Discrimination of hip fractures by quantitative ultrasound of the phalanges and the calcaneus and dual X-ray absorptiometry

The aim of the current study was to evaluate the ability of different techniques used for the assessment of bone status to discriminate between postmenopausal women with and without hip fracture. Fifty-one postmenopausal women (mean age 64.5±6.5) who had sustained a low energy hip fracture and 51 age-matched controls (mean age 64.6±6.0) were studied. Quantitative ultrasound (QUS) assessment was carried out using the Ubis 3000 device capable of measuring broadband ultrasound attenuation (BUA) and speed of sound at the calcaneus (SOS_C) and the Sunlight Omnisense device capable of estimating speed of sound at the phalanges (SOS_P). Femoral neck bone mineral density (BMD) was assessed using dual X-ray absorptiometry. Correlations between QUS variables ranged from r=0.35 to 0.72 and between QUS variables and BMD from r=0.30 to 0.36. BMD was the best discriminator of hip fractures (odds RATIO = 3.61, area under CURVE = 0.824). All QUS variables were significant discriminators of hip fractures with odds ratios ranging from 1.88 to 2.63 and areas under the ROC curves ranging from 0.663 to 0.740. Among the QUS variables, the SOS_P showed the best odds ratio and area under curve. Comparison between the areas under the ROC curve did not show any significant difference between SOS_P, BUA and BMD. On the contrary, the difference between SOS_C and BMD was significant (P<0.05). In conclusion, BMD and QUS variables investigated in the current study were significant discriminators of hip fractures. The differentiation of the hip fractures by BMD was significantly better than that of BUA measured at the calcaneus. Moreover, BMD discriminated fractured patients better than BUA and SOS_P, although the difference did not reach statistical significance.     

Brain biopsy in the diagnosis of cerebral mycosis fungoides

A case of cerebral mycosis fungoides co-existing with progressive multifocal leucoencephalopathy presented with dementia. Brain biopsy established the diagnosis of mycosis fungoides after cerebrospinal fluid examinations and computerised tomographic scanning of the brain produced non-specific abnormalities.     

Tuberculosis in Patients Infected with Human Immunodeficiency Virus 1. A Retrospective Multicentre Study of 123 Cases in France

SUMMARY In order to study the epidemiological, clinical, and progressivecharacteristics of TB in HIV-infected individuals, a retrospectivestudy was conducted in nine infectious disease centres of universityhospitals located in the southern half of France. Among the5730 HIV-seropositive in- and out-patients, 123 (2.1 per cent)had TB (121 infections caused by M. tuberculosis, 2 by M. bovis).Tuberculosis was pulmonary in 53 patients (43.1 per cent), extrapulmonaryin 36 patients (29.3 per cent), and combined in 34 patients(27.6 per cent). There was no statistically significant differenceamong these three locations as to the mean CD4 count/mm³ (160±17),the type of antituberculosis therapy, the length of treatment(10.8±0.6 months) and the outcome. Fifty-two (45.2 percent) patients received an initial antituberculosis therapeuticregimen of four drugs: isoniazid, rifampicin, ethambutol, pyrazinamide;54 (46.9 per cent) were started on three drugs: isoniazid, rifampicin,ethambutol; and nine (7.8 per cent) received a two-drug combination:isoniazid, rifampicin. Fourteen of 75 patients subsequentlyreceived secondary preventive therapy. The mean follow-up timewas 252±290 days. Clinical healing was obtained in 57.7per cent of patients. Forty-six patients died, 33 during treatment:23 from AIDS and eight from TB (in the first 3 weeks of treatment).Five patients suffered from relapses due to poor treatment compliance.Patients had a good prognosis if tuberculosis was diagnosedearly.     

Pre-B cells and other possible precursor lymphoid cell lines derived from patients with X-linked agammaglobulinemia

A group of unique Epstein-Barr virus-containing cell lines was derived from the bone marrow of three patients with X-linked agammaglobulinemia. Efforts to obtain cell lines from the peripheral blood of these patients were uniformly unsuccessful. Immunofluorescence analyses as well as biosynthetic studies with [(35)S]methionine indicated unusual patterns of Ig synthesis in many of these bone marrow derived lines. Seven of the lines were of particular interest in that two produced no Ig of any type; two others showed no Ig by fluorescence but small amounts by [(35)S]methionine labeling; one expressed only cytoplasmic μ chains without any evidence of light chain synthesis, and two produced primarily μ chains with only slight amounts of light chains. One of the lines without membrane or cytoplasmic Ig studied in detail grew like a typical lymphoid line and was carried in intermittent culture over a period of 2 yr without Ig expression. One line grew quite differently and resembled the round cell type described previously, which has been obtained from a variety of sources. The cell line with cytoplasmic μ chains and no light-chain expression had the characteristic properties of pre-B cells. Three normal type Ig-producing cell lines also were obtained from the patients. The accumulated evidence obtained in the present study indicates that these unusual cell lines represent normal precursor cells of the B-cell lineage; these grew out in these cases because of the virtual absence of mature B cells that ordinarily overgrow the culture system. However, the possibility that in certain instances they reflect abnormal Ig synthesis characteristic of the disease has not been ruled out.     

Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

Impact of genetic variations in the WRN gene on age related pathologies and mortality

Mutations in the WRN gene lead to the Werner syndrome (WS), which resembles premature aging. Here, we hypothesize that genetic variations in the WRN gene may also influence aging-trajectories in the population at large. To test this hypothesis, we assessed the impact of the i1-C/T, L1074F and C1367R polymorphisms in the WRN gene on the occurrence of cardiovascular pathologies, on cognitive performance and on the risks of all-cause, cardiovascular and cancer mortalities in the population-based Leiden 85-plus Study. This prospective follow-up study includes 1,245 participants aged 85 years and older, with a total follow-up of 5,164 person-years. At baseline the risks of myocardial infarction, myocardial ischemia, intermittent claudication, arterial surgery and stroke dependent on the i1-C/T, L1074F and C1367R polymorphisms, did not vary between the different genotypes. Also no differences in cognitive functioning were observed, except for attention, where carriers of the 1367R allele performed worse compared to the 1367C homozygotes (94.2 (4.35) versus 84.8 (1.84), p=0.04). Mortality risks, calculated separately for all SNPs, were similar between the different genotype carriers of the i1-C/T, L1074F and C1367R polymorphisms, showing no evidence of altered survival. In conclusion, the i1-C/T, L1074F and C1367R polymorphisms in the WRN gene do not influence the aging-trajectories and survival in the population at large.     

LRTOMT: a new tone in understanding the symphony of non-syndromic deafness

Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans
Ahmed et al. (2008)
Nature Genetics 40: 1335–1340.     

The effectiveness of a treatment protocol for male lower urinary tract symptoms in general practice: a practical randomised controlled trial

BACKGROUND: Randomised controlled trials have shown the efficacy of several treatment modalities for lower urinary tract symptoms (LUTS) in selected populations. The effectiveness in daily practice has hardly been investigated, especially in primary care and is dependent on choices between all possible treatment options and best investigated in a comprehensive study, including all treatment modalities (watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors, and surgery). AIM: Assessment of the effectiveness of a comprehensive treatment protocol for LUTS in primary care. DESIGN OF STUDY: Randomised controlled trial. SETTING: Fourteen general practices in the Netherlands. METHOD: Intervention: treatment protocol based on a formalised expert opinion. Control condition: usual care. Study population: 208 subjects with moderate to severe LUTS (IPSS > or =8, median = 13). OUTCOME MEASURES: symptom severity (IPSS [International Prostate Symptom Score]), bother score (Dan-PSS [Danish Prostate Symptom Score]), and maximum urinary flow (Q(max)); incidence of acute urinary retention and urinary tract infections. RESULTS: In the intervention group markedly more subjects used an alpha-blocker at end of follow-up than in the usual care group (24% versus 6%). No significant differences were found between intervention and control group in IPSS, Q(max) or Dan-PSS. CONCLUSION: alpha-blockers and watchful waiting are the most frequent treatment modalities for LUTS in primary care. Our study showed no evidence that a protocol using well-defined indications for all possible treatment modalities based on a formalised expert opinion procedure has added value. Based on our results, we cannot recommend a broadening of the indication for alpha-blockers, which, however, seems to be the current trend.     

Segmental duplications and gene conversion: Human luteinizing hormone/chorionic gonadotropin beta gene cluster

Segmental duplicons (>1 kb) of high sequence similarity (>90%) covering >5% of the human genome are characterized by complex sequence variation. Apart from a few well-characterized regions (MHC, β-globin), the diversity and linkage disequilibrium (LD) patterns of duplicons and the role of gene conversion in shaping them have been poorly studied. To shed light on these issues, we have re-sequenced the human Luteinizing Hormone/Chorionic Gonadotropin β (LHB/CGB) cluster (19q13.32) of three population samples (Estonians, Mandenka, and Han). The LHB/CGB cluster consists of seven duplicated genes critical in human reproduction. In the LHB/CGB region, high sequence diversity, concentration of gene-conversion acceptor sites, and strong LD colocalize with peripheral genes, whereas central loci are characterized by lower variation, gene-conversion donor activity, and breakdown of LD between close markers. The data highlight an important role of gene conversion in spreading polymorphisms among duplicon copies and generating LD around them. The directionality of gene-conversion events seems to be determined by the localization of a predicted recombination “hotspot” and “warm spot” in the vicinity of the most active acceptor genes at the periphery of the cluster. The data suggest that enriched crossover activity in direct and inverted segmental repeats is in accordance with the formation of palindromic secondary structures promoting double-strand breaks rather than fixed DNA sequence motifs. Also, this first detailed coverage of sequence diversity and structure of the LHB/CGB gene cluster will pave the way for studying the identified polymorphisms as well as potential genomic rearrangements in association with an individual's reproductive success.     

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.