We used both the conventional test and a modified assay, the hypocryoglobulin test, to detect cryoprecipitates in 90 patients; 79 of them had different diseases in which cryoglobulins are frequently seen. For 11, type II essential mixed cryoglobulinemia had previously been diagnosed. It is still uncertain whether dilution of serum is a real help for detection of cryoglobulins. In the group of 79 patients, we found enhancement of cryoprecipitation in hypotonic sera in 33% of the cases, all with low cryocrit levels (less than 2%). In all but one of the patients with type II cryoglobulins, the hypocryocrit was equal to or lower than the cryocrit. The hypocryoglobulin test can detect a cryoprecipitate in patients with conventional cryocrits near the limits of visibility. In a few cases of cryoglobulinemic vasculitis, dilution of the serum can disclose a cryoprecipitate otherwise not visible.

Adolescent↗

PubMedDate not supplied

Cryodependent and cryoproducing involvement of organs in type II essential mixed cryoglobulinemia.

A review of the less frequent organ damage seen in the so-called essential mixed cryoglobulinemia, and distinguishing between cryodependent and cryofavouring organ involvement, is presented in this paper. In the first group, along with the well-known renal, cutaneous and articular lesions, the peripheral neuropathy and respiratory involvement, to date too little considered, are worthy of more accurate study. Gastroenteric and cardiac participations are rare. Among the cryofavouring manifestations of the disease, we have pointed out those affecting the liver. In our experience, however, as the immunohistochemical findings suggest, the histological patterns usually considered to be chronic persistent hepatitis are frequently an expression of a lymphoproliferative lymphoma-like process. A noteworthy percentage of lymphoid cells in the bone marrow has been found in 22 type II cryoglobulinemias after either needle puncture or osteomedullary biopsy. The histological pictures often resemble a lymphoproliferative disease. Clinical and laboratory (computerized tomographic scan) researches frequently show a moderate splenomegaly, but in none of the patients was superficial or deep lymph node enlargement found. The authors conclude by considering type II essential cryoimmunoglobulin to be a sign and a marker of a low-grade proliferative disease with rare evolution into overt lymphoma. At the same time, however, cryoimmunoglobulins themselves cause important injuries that affect the prognosis of the syndrome.

Bone Marrow↗

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[The "mycoplasma pneumoniae" in pathological respiratory processes. Serological disease (author's transl)].

The AA. present the results obtained determining by the F.C. test the antibodies for respiraotry viruses and for Mycoplasma pneumoniae over 1112 patients, of which 742 affected with pathological respiratory processes, during the period 1971-1975. 104 patient have shown a significant correlation between respiratory disease and antibody movement for M. pneumoniae. They have been classified according to their clinical-radiological properties as follows: 38 affected with pneumonia; 37 affected with pleuritis; 29 affected with tracheobronchitis. Particularly interesting is the range of occurrence of the disease: we have noticed a high incidence in the period 1971-1972, followed by an almost complete disappearance of pathological instances in the period 1973-first semester of 1975, and signs of a new recrudescence in the second semester of 1975. These data have been confirmed also by investigations carried out among healthy people. It has also to be pointed out the possibility of family's epidemicity, and the AA. report two epidemic cases under personal observation.

Adolescent↗

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Hepatitis B virus-related markers in secondary and in essential mixed cryoglobulinemias: a multicentric study of 596 cases. The Italian Group for the Study of Cryoglobulinemias (GISC).

The aim of this study was to assess the prevalence of HBV-related markers in cryoglobulinemias and the possible association between hepatitis B virus (HBV) and essential mixed cryoglobulinemia (EMC). A retrospective survey of the prevalence of HBV infection in cryoglobulinemic patients was carried out in 596 cases of cryoglobulinemia. On the basis of clinical and laboratory criteria the cases were grouped as secondary to connective tissue disease, to lymphoproliferative disorders, to chronic liver diseases or to chronic infectious diseases. The cases in which an associated disease was not evidenced were considered as essential mixed cryogobulinemias. Subjects in which liver dysfunction was first diagnosed simultaneously with cryoglobulinemia, were considered as a separate group. A greater prevalence of HBsAg and anti-HBc antibodies was found in cryoglobulinemias secondary to chronic liver disease (p < 0.0001) and in those associated with liver involvement at diagnosis (p < 0.05) than that found in EMCs. The prevalence of anti-HBs antibodies did not differ significantly among the groups. Proven contact with the virus, documented by at least one positive marker, was evidenced more frequently in cryoglobulinemias secondary to liver disease than in the other groups (p < 0.01). The prevalence of HBV related markers in EMCs and in hospitalized patients not suffering from diseases associated with cryoglobulin production were similar, and seems to reflect the epidemiological situation of HBV infection in Italy. In conclusion, our findings do not support an association of HBV with EMC.

