A qualitative evaluation of patients' experiences of an enhanced recovery programme for colorectal cancer.

AIM: We explored the patients' views and experiences of surgery for colorectal cancer within an enhanced recovery programme (ERP). METHOD: Semi-structured home interviews were performed within 6 weeks of hospital discharge with participants of a randomized trial comparing laparoscopically assisted surgery with open surgery for colorectal cancer within an ERP. Interviews were tape-recorded, transcribed and analysed using qualitative techniques of constant comparison based upon grounded theory. RESULTS: Interviewees (n = 22) had similar baseline characteristics and clinical outcomes to participants in the full trial. Many participants were pleased to be discharged quickly and they considered that being in their own home-improved recovery because it allowed them to choose how and when to undertake daily activities rather than following the hospital routine. Some participants (n = 9) were less satisfied with the process, and the reasons for this were related to complications requiring readmission or needing to contact a health professional for information after discharge. CONCLUSION: Although many participants reported benefits from an ERP, the study highlighted areas for improvement. In particular participants reported the need for better access to information and specialist advice in the early days after hospital discharge.

Calcium mobilization via type III inositol 1,4,5-trisphosphate receptors is not altered by PKA-mediated phosphorylation of serines 916, 934, and 1832.

Several studies have shown that PKA-mediated phosphorylation of IP3R1 at serines S1588 and S1755 enhances the receptor's ability to mobilize Ca2+. In contrast, much less is known about whether Ca2+ mobilization via IP3R2 and IP3R3 is regulated by PKA. We report here that IP3R2 is only very weakly phosphorylated in response to PKA activation and is probably not a physiological substrate for this kinase. IP3R3, however, is known to be phosphorylated by PKA at three sites (S916, S934, and S1832) and, thus, we examined how phosphorylation of these sites affects Ca2+ mobilization in DT40-3KO cells stably expressing either exogenous wild-type or mutant IP3R3s; an antibody raised against phospho-serine 934 of IP3R3 was used to demonstrate that the exogenous IP3R3s are strongly phosphorylated in response to PKA activation. Surprisingly, our data show that IP3R3-mediated Ca2+ mobilization is unaffected by phosphorylation of S916, S934, and S1832. In contrast, phosphorylation of exogenous IP3R1 (monitored with an antibody against phospho-serine 1755) enhances Ca2+ mobilization, indicating that DT40-3KO cells have the capacity to respond to phosphorylation of IP3Rs. Overall, these data suggest that modification of Ca2+ flux may not be the primary effect of IP3R3 phosphorylation by PKA.

The influence of an enhanced recovery programme on clinical outcomes, costs and quality of life after surgery for colorectal cancer.

OBJECTIVE: Optimizing peri-operative care using an enhanced recovery programme improves short-term outcomes following colonic resection. This study compared a prospective group of patients undergoing resection of colorectal cancer within an enhanced recovery programme, with a prospectively studied historic cohort receiving conventional care. PATIENTS AND METHODS: Sixty patients underwent elective resection within an enhanced recovery programme (ERP). This incorporated pre-operative counselling, epidural analgesia, early feeding and mobilization. Clinical outcomes were compared with 86 prospectively studied historic control patients receiving conventional care (CC). All patients completed EORTC QLQ-C30, QLQ-CR38 and health economics questionnaires up to three months after surgery. RESULTS: Baseline clinical data were similar in both groups. Postoperative hospital stay was significantly reduced in the ERP, with patients staying 49% as long as those in the CC group including convalescent hospital stay (95% CI 39% to 61%P < 0.001). There were no differences in the number of complications, readmissions or re-operations. There were no significant differences in quality of life or health economic outcomes. CONCLUSION: Patients undergoing colorectal resection within an ERP stay in hospital half as long as those receiving conventional care, with no increased morbidity, deterioration in quality of life or increased cost.

2-Aminoethoxydiphenyl borate inhibits inositol 1,4,5-trisphosphate receptor function, ubiquitination and downregulation, but acts with variable characteristics in different cell types.

