A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans

Slow, rhythmic oscillations (<5 Hz) in the sleep electroencephalogram may be a sign of synaptic plasticity occurring during sleep. The oscillations, referred to as slow-wave activity (SWA), reflect sleep need and sleep intensity. The amount of SWA is homeostatically regulated. It is enhanced after sleep loss and declines during sleep. Animal studies suggested that sleep need is genetically controlled, yet the physiological mechanisms remain unknown. Here we show in humans that a genetic variant of adenosine deaminase, which is associated with the reduced metabolism of adenosine to inosine, specifically enhances deep sleep and SWA during sleep. In contrast, a distinct polymorphism of the adenosine A(2A) receptor gene, which was associated with interindividual differences in anxiety symptoms after caffeine intake in healthy volunteers, affects the electroencephalogram during sleep and wakefulness in a non-state-specific manner. Our findings indicate a direct role of adenosine in human sleep homeostasis. Moreover, our data suggest that genetic variability in the adenosinergic system contributes to the interindividual variability in brain electrical activity during sleep and wakefulness.     

Non-invasive assessment of coronary flow reserve--valuable functional information in cardiac workflow

Coronary flow reserve (CFR) can be determined echocardiographically in the LAD in about 90% and in the RCA in more than 70% of patients, respectively, by the use of modern high-resolution ultrasound equipment. For this purpose either high frequency fundamental imaging or echo-contrast enhanced harmonic Doppler technology is used. The main advantage of the method lies in its noninvasiveness and the lack of radiation exposure. In combination with coronary morphologic findings obtained from heart catheterization, CFR is helpful in the planning of further invasive procedures for coronary artery disease and in the estimation of the prognosis of such procedures. The functional status after PTCA of LAD/RCA or mammary bypass surgery can be evaluated during follow-up monitoring. Alteration in the coronary microcirculation can also be discovered in a non-invasive manner; improvement of microcirculatory disorders by adequate therapy can be assessed by serial measurements of CFR     

The ratio of plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury in patients undergoing liver transplantation

Background

Postoperative acute kidney injury (AKI) is associated with high morbidity and mortality after liver transplantation (OLT). Previous studies have shown the value of plasma neutrophil gelatinase-associated lipocalin (NGAL) taken 2 hours after reperfusion of the liver graft as an early marker predicting AKI. The study was performed to determine whether plasma NGAL concentrations obtained as early as 1 hour after reperfusion was predictive of AKI and whether the NGAL ratio was an early predictor for AKI in the first 48 hours after OLT.

Methods

Twenty-six liver transplant recipients donated plasma samples for NGAL determinations at induction (T1), at graft reperfusion (T3) as well as after 1 (T4) and hours 2 (T5), and at the end of the surgery (T7). AKI was defined at 48 hours after liver transplantation according to the acute kidney injury network criteria. Predictive ability was assessed using areas under the curve of receiver operator characteristic analyses.

Results

The area under the curve of the receiver operator characteristics curve of (plasma NGAL concentration at T4)/(plasma NGAL concentration at T1) to predict AKI was 0.717 at T5, 0.765 at T7, 0.714 at T8 (24 hours post-OLT), and 0.781 at T9 (48 hours post-OLT).

Conclusion

The plasma NGAL concentrations taken 1 hour after reperfusion of the liver graft seem to be predictive of AKI; the NGAL changing ratio may be an early predictor for AKI in the first 48 hours after OLT.     

Cardiac output derived from arterial pressure waveform analysis: validation of the third-generation software in patients undergoing orthotopic liver transplantation

Background

The upgraded third-generation software (version 3.02) for the FloTrac/Vigileo system has been developed to particularly improve the accuracy of cardiac output (CO) measurements in hyperdynamic conditions. The aim of our study was to compare the CO values obtained using the FloTrac/Vigileo system during orthotopic liver transplantation (OLT) with those obtained in the same circumstances using a Swan-Ganz catheter (bolus thermodilution method).

