Werner's syndrome: what does an aging syndrome gene reveal about cancer?
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DNA, Neoplasm↗
Biomedical subjects
M Miller
Publications and source records attributed to M Miller.
Predictors of survival and eradication of Mycobacterium avium complex bacteremia (MAC) in AIDS patients in the Canadian randomized MAC treatment trial. Canadian HIV Trials Network Protocol 010 Study Group.
OBJECTIVE: To assess the importance of baseline characteristics including medical history, indicators of current disease status, therapeutic drug use, in vitro drug susceptibility, immune status and mycobacterial load on bacteriologic response and survival in HIV-positive patients with Mycobacterium avium complex (MAC) bacteremia. DESIGN: An observational substudy of an open-label randomized controlled trial of two alternative therapeutic regimens for MAC. SETTING: Twenty-four hospital-based HIV clinics in 16 Canadian cities. MAIN OUTCOME MEASURES: The main outcome measures were survival and bacteriologic response, defined by consecutive negative blood cultures for MAC at least 2 weeks apart within 16 weeks of study entry. RESULTS: Prior AIDS diagnosis, low Karnofsky score, active unstable AIDS-related conditions, absence of antiretroviral therapy and absence of Pneumocystis carinii pneumonia prophylaxis were associated with shorter survival by univariate regression using the proportional hazards model. On multivariate analysis, antiretroviral therapy was not an independent predictor of mortality, and previous rifabutin prophylaxis was independently associated with poor survival outcomes, a result consistent across study treatment. Using a logistic regression model, baseline quantitative mycobacterial load [relative odds of clearing, 1.97 for a decrease of 1 log10 colony forming count; 95% confidence interval (CI), 1.36-2.87; P < 0.001] and Karnofsky score were the only statistically significant univariate predictors of clearance, although previous prophylaxis with rifabutin was also a significant predictor in a multivariate model (relative odds of clearing, 0.39; 95% CI, 0.17-0.88; P < 0.05). CONCLUSIONS: This study indicates that although the level of MAC bacteremia is an important predictor of clearance, it is not associated with survival.
AIDS-Related Opportunistic Infections↗
Transmission of HTLV-I to rats via peripheral blood mononuclear cells and serum from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) with amyotrophic lateral sclerosis (ALS)-like features.
We tested the possibility that lymphocytes and serum obtained directly from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) induce infection in rats. Inbred Fischer F344 immunosuppressed rats were inoculated intravenously with 10x10(6) peripheral blood mononuclear cells (PBMC; 3 rats) and serum (3 rats) obtained from a HAM/TSP patient, who was seropositive and polymerase chain reaction (PCR)-positive for the HTLV-I proviral genome. Antibodies to HTLV-I appeared in the rat sera 2 months later; rat peripheral blood lymphocytes, spleen, salivary gland, and spinal cord were found to contain the proviral genome. Control rats inoculated with normal donor PBMC and serum tested negative for the HTLV-I antibodies and for the HTLV-I proviral genome by PCR. The positive control F344 rats inoculated with 5x10(6) cells of a SLB-1 HTLV-I cell line were found to be infected after 2 months. This study demonstrates for the first time that HTLV-I can be transmitted not only by human cellular components but also by human cell-free sera in a rat model.
Adult↗
Designing ways: computer animators illustrate cancer research in 3-D imagery.
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Animals↗
[Recurrent hyponatremia, neurological symptoms and long-term administration of levomepromazine].
We present the case of an 84 year old lady with an episode of marked hyponatremia with acute neurological disturbances which in the latest case resolved completely after a 3 day period of fluid restriction. The more common causes of hyponatremia could be ruled out. There was no evidence for a neuroleptic drug associated change in serum sodium concentration. We conclude that the patient in this study belongs to a subset of geriatric patients in whom there is an intermittent SIADH which only becomes clinically evident when several factors coincide. The underlying mechanisms are not understood but could include the interaction of subclinical cerebrovascular disease and treatment with a neuroleptic drug in an elderly patient whose water and sodium homeostasis is compromised by the changes of normal aging which affect the many systems involved in maintaining water and sodium balance.
Aged↗
Superimposed single impulse and pulse train electrical stimulation: A quantitative assessment during submaximal isometric knee extension in young, healthy men.
