EFFICACY OF RAMIPRIL VERSUS ENALAPRIL IN PATIENTS WITH MILD TO MODERATE ESSENTIAL HYPERTENSION

SUMMARY This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles.     

Protective effect of interferon-α on the DNA- and RNA-degrading pathway in anti-Fas-antibody induced apoptosis

Aim: Fas membrane-associated polypeptide antigen is a receptor molecule responsible for apoptosis-mediated signals. In animal models of acute viral hepatitis, apoptosis of hepatocytes is mediated by Fas-death receptors; therefore, the aim of this study was to evaluate the effect of interferon (IFN)-alpha on apoptotic markers and nuclease activity against different coding and non-coding single and double stranded RNAs during Fas-induced liver apoptosis. Methods: An in vivo experiment was performed with simultaneous administration of anti-Fas (CD95) antibodies and IFN-alpha, and an in vitro experiment was performed in hepatocyte cultures treated with anti-Fas antibodies and IFN-alpha. Results: Detection of apoptosis using Annexin V-FITC/propidium iodide, Bcl-2 and Bax expression in hepatocyte cultures confirmed the appearance of early apoptotic events and progression toward late apoptosis after anti-Fas antibody treatment. IFN-alpha had a tendency to retard the apoptosis process in Fas-induced apoptosis by increasing the number of viable cells and decreasing the number of cells in late apoptosis, by increasing the percentage of Bcl-2 positive cells, by decreasing the percentage of Bax positive cells, and by decreasing the nuclease activity compared to the anti-Fas antibody treated group. Total DNA and RNA concentration was much reduced in the Fas group and DNA fragmentation assay provided evidence for increased DNA degradation. Enhanced nuclease activity against DNA, rRNA, poly(A), poly(C), poly(U), poly(I:C), and poly(A:U) was manifested in the anti-Fas antibody treated group, except for the inhibitory-bound alkaline RNase. Conclusions: The results demonstrate that the RNA-degrading pathway in Fas-induced apoptosis can accelerate the liberation of the latent enzyme from the inhibitor complex. IFN-alpha prevented enormous, Fas-ligand induced degradation of all the substrates used in this experimental study, most probably due to similarities in the signal transduction pathways. Investigations of death receptor-induced apoptosis may lead to novel treatment combinations for patients with acute or chronic liver diseases.     

Local Anaesthesia for Fiberoptic Intubation : A Comparison of Three Techniques

Background

The successful conduct of fiberoptic aided intubation is dependent upon effective local anaesthesia. The aim of the study was to compare three different methods of anaesthetizing the airway.

Methods

60 adult patients (American Society of Anaesthesiologists status I-III and Mallampati class III & IV), scheduled for elective surgery, received sedation followed by spraying of the nares and posterior pharyngeal wall with 4% lignocaine. Thereafter the patients received 4 ml of 4% lignocaine either by transtracheal injection (n=20, group A), via intubating fiberscope (Pentax F1-10P2) using ‘spray as you go’ technique (n=20, group B) or by nebulizer (Devilbiss 5610W) 20 min before intubation, (n=20, group C). Patients were asked to score the procedure using visual analog scale (VAS) and severity scores. Episodes of coughing, choking, stridor, extra / total local anaesthetic used and intubation times were recorded. Patients were monitored continuously for vital parameters.

Results

Group B patients showed better VAS scores with shorter intubation times and had a lower incidence of coughing and choking. The endoscopists’ VAS scores also showed a preference for group B.

Conclusion

In conclusion the ‘spray as you go’ technique was safe, provided effective local anaesthesia and was preferred by both patients and endoscopists.Key Words: Awake intubation, Difficult airway, Fiberoptic intubation     

Pain relief following Arthroscopy - a comparative study of Intra-articular Bupivacaine,Morphine and Neostigmine

Pain after arthroscopy is quite distressing. Intra-articular bupivacaine produces transient analgesia and reports of analgesia using intra-articular opioids have produced conflicting results. Recently, spinal administration of neostigmine was shown to produce dose-dependant analgesia. However, this was limited by adverse effects. The purpose of this study was to compare the effects on intra-articular neostigmine, bupivacaine and morphine. 75 patients were randomized to receive intra-articular saline, bupivacaine, morphine, neostigmine and bupivacaine-neostigmine after arthroscopic surgery under spinal anaesthesia. Visual analog pain scores (VAS), duration of analgesia as defined as time for first demand for parenteral opioids and the total subsequent consumption of morphine was evaluated. Intra-articular bupivacaine resulted in significant VAS reduction at one and four hours as compared to those receiving intra-articular saline and morphine. Analgesia lasted longer after 500ugm intra-articular neostigmine as compared with bupivacaine, morphine or saline. The need for supplementary analgesia was lowest in the neostigmine group as compared to the other groups. No significant difference was found if bupivacaine was added to neostigmine. Among all the groups, no significant side-effects were observed.Key Words: Arthroscopy, Bupivacaine, Morphine, Neostigmine     

Brinzolamide : a review of its use in the management of primary open-angle glaucoma and ocular hypertension

