Resistance of the ovary to blockade of aromatization with aminoglutethimide

Aminoglutethimide (AG) is a potent inhibitor of aromatization in placental microsomes and in peripheral tissues in postmenopausal women. Aromatase inhibitors have been used to block estrogen production and induce breast tumor regression in rodents. To inhibit ovarian estrogen production, we administered various doses of AG and its highly potent D-stereoisomer to premenopausal women with breast carcinoma. However, at no dose level did AG consistently lower estrone and estradiol concentrations in plasma below those observed in normal menstruating women. Uniform increments in LH and FSH were also not observed. Only during the luteal phase were the levels of estradiol (but not estrone) significantly suppressed. These observations are best explained by the possibility that aromatase enzymes in the ovary, as opposed to those in the placenta and in peripheral tissues, are partially resistant to the effects of AG.     

Looking for important change/differences in studies of responsiveness. OMERACT MCID Working Group. Outcome Measures in Rheumatology. Minimal Clinically Important Difference

The purpose of this paper is to describe a classification system for studies of responsiveness that was designed to help organize these studies, and identify those with the potential to provide information on minimal clinically important difference (MCID). We developed a 3 dimensional cube into which studies of responsiveness can be categorized based on their evaluation of 3 attributes: 1. individual or group setting; 2. which scores are contrasted; and 3. the type of change or difference being assessed. We present and discuss examples of studies that fit into categories in the classification cube. This classification system helps to focus attention on whether the literature is able to provide information on the specific type of change a person is interested in. It reinforces that the ability of an instrument to detect a certain category of discrimination within the cube does not mean it will necessarily be responsive to another category. The cube has been shown here as a means to separate out studies that address important change. These studies can then be examined as the source of information on MCID.     

1,25-Dihydroxyvitamin D3 and muscle strength in the elderly: a randomized controlled trial

An unexplained loss of muscle strength occurs with aging. Vitamin D deficiency can cause myopathy and administration of 1,25-dihydroxyvitamin D3 [1,25-(OH2)D3] to persons with low serum concentrations can improve strength. To test the hypothesis that the weakness associated with aging is in part due to inadequate serum concentrations of [1,25-(OH2)D3], we conducted a randomized, controlled, double blinded trial in 98 men and women volunteers over 69 yr old. Treatment consisted of 0.25 micrograms 1,25-(OH)2D3, orally, twice per day or identical placebo for 6 months. Leg muscle strength of the quadriceps was measured with an isokinetic dynamometer. There was no difference between the two groups at 1 week, 1 month, or 6 months of treatment in any of the measures of muscle strength. We conclude that oral administration of 0.5 micrograms 1,25-(OH)2D3/day does not improve muscle strength in older persons. Further research is needed to determine the etiology of the decline in muscle strength associated with aging.     

Hemoglobin Brisbane: beta68 Leu replaced by His. A new high oxygen affinity variant

Hemoglobin Brisbane is a new hemoglobin variant which produces a mile erythrocytosis. It is not detectable by electrophoresis at pH 8.6 or by isoelectric focusing but it is mildly unstable and gives a positive result with standard stability tests. The new hemoglobin has increased oxygen affinity and reduced co-operativity with a normal Bohr effect and 2,3-DPG binding. Structural analysis shows that a histidine residue has replaced the leucine normally found at position beta 68 (E12).     

Predictors and Clinical Outcomes of Next-Day Discharge After Minimalist Transfemoral Transcatheter Aortic Valve Replacement

Objectives

This study sought to investigate predictors and safety of next-day discharge (NDD) after transcatheter aortic valve replacement (TAVR).

The TNF-863A allele strongly associates with anticentromere antibody positivity in scleroderma

OBJECTIVE: Scleroderma is characterized by the presence of 3 predominant, yet almost mutually exclusive, antibodies: anticentromere antibody (ACA), antitopoisomerase antibody, and anti-RNA polymerase antibody. The purpose of this study was to investigate tumor necrosis factor (TNF) polymorphisms in scleroderma, with the specific aim of determining whether TNF polymorphisms would prove to be stronger markers for ACA than class II major histocompatibility complex (MHC). METHODS: We studied 214 UK white scleroderma patients and 354 healthy controls. All subjects were investigated for 5 TNF promoter region polymorphisms by sequence-specific polymerase chain reaction. RESULTS: We showed that an NF-kappaB binding site polymorphism (known to be functionally relevant) in the TNF promoter region was present in 51.8% of patients with ACA and 16.3% of patients without ACA (chi(2) = 25.1, P = 0.000004 [corrected P = 0.00002]). Using haplotype mapping, we showed that this was a primary TNF association that could explain the previous weak links between ACA production and class II MHC alleles. In marked contrast to our ACA results, HLA class II (especially DRB1*11) appeared to be primary in that it could explain the weaker TNF association with antitopoisomerase production. Further, we observed a separate TNF haplotype to be associated with scleroderma per se, although the level of significance was much lower (chi(2) = 8.7, P = 0.003 [corrected P = 0.02]). CONCLUSION: We believe these findings may have importance both for the directional pathogenesis of scleroderma progression and for the treatment of scleroderma with anti-TNF agents.