Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new patient with neonatal lactic acidosis due to pyruvate carboxylase deficiency is described. Since birth he developed vomiting, hypothermia, lethargy, irritability, hypoglycemia and severe metabolic acidosis. During admission a progressive deterioration was observed. Despite different attempted therapies patient died at 4 1/2 months of age. High levels of plasma and urine lactate and pyruvate were detected. Enzymatic studies in cultures skin fibroblasts and postmortem tissues showed a severe deficiency of pyruvate carboxylase.
 ...
PMID:[Neonatal lactic acidosis caused by severe pyruvate carboxylase deficiency]. 314 24

The primary cause of ischaemic neuronal damage is the reduction in the regional cerebral blood flow below the threshold critical for preservation of nervous structures. The development of infarction, however, is not determined only by the severity of ischaemia but also by the duration of a blood flow disturbance below a critical level. During the ischaemic period, and also after reperfusion, secondary mechanisms are triggered (cytotoxic and vasogenic oedema, tissue lactacidosis, entry of Ca++, synthesis of prostaglandins and leukotrienes, production of free radicals and liberation of neurotransmitters), which contribute to the ischaemic cell damage. These pathophysiological mechanisms in the development of ischaemic cell damage suggest three approaches for therapeutic intervention: a. Improvement of cell tolerance against ischaemia b. Increased cerebral blood flow c. Inhibition of secondary damage. a. An improvement of the tolerance of brain cells to ischaemia can be experimentally achieved by hypothermia and barbiturate loading; due to severe side effects, these therapeutical regimens are not clinically applicable. b. An increase in cerebral blood flow, which must be induced within a short period of time, can be obtained by various drugs with different modes of action. While vasodilators are not clinically efficient, haemodilution with low molecular dextran has been shown to be a promising therapeutic concept. Other strategies to improve rheological properties of blood (venesection, other haemodiluting infusions, hydroxyethyl starch drugs acting directly on blood rheology, such as extract of ginkgo biloba) can also be applied. Anticoagulation can be performed only in a few special cases with ischaemic infarction. The increase in perfusion pressure is helpful in hypotonic patients to improve blood supply in the ischaemic region. Cerebral perfusion can also be augmented by drugs which activate function and metabolism. c. Secondary damage to cells surviving the primary ischaemic insult can be inhibited by suppression or diminution of perifocal brain oedema; under ischaemic conditions, osmotherapy is superior to corticosteroids for this purpose. Pathological biochemical mechanisms initiated during or shortly after the ischaemic episode and causing additional cell damage can be influenced by pharmacological interaction (Ca++ entry blockers, inhibitors of prostaglandin synthesis, scavengers of free radicals, e.g. flavones, opiate antagonists). However, the routine application of these drugs in clinical practice still necessitates more controlled trials. Excessive lactacidosis can be controlled by regulation of plasma glucose levels.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Therapy of cerebral ischemia]. 332 70

The high-dose effects of chlorocitrate [(-)-threo-chlorocitric acid] were compared in vivo to another halogenated citrate analog, and a well-known inhibitor of the tricarboxylic acid (TCA) cycle, fluorocitrate. The compounds were given iv to two dogs per sex per group, and a control group received an equimolar amount of citric acid. Chlorocitrate (100 mg/kg) showed TCA cycle inhibition as did fluorocitrate (8 mg/kg) in that both caused depletion of ATP and accumulation of citrate in the liver. Chlorocitrate was a significantly weaker inhibitor of citrate metabolism than fluorocitrate as evidenced by a substantially lower accumulation of serum citrate despite a much higher dose. Both halocitrates produced a similar diabetes-like syndrome (hyperglycemia, glycosuria) mediated by a significant hyperglucagonemia and slight hypoinsulinemia. Chlorocitrate was more potent in this effect and a much greater buildup of plasma lactate ensued (18- versus 3.7-fold increase), enough to explain lethality observed in earlier studies. In contrast, fluorocitrate produced a severe life-threatening hypocalcemia (-30%), and hypercalcuria was observed. This effect on calcium distribution was only minimal with chlorocitrate. Both halocitrates had a similar depressive effect on circulation as evidenced by hypothermia, bradycardia, and elongation of the QT-interval. These changes were considered to be the result of lactic acidosis and the ongoing ion imbalance since heart ATP levels were not depleted.
 ...
PMID:Comparative acute toxicity of chlorocitrate and fluorocitrate in dogs. 359 Jan 93

Accidental hypothermia, a condition seldomly seen in Chile, is defined as a spontaneous core temperature reduction to less than 35 degrees C and is associated with great morbidity and mortality. We report a 16 years old female intoxicated with liquefied petroleum gas that was admitted in coma, hypothermic, with severe hemodynamic derangement, lactic acidosis, rhabdomyolysis and iliofemoral phlebothrombosis. Peritoneal dialysis with solutions at 27 degrees C was used as a quick and safe means to revert hypothermia and avoid its complications.
 ...
PMID:[Hypothermia: a non renal indication for peritoneal dialysis]. 773 31

