Improving diet, activity and wellness in adults at risk of diabetes: randomized controlled trial.

OBJECTIVE: The purpose of this analysis is to examine the effect of an algorithm-driven online diabetes prevention program on changes in eating habits, physical activity and wellness/productivity factors. METHODS: The intervention, Alive-PD, used small-step individually tailored goal setting and other features to promote changes in diet and physical activity. A 6-month randomized controlled trial was conducted among patients from a healthcare delivery system who had confirmed prediabetes (n =339). Change in weight and glycemic markers were measured in the clinic. Changes in physical activity, diet and wellness/productivity factors were self-reported. Mean age was 55 (s.d. 8.9) years, mean body mass index was 31 (s.d. 4.4) kg m(-2), 68% were white and 69% were male. RESULTS: The intervention group increased fruit/vegetable consumption by 3.71 (95% confidence interval (CI) 2.73, 4.70) times per week (effect size 0.62), and decreased refined carbohydrates by 3.77 (95% CI 3.10, 4.44) times per week both significantly (P<0.001) greater changes than in the control group. The intervention group also reported a significantly greater increase in physical activity than in the control group, effect size 0.49, P<0.001. In addition, the intervention group reported a significant increase in self-rated health, in confidence in ability to make dietary changes and in ability to accomplish tasks, and a decrease in fatigue, compared with the control group. These changes paralleled the significant treatment effects on glycemic markers and weight. CONCLUSIONS: In addition to promoting improvements in weight and glycemic markers, the Alive-PD program appears to improve eating habits and physical activity, behaviors important not just for diabetes prevention but for those with diagnosed diabetes or obesity. The improvements in wellness/productivity may derive from the diet and activity improvements, and from the satisfaction and self-efficacy of achieving goals.

The effects of cinacalcet on blood pressure, mortality and cardiovascular endpoints in the EVOLVE trial.

Patients with end-stage renal disease often have derangements in calcium and phosphorus homeostasis and resultant secondary hyperparathyroidism (sHPT), which may contribute to the high prevalence of arterial stiffness and hypertension. We conducted a secondary analysis of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial, in which patients receiving hemodialysis with sHPT were randomly assigned to receive cinacalcet or placebo. We sought to examine whether the effect of cinacalcet on death and major cardiovascular events was modified by baseline pulse pressure as a marker of arterial stiffness, and whether cinacalcet yielded any effects on blood pressure. As reported previously, an unadjusted intention-to-treat analysis failed to conclude that randomization to cinacalcet reduces the risk of the primary composite end point (all-cause mortality or non-fatal myocardial infarction, heart failure, hospitalization for unstable angina or peripheral vascular event). However, after prespecified adjustment for baseline characteristics, patients randomized to cinacalcet experienced a nominally significant 13% lower adjusted risk (95% confidence limit 4-20%) of the primary composite end point. The effect of cinacalcet was not modified by baseline pulse pressure (Pinteraction=0.44). In adjusted models, at 20 weeks cinacalcet resulted in a 2.2 mm Hg larger average decrease in systolic blood pressure (P=0.002) and a 1.3 mm Hg larger average decrease in diastolic blood pressure (P=0.002) compared with placebo. In summary, in the EVOLVE trial, the effect of cinacalcet on death and major cardiovascular events was independent of baseline pulse pressure.

Race, ethnicity, sex and temporal differences in Barrett's oesophagus diagnosis: a large community-based study, 1994-2006.

