PPAR-γ in Cushing's Disease

The majority of pituitary tumors that cause Cushing's disease are small (<1 cm diameter), and most disease morbidity is due to the effects of elevated, non-suppressible, ACTH levels that these tumors secrete. Tumor-derived ACTH leads to adrenal-derived steroid hypersecretion and results in many disabling and sometimes life-threatening symptoms including abnormal fat deposition, skin thinning, psychological disturbances, hypertension, diabetes, osteoporosis and muscle weakness. Cushing's disease is associated with high morbidity and ultimately mortality. In experienced specialized centers, 70% of corticotroph microadenomas can be successfully resected by transsphenoidal pituitary surgery. However, surgical “cure” rates for larger ACTH-secreting pituitary tumors are achieved in only 30% of cases, and recent reports highlight a significant recurrence rate after longer term follow-up even in smaller tumors. Post-surgical persistence of ACTH hypersecretion may require pituitary-directed radiation, but this treatment may take some time to be effective, and like extensive surgical pituitary tumor resection, ultimately leads to partial- or total hypopituitarism in ∼80% of cases. Although hypercortisolism may be completely resolved by adrenalectomy, this procedure does not suppress, and may act as a stimulus to pituitary tumor growth, and is associated with other co-morbidity. Although some currently available drug-based treatments for Cushing's disease effectively control hypercortisolism, their drawback has been that they do not impact on pituitary tumor growth. Recent studies have identified the potential utility of peroxisome-proliferator activating receptor-gamma (PPAR-γ) novel ligands in in vitro, and in vivo Cushing's disease models, and have paved the way for early clinical studies to develop novel therapeutic approaches in Cushing's disease.     

Unsuspected Coeliac Disease in Chronic ‘Cryptogenic’ Liver Disease

Lindgren S, Sjöberg K, Eriksson S. Unsuspected coeliac disease in chronic 'cryptogenic' liver disease. Scand J Gastroenterol 1994;29:661-664

Background: Earlier reports have suggested that a relationship exists between chronic liver disease and coeliac disease (CD). Gliadin antibodies (GA) have been used to screen for CD.

Methods: Using a micro-enzyme-linked immunosorbent procedure, we analysed sera from 327 consecutive patients with chronic liver disease for GA (IgA and IgG) and evaluated their clinical significance.

Results: GA were detected in 19 patients (6%), a prevalence six times greater than that found in healthy blood donors. In 9 of the 19 patients the liver disease had been classified as cryptogenic. The occurrence of GA was independent of the degree of hepatocellular impairment. A diagnosis of CD was confirmed in 5 of the 10 patients who underwent small-bowel biopsy.

Conclusions: Our findings suggest the prevalence of CD in patients with chronic liver disease to be at least 1.5%–that is, 15 times higher than in the general population. They also suggest that the possible presence of CD should be considered in cases of chronic 'cryptogenic' liver disease.     

Study of Coronary Artery Disease in Single Aortic Valvular Disease

Objectives To analyze the results of coronary angiographies (CAG) in patients with single aortic valvular heart disease; To study the relationship between aortic valve diseases and coronary artery disease (CAD). Methods 105 patients with single aortic valvular heart disease before surgery underwent angiography. The data of clinical characteristics and angiographies were analyzed. Results 51 patients had symptoms of angina pectoris among 105 patients with single aortic valvular heart disease. Seven of them were confirmed coronary artery disease by angiographies. Although the incidence of angina in aortic valve stenosis group was significantly higher than that in aortic valve regurgitation, the probability of combination of CAD in aortic valve stenosis group was similar to the later. However, the probability of combination of CAD in degenerative aortic valve group was significantly higher than the groups of rheumatic, congenitally bicuspid aortic valves, and other causes (p < 0.01 ). Conclusions Angina pe     

Is Nonalcoholic Fatty Liver Disease in Children the Same Disease as in Adults?

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children, and can present in toddlerhood. There is a differential distribution of NAFLD in children based on race and gender. The gold standard for diagnosis and classification of pediatric NAFLD is liver biopsy although ongoing studies aim to identify and define noninvasive investigations for pediatric NAFLD. Treatments that have been shown to be successful in adult NAFLD, such as insulin sensitizers and Vitamin E, have not been proven to be as definitively successful in children with NAFLD.     