To study the molecular basis of ammonia toxicity, highly reproducible models of acute liver failure and acute hyperammonemia in the rabbit were developed. Acute liver failure was induced by two-stage liver devascularization, and acute hyperammonemia by prolonged ammonia infusion such that the plasma ammonia pattern found in acute liver failure was simulated. Clinical symptoms, spectral analysis of the EEG, biochemistry (blood gases, renal function, electrolytes and markers of hepatic injury) and the presence of cerebral edema were studied. During acute liver failure severe encephalopathy developed after 10.2 +/- 1.9 h (n = 6, mean +/- SEM). Other liver-failure-associated abnormalities were cerebral edema, lactic acidosis, renal dysfunction, hypothermia and septicemia. During acute hyperammonemia, severe encephalopathy developed after 18.2 +/- 0.4 h (n = 6, mean +/- SEM). Other abnormalities found were cerebral edema and lactic acidosis. In both animal models comparable EEG changes were observed (a decrease in mean dominant frequency and theta-activity, and an increase in delta activity). However, these changes were not statistically significant, and non-specific as they also occurred in control rabbits despite their clinical wellbeing. This study demonstrates in the rabbit the similarity between encephalopathy due to acute ischemic liver failure and that due to hyperammonemia. An observed difference in hyperammonemia-induced encephalopathy was pronounced ataxia, which did not occur during acute liver failure, whereas hypothermia, sepsis and renal failure occurred exclusively in acute liver failure. Our models appear satisfactory for the study of hepatic encephalopathy and ammonia toxicity.
 ...
PMID:Encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. A clinical and biochemical study. 817 26

Hypothermia has been shown to decrease oxygen consumption requirements and improve survival during hemorrhagic shock. however, hypothermia applied therapeutically does not prevent the development of a lactic acidosis during hemorrhage. We re-examined the development of a hemorrhage-induced lactic acidosis and other metabolic parameters (glucose, plasma electrolytes, and arterial blood gases) at various temperatures (29-37 degrees C) to better define the protective action of hypothermia in hemorrhagic shock. Five groups of male, Sprague-Dawley rats were bled to a mean arterial blood pressure (MABP) of 40 mmHg over a 15 min period and held there by further blood removal until death. The final level and rate of development of the lactic acidemia was the same in all groups. However, the rate of decline in plasma glucose and rate of rise in plasma potassium were temperature dependent. These results suggest that temperature-dependent changes in serum glucose and potassium may contribute to the protective effect of hypothermia during hemorrhagic shock.
 ...
PMID:The effect of hypothermia on potassium and glucose changes in isobaric hemorrhagic shock in the rat. 888 90

Many animals respond to hypoxic stress by selecting cooler environments, the so-called 'behavioural hypothermia' response. Amphibians overwintering in ice-covered ponds and lakes offer an ecologically relevant test of this response since they must choose between the confounding metabolic effects of profound hypothermia or hypoxia; thermal and chemical conditions can vary from 0 degrees C and normoxic at the ice-water interface to 4 degrees C and markedly hypoxic at depths of 2-4 m. To mimic such environmental conditions, we constructed an experimental chamber that enabled continuous electronic surveillance of an animal's movement along a thermal gradient. When Rana temporaria pre-acclimated to 3.5 degrees C were placed in a normoxic thermal gradient ranging from 0.8 to 8 degrees C, they invariably favoured the warmer end of the chamber. Upon exposure to hypoxia, however, their preferred temperature shifted from a median of 6.8 degrees C (P02 = 158 mmHg; 1 mmHg = 0.133 kPa) to 1.9 degrees C (P02 = 25 mmHg). Metabolic rate measurements from animals exposed simultaneously to acute changes in water temperature and PO2 suggest that movement to colder conditions in hypoxia effects the greatest metabolic savings and prolongs the onset of a plasma lactacidosis.
 ...
PMID:Balancing hypoxia and hypothermia in cold-submerged frogs. 910 81

