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Biomedical subjects

Karen Smith

Publications and source records attributed to Karen Smith.

36 records · Page 2Linked to original sources

Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia.

The aim of this study was to evaluate the effects of rosuvastatin and fenofibrate alone and in combination in type 2 diabetes associated with combined hyperlipidaemia. A total of 216 patients with total cholesterol >/=200 mg/dl (>/=5.17 mmol/l) and triglycerides >/=200 and <800 mg/dl (>/=2.26 and <9.03 mmol/l) were randomised to one of two placebo groups, rosuvastatin 5 mg or rosuvastatin 10 mg for 6 weeks (fixed-dose phase). During the subsequent 18-week dose-titration phase, one placebo group received titrated rosuvastatin 10, 20 and 40 mg (placebo/rosuvastatin); one placebo group received titrated fenofibrate 67 mg once, twice and three times daily (placebo/fenofibrate); and patients receiving 5 or 10 mg rosuvastatin received titrated fenofibrate as above (rosuvastatin 5mg/fenofibrate and rosuvastatin 10 mg/fenofibrate groups). Doses were increased at 6-week intervals if low-density lipoprotein (LDL) cholesterol remained >50 mg/dl (>1.3 mmol/l). At 24 weeks, the placebo/rosuvastatin group and placebo per fenofibrate group had triglyceride reductions of 30.3% versus 33.6%, respectively (P = NS), and LDL cholesterol was reduced by 46.7% in the rosuvastatin group and increased by 0.7% in the fenofibrate group (P < 0.001). The triglyceride reduction in the rosuvastatin 10 mg/fenofibrate group (47.1%) was significantly greater than in the placebo/rosuvastatin group (P = 0.001), with no significant differences in other lipid measures found between these two groups. No significant differences in effect on high-density lipoprotein (HDL) were observed among treatment groups. In the fixed-dose phase, rosuvastatin 5 and 10 mg reduced triglycerides by 24.5 and 29.5%, respectively, and decreased LDL cholesterol by 40.7 and 45.8%, respectively. All treatments were well tolerated. These results indicated that rosuvastatin produces marked reductions in triglycerides and LDL cholesterol when used alone or in combination with fenofibrate in type 2 diabetes patients with elevated cholesterol and triglyceride levels and may constitute a valuable treatment option in the diabetic population.

Adult↗

A survey of coronary risk factors and B-type natriuretic peptide concentrations in cardiac nurses from Europe: do nurses still practice what they preach?

BACKGROUND: From a previous survey of cardiac nurses attending a scientific conference, we learned that these nurses adopted a healthier lifestyle than the general population. AIMS: The aim of this study was to determine the overall profile of cardiac risk factors in a similar cohort and determine whether cardiac nurses continue to 'practice what they preach' in this regard. Secondly, we examined the practical value of screening a large cohort of individuals within a short time frame (total of 8 hours screening time) and determined the range of BNP concentrations within a 'healthy' cohort. METHODS: Data on CHD risk factors were collected with a short self-report questionnaire. The sample consisted of 122 cardiac nurses from 19 countries attending a European cardiac nursing conference held in Stockholm. A venous blood sample was collected into a tube containing potassium ETDA. B-type natriuretic peptide was measured on-site with the use of a portable fluorescence immunoassay kit. RESULTS: Most participants were female (89%). Participants ranged in age from 23 to 60 years with a mean age of 41 (S.D. 9.4). Eleven percent - all female - reported they were current smokers, 27% (34) had a BMI >25 and 27% of the sample stated they did not exercise regularly. Almost half (48%) of the sample reported a family history of CHD. As expected, all BNP-values were within the normal range. There were significant differences in BNP on the basis of sex (P<0.05) and age (P<0.05) and a trend towards increasing BNP concentrations with progressively higher BMI scores (P=0.06). CONCLUSION: This study reconfirms the likelihood that many cardiac nurses heed their own advice on lifestyle modification to reduce cardiovascular risk and therefore provide a good role model for the promotion of primary and secondary prevention initiatives.

Adult↗

Adolescents eating diets rich in either lean beef or lean poultry and fish reduced fat and saturated fat intake and those eating beef maintained serum ferritin status.

Reducing red meat intake to lower serum cholesterol may also lower iron and zinc intake. Eighty-six seventh and eighth graders who enrolled in a study comparing serum ferritin, zinc, and cholesterol levels were randomized to a low-fat eating pattern emphasizing either lean beef or lean poultry and fish. Serum data and three 24-hour recalls were collected at baseline and 3 months. The lean beef group ate significantly more beef [26 (4, 37) g/d; P<.01] and both groups reduced total and saturated fat intake. Although serum ferritin level change between baseline and intervention was significantly different between the lean beef and lean poultry and fish groups (median [interquartile range] 0.7 [-6, 8] and -6.8 [-12, 2] microg/dL, respectively), the drop in the lean poultry and fish group was not clinically significant. No differences were observed in iron and zinc intake or in serum zinc and cholesterol levels. Teenagers eating diets low in saturated fat may benefit from adequate amounts of lean red meat.

