bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective Peripheral Regulation Of Noradrenaline And Adrenaline Release By Nitric Oxide
Authors: Elayan Hamzeh H , Kennedy Brian P , Ziegler Michael G 
Published: March 2003

SUMMARY1. Nitric oxide (NO) has complex effects on the sympathoadrenal and cardiovascular systems and may act at both central and peripheral loci. Nitric oxide appears to act directly on blood vessels and indirectly by modulating the sympathoadrenal system. In the present study, we investigated the contribution of catecholamine release from peripheral vascular and adrenal sympathetic nerves to the cardiovascular effects of the NO synthesis inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME; 10 mg/kg). Our experiments were perfomed in pithed vagotomized rats to remove the influence of central and baroreflex pathways.2. Spinal cord stimulations for 30 s periods at 1, 2, 5 and 10 Hz using pulses of 1 msec at 10 V caused marked increases in plasma adrenaline and noradrenaline. NG‐Nitro‐L‐arginine methyl ester did not alter resting plasma catecholamine concentrations. However, L‐NAME generally more than doubled stimulation‐evoked release of adrenaline while reducing the extent of noradrenaline release relative to vehicle (saline)‐treated controls.3. NG‐Nitro‐L‐arginine methyl ester significantly enhanced the vasopressor responses to spinal cord stimulation. The α1‐adrenoceptor antagonist prazosin (0.2 mg/kg) reduced the pressor responses of electrically stimulated L‐NAME‐treated rats to levels below those of vehicle‐treated control rats.4. In the absence of electrical stimulation, L‐NAME raised the blood pressure of pithed rats without altering plasma catecholamines and the pressor effect was briefly attenuated by L‐arginine, but was unaffected by prazosin.5. We conclude that the augmented pressor response to sympathetic stimulation in L‐NAME‐treated pithed rats is due largely to enhanced adrenal adrenaline release mediated by a peripheral mechanism. Stimulation of α1‐adrenoceptors plays a major role in the pressor response to electrical stimulation of L‐NAME‐treated rats, but this is not due to L‐NAME augmentation of noradrenaline release from vascular sympathetic nerves.
Different Effects Of β‐Adrenoceptor Desensitization On Inhibitory Actions In Guinea‐Pig Trachealis
Authors: Mizutani Hiroshi , Kume Hiroaki , Ito Yasushi , Takagi Kenzo , Yamaki Kenichi 
Published: March 2003

SUMMARY1. To determine the inhibitory effects of agents that pass through and bypass β‐adrenoceptors under conditions of tolerance to β‐adrenoceptor agonists, we examined the inhibition by the β‐adrenoceptor agonists forskolin and theophylline against contraction induced by methacholine (MCh) after exposure to higher concentrations of a β‐adrenoceptor agonist for a long time in guinea‐pig tracheal smooth muscle, using isometric tension records.2. After exposure to procaterol (0.0003–3 μmol/L) for 45 min, the inhibitory effect of 0.03 μmol/L procaterol on 1 μmol/L MCh‐induced contraction was attenuated in a concentration‐dependent manner, whereas after exposure to isoprenaline (0.0003–3 μmol/L) for an equivalent time, the inhibitory effect of isoprenaline was markedly attenuated at each concentration. However, after exposure to 3 μmol/L procaterol for 45 min, the inhibitory actions of forskolin and theophylline were, conversely, augmented.3. These phenomena were observed under conditions whereby the response to MCh returned to control levels 6 h after removal of 3 μmol/L procaterol. The percentage inhibition produced by 0.1 μmol/L forskolin against 1 μmol/L MCh after exposure to normal bathing solution or 3 μmol/L procaterol for 45 min was 9.8 ± 5.5 and 82.8 ± 6.5%, respectively (P < 0.001). These values for 100 μmol/L (18 μg/mL) theophylline on MCh resposnes were 9.9 ± 8.5 and 88.0 ± 4.4% (n = 6 for both), respectively (P < 0.001).4. The inhibitory action of agents that bypass β‐adrenoceptors was markedly augmented under conditions of β‐adrenoceptor desensitization in airway smooth muscle.5. In conclusion, procaterol is less potent in causing desensitization of β‐adrenoceptors than isoprenaline. The activity of adenylyl cyclase may be enhanced after exposure to a high concentration of β‐adrenoceptor agonists.
Why do neuroprotective drugs that are so promising in animals fail in the clinic? An industry perspective
Authors: Green A Richard 
Published: March 2003