Brinzolamide is a highly specific carbonic anhydrase (CA) inhibitor which lowers intraocular pressure (IOP) by reducing the rate of aqueous humour formation. Formulated as a 1% ophthalmic suspension (Azopt) and administered twice or three times daily, brinzolamide is indicated for the topical management of primary open-angle glaucoma (POAG) and ocular hypertension (OH) as either monotherapy or adjunctive therapy with topical beta-blockers. As monotherapy in patients with POAG or OH, brinzolamide 1% demonstrated IOP-lowering efficacy that was significantly greater than placebo, equivalent to three-times-daily dorzolamide 2% but significantly lower than twice-daily timolol 0.5%. Brinzolamide 1% was equally effective in twice- and three-times-daily regimens producing diurnal mean IOP reductions from baseline in the range of 13.2-21.8%. When used adjunctively twice daily with timolol 0.5%, brinzolamide 1% was as effective as dorzolamide 2% and superior to placebo in lowering IOP in patients with POAG or OH. In clinical trials, brinzolamide 1% was well tolerated causing only nonserious adverse effects that were generally local, transient and mild to moderate in severity. The incidence of the most common adverse events associated with the use of brinzolamide 1% was either similar to (blurred vision and abnormal taste) or significantly lower than (ocular discomfort) with dorzolamide 2%. Topical brinzolamide 1% does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse effects characteristic of oral CA inhibitors. It can be used in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated. Brinzolamide 1% administered twice daily is among the least costly alternatives and adjuncts to beta-blocker therapy for glaucoma and is generally associated with less direct medical cost than dorzolamide. CONCLUSION: Brinzolamide 1% ophthalmic suspension administered twice or three times daily, as monotherapy or adjunctive therapy with topical beta-blockers, has good IOP-lowering efficacy in patients with POAG or OH that is equivalent to that of dorzolamide 2% (three times daily as monotherapy, twice daily as adjunctive therapy). Brinzolamide is generally well tolerated and does not produce the systemic adverse effects associated with oral CA inhibitors. It can be used in patients who are unresponsive to, intolerant of, or unable to receive, ophthalmic beta-blockers. Thus, brinzolamide, either as monotherapy or adjunctive therapy with topical beta-blockers, should be regarded as a good second-line option in the pharmacological management of POAG and OH, and may be preferred over dorzolamide because of significantly less ocular discomfort.     

Pancreaticoduodenectomy with vascular reconstruction for adenocarcinoma of the pancreas with borderline resectability

AIM: To analyze whether pancreaticoduodenectomy with simultaneous resection of tumor-involved vessels is a safe approach with acceptable patient survival.METHODS: Between January 2001 and March 2012, 136 patients received pancreaticoduodenectomy for adenocarcinoma at our hospital. Seventy-eight patients diagnosed with pancreatic head carcinoma were included in this study. Among them, 46 patients received standard pancreaticoduodenectomy (group 1) and 32 patients received pancreaticoduodenectomy with simultaneous resection of the portal vein or the superior mesenteric vein or artery (group 2) followed by reconstruction. The immediate surgical outcomes and survivals were compared between the groups. Fifty-five patients with unresectable adenocarcinoma of the pancreas without liver metastasis who received only bypass operations (group 3) were selected for additional survival comparison.RESULTS: The median ages of patients were 67 years (range: 37-82 years) in group 1, and 63 years (range: 35-86 years) in group 2. All group 2 patients had resection of the portal vein or the superior mesenteric vein and three patients had resection of the superior mesenteric artery. The pancreatic fistula formation rate was 21.7% (10/46) in group 1 and 15.6% (5/32) in group 2 (P = 0.662). Two hospital deaths (4.3%) occurred in group 1 and one hospital death (3.1%) occurred in group 2 (P = 0.641). The one-year, three-year and five-year overall survival rates in group 1 were 71.1%, 23.6% and 13.5%, respectively. The corresponding rates in group 2 were 70.6%, 33.3% and 22.2% (P = 0.815). The one-year survival rate in group 3 was 13.8%. Pancreaticoduodenectomy with simultaneous vascular resection was safe for pancreatic head adenocarcinoma.CONCLUSION: The short-term and survival outcomes with simultaneous resection were not compromised when compared with that of standard pancreaticoduodenectomy.     

双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化

目的　在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法　 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5～ 17岁 ) ,引起短肢的病因不同。术后 7～ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果　不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%～ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%～ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论　DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。     

Experience with the Amplatz retrievable vena caval filter. Work in progress

The Amplatz retrievable vena caval filter was designed in an attempt to decrease complications associated with the placement of Mobin-Uddin or Kimray-Greenfield filters. The design allows percutaneous retrieval, thus expanding application of the filter to situations requiring temporary prophylaxis against pulmonary embolism. Filters have been placed in 16 patients, nine (56%) for prophylactic purposes. All filters were easily inserted percutaneously. Complications occurred in three patients; these included complete thrombosis of the inferior vena cava below the filter, misplacement of one filter into the pericaval retroperitoneal tissue, and development of thrombus cranial to the filter. With the current introduction system, the possibility of filter misplacement has been essentially eliminated. No patient experienced symptoms suggestive of pulmonary embolism after filter insertion. One filter retrieval has been performed, with no complications.