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1.  Sarcoidosis in the United States—1968 to 1984 
In order to provide national data on the epidemiology of sarcoidosis in the United States, data from the National Center for Health Statistics were examined for the period 1968 to 1984. Sarcoidosis appeared among the diagnoses of over 20,000 hospital discharges in recent years. It was mentioned on 605 death certificates in 1982, and as underlying cause of death on 339.
In blacks, rates of hospital discharge with the diagnosis were eight times those of whites in 1981, and death rates were 20 times those of whites at ages 15 to 44 years. Women had higher rates than men. Both hospitalization and mortality data may give distorted pictures of this frequently mild or asymptomatic condition. Furthermore, no information was available on the percentage of diagnoses confirmed by biopsy, or on severity of disease in hospitalized patients.
Race-specific hospital discharge rates must be interpreted with caution in this survey. Nevertheless, patterns were generally consistent with studies of prevalence and incidence. Further descriptive and analytic studies of the epidemiology of sarcoidosis are needed to help identify modifiable risk factors and possible causes.
PMCID: PMC2571546  PMID: 3249322
2.  Pulmonary fibrosis is associated with an elevated risk of thromboembolic disease 
The European respiratory journal  2011;39(1):125-132.
Recent epidemiological studies have suggested an increased risk of venous thromboembolism (VTE) in lung fibrosis. Large-scale epidemiological data regarding the risk of VTE in pulmonary fibrosis-associated mortality have not been published.
Using data from the National Center for Health Statistics from 1988–2007, we determined the risk of VTE in decedents with pulmonary fibrosis in the USA.
We analysed 46,450,489 records, of which 218,991 met our criteria for idiopathic pulmonary fibrosis. Among these, 3,815 (1.74%) records also contained a diagnostic code for VTE. The risk of VTE in pulmonary fibrosis decedents was 34% higher than in the background population, and 44% and 54% greater than among decedents with chronic obstructive pulmonary disease and lung cancer, respectively. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone (females: 74.3 versus 77.4 yrs (p<0.0001); males: 72.0 versus 74.4 yrs (p<0.0001)).
Decedents with pulmonary fibrosis had a significantly greater risk of VTE. Those with VTE and pulmonary fibrosis died at a younger age than those with pulmonary fibrosis alone. These data suggest a link between a pro-fibrotic and a pro-coagulant state.
PMCID: PMC3757572  PMID: 21737559
Epidemiology; idiopathic pulmonary fibrosis; mortality; pulmonary fibrosis; venous thromboembolism
3.  The epidemiology of sarcoidosis 
Postgraduate Medical Journal  1969;45(522):241-250.
The nationality, social factors, exposures, morbidity, mortality, and hospital discharge notes have been analysed in a series of patients with histologically proven sarcoidosis, and correlated with clinical and radiological features.
Compared with the expected prevalence according to the Central London population obtained from the 1961 Census, Irish and West Indians attended the Sarcoidosis Clinic twice as frequently as British, whereas African Negroes are under-represented.
Sarcoidosis is slightly commoner in women, particularly those in the childbearing years of life.
Mass miniature radiography rates per 100,000 population reveal prevalence rates of twenty overall, forty-three in those aged 25-34 years, and ten in those aged over 45 years.
Erythema nodosum, other skin lesions, and ocular involvement occurred twice as often in women.
The death-rate of about 1·7/106 population is slightly higher in women and in those living in rural districts.
Hospital discharge rates are about three per 100,000 people at risk each year.
PMCID: PMC2466592  PMID: 5821184
4.  Validation of the japanese version of the sarcoidosis health questionnaire: A cross-sectional study 
Although impaired health-related quality of life (HRQOL) has been reported in patients with sarcoidosis, there is currently no sarcoidosis-specific questionnaire in Japan. The 29-item Sarcoidosis Health Questionnaire (SHQ), originally developed in the United States, is the only sarcoidosis-specific HRQOL questionnaire currently available. The primary aim of this study was to develop and validate a Japanese version of the SHQ.
The SHQ was translated into Japanese following the forward-backward procedure. The reliability and validity of the Japanese version of the SHQ were examined. One hundred twenty-two Japanese patients with biopsy-proven sarcoidosis were evaluated by the SHQ, the Medical Outcomes Study 36-item short form (SF-36), the St. George's Respiratory Questionnaire (SGRQ), chest radiography, an electrocardiogram, laboratory blood tests, pulmonary function tests, an echocardiogram, and assessments of dyspnea and depressive symptoms. The SHQ was found to have acceptable levels of internal consistency (Cronbach's coefficient α values = 0.68 to 0.91). SHQ scores correlated significantly with scores on the SF-36 and SGRQ. The domain or total scores on the SHQ also significantly correlated with serum levels of the soluble interleukin-2 receptor, the percentage of the predicted forced vital capacity, pulmonary arterial systolic pressure, dyspnea, and depressive symptoms. Also, the SHQ scores of patients who had one or two organ systems affected by sarcoidosis were significantly different from those of patients who had three or more organ systems involvement.
