慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的相关性研究

目的:研究慢性阻塞性肺疾病与代谢综合征及颈动脉内膜厚度的关系。方法:选择2014年8月至2015年4月在我院就诊的慢性阻塞性肺疾病患者60例作为研究组,另选择同期在我院接受健康体检的60名志愿者作为对照组。比较两组空腹血糖、甘油三酯及高密度脂蛋白胆固醇水平、代谢综合征的发生率、颈动脉内膜厚度以及合并与不合并代谢综合征的慢性阻塞性肺疾病患者的肺功能和颈动脉内膜厚度,并采用多元回归分析颈动脉内膜厚度与慢性阻塞性肺疾病及代谢综合征的相关性。结果:与对照组相比,研究组患者空腹血糖(FPG)明显升高,而甘油三酯(TG)水平明显降低,差异具有统计学意义(P0.05);两组高密度脂蛋白胆固醇(HDL-C)比较差异无统计学意义(P0.05)。研究组代谢综合征的发病率、颈动脉内膜厚度均明显高于对照组,差异具有统计学意义(P0.05);慢性阻塞性肺疾病合并代谢综合征患者的肺功能明显优于无代谢综合征的慢性阻塞性肺疾病患者,差异具有统计学意义(P0.05);合并代谢综合征的慢性阻塞性肺疾病患者FEV1占预计值百分比及FEV1/FVC均明显高于无代谢综合征慢性阻塞性肺疾病患者的对应值,差异具有统计学意义(P0.05)。Logistic回归分析结果显示慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关性,而代谢综合征与颈动脉内膜厚度无直接相关性。结论:慢性阻塞性肺疾病与颈动脉内膜厚度呈独立相关,且慢性阻塞性肺疾病合并代谢综合征患者发生颈动脉粥样硬化的风险更高。     

Familial Fibrocystic Pulmonary Dysplasia: Observations in One Family

At least 31 cases of familial fibrocystic pulmonary dysplasia, within 10 families, have been described in the world literature. The mode of genetic transmission of this disease, however, has been uncertain until now. The author observed three unequivocal and five probable cases of familial fibrocystic pulmonary dysplasia among 56 members of one family. Diagnostic criteria included progressive dyspnea and cyanosis, digital clubbing, pulmonary hypertension, negative sweat tests, polycythemia, arterial hypoxia and hypocapnia, chest radiographs showing diffuse bilateral pulmonary fibrosis, and diffuse fibrocystic pulmonary dysplasia at postmortem examination (two cases). Among the three unequivocal cases one father-to-son transmission was observed. Non-sex-linked dominant transmission of familial fibrocystic pulmonary dysplasia is thereby proved for the first time. One patient also developed a bronchial carcinoma in addition to fibrocystic pulmonary dysplasia; this is considered to be a cause-and-effect relationship and not a coincidental complication.     

Connexin 43 Astrocytopathy Linked to Rapidly Progressive Multiple Sclerosis and Neuromyelitis Optica

Background

Multiple sclerosis (MS) and neuromyelitis optica (NMO) occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx) pathology and disease aggressiveness in Asian patients with MS and NMO.

Methods/Principal Findings

Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD), six with MS, and 20 with other neurological diseases (OND). Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59), chronic active (n=58) and chronic inactive (n=23). Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090). Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296). Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients.

Conclusions

These findings suggest that autoantibody-independent astrocytic Cx43 loss may relate to disease aggressiveness and distal oligodendrogliopathy in both MS and NMO.     

Causes of Death among Commercially Insured Multiple Sclerosis Patients in the United States

Background

Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes.

Objective

To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients.

Methods

Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the “principal” COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized.

Results

30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs.

Conclusions

The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide.     

