INFLUENCE OF GLANDS WITH INTERNAL SECRETION ON THE RESPIRATORY EXCHANGE : IV. EFFECT OF SUPRARENAL INSUFFICIENCY IN CATS.

1. Severe and sufficient non-fatal injury to the suprarenal cortex by freezing or by ligation in cats causes a significant and prolonged increase in heat production. 2. Lethal injury to the suprarenals by freezing, ligation, or partial excision in cats causes a fall in heat production. 3. Insufficient injury to the suprarenals by freezing, ligation, or partial excision in cats produces no significant alteration in heat production. 4. Further evidence of a dose thyroid-suprarenal cortex interrelationship is indicated by the rapidity of thyroid hyperplasia and by the effects of KI after suprarenal crippling.     

A STUDY OF THE MECHANISM OF RECOVERY FROM EXPERIMENTAL PNEUMOCOCCUS INFECTION

A study was made of the blood of cats and rabbits during experimental pneumococcus infection with a view to ascertaining the relationship of acquired immune properties to the mechanism of recovery. Observations were directed chiefly towards the detection of pneumococcidal promoting substances, but the other manifestations of anti-pneumococcus reaction were studied as well. It was found constantly that the serum of animals recovering from infection possessed the power to promote the destruction of highly virulent pneumococci in rabbit serum-leucocyte mixtures which mixtures of themselves have no growth inhibitory action. Furthermore, the presence of this serum immunity was associated with a marked increase in acquired resistance to the pneumococcus. In cats which were studied in the most detail the pneumococcidal promoting power of the serum as well as the opsonic, agglutinative, and mouse protective activities became demonstrable at the time of recovery and their appearance in the serum always marked the termination of blood invasion. These immune reactions were found to be type-specific. The animals which succumbed failed to develop detectable serum immune properties and showed persistent blood invasion. The degree of leucocytosis did not appear to bear any constant relation to the outcome of the disease. The significance of these findings is discussed.     

早期乳腺导管内癌钼靶X线表现及免疫组化分析

目的探讨乳腺导管内癌（DCIS）及导管内癌伴微浸润（DCIS-MI）的钼靶X线表现、免疫组化表达情况,分析二者之间的相关性。方法回顾性分析20例乳腺DCIS及36例乳腺DCIS-MI病人的钼靶X线表现,分析雌激素受体（ER）、孕激素受体（PR）、C-erbB-2及p53基因的表达情况,并分析影像学表现与上述标志物之间的相关性。结果钼靶X线表现为钙化33例,其中单纯钙化21例,钙化合并包块5例、结构紊乱5例、结节1例、腺体增厚1例;恶性钙化27例,中间钙化4例,良性钙化2例。表现为单纯包块2例、结节4例、结构紊乱9例、皮肤增厚2例。表现为阴性者6例。ER、PR、C-erbB-2、P53的阳性表达率分别为52.9%、52.9%、45.1%、58.8%。以非钙化组为对照组,恶性钙化与ER、PR、P53的表达无关（P〉0.05）,而与C-erbB-2表达有显著的相关性（χ2=4.850,P〈0.05）。结论乳腺DCIS及DCIS-MI的钼靶X线主要表现为钙化,恶性钙化与C-erbB-2的表达相关。     

应用改良四动脉结扎法制作猫全脑缺血再灌注损伤模型

背景：四血管结扎法制作全脑缺血模型目前主要用于小鼠、大鼠等小型动物,大型动物模型方面鲜有报道,缺少有关的解剖资料。目的：探讨四动脉结扎法制作猫全脑缺血再灌注损伤模型的方法改良。方法：参照Pulsinelli四动脉结扎法,提出电凝位于翼突与第二颈椎横突之间的椎动脉,永久性阻断双侧椎动脉。再临时阻断双侧颈总动脉,以动态脑电图监测出现静息脑电波为判定猫全脑缺血的标准。15min后恢复颈动脉供血,进行再灌注损伤。假手术组猫不进行电凝或夹闭即缝合切口。结果与结论：模型制作成功25只,模型制作不成功1只,死亡4只,成功率83%。苏木精-伊红染色示缺血脑组织呈典型的迟发性神经元坏死。提示改进后的四血管法制作猫脑缺血再灌注损伤模型,效果确切,模型制作成功率高。     

EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS : III. COMPARISON OF PLATELET INJURY INDUCED BY THROMBIN AND BY ENDOTOXIN

The platelet injury produced by bacterial endotoxin and thrombin have been compared in studies utilizing citrated rabbit platelet-rich plasma. Endotoxin-induced platelet injury is characterized by a lag period, is progressive, and does not produce gross clot formation. Thrombin-induced platelet injury is immediate, non-progressive, and is associated with clot formation. The quantity of thrombin required to produce clot formation in this citrated system is less than that required to produce release of platelet 5-hydroxytryptamine. The endotoxin-induced platelet injury required extremely large quantities of heparin for inhibition. The platelet injury induced by thrombin can be inhibited by small quantities of heparin. It is concluded that the injurious effects of endotoxin on platelets is mediated through some mechanism other than thrombin formation.     

STUDIES UPON CALCAREOUS DEGENERATION : I. THE PROCESS OF PATHOLOGICAL CALCIFICATION.

It will be seen from the above that we have studied the conditions associated with the deposit of calcareous salts: (I) in connection with normal and pathological ossification, and (2) in pathological calcification as exhibited in (a) atheroma of the vessels; (b) calcification of caseating tubercular lesions; (c) calcification of inflammatory new growth, and (d) degenerating tumors; and we have induced experimentally deposits of calcareous salts in the lower animals: (a) within celloidin capsules containing fats and soaps; (b) in the kidney, and (c) in connection with fat necrosis. I. We have found that bone formation and pathological calcareous infiltration are wholly distinct processes. In the former there is no evidence of associated fatty change, and the cells associated with the process of deposition of calcium are functionally active. In the latter there is an antecedent fatty change in the affected areas, and the cells involved present constant evidences of degeneration. The view that would seem to account best for the changes observed in the latter case is that with lowered vitality the cells are unable to utilize the products brought to them by the blood, or which they continue to absorb, so that the normal series of decompositions associated with their metabolism fails to take place and hence they interact among themselves in the cytoplasm with the result that insoluble compounds replace soluble ones. II. Besides the fact that calcification is always preceded by fatty change within the cells, another fact should be emphasized. namely: that combination of the fats present with calcium salts to form calcium soaps tends to occur. The stages immediately preceding these are difficult to follow with anything approaching certainty, perhaps because the earlier stages vary under different conditions. In fat necrosis, for instance, the cells affected are normally storehouses for neutral fats, and as long as they remain healthy neutral fats alone are present in them. When they are subjected to the action of the pancreatic juice with its fat-splitting ferment the cells are killed and coincidently the neutral fats are decomposed, fatty acids being deposited. The fatty acids now slowly combine with the calcium salts. In degenerating lipomata the process would seem to be similar. But in other cases the cells are not obviously fat-containing in the normal state; nevertheless prior to calcification they undergo so-called fatty degeneration, which is really a form of cell degeneration accompanied by fat infiltration. As regards the source of the cell fats in general we may safely accept: 1. That fats are transported in the blood as diffusible soaps. 2. That taken up by the cells these soaps may either— (a) Be reconverted into neutral fats and become stored in the cytoplasm as such, or (b) undergo assimilation proper, becoming part and parcel of the cell substance, in which case they are not recognizable by the ordinary microchemical tests. 3. If these two possibilities be accepted it follows that the appearance of fats and soaps in the degenerating cell may be due to either— (a) Absorption or infiltration of soaps from the surrounding medium, the degenerating cell retaining the power of splitting off the fat but being unable to utilize this in metabolism. (b) Cytoplasmic disintegration with dissociation of the soap-albumen combination or, more broadly, liberation of the fats from their combination with the cytoplasm. The appearances seen in the cells of atheromatous areas indicate that the first of these does occur. III. In areas undergoing calcareous infiltration we have demonstrated. the presence of soaps, and this often in such quantities that they can be isolated and estimated by gross chemical methods. By microchemical methods also we have been able to show that after removing all the neutral fats and fatty acids by petroleum ether there remains behind a substance giving with Sudan III the reaction we associate with the presence of soap. And experimentally we have produced these soaps within the organism, more particularly by placing capsules containing fats and fatty acids within the tissues and after several days finding that the capsules contain calcium soaps and possess a calcium content far in excess of that of the normal blood and lymph. IV. While these are the facts, certain of the details of this reaction demand elucidation. The existence of sodium and it may be potassium soaps in the degenerated cells is comprehensible if we accept that these are