bluuebunny/crossref_metadata_2025 huggingface dataset:
Age at Arrival, English Proficiency, and Social Assimilation Among US Immigrants
Authors: Bleakley Hoyt , Chin Aimee
Published: December 2009

Are the English proficiency and social outcomes of US immigrants the result of their cultural preferences or of more fundamental constraints? Using 2000 census microdata, we relate the English proficiency, marriage, fertility, and residential location variables of immigrants to their age at the time of arrival in the United States, and, in particular, whether that age fell within the “critical period” of language acquisition. We interpret the differences between younger and older arrivers as effects of English language skills and construct an instrumental variable for English language skills. Two-stage-least-squares estimates suggest English proficiency increases the likelihood of divorce and intermarriage. It decreases fertility and, for some, ethnic enclave residence. (JEL J11, J13, J61, R23, Z13)
Parental Education and Child Health: Evidence from a Natural Experiment in Taiwan
Authors: Chou Shin-Yi , Liu Jin-Tan , Grossman Michael , Joyce Ted
Published: December 2009

In 1968, the Taiwanese government extended compulsory education from 6 to 9 years and opened over 150 new junior high schools at a differential rate among regions. Within each region, we exploit variations across cohorts in new junior high school openings to construct an instrument for schooling, and employ it to estimate the causal effects of mother's or father's schooling on infant birth outcomes in the years 1978–1999. Parents' schooling does cause favorable infant health outcomes. The increase in schooling associated with the reform saved almost 1 infant life in 1,000 live births. (JEL I12, I21, J12, J13, R23)
Parents' Incomes and Children's Outcomes: A Quasi-Experiment Using Transfer Payments from Casino Profits
Authors: Akee Randall K. Q. , Copeland William E. , Keeler Gordon , Angold Adrian , Costello E. Jane
Published: December 2009

We examine the role an exogenous increase in household income, due to a government transfer unrelated to household characteristics, plays in children's long-run outcomes. Children in affected households have higher levels of education in their young adulthood and a lower incidence of criminality for minor offenses. Effects differ by initial household poverty status. An additional $4,000 per year for the poorest households increases educational attainment by one year at age 21, and reduces the chances of committing a minor crime by 22 percent for 16 and 17 year olds. Our evidence suggests improved parental quality is a likely mechanism for the change. (JEL D14, H23, I32, I38, J13)
Productivity Differences Between and Within Countries
Authors: Acemoglu Daron , Dell Melissa
Published: December 2009

We document substantial within-country (cross-municipality) differences in incomes for a large number of countries in the Americas. A significant fraction of the within-country differences cannot be explained by observed human capital. We conjecture that the sources of within-country and between-country differences are related. As a first step toward a unified framework, we propose a simple model incorporating differences in technological know-how across countries and differences in productive efficiency within countries. (JEL E23, I31, J31, O15, O18, O47, R23)
Development Accounting
Authors: Hsieh Chang-Tai , Klenow Peter J.
Published: December 2009

Researchers have made much progress in the past 25 years in accounting for the proximate determinants of income levels: physical capital, human capital, and Total Factor Productivity (TFP). But we still know little about why these factors vary. We argue that TFP exerts a powerful influence on output not only directly, but also indirectly, through its effect on physical and human capital accumulation. We discuss why TFP varies across countries, highlighting misallocation of inputs across firms and industries as a key determinant. (JEL E22, E23, F21, F35, O10, O40)
The New Kaldor Facts: Ideas, Institutions, Population, and Human Capital
Authors: Jones Charles I. , Romer Paul M.
Published: December 2009

In 1961, Nicholas Kaldor highlighted six “stylized” facts to summarize the patterns that economists had discovered in national income accounts and to shape the growth models being developed to explain them. Redoing this exercise today shows just how much progress we have made. In contrast to Kaldor's facts, which revolved around a single state variable, physical capital, our updated facts force consideration of four far more interesting variables: ideas, institutions, population, and human capital. Dynamic models have uncovered subtle interactions among these variables, generating important insights about such big questions as: Why has growth accelerated? Why are there gains from trade? (JEL D01, E01, E22, E23, E24, J11)
Relative efficiency of chlamydia screening in non-clinical settings in two California counties
Authors: Morris S R , Bauer H M , Chartier M , Howard H , Watson S , Yokotobi J , Taylor A F , Bolan G
Published: December 2009

We examined the relative efficiency of non-clinical sites to screen for chlamydia in youth and young adults. Chlamydia screening targeting youth (under 30 years of age) was performed at non-clinical sites in high-morbidity neighbourhoods of two California counties. Venues were subdivided into community outreach, schools, parenting centres and drug treatment/correctional facilities. Relative efficiency was estimated with multivariate Poisson regression using incidence of chlamydia per person-hours labour adjusting for strategy and county. Among the 1514 youths screened, the overall prevalence of chlamydia was 5.5%. By venue, the highest prevalence was in drug treatment/correction facilities at 11.1% followed by parenting centres at 6.3%, community outreach at 4.9% and schools at 4.6%. Drug treatment/correctional facilities were the most labour time efficient at 9.9 person-hours per chlamydia case. Schools and parenting centres had the lowest cost per screen at 0.9 person-hours per screen. Adjusted relative labour time efficiency (chlamydia cases per paid person-hour) was significantly higher in schools, 2.0 (95% confidence interval [CI] 1.0–4.2), parenting centres, 3.2 (95% CI 1.6–6.6) and drug treatment/correctional facilities, 2.9 (95% CI 1.0–7.8), compared with community outreach. In conclusion, parenting centres and drug treatment centres and correctional facilities are the most efficient venues for chlamydia screening.
Characteristics of research-related HIV testing programmes contribute to detection of more HIV infections
Authors: Woods W J , Binson D , Pollack L M , Aviña S M , Ballesteros A , Rocha D , Bingham T A
Published: December 2009

