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PubMed2004

Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases.

BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. AIM: To survey side-effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A computerized search using the term 'azathioprine' or 'imuran' was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine-toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine-induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.

Acute Disease↗

PubMed1996

Hepatic cystic disease in an adult polycystic kidney disease transplant population.

BACKGROUND: A study of the incidence of polycystic liver in a transplant population and an assessment of the impact of this disease on the group was undertaken. Clinical presentation, investigation and treatment of hepatic polycystic disease are explored. METHODS: The study examined the morbidity incurred by polycystic liver disease in patients, patient and graft survival, incidence of hepatic cysts and presentation, investigation and management of morbid hepatic cystic disease. One hundred and eleven patients were studied. RESULTS: It was found that hepatic cysts occurred in the majority of patients that underwent transplants for renal failure because of polycystic kidney disease at this institution. Symptomatic hepatic cystic disease was found to be primarily responsible for three deaths and affected between 15 and 20% of the group. Gall bladder disease was found to be associated with highly symptomatic hepatic cystic disease. CONCLUSION: Hepatic cystic disease is common in patients that have had kidney transplants because of polycystic kidney disease. Morbidity is likely to increase as patients survive for longer periods. Cholecystectomy should be considered in patients with significant hepatic cystic disease.

Adult↗

PubMed2004

Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype.

BACKGROUND AND AIMS: Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort. METHODS: One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping. RESULTS: Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype. CONCLUSION: Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.

Adolescent↗

PubMed1989

A pathological study of the association between Lewy body disease and Alzheimer's disease.

The possibility of an association between Parkinson's disease and Alzheimer's disease has been examined by studying the age-specific prevalence of Lewy bodies in the substantia nigra in a group of 273 control cases without Parkinson's disease and 121 cases of Alzheimer's disease. The substantia nigra was also studied in 14 cases of Down's syndrome, 13 of which had cortical Alzheimer pathology. Twelve (7.8%) of the controls aged over 60 years showed nigral Lewy bodies. There was mild nerve cell degeneration and/or an extranigral distribution of Lewy bodies, suggestive of presymptomatic Parkinson's disease. Twenty five (22.5%) of the Alzheimer's disease cases over 60 years showed Lewy bodies, but only 14 (14.0%) of these had mild nigral cell loss consistent with presymptomatic Parkinson's disease. No case of Down's syndrome had Lewy bodies. Counts of tangles and plaques in hippocampus, frontal and temporal cortex were lower in cases of Alzheimer's disease with Lewy bodies compared with those without, but cortical choline acetyltransferase (ChAT) activities were similar. This suggests that Lewy body degeneration in the nucleus basalis of Meynert contributes to the deficit of cortical ChAT, but not to the cortical Alzheimer pathology. The relatively small difference in the prevalence of Lewy bodies between controls and Alzheimer's disease could be explained by the additive effects of Lewy body and tangle pathology causing dementia, rather than a greater than chance association between Parkinson's disease and Alzheimer's disease.

Adult↗

PubMed1995

Subclinical disease as an independent risk factor for cardiovascular disease.

BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study. METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes. CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

Aged↗

PubMed2005

Incidence and clinical features of disease progression in adult moyamoya disease.

BACKGROUND AND PURPOSE: The progression of occlusive lesions in the major intracranial arteries was believed to be very rare in adult patients with moyamoya disease. The present study aims to clarify the incidence and clinical features of disease progression in adult moyamoya disease. METHODS: For the past 15 years, 120 adult Japanese patients were diagnosed with moyamoya disease. Of these, 63 patients were enrolled in this historical prospective cohort study on a total of 86 nonoperated hemispheres. All were followed up with a mean period of 73.6 months. MRI and magnetic resonance angiography were repeated every 6 to 12 months, and cerebral angiography was performed when disease progression was suspected on MRI and magnetic resonance angiography. RESULTS: Disease progression occurred in 15 of 86 nonoperated hemispheres (17.4% per hemisphere) or in 15 of 63 patients (23.8% per patient) during the follow-up period. Occlusive arterial lesions progressed in both anterior and posterior circulations, in both symptomatic and asymptomatic patients, and in both bilateral and unilateral types. Eight of 15 patients developed ischemic or hemorrhagic events in relation to disease progression. Multivariate analysis revealed that the odds ratio conferred by a male patient was 0.20 (95% CI, 0.04 to 0.97). CONCLUSIONS: The incidence of disease progression in adult moyamoya disease is much higher than recognized before, and female patients may be at higher risk for it than male patients. Careful follow-up would be essential to prevent additional stroke occurrence in medically treated adult patients with moyamoya disease, even if they are asymptomatic or are diagnosed as having unilateral moyamoya disease.

