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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.  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
3.  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.
doi:10.1186/1546-0096-6-16
PMCID: PMC2559831  PMID: 18811966
4.  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.
doi:10.1136/bcr.05.2009.1879
PMCID: PMC3027998  PMID: 21931581
5.  Differences in Mortality Associated with Dementia in US Blacks and Whites 
Background/Objectives
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.
Design
Analysis of the US multiple cause of death files for 1999–2004.
Setting
United States of America.
Participants
Decedents with dementia coded as underlying or contributing cause of death on the death certificate.
Measurements
Age-adjusted death rates for US Census geographic divisions for blacks and whites aged 65 years and over.
Results
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%).
Conclusion
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.
doi:10.1111/j.1532-5415.2011.03598.x
PMCID: PMC3228365  PMID: 22091495
Blacks; Aging; Dementia; Mortality; Geography; Alzheimer's Disease
6.  Discrepant comorbidity between minority and white suicides: a national multiple cause-of-death analysis 
BMC Psychiatry  2009;9:10.
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1471-244X-9-10
PMCID: PMC2667503  PMID: 19296840
7.  Chronic Liver Disease Mortality Among Male Prison Inmates in Texas, 1989–2003 
OBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
doi:10.1038/ajg.2009.106
PMCID: PMC2856927  PMID: 19491854
8.  Comparing strategies for United States veterans' mortality ascertainment 
Background
We aimed to determine optimal strategies for complete mortality ascertainment comparing death certificates and United States (US) Veterans Administration (VA) records.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1478-7954-3-2
PMCID: PMC554976  PMID: 15730553
9.  Detection of Myocardial Damage in Patients with Sarcoidosis 
Circulation  2009;120(20):1969-1977.
Background
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.
Conclusion
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.
doi:10.1161/CIRCULATIONAHA.109.851352
PMCID: PMC2778859  PMID: 19884472
cardiovascular magnetic resonance; delayed-enhancement imaging; cardiac sarcoidosis
10.  A Storage and Retrieval System for NCHS Detailed Mortality Data 
An interactive, on-line computer system to store and retrieve detailed mortality data from the National Center for Health Statistics (NCHS) has been developed for epidemiologic studies. The system contains information on every death certificate sent to NCHS for 1965 to 1976 (except for 1972). The system contains the following information on each death certificate: year of death; county of residence at time of death; cause of death by 4-digit ICDA codes; and the age, sex, and race of the decedent. Population data for 1965-76 are also in the system and used in the calculation of rates.
The user specifies year or years of interest and the causes of death by 4-digit ICDA codes. Data may be obtained for counties, states, census divisions, or the entire U.S. Output is provided for age-sex-race groups and includes the number dead or age-specific and age-adjusted mortality rates.
PMCID: PMC2581346
11.  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.
Images
PMCID: PMC2467257  PMID: 5481102
12.  Validation of the japanese version of the sarcoidosis health questionnaire: A cross-sectional study 
Background
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.
Findings
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.
Conclusions
The Japanese version of the SHQ can be used to assess the HRQOL of patients with sarcoidosis.
doi:10.1186/1477-7525-9-34
PMCID: PMC3118310  PMID: 21569587
13.  The six-minute walk test in patients with pulmonary sarcoidosis 
Annals of Thoracic Medicine  2009;4(2):60-64.
BACKGROUND:
The 6-min walk test (6MWT) is a useful tool to assess prognosis and functional impairment in various pulmonary diseases.
AIMS:
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.
MATERIALS AND METHODS:
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.
RESULTS:
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).
CONCLUSIONS:
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.
doi:10.4103/1817-1737.49414
PMCID: PMC2700479  PMID: 19561926
Functional status; pulmonary sarcoidosis; 6-min walk test
14.  Quality of Life in Sarcoidosis: Comparing the Impact of Ocular and Non-ocular Involvement of the Disease 
Ophthalmic epidemiology  2010;17(4):217-224.
Purpose
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.
Methods
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.
Results
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).
Conclusions
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.
doi:10.3109/09286586.2010.483754
PMCID: PMC2994064  PMID: 20642344
Health-related quality of life; Vision-related quality of life; Ocular sarcoidosis; Pulmonary sarcoidosis; Burden of disease
15.  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
16.  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
17.  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.
