Active abdominal tuberculosis in Canada in 1970-81.

We reviewed all 341 cases of abdominal tuberculosis reported in Canada between 1970 and 1981. Over the study period abdominal tuberculosis accounted for a stable proportion (0.8%) of all reported cases of tuberculosis in Canada. Its incidence declined steadily. It was more common in women, in native Indians and in people born in Asia. Detailed records of the 55 cases reported to Statistics Canada from British Columbia and of an additional 31 cases not reported to Statistics Canada (usually because they involved concomitant disease elsewhere, notably the lungs) were studied. Five of the 55 cases reported to Statistics Canada had been reported incorrectly. Of the 81 cases in British Columbia 51% involved peritonitis, 21% ileocecal disease, 20% anorectal disease, 10% mesenteric lymphadenitis, 1% disease of the sigmoid colon and 1% disease of the liver. The rate of bacteriologic confirmation was low (51%).     

Leg symptoms in outpatient veterans.

In a survey of outpatients at the Denver Veterans Affairs Medical Center for common leg symptoms--515 questionnaires returned in a 3-week period--56% reported nocturnal leg cramps, 29% reported the restless leg syndrome, and 49% reported symptoms of peripheral neuropathy. Only 33% of patients had no symptoms relating to their legs. Patients often did not report these symptoms to their physician but were more likely to do so if the symptoms were frequent. Conditions especially related to leg symptoms were hypertension, peripheral vascular disease, coronary artery disease, cerebrovascular disease, kidney disease, and hypokalemia. Most patients did not receive effective therapy for these symptoms.     

Dysgonic fermenter 2 infection resulting in chronic glomerulonephritis

Dysgonic fermenter 2 (DF-2) is a fastidious gram-negative pathogen that is capable of causing multiorgan disease in humans. In the case reported here infection resulted in subacute bacterial endocarditis, brain abscess and chronic type 1 membranoproliferative glomerulonephritis, a form of renal disease not previously reported in DF-2 infections. The literature is reviewed, and difficulties in diagnosis and treatment are discussed.     

Trends in ectopic pregnancy in Canada.

The incidence in Canada of one complication of sexually transmitted disease, ectopic pregnancy, was examined by age group for the years 1971 through 1980 by means of hospital statistics provided by Statistics Canada. The denominator was "reported pregnancies"--the total of live births, stillbirths, legal abortions and ectopic pregnancies in a given year. In 1980, 4123 ectopic pregnancies (9.3/1000 reported pregnancies) were reported, a 63% increase from 1970. The incidence had increased in each age stratum. This trend may be related to increasing rates of gonococcal infection and of hospitalization for pelvic inflammatory disease and lends confirmation to data from other countries that relate the increase in the rate of ectopic pregnancy to rising rates of sexually transmitted disease.     

A case of Turner's syndrome with hyperthyroidism

A female patient with classical gonadal dysgenesis associated with Graves' disease is reported. The karyotype was mosaicism of 45,X/46,X,i(Xq). The relationship among Graves' disease, Hashimoto's thyroiditis and Turner's syndrome is discussed along with a review of the reported cases.     

Tumors and polycystic renal disease in two captive woodchucks (Marmota monax)

Hepatocellular carcinoma, polycystic renal disease and pneumonia are reported in an aged woodchuck, and a metastatic fibrosarcoma is reported in a relatively young animal born and raised in the laboratory.     

Evidence that the penetrance of mutations at the RP11 locus causing dominant retinitis pigmentosa is influenced by a gene linked to the homologous RP11 allele.

A subset of families with autosomal dominant retinitis pigmentosa (RP) display reduced penetrance with some asymptomatic gene carriers showing no retinal abnormalities by ophthalmic examination or by electroretinography. Here we describe a study of three families with reduced-penetrance RP. In all three families the disease gene appears to be linked to chromosome 19q13.4, the region containing the RP11 locus, as defined by previously reported linkage studies based on five other reduced-penetrance families. Meiotic recombinants in one of the newly identified RP11 families and in two of the previously reported families serve to restrict the disease locus to a 6-cM region bounded by markers D19S572 and D19S926. We also compared the disease status of RP11 carriers with the segregation of microsatellite alleles within 19q13.4 from the noncarrier parents in the newly reported and the previously reported families. The results support the hypothesis that wild-type alleles at the RP11 locus or at a closely linked locus inherited from the noncarrier parents are a major factor influencing the penetrance of pathogenic alleles at this locus.     

Rescue of a Recombinant Machupo Virus from Cloned cDNAs and In Vivo Characterization in Interferon (αβ/γ) Receptor Double Knockout Mice

Machupo virus (MACV) is the etiological agent of Bolivian hemorrhagic fever (BHF), a reemerging and neglected tropical disease associated with high mortality. The prototypical strain of MACV, Carvallo, was isolated from a human patient in 1963, but minimal in vitro and in vivo characterization has been reported. To this end, we utilized reverse genetics to rescue a pathogenic MACV from cloned cDNAs. The recombinant MACV (rMACV) had in vitro growth properties similar to those of the parental MACV. Both viruses caused similar disease development in alpha/beta and gamma interferon receptor knockout mice, including neurological disease development and high mortality. In addition, we have identified a novel murine model with mortality and neurological disease similar to BHF disease reported in humans and nonhuman primates.     

