A more differentiated classification of hydroxyethyl starches is necessary.
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Germany↗
Biomedical subjects
K Schimrigk
Publications and source records attributed to K Schimrigk.
CSF substance P somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy.
We have measured the concentrations of substance P, somatostatin, homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of six patients suffering from narcolepsy and 12 age- and gender-matched controls using high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). Substance P and somatostatin were significantly decreased in our patients compared to controls (36.9 +/- 9.1 fmol/ml versus 52.5 +/- 9.9 fmol/ml, P < 0.05 and 30.3 +/- 7.8 fmol/ml versus 43.9 +/- 9.8 fmol/ml, P < 0.05, respectively). 5-HIAA (P < 0.05) and VMA (P < 0.05) were also significantly decreased. HVA was significantly increased (P < 0.01). The CSF concentrations of substance P and somatostatin correlated with the clinical parameters duration of disease (r = -0.68, P < 0.05 and r = -0.72, P < 0.05, respectively) and severity of cataplectic symptoms (r = -0.71, P < 0.05 and r = -0.78, P < 0.01). In addition, substance P correlated with the intensity of sleepiness and the frequency of day-sleep attacks (r = -0.69, P < 0.05 and r = -0.68, P < 0.05, respectively). Substance P affects the amount of dopamine release in the nigra-striatal region, and decreased amounts could contribute to the pathogenesis of narcolepsy. Reduced levels of substance P, which affects serotonin release, may be responsible for diminished release of serotonin which in turn could affect sleep cycles. Because somatostatin affects motor behavior through dopaminergic mechanisms and since the levels of somatostatin correlate with the intensity of cataplectic symptoms, we speculate that an interaction between somatostatin and dopaminergic neurons plays a role in the pathogenesis of narcolepsy.
Adult↗
[Substance P, somatostatin and monoaminergic transmitters in the cerebrospinal fluid of patients with chronic idiopathic trigeminal neuralgia].
The etiology of trigeminal neuralgia is unknown, but both peripheral and central causes have been suggested. To investigate the role of central neurochemical mechanisms we measured epinephrine, norepinephrine and their breakdown product, vanilly mandelic acid (VMA), in the cerebrospinal fluid (CSF) of 16 patients (53.3 +/- 8.3 years) suffering from trigeminal neuralgia. As markers for the dopaminergic system, we determined CSF levels of dopamine and its metabolite homovanillic acid (HVA). As a marker for the serotonergic system, we measured CSF levels of serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA). In addition, levels of the neuropeptides substance P and somatostatin were determined. The concentration of norepinephrine (P < 0.01), VMA (P < 0.05) and HVA (P < 0.05) were significantly decreased in patients with trigeminal neuralgia and correlated with the duration of the disease and depression scores. 5-HIAA was also significantly decreased (P < 0.05) compared to control patients. Whereas substance P was significantly elevated (P < 0.05), somatostatin was significantly decreased (P < 0.05). Various correlations between the classical neurotransmitters and the neuropeptides could be established. We hypothesize than the sum of complex neurochemical changes plays a role in the etiology of trigeminal neuralgia, which can be separated in local and more central proceedings. The increase in substance P, a major nociceptive neuromodulator, supports the concept of a local neurogenic inflammation, possibly located in the trigeminovascular system. Depending on the duration of the disease and depression, the loss of serotonergic, dopaminergic and noradrenergic innervation seems to reflect more central changes, possibly due to alterations in their antinociceptive descending pathways.
English Abstract↗
[Blood pressure adaptation and hormone regulation in Parkinson patients following orthostasis].
