Ultrastructural study of the ciliated cells from renal tubular epithelium in acute progressive glomerulonephritis

Light microscopic examination of the renal tubular epithelium of a female with a rapid progressive glomerulonephritis revealed in several areas the presence of cells bearing ciliumlike structures.

At transmission electron microscopy, normal tubular cells appeared to be partially replaced by epithelial cells showing numerous 9×2 cilia and a normally developed basal apparatus. The cilia showed several ultra-structural details (i.e., outer dynein arms, spokes) such as observed in kinocilia of the respiratory epithelium. In addition, a number of poorly differentiated cells showing cilia with a 9 + 0 pattern and at the same time cilia with a 9 + 2 pattern of microtubular arrangement were also seen.

The possible biologic significance of these cilia is discussed.     

A possible cause of acquired immune deficiency syndrome (AIDS) and other new diseases

An hypothesis is proposed to explain the surge of new diseases appearing in the world. Mass immunization with live viral vaccines increases the probability of genetic recombination between live vaccine viruses and between live vaccine viruses and other viruses. Perhaps this is the reason for origination of new diseases within the last twenty years. Nucleic acid hybridization techniques might be used to test the hypothesis.     

Epidemiology,characterization, and diagnosis of neuropsychiatric events in systemic lupus erythematosus

Introduction: Neuropsychiatric systemic lupus erythematosus (NPSLE) is characterized by a heterogeneity of clinical manifestations. The absence of diagnostic criteria and the lack of clinical trials is a challenge in clinical practice.

Areas covered: A literature review was performed to describe epidemiology, characterization (clinical, immunological, and imaging), diagnosis and treatment of NPSLE. Classification criteria have been the first step towards a uniform definition. More recently, different attribution models have been developed to help to determine if the NP event is due to SLE. Disease activity is a major risk factor for NP events. Cytokines and autoantibodies are associated with NP events, however, only a few studies have identified risk factors for individual NP events.

Expert opinion: Further research needs to search for and validate biomarkers for NPSLE and individual NP events, including neuroimaging findings, attribution models, and serologic markers. This will be a fundamental step in planning randomized control trials in the treatment of NPSLE to improve outcome.     

Succinyl derivatives of N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid: their effects on the frog neuromuscular junction.

Succinic anhydride (SA) dissolved in Ringer solution buffered with N-tris (hydroxymethyl) methyl-2-aminoethane sulphonic acid (SA-TES solution) potentiates the depolarizing action of acetylcholine (ACh, 10-40 microM) on frog muscle and the tension induced by bath application of this agonist. Applied from one side of a double-barrelled micropipette, SA-TES increases the amplitude of iontophoretically elicited ACh potentials. The potentiation of the effects of ACh by SA-TES does not involve changes in either the activity of the ACh esterase or the input resistance of the muscle membrane. For depolarizations of frog sartorius muscle, dose-response relationships obtained for ACh concentrations from 0.5 to 20 microM indicate that SA-TES increases the apparent affinity of ACh by a factor of 3. SA-TES exerts an "accelerating' effect on the responses elicited by bath-applied ACh; i.e., it increases the rate of depolarization when ACh is added to the bath and the rate of repolarization upon washing out. These effects are particularly marked in preparations treated with neostigmine (3 microM). SA-TES does not potentiate the depolarizing action of agonists which do not contain an ester group. Moreover, the time course of the responses elicited by these compounds is not influenced by SA-TES. SA-TES fails to influence significantly the effects of the neurally released transmitter. Only a 10% increase in the average amplitude of the endplate potentials was observed. SA hydrolyzes in about 30 min at room temperature; however the SA-TES solution retains its activity for several weeks. Succinate is inactive, and so is SA in Ringer buffered with phosphate. The SA-TES solution contains seven succinyl-TES derivatives, which were separated by ion-exchange chromatography and paper chromatography. At concentrations between 1 to 150 microM, these succinyl-TES derivatives affected the ACh-induced contraction of frog rectus abdominus muscle. The most abundant derivative potentiated the action of high doses of ACh, but was inhibitory at lower ones. The other derivatives were mostly inhibitory. These results are discussed in terms of two hypotheses. One postulates the presence of a diffusion barrier formed by groups that bind ACh and are saturated by SA-TES. The other assumes that SA-TES acts directly on the ACh receptor exerting its potentiating effect through a cooperative mechanism.     

Effects of the irreversible α-adrenoceptor antagonists phenoxybenzamine and benextramine on the effectiveness of nifedipine in inhibiting α 1- and α 2-adrenoceptor mediated vasoconstriction in pithed rats

