Progression of renal artery stenosis in patients undergoing cardiac catheterization

BACKGROUND: Renal artery stenosis is potentially correctable by either revascularization surgery or percutaneous methods. However, appropriate use of these techniques has been hampered by a lack of data on the natural history of this disease. This study assesses the prevalence, risk factors for progression, and effect on renal function of angiographically demonstrated renal artery disease in patients undergoing cardiac catheterization. METHODS: The severity of renal artery stenosis was quantified in all patients who underwent abdominal aortography as part of a diagnostic cardiac catheterization study at Duke University Medical Center between January 1989 and February 1996. RESULTS: There were 14,152 patients in the study (mean age 61+/-12 years, 62% male). Normal renal arteries were identified in 12,543 (88.7%) patients, insignificant disease (<50% stenosis) in 1 or more vessels in 726 patients (5.1 %), and significant stenosis in 883 patients (6.3%). Significant bilateral renal artery stenosis was present in 178 patients (1.3%). By multivariate logistic regression, elevated serum creatinine level, coronary artery disease, peripheral vascular disease, hypertension, cerebrovascular disease, older age, female sex, and family history of coronary artery disease were identified as independent predictors of significant renal arterial disease. Disease progression was assessed in 1189 patients. Mean time between cardiac catheterizations was 2.6+/-1.6 years. Significant disease progression occurred in 133 patients (11.1 %). Independent predictors of disease progression were female sex, age, coronary artery disease at baseline, and time between baseline and follow-up. At follow-up, serum creatinine level was significantly higher in patients who demonstrated > or =75% stenosis in 1 or more vessels (mean creatinine level 141+114 micromol/L compared with those with insignificant disease (mean creatinine level 97+/-44 micromol/L (P= .01). CONCLUSIONS: Renal artery disease is frequently progressive in patients who undergo cardiac catheterization for investigation of coronary artery disease. Significant stenotic disease may develop over a short period despite evidence of normal renal arteries at prior catheterization.     

Negative metabolic effects of cyclic GMP in quiescent cardiomyocytes are not related to L-type calcium channel activity

Evidence of immune system abnormalities in adult schizophrenia has prompted examination of the human leukocyte antigen (HLA) system. Childhood onset schizophrenia offers a unique opportunity to test neurodevelopmental hypotheses of schizophrenia, including those which implicate components of the immune system. In the present study, class I and II HLA antigens were typed using sequence-specific primers and the polymerase chain reaction in 28 childhood onset schizophrenics and 51 ethnically matched healthy subjects. Groups were compared for frequencies of HLA antigens reported to be associated with schizophrenia and/or autoimmune disorders. We hypothesized that antigen frequencies would differ between schizophrenic and healthy children, suggesting that some dimension of the neurodevelopmental disturbance experienced by these children may be mediated by subtle abnormalities of immune function. There were no significant differences between schizophrenic and healthy subjects in the frequency of any antigen tested. These findings do not support HLA-associated pathology in childhood onset schizophrenia.     

Structure-function studies on the inhibition of binding of alpha-thrombin to platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory activity of C-terminal E in this peptide

In papillary thyroid carcinoma lymphnode metastases at presentation do not seem to adversely affect survival, but do increase the risk of loco-regional tumor recurrence. The value of systematic versus selective lymphadenectomy is far less standardized, whereas the role of postoperative radioiodine in preventing either nodal recurrence or cancer death remains controversial. Clinical data of 36 N+ patients with papillary thyroid carcinoma who had undergone from 1990 to 1996 ipsilateral or bilateral neck dissection were retrospectively reviewed, to analyse the value of systematic lymphadenectomy. In our series of 50 extensive lymph node dissections (levels 2-6), the number of metastases in each specimen (mean value: 5) and the incidence of multiple level metastases (36%) were high. In 37.5% of the metastases at level 6 and in 11.1% at level 4, coexisting nodal involvement at level 2 was observed, without metastasization at intermediate levels. Multiple levels metastases and skip metastases were present in at least one third of the patients and could be excised only performing a complete dissection of the levels 2-6. Extra-capsular spread was found in 56% of the specimens. In 64.3% of these cases a functional neck dissection was performed. A modified radical or radical neck dissection was carried out in the other 35.7% of the cases. These patients received modified radical neck dissection (functional dissection with sacrifice of internal jugular vein) in 60% of the cases and radical neck dissection in the other 40%. In papillary thyroid carcinoma extensive lymphnode dissection at presentation has been stated to offer no advantage versus selective lymphadenectomy, causing increased morbidity. However, experienced surgeons report a low incidence (less than 5%) of accessory spinal nerve and cervical plexus permanent sequelae after functional neck dissection. In our opinion, patients with cervical lymph node metastases require a complete loco-regional neck dissection. Systematic lymphadenectomy, performed by lateral neck plus upper anterior mediastinal dissection, can yield a high disease-free survival. Moreover, this can limit the overall radio-iodine therapeutic dose and the risk of de-differentiation of recurrent tumor to the anaplastic type in patients with a long-term and near normal life-span.     

