Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. METHODS: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19-90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18-94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0-10) vs. 3 (0-12) days, p = 0.036), and reduced time to first stool (median 2 (0-10) vs. 3 (0-12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. CONCLUSIONS: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

Getting the balance right: qualitative evaluation of a holistic weight management intervention to address childhood obesity.

BACKGROUND: Childhood obesity is linked to a range of health and social problems. Solutions include the delivery of appropriate weight management interventions for those aged 16 and under. The 'Balance It! Getting the Balance Right' programme appears to be effective for those who complete the intervention, but the non-completion rate remains high. A qualitative evaluation was undertaken to explore the views of key stakeholders in the programme and identify possible reasons for non-completion. METHODS: Semi-structured interviews were conducted with a purposive sample of 16 NHS and local authority staff, and with 20 children (aged 4-16 years) and their families. A mosaic methodology was used, involving visual and verbal techniques employed to enable children of all ages to take an active role in expressing their opinions. RESULTS: Key themes included the challenges of approaching overweight children; positive outcomes for some families; and issues relating to communication and coordination. Participants spoke positively about the multi-disciplinary approach of 'Balance It!', but felt it could better meet the needs of its target population. CONCLUSIONS: Structured interventions help to ensure consistency and coherence in terms of approaches to childhood overweight and obesity. Whole family approaches may be most effective in enhancing the user experience.

P-selectin-mediated attachment of small cell lung carcinoma to endothelial cells.

Small cell lung carcinoma (SCLC) frequently metastasizes early in the course of the disease. P-selectin (P-sel), a cell adhesion molecule expressed on activated platelets and endothelial cells (EC), has previously been demonstrated to mediate binding of platelets to SCLC. We hypothesized that P-sel facilitates attachment of SCLC to EC, acting as an important factor in SCLC metastasis. To test this hypothesis, attachment of H82 cells (SCLC cell line) to EC was quantified. Attachment of H82 cells to 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated EC was increased compared with control EC. Increased attachment of H82 cells to EC was apparent after 10 min of TPA activation, reached a peak after 30 min, and returned to baseline after 120 min of exposure. The TPA-induced increase in H82 cell attachment to EC was inhibited by addition of anti-P-sel antibodies but not by addition of anti-E-selectin antibodies. The TPA-induced increase in H82 cell attachment was likely mediated by activation of EC protein kinase C (PKC). Pretreatment of the EC with PKC inhibitors effectively blocked the TPA-mediated increase in H82 cell attachment. In addition, prolonged exposure of EC to TPA resulted in decreased expression of the PKC-alpha and PKC-epsilon isoforms. These data indicate for the first time that attachment of SCLC to activated EC appears to be mediated by increased expression of P-sel on the EC surface, which may result from activation of specific isoforms of PKC.

Limit for qualitative detection of benzoylecgonine in urine using EMIT reagents and the Hitachi 705 automatic analyzer.

The limit of detection for the cocaine metabolite (hydrolysis product), benzoylecgonine, using Syva EMIT reagents and the Hitachi 705 automatic analyzer has been found to be 10 ng/mL at the 99% confidence level. For this determination 30 controls were prepared from a single urine pool known to be negative for cocaine metabolite. Urine samples of 90 patients were found to be drug-free when analyzed by selected ion monitoring gas chromatography/mass spectrometry for ecgonine methyl ester and benzoylecgonine at sensitivities of less than 0.4 ng/mL and 1.3 ng/mL, respectively. To test matrix effects on the limit of detection, these samples were screened with the Hitachi 705. Results for eight of the known negative samples fell above the 10-ng/mL limit of detection while only one presumptive positive resulted at an arbitrary 20-ng/mL cutoff. Detection limits were also determined using 20 different negative patients' urine samples fortified with benzoylecgonine. At the 99% confidence level using EMIT d.a.u. and 705 reagents the detection limits were found to be 44 ng/mL and 35 ng/mL, respectively. It was found that 62% of patients' samples positive for benzoylecgonine fell below the 300-ng/mL cutoff and above a cutoff at 50 ng/mL.

Extending the detection limit of the TDx fluorescence polarization immunoassay for benzoylecgonine in urine.