Adult↗

PubMedDate not supplied

Coronary artery disease and periodontal disease: is there a link?

BACKGROUND: Cardiovascular disease is the number one killer worldwide. The so-called classic risk factors of coronary heart disease do not account for all of its clinical and epidemiological features. Recent evidence suggests that certain infections, among them dental infections and in particular periodontal disease, are involved in the pathogenesis of coronary artery disease. AIM: To evaluate the association between periodontal disease and coronary artery disease. PATIENTS AND METHODS: Fifty patients referred for diagnostic coronary angiography were assessed for periodontal disease. All patients underwent a thorough physical examination, routine laboratory testing, cardiac evaluation and dental examination which included pantomography x-ray evaluation. RESULTS: Pantomography x-rays and coronary angiograms of the participants were scored blindly by a dentist and cardiologists respectively. The association between periodontal disease and coronary atheromatosis remained significant after adjustment for age, smoking, blood lipids, body mass index, hypertension and the presence of diabetes. IMPLICATIONS: Periodontal disease was still significantly associated after all the known risk factors were accounted for. The implication here is that periodontal disease could be a potential risk factor for heart disease by predisposing the individual to chronic low-grade infections. If so, then dental health becomes an important parameter for medical health.

Aged↗

PubMed2006

The use of different measurements and definitions of periodontal disease in the study of the association between periodontal disease and risk of myocardial infarction.

BACKGROUND: The role of periodontal disease as an independent risk factor for cardiovascular disease (CVD) has been under debate because of the inconsistency of findings across studies. One of the major issues is the method used to assess or define periodontal disease. The present study assesses if the observed association between periodontal disease and incident myocardial infarction (MI) depends on the measurements and/or criteria used to define periodontal disease. METHODS: A population-based case-control study to evaluate the association between PD and risk of MI was conducted between 1997 and 2001 in Western New York with 537 cases and 800 controls, aged 35 to 69 years. Cases were survivors of incident MI from local hospitals in Erie and Niagara counties. Controls were randomly selected from residents of the same counties. Periodontal disease was assessed using interproximal clinical attachment loss (CAL), probing depth (PD), alveolar crest height (ACH), and number of missing teeth. From these measurements, four different case definitions of periodontal disease were created. RESULTS: Using the continuous forms of periodontal measurements, the odds ratios (ORs) (95% confidence interval) of the association with incident MI were 1.46 (1.26 to 1.69), 2.19 (1.66 to 2.89), 1.30 (1.14 to 1.49), and 1.04 (1.02 to 1.07) for mean CAL, PD, ACH, and number of missing teeth, respectively. Regardless of the case definition of periodontal disease, the estimates of the association with incident MI were statistically significant. CONCLUSIONS: The observed association between periodontal disease and incident MI was consistent across different measurements and/or case definitions of periodontal disease used. The magnitude of the association varies depending on the measurements or the criteria used to define periodontal disease.

Adult↗

PubMed2003

[Association of celiac disease and Crohn's disease. A case report].

