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PubMed1997

Clinical evaluation of hepatocyte growth factor in patients with gastrointestinal and pancreatic diseases with special reference to inflammatory bowel disease.

Hepatocyte growth factor (HGF) is widely expressed in the gastrointestinal tract and pancreas. However, the clinical significance of HGF in gastrointestinal and pancreatic diseases remains unclear. To clarify its clinical significance in these diseases, we determined serum HGF in patients with gastrointestinal and pancreatic diseases. Serum HGF was measured in 81 patients with gastrointestinal diseases, pancreatic diseases, and 150 healthy individuals, using a highly sensitive immunoradiometric assay (IRMA). The patients included 55 patients with colonic disorders, 20 with gastric disorders and 6 with pancreatic disorders. Serum HGF levels in patients with inflammatory bowel diseases and chronic pancreatitis were higher than those in normal individuals (p < 0.05, each). Symptomatic patients with inflammatory bowel diseases showed higher values of HGF than symptom-free patients (p < 0.05). Patients with moderately severe or severe ulcerative colitis showed higher values of HGF than patients with mild disease (p < 0.05). Serum HGF values were correlated with C-reactive protein (CRP) and serum HGF changed in parallel with clinical courses in patients with ulcerative colitis. The immunohistochemical study showed that HGF was present around the neutrophils infiltrating into the lamina propria, which was biopsied from endoscopically active colonic mucosa in patients with ulcerative colitis, while little HGF was observed in the inactive mucosa. The results of the present study suggest that serum HGF changes in gastrointestinal and pancreatic diseases, especially in inflammatory bowel diseases.

Adult↗

PubMed2000

Nicotine binding in human striatum: elevation in schizophrenia and reductions in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease and in relation to neuroleptic medication.

Striatal nicotinic acetylcholine receptors with high affinity for nicotinic agonists are involved with the release of a number of neurotransmitters, including dopamine. Previous findings as to whether these receptors are changed in Parkinson's disease and Alzheimer's disease are inconsistent and no previous investigations have focused on these receptors in dementia with Lewy bodies and schizophrenia, which are also associated with disorders of movement. The present autoradiographic study of striatal [3H]nicotine binding in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies and schizophrenia was conducted with particular reference to the potentially confounding variables of tobacco use and neuroleptic medication. [3H]Nicotine binding in both dorsal and ventral caudate and putamen was significantly reduced in Parkinson's disease (43-67%, n=13), Alzheimer's disease (29-37%, n=13) and dementia with Lewy bodies (50-61%, n=20) compared to age-matched controls (n=42). Although tobacco use in the control group was associated with increased [3H]nicotine binding (21-38%), and neuroleptic treatment in dementia with Lewy bodies and Alzheimer's disease was associated with reduced [3H]nicotine binding (up to 29%), differences between neurodegenerative disease groups and controls persisted in subgroups of Alzheimer's disease cases (26-33%, n=6, in the ventral striatum) and dementia with Lewy body cases (30-49%, n=7, in both dorsal and ventral striatum) who had received no neuroleptic medication compared to controls who had not smoked (n=10). In contrast, striatal [3H]nicotine binding in a group of elderly (56-85 years) chronically medicated individuals with schizophrenia (n=6) was elevated compared with the entire control group (48-78%, n=42) and with a subgroup that had smoked (24-49%, n=8). The changes observed in [3H]nicotine binding are likely to reflect the presence of these receptors on multiple sites within the striatum, which may be differentially modulated in the different diseases. Further study is warranted to explore which nicotinic receptor subunits and which neuronal compartments are involved in the changes in [3H]nicotine binding reported, to aid development of potential nicotinic receptor therapy.

Aged↗

PubMed2001

Anderson-Fabry disease: clinical manifestations of disease in female heterozygotes.