Summary In pithed normotensive rats, i.v. injection of the selective ₁-adrenoceptor agonist cirazolien produced vasoconstriction which was largely resistant to inhibition by nifedipine. On the other hand, the pressor effects of the selective ₁-adrenoceptor agonists St 587 and Sgd 101/75 were much more effectively blocked by nifedipine, although not as effectively as the pressor effects to the selective ₂-adrenoceptor agonist B-HT 920. The sensitivity to inhibition of vasoconstriction in pithed rats to the different agonists increased in the order cirazoline St 587 ₁-, but not to ₂-adrenoceptor activation was dose-dependently enhanced. The potency of nifedipine to inhibit ₁-vasoconstriction by cirazoline, St 587 and Sgd 101/75 was increased maximally to the level of efficacy at which nifedipine antagonized B-HT 920-induced vasoconstriction. The dose of phenoxybenzamine required to maximally increase the potency and efficacy of nifedipine to antagonize vasoconstriction of the ₁-adrenoceptor agonists was inversely related to the level of sensitivity to blockade by nifedipine of the vasoconstriction they produced. In contrast, pretreatment of rats with the irreversible antagonist, benextramine (10 mg/kg, i.v., –100 to –60 min) did not increase the potency or efficacy of nifedipine to antagonize vasoconstriction to cirazoline, St 587, Sgd 101/75 or B-HT 920, despite irreversible blockade of ₁- and ₂-adrenoceptors. These data suggest that phenoxybenzamine, but not benextramine, selectively inhibits the ₁-adrenoceptor mediated vasoconstrictor mechanism that is independent of influx of extracellular calcium. Moreover, the results show that the existence of receptor reserve or the number of ₁-adrenoceptors activated does not determine the relative contribution of calcium influx-independent mechanisms in ₁-adrenoceptor-mediated vasoconstriction.Preliminary data were communicated at the Joint Meeting of the French and German Pharmacological and Toxicological Societies, Freiburg i. Br., September 19–22, 1983 (Timmermans et al. 1983a) and at the Winter Meeting of the British Pharmacological Society, London, January 1984 (De Jonge et al. 1984)     

Pulmonary sequestration complicated by anomalies of pulmonary venous return

Five anomalies of pulmonary venous drainage were seen among 12 children operated for lung sequestration. In two children, venous drainage from the sequestrated lobe and the rest of the right lung was via a single channel into the inferior vena cava ("scimitar syndrome"). In one of these children, the sequestrated lobe was resected and repair of the scimitar syndrome was delayed; in the second patient, the anomalous pulmonary venous drainage was not recognized preoperatively and the vein was ligated, resulting in acute hemorrhagic infarction of the right lung and death of the patient. Three patients had less severe anomalies of pulmonary venous drainage. We recommend very careful evaluation of patients with lung sequestration with special reference to pulmonary venous drainage.     

Values and limitations of transstenotic pressure gradients measured during percutaneous coronary angioplasty

The pressure gradient across coronary stenoses is measured routinely during angioplasty. Due to the finite size of the angioplasty catheter within the stenotic cross section, the remaining luminal area is further reduced and the transstenotic gradient may be overestimating the "true" pressure drop. This "true" pressure gradient can be approximated from the mean coronary blood flow and the stenosis geometry from theoretical models. Goal of this study was to assess the values and limitations of the in vivo measurements of the pressure gradient versus the calculated values. Therefore, flow in the great cardiac vein was measured in 13 patients before and/or after angioplasty of a proximal left anterior descending stenosis, not filled by collaterals. The Poiseuille and turbulent contributions to flow resistance were determined from stenosis geometry assessed by quantitative coronary angiography. A fourfold increase in the luminal area (from 0.7 mm2 pre- to 2.8 mm2 post angioplasty) was associated with a fourfold decrease in the in vivo measured transstenotic gradient (from 59 mm Hg pre- to 13 mm Hg post angioplasty). The occlusion area and the measured gradient were linearly correlated: gradient = 69-17 X occlusion area (r = 0.76). However, as expected, the transstenotic gradient systematically overestimated the theoretical gradient calculated from the laws of fluid dynamics. A nonlinear relation was found between the calculated gradient P and the occlusion area As: P = 15 X As-2 (r = 0.87).     

Aspirin and the prevention of experimental arterial thrombosis: difficulty in establishing unequivocal effectiveness

A trial of the efficacy of aspirin in the prevention of thrombotic occlusion of an "aortic loop" in rats was made simultaneously by two experimental surgeons. A relatively large dose of aspirin (80-100 mg/kg/day) was used, starting two days before operation. It appeared that aspirin was of limited benefit, reducing thrombotic occlusions by about 17% seven days after the insertion of the loop into the abdominal aorta. Although the average occlusion time was prolonged by about 17% in aspirin-treated animals, the separate trials gave no conclusive result. When the data from both operators were pooled, a statistically significant protection by aspirin was apparent (p = 0.02), by a two-tailed Student's t test. However, on using the powerful non-parametric randomization test, the occlusion times in control and aspirin-treated groups appeared not statistically different (p = 0.07). No significant difference was also found between control and treated groups when data were analyzed by X2 test. Independently of the statistical analysis, these data are quite similar to those obtained from aspirin trials in men surviving myocardial infarction. This finding points to the usefulness of the aorta loop as an animal model for arterial thrombosis.     

Aspirin kinetics and inhibition of platelet thromboxane generation-relevance for a solution of the "aspirin dilemma"

Six healthy male volunteers received aspirin (ASA) in a compressed (320 mg) and an enteric-coated (800 mg) formulation as single oral doses ten days apart. Ten plasma samples were obtained from each volunteer between 5 and 120 min after compressed ASA, and seven between 10 and 240 min after enteric-coated ASA. ASA was undetectable (less than 100 ng/ml) in plasma from three subjects receiving compressed ASA and two receiving the enteric-coated preparation. Plasma levels and kinetic parameters of salicylate were the same in subjects with undetectable and detectable ASA plasma levels. More than 98% inhibition of pre-drug serum TXB2 was noted in all samples collected one and four hours after either ASA preparation. TXB2 generation recovered on average by 3.5% at 24 hr with both preparations. Thus inhibition of platelet TXB2 generation occurred independently of the amount of ASA reaching the peripheral circulation. If this is due to inhibition of platelet function in the enterohepatic circulation followed by extensive first-pass deacetylation of ASA, vascular PGI2 synthesis could be spared. A better knowledge of the kinetic parameters of ASA for each of the formulations used in thrombosis prevention trials might help in solving the "aspirin dilemma".