Biochemical changes in apparently normal sheep from flocks affected by polioencephalomalacia.

Blood samples were obtained for determination of the activities of lactate, pyruvate and erythrocyte transketolase, and faeces as samples for estimation of thiaminase, from 190 apparently healthy sheep from 19 flocks in which at least one animal had been diagnosed with polioencephalomalacia (PEM), from 59 control animals and from 7 affected by PEM. Feed and pasture grass samples were collected for thiaminase analysis and thiaminase was assayed in ryegrass and fescue. Decreased erythrocyte transketolase activity, accompanied by a corresponding rise in the thiamin pyrophosphate effect, and estimation of the thiaminase content in faeces, may be useful diagnostic procedures by which to identify periods of greater risk, during which animals could develop PEM. The changes in the diet probably acted as a primary factor for microbial production of thiaminases in replacement ewes. In these, the prevalence was higher in the spring months.

Polioencephalomalacia induced with amprolium in buffalo calves--clinicopathologic findings.

Polioencephalomalacia was induced in eight buffalo calves, 6-12 months old, by drenching amprolium (300 mg/kg body weight per day) for 29-55 days. Four buffalo calves of the same age group were drenched with tap water only and served as control. Blood samples were collected at different intervals during amprolium administration until the onset of clinical signs. Cerebrospinal fluid was also collected prior to amprolium administration and at the onset of clinical signs. A significant progressive decrease in erythrocyte transketolase (TK) activity and an increase in the percent of thiamine pyrophosphate (TPP) effect were observed in amprolium-fed calves during amprolium administration until the onset of clinical signs. There was a significant increase in blood lactate and blood pyruvate concentrations and a significant decrease in lactate/pyruvate ratio at the onset of clinical signs. Serum electrolyte (Na, Ca, P, Mg) concentrations showed no significant changes. However, the serum potassium concentration had decreased significantly at the onset of signs. The cerebrospinal fluid analyses revealed a significant increase in lactate and pyruvate concentrations and lactate/pyruvate ratio in amprolium-fed calves. The electrolytes (Na, K, Ca, P and Mg) of cerebrospinal fluid did not show any change. It is concluded that oral administration of amprolium (300 mg/kg body weight daily) for 4-6 weeks produces biochemical changes characteristic of polioencephalomalacia in buffalo calves.

Role of thiamine status in sulphur induced polioencephalomalacia in sheep.

The effects of excess dietary sulphur were studied in sheep supplemented and unsupplemented with thiamine. The diets contained either 0.19 per cent sulphur (LS) or 0.63 per cent sulphur (HS) in combinations with 14 mg kg-1 thiamine (LB1) or 243 mg kg-1 thiamine (HB1). A total of 56 two-month-old lambs were used. Groups consisting of nine, nine, 22 and 16 lambs were fed LS-LB1, LS-HB1, HS-LB1 and HS-HB1 diets, respectively for 14 weeks. Out of 22 lambs fed the HS-LB1 diet, seven lambs developed neurological signs between the third and eighth week of the trial. Two of these lambs died, three that were in extremis were euthanased, and two recovered completely. All clinically affected animals had extensive malacic lesions in the cerebral cortex, midbrain and brainstem. None of the lambs from the LS groups or HS-HB1 group developed clinical signs. Several clinically normal lambs from the HS-LB1 group had necrotic lesions in their brains at gross and microscopic examination. Supplementation with dietary thiamine prevented development of clinical signs, but did not totally prevent development of microscopic brain lesions. Brain thiamine concentration, transketolase activity and thiamine pyrophosphate (TPP) effect were not different (P greater than 0.05) among groups. There was a strong effect (P less than 0.0001) of dietary thiamine supplementation on blood thiamine concentration and TPP effect. Blood thiamine concentration was higher whereas TPP effect was lower in the thiamine supplemented sheep. Blood and tissue thiamine concentrations in sheep exposed to high dietary sulphur did not indicate either systemic or local thiamine deficiency per se. Increased TPP effect in sheep fed the HS-LB1 diet indicated mild to moderate metabolic thiamine deficiency. Thiamine inadequacy may be an effect of an increased requirement for thiamine in animals exposed to excess dietary sulphur.

[Valduna Rehab Scale in evaluating the correlation of clinical outcome and laboratory values in follow-up of encephalomalacia]. / Die Valduna-Rehab-Skala in Bewertung der Relation von Klinik und Labor im Verlauf der Enzephalomalazie.

