Uniform vascular-endothelial-cell-specific gene expression in both embryonic and adult transgenic mice.

TIE2 is a vascular endothelial-specific receptor tyrosine kinase essential for the regulation of vascular network formation and remodeling. Previously, we have shown that the 1.2-kb 5' flanking region of the TIE2 promoter is capable of directing beta-galactosidase reporter gene expression specifically into a subset of endothelial cells (ECs) of transgenic mouse embryos. However, transgene activity was restricted to early embryonic stages and not detectable in adult mice. Herein we describe the identification and characterization of an autonomous endothelial-specific enhancer in the first intron of the mouse TIE2 gene. Furthermore, combination of the TIE2 promoter with an intron fragment containing this enhancer allows it to target reporter gene expression specifically and uniformly to virtually all vascular ECs throughout embryogenesis and adulthood. To our knowledge, this is the first time that an in vivo expression system has been assembled by which heterologous genes can be targeted exclusively to the ECs of the entire vasculature. This should be a valuable tool to address the function of genes during physiological and pathological processes of vascular ECs in vivo. Furthermore, we were able to identify a short region critical for enhancer function in vivo that contains putative binding sites for Ets-like transcription factors. This should, therefore, allow us to determine the molecular mechanisms underlying the vascular-EC-specific expression of the TIE2 gene.

William Harvey, Peter Lauremberg and cardiac output.

In 1636, the Rostock professor of medicine and the art of poetry, Peter Lauremberg (1585-1639), was one of the earliest to mention circulation which had been discovered by William Harvey and documented in his anatomical manual. In 1628 William Harvey proved the existence of the blood circulation by calculating the "cardiac output in a half an hour (semihora)". The answer to the question why Harvey chose half an hour as the time range can be found in the way of measuring time usual at that period. The sandglasses were turned half-hourly in maritime navigation and the wheel-clocks on shore had only the hour-hand. Improved chronometry was one of the prerequisites for measuring cardiac output. The minute-hand became usual after 1700 and the second-hand later on. Taking into consideration the alterations of cardiac output made the latter one of the most important circulation parameters in diagnostics, prognostication and therapeutics.

The influence of Karl Kleist on the nosology of Karl Leonhard.

Leonhard was largely influenced, during his years at the Frankfurt Mental Hospital, by the Wernicke follower Karl Kleist (1879-1960). Kleist was a representative of brain pathology. His psychopathological concepts, which he developed using the evaluation of brain injuries, look very modern. He tried to attribute different symptoms to definite functional centers and regulatory loops. His theory of the 'autonomous psychic syndromes', his categories of psychomotor activity, his concepts of cycloid psychoses and schizophrenic subgroups are described. The author emphasizes that the differentiation between unipolar and bipolar affective psychoses is based on the team work of Kleist, Edda Neele and Leonhard. Because of Kleist's great contribution to the classification of psychoses, it would be more correct to use the term 'Kleist-Leonhard classification system'.

[Friedrich Martius' studies of myocardial contraction and heart movements a century ago]. / Friedrich Martius' Untersuchungen über Herzstoss und Herzbewegungen vor einem Jahrhundert.

During the 19th century apex beat record represented the only possibility to document the movements of the heart. Friedrich Martius, head of the department of internal medicine of the university of Rostock, succeed with the acustic mark-method to divide the systole in the period of isometric contraction and in the ejection time. As a precursor to the apexcardiography being developed half a century later, he used the apex beat record in the differential diagnosis of cardiac dilatation.

Open comparative study with treatment-refractory depressed patients: electroconvulsive therapy--anesthetic therapy with isoflurane (preliminary report).

Isoflurane is the only routine volatile anesthetic which leads to a burst-suppression EEG in nontoxic concentrations and for which no memory impairments can be expected subsequent to anesthesia. After electrically induced spike-wave activity in electroconvulsive therapy (ECT), a brief period of a very flat EEG can be observed. This phenomenon may be closely related to the therapeutic effects of ECT. The results which have been achieved up to now in comparing ECT to anesthetic therapy with isoflurane, without seizures being induced, are presented.

[Development of the specialty "hypertonology"]. / Zur Herausbildung des Wissenschaftsgebietes Hypertonologie.

The general tendency of the development of the sciences to differentiation is to be seen also within the discipline of internal medicine. By the formation of special tasks with a limited aim of realization the scientific subject of hypertonology developed. According to the regularities of the genesis of the discipline the process took place gradually. In the 18th and 19th century (prehistory) above all the method of measuring the blood pressure (technical prerequisite) developed. With the intensification of the process of cognition since the beginning of the 20 the century the actual development began (preparatory or initial phase). The qualitative breach (phase of constituation) was evoked by 1950 by making available highly effective remedies decreasing the blood pressure, the recommendations of the WHO concerning the limiting values of the blood pressure and the recognition of risk factors. Nowadays the scientific subject of hypertonology is fully acknowledged in research and health policy (phase of establishment); the process leads over to the phase of consolidation.

