Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a type of cerebral lesion, which kills neuronal cells at a later stage (greater than 48 hrs) post CA, while the systemic circulation is functioning normally. Although this lesion is probably dependent on multiple factors (----multiple therapies), a keyfactor in the pathogenesis is the loss of autoregulation and "finetuning" of the cerebral bloodflow according to local tissue metabolic needs. Although beneficial effect of almost none of the following therapies has been documented in randomised clinical studies, the following suggestions are made: a) In the CA-CPR phase: efficient respiratory care and external cardiac compressions (ECC), especially during bicarbonate administration; consider open chest CPR early, especially in cases of long arrest time and ineffective ECC. The socalled new CPR does not improve neurological outcome. b) In the post CPR phase: The non-autoregulated brain (cfr. focal ischemia) is kept preferentially at pCO2 values 25-30 mmHg, pO2 values greater than 100 mmHg, and normotension. Some form of stress, seizure and hyperthermia control prevents further imbalance metabolism/bloodflow. Relative dehydration, oncotic balance, steroids, early control of sepsis and uremia, early CT scan and measurement/control of ICP. All the above is currently grouped under "standard neuro-intensive therapy". Some other therapies, presently suggested by animal research are not very obvious, need first randomised clinical studies and are not suggested at this stage for clinical use: barbiturate coma, diphantoine, streptokinase, multifaceted therapy including hemodilution-brainflushing, Ca++ influx blocking drugs (lidoflazine). One such "innovative" therapy, barbiturate coma, has already been proven to be relatively ineffective (BRCT I) (Acta anaesth. belg., 1984, 25, suppl., 219-226).
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PMID:Brain protection in the immediate post-resuscitation phase. 651 33

From March, 1976 to June, 1983, 22 patients (10 males, 12 females) treated by maintenance hemodialysis were autopsied in our department. Primary diseases of the autopsied cases were chronic glomerulonephritis (12 cases), diabetes mellitus (three cases), hydronephrosis (three cases), systematic lupus erythematosus (two cases), myeloma kidney (one case) and atherosclerosing nephropathy (one case). Direct causes of death in maintenance hemodialysis patients were bleeding (six cases), uremia (three cases), infection (three cases), carcinoma (four cases), heart failure (two cases), myocardial infarction (one case), brain ischemia (one case), cardiac tamponade (one case) and unknown (one case).
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PMID:Autopsy findings in maintenance hemodialysis patients. 653 69

The existence of treatable postischemic (PI) changes which influence neurological outcome has been documented by this group before. A global brain ischemia model without cardiac arrest was developed in monkeys. It includes high-pressure neck tourniquet inflation plus hypotension for a reproducible ischemic insult; survival with reproducible neurological deficit (ND) under continuous PI life-support for 7 days with control of extracranial variables; and new ND and histopathological damage scoring systems. Hypoxemia, hypercarbia, hypotension, uremia, sepsis, and other extracranial complications PI in 50 unsatisfactory experiments led to immediate worsening in ND and brain death (ND = 100%) in most of these monkeys. In contrast, all monkeys with the same initial insult, with life-support according to protocol, survived with a 7 day ND of 60% or less. In 46 experiments of seven treatment groups, after 16 or 18 min ischemia, life support was according to protocol for 7 days. The control 1 protocol (spontaneous breathing when feasible) resulted in a mean 7-day ND score of 53% (including quadriplegia). Immobilization with pancuronium and controlled ventilation ameliorate deficit to an ND score of 19% (P less than 0.05) (including quadriparesis); this became control 2 protocol. Immobilization resulted in less neuronal damage in the neocortex. Severe repetitive hypertension worsened ND to 46%, versus 19% in controls (P less than 0.05). In separate series, neither heparinization over 72 hours PI, nor hemodilution to hematocrit 25% with dextran 40, changed final ND significantly from that of their control groups. Histopathological damage scores correlated with ND scores.
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PMID:Effect of postcirculatory-arrest life-support on neurological recovery in monkeys. 676 78