HIV prevalence estimates from bathhouse testing programmes differ widely, ranging from 3% to 11%. The observed difference may be a consequence of whether the programme was part of a research project or a community-based programme. A research-funded testing programme was offered at a bathhouse between May 2001 and December 2002. A local community-based organization began a testing programme in July 2006 at the same bathhouse; the data for this analysis cover the period July 2006 through December 2007. County-wide HIV prevalence estimates were available across the two time periods (i.e. 2001–2002 and 2006–2007). The research-funded testing programme recruited fewer men but identified more positive individuals (10.7% of those testing in the research programme) than were identified among men who tested in the area clinics (3.8% of those men who have sex with men [MSM] testing throughout the county in the same time period). However, the community-based testing programme identified about the same proportion of positive MSM (2.6%) as county clinics (2.7%) in the same time period. In conclusion, results confirmed that even in the same venue, a community-based HIV testing programme identified a similar proportion of positive MSM as the area clinics; however, the research-funded programme identified appreciably more. Incentives may contribute to the difference.
Audit of a sexual health website email link for general practitioners
Authors: Biggs K , Lowe P , Walsh J , Lagios K
Published: December 2009

The aim of this review was to evaluate an ‘Email a Clinician’ link on a medically reviewed sexual health website, which was established to allow general practitioners (GPs) to communicate remotely with sexual health clinic specialists. The website was developed in consultation with GPs and extensively promoted throughout the relevant professional primary health-care networks. Despite this, the email link appeared to fail in its objective of facilitating GP access to specialist sexual health physician opinion within five working days. An audit examining use of the email link was conducted for a one-year period, during which time 324 emails were received. Results showed that the bulk of the emails (93.2%) were spam, and only 6.8% were genuine enquiries. Of the 22 genuine emails, 21 (95%) originated from the general public and there were no enquiries from the GPs, who were the target audience of the website, resulting in removal of the email link from the site. Direct survey of local GPs to evaluate reasons for non-utilization of the link was not possible. However, discomfort with the technology, time added to existing workload, lack of direct perceived benefit and lack of immediate response have been cited as contributing factors that may limit widespread adoption of other telemedicine services. As a new generation of recently graduated GPs enters the Australian workforce, who might be expected to be skilled and comfortable with electronic medical communication, the option of a direct email link to a sexual health clinic, with a faster turnaround time, may be worth re-visiting in the future.
Giuseppe Pasta (1742–1823): protophysician and pioneer of psychological studies in the medical field
Authors: Clerici Carlo Alfredo , Veneroni Laura , Poli Marco
Published: December 2009

Giuseppe Pasta was a pioneer of psychological support in physical disease. Born in Bergamo, Italy, he was a cousin of the physician Andrea Pasta who was a pupil of Giovanni Battista Morgagni. Giuseppe's cultural and clinical resources were the teachings of Francesco Redi's medical school in Tuscany. This paper discusses the courage and philosophical tolerance of disease and the etiquette of the physician.
Edward Meryon (1807–80) and Charles Darwin's (1809–82) On the Origin of Species
Authors: Emery Alan E H , Emery Marcia L H
Published: December 2009

London in the first half of the 19th century was a centre of scientific and medical interest. For example, the Royal Society, the Linnean Society, the Geological Society, the Chemical Society and the Royal Astronomical Society were all centred on Burlington House and, not far away, in Berner's Street was the Medical and Chirurgical Society, which in 1834 became the Royal Medical and Chirurgical Society and later the Royal Society of Medicine. It was also in this period that Edward Meryon became a member of the latter society and subsequently a Council Member, Librarian and Vice-President. His research led to the clear identification for the first time of the disease Duchenne muscular dystrophy and he published his results in the Transactions of the Royal Medical and Chirurgical Society in 1852.
Jean Martin Charcot (1825–93) and John Hughlings Jackson (1835–1911): neurology in France and England in the 19th century
Authors: Silvester Alexander
Published: December 2009

In 1862 Jean Martin Charcot was appointed Physician at the Salpêtrière Hospital in Paris, and simultaneously John Hughlings Jackson was appointed as assistant physician at the National Hospital for the Paralysed and Epileptic, Queen Square, London. Both men made significant contributions to the development of neurology, many of which remain important to contemporary neurologists. The achievements and the work of Charcot and Hughlings Jackson are considered in the light of their respective localities and medical education, and the structure of hospital institutions and political allegiances are compared in the late 19th century in France and Britain.
Dr Arnold Renshaw (1885–1980): Manchester pathologist and forensic pathologist with a clinical interest in rheumatoid arthritis
Authors: Shreeve David R
Published: December 2009

Dr Arnold Renshaw trained in both dentistry and medicine in Manchester, being actively involved in the University student organisations. He followed a career in pathology and bacteriology that was interrupted by serving in the RAMC during World War I. Bacteriological interest in the antiseptic properties of aniline dyes followed. His main interest, however, was in pathology where he was associated with the Pathology Society of Manchester for more than twenty years. He was also actively involved in the founding of the Association of Clinical Pathologists. The Association led to the formation of the Royal College of Pathologists and to Renshaw being elected one of the Founding Fellows. He also developed a special expertise in forensic pathology which he pioneered in northwest England. His later years witnessed an interest in rheumatoid arthritis to investigate a possible cause and suggest a unique treatment consisting of the small intestinal enzymes, erepsin.
Two Cases of Sudden Sensorineural Hearing Loss After Methadone Overdose
Authors: Christenson Bret J , Marjala Andrew RP
Published: December 2009

OBJECTIVE

To document the presentation of 2 cases of sudden sensorineural hearing loss (SSHL) following methadone overdose.

