Carotid artery stump pressure and associated neurological changes in predominantly symptomatic carotid artery disease patients undergoing awake carotid endarterectomy

Aim

To determine the mean carotid artery stump pressure (SP) at which patients develop neurological changes while undergoing awake carotid artery endarterectomy (CEA) under cervical block anaesthesia (CBA).

Methods

A prospective analysis was carried out of patients undergoing awake CEA under CBA between February 2004 and April 2007. All patients had mean SP measured, with selective shunting on those who developed neurological symptoms on carotid artery clamping regardless of stump pressure. A ball connected to a pressure sensor was put in the patient’s contra-lateral hand.

Results

Fifty-nine patients had awake CEA, 40 were males with a mean age of 64 years. Indications for CEA were asymptomatic high-grade stenosis in 12 (20%) patients and symptomatic stenosis in 47 (80%). Seven (12%) patients required shunting, one for transient ischaemic attack (TIA) and six for loss of consciousness. Six of these patients had presented with symptomatic disease.Taking the threshold of mean carotid SP of 50 mmHg as an indication for shunting, 22% (6/27) of patients with a mean SP of < 50 mmHg required shunting and only 3% (1/32) with a mean carotid SP of > 50 mmHg needed a shunt. This was not statistically significant. Using a mean carotid SP of ≤ 40 mmHg as the threshold for shunting, 40% (4/10) of patients required shunting and 3% (1/31) with a mean carotid SP of > 40 mmHg required shunting. This was statistically significant. Thirteen (22%) patients were complicated by transient hoarseness of voice. One (2%) had a haematoma that required re-exploration. None of these patients had any major postoperative neurological or cardiological complications.

Conclusion

Even though the sample in this study was small, awake CEA under local anaesthesia was seen as a safe procedure. It would appear to be safe to use the mean SP of 40 mmHg as a threshold for selective shunting in CEA under general anaesthesia.     

Identification of Novel ROR2 Gene Mutations in Indian Children with Robinow Syndrome

Ob­jec­ti­ve: Robinow syndrome (RS) is an extremely rare genetic disorder characterized by short-limbed dwarfism, defects in vertebral segmentation and abnormalities in the head, face and external genitalia. Mutations in the ROR2 gene cause autosomal recessive RS (RRS) whereas mutations in WNT5A are responsible for the autosomal dominant (AD) form of RS. In AD Robinow patients, oral manifestations are more prominent, while hemivertebrae and scoliosis rarely occur and facial abnormalities tend to be milder.Methods: Three unrelated patients from different parts of India were studied. These patients were diagnosed as RRS due to presence of characteristic fetal facies, mesomelia, short stature, micropenis, hemivertebrae and rib abnormalities. One of the patients had fetal facies and micropenis but unusually mild skeletal features. This patient’s mother had mild affection in the form of short stature and prominent eyes. Testosterone response to human chorionic gonadotropin was investigated in two patients and were normal. The exons and exon-intron boundaries of the ROR2 gene were sequenced for all probands. Bioinformatics analysis was done for putative variants using SIFT, PolyPhen2 and Mutation Taster.Results: Patients 1, 2 and 3 were homozygous for c.G545A or p.C182Y in exon 5, c.227G>A or p.G76D in exon 3 and c.668G>A or p.C223Y in exon 6 respectively. Prenatal diagnosis could be performed in an ongoing pregnancy in one family and the fetus was confirmed to be unaffected. Conclusion: ROR2 mutations were documented for the first time in the Indian population. Knowledge of the molecular basis of the disorder served to provide accurate counseling and prenatal diagnosis to the families.     

PROTEIN KINASE C AND TRANSMITTER RELEASE

1. Protein kinase C (PKC) is an important second messenger-activated enzyme. In noradrenergic nerves it appears to be tonically activated by diacylglycerol (DAG) to facilitate transmitter release and the steps in this involve activation of phospholipase C, generation of DAG and activation of PKC. It is suggested that the subsequent facilitation of transmitter release is due to the phosphorylation of proteins involved in the release process distal to Ca²⁺entry, presumably those involved in vesicle dynamics. 2. There are differences between central noradrenergic neurons and sympathetic nerves. In central neurons PKC appears to be tonically active and its inhibition results in a decrease in noradrenaline release under most, if not all, conditions. 3. In sympathetic nerves PKC inhibitors only decrease transmitter release during high-frequency stimulation and not during low-frequency stimulation. At high frequency there is a gradual increase in the effect of PKC inhibitors on transmitter release during the first 15 s of a stimulation train. It is suggested that this is due to a progressive rise in intracellular Ca²⁺ and a consequent activation of PKC. 4. Activation of PKC by phorbol esters produces a large enhancement in action potential-evoked noradrenaline release in both the central nervous system and in peripheral tissues. The structural requirements of the phorbol esters for maximal effect suggest that the phorbol esters must access the interior of the nerve terminal to activate PKC and the neural membrane acts as a barrier for highly lipophilic phorbol esters, thereby reducing their activity. Activation of PKC represents one of the most powerful ways to enhance transmitter release and may have therapeutic potential.     

