Development of an in vitro modified skin absorption test for the investigation of the follicular penetration pathway of caffeine.

The Organization for Economic Cooperation and Development (OECD) recommends caffeine as a reference substance for in vitro skin absorption tests using Franz diffusion cells (FDC). However, it has not been possible to investigate the follicular penetration pathway using this method until now. The aim of this study was to develop a technique to allow the examination of the follicular penetration pathway of a substance penetrating into the skin. The OECD standard method was therefore combined with the follicle closing technique (FCT), an established in vivo method. By using test skin of varying follicular densities, different penetration values were obtained for the test substance caffeine. The follicular penetration rate was determined by an indirect calculation after modifying the in vivo FCT for use in the in vitro FDC. This method is the first to allow the differentiation of penetration pathways by combining the OECD standard method (using the FDC) and the FCT. Caffeine showed a surprisingly high rate of penetration through the follicular shunts in vitro.

Establishing a baseline for organisation and outcome in burn care-basic data compiled by German burn centres, 1991-2000.

From the years 1991 to 2000, basic data from patients admitted to the intensive care unit of burn centres in Germany, Austria and Switzerland, participating in the German Speaking Association for Burn Treatment, were collected prospectively. Starting in 1991 with 7 hospitals and 618 patients included in the study; in the year 2000, 19 hospitals representing nearly 1500 patients submitted their data. Over a period of 10 years, a total number of 10,259 patients could be included in the study. The majority of patients were adult, the male/female ratio was 70/30. Most of the patients suffered from household accidents, only 25% were occupational accidents. Medium total burn surface area (TBSA) and Abbreviated Burn Severity Index (ABSI) score were quite similar in the participating hospitals, while the medium length of stay in the ICU ranged from 6 to 24 days. The overall mortality was 17.5% and showed no decrease over the period of time.

In a pig model ePTFE grafts will sustain for 6 weeks a confluent endothelial cell layer formed in vitro under shear stress conditions.

OBJECTIVE: to investigate in a pig model whether small diameter ePTFE grafts will sustain a confluent endothelial cell layer formed in vitro under shear stress conditions. MATERIALS AND METHODS: thirteen ePTFE (4 mm) grafts were implanted end to end in the right femoral artery of; 8 grafts had been endothelialized in vitro. Grafts were left in situ for 6 weeks then evaluated with ultrasound and histology. RESULTS: seven endothelialized graft were patent with confluent endothelial cell lining. None of the control grafts were patent or showed evidence of an endothelial lining. CONCLUSION: in this pig model ePTFE grafts sustained for 6 weeks a confluent endothelial cell layer formed in vitro under shear stress.

[Keloid of the earlobe after ear piercing. Not only a surgical problem]. / Keloidbildung des Ohrläppchens nach Ohrlochstechen. Nicht nur ein chirurgisches Problem.

Earlobe keloids are benign, fibrous proliferations that show a high rate of recurrence of up to 80% following surgical excision. Traumas to the earlobe such as ear piercing, burns or surgical interventions are important in the pathogenesis of the disease. In addition to surgical keloid excision and reconstruction of the earlobe, several adjuvant therapeutic concepts have been described to prevent recurrence. Here we present the case of a female patient who suffered from severe bilateral keloid development after piercing of both ears. The report gives an overview of the relevant therapeutic concepts in the treatment of earlobe keloids and their possible complications. In addition, the question of written informed consent before ear piercing is discussed.

[High pressure injection injuries of the hand with surfacer]. / Hochdruckeinspritzverletzung der Hand mit Spachtelmasse.

The most commonly injected materials in high-pressure injection injury to the hand include paint, automotive grease, solvents and diesel oil. High-pressure injection injuries are a frequently mismanaged problem, as they are often not recognized and treated early, which may result in a compromised function of the hand or even the amputation of a digit. Early diagnosis is an important factor, as well as the type and amount of injected material and the injection pressure at appliance. We present one case of high-pressure injection injury to the hand with the surfacer Caparol Accord. This report describes the principles of treatment and gives an overview of the literature about tissue injuries caused by components of different substances encountered in high-pressure injection injuries.

