A long distance-PCR derived FISH probe detects a deletion between p15 and p16 in CML and T-ALL patients.

The tumor suppressor genes p15INK4B and p16INK4A, located in the chromosomal region 9p21, are frequently inactivated by homo- or hemizygous deletions, point mutation or promotor methylation in various types of cancer. No commercial probe is yet available that allows the detection of such deletions by FISH. Long distance (LD)-PCR was successfully used to generate a FISH probe, that covers a sequence stretch of 11.68 kb, located between the tumor suppressor genes p15 and p16. The LD-PCR amplicon was cloned and biotinylated by DOP-PCR (degenerated oligonucleotide primed-PCR) or nick translation. The FISH probe was hybridized on different samples of 16 patients with leukemia (3 T-ALL, 13 CML) and normal controls. Loss of at least one FISH-signal was found in 2/3 (67%) of the T-ALL- and 2/13 (15%) of the CML-cases. The new FISH probe presented here was proven to be advantageous for the detection of deletions in chromosomal region 9p21, especially between p15 and p16.

[The problem of the impairment of the action of parasympatholytic substances. Ophthalmologic criteria and methods]. / Zur Frage der Beeinträchtigung der Handlungsfähigkeit durch parasympatholytische Substanzen. Ophthalmologische Kriterien und Methoden.

UNLABELLED: The parasympatholytic effects on the eye were investigated in 12 healthy volunteers. In a randomized cross-over double-blind trial 20 or 40 mg N-butylscopolaminium bromide (Buscopan) or placebo was given by i.v. injection. Pupillary light reaction, range of accommodation, visual acuity, and nyctometer values were measured up to 45 min after injection. RESULTS: 1. The mydriatic effect of both dosages of the drug is moderate. Pupil diameters at the end of the light reaction are only slightly greater under the influence of the drug than in control experiments. The dynamics of the reaction remains unaltered. 2. The range of accommodation diminishes in a dose-dependent manner. 9-15 min after the injection the inhibition is maximum. 45 min after injection, even of the 40 mg dosage, only a small effect remains. 3. Visual acuity and nyctometer values are not affected by N-butylscopolaminium bromide. The findings were discussed with respect to the ability to meet the requirements of road traffic.

The effect of anticholinergic drugs on the inner eye muscles.

Using 12 healthy volunteers, we tested the para-sympatholytic effects on the eye. In a randomized crossover double-blind trial, hyoscine-N-butylbromide was tested against saline. Before (20 or 40 mg IV) and up to 45 min after the injection, pupillar light reaction, accommodation, visual acuity, and nyctometer values were measured. The range of accommodation diminishes according to dosage: 9-15 min after the injection, the inhibition is maximum; 45 min after the injection, only a small effect remains, even using the 40 mg dosage. Pupillary reaction is little affected by either dosage, and the pupil diameters at the end of the reaction are only slightly greater after the injection of either dosage than after placebo injection. The time constant of the reaction remains unchanged. Visual acuity and nyctometer values remain unchanged under the influence of hyoscine-N-butylbromide. The results are discussed with respect to the potential ability of a patient to meet the requirements of modern traffic. According to our findings, there are no ophthalmologically-based reasons for an emmetropic person to assume impaired driving abilities after a single injection of hyoscine-N-butylbromide of up to 40 mg. If the accommodative capacity of a patient is impaired whose hyperopia is not fully corrected, the ability to drive in modern traffic may be impaired. After a single dose of 20 mg hyoscine-N-butylbromide (i.e., 1 ampule Buscopan), the impairment of even these patients does not last longer than about 45 min.

A method for the measurement of tremor, and a comparison of the effects of tocolytic beta-mimetics.

A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion.

[On the problem of Side Effects of Anticholinergic Drugs Depending on the Route of Application/Inhalation versus intravenous injection of ipratropiumbromide]. / Zur Frage der Nebenwirkungen anticholinerger Drogen in Abhängigkeit von der Applikationsart: Inhalation versus intravenöse Injektion von Ipratropiumbromid

In four different trial series the effect of (8r)-3alpha-hydroxy-8-isopropyl-1alphaH, 5alphaH-tropanium-bromide-(+/-)-tropate (ipratropiumbromide, Sch 1000, Atrovent) on the stimulated salivary secretion and pulse rate in a total of 43 healthy volunteers was investigated in a cross-over comparison using atropine sulphate and placebo administered by inhalation (metered dose inhaler) and by i.v. injection. All the trial preparations were administered in increasing doses at 30-min intervals in a double-blind procedure. The maximal dose by inhalation in this context was 2.4 mg (60 times the single therapeutic dose), and the maximal i.v. dose was 0.28 mg. The stimulated salivary secretion was not influenced by doses up to 2.4 mg of ipratropiumbromide by inhalation. Following inhalation of 1.6 mg and 2.4 mg atropine sulphate by means of metered dose inhaler of linear, statistically significant inhibition of stimulated salivary secretion was observed (p less than 0.001). Following i.v. administration of ipratropiumbromide, a statistically significant decrease in stimulated salivary secretion was observed following a total dose of 0.28 mg (p less than 0.001). Following inhalation the changes in pulse rate all occurred within the placebo or confidence limits. Following i.v. administration the pulse rate showed a statistically significant increase after a total dose of 0.28 mg. Dryness of the mouth was observed by several volunteers following the maximum dose of ipratropiumbromide, All volunteers in this trial series observed dryness of the mouth inhalation of atropine sulphate.

Investigation on the possible role of a work factor in thermoregulatory behavior of man.

During experiments on thermoregulatory behavior, subjects rested or exercised completely immersed in a water bath of constant temperature. They could adjust the temperature on their backs by means of a water-perfused pillow. The difference T diff between the freely selected temperature on their backs and the water temperature was taken as output of the system of thermoregulatory behavior. Tdiff depends on deep-body and mean skin temperature but not on a non-thermal work factor. In the equation Tdiff=ao + a1Tes + a2Ts, the ratio a1/a2 is approximately 3. This is much smaller than the same ratio for the correlation between sweat rate and deep-body and mean skin temperature which is of the order of 10.