Chronic fibrosing pancreatitis in childhood: report of a case and literature review.

Chronic fibrosing pancreatitis in childhood is an uncommon condition of unknown etiology with a variety of clinical presentations, histopathologic features, and outcomes. The diagnosis is one of exclusion (of hereditary or secondary pancreatitis), which should include histological assessment. The histological features of this condition have been described, to our knowledge, in nine published cases. We report a case in a 13-year-old male, who presented with obstructive jaundice and subsequently had evidence of endocrine and exocrine pancreatic insufficiency, despite a surgical decompression of the pancreatic-biliary duct system.

The interaction between endothelium-derived relaxing factor (EDRF) and eicosanoids in the regulation of the mesenteric microcirculation.

Locally produced eicosanoids and endothelium-derived factors are believed to be the mediators of vascular tone of various vascular beds including the mesentery. Using a small vessel isometric myograph which allows direct measurement of microvascular reactivity, the interaction of eicosanoids and endothelium-derived relaxing factor (EDRF) in regulating vascular tone of mesenteric microcirculation of the rat was characterized. The microvascular response to various vasoactive agents before and after inhibition of prostacyclin production with indomethacin (INDO, 5 microM) and inhibition of EDRF synthesis with N omega-nitro-L-arginine methyl ester (L-NAME, 50 microM) was compared. Analysis of dose-response curves for prostaglandin F2 alpha (PGF2 alpha), U46619, a stable thromboxane analog, and norepinephrine (NE) after pretreatment with INDO demonstrated that inhibition of endogenous eicosanoids significantly attenuated the vasoconstrictor response to PGF2 alpha and U46619 but not to NE. Inhibition of EDRF synthesis with L-NAME potentiated the vasoconstrictor response to PGF2 alpha, U46619, and NE. These results suggest that EDRF acts as the primary mediator of vasodilator tone in the mesenteric microcirculation rather than vasodilator cyclooxygenase products such as prostacyclin. It also appears that the vasoconstrictor action of PGF2 alpha and U46619 may be mediated by a release of an endogenous indomethacin-sensitive factor.

The pharmacokinetics of propofol in children using three different data analysis approaches.

BACKGROUND: Accurate dosing of propofol in children requires accurate knowledge of propofol pharmacokinetics in this population. Improvement in pharmacokinetic accuracy may depend on the incorporation of individual patient factors into the pharmacokinetic model or the use of population approaches to estimating the pharmacokinetic parameters. We investigated whether incorporating individual subject covariates (e.g., age, weight, and gender) into the pharmacokinetic model improved the accuracy. We also investigated whether the use of a mixed-effects population model (e.g., the computer program NONMEM) improved the accuracy of the pharmacokinetic model beyond the accuracy obtained with models estimated using two simple approaches. METHODS: We studied 53 healthy, unpremedicated children (28 boys and 25 girls) ranging from 3 to 11 yr of age. Twenty children only received an initial loading dose of 3 mg/kg intravenous propofol. In the remaining 33 children, an initial intravenous propofol dose of 3.5 mg/kg was followed by a propofol maintenance infusion. Six hundred fifty-eight venous plasma samples were gathered and assayed for propofol concentrations. Three different regression techniques were used to analyze the pharmacokinetics: the "standard two-stage" approach, the "naive pooled-data" approach, and the nonlinear mixed-effects modeling approach (as implemented in NONMEM). In both the pooled-data and mixed-effects approaches, individual covariates (age, weight, height, body surface area, and gender) were added to the model to examine whether they improved the quality of the fit. Accuracy of the model was measured by the ability of the model to describe the observed concentrations. RESULTS: The pharmacokinetics of propofol in children were best described by a three-compartment pharmacokinetic model. There were no appreciable differences among the pharmacokinetics estimated using the two-stage, pooled-data, and mixed-effects approaches. Weight was a significant covariate, and the weight-proportional model was supported by all three regression approaches. The pharmacokinetic parameters of the weight-proportional pharmacokinetic model (pooled-data approach) were: central compartment (V1) = 0.52 1 x kg-1; rapid-distribution compartment (V2) = 1.01 x kg-1; slow-distribution compartment (V3) = 8.2 1 x kg-1; metabolic clearance (Cl1) = 34 ml.kg-1 x min-1; rapid-distribution clearance (Cl2) = 58 ml.kg-1 x min-1; and slow-distribution clearance (Cl3) = 26 ml.kg-1 x min-1. The inclusion of age as an additional covariate of V2 statistically improved the model, but the actual improvement in the fit was small. CONCLUSIONS: The pharmacokinetics of propofol in children are well described by a standard three-compartment pharmacokinetic model. Weight-adjusting the volumes and clearances significantly improved the accuracy of the pharmacokinetics. Adjusting the pharmacokinetics for inclusion of additional patient covariates or using a mixed-effects model did not further improve the ability of the pharmacokinetic parameters to describe the observations.

Identification of dopamine1A receptors in the rat small intestine.

