A novel approach to improve undergraduate surgical teaching.

BACKGROUND: Undergraduate surgery is at an important crossroads. Many departments report significant difficulties delivering effective teaching. Our student feedback indicated a dated surgical curriculum lacking structure, quality and uniformity. We report on a new "blended" approach employing a combination of professional DVDs, case based discussions, online material and traditional bedside teaching designed to provide structure, standardization, and equality of learning . METHODS: Year 4 students who had undertaken the new course and year 5 students who had participated in the traditional teaching programme were compared. Students completed a 20 item questionnaire about their experiences of the surgical teaching programme. RESULTS: One hundred and seventy-one year 4 (70%) and 148 year 5 students (66%) responded. Domains relating to "Overall Satisfaction with the course", "Approval of innovative teaching methods and interactivity" and "Satisfaction with the clarity of course information" showed improvements when comparing the new and old programmes. However bedside teaching was not rated as highly in the new programme (p<0.05). CONCLUSION: This blended approach has resulted in improved student understanding and engagement. The apparent compromise of bedside teaching may be a reflection of higher expectations. We believe that a similar blended approach has the potential to re-invigorate surgical teaching elsewhere.

Effects of single or repeated dermal exposure to methyl parathion on behavior and blood cholinesterase activity in rats.

The effects of a single or repeated dermal administration of methyl parathion on motor function, learning and memory were investigated in adult female rats and correlated with blood cholinesterase activity. Exposure to a single dose of 50 mg/kg methyl parathion (75% of the dermal LD(50)) resulted in an 88% inhibition of blood cholinesterase activity and was associated with severe acute toxicity. Spontaneous locomotor activity and neuromuscular coordination were also depressed. Rats treated with a lower dose of methyl parathion, i.e. 6.25 or 12.5 mg/kg, displayed minimal signs of acute toxicity. Blood cholinesterase activity and motor function, however, were depressed initially but recovered fully within 1-3 weeks. There were no delayed effects of a single dose of methyl parathion on learning acquisition or memory as assessed by a step-down inhibitory avoidance learning task. Repeated treatment with 1 mg/kg/day methyl parathion resulted in a 50% inhibition of blood cholinesterase activity. A decrease in locomotor activity and impairment of memory were also observed after 28 days of repeated treatment. Thus, a single dermal exposure of rats to doses of methyl parathion which are lower than those that elicit acute toxicity can cause decrements in both cholinesterase activity and motor function which are reversible. In contrast, repeated low-dose dermal treatment results in a sustained inhibition of cholinesterase activity and impairment of both motor function and memory.

Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray.

Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS.

Comparison of once daily fluticasone propionate aqueous nasal spray with once daily budesonide reservoir powder device in patients with perennial rhinitis.

BACKGROUND: Previous studies comparing the corticosteroids fluticasone propionate (FP) and budesonide (BUD) in both perennial and seasonal rhinitis have shown no consistent difference between treatments. However, the therapeutic outcomes may have been influenced by study design. OBJECTIVE: To compare the effect of FP aqueous nasal spray (ANS; 200 microg/day) with BUD reservoir powder device (RPD; 200 microg/day) on rhinitis symptoms, productivity loss and device preference in patients with perennial rhinitis. METHODS: After a 2-week run-in period, 440 patients were randomized to receive either FPANS, BUD RPD or matched placebo (ANS or RPD) for 8 weeks, followed by an open-label 4-week follow-up treatment with FPANS. Patients completed diary card visual analogue scores for nasal symptoms, and questionnaires on satisfaction with the treatment and preferred choice of device. RESULTS: During weeks 1-4, the visual analogue total nasal symptom scores (VATNS) in the FPANS group were significantly lower than scores in the BUD RPD group (mean difference = -17.8; 95% CI = -34.4, -1.3; P = 0.036). FPANS also significantly reduced the VATNS compared with the ANS placebo at all time-points assessed (P < or = 0.005). BUD RPD did not significantly differ from the RPD placebo at weeks 5-8 (P = 0.167), or the ANS placebo at any time-point (P < or = 0.151). Over the 8-week treatment period FPANS was significantly more effective than BUD RPD at reducing sneezing (mean difference = -4.4; 95% CI = -8.6, -0.3; P = 0.036) and nasal itching (mean difference = -5.3; 95% CI = -9.9, -0.8; P = 0.022), and was significantly superior to the ANS placebo for all symptoms assessed at weeks 1-4 and 1-8 (P < 0.016). At the same time-points BUD RPD was no better at alleviating nasal itching than the RPD placebo (P < or = 0.306), and compared with the ANS placebo, significantly reduced only one symptom; nasal blockage (P < or = 0.016). After 8 weeks of treatment, patients preferred the ANS device to the RPD (P < 0.001), and at 12 weeks a significantly greater number of patients were satisfied with FPANS treatment compared with BUD RPD (P = 0.0019) or the respective placebos (P = 0.0001). CONCLUSION: FPANS and BUD RPD are effective therapies with a good safety profile for the treatment of perennial rhinitis but, in this direct placebo-controlled comparison, FPANS was more efficacious than BUD RPD, and the patients preferred the ANS device to the RPD.

