Thiazide diuretics and the risk of hip fracture. Results from the Framingham Study

Thiazide diuretics may preserve bone mass and prevent elderly women's osteopenic fractures, but studies have not distinguished between thiazide preparations or examined former users. We performed a case-control study looking at thiazide use and subsequent hip fracture in postmenopausal female members of the Framingham Study cohort. Cases who had experienced a first hip fracture (n = 176) were compared with age-matched controls (n = 672). Results showed a modest protective effect of any recent thiazide use (not significant). However, recent pure thiazide users experienced significant protection against fracture (adjusted odds ratio, 0.31; 95% confidence interval, 0.11 to 0.88), whereas recent users of combination drugs containing thiazides experienced no protection (adjusted odds ratio, 1.16; 95% confidence interval, 0.44 to 3.05). Combination drugs generally contained only 25 mg of hydrochlorothiazide, suggesting that the small amount of thiazide was insufficient to preserve bone mass. Former thiazide users were not protected against fracture. In sum, recent pure thiazide use in women protects against hip fracture.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Evidence for decline in disability and improved health among persons aged 55 to 70 years: the Framingham Heart Study.

OBJECTIVES: This study detected secular change in disability and health among persons aged 55 to 70 years, the life period when increases in disability and morbidity begin and retirement occurs. METHODS: Cross-sectional comparisons were completed with data from similarly aged members of the original (n = 1760) and offspring (n = 1688) cohorts of the Framingham Heart Study, which represent 2 generations. Analyses were conducted by gender and on chronic disease subgroups by logistic regression. RESULTS: There was substantially less disability in the offspring cohort than in the original cohort. Thirty-six percent of offspring men were disabled vs 52% of original cohort men (P = .001); among women, these proportions were 54% vs 72% (P = .001). Fewer offspring perceived their health as fair or poor and fewer had chronic diseases. Offspring were more physically active and less likely to smoke or consume high amounts of alcohol, but their average weight was greater. The secular decline in disability was strongly evident among individuals with chronic diseases. CONCLUSIONS: Our findings depict a secular change toward a less disabled and globally healthier population in the period of life when retirement occurs.     

The effect of smoking at different life stages on bone mineral density in elderly men and women

To assess the effect of smoking on bone mineral density (BMD) at different life stages, to examine whether the effect of smoking differs between men and women, and to discover whether its effect in women differs according to history of estrogen use, a cohort study was carried out with single cross-section measurement of BMD by single and dual photon absorptiometry. The setting was the Framingham Study, a population-based cohort study with over 40 years prospectively collected data on smoking. Subjects (n=1164) consisted of cohort members participating in the 20th biennial Framingham examination (1988–1989). The measurements included in the study were BMD measured at the hip, spine and radius, smoking history ascertained at all Framingham Study examinations since 1948, and other factors affecting BMD (age, weight, estrogen use, caffeine use, alcohol use and physical activity). Neither current smoking, recent (last 10 years) smoking, nor early adulthood smoking resulted in significantly lower BMD at any skeletal site among women who had not taken estrogen. Among women who had taken estrogen, BMD at most sites was lower among current or recent smokers, although the small numbers of smokers made it difficult to find significant differences at all skeletal sites. Among men, a consistently lower BMD at all skeletal sites was observed for smokers regardless of when in their life they smoked (4–15.3% lower), although the effect of smoking during early adulthood was of a lesser magnitude (4–8% lower). Former male smokers who had quit <10 years ago had lower BMD than men who had quit 10 years ago. In conclusion, in women who had used estrogen, BMD was lower in current or recent smokers than it was in non-smokers. In men, smoking at any stage of life had adverse effects on the skeleton that was independent of weight, alcohol or caffeine use, implying other mechanisms for smoking's effect on bone.     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Some roentgenologic aspects of pulmonary emphysema copd

While many of the clinical and morphologic features of emphysema have been characterixed over the years, making a roentgenologic diagnosis is still difficult. The roentgenologic signs that can be used with some assurance are presented here.