The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.
PMCID: PMC3118310  PMID: 21569587
5.  Childhood sarcoidosis: A rare but fascinating disorder 
Childhood sarcoidosis is a rare multisystemic granulomatous disorder of unknown etiology. In the pediatric series reported from the southeastern United States, sarcoidosis had a higher incidence among African Americans. Most reported childhood cases have occurred in patients aged 13–15 years. Macrophages bearing an increased expression of major histocompatibility class (MHC) II molecules most likely initiate the inflammatory response of sarcoidosis by presenting an unidentified antigen to CD4+ Th (helper-inducer) lymphocytes. A persistent, poorly degradable antigen driven cell-mediated immune response leads to a cytokine cascade, to granuloma formation, and eventually to fibrosis. Frequently observed immunologic features include depression of cutaneous delayed-type hypersensitivity and a heightened helper T cell type 1 (Th1) immune response at sites of disease. Circulating immune complexes, along with signs of B cell hyperactivity, may also be found. The clinical presentation can vary greatly depending upon the organs involved and age of the patient. Two distinct forms of sarcoidosis exist in children. Older children usually present with a multisystem disease similar to the adult manifestations, with frequent hilar lymphadenopathy and pulmonary infiltrations. Early-onset sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis in children presenting before four years of age. The diagnosis of sarcoidosis is confirmed by demonstrating a typical noncaseating granuloma on a biopsy specimen. Other granulmatous diseases should be reasonably excluded. The current therapy of choice for sarcoidosis in children with multisystem involvement is oral corticosteroids. Methotrexate given orally in low doses has been effective, safe and steroid sparing in some patients. Alternative immunosuppressive agents, such as azathioprine, cyclophosphamide, chlorambucil, and cyclosporine, have been tried in adult cases of sarcoidosis with questionable efficacy. The high toxicity profile of these agents, including an increased risk of lymphoproliferative disorders and carcinomas, has limited their use to patients with severe disease refractory to other agents. Successful steroid sparing treatment with mycophenolate mofetil was described in an adolescent with renal-limited sarcoidosis complicated by renal failure. Novel treatment strategies for sarcoidosis have been developed including the use of TNF-alpha inhibitors, such as infliximab. The long-term course and prognosis is not well established in childhood sarcoidosis, but it appears to be poorer in early-onset disease.
PMCID: PMC2559831  PMID: 18811966
6.  Quality of Life in Sarcoidosis: Comparing the Impact of Ocular and Non-ocular Involvement of the Disease 
Ophthalmic epidemiology  2010;17(4):217-224.
To compare the differences in vision and health-related quality of life (HRQOL) of individuals with ocular and non-ocular sarcoidosis; and to examine the impact of specific demographic and clinical factors on the noted differences.
A cross-sectional study using non-randomized prospective cohort was conducted at the National Eye Institute (protocol number: 06-EI-0239, NCT00379275) from August 31, 2006 until November 15, 2007. Each participant completed vision and HRQOL questionnaires, the Sarcoidosis Health Questionnaire (SHQ) and the National Eye Institute Visual Function Questionnaire (NEI-VFQ), along with a demographic/environmental exposure survey. Clinical data were collected through an ophthalmic exam as part of the research protocol.
The study enrolled 75 biopsy-proven and 20 clinically presumed sarcoidosis participants which were divided into two cohorts, ocular (N = 60) and non-ocular groups (N = 35). The ocular group had significantly lower (P < 0.01) total NEI-VFQ scores compared to the non-ocular group. Multiple linear regression analysis showed that participants with ocular sarcoidosis who had an annual household income of < $50,000 (P < 0.01) had significantly lower total SHQ scores while participants with ocular sarcoidosis whose visual acuity was 20/100 or worse had significantly lower total NEI-VFQ scores (P = 0.03).
Ocular involvement impacts both overall and vision-related quality of life among sarcoidosis patients. Lower economic status appears to have a significant impact on the quality of life of sarcoidosis patients. Assessment of visual function and general health status provide pertinent information for individuals with sarcoidosis and should be included in their care to assess burden of their disease on their quality of life.