2-Aminoethoxydiphenyl borate (2-APB) is a putative, membrane-permeable inhibitor of inositol 1,4,5-trisphosphate (InsP(3)) receptors, but it is the case that little is known about its action at the InsP(3) receptor level. Thus, we examined the effects of 2-APB on InsP(3) receptor-mediated effects in a range of cell types expressing different complements of InsP(3) receptor types. In experiments with permeabilized cells we found that 2-APB could inhibit InsP(3)-induced release of stored Ca(2+), but also that it released Ca(2+), and that the prevalence of these two effects varied between different cell types and did not correlate with the expression of a particular receptor type. These effects of 2-APB reflected an interaction distal to the ligand binding site of InsP(3) receptors, since InsP(3) binding was unaffected by 2-APB. In intact cells, we found only inhibitory effects of 2-APB on Ca(2+) mobilization, and that variation between cell types in the characteristics of this inhibition appeared to be due to differential entry of 2-APB. 2-APB also inhibited InsP(3) receptor ubiquitination and proteasomal degradation, which again was cell type dependent. In total, these data reveal a remarkable degree of variation between cell types in the effects of 2-APB, showing that its usefulness as a specific and universal inhibitor of InsP(3) receptors is limited. However, the ability of 2-APB to inhibit InsP(3) receptor ubiquitination and degradation indicates that 2-APB may block InsP(3)-induced conformational changes in the receptor, resulting in perturbation of multiple regulatory events.

Evaluation of the PuriLens contact lens care system: an automatic care system incorporating UV disinfection and hydrodynamic shear cleaning.

PURPOSE: This study evaluates lens care using the PuriLens System, an advanced way to clean and disinfect soft hydrophilic lenses using subsonic agitation and UV radiation, respectively. METHODS: A two-period crossover lens cleaning and safety investigation was conducted using 80 patients. Disinfecting efficacy was tested in accordance with standard FDA protocols. Lens compatibility was studied with Group I and Group IV lenses during the equivalent of a 6-month care regimen by measuring: lens power, base curve, wet diameter, refractive index, clarity, and tint. Safety was evaluated through slit-lamp findings, wearing time, comfort, and visual acuity. RESULTS: The mean wearing time of patients in the study was 13.79 hours. No slit lamp findings greater than grade 2 were noted. Visual acuity was 20/25 or better in 92.5% of examinations. None of the patients lost more than two lines of acuity. Lens surface evaluation showed no deposits (grade 0) to very slight deposits (grade 1) in 94.4% of examinations. Lenses cleaned with the PuriLens System were cleaner by a statistically significant margin (P=0.02) compared to lenses digitally cleaned with a leading multi-purpose solution (ReNu, Bausch & Lomb). Overall, neither the Group I nor Group IV lenses were affected after 180 cleaning cycles. CONCLUSIONS: The PuriLens System provides automatic lens care compliance, superior antimicrobial efficacy, and eliminates the need for daily digital cleaning.

Distribution of 3H-nicotine in rat tissues under the influence of simulated microgravity.

Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness. The present study was conducted in the head-down-tilt (HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30 degrees for two weeks on a 12/12 light/dark cycle. During this period, body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected i.v. with a solution containing 4 microcuries of nicotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain, blood, trachea, salivary gland, lung, heart, esophagus, spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determined and calculated as percent of total injected radioactivity. Final body weights of suspended animals were significantly (P < 0.05) lower than those of controls (309 +/- 21 vs 350 +/- 11 g). 3H-Nicotine was retained in greatest amounts by the kidneys, followed in order by salivary glands, spleen, and gastrointestinal tissues. Compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues: esophagus (25%), aorta (25%), fundus (25%), trachea (22%), adrenals (18%), spleen (17%), and pancreas (12%). The decreased retention of nicotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differences in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

Mini radial keratotomy reduces ocular integrity. Axial compression in a postmortem porcine eye model.

