Low-FODMAP vs regular rye bread in irritable bowel syndrome:Randomized SmartPill~ study

AIM To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome(IBS) symptoms and to study gastrointestinal conditions with Smart Pill?.METHODS Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion,lower intraluminal pressure,higher colonic p H,different transit times,and fewer IBS symptoms than regular rye bread.The study was a randomized,double-blind,controlled cross-over meal study.Female IBS patients(n = 7) ate study breads at three consecutive meals during one day.The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day.Intraluminal p H,transit time,and pressure were measured by Smart Pill,an indigestible motility capsule.RESULTS Hydrogen excretion(a marker of colonic fermentation) expressed as area under the curve(AUC)(0-630 min) was [median(range)] 6300(1785-10800) ppm?min for low-FODMAP rye bread and 10 635(4215-13080) ppm?min for regular bread(P = 0.028).Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption(P = 0.063).Intraluminal pressure correlated significantly with total symptom score after regular rye bread(ρ = 0.786,P = 0.036) and nearly significantly after lowFODMAP bread consumption(ρ = 0.75,P = 0.052).We found no differences in p H,pressure,or transit times between the breads.Gastric residence of Smart Pill was slower than expected.Smart Pill left the stomach in less than 5 h only during one measurement(out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus.CONCLUSION Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread.No difference was found in median values of intraluminal conditions of the gastrointestinal tract.     

RAD50 and NBS1 are breast cancer susceptibility genes associated with genomic instability

The Mre11 complex, composed of RAD50, NBS1 and MRE11, has an essential role in the maintenance of genomic integrity and preventing cells from malignancy. Here we report the association of three Mre11 complex mutations with hereditary breast cancer susceptibility, studied by using a case-control design with 317 consecutive, newly diagnosed Northern Finnish breast cancer patients and 1000 geographically matched healthy controls (P = 0.0004). RAD50 687delT displayed significantly elevated frequency in the studied patients (8 out of 317, OR 4.3, 95% CI 1.5-12.5, P= 0.008), which indicates that it is a relatively common low-penetrance risk allele in this cohort. Haplotype analysis and the screening of altogether 512 additional breast cancer cases from Sweden, Norway and Iceland suggest that RAD50 687delT is a Finnish founder mutation, not present in the other Nordic cohorts. The RAD50 IVS3-1G>A splicing mutation leading to translational frameshift was observed in one patient, and the NBS1 Leu150Phe missense mutation affecting a conserved residue in the functionally important BRCA1 carboxy-terminal (BRCT) domain in two patients, both being absent from 1000 controls. Microsatellite marker analysis showed that loss of the wild-type allele was not involved in the tumorigenesis in any of the studied mutation carriers, but they all showed increased genomic instability assessed by cytogenetic analysis of peripheral blood T-lymphocytes (P = 0.006). In particular, the total number of chromosomal rearrangements was significantly increased (P = 0.002). These findings suggest an effect for RAD50 and NBS1 haploinsufficiency on genomic integrity and susceptibility to cancer.     

Fracture-induced changes in bone turnover: a potential confounder in the use of biochemical markers in osteoporosis

To examine the short- and long-term bone metabolic effects of fracture assessed by biochemical markers, we utilized a clinical fracture model—proximal tibial osteotomy—and prospectively followed 14 patients. This model of an induced fracture of a major bone gives the advantage of assessing baseline levels prior to fracture. Follow-up occurred at 6–9 weeks, 4–7 months, 9–13 months, and 14–17 months after fracture. Serum was assayed for type 1 procollagen peptide (PICP), total alkaline phosphatase (ALP), and carboxy-terminal-telopeptide of type I collagen (ICTP), while deoxypyridinoline (Dpyr) was measured in urine. Serum osteocalcin (OC) was measured using two recently developed two-site immunofluorometric assays, which both measure full-length and fragmented forms of OC (OC_tot), with one of the assays specifically detecting only the carboxylated form of OC (OC_cxy). In addition, OC was measured in urine using the same assays as those used for serum. Serum OC_tot increased to a peak at 4–7 months after fracture (P < 0.001) and a similar increase was seen for OC_cxy (P < 0.05) and ALP (P < 0.01). Bone formation had returned to baseline after a year. Dpyr increased significantly, with a doubling at 6 weeks, while serum (S)-ICTP increased by 73% (P < 0.01 and P < 0.001). Urine OC increased to a maximum of 84% at 6 weeks. The initial percentage increase of bone resorption was greater than that of bone formation. We conclude that: (1) bone turnover as measured by biochemical markers is altered soon after fracture, (2) the major changes occur within 6 weeks to 6 months, but may persist for up to a year. (3) The initial increase in bone resorption exceeds the increase in bone formation, which may contribute to the enhanced bone loss after fracture. (4) The two novel urine OC assays show a similar pattern of change as established marks of bone resorption, which may indicate that they measure bone resorption. (5) Fracture-induced effects on bone turnover are significant and, thus, are potential confounders in the assessment of osteoporosis.     

Expression of vascular endothelial growth factor receptor 3 and Tie1 tyrosine kinase receptor on acute leukemia cells

BACKGROUND: Recent data indicate a role for angiogenesis in hematologic malignancies. In addition to promoting new vessel growth in the bone marrow microenvironment, angiogenic factors are regulators of both hematopoietic and leukemic cells. Activation of vascular endothelial growth factor receptor 3 (VEGFR-3) and Tie1 tyrosine kinase receptor are known to promote leukemia cell survival. The details of this complex angiogenesis-related interaction are still uncertain. PROCEDURE: We studied bone marrow samples from 73 patients with acute lymphoblastic (ALL) or myelogenous (AML) leukemia by using immunological methods. RESULTS: Vascular endothelial growth factor receptor 3 expression was found in 15% of the samples, particularly in samples with pediatric lymphoblastic leukemias and monocytic AMLs. Tie1 protein expression was found in 11% of the samples, all of which were from adult AML patients. CONCLUSIONS: Our findings suggest that there are angiogenesis-related differences between pediatric and adult lymphoblastic leukemias as well as between lymphoid and myeloid leukemias.     

Impact of Alzheimer’s disease on the family caregiver’s long-term quality of life: results from an ALSOVA follow-up study

Purpose

To examine caregivers’ health-related quality of life (HRQoL) and well-being during the first 3 years after their family member’s Alzheimer’s disease (AD) diagnosis and assessed the relationship between caregivers’ HRQoL, well-being, and the severity of AD. Further, to compare of caregivers’ HRQoL to general population.

Methods

Longitudinal design (36 months) after AD diagnosis of 236 caregiver–patient dyads. Linear regression was used to assess age- and gender-adjusted association between repeated measurements of caregivers’ HRQoL and the severity of AD. For comparison with general population, the National Health 2011 Health Examination Survey data was utilized.

Results

Caregivers had significantly lower HRQoL than age- and gender-standardized counterparts. Severity of AD was significantly (p < 0.05) associated with the mobility and depression dimensions of caregiver’s HRQoL but not with the total HRQoL index score.

Conclusions

Caregivers’ HRQoL seems to deteriorate earlier than previously noted. The severity of AD has not that great impact on caregiver’s HRQoL as assumed.