多层螺旋CT对肺结核合并肺癌患者的诊断价值

目的:研究多层螺旋CT对肺结核合并肺癌的鉴别诊断价值。方法:选择2013年3月至2015年9月在我院确诊的肺结核合并肺癌患者32例和单纯肺结核患者39例应用多层螺旋CT扫描患者肺部病变情况。结果:肺结核合并肺癌组:陈旧性肺结核28例、活动性肺结核4例;病灶位置经典部位29例、非经典部位3例,合并鳞癌11例、腺癌13例、小细胞癌5例、未分化癌3例;10例结核病灶与肺癌病灶不同侧、13例结核病灶与肺癌病灶同侧不同叶、9例结核病灶于肺癌病灶同侧同叶。单纯性肺结核组胨旧性肺结核36例、活动性肺结核3例;病灶位置经典部位34例(上叶尖段11例、后段9例、下叶背段14例)、非经典部位5例。肺结核合并肺癌组患者分叶征、毛刺征、胸膜凹陷征、阻塞性肺炎及肺不张以及棘状突起比例高于单纯肺结核组,而空泡影比例低于单纯肺结核组,差异具有统计学意义(P0.05);两组钙化、斑片条索影、结节影以及空洞或空腔比较,差异无统计学意义(P0.05)。结论:多层螺旋CT对肺结核合并肺癌具有较高的临床鉴别诊断价值。     

冠心病合并代谢综合征患者的冠状动脉病变特点及与 代谢综合征组分的相关性研究

目的:探讨冠心病合并代谢综合征(metabolic syndrome,MS)患者的冠脉病变特点及冠心病与MS各组分的相关性。方法:选取540例冠心病患者为研究对象,其中合并MS患者164例,非合并MS患者376例,并将所有患者根据MS的组分个数进行分组,比较冠心病合并MS的病变特点、MS组分个数对冠状动脉病变程度的影响及冠状动脉病变程度与代谢综合症各组分的相关性;结果:①冠心病合并MS组BMI、FBG、TG、LDL-C、TC、UA、FIB、高血压分级等指标较非MS组高,差异有统计学意义(P<0.01),HDL-C、LVEF较非MS组低,差异有显著性(P<0.01);②MS组冠脉Gensini积分较高,三支病变、主干病变发生率高,差异有显著性(P<0.01);③随着合并MS组分个数的增加,冠脉Gensini积分也逐渐增加,各组间比较有显著性差异(P<0.01);④冠脉Gensini积分与MS组分BMI、高血压分级、TG、TC、LDL-C、UA等指标存在正相关(P<0.05),与性别、HDL-C存在负相关(p<0.01);调整传统危险因素后,Gensini积分与MS的组分数显著相关(r=0.739、P<0.01)。结论:冠心病患者有较高的MS患病率,冠心病合并MS患者冠脉病变程度更重,且以多支病变、主干病变为主;随着合并MS组分个数的增加,冠脉病变程度也呈加重趋势;MS的各个组分均与冠状动脉病变程度显著相关,可以作为冠心病严重程度的预测指标。     

Analysis of Volatile Compounds in Exhaled Breath Condensate in Patients with Severe Pulmonary Arterial Hypertension

Background

An important challenge to pulmonary arterial hypertension (PAH) diagnosis and treatment is early detection of occult pulmonary vascular pathology. Symptoms are frequently confused with other disease entities that lead to inappropriate interventions and allow for progression to advanced states of disease. There is a significant need to develop new markers for early disease detection and management of PAH.

Methodolgy and Findings

Exhaled breath condensate (EBC) samples were compared from 30 age-matched normal healthy individuals and 27 New York Heart Association functional class III and IV idiopathic pulmonary arterial hypertenion (IPAH) patients, a subgroup of PAH. Volatile organic compounds (VOC) in EBC samples were analyzed using gas chromatography/mass spectrometry (GC/MS). Individual peaks in GC profiles were identified in both groups and correlated with pulmonary hemodynamic and clinical endpoints in the IPAH group. Additionally, GC/MS data were analyzed using autoregression followed by partial least squares regression (AR/PLSR) analysis to discriminate between the IPAH and control groups. After correcting for medicaitons, there were 62 unique compounds in the control group, 32 unique compounds in the IPAH group, and 14 in-common compounds between groups. Peak-by-peak analysis of GC profiles of IPAH group EBC samples identified 6 compounds significantly correlated with pulmonary hemodynamic variables important in IPAH diagnosis. AR/PLSR analysis of GC/MS data resulted in a distinct and identifiable metabolic signature for IPAH patients.

