[Traumatic brain injury]. / Schädel-Hirn-Trauma.

Since traumatic brain injury is the most common cause of long-term disability and death among young adults, it represents an enormous socio-economic and healthcare burden. As a consequence of the primary lesion, a perifocal brain edema develops causing an elevation of the intracranial pressure due to the limited intracranial space. This entails a reduction of the cerebral perfusion pressure and the cerebral blood flow. A cerebral perfusion deficit below the threshold for ischemia leads to further ischemic lesions and to a progression of the contusion. As the irreversible primary lesion can only be inhibited by primary prevention, the therapy of traumatic brain injury focuses on the secondary injuries. The treatment consists of surgical therapy evacuating the space-occupying intracranial lesion and conservative intensive medical care. Due to the complex pathophysiology the therapy of traumatic brain injury should be rapidly performed in a neurosurgical unit.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); p<0.05; n=14). Contusion sizes increased continuously within 72h following CCI injury, but glibenclamide-treated animals had significantly smaller volumes at any time-points, like 172.53±38.74mm(3) (glibenclamide) vs. 299.20±64.02mm(3) (control) (p<0.01; n=10; 24h) or 211.10±41.03mm(3) (glibenclamide) vs. 309.76±19.45mm(3) (control) (p<0.05; n=10; 72h), respectively. An effect on acute parameters, however, could not be detected, most likely because of the up-regulation of the channel within 3-6h after injury. Furthermore, there was no significant effect on motor function assessed by the beam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI.

Pseudohypoparathyroidism and Graves'disease: a rare combination of two endocrinological diseases.

We report a 26-year-old woman presented at the day of admission in the I.C.U. with increased perspiration, plethora and distinct tetany of both legs. Particularly unusual was an exophthalmus on both sides, a rectal temperature of 38.3 degrees Celsius and a blood pressure of high level (180/110 mmHg). Laboratory findings were a low serum calcium concentration of 2.86 mval/l, a hyperphosphataemia (5.0 mg/dl), free thyroxine of 31.7 pmol/l, TSH basal of < 0.01 U/ml and positive MAK and TRAK. Serum parathormone concentration was excessively high: 766 ng/l (12-72). Ultrasound of the thyroid gland revealed a normal size with a volume of 10.4 ml; the echosonic state was not typical for Graves' disease. The initial treatment consisted of high dose thiamazole and hydrocortisone intravenous, calciumcarbonate and propranolol per os. After acute situation the treatment continued with thyreostatics, calcitriol and calciumcarbonate. The symptoms at the day of admission (tetany) disappeared within 2 days; only local paraesthesia of fingers persisted longer. Normalization of thyroid parameters was reached after 11 days; the serum calcium concentration persisted on an increasing but still lower level than standard (3.8 mval/l). During substitution parathormone decreased to 443 ng/l. What is unusual about this case is the combined appearance of autoimmunethyreoiditis (Graves' disease) and pseudohypoparathyroidism.

RTIME: a program for time-series measurements and evaluation in electrophysiology with the AT-PC.

This work describes a program which uses a standard RS232-serial interface of an IBM-AT-compatible microcomputer to receive via four data lines input from any laboratory equipment (spike discriminators, stimulus equipment, etc.) generating pulses between 0 to -15 V (low) and +5 to +15 V (high). Therefore, program operation is independent from any hardware extensions of the computer. The time of occurrence of input pulses is recorded with a resolution of 10 microseconds. Depending on processor speed and optional on-line display of interval histograms, a maximum sampling rate of 1.3-6 kHz is attained. Designed primarily for electrophysiological applications, the program comprises an extensive set of functions for off-line analysis of data either in the time- or in the phase-domain. The program is controlled by menu-selectable commands with detailed on-line explanation and is therefore suited for use even by operators without computer experience, e.g., students on courses in experimental physiology. Elaborate schemes of evaluation can be defined as macro commands to speed up and simplify complex data analysis in actual research.

Carbamazepine monotherapy in the treatment of alcohol withdrawal.

