Biomedical subjects
C Young
Publications and source records attributed to C Young.
A method for detecting chaos in canine myocardial microcirculatory red cell flux.
OBJECTIVE: To determine whether red cell movement, as measured by laser Doppler velocimetry, in the capillary net of the beating heart is chaotic. METHODS: Using two dog hearts, in situ red blood cell flux was measured at many sites. Simultaneously, epicardial arterial flow and left ventricular pressure were recorded via transit-time flowmeter and catheter manometer, respectively. The presence or absence of chaos was tested by two methods: Lyapunov exponents and correlation dimension. RESULTS: For capillary red cell flux, the Lyapunov was strongly positive at most sites. It was less so for coronary arterial flow and least for left ventricular pressure. Correlation dimension calculation was less able to distinguish the presence or absence of chaos in capillary red cell tissue flux, coronary arterial flow, and left ventricular pressure. CONCLUSIONS: Capillary red cell flux (movement of red cells in capillaries) is nonlinear, (i.e., chaotic). This complexity suggests that the primary control for oxygen delivery to cardiac myocytes by red blood cells resides in the microcirculation. Also, capillary red cell flux is bifractal, suggesting an ordering of control.
A hazardous relationship. SNFs and laboratories.
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Quality of life before and after radiofrequency catheter ablation in patients with drug refractory atrioventricular nodal reentrant tachycardia.
In a retrospective survey of 161 highly symptomatic patients, we found significant improvements in symptoms, patient utility, and use of medical care services after radiofrequency ablation for atrioventricular nodal reentrant tachycardia.
The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group.
OBJECTIVE: To determine the effect of humanized monoclonal antibody against alpha4 integrin (reactive with alpha4beta1 integrin or very-late antigen-4) on MRI lesion activity in MS. METHODS: A randomized, double-blind, placebo-controlled trial in 72 patients with active relapsing-remitting and secondary progressive MS was performed. Each patient received two IV infusions of anti-alpha4 integrin antibody (natalizumab; Antegren) or placebo 4 weeks apart and was followed up for 24 weeks with serial MRI and clinical assessment. RESULTS: The treated group exhibited significantly fewer new active lesions (mean 1.8 versus 3.6 per patient) and new enhancing lesions (mean 1.6 versus 3.3 per patient) than the placebo group over the first 12 weeks. There was no significant difference in the number of new active or new enhancing lesions in the second 12 weeks of the study. The number of baseline-enhancing lesions (i.e., lesions that enhanced on the baseline scan) that continued to enhance 4 weeks following the first treatment was not significantly different between the two groups. The number of patients with acute MS exacerbations was not significantly different in the two groups during the first 12 weeks (9 in the treated group versus 10 in placebo) but was higher in the treatment group in the second 12 weeks (14 versus 3; p = 0.005). The study was not, however, designed to look definitively at the effect of treatment on relapse rate. Treatment was well tolerated. CONCLUSIONS: Short-term treatment with monoclonal antibody against alpha4 integrin results in a significant reduction in the number of new active lesions on MRI. Further studies will be required to determine the longer term effect of this treatment on MRI and clinical outcomes.
Identification and characterization of a myristylated and palmitylated serine/threonine protein kinase.
We report the molecular cloning and initial characterization of a novel fatty acid acylated serine/threonine protein kinase. The putative open reading frame is predicted to encode a 305 amino acid protein possessing a carboxy-terminal protein kinase domain and amino-terminal myristylation and palmitylation sites. The protein kinase has been accordingly denoted as the myristylated and palmitylated serine/threonine protein kinase (MPSK). Human and mouse MPSKs share approximately 93% identity at the amino acid level with complete retention of acylation sites. Radiation hybridization localized the human MPSK gene to chromosome 2q34-37. Northern analysis demonstrated that the human MPSK 1.7 kilobase mRNA is widely distributed. Epitope tagged human MPSK was found to be acylated by myristic acid at glycine residue 2 and by palmitic acid at cysteines 6 and/or 8. Palmitylation of MPSK in these experiments was found to require an intact myristylation site. While epitope tagged MPSK in immune complexes or purified human glutathione S transferase-MPSK was found to autophosphorylate at one or more threonine residues, the enzyme was not found to phosphorylate several other common exogenous substrates. Indeed, only PHAS-I was identified as an exogenous substrate which was found to be phosphorylated on threonine and serine residues.
Design of a state-based workers' compensation information system.
BACKGROUND: California policy makers have long been hampered by a lack of credible information for use in making legislative or administrative changes to address serious problems in the workers' compensation system. In 1993, the legislature directed the California Division of Workers' Compensation to develop a Workers' Compensation Information System (WCIS). METHODS: An advisory committee developed key questions and identified data sources regarding injury/illness incidence, costs, promptness of benefit delivery, adequacy of benefits, satisfaction with services, and other outcomes. RESULTS: Key data elements were identified, mostly from existing mandated reporting forms for employers and physicians, and from standardized medical billings. Data collection will be carried out using: 1) rapid electronic data interchange (EDI) for a minimum number of data elements; 2) electronic collection of data on medical services for a sample of claims; and 3) surveys to address adequacy of benefits, satisfaction with services, return to work, and other outcomes. A state-based repository will analyze data and provide de-identified public use data files. CONCLUSIONS: The proposed WCIS will provide information to improve the performance and to increase the accountability of all the participants in California's Workers' Compensation system. More importantly, it will provide information which will allow improved quality in the provision of mandated benefits to injured workers.