Summary1. No neuroprotective drug has yet been shown to be effective in treating acute ischaemic stroke in the clinic, despite evidence of efficacy in animal models.2. An academic/industry round‐table group recently published guidelines to be met if a drug was to be progressed to clinical trial.3. Major points included obtaining full dose–response evaluation and measurement of the therapeutic time window for efficacy, functional behavioural testing in addition to measurement of infarct volume, measurement of physiological parameters, use of appropriate models (transient and permanent focal ischaemia) and reproducibility of data by external laboratories.4. The present paper examines both failed compounds and disodium 4‐[(tert‐butylimino) methyl] benzene‐1, 3‐disulphonate N‐oxide (NXY‐059), a nitrone radical‐trapping agent currently in clinical development. It aims to determine whether these guidelines were met by compounds that have failed and, thus, determine whether following the guidelines, as is being done with NXY‐059, will increase the chances of developing efficacious drugs for treating acute ischaemic stroke.5. It is concluded that we will only achieve the goal of producing a clinically effective neuroprotective agent if the guidelines have been met by the novel compound under investigation.
Gender differences in the regulation of vascular tone
Authors: Thompson Janell , Khalil Raouf A 
Published: March 2003

Summary1. The greater incidence of hypertension and coronary artery disease in men and post‐menopausal women compared with premenopausal women has suggested vascular protective effects of the female sex hormone oestrogen. However, vascular effects of the female sex hormone progesterone and the male sex hormone testosterone have also been suggested.2. Oestrogen, progesterone and testosterone receptors have been identified in the plasmalemma, cytosol and nuclear compartments of vascular cells. The interaction of sex hormones with their specific receptors triggers not only long‐term genomic vascular effects, but also acute non‐genomic vascular responses.3. Sex hormones may activate endothelium‐dependent vascular relaxation pathways, including the nitric oxide–cGMP and prostacyclin–cAMP pathways and a hyperpolarizing factor pathway.4. Sex hormones may also inhibit the mechanisms of vascular smooth muscle contraction, such as [Ca2+]i, protein kinase C and other protein kinases.5. The sex hormone‐induced stimulation of endothelium‐dependent vascular relaxation and inhibition of vascular smooth muscle contraction may contribute to the gender differences in vascular tone and may represent potential beneficial vascular effects of hormone‐replacement therapy during natural and surgically induced deficiencies of gonadal hormones.
Green tea catechins evoke a phasic contraction in rat aorta via H2O2‐mediated multiple‐signalling pathways
Authors: Shen Jian‐Zhong , Zheng Xiu‐Feng , Wei Er‐Qing , Kwan Chiu‐Yin 
Published: March 2003

Summary1. The contractile effects of tea polyphenols (TP) and its four principle catechins, namely (–)‐epicatechin (EC), (–)‐epicatechin‐3‐gallate (ECG), (–)‐epigallocatechin (EGC) and (–)‐epigallocatechin‐3‐gallate (EGCG), on rat aorta contractility were investigated using the isometric tension recording technique.2. At concentrations of 5–100 mg/L, TP evoked phasic contraction of rat aorta in a concentration‐dependent but endothelium‐independent manner. Of the four catechins tested, EGCG and EGC (3–300 µmol/L), but not EC and ECG, mimicked the contractile response to TP, suggesting that the epigallol moiety in the B ring may be associated with the contractile effect.3. Contractions in response to EGCG and EGC were not affected by several endogenous vasoconstrictor receptor antagonists, but could be abolished by 10 µmol/L BAPTA‐AM, a membrane‐permeable Ca2+ chelator, or attenuated by removal of extracellular Ca2+, suggesting the involvement of both intracellular and extracellular Ca2+ in evoking the contraction.4. Pretreatment with non‐selective Ca2+ channel antagonists mefenamic acid (10 µmol/L), tetrandrine (30 µmol/L) and SKF 96365 (30 µmol/L), but not nifedipine (1 µmol/L), the selective inhibitor of voltage‐dependent Ca2+ channels, inhibited the contractile responses to EGC and EGCG, indicating the involvement of Ca2+ influx via non‐voltage dependent Ca2+ channels.5. Several intracellular Ca2+ channel modulators, including procaine (5 mmol/L), dantrolene (30 µmol/L) and 2‐amino ethoxydiphenyl borate (50 µmol/L; an inositol 1,4,5‐trisphosphate receptor inhibitor), also inhibited EGCG‐ and EGC‐induced contractions, thus suggesting a role of intracellular Ca2+ release in these contractions.6. Both EGCG‐ and EGC‐induced contractions were depressed, to different degrees, by inhibitors of several receptor‐coupled enzymes, including phospholipase C, protein kinase C, phospholipase A2 and tyrosine kinase. Furthermore, both EGCG‐ and EGC‐induced contractions were completely abolished by catalase, but not by superoxide dismutase or mannitol/dimethyl sulphoxide.7. Taken together, these data show, for the first time, that TP and its related catechins that contain an epigallol structure in the B ring, as in EGCG and EGC, exert direct contractile effects on rat aortic smooth muscle via a H2O2‐mediated pathway.
Cardiac mitochondrial complex activity is enhanced by heat shock proteins
Authors: Sammut Ivan A , Harrison Joanne C 
Published: March 2003