The effect of mild (32 degrees C) and moderate (27 degrees C) hypothermia was analyzed on the cell volume and intracellular pH (pHi) of C6 glioma cells at normal pH and during lactacidosis at pH 6.2 in vitro. The cells were suspended in an incubation chamber under continuous control of pH, PO2 and temperature. Cell swelling was quantified by an advanced Coulter-system. pHi was measured by flow cytometry using the fluorescent dye bis-carboxyethyl carboxyfluorescein (BCECF). Following a control period at 37 degrees C, the ambient temperature was decreased to 32 degrees C for 30 min, and subsequently to 27 degrees C for another 30 min. Hypothermia alone led to an immediate and significant cell volume increase of 107.3 +/- 0.4% (mean +/- SEM) of control after 30 min at 32 degrees C, and further swelling to 110.5 +/- 0.9% after 30 min at 27 degrees C. Yet, hypothermia (27 degrees C) afforded partial protection against the acidosis-induced cell swelling at pH 6.2, which was reaching to 120.4 +/- 0.9% in the normothermic control group after 60 min, while only to 111.3 +/- 0.9% at 27 degrees C. Hypothermia, however, was associated with a more pronounced decrease of the pHi during acidosis (6.3 +/- 0.04) as compared to that of the normothermic control falling then to 6.5 +/- 0.03. The results demonstrate that mild and moderate hypothermia induce glial cell swelling, but simultaneously inhibit cell swelling from acidosis. The protection against cell swelling, however, has its price as indicated by the enhancement of the intracellular acidification.
 ...
PMID:Effect of mild and moderate hypothermia on the acidosis-induced swelling of glial cells. 941 41

In clinical medicine, severe keto- or lactic acidosis associated with vomiting, nausea, abdominal pain, tachycardia or pathological respiration, has been described in chronic alcoholics. This study reports on fatalities of chronic alcoholics where the cause of death could not be determined by thorough autopsy, histology and toxicology including determination of alcohol concentration. In a first series, acetone was determined in the blood of such chronic alcoholics (n = 24), diabetics with metabolic decompensation (n = 7), cases of hypothermia (n = 7) and controls (n = 218). Among the 24 chronic alcoholics where the cause of death was unknown, 9 cases showed very high levels of acetone (74-400 mg/l). These comprised 6 cases without additional findings and 3 cases where a second patho-mechanism such as intoxication possibly contributed to the cause of death. In a second series, the sum values according to Traub (lactate/glucose) were determined in cerebrospinal liquor of chronic alcoholics with undetermined cause of death (n = 45), diabetics (n = 6) and controls (n = 39). Among the 45 alcoholics, 17 cases showed very high sum values (294-594 mg/dl) including 8 cases where non-lethal intoxications may have contributed to the final outcome. Other causes of a ketoacidosis or lactic acidosis (e.g. diabetes) were excluded in both groups of alcoholics. Consequently, ketoacidosis and lactic acidosis can be the cause of death of chronic alcoholics in a considerable number of cases where no pathomorphological or toxicological changes are present. A scheme for medical and laboratory examination is described.
 ...
PMID:Ketoacidosis and lactic acidosis--frequent causes of death in chronic alcoholics? 958 92

Intracranial pressure depends on cerebral tissue volume, cerebrospinal fluid volume (CSFV) and cerebral blood volume (CBV). Physiologically, their sum is constant (Monro-Kelly equation) and ICP remains stable. When the blood brain barrier (BBB) is intact, the volume of cerebral tissue depends on the osmotic pressure gradient. When it is injured, water movements across the BBB depend on the hydrostatic pressure gradient. CBV depends essentially on cerebral blood flow (CBF), which is strongly regulated by cerebral vascular resistances. In experimental studies, a decrease in oncotic pressure does not increase cerebral oedema and intracranial hypertension (ICHT). On the other hand, plasma hypoosmolarity increases cerebral water content and therefore ICP, if the BBB is intact. If it is injured, neither hypoosmolarity nor hypooncotic pressure modify cerebral oedema. Therefore, all hypotonic solutes may aggravate cerebral oedema and are contra-indicated in case of ICHT. On the other hand, hypooncotic solutes do not modify ICP. The osmotic therapy is one of the most important therapeutic tools for acute ICHT. Mannitol remains the treatment of choice. It acts very quickly. An i.v. perfusion of 0.25 g.kg-1 is administered over 20 minutes when ICP increases. Hypertonic saline solutes act in the same way, however they are not more efficient than mannitol. CO2 is the strongest modulating factor of CBF. Hypocapnia, by inducing cerebral vasoconstriction, decreases CBF and CBV. Hyperventilation is an efficient and rapid means for decreasing ICP. However, it cannot be used systematically without an adapted monitoring, as hypocapnia may aggravate cerebral ischaemia. Hyperthermia is an aggravating factor for ICHT, whereas moderate hypothermia seems to be beneficial both for ICP and cerebral metabolism. Hyperglycaemia has no direct effect on cerebral volume, but it may aggravate ICHT by inducing cerebral lactic acidosis and cytotoxic oedemia. Therefore, infusion of glucose solutes is contra-indicated in the first 24 hours following head trauma and blood glucose concentration must be closely monitored and controlled during ICHT episodes.
 ...
PMID:[The internal environment and intracranial hypertension]. 975 May 95


<< Previous 1 2 3 4 5 Next >>