Surgical trainees' attitudes to laparoscopic cholecystectomy: a regional survey.

BACKGROUND AND STUDY AIMS: Since the introduction of laparoscopic cholecystectomy (LC), numerous articles have been written emphasising its many advantages over open cholecystectomy (OC). However, reports also highlight increased complications following LC such as bile-duct, vascular and bowel injuries. We aimed to study surgical trainees as a defined population of individuals who, with increasing exposure to cholecystectomy, would become fully aware of LC's advantages and controversies. We wished to test the hypothesis that, with increasing in-depth knowledge, they might opt for OC rather than LC if they themselves required cholecystectomy. MATERIALS AND METHODS: We conducted a postal survey of all 133 Northern Ireland surgical trainees identified as having exposure to LC during their training. Trainees were asked whether they would undergo LC and if so with which preconditions. Similarly, if they stated a preference for open cholecystectomy they were asked to state the reason. A minimum time period of 18 months was considered adequate for trainees to become relatively more experienced in this field compared with their more junior counterparts. RESULTS: A response rate of 80.5% (107/133) was achieved. A total of 51 of 107 trainees had at least 18 months' experience. Of the 107 who replied, 88.8% (95/107) would be willing to undergo LC. A total of 12 of 107 trainees would opt for OC, with twice as many experienced trainees (8 vs. 4) opting for this approach (n.s. [not significant]). Significantly more experienced trainees cited the use of laparoscopic cholangiography as a precondition for LC compared with their inexperienced counterparts (7 vs. 1, p = 0.020). Of 107 trainees, 19 would request use of the open first port (Hasson) technique; 14 of these had at least 18 months' experience (p = 0.009). CONCLUSION: Our survey confirms that the majority of trainees would be willing to undergo LC. However, increased experience of LC may alter an individual's expectations about how LC should ideally be performed.

Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations.

AIMS: To measure and compare the systemic bioavailability of fluticasone propionate aqueous nasal spray and a new nasal drop formulation, using a sensitive analytical method and high dose regimen. METHODS: Volunteers received four 800 microg doses of fluticasone propionate as a nasal spray or drops over 2 days, separated by an 8 h dose interval. On day 2, blood samples were collected for assay of fluticasone propionate plasma concentrations. RESULTS: The mean systemic exposure, for both formulations was 8.5 pg x ml(-1) x h (drops) and 67.5 pg x ml(-1) x h (spray). Mean absolute bioavailabilities were estimated to be 0.06% (drops) and 0.51% (spray), by reference to historical intravenous data. CONCLUSIONS: Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.

Activation of phospholipase D in porcine tracheal smooth muscle: role of phosphatidylinositol 3-kinase and RhoA activation.

Muscarinic receptor agonists transiently activate phospholipase D in tracheal smooth muscle. Muscarinic activation of phospholipase D in this tissue is dependent on activation of protein kinase C and an unidentified pathway that is not protein kinase C dependent. Cholinergic agents have also been shown to activate phospholipase D by pathways linked to the small G protein, RhoA. This study explores the relationship between muscarinic activation of phophatidylinositol 3-kinase and activation of RhoA, and examines whether phospholipase D activation is dependent on either pathway in tracheal smooth muscle. Wortmannin or 2-(4-morphonyl)-8-phenyl-4H-1-benzopyran-4-one (LY-294002), putative specific inhibitors of phophatidylinositol 3-kinase, significantly inhibit acetylcholine-induced formation of phosphatidylethanol and also block acetylcholine-induced translocation of RhoA to the membrane. In previous experiments calphostin C, a protein kinase C inhibitor, partially inhibited both acetylcholine-induced and phorbol-12-myristate-13-acetate (PMA)-induced phosphatidylethanol formation. In the present study calphostin C did not block acetylcholine-induced RhoA translocation to the membrane. However, the Rho kinase inhibitor, N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632), significantly inhibited acetylcholine-induced phosphatidylethanol formation, but had no effect on activation of phospholipase D by PMA. Acetylcholine treatment also stimulated the phosphorylation of the 110-kDa subunit of phosphatidylinositol 3-kinase. Phosphorylation of phosphatidylinositol 3-kinase 110-kDa subunit could be blocked by wortmannin in a concentration-dependent manner, and acetylcholine-induced phosphatidylinositol 3-kinase activity was significantly inhibited by wortmannin. LY-294002 also inhibited acetylcholine-induced phosphorylation of 110-kDa subunit and activation of phosphatidylinositol 3-kinase. These results suggest that acetylcholine stimulation translocates RhoA to the membrane by a phosphatidylinositol 3-kinase-dependent mechanism and acetylcholine-induced phospholipase D stimulation is at least partly mediated via phosphatidylinositol 3-kinase, however, protein kinase C appears to activate phospholipase D independent of phosphatidylinositol 3-kinase or RhoA activation in porcine tracheal smooth muscle.