More than 135 different strategies for medical treatment have been described for the treatment of alcohol withdrawal syndromes. The substances used most frequently (benzodiazepines, barbiturates, or clomethiazol) themselves pose some risk for abuse or addiction. Anticonvulsants, especially carbamazepine (CBZ), have been discussed for the treatment of alcohol withdrawal since the early seventies. Various studies report favourable results with CBZ, usually combined with sedative agents. Nineteen out-patients and 19 in-patients took part in an open study of CBZ in alcohol withdrawal. The dose of CBZ was adjusted individually and ranged from a mean dose of 761 mg on day 1 to 616 mg on day 3 and to 388 mg on day 7 in the group of out-patients, and from 789 mg on day 1, 694 mg on day 3 to 562 mg on day 7 in the sample of in-patients. The "Objective Clinical Scale in Assessment and Measurement of Alcohol Withdrawal" (OCSAMAW) was used for treatment evaluation. Statistical analysis showed a significant improvement on the 5%-level in both groups; four in-patients needed concomitant treatment with oxazepam. Nausea and pruritus were the most common side-effects of CBZ treatment.

Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study.

A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer.

[Therapy of stomach ulcer with sucralfate and ranitidine. A multicenter double-blind study]. / Therapie des Ulcus ventriculi mit Sucralfat und Ranitidin. Eine multizentrische Doppelblindstudie.

134 outpatients with acute benign gastric ulcer confirmed by endoscopic biopsy received either 1 g sucralfate suspension four times daily or one 150 mg ranitidine tablet twice daily for six to 12 weeks in a multicentre therapy study (double-blind study according to the double-dummy technique). After six to 12 weeks, respectively, 56% and 82% of the ulcers had healed in the sucralfate group. The rates of healing in the ranitidine group were 72% and 88%, respectively. The differences in the rates of healing between sucralfate and ranitidine were not statistically significant. Ranitidine was superior to the sucralfate suspension in corpus ulcer. In the distally located ulcers, the two kinds of treatment were equivalent. There were no appreciable differences between the medications with regard to antacid consumption and compliance. Gastric pain was influenced better by ranitidine than by sucralfate.

[Acute liver necrosis caused by valproate]. / Akute Lebernekrose durch Valproinat.

After treatment with valproic acid a 19-year-old female patient with Friedreich's ataxia and generalised epilepsy died following acute hepatic failure with massive lactacidosis. The clinical symptoms were characterised by hyperventilation, increasing loss of consciousness and shock, leading to treatment-resistant hepatic coma. Morbid anatomy showed extensive confluent lytic necroses of liver acini with accentuation of centrolobular and intermediary structures as well as small and medium-sized fatty degeneration increasing from the periphery towards the centre. The disease picture is quite characteristic for being caused by valproic acid. As a safety measure liver function tests should be done should prodromal symptoms such as anorexia, weakness and apathy arise. If necessary the dosage has to be reduced or medication stopped. Serum valproic acid levels should remain in the lower half of the therapeutic range.

[Therapy of stomach ulcer with low-dose antacid gel and cimetidine. A multicenter double-blind study]. / Therapie des Ulcus ventriculi mit niedrig dosiertem Antacidumgel und Cimetidin. Eine multizentrische Doppelblindstudie.

In a multi-centre double-blind (double-dummy) trial the effectiveness of low-dose antacid gel (6 X 12 ml/d; neutralisation capacity 120 mmol) was compared with that of a standard dose of cimetidine (1 g/d) in the curative treatment of gastric ulcer. Antacid gel was given to 65 patients, cimetidine to 60. Diagnosis was confirmed by endoscopic biopsy, which was also employed in a serial follow-up. After 4 weeks antacid gel and cimetidine produced cures in 43% and 52%, respectively; after 8 weeks 76% and 89%, respectively, the difference between the two methods not being statistically significant. There was also no statistically significant difference with regard to ulcer pain. In one case each in the antacid and cimetidine groups, the treatment had to be stopped because of side effects. Diarrhoea was more common on cimetidine than on antacid gel. It is concluded that both low-dose antacids gels and cimetidine are suitable in the treatment of gastric ulcers.

[Pharmacokinetics of prednisolone in adrenal insufficiency ]. / Pharmakokinetik von Prednisolon bei Nebenniereninsuffizienz.