OBJECTIVE: To evaluate the demographics and incidence of Barrett's oesophagus diagnosis using community-based data. DESIGN: Observational study. SETTING: Kaiser Permanente, Northern California healthcare membership, 1994-2006. PATIENTS: Members with an electronic diagnosis of Barrett's oesophagus. MAIN OUTCOME MEASURES: Incidence and prevalence of a new Barrett's oesophagus diagnosis by race, sex, age and calendar year. RESULTS: 4205 persons met the study definition for a diagnosis of Barrett's oesophagus. The annual incidence in 2006 was highest among non-Hispanic whites (39/100,000 race-specific member-years, 95% confidence interval (95% CI) 35 to 43), with lower rates among Hispanics (22/100,000, 95% CI 16 to 29), Asians (16/100,000, 95% CI 11 to 22), and blacks (6/100,000, 95% CI 2 to 12). The annual incidence was higher among men than women (31 vs 17/100,000, respectively, year 2006; p<0.01). The incidence increased with age from 2 per 100,000 for persons aged 21-30 years, to a peak of 31 per 100,000 member-years for persons aged 61-70 years (year 2006). There was no increase in the incidence of new diagnoses until the last two observation years, which coincided with changes in data collection methods and may be due to bias. The overall prevalence among active members increased almost linearly to 131/100,000 member-years by 2006. CONCLUSIONS: The demographic distributions of Barrett's oesophagus differ markedly by race, age and sex and were comparable to those for oesophageal adenocarcinoma. Thus, demographic disparities in oesophageal adenocarcinoma risk may arise partly from the risk of having Barrett's oesophagus, rather than from differing risks of progression from Barrett's oesophagus to cancer. There has been an almost linear increase in the prevalence of diagnosed disease.

The association of folate, zinc and antioxidant intake with sperm aneuploidy in healthy non-smoking men.

BACKGROUND: Little is known about the effect of paternal nutrition on aneuploidy in sperm. We investigated the association of normal dietary and supplement intake of folate, zinc and antioxidants (vitamin C, vitamin E and beta-carotene) with the frequency of aneuploidy in human sperm. METHODS: Sperm samples from 89 healthy, non-smoking men from a non-clinical setting were analysed for aneuploidy using fluorescent in situ hybridization with probes for chromosomes X, Y and 21. Daily total intake (diet and supplements) for zinc, folate, vitamin C, vitamin E and beta-carotene was derived from a food frequency questionnaire. Potential confounders were obtained from a self-administered questionnaire. RESULTS: After adjusting for covariates, men with high folate intake (>75th percentile) had lower frequencies of sperm with disomies X, 21, sex nullisomy, and a lower aggregate measure of sperm aneuploidy (P

Helicobacter pylori infection and the risk of Barrett's oesophagus: a community-based study.

OBJECTIVE: Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett's oesophagus, a metaplastic change that is a probable early event in the carcinogenesis of oesophageal adenocarcinoma, were evaluated METHODS: A case-control study was carried out in the Kaiser Permanente Northern California population, a large health services delivery organisation. Persons with a new Barrett's oesophagus diagnosis (cases) were matched to subjects with gastro-oesophageal reflux disease (GORD) without Barrett's oesophagus and to population controls. Subjects completed direct in-person interviews and antibody testing for H pylori and its CagA (cytotoxin-associated gene product A) protein. RESULTS: Serological data were available on 318 Barrett's oesophagus cases, 312 GORD patients and 299 population controls. Patients with Barrett's oesophagus were substantially less likely to have antibodies for H pylori (OR = 0.42, 95% CI 0.26 to 0.70) than population controls; this inverse association was stronger among those with lower body mass indexes (BMIs < 25, OR = 0.03, 95% CI 0.00 to 0.20) and those with CagA+ strains (OR = 0.08, 95% CI 0.02 to 0.35). The associations were diminished after adjustment for GORD symptoms. The H pylori status was not an independent risk factor for Barrett's oesophagus compared with the GORD controls. CONCLUSIONS: Helicobacter pylori infection and CagA+ status were inversely associated with a new diagnosis of Barrett's oesophagus. The findings are consistent with the hypothesis that H pylori colonisation protects against Barrett's oesophagus and that the association may be at least partially mediated through GORD.

Markers of vascular disease do not differ in black and white hemodialysis patients despite a different risk profile.