Limited heterogeneity of HIV type 1 in infected mothers correlates with lack of vertical transmission.

The human immunodeficiency virus type 1 (HIV-1) envelope V3 region sequences of peripheral blood mononuclear cell DNA were analyzed from three nontransmitting mothers (infected mothers who failed to transmit HIV-1 to their infants in the absence of antiretroviral therapy), including one mother with two deliveries, and compared with the sequences of seven previously analyzed transmitting mothers. The coding potential of the envelope open reading frame, including several patient-specific amino acid motifs and previously described molecular features across the V3 region, were highly conserved. There was a low degree of heterogeneity within the sequences of each nontransmitting mother compared with the sequences of transmitting mothers. In addition, the estimates of genetic diversity of nontransmitting mother sequences were significantly lower compared with transmitting mother sequences. Phylogenetic analysis showed that the sequences of each nontransmitting mother formed distinct clusters that were well discriminated from each other and the sequences of seven transmitting mothers. In conclusion, a low degree of HIV-1 genetic heterogeneity in these infected mothers correlates with lack of vertical transmission; this finding may be useful in developing strategies for further prevention of maternal-fetal transmission.

Phosphatidylethanol stimulates calcium-dependent cytosolic phospholipase A(2) activity of a macrophage cell line (RAW 264.7).

The synthesis of inflammation mediators produced from arachidonic acid is regulated primarily by the cellular concentration of free arachidonic acid. Since intracellular arachidonic acid is almost totally present as phospholipid esters, the concentration of intracellular arachidonic acid is primarily dependent on the balance between the release of arachidonic acid from membrane phospholipids and the uptake of arachidonic acid into membrane phospholipids. Cytosolic phospholipase A(2) is a calciumdependent enzyme that catalyzes the stimulus-coupled hydrolysis of arachidonic acid from membrane phospholipids. Following exposure of macrophages to various foreign or endogenous stimulants, cytosolic phospholipase A(2) is activated. Treatment with these compounds may also stimulate phospholipase D activity, and, in the presence of ethanol, phospholipase D catalyzes the synthesis of phosphatidylethanol. A cell-free system was used to evaluate the effect of phosphatidylethanol on cytosolic phospholipase A(2) activity. Phosphatidylethanol (0.5 microM) added to 1-stearoyl-2-[(3)H]-arachidonoyl-sn-glycero-3-phosphocholine vesicles stimulated cytosolic phospholipase A(2) activity. However, high concentrations (20-100 microM) of phosphatidylethanol inhibited cytosolic phospholipase A(2) activity. Phosphatidic acid, the normal phospholipase D product, also stimulated cytosolic phospholipase A(2) activity at 0.5 microM, but had an inhibitory effect on cytosolic phospholipase A(2) activity at concentrations of 50 and 100 microM. Ethanol (20-200 mM), the precursor of phosphatidylethanol, added directly to the assay did not alter cytosolic phospholipase A(2) activity. These results suggest that phosphatidylethanol alters the physical properties of the substrate, and at lower concentrations of anionic phospholipids the substrate is more susceptible to hydrolysis. However, at high concentrations, phosphatidylethanol either reverses the alterations in physical properties of the substrate or phosphatidylethanol may be competing as the substrate. Both interactions may result in lower cytosolic phospholipase A(2) activity.

The moral justification scale: reliability and validity of a new measure of care and justice orientations.

