Occurrence of anti-C1q antibodies in IgA nephropathy

Background: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. Methods: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n=36) and SLE nephritis (n=37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulo-nephritis (n=7) and minimal change disease (n=2), in which circulating immune complexes are usually not present, and in 40 healthy controls. Results: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P<0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P<0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. Conclusions: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.     

Screening of an elderly population in primary care for primary hyperparathyroidism.

In order to assess the diagnostic outcome of a screening for primary hyperparathyroidism (PHPT) in an elderly population, we determined ionized calcium in serum from 368 individuals participating in a health control at M?lnlycke Primary Care Centre (200 women, 168 men; age range 75-95 years); four-fifths of the individuals living in their homes, the remainder in homes for aged or nursing homes. Intact parathyroid hormone was determined in the samples with oinized calcium concentration greater than mean + 3SD of the truncated population sample, and these individuals were also recalled for another blood sample. Moderate hypercalcaemia, probably due to PHPT, was found in eight individuals (2% of the complete sample, 3% of the women), five having neuropsychiatric or neuromuscular symptoms consistent with PHPT. Surgical intervention is probably indicated in only a small proportion of elderly patients. We conclude that optimal benefits in relation to costs of screening for PHPT in old people will depend on the availability of a safe and simple pharmacological treatment that could determine any causal relationship between hypercalcaemia and symptoms.     

Urinary monoamine metabolites as indices of mental stress in healthy males and females

Concentrations of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), the dopamine metabolite homovanillic acid (HVA) and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol (HMPG) were determined in urine samples from healthy male and female students by mass fragmentography. Urine samples were obtained after a demanding examination (mental stress) and a day of ordinary school work (control condition). Self-ratings were obtained of feelings induced by the examination, and of habitual psychosomatic symptoms. The results for both sexes showed that the examination stress induced a significant increase of HVA and HMPG excretion, but not of 5-HIAA. The males excreted significantly more of each of the metabolites than the females. The pattern of correlations between metabolite levels and psychological and psychosomatic variables were strikingly different for the two sexes.     

Elevations of neuropeptide Y-like immunoreactivity and catecholamines in plasma on increased intracranial pressure in the pig

Graded increases of intracranial pressure (ICP) in anaesthetized pigs induced elevations of plasma levels of neuropeptide Y (NPY)-like immunoreactivity (LI) and catecholamines, simultaneously with hypertension and tachycardia. Plasma adrenaline (ADR) increased at a lower ICP-level than did the plasma levels of noradrenaline (NA) and NPY-LI. At the maximal ICP elevation, 22.9 kPa (172 mmHg), plasma NPY-LI was increased about 10-fold, from 48 +/- 8 pmol/l in the basal state, while NA and ADR concentrations increased more than 100-fold. At this maximal ICP-level the plasma levels of NPY-LI were correlated to the concentrations of both NA (r = 0.87, P less than 0.01) and ADR (r = 0.92, P less than 0.001). Plasma NPY-LI continued to increase to about 1000 pmol/l, 10 min after the maximal elevation of ICP was discontinued, while the catecholamines then had declined considerably. A slight cardiac release of NPY-LI was observed at the maximal elevation of ICP. The half-life of NPY-LI in plasma was about 6 min upon systemic infusion. At plasma levels similar to those obtained upon maximal ICP elevation, exogenous NPY caused slight vasoconstriction in the spleen and skeletal muscle, but had no effects on coronary blood flow or systemic blood pressure. This suggests that NPY mainly exerts local actions after release from nerve endings, while levels of circulating NPY in plasma must be very high to influence blood flow in some organs. It is concluded that elevation of ICP results in hypertension and tachycardia related to elevated plasma levels of NPY-LI and catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnoses of alcohol abuse and other neuropsychiatric disorders among house painters compared with house carpenters.

The incidence of alcoholism and the incidence of other neuropsychiatric diagnoses were compared between the 767 house painters and the 1212 house carpenters, born in 1925 or later, who were members of the Stockholm branches of their respective trade unions in 1965 and who had been members for at least 10 years before 1970. Four different outcome registers were used: (1) the alcohol crime register, which contained all persons who had broken any law regulating the handling and consumption of alcohol (follow up period 1972-6). (2) The register of diagnoses at early retirement (follow up period 1971-84). (3) The register of diagnoses at discharge from inpatient psychiatric care (follow up period 1968-83). (4) The register of causes of death (follow up period 1965-86). Exposures to solvents and consumption of alcohol were evaluated by interviews with samples of the cohorts. A high average cumulative exposure to solvents was found among the painters. The mean consumption of alcohol was similar in the two cohorts. The incidence of diagnoses of neuropsychiatric disorders was higher in painters than in carpenters in all registers. Alcoholism was the most common neuropsychiatric disorder diagnosed and showed the highest relative risk. The excess of alcoholism among the painters was, however, due singularly to painters who had several registrations in the alcohol crime register or diagnoses of alcoholism in multiple registers. Thus the study implies that excessive alcohol consumption or severe damage due to alcohol, or both, but not less severe problems, were more common in painters than in carpenters. This suggests an interaction between exposure to solvents and intake of alcohol causing an increase in diagnosis of alcoholism among painters.     

