bluuebunny/crossref_metadata_2025 huggingface dataset:
Migraine Is Associated With Menorrhagia and Endometriosis
Authors: Tietjen Gretchen E. , Conway Anita , Utley Christine , Gunning William T. , Herial Nabeel A.
Published: January 2006

Objective.—To evaluate the frequency of menorrhagia and endometriosis in female migraineurs compared to age‐matched women without headache.

Background.—Migraine predominantly affects women of childbearing age and is often associated with the menstrual period, yet there is a paucity of data regarding the relationship of migraine and menstrual disorders.

Methods.—Women diagnosed with migraine, using International Headache Society criteria and an age‐ and sex‐matched control group, were administered a semistructured questionnaire regarding migraine and migraine‐related disability, menstrual history, other bleeding history, vascular event history, and vascular risk factors.

Results.—Fifty female migraineurs between the ages of 22 and 50 years and 52 age‐matched women (mean age 37 years) were enrolled in the study. Similar proportions of women in each group reported using hormone contraceptives (30% vs. 33%, P= .77) and hormone replacement therapy (12% vs. 8%, P= .69). The proportions presently menstruating (64 % vs. 80%, P= .20) and status after hysterectomy were similar (24% vs. 14%, P= .84). Menorrhagia (defined as at least three consecutive heavy periods), both current and prior, was more commonly reported in migraineurs (63% vs. 37%, P= .009), with higher likelihood of staining clothes by menses (35% vs. 8%, P= .003), and significant impact of menses on activities of daily living (on a 10‐point Likert scale) with work/school participation (P= .02), family activities (P < .0001), sleep (P= .003), life enjoyment (P= .001), mood (P= .02), and overall quality of life (P= .003). Endometriosis, which may be associated with menorrhagia, was also more commonly diagnosed in the migraineurs (30% vs. 4%, P= .001). The migraineurs more frequently described bruising (40% vs. 10%, P < .001) and rectal bleeding (18% vs. 2%, P= .017) but not more serious bleeding problems. Nonsteroidal anti‐inflammatory drug (NSAID) use was more frequent in the migraine group (28% vs. 12%, P= .036), and significance for increased menorrhagia, endometriosis, menstrual interference, and bruising was maintained, even when controlling for the use of NSAIDs. With logistic regression, menorrhagia was significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95% CI 1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95% CI 2.2 to 51.4). There were no differences in vascular events and risk factors, except for trends of increased hypertension (25% vs. 10%, P= .05), transient ischemic attack/stroke (10% vs. 2%, P= .08), and Raynaud's disease (10% vs. 2%, P= .08) in the migraineurs.

Conclusion.—Women with migraine have a higher frequency of menorrhagia, endometriosis, and associated psychosocial consequences. These findings suggest that there should be further study of factors influencing endometriosis and menstrual blood flow, such as eicosanoids and platelet function, in migraineurs.
Thomas Jefferson's Headaches: Were They Migraines?
Authors: Cohen Gary L. , Rolak Loren A.
Published: January 2006

Thomas Jefferson had severe headaches on a number of occasions during his adult life, as noted by most of his biographers. Some occurred during important historical events, including the period just before the writing of the Declaration of Independence. Historians generally have considered these headaches to be migraines, while some physician authors have considered the alternative diagnoses of tension‐type headaches and cluster headaches. A review of the literature, including Jefferson's many letters, suggests that they probably were migraines, although not all of the current diagnostic criteria can be met.
Complete DNA Sequence Variation in the Apolipoprotein H (β2‐glycoprotein I) Gene and Identification of Informative SNPs
Authors: Chen Qi , Kamboh M. Ilyas
Published: January 2006

Apolipoprotein H (APOH), also known as β2‐glycoprotein I, is a major antigen for the production of antiphospholipid antibodies in autoimmune diseases. Previously we have examined DNA variation in the coding region of the APOH gene and determined the molecular basis of the common protein polymorphism. Here we report the results of DNA sequence variation in the entire APOH gene encompassing a 20.3 kb region in 46 Caucasian Americans and 48 African American chromosomes. A total of 150 single nucleotide polymorphisms (SNPs) and one tri‐allelic polymorphism were identified, including 8 in the coding region, 14 in the 5′‐region and 2 in the 3′‐ region; the remainder were observed in introns. The observed number of SNPs was higher in the African American sample than in the Caucasian sample (130 vs. 84). We examined the race‐specific linkage disequilibrium pattern among SNPs and identified maximally informative SNPs for future association studies. Altogether, we have identified 17 informative SNPs among Caucasians and 35 in blacks. The discovery of a full range of sequence variation and identification of race‐specific informative SNPs in the APOH gene may facilitate the rapid evaluation of this variation in relation to autoimmune diseases.
Case‐Control Association Tests Correcting for Population Stratification
Authors: Köhler K. , Bickeböller H.
Published: January 2006

In case‐control association studies unobserved population stratification may act as a confounder, leading to an increased number of false positive results. Methods accounting for population structure by using additional genetic markers broadly follow one of two concepts: Genomic Control (GC) and Structured Association (SA). While extending existing methods of Structured Association we show that it is necessary to incorporate phenotypic information when inferring population structure, otherwise a systematic bias is introduced. Moreover, for moderate population stratification a Wald test statistic should be preferred as a Structured Association test statistic in comparison to a likelihood ratio test. The introduced extensions are compared to existing methods of Structured Association, as well as to Genomic Control, in a simulation study which is based on realistic situations of large case‐control studies with moderate population stratification. A disadvantage of Genomic Control turns out to be the large variation in estimating the variance inflation factor, as well as the power loss if population structure increases. We come to the overall conclusion that Structured Association, if applied correctly, is superior to Genomic Control, at least in the case of simple population structure as simulated here.
Power and Sample Size for Testing Associations of Haplotypes with Complex Traits
Authors: Schaid Daniel J.
Published: January 2006