Rats within the early maintenance phase of post-ischemic acute renal failure (ARF) can resist additional ischemic insults. This study assessed whether this protection exists directly at the tubular cell level, and if so, whether it is a consequence of prior cell injury (for example, due to heat-shock protein synthesis; HSP), or if it arises in response to reductions in functional renal mass and/or the uremic environment. Rats were subjected to either 15 or 35 minutes of unilateral or bilateral renal ischemia, and after 15 minutes to 24 hours of reflow, proximal tubular segments (PTS) were isolated for study. Their viability following oxygenation and hypoxic/reoxygenation injury (H/R) was tested (LDH release). The influence of uremia/reduced renal mass was determined by studying PTS extracted 24 hours after 1 1/2 nephrectomy, and by determining whether PTS exposure to a "uremic milieu" (urine addition) blocks H/R damage. HSP effects were gauged by correlating renal cortical HSP-70 expression with degrees of in vitro protection, and by ascertaining whether in vivo hyperthermia (42 degrees C; 15 min) mitigates subsequent PTS H/R damage. Results were compared with those obtained from normal PTS. The in vivo experimental protocols did not substantially alter PTS isolation or their viability during oxygenation. Fifteen minutes of ischemia induced neither azotemia nor PTS cytoprotection. In contrast, 35 minutes of ischemia conferred marked protection against subsequent H/R, but only when azotemia was permitted to develop (protection seen after 24 hr, but not at 4 hr of reflow; protection abrogated by retention of 1 normal kidney). Renal failure in the absence of tubular necrosis (1 1/2 uninephrectomy) protected PTS from H/R damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Post-ischemic acute renal failure protects proximal tubules from O2 deprivation injury, possibly by inducing uremia. 793 24

In chronic uremia, apart from frequent coronary lesions, further abnormalities of the heart recently reported include (1) left ventricular hypertrophy, not completely explained by hypertension, (2) interstitial myocardial fibrosis, for which parathyroid hormone is a permissive factor, (3) reduced myocardial perfusion reserve, secondary to functional and structural changes of intramyocardial arteries and to reduced capillary density, (4) abnormalities of myocardial metabolism, which act in concert with restriction of blood flow by microvascular abnormalities to reduce ischemic tolerance. Such metabolic abnormalities include diminished responsiveness to beta-adrenergic stimulation, abnormal control of intracellular calcium concentration, impaired maintenance of energy-rich nucleotide concentrations under conditions of ischemia, impaired insulin-mediated glucose uptake, and abnormalities of myocardial oxidative metabolism.
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PMID:Cardiac disease in chronic uremia: pathophysiology. 923 26

A total of 140 pathoanatomic conclusions and files collected by the author are analyzed. Morphological signs of the DIC syndrome were detected in 55% of patients who died. In 42% of lethal outcomes this syndrome was the final direct cause of death after such conditions as terminal stage of cancer, sepsis, extensive myocardial infarction, mechanical jaundice, uremia, bacteremia, etc. In 13% of autopsies fatal intravascular coagulation was a complication of the intervention or hemorrhage which was arrested before death. The DIC syndrome is diagnosed during autopsy due to a complex of peculiar changes in the viscera which are called "shock" in such cases. The signs of a shock liver are as follows: a characteristic red net pattern of the sliced surface and histological phenomena related to blocking of the sinusoidal bloodflow and lobular ischemia: abnormal hepatocyte complexes, fragmentation of liver bulks, and necrosis of the central lobules.
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PMID:[Morphological diagnosis of DIC syndrome. Shock liver]. 951 Dec 43

Experiments indicate that capillary density is reduced in the hypertrophied left ventricle of rats with subtotal nephrectomy compared to control rats with similar BP and left ventricular hypertrophy, suggesting that in uremia, hypertrophying cardiomyocytes outgrow their capillary supply. No information on myocardial capillary supply in humans is currently available. The hearts of nine dialyzed patients, nine patients with essential hypertension, and 10 normotensive control subjects at postmortem were obtained. Subjects with stenosing coronary lesions and left ventricular pump failure were excluded. Special sampling procedures were used to exclude stereologic artefacts. Capillaries were specifically stained with ulex lectin and analyzed by stereologic techniques. Length density of myocardial capillaries (Lv; mm/mm3) was significantly (P < 0.001) lower in dialyzed patients (1483 +/- 238) than in patients with essential hypertension (1872 +/- 243) or in normotensive control patients (2898 +/- 456). In parallel, myocyte diameter and volume density of myocardial interstitial tissue were significantly (P < 0.001) increased in uremic patients compared to patients with essential hypertension and control patients, respectively. Diminished left ventricular capillary supply in renal failure must increase critical oxygen diffusion distance in the myocardium, thus exposing cardiomyocytes to the risk of hypoxia. It is unknown whether such reduced ischemia tolerance can be reversed by increasing oxygen supply (e.g., by reversing anemia).
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PMID:Myocyte/capillary mismatch in the heart of uremic patients. 962 Dec 84