The clinical outcome of 65 patients with malazia alba of the brain was documented by the use of our "Valduna-Disability-Score" examining the patients at defined points of time. Simultaneously several rheological parameters of venous blood gained by punction of the cubital veine were examined before and after hemodilution therapy using dextran 40. The items or progress concerning clinical outcome and changes of the rheological parameters were correlated. There was not found any significance. We conclude, that the changes of rheological parameters in venous blood are not able to predict the clinical outcome after hemodilution therapy. The important role of disability scores--in our case the "Valduna-disability-score"--is to be stressed.

Sulfur-induced polioencephalomalacia in sheep: some biochemical changes.

The effect of high dietary sulfur (S) supplementation on blood thiamine (B1) concentration, biochemical indices of liver, muscle and kidney damage and selected plasma electrolytes was studied in six sheep. Three of these sheep received an additional 230 mg thiamine/kg diet (Group 2). After approximately 2.5-3 weeks on this diet, all three sheep in the non-B1-supplemented group (Group 1) showed loss of appetite and developed mild neurological signs: depression, intermittent signs of excitation and head pressing. Increases in blood B1 concentration and plasma creatine kinase (CK) and aspartate aminotransferase (AST) were observed during this time in all affected animals. Clinical signs lasted only for two to five days. Sheep in group 2 were clinically normal throughout the experiment, but all of these animals also had elevated blood B1 concentrations and plasma CK activity at the 3 wk sampling. Plasma magnesium concentrations of group 1 sheep were elevated at the 2.5-3 wk and 6 wk samplings but they declined significantly (p less than 0.05) to low normal levels thereafter. Magnesium concentrations of group 2 sheep were low at the beginning but progressively increased during the course of the experiment. At necropsy, brain lesions suggestive of polioencephalomalacia (PEM) were observed in all sheep but were most marked in group 1. It is speculated that PEM may be caused by a direct toxic effect of S, S metabolites or B1 antimetabolites in the brain rather than by an in vivo B1 deficiency per se.

[Apolipoproteins A and B in cerebrovascular diseases]. / Apolipoproteine A und B bei zerebrovaskulären Erkrankungen.

The present study has proved unequivocally the value of determining apolipoproteins A and B and the APO-L A/B quotient for establishing the risk for cerebrovascular disease. The determination of apolipoproteins should be preferred to the determination of HDL, LDL and VLDL, which has been practised so far. While only 30% of a group of 88 patients suffering from cerebrovascular disease had serum cholesterol levels of more than 250 mg/dl and approx. 57% showed HDL values below 40 mg/dl, a reduced APO-L A/B relation (less than 1.75) was demonstrated in 74%. A reduced APO-L A/B quotient was also observed in more than 70% of 62 CVD patients whose cholesterol level was within the range of normal. Determination of apolipoproteins may, therefore, be regarded as further progress in risk factor diagnostic of arteriosclerotic disease.

Assignment of hemorheological instruments in the angiologic ambulance: first results and experiences.

Patients with chronic arterial disorders (CAD) frequently exhibit rheological alterations of the blood beneath generalisated sclerosing of the vessels and restricted arterial diameters. Alterations of different rheological parameters were determined in more than 80% of the examined patients. The following parameters were measured: yield shear stress in the ESM, hematocrit level in the IHA, plasma viscosity in the CTPV, standardized erythrocyte aggregation index in the MEA and standardized erythrocyte rigidity index in the SER.

Effects of vitamin E and aspirin on the incidence of encephalomalacia, fatty acid status and serum thromboxane levels in chicks.

This study was initiated to examine the role of prostanoids (thromboxane) in the development of nutritional encephalomalacia (NE). Chicks were fed diets deficient in or supplemented with vitamin E in the presence or absence of a known prostaglandin inhibitor, acetylsalicylic acid (ASA). When the incidence of NE was approximately 50% in the vitamin E--deficient group without ASA supplement, the chicks were killed, and serum thromboxane B2 (TxB2) and serum and brain fatty acid (FA) composition were determined. The incidence of NE was not altered by ASA treatment. Plasma arachidonate levels were increased by ASA treatment on the vitamin E--deficient diet. Furthermore, the serum TxB2 levels in vitamin E--deficient versus vitamin E--adequate chicks, unlike changes noted for rats, were decreased. Aspirin treatment drastically reduced TxB2 levels in all groups but did not alter the incidence of NE. Therefore, it is unlikely that the development of NE is a result of thromboxane-mediated thrombosis.

Biochemistry of natural and amprolium-induced polioencephalomalacia in sheep.