Adolescent↗

Automation of a fluorescence-based multiplex PCR for the laboratory confirmation of common bacterial pathogens.

A fluorescence-based multiplex PCR was automated for the simultaneous detection of Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae in clinical samples from patients with suspected meningitis. Sensitivity of one to two genome copies per 100 microl sample and specificity of 100% for each organism were shown. Automation of DNA extraction, liquid handling, PCR and analysis are achieved on a single platform, which enables a high throughput and rapid turnaround of clinical samples that, in turn, leads to faster diagnosis. This is ultimately beneficial to the treatment of the patient and for public health management.

Adolescent↗

Lipid-modifying effects of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy.

OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial. METHODS: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5 mg, 10 mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12. RESULTS: Rosuvastatin 5 mg and 10 mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5 mg and 10 mg, respectively, vs. -0.5% for placebo; p < 0.001), as did Apo A-I levels (p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported. CONCLUSIONS: Rosuvastatin 5 mg or 10 mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.

Administration, Oral↗

Current perceptions of cardiovascular gene therapy.

Due to differences in their knowledge base, scientists, health care professionals, and the general public have varying perceptions of the expectations and risks of using gene therapy for the treatment of cardiovascular disease. Gene therapists are aware of the importance of selecting the right vector, the right gene, and the right administration procedure for a specific application and for characterization of the heterogeneity of the physiologic response to gene expression. They also recognize the need for large-scale clinical trials to demonstrate short- and long-term safety, in addition to efficacy, for widespread acceptance. Interventional cardiologists are more likely to judge a therapy primarily on its ability to improve cardiovascular pathophysiology and function, although they too will demand safety data. Once convinced of the benefits of a gene therapy, interventional cardiologists will rely on regulatory and reimbursement authorities to approve the procedure. Attitudes of less-specialized physicians toward gene therapy and, specifically, therapeutic angiogenesis will be influenced by the level of clinical trial activity in their country and opinions expressed in the media. However, all will want safety and efficacy data as well as clear guidance on the type of patients who should be referred for treatment. Nurses' roles are set to expand with the introduction of gene-based therapies; most will need further genetics education to rise to these challenges with confidence. The success of a gene therapy will also rely on patients' perceptions and their willingness to receive the treatment. Any misconceptions based on unreliable information sources need to be addressed.

Attitude↗

Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice.

The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of alpha- and beta-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients.

Acetylation↗

S-phase checkpoint controls mitosis via an APC-independent Cdc20p function.

Cells divide with remarkable fidelity, allowing complex organisms to develop and possess longevity. Checkpoint controls contribute by ensuring that genome duplication and segregation occur without error so that genomic instability, associated with developmental abnormalities and a hallmark of most human cancers, is avoided. S-phase checkpoints prevent cell division while DNA is replicating. Budding yeast Mec1p and Rad53p, homologues of human checkpoint kinases ATM/ATR and Chk2, are needed for this control system. How Mec1p and Rad53p prevent mitosis in S phase is not known. Here we provide evidence that budding yeasts avoid mitosis during S phase by regulating the anaphase-promoting complex (APC) specificity factor Cdc20p: Mec1p and Rad53p repress the accumulation of Cdc20p in S phase. Because precocious Cdc20p accumulation causes anaphase onset and aneuploidy, Cdc20p concentrations must be precisely regulated during each and every cell cycle. Catastrophic mitosis induced by Cdc20p in S phase occurs even in the absence of core APC components. Thus, Cdc20p can function independently of the APC.

Anaphase-Promoting Complex-Cyclosome↗

Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report.

STUDY HYPOTHESIS: Recent studies have shown that induced hypothermia for twelve to twenty four hours improves outcome in patients who are resuscitated from out-of-hospital cardiac arrest. These studies used surface cooling, but this technique provided for relatively slow decreases in core temperature. Results from animal models suggest that further improvements in outcome may be possible if hypothermia is induced earlier after resuscitation from cardiac arrest. We hypothesized that a rapid infusion of large volume (30 ml/kg), ice-cold (4 degrees C) intravenous fluid would be a safe, rapid and inexpensive technique to induce mild hypothermia in comatose survivors of out-of-hospital cardiac arrest. METHODS: We enrolled 22 patients who were comatose following resuscitation from out-of-hospital cardiac arrest. After initial evaluation in the Emergency Department (ED), a large volume (30 ml/kg) of ice-cold (4 degrees C) lactated Ringers solution was infused intravenously over 30 min. Data on vital signs, arterial blood gas, electrolyte and hematological was collected immediately before and after the infusion. RESULTS: The rapid infusion of large volume, ice-cold crystalloid fluid resulted in a significant decrease in median core temperature from 35.5 to 33.8 degrees C. There were also significant improvements in mean arterial blood pressure, renal function and acid-base analysis. No patient developed pulmonary odema. CONCLUSION: A rapid infusion of large volume, ice-cold crystalloid fluid is an inexpensive and effective method of inducing mild hypothermia in comatose survivors of out-of-hospital cardiac arrest, and is associated with beneficial haemodynamic, renal and acid-base effects. Further studies of this technique are warranted.