Two models for a maternal factor in the inheritance of Huntington disease

Huntington disease is a classic example of an autosomal dominant trait. Over the years, however, a number of investigators have reported anomalies regarding the age of onset of the disease that are inconsistent with this paradigm. We propose two models in which a maternal factor--cytoplasmic in one case, autosomal or X-linked in the other--acts to delay onset in a manner consistent with the previously reported anomalies. Relevant data from the Huntington's Disease Research Roster are presented that reinforce and extend the previous observations.     

Two cases of primary splenic hydatid cyst in Greece

Cystic disease of the spleen is an uncommon entity in general population. Most cases result from parasitic infection by Echinococcus granulosus, a form called splenic hydatid disease (SHD), with a reported frequency of 0.5-6.0% within abdominal hydatidosis. On the contrary, an isolated splenic involvement of hydatid disease is very uncommon even in endemic regions. Two cases of primary SHD managed with open and laparoscopic radical surgery in our department are reported herein. Primary SHD is a rare entity with non-specific symptoms underlying clinical suspicion by the physician for prompt diagnosis. Surgical treatment is the mainstay therapy, while laparoscopic approach when feasible is safe, offering the advantages of laparoscopic surgery.     

念珠菌致真菌性角膜炎3例报告

真菌性角膜炎是严重的致菌性眼病，本文报告我院于2011年诊治的3例念珠菌致真菌性角膜炎，这有助于了解在本地区该疾病的致病菌及主要特点。     

西瓜水浸病及其病原体的研究

本文报导了近年来在西瓜种植中发现的一种危害大,且发病分布广泛的新病—西瓜水浸病,描述了该病的症状,对所分离到的三株病原体进行了分类学上的鉴定,并初步地探讨了该病的发病规律。     

Transcriptional Profile of Muscle following Acute Induction of Symptoms in a Mouse Model of Kennedy's Disease/Spinobulbar Muscular Atrophy

BackgroundKennedy’s disease/Spinobulbar muscular atrophy (KD/SBMA) is a degenerative neuromuscular disease affecting males. This disease is caused by polyglutamine expansion mutations of the androgen receptor (AR) gene. Although KD/SBMA has been traditionally considered a motor neuron disease, emerging evidence points to a central etiological role of muscle. We previously reported a microarray study of genes differentially expressed in muscle of three genetically unique mouse models of KD/SBMA but were unable to detect those which are androgen-dependent or are associated with onset of symptoms.Conclusions/SignificanceBy comparing the current results with those from the three previously reported models we were able to identify KD/SBMA candidate genes that are androgen dependent, and occur early in the disease process, properties which are promising for targeted therapeutics.     

Genotype D399N/R463C in a Patient with Type 3 Gaucher Disease Previously Assigned Genotype N370S/R463C

A patient with type 3 Gaucher disease is described with a novel genotype, D399N/R463C, established by DNA sequencing. This patient was previously reported as having genotype N370S/R463C. This communication now establishes that no patients reported with mutation N370S have the neuronopathic forms of Gaucher disease and has important implications for genetic counseling.     

Health risks for marine mammal workers

Marine mammals can be infected with zoonotic pathogens and show clinical signs of disease, or be asymptomatic carriers of such disease agents. While isolated cases of human disease from contact with marine mammals have been reported, no evaluation of the risks associated with marine mammal work has been attempted. Therefore, we designed a survey to estimate the risk of work-related injuries and illnesses in marine mammal workers and volunteers. The 17-question survey asked respondents to describe their contact with marine mammals, injuries sustained, and/or illnesses acquired during their period of marine mammal exposure. Most respondents, 88% (423/483), were researchers and rehabilitators. Of all respondents, 50% (243/483) reported suffering an injury caused by a marine mammal, and 23% (110/483) reported having a skin rash or reaction. Marine mammal work-related illnesses commonly reported included: 'seal finger' (Mycoplasma spp. or Erysipelothrix rhusiopathiae), conjunctivitis, viral dermatitis, bacterial dermatitis, and non-specific contact dermatitis. Although specific diagnoses could not be confirmed by a physician through this study, severe illnesses were reported and included tuberculosis, leptospirosis, brucellosis, and serious sequelae to seal finger. Risk factors associated with increased odds of injury and illness included prolonged and frequent exposure to marine mammals; direct contact with live marine mammals; and contact with tissue, blood, and excretions. Diagnosis of zoonotic disease was often aided by veterinarians; therefore, workers at risk should be encouraged to consult with a marine mammal veterinarian as well as a physician, especially if obtaining a definitive diagnosis for an illness becomes problematic.     