PMCID: PMC2994064  PMID: 20642344
Health-related quality of life; Vision-related quality of life; Ocular sarcoidosis; Pulmonary sarcoidosis; Burden of disease
7.  Optic neuropathy, renal failure and pulmonary sarcoidosis in a 50-year-old man: where is the link? 
BMJ Case Reports  2009;2009:bcr05.2009.1879.
Eye disorders are frequently associated with renal diseases, mostly linked to underlying causes such as hypertension, diabetes or autoimmune diseases. Conversely, advanced uraemic states may also lead to progressive vision impairment. The present report concerns a 50-year-old patient who presented with a bilateral, painless, progressive vision loss, a moderate systemic inflammation and chronic renal failure due to hypertension nephrosclerosis. Steroids were given and haemodialysis was initiated, resulting in vision improvement. At 4 months later when the steroids were stopped, the patient developed dyspnoea, cough, fever and fatigue of unclear origin. A lung biopsy showed non-caseating granuloma consistent with pulmonary sarcoidosis. Re-challenge with steroids rapidly improved the respiratory disease. Ophthalmological examinations performed early and later in the course excluded anterior ischaemic optic neuropathy and ocular manifestations of sarcoidosis, leading to a diagnosis of uraemic optic neuropathy. This rare ophthalmological disorder should be promptly recognised since haemodialysis and steroid therapy are highly effective.
PMCID: PMC3027998  PMID: 21931581
8.  Reproductive and Hormonal Factors in Relation to Incidence of Sarcoidosis in US Black Women 
American Journal of Epidemiology  2012;176(7):635-641.
The authors assessed the relation of hormonal and pregnancy-related factors to the incidence of sarcoidosis in the Black Women's Health Study. On biennial questionnaires, participants (US black women aged 21–69 years at baseline) reported data on diagnoses of sarcoidosis, reproductive history, and medication use. Cox regression models, adjusted for age, education, geographic region, smoking, and body mass index, were used to estimate incidence rate ratios and 95% confidence intervals. During 694,818 person-years of follow-up from 1995 through 2009, 452 incident cases of sarcoidosis were identified. The incidence of sarcoidosis decreased as age at menopause increased (P-trend = 0.03). Both later age at first full-term birth and having a more recent birth were associated with a reduced incidence of sarcoidosis. In models that included both factors, the incidence rate ratios were 0.60 (95% confidence interval: 0.37, 0.97) for age at first birth ≥30 years versus <20 years (P-trend = 0.05) and 0.73 (95% confidence interval: 0.43, 1.24) for <5 years since last birth versus ≥15 years (P-trend = 0.15). No significant associations were observed with age at menarche, parity, lactation, oral contraceptive use, or female hormone use. These results suggest that later full-term pregnancy and longer exposure to endogenous female hormones may be related to a reduced risk of sarcoidosis.
PMCID: PMC3530373  PMID: 22967742
African Americans; hormones; prospective studies; reproduction; risk factors; sarcoidosis; women; women's health
9.  How Can the National Burden of Parkinson’s Disease Comorbidity and Mortality Be Estimated for the Japanese Population? 
Journal of Epidemiology  2011;21(3):211-216.
Good medical care results in long survival for patients with Parkinson’s disease (PD). However, little is known about the burden of PD comorbidity and mortality in Japan. This is the first study to examine comorbid diseases of PD decedents and extrapolate PD death rates from multiple-cause coding mortality data for the total population of Japan.
Data for 4589 certified deaths due to PD as the underlying cause of death (ICD-10 code: G20) were obtained from the 2008 Japanese vital statistics. Of those, comorbidities listed in the death certificates of 477 randomly selected decedents were analyzed. All diseases or conditions mentioned on death certificates were counted and ranked in descending order of frequency. The death rates (per 100 000 population) from PD were calculated using Japanese National Vital Statistics. The estimated rate of deaths with PD was extrapolated using US death data from a multiple-cause coding system, as no such system is available in Japan, with adjustment for the difference in disease structure between countries.
Average age at death was 80.9 years. The top 5 comorbid diseases ranked as contributory causes of death were cerebrovascular diseases (4.0%), dementia (3.8%), diabetes mellitus (3.6%), malignant neoplasm (2.5%), and heart diseases (2.3%). Overall, the death rates from and with PD were 3.6 and 5.8, respectively.
Analysis restricted to data from the underlying-cause coding system underestimated the national burden of PD comorbidity and mortality. Use of death certificates and multiple-cause mortality data complement the existing system.
PMCID: PMC3899411  PMID: 21422700
Parkinson’s disease; comorbidity; mortality; causes of death; Japan
10.  Undiagnosed myocardial sarcoidosis presenting as life threatening cardiac dysrhythmia 
BMJ Case Reports  2011;2011:bcr0620103092.
