The value of serial determination of MEGX and hyaluronic acid early after orthotopic liver transplantation

Abstract. Post-transplant assessment of early graft function has become an essential part of monitoring, especially when deciding on retransplantation. If primary non-function is indicated, retransplantation is inevitable; early graft dysfunction may be related to subsequent complications. In a prospective study in 84 patients after orthotopic liver transplantation (OLT) we measured aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), bilirubin (BIL), prothrombin time, MEGX formation, hyaluronic acid (HA) and soluble interleukin-2 receptor (sIL-2R) concentrations during the first 2 postoperative weeks; graft outcome was followed over 4 months. The aim of this study was to determine whether graft survival could be predicted by such variables early after OLT. Compared with patients with stable graft function (n= 25), patients with post-transplant icteric cholestasis (n= 30) exhibited no difference in graft survival, despite a decrease in MEGX formation to a nadir median of 12 μgL^-1 on day 10. Patients with rejection (n= 8) and septicaemia (n= 6) showed a marked decrease in MEGX values and an increase in HA and sIL-2R concentrations between postoperative days 3 and 7. Patients with primary non-function (PNF; n= 5) were characterized by strongly reduced MEGX formation (median 4 μgL) and increased HA values (median 2300 μgL^-1) on day 3 after OLT. A total of 24/84 grafts were lost within 120 days. In a survival analysis using the Cox proportional hazards regression, HA and MEGX values on day 1 were the only independent variables entering the model that showed an adequate prognostic sensitivity. At cut-off points of 22 μgL^-1 (MEGX) and 730 μgL^-1 (HA) the combined use of these parameters in a parallel approach yielded a sensitivity of 58% with a corresponding specificity of 95% for 120-day graft survival. These findings suggest that the inclusion of MEGX and HA in postoperative monitoring of OLT patients may be helpful in the early prediction of graft survival.     

Acute renal embolism. Forty-four cases of renal infarction in patients with atrial fibrillation

Acute renal embolus is rarely reported in the medical literature; thus, accurate data regarding presentation, laboratory tests, diagnostic techniques, and treatment are lacking. To better define this condition, we examined the medical records of all patients admitted to Kaplan Medical Center and Sheba Medical Center in central Israel from 1984 to 2002 who had a diagnosis of renal infarction and atrial fibrillation. We noted demographic, clinical, and laboratory parameters; method of diagnosis; treatment received; and patient outcome. We identified 44 cases of renal embolus: 23 females and 21 males, with an average age of 69.5 +/- 12.6 years. Thirty (68%) patients had abdominal pain, and 6 (14%) had a previous embolic event. Nine patients were being treated with warfarin on admission, 6 (66%) of whom had an international normalized ratio (INR) < 1.8. Hematuria was present in 21/39 (54%), and 41 (93%) patients had a serum lactate dehydrogenase (LDH) level > 400 U/dL. The mean LDH was 1100 +/- 985 U/dL. Diagnostic techniques included renal isotope scan, which was abnormal in 36/37 cases (97%); contrast-enhanced computed tomography (CT) scan, which was diagnostic in 12/15 cases (80%); and ultrasound, which was positive in only 3/27 cases (11%). Angiography was positive in 10/10 cases (100%). Twenty-three (61%) of 38 patients had normal renal function on follow-up. The 30-day mortality was 11.4%. Renal embolus was diagnosed mainly in patients aged more than 60 years, some of whom had a previous embolic event. Most of those receiving anticoagulant therapy had a subtherapeutic INR. Abdominal pain was common, as well as hematuria and an elevated LDH. These patients are at risk of subsequent embolic events to other organs. The most sensitive diagnostic technique in this population is a renal isotope scan, but contrast-enhanced CT scan requires further assessment.     