Crohn's disease and celiac disease are two chronic digestive diseases. The pathological mechanisms that lead to them are not known. Their association is rare leading to diagnostic and etiopathogenic problems. The aim of this study is to report clinical, endoscopical and histopathological characteristics of this association and to discuss the etiopathogenic links between these two diseases. The association of celiac disease and Crohn's disease is possible although rare. Many etiopathological mechanisms were suggested to explain such an association. In the case of celiac disease, the association with Crohn's disease is suggested by the characteristics of the diarrhea, the anoperineal lesions and will be confirmed by ileocolonoscopy and biopsy. In contrary, the diagnosis of celiac disease associated with Crohn's disease is frequently suggested by the endoscopy of upper gastrointestinal tract systematically practiced and will be confirmed by biopsy and serological celiac disease tests.

Adult↗

PubMed1995

[Collagen disease. Autoimmune disease].

Collagen disease is systemic autoimmune disease and consists of a lot of diseases with each clinical entity. for exact diagnosis, it is important to choose essential laboratory tests for the patient suspected of collagen disease in daily primary medical care. A guideline for the use of clinical laboratory tests for patients with collagen disease was proposed by the Japan Society of Clinical Pathology. This guideline was discussed repeatedly by subcommittee members of "the uses of clinical laboratory tests in daily primary medical care" and published on September of 1990. When the clinicians are suspected of the collagen disease from detailed history taking and physical examination, they must precisely interpret results of the essential laboratory tests. Urinalysis, hematology, ESR and CRP and Biochemistry show characteristic findings in the collagen disease, respectively. If further suspicion of the collagen disease is intensive, the clinicians proceed with the primary screening tests for collagen disease; rheumatoid factor, ANF, anti DNA antibody, LE test, STS and CH50. Finally, specific tests for each collagen disease are carried out to define the diagnosis; e.g. LE cell, anti-Sm antibody, IC, Coombs test and biopsy of kidney for SLE. This paper is presented on the intention of the guideline of clinical laboratory tests for the collagen disease and its issues. As it passed 4 years after published, this guideline should be more discussed and revised.

Autoimmune Diseases↗

PubMed1985

The effect of intra-abdominal resection or fecal diversion on perianal disease in pediatric Crohn's disease.

To determine whether perianal Crohn's disease responds to resection of active intra-abdominal disease or to diversion, 273 cases of Crohn's disease in children (ages 4 to 18 years) were reviewed (all had been seen between 1970 and 1983). Of these, 104 patients underwent an intestinal operation, and 42 of the 104 (40%) had documented perianal disease at the time of their operation. Follow-up averaged 8 3/4 years from time of diagnosis. Three of the 42 died, at 1, 3, and 5 months postoperatively (mortality, 7%) and one was unavailable for follow-up. In these 42 patients with active perianal disease, an intestinal resection with primary anastomosis was performed in 19; one died postoperatively and one was unavailable for follow-up. Of the remaining 17 patients, five (29%) improved and 12 (71%) had continued perianal disease, either without change or worse. At least one further intestinal resection was needed in five of the 17 and two have needed proctocolectomy. A defunctionalizing procedure was done as part of the initial operation in 11 of the 42 patients. Two showed improvement; however, both needed proctocolectomy for rectal disease, and none of the 11 with fecal diversion have had reestablishment of intestinal continuity. In 12 of the 42 patients proctocolectomy was the initial procedure, usually for severe rectosigmoid disease. Of 38 children followed, 20 had proctocolectomy, 11 initially and nine after lesser procedures; overall rate of proctocolectomy was 53%. Resection of active intra-abdominal disease is not necessarily followed by resolution of perianal lesions. Defunctionalizing the rectum with fecal diversion does not appear to alter perianal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2003

Does bulky disease at diagnosis influence outcome in childhood Hodgkin's disease and require higher radiation doses? Results from the German-Austrian Pediatric Multicenter Trial DAL-HD-90.