Binswanger's disease in the absence of chronic arterial hypertension

Summary The cerebral changes are described in a woman of 54 who suffered from Binswanger's encephalopathy: there were no signs or symptoms of chronic arterial hypertension. The disease presented as dementia of about 3 years duration. Computed tomography of the brain 2. 5 years before her death showed bilateral widespread hypodense lesions in the cerebral white matter. She died of an asthmatic attack. Autopsy disclosed extensive bilateral degeneration of the central white matter, lacunes and gliosis. Severe obliterative arteriolosclerosis occurred in the meningeal vessels and those supplying the affected parts of the brain. Light microscopy showed that the most severe lesions occurred in the arterioles. Immunohistochemistry demonstrated profound extravasation of plasma proteins chiefly albumin, indicating dysfunction of the blood-brain barrier. Thus, the lesions characteristic of Binswanger's encephalopathy may develop in the absence of chronic arterial hypertension. Additional pathogenic factors, possibly genetic predisposition to vascular injury may play a role in the development of this condition.Supported by grants from the Swedish Medical Research Council, Project No 12X-03020 and 1987 Års Stiftelse för Strokeforskning     

A critical assessment of allergen component-based in vitro diagnosis in cherry allergy across Europe

BACKGROUND: Food allergy to cherry occurs throughout Europe, typically with restricted oral reactions in the central and northern parts but with frequent systemic reactions in the Mediterranean region. Previous studies have demonstrated insufficient sensitivity of commercially available cherry extract reagents in the diagnosis of cherry allergy. OBJECTIVE: To assess the diagnostic performance of specific IgE tests based on recombinant cherry allergens in comparison with an extract-based assay and to skin prick test (SPT). A secondary objective was to analyse the frequency of systemic reactions in cherry-allergic subjects across Europe, including the largest population of LTP-sensitized subjects from central Europe studied to date. METHODS: A total of 186 subjects from central Europe and Spain were studied. Serum IgE was analysed with ImmunoCAP tests carrying rPru av 1, 3 and 4, combined and separately, and cherry extract. RESULTS: Among the central European cherry allergics, the mix of rPru av 1, 3 and 4 had a sensitivity of 95%, compared with 65% for cherry extract, and the IgE binding capacity of the recombinant mix was considerably higher. The sensitivity of the two tests was more comparable in the Spanish population, 95% and 86%, respectively. The recombinant allergen ImmunoCAP equalled SPT in terms of sensitivity and specificity. Consistent with previous reports, major geographic differences in sensitization pattern and prevalence of systemic reactions were found. A significantly higher rate of systemic reactions was found in Spanish patients sensitized to Pru av 3 whereas German patients sensitized to LTP only had oral allergy syndrome. CONCLUSIONS: The recombinant cherry allergen ImmunoCAP is a highly sensitive diagnostic tool, clearly superior to any diagnostic method based on cherry extract. Three cherry allergens are sufficient for detecting sensitization in 95% of cherry-allergic subjects. Systemic reactions are common in LTP-sensitized individuals but seem to require at least one additional causative factor.     

Characterization, localization and actions of endothelins in umbilical vessels and placenta of man.

Endothelin-like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin-like immunoreactivity (0.4-1.4 pmol g-1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin-like immunoreactivity in the amniotic fluid was much higher (77 pmol l-1) than in umbilical cord plasma (10 pmol l-1). Characterization by reverse phase HPLC revealed that most of the endothelin-like immunoreactivity eluted in the position of synthetic endothelin-1 or oxidized endothelin-1. Specific, high affinity binding sites for endothelin-1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin-1 and -3 were almost equipotent as competing ligands for endothelin-1 binding sites, whereas in the umbilical artery endothelin-3 was much less potent than endothelin-1. Scatchard analysis of the binding for placental membranes displayed a straight line (r = -0.994) indicating a single class of endothelin receptors with a Kd-value of 80 pmol l-1 and Bmax of 113 fmol mg-1. Endothelin-1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l-1 while endothelin-3 had no contractile effect up to 10(-7) mol l-1. It is concluded that endothelin-1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin-1 was observed in foetal circulation and amniotic fluid. Endothelin-receptors seem to be of different types in placenta (ETB type) and umbilical vessels (ETA type).     

Differential bronchial and pulmonary vascular responses to vagal stimulation in the pig.

The pulmonary and bronchial vascular responses and changes in bronchial tone upon vagal stimulation (240 impulses at 2 Hz or 10 Hz) were studied in anaesthetized pigs paralyzed with pancuronium. The acetylcholine-evoked vasodilatation in the tracheobronchial circulation had the same magnitude when using pancuronium or succinylcholine as skeletal muscle relaxants. Atropine-sensitive bradycardia, hypotension and bronchoconstriction were observed upon vagal stimulation. A vasoconstrictor response in the pulmonary vascular bed and clear-cut vasodilatation in the bronchial circulation supplied by the bronchial artery also occurred upon vagal stimulation. The vagally-evoked increase in pulmonary vascular resistance was markedly reduced after atropine while the bronchial vasodilatation was unchanged. This suggests that the vagally-induced increase in bronchial blood flow was not secondary to changes in the pulmonary circulation. Furthermore, the pulmonary vasoconstrictor response caused by vagal stimulation under control conditions is probably explained by reflex sympathetic activation due to the fall in systemic blood pressure. These data indicate selective vagal non-cholinergic influence of blood flow in the bronchial vascular bed compared to the pulmonary circulation.