Perioperative measures in very long chain acyl-CoA dehydrogenase deficiency.

Surgical procedures in patients with metabolic disorders require specific anesthetic measures based on the nature of the involved metabolic disorder. Illustrated by the history of two patients, the need for a specific perioperative regimen in patients with very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is discussed. One patient deteriorated, the other patient did well without any specific measurements. Although perioperative metabolic decompensation can currently not be predicted, it is a severe complication which should be avoided. We therefore advise to consider certain perioperative precautions in all VLCADD patients: 1) age and weight adapted glucose infusion, 2) stress avoiding premedication, 3) avoidance of volatile anesthetics, 4) avoidance of long chain fatty acid containing anesthetics and 5) perioperative glucose and CK monitoring.

A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma.

CONTEXT: Medullary thyroid carcinoma (MTC) metastasizes early in its clinical course. No effective systemic therapy is available. Generally (somatic or germline), mutations in the rearranged during transfection gene are considered essential in the pathogenesis of MTC. OBJECTIVE: We investigated imatinib, a tyrosine kinase inhibitor, as a potential treatment in patients with disseminated MTC. DESIGN: A phase II study was initiated using 600 mg imatinib daily with a possible dose increase to 800 mg in case of progression. Standard Response Evaluation Criteria in Solid Tumors were used using computed tomography or magnetic resonance imaging every 2 months. RESULTS: There were 15 patients with disseminated MTC treated for up to 12 months. No objective responses were observed. Four patients had stable disease over 24 months. Three patients stopped treatment due to toxic effects [fatigue (n = 2) and nausea (n = 1)]. In four cases the dose of imatinib was decreased because of toxicity [rash and malaise (n = 2) and laryngeal swelling (n = 2)]. Emergency tracheotomy was performed in two cases due to mucosal swelling of the larynx in patients with recurrent nerve palsy and a narrow vocal cleft. In nine patients with a history of a thyroidectomy, the dose of supplemental thyroid hormone was increased because of serious hypothyroidism. CONCLUSIONS: Imatinib therapy yielded no objective responses and induced considerable toxicity in patients with MTC. A minority of patients had stable disease. Patients with supplemented hypothyroidism or with recurrent nerve palsy are specifically at risk for serious adverse events and need special attention when treated with imatinib.

Complications associated with cesarean section in HIV-infected patients.

OBJECTIVE: To document complications associated with cesarean section in HIV-infected women. METHOD: A cross-sectional study was done on 307 women who delivered by cesarean section. All these patients, irrespective of their HIV-status, were managed according to the same preset protocol. RESULT: Of the 307 women, 59 (19%) were HIV-positive. The only significant differences were a higher prevalence of positive serology for syphilis (32% vs. 12%, P=0.0014) as well as more cases of post-operative endometritis in the HIV-positive group (24% vs. 7%, P=0.0003). Post-operative endometritis was documented in 44% of HIV-infected patients with a CD4 count below 400. However, the severity of endometritis, measured by antibiotic treatment and duration of hospital stay, was similar in the two groups. Overall, there was no difference in the duration of hospital stay, post-operative anemia, wound infection, birth weight and perinatal mortality between the two groups. CONCLUSION: HIV-infected patients undergoing cesarean section are at increased risk for post-operative endometritis, but the severity of the infection is not different from that in HIV-negative patients.

Beta-agonist-induced constitutive beta(2)-adrenergic receptor activity in bovine tracheal smooth muscle.

According to the two state receptor model, the beta(2)-adrenergic receptor (beta(2)-AR) isomerizes between an inactive state and a constitutively active state, which couples to the stimulatory G-protein in the absence of agonist. In bovine tracheal smooth muscle (BTSM), we investigated the effect of short and long term beta(2)-AR activation by fenoterol on constitutive receptor activity. Preincubation of the BTSM strips for 5 min, 30 min and 18 h with 10 microM fenoterol, followed by extensive washout (3 h, 37 degrees C), caused a rapid and time-dependent inhibition of KCl-induced contraction, reaching 68+/-10, 51+/-6 and 46+/-4% of control, respectively, at 40 mM KCl (P:<0.05 all). At all time points, the EC(50) values to KCl were significantly reduced as well. Preincubation of BTSM with 0.1, 1.0 and 10 microM fenoterol during 18 h caused a concentration-dependent decrease of the 40 mM KCl response to 70+/-5, 47+/-12 and 43+/-9% of control, respectively (P:<0.05 all). The reduced KCl contractions were reversed in the presence of 1 microM timolol. Moreover, the sensitivity to KCl in the presence of timolol was enhanced after fenoterol incubation. Inverse agonism was also found for other beta-blockers, with a rank order of efficacy of pindolol >/=timolol=propranolol>alprenolol>/=sotalol>labetalol. At 25 mM KCl-induced tone, the contraction induced by cumulative timolol administration was competitively antagonized by the less efficacious inverse agonist labetalol, indicating that the fenoterol-induced effects cannot be explained by residual beta-agonist binding. In conclusion, fenoterol treatment of BTSM causes a time- and concentration-dependent development of constitutive beta(2)-AR activity, which can be reversed by various inverse agonists. The beta-agonist-induced changes could represent a novel regulation mechanism of beta(2)-AR activity.

Higher order and lower order variables in the visual perception of relative pulling force.

In 7 experiments, undergraduates judged the force exerted by a videotaped standing puller, a computer-generated (stick-figure) puller, or a computer-generated inverted pendulum. Single and stepwise multiple regression analyses determined the kinematic variables exploited by the participants. Results show that (a) judgments correlated highly with force and improved with feedback; (b) judgments correlated more highly with lower order kinematic variables than with force itself; (c) participants differed in the kinematic variables exploited; (d) participants changed over blocks of trials in the variables exploited; (e) some participants used compound kinematic variables; (f) the variables exploited depended on the type of feedback; and (g) judgments to upright pullers, inverted pullers, and simple pendula showed the same qualitative patterns. Implications for theories of direct perception, directed perception, and heuristics are considered.