Sarcoidosis is a systemic disorder of unknown aetiology characterised by its pathological hallmark of non-caseating granuloma. Definitive diagnosis requires compatible clinical and imaging features as well as pathogenic identification of non-caseating granulomas in at least one organ. The disease has a wide variety of clinical and radiological manifestations but is associated with low mortality. However, cardiac involvement which is clinically only identified in 5% significantly worsens prognosis due to complications such as congestive heart failure, ventricular tachyarrhythmia, pulmonary hypertension or conduction disturbance leading to sudden death. Cardiac involvement is implicated in 77–85% of deaths directly related to sarcoidosis. Autopsy series in sarcoidosis patients show cardiac involvement with sarcoidosis in up to 79% cases. This case details the clinical course of a 56-year-old female who had experienced refractory cardiac dysrhythmias for many years in the context of also having biopsy proven pulmonary sarcoidosis. She had failed multiple antiarrhythmics as well as pacemaker and implantable cardioverter defibrillator placement. It was not until she presented as a potentially fatal ventricular tachycardia that the possibility of cardiac involvement from her sarcoidosis was entertained as the aetiology of her cardiac problems. Confirmation of myocardial sarcoidosis with PET CT imaging and subsequent treatment with prednisone resulted in her clinical improvement.
PMCID: PMC3079453  PMID: 22701002
11.  Discrepant comorbidity between minority and white suicides: a national multiple cause-of-death analysis 
BMC Psychiatry  2009;9:10.
Clinician training deficits and a low and declining autopsy rate adversely impact the quality of death certificates in the United States. Self-report and records data for the general population indicate that proximate mental and physical health of minority suicides was at least as poor as that of white suicides.
This cross-sectional mortality study uses data from Multiple Cause-of-Death (MCOD) public use files for 1999–2003 to describe and evaluate comorbidity among black, Hispanic, and white suicides. Unintentional injury decedents are the referent for multivariate analyses.
One or more mentions of comorbid psychopathology are documented on the death certificates of 8% of white male suicides compared to 4% and 3% of black and Hispanic counterparts, respectively. Corresponding female figures are 10%, 8%, and 6%. Racial-ethnic discrepancies in the prevalence of comorbid physical disease are more attenuated. Cross-validation with National Violent Death Reporting System data reveals high relative underenumeration of comorbid depression/mood disorders and high relative overenumeration of schizophrenia on the death certificates of both minorities. In all three racial-ethnic groups, suicide is positively associated with depression/mood disorders [whites: adjusted odds ratio (AOR) = 31.9, 95% CI = 29.80–34.13; blacks: AOR = 60.9, 95% CI = 42.80–86.63; Hispanics: AOR = 34.7, 95% CI = 23.36–51.62] and schizophrenia [whites: AOR = 2.4, 95% CI = 2.07–2.86; blacks: AOR = 4.2, 95% CI = 2.73–6.37; Hispanics: AOR = 4.1, 95% CI = 2.01–8.22]. Suicide is positively associated with cancer in whites [AOR = 1.8, 95% CI = 1.69–1.93] and blacks [AOR = 1.8, 95% CI = 1.36–2.48], but not with HIV or alcohol and other substance use disorders in any group under review.
The multivariate analyses indicate high consistency in predicting suicide-associated comorbidities across racial-ethnic groups using MCOD data. However, low prevalence of documented comorbid psychopathology in suicides, and concomitant racial-ethnic discrepancies underscore the need for training in death certification, and routinization and standardization of timely psychological autopsies in all cases of suicide, suspected suicide, and other traumatic deaths of equivocal cause.
PMCID: PMC2667503  PMID: 19296840
12.  Uterine Sarcoidosis: A Rare Extrapulmonary Site of Sarcoidosis 
Case Reports in Rheumatology  2013;2013:706738.
Sarcoidosis is a multisystem disease which is most commonly manifested in the pulmonary system. However, extrapulmonary manifestations have also been frequently reported. Isolated occurrence of sarcoidosis in the genital system is rare and poses a diagnostic and therapeutic dilemma. Uterine sarcoidosis can present with cervical erosions, endometrial polypoid lesions, and recurrent serometra. In majority of cases, it is diagnosed by endometrial curettage, but it has also been detected by examination of hysterectomy, polypectomy, and autopsy specimens. Nonnecrotizing granulomas are the characteristic pathologic finding of sarcoidosis. However, many infectious and noninfectious etiologies including certain neoplasms can produce similar granulomatous reactions in the female genital tract. These conditions affect the female genital tract more commonly than sarcoidosis, and therefore it is important to rule out these conditions first before making a diagnosis of sarcoidosis. Treatment of sarcoidosis is different from treating these other conditions and the most commonly used systemic or local corticosteroids can be hazardous if the underlying cause is infection. In this case report, the clinical presentation, histopathology, clinical course, and treatment of a patient with isolated uterine sarcoidosis are described, and a brief literature review of sarcoidosis of the female genital tract is provided.