OBJECTIVE: To determine whether abnormal orthostatic regulation commonly occurs in patients with Parkinson's disease (PD) and is caused by an abnormal catecholamine release (especially of noradrenaline). PATIENTS AND METHODS: Blood pressure and catecholamine concentration were measured after 10-min recumbency and 1, 3, 5, 7 and 9 min after standing up in 46 patients with PD (15 women, 31 men: mean age 64.3 +/- 11.7 years). Results were compared with those in a group of 27 healthy controls (eight women, 19 men; mean age 60.7 +/- 10.8 years). RESULTS: Among PD patients there were marked hypotonic circulatory reactions, associated with decreased catecholamine concentration and heart rate adaptation; an abnormal orthostatic regulation occurred in 30 patients. In 22 patients noradrenaline concentration changed by less than 200 pg/ml in the 9th min after standing up, while a decreased hormonal release was noted in only four of the controls, all of whom had normal orthostatic regulation. In PD patients the lowest adrenaline rise was always associated with an extremely high fall in blood pressure. Changes in mean blood pressure correlated positively with the rise in noradrenaline. There was no demonstrable correlation between medication for PD, age of patient and the duration or severity of the disease. CONCLUSION: Abnormal orthostatic regulation occurs more frequently in PD than in healthy persons and is associated with changes in noradrenaline release. This suggests multisystem degeneration as a cause of PD.
Adaptation, Physiological↗
[Lambert-Eaton syndrome].
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Autoantibodies↗
Altered activity of the sympathetic nervous system and changes in the balance of hypophyseal, pituitary and adrenal hormones in patients with cluster headache.
Twelve patients (age 43.4 +/- 6.3 years) with episodic cluster headache (CH) were examined during the cluster period. Plasma norepinephrine levels in patients suffering from CH were significantly decreased compared with the control group (p < 0.01). There were also statistically significant correlations between norepinephrine levels and clinical features of the pain attacks including duration (r = 0.75, p < 0.05), intensity (r = 0.64, p < 0.05) and frequency (r = 0.68, p < 0.06), thereby suggesting a pathophysiological involvement of the sympathetic nervous system in CH. Increased plasma levels of plasmacortisol and ACTH in patients with CH, especially in the morning and in the evening, suggest an alteration of the feedback circuit involving the hypothalamus, the pituitary and the adrenal gland, an imbalance in the hormones related to these structures, as well as an alteration of the circadian rhythm. In addition, CH patients demonstrated significantly decreased levels of norepinephrine (p < 0.05), HVA (p < 0.01) and 5-HIAA (p < 0.01) in the cerebrospinal fluid (CSF) consistent with a central genesis of CH. These significant relationships between neurochemical parameters and the clinical patterns suggest a complex interplay between the hypothalamus, neuroendocrinological parameters, activity of the autonomic nervous system and the pain of CH.
Adrenal Cortex Hormones↗
Somatostatin, its molecular forms and monoaminergic transmitter metabolites in Binswanger's disease. Neurochemical-neuropathological considerations.
Cerebrospinal fluid (CSF) concentrations of somatostatin-like immunoreactivity (SLI), high molecular weight form somatostatin (HMV-SST), somatostatin-25/28 (SST-25/28), somatostatin-14 (SST-14), Des-ala-somatostatin (Des-ala-SST), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 21 patients with Binswanger's dementia (BD). Patients were classed into three stages of intellectual deterioration according to the Global deterioration scale (GDS). Levels of SLI were significantly decreased in patients suffering from BD, compared to a control group (19.7 +/- 11.6 fmol/ml vs. 30.5 +/- 8.6 fmol/ml, P < 0.01). There was no correlation with dementia scores (r = 0.34, P = 0.51). The observed qualitative and quantitative changes in the molecular pattern of SLI suggest that occurrence of a dysregulated posttranslational processing in patients with BD. Whereas 5-HIAA levels were not significantly changed in patients with BD, HVA was significantly increased in mild to moderate dementia (GDS 2-4) and significantly decreased in severe cases (GDS 7) (224.3 +/- 69.9 nmol/ml vs. 364.9 +/- 103.8 nmol/ml, P < 0.01); this correlated with dementia scores (r = -0.59, P < 0.01). The existence of significant correlations between SLI, 5-HIAA and HVA in BD point to a heterogeneous and generalized neurochemical process affecting several transmitter systems and functions.
Aged↗
Isometric muscle contractions after double pulse stimulation. comparison of healthy subjects and patients with myotonic dystrophy.