Evaluation of the association of haplotypes with either quantitative traits or disease status is common practice, and under some situations provides greater power than the evaluation of individual marker loci. The focus on haplotype analyses will increase as more single nucleotide polymorphisms (SNPs) are discovered, either because of interest in candidate gene regions, or because of interest in genome‐wide association studies. However, there is little guidance on the determination of the sample size needed to achieve the desired power for a study, particularly when linkage phase of the haplotypes is unknown, and when a subset of tag‐SNP markers is measured. There is a growing wealth of information on the distribution of haplotypes in different populations, and it is not unusual for investigators to measure genetic markers in pilot studies in order to gain knowledge of the distribution of haplotypes in the target population. Starting with this basic information on the distribution of haplotypes, we derive analytic methods to determine sample size or power to test the association of haplotypes with either a quantitative trait or disease status (e.g., a case‐control study design), assuming that all subjects are unrelated. Our derivations cover both phase‐known and phase‐unknown haplotypes, allowing evaluation of the loss of efficiency due to unknown phase. We also extend our methods to when a subset of tag‐SNPs is chosen, allowing investigators to explore the impact of tag‐SNPs on power. Simulations illustrate that the theoretical power predictions are quite accurate over a broad range of conditions. Our theoretical formulae should provide useful guidance when planning haplotype association studies.
The gene overexpressed in polycythemia rubra vera, PRV‐1, and the gene encoding a neutrophil alloantigen, NB1, are alleles of a single gene, CD177, in chromosome band 19q13.31
Authors: Caruccio Lorraine , Bettinotti Maria , Director‐Myska Alison E. , Arthur Diane C. , Stroncek David
Published: January 2006

BACKGROUND:  PRV‐1 mRNA is overexpressed by neutrophils from polycythemia vera patients and is homologous to NB1 a gene overexpressed in reactive neutrophilia.

STUDY DESIGN AND METHODS:  These investigations were designed to confirm searches of genome databases suggesting that PRV‐1 and NB1 are alleles of the same gene, CD177, and confirm a pseudogene adjacent to CD177. Methods included polymerase chain reaction (PCR), cloning, sequencing, and fluorescent hybridization studies.

RESULTS:  The coding region of PRV‐1 was PCR‐amplified from human fetal RNA, cloned, and used to screen the RPCI‐11 bacterial artificial chromosome (BAC) library. Five BACs were reactive with the PRV‐1 probe. PCR analysis of the BACs with primers encompassing PRV‐1 exons, containing four known single‐nucleotide polymorphisms, followed by sequencing rendered amplicons identical to PRV‐1 in all five BACs. Analysis of all five by restriction digestion yielded fragments possible only if both the gene and the pseudogene are present. End sequencing of the BACs localized them to the same chromosome region. G‐banding and fluorescence in situ hybridization at the 400‐ and 850‐band levels of resolution mapped one BAC to chromosome band 19q13.2 and sublocalized the BAC to band 19q13.31, respectively.

CONCLUSION:  PRV‐1 and NB1 are alleles of the same gene now referred to as CD177. Changes in CD177 expression may be a marker of increased or decreased myelopoiesis and are therefore an effect of, rather than a cause of, myeloproliferative disorders.
Correlates of hepatitis C virus (HCV) RNA negativity among HCV‐seropositive blood donors
Authors: Busch Michael P. , Glynn Simone A. , Stramer Susan L. , Orland Jennie , Murphy Edward L. , Wright David J. , Kleinman Steven ,   NHLBI Retrovirus Epidemiology Donor Study (REDS) Group
Published: January 2006

BACKGROUND:  Approximately 20 percent of persons infected with hepatitis C virus (HCV) clear viremia. Factors associated with resolution of viremia are not well defined. Implementation of routine nucleic acid testing (NAT) of blood donors has yielded a large data set for analysis of demographic correlates of resolved viremia.

STUDY DESIGN AND METHODS:  HCV antibody and NAT data, liver enzyme (alanine aminotransferase [ALT]) results, and donor demographic characteristics were compiled for 2,579,290 allogeneic donations given at five large blood centers after NAT implementation in 1999 through December 2001. Donation HCV RNA status was compared between first‐time donors categorized by ALT levels, sex, age, race and/or ethnicity, country of birth, level of education, blood center location, and blood group, with chi‐square tests and multivariable logistic regression methods.

RESULTS:  Of 35 confirmed‐seropositive repeat donors, 19 (54.3%) tested negative for the presence of HCV RNA; there was no association between RNA status and preseroconversion intervals (p = 0.74). Of 2105 RIBA‐positive, first‐time donors, 402 (19.1%) tested negative for the presence of HCV RNA by NAT (presumptive resolved infections). There were significant differences in the frequency of RNA negativity among first‐time donors categorized by ALT levels and by race and/or ethnicity. ALT levels were more likely to be elevated in RNA‐positive, first‐time donors (p < 0.0001). Viremia was less likely to resolve in Asian (8.2%) and black non‐Hispanic (14.4%) donors than in white non‐Hispanic (20.7%), Hispanic (22.1%), and other race and/or ethnicity (22.1%) donors (p = 0.02). No significant associations were found for age, sex, country of origin, level of education, blood type, and donor center location.