Increased aortic stiffness, as measured by pulse wave velocity (PWV) and augmentation index (Aix), and vascular calcification have been associated with an unfavourable cardiovascular outcome in hemodialysis patients. However, the majority of data have been published in white patients and epidemiological data are discordant on the fate of patients of different races. In this cross sectional study we measured PWV and Aix by applanation tonometry and coronary artery and thoracic aorta calcium score (CAC and AoC) by electron beam tomography (EBT) in 81 Blacks and 61 Whites on maintenance hemodialysis. Vascular stiffness measurements and EBT scans were performed within a week of each other. There was no difference between races in age, systolic blood pressure or gender distribution. Blacks had a more frequent history of hypertension (100% versus 89%; P=0.002), lower prevalence of dyslipidemia (30% versus 66%; P<0.001), higher PTH levels (geometric mean 607 pg/ml versus 245 pg/ml; P=0.039), received calcium based phosphate binders less frequently (37% versus 60%, P=0.007) and calcium antagonists more frequently than Whites (54% versus 28%; P=0.003). Nonetheless, the unadjusted and risk adjusted PWV and Aix, as well as CAC and AoC were not statistically different between races. In this dialysis cohort there was no difference in markers of vasculopathy between black and white patients despite differences in baseline clinical characteristics. Epidemiological data from the general population indicate that Blacks have lower calcium scores and stiffer vessels than Whites. Some studies in the renal populations suggest a better and others a similar survival of Blacks and Whites on hemodialysis. Our findings raise the important question of the prognostic significance of markers of vasculopathy in patients of different races and with different risk profiles.

Cinacalcet HCI (Sensipar/Mimpara) is an effective chronic therapy for hemodialysis patients with secondary hyperparathyroidism.

AIMS: This 1-year double-blind, placebo-controlled, multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis. METHOD: Patients were randomly assigned in a 1:1 ratio to cinacalcet or control treatment groups. The initial dose of cinacalcet (or matching placebo) was 30 mg. Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone (iPTH) response and safety profile. Sequential doses included 30, 60, 90, 120 and 180 mg/d. Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus. Efficacy and safety were compared between treatment groups among patients who completed the study (52 total weeks of treatment). Reasons for withdrawal are presented for patients who did not complete the study. RESULTS: A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet (n = 99) or placebo (n = 111). Over the last 6 months of the study, a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level < or = 250 pg/ml (61.6 vs. 9.9%, p < 0.001) or a > or = 30% decrease in iPTH from baseline (81.8 vs. 21.6%, p < 0.001). Mean iPTH levels decreased by -47.8% in the cinacalcet group and increased by +12.9% in the control group. Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following: serum calcium -6.5 vs. +0.9% (p < 0.001), serum phosphorus -3.6 vs. -1.1% (p = 0.465), and Ca x P -9.9 vs. -0.3% (p = 0.006). The most commonly reported adverse events related to study drug by the investigators included nausea (13% cinacalcet, 5% control), investigator-reported hypocalcemia (11% cinacalcet, 1% control), vomiting (9% cinacalcet, 2% control), dyspepsia (5% cinacalcet, 4% control), and diarrhea (5% cinacalcet, 2% control). CONCLUSIONS: Treatment with cinacalcet is a safe and effective therapy for long-term control of secondary hyperparathyroidism. 1-year therapy with cinacalcet was associated with sustained, clinically significant reductions in calcium, Ca x P and iPTH which allowed a greater percentage of patients to achieve NKF-KDOQI target goals for PTH and Ca x P.

Cognitive ability is associated with suspected reporting errors on food frequency questionnaires.