Conclusions

These findings indicate the utility of EBC VOC analysis to discriminate between severe IPAH and a healthy population; additionally, we identified potential novel biomarkers that correlated with IPAH pulmonary hemodynamic variables that may be important in screening for less severe forms IPAH.     

房水平单向活瓣式补片对老年先天性心脏病合并重度肺动脉高压 的临床效果分析

目的:探究房水平单向活瓣式补片对老年先天性心脏病伴重度肺动脉高压患者的作用疗效。方法:选取我院心血管科收治的先天性心脏病伴重度肺动脉高压患者80例,随机分为对照组和实验组。对照组40例,予以常规基础药物治疗(波生坦);实验组,在基础药物治疗两个疗程后,采用房水平单向活瓣式补片进行手术治疗。比较两组患者治疗前后的肺动脉压(PAP)、体动脉压(SAP)、肺动脉压/体动脉压(PAP/SAP)、动脉血氧分压(Pa O2)、二氧化碳分压(Pa CO2)及吸氧浓度、右室收缩末期内径变化情况。结果:治疗后,与对照组比较,实验组肺动脉压下降幅度较大(P0.05);与治疗前比较,实验组肺动脉压与体动脉压的比值显著下降,且优于对照组(P0.05);治疗后,实验组动脉血氧分压、二氧化碳分压以及吸氧浓度显著优于对照组(P0.05);治疗后,实验组患者右室收缩末期内径显著小于对照组(P0.05);随访结果:实验组死亡1例、术后活瓣坏死2例、其余37例病情均转好且无复发情况;对照组死亡4例、出现各项并发症16例、剩余20例病情转好。结论:房水平单向活瓣式补片法可有效改善患者的肺动脉压、体动脉压、动脉血氧分压、二氧化碳分压及吸氧浓度、右室收缩末期内径及6 min步行距离,对老年先天性心脏病伴重度肺动脉高压患者疗效显著。     

Chronic pulmonary sporotrichosis

We report a case of chronic human pulmonary sporotrichosis which was not associated with superficial manifestations involving the skin or lymph nodes. As it is difficult to verify an etiology, it is possible that some undiagnosed pulmonary granulomas could represent pulmonary sporotrichosis of the chronic type. These may have been treated for other diseases, such as a mycobacterial infection as in this case. Since the immunodiffusion test is a simple procedure and is almost always positive in chronic disease, its greater utilization should help in defining this disease more frequently. The skin test, agglutination test and culture are variably useful as documented in the literature.Sporotrichosis is a common mycotic infection which is usually confined to the skin and superficial lymph nodes. In disseminated disease, the lung is very rarely involved. Pulmonary sporotrichosis then represents a second form of primary infection though less common than the lymphocutaneous disease. Scott et al. (18) reported two cases of pulmonary sporotrichosis. Ridgeway et al. (15) at about the same time reviewed the previously reported cases up to 1962 and concluded that 12 of the cases could be accepted as sporotrichosis and added two cases of their own. Subsequently, Siegrist & Ferrington (20) and Trevathan & Phillips (23) each reported a case. Presently, approximately 50 cases have been reported in the United States (1–10, 12, 13, 16). Chronic and acute involvement have been delineated by Ridgeway et al. (15) It is believed that the following case represents one of primary pulmonary sporotrichosis of the chronic type without manifest involvement of other organs.     

Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein

Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading.     

