Amplification of sumatriptan-induced contractions with phenylephrine,histamine and KCl in the isolated human mesenteric artery: in-vitro evidence for sumatriptan-induced mesenteric ischaemia

Sumatriptan, a 5-HT(1B/1D/1F) receptor agonist, is used to relieve migraine headache. Sumatriptan contracts some arteries either directly or after modest precontraction with non-serotonergic agonists. Sumatriptan can cause myocardial ischaemia and myocardial infarction. While previous in-vitro studies have shown that sumatriptan has no or only weak contractile activity in human omental arteries, recent clinical studies suggest that sumatriptan may induce mesenteric ischaemia. The aim of this study was to investigate the presence of contractile 5-HT(1B) receptors in the human mesenteric artery and to establish whether the weak sumatriptan-induced contractions are amplified by precontraction with various contractile substances. The study was performed in organ baths using endothelium-denuded isolated human mesenteric arteries. Sumatriptan induced concentration-dependent contractions in some mesenteric arteries [ E(max) 61+/-10% of the maximum contraction induced by 80 mM KCl, pD(2) (-log(10)EC(50)) 6.56+/-0.20, n=9]. In the other mesenteric arteries, sumatriptan induced only very weak ( E(max) <5%) or no contraction ( n=13). GR127935 (3 nM), a selective 5-HT(1B) receptor antagonist, antagonized sumatriptan-induced contractions insurmountably in sumatriptan-sensitive arteries. When the resting tension of the arterial rings was increased moderately by threshold concentrations (EC(10)-EC(20) of maximum contraction induced by 80 mM KCl) with the non-5-HT receptor agonists phenylephrine (10-100 nM), histamine (100 nM-1 microM) or the depolarizing agent KCl (4-10 mM), 5-HT(1B) receptor-mediated responses were amplified in sumatriptan-insensitive arteries (with phenylephrine E(max) 82+/-17%, pD(2) 6.64+/-0.20, n=7; with histamine E(max) 107+/-26%, pD(2) 6.16+/-0.14, n=6; with KCl E(max) 78+/-16%, pD(2) 6.45+/-0.15, n=7). These results show that sumatriptan induced concentration-dependent contractions in sumatriptan-sensitive mesenteric arteries and that 5-HT(1B) receptors were present and active in these vessels. However, in sumatriptan-insensitive arteries, precontraction is required for sumatriptan to induce concentration-dependent contractions. These findings suggest that sumatriptan may induce ischaemia in human mesenteric vasculature directly or in the presence of precontractile risk factors.     

Antifungal evaluation of bis Mannich bases derived from acetophenones and their corresponding piperidinols and stability studies

The development of resistance to current antifungal therapeutics drives the search for effective new agents. The fact that some acetophenone-derived Mannich bases had shown antifungal activities in our previous studies led us to design and synthesize acetophenone-derived bis Mannich bases, B1-B5, bis(beta-aroylethyl)methylamine hydrochlorides, to evaluate their antifungal activity. These bis Mannich bases were then converted to the corresponding piperidinols, C1-C5, which are structural isomers of bis derivatives, 3-aroyl-4-aryl-1-methyl-4-piperidinol hydrochlorides, to see alterations in biological activity. A stability study of B1 and Cl was also carried out to estimate whether they alkylate the thiols. All compounds studied have shown antifungal activity, especially against dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, and Microsporum canis), in the concentration range studied (2-128 microng/ml). The activity was especially apparent against T. tonsurans. All compounds had at least equal antifungal activity compared with the reference compound amphotericin-B against T. tonsurans. Bis Mannich bases were generally found to be more potent compounds than their structural isomer piperidinols. The results of our stability studies suggest that thiol alkylation may contribute to the antifungal activity of the Mannich bases synthesized. Even though all compounds showed antifungal activity against dermatophytes, bis Mannich bases B1, B2, B4, and B5 appear to have potential for developing novel antifungal agents against dermatophytes.     

