KATP‐mediated Vasodilation is Impaired in Obese Zucker Rats

Objective: Skeletal muscle blood flow during exercise is impaired in obesity. We tested the hypothesis that the attenuated vasodilation in skeletal muscle arterioles of obese Zucker rats (OZR) is due to altered K_ATP channel‐mediated vasodilation. Materials and Methods: K_ATP channel function was determined in isolated skeletal muscle arterioles in response to the K_ATP opener cromakalim (0.1–10 μ M) during normal myogenic tone and α ‐adrenergic‐mediated tone (0.1 μ M phenylephrine). The spinotrapezius muscle was prepared and the vasodilatory responses to muscle stimulation or iloprost (0.028–2.8 μ M) were observed before and after the application of the K_ATP inhibitor, glibenclamide (10 μ M). Channel subunit expression was determined by using western blot analyses. Results: Cromakalim concentration‐response curves were shifted in OZR as compared to lean controls. OZR exhibited impaired functional and iloprost‐induced vasodilation as compared to the lean controls. Glibenclamide inhibited the functional and iloprost‐induced dilation in the lean rats with no effects in the obese animals. Channel subunit expression was similar in femoral arteries. Conclusion: The impaired functional vasodilation in the OZR is associated with altered K_ATP channel sensitivity.     

Histopathologic Alterations in the Decidua in Human Spontaneous Abortion: Loss of Cells With Large Cytoplasmic Granules

ABSTRACT: The histopathology of decidua obtained from the placental bed was evaluated by phloxine-tartrazine staining, which allows clear definition of cells with cytoplasmic granules. Mononuclear cells with large granules were seen in biopsy specimens taken from women at 8–31 weeks of normal pregnancy. In contrast, cells with large granules were missing in sections taken from the decidua of five women who were aborting or were destined to abort. Since the presence of suppressor cell activity in murine decidua correlates with the success of pregnancy and since this suppression is associated with small lymphocytes with cytoplasmic granules, the observations made using human placental bed biopsy material suggest that a possible suppressor cell deficiency might occur in the early stages of spontaneous abortion in human females.     

Which Factors Determine the Development of Late Potentials After First Myocardial Infarction? A Multifactorial Analysis

A multifactorial analysis was performed to study the factors that contributed to the occurrence of late potentials on the signal-averaged electrocardiogram in 106 consecutive patients with a first myocardial infarction. Ninety-three (88%) patients received intravenous thrombolytic therapy within 6 hours of symptom onset. Thirty-two (30%) patients had a late potential on the signal-averaged electrocardiogram on day 6, including 17 of 31 (55%) in whom the infarct-related artery was occluded and 15 of 75 (20%) in whom it was patent (P = 0.0004). Twenty-three variables were analyzed by a multifactorial stepwise regression analysis. Predictors of a late potential were (1) an occluded infarct-related coronary artery (t = -3.653, P = 0.0004) and (2) the extent of myocardial necrosis as indicated by the peak serum lactate dehydrogenase level (t = 3.094, P = 0.0025). The lower incidence of late potentials when the infarct-related coronary artery was patent was independent of left ventricular election fraction and peak enzyme levels after infarction.     

A changing professional profile: ethnicity and gender issues in pharmacy employment in the United Kingdom

Objective — This research was conducted to determine whether there were significant differences between the career profiles and ambitions of United Kingdom pharmacists from different ethnic and gender sub-populations. The results were subsequently analysed to determine whether any differences found between sub-populations had varied over time. Method — The research methodology employed a postal survey and interviews, to measure parameters relating to pharmacists' current careers, career histories and career ambitions. Questionnaires were distributed to 500 ethnic minority pharmacists and 500 non-ethnic minority pharmacists; there were 1,867 valid returns. Twenty-seven ethnic minority community pharmacists working in one inner city area were interviewed. Setting — The sample for the postal survey was identified from a surname analysis of the Register of Pharmaceutical Chemists. Key findings — Ethnic minority (mainly Asian) pharmacists accounted for 15 per cent of UK pharmacists. Of pharmacists aged under 30 years, 72 per cent of white pharmacists and 50 per cent of ethnic minority pharmacists were female. Both male and female community pharmacists from ethnic minorities favoured ownership roles relative to white pharmacists in all measured age groups. Management roles were favoured by both white male and female pharmacists, while locum roles were more frequently undertaken by white female pharmacists. Family ties were found to have a relatively strong influence on the careers of ethnic minority pharmacists. Conclusion — We speculate that family involvement may have enhanced the availability of both human and financial capital for business start-up, but find indications that this influence may not persist over time. In hospital pharmacy, there were indications of underachievement and career anxiety among pharmacists from ethnic minorities, the proportion of hospital pharmacy managers from ethnic minorities being disproportionately low. Attention is drawn to some policy implications, notably for training, flexible working patterns and the need for demographic scenario planning in the profession.     

Atracurium infusions in patients with renal failure on an ITU

An infusion of atracurium was used (after an initial bolus dose) in five patients with renal and respiratory failure, who were being subjected to intermittent positive pressure ventilation before renal dialysis. Neuromuscular function was monitored by the train-of-four pattern of stimulation. In three patients, atracurium 0.6-0.7 mg/kg/hour completely abolished the twitch response; in the other two (both of whom were markedly oedematous) this did not occur, even with a dose of 1.0 mg/kg/hour, although satisfactory clinical control was obtained. In all patients, there was rapid spontaneous recovery when the infusion was stopped. One patient convulsed, but plasma laudanosine levels taken at this time were below the toxic range. Atracurium infusions appear to provide easily controllable neuromuscular blockade in the intensive therapy unit, although these preliminary results suggest that larger doses may be required in the oedematous patient.     

