Pharmacokinetics of two per cent rectal methohexitone in children

Plasma methohexitone concentrations were determined in 60 children, aged one to six years, following administration of 15 mg.kg-1, 20 mg.kg-1, 25 mg.kg-1 or 30 mg.kg-1 two per cent rectal methohexitone. Time to the onset of sleep was determined by a blinded observer and venous blood samples obtained 15, 30, 45 and 120 minutes following drug administration. Fifty of 60 children were asleep within 15 minutes. Nine of the ten children that did not fall asleep were sedate and could be separated easily from their parents to undergo inhalational induction of anesthesia. Time to the onset of sleep was inversely related to the dose of rectal methohexitone administered. Sleep was achieved more reliably following the use of 25 to 30 mg.kg-1 rectal methohexitone. In addition, plasma methohexitone concentrations following 30 mg.kg-1 rectal methohexitone were significantly higher for up to 120 minutes following drug administration than the plasma concentrations achieved after 15 mg.kg-1 or 20 mg.kg-1 methohexitone. There was no difference in the incidence of complications. The authors recommend that clinical circumstances be carefully considered and the dose of rectal methohexitone administered be individualized to meet the specific anaesthetic requirements of each child.     

Haemodynamic effects of atropine during halothane or isoflurane anaesthesia in infants and small children

In this study, two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular changes before and after IV atropine in 31 infants and small children during halothane (n = 15) or isoflurane (n = 16) anaesthesia. Prior to induction of anaesthesia heart rate (HR), mean blood pressure (MBP), and two0dimensional echocardiographic dimensions of the left ventricle and pulmonary artery bloodflow velocity were measured by pulsed Doppler echocardiography. Cardiovascular measurements were repeated while anaesthesia was maintained at 1.5 MAC halothane (n = 15) or isoflurane (n = 16). Atropine 0.02 mg·kg⁻¹ IV was then administered and two minutes later, a third set of cardiovascular data was obtained. Heart rate decreased during halothane anaesthesia but did not change significantly during isoflurane anaesthesia. Mean blood pressure, cardiac output (CO) and stroke volume (SV) decreased similarly during 1.5 MAC halothane or isoflurane anaesthesia. Ejection fraction (EF) decreased and left ventricular end-diastolic volume (LVEDV) increased significantly in bothgroups, but decreases in EF (32 ± 5 percentvs18 ± 5 per cent) and increases in LVEDV (18 ± 7 per cent vs7 ± 5 per cent) were significantly greater during halothane than during isoflurane anaesthesia. Following atropine, HR increased more in the patients maintained with halothane (31 ± 6 per cent), than during isoflurane anaesthesia (18 ± 5 per cent). Atropine increased CO in both groups of patients, but SV and EF remained unchanged. When compared with awake values, HR increased similarly and significantly (18 ± 4 per cent) following atropine in both groups, and CO returned to control levels. Halothane decreased EF and increased LVEDV more than isoflurane at 1.5 MAC end— expired anaesthetic levels. Atropine did not diminish the myocardial depression produced by halothane or isoflurane. The increase in CO following atropine during halothane and isoflurane anaesthesia in infants and small children is the result of increases in HR alone. Nous avons utilisé un appareil à échocardiographie bi-dimensionnelle couplé à un Doppler pulsé chez des bébés et de jeunes enfants pour évaluer l’impact hémodynamique de l’halothane (n = 15) et de l’isoflurane (n = 16) et la modification possible de ces effets par l’atropine. Nous avons mesure la frequence cardiaque (FC), la pression artérielle moyenne (PAM), la dimension de la cavité ventriculaire gauche (par écho bi-dimensionnelle) et la vélocité du flot sanguin pulmonaire (par Doppler) et ce, en trois occasions soit avant l’induction, après l’instauration de 1.5 MAC d’halothane ou d’isoflurane et finalement, deux minutes après l’injection IV de 0.02 mg·kg⁻¹ d’atropine. On ne nota une baisse de la frequence cardiaque qu’avec l’halothane tandis que la PAM, le débit cardiaque (DC) et le volume d’éjection (VE) diminuaient autant avec l’un ou l’autre anesthésique. La diminution de la fraction d’éjection (FE) et l’augmentation du volume télédiastolique du ventricule gauche (VTDVG) significatives pour les deux groupes, étaienl plus marqué avec l’halothane qu’avec l’isoflurane: FE 32 ± 5 pour cent vs18 ±5 pour cent; VTDVG 18 ± 7 pour cent vs 7 ± 5 pour cent. Avec l’atropine, la FC monta plus dans le groupe halothane (31 ± 6 pour cent) que dans le groupe isoflurane (18 ± 5 pour cent), le DC augmentant dans les deux groupes, alors que le VE et la FE demeuraient inchangés. Comparée aux mesures pré-induction, l’atropine amenait une hausse significative de la FC, semblable dans les deux groupes (18 ± 4 pour cent) et restaurait le DC. Donc, chez les bebes et les jeunes enfants, a 1.5 MAC, l’halothane diminue la FE et augmente le VTDVG plus que ne le fait l’isoflurane. L’atropine ne modifie pas la depression myocardique et elle ne restaure le DC que par une hausse de la FC.

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Supported by PHS Grant No. 8507300 from the College of Medicine, University of Iowa Hospital, Iowa City, IA.     

Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity.