Clinical and quality of life responses to high-dose chemotherapy plus autologous stem cell transplantation in patients with multiple sclerosis: two case reports

During the last several years high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) has been established as a therapeutic option for multiple sclerosis (MS) patients. We report on the long-term effects of HDCT + ASCT in two female patients affected by secondary progressive and relapsing-remitting types of MS, respectively. As a result, disease stabilization was achieved in the first case and disease improvement in the second one. Both patients were off immunosuppressive or immunomodulating therapy throughout the post-transplant period. Notably, HDCT + ASCT resulted in an excellent quality of life (QoL) response in both cases. Our findings demonstrate that HDCT + ASCT could be considered as an effective treatment for MS patients. Moreover, QoL measurement seems to be an effective approach to assessment of treatment outcomes at long-term follow-up of patients with MS.     

Lipidomic characterization and localization of phospholipids in the human lung

Lipids play a central role in lung physiology and pathology; however, a comprehensive lipidomic characterization of human pulmonary cells relevant to disease has not been performed. The cells involved in lung host defense, including alveolar macrophages (AMs), bronchial epithelial cells (BECs), and alveolar type II cells (ATIIs), were isolated from human subjects and lipidomic analysis by LC-MS and LC-MS/MS was performed. Additionally, pieces of lung tissue from the same donors were analyzed by MALDI imaging MS in order to determine lipid localization in the tissue. The unique distribution of phospholipids in ATIIs, BECs, and AMs from human subjects was accomplished by subjecting the large number of identified phospholipid molecular species to univariant statistical analysis. Specific MALDI images were generated based on the univariant statistical analysis data to reveal the location of specific cell types within the human lung slice. While the complex composition and function of the lipidome in various disease states is currently poorly understood, this method could be useful for the characterization of lipid alterations in pulmonary disease and may aid in a better understanding of disease pathogenesis.     

阿奇霉素联合辛伐他汀对慢性阻塞性肺疾病合并肺动脉高压患者肺功能的影响

目的:探讨阿奇霉素联合辛伐他汀治疗慢性阻塞性肺疾病合并肺动脉高压的临床疗效及对患者肺功能的影响。方法:选取2013年6月-2016年3月我院收治的慢性阻塞性肺疾病合并肺动脉高压患者107例,根据治疗方法不同分为对照组(49例)与实验组(58例)。对照组患者采用阿奇霉素治疗,实验组患者在对照组基础上给予辛伐他汀治疗。观察并比较两组患者的临床疗效、不良反应以及肺功能指标的变化情况。结果:实验组患者治疗有效率(87.93%)高于对照组(73.47%),差异具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后1 s用力呼吸容积(FEV1)、用力肺活量(FVC)及FEV1/FVC水平均升高,差异具有统计学意义(P0.05);与对照组比较,实验组患者治疗后1 s用力呼吸容积(FEV1)、用力肺活量(FVC)及FEV1/FVC水平较高,差异具有统计学意义(P0.05)。治疗后,两组患者血清总胆固醇(TC)及三酰甘油(TG)水平均降低,差异具有统计学意义(P0.05);与对照组比较,实验组患者治疗后血清总胆固醇(TC)及三酰甘油(TG)水平较低,差异具有统计学意义(P0.05)。两组患者不良反应发生率比较,差异无统计学意义(P0.05)。结论:阿奇霉素联合辛伐他汀治疗慢性阻塞性肺疾病合并肺动脉高压的临床效果显著,不仅能够改善患者肺功能,降低血脂相关指标水平,并且安全性较高,值得临床推广应用。     

Zygomycosis: A report of eleven cases and a review of the Brazilian literature

Eleven cases of zygomycosis (mucormycosis) observed throughout an eighteen year period (1982-2000) have been reviewed. The most important demographic and clinical data of seven patients were tabulated. The remaining four are related as illustrative cases. Seven patients presented with the pulmonary form of the disease; two patients presented with the pulmonary manifestation associated with sinusitis; and two patients presented with the rhinocerebral form. Predisposing conditions, in decreasing order of frequency, were diabetes mellitus (6), renal transplantation (2), associated with pancreas-kidney transplantation and diabetes (1), bone marrow aplasia (1), and chronic obstructive lung disease treated with corticosteroids (1). The diagnoses were based on the detection of characteristic zygomycetous hyphae in tissue. The causative organim was isolated and identified in only four cases; three were due to Rhizopus arrhizus, and one to Absidia corymbifera. In addition the Brazilian literature on zygomycosis is reviewed.     