Biomarkers↗

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Hepatotoxicity of hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors.

The first clinical studies on hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reported a low incidence of liver toxicity. The personal observation of a case of simvastatin-induced acute cholestatic hepatitis prompted us to evaluate the true incidence of hepatic side effects of these drugs in a large Italian population. One hundred patients taking simvastatin and ninety patients treated with pravastatin were followed-up six months with periodical evaluation of serum lipid levels and liver function test. In 5% of simvastatin-treated patients and 4.5% of pravastatin-treated patients significant liver toxicity was observed, which required drug discontinuation. The mechanism of liver damage was direct, idiosyncratic, but immunological features of drug toxicity could be hypothesized in one patient.

Chemical and Drug Induced Liver Injury↗

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Lymphoproliferative diseases of uncertain classification.

In spite of the recent progress in the biology and histogenesis of the lymphoproliferative diseases, many doubts still remain about their possible evolution. On the one hand, many cases have been studied showing a benign course in spite of a typical monoclonal phenotype; on the other, some clinically aggressive forms of lymphoproliferation prove to be polyclonal throughout their course, even when checked with highly sophisticated techniques. In this article we have reviewed, in both clinical and etiopathogenetic terms, the classification of these processes in the light of the new findings provided by extensive use of the most advanced investigational techniques of genotype and phenotype analysis. We have recognized three main groups of lymphoproliferative disorders of uncertain significance, based on pathophysiological, anatomical and developmental considerations: 1) lymphoproliferative diseases that take place on a background of either congenital or acquired immunodeficiency, referred to as "opportunistic lymphoproliferative disorders"; 2) lymphoproliferative diseases deriving from "mucosa associated lymphoid tissue" (MALT); 3) lymphoproliferative diseases of uncertain histogenesis, now classified as "T lymphomas". The opportunistic lymphoproliferative disorders, particularly in HIV+ patients and transplant recipients, often show developmental and etiopathogenetic features which may help to elucidate their natural history. Frequent involvement of Epstein-Barr virus and the related host's immune response patterns provide powerful tools to outline the alternative developmental pathways of such disorders.2+ Worthy of note is acute infectious mononucleosis which, though self-limiting when occurring in the immunocompetent host, may be considered as a lymphoproliferative process and sometimes shows some "aggressive'' morphological aspects. Special attention is paid to the obscure origin of Hodgkin's disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmune Diseases↗

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[Heart involvement in anorexia nervosa: an electrocardiographic, functional and morphological study].

Mental anorexia (MA) is the most frequent condition of malnutrition in industrialized countries. Sudden death in MA is not infrequent. Furthermore, the role of nutritional state as an important determinant of myocardial function is known. Cardiovascular function was studied in 9 patients with MA. Blood electrolytes and thyroid function were assessed, basal and dynamic ECG, chest roentgenogram, M-mode echocardiography, ergometric test, cardiac output measurement and, in two cases, magnetic nuclear resonance (MNR) were performed. Our data confirm the ECG changes which were preeminent in the clinical context, as predictors of possible major, life-threatening arrhythmic events. The correct QT interval was normal in all patients. In 4 cases with heart rate less than 40 b/min, Holter ECG showed ventricular and atrial extrasystolic beats. In one case S-A blocks with idioventricular substitutive beats were recorded; the normal performance under maximal strain stands for a normal functional reserve. Blood electrolytes were in the normal range. The hypothalamic-pituitary axis can be considered as a cocausal factor by means of autonomic nervous system modulations. Echocardiography revealed only a mild reduction of ventricular wall thickness. Scattered degenerative myocardial involvement as shown by MNR imaging, could be the anatomical counterpart of a clinically emerging cardiomyopathy with potentially severe arrhythmias.

Adolescent↗

PubMedDate not supplied

Selegiline in the treatment of mild to moderate Alzheimer-type dementia.