[Expert opinion in chronic arterial hypertension]. / Begutachtung bei chronischer arterieller Hypertonie.

The expert opinion on chronic arterial hypertension contains several problems, such as influence on choice of the profession and change of the profession, judgement of the traffic ability, judgment of the ability for military service, judgment of connective questions and judgment of capability of earning a living. Of particular importance is the expert opinion the following criteria shall be submitted to a complex valuation: etiology and degree of severity, therapeutic influencibility, physical efficiency, use of rehabilitation measures, side-effects of medicaments, prognosis of hypertension, taking into consideration the natural course and the complications after sufficiently long time fo observation and under optimum use of therapeutic and rehabilitative measures.

[Side effects of drugs, individual hypertension therapy, and drug-taking behavior of patients]. / Arzneimittelnebenwirkungen, individuelle Hypertonietherapie und Einnahmeverhalten der Patienten.

Main thought of the therapy of hypertension is the possibly far-reaching normalisation of the haemodynamics changed by hypertension with simultaneous control of undesirable side-effects. With the aim to keep the side-effects low, depending on the degree of severity and the complication of hypertension, on other basic diseases, age and situation of life important references to an individual therapy are the result for every patient. This is of importance for the selection of the drugs to be applied as well as for an individually suitable dosage. Nevertheless, the side-effects cannot always be fully avoided. The consideration of frequently appearing side-effects furthers a good patient compliance in an active doctor-patient relationship. An own study showed that in special consulting hour for hypertension only one third of the patients regularly take the drugs, another third arbitrarily had modified the therapy. The regularity of the consultation of the physician only little states about the intake behaviour of the patients.

[Haemiton compositum in the ambulatory therapy of hypertension]. / Haemiton compositum in der ambulanten Hypertonietherapie.

Comparative treatments of 14 patients suffering from arterial hypertension of the stages II to IV with haemiton and haemiton compositum (haemiton, triamteren and hydrochlorothiazide) lasting three weeks each showed that under influence of haemiton compositum the systolic blood pressure was lower in which case particularly reactions of orthostasis were practically absent. Measured on the approach of the quotient duration of pulse period to duration of basic vibration T/Tfem to the integrity and to the temporary peak value after Jungmann and coworkers which is parallel to the contractility the regulatorily better behaviour of the circulation under haemiton compositum is significantly expressed. In this case no changes of glucose content in the blood and of the potassium content in the serum appear. The sodium content of the serum slightly decreased in the medication of the combination preparation containing the saluretic. Under haemiton compositum the side effects are more insignificant.

[Hemodynamic parameters and plasma-renin activity following intravenous dihydralazine administration--a contribution to the regulation of renin]. / Hämodynamische Parameter und Plasma-Renin-Aktivität nach intravenöser Dihydralazingabe--ein Beitrag zur Reninregulation.

On account of the complex effective mechanism the control of dihydralazin is performed particularly with regard to the changes of the plasma-renin-activity. The examinations were carried out in 7 patients each with renal and essential hypertension. The plasma-renin-activity, the behaviour of blood pressure, the stroke volume and the minute volume as well as the peripheral arterial resistance should be examined concerning the influence of two doses of dihydralazin and with regard to the influence of the basic disease to the above mentioned parameters. The plasma-renin-activity is decreased as well as increased by dihydralazin. Baroreceptors are made responsible for the renin regulation. Already with 4.125 mg dihydralazin (1/8 ampoule Depressan) nearly the same permanent effect reducing the blood pressure is to be achieved as with a double dosage. Stroke volume and minute volume are reduced by dihydralazin. The peripheral arterial resistance decreases in no case, but in the renal hypertension it shows a rising tendency. With the help of these examinations it shall particularly referred to the fact that the therapeutic mechanism of the slowly beginning and long lasting decrease of blood pressure is not yet be fully clarified.

[Hospitalized hypertensiol patients with gastrointestinal disease]. / Stationär behandelte Hypertoniepatienten mit gastrointestinaler Erkrankung

A careful codification according to the rules of electronic data processing of all data given and especially of the admission number on the signature margin of th medical record gives the possiblity of a rapid return of information for the practice and of a scientific evalustion. 404 patients with hypertension (400-404) of the distric Rostock who were treated in the clinic simultaneously suffered from gastrointestinal diseases (531-536, 570-577). For a more specialized analysis of the clinical data from case histories the four largest institutions of the district were chosen. From this results a relation number of 100 patients with these diagnostic combinations. 73% of these patients were of female sex. The higher blood pressure values at the beginning of the treatment we find in hypertensive patients with simultaneous disease of the gallbladder, in which cases these patients to 44% also showed an overweight. In 74% of the patients there occurred a systolic decrease of blood pressure, in 66% a diastolic one. More frequently than on the average the decrease of the blood pressure appeared in patients with liver and gall-bladder diseases.