CONCLUSION:  These results confirm that the frequency of HCV RNA negativity among seropositive persons differs by race and/or ethnicity. Follow‐up studies of donors with resolved viremia are warranted to further elucidate viral, immunologic, and genetic factors underlying spontaneous viral clearance.
Mechanisms of dyslipidemia of chronic renal failure
Authors: VAZIRI Nosratola D. , MORADI Hamid
Published: January 2006

Chronic renal failure is associated with profound dysregulation of lipid metabolism and marked abnormalities of plasma lipid profile. This review is intended to provide an overview of the molecular basis of lipid disorders in chronic renal failure and explore their potential impact on cardiovascular disease and energy metabolism.
Visual blurring and metabolic acidosis after ingestion of bootlegged alcohol
Authors: RATHI Manish , SAKHUJA Vinay , JHA Vivekanand
Published: January 2006

Extracorporeal treatments have an important role in the management of several types of poisonings and drug overdosage. Methanol poisoning is a major problem in large parts of the developing world, especially among the economically depressed, and is responsible for innumerable deaths annually. Poisoning occurs when methanol, a contaminant of bootlegged alcohol, is consumed unknowingly. Toxicity is related to formaldehyde and formic acid formed as a result of methanol metabolism, and presents as metabolic acidosis, visual impairment, neurological manifestations, and shock. Initial symptoms are nonspecific and masked by the inebriating effect of ethanol. Appropriate management requires immediate administration of ethanol, which competitively inhibits methanol metabolism and prevents the generation of toxic formic acid and hemodialysis to achieve expeditious clearance of methanol and formic acid. Fomepizole, a safer metabolic inhibitor, has largely replaced ethanol in the western world. Delay in seeking medical attention contributes to mortality and morbidity. We report on a patient who presented to us 8 hr after consumption of countrymade alcohol with symptoms of methanol poisoning. Prompt administration of ethanol and institution of hemodialysis resulted in complete reversal of all manifestations.
Looking at calcimimetics impact on hypercalcemia of immobilization: Hypotheses and a case study
Authors: ROUEFF Stéphane , GEORGES Martine SAINT , CHUONG Van Thoai , ABBASSI Abdelhamid , GUÉDON Catherine , de VERNEJOUL Marie C. , TORRES Pablo UREñA
Published: January 2006

For the treatment of secondary hyperparathyroidism (HPTH‐II) in dialysis patients and hypercalcemia in patients with parathyroid carcinoma. Calcimimetics are a new class of drugs approved in the European Community and the United States by the Food and Drug Administration that were designed to suppress parathyroid hormone (PTH) levels with a simultaneous reduction in serum calcium and phosphorus levels, and calcium phosphorus product (Ca × P). Hypocalcemia is a frequent finding during the correction phase of the HPTH‐II with calcimimetics. By contrast, the appearance of a hypercalcemia has yet to be described. In this paper, we report a case of severe hypercalcemia of immobilization in a 40‐year‐old hemodialyzed woman treated by cinacalcet HCl for a severe HPTH‐II (PTH>1,000 pg/mL). A kidney transplantation recipient 1983 to 1995, she was diagnosed with Charcot‐Marie Tooth disease in 1991. She had multiple orthopedic interventions for kidney‐related osteoarticular problems probably favored by the kidney graft and the immunosuppressive treatment. While she was receiving the maximum dose of 180 mg/day of cinacalcet HCl and PTH at 443 pg/mL, she needed to be hospitalized for a right hip prothesis. Two weeks after the intervention she developed a symptomatic hypercalcemia of 3.57 mmol/L which was resistant to several measures including lowering the calcium concentration in the dialysate, withdrawing all vitamin D and calcium supplementation and the administration of calcitonin. Her serum calcium level was finally stabilized in the 2.37–2.95 mmol/L by administration of a single intravenous dose of pamidronate. This observation illustrates that the pharmacological activation of the parathyroid CaR and other putative CaR on bone cells by calcimimetics did not protect against the occurrence of hypercalcemia of immobilization favored by a severe HPTH‐II in a hemodialysis patient.
Screening for depression in chronic hemodialysis patients: Comparison of the Beck Depression Inventory, primary nurse, and nephrology team
Authors: WILSON Barbara , SPITTAL Joan , HEIDENHEIM Paul , HERMAN Margaret , LEONARD Margaret , JOHNSTON Ann , LINDSAY Robert , MOIST Louise
Published: January 2006

Depression in patients with end‐state renal disease (ESRD) is both underdiagnosed and treated, which may contribute to an increase in morbidity and mortality. Efforts aimed at screening, diagnosing, and treating depression could potentially modify outcomes in this population. The purpose of this study was to compare the prevalence of depression, as measured by the Beck Depression Inventory (BDI‐II), the primary nurse, and nephrology team, among a cohort of patients receiving chronic hemodialysis (HD). A secondary objective was to identify patient variables associated with depression. Patients were screened for depression at the same time point, using the BDI‐II, the primary nurse and the nephrology team. Depression was defined as a BDI‐II score ≥14. Agreement between the BDI‐II score, nurse, and nephrology team assessment of depression was compared using a kappa score and receiver‐operating characteristic (ROC) curves were generated. One hundred and twenty‐four of an eligible 154 patients completed the study. Depression as measured by a BDI‐II≥14, the nurse and the team was diagnosed in 38.7%, 41.9%, and 24.2% of patients, respectively. With the BDI‐II as the gold standard, the nurses' diagnosis of depression had an agreement of 74.6% vs. only 24.2% agreement with the nephrology team. A previous history of malignancy was the only variable associated with the diagnosis of depression. Depression is common among patients on HD, supporting the need for a routine depression‐screening program. The primary dialysis nurse is in a key position to identify patients with depression and should be considered as an integral part of the nephrology team.
Protecting the endothelium: A new focus for management of chronic kidney disease
Authors: DIAZ‐BUXO Jose A. , WOODS H. Feidhlim
Published: January 2006