Methods

Twenty consecutive recipients scheduled for OLT were studied. Simultaneous CO values measured by both devices were obtained at 10 predefined time points throughout the surgery. A percentage error of not more than 30% was established as the criterion for device interchangeability.

Results

A total of 200 paired measurements were obtained. The CO values derived from the FloTrac/Viligeo ranged from 2.8 to 10.9 L/min, with a mean of 5.91 ± 1.81 L/min. The values from bolus thermodilution ranged from 2.2 to 13.2 L/min, with a mean of 6.12 ± 2.07 L/min. The bias was 0.22, and the limits of agreement were −3.13 to 3.56 L/min. The percentage error between the FloTrac/Viligeo and bolus thermodilution measurements was 54.93%. The percentage errors of paired measurements in three surgical phases by subgroup analysis were 43.50% (dissecting phase), 62.9% (anhepatic phase), and 56.05% (reperfusion phase), respectively.

Conclusion

CO measurements obtained using the less invasive arterial waveform FloTrac/Vigileo system upgraded with the third-generation software had poor intraoperative agreement with pulmonary artery thermodilution CO measurements in patients undergoing OLT.     

Propofol attenuates ischemic reperfusion-induced formation of lipid peroxides in liver transplant recipients

Objective

Ischemic reperfusion (IR) injury is known to have an important influence on the success of transplant surgery and the occurrence of complications. Malondialdehyde (MDA) is an intermediate metabolite of lipid peroxidation resulting from IR-induced reactive oxygen species. This study was designed to investigate the protective effects of propofol on IR injury in liver transplant recipients.

Methods

We analyzed 19 recipients prospectively by measuring the blood levels of MDA at nine predefined intervals; before induction of anesthesia (baseline, T0), 1 hour after surgical incision (T1), 1 minute before reperfusion (T2), 30 seconds after reperfusion (T3), as well as 1, 3, 5, 30, and 60 minutes thereafter (T4-8). These patients were randomly allocated to two groups. The propofol group received an infusion (2 mg/kg per hr) after an induction bolus (2 mg/kg). The control group was prescribed midazolam (0.2 mg/kg) for induction without intravenous anesthetic infusion for maintenance.

Results

The highest MDA level occured at T6 in the controls and T7 in the propofol group. Compared with the blood levels at baseline, the MDA levels increased significantly at T2-T8 among controls versus T2, T3, T4, and T7 in the propofol group. Compared to the control group, propofol significantly lowered MDA values at T5-T8.

Conclusion

There were significantly higher MDA levels among the control versus the propofol group at 3, 5, 30, and 60 minutes after reperfusion in liver transplant recipients.     

Surgical Treatment and Prognosis of Rectovaginal Fistulae According to their Origin

Introduction: The rectovaginal fistula is a rare entity with heterogenic causality. Its genesis seems to predict the extent of operative treatment and the prognostic outcome. The aim of this study was to present different surgical techniques in the treatment of rectovaginal fistulas and their results in correspondence to the genesis. Material and Methods: Between 1 /?2000 and 1 /?2010, the data of patients with rectovaginal fistulas were collected. The retrospective analysis included biographic and anamnestic data as well as clinical parameters, general and specific complications and postoperative data. Results: In a timespan of ten years 36?patients with rectovaginal fistulas were treated. The most common causes were inflammatory diseases (n?= 21) and earlier surgical measures (n?= 6). Moreover tumour-associated fistulas (n?= 5) and fistulas with unknown genesis (n?= 4) were seen. As surgical techniques anterior resection (n?= 21), transrectal flap plasty (n?= 7), subtotal colectomy (n?= 3), pelvine exenteration (n?= 2) and rectal exstirpation (n?= 1) were used. The closure of the vaginal lesion was performed by single suture (n?= 25), flap plasty (n?= 6), transvaginal omental plasty (n?= 2) and posterior vaginal plasty (n?= 1). All patients were provided with an omental plasty to perform a safe division of the concerned regions. Patients with a low fistula ( < 6 cm) were treated with transperineal omental plasty. The median follow-up was 12?months (6 - 36). Within this timespan 6?patients suffered from major complications [ARDS, anastomosis insufficiency, postoperative bleeding, recurrence of fistula (n?= 3)]. Three patients died in the postoperative period (cerebellar infarct, septic complication associated with Crohn's disease, multiorgan failure in tumour recurrence). Conclusion: The genesis of rectovaginal fistulae is an important predictor for the size of resection which can range from simple excision to exenteration. For optimal therapy the surgical intervention needs to be integrated into an interdisciplinary therapy concept.     