Stiffness of the Distal Tip of Bipolar Pacing Leads

CAMERON, J., ET AL.: Stiffness of the Distal Tip of Bipolar Pacing Leads. The stiffness of a bipolar pacing lead, particularly between anode and cathode, may be responsible for myocardial penetration and perforation. Following an unprecedented 7% incidence of high threshold exit block with a single model bipolar ventricular endocardial lead, a study was undertaken to compare pacing lead stiffness between anode and cathode of six models of bipolar leads from two manufacturers; Telectronics (T) and Medtronics (M). Four leads had polyurethane insulation; T 030–284 (Laser Dish), T 329–259 (Cordis, Encor), M4012 (Target Tip), and M 4004 (Capsure). Two leads had silicone rubber insulation; M 5026 (Capsure) and M 5024 (Capsure SP). All leads were subjected to two stiffness tests. The Tip Deflection Test involved securing the lead at 45° at the indifferent electrode and applying a force to deflect the tip 5 mm. The three point bending test involved placing the lead over two fixed bars in contact with the anode and cathode. Midway a third bar was pushed onto the lead and the force to deflect the lead 2 mm was recorded. The results showed that pacing leads with polyurethane insulation were much stiffer than those with silicone rubber insulation. The T 030–284 because of its construction was found to be the stiffest. The next stiffest was the M 4012. Both these leads had an unacceptable incidence of high threshold exit block; 7% with the T 030–284 (89 implants) and 3% with the M 4012 (102 implants). No cases of high threshold exit block were documented with the other four pacing leads and in particular the silicone rubber M 5026 (344 implants). It is recommended that bipolar pacing leads with low stiffness between anode and cathode be used and that all new pacing leads be tested for stiffness prior to human implants.     

Outcomes in Adolescents with Postural Orthostatic Tachycardia Syndrome Treated with Midodrine and β-Blockers

Background: Postural orthostatic tachycardia syndrome (POTS) is associated with debilitating fatigue, dizziness, and discomfort in previously healthy adolescents. The effects of medical therapy have not been well studied in this patient population. This study assessed the relative efficacy and impact of drug therapy on the functioning and quality of life in adolescents with POTS.
Methods: A retrospective, single center, chart review analysis with a follow-up written survey was conducted on a group of 121 adolescents who had undergone autonomic reflex screening at the Mayo Clinic from 2002 to 2005 as part of an evaluation for possible POTS.
Results: Of 121 surveys sent, 47 adolescents returned a completed survey. In this cohort of patients, the two most commonly prescribed drug therapies were midodrine (n = 13) and β-blockers (n = 14). Patients in the midodrine group were comparable to patients in the β-blocker group in gender, age, pretreatment postural heart rate changes, and months from initial evaluation to survey completion. More patients treated with a β-blocker reported improvement after visiting Mayo Clinic (100% vs 62%, P = 0.016) and more attributed their progress to medication (63.6% vs 36.4%, P = 0.011) than did those treated with midodrine.
Conclusion: Treatment with both midodrine and β-blockers was associated with overall improvement in POTS patients' general health; however, adolescents taking β-blockers were more likely than those taking midodrine to credit the role of medications in their improvement.     

Mutations in Conserved Amino Acids in the KCNQ1 Channel and Risk of Cardiac Events in Type-1 Long-QT Syndrome

Background: Type-1 long-QT syndrome (LQT1) is caused by mutations in the KCNQ1 gene. The purpose of this study was to investigate whether KCNQ1 mutations in highly conserved amino acid residues within the voltage-gated potassium channel family are associated with an increased risk of cardiac events.
Methods and Results: The study population involved 492 LQT1 patients with 54 missense mutations in the transmembrane region of the KCNQ1 channel. The amino acid sequences of the transmembrane region of 38 human voltage-gated potassium channels were aligned. An adjusted Shannon entropy score for each amino acid residue was calculated ranging from 0 (no conservation) to 1.0 (full conservation). Cox analysis was used to identify independent factors associated with the first cardiac event (syncope, aborted cardiac arrest, or death). Patients were subcategorized into tertiles by their adjusted Shannon entropy scores. The lowest tertile (score 0–0.469; n = 146) was used as a reference group; patients with intermediate tertile scores (0.470–0.665; n = 150) had no increased risk of cardiac events (HR = 1.19, P = 0.42) or aborted cardiac arrest/sudden cardiac death (HR = 1.58, P = 0.26), and those with the highest tertile scores (>0.665; n = 196) showed significantly increased risk of cardiac events (HR = 3.32, P <0.001) and aborted cardiac arrest/sudden cardiac death (HR = 2.62, P = 0.04). The increased risk in patients with the highest conservation scores was independent of QTc, gender, age, and beta-blocker therapy.
Conclusions: Mutations in highly conserved amino acid residues in the KCNQ1 gene are associated with a significant risk of cardiac events independent of QTc, gender, and beta-blocker therapy.     

Laparoscopic Hernia Repair of an Incisional Hernia Secondary to Placement of an Implantable Cardioverter Defibrillator

We present the lapamscopic repair of a large incisional hernia secondary to placement of a subcostal ICD pulse generator. Laparoscopic repair of large incisional hernias provides a unique and technically feasible form of repair in the 2%–13% of patients who will develop an incisional hernia following an abdominal surgery. This form of hernia repair is associated with minimal morbidity and prompt resumption of patient activities and work.