NHS modernisation agency--critical care programme.
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Critical Care↗
Biomedical subjects
M Spencer
Publications and source records attributed to M Spencer.
The effect of shiftwork on driving to and from work.
A questionnaire study was conducted to obtain information from shiftworkers on the levels of tiredness experienced on the drive to and from work at different times of the day. The results demonstrated that, compared to non-shiftworkers, shiftworkers were more tired on the drive between their home and the workplace and more at risk of falling asleep behind the wheel. The main factors contributing to this increased level of sleepiness and associated driving impairment were the length of the sleep period prior to work, the type of shift and the travelling time. There was some evidence to suggest that on working days shiftworkers were more likely to be involved in an accident than non-shiftworkers. However, there were insufficient data to determine whether accidents were correlated with driver sleepiness.
Accidents, Traffic↗
Evidence for colorectal cancer micrometastases using reverse transcriptase-polymerase chain reaction analysis of MUC2 in lymph nodes.
Poor survival in patients following resection for early stage colorectal cancer is thought to be due in part to the presence of occult micrometastases at the time of surgery. The MUC2 mucin gene is highly expressed in the colon and associated colorectal tumors and may be a candidate marker for colorectal cancer micrometastases. We have used RT-PCR to detect expression of MUC2 mRNA transcripts in order to identify possible lymph node micrometastases in node negative (Stage I and II, or Dukes A and B) colorectal cancer patients. A total of 396 nodes (histologic stage N0) from 34 colon and nine rectal cancers were studied by RT-PCR analysis with nested primers for MUC2 (an average of 7.6 nodes per case). In the primary tumors, 42/43 (98.1%) were positive for MUC2 by RT-PCR. Evidence of the presence of MUC2 was demonstrated in nodes from 0 of 10 (0%) patients with Tis or T1, one of six (16.7%) from T2, 10 of 25 (40.0%) from T3, and one of two (50%) from T4 tumors. MUC2 RT-PCR was negative in six nodes from three patients with non-malignant colon disease and positive in histologically positive lymph nodes from six of six (100%) stage III colon cancers. In this study, using RT-PCR to detect the presence of MUC2 transcripts, we have found preliminary evidence for possible micrometastatic disease in approximately a third of histologically negative N0 colorectal cancer patients. The increased presence of MUC2 expression also correlated with more advanced T stage. We conclude that MUC2 RT-PCR may be a sensitive and specific marker for occult micrometastases. This technique has the potential to identify a group of colorectal cancer patients at risk for early cancer recurrence.
Biomarkers, Tumor↗
Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase.
Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the single-photon response to become larger and longer lasting than normal. These results demonstrate that RK is required for normal rhodopsin deactivation. When the photon responses of RK-/- rods did finally turn off, they did so abruptly and stochastically, revealing a first-order backup mechanism for rhodopsin deactivation. The rod outer segments of RK-/- mice raised in 12-hr cyclic illumination were 50% shorter than those of normal (RK+/+) rods or rods from RK-/- mice raised in constant darkness. One day of constant light caused the rods in the RK-/- mouse retina to undergo apoptotic degeneration. Mice lacking RK provide a valuable model for the study of Oguchi disease, a human RK deficiency that causes congenital stationary night blindness.
Animals↗
Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples.
BACKGROUND: Prion diseases are associated with the accumulation of an abnormal isoform of cellular prion protein (PrPSc), which is the principal constituent of prions. Prions replicate in lymphoreticular tissues before neuroinvasion, suggesting that lymphoreticular biopsy samples may allow early diagnosis by detection of PrPSc. Variant Creutzfeldt-Jakob disease (variant CJD) is difficult to distinguish from common psychiatric disorders in its early stages and definitive diagnosis has relied on neuropathology. We studied lymphoreticular tissues from a necropsy series and assessed tonsillar biopsy samples as a diagnostic investigation for human prion disease. METHODS: Lymphoreticular tissues (68 tonsils, 64 spleens, and 40 lymph nodes) were obtained at necropsy from patients affected by prion disease and from neurological and normal controls. Tonsil biopsy sampling was done on 20 patients with suspected prion disease. Tissues were analysed by western blot to detect and type PrPSc, by PrP immunohistochemistry, or both. FINDINGS: All lymphoreticular tissues obtained at necropsy from patients with neuropathologically confirmed variant CJD, but not from patients with other prion diseases or controls, were positive for PrPSc. In addition, PrPSc typing revealed a consistent pattern (designated type 4t) different from that seen in variant CJD brain (type 4) or in brain from other CJD subtypes (types 1-3). Tonsil biopsy tissue was positive in all eight patients with an adequate biopsy sample and whose subsequent course has confirmed, or is highly consistent with, a diagnosis of variant CJD and negative in all patients subsequently confirmed to have other diagnoses. INTERPRETATION: We found that if, in the appropriate clinical context, a tonsil biopsy sample was positive for PrPSc, variant CJD could be diagnosed, which obviates the need for a brain biopsy sample to be taken. Our results also show that variant CJD has a different pathogenesis to sporadic CJD.