PURPOSE: The identification of risk factors is required for risk-adapted treatment strategies in the treatment of Hodgkin's disease. To assess the influence of bulky disease at diagnosis as compared with other risk factors on event-free survival (EFS) in pediatric Hodgkin's disease such as stage, B-symptoms, number of involved lymph node regions, histology, and remission status after chemotherapy, we analyzed the outcome of 552 patients treated with a risk-adapted treatment strategy consisting of OPPA(OEPA)/COPP (vincristine, procarbazine, etoposide, prednisone, adriamycin, cyclophosphamide) and involved-field radiotherapy. METHODS AND MATERIALS: Between 1990 and 1995, 578 patients with primary Hodgkin's disease (HD) were enrolled in the German/Austrian Pediatric Hodgkin's Disease Study Group (DAL) Multicenter Study (HD-90). Patients were stratified into three treatment groups (TGs) for early, intermediate, and advanced stage. All patients received induction chemotherapy (CT) with two cycles of OEPA for boys and two cycles of OPPA for girls. Patients in TG2 and TG3 received another two or four cycles, respectively, of COPP. Chemotherapy was followed by involved-field radiotherapy. The radiation field, which was prescribed by the study center, was treated with a dose of 25 Gy/25 Gy/20 Gy (TG1/TG2/TG3), and in case of insufficient remission with a local boost of 5 Gy to 10 Gy. The following prognostic factors were analyzed with regard to their impact on EFS: bulky disease, mediastinal tumor, number of involved lymph node regions, histology, treatment group, B-symptoms, sex, age, and remission status after chemotherapy. RESULTS: Significant univariate predictive factors for the EES were: nodular sclerosis type 2 (NS2) histology (relative risk [RR] 3.43; p = 0.0002), presence of B-symptoms (RR 2.70; p = 0.0014), number of involved regions (1.55; p = 0.019), and treatment groups (RR 1.33; p = 0.017). There was a higher risk (RR 1.92; p = 0.040) for patients with bulky compared with nonbulky disease (5-year EFS 89.6%/94.6%). In the multiple regression model, only NS2 and B-symptoms remained strong predictive factors. The remission status after chemotherapy did not correlate with EFS (p = 0.66). CONCLUSION: Treatment strategies in Hodgkin's disease have an impact on different risk factors. In the risk-adapted treatment strategy of the HD-90 study, tumor burden indicated as bulky disease or as number of involved lymph nodes loses its importance, whereas NS2 histology and B-symptoms have a major impact on treatment outcome. Bulky disease at diagnosis might require higher radiation doses only in case of insufficient remission.

Adolescent↗

PubMed2000

The differentiation of classic Kawasaki disease, atypical Kawasaki disease, and acute adenoviral infection: use of clinical features and a rapid direct fluorescent antigen test.

OBJECTIVE: To compare the clinical and laboratory features of children with Kawasaki disease with those with acute adenoviral infection, which may mimic Kawasaki disease. DESIGN: We retrospectively compared the medical records of children with Kawasaki disease and atypical Kawasaki disease with those of children with acute adenoviral infection. All children included were initially evaluated because their primary care physicians were concerned that they might have Kawasaki disease. The utility of a rapid direct fluorescent antigen test for adenovirus was evaluated. Thirty-six children with Kawasaki disease (23 with classic and 13 with atypical presentations) and 7 patients with acute adenoviral infection were studied. SETTING: A tertiary care pediatric hospital. RESULTS: Children with Kawasaki disease were more likely to have conjunctivitis (36 of 36 vs 4 of 7), strawberry) tongues (23 of 36 vs 1 of 7), perineal peeling (19 of 36 vs 0 of 7), and distal extremity changes (22 of 36 vs 0 of 7) than those with acute adenoviral infection. Children with acute adenoviral infection were more likely to have purulent conjunctivitis (3 of 7 vs 1 of 36) and exudative pharyngitis (3 of 7 vs 1 of 35). In addition to pyuria (13 of 26 vs 0 of 6), patients with Kawasaki disease had higher mean white blood cell counts (15.3 +/- 3.5 vs 11.5 +/- 6.0 x 10(9)/L), erythrocyte sedimentation rates (56 vs 42 mm/h), platelet counts (426 vs 259 x 10(9)/L), and levels of alanine aminotransferase (101 vs 18 U/L) than those with acute adenoviral infection. Children with Kawasaki disease had lower mean albumin levels (32 vs 36 g/L). A rapid antigen test for adenovirus had a specificity and sensitivity of 100% compared with viral culture. CONCLUSIONS: Kawasaki disease and acute adenoviral infection can present with many of the same clinical characteristics. A rapid direct fluorescent antigen assay for adenovirus may be a helpful adjunctive test for distinguishing acute adenoviral infection from Kawasaki disease.