Dysphagia in Parkinson’s Disease

More than 80 % of patients with Parkinson’s disease (PD) develop dysphagia during the course of their disease. Swallowing impairment reduces quality of life, complicates medication intake and leads to malnutrition and aspiration pneumonia, which is a major cause of death in PD. Although the underlying pathophysiology is poorly understood, it has been shown that dopaminergic and non-dopaminergic mechanisms are involved in the development of dysphagia in PD. Clinical assessment of dysphagia in PD patients is challenging and often delivers unreliable results. A modified water test assessing maximum swallowing volume is recommended to uncover oropharyngeal dysphagia in PD. PD-specific questionnaires may also be useful to identify patients at risk for swallowing impairment. Fiberoptic endoscopic evaluation of swallowing and videofluoroscopic swallowing study are both considered to be the gold standard for evaluation of PD-related dysphagia. In addition, high-resolution manometry may be a helpful tool. These instrumental methods allow a reliable detection of aspiration events. Furthermore, typical patterns of impairment during the oral, pharyngeal and/or esophageal swallowing phase of PD patients can be identified. Therapy of dysphagia in PD consists of pharmacological interventions and swallowing treatment by speech and language therapists (SLTs). Fluctuating dysphagia with deterioration during the off-state should be treated by optimizing dopaminergic medication. The methods used during swallowing treatment by SLTs shall be selected according to the individual dysphagia pattern of each PD patient. A promising novel method is an intensive training of expiratory muscle strength. Deep brain stimulation does not seem to have a clinical relevant effect on swallowing function in PD. The goal of this review is giving an overview on current stages of epidemiology, pathophysiology, diagnosis, and treatment of PD-associated dysphagia, which might be helpful for neurologists, speech-language therapists, and other clinicians in their daily work with PD patients and associated swallowing difficulties. Furthermore areas with an urgent need for future clinical research are identified.     

Brainstem Involvement in Legionnaires’ Disease

Abstract Objective: To report a case of Legionella pneumonia with unusual neurologic involvement. Intervention: Chest X-ray, lumbar puncture, magnetic imaging of the brain, electroencephalography, audiometry, brainstem acustic evoked potentials and institution of oral antibiotics and steroids. Main Result: Gradual clinical improvement of neurologic and pulmonary illness within 4 weeks. Conclusion: Legionellosis should be considered in the differential diagnosis of neurologic involvement in the setting of pneumonia.     

Assessment of Endothelial Function in Alzheimer's Disease: Is Alzheimer's Disease a Vascular Disease?

OBJECTIVES: To compare endothelial function of people with Alzheimer's disease (AD) with that of people without. DESIGN: Case-control study. SETTING: Geriatric medicine outpatient clinic of a university hospital. PARTICIPANTS: Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment. MEASUREMENTS: Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery. RESULTS: Mean age +/- standard deviation was 78 +/- 5.9 in the group with AD (11 female and 14 male) and 72.1 +/- 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0-7) than controls (median 8.41, range 1-14) (P < .001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=-0.603, P < .001). CONCLUSION: Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.     

Lymphocyte-Platelet Crosstalk in Graves’ Disease

ObjectivePlatelets can modulate lymphocytes’ role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves’ disease (GD).MethodsOne hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation.ResultsThe group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3 +, HLA-DR + lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10³ cells/μL) than TMG group (251 ± 97 × 10³ cells/μL; P < 0.05) and control group (262 ± 95 × 10³ cells/μL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /μL) were found than that in TMG group (116 ± 67/μL, P < 0.005) and control group (104 ± 58 /μL; P < 0.001).ConclusionsGD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.     

Impaired Sleep Quality in Crohn’s Disease Depends on Disease Activity

Background

Little is known concerning the relationship of disease activity and sleep disturbances in inflammatory bowel disease (IBD) and specifically in patients with Crohn’s disease.

Aim

This study examined the prevalence of poor sleep quality in patients with active and inactive Crohn’s disease compared with healthy controls.

Methods

Participants included 108 patients with Crohn’s disease attending the IBD clinic of a tertiary medical center in 2009–2010 and 36 healthy volunteers. All prospectively completed a demographic questionnaire and the Pittsburgh sleep quality index (PSQI). Patients with Crohn’s disease completed the Crohn’s disease activity index (CDAI) and were divided into two groups accordingly: inactive disease (CDAI ≤150) and active disease (CDAI >150). Data on disease duration, medications, complications, and treatment were collected from the medical files.

Results

Seventy-one patients had inactive Crohn’s disease and 37 had active disease. All three groups were similar in mean age, sex distribution, and body mass index. Mean duration of Crohn’s disease was 10.22 ± 8.6 years; 40 patients (37 %) had ileal disease, 16 (15 %) colonic disease, and 56 (50 %) ileo-colonic disease. Patients with active disease had a significantly higher mean ± SD global score on the PSQI (8.6 ± 2.4; indicating poorer sleep quality) than patients with inactive disease (4.6 ± 1.9) or control subjects (5.1 ± 1.7) (p < 0.0001 for both), with no significant difference between the inactive-disease and control groups. The correlation between the CDAI and PSQI scores was statistically significant (p < 0.001).