Adolescent↗
Nightly home hemodialysis: improvement in nutrition and quality of life.
In September, 1997, we began a Nightly Home Hemodialysis Program modeled after a program in Toronto, Canada. We have assessed nutritional parameters and quality of life indicators before initiation of the program, and at 3, 6, 12, and 18 months. Data suggest that patients have improved overall quality of life as measured by the CHOICE Health Experience Questionnaire. Three-day dietary recalls at 0, 3, 6, 12, and 18 months also show patients are eating healthy and maintaining adequate kilocalorie and protein intakes, as well as maintaining adequate dry weight and protein stores.
Adult↗
The spheroplast lysis assay for yeast in microtiter plate format.
A yeast lysis assay in the microtiter plate format improved precision and throughput and led to an improved algorithm for estimating lag time. The assay reproducibly revealed differences of 10% or greater in the maximal lysis rate and 50% or greater in the lag time. Clonal differences were determined to be the major source of variation. Microtiter-based assays should be useful for screening for drug susceptibility and for analyzing mutant phenotypes.
Cell Wall↗
Rhodopsin phosphorylation and its role in photoreceptor function.
Light-stimulated phosphorylation of rhodopsin was first described 25 years ago. This paper reviews the progress that has been made towards (i) understanding the nature of the enzymes that phosphorylate and dephosphorylate rhodopsin (ii) identifying the sites of phosphorylation on rhodopsin and (iii) understanding the physiological importance of rhodopsin phosphorylation. Many important questions related to rhodopsin phosphorylation remain unanswered and new strategies and methods are needed to address issues such as the roles of Ca2+ and recoverin. We present one such method that uses mass spectrometry to quantitate rhodopsin phosphorylation in intact mouse retinas.
Animals↗
Health-related behaviours and psycho-social characteristics of 18 year-old Australians.
Psychosocial variables associated with health-related behaviours for diet, physical activity, alcohol consumption and smoking were examined in 18 year-old Australian men (n = 301) and women (n = 282). These psychosocial variables included Type A behaviour and depression, perceived self-efficacy for engaging in healthy behaviours and perceived barriers to performing these behaviours. Self-efficacy for following a healthy diet and moderating alcohol intake was greater in females but males had higher self-efficacy for physical activity. Self-efficacy for smoking did not differ according to gender. Lack of willpower was perceived as a barrier to desirable dietary, smoking and physical activity behaviours. Other perceived diet-related barriers included buying suitable foods when eating out, ignorance about appropriate foods and, in young women, perceived expense. Barriers for desirable levels of physical activity included planning time, tiredness, limiting social life and lack of social support. Social occasions were the main perceived barriers preventing both alcohol moderation and quitting smoking. Lack of family support, stress and concerns about weight gain, particularly in women, were perceived barriers to smoking cessation. Type A behaviour was associated with smoking and "unsafe" drinking in both men and women, generally unhealthy dietary choices in young women but with greater physical activity in young men. Depressive affect was significantly higher in female smokers and "unsafe" drinkers and tended to have an inverse relationship with physical activity in men and women. Depressive affect was inversely related to self-efficacy in both men and women for each of the health behaviours examined. Health promotion in young adults should therefore attempt to increase self-efficacy and address perceived barriers to change, taking into account gender-related differences in attitudes and the influence of depression and Type A characteristics on health-related behaviours.
Adolescent↗
Associations between lifestyle and cardiovascular risk factors in 18-year-old Australians.
