From a forester's boy to a university professor.

Austrian ophthalmologist, Dr. Karl B. Hruby, is well known for his present lens, which allows slit-lamp examination of the vitreous and fundus. He is also known as one of the first to use microsurgical methods for intraocular operations and scleral buckling for retinal detachments. In this memoir, Dr. Hruby shares the fascinating personal account of his experiences as a prisoner and physician during World War II, and as an outstanding teacher and clinician thereafter. The article is followed by the editorial comment of Dr. Fred Blodi, who invited Dr. Hruby to contribute this article.

Potential cancerostatic benfluron is metabolized by peroxidase: in vitro biotransformation of benfluron by horseradish peroxidase.

Horseradish peroxidase (HRP) was used to investigate whether benfluron (a potential cytostatic drug) can be biotransformed extra-hepatically by systems other than flavin-containing monooxygenase and cytochromes P450. Three types of incubation mixtures differing in buffers (Na-phosphate buffer 50 mmol/l, pH 6.8 and 8.4 and Tris-HCl buffer 25 mmol/l, pH 7.5) were tested. The amount of N-demethylated benfluron (demB) formed was significantly higher (up to 4 times in the Na-phosphate buffer, pH 8.4, and 5 times in the Na-phosphate buffer, pH 6.8, and in the Tris-HCl buffer, pH 7.5) compared to control experiments. The highest yields of demB were obtained with the moderately alkaline Na-phosphate buffer (50 mmol/l, pH 8.4). The concentration of demB increased during thirty minutes of incubation, and then remained constant through the end of two-hour incubation. The results support the hypothesis that benfluron can be metabolized extra-hepatically by N-demethylation reaction catalyzed by peroxidases.

[Artificial corneal implants (keratoprostheses) (author's transl)]. / Kunstliche Hornhautimplantate (Keratoprothetik).

The history of keratoprosthetics and the pioneer work of Cardona et al. is described and the technical improvements in this method over the past two decades are reviewed. In addition, the results achieved in 17 personal cases are recorded. Visual acuity was definitely improved in 7 cases, transient improvement was obtained in 5 cases, 3 patients retained poor vision, and 2 cases showed deterioration. Implantation of artificial keratoprostheses is still at a pioneer stage and further progress can be expected in this field.

[Was Dr. Carl Koller driven from Vienna in 1885?]. / Wurde Dr. Carl Koller 1885 aus Wien vertrieben?

In this article the principal reason for the emigration of Dr. Carl Koller is examined on the basis of the available literature. In fact, antisemitism did not play a crucial role. After his colleague, Dr. Fritz Zinner, called him an impudent Jew in public in the General University Hospital of Vienna, Koller reacted by hitting the man in the face. A duel with heavy sabres was the outcome; Koller was unharmed, whilst his opponent received two deep gashes. Such duels were strictly forbidden at that time already, but were nonetheless still executed. In consequence, Koller's hopes of obtaining a position in the Eye Department, for which he was very well qualified, and of an academic career in Vienna were dashed and he had to emigrate. Koller eventually settled in New York in 1888, where he received many distinctions during his life span. The Medical Association of Vienna also honoured him in 1930. Dr. Koller was proposed several times for the Nobel prize in Physiology and Medicine, since his discovery of cocaine as local anaesthetic in ophthalmology was undoubtedly worthy of this prize, but his discovery had been published too long previously, so that according to the statutes of the Nobel prize this distinction could not be granted. Hence, it can be concluded that although Dr. Koller was forced to leave Vienna in 1885, it was not principally for antisemitic reasons. There were Jewish professors in the Medical Faculty of Vienna University at the time and, indeed, when the author studied medicine in 1931 to 1936, four Jewish professors held chairs in Vienna and one of his predecessors as chief of the First Department of Ophthalmology, Isidor Schnabel, was Jewish.

[Prospects and limitations of the treatment of senile maculopathies with phosphatides (author's transl)]. / Aussichten und Grenzen der Behandlung seniler Makulopathien mit Phsophatiden.

