Double filtration plasmapheresis in the treatment of hyperproteinemia in dogs affected by Leishmania infantum.

Three dogs were evaluated for severe hyperproteinemia and hyperglobulinemia secondary to Leishmania infantum. Double filtration plasmapheresis (DFPP) was performed in two dogs at days 1, 2, and 6 after presentation. The third dog received DFPP at days 1 and 3 after presentation and eleven hemodialysis treatments. Significant reduction in serum total protein (p ＜ 0.0001), alpha-1 (p = 0.023), alpha-2 (p = 0.018), gamma globulins (p = 0.0105), and a significant increase in albumin/globulin ratio (p = 0.0018) were found. DFPP may be a promising therapeutic technique for rapid resolution of signs of hyperproteinemia in dogs affected by L. infantum.

Complement regulators in human disease: lessons from modern genetics.

First identified in human serum in the late 19th century as a 'complement' to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating 'hyperinflammatory complement phenotypes'. To treat these 'complementopathies', a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.

Plasmapheresis in the dysproteinemias.

The dysproteinemias consist of a broad range of serious disease states with the common thread of excessive production of an abnormal, or para-protein. Various clinical syndromes may arise, either from the underlying disease process, the excess paraprotein, or both. Clinical presentation depends upon the organ system(s) affected by the abnormal protein. Diseases included under the classification of dysproteinemias include cryoprotein-related diseases, Waldenström's macroglobulinemia, hyperviscosity syndrome, monoclonal gammopathy, multiple myeloma, light chain disease, and amyloidosis. Plasmapheresis, often in conjunction with other therapies, has been widely used to treat the dysproteinemias and their resulting clinical syndromes. Automated plasmapheresis, which separates plasma from the cellular blood elements by centrifugation, is used most commonly in the United States. Membrane separation and immunoadsorption techniques are more commonly used in Europe and Japan. In automated plasmapheresis, the plasma is removed from the patient's circulation and replaced with a protein-based fluid such as 5% human albumin solution or plasma protein fraction or with fresh frozen plasma. Membrane separation and immunoadsorption allow the offending proteins to be removed more selectively from the patient's plasma prior to the plasma being returned to the patient. This review article presents a description of each disease, the rationale for plasmapheresis therapy, recommended schedules of plasmapheresis, and the use of adjunctive therapies. Results of published studies, case reports, and the author's experience in treating these diseases will serve as the foundation for discussion.

Correction of genetic blood defects by gene transfer.

Recent clinical trials in patients with a severe combined immunodeficiency disease demonstrate that gene therapy is a powerful tool in the treatment of genetic blood defects. Recent identification of the genes involved in the pathogenesis of inherited lymphohemopoietic disorders led to animal models of gene transfer. Extensive preclinical studies have overcome some of the obstacles involved in the transduction of hemopoietic cells. These promising results led to the approval of several clinical trials that are currently underway. This review focuses on the clinical outcome in patients with genetic blood defects treated by gene transfer and examines the progress achieved to date and the problems that have been encountered. Despite the obstacles, improved clinical results for several of these diseases are expected within the next 5 years.

[Therapeutic plasmapheresis--a critical review in the light of the current literature]. / Therapeutische Plasmapherese--eine kritische Würdigung unter Berücksichtigung der aktuellen Literatur.

For centuries it has been the dream of many physicians to cure illnesses by eliminating disease provoking substances which are thought to circulate in the human body. Technical developments during the past 20 years have made therapeutic plasma exchange (TP) a useful procedure for clinical application. Because of the lack of well controlled studies the true benefit of the method remains speculative in many clinical situations. Since the report of the American Medical Association (AMA) Panel on Therapeutic Plasmapheresis in 1985 several controlled studies on this subject have been published in recent literature; they are reviewed in this article. In summary, TP seems justified only in some area and well defined situations such as thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acute and severe myasthenia gravis, severe Guillain-Barré-syndrome, hyperviscosity syndromes such as hyper- and paraproteinemia, and in several intoxications and metabolic disorders such as Refsum disease or hereditary hyperlipidemia type IIa.

