Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: an in vitro study.

The mode of action of the antipsychotic drugs clozapine, haloperidol and iloperidone was investigated in layer V of prefrontal cortex slices using extracellular field potential, intracellular sharp-electrode as well as whole-cell voltage clamp recording techniques. Intracellular investigations on a broad range of concentrations revealed that the typical neuroleptic haloperidol at higher concentrations significantly depressed the excitatory postsynaptic component induced by electrical stimulation of layer II. This was not seen with the atypical neuroleptics clozapine and iloperidone. None of the three compounds had any effect on the resting membrane potential, spike amplitude or input resistance at relevant concentrations. Synaptic plasticity was assessed by means of extracellular field potential recordings. Clozapine significantly facilitated the potentiation of synaptic transmission, whereas haloperidol and iloperidone showed no effects. In line with its facilitating effect on synaptic plasticity, it could be demonstrated by whole-cell voltage clamp recordings that clozapine increased N-methyl-D-aspartic acid receptor-mediated excitatory postsynaptic currents in the majority of prefrontal cortical neurones. These investigations were made with neuroleptic drugs applied to the bath in the micromolar concentration range in order to approach clinical brain concentrations that are reached after administration of therapeutic doses. The drug concentrations reached in the slices after the experiments were assessed by means of high-pressure liquid chromatography coupled with mass-spectrometric detection. Surprisingly, drug accumulation in the in vitro preparation was of similar degree as reported in vivo. In conclusion, the typical neuroleptic haloperidol significantly depressed excitatory synaptic transmission in layer V neurones of the prefrontal cortex. In contrast, the two atypical neuroleptics iloperidone and clozapine revealed no depressing effects. This feature of the atypical neuroleptics might be beneficial since a hypofunctionality of this brain area is thought to be linked with the pathophysiology of schizophrenia. Additionally, clozapine facilitated long-term potentiation, which might be linked with the clinically observed beneficial effects on certain cognitive parameters. The clozapine-induced increase of N-methyl-D-aspartic acid receptor-mediated currents suggests that clozapine facilitates the induction of long-term potentiation. Furthermore, the present study points to the importance of considering the significant accumulation of neuroleptic drugs in in vitro studies.

[Ligation of the cystic duct--experience in 1,750 laparoscopic cholecystectomies]. / Verschluss des Ductus cysticus--Erfahrungen bei 1750 laparoskopischen Cholecystektomien.

Between 3/1990-3/1993 laparoscopic cholecystectomy was performed in 1750 patients in the mean age of 49.8 (7-83). In 48 patients (2.7%) the procedure had to be shifted to open surgery. The overall complication rate was 3.9%, the mortality 0.11%. The PDS-clip Absolok 300 was regularly used for occluding the cystic duct and the cystic artery. Clip-associated complications were never observed. The induced duct occlusion proved save even against operative manipulation. But special characteristics of the clip and its application had to be considered.

[Use of laparoscopic surgical methods in mechanical ileus of the small intestine and in stomach perforation]. / Der Einsatz laparoskopischer Operationsmethoden beim mechanischen Dünndarmileus und bei der Magenperforation.

We report on the application of laparoscopic operative methods in ten patients with mechanical bowel obstruction and in seven patients with gastric perforation. From these experiences conclusions were drawn concerning the principles of trocar positioning as well as tactical and strategical considerations in acute abdominal surgery with known and unknown target regions.

[Comparative analysis of mezlocillin/metronidazole and amoxicillin/clavulanic acid as "one shot" preventive antibiotic administration in colorectal interventions]. / Vergleichsanalyse von Mezlozillin/Metronidazol und Amoxicillin/Clavulansäure als "one shot"-Antibiotikaprophylaxe bei kolorektalen Eingriffen.