Acid-Base Equilibrium↗

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.

BACKGROUND: Cardiac arrest outside the hospital is common and has a poor outcome. Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome, but there have been no conclusive studies in humans. In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest. METHODS: The study subjects were 77 patients who were randomly assigned to treatment with hypothermia (with the core body temperature reduced to 33 degrees C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours) or normothermia. The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility. RESULTS: The demographic characteristics of the patients were similar in the hypothermia and normothermia groups. Twenty-one of the 43 patients treated with hypothermia (49 percent) survived and had a good outcome--that is, they were discharged home or to a rehabilitation facility--as compared with 9 of the 34 treated with normothermia (26 percent, P=0.046). After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation, the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 (95 percent confidence interval, 1.47 to 18.76; P=0.011). Hypothermia was associated with a lower cardiac index, higher systemic vascular resistance, and hyperglycemia. There was no difference in the frequency of adverse events. CONCLUSIONS: Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest.

Adult↗

Investigating six-month health outcomes of patients with angina discharged from a chest pain service.

Hospital admissions for patients with suspected cardiac chest pain are increasing. The development of a chest pain service allows rapid diagnosis, investigation and treatment. Since the in-patient stay is often short, there is limited time for education and risk factor management. Little is known about the patients' recovery post discharge. This study was completed to investigate the 6-month health outcomes of 57 patients discharged from the chest pain service by measuring cardiovascular symptoms and risk profiles, mood and quality of life, adherence to secondary prevention, morbidity and mortality. The results of this study showed that 58% of the sample still suffered angina, 72% reported breathlessness, and 79% reported lethargy. Assessment of mood showed that 76% suffered from anxiety and 78% depression. Quality of life was impaired. A reduction of cholesterol level was the only significant change in risk factors. Secondary prevention measures showed that there was still room for improvement. Twenty-five percent of the sample was readmitted to hospital due to their cardiac condition. Patients had an average of eight contacts with their general practitioner, four of which were cardiac related. The ongoing symptoms, anxiety and depression and uncorrected risk factors can impact on their recovery. Currently, however, no programme of rehabilitation is available for angina patients, despite the potential for up to 30% of patients suffering a subsequent cardiac event (Ghandi et al., British Heart Journal 73 (1995) 193-198). This study suggests the need to develop, implement and evaluate a CR programme in this client group.

Adult↗

The use of rapid sequence intubation by ambulance paramedics for patients with severe head injury.

OBJECTIVE: To determine the effects of rapid sequence intubation in patients with severe head injury performed by paramedics on a helicopter emergency medical service. METHODS: The patient care records for patients with severe head injury who underwent rapid sequence intubation between November 1999 and February 2002 (inclusive) were examined. Data were extracted on the demographics of the patients, as well as the physiological changes before and after rapid sequence intubation. RESULTS: There were 122 patients with severe head injury evaluated at the scene during the study period. Rapid sequence intubation was attempted in 110 patients and was successful in 107 (97%). Intubation was associated with improvements in systolic blood pressure, oxygen saturation and end-tidal carbon dioxide levels, compared with baseline levels. CONCLUSION: Rapid sequence intubation in patients with severe head injury may be safely undertaken by helicopter-based ambulance paramedics and is associated with improvements in oxygenation, ventilation and blood pressure. Further studies of this skill undertaken by road-based paramedics are warranted.

Adult↗

Posterior-stabilized versus cruciate-retaining total knee arthroplasty: balancing the gap.

A prospective, randomized, double-blind trial was carried out to compare cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasties (TKAs). A total of 40 knees were randomized to receive either a NexGen CR (Zimmer, Warsaw, IN) or a Legacy PS (Zimmer, Warsaw, IN) TKA. All knees were implanted with identical surgical technique, making sure to balance precisely the flexion-extension gaps before implantation of the components. At 2-year follow-up, there was no difference between the CR and the PS TKAs with respect to their Knee Society clinical, functional, and radiographic scores. These findings suggest that with careful attention to surgical technique and balancing the knee, orthopaedic surgeons should expect similar results whether they use a CR or PS TKA.