All kinds of treatment attempted so far in cases of senile maculopathies were unsatisfactory. Intramuscular injections of retinal phosphatides were introduced six years ago. In this follow-up study 216 eyes of patients with senile maculopathy treated by Etaretin have been checked. The former experience was confirmed that an improvement in visual acuity can be obtained only in early cases of the dry type. In such cases i.m. injections of Etaretin are actually the treatment of choice. In fairly advanced cases eventually some stabilization of the process may be obtained. In terminal stages no effect can be expected. Experimental observations revealed that the therapeutic effect of a phosphatide compound depends on the content of the polyunsaturated fatty acid C 22:6, but not on the animal organ which serves as the source of the extract. From an economic point of view these findings are of importance for further experimental work, as well as for broad clinical application.

[Veratrum album poisoning (author's transl)]. / Vergiftung mit Veratrum album (weisser Germer).

Ingestion of plant material rarely gives rise to manifest clinical intoxication. This is due to the relatively low toxicity of most of the poisonous plants of Central Europe. Veratrum album is an important exception on account of its highly toxic alkaloids. Seven cases of overt intoxication from veratrum album have been reported to the Austrian Poison Information Centre during the past 5 years. On the basis of these case reports toxicological and clinical aspects of this rare form of poisoning are discussed.

[Acute poisoning with tricylic antidepressants and treatment with physostigmine salicylate (author's transl)]. / Die akute Vergiftung durch trizyklische Antidepressiva und ihre Therapie mit Physostigminsalizylat

Three cases of self poisoning with tricyclic antidepressants (TAD) are reported, one of them with a potentially lethal dose. All three cases were treated with physostigmine salicylate (PS) and in two cases there was complete reversal of coma within a few minutes. In striking contrast to the reported high incidence of cardiac arrhythmias no cardiac complications were observed in any of the cases. Therefore we think that the use of PS should be considered when treating cases of TAD poisoning.

[Pharmacotherapy of Amanita phalloides poisoning using silybin]. / Pharmakotherapie der Knollenblätterpilzvergiftung mit Silibinin.

A total of 18 cases of Amanita phalloides poisoning was treated by combined chemotherapy during 1980 and 1981. After attempted primary elimination of the toxin all patients received silybin as basic therapy mainly by infusion and, in two instances, silymarin orally. In order to investigate the effect of silybin therapy a retrospective study of the followed-up case records was made. The cases were arbitrarily classified into three groups of severity (light, medium and severe) according to clinical and laboratory findings. A close relationship was found between the severity of the intoxication and the time elapsed before commencement of silybin therapy. The time interval between mushroom intake and the commencement of the silybin administration averaged 71.5 hours in the "severe" group compared with 46 and 33.8 hours, respectively, in the "medium" and "light" groups. The mean silybin dosage was 33 mg/kg body weight/day; the mean duration of silybin therapy was 81.6 hours. With the exception of one fatality in a particularly high dosage suicidal intoxication, all patients survived. Administration of silybin within about 48 hours after mushroom intake seems to be an effective measure to prevent severe liver damage in Amanita phalloides poisoning.

[Pharmacokinetics of beta-methyldigoxin and beta-acetyldigoxin in patients with cirrhosis of the liver (author's transl)]. / Zur Pharmakokinetik von beta-Methyldigoxin und beta-Acetyldigoxin bei Patienten mit Leberzirrhose.

In this prospective randomised study 12 patients suffering from cirrhosis of the liver (stable phase) and 12 healthy male volunteers were treated with either 0.3 mg beta-methyldigoxin (Lanitop) or 0.4 mg beta-acetyldigoxin (Novodigal) daily, orally. Every day the total serum digoxin concentrations of the patients and volunteers were measured by radioimmunoassay. Both digoxin and beta-methyldigoxin are measured by this method. In subjects receiving beta-methyldigoxin therapy the ratio of beta-methyldigoxin to digoxin in the serum was determined by liquid chromatography. The digoxin levels in patients with cirrhosis treated with beta-methyldigoxin were statistically significantly higher than in healthy volunteers. In patients with cirrhosis the proportion of serum beta-methyldigoxin averaged 77.7% of the total digoxin concentration, whereas the proportion was only 37.5% in healthy volunteers. With beta-acetyldigoxin there was no statistically significant difference between patients with cirrhosis and healthy volunteers. Alterations in pharmacokinetics may cause the higher total serum digoxin concentrations in cirrhotic patients. The following factors seem to be important: longer elimination half life, changes in distribution volume and reduced renal clearance. There is greater danger of digitalis toxicity in patients with cirrhosis of the liver on standard dosage of beta-methyldigoxin than on standard dosage of beta-acetyldigoxin.

