Prevalence of neuropsychiatric syndromes in Alzheimer's disease (AD)

This study aimed to estimate the prevalence and explore the multidimensional complexity of the neuropsychiatric syndromes of AD. Neuropsychiatric symptoms and syndromes of 216 subjects with probable and possible AD diagnosed by NINCDS-ADRDA criteria were evaluated by the Korean version of behavior rating scale for dementia (BRSD-K). The prevalence rate of six neuropsychiatric syndromes (depressive symptoms, inertia, vegetative symptoms, irritability/aggression, behavioral dysregulation, psychotic symptoms) and comorbid neuropsychiatric syndromes were calculated according to the Clinical Dementia Rating scale. To investigate the relationship among neuropsychiatric syndromes, logistic regression analyses were performed. About 95% of patients with AD had one or more neuropsychiatric symptoms and syndromes during the past month. Among the neuropsychiatric syndromes, irritability/aggression (76.2%) was the most frequent, followed by apathy (72.3%) and depressive symptoms (68.0%). About 90% of the subjects had one or more comorbid neuropsychiatric syndromes. The mean numbers of comorbid neuropsychiatric syndromes were significantly varied according to the severity of disease (p < 0.05). Depressive symptoms were significantly associated with vegetative symptoms and irritability/aggression (p < 0.05). Inertia and psychotic symptoms were significantly associated with vegetative symptoms and behavioral dysregulation, respectively (p < 0.05). This study demonstrated that neuropsychiatric syndromes of AD were highly prevalent and involved complex relationships among them.     

Hypoglycemia associated with liver disease and ethanol

The liver is key to glucose homeostasis. Any disruption of its metabolism, structural integrity, or intracellular dynamics may alter the liver's ability to maintain normal glucose homeostasis. When such disruption affects hepatic glucose output, hypoglycemia may eventuate. Multiple drugs including alcohol may alter the intrahepatic pathways that are vital for normal glucose production by the liver. Spontaneous hypoglycemia always warrants an evaluation of hepatic function and a careful scrutiny of medications that affect hepatic structural or biochemical integrity.     

Genetic basis of syndromes associated with congenital heart disease

Numerous syndromes affecting patients have phenotypes that include congenital heart defects (CHDs). These disorders have fascinated physicians for many years, raising questions about how seemingly disparate aspects of human development can be perturbed together in striking, but consistent, ways. Paralleling the major advances in human genetics during recent decades, we have come to understand that some of these syndromes arise from gross defects in chromosomal number, some from subtler alterations in genomic regions, and still others from point mutations in specific genes. These disorders, largely mendelian in nature, have provided researchers with the wherewithal to discover disease genes underlying CHD. Although some of these medical conditions are relatively rare, their solution has often provided insights that could be applied toward understanding the basis of nonsyndromic CHD. In this review, recent progress toward uncovering the molecular basis of several forms of syndromic CHD is discussed.     

Clinical syndromes of alcoholic liver disease

BACKGROUND AND AIMS: Alcoholic liver disease continues to be a major health problem with respect to both morbidity and mortality. To understand the clinical syndromes of alcoholic liver disease, this review highlights the papers on both clinical and basic research of alcoholic liver disease, especially on steatosis, alcoholic hepatitis and fibrosis. METHODS: The various forms of alcoholic liver disease are described, and knowledge about the clinical and pathophysiological features of different stages of alcoholic liver disease are summarized. RESULTS: Clinical studies combined with basic research have established a spectrum of alcoholic liver disease from steatosis to steatohepatitis, fibrosis, and cirrhosis. New insights into the pathogenesis of alcoholic liver disease include the key roles of the excess production of cytokines, reactive oxygen species, and the shortage of protective mediators, including adiponectin. CONCLUSION: These new insights will lead to new specific therapies for the treatment of alcoholic hepatitis and alcoholic liver fibrosis.     