Conclusions

Impaired sleep quality is associated with active Crohn’s disease, but not inactive disease.     

Prevalence of Celiac Disease Among Patients with Behcet’s Disease in Iran

Background Behcet's disease and Celiac disease, both common in Iran, share many immunopathogenic and clinical features. Based on the possible association between these two diseases, this study is designed to determine the frequency of non-diagnosed celiac disease in patients with Behcet’s disease. Methods The sera of 288 consecutive patients with Behcet’s disease were screened with anti-endomysial antibody and anti-tissue transglutaminase antibody for celiac disease. Those with a positive test underwent upper gastrointestinal endoscopy and duodenal biopsies to confirm the diagnosis of celiac disease. The patients with celiac disease were put on a gluten free diet to evaluate its efficacy on the improvement of their lesions. Results Fourteen patients had positive anti-tissue transglutaminase antibody test (two with positive anti-endomysial antibody as well). Duodenal biopsies showed findings compatible with Marsh 3 in one and Marsh 1 in three other patients. All the diagnosed patients with celiac disease responded to the gluten free diet. Conclusion Our findings didn’t support any association between celiac disease and Behcet’s disease in Iranian patients compared to the general population of Iran.     

Rheumatic Heart Disease in Pregnancy: New Strategies for an Old Disease?

RHD in pregnancy (RHD-P) is associated with an increased burden of maternal and perinatal morbidity and mortality. A sequellae of rheumatic fever resulting in heart valve damage if untreated, RHD is twice as common in women. In providing an historical overview, this commentary provides context for prevention and treatment in the 21 st century.Four underlying themes inform much of the literature on RHD-P: its association with inequities; often-complex care requirements; demands for integrated care models, and a life-course approach. While there have been some gains particularly in awareness, strengthened policies and funding strategies are required to sustain improvements in the RHD landscape and consequently improve outcomes.As the principal heart disease seen in pregnant women in endemic regions, it is unlikely that the Sustainable Development Goal 3 target of reduced global maternal mortality ratio can be met by 2030 if RHD is not better addressed for women and girls.     

Circulating Cell-Derived Microparticles in Crohn’s Disease

Procoagulant membrane microparticles can be released from activated or apoptotic cells in response to various environmental stimuli. The aim of this study was to investigate the presence of microparticles in Crohns disease and to assess their variations after infliximab therapy. We compared the levels of circulating microparticles in 38 patients with Crohns disease, 16 patients with ulcerative colitis, 7 patients with infectious colitis, and 17 control subjects. The evolution of microparticle levels was assessed after infliximab therapy in 13 patients with Crohns disease. Circulating microparticle levels were elevated in patients with Crohns disease (9.31 ± 0.66 nmol/L phosphatidylserine equivalent [PS Eq]) or infectious colitis (10.71 ± 0.92 nmol/L PS Eq) compared to patients with ulcerative colitis (5.75 ± 0.59 nmol/L PS Eq) and control subjects (4.06 ± 0.37 nmol/L PS Eq) (P = 0.001). Infliximab induced a significant diminution of the amounts of circulating microparticles, from 10.33 ± 1.20 to 6.45 ± 0.90 nmol/L PS Eq (P = 0.002). Generation of circulating microparticles occurs in Crohns disease; infliximab induces significant diminution. Release of microparticles could be linked to the type of inflammatory response underlying Crohns disease.     

Usefulness of C-Reactive Protein as a Disease Activity Marker in Crohn’s Disease according to the Location of Disease

Background/Aims

C-reactive protein (CRP) is a serologic activity marker in Crohn’s disease (CD), but it may be less useful in evaluating CD activity in ileal CD patients. We aimed to investigate the usefulness of CRP as a disease activity marker in CD according to disease location.

Methods

Korean CD patients in a single hospital were evaluated. Factors associated with elevated CRP concentration at the time of diagnosis of CD and the association between the physician’s prediction regarding upcoming surgery and the sites of the lesions directly related to surgery were analyzed.

Results

Of 435 CD patients, 25.7%, 6.9%, and 67.4% had ileal, colonic, and ileocolonic CD, respectively. Multivariate analysis revealed that an elevated erythrocyte sedimentation rate, reduced serum albumin, CD activity index (CDAI) >220, and ileocolonic/colonic location were associated with an elevated CRP level and that the CRP level was significantly correlated with the CDAI in all CD patients (γ=0.466, p<0.01). However, the correlation coefficient was dependent on the location, with values of 0.395, 0.456, and 0.527 in patients with an ileal, ileocolonic, and colonic disease location, respectively. Surgery for ileal lesions was less predictable than surgery for ileocolonic or colonic lesions during follow-up.

Conclusions

CRP is less useful as a disease activity marker in patients with ileal CD than those with ileocolonic or colonic CD.