Aged↗

Isothiocyanato boron dipyrromethenes--the first BODIPY analogues of fluorescein isothiocyanate.

Two boron complexes of 5-phenyldipyrromethenes bearing isothiocyanate groups on the phenyl ring have been synthesized for the first time. The utility of these new fluorescence probes for labeling biologically relevant proteins is demonstrated on two monoclonal antibodies that bind to antigens overexpressed on cancer cells. Spectral comparison of the two structures reveals significant photophysical differences, including bathochromically shifted excitation and emission bands, increased molar absorptivity and a large increase in fluorescence quantum yield of approximately 10 times. Differences in photophysical parameters are linked to hindered rotation of the phenyl ring in one of the probes.

Antibodies, Monoclonal↗

Lifetime distributional effects of Social Security retirement benefits.

This article presents three measures of the distribution of actual and projected net benefits (benefits minus payroll taxes) from Social Security's Old-Age and Survivors Insurance (OASI) for people born between 1931 and 1960. The results are based on simulations with the Social Security Administration's Model of Income in the Near Term (MINT), which projects retirement income through 2020. The base sample for MINT is the U.S. Census Bureau's Survey of Income and Program Participation panels for 1990 to 1993, matched with Social Security administrative records. The study population is grouped into 5-year birth cohorts and then ranked by economic status in three ways. First, the population is divided into five groups on the basis of individual lifetime covered earnings, and their lifetime present values of OASI benefits received and payroll taxes paid are calculated. By this measure, OASI provides much higher benefits to the lowest quintile of earners than to other groups, but it becomes less redistributive toward lower earners in more recent birth cohorts. Second, people are ranked by shared lifetime covered earnings, and the values of shared benefits received and payroll taxes paid are computed. Individuals are assumed to split covered earnings, benefits, and payroll taxes with their spouses in the years they are married. By the shared covered earnings measure, OASI is still much more favorable to persons in the lower income quintiles, although to a lesser degree than when people are ranked by individual covered earnings. OASI becomes more progressive among recent cohorts, even as net lifetime benefits decline for the entire population. Finally, individuals are ranked on the basis of their shared permanent income from age 62, when they become eligible for early retirement benefits, until death. Their annual Social Security benefits are compared with the benefits they would have received if they had saved their payroll taxes in individual accounts and used the proceeds to buy either of two annuities that provide level payments from age 62 until death: a unisex annuity that is based on the average life expectancy of the birth cohort or an age-adjusted annuity that is based on the worker's own life expectancy. On the permanent income measure, OASI is generally more favorable to people in higher income quintiles. Moreover, it is particularly unfavorable to those in the lowest quintile. Because people in the lowest quintile have a shorter life expectancy, they receive OASI benefits for a shorter period. This group would receive greater benefits in retirement if they invested their payroll taxes in the age-adjusted annuity. OASI is more favorable to them than the unisex annuity, however, OASI is becoming more progressive in that the net benefits it provides drop more rapidly among higher income quintiles than lower ones. This article also examines how OASI affects individuals by educational attainment, race, and sex. On both the lifetime covered earnings and the permanent income measures, OASI is more favorable to workers with less education and more favorable to women. The results by race and ethnicity are mixed. When people are ranked by the present value of their shared lifetime covered earnings, OASI appears more favorable to non-Hispanic blacks and Hispanics than to non-Hispanic whites. When people are ranked by shared permanent income in retirement, however, OASI produces negative returns for both non-Hispanic blacks and non-Hispanic whites in the most recent birth cohorts, with non-Hispanic blacks faring relatively worse. The changes across cohorts occur partly because of changes in tax rates and benefits, but more importantly because of changing demographics and earnings patterns of the workforce. Of particular importance is the increasing share of beneficiaries who receive worker benefits instead of auxiliary benefits as wives or widows. OASI benefits are based on the lifetime covered earnings of current or former married couples, as well as on earned retirement benefits of individuals. The reduced importance of auxiliary benefits (due to the higher lifetime covered earnings of women) and the increased proportion of divorced retirees make OASI more progressive--even as net benefits decline--for current and future cohorts than for cohorts who retired in the 1990s. Analysis of these findings suggests that simulations of policy changes in Social Security must take into account the decreasing importance of auxiliary benefits across birth cohorts and the complex changes in individuals' marital histories.

Actuarial Analysis↗

Asthma management in children.

Asthma can be very serious. In the United States approximately 5,000 deaths, 2 million emergency room visits and 500,000 hospitalizations occur each year. As each individual learns more about asthma, adheres to their treatment plan and visits their healthcare provider for regular follow-up care, the goals for better asthma care can be achieved.

Asthma↗