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Biomedical subjects

A Brinkmann

Publications and source records attributed to A Brinkmann.

At least 55 records · Page 3Linked to original sources

[Analgesia and hemodynamics under 8 mu/kg clonidine for pain therapy following major abdominal surgery].

OBJECTIVE: To characterise the haemodynamic profile after epidural injection of high-dose clonidine for postoperative pain management and to establish recommendations for the therapy of haemodynamic instabilities. DESIGN: 20 patients with major surgery on pancreas, stomach or infrarenal aorta took part in the study. Anaesthesia was a combined epidural/inhalational regimen with bupivacaine 0.25%, enflurane, oxygen/nitrous oxide, fentanyl 0.1 mg and pancuronium. Postoperative analgesia consisted of morphine 50 micrograms/kg in 10 ml NaCl 0.9% for the first 12 postoperative hours; if pain > = 5 points on the VAS occurred after > 12 h postoperatively clonidine 8 micrograms/kg in 10 ml NaCl 0.9% was injected epidurally and the pain intensity (self-assessment by the patient using the visual analog scale) and circulation (invasive pressure monitoring, pulmonary artery catheter) was monitored for 60 minutes in ten minutes intervals. RESULTS: The reduction of the initial VAS score of 6 was 50% after 20 minutes and 100% after 60 minutes. We observed a significant decline in heart rate (87 +/- 11 (t0), 74 +/- 10 min-1 (t60)), mean arterial pressure (97 +/- 17 (t0), 72 +/- 15 mmHg (t60)) and cardiac output (8.7 +/- 1.3 (t0), 7.0 +/- 1.3 l.min-1 (t60)) (all p < 0.001) and no change of systemic vascular resistance. Filling pressures (CVP and PCWP) remained stable. In 9 patients the mean arterial pressure fell below 60 mmHg (always within the first 40 min); 6 of these patients responded to infusion of a colloid (500 ml of hydroxyethyl starch at > = 2 ml/kg.min) whereas the other 3 patients needed a bolus injection of a betamimetic catecholamine (theodrenaline/cafedrine, Akrinor). CONCLUSION: Epidural clonidine 8 micrograms/kg causes rapid and intense analgesia. Haemodynamic instability is a consequence of a drop in heart rate and has to be treated accordingly. The application of a pure vasopressor does not seem to be indicated taking in account the fact that the total peripheral resistance remains unchanged and in the normal range.

Abdomen↗

Effect of vasopressin on hemodynamic variables, organ blood flow, and acid-base status in a pig model of cardiopulmonary resuscitation.

Based upon the hypothesis that vasopressin (antidiuretic hormone) may increase vascular resistance during ventricular fibrillation, the effects of this potent vasoconstrictor were studied in a porcine model of ventricular fibrillation. Vasopressin therapy was compared to epinephrine by randomly allocating 14 pigs to receive either 0.045 mg/kg of epinephrine (n = 7) or 0.8 U/kg of vasopressin (n = 7) after 4 min of ventricular fibrillation and 3 min of open-chest cardiopulmonary resuscitation. During cardiopulmonary resuscitation, myocardial blood flow before and 90 s and 5 min after drug administration was 57 +/- 11, 84 +/- 11, and 59 +/- 9 mL.min-1 x 100 g-1 (mean +/- SEM) in the epinephrine group, and 61 +/- 5, 148 +/- 26, and 122 +/- 22 mL.min-1 x 100 g-1 in the vasopressin group (P < 0.05 at 90 s and 5 min). At the same times, mean cardiac index was not significantly different between the groups. After drug administration, coronary venous PCO2 was significantly higher and coronary venous pH was significantly lower in the epinephrine as compared to the vasopressin group. All pigs in both groups were resuscitated and survived the 2-h observation period. We conclude that vasopressin improves vital organ perfusion during ventricular fibrillation and cardiopulmonary resuscitation. Vasopressin seems to be at least as effective as epinephrine in this pig model of ventricular fibrillation.

Acid-Base Equilibrium↗

Malaria and health in Africa: the present situation and epidemiological trends.