Pancreatitis associated with alcoholic liver disease

The prevalence with which alcoholic pancreatitis is associated with alcoholic liver disease is unclear. To investigate this association further, we have reviewed the autopsy findings of 1022 patients who died from alcoholic liver disease and compared these findings with those from 352 patients who died from cardiac or pulmonary disease. All patients who died from liver disease had a history of chronic alcoholism with clinical and biochemical evidence of severe liver damage. Death resulted from hepatic coma, gastrointestinal bleeding, or infection. Liver disease patients were classified into two groups: (1) those with cirrhosis (77%) and (2) those without cirrhosis but with acute and/or chronic sclerosing hyaline necrosis (23%). Anatomic and histopathologic changes characteristic of chronic pancreatitis were found in 203 patients in approximately the same frequency (20% and 18%, respectively) in both groups. Acute pancreatitis without chronic lesions was observed in 8% and 10% of both groups, respectively. In the control group of 352 autopsies (122 cardiac and 230 pulmonary patients), the overall prevalence of pancreatitis, at 2.6%, was significantly (P<0.001) lower than that observed in the alcoholic liver disease groups. A total of 22 cases (50%) dying from acute or chronic sclerosing hyaline necrosis had severe chronic calcifying pancreatitis compared to 29 patients (18%) (P<0.001) dying from cirrhosis. By contrast, dense fibrosis was significantly (P<0.001) more commonly observed in patients with cirrhosis. We conclude that pancreatitis occurs frequently in patients dying from alcoholic liver disease but is an uncommon finding in patients dying from other causes. Biliary tract pathology was more prevalent (P<0.05) in patients dying from cirrhosis without pancreatitis than those patients dying from liver disease with pancreatitis. In the control group of patients dying from pulmonary or cardiac disease, biliary pathology was far less frequently (P<0.01) observed.     

Thrombocytopenia associated with chronic liver disease

Thrombocytopenia (platelet count <150,000/microL) is a common complication in patients with chronic liver disease (CLD) that has been observed in up to 76% of patients. Moderate thrombocytopenia (platelet count, 50,000/microL-75,000/microL) occurs in approximately 13% of patients with cirrhosis. Multiple factors can contribute to the development of thrombocytopenia, including splenic platelet sequestration, bone marrow suppression by chronic hepatitis C infection, and antiviral treatment with interferon-based therapy. Reductions in the level or activity of the hematopoietic growth factor thrombopoietin (TPO) may also play a role. Thrombocytopenia can impact routine care of patients with CLD, potentially postponing or interfering with diagnostic and therapeutic procedures including liver biopsy, antiviral therapy, and medically indicated or elective surgery. Therapeutic options to safely and effectively raise platelet levels could have a significant effect on care of these patients. Several promising novel agents that stimulate TPO and increase platelet levels, such as the oral platelet growth factor eltrombopag, are currently in development for the prevention and/or treatment of thrombocytopenia. The ability to increase platelet levels could significantly reduce the need for platelet transfusions and facilitate the use of interferon-based antiviral therapy and other medically indicated treatments in patients with liver disease.     

Lymphopenia is associated with neuropsychiatric manifestations and disease activity in paediatric systemic lupus erythematosus patients

OBJECTIVES: To investigate if lymphopenia is associated with clinical manifestations, disease activity and prognosis in systemic lupus erythematosus (SLE). METHODS: The charts of 186 paediatric patients with SLE diagnosed between 1985 and 2006 in a medical centre were retrospectively reviewed. Lymphocyte counts were recorded at the time of SLE diagnosis and SLE flares. Global disease activity was quantified by the SLE Disease Activity Index (SLEDAI). Cumulative organ damage was assessed by the ACR/Systemic Lupus International Collaborating Clinics (SLICC) damage index. RESULTS: Lymphopenia (<1500/mm(3)) and marked lymphopenia (<500/mm(3)) was observed in 62.8 and 12.2% at the time of SLE diagnosis. At the time of SLE diagnosis, lymphopenia was significantly associated with oral ulcers, leucopenia, anti-dsDNA antibodies and C4 decrease. At the time of flares, lymphopenia was significantly associated with anti-dsDNA antibodies, methylprednisolone pulse therapy, disease activity and organ damage. Using multivariate logistic regression, marked lymphopenia was independently associated with neuropsychiatric manifestations [odds ratio (OR) 7.41, 95% confidence interval (CI) 1.99-27.0], and protective from LN (OR 0.13, 95% CI 0.03-0.53). CONCLUSIONS: Lymphopenia at SLE flares is associated with disease activity and organ damage. Marked lymphopenia is independently associated with neuropsychiatric manifestations.     

慢性肝病伴糖尿病:再行审视

约100年前,即在1906年,已经发现肝硬化患者可伴糖尿病.在20世纪前半期,已将此种合并情况称为肝源性糖尿病(hepatogenous diabetes).嗣后,随着肝病研究进展,见到多种临床慢性肝病常伴糖尿病或糖耐量异常.过程中不时有学者以"肝源性糖尿病"为题研究肝硬化或各种慢性肝病与糖尿病的关系.     

