind and the philosophy of science can help to place cognitive studies on a firm methodological and philosophical foundation. Ultimately, this is an interdisciplinary task, involving scientists and philosophers. Animal scientists are well-positioned to contribute to the study of animal cognition because they typically have access to a large pool of potential research subjects whose habitats are more controlled than in most field studies while being more natural than most laboratory psychology experiments. Despite some formidable questions remaining for analysis, the prospects for progress in assessing animal cognition are bright.
Management of constipation in children.
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The care programme approach: the experiences and views of carers.
Integral to the care programme approach is the involvement of carers in the planning of after-care and treatment post-discharge of people with mental health problems. That is the theory. In practice, carers still feel excluded and ignored by mental health professionals, as a qualitative survey in one inner city area revealed. In the first of two linked papers on the CPA, CHARLOTTE ALLEN reports from the carer's perspective.
Incompletely excised basal cell carcinomas of the skin.
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Risk factors for hospitalization in a cohort with type 1 diabetes. Wisconsin Diabetes Registry.
The authors investigate the postonset hospitalization rate and risk factors during 1987-1994 in Wisconsin, in a population-based, incidence cohort followed from diagnosis of Type 1 diabetes mellitus at ages 0-29 (n = 577). The overall rate was 8.9 +/- 0.60 (standard error) per 100 person-years of diabetes, whereof 5.7 was due to hyperglycemia, 1.9 to hypoglycemia, and 1.3 to other and undetermined causes. Major risk factors for hospitalization were longitudinally measured glycosylated hemoglobin level (rate ratio = 1.5 per 2% increase, 95% confidence interval 1.4-1.7), black/other race (rate ratio = 1.9, 95% confidence interval 1.0-3.6), diagnosis in a non-university-based setting (rate ratio = 1.9, 95% confidence interval 1.2-3.2), female sex (rate ratio = 1.5, 95% confidence interval 1.0-2.4 at age 11), age in males (rate ratio = 0.6, 95% confidence interval 0.4-0.8 per 5-year increase), and public or no insurance up to 18 months postdiagnosis (rate ratio = 2.2, 95% confidence interval 1.1-4.4). For individuals less than 18 years, "black/other race" was replaced in the model by "having other than two biologic parents in the home" (rate ratio = 2.0, 95% confidence interval 1.1-3.5). Hence, hospitalization is common in children, adolescents, and young adults with diabetes, primarily for problems with glycemic control.
Study of adenovirus-mediated dystrophin minigene transfer to skeletal muscle by combined microscopic display of adenoviral DNA and dystrophin.
In situ DNA hybridization of an E4 adenoviral sequence amplified by in situ polymerase chain reaction (PCR) was used to mark adenovirus-containing myonuclei in muscles of immunocompetent and immunosuppressed mdx mice following intramuscular injection of adenoviral recombinants. The adenoviral recombinants contained a 6.3-kb dystrophin cDNA (minigene) driven by a cytomegalovirus (CMV) promoter/enhancer and thus, immunostaining for dystrophin of the same sections permitted correlation of adenoviral recombinant-containing myonuclei with dystrophin positivity of the same muscle fiber segments. As early as 2 hr post-injection of adenoviral recombinant, an appreciable number of adenoviral recombinant-positive (AVR+) myonuclei, and some partial dystrophin positive (pdys+) fibers were observed. Some fully dystrophin-positive (dys+) muscle fibers were present as early as 6 hr. The maximum number of fibers containing AVR+ myonuclei (observed by 72 hr) was maintained until 60 days in immunosuppressed, but not in immunocompetent, animals. In immunocompetent animals, the maximum number of dys+ fibers was observed at 10 days. The vast majority of these fibers contained AVR+ myonuclei; however, by 60 days, dys+ fibers disappeared with some AVR+ myonuclei persisting. Our studies suggest that widespread delayed inactivation of the dystrophin expression cassette is probably unlikely. Thus, optimization of immunosuppression could assure successful long-term dystrophin gene transfer for gene therapy.
Mental health. Changing of the old guard.
Government policy requiring community mental health nurses to target services to patients with severe mental health problems demands considerable change. The proposed ways of working have implications for other parts of the mental health services and those referring patients to them. A service review should involve and inform all those affected.