Anderson-Fabry disease is a rare, X-chromosomal lipid storage disorder caused by a deficiency of lysosomal alpha-galactosidase A. Clinical manifestations of Anderson-Fabry disease include excruciating pain in the extremities (acroparaesthesia), skin vessel ectasia (angiokeratoma), corneal and lenticular opacity, cardiovascular disease, stroke and renal failure, only renal failure being a frequent cause of death. Heterozygote female carriers have often been reported as being asymptomatic or having an attenuated form of the disease. To evaluate the spectrum of clinical signs in heterozygotes, a comprehensive clinical examination was performed on 20 carriers of Anderson-Fabry disease. This revealed that, in addition to the skin manifestation, various other clinical manifestations of the disease are present, including acroparaesthesia, kidney dysfunction, cerebrovascular disease, and gastrointestinal and heart problems. It therefore appears that Anderson-Fabry disease affects both hemizygotes and heterozyotes and therefore should be considered to be an X-linked dominant disease.

Adolescent↗

PubMed2006

Australia's notifiable diseases status, 2004, annual report of the National Notifiable Diseases Surveillance System.

In 2004, 60 diseases and conditions were nationally notifiable in Australia. States and Territories reported a total of 110,929 cases of communicable diseases to the National Notifiable Diseases Surveillance System (NNDSS): an increase of 4 per cent on the number of notifications in 2003. In 2004, the most frequently notified diseases were sexually transmissible infections (46,762 cases; 42% of total notifications), gastrointestinal diseases (25,247 cases; 23% of total notifications) and bloodborne diseases (19,191 cases; 17% of total notifications). There were 13,206 notifications of vaccine preventable diseases, 6,000 notifications of vectorborne diseases, 1,799 notifications of other bacterial infections (includes, legionellosis, leprosy, meningococcal infections and tuberculosis) and 877 notifications of zoonotic diseases.

Adolescent↗

PubMed1994

Quantitative neuropathologic analysis of Pick's disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer's disease.

Pick's disease is characterized morphologically by severe atrophy of the frontal and temporal lobes and the presence in the cerebral cortex of degenerative neuronal lesions referred to as Pick bodies. In the present study, we analyzed the regional and laminar distribution of Pick bodies in a series of 16 Pick's disease cases. These distribution and density patterns were compared with those observed for neurofibrillary tangles in Alzheimer's disease. Very high densities of Pick bodies were observed Ammon's horn, subiculum, entorhinal cortex, and in the granule cell layer of the dentate gyrus. In the frontal and temporal neocortex, they were preferentially distributed in layers II and VI. All of the Pick's disease cases also exhibited neurofibrillary tangles in the frontal and temporal areas and in the hippocampal formation, with higher densities in layers II-III than in layers V-VI of the neocortical regions. Interestingly, this laminar distribution of neurofibrillary tangles was strikingly different from that observed in Alzheimer's disease cases, where they were more numerous in the infragranular layers than in the supragranular layers. In addition, a few Pick's disease cases also had cortical senile plaques. These results suggest that the presence of neurofibrillary tangles in Pick's disease may be more frequent than previously reported, and that Pick's disease and Alzheimer's disease may coexist in certain cases. The lesion distribution patterns suggest that different populations of cortical neurons are affected in Pick's and Alzheimer's disease, and that alterations of select corticocortical and corticosubcortical projections may distinguish these forms of dementia. It is also possible that these two disorders share certain pathogenetic mechanisms, even though both display specific patterns of regional and neuronal vulnerability to the degenerative processes.

Aged↗

PubMed1995

Soluble interleukin-2 receptor in Crohn's disease. Assessment of disease activity and prediction of relapse.

