Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure

Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because microparticles can affect endothelial cells, this study investigated the relationship between circulating microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V+ microparticles were increased compared with 32 healthy subjects, as were levels of microparticles derived from endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only endothelial microparticle levels correlated highly with loss of flow-mediated dilation (r = -0.543; P = 0.004), increased aortic pulse wave velocity (r = 0.642, P < 0.0001), and increased common carotid artery augmentation index (r = 0.463, P = 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V+ microparticle levels did not. In vitro, microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas microparticles from healthy subjects did not. Moreover, in vitro endothelial dysfunction correlated with endothelial-derived (r = 0.891; P = 0.003) but not platelet-derived microparticle concentrations. In fact, endothelial microparticles alone decreased endothelial nitric oxide release by 59 +/- 7% (P = 0.025). This study suggests that circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction in ESRF.     

Uremia accelerates both atherosclerosis and arterial calcification in apolipoprotein E knockout mice

Chronic renal failure (CRF) favors the development of atherosclerosis and excessive calcification of atheromatous lesions. CRF was induced in apolipoprotein E knockout (apoE(-/-)) mice to study (1) a possible acceleration of aortic atherosclerosis, (2) the degree and type of vascular calcification, and (3) factors involved in the calcification process. For creating CRF, 8-wk-old apolipoprotein E gene knockout (apoE(-/-)) mice underwent partial kidney ablation. Control animals underwent sham operation. Aortic atherosclerotic plaques and calcification were evaluated using quantitative morphologic image processing. At 6 wk after nephrectomy, CRF mice had significantly higher serum urea, cholesterol, and triglyceride concentrations than non-CRF controls. The serum levels of advanced oxidation protein products were elevated in the uremic group and were correlated with serum urea levels. Atherosclerotic lesions in thoracic aorta were significantly larger in uremic apoE(-/-) mice than in nonuremic controls. The relative proportion of calcified area to total surface area of both atherosclerotic lesions and lesion-free vascular tissue was increased in aortic root of uremic apoE(-/-) mice when compared with controls. The calcium deposits were made of hydroxyapatite and calcite crystals. In addition, plaques from uremic animals showed a significant increase in collagen content, whereas the degree of macrophage infiltration was comparable in both groups. There was no difference in mean arterial BP. These findings demonstrate that CRF aggravates atherosclerosis in apoE(-/-) mice. Moreover, CRF enhances arterial calcification at both atheromatous intimal sites and atheroma-free medial sites. We anticipate that this experimental model will be useful to test treatment strategies aimed at decreasing the accelerated atherosclerosis and arterial calcification in uremia.     

Oral manifestations of juvenile hyaline fibromatosis: a case report

Hyaline fibromatosis is a rare autosomal recessive disease of connective tissue, characterised by an accumulation of hyaline in the skin as well as various organs. The clinical features include: multiple cutaneous nodules, joint contractures, osteolytic lesions and gingival hypertrophy. This paper reports the case of an 11-year-old boy, who was referred to our dental clinic complaining of pain in his mouth. On examination, the patient had gross maxillary and mandibular gingival hyperplasia, which caused severe feeding difficulties. He also had severe dental decay, mal-positioned teeth and limited mouth opening. Treatment was done under general anesthesia to remove excess gingival tissue and extract the severely decayed teeth. Histological examination confirmed the diagnosis of juvenile hyaline fibromatosis. It was concluded that patients with this condition have special dental needs. Early diagnosis of the affected children is important in order to start early preventive dental therapy.     

Functional neuroanatomy of subcomponent cognitive processes involved in verbal working memory

Recent research has used functional magnetic resonance imaging (fMRI) to examine brain regions related to specific subcomponent cognitive processes of verbal working memory, which include initial encoding of material, maintenance of the information over a brief delay interval, and later retrieval of the information. The present study examined each of these subcomponents in 14 healthy adults using a Sternberg verbal working memory task and fMRI. Group analysis revealed several brain regions active during all subcomponent processes, which included dorsolateral and ventrolateral prefrontal, parietal, hippocampal, and premotor cortex. Several other brain regions showed activation limited to specific subcomponent processes.     