present in the circulating lymph and simply undergoing absorption. But even then, as these are diffusible substances how is it to be explained that they become stored up in these particular areas? We have found that, as a matter of fact, in regions which give the reaction for soaps, but which give no reaction for calcium (which therefore presumably contain at most amounts of the insoluble calcium soap too small to need consideration, the ordinary solvents for potassium and sodium soaps do not forthwith remove the stainable material; they are relatively insoluble. The reason for this insolubility is suggested by the observations made in the test tube, that soap solutions mixed with solutions of white of egg or blood serum form a precipitate of combined soap and albumen, which likewise is insoluble in water and alcohol. The indications are therefore that in cells undergoing degeneration, with degeneration of the cytoplasm, certain albuminous molecules unite with the soaps present to form relatively insoluble soap-albuminate. V. With regard to calcium soaps, these are also present and in certain stages appear to be the dominating form in the affected tissues. Two questions suggest themselves, viz.: what is the source of calcium, and what is the process by which they become formed? As to the source, the amount present in well-marked calcification is far in excess of the normal calcium contents of the affected tissue. If in the kidneys of experimental calcification three hundred times as much calcium may be present as in the normal kidney (von Kossa), the calcium must be conveyed to the part by the blood and lymph, and that this is so is demonstrated, as we have pointed out, by the distribution of the infiltration in solid organs, that like ovarian fibroids have undergone necrosis, in which the earliest deposits are superficial. As to the process, there are three possibilities: 1. That sodium and potassium soaps and soap albuminates are first formed and that interaction occurs between them and the diffused calcium salts from the lymph, the less soluble-calcium replacing the sodium and potassium. 2. That under certain conditions the calcium salts act directly on the neutral fats present in the degenerating cells. 3. That the neutral fats are first broken down into fatty acids and that these react with the calcium salts to form the soaps. We are assured that the first process occurs and that because in the boundary zone of areas of calcification we can detect soapy particles devoid of calcium, identical in position and arrangement with the particles more deeply placed which give the calcium reactions. But this is not the only reaction. In case of fat necrosis we see clearly that the third process is in evidence. And we are far from being convinced that the second does not also obtain. We have been impressed by the large accumulation of neutral fats in the cells in cases of early atheroma and the absence at any stage of the process of recognizable fatty acid. While soaps, it is true, are compounds of fatty acids with alkalies, it is recognized in ordinary domestic life that they can be formed by the direct action of strong lye upon ordinary fats, and this even in the cold. It is quite possible therefore that there occurs a similar direct process in the organism. The point is worth noting, however, that this does not occur in healthy cells the seat of fatty infiltration. We therefore leave this an open question, only laying down that, as indicated by the hyalin albuminous matrix left when calcium salts are dissolved out of an area of calcification, there must exist a calcium soap- or fat-albuminate similar to the potassium and sodium soap-albuminates already mentioned—such an albuminate as we can form with calcium soaps in the test tube. VI. In old areas of calcification soaps are largely if not entirely wanting, although these are to be detected at the periphery, when the process is still advancing. The reactions given by these older areas are almost entirely those of calcium phosphate, though some calcium carbonate is at times to be made out. This seems surely to indicate that the final stage in calcification is an interaction between the calcium soap-albuminates and substances containing phosphoric and carbonic acids. Such substances, it is needless to say, are present in considerable amounts in the lymph and blood. We must conclude that the acid sodium phosphates of the lymph act on the calcium soap, the highly insoluble calcium phosphates being formed (plus the albuminous moiety of the original compound) and diffusible sodium soap being liberated, while similarly alkaline carbonates form calcium carbonate and liberate sodium and potassium soaps. Calcium phosphate and calcium carbonate thus become the insoluble earthy salts of old crystalline areas of calcification. VII. As already stated very little soap is to be found in these old areas. It is possibly worth suggestion that the soaps liberated in this last reaction, as they diffuse out, again react with diffusible calcium salts and form calcium soaps which once more react with the alkaline salts to produce the phosphates and carbonates; that, in short, they have a katalytic action. Certain it is that old calcareous areas are extraordinarily dense, and have a coarse crystalline structure, wholly at variance with the finely granular appearance of the more recent areas, and these large crystalline masses, it would seem, can only be formed by successive deposition of new material and eventual fusion, as the interspaces become filled in between the original masses.     