[New aspects of chlorprothixen-poisoning (author's transl)]. / Neue Aspekte der Chlorprothixenvergiftung.

Over the past 8 years the Poison Information Centre of Vienna was confronted 24 times with acute chlorproxithene (CPTX) poisoning. In adults doses of 2 g and more caused severe intoxication, but serious toxic manifestations were observed already at low dosage in children (after the ingestion of less than 5 mg/kg body weight). In one case unexpected death due to cardiac failure occurred as long as 49 hours after CPTX intake. The favorable outcome in one patient treated with gut, as well as gastric lavage indicates that this therapeutic strategy may be of value in the management of CPTX intoxication.

[Amanita phalloides poisoning in Austria (author's transl)]. / Knollenblätterpilzvergiftungen in Osterreich.

An analysis of 28 cases of amanita phalloides poisoning serves as basis for a discussion of the clinical features and therapeutic problems involved. A critical review of recent experimental investigations in animals points to new possibilities in the treatment of amanita phalloides poisoning.

[Poisoning with clonidin hydrochloride in children and adults]. / Die Intoxikation mit Clonidinhydrochlorid im Kindes- und Erwachsenenalter.

In this study clinical findings are presented of 31 patients with clonidinee intoxication and the therapeutic measures taken in these cases are discussed. In toddlers poisoning is seen after ingestion of a single tablet of 150 micrograms clonidine, whilst in adults poisoning may occur already at a dosage just exceeding the therapeutic limit, which is subject to wide individual variation (1 to 3 tablets). Primary elimination procedures must be instituted at these dosages, but, because of the rapid absorption of clonidine, gastric lavage and induced emesis provide no benefit to patients with complete symptomatology or those who took the overdose several hours before. Chlorpromazine-like effects, hypotension and bradycardia proved to be the outstanding features. Respiratory depression, disturbances of myocardial conduction or hypertension were less frequent. Symptoms lasted for a mean of 15.5 +/- 8.6 hours, with a range of 4 to 36 hours. Fluid therapy and, as necessary, dopamine for hypotension, phentolamine for hypertension and atropine for bradycardia caused prompt improvement in addition to essential measures such as meticulous control of respiratory function, body temperature and of ECG changes. There was no need to implement the central clonidine antagonist, tolazoline in any of these cases.

[Accidental fatal formaldehyde poisoning]. / Akzidentelle tödliche Formalinvergiftung.

A previously healthy man accidentally swallowed 20 to 50 ml of Formalin (25%). Relevant clinical findings after the accident were: severe metabolic acidosis, severe disseminated intravascular coagulation and renal failure. He died 7 hours after formaldehyde ingestion-presumably from toxic pulmonary oedema. Relevant post-mortem findings were: massive pulmonary damage (toxic oedema), leather-like thickening of the gastric wall and multiple subendocardial haemorrhages. The treatment of formaldehyde poisoning is briefly discussed.

[Comparison of the cost of treatment of premature labor with atosiban or beta-sympathomimetics from the perspective of the health care payer--a pharmacoeconomic model]. / Srovnání nákladu na lécbu predcasného porodu atosibanem nebo beta-sympatomimetiky z perspektivy plátce zdravotní péce--farmakoekonomický model.

