Obesity and thrombotic vascular diseases

Obesity may either be unspecific as indicated by an increased body mass index (BMI) or due to an abnormal fat-distribution as indicated by an increased waist-to-hip ratio (WHR). The latter is frequently associated with deteriorations of glucose tolerance, hypertriglyceridaemia and hypertension (the metabolic syndrome), a syndrome which is among the strongest risk factors of ischemic heart disease. It is important to note that visceral obesity is a frequent feature of the polycystic ovary syndrome. Also, weight gain after menopause is often associated with a particular increase of the WHR. Obesity as indicated by an increased BMI (> 30 kg/m2) is a weak but easily detectable risk marker of venous thrombotic disease. This risk needs to be considered in clinical practice since obesity was shown to enhance the power of precipitating risk factors of venous disease such as pregnancy, surgery or estrogen treatment.     

Environmental stress and biobehavioral antecedents of coronary heart disease.

This article provides an overview of research on the biobehavioral antecedents of coronary heart disease. Attention is given first to evidence that stressful occupational settings characterized by high demands and low levels of control over the job are associated with increased coronary risk. Also discussed is a promising animal primate model of social stress and coronary atherosclerosis. Next, the current status of the Type A behavior pattern is reviewed, with recent evidence suggesting that Type A may not be a potent risk factor in all populations. However, specific Type A components such as hostility as well as mode of anger expression (anger-in) have been related to coronary disease in recent studies. Next discussed is research on physiologic responsiveness (reactivity) to emotional stress, which is being studied as a marker of processes involved in the development of cardiovascular disease. Stress, Type A components, and psychophysiologic reactivity are promising candidates for research on clinical intervention. However, further evidence is needed before stress and reactivity can be regarded as proven risk factors for coronary disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role and long-term results of laparoscopic decortication in solitary cystic and autosomal dominant polycystic kidney disease

PURPOSE: Access to retroperitoneal structures via the laparoscope has become established for various conditions. This minimally invasive approach has distinct advantages over conventional open surgery. We document our experience with laparoscopic cyst decortication for diseases of the kidney, including simple and complex cysts, multiple cysts and autosomal dominant polycystic kidney disease. MATERIALS AND METHODS: We retrospectively reviewed the records of 17 patients who underwent a total of 20 procedures. Cases were categorized as polycystic kidney disease and nonpolycystic kidney disease. Factors analyzed were estimated blood loss, length of surgical procedure, hospital stay and complications. Followup included radiographic studies (computerized tomography and/or renal sonography) and patient subjective pain relief, as determined by clinical records and telephone interview. RESULTS: Nine and 11 procedures were done for nonpolycystic kidney disease and polycystic kidney disease, respectively. Of the 8 patients with polycystic kidney disease 3 underwent repeat procedures. Followup was 3 to 63 months (average 26). All patients with simple cysts who were treated for pain were pain-free at the latest followup. Of the 10 procedures 9 (90%) performed for pain relief in polycystic kidney disease successfully produced immediate pain relief. Pain-free status decreased with time with 7 of 8 (87.5%) pain-free after 6 months, and 5 of 7 (71.4%) at 1, 4 of 6 (66.7%) at 2 and 1 of 4 (25%) at 3 years. A repeat operation successfully relieved recurrent pain in 2 of 3 cases (66.7%). Of the 7 patients with polycystic kidney disease who underwent surgery for pain relief 5 (71%) are currently pain-free. CONCLUSIONS: Laparoscopic renal cyst decortication is an effective minimally invasive treatment for painful simple cysts. It is also effective for short to intermediate pain relief in autosomal dominant polycystic kidney disease. Long-term followup suggests that a repeat procedure may be necessary to maintain adequate control of symptoms in polycystic kidney disease.     

Osteolytic form of Paget's disease. Differential diagnosis and pathogenesis

Of fourteen patients with Paget's disease for whom adequate roentgenograms and pathological material were available, six had lesions showing significant or predominant osteolysis. Based on a study of these six patients and a review of the literature, the following mechanisms were identified as causes of the so-called osteolytic type of the disease: (1) an "early" destructive Paget's lesion; (2) "advanced" Paget's disease with secondary degenerative changes; (3) "seeding" of an independent osteolytic lesion, particularly tumor in pre-existing Paget's disease; (4) sarcomatous transformation; and (5) immobilization after fracture. An osteolytic lesion in a patient without other bone disease may be due to Paget's disease, while an associated lytic lesion may be the result of a variety of conditions. Accurate pathological diagnosis is essential.     

Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans' cell histiocytosis

Langerhans' cell histiocytosis (LCH) is a disease with an unpredictable course and unpredictable reactivations. Since active disease may cause life-long sequelae, early detection of reactivation is important. The usefulness of erythrocyte sedimentation rate (ESR) and thrombocytosis as indicators of disease activity in patients with LCH were examined. The mean values for ESR and platelet count for each quarter of a year were compiled. The means of all the ESR estimates (n = 76) during each quarter of a year with active disease was 21 mm h(-1), with intermediate disease activity 11 mm h(-1) and with resolution 7 mm h(-1). The corresponding platelet count estimates (n = 139) were 433 x 10(9) l(-1), 365 x 10(9) l(-1) and 304 x 10(9) l(-1), respectively. In conclusion, elevated ESR and platelet count may be clinically valuable indicators of disease activity in LCH.     

Lipoprotein(a) and general risk factors in patients with angiographically assessed peripheral arterial disease

High lipoprotein(a) [Lp(a)] has been observed in patients with ischemic heart disease and cerebrovascular disease. Lp(a) is actually thought to be an independent risk factor for coronary disease. We therefore carried out a case-control study, evaluating plasma Lp(a) in 61 patients with angiographically documented peripheral arterial disease (PAD) and in 61 age- and sex-matched patients with no cardiovascular disease. General risk factors for vascular disease were also taken into account. Lp(a) was significantly higher in patients than controls (257.0 +/- 34.8 vs 146.5 +/- 23.5 mg/l p < 0.05), as were cigarette smoking, diabetes, cholesterolemia, fibrinogenemia and the waist-to-hip circumference ratio. Stepwise logistic regression analysis showed that, in addition to cigarette smoking, diabetes, cholesterol and fibrinogen, Lp(a) is a significant independent risk indicator for PAD. This result suggests that high plasma Lp(a) is associated with enhanced risk of PAD and must therefore be evaluated alongside traditional risk factors.     

The composition and structure of depressive symptomatology in renal disease.

Renal disease is an increasingly common illness among middle-aged and older adults, and is often associated with depression. The Center for Epidemiologic Studies Depression Scale (CES–D) is a widely used self-report screening measure on which responses generally conform to a 4-factor structure, with each factor loading onto a higher-order Depression factor. The current study examines whether this structure is supported among individuals with renal disease (both predialysis and posttransplant kidney disease patients). Persons with renal disease (n = 225) and healthy control participants (n = 230) were recruited from Vancouver General Hospital and the community. Participants completed the CES–D as part of an extended assessment. Confirmatory factor analytic models were computed for the renal disease and healthy control groups. Results support a 4-factor structure for CES–D responses in persons with renal disease and healthy controls. The hierarchical structure of CES–D responses also appears invariant between groups. Factor structure was similar between groups; only for Depressive Affect was the strength of association with the second-order factor greater among the renal disease than healthy control participants. Findings support similarity of CES–D factor structures between patients with renal disease and healthy individuals. Results suggest that the CES–D's 4 factors contribute to measurement of a higher-order Depression factor in both groups; furthermore, 3 of 4 factors appear invariant between groups. As such, this measure can be used confidently to quantify depressive symptoms in individuals with renal disease. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Psychoneuroimmunology and HIV-1.

Recent psychoneuroimmunologic findings have suggested that it may be useful to evaluate the influence of behavioral factors on immune functioning and disease progression among human immunodeficiency virus-Type 1 (HIV-1) infected individuals. Behavioral interventions with immunomodulatory capabilities may help restore competence and thereby arrest HIV-1 disease promotion at the earliest stages of the infectious continuum. Evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high-risk HIV-1 seronegative and very early stage seropositive gay men is presented. The HIV-1 infection is cast as a chronic disease for which early immunomodulatory behavioral interventions may have important physical and psychological impact. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Initial response and subsequent course of Crohn's disease treated with elemental diet or prednisolone

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone.     

Esophageal mucosal lesions and scleroderma: prevalence, symptoms and risk factors

There is a strong genetic influence on the susceptibility to celiac disease. Although in the vast majority of patients with celiac disease, the HLA-DQ(alpha1*0501, beta1*0201) heterodimer encoded by the alleles HLA-DQA1*0501 and HLA-DQB1*0201 seems to confer the primary disease susceptibility, it cannot be excluded that other genes contribute to disease susceptibility, as indicated by the difference in concordance rates between monozygotic twins and HLA identical siblings (70% vs. 30%). Obviously other genes involved in the genetic control of T cell mediated immune response could potentially influence susceptibility to celiac disease. The density of T cells using the gammadelta T cell receptor (TCR) is considerably increased in the jejunal epithelium of patients with celiac disease, an abnormality considered to be specific for celiac disease. This suggests an involvement of gammadelta T cells in the pathogenesis of the disease. To ascertain whether the TCR delta (TCRD) gene contributes to celiac disease susceptibility we carried out an association study and genetic linkage analysis using a highly polymorphic microsatellite marker at the TCRD locus on chromosome 14q11.2. The association study demonstrated no significant difference in allele frequencies of the TCRD gene marker between celiac disease patients and controls; accordingly, the relative risk estimates did not reach the level of statistical significance. In the linkage analysis, performed in 23 families, the logarithm of the odds (LOD) scores calculated for celiac disease versus the TCRD gene marker excluded linkage, suggesting that there is no determinant contributing to celiac disease status at or 5 cM distant to the analyzed TCRD gene marker. In conclusion, the results of the present study provide no evidence that the analyzed TCRD gene contributes substantially to celiac disease susceptibility.     

