Statistical testing of drug accumulation in skin tissues by linear regression versus contents of stratum corneum lipids.

This investigation is a contribution to standardization in in vitro drug penetration measurements using excised human skin and to statistical treatment of the observations. The wide variations observed in measurements of drug accumulation in and drug permeation through the stratum corneum are caused not only by analytical errors but also by the variability of the horny layer lipid composition. The last-mentioned systematic influence can be compensated for by stepwise (multiple) linear regression using the contents of the main lipid classes as independent variables. In consequence, the S.E. of estimate given by the regression calculation is lower than the S.E. of the means of the observations. Significant differences in drug quantities accumulated in skin tissues (stratum corneum and dermis) are sensitively detected by Chow's F-test of structural change. Accumulation data of flufenamic acid and hydrocortisone penetrated from different bases are given as examples. The calculation mode is exemplarily explained and discussed. The results of the test for structural change, two-independent-groups t-test and paired-samples t-test are compared. The F-test of structural change proves to be a helpful statistical method suitable to the assessment of biopharmaceutical quality parameters and to measurements using biological materials.

[Improvement in the diagnosis of scrotal diseases using color-coded duplex sonography]. / Verbesserung der Diagnostik skrotaler Erkrankungen mit der farbkodierten Duplexsonographie.

Two hundred and twenty-two patients with abnormalities of their scrotal contents were examined with colour-coded duplex sonography. The aim of this prospective study was to evaluate this new procedure for the investigation of the scrotal organs. Differentiation between testicular torsion and inflammation by colour-coded duplex sonography achieved 95% accuracy. The diagnosis of varicoceles was simplified and expedited (accuracy = 99%). In other abnormalities of the scrotum, particularly testicular tumours, a knowledge of the blood flow did not provide any important additional diagnostic information compared with conventional sonography.

Light and electron microscopy of the structural organization of the tissue-lymphatic fluid drainage system in the mesentery: an experimental study.

Supplementing vital microscopy and histophysiology, we examined using combined light and electron microscopy the tissue fluid-lymphatic drainage system of the mesentery isolated from guinea pigs, rabbits, and tree shrews. In silver impregnated tissue, different types of lymphatics and blood vessels were able to be distinguished along with argyrophilic and argyrophobic structures in the connective tissue. Some initial lymphatic pathways were interrupted by non-endothelialized tissue zones thus forming separate but discrete vascular "islands". After carbon labeling of the lymphatic collectors, carbon particles were seen to escape from the initial lymphatic lumen at various sites. Electron microscopy revealed wide apertures in the lymphatic endothelial cells of these microvessels. These morphological findings support the concept of an "open" prelymphatic-lymphatic system in the mesentery. The special histometrical features exhibited by a flat membranous organ like the mesentery are discussed in terms of physiologic function of mesenteric tissue fluid transport.

[Capillary permeability and micro-lymph drainage]. / Kapilläre Permeabilität und Mikro-Lymphdrainage.

Vital microscopic findings confirm the existence of an organized prelymphatic system favoring the fluid and substance drainage by the initial lymphatics. By means of open connections of solphasic tissue channels with the initial lymphatics-together with the system of open junctions-the contribution to the maintenance of the interstitial fluid balance is essentially increased. In connection with the permeability for fluid and proteins of the capillary bed itself this contribution appears important. The trans-interstitial fluid transport is favored additionally by the fluid movement along the connective tissue fibres.

[Diagnosis of "fatal ethanol poisoning in the absorption phase"]. / Zur Diagnose "Tödliche Ethanolvergiftung in der Resorptionsphase".

In cases of disputed fatal alcohol intoxication during the absorption (pre-peak) period it is strongly recommended to examine the blood ethanol level not only in blood taken from a peripheral vessel but also simultaneously in blood from at least one central. In the case reported, without such a duplex determination of the blood ethanol concentration it would have been impossible to establish the actual cause of death.

[Physiology of the lymph vessel system]. / Zur Physiologie des Lymphagefässsystems.

Using an incomplete darkfield transillumination technique a prelymphatic network of tissue channels, connected with the initial lymphatics could be observed vitalmicroscopically in the mesentery of homeotherm animals. Furthermore, channels are found also paravascularly along the venules marked by a maximum of protein permeation in the capillary bed. Here exists a short way for the protein uptake by the prelymphatic system and initial lymphatics. This is important for the osmotically released movement of fluid into the lymphatic vessels. Supported by the connecting tissue fibres the prelymphatic system represents a preformed low resistance pathway for fluid movement convected to the initial lymphatics through the interstitial spaces.

[The formation of lymph]. / Zur Bildung der Lymphe.

Fundamental physical properties of lymph formation are described in connection with the permeability of the terminal vascular system (Ludwig Stahling's hypothesis). In view of the current image of this system, as far as it is derived from the isogravimetric model, this can no longer be considered generally valid. Above all the recent vital microscopic studies clearly show that the venous system is of special importance for lymph formation as it possesses special permeability properties and is enclosed by a system of paravascular interstices. They form a protein pool in the tissue releasing a colloid-osmotic energy for the lymph motion. The lymph is drained away by means of "low resistance pathway" correlated with the elastic fiber system and by slow resistance pathways filled with ground substance to reach the efferent lymphatic vessels via an open communication system.

[Contribution of prelymphatic structures to lymph drainage]. / Beitrag prälymphatischer Strukturen zur Lymphdrainage.