CASE SUMMARY

We report 2 cases of acute, bilateral methadone-induced hearing loss that took place on the same night in our emergency department. A 30-year-old male and his 25-year-old wife were found unresponsive in their home after ingesting an unknown, but presumably large, quantity of methadone. Drugs that are typically categorized as ototoxic were ruled out in each patient via rapid in-house urine drug screens as well with a comprehensive analysis via gas chromatography mass spectrometry. Methadone and tetrahydrocannabinol (THC) were the only drugs found in the toxicology screenings that were common to both patients. The man had a long treatment course that included several days in the intensive care unit. The woman recovered completely and was discharged within a day of admission. The hearing loss in both patients reversed completely within 24 hours.

DISCUSSION

Several medications are commonly associated with ototoxicity, including nonsteroidal antiinflammatory drugs, antibiotics, loop diuretics, and chemotherapy agents. Although rare, drug-induced SSHL has been documented particularly among intravenous drug abusers after heroin injection. Until now, there has been only one published case report documenting drug-induced SSHL attributed to methadone.

CONCLUSIONS

We believe methadone to be the probable cause of SSHL in both patients, because it and THC were the only common drugs found on toxicology screens, a recent case report involved methadone-induced SSHL, and because of the suddenness of the onset and recovery of the patient's hearing coinciding with the time frame of the ingestion. The Naranjo probability scale score revealed that the adverse reaction was probable for each patient.
Evaluation of a Pharmacist-Managed Telephone Lipid Clinic at a Veterans Affairs Medical Center
Authors: Fabbio Kristin L , Bradley Matthew , Chrymko Margaret
Published: December 2009

BACKGROUND

Heart disease is one of the leading causes of death and disability in the US, with dyslipidemia being a significant risk factor. Pharmacist-managed lipid clinics have been shown to be effective in lowering low-density lipoprotein cholesterol (LDL-C) values in the veteran population. In addition, telephone-managed clinics are known to be an effective method to manage anticoagulation therapy. This type of appointment is very convenient; it reduces travel and waiting times, costs, and potential no-show rates.

OBJECTIVE

To assess changes in LDL-C levels from baseline to follow-up and number of patients attaining LDL-C goals during enrollment in the pharmacist-managed telephone lipid clinic (PMTLC).

METHODS

A retrospective chart review was conducted on all patients enrolled in the clinic who had follow-up laboratory data available. Baseline LDL-C values were compared with values obtained at follow-up. Patients' total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) values were also collected and analyzed for improvement. The agents used, number of antidyslipidemic medications, and the incidence of adverse drug reactions prior to and during clinic enrollment were also collected.

RESULTS

Patients in the PMTLC had a mean ± SD reduction in LDL-C of 44.3 ± 45.2 mg/dL (p < 0.001). In addition, 10 (28%) patients achieved the LDL-C goal (p = 0.002). Mean reductions in TC and TG levels were 44 mg/dL (18%) and 14.6 mg/dL (8%), respectively. There was no significant change in HDL-C levels.

CONCLUSIONS

The PMTLC at the Erie, PA, Veterans Affairs Medical Center demonstrated statistically significant reduction in patients' LDL-C levels and increase in the number of patients attaining LDL-C goal.
Melatonin Treatment for Insomnia in Pediatric Patients with Attention-Deficit/Hyperactivity Disorder
Authors: Bendz Lisa M , Scates Ann C
Published: December 2009

OBJECTIVE

To evaluate the efficacy and safety of melatonin for the treatment of insomnia in pediatric patients with attention-deficit/hyperactivity disorder (ADHD).

DATA SOURCES

Literature was accessed through MEDLINE (1948-August 2009), EMBASE (1950-August 2009), and Scopus (1960-August 2009) using the terms melatonin, attention-deficit/hyperactivity disorder (ADHD), pediatric, insomnia, sleep disorder, and sleep. In addition, reference citations from publications identified were reviewed for relevant information.

STUDY SELECTION AND DATA EXTRACTION

All English-language articles and human studies were identified and evaluated. Results from all identified randomized trials (n = 5), safety studies (n = 1), long-term follow-up studies (n = 1), post hoc retrospective analyses (n = 1), meta-analyses (n = 2), review articles (n = 9), and letters (n = 1) were summarized.

