Respiratory muscle dysfunction in facioscapulohumeral muscular dystrophy

Sleep and Breathing -     

Effect of the menstrual cycle and oral contraceptives on aromatase and cyclooxygenase-2 expression in adenomyosis.

OBJECTIVES: To determine whether aromatase expression in the eutopic endometrium and adenomyotic foci is affected by previous use of oral contraceptives containing gestodene, and to determine whether changes in cyclooxygenase-2 (COX-2) expression occur in adenomyosis during the menstrual cycle. PATIENT AND METHODS: This was a retrospective cohort study carried out in paraffin-embedded endometrial tissue obtained from patients with a histological diagnosis of adenomyosis obtained during the proliferative (n = 25) and luteal (n = 10) phases of the menstrual cycle and following the use of continuous oral contraception with gestodene/ethinyl estradiol (n = 7). COX-2 and aromatase expression were measured in both eutopic endometrium and adenomyotic foci using immunohistochemical methods. RESULTS: Aromatase expression was detected in 80% of the endometrial slices by immunohistochemistry. In positive cases, aromatase was mainly detected in the stromal cells of the eutopic endometrium, whereas in the adenomyotic foci this expression was negative in the majority of the cases. Oral contraceptives containing gestodene, on the other hand, were effective in suppressing aromatase expression in both eutopic and ectopic endometrium. COX-2 expression was detected by immunohistochemistry in the glandular epithelium of both eutopic endometrium and adenomyotic foci and there were no significant changes in its intensity throughout the menstrual cycle. CONCLUSION: Aromatase expression in the eutopic endometrium and adenomyotic foci is suppressed by oral contraceptives containing gestodene. Increased aromatase activity may be responsible for the persistent COX-2 expression during the luteal phase.     

Evaluation of bone height and bone density after tooth extraction: an experimental study in minipigs.

OBJECTIVE: The objective of this study was to radiographically quantify bone density and bone height preservation in tooth extraction alveolus filled with xenograft. STUDY DESIGN: The maxillary and mandibular fourth deciduous molars and fourth premolars of 6 minipigs were removed. Randomly, in 3 animals the right side was used as the test side and in the other 3 animals the left side was the test side. Intraoral radiographs were performed to compare the condition at the initial time and 3 months later. Measurements of bone height and bone density were performed using KS300 (Zeiss) software. RESULTS: After 3 months, there was a statistically significant smaller bone height loss for the test group. The test group presented a statistically greater bone density immediately after tooth extraction. However, after 3 months there was no statistically significant difference between the groups. CONCLUSIONS: The results suggest that treatment of postextraction alveolus with xenograft can preserve bone height initially but differences in bone density compared to when no xenograft is used are not sustained.     

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.     

Liver regeneration in acute severe liver impairment: a clinicopathological correlation study.

BACKGROUND: Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injury. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired, hepatic progenitor cells (HPCs) are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells generate new hepatocytes and biliary cells to restore liver homeostasis. AIMS/METHODS: To study the relationship between different histopathological parameters as well as their correlations with clinical parameters and outcome, we examined liver specimens from 74 patients with acute or subacute severe liver impairment by immunohistochemistry for CK7/CK19 (evaluation of HPCs activation/differentiation), Mib1(Ki 67)/P21 (evaluation of proliferative activity/proliferation arrest of hepatocytes) and hematoxylin and eosin (evaluation of hepatocyte loss). RESULTS: Of the 74 patients, 32% survived without transplantation, 14% died without transplantation and 54% were transplanted. Our results show that a threshold of 50% loss of hepatocytes, associated with significant decrease in the proliferative activity of remaining mature hepatocytes, is needed for extensive hepatic progenitor cell activation. Such activation is a sign of disease severity and occurs early (within 1 week) in the disease course. However, development of intermediate hepatocytes, suggesting HPCs differentiation towards mature hepatocytes, takes at least 1 week's time. We found a positive correlation between histopathological parameters (percentage hepatocyte loss, number of proliferating hepatocytes and number of HPCs) and clinical parameters of liver impairment such as model for end stage liver diseases (MELD). Surviving patients compared with those who either died or were transplanted had significantly less hepatocyte loss, less HPCs activation and more mature hepatocyte proliferative activity. Hepatocyte proliferative activity and degree of hepatocyte loss were the most important independent histopathological parameters in predicting outcome. CONCLUSION: Liver biopsy can provide important additional information in a patient with severe acute liver impairment.     

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.