Immunomodulation of autoimmune and inflammatory diseases with intravenous immunoglobulin

Abstract Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and secondary antibody deficiencies for over two decades. Since the early 1980s, the therapeutic efficacy of IVIg has been established in idiopathic thrombocytopenic purpura, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, dermatomyositis and Kawasaki syndrome, and the prevention of graft versus host disease in recipients of allogeneic bone marrow transplants. Its use has also been reported in a large number of other autoimmune and systemic inflammatory conditions. In this review, we discuss the mechanisms by which IVIg exerts immunomodulatory effects in immune pathologies.     

The involvement of glutamatergic transmission in the mechanism of movement disorders induced by reversive rotation of white mice

The ability of the selective non-competitive NMDA receptor blocker MK-801 and a series of new glutamate antagonists—the adamantane derivatives IEM-1754 and IEM-1857 and phencyclidine (IEM-1925)—to prevent movement disorders induced by reversive rotation in mice was studied. I.p. MK-801 at a dose of 0.15 ml and IEM-1754 at a dose of 5.0 mg/kg prevented the development of akinesia in response to reversive rotation, as effectively as scopolamine, a known agent which provides effective prophylaxis for movement diseases. IEM-1857, the quaternary analog of IEM-1754, was not effective. IEM-1925 significantly increased the responses of mice to reversive rotation, possibly because of its high activity in relation to other subtypes of glutamate receptors. These data provide evidence for the involvement of glutamatergic transmission in the mechanism of movement disorders of vestibular origin. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 4, pp. 497–501, May, 1999.     

Risk of obstetric cholestasis in sisters of index patients

The aim of the present study was to evaluate the rate of intrahepatic cholestasis of pregnancy in first-degree relatives of index patients. Index patients (n=65) with singleton pregnancies complicated by intrahepatic cholestasis were identified among the women (n=11 984) who gave birth at Kuopio University Hospital in 1994-1998. The pregnancy histories of relatives of 56 index patients were reviewed and the rate of cholestasis in first-degree relatives was compared with that in the general obstetric population. Obstetric cholestasis was experienced by 9% of the parous sisters and 11% of the mothers of the index patients. The risk per delivery was 6% in the first-degree relatives. The rate in the general obstetric population was 0.54%. The odds ratios and 95% confidence intervals were 12.6 (5.6-28.1) for the sisters and 12.2 (6.2-24.2) for the mothers. Obstetric cholestasis clusters within some families and is under strong genetic influence, although the precise genetic pattern remains obscure. The sisters of index patients are at an increased risk of the disorder and may benefit from close obstetric care.     

Primary Immunodeficiency Syndrome in Spain: First Report of the National Registry in Children and Adults

The Spanish Registry for Primary Immunodeficiency Diseases (REDIP) was organized in 1993. One thousand sixty-nine cases of primary immunodeficiency diseases (PID) were registered in patients diagnosed between January 1980 and December 1995. PID diagnosis was made according to the World Health Organization criteria. The most frequent disorders were IgA deficiency (n = 394) and common variable immunodeficiency (n = 213), followed by severe combined immunodeficiency (n = 61), C1 inhibitor deficiency (n = 52), X-Iinked agammaglobulinemia (n = 49), IgG subclass deficiency (n = 48), and chronic granulomatous disease (n = 32). A comparative study between REDIP and data recently obtained from the European registry (ESID Report, 1995) revealed important differences between phagocytic disorders and complement deficiencies reported in both registries, 4.9 vs 8.7 and 6.0 vs 3.6, while percentages of predominantly antibody deficiencies and T cell and combined deficiencies concurred with those reported in the European registry, 69.3 vs 64.7 and 14.7 vs 20.2, respectively. The heterogeneous nature of the geographical distribution of cases submitted may indicate underdiagnosis of PID in some country areas; surprisingly, the interval between the onset of clinical symptoms and diagnosis was significant, even in immunodeficiency diseases, such as IgA deficiency, which are easy to diagnose.     