DATA SYNTHESIS

Pediatric insomnia is prevalent in children with ADHD and impacts academic performance, social functioning, overall health, and family life. First-line therapy includes ruling out differential diagnoses, optimizing ADHD stimulant treatment, and initiating good sleep hygiene and behavioral therapy. Adjuvant pharmacotherapy is then an option and melatonin is often prescribed. Melatonin regulates circadian rhythm sleep disorders such as sleep-onset insomnia (SOI) in children with ADHD. Four studies in children with ADHD and insomnia showed improvement in sleep onset and sleep latency. Studies included children 6–14 years old and melatonin doses ranged from 3 to 6 mg administered within a few hours of a scheduled bedtime. In all studies, adverse events were transient and mild. The available melatonin studies are limited by small size and short duration; variable SOI criteria, ADHD criteria, and treatment assessments; and lack of generalizability.

CONCLUSIONS

Available data suggest that melatonin is a well-tolerated and efficacious treatment option for pediatric patients with chronic SOI and ADHD. Regulated melatonin products and larger, well-designed trials to establish optimal dosing regimens and long-term safety are needed.
A Pharmacist and Health Promoter Team to Improve Medication Adherence Among Latinos with Diabetes
Authors: Gerber Ben S , Cano Alejandra I , Caceres Maria L , Smith Daphne E , Wilken Lori A , Michaud Jessica B , Ruggiero Laurie A , Sharp Lisa K
Published: December 2009

BACKGROUND

There is a need to improve blood glucose levels of underserved Latino patients with uncontrolled diabetes.

OBJECTIVE

To determine the feasibility of a pharmacist and health promoter team designed to address the barriers to medication adherence and adjustment and improve self-care among Latinos with type 2 diabetes.

METHODS

Clinical staff at the University of Illinois at Chicago Medical Center referred Latino patients with uncontrolled diabetes (hemoglobin A1c [A1C] ≥8.0%) to the study. A research assistant assessed patients on diabetes and medical history, medication list, medication adherence and related habits, health literacy, diabetes knowledge and numeracy, beliefs in benefits of diabetes therapy, depression, social support, and access to care. A bilingual, bicultural health promoter reviewed these assessments and worked with patients through home and clinic visits and telephone calls. The health promoter communicated with a pharmacist to receive assistance in medication management (reconciliation and adjustment). Participants received case management for 6 months.

RESULTS

Nine patients were successfully recruited. The mean age was 58 years and mean duration of diabetes was 21 years. Successful collaboration between pharmacists and the health promoter required frequent communication and intense effort to address complex patient barriers. Health promoter contact time, in person, per participant ranged from 0 minutes to 640 minutes, and telephone call time ranged from 27 minutes to 111 minutes during the study period. Eight participants had medication adjustments during the study period, with a maximum of 7 adjustments per participant. Mean hemoglobin A1C declined from an average of 9.6% to 9.0%. Two patients are presented as case studies to describe how the pharmacist-health promoter team functioned. Information was obtained from health promoter records, survey results, and chart reviews.

CONCLUSIONS

The pharmacist and health promoter team management of uncontrolled diabetes among Latinos appears to be a feasible approach to improving medication management.
Phosphorylase and the origin of reversible protein phosphorylation
Authors: Fischer Edmond H.
Published: December 2009

This article presents a historical account of the discovery of reversible protein phosphorylation. The process was uncovered in the mid-1950s in a study designed to elucidate the complex hormonal regulation of skeletal muscle glycogen phosphorylase. This enzyme was originally thought to be regulated by AMP now known to serve as an allosteric effector. By contrast, hormonal regulation was found to result from a phosphorylation of the protein triggered by Ca2+ and ATP which activate phosphorylase kinase; the reverse reaction is catalyzed by a phosphorylase phosphatase. Although that reaction is extremely simple, it came nevertheless as a complete surprise because essentially nothing was known at that time about the structure and function of phosphoproteins. This study led to the establishment of the first hormonal cascade of successive enzymatic reactions, kinases acting on kinases, initiated by cAMP discovered by Earl Sutherland. It also showed how two different physiological processes (carbohydrate metabolism and muscle contraction) could be regulated in concert. The regulation of phosphorylase was so straightforward that it was thought to represent the prototype for these kinds of interconversions. We know today that it was almost the absolute exception.
Principles, implementation, and application of biology-oriented synthesis (BIOS)
Authors: Wilk Wolfram , Zimmermann Tobias J. , Kaiser Markus , Waldmann Herbert
Published: December 2009

Biology-oriented synthesis (BIOS) represents an alternative approach for the generation of compound collections for biological applications. In BIOS, biologically relevant and prevalidated scaffold structures, such as core structures of natural products or known drugs, are employed as scaffolds for the generation of compound collections with focused diversity. In this review, we discuss the underlying concept of the BIOS approach, and its practical implementation in library design and synthesis. To highlight its relevance for chemical biology applications, we finally present examples in which compound collections generated under the BIOS principle have been used to elucidate biological questions.
An examination of the proteolytic activity for bovine pregnancy-associated glycoproteins 2 and 12
Authors: Telugu Bhanu Prakash V.L. , Palmier Mark O. , Van Doren Steven R. , Green Jonathan A.
Published: December 2009