Cholestatic liver disease associated with diphenylhydantoin therapy

Summary A ten-year-old boy presented with a prolonged cholestatic liver disease 5 weeks after starting diphenylhydantoin therapy. The initial phase of his illness was characterized by hepatocellular damage with swollen liver cells and centrilobular cholestasis. Severe hyperlipoproteinemia with eruptive xanthomata developed within 3 weeks of his initial jaundice. The second phase of his illness was characterized by portal tract inflammation with bile ductular proliferation and chronic cholestasis gradually resolving over a period of 15 months.It is postulated that diphenylhydantoin sensitivity produced swollen hepatocytes with hypertrophy of the smooth endoplasmic reticulum, reducing hepatic sinusoidal blood flow and the clearance of secondary bile salts. A fall in clearance of lipoproteins, including the cholesterol precursor of primary bile acid synthesis, may have been responsible for a reduction in serum bile acid concentration. High levels of serum lithocholic acid, largely unsulfated presumably due to decreased hepatic uptake, may have produced the prolonged second phase of this illness when histological changes resembled that seen in experimental animals following lithocholic acid administration.     

IgM anti-histone H-3 antibody associated with undifferentiated rheumatic disease syndromes

A distinctive type of speckled antinuclear antibody staining pattern was identified by indirect immunofluorescence on mouse kidney substrate in 4.8% of 5,976 specimens analyzed for antinuclear antibodies. This pattern, termed variable large speckles (VLS), consisted of 3-10 nuclear speckles ranging in size from approximately 0.2-2.0 mu. The pattern could be differentiated from other indirect immunofluorescence patterns related to specific antibodies. The predominant immunoglobulin isotype demonstrating the VLS pattern was IgM in 27 of 28 sera examined and IgG in 1 serum. VLS sera had substantial IgM antibodies to histone demonstrated by enzyme immunoassay, and further analysis of representative sera showed predominant antibody activity to histone class 3 (H-3). Adsorption with histone H-3 resulted in decrease or removal of antibody producing the VLS pattern. Available information showed that most patients with IgM antibodies of the VLS pattern had undifferentiated connective tissue disease symptoms. They were characterized by a heterogeneity of chronic symptoms including arthralgias, myalgias, inflammatory polyarthritis, myositis, sicca symptoms, and pleurisy associated with elevation of the erythrocyte sedimentation rate. It remains to be determined whether the IgM anti-histone H-3 profile of these patients is a transient or long-standing serologic characteristic.     

The prevalence of vascular occlusive disease associated with antiphospholipid syndromes.

The association of anticardiolipin antibodies (aCL) with unexplained vascular occlusive disease (VOD) is well known. We reviewed the records of 102 consecutive patients seen over a 9 months period who had positive IgG or IgM aCL to determine the frequency and types of VOD in this unselected group of patients. Lupus anticoagulant was detectable in 17 of 67 (25%) patients tested. VOD occurred in 80 of 102 (78%) aCL-positive patients comprised of 17 (16.7%) with systemic venous VOD or pulmonary embolism; 27 (26.5%) with cerebral VOD: 11 (10.8%) with systemic arterial VOD; 3 (2.9%) with coronary thrombosis; and 5 (4.9%) with visceral venous or arterial VOD. Of the 19 obstetric patients with positive aCL, 17 (89%) had at least one unexplained fetal loss and 8 of the 17 (47%) had multiple or recurrent fetal losses. Twelve (11.7%) of the 102 patients met the ACR criteria for systemic lupus erythematosus (SLE). Additionally, 12 (11.7%) patients were identified as nonSLE or undifferentiated connective tissue disease (CTD). The remaining 78 (76%) had no known underlying disease (primary antiphospholipid syndrome). We conclude that IgG and IgM aCL with or without lupus anticoagulant are associated with diverse types of VOD but cerebral VOD appears predominant. aCL-associated unexplained VOD occurs frequently in patients without evidence of CTD-65 of 80 (81%) in our series. Testing for aCL is essential for identifying patients with unexplained VOD, and it should be performed in prospective clinical studies of such patients to better define the pathogenic role of aCL in the natural history of unexplained VOD.     

Atorvastatin associated liver disease

Atorvastatin, a HMG-CoA reductase inhibitor, is widely used in the treatment of dyslipidaemia. A transient rise in serum transaminases occurs in up to 3% of patients using atorvastatin but this is usually self-limiting and inconsequential. Recent literature has indicated some potential for more serious but rare idiosyncratic reactions related to this drug. Seven patients with significant liver dysfunction from one centre during 2002-2005 are reported, with one death, that raises some concern over the safety of atorvastatin. A total of seven other patients are reported in the literature. The 14 patients were usually over 60 years, had a female:male ratio of 2:1 and showed a mixed cholestatic/hepatocellular reaction. The mean interval to onset of reaction was approximately 9 weeks and the liver often took several months to recover. Three deaths occurred. Adverse drug reaction reports from the UK Committee on Safety of Medicines reveal that four deaths due to hepatobiliary disease (0.5 deaths per annum) have been reported in association with atorvastatin treatment over 8 years. Simvastatin has had no hepatobiliary-related fatalities reported over 15 years. While acute hepatotoxicity with atorvastatin remains uncommon, any persistent abnormality in liver function should be treated with caution.