Prednisolone was measured in serum and urine after oral and intravenous administration of prednisone and prednisolone in 16 patients with adrenal insufficiency and after bilateral adrenalectomy. Thus, the problem of cross-reactivity with endogenous steroids, the main factor disturbing the measurement of prednisolone, was completely eliminated. Prednisolone was detected by a simple competitive protein-binding radioassay. Distribution, elimination and other bioavailability parameters were calculated from the obtained data. No significant differences between serum levels were detected after oral administration of these drugs. Peak levels were reached after 2-3 h. After 5, 7.5 and 10 mg prednisone peak serum levels averaged 11.9 +/- 2.2, 15.9+/-3.4 and 21.5+/-5.9 microgram/dl, respectively. Prednisolone was still detectable 24 h after administration of 10 mg. The plasma half-time of approximately 5 1/2 h suggests that prednisolone is present in serum far about 2 days after application of higher doses. Since prednisolone interferes in most assays for cortisol, prednisone therapie has to be stopped at least 2 days before cortisol determinations. Urinary excretion was proportional to the applicated doses. The metabolic clearance rate of prednisolone was decreased (56.0+/-7.2 1/24 h/m2) in patients with adrenal insufficiency. This can be attributed to alterations in corticosteroid metabolism, probably due to an increased transcortin production.

The metabolic serum clearance of GnRH. Relationship to age, sex and male puberty.

UNLABELLED: The MCR of constantly infused synthetic GnRH (1.53 micrograms/min) was studied in relation to age, sex, and male sexual maturation. GnRH was determined by a radioimmunoassay using a specific GnRH antiserum and 125I-GnRH, prepared by the chloramine T technique and purified on Sephadex G 25. Serum LH and FSH were measured by RIA. The results (mean values +/- SEM) of MCR expressed here as ml/min/1.86 m2 showed a statistically significant difference: infants (6-13 yrs) 1170 +/- 79, sexually mature males (22-29 yrs) 639 +/- 28, elderly men (64-79 yrs) 520 +/- 38, sexually mature females (20-24 yrs) follicular phases: 1354 +/- 90, luteal phases: 1736 +/- 242, postmenopausal women (53-74 yrs) 598 +/- 45. We found a linear negative correlation between serum LH and MCR of GnRH in both sexes. During male puberty the MCRLH-RH decreased simultaneously to the stages of pubic hair development. IN CONCLUSION: 1) The MCR of GnRH is a function of age, sex, and sexual maturation, 2) its negative linear correlation with LH in both sexes indicates that the MCR presumably reflects endogenous GnRH levels, 3) the MCRGnRH seem to be subject to endocrine regulation.

[Endocrinologic findings in Crohn's disease]. / Endokrinologische Befunde bei Morbus Crohn.

In 45 patients with radiologically and endoscopically/histologically proven Crohn's disease the partial functions of the anterior pituitary gland were measured prior to steroid therapy. No deficiencies were observed with respect to cortico-, thyro-, gonado-, and somatotropic functions. In 25 out of 40 patients (63%) the typical diurnal rhythm of cortisol secretion was absent when assessed by a distinctly elevated 6 p.m. cortisol serum level. In about one fourth of 22 patients T3-RIA was reduced, indicating deficiency of conversion from T4 to T3. Six (43%) out of 14 males showed reduced basal testosterone levels at 8 a.m. and 6 p.m. which, in 4 out of 14 cases, did not increase sufficiently in response to HCG. The basal LH-level was elevated in 9 (50%) of 18 males. The lack of diurnal rhythm of cortisol secretion and primary insufficiency of Leydig's cells did not correlate with the activity of the disease.

Effects of a single high oral dose of thyroxine on the pituitary-thyroid-axis.

Ten euthyroid and 9 hypothyroid volunteers were orally administered 2 mg L-thyroxine (T4) to study the interaction between substitutive and suppressive effects of a single high T4 dose. After a significant rise the serum T4 concentration for 5 days in euthyroid and for 11 days in hypothyroid patients an inhibition of basal and of TRH stimulated TSH release was observed. Maximal inhibition of the TSH response in hypothyroid patients occurred 1 to 7 days after the individual T4 peak. This interval was significantly correlated to the extent of the respective T4 rise. In euthyroid subjects TSH response was significantly inhibited for 8, in hypothyroid patients for 22 days. In all but 3 of the euthyroid patients there was a significant inhibition of the thyroidal 132I uptake on day 8. Normalization of thyroidal 132I uptake and of pituitary TSH secretion generally coincided.