Left stellate ganglion and vagal nerve activity and cardiac arrhythmias in ambulatory dogs with pacing-induced congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the patterns of autonomic nerve activity in congestive heart failure (CHF). BACKGROUND: The relationship between autonomic nerve activity and cardiac arrhythmias in CHF is unclear. METHODS: We implanted radiotransmitters in 6 dogs for continuous (24/7) simultaneous monitoring of left stellate ganglion nerve activity (SGNA), vagal nerve activity (VNA), and electrocardiography before and after pacing-induced CHF. RESULTS: Congestive heart failure increased both SGNA and VNA. The SGNA but not VNA manifested a circadian variation pattern. There was extensive sinus node fibrosis. We analyzed 2,263 episodes of prolonged (>3 s) sinus pauses (PSP) and 1,420 long (>10 s) episodes of paroxysmal atrial tachycardia (PAT). Most (95.3%) PSP episodes occurred at night, and 56% were preceded by a short burst of SGNA that induced transient sinus tachycardia. Long PAT episodes were typically (83%) induced by simultaneous SGNA and VNA discharge, followed by VNA withdrawal. Premature ventricular contractions and ventricular tachycardia were preceded by elevated SGNA. CONCLUSIONS: The reduction of sympathovagal balance at night in ambulatory dogs was due to reduced sympathetic discharge rather than a net increase of vagal discharge. The tachybrady syndrome in CHF might be triggered by an intermittent short burst of SGNA that resulted in tachycardia and sinus node suppression. Simultaneous sympathovagal discharge is a cause of long PAT episodes. These data indicate that there is an association between the specific patterns of autonomic nerve discharges and cardiac arrhythmia during CHF.     

Gastric mucosal blood flow response to stimulation and inhibition of gastric acid secretion

The effect of stimulation (with graded doses of intravenous pentagastrin) and inhibition (with an H2-blocker or a proton pump inhibitor) of acid secretion on corpus mucosal blood flow was investigated. Hydrogen gas clearance was used to measure blood flow in the basal portion of the mucosa of anesthetized rats. A dose-related increase in acid output increments above resting level was observed with the doses of pentagastrin from 0 (saline infusion) to 40 micrograms/kg.h. With the doses of pentagastrin from 0 to 80 micrograms/kg.h there was a dose-related increase in mucosal blood flow increments above resting levels. A linear correlation (r = 0.7) was observed between increments in acid output and increments in mucosal blood flow with increasing doses of pentagastrin from 0 to that producing maximal acid secretion (40 micrograms/kg.h). Inhibition of pentagastrin-stimulated acid secretion by cimetidine or omeprazole returned stimulated gastric mucosal blood flow to baseline levels.     

Diagnostic precision of endoanal MRI in the detection of anal sphincter pathology—a meta-analysis

Objective This study aims to evaluate the diagnostic precision of endoanal magnetic resonance imaging in identifying anal sphincter injury and/or atrophy when compared with either endoanal ultrasound or surgical diagnosis. Materials and methods Quantitative meta-analysis was performed on nine studies, comparing endoanal MRI with endoanal ultrasound or surgical diagnosis in 157 patients. Sensitivity, specificity, and diagnostic odds ratio were calculated for each study. Summary receiver operating characteristic curves (SROC) and subgroup analysis were undertaken. Results The overall sensitivity and specificity of endoanal MRI for external sphincter injury was 0.78 (95%CI: 0.66–0.84) and 0.66 (95%CI: 0.51–0.79), respectively. For internal sphincter injury detection, this was 0.63 (95%CI: 0.50–0.74) and 0.71 (95%CI: 0.60–0.81), respectively. For detection of atrophy, this was 0.86 (95%CI: 0.71–0.95) and 0.82 (95%CI: 0.65–0.93), respectively. The area under the SROC curve and diagnostic odds ratio were 0.84 (SE = 0.07) and 6.14 (95%CI: 2.17–17.4) for external sphincter injury, 0.79 (SE = 0.07) and 4.60 (95%CI: 1.75–12.15) for internal sphincter injury, and 0.92 (SE = 0.08) and 21.49 (95%CI: 2.87–160.64) for sphincter atrophy. Conclusion Endoanal MRI was sensitive and specific for the detection of external sphincter injury and especially sphincter atrophy. It may be useful as an alternative to endoanal ultrasound in patients presenting with fecal incontinence, although further clinical studies are needed to identify its best application in clinical practice.     

