Effects of dexmedetomidine on kidney and brain tissue microcirculation and histology in ovine cardiopulmonary bypass: a randomised controlled trial.

Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α2 -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 µg.kg-1 .h-1 ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.

Value of subtraction MRI in assessing treatment response following image-guided loco-regional therapies for hepatocellular carcinoma.

AIM: To compare contrast-enhanced subtraction magnetic resonance imaging (MRI) with contrast-enhanced standard MRI in assessing treatment response following loco-regional therapies for hepatocellular carcinoma (HCC). METHOD AND MATERIALS: Institutional review board approval was obtained and informed consent was waived for this retrospective study. All patients were analysed from our institution's liver tumour database that had loco-regional HCC therapy and the following: (1) a contrast-enhanced MRI ≤6 weeks post-treatment, (2) an unenhanced T1-weighted high-signal treatment zone (TZ) ≥1 cm, (3) follow-up contrast-enhanced MRI performed ≥6 months post-treatment. Randomized standard and subtraction TZ datasets were independently assessed by three blinded radiology readers for either complete treatment necrosis or residual disease. The standard of reference (SOR) comprised a consensus read by two radiologists with knowledge of the follow-up MRI and all available clinical data. Statistical analyses were performed using receiver operating characteristics (ROC), t-test, and kappa statistic. RESULTS: Twenty-six patients (19 male and seven female patients; mean age 60 years, standard deviation 10.9 years, range 46-88 years) had a total of 45 corresponding HCCs and TZs. For ROC, the area under the curve (AUC) was 0.93 (subtraction protocol) versus 0.90 (standard protocol; p = 0.49). For the t-test, the mean reader confidence level was 4.4, 3.6, and 4.4 (subtraction protocol) versus 3, 3, and 3.7 (standard protocol; p ≤ 0.011). The kappa statistic for reader-to-SOR agreement was 0.83, 0.63, and 0.71 (subtraction protocol) versus 0.51, 0.36, and 0.64 (standard protocol). CONCLUSION: Subtraction MRI significantly improves the reader confidence level in the assessment of treatment response following loco-regional therapies for HCC.

Evaluation of biliary ductal anatomy in potential living liver donors: comparison between MRCP and Gd-EOB-DTPA-enhanced MRI.

PURPOSE: To compare magnetic resonance cholangiopancreatography (MRCP) and Gd-EOB-DTPA-enhanced MRI in the evaluation of the biliary anatomy in potential living liver donors (LLDs). METHODS: A retrospective study was conducted in a tertiary care liver transplant center after obtaining ethics and institutional approvals. A total of 42 potential LLD MRI examinations were performed between November 2013 and March 2016. All patients underwent a standard MRI protocol which included MRCP and Gd-EOB-DTPA-enhanced MRI sequences in a single session. Three abdominal MR radiologists independently reviewed the studies and completed a customized data collection sheet for each MR sequence. The readers subjectively scored the bile duct visualization on each MR sequence on a Likert scale and classified the biliary anatomic configuration. Statistical analysis was performed using intraclass correlation coefficient and the McNemar Chi-square (χ 2) test. RESULTS: The 42 potential LLDs included 22 males and 20 females with an age range of 18-60 years. There was 'good' or 'excellent' inter-reader agreement on either MRI examination for the visualization of the first- and second-order ducts and the majority of third-order ducts. 'Good' inter-reader agreement on Gd-EOB-DTPA-enhanced MRI and 'fair' inter-reader agreement on MRCP was noted for the left third-order medial duct. There was significantly better visualization of the cystic duct, left hepatic duct, and right second-order ducts on Gd-EOB-DTPA-enhanced MRI compared with MRCP. A 12.6% improvement in classifying the biliary branch pattern was also observed on Gd-EOB-DTPA-enhanced MRI compared with MRCP (P = 0.03). CONCLUSION: Gd-EOB-DTPA-enhanced MRI provides additional diagnostic confidence over MRCP in the evaluation of the biliary ductal anatomy in potential LLDs.

Role of the renal medulla in adrenocorticotrophin-induced hypertension in rats.