Development of selected reaction monitoring‐MS methodology to measure peptide biomarkers in prostate cancer

Prostate cancer is a leading cause of cancer‐related death. The current modality of diagnosis, the measurement of serum PSA, not only suffers from lack of specificity, but does not distinguish clinical cases in which current treatment measures would be most successful, i.e. aggressive, life‐threatening tumors. A multiplexed MS methodology, selected reaction monitoring‐MS/MS coupled with stable isotope dilution (SID), was developed and tested in both cells lines and clinical tissue samples. Standard curves were generated for two peptides representing PSA and one peptide from each of two additional orthogonally validated biomarkers, AMACR and EZH2. The standard curves show high reproducibility, sensitivity, and good linearity. All four peptides were then measured in six clinically relevant cell lines and are in agreement with the biochemical characteristics of each individual cell line. The SID selected reaction monitoring‐MS/MS methodology was then transferred to tissue samples, in which the assay shows potential to differentiate benign disease from localized cancer and localized cancer from aggressive metastatic disease. These results establish the preliminary development of a rational targeted MS platform that strives to bridge the gap between discovery and validation of biomarkers for the detection of prostate cancer.     

沙美特罗联合噻托溴铵对慢性阻塞性肺疾病患者血清MMP-2, MMP-9及IL-8水平的影响

目的:探讨沙美特罗联合噻托溴铵对慢性阻塞性肺疾病患者血清炎症因子水平及肺功能的影响。方法:选择2014年5月-2016年5月我院收治的慢性阻塞性肺病患者83例作为研究对象,根据治疗方法不同,将所选患者分为研究组(45例)和对照组(38例)。研究组患者采用沙美特罗联合噻托溴铵吸入治疗,对照组患者采用沙美特罗治疗。观察并比较两组患者治疗前后血清MMP-2,MMP-9及IL-8水平及肺功能指标的变化情况。结果:治疗前两组患者血清MMP-2,MMP-9及IL-8水平比较,差异无统计学意义(P0.05);治疗后两组患者血清MMP-2,MMP-9及IL-8水平均低于治疗前,且研究组低于对照组,差异均具有统计学意义(P0.05)。与治疗前比较,两组患者治疗后FEV1/FVC,FEV1及MVV均升高,差异具有统计学意义(P0.05);与对照组比较,研究组患者治疗后FEV1/FVC,FEV1及MVV较高,差异具有统计学意义(P0.05)。结论:沙美特罗联合噻托溴铵治疗慢性阻塞性肺疾病的临床效果显著,不仅能够降低患者血清炎症因子水平,还可改善患者肺功能,值得临床推广应用。     

Genetic associations with brain cortical thickness in multiple sclerosis

Multiple sclerosis (MS) is characterized by temporal and spatial dissemination of demyelinating lesions in the central nervous system. Associated neurodegenerative changes contributing to disability have been recognized even at early disease stages. Recent studies show the importance of gray matter damage for the accrual of clinical disability rather than white matter where demyelination is easily visualized by magnetic resonance imaging (MRI). The susceptibility to MS is influenced by genetic risk, but genetic factors associated with the disability are not known. We used MRI data to determine cortical thickness in 557 MS cases and 75 controls and in another cohort of 219 cases. We identified nine areas showing different thickness between cases and controls (regions of interest, ROI) (eight of them were negatively correlated with Kurtzke's expanded disability status scale, EDSS) and conducted genome‐wide association studies (GWAS) in 464 and 211 cases available from the two data sets. No marker exceeded genome‐wide significance in the discovery cohort. We next combined nominal statistical evidence of association with physical evidence of interaction from a curated human protein interaction network, and searched for subnetworks enriched with nominally associated genes and for commonalities between the two data sets. This network‐based pathway analysis of GWAS detected gene sets involved in glutamate signaling, neural development and an adjustment of intracellular calcium concentration. We report here for the first time gene sets associated with cortical thinning of MS. These genes are potentially correlated with disability of MS.     