Images
PMCID: PMC341894  PMID: 15226999
18.  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
19.  Sarcoidosis 
Sarcoidosis is a multisystemic disorder of unknown cause characterized by the formation of immune granulomas in involved organs. It is an ubiquitous disease with incidence (varying according to age, sex, race and geographic origin) estimated at around 16.5/100,000 in men and 19/100,000 in women. The lung and the lymphatic system are predominantly affected but virtually every organ may be involved. Other severe manifestations result from cardiac, neurological, ocular, kidney or laryngeal localizations. In most cases, sarcoidosis is revealed by persistent dry cough, eye or skin manifestations, peripheral lymph nodes, fatigue, weight loss, fever or night sweats, and erythema nodosum. Abnormal metabolism of vitamin D3 within granulomatous lesions and hypercalcemia are possible. Chest radiography is abnormal in about 90% of cases and shows lymphadenopathy and/or pulmonary infiltrates (without or with fibrosis), defining sarcoidosis stages from I to IV. The etiology remains unknown but the prevailing hypothesis is that various unidentified, likely poorly degradable antigens of either infectious or environmental origin could trigger an exaggerated immune reaction in genetically susceptible hosts. Diagnosis relies on compatible clinical and radiographic manifestations, evidence of non-caseating granulomas obtained by biopsy through tracheobronchial endoscopy or at other sites, and exclusion of all other granulomatous diseases. The evolution and severity of sarcoidosis are highly variable. Mortality is estimated at between 0.5–5%. In most benign cases (spontaneous resolution within 24–36 months), no treatment is required but a regular follow-up until recovery is necessary. In more serious cases, a medical treatment has to be prescribed either initially or at some point during follow-up according to clinical manifestations and their evolution. Systemic corticosteroids are the mainstay of treatment of sarcoidosis. The minimal duration of treatment is 12 months. Some patients experience repeated relapses and may require long-term low-dose corticosteroid therapy during years. Other treatments (immunosuppressive drugs and aminoquinolins) may be useful in case of unsatisfactory response to corticosteroids, poor tolerance and as sparing agents when high doses of corticosteroids are needed for a long time. In some strictly selected cases refractory to standard therapy, specific antiTNF-α agents may offer precious improvement. Some patients benefit from topical corticosteroids.
doi:10.1186/1750-1172-2-46
PMCID: PMC2169207  PMID: 18021432
20.  Case Review of Sarcoidosis Resembling Sjogren's Syndrome 
We would like to report a case of a 29-year-old male patient who presented with multiple lymphadenopathy and vague symptoms of low grade fever, cough, weight loss, rashes, vomiting, dry eyes and dry mouth. Physical examination revealed submandibular lymphadenopathy, vasculitic rashes over both lower limbs, and parotid gland enlargement. Blood investigations showed mild anemia with leukocytosis, predominantly eosinophilia and high erythrocyte sedimentation rate and C-reactive protein. Computed tomography of the neck, thorax and abdomen showed bilateral submandibular, submental adenopathy, mediastinal and para-aortic lymphadenopathy with generalized reticulonodular densities in both lower lobes. There were hepatomegaly and bilateral enlarged kidneys with renal cyst. Histopathological examination from the cervical lymph node later revealed non-caseating granuloma, consistent of sarcoidosis. Patient responded well to prednisolone 50 mg daily with subsequent reduction in the size of cervical lymphadenopathy and parotid swelling.
Keywords
Lymphadenopathy; Granuloma; Sjogren; Sarcoidosis
doi:10.4021/jocmr482w
PMCID: PMC3194035  PMID: 22043264
21.  Asymptomatic stage I sarcoidosis complicated by pulmonary tuberculosis: a case report 
Introduction
Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Depressed cellular immunity predisposes patients to infections with certain intracellular organisms, mostly fungi, Mycobacterium tuberculosis and Nocardia species. As these infections are mainly insidious and difficult to differentiate from the underlying disease, a possible misdiagnosis may lead to fatal complications for the patient.
Case presentation
We present a case of a 67-year-old woman with undiagnosed asymptomatic stage I sarcoidosis for at least 8 years before her admission and a 1-month history of fever, exertional dyspnea and dry cough, in whom pulmonary tuberculosis was documented.
Conclusion
This case highlights the need for great vigilance among physicians in order to rule out any possible infection before establishing the diagnosis of sarcoidosis.
doi:10.1186/1752-1947-2-226
PMCID: PMC2474644  PMID: 18605996
22.  The Incidence of Malignant Tumours in Patients with Respiratory Sarcoidosis 
British Journal of Cancer  1974;29(3):247-251.