血清白细胞介素-8与溃疡性结肠炎的关系

背景:炎症细胞因子在溃疡性结肠炎（UC）的发病中可能起一定作用。目的:检测UC患者的血清白细胞介素（IL）-8含量,并分析其与UC病变范围、病变程度和复发与否的关系。方法:收集64例经内镜检查证实的UC患者的血清标本,用酶联免疫吸附测定（ELISA）检测IL-8含量,并与正常对照组进口比较。结果:UC患者的血清IL-8含量为685pg/ml±790pg/ml,正常对照组为25pg/ml±21pg/ml（P<0.000）。不同病变范围UC的血清IL-8含量分别为:愈合期病变289pg/ml±373pg/ml,直肠病变499pg/ml±736pg/ml,直乙状结肠病变686pg/ml±755pg/ml,左半结肠病变 1407pg/ml±846pg/ml,全结肠病变815 pg/ml±926pg/ml;左半结肠病变者的IL-8含量最高,与愈合期和直肠病变者相比有显著差异（P<0.01）。不同病咎程度UC的血清IL-8含量分别为:0级267pg/ml±364pg/ml,1级332pg/ml±418pg/ml,2级999pg/ml±943pg/ml,3级894pg/ml±851pg/ml;2级和3级病变者的含量较0级和1级病变者明显增高（P<0.05和P<0.01）,0级者的含量亦高于正常对照组（P<0.01）。初发患者的血清IL-8含量为758pg/ml±833pg/ml,与复发患者（696pg/ml±803pg/ml）相比无显著差异（p=0.77）。19例患者在正规5-氨基水杨酸（5-ASA）制剂治疗前后分别测定了血清IL-8含量,治疗前的IL-8含     

Suppression of transfusion-related alloimmunization in intensively treated cancer patients

A retrospective review of HLA antibody testing and transfusion records of 100 cancer patients who required extensive platelet support revealed that 27 of 100 patients exhibited positive HLA antibody tests; only 13 remained positive on repetitive examination, while 88% of aplastic anemia patients so tested were positive. Sixty-five patients with leukemia, 16 with Ewing's sarcoma, and 19 with recurrent undifferentiated lymphoma were studied. Each patient received at least 10 U of platelets (mean of 72). HLA antibodies were detected in 31% (20/65) of the leukemias, 12% (2/16) of the Ewing's, and 26% (5/19) of the lymphoma patients. Fourteen of the 27 patients who developed antibodies became antibody negative again within 2 mo and remained so. There were no significant differences in quantity of platelet transfusions between antibody-negative patients and alloimmunized patients. A smaller group (n = 8) of aplastic anemia patients followed at the NCl exhibited a frequency of alloimmunization of 88% (7/8) after a mean of 44 U of platelets were transfused. Granulocyte transfusions given therapeutically for granulocytopenia and documented infection did not appear to influence HLA antibody formation. These data indicate that significant immunosuppression occurs in intensively treated cancer patients, as measured by their ability to from antibodies to HLA antigens expressed on the surface of transfused platelets.     

Comparison of bone mineral density in both hips

Dual-photon absorptiometry (DPA) was performed on both hips of 40 patients to determine if the calculated bone-mineral density (BMD) of one hip could be used to predict the BMD of the opposite hip. For the Ward triangle, femoral neck, and greater trochanter the correlation coefficients between the BMD of the two hips was .920, .917, and .843, and the standard errors (SE) of the estimate for the linear regression of the left hip on to the right were 0.067, 0.063, and 0.077 g cm-2. The absolute error of predicting one hip from the other was not a function of BMD and thus the relative error increases with lower BMD values. The relative errors were 17%, 8%, and 7% for BMDs of 0.4, 0.8, and 1.0 g cm-2, respectively. The interobserver variability was small, with an r value of .96 and an SE of the estimate value of 0.036 g cm-2. The relative error in the mild-to-moderate osteoporosis categories was 2.5 times the precision of the instrument, indicating that the asymmetry of BMD is due to real differences between hips. Therefore the BMD of one hip cannot be used to predict that of the other with sufficient accuracy to discriminate clinically relevant trends in BMD.     

Liver tissue engineering and cell sources: issues and challenges

Liver diseases are of major concern as they now account for millions of deaths annually. As a result of the increased incidence of liver disease, many patients die on the transplant waiting list, before a donor organ becomes available. To meet the huge demand for donor liver, alternative approaches using liver tissue engineering principles are being actively pursued. Even though adult hepatocytes, the primary cells of the liver are most preferred for tissue engineering of liver, their limited availability, isolation from diseased organs, lack of in vitro propagation and deterioration of function acts as a major drawback to their use. Various approaches have been taken to prevent the functional deterioration of hepatocytes including the provision of an adequate extracellular matrix and co‐culture with non‐parenchymal cells of liver. Great progress has also been made to differentiate human stem cells to hepatocytes and to use them for liver tissue engineering applications. This review provides an overview of recent challenges, issues and cell sources with regard to liver tissue engineering.