In Crohn's disease, the activity of the disease is difficult to evaluate and the evolution of the disease is difficult to predict. The soluble interleukin-2 receptor serum level has been reported to correlate with clinical activity of the disease and with mucosal immune activation. We compared serum soluble interleukin-2 receptor to classical inflammatory markers and other immune parameters in the assessment of clinical disease activity and prediction of relapse in patients with Crohn's disease. Soluble interleukin-2 receptor serum levels correlated well with the Crohn's disease activity index, and multivariate analysis showed that this correlation was independent of the other inflammatory and immune markers. The correlation was not greater, However, than that between some inflammatory markers, such as ESR, and Crohn's disease activity index. Longitudinal follow-up showed that a high soluble interleukin-2 receptor serum level was highly predictive of relapse. Multivariate analysis showed that the soluble interleukin-2 recepteur serum level was complementary to other inflammatory and clinical markers in the prediction of relapse of disease. We conclude that soluble interleukin-2 receptor is of use in monitoring Crohn's disease, particularly in prediction of relapse.

Adolescent↗

PubMedDate not supplied

Systemic levels of free 5-aminosalicylic acid depend on the nature of the 5-aminosalicyclic acid derivative and not on disease activity or extent in patients with inflammatory bowel disease.

INTRODUCTION: Several new derivatives of sulphasalazine that make use of its active moiety, 5-aminosalicylic acid (5-ASA), have been introduced for the treatment of inflammatory bowel disease (IBD). In rats short term intravenous administration of 5-ASA has been associated with nephrotoxicity. A number of cases of nephrotoxicity have been reported recently in IBD patients taking oral maintenance treatment with 5-ASA compounds. OBJECTIVE: To study the urinary and serum levels of acetylated 5-ASA (Ac-5-ASA) and the unacetylated 5-ASA (5-ASA) in patients with IBD maintained on sulphasalazine, olsalazine and mesalazine (pH dependent release form). We also sought correlation between levels of 5-ASA, clinical disease activity and extent of disease. METHODS: We studied 79 patients (male, n = 30; female, n = 49) with established IBD [ulcerative colitis (UC), n = 48; Crohn's disease (CD), n = 31], 72 maintained on 5-ASA compounds (sulphasalazine = 27; olsalazine = 28; mesalazine = 17) and 7 patients were receiving no medication. Urinary and serum analysis of 5-ASA was performed by high performance liquid chromatography (HPLC). Clinical disease activity was quantified using simple index of Harvey and Bradshaw. RESULTS: Patients receiving mesalazine had significantly higher levels of serum free 5-ASA compared to those who were receiving olsalazine and sulphasalazine (mesalazine mean +/- SEM; range; 2.84 +/- 1.21 (0.00-16.00) vs olsalazine 0.45 +/- 0.18 (0.00-16.20); mumol/L; p < 0.04; sulphasalazine 0.37 +/- 0.25 (0.00-3.74); p < 0.03). Similarly levels of urinary free 5-ASA were significantly higher in patients maintained on mesalazine compared to those on olsalazine or sulphasalazine (mesalazine 219 +/- 80.43 (0.00-1050) vs olsalazine 33.3 +/- 17.23 (0.00-317) mumol/L; p < 0.01; and sulphasalazine 15 +/- 8.86 (0.00-192); p < 0.05). However, no significant difference was observed in the levels of urinary free 5-ASA between olsalazine and sulphasalazine. No significant difference was observed in the levels of free-5-ASA in UC patients with left sided disease and those with extensive disease. Furthermore, no significant difference was observed in the levels of serum and urinary 5-ASA in CD patients with ileo-colic disease and colonic disease. Urinary and serum free-5-ASA did not correlate with the clinical disease activity. CONCLUSION: Systemic absorption of 5-ASA from sulphasalazine and olsalazine is relatively low. However, pH-dependent mesalazine formulations may release their contents rapidly in the small intestine and proximal colon resulting in higher plasma and urinary concentrations of free 5-ASA. The effects of free 5-ASA on renal function in the human require further evaluation.

Adolescent↗

PubMed1975

The use of noninvasive methods in the evaluation of left ventricular performance in coronary artery disease. I. Relation of systolic time intervals to angiographic assessment of coronary artery disease severity.