Isometric contractions of the adductor pollicis muscle were studied in healthy subjects and patients with myotonic dystrophy after single and double stimuli of the ulnar nerve using a wide range of interstimulus intervals (ISI, 0.4-180 ms). In healthy subjects, the force contributed by a second stimulus was greater than the single twitch force being maximal (mean + 140%) at 12-ms ISI. In myotonic dystrophy, the force contributed by the second stimulus was (relative to a reduced twitch amplitude) increased (mean + 204%) with a maximum at 4.8-ms ISI. An abnormal increase of force was only recorded if the single twitch force was clearly reduced. The absolute refractory period of muscle contraction (normal range 1.2-1.6 ms, mean 1.35 ms) was shortened in all patients (mean 1.01 ms) except one (1.2 ms). The ISI showing the maximal force were related to those showing the maximal prolongation of the contraction time in healthy subjects (r = 0.71) but not in patients. The rate of force development contributed by a second stimulus was slower than expected from the summation of two single twitches with short stimulus intervals (3-40 ms) a phenomenon called early depression. In patients, the early depression was reduced or abolished within this range of ISI as has been found in dystrophic mouse muscles. The optimal ISI in patients was shifted towards very short times and together with the other disturbances it is suggested that activation of diseased muscle by motoneurons may be less effective, being an additional factor leading to weakness in myotonic dystrophy.
Adult↗
Cardiac output in patients with acute stroke.
It is well known that blood pressure is elevated during acute stroke. Despite its importance for cerebral haemodynamics, cardiac output (CO) has been determined only in individual cases during acute stroke. We measured CO and blood pressure in patients with no history of heart disease who suffered from acute stroke (n = 30) and in a control group comparable with regard to age, gender and cardiac health (n = 30). CO, blood pressure and heart rate were significantly (P < 0.01) higher in the group of stroke patients than in the control group. There was a tendency for more time to have elapsed between the onset of symptoms and measurements, the higher the CO [b = 0.08 l/min per hour (-0.01; 0.17)]. Adjusted for age in a multiple regression model, the regression coefficient was significant (CO = 10.35 +0.094 x time -0.077 x age). The present study shows for the first time that patients with a healthy cardiovascular system who suffer from acute stroke have a higher CO than a group of comparable controls.
Acute Disease↗
Somatostatin-like immunoreactivity, its molecular forms and monoaminergic metabolites in aged and demented patients with Parkinson's disease--effect of L-Dopa.
There is some evidence that Parkinson's disease (PD) seems to be a heterogenous and generalized brain disorder reflecting a degeneration of multiple neuronal networks, including somatostatinergic neurons. Somatostatin-like immunoreactivity (SLI) and its molecular forms, high molecular weight form (HMV-SST), somatostatin-14 (SST-14), somatostatin-25/28 (SST-25/28) and Des-ala-somatostatin (Des-ala-SST), as well as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were estimated using HPLC and radioimmunoassay in the cerebrospinal fluid (CSF) of 35 aged parkinsonian patients with different stages of intellectual deterioration. The influence of L-dopa-treatment on these neurochemical parameters was evaluated. Without a correlation with dementia scores (p = 0.11), SLI was significantly reduced in PD in comparison to the control group (p < 0.05). The reduction was related to the progression of the disease. Correlations between SLI, HVA and 5-HIAA indicate a heterogenous brain disorder in PD with alterations of several transmitter systems and functions. Complex qualitative and quantitative changes in the molecular pattern of SLI are compatible with a dysregulated synthesis and/or posttranslational processing. L-dopa-treatment was associated with a significant increase of HVA (p < 0.05) and HMV-SST (p < 0.05) and a slight, but insignificant increase of SLI (p = 0.11).
Aged↗
[Involvement of the central nervous system in hemolytic uremic syndrome/thrombotic thrombocytopenic purpura].