The prophylactic effect of intraoperative "one shot" antibiotic application in colorectal surgery was investigated. Patients were randomised and the antibiotic combination Mezlocillin/Metronidazole (group A) or Amoxicillin/Clavulamid acid (group B) was applicated in 160 patients. 111 patients were selected for the study (group A: 59; group B: 52 patients). In the postoperative course 53% (group A) and 67% (group B) of the patients developed bacterial infections. Abdominal wound healing was complicated by infection in 15% (A) and 12% (B) of the patients. A significant difference between the two groups could not be proven, 24% of all patients with documented intraoperative bacterial contamination and 10% of the patients with negative findings developed wound infections. In colorectal surgery patients are still at high risk for infectious complications. Applicated antibiotics should basically cover aerobic and anaerobic germs.

[Bladder cancer and old age. Study of the occurrence and status of diagnosis in the GDR with respect to old age]. / Blasenkrebs und Alter. Studie zur Häufigkeit und zum Stand der Erfassung und Behandlung in der DDR unter Berücksichtigung des Alters.

Bladder cancer and age. A study on the morbidity and on the state of detection and treatment with respect to age in the G.D.R. Malignant neoplasms of the urinary bladder account for about 1,400 registered new cancer cases and 1,100 deaths annually in the G.D.R. As compared with other developed industrialized countries, incidence and mortality from bladder cancer is relatively low in the G.D.R. Analysis of age-standardized incidence and mortality from 1956 to 1974 gives no clearcut evidence of an increase of bladder cancer morbidity. A regional analysis of the state of detection and treatment of bladder cancer was performed in the capital Berlin (1955-1974) and the city of Dresden (1969/70). It can be shown that there is a decrease of localized stages, of radically operated tumours and of survival rates with increasing age at time of diagnosis. In Berlin more than 30 per cent of new cases are 75 years and older. Localized stages I and II amount to nearly 50 per cent of newly registered bladder cancer cases. While mean age of patients increased in the observation period and stage distribution remained about equal, rate of radical interventions showed a slight increase reflecting a more aggressive approach to treatment. Higher survival rates can be expected in the future.

[An attempt to analyze the state of gastric cancer control in the German Democratic Republic (author's transl)]. / Zum Stand der Bekämpfung des Magenkrebses in der DDR. Versuch einer Analyse.

Starting from the records of the county cancer control offices, an attempt is made to analyze the quality of detection and treatment of gastric cancer in the G.D.R. Possibilities and results of curative treatment strongly depend upon the extent of the disease and the age of the patient at the time of diagnosis. During the period of observation (Berlin 1955--1974, county Königs Wusterhausen 1960--1974), the proportion of elderly patients (65-yrs.) increased, stage distribution remained about the same, the rate of curative operations increased a little. When comparing the situation in the capital Berlin with the district Erfurt, the city of Dresden and the rural county Königs Wusterhausen, it can be demonstrated that the quality of diagnosis and treatment in Berlin is somewhat better then in the other teritories.

[Bronchial cancer in Berlin, capital of the G.D.R. 2. communication. lung cancer detection between 1955 and 1973 (author's transl)]. / Bronchialkrebs in Berlin, Hauptstadt der DDR. II. Die Erfassungssituation von 1955 bis 1974

In Berlin, capital of the G.D.R., more than 8,600 cases of bronchial cancer were observed in the period 1955 to 1969 and in 1973/4. Number of cases has increased from one 5-years period to the following period. Incidence of lung cancer in men increased especially in higher age groups whereas in female a rising incidence can be seen in all age groups. Duration of history is no good measure of health behaviour and of diagnostic quality. Distribution of clinical stages gives reliable information on the situation of detection. With rising age, the proportion of advanced stages increases. Stage distribution has not changed during the observation period and no measurable progress towards earlier detection of lung cancer has been achieved. In the same time, proportion of elderly lung cancer patients rose considerably and the chances of radical surgical treatment grew worse. Nevertheless the resection rate has increased. It seems that the quality of specialized surgical care has made some progress. Some conclusions can be drawn for cancer control: Prophylactic examinations are to be concentrated on high risk groups. Patients with suspicion of lung cancer shall be admitted to the specialist without delay. Development of nonsurgical methods of therapy for cancer of the lung is an important goal.