Comparison of long-term immunosuppression for limb transplantation using cyclosporine, tacrolimus, and mycophenolate mofetil: implications for clinical composite tissue transplantation.

This study compared the efficacy of long-term intermittent immunosuppression in preventing the rejection of a limb transplant across the strongest histocompatibility barrier in ACI --> Lewis rats using the conventional immunosuppressive agent cyclosporine-A and the newer immunosuppressive agents FK-506 (tacrolimus) and RS-61443 (mycophenolate mofetil). The recipient animals were immunosuppressed daily for 14 days postoperatively, followed by long-term intermittent, twice-weekly immunosuppression using cyclosporine 25 mg/kg, RS-61443 30 mg/kg, or FK-506 2 mg/kg. All three immunosuppressive agents were able to prolong the rejection of the skin component of a limb transplant compared with nonimmunosuppressed controls. Eight of nine animals receiving cyclosporine immunosuppression showed signs of rejection of the skin component of the limb transplant while continuing to receive long-term immunosuppression and had a mean rejection time of 61.6 days. Seven of 10 animals immunosuppressed with RS-61443 also showed signs of rejection while still receiving immunosuppression, with a mean rejection time of 43.6 days. Nine of 10 animals receiving FK-506 immunosuppression showed no signs of skin rejection, but died of bacterial pneumonia between 273 and 334 days after transplantation, with a mean rejection time of 296.1 days. There was no statistically significant difference between intermittent immunosuppression with cyclosporine and RS-61443, but FK-506 was significantly superior to both cyclosporine and RS-61443. The implication of this study is that FK-506, but not cyclosporine or RS-61443, is probably the only single immunosuppressive agent capable of preventing rejection of the skin component of a composite tissue transplant. Combination immunosuppression with FK-506 and RS-61443, therefore, may be required to allow composite tissue transplantation to become a predictable clinical reality in the future.

A novel perfusion system for the endothelialisation of PTFE grafts under defined flow.

OBJECTIVES: to develop a perfusion system for culturing human endothelial cells on small-diameter PTFE grafts under defined pulsatile shear stress. METHODS: to benefit from a stronger adhesion of endothelial cells to the substrate, we developed a perfusion system which enables culture of endothelial cells on PTFE grafts to confluence under a wide range of shear stress. We also developed an in situ staining method for the determination of the endothelialisation stage by upper light microscopy. RESULTS: the application of pulsatile flow with high shear stress (6.6 dyn/cm2, 5 min) to a graft endothelialised under perfusion did not lead to a disruption of the confluent cell layer. In contrast, a shear stress of 3 dyn/cm2 applied for 5 min was sufficient to wash more than 50% of endothelial cells off the PTFE graft when cultured to confluence under static conditions. CONCLUSIONS: this technique induces a stronger cell adherence of endothelial cells to a PTFE graft in comparison with grafts endothelialised under static conditions. Endothelialised vascular grafts can be pre-conditioned to defined shear stress values.

[Adjustable "banding" of the hepatic artery in treatment of shunt-induced heart failure in Osler-Rendu-Weber disease]. / Justierbares "banding" der Leberarterie zur Behandlung der shuntbedingten Herzinsuffizienz bei Morbus Osler-Rendu-Weber.

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is rare. Among local pathologic alterations like fibrosis and cirrhosis, arteriovenous shunts lead to hypercirculatory heart failure and require efficient therapy. Present therapeutic strategies consist of percutaneous selective embolization or complete ligation of the hepatic artery. We describe a 53-year-old woman with HHT in whom percutaneous selective embolization of the left hepatic artery failed because of unfavorable anatomy. Instead of ligation a new method of adjustable banding of the hepatic artery was tested. After small-incision laparotomy an expander prosthesis was put on the proper hepatic artery. By filling the prosthesis via the implanted port system the hepatic perfusion could be reduced under control. This method led to effective reduction of the liver perfusion and heart time volume and to successful treatment of heart failure. The method described is an alternative treatment to ligation of the hepatic artery in cases in which percutaneous embolization failed or is not possible.

