Dolichol content in isolated sinusoidal liver cells after in vivo chronic treatment with thioacetamide.

The content of dolichol, an isoprenoid present in all biological membranes, was determined in isolated sinusoidal liver cells after treatment of rats for 2 and 4 months with a low dosage of the hepatotoxin thioacetamide. The significant decrease in dolichol observed in hepatocytes after 2 months might be explained by peroxidation of the isoprenoid. At the same time point, retinol was retained, and decreased only after 4 months of treatment. After 4 months of treatment therefore both lipids decreased. In a subfraction of hepatic stellate cells, Ito-1 cells, the main storage site of vitamin A, dolichol decreased significantly only after 4 months. A remarkable difference from hepatocytes is that in Ito-1 cells retinol content significantly decreased after 2 months of treatment. In another subfraction, Ito-2 cells, the content of the two isoprenoids decreased in parallel. This heterogeneous subfraction might represent those transitional hepatic stellate cells that, while losing retinol, are in the process of differentiating into myofibroblasts secreting extracellular matrix components. In Kupffer cells and sinusoidal endothelial cells, impairment of dolichol might be observed later, only after 4 months of treatment, while retinol decreases uniformly over time. Starting after two months of treatment, the decrease of dolichol and the increase of retinol in hepatocytes, at the same time as retinol decreases in hepatic stellate cells, might be taken as an early index of incipient liver injury due to thioacetamide. This hypothesis is discussed with regard to a role of dolichol in the modulation of membrane fluidity for intracellular and intercellular retinol transport.     

Liver transplantation for erythropoietic protoporphyria liver disease.

In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin, primarily in the bone marrow, resulting in increased biliary excretion of this heme precursor. Some patients will develop progressive liver disease that may ultimately require liver transplantation. However, excessive production of protoporphyrin by the bone marrow continues after transplantation, which may cause recurrent disease in the allograft. This study was performed to define post-transplant survival, the risk of recurrent disease, and specific management issues in patients transplanted for EPP liver disease. The patients studied consisted of twelve males and eight females, with an average age of 31 (range, 13-56) years at the time of transplantation. The estimated maximum MELD score prior to transplant was 21 (range, 15-29). Unique complications in the perioperative period were light induced tissue damage in four patients and neuropathy in six, requiring prolonged mechanical ventilation in four. Patient and graft survival rates were 85% at 1 year, 69% at 5 years, and 47% at 10 years. Recurrent EPP liver disease occurred in 11 of 17 patients (65%) who survived more than 2 months. Three patients were retransplanted at 1.8, 12.6, and 14.5 years after the initial transplant for recurrent EPP liver disease. In conclusion, the 5-year patient survival rate in patients transplanted for EPP liver disease is good, but the recurrence of EPP liver disease appears to diminish long term graft and patient survival.     

Hypoosmolare Hyponatri?mie als Leitsymptom bei Hypothyreose

Zusammenfassung Anamnese und Diagnostik: Ein 75-jähriger Patient wies neben unspezifischen anamnestischen Symptomen (Appetitverlust, Merkfähigkeitsstörung und Muskelschwäche) klinisch diskrete Beinödeme, abgeschwächte Muskeleigenreflexe und eine deutliche Gedächtnisstörung auf. Aufgrund einer euvolämischen, laborchemisch hypoosmolaren Hypoatriämie und eines Urinnatriums im Normbereich wurde als Arbeitsdiagnose von einem Syndrom der inadäquaten ADH-Sekretion (SIADH) ausgegangen. Während sich weder in der Anamnese noch in den folgenden Untersuchungen eine dem SIADH zugrunde liegende Pathologie eruieren ließ, ergab sich in den weiteren Laboruntersuchungen der Befund einer ausgeprägten Hypothyreose. Die Hyponatriämie bei Hypothyreose spiegelt eine Komponente der renalen Funktionsstörung bei Schilddrüsenhormonmangel wider. Therapie und Verlauf: Nach Flüssigkeitsrestriktion und Hormonsubstitution erreichte der Patient schnell normale Natriumwerte und zeigte eine deutliche Besserung seiner kognitiven Fähigkeiten. Schlussfolgerung: Als Schlussfolgerung aus dieser Kasuistik wird Zurückhaltung bei der Diagnose eines SIADH empfohlen, bevor nicht eine sorgfältige Untersuchung des Nebennieren- und Schilddrüsenhormonstatus erfolgt ist. Abstract Case History and Diagnosis: A 75-year-old male patient presented with a history of anorexia, muscle weakness, and increasing memory loss. He had mild pedal edema and decreased deep tendon reflexes. As the laboratory tests showed hypoosmolar hyponatremia and urinary sodium within the normal range, a syndrome of inappropriate ADH secretion (SIADH) was presumed. While neither the medical history nor any of the diagnostic procedures revealed any underlying pathology explaining the SIADH, laboratory tests showed significant hypothyroidism. Hypothyroid states are associated with significant changes in renal function, one of which is hypoosmolar hyponatremia. Treatment and Course: Treatment included fluid restriction and hormone substitution and resulted in a quick correction of the hyponatremia and a clear improvement of the patient's cognitive function. Conclusion: It is concluded that the diagnosis of SIADH should only be made after thorough investigation of the adrenal and thyroid hormone status.     

Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study.

OBJECTIVE: To investigate the association between the use of fluoroquinolone agents and the risk of tendinitis in a large population-based case-control study. METHODS: The study was performed by linking automated health databases from the Region of Lombardia, Italy. Cases were patients aged > or =18 years who had a hospital discharge diagnosis of non-traumatic tendinitis in 2002-3. For each case, up to five controls were randomly selected among those eligible for inclusion in the study. A conditional logistic regression model was used to estimate the odds ratio of tendinitis associated with the current, recent and past use of fluoroquinolones. Odds ratios were adjusted for exposure to other antibacterials and other drugs. RESULTS: 22,194 cases and 104,906 controls met the inclusion criteria. Current use of fluoroquinolones significantly increased the risk of tendon disorders as a whole (odds ratio [OR] = 1.7; 95% CI 1.4, 2.0), tendon rupture (OR = 1.3; 95% CI 1.0, 1.8) and rupture of the Achilles' tendon (OR = 4.1; 95% CI 1.8, 9.6). Concomitant use of corticosteroids and fluoroquinolones increased the risk of both tendon rupture (OR = 3.1; 95% CI 1.5, 6.3) and rupture of the Achilles' tendon (OR = 43.2; 95% CI 5.5, 341.1). DISCUSSION: Evidence that exposure to fluoroquinolones is associated with the sudden occurrence of tendinitis is supported by this large population-based study. We can estimate that a single case of rupture of the Achilles' tendon would occur for every 5958 persons treated with fluoroquinolones (95% CI 2148, 23,085). The corresponding number needed to harm is 979 (95% CI 122, 9172) for patients who concomitantly use corticosteroids and 1638 (95% CI 351, 8843) for those aged >60 years. CONCLUSION: Clinicians should be aware of this adverse effect, and the increased risk for fluoroquinolone-associated tendinitis in elderly patients with corticosteroid use must be considered when these agents are prescribed.     

Poly(2,6-Dimethyl-1,4-Phenylene oxide)/crosslinked polystyrene semi-interpenetrating networks: Synthesis and properties

Semi-interpenetrating networks (semi-IPN's) based on linear poly(phenylene ether)s and crosslinked polystyrene can be prepared by reactive moulding of crosslinkable polymeric mixtures. These materials show thermomechanical properties which strongly depend on both the ratio of the two polymeric matrices and the degree of crosslinking in the polystyrene network. Samples based on a 50/50 weight ratio of poly(2,6-dimethyl-1,4-phenylene oxide)/crosslinked polystyrene show glass transition temperatures (T_g) which are very dependent on the degree of crosslinking. It is therefore possible to obtain materials with desired T_g, ranging from the T_g of the corresponding linear blend to that of poly(2,6-dimethyl-1,4-phenylene oxide) alone.     

Habitual physical activity and estradiol levels in women of reproductive age.

Variation in the risk of breast cancer observed among women and among populations may be explained by variation in lifetime exposure to estrogens. The suppressive effect of exercise on estradiol levels in women is well documented, but it is unknown whether habitual (i.e. typical daily) physical activity has a similar effect. Epidemiological data suggest that physical activity is one of the few modifiable factors capable of reducing the risk of breast cancer in women. We investigated whether variation in the amount of habitual activity corresponds to variation in estradiol levels in women of reproductive age. One hundred and thirty-nine regularly menstruating women 24-37 years of age collected daily saliva samples for one complete menstrual cycle and kept a daily log of physical activity. Saliva samples were analyzed for concentration of estradiol. We observed a negative relationship between habitual physical activity and salivary levels of estradiol. Mean estradiol was 21.1 pmol/l in the low, 17.9 pmol/l in the moderate and 16.6 pmol/l in the high activity group (all pairwise differences were statistically significant at P<0.009). A strong association exists between physical activity and levels of estradiol among women of reproductive age. A modern lifestyle, characterized by reduced physical activity, may therefore contribute to a rise in the levels of estradiol produced during menstrual cycles and thus to higher cumulative lifetime exposure to estradiol, resulting in a higher risk of breast cancer.     

Knee-ankle-foot orthosis in children with duchenne muscular dystrophy: user views and adjustment.

BACKGROUND: The use of knee ankle foot orthoses (KAFOs) to prolong independent mobility is a widely used rehabilitation strategy for children with Duchenne muscular dystrophy (DMD). AIMS: To explore views and adjustment of families with a child with Duchenne muscular dystrophy to the use of KAFOs. METHODS: interviews with families of children aged 8-18 years with DMD; questionnaires on psychiatric adjustment (SDQ for children; GHQ for parents). RESULTS: In total, 17 parents and 9 children took part. Families experienced the introduction of KAFOs as a signal for illness deterioration and a re-awakening of the feelings experienced at diagnosis. Nevertheless, the majority expressed a positive attitude and over two-thirds satisfaction with KAFOs use. High psychiatric risk was found in 2/17 children (12%; expected 10%) and 7/17 main carers (41%; expected 20-30%). CONCLUSION: Most families were satisfied with KAFOs use, and its implementation was well tolerated especially by the children. However, mental distress was high in main carers who emphasized the importance of full preparation and support in this rehabilitation technique.