GENE TRANSFER INTO PORCINE MYOCARDIUM VIA PERICARDIAL CAVITY BY HOMEMADE EASY PUNCTURE DEVICEA

Objective To explore the feasibility and safety of gene transfer into porcine myocardium via the pericardial cavity by a homemade easy device.Methods Replication-deficient recombinant adenoviral vector carrying LacZ report gene (Ad-LacZ) was constructed by the calcium phosphate precipitation method. Twelve healthy Chinese mini-swine were randomly divided into experimental group (n = 6) and control group (n =6). Acute myocardial infarction (AMI) model was established by balloon occlusion of the distal part of D[ branch of left anterior descending (LAD) artery, at the same time the intra-pericardial cavity injections were performed through the small incision of the abdominal wall below the xyphoid appendix using a homemade device. Then gene transfer was performed using a central venous catheter. The pericardium was pre-treated with injection of a mixture of collagenase (1 200 U) and hyaluronidase (3 000 U) in both groups. Then 2. 0 × 109 plaque formation unit (PFU) Ad-LacZ was injected into the pericardial cavity in experimental group, while 1 mL of normal saline was injected in the control group. The p-galactosidase activity detection and X-gal staining of the ischemic myocardium were performed on the 3rd, 7th, and 28th day after injection.Results The LAD artery was occluded completely and infarction and ischemia were detected by histological assessment In experimental group, the X-gal staining positive cells and (3-galactosidase activity quantification were detectable on the 3rd day after injection, increased markedly on the 7th day, and then declined on the 28th day. The transfer efficiencies indicated by the positive myocardial cells were 16. 7% , 45. 6% , 22. 8% on the 3rd, 7th, 28th day, respectively. In control group, no positive cells and (3-galactosidase activity were observed.Conclusion Adenovirus can be transferred into ischemic myocardium and express target gene in the AMI model for four weeks with the homemade easy device via pericardial cavity pretreated by collagenase and hyaluronidase.     

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM： To investigate the effects of vitamins （A, C and E） on liver injury induced by ethanol administration during liver regeneration in rats. METHODS： Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups （groups 1-5）. During the experiment, animals of Group 1 drank only water. The other four groups （2-5） drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, albumin and bilirubin were measured colorimetrically. Lipid peroxidation （thiobarbituric-acid reactive substances, TBARS） both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS： Compared with sham group, serum AST and ALT increased significantly under ethanol treatment （43% and 93%, respectively, with P 〈 0.05）. Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group （3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P 〈 0.05）. During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation （4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P 〈 0.05）. In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins （C and E） treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION： Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.     

Increased pfmdr1 copy number in Plasmodium falciparum isolates from Suriname

Amplification of the pfmdr1 gene is associated with clinical failures and reduced in vivo and in vitro sensitivity to both mefloquine and artemether–lumefantrine in South‐East Asia. Several African countries have reported the absence or very low prevalence of increased copy number, whilst South American reports are limited to Peru without and Venezuela with increased pfmdr1 multiplication. The relative pfmdr1 copy numbers were assessed in 68 isolates from Suriname collected from different endemic villages (2005) and from mining areas (2009). 11% of the isolates harbour multiple copies of the pfmdr1 gene. Isolates originating from mining areas do not yet display a higher tendency for increased copy number and no significant differences could be registered within a time span of 4 years, but the mere presence of increased copy number warrants caution and should be considered as an early warning sign for emerging drug resistance in Suriname and South America.     

Preliminary observations on the use of corynebacterium parvum in patients with primary intracranial tumors: Effect on intracranial pressure

It has been observed that patients with metastatic brain lesions developed neurologic symptoms when given Corynebacterium parvum. To obtain more information in patients with intracranial mass lesions, intracranial pressures (ICP) were measured or observed in six patients undergoing C. parvum therapy. All patients except two (one previously shunted, one recently operated) demonstrated a profound increase in ICP. It is presumed that either edema is formed within brain and tumor tissue (inasmuch as neurologic deterioration has not been observed in patients without an intracranial lesion) or transient increases in cerebral blood flow adversely alter an already compromised intracranial volume. Surgical decompression of tumor volume or use of Lasix® may abort this response to C. parvum infusion.     

Pseudotumor cerebri

The authors evaluate the case of a 20-year-old, four-month-pregnant woman who presented with papilledema and visual field loss, and developed headache, intermittent diplopia and impairment of color vision over the next month. The procedures and considerations leading to the diagnosis of pseudotumor cerebri are discussed, as are the various modes of therapy and their indications.     

Postmenopausal endometriosis

The frequency of postmenopausal endometriosis (ovarian endometriosis and adenomyosis) was 2.2%. The mean of the menopausal ages in 11 patients with ovarian endometriosis was 50.3 yr and the average time elapsed since menopause, 7.3 yr. The corresponding values in 8 patients with adenomyosis were 52.1 and 8.8 yr. Carcinoma was a common associated finding in patients with ovarian endometriosis. Increased estrogen activity was observed more frequently in patients with adenomyosis than in those with ovarian endometriosis. Only one of the patients had received estrogen therapy. Hormone-producing tumors in the ovaries or adrenal glands were not confirmed. 70% of the patients were obese and the signs of increased estrogen activity could be explained by extraglandular estrogen formation.     