OBJECTIVE: To examine potential for bias in reported total energy intake on a Food Frequency Questionnaire (FFQ) among older adults. DESIGN: Longitudinal cohort study. SUBJECTS/SETTING: 2,706 Community-dwelling Black and White older adults, aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Multivariate logistic regression analyses were conducted with potential errors on reported total energy intake on the Food Frequency Questionnaire (FFQ) as the outcome variable and with cognitive ability, measured by the Modified Mini Mental State Exam (3MS) as the primary independent variable. The regression model controlled for site, race, gender, age, body size, and physical activity. Separate models were fit using 3MS as a continuous variable and for multiple 3MS cutpoints. All models revealed similar findings. RESULTS: Cognitive ability was inversely associated with potential errors in reporting total energy intake, whereby a five-point increase in 3MS scores was associated with a 14% decreased likelihood of reporting errors (Odds Ratio=0.86, 95% Confidence Interval: 0.77, 0.95). Additionally, compared to White women, White men were 2 times more likely, and Black women and Black men were 3 times more likely, to have errors in reporting total energy intake. CONCLUSION: This study provides evidence that for older adults, lower cognition scores are associated with increased potential errors in reporting total energy intake. APPLICATIONS: Dietary reporting from older adults may be inaccurate due to cognitive deficits. A brief assessment of cognitive function may assist clinicians in dietary evaluations and recommendation and may benefit studies using FFQ data where the measure of cognitive function could be utilized to stratify data analyses and conduct sensitivity analyses.

Association of pulse wave velocity with vascular and valvular calcification in hemodialysis patients.

The recent Kidney Disease: Improving Quality Outcomes (KDIGO) recommendations called for an investigation of the relationship between various radiological methods to assess cardiovascular calcification and measures of arterial stiffness. Accordingly, in 131 adult maintenance hemodialysis patients, we investigated the association of aortic pulse wave velocity (PWV) with calcification of cardiac valves on echocardiography, coronary artery, and thoracic aorta calcium on computed tomography and a calcification score of the abdominal aorta obtained on a plain abdominal X-ray. All tests were performed within a week. Mean PWV increased as the severity of coronary artery, thoracic, and abdominal aorta calcium scores increased (each P<0.05). No trend was present for number of valves with calcification. After multivariable adjustment, abdominal aorta X-ray calcium scores remained associated with PWV (P=0.004), whereas the association of PWV with thoracic aorta and coronary artery calcium scores became marginal (P=0.308 and P=0.083, respectively). No association was found between number of calcified valves and PWV. This study demonstrates a strong association between abdominal aorta calcification on plain X-ray and PWV and a borderline association with thoracic aorta and coronary artery calcification. Sudden death and congestive heart failure, two frequent causes of death in hemodialysis, are likely caused by increased arterial stiffness that can be closely predicted by the presence of aortic calcification on plain X-rays.

Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.

The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders.

A randomized, double-blind, crossover design study of sevelamer hydrochloride and sevelamer carbonate in patients on hemodialysis.

AIMS: Sevelamer carbonate is an anion exchange resin with the same polymeric structure as sevelamer hydrochloride in which carbonate replaces chloride as the anion. The study investigated the effects of sevelamer carbonate and sevelamer hydrochloride on serum phosphorus, lipids and bicarbonate levels in hemodialysis patients. MATERIALS AND METHODS: This was a double-blind, randomized, crossover study. 79 hemodialysis patients were randomly assigned to either sevelamer carbonate or sevelamer hydrochloride for 8 weeks followed by a crossover to the other regimen for an additional 8 weeks of treatment. RESULTS: The mean serum phosphorus was 4.6+/-0.9 and 4.7+/-0.9 mg/dl during sevelamer carbonate and sevelamer hydrochloride treatment, respectively. Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus, the geometric least square mean ratio was 0.99 (90% CI, 0.95-1.03). Mean total and LDL cholesterol were 144.0+/-33.9 and 59.5+/-24.9 mg/dl, respectively, during sevelamer carbonate treatment and 139.0+/-33.6 and 56.0+/-23.3 mg/dl, respectively, during sevelamer hydrochloride treatment. Serum bicarbonate levels increased by 1.3+/-4.1 mEq/l during sevelamer carbonate treatment. There were fewer gastrointestinal adverse events with sevelamer carbonate. CONCLUSIONS: Sevelamer carbonate and sevelamer hydrochloride were equivalent in controlling serum phosphorus and serum bicarbonate levels increased with sevelamer carbonate. Lipid profiles for both were well-below the levels suggested by KDOQI. Sevelamer carbonate may have advantages over sevelamer hydrochloride in the treatment of hyperphosphatemia in hemodialysis patients.