The pregnancy-associated glycoproteins (PAGs) represent a complex group of putative aspartic peptidases expressed exclusively in the placentas of species in the Artiodactyla order. The ruminant PAGs segregate into two classes: the ‘ancient’ and ‘modern’ PAGs. Some of the modern PAGs possess alterations in the catalytic center that are predicted to preclude their ability to act as peptidases. The ancient ruminant PAGs in contrast are thought to be peptidases, although no proteolytic activity has been described for these members. The aim of the present study was to investigate (1) if the ancient bovine PAGs (PAG-2 and PAG-12) have proteolytic activity, and (2) if there are any differences in activity between these two closely related members. Recombinant bovine PAG-2 and PAG-12 were expressed in a baculovirus expression system and the purified proteins were analyzed for proteolytic activity against a synthetic fluorescent cathepsin D/E substrate. Both proteins exhibited proteolytic activity with acidic pH optima. The k
cat/K
m for bovine PAG-2 was 2.7×105 m
-1 s-1 and for boPAG-12 it was 6.8×104 m
-1 s-1. The enzymes were inhibited by pepstatin A with a K
i of 0.56 and 7.5 nm for boPAG-2 and boPAG-12, respectively. This is the first report describing proteolytic activity in PAGs from ruminant ungulates.
6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of smallde novoproducts
Authors: Wurm Reinhild , Neußer Thomas , Wagner Rolf
Published: December 2009

6S RNA fromEscherichia coliis known to bind to RNA polymerase, preventing interaction with many promoters during stationary growth. The resulting repression is released under conditions of nutritional upshift, when the growth situation improves. 6S RNA, which binds to the active site of RNA polymerase, has the particularly interesting feature to act as a template, causing the transcription of definedde novoRNAs (dnRNA) that are complementary to a specific sequence region of the 6S RNA. We analyzed the conditions of dnRNA synthesis and determined their effect on the 6S RNA-mediated inhibition of RNA polymerasein vitroandin vivo. Upon nutritional upshift the RNA polymerase/6S RNA complex induces the rapid synthesis of dnRNAs, which form stable hybrids with the 6S RNA template. The resulting structural change destabilizes the inactivated RNA polymerase complex, causing σ subunit release. Both dnRNA and 6S RNA are rapidly degraded after complex disintegration. Experiments using the transcriptional inhibitor rifampicin demonstrate that active transcription is required for the disintegration of the RNA polymerase/6S RNA complex. Our results support the conclusion that 6S RNA not only inhibits transcription during stationary growth but also enables cells to resume rapid growth after starvation and help to escape from stationary phase.
Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1
Authors: Weinheimer Isabel , Boonrod Kajohn , Moser Mirko , Zwiebel Michèle , Füllgrabe Marc , Krczal Gabi , Wassenegger Michael
Published: December 2009

Ectopically expressedrice yellow mottle virusP1 fusion proteins were found to be cleavedin plantaand inEscherichia coli. Cleavage takes place in the absence of bacterial protease activity, indicating that the P1 fusion is autocatalytically processed independently of host factors. N-terminal sequencing of the C-terminal cleavage product of transiently expressed P1/GFP (green fluorescence protein) inNicotiana benthamianashowed that the cleavage site is located between the first two amino acids (aa) downstream of the P1 sequence. Mutagenesis experiments revealed that a phenylalanine to valine substitution at position 157 of the P1 aa sequence impairs proper cleavage, which is nearly unaffected by replacement of phenylalanine with tyrosine. Deletion of methionine159(first GFP aa residue) appeared to not affect P1/GFP cleavage. N-terminal P1-tagging with GFP turned out to impair autocleavage, whereas a small His-tag could not fully prevent cleavage. Additionally, a modified P1/GFP carrying an N-terminal deletion of 81 aa was not cleaved. These findings indicate that this region is involved in the proteolysis mechanism and that large N-terminal fusion partners might affect correct folding of the P1 necessary for self-catalysis.
Warm-Blooded: True Blood and Let the Right One In
Authors: Tyree J. M.
Published: December 2009

An essay about the 2008 vampire boom, from the bland teen favorite Twilight to, more notably, Let the Right One In (which combines “dirty realism” with a misfit love story) and the TV series True Blood (whose liberal politics of tolerance for minorities opens up to less easily classifable forms of sex and violence).
Links between diabetes mellitus and sleep disorders: focusing on obstructive sleep apnea
Authors: Véber Orsolya Ágnes , Dunai Andrea , Novák Márta , Mucsi István
Published: December 2009

A legutóbbi évtizedek során az iparosodott társadalmakban folyamatosan emelkedik a diabetes és az obesitas incidenciája, és ezzel párhuzamosan egyre gyakrabban lépnek fel alvászavarok, rövidebb az alvással töltött idő, nő a krónikus alváshiány gyakorisága. Egyre több adat támasztja alá azt a feltételezést, amely szerint az elhízás és a cukorbetegség, valamint az alvászavarok között egy önrontó kör teremt kapcsolatot: az alvás-ébrenlét zavarok hatnak az endokrin és az anyagcsere-állapotra, ugyanakkor a metabolikus eltérések befolyásolják az alvás szabályozását. Az alvászavarok közül az alvásfüggő légzészavarok, azon belül is az obstruktív alvási apnoe mutat leginkább összefüggést a kóros szénhidrát-anyagcserével. A cukorbetegeknél magasabb az alvási apnoe prevalenciája és a középsúlyos, illetve súlyos alvási apnoéban szenvedők aránya az átlagpopulációhoz képest. A centrális obesitas az alvási apnoénak és a cukorbetegségnek is fontos rizikófaktora, de az obesitastól független, közvetlen kapcsolatot is sikerült igazolni a diabetes és az apnoe között. A diabeteses neuropathia és a metabolikus szindróma összefüggést mutat az apnoe előfordulásával és súlyosságával. Kapcsolat mutatható ki az apnoés epizódok következtében fellépő intermittáló hypoxia és az inzulinrezisztencia között, aminek következtében megnőhet a diabetesrizikó, vagy a meglévő diabetes glykaemiás kontrollja romolhat. A diabetológus és az alvásdiagnosztikában jártas szakorvosok összehangolt, preventív munkájával a betegek életminősége és a betegség kimenetele javítható.
Association of Aldosterone Concentration and Mineralocorticoid Receptor Genotype with Potassium Response to Spironolactone in Patients with Heart Failure
Authors: Cavallari Larisa H. , Groo Vicki L. , Viana Marlos A. G. , Dai Yang , Patel Shitalben R. , Stamos Thomas D.
Published: December 2009

