Further evidence for the heterogeneity of functional muscarinic receptors in guinea pig gallbladder

Previous studies have suggested the presence of multiple muscarinic receptor subtypes in guinea pig gallbladder smooth muscle, although the relative abundance and functional role of these subtypes remains an area of significant research efforts. The present study utilized both radioligand kinetic and functional experiments to further probe the nature of the muscarinic receptors in gallbladder smooth muscle and their mode of coupling to intra- and extra-cellular Ca(2+) sources. Dissociation kinetic studies using [3H]N-methylscopolamine ([3H]NMS) indicated that the binding profile in guinea pig gallbladder smooth muscle could not be reconciled with that expected for a single muscarinic receptor subtype, the latter determined in parallel experiments conducted on the cloned muscarinic M(1)-M(5) subtypes in Chinese hamster ovary (CHO) cells. Furthermore, comparison of the gallbladder data with the dissociation characteristics of [3H]NMS in guinea pig urinary bladder revealed a significantly different kinetic profile, with the urinary bladder, but not the gallbladder, demonstrating biphasic radioligand dissociation kinetics. In functional experiments, carbachol caused a concentration-dependent contraction of guinea pig gallbladder smooth muscle strips in Ca(2+)-free or 5 mM Sr(2+)-substituted physiological salt solutions (PSS) with amplitudes of the maximal contractions corresponding to 45.8+/-8.0% and 33.2+/-6.6% of control responses in normal PSS, respectively. Furthermore, the stimulus-response characteristics of carbachol-mediated contraction appeared significantly altered in Ca(2+)-free PSS relative to normal or Sr(2+)-substituted PSS. The antagonist, methoctramine (1x10(-7)-3x10(-5) M), exerted only a slight inhibition of carbachol (10(-5) M)-induced contractions in 5 mM Sr(2+)-substituted medium, whereas it was significantly more potent in antagonizing gallbladder contractions in response to 10(-5) M carbachol in the absence of extracellular Ca(2+). Both atropine and tripitramine were equipotent in antagonizing carbachol-induced contractions in Ca(2+)-free (pIC(50): 6.85+/-0.11 for atropine and 5.75+/-0.32 for tripitramine) and Sr(2+)-substituted media (pIC(50): 6.88+/-0.25 for atropine and 5.70+/-0.16 for tripitramine), and pirenzepine was only slightly more potent in Ca(2+)-free PSS (pIC(50): 5.66+/-0.23) than in Sr(2+)-substituted PSS (pIC(50): 5.33+/-0.21). Taken together, our data indicate that carbachol contracts guinea pig gallbladder by stimulating two distinct muscarinic receptor subtypes linked to extracellular Ca(2+) influx and intracellular Ca(2+) release. These two subtypes may represent the muscarinic M(3) and M(4) receptors, although the presence of the muscarinic M(2) receptor subtype is also suggested from the binding data.     

Paclitaxel‐induced ST‐Segment Elevations

A 51‐year‐old woman presented with severe chest pain minutes after starting intravenous paclitaxel as a part of the systemic chemotherapy due to ovarian carcinoma. The electrocardiogram (ECG) revealed sinus rhythm with ST‐segment elevations in inferior and anterior leads. The ST‐segment elevations resolved immediately after sublingual nitroglycerine. Cardiac troponin T and CPK MB levels remained in the normal range at repeat measurements. It was presumed that in spite of standard premedication, paclitaxel had induced acute coronary syndrome with ST‐segment elevations in this patient. Copyright © 2009 Wiley Periodicals, Inc.     

Gossypiboma mimicking a distal pancreatic mass: Report of a case

Gossypiboma (retained surgical sponge) is a pseudotumor within the body that is composed of non-absorbable surgical material with a cotton matrix. Because the symptoms of gossypiboma usually are nonspecific and may appear years after surgery, the diagnosis of gossypiboma may be difficult because the condition may mimic a benign or malignant soft-tissue tumour in the abdomen and pelvis. A 61-year-old woman with a one-year history of left upper-quadrant pain and weight loss was referred to our center. She had undergone peptic ulcer perforation 23 year ago. Physical examination revealed dullness and palpable mass in the left upper abdomen. On examination by computed tomography (CT), a hypodense mass of 12 cm in diameter between the greater curvature of the stomach, pancreas, and splenic hilus was detected. Upon exploration, a mass lesion of 10 cm in diameter was detected between the greater curvature of the stomach and splenic hilus, which caused dense adhesions not in communication with the pancreas. It was excised and a splenectomy was performed. After a macroscopic examination, the mass lesion was diagnosed as gossypiboma. Although ultrasonography (US), CT, angiography, and magnetic resonance imaging (MRI) may be used to diagnose gossypiboma, definitive diagnosis is possibile only upon surgery or histopathological examination. As a result, when an abdominal mass is observed, surgeons should carefully investigate the patient’s past surgical history while taking the possibility of gossypiboma into consideration.     