The efficiency of magnetic-activated cell sorting and fluorescence-activated cell sorting in the decontamination of testicular cell suspensions in cancer patients.

BACKGROUND: Before clinical application, the feasibility and safety of autologous testicular stem cell transplantation should be explored. Apart from limitations in their numbers, spermatogonial stem cells may also be contaminated by malignant cells. Therefore, both enrichment and decontamination before transplantation may be necessary. This study aimed at evaluating the decontaminating potential of magnetic-activated cell sorting (MACS) and/or fluorescence-activated cell sorting (FACS) for both murine and human testicular cell suspensions. In the mouse, the effectiveness of the transplantation technique after cell sorting was also assessed. METHODS: Murine testicular cells were contaminated with 5% EL4 cells. Fresh and frozen-thawed suspensions were sorted using MACS (CD49f (+)) and FACS (CD49f(+), H-2Kb(-)) and evaluated by FACS, cell culture and transplantation into W/W(v) mice. Human testicular cells were contaminated with 5 or 0.05% CCRF-SB (SB) cells. Frozen-thawed suspensions were sorted using FACS (HLA class I(-)) and evaluated by FACS, cell culture and PCR for the B-cell receptor. RESULTS: In the mouse, the sorted fractions contained 0.39% H-2K(b)-positive and 76.55% CD49f-positive cells. After transplantation, 1 in 20 recipient mice developed a malignancy. In the human experiments, an average of 0.58% SB cells was detected after sorting. In only 1 of 11 samples, there were no SB cells observed. CONCLUSION: MACS and/or FACS are insufficient for completely depleting testicular tissue of malignant cells. Although more research on alternative decontamination techniques is necessary, developing a reliable method to screen a priori testicular tissue for malignant cells may be equally important.

Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients.

Vascular calcification is associated with an adverse prognosis in end-stage renal disease. It can be accurately quantitated with computed tomography but simple in-office techniques may provide equally useful information. Accordingly we compared the results obtained with simple non-invasive techniques with those obtained using electron beam tomography (EBT) for coronary artery calcium scoring (CACS) in 140 prevalent hemodialysis patients. All patients underwent EBT imaging, a lateral X-ray of the lumbar abdominal aorta, an echocardiogram, and measurement of pulse pressure (PP). Calcification of the abdominal aorta was semiquantitatively estimated with a score (Xr-score) of 0-24 divided into tertiles, echocardiograms were graded as 0-2 for absence or presence of calcification of the mitral and aortic valve and PP was divided in quartiles. The CACS was elevated (mean 910+/-1657, median 220). The sensitivity and specificity for CACS > or = 100 was 53 and 70%, for calcification of either valve and 67 and 91%, respectively, for Xr-score > or = 7. The area under the curve for CACS > or = 100 associated with valve calcification and Xr-score was 0.62 and 0.78, respectively. The likelihood ratio (95% confidence interval) of CACS > or = 100 was 1.79 (1.09, 2.96) for calcification of either valve and 7.50 (2.89, 19.5) for participants with an Xr-score > or = 7. In contrast, no association was present between PP and CACS. In conclusion, simple measures of cardiovascular calcification showed a very good correlation with more sophisticated measurements obtained with EBT. These methodologies may prove very useful for in-office imaging to guide further therapeutic choices in hemodialysis patients.

Blastocyst development after assisted reproduction using spermatozoa obtained after testicular stem cell transplantation in mice.