Correlation between insulin resistance and intramyocellular lipid levels in rats.

Increased intramyocellular lipid (IMCL) content has been proposed as biomarker for insulin resistance (IR). An inverse correlation between IMCL and insulin sensitivity (IS) was found in nonathletic humans, whereas in animal models only a few validation studies have been performed. The aim of this study was to investigate the interrelation between IS indices determined by the glucose clamp technique (glucose disposal (GD), exogenous glucose infusion rates (GIR)) and IMCL content in the tibialis (TIB) and the soleus (SOL) muscle obtained by magnetic resonance spectroscopy in different rat models of IR. Diet-induced insulin-resistant Wistar rats as well as genetic disease models (ZDF rats) were used. In both muscles, elevated IMCL correlated with an impaired IS in all models of IR. The correlation of IMCL with both parameters for IS was comparable in TIB and SOL. The best fit between IMCL and IS was obtained using TIB and GIR data (r = -0.69, P < 0.001). Diabetic male ZDF rats exhibited comparatively low IMCL levels due to their catabolic state: exclusion of this group improved r. In summary, IMCL, especially in TIB, is a valid biomarker for IS in various rat models of IR with the advantage of a fast repeatable noninvasive measurement in individual animals.     

Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia

Abstract: Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia. Four years later his general condition deteriorated, accompanied by an increase in leukocytes to 200 000/μl blood. The bone marrow histology was interpreted as compatible with a diagnosis of chronic myelomonocytic leukemia. Two months before he died, the patient developed generalized lymphadenopathy clinically simulating malignant lymphoma. Histologic examination of an axillary lymph node revealed diffuse infiltration by PM. The PM in the lymph node and some circulating cells closely resembling PM expressed L-selectin, a finding that could be interpreted as a morphologic correlate of their marked lymphotropism. The detection of large numbers of CD56/CD33 double-positive circulating blast cells by FACS analysis strongly supported the diagnosis of a leukemia of myelogenous origin. The patient died of tumor cachexia. Autopsy revealed widespread leukemic infiltrates (always containing clusters of PM) in bone marrow, spleen, liver, lymph nodes, and mucosa-associated lymphoid tissue of the oropharynx. The final diagnosis was one of chronic myelomonocytic leukemia with marked lymphotropism and partial differentiation towards PM. We consider that the rare instances of a hematologic tumor with differentiation towards PM should be classified amongst the myelogenous leukemias.     

Squamous cell carcinoma of the gastric stump. A case report and review of the literature

Adenosquamous and pure squamous cell carcinomas of the stomach are very rare. This report is apparently the first published case of pure squamous cell carcinoma of the gastric stump. It occurred in a 67-year-old patient 37 years after Billroth II resection. This case satisfied the criteria established in the literature for the diagnosis of gastric squamous cell carcinoma. A diagnosis of adenosquamous carcinoma was excluded by extensive histologic investigation of a large number of tissue samples--a total 122 sections from 25 blocks--that revealed neither glandular structures nor mucin. The tumor stroma contained an unusually large number of eosinophils. Immunohistochemically, the tumor cells reacted with a monoclonal antibody against keratin (KL1), but not with antibodies against neuroendocrine or endothelial markers, or alpha 1-antichymotrypsin. The tumor may possibly originate from ectopic squamous epithelium, squamous metaplasia of the gastric mucosa, or an undifferentiated mucosal stem cell. However, we excluded an endothelial origin (which has been proposed by other authors) on the basis of immunohistochemical findings.