Cardiac troponin T for early detection of cardiotoxicity in breast cancer patients treated with epirubicin

The aim of the study was to investigate the role of cTnT for the prediction of long term cardiac dysfunction after epirubicin-containing adjuvant chemotherapy for breast cancer. The study group comprised of 45 patients (all female; mean age 48 ±8 years), treated with epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer. Patients received either 4 cycles of cyclophosphamide plus epirubicin (90 mg/m²) (n=23; stage 2 breast cancer) or 6 cycles of cyclophosphamide plus epirubicin (75 mg/m²) plus fluorouracil (n=18; stage 3 breast cancer). Venous blood samples were drawn, before and 72 hours after, every cycle of chemotherapy for the measurement of cTnT. Cardiac assessment was carried out at baseline and 1 year after chemotherapy by clinical evaluation, electrocardiography, radio-nuclide ventriculography (RNV) and transthoracic echocardiography. All patients remained free of clinical heart failure during the study period. In 26 patients (63%), cTnT was elevated after chemotherapy. Mean left ventricular ejection fraction, assessed by RNV at baseline and one year after chemotherapy, were 61±8% and 56±7% (p<0.0001). The sensitivity and specifity of cTnT for the detection of left ventricular systolic dysfunction at one year were 69% and 39% respectively. Echocardiographic examinations at baseline and one year after chemotherapy revealed a significant decrease in E/A ratio from 1.15±0.3 to 0.9±0.2 in cTnT positive patients, suggesting diastolic dysfunction. In conclusion, elevated serum cTnT levels after epirubicin-containing adjuvant chemotherapy for stage 2 and stage 3 breast cancer, predict future cardiac dysfunction with moderate sensitivity and poor specificity.     

The respiratory effects of occupational polypropylene flock exposure.

The present study evaluated the possible effects of exposure to polypropylene flock on respiratory health and serum cytokines in a cross-sectional study of workers from a plant in Turkey. A total of 50 polypropylene flocking workers were compared to a control group of 45 subjects. All subjects filled out a respiratory questionnaire and underwent a physical examination, a chest radiograph and pulmonary function testing, including single breath carbon monoxide diffusing capacity (DL,CO). Serum interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) were measured. Additionally, high resolution computed tomography (HRCT) of the chest was performed in 10 exposed workers with low DL,CO. Work-related respiratory symptoms were reported in 26% of the exposed subjects and in 13.3% of the controls. Logistic regression analysis showed that the risk of respiratory symptoms increased 3.6 fold in polypropylene flocking workers when compared to controls. Parameters of the study group, including per cent predicted: forced vital capacity, forced expiratory volume in one second, forced mid-expiratory flow 25-75% and DL,CO, were significantly lower than in controls. Multivariate analyses showed that being a polypropylene flocking worker was a predictive factor for impairment of pulmonary function. Serum IL-8 and TNF-alpha levels were increased in the study group compared with the controls. HRCT revealed peribronchial thickening and diffuse ground glass attenuation in some subjects. The present study suggests the presence of subtle or the beginning of interstitial lung disease in these polypropylene flocking workers.     

Magnesium efficacy in magnesium deficient and nondeficient patients with rapid ventricular response atrial fibrillation.

We assessed the effect of magnesium sulphate (MgSO4) on lowering the rate in ventricular atrial fibrillation (AF), and evaluated the effect of this therapy in magnesium (Mg) deficient and nondeficient patients. This experimental clinical study was performed on 34 patients with rapid AF (ventricular rate [VR] > 120/minute) presenting to the emergency department of a tertiary care university hospital. Patients with systolic blood pressure < or = 100 mmHg, Hb level < or = 11.8, saO2 of < or = 96%, BUN > or = 40 or creatine > or = 1.8 were excluded (n = 15). Nineteen patients were given an initial 2 g MgSO4 bolus i.v. and a 1 g/hour continuous infusion over 6 hours. To evaluate the presence of Mg deficiency, urine was collected from the onset of treatment and continued for the next 24 hours, and the excretion rate of administered Mg was calculated. Ventricular rates were obtained at baseline, after MgSO4 bolus, and every 15 minutes for the first hour. The decrease in the VR was statistically significant at 15, 30 and 60 minutes after Mg therapy (p = 0.0025, p < 0.001, p > 0.001). There was no difference in the response to Mg therapy between Mg deficient and nondeficient patients at 15, 30 or 60 minutes after therapy (p = 0.41, p = 0.28, p = 0.08). It is concluded that i.v. MgSO4 has a statistically significant but clinically limited effect on VR and this effect did not differ between patients with and without Mg deficiency.