Freier Paraskapular-/Skapularlappen bei frakturbegleitendem Weichteildefekt an Talus oder Kalkaneus

BASIS: Fractures of the talus or calcaneus with accompanying soft tissue damage require precisely planned treatment to prevent infection of the wound over time, especially in severely injured patients. MATERIAL AND METHODS: Seven patients with fractures of the talus or calcaneus and accompanying 2nd and 3rd degree open or 3rd degree closed soft tissue injuries were followed up retrospectively. These patients were operated on between January 1999 and January 2006 with free fasciocutaneous scapular or parascapular flaps. The average age was 34 (range 16-54). Follow-up was at 6-36 months. RESULTS: Osteosynthesis was primarily in six cases, post-primarily in one, and in four cases exterior fixation was used additively. Temporary vacuum therapy was performed for a mean of 28 days (6-42). Parascapular, scapular, and Latissimus dorsi flap coverage was performed six, one, and one times, respectively. Six flaps healed without complication. One necrosis of a parascapular flap occurred and made a Latissimus dorsi flap necessary. In one case of donor-site wound dehiscense, a local rotation flap became necessary. There was no joint infection or osteomyelitis. Bony consolidation was achieved within all fractures. CONCLUSION: Traumatic soft tissue damage must be taken into account when primary or secondary internal fixation is performed and should influence the choice of implant. Free fasciocutaneous parascapular or scapular flaps are a powerful tool for preventing infection if local flaps are not sufficient to achieve stable soft tissue coverage.     

Mitogenic effects of thyrotropin and adenosine 3',5'-monophosphate in differentiated normal human thyroid cells in vitro

Previous studies of human thyroid cells in culture (mostly from pathological tissues) failed to demonstrate a mitogenic effect of TSH, leading to the proposal that the growth effect of TSH in vivo might be indirect. To reexamine the influence of TSH on DNA synthesis and cell proliferation, we established primary cultures of normal thyroid tissue from nine subjects. When seeded in a 1% serum-supplemented medium, thyroid follicles released by collagenase/dispase digestion developed as a cell monolayer that responded to TSH by rounding up and by cytoplasmic retraction. When seeded in serum-free medium, the cells remained associated in dense aggregates surrounded by few slowly spreading cells. In the latter condition, the cells responded to TSH and other stimulators of cAMP production, such as cholera toxin and forskolin, by displaying very high iodide-trapping levels. Exposure to serum irreversibly abolished this differentiated function. TSH stimulated the proliferation (as shown by DNA content per culture dish) of 1% serum cultured cells (doubling times were reduced from 106 to 76 h) and increased by 100% the [3H]thymidine labeling indices. In serum-free cultured cells (dense aggregates or cell monolayers after initial seeding with serum), control levels of DNA synthesis were lower, and up to 8-fold stimulation of DNA synthesis occurred in response to 100 mU/L TSH (stimulation was consistently detected with 20 mU/L), based on measurements of [3H]thymidine incorporation into acid-precipitable material and counts of labeled nuclei on autoradiographs (up to 40% labeled nuclei within 24 h). The mitogenic effect of TSH required a high insulin concentration (8.3 X 10(-7) mol/L) or a low insulin-like growth factor I concentration. The mitogenic effects of TSH were mimicked in part by cholera toxin, forskolin, and dibutyryl cAMP. Epidermal growth factor and phorbol myristate ester also stimulated thyroid cell proliferation and DNA synthesis, but they potently inhibited TSH-stimulated iodide transport. We conclude that TSH, acting at least in part through cAMP, is a potent growth factor for human thyroid cells and thus provide an experimental basis in vitro for the well established in vivo goitrogenic action of TSH.     

Prospective evaluation of endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis in 45 patients with normal conventional ultrasonography.

The aim of this study was to prospectively evaluate endoscopic ultrasonography and microscopic examination of duodenal bile in the diagnosis of cholecystolithiasis not detected by conventional ultrasonography. Forty five consecutive patients (26 females, 19 males, mean age: 50 years) with suspected cholecystolithiasis and at least two normal transcutaneous ultrasonography examinations were included. Endoscopic ultrasonographic criteria for the diagnosis of cholecystolithiasis were the presence of stones with or without acoustic shadowing or sludge. Criteria of microscopic examination of bile were cholesterol or bilirubinate crystals or spheroliths. Thirty three patients underwent cholecystectomy and lithiasis was found in gall bladder bile in 24. Twelve patients who were not operated on and were followed up (median: 17 months), had no evidence of cholecystolithiasis. Endoscopic ultrasonography and duodenal bile examination were 96% and 67% sensitive, respectively (p < 0.03). The specificity was not different (86 and 91%, respectively). None of the 16 patients with negative results in both procedures had evidence of cholecystolithiasis. It was found that for the diagnosis of cholecystolithiasis in patients with normal conventional ultrasonography, the sensitivity of endoscopic ultrasonography is higher than that of microscopic examination of duodenal bile. If endoscopic ultrasonography and microscopic examination of duodenal bile are negative, the risk of underdiagnosing cholecystolithiasis is negligible.     