[Thrombosis and tissue protection in microvascular surgery--an overview]. / Thrombose- und Gewebeschutz in der Mikrovaskularchirurgie--Eine Ubersicht.

Although microvascular surgery has become a safer procedure in recent years, failure still occurs. The main cause of failure is thrombosis of the anastomosed vessels. Thrombosis involves the vascular wall, platelets and the coagulation system. Sometimes the transferred tissue dies with the anastomoses open. This is caused by an insufficient perfusion at the microcirculatory level, e.g. a reduction of capillary inflow by arteriolar vasoconstriction. Tissue damage also occurs after ischemia and reperfusion. Oxygen free radicals and activated leukocytes are responsible for this phenomenon. Thrombosis can be reduced by antiplatelet and anticoagulant drugs, substances increasing fibrinolysis and other agents. In the clinical situation, aspirin, heparin and dextrane have proven reliable. The microcirculation can be protected by aspirin. Reperfusion injury is affected with superoxide-dismutase, allopurinol and perfusion solutions. Future developments in this field will include locally applied antithrombotic agents and substances acting more specifically.

Rejection of the component tissues of limb allografts in rats immunosuppressed with FK-506 and cyclosporine.

One-hundred and fourteen limb transplantations have been performed across a major histoincompatibility barrier between donor ACI (RT1a) and recipient Lewis (RT1l) rats immunosuppressed with various dosages of FK-506 and cyclosporine. Three-hundred and thirty biopsy specimens from 64 animals have been evaluated histologically for signs of rejection. A new histologic grading system is introduced to classify the process of rejection in the component tissues (skin, muscle, bone, and articular cartilage) of a limb allograft. The results indicate that FK-506 is a more potent immunosuppressive agent than cyclosporine in preventing the rejection of the skin component of a limb transplant. With twice-weekly intermittent immunosuppression with FK-506, the rejection of muscle, bone, and cartilage can be prevented for an indefinite time, although all long-term surviving animals died at around 300 days, probably of graft-versus-host disease. Based on the histologic stages of rejection in the different tissues at the same point in time, it is evident that each component tissue of a limb transplant rejects over a different time period. This probably reflects a hierarchy of antigenicity, with skin being most antigenic, muscle being intermediate in antigenicity, and bone and cartilage being least antigenic. Although this grading system is not the ultimate solution, it may allow a more objective comparison of experimental limb transplantation in the future.

[Prognosis and treatment of burns in elderly patients]. / Prognose und Behandlung der Verbrennung beim alten Patienten.

In a retrospective study victims of burn accidents over 65 years of age were analysed. The total number was 40, with an average age of 77 years. In 95% the burns were caused by accidents at home such as residential fires, highly inflammable clothing and scalds from hot showers. Patients were admitted late to hospital on average after 4.4 days, combined with a wound infection rate of 50% by this time. Of these 81.1% showed severe additional diseases. The letality rate was 24%, almost in every case caused by additional cardiopulmonary disease. A total of 95% were able to return to their previous home after treatment. The focus was on prevention by means of smoke-detectors and hotwater thermostats.

Peripheral nerve allograft transplantation with FK506: functional, histological, and immunological results before and after discontinuation of immunosuppression.