It is being increasingly recognized that cardiovascular disease (CVD) and its complications are the most important cause of morbidity and mortality in patients with chronic kidney disease (CKD) and dialysis patients. If outcomes for these patients are to be improved, therapeutic strategies at all stages of CKD will have to target the etiologies and mechanisms that lead to CVD. In this review, we focus on the central role of endothelial dysfunction as the critical precursor of CVD. We argue that a better understanding of endothelial dysfunction by nephrologists and dialysis physicians is necessary if there is to be success in limiting the CVD epidemic that kills and maims our patients. The extensive studies to explain the high prevalence of vascular disease in patients with CKD have shown the close relationship among endothelial dysfunction, inflammation, and atherosclerosis. The pathogenesis starts with endothelial cell injury from any of many possible causes, and strategies to reduce the burden of CVD in uremic and dialysis patients must be directed at restoring normal endothelial function or, at the least, preventing aggravation of endothelial damage. At the center of the exploration of endothelial dysfunction and atherosclerosis are oxidative stress and inflammation. Of these, which is the chicken and which is the egg is unknown, but in the setting of uremia, endothelial injury because of free radical, oxidative stress is likely to precede inflammation. The issues raised here are highly complex and most renal practitioners may not have been adequately exposed to the background research underlying current thinking of the pathogenesis of vascular disease. Clearly, progress in management of CVD in patients with CKD will require collaboration with experts in the research and treatment of vascular disease. Nephrologists seeking optimum outcomes for patients with CKD will need to become “endotheliologists” or, at the least, subscribe to a mission “to protect the endothelium.”
Primary high‐dose intradermal hepatitis B vaccination in hemodialysis: Cost‐effectiveness evaluation at 2 years
Authors: MAT Olivier , MESTREZ Fabienne , BEAUWENS Renaud , MUNIZ‐MARTINEZ Marie‐Carmen , DHAENE Michel
Published: January 2006

Reinforced hepatitis B (HB) vaccination schedules have been tested in nonresponsive hemodialysis (HD) patients. Primary high‐dose intradermal (ID) vaccination in HD has been proposed in one study with higher seroconversion rate, but no cost analysis was made. The aim of this prospective study was to confirm this previous report and focus on a cost‐effectiveness evaluation of the thorough vaccination with a maintenance program. Thirty‐five chronic incident HD patients received primary ID HB vaccination with a reinforced schedule (20 μg Engerix‐B® every 2 weeks). Revaccination with a monthly single ID dose of 20 μg was performed whenever anti‐HBs titer fell under 20 IU/L and continued until a titer of 20 U/L was reached. Outcome measures were cumulative seroconversion rates, mean levels of anti‐HBs, maintenance booster doses, rate of seroprotection at the end of the 2‐year follow‐up and subsequent costs. The present study was associated with an earlier peak of anti‐HBs titer (3.9±1.7 months) and a higher cumulative seroconversion rate (96.9%) after 1 year. Moreover, a low‐booster shot (17.4 μg) of ID Engerix‐B®/year/patient confers a 100% seroprotection for all responders for a second‐year period. The mean cost of our schedule is 127.7€/patient for a 2‐year period, revaccination included. This current study demonstrates that primary reinforced ID HB vaccination with a maintenance program for a 2‐year period warrants the best cost‐effectiveness ratio with rapid and sustained seroprotection in almost all HD patients.
Comparison of side hole versus non side hole high flow hemodialysis catheters
Authors: TAL Michael G. , PEIXOTO Aldo J. , CROWLEY Susan T. , DENBOW Neil , ELISEO Donna , POLLAK Jeffrey
Published: January 2006

Current literature suggests that side holes may be detrimental to dialysis catheter performance. Today, these catheters are primarily available with side holes. The purpose of this study was to compare flow rates, infection rate, and survival of side hole vs. non side hole hemodialysis catheters. Over a 16‐month period patients were arbitrarily assigned to either a 14.5 F MAHURKAR® MAXID™ cuffed dual lumen tunneled catheter with side holes or a 14.5 F MAHURKAR MAXID cuffed dual lumen tunneled catheter without side holes (“non side hole catheters”). We performed a retrospective analysis of catheter flow rates, patency, catheter survival, and catheter‐related infections. Information was gathered for the life of the catheter or up to 28 weeks. A total of 54 patients were enrolled in the study. Thirty‐seven of 54 (68%) patients received a catheter with side holes for a total of 3,930 catheter days and 17/54 (32%) received a similar catheter without side holes for a total of 2,188 catheter days. Catheter infection necessitating removal of the catheter occurred in 10/37 catheters with side holes and 1/17 without side holes. Infection rates per 1,000 catheter days were 2.545 with side holes and 0.254 without side holes (p<0.001). Slightly improved catheter survival (p<0.05) was recorded with the non side hole catheters. No insertion complication (e.g., air embolization, bleeding, or kinking) occurred with either catheter. One catheter without side holes had to be repositioned 5 days after insertion because of poor flows. No significant difference was recorded in mean blood flow rates between the catheters. Results indicate reduced catheter infection rate in hemodialysis patients with the use of non side hole dual lumen tunneled cuffed catheters.
Clinical use of high‐efficiency hemodialysis treatments: Long‐term assessment
Authors: BOSCH Juan P. , LEW Susie Q. , BARLEE Viroj , MISHKIN Gary J. , von ALBERTINI Beat
Published: January 2006