Combinations of Susceptibility Genes Are Associated with Higher Risk for Multiple Sclerosis and Imply Disease Course Specificity

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system that predominantly affects young adults. The genetic contributions to this multifactorial disease were underscored by a genome wide association study (GWAS) conducted by the International Multiple Sclerosis Genetic Consortium in a multinational cohort prompting the discovery of 57 non-MHC MS-associated common genetic variants. Hitherto, few of these newly reported variants have been replicated in larger independent patient cohorts. We genotyped a cohort of 1033 MS patients and 644 healthy controls with a consistent genetic background for the 57 non-MHC variants reported to be associated with MS by the first large GWAS as well as the HLA DRB1*1501 tagging SNP rs3135388. We robustly replicated three of the 57 non-MHC reported MS-associated single nucleotide polymorphisms (SNPs). In addition, our study revealed several genotype-genotype combinations with an evidently higher degree of disease association than the genotypes of the single SNPs. We further correlated well-defined clinical phenotypes, i.e. ataxia, visual impairment due to optic neuritis and paresis with single SNPs and genotype combinations, and identified several associations. The results may open new avenues for clinical implications of the MS associated genetic variants reported from large GWAS.     

剑阁县2001～2010 年法定传染病流行特征及防治对策分析

目的:通过分析10年法定传染病疲情的流行趋势和三间分布特征,为制定传染病预防控制策略和措施提供依据.方法:采用描述性流行病学方法分析疫情趋势和三间分布情况,数据资料用SPSS10.0和Excel 2003进行统计分析.结果:2001～2010年共报告乙、丙类传染病25种26 129例,年均发病率386.89/10万,年均死亡率0.15/10万,10年间报告法定传染病以血源及性传播传染病和呼吸道传染病为主,居第1位的是血源及性传播传染病,共报告5种12 453例,占53.03％;其次是呼吸道传染病,共报告5种9828例,占41.85％,近3年发病居于各类传染病首位;第三位的是肠道传染病,共报5种1149例,占4.89％.发病居前5位的传染为乙肝、肺结核、流行性腮腺炎、痢疾、麻疹,主要传染病以乙肝、肺结核为主,近年性传播疾病呈快速增长趋势.结论:血源及性传播传染病和呼吸道传染病是今后重点防控传染病.     

Symptoms of respiratory tract infection and associated care-seeking in subjects with and without obstructive lung disease; The Tromso Study: Tromso 6

ABSTRACT: BACKGROUND: Respiratory tract infections (RTIs) may be more severe in those with asthma or COPD and these patients are more frequently in need of health care. The aim of the study was to describe the frequency of RTI symptoms in a general adult population and how care-seeking is associated with the presence of obstructive lung disease. METHODS: Cross-sectional data including spirometry and self-reported chronic diseases were collected among middle-aged and elderly subjects in the Tromso population survey (Tromso 6). Self- reported RTI symptoms, consultations and antibiotic use were the main outcome variables. Possible predictors of RTI symptoms were evaluated by multivariable logistic regression. RESULTS: Of the 6414 subjects included, 798 (12.4 %) reported RTI symptoms in the previous week. RTI symptoms were reported less frequently by subjects aged 75 years or above, than by those younger than 55 years (OR 0.5). Winter season (OR 1.28), current smoking (OR 1.60), low self-rated health (OR 1.26) and moderate to severe bronchial obstruction (OR 1.51), were also statistically significant independent predictors of RTI symptoms, but these variables did not predict RTI symptoms that had started within the previous seven days. Among subjects with RTI symptoms, 5.1 % also reported a consultation with a doctor. In those with bronchial obstruction by spirometry, who did not report asthma or COPD, this frequency was 2.4 %. Antibiotic treatment was reported by 7.4 % of the participants, among whom one third had consulted a doctor. Antibiotics were taken more frequently when asthma or COPD was reported (13.7 %), but not in subjects with bronchial obstruction who did not report these diseases (7.2 %). CONCLUSIONS: RTI symptoms seldom led to consultation with a doctor and not even in subjects with obstructive lung disease. This was in particular the case in subject who did not know about their obstructive lung disease. Strategies for early diagnosis of COPD and providing health care to subjects with such disease cannot rely on their doctor visits due to respiratory symptoms.     

Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints

Inhibition of BACE1 has become an important strategy in the quest for disease modifying agents to slow the progression of Alzheimer’s disease. We previously reported the fragment-based discovery of LY2811376, the first BACE1 inhibitor reported to demonstrate robust reduction of human CSF Aβ in a Phase I clinical trial. We also reported on the discovery of LY2886721, a potent BACE1 inhibitor that reached phase 2 clinical trials. Herein we describe the preparation and structure activity relationships (SAR) of a series of BACE1 inhibitors utilizing trans-cyclopropyl moieties as conformational constraints. The design, details of the stereochemically complex organic synthesis, and biological activity of these BACE1 inhibitors is described.