BACKGROUND: Combined modality therapy (CMT) is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC); however, insufficient data are available regarding prognostic factors in this disease setting. PATIENTS AND METHODS: Six hundred and ninety-four patients included in five trials conducted by the Cancer and Leukemia Group B evaluating CMT in stage III NSCLC were included in this analysis. The primary objective was to identify factors that were predictors of survival and selected radiation-related toxicities using Cox regression models and logistic regression analysis. RESULTS: The Cox model shows that performance status (PS) 1 [hazard ratio (HR) 1.24; 95% confidence interval (CI) 1.06-1.45; P=0.009] and thoracic radiation therapy (TRT) only (HR 1.58; 95% CI 1.22-2.05; P=0.001) predicted for poorer survival, while baseline hemoglobin >/=12 g/dl predicted for improved survival (HR 0.67; 95% CI 0.55-0.81; P 5% weight loss (OR 2.9; 95% CI 1.3-6.6; P=0.008) and patients receiving concurrent chemoradiation (OR 7.3; 95% CI 3.4-15.6; P=0.0001). CONCLUSIONS: Baseline hemoglobin and PS, as well as the use of CMT, have the greatest effect on survival in unresectable stage III NSCLC. The use of concurrent chemoradiation increases the risk of esophagitis, which remains the primary radiation-related toxicity.     

Ileal dysgenesis coexisting with multiple enteric duplication cysts in a child—MR enterography, CT, and Meckel scan appearances

There are numerous causes of iron deficiency anemia due to gastrointestinal tract bleeding in children. While a very thorough history may elucidate common etiologies, such as cow’s milk protein-induced colitis and nonsteroidal anti-inflammatory drug-related gastritis or peptic ulcer disease, other less frequent causes often present a diagnostic challenge. We present the MR enterography (MRE), CT and Meckel scan findings of ileal dysgenesis coexisting with multiple enteric duplication cysts in a young child who presented with chronic iron deficiency anemia, recurrent gastrointestinal tract bleeding and unexplained bowel perforation. In this case, MRE was able to identify and characterize each individual lesion and directly guide appropriate surgical management.     

Acoustic radiation force imaging (ARFI) in the non-distended bladder does not predict abnormal urodynamic parameters in children

IntroductionAcoustic radiation force imaging (ARFI) is a recently developed form of ultrasound imaging that allows in vivo measurement of tissue stiffness. This technology could be useful at predicting bladder compliance in children. We hypothesize that tissue stiffness, as measured by ARFI, correlates with abnormal bladder compliance and capacity in patients with bladder dysfunction.MethodsPatients who presented for cystometrography (CMG) underwent ARFI of the bladder wall. Nine bladder wall shear wave speed (SWS) measurements were acquired using point and 2D ultrasound shear wave elastography. The mean for each ARFI technique was correlated to bladder compliance, calculated using Wahl’s dimensionless number. ARFI parameters also were correlated with bladder capacity.ResultsA total of 25 patients were enrolled. Mean age at time of enrollment was 4.2±3.9 years (range two months to 15 years). There was no significant correlation between bladder compliance and point shear wave speed measurements (r=−0.22, p=0.31) or 2D shear wave speed measurements (r=−0.35, p=0.1). A total of 19 patients had bladder capacity below expected bladder capacity (EBC). There was no significant correlation between bladder capacity and point shear wave speed measurements (r =−0.08, p=0.7) or 2D shear wave speed measurements (r=−0.36, p=0.09).ConclusionsOur results did not demonstrate a significant correlation between bladder wall ARFI shear wave measurements and bladder compliance or bladder capacity. Further studies are warranted to determine whether ARFI may be used to predict abnormal urodynamic parameters in children.     

MR urography in children and adolescents: techniques and clinical applications

Renal and urinary tract imaging is commonly performed in the pediatric population, particularly in the setting of suspected or known congenital anomalies. In most cases, adequate anatomic assessment can be achieved using ultrasound and fluoroscopic techniques, and evaluation of differential renal function and urinary tract drainage can be accomplished with renal scintigraphy. However, in a subset of children, anatomic or functional questions may remain after this routine evaluation. In this setting, magnetic resonance imaging (MRI) tailored to evaluate the kidneys and urinary tract, known as MR urography (MRU), can be used to depict the kidneys, ureters, and urinary bladder in detail and to determine differential renal function and assess urinary tract drainage. The objectives of this review article are to (1) describe pediatric-specific MRI techniques for assessment of the kidneys and urinary tract and (2) present common clinical applications for pediatric MRU where imaging can “add value” in terms of diagnosis and patient management.     

2′ deoxycoformycin (pentostatin) for refractory non-Hodgkin's lymphoma: A calgb phase II study

Seventy-six eligible patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were treated with 2′-deoxycoformycin (pentostatin) at a dose of 4 mg/m² intravenously weekly for three weeks and then every other week for a minimum of five total treatments. All patients had measurable disease, near normal hematologic, renal, and hepatic function, and a performance status of 0 or 1. Severe hematologic toxicity was observed in 13% of patients; severe renal or neurologic toxicity was observed in less than 5% of patients. There were no treatment-related deaths. Objective therapeutic responses were seen in 16% of patients (five complete response [CR] and seven partial response [PR]). However, in three of the patients achieving CR and one patient achieving PR, dexamethasone was employed as an anti-emetic, making the response of these patients to pentostatin difficult to evaluate. There were eight responses (3 CR) in patients with diffuse histologies and four responses (2 CR) in patients with nodular or mixed histologies. Three responses were in patients with a T-cell phenotype. Three of five patients with diffuse well-differentiated lymphoma (IWF A) responded. We conclude that 2′ deoxycoformycin is only minimally active at this dose and schedule against refractory or relapsed NHL. The possibility that low grade B- and T-cell malignancies are more sensitive to 2′ deoxycoformycin deserves further investigation.