Superimposed electrical stimulation techniques can be used to detect central activation failure (CAF), defined as incomplete central nervous system recruitment, suboptimal activation of motor units, or both. The purpose of this study was to evaluate superimposed electrical stimulation techniques to be used to detect CAF during isometric knee extension. We performed three sets of experiments and compared the torque increments from transcutaneous electrical stimulation with: (i) single impulses of different amplitudes (100 V, 150 V, and 200 V) and a pulse train of 100 Hz (100 V, 100 ms); (ii) pulse trains (100 Hz, 100 V) of different lengths (100 ms, 200 ms, and 300 ms); and (iii) pulse trains (100 Hz, 100 ms) of different amplitudes (50 V, 100 V, 150 V, and 200 V). Stimulation was evaluated at submaximal (80% of MVC) isometric knee extension in 24 healthy young men using a Biodex isokinetic dynamometer. Electrodes were placed over the rectus femoris muscle and all stimulation impulses were monophasic, rectangular waves of 0.2-ms duration. Pulse train stimulation at 100 V always elicited a torque increment, whereas single impulse stimulation, even at 200 V, only caused a torque increment in about half of the trials. For each subject, the pulse train generated a significantly larger torque increment than for any of the three single impulses. There was no significant difference in torque increment between the three pulse trains of different lengths. Pulse trains at 150 V and 200 V generated significantly larger torque increments than at 50 V and 100 V. High-frequency maximal train stimulation may thus improve the detection of CAF during isometric knee extension. Detection of CAF may be important in the clinical assessment of muscle weakness, investigating the mechanisms underlying muscle weakness, and evaluating potential therapeutic strategies.
Adult↗
The epidemiology of triglyceride as a coronary artery disease risk factor.
Triglyceride (TG) has long been associated as a risk factor for coronary artery disease. A recent meta-analysis of various epidemiologic studies has confirmed this link. An important issue is to assess further the appropriate cutpoints to classify desirable TG because recent data indicate that levels < 200 mg/dl confer elevated risk. The dietary habits of present hunter-gatherer populations reveal the impact of a Westernized diet on both TG and cholesterol and suggest that a desirable TG is < 100 mg/dl. The epidemiologic and observational data in support of this concept are explored.
Adolescent↗
Challenges faced in recruiting patients from primary care practices into a physical activity intervention trial. Activity Counseling Trial Research Group.
BACKGROUND: Special challenges are encountered when clinical trial recruitment targets a physician practice-based population, as opposed to recruiting from the community. Since most published information about recruitment has focused on the latter group, summation of successful primary-care-based recruitment strategies could prove useful for future trials recruiting from this population. METHODS: The Activity Counseling Trial (ACT) is a multicenter, randomized clinical trial that evaluated approaches to primary care-based interventions to increase physical activity in sedentary adults 35-75 years of age. Fifty-four clinicians from eight practices recruited 874 participants from three U.S. sites. Recruitment challenges that related, in great part, to the primary care setting included: (1) focusing on patients from ACT physician practices who had regularly scheduled or intend-to-schedule appointments within the next year; (2) placing trial staff in the clinical offices for recruitment purposes; and (3) placing trial interventionists in the physicians' offices. Other challenges were related to recruitment of minorities and men. RESULTS: Patient mailing yielded 43.4% of all randomized participants, followed by office-based questionnaires (32.5%) and direct telephone contact (21.6%). Based on a retrospective cost-effective analysis (indirect costs excluded), the self-administered office-based questionnaire was the least costly strategy for one site ($14/randomized participant), followed by patient mailing at another site ($58). The direct telephone contact method utilized at one site serving primarily a minority population yielded a per randomized participant cost of $80. CONCLUSIONS: Recruitment of clinical trial participants from practice-based populations requires modification of the strategies used to recruit from the community. Multiple strategies should be employed, followed closely for their respective yields, and adapted as needed.
Adult↗
Triglyceride as a risk factor, epidemiology.
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Biomarkers↗
A vitamin D(3) derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats.