The World Health Organization does not give any data on the malaria situation in Africa in its regular reports because of the "insufficiency and irregularity of reporting". Estimates on the total number of cases and the number of deaths vary considerably. They range from 35 million to 189 million per year depending on whose figures one uses. An intensive search of the literature using computer-based systems identified more than 1000 titles on the epidemiology of malaria. Out of them and from other sources finally 426 articles were used to describe the current malaria situation and observable trends in Africa. Major findings were that malaria is responsible for about 40% of fever cases, mortality is about 5 per 1000 per year, case fatality ranges from 2% to 24%. Admissions for malaria account for 20% to 50% of all admissions in African health services although only 8% to 25% of persons with malaria visit health services. Self-treatment is more common in urban areas (more than 60%) but an increasing number of people use some form of self protection in rural areas (2% to 25%). The resistance of malaria parasites to chloroquine and other drugs is widespread. Chloroquine resistance has reached a prevalence of about 30% at the RII level in most countries. Malaria incidence shows annual growth rates of 7.3% for Zambia, 10.4% for Togo, and 21.0% for Rwanda. The data for Burkina Faso show a downward trend of--14.7% during the years from 1973 to 1981. Since then malaria incidence is increasing at 11.0% per year. Hospital data reported from Zambia indicate that mortality is rising 5.2% per annum in children and 9.7% per annum in adults. Reasons for the increase of malaria and its role for development are discussed.

Africa↗

Neuromuscular function and plasma drug levels in pyridostigmine treatment of myasthenia gravis.

In 18 patients with generalised myasthenia treated with oral pyridostigmine, muscular strength, decrement of neuromuscular transmission in the trapezius muscle on repetitive accessory nerve stimulation, and pyridostigmine plasma level were measured repeatedly during 1-3 dosing intervals. Significant correlations between pyridostigmine concentrations and functional parameters were present in three out of 11 cases in which plasma levels changed by at least 25 ng/ml during the investigational period and peak levels did not exceed 100 ng/ml. Several other observations indicated that pyridostigmine at levels above 100 ng/ml may impair neuromuscular function.

Adult↗

Complications and efficacy of transsternal thymectomy in myasthenia gravis.

Between January 1977 and September 1985, 75 patients in our department underwent elective surgery for myasthenia gravis through a median sternotomy. The main prerequisite was optimal stabilization by medical treatment with the best possible vital capacity. The Osseman types were as follows: type I (22), type IIa (19), type IIb (26), type III (7), and type IV (1). All patients, except for 3 who were mechanically ventilated for a few hours after surgery, were immediately extubated at the end of the operation. The most frequent histologic finding was thymic hyperplasia (36%); 21.3% of the patients had thymomas. No surgery-related deaths occurred. Wound healing was impaired in 6.7% of the patients, including one patient with complete sternal instability, while 5.3% developed pneumonia. The most serious complications were myasthenic (9.3%) and cholinergic (2.7%) crises. Paresis of the phrenic (2.7%) and recurrent laryngeal (1.3%) nerves occurred only in the thymoma patients, who also had a higher frequency of all other complications. The effect on the myasthenic symptoms 3 months after surgery was as follows: 7.5% of the patients were in complete remission, 61.2% had improved, 9% had deteriorated. In a logistic regression model, the parameters age, sex, duration of disease, Osserman type, histology, pre-operative antibody titer to acetylcholine receptors, and post-operative change in titer were examined with respect to their influence on the effect of surgery. Only thymic histology had an appreciable influence (p = 0.057). The effect of these parameters on the success of surgery as well as the type and frequency of complications in relation to perioperative procedure are discussed in detail.

Adolescent↗

Risk in a national malaria control programme in Mali: underdosage of antimalarials.

In order to be able to start malaria control activities based on the systematic treatment of episodes of fever in the context of a primary health care programme in the Sélingué dam area, it was necessary to determine the sensibility of P. falciparum to chloroquine given at 25 mg/kg body weight for 3 days. The WHO 7-day test was adopted and administered to schoolchildren aged 7 to 14 years. Out of a total of 259 children screened, the parasitological examination of the thick blood film revealed the presence of hematozoids in 107 children (i.e. a parasite index of 41.3%). Of the 107,59 had parasitaemia appropriate for the in vivo test, but only 43 could be observed till the end of the 7-day test period. The results of the in vivo study indicated a single case where no elimination of the parasites was observed until day 6. The remaining 42 cases became negative between day 3 and day 4. The mean elimination time for the parasite in our study was 3.6 days. The prolonged parasite clearance rate was explained by the fact that the chloroquine tablets contained only 65% of the declared contents of chloroquine base.