Acute Disease↗

PubMed2004

Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring.

CONTEXT: Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events. OBJECTIVE: To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events. DESIGN: Inception cohort study. SETTING: Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971. PARTICIPANTS: All Framingham Offspring Study participants (aged > or =30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort. MAIN OUTCOME MEASURES: We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression. RESULTS: Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk. CONCLUSIONS: Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.

Adult Children↗

PubMed2000

Comparison of progression of macrovascular diseases after kidney or pancreas and kidney transplantation in diabetic patients with end-stage renal disease.

AIMS/HYPOTHESIS: The aim of the study was to examine the effect of pancreas-kidney transplantation on the progression of macrovascular diseases in Type I diabetic patients with end-stage renal disease. METHODS: The progression of cerebrovascular disease, coronary heart disease and peripheral vascular disease in uraemic patients with Type I (insulin-dependent) diabetes mellitus and who had had simultaneous pancreas-kidney transplantation was compared with that of recipients of a kidney transplant alone. Between 1986 and 1998 a total of 11 uraemic diabetic patients received a simultaneous pancreas-kidney transplantation and 10 diabetic patients a kidney transplant alone. All transplants functioned for at least 24 months, the mean observation period was 69 +/- 37 compared with 70 +/- 33 months in both patient groups. Macroangiopathic diseases were classified in four stages as described earlier. RESULTS: In the group with simultaneous pancreas-kidney transplantation progression of cerebrovascular and coronary heart disease was observed in four patients (36%) and progression of peripheral vascular disease in five subjects (45%). In the cohort with kidney transplant alone four patients (40%) showed progression of cerebrovascular and coronary heart disease and five progression of peripheral vascular disease (50%); the difference is not significant. Mean values of HbA1c (5.8 +/- 0.2 vs 7.5 +/- 0.6%, p < 0.001) and serum triglycerides (1.2 +/- 0.4 vs 2.0 +/- 1.0 mmol/l, p < 0.05) were significantly lower in the patients with pancreas-kidney transplantation than in the patient group with kidney transplant alone. Serum cholesterol concentrations and blood pressures were similar in both cohorts. CONCLUSION/INTERPRETATION: From our results we concluded that pancreas-kidney transplantation reduces risk factors for the development of macroangiopathy but fails to halt progression of macrovascular diseases similar to Type I diabetic patients with kidney transplant alone.

Adult↗

PubMed1983

Uptake and metabolism of radioactively labeled sphingomyelin in cultured skin fibroblasts from controls and patients with Niemann-Pick disease and other lysosomal storage diseases.