Effect of topically applied charged particles on healing of colonic anastomoses

HYPOTHESIS: Various forms of electrical stimulation can improve wound healing in different tissues, but their application to gastrointestinal tract healing has not been investigated. We assumed that positively charged diethylaminoethyl cross-linked dextran bead (diethylaminoethyl Sephadex [DEAE-S]) particles would have a beneficial effect on the healing of colonic anastomoses. DESIGN: Experimental animal study. SETTING: Animal research laboratory of a university hospital. ANIMALS: Forty female Wistar albino rats. INTERVENTIONS: Right colonic transection and anastomosis was performed in 5 animal groups. The control group received no treatment; the placebo group, methylcellulose gel; and the DEAE-S group, DEAE-S in methyl cellulose gel applied topically around the anastomoses. The fecal peritonitis (FP) group underwent cecal ligation and perforation simultaneously with the anastomosis to cause FP; the FP + DEAE-S group also received DEAE-S applied around the anastomoses. MAIN OUTCOME MEASURES: After the completion of postoperative day 4, all rats were killed. Anastomotic bursting pressures and hydroxyproline concentrations in perianastomotic tissue were measured and compared. RESULTS: Mean bursting pressures were 115.1 mm Hg in the control group, 113.6 mm Hg in the placebo group, 159.4 mm Hg in the DEAE-S group, 62.8 mm Hg in the FP group, and 121.1 mm Hg in the FP + DEAE-S group (P =.001, 1-way analysis of variance [ANOVA]). The differences between the control vs DEAE-S groups, placebo vs DEAE-S groups, and FP vs FP + DEAE-S groups were significant (P<.05, t test). Mean hydroxyproline concentrations were 5.2 microg/mg in the control group, 4.9 microg/mg in the placebo group, 5.6 microg/mg in the DEAE-S group, 4.5 microg/mg in the FP group, and 5.4 microg/mg in the FP + DEAE-S group (P =.09, 1-way ANOVA). The difference between the FP and FP + DEAE-S groups was significant (P =.04, t test). CONCLUSIONS: A positively charged particle, DEAE-S, improves healing of colonic anastomoses in healthy rats and in rats with FP. This inexpensive, nontoxic material is easily applied and deserves further evaluation in gastrointestinal tract healing.     

Decreased mitochondrial proton leak and reduced expression of uncoupling protein 3 in skeletal muscle of obese diet-resistant women

Weight loss in response to caloric restriction is variable. Because skeletal muscle mitochondrial proton leak may account for a large proportion of resting metabolic rate, we compared proton leak in diet-resistant and diet-responsive overweight women and compared the expression and gene characteristics of uncoupling protein (UCP)2 and UCP3. Of 1,129 overweight women who completed the University of Ottawa Weight Management Clinic program, 353 met compliance criteria and were free of medical conditions that could affect weight loss. Subjects were ranked according to percent body weight loss during the first 6 weeks of a 900-kcal meal replacement protocol. The highest and lowest quintiles of weight loss were defined as diet responsive and diet resistant, respectively. After body weight had been stable for at least 10 weeks, 12 of 70 subjects from each group consented to muscle biopsy and blood sampling for determinations of proton leak, UCP mRNA expression, and genetic studies. Despite similar baseline weight and age, weight loss was 43% greater, mitochondrial proton leak-dependent (state 4) respiration was 51% higher (P = 0.0062), and expression of UCP3 mRNA abundance was 25% greater (P < 0.001) in diet-responsive than in diet-resistant subjects. There were no differences in UCP2 mRNA abundance. None of the known polymorphisms in UCP3 or its 5' flanking sequence were associated with weight loss or UCP3 mRNA abundance. Thus, proton leak and the expression of UCP3 correlate with weight loss success and may be candidates for pharmacological regulation of fat oxidation in obese diet-resistant subjects.     

Requirements of clinical excellence

The history of the evidence based medicine, health technology assessment, health economics and quality improvement proved to be a success story in developed countries. It is partly due to that change in the attitude towards health care occurred in the past ten or fifteen years. Two major factors played important roles in this process. On the one hand, the booming health care costs in developed countries, and on the other, the health benefit was not proportional to costs. First, governments around the world applied the tool of cutting costs, which proved to be uneffective even in mid-term. It was soon revealed that people prefer good-quality health care rather than the cheap one. These disciplines are having a more and more considerable influence on medical care and nursing. However, impacts on health care are not automatic and can be most different regarding both their quantity and nature. They may result in a significant improvement in prevention, diagnostics, cure and care, and may yield a more appropriate use of ever-limited resources.     

Reinterpretation of cross-sectional images in patients with head and neck cancer in the setting of a multidisciplinary cancer center

BACKGROUND AND PURPOSE: Patients referred to tertiary care centers frequently arrive with images obtained at outside institutions; these images require reinterpretation. We assessed the clinical value of reinterpreting cross-sectional imaging studies of patients with head and neck cancer, in the setting of a multidisciplinary cancer center. METHODS: Outside CT and MR images of 136 patients with known or presumed head and neck cancer were reinterpreted by a neuroradiologist. Clinical history and findings on physical examination were available. Reinterpretation was performed before review of outside reports, which were subsequently compared with those generated at the cancer center. Changes in interpretation were noted, and their effects on TNM staging, patient care, and prognosis were assessed. Reliability and statistical significance of rates of change in diagnosis were analyzed with 95% confidence intervals (CIs) and the sign test, respectively. Verification of change in diagnosis was confirmed by pathologic analysis (75%), characteristic radiologic findings (18%), or clinical and imaging follow-up (7%). RESULTS: Change in interpretation occurred in 56 patients (41%) (95% CI: 33-49%, P <.001). Forty-six patients (34%) had a change in T, N, and/or M staging (26-42%, P <.001). Change in T stage occurred in 27 cases (20%) (13-27%, P <.001) (upstaged in 22, downstaged in five), and a change in N stage in 26 cases (19%) (12-26%, P <.001) (upstaged in 20, downstaged in six). Two patients (1.5%) had missed systemic metastases. Three patients with an initial diagnosis of cancer were found to be cancer-free, and six patients had a diagnosis of new second primary cancers that were missed at original interpretation. One patient had a missed middle cerebral artery aneurysm. Changes in image interpretation altered treatment in 55 (98%) of 56 patients and affected prognosis in 53 patients (95%) (P <.001). CONCLUSION: Reinterpretation of cross-sectional images in the setting of a multidisciplinary cancer center has a significant effect on staging, management, and prognosis in patients with head and neck cancer.     