During the period 1962-71 a total of 2544 patients with respiratory sarcoidosis were reported to the Danish Institute of Clinical Epidemiology. Among them 48 patients developed a malignant tumour, the follow-up period ending on 31 December 1971. Only 33·8 cases of cancer were expected if sarcoidosis patients had had the same rates as the general population; the difference between the expected and observed number is statistically significant (0·02 > P > 0·01). Malignant lymphomata occurred 11 times and lung cancer 3 times more frequently than expected. For all other forms of cancer taken together, there was no significant difference between the expected and the observed number of cases.
The increased cancer incidence may result from immunological deficiencies in patients with sarcoidosis.
PMCID: PMC2009094  PMID: 4830144
23.  Temporal Trends in Recording of Diabetes on Death Certificates 
Diabetes Care  2011;34(7):1529-1533.
OBJECTIVE
To determine the frequency that diabetes is reported on death certificates of decedents with known diabetes and describe trends in reporting over 8 years.
RESEARCH DESIGN AND METHODS
Data were obtained from 11,927 participants with diabetes who were enrolled in Translating Research into Action for Diabetes, a multicenter prospective observational study of diabetes care in managed care. Data on decedents (N = 2,261) were obtained from the National Death Index from 1 January 2000 through 31 December 2007. The primary dependent variables were the presence of the ICD-10 codes for diabetes listed anywhere on the death certificate or as the underlying cause of death.
RESULTS
Diabetes was recorded on 41% of death certificates and as the underlying cause of death for 13% of decedents with diabetes. Diabetes was significantly more likely to be reported on the death certificate of decedents dying of cardiovascular disease than all other causes. There was a statistically significant trend of increased reporting of diabetes as the underlying cause of death over time (P < 0.001), which persisted after controlling for duration of diabetes at death. The increase in reporting of diabetes as the underlying cause of death was associated with a decrease in the reporting of cardiovascular disease as the underlying cause of death (P < 0.001).
CONCLUSIONS
Death certificates continue to underestimate the prevalence of diabetes among decedents. The increase in reporting of diabetes as the underlying cause of death over the past 8 years will likely impact estimates of the burden of diabetes in the U.S.
doi:10.2337/dc10-2312
PMCID: PMC3120163  PMID: 21709292
24.  Safer storage of firearms at home and risk of suicide: a study of protective factors in a nationally representative sample 
Objective: To estimate the protective effect of storing firearms locked or unloaded, or both, on the risk of suicide by firearms among people with relatively low intention to die.
Design and setting: Cross sectional survey. The 1993 National Mortality Followback Survey of 22 957 deaths in the United States, representing 2.2 million people, conducted by the National Center for Health Statistics.
Participants: Decedent's next of kin answered questions regarding various aspects of decedent's life to supplement information from death certificates.
Main results: Compared with decedents who stored their firearm unlocked or loaded, those who stored their firearms locked or unloaded, or both, were less likely to commit suicide by firearms (locked: OR = 0.39, 95% CI = 0.24 to 0.66; unloaded OR = 0.30, 95% CI = 0.18 to 0.49).
Conclusions: This study further supports the utility of devices and practices intended to reduce the likelihood of unauthorised or impulsive use of firearms.
doi:10.1136/jech.2003.017343
PMCID: PMC1763337  PMID: 15365110
25.  Multiple-race mortality data for California, 2000-2001. 
Public Health Reports  2004;119(2):187-191.
OBJECTIVES: To examine mortality rates and quality of race reporting for multiple-race individuals in California using the new multiple-race data available on the death certificate. METHODS: Death date were drawn from California vital statistics for 2000 and 2001. Denominator data were drawn from the 2000 census Modified Race Data Summary File. The authors calculated mortality rates and relative standard errors for multiple-race individuals as a whole and by county, and for the three largest reported multiple-race groups (African American and white, American Indian/Alaska Native and white, and Asian and white). RESULTS: Decedents reported to be of more than one race were disproportionately young, Hispanic, male, and never-married. Age-adjusted mortality rates for multiple-race groups were approximately one-sixth as high as rates for single-race individuals. There was substantial variability in rates for multiple-race decedents according to county of residence. CONCLUSIONS: Mortality rates for multiple-race people were implausibly low, and death certificates for multiple-race individuals were geographically clustered. Race reporting on death certificates will need to be improved before accurate death rates can be calculated for those of multiple races.
PMCID: PMC1497614  PMID: 15192906

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