Summary1. Prolonged ischaemia and reperfusion in heart transplantation results in mitochondrial dysfunction and loss of cardio‐energetics. Improved myocardial tolerance to ischaemia–reperfusion can be increased by de novo synthesis of heat shock protein (Hsp) groups, transiently expressed following mild hyperthermic or oxidative stress. Consideration of the roles of various Hsp in ischaemic–reperfused myocardium can provide new insights into potential therapeutic adjuncts to cardiac surgery.2. Several Hsp classes have been located within or in association with mitochondrial elements. Cardiac Hsp research has focused primarily on the 70 kDa group, involved in protein folding functions within the cytosol and matrix. Similarly, Hsp 60 and 10 have been shown to form a mitochondrial chaperonin complex conferring protection to ischaemia‐challenged myocytes. Equally pertinent is Hsp 32, an isoform of the haem‐metabolizing enzyme heme oxygenase.3. Our studies have shown that mitochondrial respiratory enzyme activity can be protected by Hsp, affording protection to cardiac energetics during preservation for transplantation. Upregulation of Hsp 32, 60 and 72 in rats, achieved by mild hyperthermic stress, improved cardiac function, ultrastructure and mitochondrial respiratory and complex activities in ex vivo perfused hearts subjected to cold cardioplegic arrest and ischaemia–reperfusion. Pre‐ischaemic mitochondrial complex activities were increased in heat stress versus sham‐treated groups for complex I, IV and V.4. Investigation of the direct effect of upregulation of Hsp 72 by gene transfection resulted in a similar pattern of response, with increased complex I activity and improved ventricular function.5. These studies provide the first evidence of Hsp‐mediated enhancement of mitochondrial energetic capacity. Enhanced protection of mitochondrial energetics, as a result of increased Hsp expression, contributes to the recovery of myocardial function in ischaemia–reperfusion.
Fatal methanol poisoning following home distillation of methylated spirits
Authors: Foley Bernard , Rogers Ian R 
Published: March 2003

AbstractWe present the case report of a 47‐year‐old man fatally poisoned by ingestion of a home‐distilled liquor produced from ‘methylated spirits’ containing 5% methanol and 90% ethanol. Classical signs of severe methanol poisoning, including altered conscious state, shock and profound acidosis were manifest at the time of presentation. Despite an ethanol infusion and haemodialysis he was declared brain dead 36 h after arrival at the emergency department.
Setting the benchmark for research in the management of acute pain in emergency departments
Authors: Kelly Anne‐Maree 
Published: March 2003