Acute response of the arterial wall to pulsed laser irradiation

This study was designed to examine the acute response of normal arterial wall to pulsed laser irradiation. Irradiation with an Excimer or a Holmium YAG laser was performed in 15 normal iliac sites of 8 male New Zealand white rabbits. The excimer laser was operated at 308 nm, 25 Hz, 50 mj/mm²/pulse, and 135 nsec/pulse and the Ho:YAG laser was operated at 2.1 μm, 3.5 Hz, 400 mj/ pulse, 250 μsec/pulse. The excimer and Ho:YAG laser were coupled into a multifiber wire-guided catheter of 1.4 and 1.5 mm diameter, respectively. The mean luminal diameter increased similarly from 2.01 ± 0.29 to 2.46 ± 0.27 mm (P < 0.0005) and from 2.09 ± 0.53 to 2.45 ± 0.30 mm (P < 0.005) after excimer and Ho:YAG laser irradiation, respectively. Perforation occurred in 3 of 15 Ho:YAG irradiated sites and 0 of 15 excimer laser irradiated sites. The sites irradiated with excimer or Ho:YAG laser had similar histologic features, consisting of shedding of the endothelium, disorganization of internal elastic lamina, localized necrosis of vascular smooth muscle cells, and fissures in the medial layer. However, the sites irradiated with excimer laser had lower grading scores than those irradiated with the Ho:YAG laser (P<0.05). Irradiation with excimer or Ho:YAG laser of normal arteries results in: (1) vasodilation of the irradiated artery; (2) localized mechanical vascular injury, and (3) Ho:YAG laser induces more severe damage to the arterial wall than excimer. © 1993 Wiley-Liss, Inc.     

Nucleoside analogues: 8. Some isomers of B.3839, the original 5-fluorouracil/nitrosourea molecular combination, and their effect on colon, breast and lung tumours in mice

This study describes the manipulation of secondary products arising from the synthesis of the prototypical molecular combination of 5-fluorouracil (5-FU) and chloroethylnitrosourea (CNU), B.3839, in order to investigate the effects produced by connecting the C-S-C-C-CNU chain to the 5-FU ring in different ways. The isolation of phthalimide precursors of these compounds and the transformation into CNUs is described. Anti-tumour activity of these molecular combinations against a series of experimental murine colon, lung and mammary tumours is presented. The spectrum of anti-tumour activity displayed is interesting but defies simple explanation without further detailed in vivo pharmacokinetic and metabolism studies in order to define optimal profiles for activity.     

Selective Effect of Adjuvant Arthritis on the Disposition of Propranolol Enantiomers in Rats Detected Using a Stereospecific HPLC Assay

Nonstereospecific studies have indicated that the pharmacokinetics of propranolol (PR) are altered in inflammatory conditions such as arthritis. However, as the kinetics and dynamics of PR are stereoselective, we examined the effect of adjuvant arthritis (AA) on the disposition of the individual enantiomers. A novel normal-phase stereospecific HPLC assay for PR was developed involving chiral derivatization with S-(naphthyl)ethyl isocyanate and fluorescence detection. Oral and iv doses of racemic PR were administered to control and AA rats (n = 6). AA had no significant effect on either clearance or S:R ratio after iv doses. On the other hand, after oral doses, clearance was significantly decreased in AA. Although significant for both enantiomers, this effect was more pronounced on the less active R-enantiomer. The AUC R:S ratio was, therefore, significantly altered (AA, 14 ± 3.0; control, 4.3 ± 1.2). Increased total (S + R) plasma concentrations of PR in AA, possibly due to a reduced intrinsic clearance, therefore, reflect mainly increased concentrations of the less active R-enantiomer.     

Analysis of the Inhibitory Effect of Oestradiol on Functional GABA/5-HT Relationship in the Rat Suprachiasmatic Area

The purpose of this study was to test the capacity of oestradiol to modulate the stimulating effect of a-aminobutyric acid (GABA) on serotonin (5-HT) metabolism, previously described in the Suprachiasmatic area of the male rat. After an in vivo stimulation of GABA transmission by systemic administration of a GABA-transaminase inhibitor (amino-oxyacetic acid) or a GABA_B agonist (RS-baclofen), the 5-HT metabolism was studied in the Suprachiasmatic area of ovariectomized, and ovariectomized oestradiol-treated rats. Amino-oxyacetic acid or RS-baclofen treatment increased the endogenous content of 5-HT in the Suprachiasmatic area of males and ovariectomized rats. These two treatments were without effect in ovariectomized oestradiol-treated rats. GABA transmission stimulation induced by amino-oxyacetic acid treatment failed to affect the release and synthesis of 5-HT in ovariectomized oestradiol-treated rats while it increased these two parameters of 5-HT metabolism in the Suprachiasmatic area of male and ovariectomized rats. To investigate the main target of oestradiol effect, comparative studies of the serotoninergic and GABAergic metabolism in the Suprachiasmatic area were performed in the three experimental groups. Under our experimental conditions the endogenous 5-HT metabolism was similar between ovariectomized and ovariectomized oestradiol-treated rats. Nevertheless, 5-HT metabolism was higher in the two female groups than in the male group. Neither GABA metabolism nor GABAergic response to GABA-related drug treatment differed between ovariectomized, and ovariectomized oestradiol-treated rats. However, the turnover of GABA was higher when compared to the two female groups. It is concluded that the lack of 5-HT responsiveness to GABA transmission stimulation in ovariectomized oestradiol-treated rats was not related to an effect of oestradiol on 5-HT metabolism or to an effect of the steroid on GABA turnover. Furthermore, our results suggest a sex difference in the activity of serotoninergic and GABAergic systems in the Suprachiasmatic area.