Determination of left ventricular performance by external STI was evaluated in 113 patients with possible coronary artery disease undergoing selective coronary artery disease undergoing selective coronary arteriography and left ventriculography. Angiographically determined significant coronary artery disease was considered as 70 per cent obstruction of a coronary vessel. PEPI and PEP/LVET increased with increasing severity of coronary artery disease. LVETI decreased with increasing coronary artery involvement. Presence of prior myocardial infarction or clinically apparent congestive heart failure did not significantly alter mean STI values when groups were compared according to severity of coronary artery disease. LVETI was significantly less for patients with three-vessel coronary artery disease than for those with no significant disease; PEPI and PEP/LVET were significantly greater in those with two- or three-vessel disease than in those without significant disease. Angiographically determined LVEF correlated directly with LVETI and inversely with PEPI and PEP/LVET. Abnormal left ventricular wall motion was associated with decreased LVETI and increased PEPI and PEP/LVET. LVEDP was not significantly different in any of the groups. These findings indicate that externally determined systolic time intervals reflect abnormalities in left ventricular performance which in turn appear more pronounced with increasingly extensive coronary artery disease.

Adult↗

PubMed1975

Left main coronary artery disease. Risks of angiography, importance of coexisting disease of other coronary arteries and effects of revascularization.

To elucidate the determinants of the poor prognosis of patients with left main coronary artery disease and to assess the efficacy of diagnostic and therapeutic interventions the angiographic features and clinical course of 58 patients with left main coronary artery disease studied between September 1967 and June 1974 were analyzed. Eighty-three coronary arteriograms were obtained in these 58 patients using the Judkins technique; there were no immediate complications although one patient died 3 days after study. Previously cited predictors of left main coronary artery, unstable or nonexertional angina and marked S-T segment depression with exercise were found in a minority of patients; thus, the presence of the disease could not reliably be predicted before arteriographic study. Coexisting disease was found in either two or three other coronary arteries in 46 of 58 patients; only 2 patients had isolated left main coronary artery disease. Because the criteria for operability have changed in recent years, current criteria without knowledge of the treatment actually given or its outcome. The condition of 10 of 58 patients was judged inoperable in retrospect because of severe coexisting distal coronary artery disease (8 patients) or ventricular dysfunction (2 patients). Of 19 patients whose condition was judged operable in retrospect but who were treated without surgery, 9 died, 8 within 18 months; 10 have survived 12 to 83 months. Another 27 patients with a condition judged operable in retrospect had received saphenous vein bypass grafts. In this group, there were four operative and three late deaths. The severity of angina decreased in survivors treated surgically but was unchanged in survivors treated without surgery. The improvement in survival rates of surgically treated patients was not statistically significant. The data indicate that coronary arteriography can be performed at low risk with the Judkins technique even though preangiographic prediction of left main coronary artery disease is unreliable. Coexisting disease in oter major coronary arteries is an important determinant of the poor prognosis of patients with left main coronary artery disease and precludes surgery in 13 percent. Isolated left main coronary artery disease is uncommon. Surgical therapy relieves symptoms more effectively than nonsurgical therapy.

Angina Pectoris↗

PubMed1976

Community surveillance for coronary heart disease: the Framingham Cardiovascular Disease survey. Comparisons with the Framingham Heart Study and previous short-term studies.