Vitalmicroscopic findings confirm the existence of a "low resistance pathway" for the transinterstitial fluid movement from the pillaries to the initial lymphatics. One part of this prelymphatic system is represented by submicroscopical spaces along the connective tissue fibres between ground substance (high resistance pathway) and fibre surface. The other part is represented by a network of prelymphatic tissue channels which are open connected with the initial lymphatic system.

[Control of the intensive treatment of thallium intoxications (author's transl)]. / Verlaufskontrolle der Intensivtherapie von Thalliumintoxikationen.

A report is given on the control of the thallium level at poisoning during therapy with forced diuresis and extracorporeal hemodialysis. The success of these methods was controlled ty the determination of the thallium level in vomit, blood, urine and dialysate by flameless atomic absorption spectrophotometry. Since the results are obtained within a few minutes, thallium measurements may be helpful for the decision on the therapy to be applied.

The effect of the gradient of vascular permeability on fluid and plasma protein exchange in the mesenteric microcirculation.

The present work is a theoretical analysis of the intramural and transmural flows of fluid and plasma proteins. The transvascular fluxes are treated on the basis of a phenomenological approach resulting from the irreversible thermodynamics. The concept leads to a generalization of the well known Starling equation for the fluid exchange and to an additional equation which accounts for the exchange of plasma proteins. The key element in the theory is the incorporation of axial variations of the vascular permeability in the model. Numerical results are obtained for the cat mesentery taking into account the particular angioarchitecture of that tissue. The strength of the present model lies in the precise localization of the transvascular fluxes which results from the differential treatment of the fluid dynamic and mass transfer problem. The results confirm vital microscopic findings of various authors that fluid filtration and the plasma exchange occur predominantly on the arteriolar and venular side of the microcirculatory bed. In contrast, the exchange in the capillaries is relatively small regardless of the actual value of the gradient of permeability. In the organ specific situation studied, the transvascular fluxes are directed outward everywhere to the tissue. The general effect of the vascular gradient of permeability is to enhance the local transvascular fluxes on the venous side.

[Trends in the incidence of poisoning reported to the Dresden Institute of Forensic Medicine 1964-1989]. / Trends im Intoxikationsgeschehen des Dresdner Instituts für Gerichtliche Medizin 1964-1989.

In a retrospective study of all cases due to poisoning investigated by the Dresden Department of Forensic Medicine, over a twenty-six-year period between 1964 and 1989 were studied. Most of all cases were carbon monoxide or medicinal drug poisonings. Some interesting trends in the frequency distribution over the years have been highlighted.

Changes in lymphocyte subpopulations after prolonged exercise.

In order to assess the changes in the cellular immune system, 27 healthy male subjects were selected who participate in leisure-time sports and in whom measurements of the lymphocyte subsets in venous blood were carried out before and after a standardized endurance exercise test (EI, 60 minutes in length, intensity: 63% of maximum performance). The percentages of the following parameters were measured: total T-lymphocytes, B-lymphocytes and O-lymphocytes as well as T4-lymphocytes (helper T-lymphocytes, CD4+) and T8-lymphocytes (cytotoxic/suppressor T-lymphocytes, CD8+). In a subgroup consisting of 8 subjects, the parameters indicated above were measured again 24 hours following E. In order to check the reproducibility of the findings, the endurance exercise test was repeated 21/2 weeks later (EII).

[Selection of various types of lasers in the treatment of surface and deep vascular anomalies]. / Auswahl verschiedener Lasertypen bei der Behandlung von oberflächlichen und tiefen Gefässanomalien.

Laser therapy can be used to great advantage in the treatment of haemangiomas in childhood in specially selected cases. We were able to collect experiences in 101 children and to utilise both the coagulation effect for percutaneous induction of regression and the cutting effect in the resection of haemangiomas at the body surface and the thoracic and abdominal cavities. Among the commercially available laser equipment we would prefer the argon laser for intracutaneous lesions (naevi teleangiectatici, spider naevi, plane haemangiomas), whereas for the cavernous or planotuberous or tuberonodous haemangiomas it is better to use the neodym-YAG laser. Patients must be very carefully selected and selection must be restricted to haemangiomas with complications. Treatment via neodym-YAG laser must be complemented by protecting the skin against cold, by compressing the angiomas and by an appropriate after treatment.

Enhanced rate response algorithm for orthostatic compensation pacing.

Upon orthostatic stress after a period of rest, the heart rate increases rapidly to maintain cardiac output and minimize the fall in arterial pressure. Pacemaker patients are often prone to a deficient response to orthostatic stress. This may cause lightheadedness and, in rare patients with autonomic dysfunction, syncope. To alleviate these undesirable consequences, an enhanced rate response algorithm was developed using an accelerometer. The pacemaker generates two signals from its accelerometer: instantaneous activity level (Act) and long-term change in activity level (ActVar). Low values of both Act and ActVar indicate a resting state. An increase in Act while ActVar remains low indicates the onset of motion after prolonged rest. Upon detecting this transition, the algorithm increases the pacing rate to a programmable orthostatic compensation rate for a programmable duration. A taped-on pacemaker with this algorithm was evaluated in three healthy women and two healthy men, 36 +/- 8 years of age. Electrocardiogram and ventricular pacing pulses were recorded by a 24-hour ambulatory system. Each trigger of the orthostatic compensation rate was verified against a > 10 beats/min increase in heart rate, a response classified as appropriate. The overall specificity of the algorithm among the five subjects was 78%. The nocturnal specificity (10 PM to 7 AM) was 98%, considerably higher than during daytime (72%). In conclusion, a pacing algorithm to alleviate orthostatic stress was developed, which was highly specific during the night hours.