The Myocardial Lesions Produced by the Potassium Channel Opener Aprikalim in Monkeys and Rats Are Prevented by Blockade of Cardiac {beta}-Adrenoceptors

Aprikalim is a potent, specific, and selective opener of ATP-sensitiveK⁺ (K_ATP) channels. By virtue of this pharmacological property,aprikalim affords cardioprotection in experimental models ofischemia/reperfusion injury, and, at higher doses, also causesperipheral or coronary vasodilatation. Direct-acting peripheralvasodilators can cause myocardial lesions, particularly in ratsand dogs. However, unexpectedly, aprikalim produced this effectalso in monkeys. Thus, the primary aim of this investigationwas to assess whether in monkeys these myocardial lesions werethe direct or indirect consequence of the vascular effects ofaprikalim. Cyno-mologus monkeys were given the ß-adrenoceptorantagonist nado-lol (2 mg/kg po, twice daily) for 4 consecutivedays. On the third and fourth day of the experiment, they receivedaprikalim (1 mg/kg po). In another series, two monkeys carryingtelemetry transmitters for blood pressure and heart rate measurementswere also given aprikalim or its vehicle. Finally, aprikalim(1 mg/kg po for 2 days) or its vehicle was administered to ratswhich were concurrently treated with the ß-adrenoceptorantagonist atenolol (5 mg/ kg sc) or its vehicle. In cynomologusmonkeys, aprikalim produced focal and multifocal myocardialnecrosis of minimal to moderate intensity in or near the papillarymuscles of the left ventricle. These effects were abrogatedby nadolol. Similarly, necrotic lesions were caused by aprikalimonly in those rats which had not been pretreated with atenolol.In monkeys, aprikalim produced a marked and long-lasting decreasein aortic blood pressure, accompanied by an even more prolongedtachycardia. These results demonstrate that aprikalim can producemyocardial necrosis not only in rats but also in monkeys. Toour knowledge, this is the first time that such adverse effectsare reported for a vasodilator in monkeys. More importantly,these effects were prevented by blocking cardiac ß-adrenoceptors.Thus, the myocardial lesions produced by aprikalim may be attributedto its profound and prolonged hemodynamic effects.     

A comparison of bonfils fiberscope‐assisted laryngoscopy and standard direct laryngoscopy in simulated difficult pediatric intubation: a manikin study

Introduction: Difficult airway management in children is challenging. One alternative device to the gold standard of direct laryngoscopy is the STORZ Bonfils fiberscope (Karl Storz Endoscopy, Tuttlingen, Germany), a rigid fiberoptic stylette‐like scope with a curved tip. Although results in adults have been encouraging, reports regarding its use in children have been conflicting. We compared the effectiveness of a standard laryngoscope to the Bonfils fiberscope in a simulated difficult infant airway. Methods: Ten pediatric anesthesiologists were recruited for this study and asked to perform three sets of tasks. For the first task, each participant intubated an unaltered manikin (SimBaby ^TM, Laerdal, Puchheim, Germany) five times using a styletted 3.5 endotracheal tube (ETT) and a Miller 1 blade (group DL‐Normal). For the second task, a difficult airway configuration simulating a Cormack‐Lehane grade 3B view was created by fixing a Miller‐1 blade into position in the manikin using a laboratory stand. Each participant then intubated the manikin five times with a styletted 3.5 ETT using conventional technique but without touching the laryngoscope (group DL‐Difficult). In the third task, the manikin was kept in the same difficult airway configuration, and each participant intubated the manikin five times using a 3.5‐mm ETT mounted on the Bonfils fiberscope as an adjunct to direct laryngoscopy with the Miller‐1 blade (group BF‐Difficult). Primary outcomes were time to intubate and success rate. Results: A total of 150 intubations were performed. Correct ETT placement was achieved in 100% of attempts in group DL‐Normal, 90% of attempts in group DL‐Difficult and 98% of attempts in BF‐Difficult. Time to intubate averaged 14 s (interquartile range 12–16) in group DL‐Normal; 12 s (10–15) in group DL‐Difficult; and 11 s (10–18) in group BF‐Difficult. The percentage of glottic opening seen (POGO score) was 70% (70–80) in group DL‐Normal; 0% (0–0) in group DL‐Difficult; and 100% (100–100) in group BF‐Difficult. Discussion: The Bonfils fiberscope‐assisted laryngoscopy was easier to use and provided a better view of the larynx than simple direct laryngoscopy in the simulated difficult pediatric airway, but intubation success rate and time to intubate were not improved. Further studies of the Bonfils fibrescope as a pediatric airway adjunct are needed.     