Adoptive immunotherapy with donor lymphocyte infusions and interleukin-2 after high-dose therapy and autologous stem cell rescue for multiple myeloma

In an attempt to induce a graft-versus-myeloma effect, we administered donor lymphocyte infusions (DLI) after high-dose therapy with autologous stem cell transplant rescue to seven patients with refractory or relapsed multiple myeloma. High-dose therapy consisted of melphalan, idarubicin and etoposide (days -9 to -6) followed by autologous stem cell infusion on day 0. DLI (five of seven donors with two or three HLA antigens mismatched) were administered on days +1, +5 and +10 along with IL-2 (from day +1 through +12). Six of the seven patients developed acute graft-versus-host disease (GVHD), which resolved spontaneously, coincidentally with autologous hematopoietic reconstitution. One patient failed to engraft and received a second autologous graft. One patient died from complications of a pulmonary hemorrhage after experiencing GVHD. With a minimum follow-up of 38 months, five patients remain without disease progression in complete remission or with minimal residual disease. In this setting, DLI/IL-2 is biologically active resulting in GVHD. A graft-versus-myeloma effect is suggested by the improved outcome of our small cohort of high-risk patients. The use of partially mismatched related donors makes this approach potentially available to nearly all patients.     

愈肝胶囊抗鸭乙型肝炎病毒作用实验研究

观察愈肝胶囊抗鸭乙型肝炎病毒作用。方法选1日龄广州麻鸭50只接种病毒,分ACV200μg/kg,愈肝胶囊6.5g/kg,3.25g/kg及病毒对照组,1/d,口服。分别观察其抗DHBV的作用。试验结束时,取肝组织作病理切片光镜观察。结果 6.5g/kg愈肝胶囊组在给药后第5天,第10天和停药后第3天,鸭血清DHBV DNA水平均明显下降,与给药前自身比及病毒对照组比较,差异均有显著性(P相似文献   

Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits.

The pharmacokinetics of 5-fluorouracil (5FU) were studied in vivo in patients with discrete tumors and in rabbits bearing VX2 tumors by using 19F NMR spectroscopy. The human studies were conducted in a 1.5-T Magnetom magnetic resonance imager (Siemens), and the rabbit studies were conducted in a 4.7-T GE/Nicolet 33-cm bore magnet. Free 5FU was detected in the tumors of four of the six patients and in all VX2 tumors but not in normal rabbit tissues. No other metabolites were seen in these tumors, contrary to the extensive catabolism we had previously documented using 19F NMR spectroscopy in both human and animal livers. The tumor pool of free 5FU in those human tumors that trapped 5FU was determined to have a half-life of 0.4-2.1 hr, much longer than expected and significantly longer than the half-life of 5FU in blood (5-15 min), whereas the half-life of trapped 5FU in the VX2 tumors ranged from 1.05 to 1.22 hr. In this initial experience, patient response to chemotherapy may correlate with extent of trapping free 5FU in the human tumors. These studies document that NMR spectroscopy is clinically feasible in vivo, allows noninvasive pharmacokinetic analyses at a drug-target tissue in real time, and may produce therapeutically important information at the time of drug administration. Demonstration of the trapping of 5FU in tumors provides both a model for studying metabolic modulation in experimental tumors (in animals) and a method for testing modulation strategies clinically (in patients).     