BACKGROUND: Since its introduction in 1994, testicular stem cell transplantation (TSCT) has been widely used for research. This technique may also become important for preserving fertility in pre-pubertal cancer patients. Therefore, it is necessary to investigate the safety aspects of reproduction using spermatozoa obtained after TSCT. In this study, preimplantation development of mouse embryos, using spermatozoa obtained after TSCT, was examined. METHODS: TSCT-derived spermatozoa were used for IVF and ICSI. Embryos were cultured for five days until they reached blastocyst stage and were evaluated by differential staining. RESULTS: IVF revealed significantly lower fertilization and development rates after TSCT-IVF compared to control-IVF. Blastocysts derived from TSCT-IVF had significantly lower inner cell mass numbers (ICMs) and lower ICM/trophectoderm (TE) ratios compared to control-IVF blastocysts. No differences in fertilization and development rates were observed between TSCT-ICSI and control-ICSI, and blastocyst quality in the transplanted group was similar to that of the control blastocysts. CONCLUSION: Our study showed that after TSCT-IVF, fertilization and preimplantation development were disturbed and blastocysts showed reduced ICM and ICM/TE ratio. However, after TSCT-ICSI, both fertilization and preimplantation development were normal and blastocyst formation was comparable to control-ICSI.

Breastfeeding patterns and risk of childhood acute lymphoblastic leukaemia.

The risk of childhood acute lymphoblastic leukaemia (ALL) was investigated in relation to breastfeeding patterns in the Northern California Childhood Leukaemia Study. Data collected by self-administered and in-person questionnaires from biological mothers of leukaemia cases (age 0-14 years) in the period 1995-2002 were matched to birth certificate controls on date of birth, sex, Hispanic ethnic status, and maternal race. Ever compared to never breastfeeding was not associated with risk of ALL at ages 1-14 years (odds ratio=0.99; 95% CI=0.64-1.55) and ages 2-5 years (OR=1.49; 95% CI=0.83-2.65). Various measures of breastfeeding duration compared to absence of breastfeeding also had no significant effect on risk. Complimentary feeding characteristics such as type of milk/formula used and age started eating solid foods among breastfed children were not associated with ALL risk. This study provides no evidence that breastfeeding affects the occurrence of childhood ALL.

Cardiovascular tissues contain independent circadian clocks.

Acute cardiovascular events exhibit a circadian rhythm in the frequency of occurrence. The mechanisms underlying these phenomena are not yet fully understood, but they may be due to rhythmicity inherent in the cardiovascular system. We have begun to characterize rhythmicity of the clock gene mPer1 in the rat cardiovascular system. Luciferase activity driven by the mPer1 gene promoter is rhythmic in vitro in heart tissue explants and a wide variety of veins and arteries cultured from the transgenic Per1-luc rat. The tissues showed between 3 and 12 circadian cycles of gene expression in vitro before damping. Whereas peak per1-driven bioluminescence consistently occurred during the late night in the heart and all arteries sampled, the phases of the rhythms in veins varied significantly by anatomical location. Varying the time of the culture procedure relative to the donor animal's light:dark cycle revealed that, unlike some other rat tissues such as liver, the phases of in vitro rhythms of arteries, veins, and heart explants were affected by culture time. However, phase relationships among tissues were consistent across culture times; this suggests diversity in circadian regulation among components of the cardiovascular system.

Antioxidant intake is associated with semen quality in healthy men.