THE INFLUENCE OF CERTAIN FACTORS,ESPECIALLY EMOTIONAL DISTURBANCES,ON THE EPINEPHRIN CONTENT OF THE ADRENALS

1. No evidence has been obtained that in cats and dogs with the nerves of one adrenal cut, emotional disturbances cause depletion of the epinephrin store of the normally innervated adrenal as compared with its fellow. 2. The depletion of the epinephrin store in cats under morphine is not dependent upon so called morphine fright, since a similar depletion is found in dogs in which, as is known, morphine produces symptoms the reverse of those of fright. 3. The signs of morphine fright can all be elicited by administering morphine to a cat in which one adrenal has been removed and the nerve supply of the other cut, and in which accordingly no detectable liberation of epinephrin takes place. 4. The reactions of the denervated iris elicited by emotional disturbance, asphyxia, or etherization in a cat, one of whose adrenals has been removed and the nerves of the other cut, do not differ from these reactions in cats whose adrenals have not been interfered with. 5. The influence of postoperative edema of the adrenal in diminishing the epinephrin load, and the recuperation of the load after a time, have been studied in rabbits. 6. The diminution in the epinephrin store of the adrenals which follows operations on animals (postoperative depletion) has been studied. It is only in part associated with the anesthesia, since it may be as marked 6 or 8 hours after an operation lasting less than 1 hour as after 6 or 8 hours'' anesthesia without operation. 7. One adrenal was removed in rabbits and the epinephrin content of the remaining gland assayed at varying periods of time after removal of the first, the periods being longer than the time necessary for recovery from the postoperative depletion. In general, the second adrenal contained more epinephrin than the first, sometimes double the amount. 8. Marked depletion of the epinephrin store of innervated adrenals as compared with the corresponding denervated glands was seen in animals dead of infections of various kinds. 9. As shown by Elliott, diminution of the stock of epinephrin in the adrenal through electrical stimulation of the splanchnics is not easy to demonstrate, despite the fact that the liberation of epinephrin into the blood is notably increased by the stimulation. With short periods of stimulation, however, repeated over a long time at intervals just long enough to prevent fatigue, it has proved possible to demonstrate a distinct depletion.     

STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION : II. THE EFFECT OF NON-SPECIFIC INFLAMMATION

Studies have been described in which the effect of early and late or established inflammation, upon staphylococcus infection of rabbit skin has been evaluated. Inflammation was produced in skin by thermal, chemical, bacterial and immunological injury, and it was found that the area of inflammation was more susceptible to staphylococcus infection than was normal skin if the bacteria were injected within 2 to 3 days after the injury. When staphylococci were injected into an area of inflammation of over 3 days' duration, there appeared to be an increase in local resistance to infection. The way in which inflammation was produced seemed to have a little influence upon the effects observed. This influence of non-specific inflammation upon staphylococcus infection was compared with the influence of specific bacterial hypersensitivity, which also is associated with an increase in infectivity of the microorganism in sensitized animals. It was concluded that specific bacterial hypersensitivity probably increases susceptibility to infection with the staphylococcus in the same way as non-specific inflammation. The general significance of non-specific inflammation upon infection is also discussed.     