Arrhythmias associated with intermittent outpatient dobutamine infusion

The use of intermittent outpatient dobutamine infusion has recently been studied as an alternative therapy modality for patients with refractory congestive heart failure. We studied the arrhythmogenic effects of intermittent outpatient dobutamine infusion in two patients with NYHA class IV heart failure. The patients received dobutamine at 5mcg./kg./min. for four hours per day for an eight week period. Ambulatory Holter monitoring was obtained during the infusion periods and compared to infusion-free periods. A significant increase of complex ventricular arrhythmias, including multifocal PVC's and ventricular tachycardias, was observed during the infusion period. The incidence of complex ventricular ectopy was dose related and could be suppressed to baseline levels with appropriate antiarrhythmic therapy. We concluded that dobutamine is extremely arrhythmogenic when used in patients with heart failure and that this effect was controllable with antiarrhythmics. Extreme caution and careful monitoring is required for this new therapeutic modality in the treatment of refractory heart failure.     

Genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever

OBJECTIVE: To study genotype-phenotype correlation for the 4 most common genotypes found among patients with familial Mediterranean fever (FMF). METHODS: Thirty patients with the M694V/M694V genotype, 32 with M694V/V726A genotype, 25 with M694V/E 148Q genotype, and 21 with V726A/V726A genotype were assessed for various clinical manifestations of FMF, and overall disease severity. RESULTS: Patients with the M694V/M694V genotype were found to have an earlier age of onset, higher frequency of joint involvement, higher frequency of erysipelas-like erythema, and required higher doses of colchicine to control the disease compared to the other 3 genotypes. CONCLUSION: The M694V/M694V genotype is associated with more severe disease compared to other common genotypes in patients with FMF.     

Fluorescence lifetime snapshots reveal two rapidly reversible mechanisms of photoprotection in live cells of Chlamydomonas reinhardtii

Photosynthetic organisms avoid photodamage to photosystem II (PSII) in variable light conditions via a suite of photoprotective mechanisms called nonphotochemical quenching (NPQ), in which excess absorbed light is dissipated harmlessly. To quantify the contributions of different quenching mechanisms to NPQ, we have devised a technique to measure the changes in chlorophyll fluorescence lifetime as photosynthetic organisms adapt to varying light conditions. We applied this technique to measure the fluorescence lifetimes responsible for the predominant, rapidly reversible component of NPQ, qE, in living cells of Chlamydomonas reinhardtii. Application of high light to dark-adapted cells of C. reinhardtii led to an increase in the amplitudes of 65 ps and 305 ps chlorophyll fluorescence lifetime components that was reversed after the high light was turned off. Removal of the pH gradient across the thylakoid membrane linked the changes in the amplitudes of the two components to qE quenching. The rise times of the amplitudes of the two components were significantly different, suggesting that the changes are due to two different qE mechanisms. We tentatively suggest that the changes in the 65 ps component are due to charge-transfer quenching in the minor light-harvesting complexes and that the changes in the 305 ps component are due to aggregated light-harvesting complex II trimers that have detached from PSII. We anticipate that this technique will be useful for resolving the various mechanisms of NPQ and for quantifying the timescales associated with these mechanisms.     

Cholesterol crystal embolization to the digestive system: characterization of a common,yet overlooked presentation of atheroembolism

In the 1359 published patients with multiorgan cholesterol crystal embolism (CCE), the digestive system seems to be the third most frequently affected system. Yet, this system received hitherto only little attention in the medical literature. Therefore, the aim of the present study was to clinically characterize the subset of patients with CCE involving the digestive system, based on our institutional experience and a review of the literature. Cases with CCE in a 7-yr period (1995-2001) were sought in the computerized records of our medical center. Of the CCE patients, those with digestive system involvement that could be related to CCE were included in this study. The clinical features of CCE were determined and compared with those found in published series. Fourteen cases with CCE were identified, giving an annual incidence of 0.8 per 10(5). Digestive system involvement was found in five (36%) of the 14 patients. All five patients had established atherosclerosis. Precipitating factors were vascular manipulations or anticoagulation treatment in four of these five patients. Two patterns of disease appeared: acute catastrophic multiorgan disorder with poor prognosis and chronic and more indolent GI disease. Abdominal pain, GI bleeding, fever, and diarrhea were the most common manifestations, resulting from bowel infarction, mucosal ulcerations, hepatocellular liver disorder, and/or pancreatitis. CCE is a systemic disorder with a frequent involvement of the digestive system and protean clinical manifestations. It should, therefore, be considered in any gastroenterological patient with atherosclerosis and recent vascular manipulations or systemic anticoagulation.