AIMS/HYPOTHESIS: Streptozotocin-diabetic rats show impaired neurotrophic support by deficient nerve growth factor (NGF) in muscle and skin. We, therefore, examined a novel agent (CB1093; 1(S), 3(R)-Dihydroxy-20(R)-(1-ethoxy-5-ethyl-5-hydroxy-2-heptyn-1-yl)-9, 10-seco-pregna-5(Z),7(E),10(19)-triene), which induces expression of endogenous nerve growth factor. METHODS: We gave CB1093 orally followed by measurements of mechanical nociception, nerve growth factor, neuropeptides (immunoassay) and nerve growth factor receptors (western blots). RESULTS: In non-diabetic rats CB1093 caused dose-dependent increases in nerve growth factor production (140 % in soleus muscle and 190 % in sciatic nerve) and a mechanical hyperalgesia in the foot. There was also increased sciatic nerve expression of neuronal NGF target gene products, substance P (16 %) and calcitonin gene-related peptide (CGRP; 52 %). Depletions of nerve growth factor, substance P and CGRP in sciatic nerves of diabetic rats were prevented by CB1093, which also increased soleus nerve growth factor concentrations to 30 % over those seen in non-diabetic rats and increased its mRNA expression in skin. The CB1093 did not affect expression of nerve growth factor receptors (trkA and p75(NTR)) in dorsal root ganglia in control or diabetic rats, though the p75(NTR) expression was reduced by diabetes. The mechanical hyperalgesia seen in diabetic rats treated with vehicle was not exacerbated by CB1093. CONCLUSION/INTERPRETATION: These findings show that in animal models of diabetes it is possible to prevent depletions of nerve growth factor and the products of its neuronal target genes by oral treatment of a highly potent inducer of NGF gene expression. Pain is a possible side-effect, though this was a function of dose and was manifest more in controls than in diabetic rats. [Diabetologia (1999) 42: 1308-1313]
Animals↗
[Aging and water metabolism in health and illness].
Normal aging is associated with changes in body composition, thirst perception, renal function, and the hormonal regulatory systems involved in the maintenance of water and sodium balance. The presence of many diseases and drugs common in the elderly can interact with the impaired homeostatic systems to result in clinically significant disturbances of water and sodium with accompanying symptoms, morbidity, and mortality. These disorders, which include dehydration, hypernatremia, hyponatremia, urinary frequency, and urinary incontinence can either be prevented or promptly recognized and appropriately treated by understanding the physiological changes and clinical circumstances which put the elderly person at increased risk for deranged water and sodium balance.
Aged↗
New developments in the treatment of low high-density lipoprotein cholesterol.
Reduced levels of high-density lipoprotein (HDL) cholesterol represent an important risk factor for the development and progression of coronary artery disease. In recent years, clinical outcome studies have verified that statin therapy may reduce the risk of initial or recurrent cardiovascular events in subjects with elevated or "normal" cholesterol levels. Subgroup analysis has also revealed that patients with low HDL benefit from this therapy. Two recently presented outcome trials using fibrate therapy also demonstrated a potential role for these medications in subjects with low HDL. The use of various HDL raising agents, singly or in combination on arteriographic progression and their potential mechanisms of action are reviewed. The latter may be an important consideration in the treatment of high-risk patients with low HDL.
Bezafibrate↗
Aggressive preoperative use of intraaortic balloon pump in elderly patients undergoing coronary artery bypass grafting.