PMCID: PMC3671678  PMID: 23762732
13.  Detection of Myocardial Damage in Patients with Sarcoidosis 
Circulation  2009;120(20):1969-1977.
In patients with sarcoidosis, sudden death is a leading cause of mortality, which may represent unrecognized cardiac involvement. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) can detect minute amounts of myocardial damage. We sought to compare DE-CMR with standard clinical evaluation for the identification of cardiac involvement.
Methods and Results
Eighty-one consecutive patients with biopsy proven extra-cardiac sarcoidosis were prospectively recruited for a parallel and masked comparison of cardiac involvement between: (1) DE-CMR, and (2) standard clinical evaluation using consensus criteria (modified Japanese Ministry of Health [JMH] guidelines). Standard evaluation included 12-lead electrocardiography and at least one dedicated non-CMR cardiac study (echocardiography, radionuclide scintigraphy, or cardiac catheterization). Patients were followed 21±8 months for major adverse events (death, defibrillator shock, or pacemaker requirement).
Patients were predominantly middle-aged (46±11 years), female (62%), African-American (73%), had chronic sarcoidosis (median, 7 years), and preserved LVEF (median, 56%). DE-CMR identified cardiac involvement in 21 patients (26%) and JMH criteria in 10 (12%, 8 overlapping), a more than two-fold higher rate for DE-CMR (p=0.005). All patients with myocardial damage on DE-CMR had coronary disease excluded by x-ray angiography. Pathology evaluation in 15 patients (19%) identified 4 with cardiac sarcoidosis; all 4 were positive by DE-CMR whereas 2 were JMH positive. On follow-up, 8 had adverse events including 5 cardiac deaths. Patients with myocardial damage on DE-CMR had a 9-fold higher rate of adverse events and a 11.5-fold higher rate of cardiac death than patients without damage.
In patients with sarcoidosis, DE-CMR is more than twice as sensitive for cardiac involvement than current consensus criteria. Myocardial damage detected by DE-CMR appears to be associated with future adverse events including cardiac death, but events were few and this needs confirmation in a larger cohort.
PMCID: PMC2778859  PMID: 19884472
cardiovascular magnetic resonance; delayed-enhancement imaging; cardiac sarcoidosis
14.  Use of Insurance Claims Data to Determine Prevalence and Confirm a Cluster of Sarcoidosis Cases in Vermont 
Public Health Reports  2009;124(3):442-446.
In 2006, the Vermont Department of Health was asked to respond to a potential cluster of sarcoidosis cases related to a Vermont office building. Sarcoidosis prevalence has not been formally described for the United States. A range of <1–40/100,000 is commonly reported; however, we have not identified primary sources supporting this conclusion. Because of the wide prevalence range and lack of a local estimate, confirming existence of a cluster was difficult.
We ascertained the prevalence of sarcoidosis cases in Vermont by using insurance claims data to determine whether or not a cluster of sarcoidosis cases was related to the office building. We calculated county and state annual prevalence proportions for sarcoidosis for 2004 and 2005 and annual building prevalences for 1992–2006.
The pooled sarcoidosis case prevalence for Vermont was 66.1/100,000. The pooled building annual prevalence (1,128/100,000) was statistically different from the county in which the building is located (odds ratio = 15.5, 95% confidence interval 3.0, 50.3).
We reported the first statewide sarcoidosis prevalence in the United States. This prevalence exceeded previous limited and unsubstantiated U.S. reports. Even with Vermont's elevated sarcoidosis prevalence, the presence of a cluster in this building was apparent.
PMCID: PMC2663881  PMID: 19445421
15.  Differences in Mortality Associated with Dementia in US Blacks and Whites 
Geographic variation in racial differences in occurrence of dementia within the US has received little attention despite its importance for generation of new etiologic hypotheses and health disparities research. We test the hypothesis that the geographic pattern of mortality with dementia coded on the death certificate varies by race and racial differences vary by geography in the US.
Analysis of the US multiple cause of death files for 1999–2004.
United States of America.
Decedents with dementia coded as underlying or contributing cause of death on the death certificate.
Age-adjusted death rates for US Census geographic divisions for blacks and whites aged 65 years and over.