It appears likely that intervention trials on a community scale against one or more coronary heart disease risk factors will begin in the near future. Prerequisite to the evaluation of the effectiveness of these trials is the accurate determination of coronary heart disease incidence rates. The Framingham Cardiovascular Disease Survey was undertaken to test the hypothesis that a short-term surveillance study of a defined population can generate accurate incidence rates for at least some categories of cardiovascular disease and that these rates are comparable with those obtained by longitudinal survey of the same population. In conjunction with the 1970 U.S. census, a 1 year survey was made of all new coronary heart disease events occurring in the town of Framingham, Mass. Surveillance was performed by several methods that were intentionally overlapping. During the study period, 244 coronary heart disease events occurred. Despite the relatively small size of the population, many of the well established epidemiologic characteristics of this disease were evident. The rates obtained by the cardiovascular disease survey were comparable with those obtained by the Framingham Heart Study, for the harder end points of myocardial infarction and death from coronary heart disease, but much smaller for the softer end point of angina pectoris, especially in women. These data and those from similar studies indicate that periodic short-term surveillance studies of target populations of major intervention programs can provide an economic method of generating incidence data for the evaluation of the impact of such programs on myocardial infarction and death from coronary heart disease.

Age Factors↗

PubMed1993

Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease.

BACKGROUND: Intestinal and peripheral blood mononuclear cell interleukin 6 (IL-6) production in inflammatory bowel disease might present an increased quantity of IL-6 into the systemic circulation. The aim of the present study was to examine the relationship of circulatory IL-6 to the clinical and laboratory expression of inflammatory bowel disease in children. METHODS: Sera were obtained from 26 children with ulcerative colitis, 49 with Crohn's disease, and 29 control patients. Serum functional IL-6 was measured by a bioassay and antigenic IL-6 by enzyme linked immunosorbent assay. RESULTS: Functional and antigenic serum IL-6 levels were higher in Crohn's disease than in ulcerative colitis or controls (P < 0.0001) and higher in ulcerative colitis than controls (P < 0.04). In Crohn's disease affecting the colon, functional and antigenic serum IL-6 levels were greater than in disease limited to the small bowel (P < 0.002). Increasing disease severity was reflected by increasing antigenic but not functional IL-6 levels in both Crohn's disease (P < 0.001) and ulcerative colitis (P < 0.02). Serum antigenic IL-6 levels were related to acute phase reactants in both diseases (P < 0.001) whereas functional levels were not. CONCLUSIONS: Our results underscore the importance of using both functional and antigenic methodologies in examining the relationship of circulating cytokines to the clinical manifestations of inflammatory bowel disease.

Acute-Phase Proteins↗

PubMed1994

Computed tomography assessment of splenic size as a predictor of splenic weight and disease involvement in laparotomy staged Hodgkin's disease.

PURPOSE: To evaluate how well splenic size predicts the risk of splenic Hodgkin's disease and to assess how accurately splenic dimensions on computerized tomographic scans predict spleen size and involvement by Hodgkin's disease. METHODS AND MATERIALS: Splenic weights were obtained from laparotomies performed on 897 patients who presented with Hodgkin's disease and were compared with histologic involvement using logistic regression. Splenic dimensions were measured from preoperative computerized tomographic scans in 94 of these patients, and unidimensional splenic measurements [length (L), width (W), thickness (T)] and their products were compared with splenic weight at laparotomy using linear regression. RESULTS: Hodgkin's disease involved 42% of the spleens at laparotomy and 31% of those assessed by computerized tomography. Splenic weight averaged 198 +/- 5 g (range 40-2000 g). Weight and involvement were greater with "unfavorable" histologies (mixed cellularity, lymphocyte depletion, and unclassified Hodgkin's disease: 229 +/- 12 g; 62.7% involved) than with "favorable" histologies (nodular sclerosing, lymphocyte predominant, and interfollicular Hodgkin's disease: 191 +/- 5 g; 37.8% involved). Splenic weight was the strongest independent risk factor correlated with Hodgkin's disease in univariate and multivariate analyses in all patients and the only identifiable univariate risk factor among those with computerized tomographic scans. For most patients, however, splenic weight poorly predicted involvement: The probability of involvement never fell below 20% and exceeded 80% when splenic weight exceeded 270 g with unfavorable histologies or 685 g in favorable histologies. Spleens of average weight had a probability of involvement of 36% with favorable histologies, 70% with unfavorable histologies. Unidimensional measurements of the spleen on computed tomography correlated poorly with splenic weight, but their product correlated well (Correlation coefficients: L: 0.73; W: 0.65; T: 0.78; [0.344485 x L x W x T]: 0.94). CONCLUSIONS: Splenic weight is the strongest factor correlating with the risk of splenic involvement by Hodgkin's disease and can be accurately estimated from three-dimensional measurements on computed tomographic scans, but not from unidimensional measurements. However, splenic weight is not a sensitive predictor of involvement of the spleen by Hodgkin's disease. Therefore, treatment approaches to Hodgkin's disease must be based upon intermediate risks of splenic involvement for most clinically staged patients.

