Alpha-1-antitrypsin, autism, and cœliac disease
About: This article is published in The Lancet.The article was published on 1972-10-21. It has received 553 citations till now. The article focuses on the topics: Alpha (ethology) & Autism.
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TL;DR: The aim has been not only to review the 65-odd randomized beta blocker trials but also to demonstrate that when many randomized trials have all applied one general approach to treatment, it is often not appropriate to base inference on individual trial results.
3,131 citations
TL;DR: In this paper, the authors investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder, and identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers.
2,505 citations
TL;DR: A substantial elevation of the calcitonin gene‐related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine, and may have importance in the pathophysiology of migraine.
Abstract: The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and the cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.
1,419 citations
TL;DR: The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.
Abstract: Nervous connections between the trigeminal ganglia and cerebral blood vessels have recently been identified in experimental animals and have been termed the trigeminovascular system. Existence of this system in humans is inferential. Trigeminovascular neurons and their peripheral unmyelinated nerve fibers contain the neurotransmitter peptide substance P. Most newly synthesized substance P is transported from ganglion cell bodies to afferent nerve fibers, where depolarization-induced release of neurotransmitter into the wall of the cerebral blood vessel occurs. Substance P dilates pial arteries, increases vascular permeability, and activates cells that participate in the inflammatory response. The relationship of trigeminovascular fibers to the pathogenesis of vascular head pain sheds light on possible mechanisms of migraine and other central nervous system conditions associated with headache and inflammation.
899 citations
TL;DR: It is concluded that administration of intravenous streptokinase to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.
Abstract: In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low-dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.
613 citations
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TL;DR: It is suggested that the anergy of early Hodgkin's disease is a peripheral defect; a manifestation of abnormal lymphocyte function; this suggestion is supported by preliminary work with Hodgkins lymphocytes in vitro and following lymphocyte transfer.
Abstract: The immunologic defect of early Hodgkin's disease is characterized by a depression of delayed hypersensitivity and can be assessed by negative reactions to a battery of delayed allergens or by inability to acquire contact sensitivity. While the homograft reaction is depressed in these patients, antibody formation is largely intact and the lymphocyte count is normal or but slightly depressed. It is suggested that the anergy of early Hodgkin's disease is a peripheral defect; a manifestation of abnormal lymphocyte function. This suggestion is supported by preliminary work with Hodgkin's lymphocytes in vitro and following lymphocyte transfer. Later in the course of the condition profound lymphopenia develops and most probably contributes to the more severe and complex immunologic deficiencies of advanced Hodgkin's disease.
97 citations
TL;DR: Zinc deficiency has been showed to impair DNA and protein synthesis in brain of the suckling rat as it has previously been shown to do in other tissues including liver and epiphyseal plate.
Abstract: Extract: The effect of zinc deficiency on the brain of the suckling rat was studied by feeding a zinc-deficient (Zn-) diet to dams from parturition and measuring the in vivo uptake of 3H-thymidine by brain DNA and the 35S uptake by brain protein as well as the brain lipid composition of their pups. These results were compared with similar data obtained on pups nursed by pair-fed (PF) and ad libitum-fed control dams which had been given zinc in addition to the diet. The specific activities (SA) of DNA and protein were decreased in the brains and livers of the pups nursed by the zinc-deficient dams compared with pups nursed by dams pair-fed with the zinc-deficient dams and hence semistarved (SA of brain DNA: Zn- = 5.90 versus PF = 11.36; SA of liver DNA: Zn- = 5.16 versus PF = 15.8; SA of brain protein: Zn- = 50.20 versus PF = 85.30; SA of liver protein: Zn- = 56.02 versus PF = 79.20). On the other hand, similar concentrations of DNA, RNA, and protein were present in their brains as well as their livers. The concentrations of total lipid were decreased in the brains of the deficient pups compared with the controls (Zn- = 0.215 versus PF = 0.309 mg/mg of brain), while the concentrations of brain phospholipid and the brain fatty acid patterns were similar. Zinc deficiency has thus been shown to impair DNA and protein synthesis in brain of the suckling rat as it has previously been shown to do in other tissues including liver and epiphyseal plate. Speculation: Zinc is essential for synthesis of nucleic acids and protein. In individuals with protiencalorie malnutrition, an associated zinc deficiency may compound the effects of protein deprivation by impairing utilization of the limited protein available. Zinc deficiency in the human may thus contribute to the impaired brain growth reported to occur in infants with protein-calorie malnutrition.
79 citations
TL;DR: Genetic studies of sera from 55 family members were performed by means of functional assays of elastase inhibition and total antitryptic activity and by measurements of alpha-1-antitrypsin concentration with a newly developed sensitive electroimmunodiffusion method.
48 citations
Journal Article•
28 citations