Abnormal maturation pathway of keratinocytes in psoriatic skin

We compared the maturation pathway of normal and psoriatic epidermis using three different markers: (1) Involucrin, which is normally detected in the stratum granulosum in normal skin, was detected in all but the basal layer of involved psoriatic skin; (2) an antigen, recognized by the murine monoclonal antibody psi 3, was present in all but the basal layer of involved psoriatic skin but was absent from uninvolved and normal skin; (3) fibronectin, which normally localizes in the dermis and the epidermal-dermal junction, was also detected intra- and extracellularly in the psoriatic epidermis. These results indicate that the alterations in keratinocyte maturation found in psoriasis do not arise from a truncation of the normal maturation pathway but rather reflect the onset of an abnormal pathway of differentiation characterized by the expression of psi 3 antigen and fibronectin and the premature appearance of involucrin.     

POSTOPERATIVE ANALGESIA WITH EXTRADURAL CLONIDINE

The analgesic effect of extradural clonidine was evaluated ina double-blind study. In the recovery room, following orthopaedicor perineal surgery 20 ASA I and II patients were allocatedrandomly to two groups. The extradural clonidine (EC) groupreceived clonidine 2 µg kg^–1 in isotonic salinesolution 15 µg ml^–1. The extradural saline (ES)group received the equivalent volume of plain isotonic salinesolution. Pain was evaluated by a visual analogue scale (VAS)at 15-min intervals for the first 2 h and subsequently at 30-minintervals for the following 4 h. Morphine 5 mg was given s.c.when patients complained of pain after extradural saline orclonidine. In the EC group, the mean (SD) maximum pain reliefwas 68.2 (24.1)% of the initial VAS score, but it was only 14.7(25.2)% in the ES group. The mean duration of analgesia, beforeinjection of morphine, was significantly longer in the EC group(210 (87) min) compared with the ES group (45 (27) min) (P <0.001). Drowsiness and moderate hypotension were observed inthe EC group.     

A comparison of the STORZ video laryngoscope and standard direct laryngoscopy for intubation in the Pediatric airway – a randomized clinical trial

Introduction:  Direct laryngoscopy can be challenging in infants and neonates. Even with an optimal line of sight to the glottic opening, the viewing angle has been measured at 15°. The STORZ DCI video laryngoscope (Karl Storz, Tuttlingen, Germany) incorporates a fiberoptic camera in the light source of a standard laryngoscope of variable sizes. The image is displayed on a screen with a viewing angle of 80°. We studied the effectiveness of the STORZ DCI as an airway tool compared to standard direct laryngoscopy in children with normal airway.
Methods:  In this prospective, randomized study, 56 children (ages 4 years or younger) undergoing elective surgery with the need for endotracheal intubation were divided into two groups: children who underwent standard direct laryngoscopy using a Miller 1 or Macintosh 2 blade (DL) and children who underwent video laryngoscopy using the STORZ DCI video laryngoscope with a Miller 1 blade (VL). Time to best view (TTBV), time to intubate (TTI), Cormack–Lehane (CL), and percentage of glottis opening seen (POGO) score were recorded.
Results:  TTBV in DL was 5.5 (4–8) s and 7 (4.2–9) s in VL. TTI in DL was 21 (17–29) s and in VL 27 (22–37) s ( P  = 0.006). The view as assessed by POGO score was 97.5% (60–100%) in DL and 100% (100–100%) in the VL ( P  = 0.003). Data are presented as median and interquartile range and analyzed using t -test.
Discussion:  This study demonstrates that the STORZ DCI video laryngoscope provides an improved view to the glottis in children with normal airway anatomy, but requires a longer time for intubation.     