AbstractObjective:The aim of this study was to define the degree of change on a visual analogue scale that corresponded to a clinically meaningful reduction in the level of pain reported by patients experiencing acute pain.Method:Secondary analysis of data was performed from prospective, descriptive studies of 152 adults and 73 children presenting to emergency departments with acute pain. At presentation and at 20 min intervals to a maximum of three measurements, patients marked the level of their pain on a 100 mm, non‐hatched visual analogue scale. At each follow up, they also gave a verbal rating of their pain as ‘a lot better’, ‘a little better’, ‘much the same’, ‘a little worse’ or ‘much worse’. Data from the groups reporting that pain was ‘a lot better’ and ‘about the same’ were analysed for mean and median absolute change in visual analogue scale and compared.Results:Of 559 pain comparisons, 60 were rated as ‘a lot better’ and 257 as ‘about the same’. The mean absolute change in visual analogue scale for the group reporting that pain was ‘a lot better’ was 24 mm (median = 19 mm, 95% confidence interval = 17–31 mm). For the group reporting that pain was ‘about the same’, the mean visual analogue scale change was 0 mm (median = 0 mm, 95% confidence interval = −1 to 1 mm).Conclusion:When evaluating treatments for acute pain, a difference in visual analogue scale pain score of less than about 20 mm is unlikely to be clinically meaningful. Studies should be designed and reported relative to this benchmark rather than the minimum clinically significant difference in visual analogue scale pain score.
Implementation and evaluation of an undergraduate emergency medicine curriculum
Authors: Celenza Antonio , Jelinek George A , Jacobs Ian , Kruk Chris , Graydon Robert , Murray Lindsay 
Published: March 2003

AbstractObjective:To describe the implementation and evaluation of an undergraduate course in the first Australian academic emergency medicine unit.Methods:A descriptive study of a course involving fifth year medical students at the University of Western Australia was undertaken. Teaching included self‐directed case problem solving, small group tutorials, practical‐skills teaching, clinical attachments and information handouts. Evaluation involved questionnaire scores and written feedback regarding life‐support skills, tutorial teaching, course materials, clinical attachments and the course in general. Some groups of students underwent pre‐course and post‐course examinations.Results:Subjective and objective testing showed that student knowledge significantly improved. Feedback was especially positive toward clinical attachments in emergency departments, practical skills tutorials and the case‐based learning method. Students requested longer attachments to emergency departments, and more practical, case‐based, interactive and bedside teaching. Problems encountered included inadequate time for teaching, vagueness about student roles and objectives, and dealing with death for the first time without adequate preparation.Conclusion:Undergraduate emergency medicine education should become an essential part of Australian and international undergraduate medical education. Emergency medicine is enjoyable and eminently suitable for problem‐based, interactive and integrated teaching and improves confidence, clinical experience in emergencies, practical skills and teamwork. Improvements include more problem‐based teaching, more practical skills sessions and better definition of student roles. These are general principles that can be applied to other undergraduate courses and to designers of other emergency medicine courses, both undergraduate and postgraduate.
Hepatocellular carcinoma: Screening and non‐surgical treatment
Authors: Man‐Fung Yuen , Ching‐Lung Lai 
Published: March 2003

Hepatocellular carcinoma (HCC) is the second commonest cancer in Hong Kong. Recent advances show that HCC can be derived from hepatocytes and from progenitor oval cells. Those from progenitor oval cells express both hepatocyte and biliary markers and are associated with poorer differentiation, more cellular proliferation, more aggressive clinical course and poorer prognosis. Patients with HCC usually present late and the choice of treatment modalities will be limited. Screening for early subclinical HCC in high‐risk groups is indicated. In patients diagnosed by screening, the clinical parameters were significantly more favourable, with a higher resectability rate, a higher chance of responding to transarterial chemoembolization (TACE) and a better survival. Treatment for HCC at present is still not satisfactory because of the late presentation, low resection rate, the high recurrence/new occurrence rate and the high prevalence of background cirrhosis. Surgical resection remains the first choice of treatment. However, there is a high recurrence rate. Medical treatment for inoperable HCC can be divided into systemic and local/regional therapy. To date, there are relatively few randomized controlled trials. Systemic therapy consists of the use of doxorubicin, alpha‐interferon, tamoxifen or combination therapy. For the local/regional therapy, alcohol injection and TACE with lipiodol are the two commonly used methods. Selective intra‐arterial infusion of 90yttrium has also been described. Randomized controlled trials are urgently needed to assess the efficacy of various medical treatments.
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Biliary‐enteric bypass in unresectable malignant hilar biliary obstruction: Kwong Wah Hospital experience
Authors: Yeung YP , AhChong AK , Wong WC , Yip AWC 
Published: March 2003