BACKGROUND: The use of the intraaortic balloon pump (IABP) in patients undergoing coronary artery bypass grafting has been traditionally associated with a high complication rate and adverse outcomes. However, recent reports show that many of these catastrophic outcomes can be avoided by preoperatively placing the IABP in high-risk patients. To further validate these reports, we defined a set of liberal criteria for preoperative IABP insertion and applied them to a series of elderly patients (70 years or older) undergoing isolated coronary artery bypass grafting. METHODS: Two hundred six consecutive patients who underwent isolated coronary artery bypass grafting with cardiopulmonary bypass were retrospectively reviewed. A rapid recovery protocol emphasizing reduced cardiopulmonary bypass time, an anesthetic protocol for early extubation, perioperative administration of corticosteroids and thyroid hormone, and aggressive diuresis was applied to all patients. Patients who required an urgent operation because of failed percutaneous transluminal coronary angioplasty, a critical left main stenosis (70% or greater), pronounced left ventricular dysfunction (left ventricular ejection fraction 40% or less), or unstable angina refractory to medical therapy or who required an emergency reoperation received preoperative IABP support. RESULTS: The 30-day mortality rate for the entire group was 4.4%. There were 97 patients (47%) who received a preoperative IABP (group II) in comparison with 109 patients (53%) who did not fulfill the preoperative insertion criteria (group I). Patients in group II had a lower left ventricular ejection fraction (mean, 46% versus 59%, p<0.001) and a higher incidence of congestive heart failure (35% versus 17%, p<0.01) and acute myocardial infarction (37% versus 17%, p<0.01) than patients in group I. The average postoperative hospital length of stay for patients in group II was slightly longer than for those in group I (9.0+/-10.5 versus 6.0+/-3.7 days, p<0.01). However, there were no statistically significant differences in complication or mortality rates between the two groups. Only 2 patients (2.2%) had complications related to IABP insertion. Lower extremity ischemia occurred in both patients, and both were treated successfully with thromboembolectomy. CONCLUSIONS: Liberal preoperative insertion of the IABP can be performed safely in high-risk elderly patients undergoing coronary artery bypass grafting, with results comparable to those in lower risk patients.
Age Factors↗
Etiology and incidence of rehospitalization after traumatic brain injury: a multicenter analysis.
OBJECTIVE: To investigate incidence and etiology of rehospitalizations at 1, 2, and 3 years after traumatic brain injury. DESIGN: Descriptive statistics were computed in a prospective study of etiology and incidence of rehospitalization at years 1, 2, and 3 postinjury. Analysis of variance (ANOVA) and chi2 were used to identify factors relating to rehospitalization; factors included length of stay, admission and discharge functional status, payer source, medical complications, injury severity, and demographics. SETTING: Four medical centers in the federally sponsored Traumatic Brain Injury Model Systems. In each setting, the continuum of care includes emergency medical services, intensive and acute medical care, inpatient rehabilitation, and a spectrum of community rehabilitation services. PARTICIPANTS: Six hundred sixty-five rehabilitation patients admitted to acute care within 24 hours of traumatic brain injury between 1989 and 1996. MAIN OUTCOME MEASURES: Annual incidence and etiology of rehospitalization. RESULTS: The annual incidence of rehospitalization ranged from 20% to 22.5%. Approximately half the rehospitalizations were for elective reasons. The most common reason for rehospitalization was for orthopedic or reconstructive surgery, followed by infectious disorders and general health maintenance. After the first year, the incidence of readmissions for seizures and psychiatric difficulties increased substantially. ANOVA and chi2 analyses were performed on data from the first year postinjury. No statistically significant associations were noted between incidence and etiology of rehospitalization and: demographics; injury severity; payer source for rehabilitation; concurrent injuries; acute care and rehabilitation length of stays; discharge Functional Assessment Measure; and discharge residence (p > .05). CONCLUSIONS: There is a relatively stable but high rate of rehospitalization for at least 3 years after injury. The costs of rehospitalization should be considered when evaluating the long-term consequences of injury.
Adolescent↗
Elevated CO2 alters community-level physiological profiles and enzyme activities in alpine grassland.
Plots of an alpine grassland in the Swiss Alps were treated with elevated (680 microl l(-1)) and ambient CO2 (355 microl l(-1)) in open top chambers (OTC). Several plots were also treated with NPK-fertilizer. Community level physiological profiles (CLPPs) of the soil bacteria were examined by Biolog GN microplates and enzyme activities were determined through the release of methylumbelliferyl (MUF) and methylcoumarin (MC) from MUF- or MC-labelled substrates. A canonical discriminant analysis (CDA) followed by multivariate analysis of variance showed a significant effect of elevated CO2 on the CLPPs both under fertilized and unfertilized conditions. Further, the installation of the OTCs caused significant shifts in the CLPPs (chamber effect). Of the four enzyme activities tested, the beta-D-cellobiohydrolase (CELase) and N-acetyl-beta-D-glucosaminidase (NAGase) activity were enhanced under elevated CO2. L-Leucin-7-aminopeptidase (APEase) activity decreased, when the plots received fertilizer. Beta-D-glucosidase (GLUase) remained unaffected. The results suggest effects of elevated CO2 on specific microbial activities even under low mineral nutrient conditions and when bulk parameters like microbial biomass or respiration, which have been investigated on the same site, remain unaffected. The observed medium-term changes point at possible long-term consequences for the ecosystem that may not be specified yet.