Cerebral involvement is typical for thrombotic microangiopathies like haemolytic uremic syndrome (HUS) and thrombotic-thrombopenic purpura (Moschcowitz disease or TTP). Symptoms are irritation, restless behaviour, disorientation, disturbance of consciousness, seizures, and focal neurological deficits. The lack of typical imaging changes or pathological observations may explain the unknown pathophysiological cascade leading to the neurological symptoms. We describe the development of HUS/ TTP in a 52-year-old woman after acute pneumonia caused by Diplococcus pneumoniae. The patient showed an increasing psycho-organic syndrome with disorientation, followed by severe loss of consciousness and coma. Initially, computed tomography showed slight diffuse brain oedema, which was not found in later follow-up images. Magnetic resonance imaging was normal. The TCD examination revealed general velocity increases and vasospasms (especially MCA, ACA and PCA bilateral and BA). The reduction in blood flow velocities in the basal arteries was accompanied by a marked clinical improvement. The development of vasospasms may be an explanation for the neurological deficits in HUS/TTP. The origin of the vasospasms may be found in disturbed prostacyclin production, increased serotonin or platelet factor IV release, and leucocyte activation with consecutive endothelial damage.
Blood Flow Velocity↗
Transcranial Doppler sonography at the early stage of acute central nervous system infections in adults.
Transcranial Doppler sonography (TCD) of the middle, anterior and posterior cerebral arteries and of the basilar artery was used to evaluate the mean blood velocity (V mean) and the pulsatility index [PI = (V systolic-V diastolic)/V mean] as a vascular resistance index in 63 patients (male 40, female 23, mean age 43 +/- 19 y) with bacterial meningitis (n = 33, including 2 patients with fungal meningitis) and viral meningitis (n = 30) within 12 h after admission of the patients. The findings were similar for all intracranial arteries. Compared with reference values of 69 healthy volunteers [V mean of middle cerebral artery [MCA] 57 +/- 13 cm/s, MCA-PI 0.83 +/- 0.15], MCA-V mean was increased in patients with Glasgow coma scale (GCS) scores of 14 and 15 (71 +/- 18 cm/s; t-test: p < 0.001), not significantly different in the patients with GCS scores of 10-13 (55 +/- 21 cm/s) and decreased in those with GCS scores of 3-9 (42 +/- 21 cm/s, p < 0.01). The MCA-PI increased from 0.93 +/- 0.22 in the patients with GCS scores of 14-15 to 2.81 +/- 2.06 in those with GCS scores of 3-9 (p < 0.001 vs. controls). By regression analysis, MCA-V mean decreased and MCA-PI increased with decreasing GCS scores (p < 0.001). Only in patients with bacterial meningitis was the Glasgow outcome scale (GOS) score lower the more the MCA-PI was increased (regression analysis p < 0.001). We conclude that in patients with bacterial and viral meningitis, and in a good clinical state, the cerebral blood flow seems increased by hyperemia; with clinical deterioration the cerebral haemodynamics worsen. However, the early assessment of the cerebral blood flow by TCD seems useful for predicting outcome in bacterial meningitis only.
Acute Disease↗
Autonomic nervous system and neuroendocrine changes in patients with idiopathic trigeminal neuralgia.
To investigate sympathetic nervous system and neuroendocrine changes in idiopathic trigeminal neuralgia, we determined the plasma level of the catecholamines norepinephrine and epinephrine, as well as cortisol and ACTH in 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia at four different times during the day (7.00, 13.00, 17.00 and 23.00). Morning and evening values of plasma norepinephrine as well as the daily mean value (dmv) were significantly higher (p < 0.01) in patients with trigeminal neuralgia than in an age- and gender-matched control group. Moreover, morning, afternoon and dmv epinephrine values were also significantly elevated. The dmv norepinephrine levels correlated with the intensity of the attacks (r = 0.68, p < 0.01), the frequency of the attacks (r = 0.75, p < 0.01) and the duration of the disease (r = 0.78, p < 0.01). In addition to elevated catecholamines, trigeminal neuralgia patients also demonstrated significantly increased morning, evening and daily mean values of plasma cortisol. Thus, patients with trigeminal pain have an increased sympathetic nervous system activity for an extended period of time without a direct link to pain attacks, which suggests that the sympathetic nervous system itself is at least co-activated in trigeminal neuralgia and perhaps plays a role in the induction and maintenance of trigeminal pain. The neuroendocrine changes are similar to cluster headache and point to a central dysregulation of the hypothalamic-pituitary-adrenal axis, possibly due to the cyclic phenomena in idiopathic trigeminal neuralgia.