Incorporation of a GnRH agonist, leuprolide acetate, into regimens with exogenous gonadotropins to produce ovarian stimulation and ovulation in the nonpregnant squirrel monkey.
This study was designed to measure the effects of variations in the length of pretreatment with a GnRH agonist, leuprolide acetate (LA), on subsequent follicular development and ovulation. The hypothesis was that the duration of LA suppression of pituitary function does not adversely affect ovarian response to standardized ovulation induction protocols in squirrel monkeys. The first phase determined the dose and duration of LA needed to achieve a hypogonadal state. One of two groups received daily subcutaneous injections of 50 microg of LA. The other received a single injection of 175 microg of a depot suspension of LA. Sera were assayed for estradiol (E2) and progesterone (P). E2 and P levels increased 2- to 5-fold with peak levels on days 4 and 7, respectively. Suppression of steroid levels took 10 to 15 days in the LA-treated group. Depot-LA did not effectively suppress steroid production. After suppression, females receiving daily LA received five daily injections of hMG to stimulate follicular development. E2 and P increased in these animals. These results suggest that cycling squirrel monkeys have P-secreting capacity throughout the cycle. This may explain how the squirrel monkey is able to accommodate both a short (4-5 day) luteal phase of their 9 day cycle and implantation from 5 to 7 days after ovulation. A second study compared exogenous follicle stimulating hormone (FSH) to endogenous gonadotropins released as a response to LA in ovulation induction. Steroid production and hCG-induced ovulation were assessed. LA treatment was compared to a standard ovulation induction protocol by using a randomized cross-over measures design. There were no differences in E2 and P levels in response to dosages of either LA or hMG. The ovulatory response following LA treatment was not significantly greater than that using FSH. The number of animals with unovulated, large follicles was greater on the FSH protocol (12/18) compared to the LA protocol (3/18). Thus, a single injection of a depot preparation of LA is sufficient to stimulate follicular development and ovulation when followed by an hCG injection. Based on this observation and the data on unovulated large follicles, it is suggested that the ovary responds more readily to endogenous gonadotropins released by LA than to exogenous FSH.
Effects of nasogastric tubes on the young, normal swallowing mechanism.
The present study aimed to investigate the effects of different-sized nasogastric tubes on swallowing speed and function in 10 young normal volunteers. Using X-ray visualization, liquid barium swallows were recorded on video (videofluoroscopy) under three experimental conditions: no nasogastric tube, fine-bore nasogastric tube, and wide-bore nasogastric tube. Nasogastric tubes slowed swallowing but did not alter swallowing function, namely bolus transit and clearance, and airway protection. The presence of a wide-bore nasogastric tube caused significant duration changes in several swallowing measures, namely duration of stage transition, duration of pharyngeal response, duration of pharyngeal transit, and duration of upper esophageal sphincter opening. Similar trends were seen for the fine-bore tube. The implications for nonoral feeding of patients with swallowing disorders are discussed.
Predictors of time to completion of the hepatitis B vaccination series among adolescents.
OBJECTIVES: To determine adolescents' completion rates and factors affecting completion time of hepatitis B (HBV) vaccination. METHODS: Prior to vaccination, participants from a hospital-based and school-based adolescent clinic completed questionnaires assessing sociodemographic variables, family/friend experience with HBV and the vaccine, likelihood of completing the vaccinations, HBV and vaccine knowledge, risk behaviors, chronic illness, and access to clinic. Vaccination times were recorded. RESULTS: Twenty-six months after initiation of the study, 72% of 896 eligible participants had completed the vaccination series. The independent predictors of shorter time to completion were: higher estimated mean household income [odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.06-1.25), white race (OR = 1.27, 95% CI = 1.01-1.58), female gender (OR = 1.58, 95% CI = 1.31-1.92], and not having smoked cigarettes (OR for smoking in the past 30 days = 0.74, 95% CI = 0.60-0.92). Site of care, risk factors for acquiring HBV, disease and vaccine knowledge, and self-reported desire to complete the series were not associated with completion time. CONCLUSIONS: The primary factors associated with completion of immunization may not be amenable to intervention; mandated strategies for immunization may be more likely to result in protection for adolescents.
The clinical use of an esophageal Doppler monitor for hemodynamic monitoring in sepsis.
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An evaluative study of clinical supervision based on Proctor's three function interactive model.