Research increasingly suggests that there are limitations to Kohlberg's theory of moral development. Gilligan in particular has observed that Kohlberg's theory considers abstract principled reasoning as the highest level of moral judgment, and penalizes those who focus on the interpersonal ramifications of a moral decision. Gilligan calls these justice and care orientations. The present paper describes the development of the Moral Justification Scale, an objective measure of the two orientations. The scale consists of six vignettes, of which two are justice oriented, two are care oriented, and two are mixed, incorporating both orientations. Construct validity was evaluated by expert judges and, overall, was high. Cronbach's alpha was .75 for the Care subscale and .64 for the Justice subscale, indicating adequate internal consistency. Split-half reliabilities were as follows: Care, r = .72, p < .01, and Justice, r = .60, p < .05. Regarding test-retest reliability (approximately two weeks), r = .61, p < .05, for Care; r = .69, p < .05, for Justice. Neither subscale correlated significantly with the Marlowe-Crowne Social Desirability Scale. Thus, the Moral Justification Scale shows promise as an easily administered, objectively scored measure of Gilligan's constructs of care and justice.

Lipopolysaccharide-stimulated nitric oxide production and inhibition of cell proliferation is antagonized by ethanol in a clonal macrophage cell line.

Both chronic and acute ethanol exposure have been shown to be cytotoxic and also to disrupt normal cell function or responses in a variety of cell types. Macrophage function has specifically been shown to be disrupted by chronic ethanol exposure by mechanisms that have not been elucidated. It is known that exposure of macrophages to lipopolysaccharide (LPS) from gram-negative bacteria will decrease the number of cells. Since increased exposure to endotoxin is often associated with chronic alcoholism, this may be one mechanism to account for loss of macrophages in alcoholic patients. The loss of macrophages, as a consequence of endotoxin treatment, appears to be linked to cell activation and, in particular, LPS-stimulated synthesis of nitric oxide which has been suggested to cause an increase in apoptosis. Ethanol also increases apoptosis in some cell types but, in general, ethanol inhibits activation of macrophages. Thus, the overall effect on cell numbers and cell proliferation elicited by treating macrophages concomitantly with ethanol and LPS depends on the balance between inhibiting LPS-mediated activation and the actions of ethanol. The interaction between ethanol and LPS was investigated in a macrophage cell line (RAW 264.7 cells) by measuring nitric oxide production and cell proliferation. A 24-h exposure to ethanol (100 mM) decreased [3H]-thymidine incorporation significantly. LPS treatment elicited a concentration-dependent decrease in [3H]-thymidine incorporation at LPS concentrations of 0.1 ng/ml to 1000 ng/ml and stimulated nitric oxide production at concentrations above 1 ng/ml. LPS-stimulated nitric oxide production was inhibited by ethanol (20 to 100 mM) and the nitric oxide synthesis inhibitor, N(G)Nitro-L-arginine methyl L-NAME) ester (100 and 500 microM). However, LPS-inhibited [3H]-thymidine incorporation was not be totally reversed by ethanol- or L-NAME-treatment. A direct correlation between nitric oxide production and inhibition of cell proliferation could not be demonstrated. However, it appears that ethanol and LPS do affect some common mechanism(s) in this cell line.

Activation of protein kinase A increases phospholipase D activity and inhibits phospholipase D activation by acetylcholine in tracheal smooth muscle.

Increased cAMP by stimulation of adenylyl cyclase with forskolin or by beta-adrenoceptor activation with isoproterenol increased phospholipase D (PLD) activity in tracheal smooth muscle strips. PLD activity was measured by the accumulation of phosphatidylethanol. A linear increase in the concentration of phosphatidylethanol was observed over 20 min in muscle strips treated with either forskolin or isoproterenol. Cholinergic stimulation with acetylcholine (ACh), by contrast, caused a rapid increase in phosphatidylethanol followed by a slow decline in the concentration of phosphatidylethanol from 5 to 20 min in the continued presence of ACh. Concomitant treatment with ACh and either forskolin or isoproterenol eliminated the rapid increases in phosphatidylethanol associated with ACh treatment. The response to forskolin or isoproterenol was not influenced by ACh. Inhibition of protein kinase C with calphostin C or bisindolylmaleimide I had no effect on isoproterenol- or forskolin-stimulated PLD activity but inhibited ACh-activated PLD activity. Protein kinase A (PKA) inhibitors H-89 and KT5720 significantly decreased forskolin- and isoproterenol-mediated activation of PLD activity. PKA inhibition also eliminated inhibition of ACh-stimulated PLD activity by forskolin or isoproterenol. Activation of adenylyl cyclase by forskolin or by isoproterenol caused increased phosphorylation of phospholipase C-beta(2) isoform and reduced the formation of inositol phosphates after ACh stimulation of muscarinic receptors. These results suggest that increasing the concentration of cAMP activates PLD via activation of PKA and that the increased activity of PKA also inhibits cholinergic stimulation of PLD, in part at least by inhibiting the activation of phospholipase C by ACh.