Characterization and immunological identification of cDNA clones encoding two human DNA topoisomerase II isozymes

Several DNA topoisomerase II (Topo II; EC 5.99.1.3) partial cDNA clones obtained from a human Raji-HN2 cDNA library were sequenced and two classes of nucleotide sequences were found. One member of the first class, SP1, was identical to an internal fragment of human HeLa cell Topo II cDNA described earlier. A member of the second class, SP11, shared extensive nucleotide (75%) and predicted peptide (92%) sequence similarities with the first two-thirds of HeLa Topo II. Each class of cDNAs hybridized to unique, nonoverlapping restriction enzyme fragments of genomic DNA from several human cell lines. Synthetic 24-mer oligonucleotide probes specific for each cDNA class hybridized to 6.5-kilobase mRNAs; furthermore, hybridization of probe specific for one class was not blocked by probe specific for the other. Antibodies raised against a synthetic SP1-encoded dodecapeptide specifically recognized the 170-kDa form of Topo II, while antibodies raised against the corresponding SP11-encoded dodecapeptide, or a second unique SP11-encoded tridecapeptide, selectively recognized the 180-kDa form of Topo II. These data provide genetic and immunochemical evidence for two Topo II isozymes.     

Association of a polymorphism in the lipin 1 gene with systolic blood pressure in men

BACKGROUND: Lipin 1 plays a role in abdominal obesity, insulin resistance, and hypertriglyceridemia. The gene is located at 2p25.1, a susceptibility locus for hypertension. We studied the association of tagging single-nucleotide polymorphisms (SNPs) in the lipin 1 (LPIN1) gene with hypertension and blood pressure. METHODS: Twelve tagging SNPs from the HapMap database were genotyped using Sequenom MassArray in 268 hypertensive subjects and 407 normotensive controls, of whom 268 matched the cases in age and sex. RESULTS: None of the tagging SNPs were found to be associated with hypertension after correcting for multiple testing, although carriers of the minor allele of rs10520097 had nominally lower odds for hypertension (P = 0.014). After excluding subjects who were on antihypertensive medications, the minor allele of rs10495584 was nominally associated with lower mean systolic and diastolic blood pressures in men (121.1 +/- 14.2 and 76.3 +/- 10.2 mm Hg vs. 127.4 +/- 15.2 and 80.1 +/- 10.5 mm Hg, P = 0.002 and 0.007, respectively), but not in women (P > 0.05). The association of rs10495584 with systolic blood pressure in men remained significant after correcting for multiple testing and adjustment for age, waist circumference, insulin resistance, triglyceride, and high-density lipoprotein (HDL) cholesterol (beta = -0.158, P = 0.005). An analysis of statistically similar SNPs (ssSNPs) in the regions surrounding rs10495584 suggested that its effect may be caused by its high linkage disequilibrium (LD) with the SNP, rs11524, in which the major allele forms an exonic splicing silencer sequence. CONCLUSION: Our study provides further evidence that lipin 1 may play a role in blood pressure regulation, especially in men.     

肺腺癌T1N0M0的预后因素分析

目的：探讨肺腺癌T1N0M0患预后的病理因素与生存率的关系。方法：回顾1994年－1997年经手术治疗的肺腺癌T1N0M0 34例。观察病理学特征并随访。结果：34例病例术后平均随访时间为5．1年，5年生存率为67．7％。肿瘤直径2－3cm；中心性纤维化＞30％；有淋巴管腔的侵犯；细胞核Ⅲ级与肿瘤坏死＞50％，明显降低5年生存率。结论：研究有利于检测出转移风险较大的患，使其及时接受辅助性系统治疗。     

Cardiovascular Assessment of Falls in Older People

Falls in older people can be caused by underlying cardiovascular disorders, either because of balance instability in persons with background gait and balance disorders, or because of amnesia for loss of consciousness during unwitnessed syncope. Pertinent investigations include a detailed history, 12-lead electrocardiography, lying and standing blood pressure, carotid sinus massage (CSM), head-up tilt, cardiac electrophysiological tests, and ambulatory blood pressure and heart rate monitoring, which includes external and internal cardiac monitoring. The presence of structural heart disease predicts an underlying cardiac cause. Conversely, the absence of either indicates that neurally mediated etiology is likely. CSM and tilt-table testing should be considered in patients with unexplained and recurrent falls. Holter monitoring over 24 hours has a low diagnostic yield. Early use of an implantable loop recorder may be more cost-effective. A dedicated investigation unit increases the likelihood of achieving positive diagnoses and significantly reduces hospital stay and health expenditure.