Lipids and cardiovascular disease: do the findings and therapy apply equally to men and women?

Dyslipoproteinemia is prevalent in women as well as in men. In both, its consequences--premature atherosclerosis and CAD morbidity and mortality--are more common. Although clinical evidence of the benefits of cholesterol lowering is less abundant in women, it is not entirely absent. As in men, cholesterol lowering in women is associated with a decline in CAD risk and with regression of coronary atherosclerosis. Lipoprotein risk factors have some special characteristics in women. Low-density lipoprotein cholesterol may be a less important risk factor in women, perhaps because estrogen protects the arterial wall against LDL deposition. High-density lipoprotein cholesterol is a better predictor of risk in women than in men. Triglycerides are an independent predictor of CAD risk in postmenopausal women. The effects of endogenous gonadal hormones in life-cycle changes in women is evident. As girls pass through puberty, HDL-C levels do not fall as they do in boys of the same age. In pregnancy, LDL-C, HDL-C, and triglyceride levels all rise. However, LDL-C stays elevated until well after delivery, whereas triglycerides fall to baseline at about the time of delivery, and HDL-C levels begin to fall at about 24 weeks. Interestingly, this fall in HDL-C is not accompanied by a fall in apoA-I levels, implying a change in HDL composition during the latter portion of pregnancy. After menopause, LDL-C levels rise sharply, whereas HDL-C levels decline modestly. Again, this decline in HDL-C is accompanied by a rise in apoA-I levels, implying a change in HDL composition. Diet, weight loss, and exercise are less effective in altering lipoprotein levels in women than in men. The reasons for this are not clear, although it is reasonable to speculate that endogenous gonadal hormones play a role. Genetic dyslipoproteinemia occurs in women, although the effect on CAD rates may be mitigated by the generally higher levels of HDL-C enjoyed by women. Exogenous hormones in the form of OCs and postmenopausal HRT affect circulating lipoprotein levels according to their composition. Generally, estrogens have favorable effects, raising HDL-C and lowering LDL-C levels. Progestins are either neutral or oppose estrogen effects, depending on their dose and androgenicity. Use of modern OCs probably does not adversely affect CAD risk except in combination with cigarette smoking. However, HRT has a strong favorable effect on CAD risk when unopposed estrogen is used, probably due to increases in HDL-C levels.(ABSTRACT TRUNCATED AT 400 WORDS)

PIP: Heart disease is the number 1 cause of death among women in the US, yet health providers, the public, women's health organizations, and women overlook this fact. Risk factors and the progression of cardiovascular disease (CVD) are different in women than in men. For example, women are more likely to develop and succumb to heart disease at more advanced ages than men. This may be due to the protective effect of estrogen that occurs to at least middle age when menopause occurs. The clinical studies examining means to prevent CVD in the 1960s and 1970s basically included only middle aged or older men. Yet scientists have since learned that reproductive hormones do not allow them to extrapolate the results of these studies to women. For example, some interventions identified in those trials do not as effectively affect lipoprotein levels in women as they do in men. These interventions include diet, weight loss, and exercise. Instead, cholesterol screening and management, hormone replacement therapy for cardiovascular indications, and public health messages promoting a low fat diet can be effective in women. As is the case with men, women often have a genetic predisposition for dyslipoproteinemia. High density lipoprotein cholesterol is a more significant CVD risk factor in women than in men while low density lipoprotein is more significant in men than in women. Even though estrogen therapy may prevent heart attacks, its price may be too high since it increases the risk of breast cancer. Many obstetrician-gynecologists feel confident of their ability to screen for cholesterol, yet they are not as confident in their ability to provide dietary counseling or managing drug therapy.

[The cryopathies]. / Kryopatier.