Adolescent↗

PubMed2004

Focused screening for occult carotid artery disease: patients with known heart disease are at high risk.

OBJECTIVES: Stroke puts a major financial burden on our healthcare system. However, carotid duplex scanning performed as a screening test for occult carotid artery stenosis (CAS) currently is not reimbursed by Medicare. The goals of this study were to develop a cost-effective stroke screening program, to determine the prevalence of potential causes of stroke in this population, and to define a population at high risk in which screening would be most effective. METHODS: In a community-based stroke screening program, patients were eligible if they were older than 60 years and had a history of either hypertension, heart disease, or cigarette smoking, or a family history of stroke. Screening included blood pressure determination, an electrocardiographic rhythm strip, and a previously validated modified carotid duplex ultrasound examination to detect CAS 50% or greater. The relationships between standard demographic risk factors and screening outcomes were analyzed. RESULTS: Screening was performed in 610 patients. Unilateral or bilateral CAS was detected in 66 patients (10.8%). The finding of occult CAS was more prevalent than that of new hypertension (2.6%) or new atrial fibrillation (0.5%). Patients with known hypertension were significantly more likely to have CAS than were those without hypertension (12.7% vs 7.8%; P =.05). Patients with heart disease were significantly more likely to have CAS than were those without heart disease (18.2% vs 8%; P <.0001). Patients with both risk factors were significantly more likely to have occult carotid artery disease than were patients without either risk factor (22.1% vs 8.5%; P <.0001). Multivariate analysis with logistic regression revealed a history of heart disease as an independent predictor of occult carotid artery disease (odds ratio 95% confidence interval, 1.4-4.4). Type of heart disease was not a significant factor in predicting occult CAS. Direct cost of the screening, including community outreach, nurses, technicians, support staff, and miscellaneous expenses, was less than $75 per patient. CONCLUSIONS: In a screening program for treatable causes of potential stroke, CAS was the most commonly diagnosed disease. More than one of every five patients with known hypertension and heart disease had occult CAS. Known heart disease of any type was a significant independent predictor of occult CAS. Screening for treatable causes of potential stroke can be cost-effective. This information could help to further target populations to screen for occult CAS and to justify reimbursement for screening carotid duplex scanning examinations.

Aged↗

PubMed1990

Assessment of functional gastrointestinal disease: the bowel disease questionnaire.

A need exists for a self-report questionnaire that reliably and accurately measures symptoms and that distinguishes patients with functional gastrointestinal disease from those with other conditions. We have developed such an instrument, the bowel disease questionnaire, and herein describe details of its discriminatory validity. Data from 399 subjects were analyzed. Patients with gastrointestinal symptoms were ultimately diagnosed as having functional gastrointestinal disease (82 with the irritable bowel syndrome and 33 with functional dyspepsia) or organic gastrointestinal disease (N = 101). There were 145 healthy control subjects and 38 patients with a psychiatric disease, somatoform disorder (which includes those with a diagnosis of hypochrondriasis, psychogenic pain, and somatization or conversion disorder). All subjects completed the questionnaire before undergoing an independent diagnostic assessment by experienced physicians. Functional gastrointestinal disease could be distinguished from organic disease, somatoform disorder, and health by using models derived from logistic discriminant analysis. With use of these models, the estimated probability of functional gastrointestinal disease was then calculated. Descriptive symptom scores were of less value than the scores derived from the data sets by logistic discriminant analysis. Age did not significantly affect the responses to the questionnaire items. We conclude that, in the population studied, the bowel disease questionnaire is a valid measure of symptoms of functional gastrointestinal disease, and this instrument may have clinical and research applications.