In 1999–2004 the US age-adjusted annual death rate per 100,000 for dementia was 628 in blacks and 647 in whites. The difference between rates in blacks and whites ranged from −130 deaths per 100,000 (−36%) in the Middle Atlantic to +55 (+8%) in the South Atlantic division. Blacks had higher rates in three divisions and whites in five. In the Middle Atlantic and US, blacks were relatively more likely to receive a diagnosis of unspecified dementia/senility (66%) than Alzheimer’s disease (30%) compared to whites (58% versus 41%).
Although overall rates were similar, geographic variation in racial differences in rates of death with dementia occurred among US regions. Further research is needed to assess geographic and racial variation in artifacts of certification versus biological variation as possible causes of variation to enhance utility of mortality data for disease monitoring and health disparities research.
PMCID: PMC3228365  PMID: 22091495
Blacks; Aging; Dementia; Mortality; Geography; Alzheimer's Disease
16.  The clinical and immunologic features of pulmonary fibrosis in sarcoidosis 
Sarcoidosis is a multisystem, granulomatous disease that most often affects the lungs. The clinical course is highly variable; many patients undergo spontaneous remission, but up to a third of patients progresses to a chronic disease course. The development of pulmonary fibrosis (PF) in a subset of patients with chronic disease has a negative impact on morbidity and mortality. While sarcoidosis-associated PF can be progressive, it is often referred to as “burnt out” disease, a designation reflecting inactive granulomatous inflammation. The immune mechanisms of sarcoidosis-associated PF are not well understood. It is not clear if fibrotic processes are active from the onset of sarcoidosis in predisposed individuals, or whether a profibrotic state develops as a response to ongoing inflammation. Transforming growth factor β (TGF-β) is an important profibrotic cytokine, and in sarcoidosis, distinct genotypes of TGF-β have been identified in those with PF. The overall cytokine profile in sarcoidosis-associated PF has not been well characterized, although a transition from a T helper 1 to a T helper 2 signature has been proposed. Macrophages have important regulatory interactions with fibroblasts, and the role of alveolar macrophages in sarcoidosis-associated PF is a compelling target for further study. Elucidating the natural history of sarcoidosis-associated PF will inform our understanding of the fundamental derangements, and will enhance prognostication and the development of therapeutic strategies.
PMCID: PMC3910531  PMID: 22683422
17.  Chronic Liver Disease Mortality Among Male Prison Inmates in Texas, 1989–2003 
Alcohol abuse and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major etiologic factors for chronic liver disease/cirrhosis (CLD) in the United States. These CLD risk factors are highly prevalent in US adult incarcerated populations, but CLD-related mortality data from these populations are lacking. The primary objective of this study was to assess CLD-related mortality over time and across categories of race–ethnicity from 1989 through 2003 among male inmates in the Texas state prison system. The secondary objective was to examine patterns of recorded underlying, intervening, and contributing causes of death for CLD-related deaths.
Prisoner decedent data were linked with Texas Vital Statistics multiple-cause-of-death data. Deaths were considered CLD-related if CLD or common sequelae were recorded as the underlying, intervening, or contributing causes of death. CLD-related crude annual death rates, 5-year average annual death rates, and average annual percentage changes were estimated.
Among male Texas prisoners from 1989 to 2003, CLD-related deaths accounted for 16% of deaths (688/4,316). CLD-related crude annual death rates were high and increased over the study period by an average of 4.5% annually, with similar rate increases across categories of race–ethnicity. CLD-related average annual death rates were higher among Hispanic prisoners than among black prisoners in each 5-year period, and were higher than those for white prisoners in the 1994–1998 and 1999–2003 periods. HBV or HCV was identified as a causal factor in more than a third (34%) of CLD-related deaths.
From 1989 to 2003, CLD-related death rates among male Texas prisoners were high and increased over time, particularly among Hispanics. Targeted prevention, screening, and treatment of CLD risk factors, especially HCV, and early detection and treatment of CLD should be considered as priorities of the US prison healthcare systems.
PMCID: PMC2856927  PMID: 19491854
18.  Skin changes in sarcoidosis 
Postgraduate Medical Journal  1970;46(538):507-509.
The skin changes which occur in sarcoidosis are erythema nodosum and specific granulomata.
The incidence of erythema nodosum and its frequency in England and Scandinavia is contrasted with its comparative rarity among Negro patients in the United States. The various types of granulomata are described and classified. In contrast with erythema nodosum, granulomata are more common in Negro than in Caucasian patients.
PMCID: PMC2467257  PMID: 5481102
19.  The six-minute walk test in patients with pulmonary sarcoidosis 
Annals of Thoracic Medicine  2009;4(2):60-64.
The 6-min walk test (6MWT) is a useful tool to assess prognosis and functional impairment in various pulmonary diseases.