Echocardiographic Assessment of the Interventricular Delay of Activation and Correlation to the QRS Width in Dilated Cardiomyopathy

The aim of the study was to define criteria for left ventricular pacing in dilated cardiomyopathy (DCM) using an echocardiographic evaluation of interventricular electromechanical delay (IMD) and a correlation of IMD to QRS duration. Standard 12-lead ECG and echocardiography with pulsed Doppler tissue imaging (DTI) were recorded in 35 DCM patients (mean age 58 +/- 11 years) with QRS duration from narrow (80 ms) to broad (222 ms) patterns. The timefor left ventricular activation was evaluated from the onset of QRS to the onset of aortic flow (Q-Ao) by standard pulsed Doppler (SP) or to the onset of mitral annulus systolic wave (Q-Mit) (DTI). The time for right ventricular activation was determinedfrom the onset of QRS to the onset of pulmonary flow (Q-Pulm) (SP) or to the onset of tricuspid annulus systolic wave (Q-Tri) (DTI). (Q-Ao)-(Q-Pulm) and (Q-Mit)-(Q-Tri) determined IMD for each method, respectively. QRS width and IMD showed correlation coefficients of r = 0.86 ([Q-Ao]-[Q-Pulm]) and r = 0.82 ([Q-Mit]-[Q-Tri]) (P < or = 0.001 ). Mean IMD of 77 +/- 15 ms (SP) and 88 +/- 26 ms (DTI) were noted for QRS width above 150 ms. Left ventricle delayed activation was positively correlated to QRS widening with both methods, (r = 0.90, [Q-Ao]), (r = 0.83, [Q-Mit]) (P < or = 0.001). In conclusion, QRS duration is a good marker of an interventricular mechanical asynchrony. According to IMD correction, left ventricular pacing may be mainly proposed to symptomatic DCM patients with QRS duration > 150 ms.     

National opportunities for health promotion: the Canadian experience

Health promotion is a fundamental strategy to address the majorissues which confront health systems in developed and developingcountries alike. Chief amongst these issues are unhealthy environments,health inequities and non-communicable diseases. The infrastructuresfor health promotion include mechan isms for development andimplementation of health policy; policies and programs supportiveof community involvement in health promotion programs; reorientationof the health care system towards prevention; and research.Consensus building among key stakeholders from the public andprivate sectors is at the core of the policy development process.A New Perspective for the Health of Canadians (1974) and theWHO Ottawa Charter for Health Promotion (1987) have guided healthpromotion policy and program development at both the nationaland provincial levels, in Canada, a number of initiatives haveplaced into pra ctice the policy frameworks, among them: HealthyCommunities, the Canadian Heart Health initiative, integrationofpreven lion into clinical practice, and structures to supportresearch in health promotion.     

THE SPECTRUM OF 67-kD LAMININ RECEPTOR EXPRESSION IN BREAST CARCINOMA PROGRESSION

Laminin is a glycoprotein of the basement membrane (BM), involved in a variety of normal and pathological cellular events including tumour invasion and metastasis. Cells bind laminin through different types of receptor. The 67-kD laminin receptor (67LR) is a cell-surface protein which binds laminin with high affinity. 67LR expression has been shown to increase in neoplastic cells, compared with normal tissues, and 67LR seems to play an important role during the first steps of neoplastic progression. In this study, 67LR expression was analysed during the morphological phases of breast cancer progression from normal tissue to invasive carcinoma. A total of 506 formalin-fixed, paraffin-embedded normal breast structures and lesions were stained by immunohistochemistry using the MLuC5 monoclonal antibody, which is specific for 67LR. The results show that in normal breast and in any kind of breast lesion, myoepithelial and endothelial cells express 67LR. While 67LR is not seen in the epithelium of normal breast, cysts, adenosis, and benign tumours, it is expressed in the epithelial cells of several hyperplasias and carcinomas in situ, both ductal and lobular, as well as in all invasive carcinomas. The 67LR-positive cell subpopulation expands from hyperplastic lesions to invasive carcinoma, suggesting that 67LR could be related to the induction and progression of breast cancer. © 1997 John Wiley & Sons, Ltd.     

Comparison of 55% TFA/CH2Cl2 and 100% TFA for Boc group removal during solid-phase peptide synthesis

Two parallel syntheses of 40 C-terminal amide peptides, ranging in length from 4 to 20 residues, have been carried out using simultaneous multiple peptide synthesis. All synthetic steps, other than the removal of the Boc group, were performed simultaneously under identical experimental conditions. The two sets of peptides were deprotected with either 55% TFA/DCM for 30 min or 100% TFA for 5 min. The purity of the peptides obtained when deprotecting with 55% TFA/DCM was, on average, 9% higher than with 100% TFA. The major impurity obtained during synthesis when 100% TFA was used for Boc removal corresponded to the omission of the second amino-acid residue added. Volumetric measurements of the swelling of the resin in the different deprotection solvents were carried out. These showed that the omission analogs generated are probably due to insufficient swelling of the resin, resulting in limited solvent transfer of 100% TFA into the resin and, in turn, incomplete Boc removal.