Polioencephalomalacia (PEM) induced in sheep was compared with the disease found in naturally occurring cases. Blood biochemical indicators measured were pyruvate, lactate, glucose, erythrocyte transketolase (TK) and stimulation of TK by addition of thiamine pyrophosphate (TPP effect). Faeces and rumen contents were assayed for thiaminase activity. The effect of treating affected sheep with thiamine was also noted. It was found that amprolium treatment could induce thrombocytopenia, but once the sheep became accustomed to amprolium in the diet they seemed to be resistant to this effect. In sheep receiving amprolium significant weight losses preceded the onset of clinical signs. Further weight loss continued throughout the recovery period despite removal of amprolium from the diet and treatment with thiamine. Blood glucose was variable, and was elevated only when marked clinical signs were present. Pyruvate and lactate levels showed marked variation throughout the trial. TK values were depressed and TPP effects increased well before the onset of clinical signs, although some naturally occurring cases had normal levels. Faecal thiaminase activity was negligible in all the sheep on the amprolium trial but most field cases had a high level. High faecal thiaminase was observed in about 5% of clinically normal animals from affected flocks. Depression of erythrocyte TK activity coupled with the presence of faecal thiaminase appeared to be the most reliable diagnostic biochemical parameters for PEM. Treatment of PEM affected sheep with thiamine rapidly brought the biochemical status of the animals to normal. However where advanced brain lesions were present the damage was permanent and such sheep treated with thiamine remained partially decorticate.

Erythrocyte transketolase activity in suspected cases of Leigh's disease, or subacute necrotising encephalomyelopathy.

Erythrocyte transketolase activity and the effect of adding thiamine pyrophosphate (% thiamine pyrophosphate effect) were measured in 111 subjects suspected to suffer from Leigh's disease (subacute necrotising encephalomyelopathy). From clinical evidence these subjects were divided into five groups: (1) necropsy-proved cases of subacute necrotising encephalomyelopathy, (2) cases positive for urinary thiamine pyrophosphate: adenosine triphosphate phosphotransferase inhibitor, (3) clinically likely cases of subacute necrotising encephalomyelopathy (patients still alive, or on whom no necropsy was performed), (4) cases diagnosed as diseases other than subacute necrotising encephalomyelopathy (control group), (5) cases for which no diagnosis had been made. Comparison of erythrocyte transketolase activities with and without added thiamine pyrophosphate and of the % thiamine pyrophosphate effect for each group compared with the control group showed no statistically significant differences from normal values for any of these parameters. Similarly, there were no differences between the two sexes in transketolase activity, and no correlation between transketolase activity and age. These results indicate that erythrocyte transketolase activity is not altered in subacute necrotising encephalomyelopathy and is unlikely to be of value for the diagnosis of Leigh's disease.

Periventricular leukomalacia complex.

At autopsy in the past three years, a new complex of CNS lesions has appeared in 54% (50/93) of the brains of premature infant cadavers that have come from our neonatal intensive care unit. This complex consists of necrotizing lesions in the periventricular white matter and in the gray nuclei of the cerebral hemispheres, the hippocampus and subiculum, cerebellar folia and white matter, and basis pontis. This entity is called the periventricular leukomalacia complex, since the distribution of lesions is similar, yet much more severe, than that described by Banker and Larroche in 1962. Clinical studies have indicated that these lesions may be related to long periods of time at high blood oxygen or prolonged periods in which PO2 and pH fluctuated widely.

[Blood clotting disorders in cases of encephalomalacia]. / Zaburzenia krzepliwosci krwi w przypadkach ognisk rozmiekania mózgu.

In a group of 22 patients with foci of brain softening certain blood clotting factor were determined at different stages of the disease. The control group consisted of 16 healthy subjects. Shortening of the prothrombin time was observed after 4 weeks in the group of patients as compared with the control group. The fibrinolytic activity was higher in the plasma on the 4th day of the disease and a fall of plasma fibrinolytic activity after 4 weeks to normal values was observed.

[Levels of ammonia in patients with stroke]. / Zawartosc amoniaku w krwi zylnej chorych z udarem mózgu.

The authors determined peripheral-blood ammonia level in patients with cerebral strokes. The determinations were done by the method of Konitzer et al. on the 1st, 3rd and 7th days of the disease. The results of determinations were subjected to statistical analysis with the t test of Student. It was found that the mean serum ammonia level in patients with cerebral stroke on the 1st day of the disease was higher than in the control group. The difference was statistically significant. The level of ammonia in the blood of patients with cerebral haemorrhage was significantly higher on the 1st day of the disease than in patients with encephalomalacia. The difference was statistically significant with error probability of 0.05.