Adolescent↗

Characterization of the calf uterine androgen receptor and its activation to the deoxyribonucleic acid-binding state.

The androgen receptor (AR) from calf uterine cytosol has been studied in terms of steroid-binding affinity, hormone dissociation kinetics, and DNA-cellulose-binding capacity. The binding affinity for three androgens, analyzed under conditions where binding to progesterone receptor did not occur, decreased in the order: methyltrienolone greater than 5 alpha-dihydrotestosterone greater than testosterone. Activation of the receptor to the DNA-binding state involved the following changes of the receptor: decrease in dissociation rate for the steroid, disaggregation of the receptor, and increase in affinity for DNA. Dissociation studies with methyltrienolone and 5 alpha-dihydrotestosterone revealed that the AR can exist in two affinity states which differ 13- to 30-fold in their affinity for the steroid. Molybdate (10-20 mM) prevented the formation of the high affinity state. The high affinity state receptor was formed in the absence of molybdate or after ammonium sulfate precipitation (0-40% saturation) of the molybdate-stabilized low affinity state receptor. During formation of the high affinity state, the sedimentation coefficient of the receptor in low ionic strength buffer decreased from 8-9S to 4.5S, indicating receptor disaggregation. DNA-cellulose binding capacity increased from 3 to 65% upon formation of the high affinity state. The DNA-binding form could be eluted from DNA-cellulose at 0.14 M NaCl. After elution the DNA-binding form maintained its sedimentation coefficient of 4.5S and chromatographed as a protein with a Stokes radius of 44 A. From these results it can be concluded that the activated, DNA-binding form of the AR in calf uterus is a protein with a molecular mass of approximately 85,000, which acquires a higher affinity for the ligand upon its formation.

Ammonium Sulfate↗

[Antibody-controlled cytostatic therapy of malignant thymoma with concomitant myasthenia gravis].

In a 46-year-old female patient with malignant thymoma and concomitant myasthenia gravis relapse with gravitational metastases occurred 6 1/2 years after the first operation. Metastases could be removed surgically only partially and were subsequently irradiated with 50 Gy. After 3 1/2 years renewed metastatic growth occurred. Until then the concomitant myasthenia had been stable during treatment with pyridostigmine and azathioprin and intermittent prednisone; acetylcholine receptor antibody titres had remained largely stable. Combined cytostatic treatment with vincristine, cyclophosphamide, prednisone and doxorubicin or cisplatin led to regression of metastases during the observation period of 1 1/2 years and at the same time to stabilisation of the myasthenia. Acetylcholine receptor antibody titres decreased and this was roughly paralleled by clinical improvement. Whereas there is no obvious correlation of antibodies against acetylcholine-receptor protein and tendency of tumour growth there is good agreement with the course of the accompanying myasthenia.

Acetylcholine↗

Translocation of the testicular estradiol receptor is not an obligatory step in the gonadotropin-induced inhibition of C17-20-lyase.

We have investigated the effects of hCG and estradiol on the time course of the inhibition of C17-20-lyase and the depletion of the estradiol cytosol receptor in testicular tissue of male rats. In hCG-treated animals the first significant decrease in C17-20-lyase activity was observed 16 h after injection of the hormone. The C17-20-lyase activity decreased further during the following 56 hours. Estradiol-cytosol receptor levels were significantly decreased 7 hours after the hCG injection, and after a nadir at 16 hours increased to 130% of control values at 72 hours. In contrast, in the estradiol-treated animals the first significant inhibition of C17-20-lyase activity could be observed only after 24 h, while a 95% depletion of estradiol-cytosol receptor levels was observed already within 1 h after administration of the hormone. These results demonstrate that a rapid estradiol-induced depletion of the estradiol receptor as such does not necessarily result in a subsequent immediate inhibition of the C17-20-lyase. The rapid inhibition of this enzyme after hCG indicates, therefore, that other mechanisms are involved.

Aldehyde-Lyases↗

Increase of the gluconeogenic and decrease of the glycolytic capacity of rat liver with a change of the metabolic zonation after partial hepatectomy.