Study Objective.To identify patient‐specific factors associated with spironolactone‐induced potassium level elevation in patients with heart failure.

Design.Prospective cohort study.

Setting.Two adult heart failure clinics.

Patients.Sixty‐two adult (mean ± SD age 54 ± 16 yrs) aldosterone antagonist‐naïve patients with heart failure.

Intervention.Patients received spironolactone 12.5 mg/day, titrated to 25 mg/day if tolerated.

Measurements and Main Results.Blood samples were obtained at baseline, 1 week after spironolactone initiation, and 1 week after spironolactone dose titration for assessment of baseline aldosterone level, serum chemistry, and angiotensinogen (AGT)c.‐6G>A and p.M268T and mineralocorticoid receptor (NR3C2)c.215C>G and p.I180V genotypes. Patient characteristics, laboratory values, and genotypes were compared between those whose potassium levels increased by more than 0.5 mEq/L (15 patients) and those with lower potassium level elevations (47 patients) after spironolactone initiation and dose titration. Patients with a greater potassium level elevation had a higher mean ± SD aldosterone concentration (178 ± 92 vs 102 ± 57 pg/ml, p=0.007) andNR3C2215G allele frequency (50% vs 22%, p<0.01). Aldosterone concentrations positively correlated with diuretic dose (r=0.313, p=0.014) and negatively correlated with serum potassium level (r=‐0.319, p=0.012). On regression analysis, factors predictive of potassium level increases greater than 0.5 mEq/L with spironolactone were aldosterone level greater than 150 pg/ml (odds ratio [OR] 30, 95% confidence interval [CI] 3.2–287] andNR3C2215G carrier status (OR 17, 95% CI 1.6–167).

Conclusion.Our data suggest that potassium should be monitored with particular caution when spironolactone is started in patients with heart failure who have evidence of elevated aldosterone levels, such as high diuretic requirements, or theNR3C2215G allele.
Decreased T‐Cell Responses to Influenza Vaccination in Patients with Heart Failure
Authors: Vardeny Orly , Moran John J. M. , Sweitzer Nancy K. , Johnson Maryl R. , Hayney Mary S.
Published: December 2009

Study Objective. To determine whether T‐cell immune responses to influenza vaccination in patients with chronic heart failure (CHF) are less vigorous than the responses of healthy control subjects.

Design. Prospective, single‐center study

Setting. University hospital and research laboratory

Participants. Eighteen adults with stable CHF receiving optimal treatment and 16 healthy control subjects.

Intervention. Participants were immunized with the 2006–2007 trivalent inactivated (killed) influenza vaccine during October‐December of 2006.

Measurements and Main Results. Blood samples were taken from the participants before and 2–4 weeks after vaccination to measure antibody titers, which were measured with a hemagglutination inhibition assay, then 3–4 months after vaccination to assess T‐cell responses, measured by using the trans vivo delayed‐type hypersensitivity method. As part of this method, which mimics physiologic conditions, peripheral blood mononuclear cells were isolated from the blood samples. The cells were mixed with influenza vaccine antigens A/H1N1, A/H3N2, and B type and injected into the footpads of SCID mice (mice with severe combined immunodeficiency), as their resulting swelling is an index of human T‐cell sensitization. Median T‐cell‐mediated immune responses to A/H3N2 were less vigorous in patients with CHF than in control subjects (62.5 vs 87.5 μm, unadjusted p=0.031, age‐adjusted p=0.006). Median responses to A/H1N1 were not significantly different between the groups (56.3 vs 75 μm, p=0.11). Median responses to B type were also similar between the groups (62.5 vs 75 μm, p=0.47). All participants mounted an antibody response to the influenza vaccine.

Conclusion. Patients with CHF had reduced T‐cell responses to the influenza vaccine compared with healthy control subjects, as demonstrated by a lower response to A/H3N2, the newest antigen in the 2006–2007 vaccine. However, differences in T‐cell immune responses to the A/H1N1 and B type strains were not found to be significant between the two groups, which suggests that patients with CHF can mount an appropriate response to vaccine antigens to which they have been previously exposed, but less so to new antigens. These findings suggest that patients with CHF may be at increased risk for influenza infection, and clinicians may want to investigate other or additional strategies for influenza vaccination.
Effects of Acetaminophen, Naproxen, and Acetylsalicylic Acid on Tapentadol Pharmacokinetics: Results of Two Randomized, Open‐Label, Crossover, Drug‐Drug Interaction Studies
Authors: Smit Johan W. , Oh Charles , Rengelshausen Jens , Terlinden Rolf , Ravenstijn Paulien G. M. , Wang Shean‐Sheng , Upmalis David , Mangold Bernhard
Published: December 2009

Study Objective.To evaluate the effects of acetaminophen, naproxen, and acetylsalicylic acid on the pharmacokinetics of the centrally acting analgesic tapentadol in healthy subjects.