[Serum content of alpha-amino nitrogen in patients with stroke]. / Zawartosc azotu alfa-aminowego w surowicy krwi chorych z udarem mózgu

The concentration of alpha-amino nitrogen in the serum of 18 healthy subjects, 17 patients with cerebral haemorrhage, and 23 patients with encephalomalacia due to thrombosis was determined by the colorimetric ninhydrin method of Moore and Stein modified by Slavik. The determinations were done on the 1st, 3rd and 10th days of the disease. The mean concentration of alpha-amino nitrogen in the serum of patients with cerebral haemorrhage was lower than in controls on the 1st and 3rd days of the disease but the difference was not significant statistically. The mean level of alpha-amino nitrogen in the serum of patients with encephalomalacia was lower on the 1st day than in controls while on the 3rd and 10th day it was slightly higher as compared with controls, however, statistically the differences were not significant. The mean values of alpha-amino nitrogen in the serum of patients with cerebral haemorrhage and those with encephalomalacia gradually approached the control values.

[Gasometric studies of arterial blood in patients with stroke]. / Badania gazometryczne krwi tetniczej u chorych z udarem mozgu

Gasometric determinations of pCO2, pO2, HCO3 and SO2 were performed in arterial blood in 100 patients with brain stroke. The following conclusions have been drawn. 1. In 2/3 of cases of brain stroke decreased partial oxygen pressure and in 1/3 of cases acid-base equilibrium disturbances are observed. 2. Hypoxia occurs in brain stroke mainly in patients with consciousness disturbances, which suggests that impaired airways patency plays a role in the pathomechanism of this disturbance. 3. Acid-base equilibrium disturbances in cases of brain stroke have in most patients the character of respiratory alkalosis which seems to be due to hyperventilation determined by central nervous mechanisms as well as to hypoxia caused by insufficient patency of airways. 4. Gasometric investigations of arterial blood in brain stroke are important for establishing the degree of homeostasis disturbances and for choice of methods of therapeutic management.

Induction of bovine polioencephalomalacia with a feeding system based on molasses and urea.

Polioencephalomalacia (PEM), a disease first described in the United States and related to intensive beef production, appeared in Cuba coincident with the use of a new, molasses-urea-based diet to fatten bulls. Because the only experimental means so far of reproducing PEM has been with amprolium, a structural analog of thiamin, the present study attempted to induce the disease using the molasses-urea-based diet. Six Holstein bulls (200-300 kg) were studied during consumption of three successive diets: 1) commercial molasses-urea-restricted forage diet of Cuban feedlots, 2) a period in which forage was gradually withdrawn and 3) a forage-free diet composed only of molasses, urea and fish meal. PEM was reproduced in this way. At ten-day intervals, blood concentrations of glucose, lactate, pyruvate and urea were measured, as well as when clinical signs of PEM appeared. The signs, clinical course and lesions of the experimentally induced disease were comparable to those of field cases. The biochemical results suggested a block in pyruvate oxidation as in PEM elsewhere in the world. No evidence existed of urea intoxication. In addition, brain and liver concentration of total thiamin from field cases and normal animals were found to be similar.

[Clinical significance of changes in blood viscosity in cerebrovascular insufficiency (author's transl)]. / Klinische Bedeutung von Blutviskositätsveränderungen im Rahmen der zerebrovaskulären Insuffizienz

In 50 patients with encephalomalacia and 50 patients with a transient cerebral ischemic attack (TIA) the risk factors and viscosity of the whole blood as well as the hematocrit were determined before the start of treatment. Compared to a control group, the blood viscosity in patients with encephalomalacia was significantly increased (p less than 0.001) in all ranges of shearing velocity tested, in patients with TIA only at that shearing velocity which may be assumed for the area of microcirculation. This increase was related to the presence of arterial hypertension, hyperlipemia, heart failure, diabetes mellitus, hyperfibrinogenemia and increased tendency of thrombocytes and erythrocytes to aggregate. From the results obtained it was concluded that increased blood viscosity in the cerebral area of microcirculation with insufficient cerebral collateral circulation may decisively favor the development of encephalomalacia.

[Serum neuraminic acid level in patients with cerebrovascular disorders]. / Zawartosc kwasu neuraminowego w surowicy krwi chorych z naczyniowym uszkodzeniem mózgu

The authors determined the level of neuraminic acid in the serum of 50 patients with encephalomalacia and 25 patients with cerebral haemorrhages on the 1st, 3d and 7th days of the disease. Twenty healthy subjects served as controls. A statistically significant rise in the concentration of this substance was observed in both groups of patients throughout the whole period of observations.