To evaluate functional capacity during various stages of pulmonary sarcoidosis and develop a scoring system clinical radiological physiological score (CRP) that can potentially be used to assess the functional status among patients with sarcoidosis.
We performed a retrospective study on 26 patients diagnosed with pulmonary sarcoidosis from 2001 to 2007. All patients completed the 6MWT. The parameters assessed during the test included spirometry, arterial blood gas, 6-min walk distance (6MWD), Borg dyspnea score, and initial and end oxygen saturation.
Females covered a significantly shorter distance than males (343 m (223–389) vs. 416.5 m (352–500); P < 0.0001). In addition, females had a significantly lower SpO2 at the end of the 6MWT than males (90.5 (61–99) vs. 96 (75–98); P < 0.03). The 6MWD was inversely correlated with the final Borg score (ρ = −0.603, P = 0.004) and the CRP score (ρ = −0.364, P = 0.047) and positively correlated with forced expiratory volume in 1 s (FEV1) % (ρ = 0.524, P = 0.006) and forced vital capacity (FVC) % (ρ = 0.407, P = 0.039).
Female gender, FEV1%, final Borg score, FVC%, CRP score, and SpO2 at the end of the 6MWT are associated with reduced 6MWD. It appears that Saudi patients diagnosed with sarcoidosis have a markedly reduced walking distance compared with other races. The effect of race and ethnicity and the utility of the CRP score as a potential marker to assess functional status require further exploration.
PMCID: PMC2700479  PMID: 19561926
Functional status; pulmonary sarcoidosis; 6-min walk test
20.  Comparing strategies for United States veterans' mortality ascertainment 
We aimed to determine optimal strategies for complete mortality ascertainment comparing death certificates and United States (US) Veterans Administration (VA) records.
We constructed a cohort of California veterans who died in fiscal year (FY) 2000 and used VA services the year before death. We determined decedent status using California death certificates linked to VA utilization data and the VA Beneficiary Identification and Records Locator System (BIRLS) death file. We compared the characteristics of decedents who would not have been identified by either single source (e.g., VA BIRLS alone or California death certificates alone) with the rest of the cohort.
A total of 8,813 veteran decedents were identified from both VA decedent files and death certificates. Of all decedents, 5,698 / 8,813 (65%) veterans were identified in both source files, but 2,426 / 8,813 (28%) decedents were not identified in VA BIRLS, and 689 / 8,813 (8%) were not identified in death certificates. Compared to the rest of the cohort, decedents whose mortality status was ascertained through either single source differed by race / ethnicity, marital status, and California residence. Clinically, veterans identified from either single source had less comorbidity and were less likely to have been users of VA inpatient or long term care, but equally or more likely to have been users of VA outpatient services.
As single sources, VA decedent files and death certificates each provided an incomplete record, and death ascertainment was improved by using both source files. Potential bias may vary depending on analytic interest.
PMCID: PMC554976  PMID: 15730553
21.  Risk of malignant neoplasms in patients with pulmonary sarcoidosis 
Thorax  1997;52(10):892-894.
BACKGROUND: For over 20 years the association between sarcoidosis and malignancy, particularly lymphoma and lung cancer, has been disputed with misclassification being the major concern. The aim of the present study was to analyse the incidence of malignancies in a cohort of patients with sarcoidosis by linkage to a nationwide population based cancer register. METHODS: The cohort comprised 254 patients followed for a median of 25 years until death, emigration, or 31 December 1992, whichever came first. The expected number of cancer cases was calculated using the annual age and sex specific cancer rates from the Danish Cancer Registry. RESULTS: Thirty six cancers were registered, three of which were misclassified as sarcoidosis, leaving 33 cancers compared with 23 expected (standardised incidence ratio (SIR) = 1.4; 95% CI 0.99 to 2.0). Five lung cancers were observed compared with 2.5 expected, yielding an SIR of 2.0 (95% CI 0.7 to 4.7). There was no incidence of lymphoma and only one case of leukaemia. There was a significant excess number of pharyngeal cancers based on two cases (SIR = 15.4; 95% CI 1.7 to 56). CONCLUSIONS: This study does not support the theory of an association between sarcoidosis and malignancy, and the main reason other studies have shown such an association is most likely to have been due to selection bias and misclassification. 

PMCID: PMC1758430  PMID: 9404377
22.  Ductopenia related liver sarcoidosis 
World Journal of Hepatology  2011;3(6):170-174.