During the first 72 h after 67% partial hepatectomy of female Wistar rats (160 g) the specific activities [mumol X min-1 X (g liver)-1] of the glucogenic glucose-6-phosphatase and fructose-bisphosphatase and of the glycolytic hexokinase and 6-phosphofructokinase remained essentially constant. However, the activity of the glycolytic pyruvate kinase (L- plus M2-type) was decreased slightly and that of glucokinase was decreased markedly to below 30%, while the glucogenic phosphoenolpyruvate carboxykinase was increased to over 200%. Between 10 and 40 h after partial hepatectomy, when the proliferation started in the periportal area, a shift of the glucogenic glucose-6-phosphatase-rich zone from its normal periportal to an intermediate or even perivenous position was observed histochemically. After 48 h, when the proliferation was no longer restricted to the periportal zone, the normal glucose-6-phosphatase zonation (as before partial hepatectomy) was restored. Glycogen was degraded rapidly during the first 4 h after operation; it was later repeatedly resynthesized and degraded in correlation with the feeding rhythm of the animals. The zonation of glycogen metabolism was in accord with the observed zonation of glucose-6-phosphatase.

Animals↗

[Expression of AC133 vs. CD34 in acute childhood leukemias].

AC133, a newly discovered antigen on human progenitor cells, demonstrating 5-transmembranous domains is expressed by 30-60% out of all CD34+ cells. Our aim therefore was to investigate the extent of human stem-/progenitor cells expressing AC133 antigen in umbilical cord blood, peripheral blood without or following an application of granulocyte-colony stimulating factor (rhG-CSF). The main task was the investigation of bone marrow aspirates derived from children suffering from newly diagnosed acute leukemias, as well as from patients with a relapse or during a complete remission. The determination of antigen expression was done by application of flow cytometry (FACScan analysis) and the usage of newly developed monoclonal antibodies (AC133/1 and AC133/2; Miltenyi Biotec GmbH) in combination with monoclonal antibody directed against CD34-antigens (HPCA-2; BD). Our studies till now show average percentages in umbilical cord blood derived from 43 newborns about 0.294 +/- 0.165% AC133+ vs. 0.327 +/- 0.156% CD34+ hematopoietic stem-/progenitor cells (HSPC). In peripheral blood from 11 healthy donors we verified up to 0.15% CD34+ as well as AC133+ HSPC's. The concentration of progenitor cells was found to be obviously higher in peripheral blood from children with various diseases (neuroblastoma, rhabdomyosarcoma, ALL/AML) and undergoing application with rhG-CSF in order to be prepared for PBSC-transplantation. In those cases we found up to 3.51% AC133+ cells as well as slightly higher values (3.94%) for CD34 antigens. Additionally we quantified 128 bone marrow (BM) samples for AC133+ and CD34+ cells. In 10 BM samples, derived from patients without any neoplasia, the CD34+ cells were about 0.03% and 1.49%, whereas AC133 values were up to 0.64%. Bone marrow aspirates from 53 children with acute leukemias at time of diagnosis (ALL: n = 41/AML: n = 12) have been immunophenotyped and leukemic blast cells have been proved for AC133- and CD34 antigen expression. 32/41 (78%) of lymphoblastic leukemic cells showed to be positive for CD34 antigen and 24/41 (58%) demonstrated AC133 antigens. Interestingly there were 2 ALL-patients with pathological blast cells positive for AC133 but lacking of any CD34 antigens. 42% (5/12) of investigated AML patients showed CD34+ phenotype, on the other hand there were only 25% (3/12) with AC133+ phenotype. Similar values were found in relapsed patients (n = 18). In BM samples from patients during complete remission (n = 47) we could detect percentages up to 5.55% for CD34 and up to 1.25% for AC133 positive stem-/progenitor cells. Such quite high data may be explained by occasionally application of rhG-CSF therapy. Our results till now lead to the conclusion, that it seems to be useful, to recruit quantification of CD34+ HPSC by additionally detecting AC133 antigens. This new stem cell marker (AC133) may be of great value in case of autologous peripheral blood stem cell transplantation (PBSCT) because it could be an alternative to the usual CD34+ MACS selection system.

AC133 Antigen↗