Relationship between use of proton pump inhibitors and IGF system in older subjects

Objectives

to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly.

Design

cross-sectional.

Setting

InCHIANTI study.

Participants

938 older subjects (536 women, 402 men, mean age 75.7±7.4 years).

Measurements

complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3).

Results

Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1–113.8] than nonusers 110 [77.8–148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (β±SE=?19.60±9.83, p=0.045).

Conclusion

Use of PPIs was independently and negatively associated with IGF-1 levels.     

Apo E genotype, diabetes, and peripheral arterial disease in older men: the Honolulu Asia-aging study

The epsilon4 allele of the gene coding for apolipoprotein (apo) E is associated with an atherogenic lipid profile that has been linked to increased risk of coronary artery disease (CAD). Apo E genotype may also be associated with peripheral arterial disease (PAD). If present, this association may be modified by diabetes, which is also associated with dyslipidemia that predisposes to macrovascular disease. Observable associations between both ApoE genotype and diabetes with PAD may be confounded by smoking, a potent PAD risk factor that is unrelated to lipids. From 1991 to 1993, apo E genotypes (2/3, 3/3, 3/4), PAD (defined as ankle-brachial index [ABI] <0.9), diabetes (prevalent and newly-diagnosed), and smoking history (ever/never) were determined for 3,161 Japanese-American men aged 71-93. Data on hypertension and other potential confounders were also collected. Logistic regression was used to determine odds ratios (OR) between groups cross-categorized by apo E genotype and diabetes with prevalence of PAD, within strata of smoking. In each smoking stratum, non-diabetic apo epsilon3/3 carriers were considered the reference. Among ever-smokers, there was no association between apo E and PAD, regardless of diabetes status. Among never-smokers there appeared to be both apo E- and diabetes effects on PAD prevalence. Compared to the non-diabetic epsilon3/3 group, the ORS of PAD were 2.3 (1.2-4.4) and 2.0 (1.1-3.4) for epsilon3/3 newly-diagnosed and epsilon3/3 prevalent diabetic subjects, respectively. Associations were stronger among diabetic individuals in the epsilon3/4 group: the ORS were 3.0 (1.1-8.8) and 4.1 (1.9-8.7) for epsilon3/4 newly-diagnosed and epsilon3/4prevalent diabetic subjects, respectively. Despite associations whose pattern and magnitude suggested interaction between apo E genotype and diabetes on PAD prevalence among never-smokers, formal testing of this interaction did not reach statistical significance. Our finding of an apo E-PAD association among never-smokers may result from the effects of an apo epsilon4-related atherogenic lipid profile on peripheral arteries. Further studies are needed to clarify the potential mediating role of diabetes on the apo E-PAD association.     

Frailty of older age: the role of the endocrine--immune interaction

The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimer's dementia and Congestive Heart Failure.     

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

Background

Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI.

Methods/Design

We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI.Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included.Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm).

Discussion

The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.

Trial registration number

Netherlands Trial register NTR1449

     

Serum carotenoids and pulmonary function in older community-dwelling women

Background and Objectives

Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake.

Subjects and Methods

We examined the relationship between serum ??-carotene, ??-carotene, ??-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV₁] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women??s Health and Aging Study I) in Baltimore, Maryland, USA.

Results

Higher serum ??-carotene and ??-carotene concentrations were positively associated with both FEV₁ and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between ??-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV₁ or FVC.

Conclusions

Higher serum ??-carotene and ??-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints.     

Circulating selenium and carboxymethyl-lysine, an advanced glycation endproduct, are independent predictors of anemia in older community-dwelling adults