Adrenocorticotropic Hormone↗
All medium starches are not the same: influence of the degree of hydroxyethyl substitution of hydroxyethyl starch on plasma volume, hemorrheologic conditions, and coagulation.
BACKGROUND: After the application of high volumes of high-molecular-weight starch (hetastarch), bleeding complications have repeatedly been observed. Later studies showed that the application of medium-molecular-weight starch led to far fewer disturbances of the blood coagulation system. However, the relationships among the degree of hydroxyethyl substitution, the rate of degradation, and the average in vivo molecular weight have not been investigated. STUDY DESIGN AND METHODS: A 10-day hemodilution treatment (n = 20) was carried out using two medium-molecular-weight hydroxyethyl starches (HES) with a degree of hydroxyethyl substitution of 0.5 and 0.62, respectively (10% HES 200 was used for a substitution of 0.5 and 6% HES 200 for a substitution of 0.62). After a loading dose of 500 mL was administered, 1000 mL of HES was infused daily for 4 days, and then 500 mL was infused daily for 6 days. RESULTS: The more highly substituted starch was broken down more slowly and eliminated renally. This resulted in a higher intravascular molecular weight than for the less highly substituted HES (120 vs. 84 kDa) and a greater increase in serum concentration (20.3 vs. 9.0 mg/mL). Initially, the more highly substituted 6-percent HES had a lesser effect on plasma volume (p < 0.01). Because of HES accumulation, there was no longer a significant difference between the starches by the end of treatment, even though a higher dose of the 10-percent low-substitution starch was infused. Six-percent HES caused an increase in plasma viscosity (+9%, p < 0.01) that was due to an accumulation of macromolecules. Ten-percent HES 200/0.5 had no effect on the coagulation system beyond the dilution effect. Six-percent HES, on the other hand, led to an acquired von Willebrand syndrome during the course of the 10-day therapy. Factor VIII function was reduced by 72.2 percent, von Willebrand ristocetin cofactor by 61.3 percent, and von Willebrand factor antigen by 64 percent (p < 0.01). CONCLUSION: It is the intravascular and not the initial (in vitro) molecular weight that determines the properties of HES. Especially after repeated administration, a high degree of hydroxyethyl substitution leads to an accumulation of macromolecules that affect hemorrheologic measures and the coagulation system just as adversely as high-molecular-weight starch does. Depending on the degree of substitution, medium-molecular-weight starches can have widely differing properties.
Blood Coagulation↗
[Transcranial Doppler examination on effect of hemodynamics on cerebral autoregulation in acute cerebral infarct].
AIM: We treated 24 patients suffering from an acute ischemic stroke of the middle cerebral artery, with a hypervolemic hemodilution combined with dopamine/dobutamine. METHOD: The influence of blood pressure and cardiac output on the blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography (TCD). RESULTS: Under the hypervolemic hemodilution supported with dopamine/dobutamine a dosage-dependent increase of 12% in blood pressure and a 53% increase in cardiac output was observed. In the affected hemisphere, flow velocity was one fourth lower (significance p < 0.05) than in the unaffected hemisphere. With therapy, the systolic flow velocity was increased in the unaffected hemisphere by 27%, on the side of the lesion only 11%. Mean flow velocity remained nearly constant. The pulsatility index (PI) increased simultaneously by 46% in the affected and 47% in the unaffected hemisphere. CONCLUSION: Similar effects on TCD-flow velocity and PI under comparable slight increases in blood pressure are not known. The increase in cerebrovascular resistance can be ascribed to a counter-regulation of the cerebral autoregulation, triggered by an increase of cardiac output.
Aged↗
Cerebral hemodynamics in the posterior circulation of patients with bacterial meningitis.