Aortic arch calcification and clinical outcome in patients with end-stage renal disease

Vascular calcification is very common in end-stage renal disease, especially in hemodialysis patients. Vascular calcification is associated with poor prognosis in hemodialysis patients. The transformation of vascular smooth muscle cells into osteoblast-like cells seems to be a key element in the pathogenesis of vascular calcification. In addition to traditional risk factors including hypertension and dyslipidemia, hemodialysis patients possess a number of non-traditional cardiovascular risk factors, which may be associated with the pathogenesis of vascular calcification, such as duration of dialysis and imbalance of mineral metabolism. The severity of vascular calcification can be assessed with computed tomography (CT), but a simple technique is required as a routine practice. In an attempt to evaluate the extent of vascular calcification, we have proposed a simple non-invasive technique for estimating aortic arch calcification (AoAC) in hemodialysis patients. The present review summarizes the following aspects: (i) a method of estimating AoAC and the correlation between AoAC score estimated by chest X-ray and AoAC volume evaluated by multi-detector CT as a gold standard, (ii) relation of the presence of AoAC to the prevalence of cardiovascular diseases, and (iii) Kaplan-Meier analysis in terms of cardiovascular mortality in patients with AoAC compared to those without AoAC. We suggest that screening patients undergoing dialysis for the presence of AoAC is a cost-effective, efficient way to identify those patients at the highest risk of cardiovascular events and will allow for the treatment strategies to prevent vascular calcification.     

THE RELATION OF THE SPINAL CORD TO THE SPONTANEOUS LIBERATION OF EPINEPHRIN FROM THE ADRENALS

1. After section of the spinal cord in cats in the cervical region, as low as the last cervical segment, epinephrin continues to be liberated from the adrenal glands. This liberation has all the characters of the normal secretion with intact central nervous system. It is sustained through the same nerve paths connecting the cord with the adrenals. 2. After section of the cord in the middorsal region the spontaneous liberation of epinephrin from the adrenals is abolished within the limits of detectability by the methods employed (denervated eye reactions of Meltzer, and rabbit intestine and uterus segments). 3. The portion of the cord concerned in the liberation of epinephrin does not appear to extend much below the third thoracic segment. 4. In acute experiments on cats under urethane anesthesia no change in the rate of liberation of epinephrin, which could be detected by the tests employed, was observed when the cord was severed in the cervical region.     

Caseous calcification and liquefaction of the mitral annulus: a diagnostic confounder

Caseous calcification of the mitral annulus is a rare form of periannular calcification that has a distinct appearance. It generally appears as a large spheric mass like calcification with a central echolucent area that may lead to diagnostic errors. Cardiac imagers should be familiar with this rare form of periannular calcification. We report the case of a 62-year-old woman in whom a suspicious spheric mass like calcification was detected with multislice computed tomography which was performed for coronary artery calcium scoring. Echocardiography displayed the typical findings of caseous calcification of the mitral annulus with central liquefaction.     

中脑网状结构损伤对意识及生命体征影响的实验研究

目的 研究中脑网状结核损伤对意识和生命体征的影响以及它们之间的了解中脑损伤后意识障碍及其恢复机制。方法：定向电解的方法造成没和蔼的中脑网状结构损伤，观察猫意识及生命体征的变化并对照病理改变，了解中脑损伤与意识障碍及本征变化的关系，及其恢复的可能性。结果 中脑风状结构损伤造成猫意识障碍及生命体征的明显变化，两者间有一致性，同步性发作和且与中脑损伤程度密切相关。结论 中脑网状结构损伤可致意识障碍及生命     

Vascular calcification and hypertension: cause and effect

Vascular calcification is an active and regulated process which is integral to cardiovascular disease and intimately linked to hypertension. Dysfunctional vascular smooth muscle cells, microvesicles, and dysregulated mineralization inhibitors play key roles in the calcification process, which occurs in the vessel intima in association with atherosclerosis as well as in the vessel media during ageing. Historically hypertension was considered a risk factor promoting atherosclerosis and associated intimal calcification. However, it is now recognized that not all vascular calcification occurs with atherosclerosis, and calcification of the vessel media is associated with arterial stiffening and is a major cause of isolated systolic hypertension in the elderly. Importantly, vascular calcification, regardless of its anatomical site, is an independent risk factor for cardiovascular mortality. Therefore, understanding the factors and mechanisms driving these processes will provide novel therapeutic targets for its prevention and perhaps ultimately its regression.     