Assessment of possible protective roles of selenium, zinc, and cis-stilbene oxide against acute T-2 toxin poisoning: a preliminary report

The efficacy of two free radical scavengers, selenium and zinc, and a microsomal epoxide hydrolase-inducing agent, cis-stilbene oxide on the acute toxicity of T-2 toxin, a potent cytotoxic trichothecene, was investigated. Mice were pretreated daily for 3 consecutive days with either zinc sulfate (4.4 mg/kg, intraperitoneally [i.p.]), sodium selenite (1, 2, and 3 mg/kg i.p.) or cis-stilbene oxide (50 mg/kg i.p.). A full 24-hr after the final dosing with these agents, mice were given T-2 toxin (2, 2.5, or 3 mg/kg i.p.). The acute lethal toxicity of T-2 toxin (2.5 mg/kg) was reduced by administration of only sodium selenite (3 mg/kg) and cis-stilbene oxide (50 mg/kg). No significant effect on weight gain was observed.     

Leukocytes, cell adhesion molecules and ischemic acute renal failure

Ischemic acute renal failure (ARF) is a common clinical syndrome, associated with high morbidity and mortality, for which there is no specific therapy. Polymorphonuclear neutrophils (PMN) recruited during reperfusion have been implicated as mediators of renal parenchymal injury in ischemic ARF. Leukocyte adhesion molecules appear to facilitate PMN recruitment in this setting. Complementary studies using monoclonal antibodies, antisense oligonucleotides and gene "knock-out" indicate that blockade of CD11/CD18 integrins and intercellular adhesion molecule-1 (ICAM-1) attenuates ARF in some experimental models of renal ischemia. These exciting observations may herald the development of novel anti-adhesion strategies for use in human disease.     

Complex orofacial movements and the disappearance of cerebellar mutism: report of five cases

Intoxications with poisonous mushrooms, in particular toadstools, are still a serious medical problem. The author presents contemporary views on the etiopathogenesis of intoxications with Amanita phalloides, the clinical picture of the phalloid syndrome and its prognosis. He emphasizes the importance of a comprehensive therapeutic approach, incl. the administration of antidotes (penicillin G and silibinin) and extracorporeal haemoelimination treatment. Early sorption haemoperfusion, either alone or combined with haemodialysis or plasmapheresis, prevent the development of hepatic and renal failure and significantly reduce the mortality from mushroom poisoning. The results of amanitine sorption in in vitro experiments and in the treatment of human intoxications justify the use of biocompatible synthetic resin sorbents (Amberlite XAD-2) in the treatment of mushroom poisoning rather than active charcoal.     