Two-centimeter nerve allografts were transplanted across a major histocompatibility barrier from donor ACI rats into a 0.5-cm gap in the sciatic nerve of recipient Lewis rats and immunosuppressed with FK506, 2 mg/kg per day for 3 months. One group of animals continued to receive intermittent immunosuppression with FK506, 2 mg/kg twice a week for another 2 months, whereas the second group of animals received no further immunosuppression in order to determine whether rejection of nerve allografts can still occur after immunosuppression is withdrawn, even after the axons have regenerated through the nerve graft. The sciatic function index improved from -76.3 at 3 months to -46.6 at 5 months in those animals continuing to receive intermittent immunosuppression, but only improved to -66.8 at 5 months when immunosuppression was discontinued. Similarly, somatosensory evoked potentials demonstrated an improvement in relative latency from 2.3 msec at 3 months to 0.34 msec at 5 months in animals continuing to receive intermittent immunosuppression, but only improved to 1.29 msec at 5 months when immunosuppression was discontinued. Nerve allografts continuing to receive intermittent immunosuppression showed no signs of rejection by light or electron microscopy and no significant difference compared with isografts, whereas nerve allografts whose immunosuppression had been stopped at 3 months showed mild signs of rejection, less regeneration, and a smaller number of nerve fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

[Preoperative patient education in plastic surgery]. / Das präoperative Aufklärungasgespräch in der Plastischen Chirurgie.

Federal guidelines requires written informed consent for each operation. The patient has to be informed about important facts concerning the treatment. The specific risks always have to be mentioned in detail. If the patient is not able to agree expressly because of his serious injury, he can be treated without express consent. The extent of the preoperative information depends on the indication: the more urgent the treatment, the less detailed the amount of information and vice versa.

[Ultrasound morphology of the healthy and diseased hand]. / Die Sonomorphologie der gesunden und der kranken Hand.

Ultrasonography of the hand is rarely applied, so normal and pathological findings remain unfamiliar to daily routine. Although all anatomical structures can be identified by this method, the median and ulnar nerves may be difficult to demonstrate, so they are often identified only by exclusion. Ultrasound is a non-invasive method and very helpful in diagnosing pathological changes, such as ganglions and other tumors, synovialitis, carpal tunnel syndrome, tendon injuries, and anatomical malformations.

[Abductor digiti minimi-plasty: a local muscle flap for treatment of calcaneus fractures with limited soft tissue injuries]. / Die Abductor digiti minimi-Plastik: Ein lokaler Muskellappen zur Behandlung von Fersenbeinbrüchen mit begrenztem Weichteilschaden.

Wound healing complications and osteitis following calcaneus fractures are common problems due to compromised local soft-tissue perfusion. Transposition of the M. abductor digiti minimi was successfully performed in 12 cases. The problem of soft tissue coverage could be solved by this procedure. Up to now, no negative influence on the myo-osseous architecture of the feet could be observed.

[Preventing blood transfusion in a severely burned Jehovah's witness]. / Einsparung von Fremdblutgaben bei schwerbrandverletzten Zeugen Jehovas.

The treatment rationale of a burn victim (35% TBSA) who was child of Jehova's witnesses is described. Following a combined approach including erythropoetin and blood saving surgical techniques we were able to excise and graft the burn areas without blood transfusion. An extremely low hemoglobin of 3.4 g/dl was tolerated postoperatively and showed an increase to 10.9 g/dl 25 days later when the child was dismissed from the burn unit in stable condition. Possibilities to minimize blood loss and to avoid blood transfusions are discussed.

[Assessment of central nervous system functional disorders in severely burned patients by auditory evoked brain stem potentials]. / Erfassung zentralnervöser Funktionsstörungen bei Schwerbrandverletzten mittels akutsich evozierter Hirnstammpotentiale.

The recording of brainstem auditory evoked potentials (BAEP) in severely burned patients can be used for judgement of brainstem function independent of consciousness and CNS-effective drugs. The frequency of central-nervous system complications due to burn injuries is between 7 and 30%. Using BAEP-recordings, we found objective neurophysiological parameters of central-nervous dysfunction in 12 of 25 severely burned patients (48%). Specific BAEP-parameters for burn injuries could not be detected. Specifically, very different time courses of BAEP-changes were found. In two patients, who died after severe burn injury, typical neurophysiological patterns of progressive cerebral pressure were observed. The measurement of BAEP is a useful diagnostic tool in detecting central-nervous dysfunction after burn injuries, especially for monitoring in non-cooperative patients.