Design.Two randomized, open‐label, crossover, drug‐drug interaction studies.

Setting.Clinical research facilities in the United States and Belgium.

Participants.Twenty‐four healthy adults (2‐way crossover study) and 38 healthy adults (3‐way crossover study).

Interventions.In both studies, tapentadol immediate release (IR) 80 mg was administered as a single oral dose alone. In the 2‐way crossover study, tapentadol IR was also given with the fifth of seven doses of acetaminophen 1000 mg; in the 3‐way crossover study, tapentadol IR was also given with the third of four doses of naproxen 500 mg and the second of two doses of acetylsalicylic acid 325 mg. All treatments were separated by a washout period of 7–14 days.

Measurements and Main Results.Overall, mean serum concentrations were similar after administration of tapentadol IR alone and after coadministration with acetaminophen or acetylsalicylic acid, and the 90% confidence intervals (CIs) for the ratios of the mean area under the serum concentration‐time curve (AUC) from time zero to time of the last measurable concentration (AUC0‐t) and from time zero extrapolated to infinity (AUC0‐$iF) and the maximum serum concentration (Cmax) of the combined treatments to those parameters of tapentadol alone were well within 80–125%, representing the accepted range for bioequivalence. Coadministration of naproxen did not significantly alter the Cmax of tapentadol, although a slightly higher serum tapentadol exposure relative to tapentadol alone was observed. Coadministration of naproxen resulted in a mean increase of 17% in AUCs, and the upper limits of the 90% CIs for the ratios of the mean AUC0‐tand AUCo‐$iFwere slightly outside the upper limit of bioequivalence range of 80–125% (126.47% AUC0‐tand 126.14% AUC0‐$iF).

Conclusion.No clinically relevant changes were noted in the serum concentrations of tapentadol, and accordingly, no dosage adjustments with respect to the investigated pharmacokinetic mechanism of interaction are warranted for the administration of tapentadol given concomitantly with acetaminophen, naproxen, or acetylsalicylic acid.
Once‐Daily Gentamicin Dosing in Children with Febrile Neutropenia Resulting from Antineoplastic Therapy
Authors: Inparajah Miriam , Wong Cecile , Sibbald Cathryn , Boodhan Sabrina , Atenafu Eshetu G. , Naqvi Ahmed , Dupuis L. Lee
Published: December 2009

Study Objectives. To evaluate an existing once‐daily gentamicin dosing guideline in children with febrile neutropenia resulting from antineoplastic therapy and, if necessary, to develop a new simulated dosing guideline that would achieve pharmacokinetic targets more reliably after the first dose.

Design. Pharmacokinetic analysis of data from a retrospective medical record review Setting. Hematology‐oncology unit of a university‐affiliated pediatric hospital in Canada.

Patients. One hundred eleven patients aged 1–18 years who received once‐daily gentamicin between April 2006 and 2008 for the treatment of febrile neutropenia resulting from antineoplastic therapy, and who had plasma gentamicin concentrations determined after their first dose.

Measurements and Main Results. Demographic data, gentamicin dosing information, blood sampling times, and plasma gentamicin concentrations were noted. Plasma gentamicin concentrations were determined at approximately 3 and 6 hours after the start of the 30‐minute infusion of the first dose. Pharmacokinetic parameters were calculated according to standard first‐order, one‐compartment equations. The proportion of children who achieved pharmacokinetic targets after the first gentamicin dose was used as a measure of dosing guideline performance; the guideline achieved maximum concentration (Cmax) values below the target range (20–25 mg/L) in 51% of patients. Ideal dosing guidelines were then developed using the mean dose required to achieved a Cmax of 23 mg/L for each patient. Univariate analysis or the Student t test was used to determine the existence of significant relationships between pharmacokinetic parameters and patient age and sex. The recursive binary partitioning method was used to determine critical values of age for dosage guideline development; analysis of variance was then used to compare the different levels obtained after use of this technique. Simulated administration of once‐daily gentamicin in the following doses achieved a Cmax within or above target in 73% of patients: 1 year to < 6 years, 10.5 mg/kg/dose; girls > 6 years, 9.5 mg/kg/dose; and boys > 6 years, 7.5 mg/kg/dose. Doses were based on actual body weight for children who weighed less than 125% of ideal body weight or based on effective body weight for children 125% or more of ideal body weight.

Conclusion. The initial gentamicin dosing guidelines were not effective in achieving Cmax. The new proposed dosing guidelines are predicted to achieve a Cmax within or above the target range in almost three quarters of patients. Subsequent dosing should be tailored according to plasma gentamicin concentrations.
Lack of Association Between Excretion of Sorafenib in Sweat and Hand‐Foot Skin Reaction
Authors: Jain Lokesh , Gardner Erin R. , Figg William D. , Chernick Milica S. , Kong Heidi H.
Published: December 2009

Study Objective. To determine if excretion of sorafenib in sweat is associated with hand‐foot skin reaction in patients receiving sorafenib.

Design. Prospective pilot study.

Setting. Outpatient clinic of a cancer research institution.

Patients. Two patients who were receiving sorafenib and developed a hand‐foot skin reaction of at least grade 1 and two healthy subjects (controls).