Significant technological changes in blood flow rate, dialyzer membrane permeability, bicarbonate dialysate, and ultrafiltration‐controlled delivery systems permitted the implementation of 3 modifications to conventional hemodialysis as follows: high‐efficiency hemodialysis (HEHD), high‐flux hemodialysis (HFHD), and double‐high‐flux hemodiafiltration (HDF). The impact of these techniques on the quantity of the treatment administered and treatment time were assessed. One hundred and eighty‐three patients were enrolled over 6 years. Monthly Kt/Vurea and dialysis treatment time were compared among the treatment techniques. In vivo extracorporeal clearances were measured for the dialyzers used. In vivo kinetically derived effective dialyzer clearances were calculated from Kt/V. Patient survival and standardized mortality ratio (SMR) were determined for each treatment modality. Treatment time averaged 192±28, 176±29, and 159±32 min, Kt/Vurea averaged 1.33±.34, 1.29±.30, 1.41±.32, and in vivo delivered urea clearance averaged 222±51, 272±34, and 333±43 mL/min for HEHD, HFHD, and HDF, respectively. These results were achieved even in patients with body weights in excess of 80 kgs. Net ultrafiltration rate during the treatment reached 20–30 mL/min, without clinical untoward effects. Blood flow rate ranged between 450–650 mL/min in all patients. Kaplan‐Meier Survival analysis yielded a significant difference when high‐efficiency treatments were compared with USRDS outcomes. Standardized mortality ratio analysis showed significance for only HDF vs. USRDS. High‐efficiency treatments can provide the same quantity of treatment in a shorter period of time without affecting mortality. The increased spectrum of solutes removal provided by HFHD and HDF may be a further advantage of these treatments.
HCO3 increment in arterial line can reveal significant vascular access recirculation in high‐flux hemodialysis: A preliminary report
Authors: SOMBOLOS Kostas I. , CHRISTIDOU Fotini N. , BAMICHAS Gerasimos I. , GIONANLIS Lazaros D. , KARAGIANNI Anna C. , ANAGNOSTOPOULOS Theodoros C. , NATSE Taïsir A.
Published: January 2006

We report a new and simple way that can reveal the presence of vascular access recirculation (VAR) in patients undergoing hemodialysis (HD). Acid‐base and blood gas parameters (pH, pO2, pCO2, and HCO3) were measured in blood samples drawn from an arterial fistula needle before the initiation of HD and from arterial and venous lines simultaneously 5 min later, in 31 patients (group A). Vascular access recirculation was measured using the glucose infusion test (GIT) immediately after the withdrawal of the 5‐min samples. The same study was repeated in 30 patients in whom HD lines were reversed (group B). A comparison with baseline (predialysis) values of an analysis of the arterial line in group A at 5 min revealed that pCO2 increased by 1.14±2.5 mmHg and HCO3 by 0.6±0.6 mM/L (p<0.02 and p<0.00001, respectively). The corresponding pO2 and pH values did not show significant differences. Glucose infusion test at 5 min (GITa) was −0.058±0.03%. A comparison with baseline (predialysis) values of an analysis of the arterial line in group B at 5 min revealed that pCO2 increased by 7.7±3.5 mmHg and HCO3 by 2.9±1.0 mM/L (p<0.000001 in each case). The pH level was significantly lower in comparison with baseline values (p<0.00001), while pO2 did not show a significant difference. Glucose infusion test at 5 min (GITb) was 12.0±6.1% (p<0.000001 in comparison with GITa values). Clinically significant VAR was defined as HCO3 increment >1.8 mM/L, based on the receiver‐operating characteristics curve, which showed a threshold value of HCO3 increment >1.8 mmol/L as a predictor of GIT recirculation. Five minutes after the initiation of high‐flux HD with a 0 ultrafiltration rate, there is a small increment in arterial HCO3 values relative to predialysis values. Clinically significant VAR is present when this increment is higher than 1.8 mM/L.
Atypical clinical presentation of pigmented purpuric dermatosis
Authors: Zalaudek Iris , Ferrara Gerardo , Brongo Sergio , Giorgio Caterina M. , Argenziano Giuseppe
Published: January 2006

The term pigmented purpuric dermatosis (PPD) is used for a group of mainly asymptomatic, sometimes pruritic dermatoses that are clinically characterized by an eruption of pinpoint purpuric lesions along with yellow, orange, red and/or brown, often patchy pigmented areas. Traditionally five subtypes have been distinguished, but atypical clinical patterns may also occur. Because of the variable clinical spectrum and the similar histopathologic findings, a strict nosological classification is sometimes difficult or even impossible to achieve. We report a case of PPD with atypical clinical features in a young woman, underlining the difficulties in the clinical classification of this spectrum of diseases.
Dye laser treatment of periungual pyogenic granuloma
Authors: Tscharner Gion G. , Hunziker Thomas
Published: January 2006

Treatment of pyogenic granuloma may be difficult in locations such as the face and fingertips. We successfully treated a 1 cm periungual fingertip pyogenic granuloma with a dye laser.
Treatment of actinic keratoses with birch bark extract: a pilot study
Authors: Huyke Constance , Laszczyk Melanie , Scheffler Armin , Ernst Reinhard , Schempp Christoph M.
Published: January 2006

Background: Birch bark contains a variety of apoptosis‐inducing and anti‐inflammatory substances such as betulinic acid, betulin, oleanolic acid and lupeol. Therefore, birch bark extract may be effective in the treatment of actinic keratoses. To address this issue, a pilot study using a standardized birch bark ointment was performed.