The term cryopathies includes conditions in which abnormal sensitivity to cold is a prominent feature and includes the cold agglutinin syndrome, the cold hemolysin syndrome, the cold urticarias, the cryoglobulinemias, and cryofibrinogenemia. The cryopathies may be secondary to lymphoproliferative, autoimmune, and infectious diseases, but in many patients no underlying disease can be found (essential cryopathy). Avoidance of cold is of prime importance in all patients. Underlying disease should be treated, if possible. Severe therapeutic problems may arise in patients with essential cryopathies.

Therapeutic applications of plasma exchange.

Therapeutic plasma exchange has been used in a wide range of disorders in which circulatory macromolecules are thought to be pathogenic. In this review, we discuss briefly the practical aspects of the procedure, and consider the evidence for its benefit.

Lung function, smoking and survival in severe alpha 1-antitrypsin deficiency, PiZZ.

Lung function, smoking, age and mortality data in 158 adult severe alpha 1-antitrypsin deficient, PiZZ individuals, followed from 1963 to 1982 were analyzed. Low initial FEV1 value was significantly associated with increased mortality (p less than 0.005). A 3 yr mortality rate of 40% was found in individuals whose initial FEV1 values were less than 30% of that predicted. In contrast, the corresponding 3-yr mortality among those whose initial FEV1 values were between 30 and 65% of that predicted was only 7%. Smokers were found to have significantly lower FEV1 levels (p = 0.008) and higher mortality (p less than 0.005) than non-smokers. The difference between current and ex-smokers in mortality and FEV1 level were not statistically significant (p = 0.9 and p greater than 0.25, respectively). Cross-sectional analysis of the initial FEV1 values indicated a significant decline (p less than 0.005) of FEV1 with increasing age. This decline was greater among smokers than non-smokers. Longitudinal analysis of FEV1 rates of decline in 80 cases with follow-up FEV1 measurements failed to detect any significant differences between smokers and non-smokers, but was performed late in the disease process. The application of these results to the planning of studies on replacement therapy, smoking intervention strategy and longitudinal follow-up is discussed.

[Evaluation of an automated system of measuring erythrocyte aggregation in dysglobulinemia treated by plasma exchange]. / Evaluation d'un système automatique de mesure de l'agrégation érythrocytaire dans les dysglobulinémies traitées par échange plasmatique.

Characteristics of a new erythrocyte aggregameter were evaluated in 7 patients with monoclonal dysglobulinemia (5 multiple myeloma, 1 Waldenström disease, 1 CLL with monoclonal immunoglobulin) treated by plasma exchange. This apparatus measures modifications of light retro-diffused by erythrocytes suspension after shear arrest. All parameters measured: Ta, Tf, S10, gamma D, gamma S were modified after plasma exchange: either immediately after the first or after the second or third plasma exchange. These findings demonstrate the value of this new technique for evaluating red cell aggregation. These data should be completed by rheological assessment of dysglobulinemia treated by plasma exchange.

[IgG-IgM cryoglobulinemia with a purpura-arthralgia-nephritis syndrome]. / IgG-IgM-Kryoglobulin ämie mit Purpura-Arthralgie-Nephritis-Syndrom.

The clinical and laboratory features in 7 patients with essential mixed cryoglobulinemia are presented. The clinical picture was characterized by arthralgia, purpura and glomerulonephritis (3 patients). The cryoprecipitate consisted of IgM and IgG, the IgM being monoclonal (3 patients) with anti-IgG activity. Depressed C4 and/or C3 values were detected in 5 patients and were not correlated with the presence of nephritis. The IgM levels were elevated in 5 patients. The possibility that the disorder represents an immune complex mediated vasculitis is supported by the ability of the cryoglobulins to activate the complement system and by the detection of immunoglobulins and/or complement in the vasculitic lesions in the glomerula or the skin. Treatment by plasma exchange, steroids and azathioprine or cyclophosphamide was followed by a definite improvement in the purpura and the arthralgia, whereas the proteinuria, microhematuria and hypocomplementemia were not affected by therapy.