The use of proteomics in biomarker discovery in neurodegenerative diseases

Biomarkers for neurodegenerative diseases should reflect the central pathogenic processes of the diseases. The field of clinical proteomics is especially well suited for discovery of biomarkers in cerebrospinal fluid (CSF), which reflects the proteins in the brain under healthy conditions as well as in several neurodegenerative diseases. Known proteins involved in the pathology of neurodegenerative diseases are, respectively, normal tau protein, beta-amyloid (1-42), synaptic proteins, amyloid precursor protein (APP), apolipoprotein E (apoE), which previously have been studied by protein immunoassays. The objective of this paper was to summarize results from proteomic studies of differential protein patterns in neurodegenerative diseases with focus on Alzheimer's disease (AD). Today, discrimination of AD from controls and from other neurological diseases has been improved by simultaneous analysis of both beta-amyloid (1-42), total-tau, and phosphorylated tau, where a combination of low levels of CSF-beta-amyloid 1-42 and high levels of CSF-tau and CSF-phospho-tau is associated with an AD diagnosis. Detection of new biomarkers will further strengthen diagnosis and provide useful information in drug trials. The combination of immunoassays and proteomic methods show that the CSF proteins express differential protein patterns in AD, FTD, and PD patients, which reflect divergent underlying pathophysiological mechanisms and neuropathological changes in these diseases.     

心脑血管病患者微血栓与D－2聚体、血小板聚集的相互关系

观察２０例急性脑梗塞，３０例冠心病在微循环中微血栓的变化，同时检测血小板聚集率、Ｄ－２聚体。结果表明微血栓阳性组血小板聚集率、Ｄ－２聚体均高于微血栓阴性组。治疗后二组血小板聚集、Ｄ－２聚体明显减少。提示微血栓、Ｄ－２聚体及血小板聚集率可作为评定冠心病、脑梗塞病情变化的一种指标     

Subcortical arteriosclerotic encephalopathy (Binswanger''s disease): a report of five patients

Five patients with variable clinical symptoms were diagnosed as having--subcortical arteriosclerotic encephalopathy (Binswanger disease) based on the presence of lacunar infarcts in basal ganglia, various abnormalities of subcortical white matter and severe thickening and hyalinization of penetrating arteries and arterioles. One case had a classical clinical picture while in the others the course of the disease was short and was associated with severe systemic abnormalities. The variability of the clinical features, the identify of "classical" clinical symptoms with other forms of cerebral arteriosclerosis, the similarity between "atypical" cases and other entities, and the high frequency of associated conditions makes it difficult to characterize the clinical pathological entity called subcortical arteriosclerotic encephalopathy.     

Pharmacokinetics of cefradine, sulfamethoxazole and trimethoprim and their metabolites in a patient with peritonitis undergoing continuous ambulatory peritoneal dialysis

Cefradine and co-trimoxazole pharmacokinetics were studied in a patient with peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD). Concentrations in the plasma reached after oral administration of 500 mg cefradine four times daily and 400/80 mg co-trimoxazole four times daily were for cefradine 100g/ml, for trimethoprim 15g/ml, and for sulfamethoxazole 100/ml, respectively. In the dialysate concentrations were reached of 35–70/ml cefradine, 2–5/ml trimethoprim and 8–17g/ml sulfamethoxazole. The values for sulfamethoxazole are regarded too low to be clinically effective. Half-lives protein binding values and CAPD clearances are presented. Low CAPD clearances were obtained during the night and high values during the day. The dosage yielded too high plasma trimethoprim concentrations, while sulfamethoxazole dialysate concentrations were too low. It seems questionable therefore whether co-trimoxazole can be used orally for the treatment of CAPD peritonitis.     

Ten years of Pan-InfORM: modelling research for public health in Canada

Modelling and simulation methods can play an important role in guiding public health responses to infectious diseases and emerging health threats by projecting the plausible outcomes of decisions and interventions. The 2003 SARS epidemic marked a new chapter in disease modelling in Canada as it triggered a national discussion on the utility and uptake of modelling research in local and pandemic outbreaks. However, integration and application of model-based outcomes in public health requires knowledge translation and contextualization. We reviewed the history and performance of Pan-InfORM (Pandemic Influenza Outbreak Research Modelling), which created a national infrastructure in Canada with a mandate to develop innovative knowledge translation methodologies to inform policy makers through modelling frameworks that bridge the gaps between theory, policy, and practice. This review demonstrates the importance of a collaborative infrastructure as a “Community of Practice” to guide public health responses, especially in the context of emerging diseases with substantial uncertainty, such as the COVID-19 pandemic. Dedicated resources to modelling and knowledge translation activities can help create synergistic strategies at the global scale and optimize public health responses to protect at-risk populations and quell socioeconomic and health burden.