The challenge of informed consent for increased risk living donation and transplantation

The Organ Procurement and Transplantation Network (OPTN) mandates that organ recipients provide "specific informed consent" before accepting organs that the OPTN defines as "increased risk". However, the OPTN does not provide specific guidelines for what information should be disclosed to potential recipients. Such vagueness opens the door to inadequate informed consent. This paper examines the ethical dimensions of informed consent when the prospective living donor has self-reported behaviors associated with increased risk for infection transmission. Donor privacy is a primary ethical concern that conflicts with recipients' informed consent for use of increased risk organs. We propose that both the increased risk status and the specific behavior be disclosed to the recipient. Because the actual risk posed is linked to the type of risk behavior, disclosure is therefore needed to make an informed decision. The donor's risk behavior is material to recipients' decision making because it may impact the donor-recipient relationship. This relationship is the foundation of the donation and acceptance transaction, and thus comprises a critical feature of the recipient's informed consent. Optimizing a recipient's informed consent is essential to protecting patient safety and autonomy.     

Quantitative sensory testing in cluster headache: increased sensory thresholds

To determine if recently reported changes in sensory thresholds during migraine attacks can also be seen in cluster headache (CH), we performed quantitative sensory testing (QST) in 10 healthy subjects and in 16 patients with CH. Eight of the patients had an episodic CH and the other eight a chronic CH. The tests were performed on the right and left cheeks and on the right and left side of the back of the hands to determine the subjects' perception and pain thresholds for thermal (use of a thermode) and mechanical (vibration, pressure pain thresholds, pin prick, von Frey hairs) stimuli. Six patients were examined in the attack-free period. Three were also willing to repeat the tests a second time during an acute headache attack, which was elicited with nitroglycerin. The healthy subjects performed the experiments in the morning and evening of the same day to determine if sensory thresholds are independent of the time of day. If they were, this would allow estimation of the influence of the endogenous cortisone concentration on these thresholds. The control group showed no influence of the time of day on the thresholds. There was a significant difference in pain sensitivity between the back of the hands and the cheeks (P<0.05): higher thresholds were found on the back of the hands. The thresholds generally exhibited little intersubject variability, indicating that QST is a reliable method. There was also a significant difference between the test areas in the patient group (P<0.001): the cheeks were also more sensitive than the back of the hands. In comparison with reference data of healthy volunteers, the detection thresholds were increased in the patients on both test areas. These were statistically significant for warmth, thermal sensory limen (TSL), heat and pressure on the back of the hands (P<0.04) and for the warmth and TSL thresholds on the cheeks (P<0.05). There were no differences in the thresholds regardless of whether the patients were examined in or outside of a cluster bout. Furthermore, we found no cutaneous allodynia in the three patients tested during an attack. The increased sensory thresholds on the cheeks as well as on the back of the hands are in agreement with an increased activation of the patients' antinociceptive system. The seasonal variation and the temporal regularity of single attacks as well as the findings in imaging studies indicate that the hypothalamus is involved in the pathophysiology of CH. In view of the strong connectivity between the hypothalamus and areas involved in the antinociceptive system in the brainstem, we hypothesize that this connection is the reason for the increased sensory thresholds in CH patients found in our study.     

ASSOCIATION BETWEEN PEMPHIGUS VULGARIS AND HUMAN LEUKOCYTE ANTIGEN IN HAN NATION OF NORTHEAST CHINA

Objective To investigate the relationship between pemphigus vulgaris （PV） and human leukocyte antigen （HLA） in Han nation of northeast China. Mothods Standard microcytotoxicity test and polymerase chain reaction-sequence specific primers method were used to detect the HLA class Ⅰ antigens and HLA-DRBI and DQBI alleles in 27 patients with PV and results were compared with control group. Gene and phenotype frequencies of HLA-A3, A26（10）, B60（40）, and B13 （27.99%, 48%; 16.11%, 30%; 23.02%, 41%; 16.11%, 30%, respectively） increased significantly in PV group compared with control （1.01%, 2%; 0.5%, 1%; 4.61%, 9%; 5,13%, 10%, respectively）. After P value correction, the difference of A3, A26 （10）, and B60 （40） between the two groups was still significant. The gene frequencies of HLA-DRB 1^＊ 140x （1401, 1404, 1405, 1407, 1408）, DRBI^＊I20x, and DQBI＊0503 alleles in PV group （42.26%, 25.46%, and 23.02%） were significantly higher than control group （5.09%, 7.74%, and 1.89%）. After P value correction, the difference was still significant between the two groups. Collusion PV significantly relates with HLA in PV patients of Han nation of northeast China.