Lectin-like inhibition of immune complex receptor-mediated stimulation of neutrophils. Effects on cytosolic calcium release and superoxide production

We have tested the role of lectin-like interactions, with particular emphasis on CR3, in insoluble immune complex (IC)-mediated activation of human polymorphonuclear leukocytes (PMN). The ability of IC to trigger intracellular Ca2+ release and O2- production by normal PMN, saccharide-treated cells, and CR3-deficient PMN (leukocyte adhesion deficiency, LAD, patients) were tested. When indo-1-labeled normal PMN were stimulated with IC in Ca(2+)-free buffer, intracellular Ca2+ rose from approximately 100 nM to approximately 230 nM. However, when LAD PMN were tested, a small rise in intracellular Ca2+ was observed. Because previous studies have shown that certain saccharides inhibit CR3-Fc gamma RIII co-capping, we tested a panel of saccharides to determine their ability to influence IC-mediated intracellular Ca2+ release. When normal PMN were exposed to 0.15 M N-acetyl-D-glucosamine (NADG), D-mannose, or alpha-methyl-mannoside, the Ca2+ response to IC was significantly reduced. However, addition of 0.15 M glucose, raffinose, sucrose, galactose, fructose, or sorbitol did not significantly affect the Ca2+ response, suggesting that the response was specific for certain saccharides. To test the physiologic consequences of these Ca2+ signals, we have examined the ability of saccharides to influence O2- production by normal PMN and the ability of LAD PMN to produce O2- upon triggering by IC. Normal PMN stimulated with IC generated 4.3 +/- 1.7 nmol/10(6) cells/30 min of O2-. In contrast, O2- production was inhibited by 0 to 20% by glucose, galactose, sucrose, sorbitol, fructose, and raffinose and > or = 50% by NADG and mannose. LAD PMN, which display diminished Ca2+ signals, were found to produce O2- at 47 +/- 6% of control levels. NADG and mannose dose-response studies indicated that they cooperatively block O2-.     

PGE2 attenuates PGF2 alpha-induced increases in free intracellular calcium in ovine large luteal cells

When ovine large luteal cells are placed in culture and exposed to PGF2 alpha, there is a rapid and sustained increase in the concentration of free intracellular calcium which is believed to play a major role in the luteolytic and cytotoxic effects of PGF2 alpha. Since administration of exogenous PGE2 can prevent spontaneous and PGF2 alpha-induced luteolysis in vivo, and the cytotoxic effects of PGF2 alpha on large luteal cells in vitro, the objective of this study was to determine if one mechanism by which PGE2 acts is to attenuate increases in free intracellular calcium induced by PGF2 alpha. At concentrations of 10 nM or greater, PGF2 alpha caused a significant and sustained increase in free intracellular calcium in large luteal cells. Similarly, PGE2 also induced increases in free intracellular calcium but required doses 20-fold greater than PGF2 alpha. When PGE2 (1, 10 or 100 nM) was incubated with PGF2 alpha (100 nM) increases in free intracellular calcium induced by PGF2 alpha were attenuated (P < 0.05) when measured 5 min, but not at 30 min, after initiation of treatment. The observed decrease in the concentration of free intracellular calcium at 5 min in response to PGF2 alpha was the result of fewer cells responding to PGF2 alpha. In addition, the concentrations of free intracellular calcium attained in the cells that did respond was reduced 25% compared to cells treated with PGF2 alpha alone. Thus, part of the luteal protective actions of PGE2 appears to involve an inhibition of the early (5 min) increase in free intracellular calcium induced by PGF2 alpha.     

Influence of age and hemodynamics on myocardial blood flow and flow reserve

Colostrum from French-Alpine and Anglo-Nubian goats and Holstein cows was collected and analyzed for both total and FFA of 12 and fewer carbon atoms. Short-chain VFA were separated from long-chain fatty acids using simultaneous distillation extraction. The n-butyl esters of fatty acids were quantified by gas chromatography, and their identity was confirmed by gas chromatography-mass spectrometry. The concentration of decanoic acid was 33 and 83% less in Holstein colostrum than in colostrum from Alpine and Nubian goats, respectively. Colostrum from Nubian goats had twice as much decanoic acid as colostrum from Alpine goats. The FFA in colostrum that differed between species but not between goat breeds were octanoic and decanoic acids. These respective fatty acids were approximately two and three times greater in colostrum from goats than in colostrum from Holsteins. The quantity of decanoic acid was different between goat breeds and between animal species. The ratio of total fatty acid concentration to free-state concentration for hexanoic acid appeared to be useful for differentiating between Nubian and Alpine goat colostrum as well as between Nubian and Holstein colostrums.