OBJECTIVES: Stenoses of the middle and anterior cerebral artery (MCA,ACA) are a clinical relevant complication of bacterial meningitis. We examined the involvement of the posterior cerebral (PCA) and of the basilar artery (BA) into the inflammatory process. MATERIAL & METHODS: 39 unselected patients (26 men, 13 women; mean +/- SD age, 49 +/- 17 years) with bacterial (n = 37) and fungal (n = 2) meningitis underwent serial transcranial Doppler sonography recordings of the mean blood velocity (MBV) and the pulsatility index (PI) in the MCA, ACA and PCA, in the BA and in the submandibular internal carotid artery on Days 1, 3, 5, 8, 14 and 21 after admission. The results of the PCA and of the BA were compared to normal reference values and correlated to corresponding neurological signs. The criterion to assume a stenosis was: for the BA an MBV > or = 95 cm/s, for the PCA an MBV > or = 85 cm/s. RESULTS: Compared with the controls MBV in both arteries was normal on Days 1 and 8-21, but significantly increased on Days 3 and 5. The PI was significantly increased in the BA on all days and in the PCA on Days 1 and 8-21. Stenoses of the PCA (4 of 43) and of the BA (4 of 32) remained without corresponding neurological signs, and occurred only in patients with two or more narrowed arteries of the anterior circulation (p < 0.05). CONCLUSION: In bacterial meningitis, hemodynamic disturbances in the posterior circulation are less severe than in the anterior circulation and are clinically well tolerated.
Adolescent↗
Influence of intravascular molecular weight of hydroxyethyl starch on platelets.
Complications concerning the blood coagulation have been observed repeatedly after administration of highly substituted, high molecular weight hydroxyethyl starch (HES), but it has not been examined as to how intravascular molecular weight and degree of substitution of HES influence platelet number and volume after repeated administration. Thirty patients with cerebrovascular diseases were treated for 10 days with hemodilution. 500 to 1500 ml of HES 200/0.62(n=10), HES 200/0.5(n=10) or HES 40/0.5(n=10) were infused daily. During the first days, the number of platelets was not lowered beyond the dilution effect, but at the end of the therapy the number of platelets had increased in all 3 groups beyond the initial value. Platelet volume was lowered significantly in the 3 groups. HES 200/0.62 caused the largest drop in platelet volume (-10%, p<0.01). A possible explanation could be that HES macromolecules are attached to platelets or are phagocytized by them. The larger platelets are then broken down and, to compensate the loss, more thrombocytes are released. A correlation between the molecular weight of HES and the breakdown rate of the platelets can be suspected, because HES 200/0.62 has the highest intravascular mean molecular weight(121 kD) and the largest effect on platelet volume.
Blood Platelets↗
Time course of acetazolamide effect in normal persons.
The intravenous injection of the carbonic anhydrase inhibitor acetazolamide causes a sustained increase of blood flow velocity in the middle cerebral artery. This effect is used in the acetazolamide test of the so-called cerebrovascular reserve capacity. The acetazolamide test is performed routinely as a two-point measurement of the blood flow velocity by transcranial Doppler before and 15 to 20 minutes after drug injection. Based on the assumption that evaluation of the time course will more sensitively detect an impaired cerebrovascular reserve capacity, suitable parameters for description of the time course were developed and normal values were established from 18 healthy persons (31 hemispheres). The mean value for the maximal increase of the mean flow velocity (MFV) was 29.7 +/- 8.3 cm/sec (as percentage of increase, 62.0 +/- 17.3%) and the time of the maximal increase was 15.35 +/- 8.46 seconds. Also calculated were the velocity of the MFV rise to the maximal value (3.0 +/- 3.2 cm/sec/min), the mean of the changes of the continuously measured MFV to the baseline value (21.0 +/- 7.4 cm/sec), and the integral of MFV represented by the plane under the MFV curve (967.8 +/- 350.0 cm). The best parameter for the description of the time dependency of the acetazolamide effect is the integral of MFV.
Acetazolamide↗