Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Value of Doppler ultrasound for the diagnosis of renal artery stenosis in children

To evaluate the reliability of Doppler ultrasonography (US) in identifying children with renal artery stenosis (RAS) among those with hypertension, we compared Doppler US results in 22 hypertensive children (mean age 8.9±4.3 years), with (13 cases) and without RAS at angiography, and in 33 normotensive children (mean age 8.8±4.7 years). We observed 2 false-negatives and 2 false-positives with Doppler US. Of the 2 false-negative diagnoses, 1 had RAS on an accessory renal artery located behind a normal upper polar artery and the other was observed in a patient with bilateral multiple stenosis of the very distal segments of renal arteries. The 2 false-positive diagnoses were due to sinuous left renal artery and to technical reasons, respectively. In another patient, Doppler US showed a tight RAS, while arteriography was normal. RAS was subsequently confirmed by a second arteriography. Peak systolic velocity values of Doppler US were significantly higher in patients with proven angiographic RAS (3.44±0.66 m/s) than in hypertensive patients with normal renal arteries at angiography (0.99±0.35 m/s, P <0.0001) and normotensive healthy children (1.04±0.23 m/s, P <0.0001). With the use of multiple views, and the experience acquired with practice, false-negatives or false-positives due to the geometry of the renal artery can be avoided. Nevertheless, very distal stenosis can be missed by Doppler US. Received October 30, 1995; received in revised form April 16, 1996; accepted May 14, 1996     

Risk factors for placental abruption in a socio-economically disadvantaged region.

OBJECTIVE: This study was undertaken in order to determine the risk factors for pregnancies complicated by placental abruption in a socio-economically disadvantaged region in metropolitan Adelaide. METHODS: This was a retrospective case-control study including all singleton pregnancies resulting in placental abruption between 2001 and 2005. RESULTS: The overall incidence of placental abruption was 1.0%; the overall perinatal mortality among the births with abruption was 13%. Univariate analyses showed the following significant risk factors for placental abruption: preterm pre-labor rupture of the membranes (PRE-PROM; odds ratio (OR) 4.79, 95% confidence interval (CI) 1.52-15.08), non-compliance with antenatal care (OR 2.93, 95% CI 1.06-8.90), severe intrauterine growth restriction (IUGR), and elevated homocysteine levels (OR 45.55, 95% CI 7.05-458.93). Severe IUGR was significantly more common in the abruption group compared with the control group (p = 0.032). In the multivariate analysis, PRE-PROM remained a significant independent risk factor for placental abruption. Marijuana use, domestic violence, and mental health problems were more common (borderline significance) in the abruption group. Smoking and preeclampsia were not found to be associated with placental abruption in this study. CONCLUSIONS: In this high-risk population, PRE-PROM and elevated homocysteine levels appear to represent the major risk factors for placental abruption.     

在免眼中进行经瞳孔阈值下温热疗法的组织学效应和蛋白表达

目的：研究阈值下经瞳孔温热疗法（TTT）对视网膜组织学的效应。方法：对正常视网膜色素的兔眼进行TTT，通过1个810nm激光二极管产生直径为1．2mm能量为50mW的光斑，持续时间为15、30和60秒。4周后进行荧光血管造影并摘除眼球，通过电子显微镜和免疫组化染色来检查。     

Ileogastrostomy for morbid obesity

Jejunoileal bypass procedures for morbid obesity have been associated with numerous side effects, due mainly to the blind-loop syndrome. To overcome this, the authors describe a new procedure, ileogastrostomy, that they have performed in 50 patients. All had good weight loss and returned to work. Patient satisfaction with the operation was high and self-esteem increased. There were no deaths or severe complications. Stool frequency and foul-smelling stools were still problems but improved with time. Stomal ulceration occurred at 3 months in three patients but resolved within 1 month when treated with H2 blocking agents and was not encountered later than 3 months in any patient.     

Determinants of plasma concentrations of nicotine and cotinine during cigarette smoking and transdermal nicotine treatment

Objective: Interindividual variability in plasma concentrations of nicotine and its proximate metabolite, cotinine, is considerable during smoking and transdermal nicotine treatment, even among individuals taking in nominally similar doses of nicotine. This report explores the determinants of this variability and the utility of baseline (smoking) plasma concentrations to predict concentrations during transdermal nicotine treatment. Methods: Data were analysed from a smoking cessation study (n = 466), and from a pharmacokinetic study (n = 12). Multiple regression models examined the relationships of plasma concentrations to individual characteristics such as smoking pattern, absorbed dose of nicotine, and pharmacokinetic parameters. Results: Plasma concentrations of nicotine and cotinine were highly variable in both studies. Indirect estimates of plasma clearance (baseline plasma concentration divided by cigarettes per day) together with other factors could account for 18 to 33% of the variability during transdermal nicotine treatment in the smoking cessation study. In contrast, 75 to 99% was accounted for by direct measurements of plasma clearances and systemic dose of nicotine in the pharmacokinetic study. Conclusion: Plasma concentrations of nicotine and cotinine during transdermal nicotine treatment are poorly predicted by clinical history or baseline plasma concentrations. This is a result of inadequate characterisation of highly variable individual pharmacokinetic parameters and absorbed dose of nicotine. Considering the interindividual variability of plasma nicotine and cotinine concentrations together with the lack of clinical end-points for transdermal nicotine dosing, it seems logical to investigate the utility of a therapeutic drug monitoring approach for transdermal nicotine treatment – particularly for high dose regimens (> 22 mg per 24 hours). Received: 7 May 1996 / Accepted in revised form: 21 August 1996     

Follow-up of patients who have undergone ileogastrostomy

Patients who have had ileogastrostomy for the treatment of morbid obesity require close, long-term follow-up. From a prospective study of a large number of variables in 12 consecutive patients, and from experience with more than 200 patients who have undergone this procedure since 1982, a protocol has evolved. The authors outline the associated morbid conditions, operative complications and biochemical alterations that are important in the management of these patients.     