OBJECTIVE: To evaluate the cost of treating premature delivery with atosiban or beta-sympatomimetic drugs (fenoterol and hexoprenalin) from the perspective of health care payer--the medical insurance company. DESIGN: A pharmaco-economic model based on the results of randomized, controlled clinical study. SETTING: Hospital Pharmacy at Vitkovice Hospital of Blessed Mary Antonia, Ostrava. METHODS: The study is based on the application of clinical decision-making analysis, which includes results of a randomized controlled clinical study as well as data on the cost of clinical interventions and cost of drug therapy. The pharmaco-economic model was created from the perspective of the payer of health care--the insurance company. This model presumes the administration of atosiban or beta-sympatomimetic drugs (fenoterol and hexoprenalin) for the period of 18 and 48 h and the therapy of possible untoward effects for the next 72 h after the administration of the drugs. The analysis of sensitivity of pharmacokinetic model also employs so called low and high estimate of supplementary cost for the treatment of untoward effects. RESULTS: After the administration of the drugs for the period of 18 h the total cost of the payer of medical care was in the range of 21,914.5-21,974.4 CKr in atosiban, 19,878.7-22,661.4 CKr in fenoterol and 19,942.9-21,974.4 CKr in hexoprenalin. In the administration of the drugs for 48 h, the overall cost of the payer of medical care was in the range of 43,082.5-43,142.4 CKr in atosiban, 19,960.3-23,150.7 CKr in fenoterol and 20,131.3-23,574.0 in hexoprenalin. CONCLUSIONS: This study compared overall cost associated with hospitalization of a premature delivery from the perspective of the medical care payer, i.e. the health insurance company. The authors applied a pharmaco-economic model evaluating hospitalization for the period of 48 h and subsequent therapy of possible untoward effects for the period of up to 72 h. In case of a shorter administration of atosiban (up to 18 h) the overall cost of hospitalization for premature delivery for the period of 48 h from the point of view of medical insurance company is basically comparable with the administration of beta-sympatomimetic drugs. If atosiban is administered for more than 18 h, the overall cost of hospitalization is higher than with beta-sympatomimetic drugs, and the cost increases in relation to the duration of atosiban administration.

[Availability of antidotes in hospital pharmacies in the Czech Republic]. / Dostupnost antidot v nemocnicních lékárnách Ceské republiky.

Availability of antidotes in the Czech Republic (CR) is insufficient. Many antidotes are not approved in CR, so their obtaining is problematic. The purpose of this study is to examine the real availability of antidotes in Czech hospital pharmacies and to assess the influence of hospital size, hospital localisation, antidote cost, and the fact of antidote approval in CR on antidote availability. Finally, some proposals for the solution of the situation are mentioned. A structured questionnaire was constructed and mailed to 85 hospital pharmacies. A total of 46 hospital pharmacies sent back completely answered questionnaires and they were statistically assessed. The questionnaire included a summary of poisonings and usable antidotes. The recommended quantity of each antidote was included. Availability of antidotes (D) and sufficient availability of antidotes (DD) were calculated for each answering hospital pharmacy as a ratio of poisonings for which the antidote was available or available in a sufficient quantity, to all poisonings mentioned in the questionnaire. The other calculated parameter was the availability of an individual antidote (d) and the sufficient availability of an individual antidote (dd)--they were calculated as a ratio of pharmacies stocking the antidote, or stocking the antidote in a sufficient quantity, to evaluated pharmacies. Availability of 23 different antidotes for 20 poisonings was assessed. Antidotes for roughly one half of assessed poisonings are available (D 55.69 +/- 12.42%) and for about one third of poisonings the antidotes are available in a sufficient quantity (DD--37.23 +/- 14.10%). The D and DD have been dependent on hospital size (measured as the number of beds). D and DD have not been dependent on the localisation of the hospital (measured as a period of transport time to the hospital of higher type of care), d and dd ranged between 0-100% and were dependent on the antidote cost. There were significant differences between d and dd of antidotes approved (R) and unapproved (NR) in CR (d(R)--70.51 +/- 33.26%, d(NR)--10.19 +/- 9.26%, p < 0.001; dd(R)--47.55 +/- 29.94%, dd(NR)--6.93 +/- 7.76%, p < 0.001). The results of the study confirm a very unsatisfactory situation in antidote availability in Czech hospital pharmacies. Hospital stocks of many antidotes are inadequate. Often, the antidotes are available, but their quantity is insufficient. The worst situation is in small hospitals, in the very costly antidotes, and in the antidotes not registered in CR.

[Antidotes in clinical toxicology]. / Antidote in der klinischen Toxikologie.

This overview describes antidotes, and their clinical pharmacology, that have an established significance in the currently practiced clinical toxicology because of their proven effectiveness in the treatment of serious poisonings. For the proper, efficient, and targeted use of an antidote, pharmacological knowledge is required, which is a central subject of this article. Current data from the literature are used as reference along with the accumulated experiences about possible adverse effects in order to include them in therapeutic considerations. The dosage of antidotes is the subject of several other review articles and is therefore not included in this synopsis.