PURPOSE: This study aimed to examine associations between cardiovascular risk factors and variables reflecting health-related behaviors in 18-year-old Australians. METHODS: Anthropometry, blood pressure, nonfasting serum cholesterol, and physical fitness were measured in 301 male and 286 female Australian 18-year-olds. Usual physical activity, smoking, and drinking habits were assessed by questionnaire. RESULTS: Systolic (SBP), with mean SBP higher by 14 mm Hg in males, related positively to weight for height for age and "unsafe" drinking (exceeding Australian national guidelines) and negatively to fitness and birth weight. Total cholesterol, which was positively associated with waist-hip ratio and negatively with fitness, was higher in females [mean 4.4 mmol/L, 95% confidence interval (CI) 4.3, 4.5] than in males (mean 4.1 mmol/L, 95% CI 4.0, 4.2). In 24% of males and 48% of females, usual levels of physical activity were low, consistent with lower scores on fitness tests in females. Thirty percent of males and 24% of females regularly drank at "unsafe," levels while 26% of males and 29% of females smoked. Smoking was associated with "unsafe" drinking. CONCLUSION: Cardiovascular risk factors in 18-year-olds are related to smoking, "unsafe" drinking, and physical inactivity, particularly in females. These behaviors should be targeted in designing multimodal health promotion programs appropriate for these young adults.
Adolescent↗
A case of intractable epistaxis.
The surgical management of intractable epistaxis by external carotid artery ligation may become complicated if there is a high bifurcation of the common carotid artery. Occlusion of the bleeding vessels by catheter embolization is described in a patient in whom exploration of the neck had failed to locate the external carotid artery.
Aged↗
Severe position effects imposed on a 1 kb mouse whey acidic protein gene promoter are overcome by heterologous matrix attachment regions.
Matrix attachment regions (MARs) have been shown to participate in the insulation of transcription elements from surrounding chromatin in tissue culture cells and transgenic mice. A whey acidic protein (WAP) transgene containing 1 kb promoter sequence was active in mammary tissue from 1 out of 17 lines of mice, demonstrating that the transcription elements were highly susceptible to position effects. To test whether MARs could insulate this WAP gene promoter and thereby restore transcription, we ligated MARs from the chicken lysozyme gene to the WAP transgene. Seven of the nine lines generated exhibited WAP transgene activity, expression was confined to mammary tissue, and correct regulation was observed in three of the four lines analyzed. This study provides strong additional evidence that the MAR fragments from the chicken lysozyme gene have the capacity to insulate transgenes from severe position effects.
Animals↗
Improving analgesic prescribing in a general teaching hospital.
Patients suffering from cancer and human immunodeficiency virus (HIV) disease at a teaching hospital were found to have poorly controlled pain. Many were prescribed inappropriate analgesia. A palliative care service was established to provide symptom control for patients and education for staff. Educational materials were developed, didactic teaching organized, and one-to-one education by case discussion provided to improve patient management. A repeat survey to evaluate the service showed an increase in the use of appropriate opioids, such as morphine and diamorphine, and a decrease in the use of buprenorphine and papaveretum, which are less suitable for use in chronic cancer pain. The acceptability of the guidelines and rapid availability of a palliative care opinion has improved analgesic prescribing.
Adolescent↗
Implementation and evaluation of an algorithm for isolation of patients with suspected pulmonary tuberculosis.
OBJECTIVE: To implement and evaluate an algorithm designed to assist in the consistent placement of patients with suspected pulmonary tuberculosis into negative-pressure isolation rooms (NPIRs). DESIGN: A standard algorithm was designed for the appropriate room placement of patients with suspected pulmonary tuberculosis using clinical, radiographic, and laboratory criteria and reported risk factors. A case-patient was defined as an inpatient who had at least one Mycobacterium tuberculosis culture-positive respiratory specimen from January 1, 1993, through December 31, 1994. Demographic, clinical, laboratory, case contact, and isolation and room placement data were collected prospectively on all case patients. SETTING: A 900-bed university teaching and referral center. RESULTS: During 1993 and 1994, 69 patients were evaluated for possible pulmonary tuberculosis, and 31 case-patients were identified. Of the 31 case-patients, 26 (84%) were placed on respiratory isolation in NPIRs, including 19 (61%) who were isolated within 24 hours of admission (1993, 14 of 20 [70%]; 1994, 5 of 11 [45%]). Seven case-patients (23%) were isolated in NPIRs following delays that ranged from 2 to 31 days (median, 9 days), and five case-patients (16%) never were isolated during admissions of from 3 to 28 days (median, 4 days). These 12 case-patients contributed a total of 136 patient-exposure days during their hospitalizations. Misclassification of patient risk status by user error delayed isolation of five (42%) of the 12 improperly isolated case-patients. CONCLUSIONS: The use of an algorithm incorporating radiographic, laboratory, and clinical criteria and reported risk factors may assist in the rapid isolation of patients with suspected pulmonary tuberculosis.