OBJECTIVE: This study aimed to examine ocular rupture force in pig eyes after "minimally invasive radial keratotomy" (MRK) and standard radial keratotomy (SRK). DESIGN: Experimental study. MATERIALS: A total of 71 pairs of pig eyes (51 control eyes) were examined. INTERVENTION: An axial-torsional Materials Testing System (MTS, Eden Prairie, MN) was used to apply blunt force to the corneal surface. A force transducer measured the rupture forces in control eyes and in eyes with MRK or SRK. Five groups of paired eyes were compared: 2.0-mm MRK versus control (N = 12), 3.5-mm MRK versus control (N = 21), 6.5-mm SRK versus control (N = 18), SRK versus 3.5-mm MRK versus 2.0-mm MRK (N = 10). MAIN OUTCOME MEASURE: Ocular rupture force (newtons) was measured. RESULTS: The mean rupture force in newtons was 746.3 for control eyes, 514.2 for 2.0-mm MRK, 353.1 for 3.5-mm MRK, and 246.2 for SRK. Analysis of variance showed a statistically significant difference (P < or = 0.04) between paired comparisons. CONCLUSION: The MRK and SRK significantly weakened ocular integrity compared with control eyes not operated on. MRK required significantly more force to rupture than SRK. MRK eyes, however, ruptured at 50% to 70% of the force required to rupture eyes not operated on. Any patient considering radial keratotomy should be counseled about the risk of greater ocular damage in trauma.

Effects of lidocaine on atrial natriuretic peptide concentrations in plasma and urine.

The antiarrhythmic agent lidocaine reduces inward sodium current and increases outward potassium current. Described studies investigated the effect of lidocaine on circulating and urinary levels of atrial natriuretic peptides in an intact canine model. Surface electrocardiography was monitored along with right ventricular, left ventricular and aortic pressures, and cardiac output. Plasma and urine atrial natriuretic peptides were measured immediately before and five minutes after a five minute, 2 mg/min, intravenous lidocaine infusion. Long acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) were monitored by RIA. There were no measured hemodynamic or cardiomechanical changes noted after lidocaine infusion. Similarly, there was no change in plasma sodium or potassium, or urine sodium. There was, however, an increase in urine potassium levels. Additionally, plasma and urine LANP and ANF peptide levels were increased following lidocaine infusion, while plasma and urine concentrations of vessel dilator were not changed. These data suggest that lidocaine increases plasma and urine atrial natriuretic peptides by mechanisms other than cardiodepression and/or vasodilation.

Tensile strength of insertional suture techniques in strabismus surgery.

BACKGROUND: The "lost" extraocular muscle is a serious adverse outcome of seemingly uncomplicated strabismus surgery. One potential cause of this complication is suture slippage in the operated muscle or tendon. The purpose of this study was to determine the relative tensile strengths of three suture techniques commonly used in strabismus surgery and to compare the incidence of suture slippage in the tendon or muscle among these techniques. METHODS: The horizontal rectus muscles of 18 adults pigs were assigned to undergo either recession or resection and were randomized to one of three suture techniques studies. Tension applied to the free ends of the suture was incrementally increased until failure occurred. The two techniques were compared in terms of the mean applied tensions at the time of failure and the incidence of slippage. RESULTS: No statistically significant difference in mean tension at failure between the three techniques used in recessed or resected muscles was found. Suture slippage in the tendon or muscle occurred in 25% of the trials and was almost evenly distributed among the techniques. Mean tension at slippage did not differ significantly between the techniques. No failure of any kind occurred at less than 100 g applied tension. CONCLUSION: Each suture technique appeared to adequately secure to tendon or muscle for recession and resection procedures. Changing techniques is unlikely to alter the incidence of lost muscles in strabismus surgery.

Effect of antagonist weakening on developed tension in cat extraocular muscle.

PURPOSE: In a previous study, the authors found that recession of an extraocular muscle resulted in atrophy of both the recessed muscle and its antagonist. To determine if atrophy, caused by weakening of an extraocular muscle, results in changes in developed tension in the antagonist, the authors studied force development of the cat lateral rectus muscle after adductor weakening. METHODS: Tenotomy of the left inferior, medial, and superior rectus muscles was performed in 18 cats. At 3, 6, and 12 weeks after surgery, the right (control) and left lateral rectus muscles were exposed through a lateral orbitotomy and were attached to isometric force transducers. Length-tension curves were obtained by direct muscle stimulation using bipolar contact electrodes at 0.1 Hz and 50% suprathreshold stimulus intensity. In addition, peak tetanic tension was measured at the optimal resting tension using a 5-second stimulus train at 200 Hz. Pooled data from the operative and control muscles at each postoperative interval were compared. RESULTS: Three weeks after adductor weakening, a 28% decrease in maximal single-twitch tension was seen in the left lateral rectus muscle when compared with controls. This difference disappeared at 6 weeks. No statistically significant changes in peak tetanic tension occurred at any time interval after surgery. CONCLUSIONS: Adductor weakening results in a transient decrease in single-twitch tension in the antagonist lateral rectus muscle in the cat.

