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.     

Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy

Human Molecular     

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.     

Personality variables as moderators between hassles and subjective indications of distress

The research was designed to investigate the moderating effect of some personality traits on subjective distress caused by daily hassles. The traits were internal locus of control, repression, ego strength, and barrier (as studied and defined by S. Fisher). The last two variables were negatively correlated both with the somatic and emotional distress indications and with the frequency of hassles reportED; internal locus of control showed an inverse relationship only with frequency of hassles. The hypothesis is formulated that ego strength and barrier are personality factors influencing not only the outcomes of coping (ie the stress response), but also event appraisal.     

Type 2 diabetes: assessment of endothelial lesion and fibrinolytic system markers.

This study aimed to investigate whether endothelial cells are damaged and to evaluate fibrinolytic system function in patients with type 2 diabetes. For this proposal, plasma levels of von Willebrand factor (an endothelial marker of injury), homocysteine (an inductor of endothelial injury), D-dimer (a marker of coagulation cascade activation) and plasminogen activator inhibitor-1 (a fibrinolysis marker) were measured in individuals with both type 2 diabetes and high blood pressure, with type 2 diabetes, with high blood pressure and in healthy control individuals. No significant differences among groups were observed for von Willebrand factor and homocysteine plasma levels. The type 2 diabetes and high blood pressure group presented a significant difference to the other groups for D-dimer and also presented high values for plasminogen activator inhibitor-1. The high blood pressure group and type 2 diabetes group presented separately higher values of plasminogen activator inhibitor-1 compared with the control group. High levels of D-dimer and plasminogen activator inhibitor-1 in patients with type 2 diabetes and high blood pressure with normoalbuminuria therefore indicate a state of hypercoagulability and hypofibrinolysis, despite no evident microvascular injury supported by normal levels of von Willebrand factor and homocysteine.     

Incontinence pad use in patients admitted to medical wards: an Italian multicenter prospective cohort study.

PURPOSE: The purpose of the study was to evaluate the incidence of incontinence pad use among patients admitted to medical wards, the reasons why nurses decide to use an incontinence pad, the extent to which the use of pads is avoidable, and the outcome of inappropriate pad use after discharge from the hospital. METHODS: A prospective cohort study was conducted; patients admitted to medical wards were observed during hospitalization and a 7-day follow-up period after discharge. SUBJECTS AND SETTING: The study was conducted in 2 acute-care units in Northern Italy. All new patients admitted to the units were recruited. RESULTS: At the time of admission to the hospital, in addition to the 120 patients who already used incontinence pads, there was a 34% incidence of new cases (98/286). The most frequent reason why nurses decided to use this aid was incontinence caused by space-time disorientation, followed by limited mobility, incontinence, patient request, nursing shortage, and involuntary urine leakage not perceived by patient. Seventy patients out of 208 used incontinence pads unnecessarily for a total of 544 days. CONCLUSIONS: Decisions about the use of the incontinence pads are not always consistent with research-based or literature-based suggestions. Nurses should develop clinical guidelines or protocols for the appropriate use of incontinence pads.     

Superior vena cava syndrome and syncope in an implantable cardioverter defibrillator recipient.

We describe the case of a recipient of an implantable cardioverter defibrillator with multiple syncopal episodes due both to superior vena cava obstruction and electrical instability. These complications occurred in the presence of two transvenous implantable cardioverter defibrillator leads. The patient has been managed conservatively with anticoagulants and new antiarrhythmic drugs with improvement in both his clinical problems.     

Lymphocyte subpopulations in middle ear effusions: flow cytometry analysis.

OBJECTIVE: The aim of this study was to identify lymphocyte subpopulations in middle ear effusions, peripheral blood, and adenoids in children suffering from otitis media with effusion. SETTING: Tertiary referral center. PATIENTS: Thirty-three children (55 ears) undergoing myringotomy for otitis media with effusion. METHODS: CD3, CD4, CD8, CD19, and natural killer cell populations were investigated in middle ear effusion, peripheral blood, and adenoids using a three-color monoclonal antibody and flow cytometry method for quantitative estimation. RESULTS: T cells (CD3) are dominating lymphocytes in middle ear effusion. Among T lymphocytes, the majority are those of the helper type (CD4). The dominating isoform among CD4 lymphocytes are memory cells (CD4CD45RO); among CD8 lymphocytes, naive cells (CD8CD45RA). The percentage of CD4 cells, CD8 cells, and the CD4/CD8 ratio was significantly higher in middle ear effusions than in blood. The percentage of memory CD4 lymphocytes and naive CD8 lymphocytes was significantly lower in the middle ear effusion. Lymphocyte subsets were compared between 22 pairs of effusions from each patient. The percentage of each type of cell did not differ significantly. CONCLUSION: The results of this study indicate local regulation of the lymphocyte profile in middle ear effusions and the same phase of immune response in two ears of the same patient.     

Mechanisms of opioid-induced tolerance and hyperalgesia.

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be unrelated to the original nociceptive stimulus. Complex intracellular neural mechanisms, including opioid receptor desensitization and down-regulation, are believed to be major mechanisms underlying opioid tolerance. Pain facilitatory mechanisms in the central nervous system are known to contribute to opioid-induced hyperalgesia. Recent research indicates that there may be overlap in the two conditions. This article reviews known and hypothesized pathophysiologic mechanisms surrounding these phenomena and the clinical implications for pain management nurses.