The metabolism of [stearoyl-1-14C]- and [choline-methyl-14C]sphingomyelin, [stearoyl-1-14C]ceramide-1-phospho-N,N-dimethylethanolamine (demethylsphingomyelin) and [choline-methyl-14C]phosphatidylcholine was measured 1, 3 and 5 days after uptake from the media of cultured skin fibroblasts. This was done to measure the relative contributions of lysosomal sphingomyelinase and plasma membrane phosphocholine transferase on the metabolism of sphingomyelin, a component of all cell membranes. By using cell lines from controls and from patients with Niemann-Pick disease and other lysosomal storage diseases, it was concluded that a significant portion (10-15%) of the observed degradation of sphingomyelin is due to exchange of the phosphocholine moiety producing phosphatidylcholine. Although cell lines from type A and B Niemann-Pick disease have only 0-2% of lysosomal sphingomyelinase activity measured in vitro, three cell lines from type B Niemann-Pick disease could metabolize 54.4% of the labeled sphingomyelin by day 3 while cell lines from type A Niemann-Pick disease could only metabolize 18.5% by day 3. This compares to 86.7% metabolized in control cells by day 3. Cells from one patient with juvenile Niemann-Pick disease and one with type D Niemann-Pick disease metabolized sphingomyelin normally while cells from two other patients with juvenile or type C Niemann-Pick disease could only metabolize 58.2% by day 3. Cells from patients with I-cell disease and 'lactosylceramidosis' also demonstrated decreased metabolism of sphingomyelin (55.1 and 54.9% by day 3, respectively). Cells from the patient with Farber disease accumulated [14C]stearic acid-labeled ceramide produced from [14C]sphingomyelin. Studies with choline-labeled sphingomyelin and phosphatidylcholine demonstrated that phosphocholine exchange takes place in either direction in the cells, and this is normal in Niemann-Pick disease. Studies in cells from patients with all clinical types of sphingomyelinase deficiency have led to new methods for diagnosis and prognosis and to a better understanding of sphingomyelin metabolism.

Cell Line↗

PubMed1976

A disease-conscious method for sequential diagnosis by use of disease probabilities without assumption of symptom independence.

A method for automatic diagnosis of disease is formulated and applied to a data base of several hundred gastroenterological patients who were each known to have one of six diseases. Application of the method requires no assumptions regarding statistical independence of symptoms. Each disease is associated with its own disease-symptom function, and any order of dependence between the symptoms and each disease may be allowed for. A patient's symptoms are used to determine the value of any specified disease-symptom function. This value is then used to determine the probability that the patient has the corresponding disease. The method is applied to a sequential diagnosis of patients not contained in the initial data base. Additional symptoms are chosen according to their diagnostic value. The entire model is disease-conscious in that disease-symptom functions, disease probabilities and diagnostic values need be evaluated only for those diseases that are considered relevant to the diagnosis.

Bayes Theorem↗

PubMed1995

Risk factors of coronary heart disease and total mortality among elderly men with and without preexisting coronary heart disease. Finnish cohorts of the Seven Countries Study.

OBJECTIVES: We attempted to determine whether elevated levels of the classic coronary heart disease risk factors are associated with increased coronary risk and all-cause mortality among elderly men with and without coronary heart disease at baseline. BACKGROUND: The strength of any association between the classic coronary risk factors and survival among elderly men with and without coronary heart disease has not been established. METHODS: The classic coronary risk factor levels and risk of coronary events and total mortality during a 5-year follow-up interval were studied among men aged 65 to 84 years. Coronary events were fatal myocardial infarction (n = 71), any myocardial infarction (n = 96) and, among the men without disease, other nonfatal coronary heart disease events (n = 80). RESULTS: Among the 171 men with prevalent coronary heart disease, significant (p < 0.05) risk factors for fatal myocardial infarction (n = 42) in multivariate analyses were low high density lipoprotein cholesterol (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1 to 0.8 for 1-mmol/liter increase), high ratio of total to high density lipoprotein cholesterol (OR 1.4, 95% CI 1.1 to 1.7 for 1-U increase), and smoking more than nine cigarettes daily (OR 6.0, 95% CI 1.5 to 24.9 vs. values in men who had never smoked). Among the 476 men without prevalent coronary heart disease, only high serum total cholesterol was a risk factor for fatal myocardial infarction (n = 29) (OR 1.4, 95% CI 1.0 to 2.0 for 1-mmol/liter increase). Among men with prevalent coronary heart disease, the only significant (p < 0.05) risk factor for total mortality was smoking more than nine cigarettes daily (OR 3.9, 95% CI 1.1 to 13.4 vs. values among men who had never smoked). Among men without prevalent coronary heart disease, only the use of antihypertensive medication (OR 2.0, 95% CI 1.2 to 3.3 between men with and without such medication) was a risk factor for total mortality. CONCLUSIONS: The classic risk factors for coronary heart disease appear to be of importance even in old age, especially among men with prevalent coronary heart disease.

Age Factors↗