Methods: Twenty‐eight patients with actinic keratoses were enrolled in this prospective, non‐randomized pilot study. Fourteen patients were treated with birch bark ointment only; fourteen patients received a combination therapy with cryotherapy and birch bark ointment. Treatment response was assessed clinically after two months.

Results: Clearing of more than 75 % of the lesions was seen in 79 % of the patients treated with birch bark ointment monotherapy. The response rate of the combined treatment modality was 93 %. Therapy with birch bark ointment was well tolerated.

Conclusion: In this pilot study, a standardized birch bark extract was effective in the treatment of actinic keratoses. This therapy is easy to perform and it has no side effects. Birch bark ointment may be a new therapeutic option for actinic keratoses.
ADDITION OF SORBITOL WITH KMnO4 IMPROVES BROCCOLI QUALITY RETENTION IN MODIFIED ATMOSPHERE PACKAGES
Authors: DeELL J.R. , TOIVONEN P.M.A. , CORNUT F. , ROGER C. , VIGNEAULT C.
Published: January 2006

The objective of this study was to determine if the addition of sorbitol (a water absorbent) to packages containing potassium permanganate (KMnO

4

) on an inert carrier (a volatile adsorber) could be used to enhance the removal of volatiles associated with off‐odors in broccoli (Brassica oleracea L., Italica group) during storage in modified atmosphere packaging (MAP). Broccoli heads were held in PD‐961EZ bags (five per bag), to allow CO2 to accumulate above the recommended 5–10%. Six treatments within MAP were investigated: (1) control − 0‐g sorbitol + 0 g‐KMnO4; (2) 0‐g sorbitol + 20.0‐g KMnO4; (3) 2.5‐g sorbitol + 20.0‐g KMnO4; (4) 5.0‐g sorbitol + 20.0‐g KMnO4; (5) 10.0‐g sorbitol + 20.0‐g KMnO4; and (6) 20.0‐g sorbitol + 20.0‐g KMnO4. Broccoli heads in MAP with sorbitol had better appearance, firmness and odor ratings after 29 days of storage at 0–1C, compared to the controls. Furthermore, the odor rating was higher (less off‐odor) as the amount of sorbitol was increased (1.9 control versus 3.9 for 20‐g sorbitol). Slight increases in weight loss (≤1.3%) of the broccoli were also noted with the addition of sorbitol, although not near an amount that would affect marketability. Acetaldehyde concentrations were higher in the control bags with no sorbitol or KMnO4 after 29 days of storage at 0–1C (0.21 versus 0.00–0.02 μL/L with KMnO4 and/or sorbitol), while ethanol content was greater in both control bags and those with only KMnO4 (0.12–0.13 versus 0.00–0.06 μL/L with sorbitol). Chlorophyll fluorescence (ΦPSII) began to decrease more rapidly in the control broccoli, as the ethanol and acetaldehyde began to accumulate. Overall, the use of sorbitol (≥2.5 g) with KMnO4 in MAP could enhance the removal of volatiles that are responsible for off‐odors and off‐flavors in broccoli, and thus maintain the quality and marketability longer.
How we do it: Laser reduction of peri‐tubal adenoids in selected patients with otitis media with effusion
Authors: Smith W. , Yung M.
Published: January 2006

Keypoints

• The literature supports the benefit of adenoidectomy in patients with otitis media with effusion (OME).

• It is difficult to clear adenoid tissue from around the Eustachian tubes using curettes and this conventional method of adenoidectomy is contra‐indicated in patients with cleft palates.

• Laser reduction of peri‐Eustachian adenoid tissue without myringotomies or grommet insertion was performed in three patients with OME. Two patients had previous adenoidectomies performed with curettes and one patient had a cleft palate.

• In all three patients, the OME resolved and all had closure of the air‐bone gap that was maintained during long‐term follow‐up (14 months–4 years).

• This technique resolved OME without the need for myringotomies or grommet insertion and should be considered particularly in patients who have peri‐tubal recurrence of adenoidal tissue following conventional adenoidectomy or in patients with cleft palate where there is concern with regards to palatal incompetence.
Tonsil size and body mass index are important factors for efficacy of simple tonsillectomy in obstructive sleep apnoea syndrome
Authors: Nakata S. , Noda A. , Yanagi E. , Suzuki K. , Yamamoto H. , Nakashima T.
Published: January 2006

Objectives:  To evaluate the efficacy of simple tonsillectomy to treat obstructive sleep apnoea syndrome (OSAS) in adults.

Design:  Prospective study.

Setting:  Tertiary referral centre.

Participants:  Thirty patients (28 males) underwent simple tonsillectomy under general anaesthesia. The patients’ mean age was 33.2 ± 6.8 years and body mass index was 30.7 ± 6.0 kg/m2. Seven patients (23%) were classified with grade 4, 16 patients (53%) with grade 3, and seven patients (23%) with grade 2 according to the tonsil size of Friedman's classification.

Main outcome measures:  The number of apnoea episodes per hour (apnoea index), the number of apnoea and hypopnoea episodes per hour (apnoea‐hypopnoea index), lowest nocturnal oxygen saturation and oxygen desaturation time were measured during overnight polysomnography before and after surgery. A successful tonsillectomy was defined as an apnoea–hypopnoea index improvement ratio of ≥50% and an apnoea–hypopnoea index <20 after operation.

Results:  Apnoea–hypopnoea index decreased from 69.0 ± 28.4/h to 30.1 ± 24.0/h (P < 0.0001). Simple tonsillectomy was successful in all six patients with body mass index <25 kg/m2. Concerning success rate of simple tonsillectomy with tonsil, size 2 was lowest (42.9%). Eight of the 13 patients who used continuous positive airway pressure before simple tonsillectomy did not use continuous positive airway pressure after simple tonsillectomy because of a significant reduction of excessive daytime sleepiness. Continuous positive airway pressure decreased significantly after simple tonsillectomy from 13.6 ± 2.5 cmH2O preoperatively to 10.6 ± 1.3 cmH2O postoperatively (P < 0.05).