Vessel dilator is associated with survival after acute myocardial infarction.

To assess whether infarct size, ischemic area and/or survival correlates with circulating atrial natriuretic peptides (long acting sodium stimulator, vessel dilator, or atrial natriuretic factor), these peptides were measured in a canine model of acute myocardial infarction. Elevations in the circulating concentrations of atrial natriuretic factor, vessel dilator, and long acting sodium stimulator were significant (P < 0.05) within 6 min of coronary occlusion of the left anterior descending coronary artery. The percentage of ischemic myocardium ranged from 20 to 67% with a mean of 37 +/- 17%. The area of infarction ranged from 1 to 13% with the infarcted area of non-survivors being twice that of survivors. Both the ischemic and infarcted areas correlated (P < 0.05) with the circulating concentrations of these atrial natriuretic peptides. Survival correlated also with the circulating plasma concentrations of vessel dilator, atrial natriuretic factor and long acting sodium stimulator (P < 0.05). When these circulating concentrations were evaluated, however, by determining their area under their respective concentrations curves and expressing each as the log area under plasma concentration-time curve (area under the curve) per kg of weight (Y = 58.48X-23.62; r = 0.825; P = 0.0009), vessel dilator was the only atrial natriuretic peptide that correlated with survival.

Effects of norepinephrine on BAY K-8644-induced contraction in porcine coronary artery.

BAY K-8644 is a dihydropyridine calcium agonist which produces contraction in several isolated vascular preparations--including porcine coronary artery. This study examined the ability of norepinephrine to relax porcine coronary artery previously contracted with BAY K-8644 and compared this to effects on preparations contracted with histamine. Norepinephrine relaxed BAY K-8644 and histamine-treated preparations to approximately base line developed tension. The ED50 value for norepinephrine was the same in the presence of increasing concentrations of either BAY K-8644 or histamine.

The antiseptic efficacy of chlorxylenol-containing vs. chlorhexidine gluconate-containing surgical scrub preparations.

The studies described here evaluate the efficacy of the chlorxylenol-containing surgical scrub formulations against the chlorhexidine gluconate-containing formulations using the Glove Juice Test, as recommended by the FDA's panel to develop guidelines for the study of antiseptic agents. Similar reports from the literature evaluating the relative efficacies of the iodophor-containing and the hexachlorophene-containing formulations are cited. Results fail to detect any significant differences in the efficacy of these two preparations, each significantly reducing the bacterial flora on the hands as indicated by immediate post-wash colony counts, and each demonstrating the continuing ability to significantly reduce bacterial growth with continued regular use.

Protection of myocardial function during endotoxin shock by ibuprofen.

We have concluded that Ibuprofen, a cyclooxygenase inhibitor with high specificity for the preferential blockage of thromboxane synthetase, significantly improves arterial blood pressure, cardiac index, and arterial pH during endotoxin shock in dogs (J. Clin. Invest. 70:536, 1982). This study was undertaken to determine whether Ibuprofen (25 mg/kg i.v.) administered 20 min prior to endotoxin (2 mg/kg i.v.) is able to overcome the depressed ability of cardiac microsomes to actively sequester calcium after 2 hrs of endotoxin shock. Results indicate that microsomes isolated from hearts of animals pretreated with Ibuprofen and then given endotoxin are able to sequester calcium at rates similar to microsomes isolated from control hearts. Microsomes isolated from hearts of animals in endotoxin shock without Ibuprofen show the anticipated depression of calcium sequestering ability. The improved ability of microsomes from the hearts of animals pretreated with Ibuprofen to sequester calcium is the result of normal Ca+2-Mg+2 ATPase activity in the microsomal membrane. We conclude that Ibuprofen protects against the detrimental hemodynamic derangements of endotoxin induced shock in the dog, and thereby also improves cardiac subcellular calcium transport; the factor regulating contractility. Ibuprofen may warrant evaluation as a protective agent to be used prophylactically in high risk cases of endotoxemia.