Adult↗

PubMed1999

Ischemic heart disease after mantlefield irradiation for Hodgkin's disease in long-term follow-up.

BACKGROUND AND PURPOSE: In patients with Hodgkin's disease treated by radiotherapy with a moderate total dose and a low (mean) fraction dose to the heart, the risk of ischemic heart disease was investigated during long-term follow-up. MATERIALS AND METHODS: The medical records of 258 patients treated in the period 1965-1980 with radiotherapy alone as the primary treatment were reviewed. The median follow-up was 14.2 years (range 0.7-26.2). The mean total dose and fraction dose to the heart were 37.2 Gy (SD 2.9) and 1.64 Gy (SD 0.09), respectively. The impact on the development of ischemic heart disease of treatment-related parameters, such as the applied (fraction) dose, irradiation technique (one or two fields per day), and chemotherapy in case of a relapse, was investigated. The incidence of ischemic heart disease in this patient population was compared with the expected incidence based on gender, age and calendar period-specific data for the Dutch population. RESULTS: Thirty-one patients (12%) experienced ischemic heart disease (actuarial risk at 20-25 years: 21.2% (95% C.I. 15-30). Twenty-five of them were hospitalized. When compared with the expected incidence, the relative risk (RR) of hospital admission for ischemic heart disease was 2.7 (95% C.I. 1.7-4.0). There were 12 deaths (4.7%) due to ischemic myocardial or sudden death (actuarial risk at 25 years: 10.2% (95% C.I. 5.3-19), compared to 2.3 cases that were expected to have died from these causes, yielding a standardized mortality ratio (SMR) of 5.3 (95% C.I. 2.7-9.3). Gender (male), pretreatment cardiac medical history and increasing age appeared to be the only significant factors for the development of ischemic heart disease. CONCLUSIONS: Despite the moderate total dose and the low (mean) fraction dose to the heart, the observed incidence of ischemic heart disease is high, especially after long follow-up periods. Treatment related cardiac disease in patients treated for Hodgkin's disease has only been reported for doses above 30 Gy. Although the optimum curative dose is still under debate, some studies recommend a dose as low as 32.5 Gy. The observed high rate of severe heart complications in this study advocates a dose reduction to this level, particularly in the regions where the coronary arteries are located.

Adolescent↗

PubMed1997

Screening for Wilson's disease in patients with liver diseases by serum ceruloplasmin.

BACKGROUND/AIMS: A low serum ceruloplasmin level is considered a diagnostic test for Wilson's disease. To examine whether it is useful to detect presymptomatic patients with Wilson's disease, serum ceruloplasmin was determined by radial immunodiffusion (normal: 20-60 mg/dl) in all patients (n = 2867) admitted for evaluation of a liver disease in 1993 and 1994. METHODS: Patients with levels lower than 20 mg/dl were further evaluated by determination of serum copper concentration, urine copper excretion and ophthalmological examination. If possible, a liver biopsy was performed and the hepatic copper content was determined by flame atomic absorption spectroscopy. RESULTS: Seventeen patients had serum ceruloplasmin levels < 20 mg/dl. One had asymptomatic Wilson's disease (no Kayser-Fleischer rings or neurological symptoms). In the other 16 patients Wilson's disease was excluded. Based on elevated hepatic copper concentration, there were considered as heterozygous carriers of the WD gene. The remaining patients had various liver diseases (acute viral hepatitis in three, chronic hepatitis in two, drug-induced liver disease in three, alcoholic induced liver disease in two) or malabsorption (n = 3). CONCLUSIONS: The positive predictive value of low serum ceruloplasmin was only 5.9%. Although helpful for identifying presymptomatic Wilson's disease, screening by determination of serum ceruloplasmin in unselected patients with clinical or laboratory evidence of liver disease is neither feasible nor cost effective.