Conclusions:  These data suggest that simple tonsillectomy is a beneficial modality to treat OSAS in selected patients (larger tonsil, low body mass index), even in adults.
A systematic review of the role of proton pump inhibitors for symptoms of laryngopharyngeal reflux
Authors: Sen P. , Georgalas C. , Bhattacharyya A.K.
Published: January 2006

Keypoints

• Proton pump inhibitors are currently used widely for the treatment of laryngopharyngeal reflux.

• This systematic review assessed the efficacy of proton pump inhibitors in the treatment of symptoms of laryngopharyngeal reflux.

• Outcome measures used to assess efficacy of proton pump inhibitors included endoscopic laryngeal signs and pH recordings.

• Only two small randomized‐controlled trials included patients with objective evidence of reflux in the 24‐h ambulatory oesophageal pH monitoring.

• Pooled analysis of these two randomized‐controlled trials failed to show any effect in favour of treatment with proton pump inhibitors.

• Further randomized‐controlled trials are required to ascertain the role of proton pump inhibitors in the treatment of laryngopharyngeal reflux.
Cerebellar Limb Ataxia
Authors: BASTIAN AMY J.
Published: January 2006

Abstract: Our work has been focused on understanding the mechanism of movement abnormalities associated with cerebellar ataxia. The hypothesis tested is that the cerebellum acts to modulate muscle activity across multiple joints in anticipation of the mechanical interaction torques generated by one's own movement and by external forces. Individuals with cerebellar damage were studied in two sets of experiments. In the first experiment, we studied how cerebellar subjects' movement changed when interaction torques were present, and then reduced via mechanically constraining movement to a single joint. Consistent with the hypothesis, it was found that cerebellar endpoint errors were greatly improved when interaction torques were reduced. We also found that cerebellar deficits in the unconstrained condition were not explained by a general failure of torque timing or magnitude scaling. This supports the idea that the cerebellum plays a specific and important role in adjusting for the dynamics of one's own body movements. In the second experiment, we studied how well cerebellar subjects could adapt arm movements to external loads. Cerebellar subjects were tested as they adapted a catching movement to balls of different weight. It was found that they were slow or unable to adapt through practice and did not show evidence of storage of the adaptation. This suggests that the cerebellum is needed for rapid adaptations for loads in movement. Given these findings, we think that the cerebellum is important in anticipating and adjusting for the mechanical demands of movement though trial‐and‐error practice.
Human TRPC6 expressed in HEK 293 cells forms non‐selective cation channels with limited Ca2+ permeability
Authors: Estacion Mark , Sinkins William G. , Jones Stephen W. , Applegate Milana A. B. , Schilling William P.
Published: January 2006

TRPC6 is thought to be a Ca2+‐permeable cation channel activated following stimulation of G‐protein‐coupled membrane receptors linked to phospholipase C (PLC). TRPC6 current is also activated by exogenous application of 1‐oleoyl‐acetyl‐sn‐glycerol (OAG) or by inhibiting 1,2‐diacylglycerol (DAG) lipase activity using RHC80267. In the present study, both OAG and RHC80267 increased whole‐cell TRPC6 current in cells from a human embryonic kidney cell line (HEK 293) stably expressing TRPC6, but neither compound increased cytosolic free Ca2+ concentration ([Ca2+]i) when the cells were bathed in high‐K+ buffer to hold the membrane potential near 0 mV. These results suggested that TRPC6 channels have limited Ca2+ permeability relative to monovalent cation permeability and/or that Ca2+ influx via TRPC6 is greatly attenuated by depolarization. To evaluate Ca2+ permeability, TRPC6 currents were examined in extracellular buffer in which Ca2+ was varied from 0.02 to 20 mm. The results were consistent with a pore‐permeation model in which Ca2+ acts primarily as a blocking ion and contributes only a small percentage (∼4%) to whole‐cell currents in the presence of extracellular Na+. Measurement of single‐cell fura‐2 fluorescence during perforated‐patch recording of TRPC6 currents showed that OAG increased [Ca2+]i 50–100 nm when the membrane potential was clamped at between −50 and −80 mV, but had little or no effect if the membrane potential was left uncontrolled. These results suggest that in cells exhibiting a high input resistance, the primary effect of activating TRPC6 will be membrane depolarization. However, in cells able to maintain a hyperpolarized potential (e.g. cells with a large inwardly rectifying or Ca2+‐activated K+ current), activation of TRPC6 will lead to a sustained increase in [Ca2+]i. Thus, the contribution of TRPC6 current to both the kinetics and magnitude of the Ca2+ response will be cell specific and dependent upon the complement of other channel types.
Antioxidants reverse depression of the hypoxic ventilatory response by acetazolamide in man
Authors: Teppema Luc J. , Bijl Hans , Romberg Raymonda R. , Dahan Albert
Published: January 2006