Acute and subacute extrapyramidal movement disorders are rarely reported in uremic patients. We report three such cases with basal ganglia lesions. All three had advanced renal failure with high serum creatinine levels. One of the patients had a history of ischemic heart disease and acute pulmonary edema with hypoxemia. Another patient had experienced arterial hypotension during previous hemodialysis. The third had prominent metabolic acidosis. One of the patients developed generalized dyskinesias, whereas the other two developed gait disturbances. Neuroimaging studies in all three cases showed bilateral changes in the basal ganglia. The natural history was self-limiting with gradual improvement. Diminution of the basal ganglia lesions was demonstrated on follow-up imaging in two of the three cases. We conclude that acute or subacute movement disorders with bilateral basal ganglia lesions may occur in uremia. Hypoperfusion with global brain ischemia and selective vulnerability of the basal ganglia to uremic toxins may account for these lesions.
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PMID:Acute movement disorders with bilateral basal ganglia lesions in uremia. 982 21

Nephrovasculopathies are an increasing cause of end-stage renal failure. Nephrosclerosis is a common finding in the hypertensive patient. However, genetic factors play a prominent role in its incidence. Nephrosclerosis is a common cause of early renal failure in blacks of African ancestry, as opposed to white Europeans, in whom hypertensive nephrosclerosis rarely and slowly leads to uremia. That primary hypertension is accompanied by arterionephrosclerosis and arteriolonephrosclerosis, by focal and segmental glomerulosclerosis leading to glomerular obsolescence and by interstitial fibrosis has been established for nearly a century. However, renal vascular lesions can be observed in animal models as well as in some humans, especially blacks, in the absence of, or preceding the onset of hypertension. This suggests that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed, a defect closely associated with the hypertensive trait. Atherosclerotic renal artery stenosis is a major, potentially remediable cause of chronic renal failure, especially in whites. Its prevalence in the atherosclerotic population is in the order of 15 percent. This figure has obvious bearing in terms of health cost. Early diagnosis and treatment by angioplasty or surgery can preclude development to end-stage renal disease and maintenance hemodialysis, as renal atrophy due to chronic ischemia resulting from renal artery stenosis can be halted or partially reversed by revascularization before extensive fibrosis sets in. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension. The relationship between fibrogenesis and these vascular lesions, which develop along with interstitial fibrosis and entail an unfavorable prognosis in various glomerulopathies, remains to be elucidated. This is especially the case for focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis. The pathophysiology of renal fibrosis induced by ischemia is centered on increased generation of angiotensin II that is fibrogenic owing to interaction with endothelin 1, PDGF-BB and TGF-beta. These notions open perspectives toward pharmacologic means to retard or even prevent the development of such various ischemic conditions to end-stage renal failure.
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PMID:[Vascular mechanisms of renal fibrosis. Vasculonephropathies and arterial hypertension]. 1037 63

MAPK activities, including JNK, p38, and ERK, are markedly enhanced after ischemia in vivo and chemical anoxia in vitro. The relative extent of JNK, p38, or ERK activation has been proposed to determine cell fate after injury. A mouse model was established in which prior exposure to ischemia protected against a second ischemic insult imposed 8 or 15 days later. In contrast to what was observed after 30 min of bilateral ischemia, when a second period of ischemia of 30- or 35-min duration was imposed 8 days later, there was no subsequent increase in plasma creatinine, decrease in glomerular filtration rate, or increase in fractional excretion of sodium. A shorter period of prior ischemia (15 min) was partially protective against subsequent ischemic injury 8 days later. Unilateral ischemia was also protective against a subsequent ischemic insult to the same kidney, revealing that systemic uremia is not necessary for protection. The ischemia-related activation of JNK and p38 and outer medullary vascular congestion were markedly mitigated by prior exposure to ischemia, whereas preconditioning had no effect on post-ischemic activation of ERK1/2. The phosphorylation of MKK7, MKK4, and MKK3/6, upstream activators of JNK and p38, was markedly reduced by ischemic preconditioning, whereas the post-ischemic phosphorylation of MEK1/2, the upstream activator of ERK1/2, was unaffected by preconditioning. Pre- and post-ischemic HSP-25 levels were much higher in the preconditioned kidney. In summary, post-ischemic JNK and p38 (but not ERK1/2) activation was markedly reduced in a model of kidney ischemic preconditioning that was established in the mouse. The reduction in JNK and p38 activation can be accounted for by reduced activation of upstream MAPK kinases. The post-ischemic activation patterns of MAPKs may explain the remarkable protection against ischemic injury observed in this model.
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PMID:Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. 1115 Feb 93


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