This paper reports on a study of the benefits reported from participation in clinical supervision by registered nurses (n=201) working in a large English community and mental health NHS Trust. It summarizes the emergent practical and theoretical 'key ingredients' of clinical supervision in the United Kingdom and argues that these provide a basis for generalizable research practice. The study is based on Proctor's three function interactive model previously commended as a guide for supervisory practice and evaluation. Within this study, the three functions underpin instrument design but are also a primary focus of evaluation. The development of this instrument through semi- structured interviews with supervisors and supervisees is described. The study aims to assess and compare reported benefits in each of the three functions of accountability, skill development and support in order to examine the effects of contract use, length of experience of clinical supervision and length of service as a registered nurse on reported benefits by using non-parametric statistical analysis. The results indicate that reported benefits are experienced in almost equal proportion across each of these three functions. Statistical analysis indicates a significant positive correlation between experience of clinical supervision and its reported benefits. An inverse correlation is reported between length of service and overall benefits; however, no similar reduction over time against normative benefits was found. There was no relationship between contract use and reported benefits. Limitations of the study are discussed with reference to bias, interview transcription and overlap between the three functions. The paper concludes that nurses report clear benefits from clinical supervision in each of the three functions. This validates the three function interactive model and demonstrates that clinical supervision is used to critically examine and change nursing practice. The content and usage of contracts is identified as an aspect that merits further study.
Dysferlin is a plasma membrane protein and is expressed early in human development.
Recently, a single gene, DYSF, has been identified which is mutated in patients with limb-girdle muscular dystrophy type 2B (LGMD2B) and with Miyoshi myopathy (MM). This is of interest because these diseases have been considered as two distinct clinical conditions since different muscle groups are the initial targets. Dysferlin, the protein product of the gene, is a novel molecule without homology to any known mammalian protein. We have now raised a monoclonal antibody to dysferlin and report on the expression of this new protein: immunolabelling with the antibody (designated NCL-hamlet) demonstrated a polypeptide of approximately 230 kDa on western blots of skeletal muscle, with localization to the muscle fibre membrane by microscopy at both the light and electron microscopic level. A specific loss of dysferlin labelling was observed in patients with mutations in the LGMD2B/MM gene. Furthermore, patients with two different frameshifting mutations demonstrated very low levels of immunoreactive protein in a manner reminiscent of the dystrophin expressed in many Duchenne patients. Analysis of human fetal tissue showed that dysferlin was expressed at the earliest stages of development examined, at Carnegie stage 15 or 16 (embryonic age 5-6 weeks). Dysferlin is present, therefore, at a time when the limbs start to show regional differentiation. Lack of dysferlin at this critical time may contribute to the pattern of muscle involvement that develops later, with the onset of a muscular dystrophy primarily affecting proximal or distal muscles.
Monitoring and evaluation of nutrition programs in developing countries.
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Attitudes toward colon cancer gene testing: factors predicting test uptake.
OBJECTIVES: Genetic discoveries in hereditary nonpolyposis colorectal cancer (HNPCC) have made possible genetic testing to determine susceptibility to this form of colorectal cancer (CRC). This study measured the uptake of genetic testing for HNPCC among first-degree relatives of CRC patients and conducted a preliminary analysis of the predictors of test uptake. MATERIALS AND METHODS: We compared 77 test acceptors and 181 decliners on demographic, medical history, and psychological characteristics, controlling for distance from the testing center. The psychological factors studied were risk perception for CRC, frequency of cancer thoughts, and perceived ability to cope with unfavorable genetic information. RESULTS: In the final regression model, after accounting for all variables, the significant predictors of test uptake were increased risk perception, greater perceived confidence in ability to cope with unfavorable genetic information, more frequent cancer thoughts, and having had at least one colonoscopy. The association between risk perception and uptake was dependent on frequency of cancer thoughts. Among those who thought about getting CRC more often, the probability of testing increased as perceived risk increased to approximately 50% likelihood of getting CRC and then leveled off. In contrast, among those who never or rarely thought about getting CRC, risk perception was unrelated to testing decision. CONCLUSIONS: Our findings are consistent with the associations reported between psychological factors and other cancer screening behaviors.
Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras.
UNLABELLED: Accurate assessment of lung carcinoma remains a significant clinical problem, often leading to surgical procedures without curative potential. PET with 18F-fluorodeoxyglucose (FDG) has shown promise in differentiating benign from malignant lesions and in staging the extent of disease, resulting in improved treatment at a significant cost savings. This multicenter prospective study used dual-detector coincidence imaging with FDG to categorize pulmonary lesions as benign or malignant. The goal of this study was to determine the sensitivity and specificity of dual-detector coincidence imaging of FDG in patients with pulmonary lesions who were scheduled to have a diagnostic procedure for histopathologic confirmation. METHODS: A total of 96 patients with pulmonary lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on their chest radiograph or CT scan were studied using FDG scans with a dual-detector coincidence detection system. An additional 24 patients were entered as control subjects. The studies of 120 subjects were interpreted in random order by three physicians experienced in the use of FDG in patients with lung cancer. Surgical pathology was used as the standard for identifying malignant lesions. RESULTS: There was 94% agreement between the readers in the independent interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG studies were 97% sensitive and 80% specific in identifying proven malignant lesions. CONCLUSION: The results of this prospective study provide evidence that dual-detector coincidence imaging with FDG provides an accurate, sensitive and specific means of diagnosing malignancy in patients with pulmonary lesions.