This modified calibration method decreases from 300 to 27 micrograms/L the limit of detection for the cocaine metabolite (hydrolysis product), benzoylecgonine, by the Abbott Laboratories TDx fluorescence polarization immunoassay. For this determination we used 30 controls prepared from a single urine pool known to be negative for cocaine metabolite. Assay of 80 controls prepared from 20 different patients' urine samples yielded a limit of detection of 44 micrograms/L. To test these limits of detection, we analyzed 90 patients' urine samples known to be negative for cocaine metabolite and 74 patients' samples known to be positive for cocaine metabolite, using the TDx with our revised calibration. Results for two of the known negative samples and 96% of the samples containing cocaine in the 50 to 100 micrograms/L range fell above the 44 micrograms/L limit. The TDx showed excellent calibration stability. For 28 days during the test, the instrument was not recalibrated. During this period the day-to-day analysis of 50 micrograms/L controls produced a mean TDx response of 0.485 (SD 0.007) with a coefficient of variation of 1.5%.

Failure of triiodothyronine to inhibit TSH-mediated thyroid hormone release in man.

We studied the effect of short-term triiodothyronine administration on thyroid gland responsivity to exogenous thyrotropin in four euthyroid human subjects. Thyroidal iodine release and serum thyroxine during daily im injections of bovine TSH were not significantly inhibited, despite a four-fold elevation in serum T3 concentrations. This negative finding contrasts with earlier positive reports of a regulatory "short-loop" effect of elevated circulating T3 on the thyroid gland. This difference may be due either to the use in previous murine or in vitro studies of non-physiologic, high doses of exogenous T3, or failure to control the withdrawal of the trophic effect of endogenous TSH in man on the subsequent glandular response.

Lack of indomethacin effect on thyroid function in man.

Administration of indomethacin 200 mg daily for 2 days to four euthyroid volunteers was without significant effect on serum triiodothyronine or thyroxine and caused no cinsistent alteration of serum TSH. There were minor and variable changes in the pattern of thyroidal iodine release (TIR) in these euthyroid subjects. In one subject both the TIR pattern and serum TSH concentration were altered in the same direction, suggesting that these minor changes were of central origin. Indomethacin also had no effect on the stimulated pattern of TIR in one euthyroid subject receiving daily exogenous TSH injections, or in a patient with untreated hyperthyroid Graves' disease. Prostaglandin A1 infusion in one subject did not alter serum TSH or thyroidal iodine release. It is concluded that prostaglandins probably have no obligatory physiological role in modulating TSH or thyroid hormone secretion in man.

In vitro steroid metabolic studies in testicular 17 beta-reduction deficiency.

In order to document testicular 17beta-reduction deficiency (17RD) and to search for additional metabolic aberrations possibly associated with this disorder, the metabolism of 14C-labeled pregnenolone (delta5P), 17-HYDROXYPROGESTERONE (17OHP), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T) and estrone (E1) was studied in testicular minces from a 46-year-old male pseudohermaphrodite (MPH) with highly elevated testicular A and minimal T secretion but normal extragonadal conversion of A to T. Testicular minces from a 20-year-old MPH with apparently normal testicular T biosynthesis served as a control. The results of this investigation show that the 17RD testes metabolized delta5P along delta5- and delta4- pathways but, in contrast to the control, converted more 17OHP, metabolizing it predominantly to A rather than T, failed to reduce DHEA to androst-5-ene-3beta,17beta-diol, metabolized DHEA very efficiently to A and produced little T, and converted only minimal quantities of A and E1 to their 17beta-reduced counterparts. 17beta-Reduction increased slightly but was far from being restored to control levels upon addition of NADH plus NADPH. However, oxidation of T to A by 17RD testicular minces, with and without additional NAD plus NADP, was comparable to that by the control. These results document 17RD for A, DHEA and E1 and suggest that the lack of elevated 17OHP and DHEA secretion by the 17RD testes was due to increased 17, 20-lyase and perhaps elevated 3beta-hydroxysteroid dehydrogenase and/or isomerase activity. The observation that 17beta-reduction was only slightly increased upon addition of NADH plus NADPH, but that oxidation of T to A was normal, is consistent with the assumption that more than one 17beta-hydroxysteroid dehydrogenase may be involved in testicular 17beta-reduction and/or 17-oxidation, and that the 17RD testes studied either lacked the enzyme which acts predominantly as 17beta-reductase or that the affinity of this 17beta-reductase for reduced cofactor(s) and/or substrates was abnormal.