Risk-adjusted infection rates in surgery: a model for outcome measurement in hospitals developing new quality improvement programmes

Assessment of healthcare quality is a major challenge in countries such as Hungary where there is limited experience with measurement of patient outcomes. We sought to develop the capacity for valid outcome measurement in Hungarian hospitals using surgical site infection (SSI) surveillance as a model and to identify areas for improvement by comparing SSI rates in Hungarian hospitals to benchmarks published by the United States Centers for Disease Control and Prevention's National Nosocomial Infection Surveillance (NNIS) System. We surveyed the incidence of SSI among 5126 patients undergoing 6006 procedures in 20 public hospitals in Hungary during 1996 using the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) protocol, a protocol consistent with the methods used by the NNIS System. Cholecystectomy, herniorrhaphy, appendectomy, and open reduction of fracture--four of the five most commonly performed procedures in Hungary in 1996--comprised 85% of the procedures analysed. Cumulative SSI rates for herniorrhaphy and appendectomy were comparable to NNIS System benchmarks. Cumulative SSI rates for cholecystectomy were significantly higher in Hungarian hospitals among risk categories that included open procedures. Nearly half of the hospitals had SSI rates for cholecystectomy that were high outliers (>90% percentile) compared to NNIS System benchmarks. Cumulative SSI rates for open reduction of fracture and mastectomy were significantly higher in Hungarian hospitals due to high rates in a few hospitals. The duration of surgery for all procedure types was substantially shorter in Hungarian hospitals compared with NNIS System hospitals. Future work should focus on optimizing prevention strategies for patients undergoing cholecystectomy, open reduction of fracture, and mastectomy. The effect of the utilization of open vs. laparoscopic cholecystectomy, short procedure duration, and procedure volume on SSI rates should be evaluated further. This programme expanded the capacity of Hungarian hospitals to perform surgical site infection surveillance and can serve as a model for hospitals in other countries with limited experience with outcome measurement.     

TRANSSCLERAL DIODE LASER CYCLOPHOTOCOAGULATION IN REFRACTORY GLAUCOMA

Purpose: To evaluate the effecacy of contact transscleral diode laser cyclophotocoagulationfor patients with refractory glaucoma Methods: Thirty-five eyes of 35 patients were treated by diode laser cyclophotocoagulation (DLCPC). Intraocular pressure (IOP), visual acuity, glaucoma medications and complica-     

Outcome of surgery for parotid tumours: 5-year experience of a general surgical unit in a teaching hospital

BACKGROUND: Most of the recent reports on the surgical management of parotid gland disorders come from specialist divisions of otolaryngology, head and neck, or faciomaxillary surgery. The aim of the present study was to evaluate the outcome of surgery for parotid tumours in a general surgical unit of a teaching hospital. METHOD: A prospective clinicopathological study was undertaken over a 5-year period for consecutive patients operated on for parotid gland tumours in the King Saud University Unit of Riyadh Medical Complex. Parameters analyzed were demographic details, clinical presentation, diagnostic work-up, type of surgery, and outcome in terms of early and late morbidity. RESULTS: Thirty seven parotid operations were performed on 36 consecutive patients. All patients presented with parotid gland swelling. Mean age was 51.6 years with a male preponderance. Fine-needle aspiration diagnosed the pathology in 33 out of 37 lesions. Pleomorphic adenoma was the commonest pathology observed in 24 patients (64.9%). Warthin's tumour was more common among male patients and was the only pathology with bilateral involvement. Malignant tumour was found in five patients (13.5%). Superficial conservative parotidectomy was the most frequently performed operation (84%). Overall postoperative morbidity was 13.5%. Transient facial nerve palsy was observed in seven cases (19%). There was no recurrence identified in patients with benign diseases during the mean follow up of 38.5 months. CONCLUSION: Parotid gland surgery can still be performed in a general surgery unit with comparable outcome. However, the operation should be performed in units with special interest and experience in surgery for parotid gland disorders.