Adult↗
Cloning and expression of a second photoreceptor-specific membrane retina guanylyl cyclase (RetGC), RetGC-2.
One of the membrane guanylyl cyclases (GCs), RetGC, is expressed predominantly in photoreceptors. No extracellular ligand has been described for RetGC, but it is sensitive to activation by a soluble 24-kDa protein (p24) and is inhibited by Ca2+. This enzyme is, therefore, thought to play a role in resynthesizing cGMP for photoreceptor recovery or adaptation. By screening a human retinal cDNA library at low stringency with the cytoplasmic domains from four cyclases, we cloned cDNAs encoding a membrane CG that is most closely related to RetGC. We have named this GC RetGC-2, and now term the initially described RetGC RetGC-1. By in situ hybridization, mRNA encoding RetGC-2 is found only in the outer nuclear layer and inner segments of photoreceptor cells. By using synthetic peptide antiserum specific for each RetGC subtype, RetGC-2 can be distinguished from RetGC-1 as a slightly smaller protein in immunoblots of bovine rod outer segments. Membrane GC activity of recombinant RetGC-2 expressed in human embryonic kidney 293 cells is stimulated by the activator p24 and is inhibited by Ca2+ with an EC50 value of 50-100 nM. Our data reveal a previously unappreciated diversity of photoreceptor GCs.
Amino Acid Sequence↗
Acceptable AC IOLs in the 1990s.
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Anterior Chamber↗
Who will provide preventive services? The changing relationships between medical care systems and public health agencies in health care reform.
Health care reform in the United States will likely attempt to expand the health insurance coverage to uninsured groups, control costs, enhance quality, and expand access to care. Preventive services will be assigned to the medical care system, while new roles and responsibilities will be defined for public health agencies. The clinical preventive services likely required are examined in a population of 44,565 persons residing in Otsego County, New York. Expansion of preventive services to Medicaid requests and the uninsured will require considerable resource expenditure to correct the current deficit in preventive services received by these groups. Moreover, the uninsured and Medicaid recipients have high levels of risk behaviors, identifying a need for health education services effective to that population subgroup. The transfer of responsibilities for clinical preventive services to the medical care system may free up resources for public health agencies to focus on other initiatives such as disease surveillance, health education, and quality assurance. New interrelationships, some cooperative and some adversarial, are likely to emerge, due to a closer working relationship between the medical care system and public health agencies than previously seen in American health care.
Delivery of Health Care↗
Use of the CRIB (clinical risk index for babies) score in prediction of neonatal mortality and morbidity.
A prospective study of the outcome of care of a regional cohort of very low birthweight (< 1500 g) and very preterm (< 32 weeks) infants was carried out. Its aims were to assess the ability of the CRIB (clinical risk index for babies) score, rather than gestational age or birthweight, to predict mortality before hospital discharge, neurological morbidity, and length of stay, and to access CRIB score as an indicator of neonatal intensive care performance. 676 live births fulfilled the criteria and complete data were available for 643 (95%). Compared with gestation and birthweight, CRIB was better for the prediction of mortality, was as good for the prediction of morbidity, and was not as good for the prediction of length of stay. CRIB adjusted mortality did not demonstrate better performance in units providing the highest level of care. Either the CRIB score was not sensitive to performance or the level 3 hospitals in this study were performing badly. On the basis of this analysis purchasers and providers of neonatal intensive care cannot yet rely on the CRIB score as a performance indicator.
Birth Weight↗