Adult↗

PubMed2000

The pattern of neurodegeneration in Huntington's disease: a comparative study of cannabinoid, dopamine, adenosine and GABA(A) receptor alterations in the human basal ganglia in Huntington's disease.

In order to investigate the sequence and pattern of neurodegeneration in Huntington's disease, the distribution and density of cannabinoid CB(1), dopamine D(1) and D(2), adenosine A(2a) and GABA(A) receptor changes were studied in the basal ganglia in early (grade 0), intermediate (grades 1, 2) and advanced (grade 3) neuropathological grades of Huntington's disease. The results showed a sequential pattern of receptor changes in the basal ganglia with increasing neuropathological grades of Huntington's disease. First, the very early stages of the disease (grade 0) were characterized by a major loss of cannabinoid CB(1), dopamine D(2) and adenosine A(2a) receptor binding in the caudate nucleus, putamen and globus pallidus externus and an increase in GABA(A) receptor binding in the globus pallidus externus. Second, intermediate neuropathological grades (grades 1, 2) showed a further marked decrease of CB(1) receptor binding in the caudate nucleus and putamen; this was associated with a loss of D(1) receptors in the caudate nucleus and putamen and a loss of both CB(1) and D(1) receptors in the substantia nigra. Finally, advanced grades of Huntington's disease showed an almost total loss of CB(1) receptors and the further depletion of D(1) receptors in the caudate nucleus, putamen and globus pallidus internus, and an increase in GABA(A) receptor binding in the globus pallidus internus. These findings suggest that there is a sequential but overlapping pattern of neurodegeneration of GABAergic striatal efferent projection neurons in increasing neuropathological grades of Huntington's disease. First, GABA/enkephalin striatopallidal neurons projecting to the globus pallidus externus are affected in the very early grades of the disease. Second, GABA/substance P striatonigral neurons projecting to the substantia nigra are involved at intermediate neuropathological grades. Finally, GABA/substance P striatopallidal neurons projecting to the globus pallidus internus are affected in the late grades of the disease. In addition, the finding that cannabinoid receptors are dramatically reduced in all regions of the basal ganglia in advance of other receptor changes in Huntington's disease suggests a possible role for cannabinoids in the progression of neurodegeneration in Huntington's disease.

Aged↗

PubMed2001

Principles behind definitions of diseases--a criticism of the principle of disease mechanism and the development of a pragmatic alternative.

Many philosophers and medical scientists assume that disease categories or entities used to classify concrete cases of disease, are often defined by disease mechanisms or causal processes. Others suggest that diseases should always be defined in this manner. This paper discusses these standpoints critically and concludes that they are untenable, not only when 'disease mechanism' refers to an objective mechanism, but also when 'mechanism' refers to a pragmatically demarcated part of the total "objective" causal structure of diseases. As an alternative to principles that use the concept of disease mechanism or analogous concepts, a pragmatic approach is suggested and described. This approach has been suggested before, but in problematic or inadequate versions. This paper proposes a version compiled of two "pragmatic principles" and shows that they are much more adequate than the principle of disease mechanism. With reference to a case study of a still ongoing international discussion of various candidates for a classification system for malignant lymphomas, including REAL (Revised European-American Classification of Lymphoid Neoplasms) in which the concept of disease mechanism or analogous concepts plays a very small part, it is shown just how pivotal these two pragmatic principles can be in actual discussions of definitions of diseases. Finally, it is pointed out that with regard to modern philosophy of language it may, at least in some cases, be problematic to distinguish between the two pragmatic principles as they stand.

Bioethics↗