An unusual iatrogenic cause of right coronary air embolism.

A 62-year-old woman undergoing redo mitral valve replacement was noted to have persistent intracardiac air following standard deairing procedures. Transesophageal echocardiography (TEE) identified air bubbles entering the left atrium from the right superior pulmonary vein. Exploration of the pleural cavity revealed a fistula between the pulmonary parenchyma and the right superior pulmonary vein caused by the atriotomy closure suture transfixing the edge of the lung, which was repaired with immediate disappearance of the air emboli. This demonstrates that transesophageal echocardiography is an invaluable aid to ensuring complete deairing after open heart procedures.

How can obese weight controllers minimize weight gain during the high risk holiday season? By self-monitoring very consistently.

This study examined the efficacy of augmenting standard weekly cognitive-behavioral treatment for obesity with a self-monitoring intervention during the high risk holiday season. Fifty-seven participants in a long-term cognitive-behavioral treatment program were randomly assigned to self-monitoring intervention or comparison groups. During 2 holiday weeks (Christmas-New Years), the intervention group's treatment was supplemented with additional phone calls and daily mailings, all focused on self-monitoring. As hypothesized, the intervention group self-monitored more consistently and managed their weight better than the comparison group during the holidays. However, both groups struggled with weight management throughout the holidays. These findings support the critical role of self-monitoring in weight control and demonstrate the benefits of a low-cost intervention for assisting weight controllers during the holidays.

Cytotoxicity of short-chain alcohols.

Ethanol and other short-chain alcohols elicit a number of cellular responses that are potentially cytotoxic and, to some extent, independent of cell type. Aberrations in phospholipid and fatty acid metabolism, changes in the cellular redox state, disruptions of the energy state, and increased production of reactive oxygen metabolites have been implicated in cellular damage resulting from acute or chronic exposure to short-chain alcohols. Resulting disruptions of intracellular signaling cascades through interference with the synthesis of phosphatidic acid, decreases in phosphorylation potential and lipid peroxidation are mechanisms by which solvent alcohols can affect the rate of cell proliferation and, consequently, cell number. Nonoxidative metabolism of short-chain alcohols, including phospholipase D-mediated synthesis of alcohol phospholipids, and the synthesis of fatty acid alcohol esters are additional mechanisms by which alcohols can affect membrane structure and compromise cell function.

Activation of muscarinic receptors in porcine airway smooth muscle elicits a transient increase in phospholipase D activity.

Phospholipase D (PLD) is a phosphodiesterase that catalyses hydrolysis of phosphatidylcholine to produce phosphatidic acid and choline. In the presence of ethanol, PLD also catalyses the formation of phosphatidylethanol, which is a unique characteristic of this enzyme. Muscarinic receptor-induced changes in the activity of PLD were investigated in porcine tracheal smooth muscle by measuring the formation of [3H]phosphatidic acid ([3H]PA) and [3H]phosphatidylethanol ([3H]PEth) after labeling the muscle strips with [3H]palmitic acid. The cholinergic receptor agonist acetylcholine (Ach) significantly but transiently increased formation of both [3H]PA and [3H]PEth in a concentration-dependent manner (>105-400% vs. controls in the presence of 10(-6) to 10(-4) M Ach) when pretreated with 100 mM ethanol. The Ach receptor-mediated increase in PLD activity was inhibited by atropine (10(-6) M), indicating that activation of PLD occurred via muscarinic receptors. Activation of protein kinase C (PKC) by phorbol-12-myristate-13-acetate (PMA) increased PLD activity that was effectively blocked by the PKC inhibitors calphostin C (10(-8) to 10(-6) M) and GFX (10(-8) to 10(-6) M). Ach-induced increases in PLD activity were also significantly, but incompletely, inhibited by both GFX and calphostin C. From the present data, we conclude that in tracheal smooth muscle, muscarinic acetylcholine receptor-induced PLD activation is transient in nature and coupled to these receptors via PKC. However, PKC activation is not solely responsible for Ach-induced activation of PLD in porcine tracheal smooth muscle.