OBJECTIVES: The mechanism of hypertension induced by adrenocorticotrophin (ACTH) remains unclear. The antihypertensive renomedullary lipids are vasodilators and it has been proposed that a deficiency of these lipids may contribute to the hypertension produced by destruction of the renal papilla. The aim of the present work was to study ACTH hypertension in both control and chemically renomedullectomized rats. METHODS: Renomedullectomy was produced by single intraperitoneal injection of 2-bromoethylamine (BEA) at 400 mg/kg. RESULTS: BEA-treated rats all developed increases in water intake and urine volume, with loss of papillae and medullary and cortical fibrosis. There was a significant correlation between papillary ablation and systolic blood pressure (SBP). SBP in renomedullectomized rats was higher after ACTH than sham injection, and higher than after ACTH injection in intact rats. CONCLUSION: Chemical renomedullectomy with BEA did not block or attenuate the onset or magnitude of ACTH hypertension in the rat.

Effect of dietary calcium on the development of hypertension and hypertensive vascular lesions in DOCA-salt and two-kidney, one clip hypertensive rats.

OBJECTIVE: To examine the effect of modest changes in dietary calcium on systolic blood pressure (SBP) and myocardial and renal vascular lesions in Sprague-Dawley rats. DESIGN: Regular- (0.4%, by weight), high- (0.8%) or low-calcium (0.24%) diets were fed to normotensive control, deoxycorticosterone acetate (DOCA)-salt and two-kidney, one clip (2-K, 1C) hypertensive rats for 8 weeks. METHODS: Tail-cuff SBP and metabolic balance were measured once a week. At the end of the study the kidneys and hearts were collected for histological study. RESULTS: Dietary calcium had no effect on SBP in the DOCA-salt rats, but loading with calcium accelerated the rise in SBP in 2-K,1C rats (P < 0.01, high- versus regular-calcium diet). The high-calcium diet reduced the percentage medial area of intramyocardial arteries in the DOCA-salt and 2-K,1C hypertensive rats. The DOCA-salt rats on the low-calcium diet had a higher renal vascular lesions score than those on the regular- or high-calcium diet (P < 0.05). CONCLUSIONS: A high-calcium diet appears to prevent intramyocardial vascular wall thickening in DOCA-salt and 2-K,1C hypertensive rats, and a low-calcium diet aggravates renal vascular lesions in DOCA-salt hypertensive rats. These effects are not related simply to changes in blood pressure.

Retention of endothelium on ovine collagen biomatrix vascular conduits under physiological shear stress.

This study evaluates the adhesion of endothelial cells to 4 mm internal diameter, ovine collagen biomatrix vascular conduits. The biomatrix conduit is formed in a living animal and the wall consists of a complete, naturally produced matrix reinforced with polyester mesh. We propose that the microarchitecture of the matrix lining the lumen may promote endothelial cell attachment without pretreatment with adhesive proteins or extra cellular matrix components. Endothelial cell adhesion to the biomatrix surface was assessed by subjecting conduits seeded with ovine aortic endothelial cells (OAEC) to physiological range shear stresses of 16 and 32 dyn/cm2 in vitro. OAECs were isolated, cultured and seeded (1 x 10(6) cells/ml) by rotation onto the luminal surface of 20 cm lengths of biomatrix vascular conduits (n = 36). The seeded conduits were divided into three groups and cultured either for 24 h (n = 12), 48 h (n = 12) or 72 h (n = 12). Following culture, the conduits from each group were subjected to flow rates of either 240 ml/min (n = 6) or 480 ml/min (n = 6) with heparinized sheep blood for 1 h. Luminal surface cell cover was determined pre- and post-flow from Datura stramonium lectin labeled en face preparations. Histological analysis demonstrated that OAECs attach to the luminal surface of biomatrix conduits and form confluent monolayers within 24-48 h. Flow testing revealed that, for both flow rates and independent of the time in culture, there was no significant decrease in cell cover after flow (p = 0.13). The results support the hypothesis that a vascular conduit, engineered from a naturally formed biomatrix, provides a suitable substrate for the formation of flow resistant endothelium.