ObjectiveTo assess whether selenium and carboxymethyl-lysine (CML), two biomarkers of oxidative stress, are independent predictors of anemia in older community-dwelling adults.MethodsPlasma levels of selenium, CML, folate, vitamin B12, and testosterone and markers of iron status and inflammation were measured at baseline in 1036 adults at least 65 y old in the Invecchiare in Chianti Study, a population-based cohort study of aging in Tuscany, Italy, and examined in relation to prevalent anemia and incident anemia over 6 y of follow-up.ResultsAt enrollment, 11.6% of participants were anemic. Of 472 participants who were non-anemic at enrollment, 72 (15.3%) developed anemia within 6 y of follow-up. At enrollment, plasma CML in the highest quartile (>425 ng/mL) and plasma selenium in the lowest quartile (<66.6 μg/L) predicted incident anemia (hazard ratio 1.67, 95% confidence interval 1.07–2.59, P = 0.02; hazard ratio 1.55, 95% confidence interval 1.01–2.38, P = 0.05, respectively) in a multivariate Cox proportional hazards model that adjusted for age, education, body mass index, cognition, inflammation, red blood cell distribution width, ferritin, vitamin B12, testosterone, and chronic diseases.ConclusionElevated plasma CML and low plasma selenium are long-term independent predictors of anemia in older community-dwelling adults. These findings support the idea that oxidative stress contributes to the development of anemia.     

Percutaneous drainage of subphrenic abscess: a review of 62 patients

Sixty-two patients who presented with subphrenic abscesses had the abscesses drained percutaneously. Diagnosis of a subphrenic collection was usually made with sonography. Initial percutaneous drainage was accomplished with a combination of sonography and fluoroscopic guidance. More recently (in the last 31 cases) most drainages were done with sonographic guidance alone. Successful catheter drainage was achieved in 85% with a complication rate of 4.8%. Failure of catheter drainage (defined as any patient who was not cured by percutaneous drainage alone) occurred in patients with multiple collections or in whom the primary cause of the abscess necessitated surgery, for example, perforated ulcer, acute cholecystitis. Considerations for successful drainage include understanding the anatomy of the subphrenic space, recognizing the importance of a correct access route (avoidance of the pleura and lung), and the long time necessary for adequate drainage (longer than 10 days in 60%). An angled subcostal approach to the subphrenic space was used in 56 (90%) of 62 cases. No complications occurred in this group. The one pneumothorax that occurred in the remaining six cases was a direct result of using an intercostal approach through the parietal pleura into a subphrenic collection. We conclude that percutaneous drainage is a safe and effective method of treatment of subphrenic abscesses.     

Osteosarcoma: use of MR imaging and MR spectroscopy in clinical decision making

Magnetic resonance (MR) imaging was performed on 14 patients with histologically proved osteosarcoma (mean age, 14.4 years). There was excellent correlation of intramedullary tumor extent as determined with MR imaging and pathologic examination (r = 99%). This was facilitated by the presence of a chemical shift artifact at the tumor-marrow interface on the T1-weighted images. The correlation between CT and pathologic findings was not as good (r = 84%). In a single patient, however, a 10-cm length of sclerotic bone was incorrectly interpreted as being tumor. If this case is excluded, the correlation between CT and pathologic findings improves significantly (r = 96%). T2-weighted images were optimal in demonstrating soft-tissue bulk and breach of the epiphysis or cortex. Vascular involvement was also readily defined. The T2 value of the tumor soft-tissue component decreased in patients who were deemed to have responded well to therapy. Two patients with very high T2 values after chemotherapy developed wide-spread metastatic disease and died. Phosphorus-31 MR spectroscopy of five patients with osteosarcoma showed elevated levels of phosphomonoesters (PMEs), inorganic phosphate (Pi), and phosphodiesters (PDEs). PME and PDE peak areas decreased in three patients after chemotherapy, while Pi peak areas increased.     

Preoperative evaluation of abdominal aortic aneurysms by computed tomography

A prospective, preoperative study was conducted of 50 electively repaired abdominal aortic aneurysms comparing the CT and angiographic findings with those described at surgery. CT demonstrated all 50 aneurysms and correctly identified their proximal extent in relation to the takeoff of the renal arteries in 47 patients (94%), while angiography detected 48 aneurysms (96%) and their correct relation to the renal arteries in all (100%). CT correctly identified 40 (98%) of 41 patients with two renal arteries, but only two (29%) of seven with three and none of two patients with four arteries. Common iliac artery involvement or lack thereof was accurately predicted in 42 (84%) of the 50 patients and internal iliac artery aneurysms found in one (33%) of three patients. It was concluded that CT is not sufficiently accurate for documenting location and patency of the renal arteries to allow its routine substitution for angiography in patients undergoing preoperative assessment of abdominal aortic aneurysms.