Ibuprofen in canine endotoxin shock.

The participation of prostaglandins in the physiologic alterations of endotoxin shock has been well established with the aid of prostaglandin synthetase inhibitors. Our study was designed to investigate the potential of ibuprofen, a highly specific cyclooxygenase inhibitor, to reverse the hemodynamic and acid base abnormalities of canine endotoxin shock. Mean blood pressure fell to 49.8 +/- 6.6 mm Hg in dogs given endotoxin by 5 min after injection, and remained below 83 mm Hg for the duration of the 120-min observation period. In animals given endotoxin followed by ibuprofen, a similar initial drop of systemic blood pressure was seen, but it subsequently recovered to 150.2 +/- 4.1 mm Hg by 120 min (P less than 0.001). Cardiac index increased in animals given ibuprofen (2.3 +/- 0.28 liter/m2 per min) compared with animals given endotoxin alone (1.0 +/- 0.09 liter/m2 per min) by termination of the experiment. The arterial pH dropped in endotoxin treated animals to 7.18 +/- 0.03 by 120 min. Ibuprofen prevented the acidosis, the final pH in ibuprofen and endotoxin treated animals measuring 7.36 +/- 0.01. We conclude that ibuprofen protects against the hypotension, acidosis, and depression of cardiac index of canine endotoxin shock.

The effect of contraceptive steroids on the incorporation of U14C-glucose into porcine aortic lipids.

The in vitro effect of 17 alpha-ethinylestradiol (E) and/or medroxy progesterone acetate (P) was determined on their abilities to alter conversion of glucose to lipid by porcine aorta. The combination of steroidal agents EP/HI (combination at high concentration) at a concentration of 9.5 X 10(-9) moles/ml caused a significant (p less than 0.01) reduction in 14C incorporation into total lipid. When the concentration of each hormone was reduced by one-half EP/LO (combination at low concentration) to give a final concentration of 4.8 X 10(-9) moles/ml the incorporation was also significantly reduced (p less than 0.05). The aforementioned reductions were subsequently found to be the result of depressed incorporation of the substrate glucose for the synthesis of phospholipid (PL), triacylglyceride (TG), a combined fraction of free cholesterol, diacylglyceride and free fatty acid (FC+DG+FFA), and cholesteryl ester (CE). The hormones individually had no effect on the incorporation of U14C-glucose into lipid. The study suggests that these oral contraceptives, when administered in pharmacological doses, can depress the conversion of glucose into arterial wall lipid.

The role of prostaglandins E2 and F2 alpha on canine arterial in vitro lipid biosynthesis from 14C-acetate.

This study was designed to investigate the influence of prostaglandin on in vitro incorporation of 14C acetate into canine aortic lipid. Aortae were excised from pentobarbital-anesthetized dogs, stripped of their adventitial layer and incubated four hours in the presence of labeled substrate alone or labeled substrate plus prostaglandin. The tissue was subsequently homogenized and the lipid phase extracted. Thin layer chromatography was used to separate lipid subfractions. Incorporated 14C was measured by liquid scintillation. PGE2 (0.05-0.10 microgram/ml) significantly decreased (p less than 0.01) incorporation of 14C acetate into phospholipid. Other lipid subfractions were not affected. PGF2 alpha (0.01-0.05 microgram/ml) significantly increased (p less than 0.01) incorporation of 14C acetate into phospholipid, triglyceride and FFA. Other subfractions were not affected. Studies conducted on intimal and medial layers separately failed to alter the extent to which 14C was incorporated into these tissue layers. Tissue "blanks" performed following destruction of enzymatic activity failed to demonstrate any significant background uptake of 14C. Therefore, in vitro effect of PGE2 is to decrease aortic wall lipid synthesis from acetate, while the effect of PGF2 alpha is to increase aortic lipid synthesis from acetate.