Intervention. Sweat production was stimulated in both the patients with hand‐foot skin reaction and the healthy subjects by means of pilocarpine iontophoresis.

Measurements and Main Results. Sweat samples were collected from the patients with hand‐foot skin reaction and from the healthy subjects. Using liquid chromatography‐tandem mass spectrometry, sorafenib concentrations were measured in the sweat samples. Sweat samples from the healthy subjects were spiked with known concentrations of sorafenib to determine the lower limit of quantification of the assay, which was determined to be 5 ng/ml. Sorafenib concentrations in the samples from the patients with hand‐foot skin reaction were undetectable based on the assay's sensitivity.

Conclusion. Our results suggest that hand‐foot skin reaction in patients receiving sorafenib is not associated with excretion of sorafenib in sweat. Further studies are needed to understand the mechanism of hand‐foot skin reaction, a treatment‐limiting adverse effect of multikinase inhibitors.
A Comparative Review of the Lipoglycopeptides: Oritavancin, Dalbavancin, and Telavancin
Authors: Guskey Michael T. , Tsuji Brian T.
Published: December 2009

Resistance to antibiotics among gram‐positive bacteria, especially enterococci and staphylococci, has led to the need to develop new antibiotics. Vancomycin, a glycopeptide antibiotic, has been used for over 3 decades to treat serious methicillin‐resistant Staphylococcus aureus infections. The increased frequency of multidrug‐resistant bacteria, especially vancomycin‐resistant strains, has focused interest on three new lipoglycopeptides for the treatment of infections caused by gram‐positive bacteria: oritavancin, dalbavancin, and telavancin. Although oritavancin and dalbavancin are still in development, telavancin received approval from the United States Food and Drug Administration in September 2009 for treatment of complicated skin and skin structure infections. Structurally different from vancomycin and teicoplanin, all three lipoglycopeptides have greater potency and less potential for development of resistant organisms. Of particular importance is the activity of oritavancin, dalbavancin, and telavancin against vancomycin‐resistant organisms. In addition, the pharmacokinetic properties of these new antimicrobials substantially differ from those of vancomycin. Both oritavancin and dalbavancin have long terminal half‐lives, which may allow for infrequent dosing. In addition, oritavancin is primarily cleared through hepatic pathways, which makes it potentially useful in patients with renal compromise. In animal models, these new lipoglycopeptides were effective in treating serious gram‐positive infections, including complicated skin and skin structure infections, endocarditis, bacteremia, and pneumonia; in clinical studies, however, efficacy was shown only in complicated skin and skin structure infections for all three agents. According to preliminary data, the adverse‐effect profile of these lipoglycopeptides is generally similar to that of drugs currently used to treat severe gram‐positive infections. However, further evaluation and monitoring is necessary as more patients are exposed to these agents. As antimicrobial resistance continues to increase worldwide, the lipoglycopeptides may provide clinicians with a useful antimicrobial in the continued fight against multidrug‐resistant gram‐positive bacteria.
Extended‐Interval Once‐Daily Dosing of Aminoglycosides in Adult and Pediatric Patients with Cystic Fibrosis
Authors: Prescott William A. , Nagel Jerod L.
Published: December 2009

Extended‐interval once‐daily dosing with the aminoglycoside tobramycin has been proven to be equally efficacious as traditional thrice‐daily dosing for treatment of the pulmonary exacerbations of cystic fibrosis in adults and children older than 5 years. The frequencies of acute ototoxicity and nephrotoxicity do not appear to be significantly different between patients treated with once‐versus thrice‐daily dosing, and the risk of acute nephrotoxicity may actually be lower in pediatric patients when once‐daily dosing is used. Long‐term studies are needed to fully assess the impact that cumulative treatments with once‐daily dosing have on renal and auditory function. An increase in antimicrobial resistance has been suggested with once‐daily dosing in the cystic fibrosis population. The extended‐interval aminoglycoside dose should be determined based on previous therapeutic drug monitoring. If the patient is aminoglycoside (tobramycin) naïve, a dose of 10 mg/kg once/day is suggested, with the dose adjusted by using therapeutic drug monitoring to individualize therapy.
Laboratory Investigation on the Effect of Water Injection Process on Rock Structure and Permeability Reduction
Authors: Abbasi S. , Tavakkolian M. , Shahrabadi A. , Oskui G. P.
Published: December 2009

The nature of some water injection processes can cause unavoidable formation damage. In most cases, by optimal design of the process, the formation damage can be minimized or avoided. The estimation and assessment of formation damage on reservoir core samples is an important measurement which will be presented in this paper by monitoring rock permeability changes.

Laboratory tests were set up to investigate the effects of injection pressure, flow rate and also induced fracture on the rock sample with respect to formation damage. Reservoir core nature, structure and its heterogeneity make the phenomenon of formation damage more complex. In this research, selected rock samples from one of Iranian giant oil fields, which is undergoing water injection, were used as the laboratory physical model. Using injection water samples, different scenarios were performed on this model. Permeability reduction was observed for un-fractured samples: however, it was more interesting that no injection pressure build up was detected in fractured samples. It appears that fractures in sandstones, especially with weak cementation, can play the role of an agent for particle movement in causing damage to different parts of the formation. Over a long period of time, this phenomenon can cause more complicated situations in the reservoir, the degree of which being a function of several parameters, such as rock type and structure, pore size distribution and reservoir heterogeneity.