Laboratory evaluation of the Pall LG6 leukocyte depleting arterial line filter

The Pall LG6 arterial line filter has been designed to remove free circulating leukocytes from the arterial line of the extracorporeal circuit employed in openheart surgery. The filter was evaluated and compared to a control filter (Pall Stat-Prime) in terms of its general blood handling characteristics, particularly with regard to the associated level of leukocyte removal. The gross air handling characteristics of the filters were also assessed together with pressure drop. It was found that the filters differed little in terms of all factors studied other than the level of leukocyte depletion. The LG6 filter was associated with substantial levels of leukocyte depletion, particularly the depletion of neutrophils. Over the 90 minute perfusion period the LG6 filter was found to be associated with a neutrophil depletion rate of around 70% while preferentially sparing lymphocytes. This compared to a 10-20% depletion rate in the control filter. This was achieved without apparently compromising the performance of the filter in terms of the other factors studied.     

Pharmacokinetics of rhuMAb CD18, a Recombinant Humanised Monoclonal Antibody Fragment to CD18, in Normal Healthy Human Volunteers

Background and Objectives: Leucocyte β2 integrin adhesion receptors are hypothesised as a therapeutic target to modify immune responses to ischaemia-reperfusion injury that may be detrimental to recovery in a variety of disease states. Two phase I studies were designed to evaluate the pharmacokinetics, immunogenicity and safety of rhuMAb CD18, ahumanised monoclonal antibody F(ab’)₂ fragment to the CD18 receptor, in normal healthy human volunteers. Study Design and Methods: The first study evaluated six escalating doses of rhuMAb CD18 (0.06, 0.12, 0.25, 0.5, 1.0, 2.0 mg/kg) in 36 subjects given two intravenous (IV) bolus injections 12 hours apart. In the second study, 16 subjects received IV doses of 1.0 and 2.0 mg/kg as a single dose or as two doses given 12 hours apart. Study endpoints were rhuMAb CD18 serum pharmacokinetics, change in white blood cell (WBC) count, and safety and tolerability. The two studies enrolled a total of 53 subjects. Results: Serum concentration-time profiles demonstrated a monophasic decline and were best characterised by a one-compartment pharmacokinetic model. At the doses administered, the volume of distribution approximated the serum volume (range of means: 42 to 58 ml/kg). The serum clearance decreased with increasing dose until becoming consistent at doses of 0.5 to 2.0 mg/kg (range of means: 3.1 to 5.0 ml/h/kg). At doses of 0.5 to 2.0 mg/kg, the mean elimination half-life ranged from 7.0 to 9.6 hours. WBC counts increased at doses of above 0.06 mg/kg, returning to within 20% of predose values by day 7. Antibodies to rhuMAb CD18 were not detected at day 28. Mild-to-moderate adverse events were observed in both the placebo and treated groups, and were limited to flu-like symptoms. One subject experienced a serious adverse event (febrile reaction) and recovered with minimal intervention. There was no evidence of an increase in infection in subjects who received rhuMAb CD18. Conclusions: Upon IV bolus administration, rhuMAb CD18 serum concentration-time data fit a one-compartment pharmacokinetic model. At doses of 0.5 to 2.0 mg/kg, the pharmacokinetics were linear and the half-life ranged from 7.0 to 9.6 hours with a volume of distribution that approximated the serum volume. No antibodies to rhuMAb CD18 were detected. A transient, dose-dependent increase in the WBC count was observed, consistent with the expected effect of rhuMAb CD18 on leucocyte demargination. No increase in infection was observed. rhuMAb CD18 administered by IV bolus was well tolerated, with the exception of one febrile reaction.     

Outcomes of gastrostomy placement with and without concomitant tracheostomy among ventilator dependent children

IntroductionSimultaneous gastrostomy tube (GT) and tracheostomy placement in young children offers potential benefit in limiting anesthetic exposure, but it is unknown whether combining these procedures introduces additional morbidity. This study compared outcomes after combined GT and tracheostomy placement versus GT placement alone among similar ventilator-dependent patients.MethodsVentilator-dependent children <2-years-old who underwent GT placement alone (MV-GT), simultaneous GT and tracheostomy placement (GT+T), and GT placement alone with a pre-existing tracheostomy (T-GT) were identified using 2012–2018 NSQIP-Pediatric Participant User Files. Multiple logistic regression models were used to compare outcomes while adjusting for other group differences.ResultsAmong 1100 children, 351 underwent MV-GT, 494 GT+T, and 255 T-GT. Major complications occurred in 23.6%, 17.0%, and 14.5% of the respective groups (p = 0.01). Major complications with GT+T were similar to T-GT (adjusted odds ratio [aOR]=1.19, 95%CI:0.78–1.83, p = 0.4) and lower than MV-GT (aOR=0.67, 95%CI:0.47–0.95, p = 0.02). Severe complications including mortality, cardiac arrest, and stroke were similar between the three groups (p = 0.8).ConclusionsChildren <2-years-old undergoing GT+T did not experience higher post-operative complications compared to children undergoing T-GT or MV-GT. Utilizing GT+T to limit anesthetic exposure may be reasonable within this high-risk population.Type of StudyTreatment StudyLevel of EvidenceLevel III