Sarcoidosis is a systemic granulomatous disease which may involve many organs. In approximately 95% of patients there is liver involvement, with noncaseating hepatic granulomas occurring in 21 to 99% of patients with sarcoidosis. Liver involvement is usually asymptomatic and limited to mild to moderate abnormalities in liver biochemistry. The occurrence of jaundice in sarcoidosis is rare; extensive imaging procedures and the examination of liver biopsies permit a precise diagnostic. Ductopenia associated with sarcoidosis has been reported in less than 20 cases and can lead to biliary cirrhosis and liver- related death. We report here on a case of ductopenia-related sarcoidosis in which primary biliary cirrhosis and extrahepatic cholestasis have been carefully excluded. The patient follow up was 8 years. Although ursodesoxycholic acid appears to improve liver biochemistry it does not preclude the rapid occurrence of extensive fibrosis. A review of the literature of reported cases of ductopenia related to sarcoidosis is provided.
PMCID: PMC3326726  PMID: 22509431
Sarcoidosis; Cholestasis ductopenia; Ursodeoxycholic acid
23.  Cardiac Sarcoidosis with a Rare Initial Manifestation 
Texas Heart Institute Journal  2011;38(1):74-76.
Sarcoidosis is a multisystem disease of unknown cause. Life-threatening complications or sudden death can occur when the disease involves the heart. Because cardiac sarcoidosis has diverse clinical presentations, its diagnosis can be a major challenge for clinicians. It is very rare for the initial manifestation of cardiac sarcoidosis to be sustained ventricular tachycardia, especially in a patient with no prior symptoms or history of the disease.
Herein, we discuss the case of a 41-year-old black man who presented with nausea, vomiting, and palpitations on the day after he had consumed alcoholic beverages heavily. Electrocardiographic examination revealed sustained monomorphic ventricular tachycardia. An automatic implantable cardioverter-defibrillator corrected the patient's abnormal heart rhythm, and therapy with steroids and β-blockers resolved his symptoms. We describe the process that led to the diagnosis of cardiac sarcoidosis in this patient.
PMCID: PMC3060742  PMID: 21423476
Cardiomyopathies/diagnosis/physiopathology; defibrillators, implantable; diagnosis, differential; echocardiography; magnetic resonance imaging/methods; sarcoidosis/diagnosis/drug therapy/physiopathology/radiography; tachycardia, ventricular/etiology/physiopathology/therapy; treatment outcome
24.  Cardiac Sarcoidosis: Two Cases with Ventricular Tachycardia and Review of Cardiac Involvement in Sarcoid 
Texas Heart Institute Journal  1985;12(4):377-383.
Patients with significant cardiac sarcoidosis are at increased risk of sudden death from ventricular dysrhythmias or conduction disturbances. We report two patients whose initial manifestation of cardiac sarcoidosis was nonsustained ventricular tachycardia unresponsive to standard antiarrhythmic measures. Endomyocardial biopsy aided the diagnosis in each patient. This technique is helpful in establishing the diagnosis of cardiac sarcoidosis, which causes life-threatening ventricular dysrhythmias.
PMCID: PMC341894  PMID: 15226999
25.  Release of prostaglandin E2 and leukotriene B4 by alveolar macrophages from patients with sarcoidosis 
Thorax  1997;52(1):76-83.
BACKGROUND: Mediators released by alveolar macrophages, as well as by T cells, play an important part in modulating local immune processes in sarcoidosis. Among alveolar macrophage secretory products, arachidonic acid metabolites are known to regulate inflammatory and immune reactions. It has been suggested that cyclo-oxygenase and lipoxygenase pathway metabolites of arachidonic acid modulate the evolution of the granulomatous inflammatory response in the lung differently. METHODS: Alveolar macrophages recovered from the bronchoalveolar lavage (BAL) fluid of 32 patients with sarcoidosis in different states of disease activity and 10 normal subjects were evaluated for their ability to release prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). Alveolar macrophages were cultured in the presence or absence of opsonised zymosan (500 micrograms/ml), and PGE2 and LTB4 levels in the culture supernatants were determined by enzyme immunoassay (EIA). RESULTS: Stimulated alveolar macrophages from patients with active sarcoidosis released higher LTB4 levels than those from normal subjects, but no differences in PGE2 release were observed between the two groups. The time course of LTB4 release by activated alveolar macrophages showed that normal cells produced similar levels of the hydroxyacid during the early and late times of culture while LTB4 release by activated cells from patients with sarcoidosis increased markedly after 60 minutes of culture, remaining elevated until 24 hours. Indomethacin (3 x 10(6) M) caused the expected inhibition of PGE2 formation without affecting LTB4 release. CONCLUSIONS: These results suggest that alveolar macrophages from the BAL fluid of patients with active sarcoidosis are primed to release LTB4, which may contribute to the locally heightened immune response. 

PMCID: PMC1758401  PMID: 9039241

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