Objective: To evaluate the efficacy of biliary‐enteric bypass in the palliation of malignant hilar biliary obstruction. Materials and Methods: Records of 19 patients from 1995 to 1998 were reviewed. There were 13 patients with cholangiocarcinoma and 6 patients with carcinoma of the gallbladder. Single biliary‐enteric bypass had been performed in 13 of the patients; the rest had more than one biliary‐enteric anastomosis. Results: The 30‐day mortality was 21% (4/19 patients). Bile leakage occurred in 2 patients, leading, in both, to fatality. Excluding the 30‐day mortality, the median survival of patients with carcinoma of the gallbladder and cholangiocarcinoma was 116 days (43–200) and 202 days (47–1207), respectively. The mean hospital stay was 31 days (13–59) and all patients were discharged with their symptoms relieved and a drop in bilirubin of at least two‐thirds their pre‐operative level. The late complication rate was 26.7% (4/15 patients). Conclusion: Biliary‐enteric bypass is effective in the palliation of symptoms of patients suffering from unresectable hilar biliary obstruction, although it carries considerable mortality and morbidity. Stenting, rather than surgery, should be considered for patients with unresectable gallbladder cancer.
Management of overdrainage in cerebrospinal fluid shunting
Authors: Leung Km , Yam Ky , Fong Dawson 
Published: March 2003

Objective: To reveal the effectiveness and safety of adding a single slit valve serially to the ventriculoperitoneal shunt system in order to reverse overdrainage. Materials and Methods: The study is a retrospective review of clinical experience in a regional hospital (Tuen Mun Hospital, Hong Kong). A series of 10 cases are reported. All cases showed evidence of cerebrospinal fluid overdrainage after a ventriculoperitoneal shunt procedure. The advantages and disadvantages of other treatment options are also reviewed. Results: The symptoms of all six patients who presented symptomatically subsided or improved after the procedure. Nine of the 10 patients had radiological improvement in their postoperative computed tomography scan. No procedure‐related complication occurred. Conclusion: The early results of such a treatment option appeared safe and rewarding. However, longer term follow up and more experience is needed before the treatment’s efficacy can be proved definitely.
Is the change of bacterial flora after circumcision persistent?
Authors: Wong Wai‐Man , Lau Kwong‐Yau , Wong Che‐Yung , Tsui King‐Yiu , Lau Kwok‐Wai 
Published: March 2003

A prospective study of 60 boys who had undergone circumcision in the summer of 1996 was performed at Department of Surgery, Tuen Mun Hospital, Hong Kong. In our previous study in 1996, we showed that there was significant reduction in uropathogens after circumcision in the early postoperative period (up to day 30). In the present longitudinal study, we showed that the change of peri‐urethral bacterial flora after circumcision persists for 18 months after operation in the same group of patients (51 of 60 patients from the previous study were recruited). There was no Staphylococcus aureus colonization in this study. The present study provides circumstantial evidence supporting the idea that circumcision in selected patients may confer long‐term protection from urinary infection.
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Supratentorial extraventricular ependymoma: Literature review and case report
Authors: Pang Kai‐Yuen , Ho Wilson Wai‐Shing , Wong Chi‐Keung 
Published: March 2003

A 20‐year‐old male underwent surgery for an occipital extraventricular multicystic tumour. The tumour’s histology was high‐grade anaplastic ependymoma. The clinical course, its radiological appearance and the prognosis are discussed. Chinese Abstract imageimage
A study of the indications and changing trends of evisceration in north India
Authors: Dada Tanuj , Ray Manotosh , Tandon Radhika , Vajpayee Rasik B 
Published: March 2003

Abstract Aim: To study the demographic pattern and indications for evisceration in north India and to evaluate the changing trends over the last decade. Methods: In a retrospective hospital‐based study, case records of all patients who underwent evisceration at Rajendra Prasad Centre for Ophthalmic Sciences from January 1990 to December 1999 were reviewed. The parameters evaluated were the age and sex distribution, the place of residence (urban/rural) and the indications for evisceration. The aetiology responsible for evisceration was determined on the basis of history, clinical examination and investigations as determined from previous records. Results: One hundred and sixty‐four patients had one eye eviscerated
during the study period. The mean age of the patients was 51 ± 13.84 years
(range 6 months to 90 years). Panophthalmitis
was the most common indication for evisceration (78.6%, n = 129),
followed by irreparable globe injury (21.3%, n = 35). There was a significant decrease in the eviscerations performed due to pano‐phthalmitis from 104 cases during the period 1990−1994, to 25 cases in the period 1995−1999. Conclusion: Panophthalmitis and severe ocular injury are the major indications of evisceration in north India. There has been a significant decrease in the number of eviscerations related to panophthalmitis over the last decade.