TRANSPLANTATION IN MASS OF THE KIDNEYS

Among so many etiological factors, it is impossible to discriminate which are responsible for the complications which took place in our experiments. An attempt to explain the occurrence of nephritis, cedema or calcification of the arterial system, for instance, will not be made, but the technique of the operations will be modified in order to suppress as much as possible the causes which may originate these secondary changes. The purpose of this article was not to analyze minutely the physiological or pathological character of the functions of transplanted kidneys, but merely to ascertain whether these functions are efficiently reëstablished. It is to be concluded that an animal which has undergone a double nephrectomy and the grafting of both kidneys from another animal can secrete almost normal urine with his new organs, and live in good health at least for a few weeks. This demonstrates that it is possible to reëstablish efficiently the functions of transplanted kidneys.     

Genetic determinants of arterial calcification associated with atherosclerosis

Increasing research interest has focused on arterial calcification in the setting of atherosclerosis. Many features of atherosclerosis-related calcification provide useful clinical information. For example, calcium mineral deposits frequently form in atherosclerotic plaque, and intimal arterial calcification can be used as a surrogate marker for atherosclerosis; also, calcium deposits are readily and noninvasively quantified, which is useful because greater amounts of coronary calcification predict a higher risk of myocardial infarction and death. Several mechanisms leading to calcification associated with atherosclerosis have been proposed; however, no direct testing of proposed mechanisms has yet been reported. Studies in genetically altered animals and in humans have shed light on potential genetic determinants, which in turn could form the basis for a more comprehensive understanding of the factors affecting calcification within plaque and the associated pathobiologic implications. We review proposed molecular and cellular mechanisms of atherosclerosis-associated arterial calcification, summarize genetic influences, and suggest areas in which further investigation is needed. Understanding the molecular and genetic determinants of specific structural plaque components such as calcification can provide a solid foundation for the development of novel therapeutic approaches to favorably alter plaque structure and minimize vulnerability to arterial rupture.     

PROTEOSE INTOXICATIONS AND INJURY OF BODY PROTEIN : II. THE METABOLISM OF DOGS WITH DUODENAL OBSTRUCTION AND ISOLATED LOOPS OF INTESTINE.

Dogs with isolated loops of small intestine show many evidences of intoxication. A study of the total nitrogen elimination shows a great rise above the normal base-line minimum of the fasting period (Table II). This means that the intoxication is associated with a great destruction of body protein, and explains the high non-protein nitrogen of the blood which was observed and reported previously (2). Injection of a proteose obtained from a closed intestinal loop will cause a similar rise in the nitrogen elimination curve. This furnishes more evidence that the intoxication observed in association with a closed intestinal loop is in reality a proteose intoxication. Dogs injected with sublethal doses of proteose will show a definite tolerance to subsequent injection, and will show much less acute intoxication after the isolation of a closed intestinal loop (Table 1). These immune or tolerant dogs show a much less pronounced rise in the nitrogen elimination curve during proteose intoxication of any type. This indicates that the tolerance or immunity to proteose gives more protection for the body proteins against the injury which these toxic proteoses inflict upon the body cells. Complete duodenal obstruction combined with a gastrojejunostomy gives a chronic type of intestinal obstruction associated with little vomiting, which is peculiarly suited to metabolism study (Table IV). Such duodenal obstructions show a definite and sustained rise in the curve of nitrogen elimination above the normal base-line level. These dogs, too, are tolerant to injections of standard toxic proteoses. Control ether anesthesia experiments show little if any rise in the curve of nitrogen elimination (Table VI). Control laparotomy experiments show a definite rise in the curve of nitrogen elimination, but a rise which is small compared with the rise noted in the intoxication of duodenal obstruction or of isolated intestinal loops. It is probable that the tissue injury and disintegration associated with the wound reaction are responsible for the general reaction. We may assume that protein split products from the wound area are absorbed and are responsible for the general reaction observed. We propose to assume that the intoxications here studied are associated with a definite proteose intoxication, which is capable of initiating and continuing a profound injury of tissue protein. One index of this protein injury is the great and sustained rise in the curve of total nitrogen elimination.     