Roles of a neuronal cell-surface molecule, neuropilin, in nerve fiber fasciculation and guidance

PURPOSE: To determine whether infiltrative lung, airway, or vascular disease can be differentiated as the cause of mosaic attenuation on thin-section computed tomographic (CT) scans of the lung. MATERIALS AND METHODS: Thin-section CT scans were reviewed in 70 patients examined at three institutions. A mosaic attenuation pattern and pathologic or clinical proof of a specific type of disease were demonstrated. Causes of the mosaic pattern included infiltrative lung disease (n = 37), airway disease (n = 22), and vascular disease (n = 11). Thin-section CT findings were assessed independently by two observers blinded to clinical findings. RESULTS: The type of disease was identified correctly at CT in 58 (83%) of 70 patients by observer 1 and 57 (81%) of 70 patients by observer 2. Infiltrative lung disease was diagnosed correctly by both observers in 34 (92%) of 37 cases. Observer 1 identified 21 (95%) of 22 cases of airway disease and three (27%) of 11 cases of vascular disease. Observer 2 identified 19 (86%) of 22 cases of airway disease and four (36%) of 11 cases of vascular disease. CONCLUSION: Infiltrative lung disease and airway disease may be differentiated reliably as the cause of mosaic attenuation on lung CT scans, whereas vascular disease is often misinterpreted as infiltrative lung disease or airway disease.     

Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia: relationship to the location of atherosclerotic disease, smoking, and in the prediction of adverse events

We examined the relationship of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) with smoking and hypercholesterolaemia in peripheral artery disease (PAD). Serum samples were obtained from 119 patients with objectively-proven PAD, 39 patients with hypercholesterolaemia but asymptomatic for PAD, and 132 age and sex matched asymptomatic controls. Using ELISAs, we found increased sICAM-1 and sVCAM-1 (both p <0.01) in the patients with PAD relative to the controls, but no significant change in patients with hypercholesterolaemia. However, the effect for sVCAM-1 was lost when smoking was entered as a covariate. Only sICAM-1 was higher in patients with PAD in the femoral/iliac arteries compared to the carotid arteries (p <0.05). In a 39-month follow-up of 112 patients with PAD, increased ICAM-1 weakly (univariate p <0.05) predicted those 57 whose disease progressed (i.e. to end points such as myocardial infarction and arterial surgery). However, high fibrinogen was a much better (univariate p = 0.001, multivariate p <0.05) predictor of disease progression. We suggest (i) that increased levels of sVCAM-1 in atherosclerosis are due to smoking, (ii) that increased sICAM-1 is independent of this risk factor, (iii) that both these changes are independent of hypercholesterolaemia, and (iv) that increased sICAM-1 is a weak predictor of disease progression in peripheral atherosclerosis.     

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods

OBJECTIVES: The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND: Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS: A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS: Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS: In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.     

Expression of apolipoprotein E in normal and diverse neurodegenerative disease brain

Brains from 21 patients with Alzheimer's disease (AD), nine with diffuse Lewy body disease (DLBD), six with progressive supranuclear palsy (PSP) and five with Parkinson's disease (PD) as well as 20 normal subjects were examined to detect apolipoprotein E (ApoE) by immunohistochemistry and immunoblotting. ApoE antigenicity was optimally preserved in Bouin-fixed tissues compared with those fixed in neutral-buffered formalin, 70% ethanol or denatured by microwave energy. ApoE immunoreactivity was prominent in senile plaques and in intra- and extra-neuronal tangles, as well as in a diverse neurones and their processes and astroglial cells. Notably, tangles in PSP and Lewy bodies in PD and DLBD were both devoid of ApoE immunoreactivity. Western blots of cerebral cortex revealed an immunoreactive ApoE band with mol. wt of 34 kDa. Our results suggest that ApoE is not a crucial factor in the development of neuronal inclusions in DLBD, PSP and PD.     

Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegative polyarthritis

The relationships between synovial fluid (SF) interleukin-8 (IL-8) and neutrophil turnover as measured by cytidine deaminase (CD), and SF metabolites were studied in 28 patients, 16 with rheumatoid arthritis (RA; median age and disease duration 62 and 14 yr, respectively) and 12 with seronegative polyarthritis (SNP; median age and disease duration 32 and 5 yr, respectively). Knee SF samples were aspirated using indwelling cannulae following a period of rest for 1 h. SF IL-8 levels (measured by an ELISA) were significantly elevated in RA compared to SNP (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11 U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs 84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001). Measures of disease activity, C-reactive protein, plasma viscosity and articular index were also elevated in RA compared to SNP (P < 0.05). SF IL-8 levels correlated strongly with CD, lactate, glucose and the lactate to glucose ratio when both disease groups were considered together (P < 0.001). These parameters also showed some association with the measures of disease activity (P < 0.05). All these associations were less marked when the individual disease groups were analysed separately. These results suggest that factors responsible for neutrophil accumulation and priming (probably IL-8) are present in SF, and these coincide with products of their activation (CD). The degree of neutrophil turnover is linked to the anaerobic metabolism of the synovial cavity.     

Crohn's disease and intestinal carcinoma: presentation of 2 cases and review of the literature

We present the cases of two patients with Crohn's disease with consequent adenocarcinoma of the bowel. The first patient underwent an ileo-colic bypass 23 years before, a mucinous adenocarcinoma (Duke's stage C) was found on the anastomotic tract and on the excluded bowel, in areas within histologically recognizable Crohn's disease. In the second patient both the adenocarcinoma (Duke's stage C) of the transverse colon and the Crohn's disease (without any clinical evidence) in active phase has been found at the same time. We underline that such association seems to be not so rare as it seemed in the past. Accurate observation of patients, long time sufferers from the Crohn's disease, is advised to single out possible neoplastic complications at an early stage.     

Serum levels of sCD23, interleukin-10 and interferon-gamma in patients with coeliac disease

The role of cellular and humoral immunity coeliac disease was investigated by the measurement of serum levels of interleukin-10 (IL-10), interferon-gamma (IFN-gamma) and soluble CD23 (sCD23). Coeliac disease was diagnosed by duodenal biopsy and response to a gluten-free diet (GFD). The results were compared with age and sex-matched patients with non-specific upper gastrointestinal symptoms and normal duodenal histology. While the levels of serum IL-10 were significantly elevated (P < 0.01) in patients with coeliac disease taken as a whole, the levels of serum IFN-gamma were normal and sCD23 significantly decreased (P < 0.002). The median serum sCD23 was significantly lower in the coeliac disease patients not on a GFD compared with those asymptomatic on a GFD (P < 0.03) and the control group (P < 0.0004). The coeliac disease patients on a GFD also had significantly lower serum sCD23 and higher IL-10 compared with the control group (P < 0.01 and P < 0.015). There was no significant difference in the serum IL-10 between the coeliac disease patients on a GFD and those not on a GFD and between the latter and the control group. The low levels of serum sCD23 in coeliac disease suggest diminished humoral immunity and, conversely, exaggerated cellular immunity. The aetiology of the raised levels of IL-10 in coeliac disease is unclear and similar to that observed in patients with inflammatory bowel disease. However, this may represent a regulatory response to the elevated levels of proinflammatory cytokines described in coeliac disease. A combination of diminished sCD23 and raised IL-10 is clearly unusual as both are associated with Th2-type functions. The possible causes of this finding are discussed.     

Current status of clinical diagnosis and DNA test of von Hippel-Lindau disease in Japan

An outline of the clinical diagnosis including the DNA testing in von Hippel-Lindau (VHL) disease is briefly explained. The current status of the diagnosis and treatment of VHL disease in Japan is also compared with those in European countries. According to the current experience in the world, DNA testing of VHL disease is regarded as one of the important references for the clinical diagnosis of this disease. We have to improve various points in the Japanese status of the clinical diagnosis, genetic counseling, treatment and follow-up in patients with VHL disease.     

Current and future therapies for HCV infection: what should the end point for treatment be?

Based upon all of the available data relating to the natural history, chemical course, and response to therapy of HCV, the following recommendations are made: 1) The primary end point for HCV therapy should be HCV clearance from all tissue sites, eg plasma, liver and others 2) Therapy should be provided for patients with early infections as they have the best chance of achieving a virologic response 3) Therapy should be offered to patients with cirrhotic disease, as prevention of hepatic decompensation and degeneration to hepatic cancer is possible 4) End stage decompensated disease should be treated, particularly if liver transplantation is being considered, in an effort to either eliminate or ameliorate disease recurrence 5) Combination therapies are preferable to monotherapy as they enhance the likelihood of a therapeutic response. Some of these include agents that reduce the frequency of IFN-induced untoward events (NSAIDs) 6) The approach to HCV infection should be to view it as an infectious disease. In this way, multi-agent therapy could be used to prevent the emergence of drug resistant mutants as well as to obtain earlier clearance of the infection than is possible with monotherapy.