Alpha1-antitrypsin phenotypes and lung function in a moderately polluted northern Ontario community.

To determine whether persons with intermediate value alpha1-antitrypsin phenotypes living in a polluted environment manifest significant abnormalities in lung function, a study was undertaken of an age-, sex- and smoking-stratified sample of 391 persons from the town of Fort Frances, Ont., which has elevated values of total dustfall, suspended particulates and hydrogen sulfide. Indices of pulmonary function were derived from the maximum expiratory flow and the single breath expiratory flow and the single breath expiratory nitrogen washout curves. The percentage frequency of the M, MS and MZ pheontypes was 91.7, 7.3 and 0.8, respectively. There was no significant difference between the M and MS groups as indicated by the nitrogen washout curve and maximum expiratory flow curve. There was no significant difference between the three MZ subjects and the M group. In both M and MS groups smokers displayed evidence of airflow obstruction when compared with nonsmokers. It would appear that, when compared with M subjects, persons with the MS phenotype living in a moderately polluted area show no changes in indicators of pulmonary function, including tests of early airway disease, that cannot be attributed to their smoking habit.     

Rib lesions in chronic pulmonary tuberculosis

The diagnosis of skeletal tuberculosis in human remains has traditionally been based upon the detection of secondary skeletal lesions which result from hemotogenous dissemination of tubercle bacilli (e.g., Pott's disease). Since such lesions develop in less than 7% of cases of human tuberculosis, the paleodemography and paleoepidemiology of this disease have been difficult to assess from skeletal remains. This study presents a new diagnostic approach to tuberculosis, focusing on the skeletal manifestations of chronic pulmonary disease (which comprises approximately 90% of human-form tuberculosis). Four hundred forty-five skeletal remains from persons dying of tuberculosis during the first half of the 20th century were examined. A total of 70/445 (16%) exhibited skeletal lesions in one or more locations as a response to infection. Of these 70, 39 (56%) were found to display a specific set of lesions restricted to the internal aspect of the ribs. These lesions take one of two forms: (1) diffuse periostitis or (2) localized abscess, and appear to correspond to areas of chronic pulmonary infection. The diffuse type of rib lesion is more commonly observed than the localized type. In our observations (and according to the natural history of tuberculosis) the occurrence of chronic pulmonary tuberculosis is usually mutually exclusive with hematogenous dissemination to secondary bone locations. Thus, the detection of rib lesions in cases of chronic pulmonary disease increases the absolute sample size of skeletal tuberculosis by a factor of two in this study.     

Accuracy of clinical diagnosis in a Canadian teaching hospital.

Two hundred autopsies were investigated to determine the correlation between the clinical and pathological diagnoses in three categories--major underlying disease, cause of death and significant incidental pulmonary findings. There was concurrence in diagnosis of the major underlying disease in 76% of cases, with 12% of disagreements being considered minor and 12% major. In only three cases might different management have affected the outcome had the correct diagnosis of the major underlying disease been made during life. There was concurrence of the diagnosis of the cause of death (which was often different from the underlying disease) in 64% of cases, and in 10% of cases the outcome might have been different had the clinical diagnosis been accurate. The clinical opinion that lung disease was the cause of death was confirmed at autopsy in 54% of cases, and 45% of the pulmonary causes of death as determined at autopsy had been recognized clinically. Major incidental pulmonary findings diagnosed clinically were confirmed in 76% of cases, and major pulmonary findings diagnosed at autopsy had been recognized clinically in 83%. The major sources of these discrepancies were pulmonary embolism and pneumonia. If autopsies are to play a role in patient management, clinicians will have to be made aware of discrepancies between clinical and autopsy diagnosis. The real test of efficacy would be modification of patient management for the good.