Right upper quadrant calcification: porcelain gallbladder disease.

Large solitary calcification in the right upper quadrant is rarely seen in the United States. It may indicate disease in the gallbladder, adrenal glands, kidneys, pancreas, lungs or chest wall. Disease processes associated with calcification in these organs include echinococcal cysts, calcified renal cysts, chest wall masses and degenerative cystic lesions of the pancreas and adrenal glands. However, if calcification is associated with porcelain gallbladder, the incidence of carcinoma is high. Treatment consists of cholecystectomy with a careful search for malignancy.     

Vascular calcification in chronic renal failure

The prevalence and extent of vascular calcification (VC) increases rapidly with time on dialysis. There is increasing evidence that medial calcification of conduit arteries, without intimal disease, is associated with important abnormalities of vascular compliance and increased risk of cardiovascular death. Coronary artery calcification is also common in end-stage renal disease, but further research is required to determine how much of this calcification is in the form of calcified intimal atherosclerotic plaque and how much in the tunica media. Calcific uraemic arteriolopathy causes a syndrome of ischaemic necrosis of the skin and subcutaneous tissue and appears to be increasing in incidence. At all sites, arterial calcification is a biologically controlled process, with expression in vascular smooth muscle cells of genes usually expressed in osteoblasts and the formation of hydroxyapatite. High extracellular phosphate concentration induces these phenotypic changes in vitro, and much of the clinical evidence supports hyperphosphataemia as the major driver of VC. Whether warfarin treatment plays a role, by inhibiting production of vitamin-K-dependent inhibitors of calcification in humans, remains uncertain but possible. High doses of prescribed calcium-based phosphate binders are associated with VC, whereas use of sevelamer to achieve the same serum phosphate level greatly retards progression of coronary and aortic calcification. The biological mechanism by which positive calcium balance and/or episodes of hypercalcaemia promotes VC remains unclear. Treatment of established calcific uraemic arteriolopathy consists of aggressive reduction of serum calcium x phosphate product; the roles of hyperbaric oxygen, steroid therapy, and non-warfarin anticoagulation remain uncertain.     

THE PRODUCTION OF EXPERIMENTAL NEPHRITIS BY REPEATED PROTEID INTOXICATION

The repeated injection of small doses of horse serum and egg-white in dogs, cats, rabbits, and guinea pigs that have been sensitized to these proteins, causes injury to the cells of various organs and tissues with resulting inflammatory reactions. The changes are especially marked after intraperitoneal injections in the peritoneum and after intravenous injections in the livers of rabbits and cats, and in the myocardium and kidneys of all groups of animals. In dogs and rabbits, especially, there develops a well marked nephritis characterized by degeneration and necrosis of the epithelium of the loops of Henle, of the collecting tubules, and less frequently of the convoluted tubules. This is accompanied by an extensive small round cell infiltration of the interstitial tissue and later the formation of connective tissue. Together with these changes there are acute and chronic alterations in the glomeruli of all groups of animals. Egg-white in large doses is itself injurious to the kidney of animals, but this slight primary toxicity is probably greatly enhanced through previous sensitization of the animal.     

Myocardial calcifications in neonates and infants: a unique tissue reaction

The deposit of calcium salts into myocardial cells represents the process of dystrophic calcification. Once it causes alterations in cellular calcium hemostasis, it can initiate deleterious events leading to ischemic myocardial injury and cell death. Myocardial calcifications in infants are markedly different from those in adults; calcifications are significantly more frequent in cases of myocardial necrosis in the young, and can be demonstrated microscopically without removal of necrotic fibers and scar formation, which are the adult's usual stages of response to myocardial necrosis. Important functional and clinical implications in myocardial calcification, other than serving as a marker for necrosis, relate to accelerated myocardial calcification after cardiac surgery in infants.