BACKGROUND: We seek to determine whether dietary and supplement intake of specific micronutrients (zinc and folate) and antioxidants (vitamins C, E and beta-carotene) is associated with semen quality. METHODS: Ninety-seven healthy, non-smoking men provided semen and were interviewed. Average daily nutrient intake from food and supplements was derived from a self-administered food frequency questionnaire. Intake levels were summarized as low, moderate and high. Semen volume, sperm concentration, total sperm count, motility, progressive motility and total progressively motile sperm count (TPMS) were measured. RESULTS: After controlling for covariates, a high intake of antioxidants was associated with better semen quality but, in almost all cases, there was no clear dose relationship in that moderate intake groups had the poorest semen quality. For example, positive associations were observed between vitamin C intake and sperm number as reflected in the higher mean count (P=0.04), concentration (P=0.05) and TPMS (P = 0.09); between vitamin E intake and progressive motility (P = 0.04) and TPMS (P = 0.05); and between beta-carotene intake and sperm concentration (P = 0.06) and progressive motility (P = 0.06). Folate and zinc intake were not associated with improved semen quality. CONCLUSIONS: In a convenience sample of healthy non-smoking men from a non-clinical setting, higher antioxidant intake was associated with higher sperm numbers and motility.

Recovery, survival and functional evaluation by transplantation of frozen-thawed mouse germ cells.

BACKGROUND: Establishing a successful method for testicular stem cell transplantation of frozen-thawed testicular cells would be of immense benefit to boys with childhood cancer undergoing a sterilizing treatment. In this study, we evaluated different cryopreservation protocols in a mouse model by means of testicular germ cell transplantation (TGCT), in order to establish an optimal freezing protocol. METHODS AND RESULTS: In a first series of experiments, we compared an uncontrolled protocol with 1.5 mol/l dimethyl sulphoxide (DMSO) versus a controlled long protocol (cooling to -80 degrees C) and observed a better viability with the latter protocol (36% versus 48%, P < 0.05). We then compared survival after two thawing methods (37 degrees C water versus ice water) in either a DMSO- or an ethylene glycol (EG)-based protocol, and found no difference. In order to evaluate the functional capacity of the cryopreserved testicular suspension, TGCT was performed with both fresh and frozen-thawed suspensions. In 90% of the successfully injected testes, spermatogenesis was reinitiated using fresh suspensions. In contrast, this figure was only 12.5 and 22.7% after cryopreservation, for the short controlled EG protocol and the uncontrolled DMSO protocol, respectively. CONCLUSION: Reinitiation of spermatogenesis is possible after cryopreservation of testicular germ cell suspensions. Although cell survival was acceptable, our results after TGCT show that our protocols need further improvement.

Rofecoxib: no effect on Alzheimer's disease in a 1-year, randomized, blinded, controlled study.

BACKGROUND: Inflammatory mechanisms have been implicated in the pathogenesis of Alzheimer's disease (AD) and may be mediated via the cyclo-oxygenase-2 enzyme. This study sought to evaluate the effect of rofecoxib, a nonsteroidal anti-inflammatory drug that selectively inhibits cyclo-oxygenase-2, in slowing the progression of dementia in patients with established AD. METHODS: A double-blinded, multicenter trial was conducted in which 692 patients with mild or moderate AD aged 50 years or older were randomly assigned to receive 25 mg rofecoxib or placebo daily for 12 months. The key efficacy measures were mean change from baseline at month 12 on the cognitive subscale of the AD Assessment Scale (ADAS-cog) and score on the Clinician's Interview Based Impression of Change with caregiver input (CIBIC+). RESULTS: Four hundred eighty-one patients (70%) completed assessments and remained on treatment at 12 months. No significant differences between treatments were found on the mean change from baseline error score for the ADAS-cog (rofecoxib = 4.84; placebo = 5.44; difference = -0.60) or mean score on the CIBIC+ (rofecoxib = 4.90; placebo = 4.87; difference = 0.03) over 12 months. This result persisted after adjusting for severity of dementia at baseline, presence of the APOE-epsilon4 allele, and donepezil use. Secondary analyses did not reveal any significant differences on any other measures. CONCLUSION: The failure of selective cyclo-oxygenase-2 inhibition to slow the progression of AD may indicate either that the disease process is too advanced to modify in patients with established dementia or that cyclo-oxygenase-2 does not play a significant role in the pathogenesis of the disorder.