Effects of mood state and psychosocial functioning on plasma Interleukin-6 in adult patients before cardiac surgery

OBJECTIVE: The purpose of this study was to examine the potential effect of mood states and psychosocial functioning during the waiting weeks prior to major cardiac surgery on the plasma Interleukin-6 (IL-6) levels in 236 patients immediately before their operation. METHOD: The sample was recruited from patients at the cardiac clinic of the University of Michigan Medical Center (Ann Arbor). Two weeks before cardiac surgery, trained research assistants conducted a face-to-face interview with these middle-aged and older patients on their preoperative physical examination date at the clinic. Standardized instruments were used to assess mood states and psychosocial functioning. The blood samples of 236 patients, obtained on the morning of the operation, were analyzed for plasma IL-6. RESULTS: In bivariate analysis, poor psychological functioning and anxiety, as well as bodily pain and body mass index (BMI), were correlated with plasma IL-6 (p < .05), but sociodemographics, chronic illness and use of psychotropic medications were not. When the effect of bodily pain and BMI were taken into account, partial correlation analysis showed that psychological functioning continued to be associated with plasma IL-6 (p < .05); the association of IL-6 with depression now became significant (p < .05), whereas that with anxiety became even more significant (p < .001). CONCLUSIONS: Preoperative psychological disturbances during the waiting weeks before cardiac surgery may influence the plasma levels of IL-6 immediately prior to the procedure. The clinical implications of these findings remain to be determined.     

Allogenic blood transfusion does not predispose to infection after cardiac surgery

Background

Many retrospective studies report increased postoperative infection after allogenic blood transfusion. To investigate this phenomenon, we prospectively studied 232 patients undergoing cardiac surgery.

Methods

Patients were screened daily for evidence of culture positive infections. Wounds were examined daily and defined on the ASEPSIS score. Chest radiographs and white cell counts and differentials were recorded on days 1, 2, and 4. The use of blood products was monitored blindly and independently. Patients were grouped according to transfusion status and compared using χ² or Fisher's test. Logistic regression analyses were performed to identify predictors of transfusion and infection.

Results

Of 232 patients, 116 (50%) received blood product transfusion. Patients receiving blood had lower preoperative hemoglobin, were older, with a greater proportion of urgent/emergency or revision surgery, and were higher risk. Despite this, there were no differences in the frequency of chest infection (20% versus 15%, p = 0.38), urinary infection (3.5% versus 5.3%, p = 0 0.75), wound infection (3.5% versus 8.0%, p = 0.16), or overall infection (28% versus 30%, p = 0.89) comparing the transfused versus untransfused groups. There was no evidence to suggest that administration of blood products was associated with infection (odds ratio 0.92, p = 0.77).

Conclusions

The administration of blood per se did not lead to increased postoperative infection. Clinicians should reconsider withholding blood transfusion in patients solely owing to concerns of predisposition to infection.     

Peritoneovenous Shunt Insertion for Intractable Ascites-A District General Hospital Experience

Ascites often contributes to patient morbidity and discomfort. When refractory to medical management, it has been managed with repeated paracentesis, implantable ports for drainage, or diversion to the urinary bladder. Peritoneovenous shunt insertion has been a technique that was traditionally performed only by surgeons but is now within the realm of interventional radiologists. Its advantage is that protein-rich ascitic fluid is returned to the intravascular compartment. This retrospective study elaborates on the successes and problems encountered during shunt insertion in our first 13 patients. Two patients are well with a functioning shunt at 14 and 32 weeks. In 6 the shunt functioned until the patients death from the underlying malignancy. Two required revision with variable success and in 2, shunt function could not be salvaged. There was one procedure-related mortality. Radiological insertion of these shunts is feasible and should be considered for selected patients. Options are available for assessment and salvaging of dysfunctional shunts.     

Small volume albumin administration protects against hemorrhagic shock-induced bone marrow dysfunction

BACKGROUND: Unexpected immunomodulatory effects of colloids and crystalloids prompted an investigation of albumin's ability to prevent bone marrow (BM) suppression following trauma/hemorrhagic shock (T/HS: laparotomy + MAP 30 for 90 mins). METHODS: In vitro: Normal rat BM was plated for granulocyte-macrophage (CFU-GM) and erythrocyte colony forming units (BFU-E) with 2% v/v plasma from sham (T/SS) or T/HS rats and albumin (2-8 mg/mL). In vivo: Male rats (n = 4/group) were subjected to T/SS or T/HS and resuscitated with shed blood and twice the volume as Lactated Ringer's (LR) or blood and 1, 2, or 3 mL of albumin (50 mg/mL). Bone marrow harvested 3 hours post-resuscitation was plated for CFU-GM and BFU-E. RESULTS: In vitro: T/HS plasma decreased both CFU-GM and BFU-E growth as compared with T/SS, whereas increasing doses of albumin showed dose-dependent improvement in progenitor growth (p < 0.05). In vivo: The suppression of BM red and white cell progenitor growth seen in T/HS+LR rats as compared with T/SS was fully prevented by as little as 1 mL of albumin (p < 0.05). CONCLUSIONS: Small doses of albumin fully restore CFU-GM and BFU-E to sham values. We postulate that the binding of circulating toxic factors by albumin may play a role in this prevention of T/HS-induced BM suppression.