The carbonic anhydrase inhibitor acetazolamide may have both inhibitory and stimulatory effects on breathing. In this placebo‐controlled double‐blind study we measured the effect of an intravenous dose (4 mg kg−1) of this agent on the acute isocapnic hypoxic ventilatory response in 16 healthy volunteers (haemoglobin oxygen saturation 83–85%) and examined whether its inhibitory effects on this response could be reversed by antioxidants (1 g ascorbic acid i.v. and 200 mg α‐tocopherol p.o.). The subjects were randomly divided into an antioxidant (Aox) and placebo group. In the Aox group, acetazolamide reduced the mean normocapnic and hypercapnic hypoxic responses by 37% (P < 0.01) and 55% (P < 0.01), respectively, and abolished the O2–CO2 interaction, i.e. the increase in O2 sensitivity with rising PCO2. Antioxidants completely reversed this inhibiting effect on the normocapnic hypoxic response, while in hypercapnia the reversal was partial. In the placebo group, acetazolamide reduced the normo‐ and hypercapnic hypoxic responses by 33 and 47%, respectively (P < 0.01 versus control in both cases), and also abolished the O2–CO2 interaction. Placebo failed to reverse these inhibitory effects of acetazolamide in this group. We hypothesize that either an isoform of carbonic anhydrase may be involved in the regulation of the redox state in the carotid bodies or that acetazolamide and antioxidants exert independent effects on oxygen‐sensing cells, in which both carbonic anhydrase and potassium channels may be involved. The novel findings of this study may have clinical implications, for example with regard to a combined use of acetazolamide and antioxidants at high altitude.
Design and Evolution of New Catalytic Activity with an Existing Protein Scaffold
Authors: Park Hee-Sung , Nam Sung-Hun , Lee Jin Kak , Yoon Chang No , Mannervik Bengt , Benkovic Stephen J. , Kim Hak-Sung
Published: January 2006

The design of enzymes with new functions and properties has long been a goal in protein engineering. Here, we report a strategy to change the catalytic activity of an existing protein scaffold. This was achieved by simultaneous incorporation and adjustment of functional elements through insertion, deletion, and substitution of several active site loops, followed by point mutations to fine-tune the activity. Using this approach, we were able to introduce β-lactamase activity into the αβ/βα metallohydrolase scaffold of glyoxalase II. The resulting enzyme, evMBL8 (evolved metallo β-lactamase 8), completely lost its original activity and, instead, catalyzed the hydrolysis of cefotaxime with a (
k
cat
/
K
m
)
app
of 1.8 × 10
2
(mole/liter)
–1
second
–1
, thus increasing resistance to
Escherichia coli
growth on cefotaxime by a factor of about 100.
Response to Comment on "Reconstructing the Origin of Andaman Islanders"
Authors: Thangaraj Kumarasamy , Chaubey Gyaneshwer , Kivisild Toomas , Reddy Alla G. , Singh Vijay Kumar , Rasalkar Avinash A. , Singh Lalji
Published: January 2006

The mitochondrial DNA coding region substitutions shared by the Andamanese and two Rajbanshi individuals suggests the early split of M31 from some continental Indian mitochondrial DNA lineages at the time depth 11/14 of the age of haplogroup M. This is still consistent with the ancient isolation of these gene pools, albeit not as early as the initial phase of human migration out of Africa.
Optical Detection of DNA Conformational Polymorphism on Single-Walled Carbon Nanotubes
Authors: Heller Daniel A. , Jeng Esther S. , Yeung Tsun-Kwan , Martinez Brittany M. , Moll Anthonie E. , Gastala Joseph B. , Strano Michael S.
Published: January 2006

The transition of DNA secondary structure from an analogous B to Z conformation modulates the dielectric environment of the single-walled carbon nanotube (SWNT) around which it is adsorbed. The SWNT band-gap fluorescence undergoes a red shift when an encapsulating 30-nucleotide oligomer is exposed to counter ions that screen the charged backbone. The transition is thermodynamically identical for DNA on and off the nanotube, except that the propagation length of the former is shorter by five-sixths. The magnitude of the energy shift is described by using an effective medium model and the DNA geometry on the nanotube sidewall. We demonstrate the detection of the B-Z change in whole blood, tissue, and from within living mammalian cells.
A Virus Reveals Population Structure and Recent Demographic History of Its Carnivore Host
Authors: Biek Roman , Drummond Alexei J. , Poss Mary
Published: January 2006

Directly transmitted parasites often provide substantial information about the temporal and spatial characteristics of host-to-host contact. Here, we demonstrate that a fast-evolving virus (feline immunodeficiency virus, FIV) can reveal details of the contemporary population structure and recent demographic history of its natural wildlife host (
Puma concolor
) that were not apparent from host genetic data and would be impossible to obtain by other means. We suggest that rapidly evolving pathogens may provide a complementary tool for studying population dynamics of their hosts in “shallow” time.
Ethanol Can Contribute to Energy and Environmental Goals
Authors: Farrell Alexander E. , Plevin Richard J. , Turner Brian T. , Jones Andrew D. , O'Hare Michael , Kammen Daniel M.
Published: January 2006

To study the potential effects of increased biofuel use, we evaluated six representative analyses of fuel ethanol. Studies that reported negative net energy incorrectly ignored coproducts and used some obsolete data. All studies indicated that current corn ethanol technologies are much less petroleum-intensive than gasoline but have greenhouse gas emissions similar to those of gasoline. However, many important environmental effects of biofuel production are poorly understood. New metrics that measure specific resource inputs are developed, but further research into environmental metrics is needed. Nonetheless, it is already clear that large-scale use of ethanol for fuel will almost certainly require cellulosic technology.
Early and Profound Human Impact?
Authors: White James
Published: January 2006

Plows, Plagues, and Petroleum
. How Humans Took Control of Climate.
By William F. Ruddiman
. Princeton University Press, Princeton, NJ, 2005. 216 pp. $24.95, £15.95. ISBN 0-691-12164-8.

The author argues for his controversial thesis that preindustrial human societies--through their release of carbon dioxide and methane--changed Earth's climate to the extent that a minor glaciation was averted.