Acetylglucosaminidase↗
Measles among adults, United States, 1985-1995.
OBJECTIVE: To report the incidence and characteristics of adult measles cases in the United States and address the adequacy of current vaccination policies to eliminate measles transmission. METHODS: Confirmed measles cases reported to the Centers for Disease Control and Prevention (CDC) from 1985 through 1995 were reviewed. Demographic data, exposure setting, and vaccination status of cases were analyzed and incidence rates calculated based on U.S. census data. MAIN OUTCOME MEASURES: Age-specific incidence rates of measles and exposure setting. RESULTS: Of the 75,204 reported measles cases of known age, 16,006 (21.3%) occurred in adults (persons > 19 years of age). The incidence in persons < 19 years of age (7.8/100,000) was 9.6 times that of all adults. Of 11,520 adult measles cases for whom vaccination status was reported, 8,055 (69.9%) indicated no prior receipt of measles vaccine. Exposure setting was unknown for the majority of adult measles cases (8,475, 52.9%); most frequently reported were college or school (2840, 17.7%), home (1443, 9.0%), or a medical setting (1286, 8.0%). International travel was associated with 289 (1.8%) adult cases. From 1993 to 1995, incidence rates in all age groups were at record low levels, with adults contributing 29.5% (467/1584) of reported cases. CONCLUSION: Although adults accounted for a steadily increasing proportion of measles cases during the study period, incidence rates in all age groups have decreased. Most adults who had measles were susceptible because of lack of vaccination rather than vaccine failure. This analysis supports current strategies to ensure the immunity of school/college-aged populations, and health care workers.
Adolescent↗
Video-assisted thoracoscopic sympathectomy for severe intractable angina.
OBJECTIVE: Endoscopic trans-thoracic sympathectomy is a well documented, safe and successful treatment for palmar and axillary hyperhidrosis. This may also be helpful in the management of patients with intractable angina and advanced coronary disease unsuitable for coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA). We evaluated video assisted thoracoscopic sympathectomy (VATS) in such patients with the aim of improving symptoms and quality of life. METHODS: Video assisted thoracoscopic sympathectomy, a minimally invasive procedure, was performed under general anaesthesia with alternating single lung ventilation. Three stab incisions were made at the level of the fourth intercostal space in the anterior and posterior axillary lines, and at the fifth intercostal space in the mid-axillary line through which an extensive thoracic sympathectomy was performed to include second to the fourth ganglia, bilaterally. RESULTS: A total of 16 patients aged 46-76 (mean 61) years were assessed for VATS. Of these 10 patients had the procedure performed; nine with previous CABG and one with diffuse coronary disease. Six patients were excluded because of an evolving MI (n = 1), left ventricular ejection fraction (LVEF) < 30% (n = 2), and chronic stable angina with no objective evidence of ischaemia (n = 3). All 10 patients had marked symptomatic improvement with reduction of both angina frequency and intensity of attacks. Mean follow-up period 11.5 months. Exercise tolerance and time to onset of angina measured on exercise treadmill was significantly increased post-VATS (P = 0.028) and maintained 1 year post-operative. CONCLUSION: VATS was associated with both reduction in angina symptoms and an increase in exercise time to onset of angina. An improved quality of life was evident.
Aged↗
Characterization of Royal Gala apple aroma using electronic nose technology-potential maturity indicator.
Changes in aroma of apple harvested at four different maturities were measured at harvest and after short-term storage using electronic aroma sensors ("electronic nose") and classical headspace/gas chromatography methods. Stored fruits were also evaluated by a trained sensory panel. Compared with headspace/gas chromatography, the electronic nose was found to be more sensitive ( approximately 40 times) in terms of sample size. The sampling procedure for the electronic nose was much less complex. Using discriminant function analysis, both methods classified the apples tested into groups according to harvest date. After storage, the groupings were more diffuse. Results from sensory testing showed partial separation along the first linear discriminant but did not classify the apple into distinct groups. Important differences between treatments were found for "overall flavor", "acid flavor" intensity, "crispness", "cider/fermented aroma", "vegetative aroma", and "canned pear aroma".
Electronics↗