Selegiline, an inhibitor of monoamine oxidase B, was tested on patients with mild to moderate dementia of the Alzheimer type. Its efficacy and tolerability were compared with that of phosphatidylserine in a randomized, single-blind, parallel fashion. Forty patients (24 men and 16 women) entered the trial. Selegiline was administered in 10-mg tablets once daily and phosphatidylserine in 100-mg capsules twice daily, both treatments lasting three months. Drug efficacy was assessed at baseline and then each month by means of an extensive battery of neuropsychological tests. The assessment of drug safety was based on monitoring for adverse drug reactions and on routine laboratory tests performed before and after treatment. At the end of the study the selegiline group showed improvements statistically significantly superior to those obtained in the phosphatidylserine group on most of the cognitive areas examined. Furthermore, of particular interest was the discovery, found only in the selegiline group, of an increased degree of autonomy in day-to-day activities. Tolerability was good, the only side effect reported in both groups being slight or moderate nausea, which was severe enough to warrant withdrawal from treatment only in one case, a patient in the selegiline group with a history of gastroduodenitis.

Aged↗

PubMedDate not supplied

[Lipoprotein (a)].

Lipoprotein(a) [Lp(a)] is a high molecular weight plasma protein structurally related to low density lipoprotein (LDL), but with distinct metabolic and biologic features. Six different isotypes may be found among the general population; they are inherited as a codominant autosomic monogenic trait. Lp(a) levels in the blood are strictly conditioned by the isotype and much less, if at all, by other environmental or metabolic factors. The Lp(a) catabolic rate is very similar among different individuals and comes from the balance of two complementary pathways: uptake from blood by tissue cells via LDL-receptors, and non-receptor macrophagic internalization at the level of the reticulo-endothelial system. Its high content in lysolecithins and cholesterol, and the close structural similarity of its peptidic component to plasminogen, make Lp(a) a crucial "meeting point" of two main physiopathologic elements of atherogenesis:lipoprotein metabolism and fibrinolysis. This particular role would seem to explain the experimental finding of a close relation between Lp(a) plasmatic levels and the severity of atheromatous processes. Deep understanding of Lp(a) physiopathology is therefore expected to be a powerful tool for the creation of a comprehensive and practical model of atherogenesis and to enable us to deal with prognostic, preventive and therapeutic problems in this field from a new view point.

Arteriosclerosis↗

PubMedDate not supplied

Primary lymphoma of the central nervous system. A clinical and immunohistological study of 8 patients.

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Adult↗

PubMedDate not supplied

[Blood cryoglobulins and liver diseases].

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Acute Disease↗

PubMedDate not supplied

Reliability of immunoassays for anti-HCV antibodies (ELISA and RIBA II) in patients with essential mixed cryoglobulinemia (EMC).

The recent reports of a very high frequency of signs of hepatitis C virus (HCV) infection among patients with essential mixed cryoglobulins (EMC) suggest new hypotheses for the pathogenesis of this disease. However, most of these studies have been seriously criticized. The serologic test designed for detection of anti-HCV antibodies (ELISA, RIBA I and II) may yield a significant rate of false-positive results when performed on cryoglobulinemic sera, and the detection of the HCV genome by PCR is still heavily conditioned by practical problems. Indirect, but possibly more reliable, evidence of HCV infection in cryoglobulinemic patients might come from the demonstration of anti-HCV antibodies by a conventional technique (ELISA or RIBA) in the purified polyclonal non-rheumatoid immunoglobulinemic fraction excreted in the urine by glomerular filtration. Fifty-two patients whose serum had tested positive for HCV antibodies (by ELISA and RIBA) on multiple occasions were enrolled in this study. They were diagnosed as having either EMC or HCV chronic hepatitis without cryoglobulinemia at least one year ago. The urine samples of these patients were tested for anti-HCV antibodies by ELISA and RIBA. In patients with chronic C hepatitis the antibodies most frequently found in the serum were anti-C33c and anti-C22-3. The results of the RIBA were substantially confirmed by ELISA, with a positive test in the urine of 30 of 32 seropositive patients. Similar results were obtained in patients with EMC II. We conclude that the specificity of the RIBA and ELISA tests for HCV antibodies in patients with EMC appears to be as high as in HCV+ patients without serum cryoglobulins. EMC patients have a high incidence of HCV infection and active chronic liver disease.

Aged↗