Occult infection as a cause of hip pain in a patient with metastatic breast cancer.

A 39-year-old woman with breast cancer metastatic to bone presented with acute hip pain marginally responsive to escalating doses of opioid analgesics. Pathologic pelvic fractures were present and there were minimal clinical indicators of infection, but the severity and intractable nature of the pain prompted further investigation. Computed tomography revealed a pelvic abscess. Antibiotic therapy and drainage of the abscess resulted in markedly improved pain control, decreased analgesic requirements, and improved quality of life. We suggest that, in patients with malignancy, the diagnosis of occult infection should be aggressively pursued as a potentially reversible cause of intractable pain.

Morphology of renal parenchymal culture in collagen gels.

Explants of rabbit renal parenchyma have been grown in primary tissue culture suspended within hydrated collagen gels. Light and phase contrast microscopic analysis of the first 17 days in culture is described. Pieces of NZW rabbit renal parenchyma were suspended in collagen gels and bathed in supplemented RPMI 1640 medium and incubated at 37 degrees C in 5% CO2 in air. Tubules demonstrated a fine granularity by phase contrast microscopy and glomeruli appeared as red spheres. Blebs formed at the sides and ends of the explant and a monolayer outgrowth of tightly packed polygonal cells occurred from day 4. Histologically an immediate phase of necrosis was followed by regeneration whereby tubules became lined with a confluent epithelium composed of a single layer of flat to cuboidal-shaped cells sitting on an intact tubular basement membrane (TBM). Intraluminal casts of organized cellular debris as well as material presumed to be Tamm Horsfall protein were present. Glomeruli demonstrated collapsed capillary loops. The interstitium became widened by eosinophilic material. The tissue surface contained epithelial cells arranged in places into sac-like structures enclosing a space.

The role of dacryocystography in the management of patients with epiphora.

A retrospective study has been carried out on 114 patients who have undergone dacryocystography (DCG) for epiphora, to assess the role of DCG in their management. It was found that 16/66 (24%) patients who were offered surgery after DCG refused it or were assessed as unfit for surgery, demonstrating the need for careful counselling and assessment of patients prior to investigation. The presence of lacrimal system obstruction on DCG was an important factor in determining whether a patient underwent lacrimal surgery. However, the actual level of the obstruction influenced neither the likelihood of a patient undergoing lacrimal surgery nor the form of lacrimal surgery undertaken. This suggests that, unless the surgical approach will be modified in the light of the anatomical information furnished by DCG, DCG is not necessary. Lacrimal scintigraphy would provide sufficient information for the practical management of epiphora. Syringing of the lacrimal system correlates poorly with DCG in detecting obstruction.

Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy.

Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identification of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported.

Artificial aortic valves: an overview.

This review discusses strategies that may address some of the limitations associated with replacing diseased or dysfunctional aortic valves with mechanical or tissue valves. These limitations range from structural failure and thromboembolic complications associated with mechanical valves to a limited durability and calcification with tissue valves. In pediatric patients there is an issue with the inability of substitutes to grow with the recipient. The emerging science of tissue engineering potentially provides an attractive alternative by creating viable tissue structures based on a resorbable scaffold. Morphometrically precise, biodegradable polymer scaffolds may be fabricated from data obtained from scans of natural valves by rapid prototyping technologies such as fused deposition modelling. The scaffold provides a mechanical profile until seeded cells produce their own extra cellular matrix. The microstructure of the forming tissue may be aligned into predetermined spatial orientations via fluid transduction in a bioreactor. Although there are many technical obstacles that must be overcome before tissue engineered heart valves are introduced into routine surgical practice these valves have the potential to overcome many of the shortcomings of current heart valve substitutes.

Magnetic resonance imaging of limbic encephalitis.

The authors describe the imaging appearance of limbic encephalitis. This condition may be the presenting complaint of patients with an occult malignant lesion, as in the case reported here. The contrast-enhanced cerebral computed tomography scans of patients with limbic encephalitis may be normal, yet magnetic resonance imaging may show distinctive features. Because neurologic improvement may follow treatment of the primary tumour, early diagnosis is important.