Dopamine receptors have been localized to several tissues outside the central nervous system including the kidney and mesenteric vessels. To determine if there are dopamine1 receptors within the small intestine, homogenates of the antimesenteric halves of the entire jejunum and ileum of adult rats were prepared and competitive inhibition studies and Scatchard analysis were performed at room temperature using 125I-SCH 23982 and SCH 23390. The specific binding of 125I-SCH 23982 to the intestinal tissue homogenates was rapid, saturable with ligand concentration, and reversible. Analysis of the Scatchard plots revealed a single class of receptors with an apparent dissociation constant of 10.77 +/- 2.32 nM and maximum receptor density of 1.37 +/- 0.34 fmole/mg protein. Emulsion autoradiography performed using 125I-SCH 23982 on antimesenteric sections of the rat small intestine revealed that the dopamine1 receptors are located on cells at the base of the intestinal crypts. Two dopamine1 subtypes (D1A and D1B) have been identified by molecular biological techniques. Using a ribonuclease protection assay we found expression of the D1A receptor gene in the small intestinal tissue. These studies are the first to identify, characterize, and localize receptors for the endogenous catecholamine, dopamine, within the rat small intestine and to confirm the expression of the D1A receptor gene.

Recurrent abdominal pain due to chronic appendiceal disease.

Recurrent appendicitis and chronic appendicitis are the subjects of much controversy, but long-standing inflammation of the appendix and surrounding tissues has been reported in rare instances. We have described two patients, both with recurrent episodes of abdominal pain, who subsequently were shown to have chronic appendiceal disease. Appendiceal disease should be considered in the differential diagnosis in patients with recurrent abdominal pain.

Gingival granular cell tumors of the newborn. An ultrastructural and immunohistochemical study.

Gingival granular cell tumor of the newborn, or congenital epulis, is a rare congenital lesion of uncertain histogenesis located exclusively on the alveolar ridge with marked predilection for female infants. Although histologically similar to the more ubiquitous granular cell tumor or myoblastoma, ultrastructural and immunohistochemical studies support separate histogenetic pathways for the two lesions. A newborn female infant with three gingival granular cell tumors is described herein along with immunohistochemical and ultrastructural observations. There was positive immunostaining for vimentin but staining for S100 protein was uniformly negative. Immunocytochemical assay for estrogen and progesterone receptors was also negative. The findings indicate a mesenchymal origin and the demonstration of intermediate filaments with fusiform electron densities suggests that some of the granular cells have morphologic attributes of myofibroblasts.

Extracorporeal membrane oxygenation for neonatal respiratory failure. A report of 50 cases.

From February 1985 through June 1987, 50 newborn infants in whom maximal ventilator therapy failed (80% predicted mortality) were treated with extracorporeal membrane oxygenation (ECMO) according to the following inclusion criteria: arterial oxygen tension less than 50 torr (alveolar-arterial oxygen gradient greater than 630 torr) for 2 hours or arterial oxygen tension less than 60 torr (alveolar-arterial oxygen gradient greater than 620 torr) for 8 hours. Criteria for exclusion from ECMO therapy included birth weight less than 2000 gm, gestational age less than 35 weeks, presence of intracranial hemorrhage, presence of other major congenital anomalies including cyanotic heart disease, and high levels of ventilatory support for more than 7 days. Mean birth weight was 3.28 +/- 0.56 kg, mean gestational age was 39.6 +/- 1.7 weeks, and mean age at the start of ECMO was 48.6 +/- 36.9 hours. Meconium aspiration, usually associated with persistent pulmonary hypertension, was the most common cause of pulmonary failure (62%). Mean pre-ECMO arterial oxygen tension during maximal ventilatory and pharmacologic support was 34.5 +/- 14.5 torr. Mean ventilatory support immediately before the institution of ECMO was as follows: peak inspiratory pressure 46.8 +/- 9.9 cm H2O, positive end-expiratory pressure 4.6 +/- 1.6 cm H2O, and intermittent mandatory ventilation rate 101.0 +/- 22.7 breaths/min with all patients receiving an inspired oxygen fraction of 1.0. Lung management to prevent pulmonary atelectasis during ECMO consisted of moderate levels of positive end-expiratory pressure (mean 10.3 +/- 2.6 cm H2O, range 8 to 14 in 94% of patients. Other mean ventilator parameters during ECMO were as follows: peak inspiratory pressure 22.8 +/- 1.6 cm H2O, intermittent mandatory ventilation rate 11.8 +/- 2.9, and inspired oxygen fraction 0.21. The overall long-term patient survival rate was 90%. Mean values for arterial blood gases and ventilator settings immediately after the discontinuation of ECMO were as follows: oxygen tension 78.4 +/- 22.1 torr, pH 7.39 +/- 0.10, carbon dioxide tension 37.4 +/- 10.7 torr, peak inspiratory pressure 25.2 +/- 3.9 cm H2O, positive end-expiratory pressure 5.6 +/- 1.2 cm H2O, and intermittent mandatory ventilation rate 41.3 +/- 12.6 with an inspired oxygen fraction of 0.42 +/- 0.17. Despite slightly higher levels of ventilator support (peak inspiratory pressure 46.8 versus 45.0 cm H2O, not significant) mean pre-ECMO oxygen tension was significantly lower than that reported from the National ECMO Registry (34.5 versus 42.0 torr, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

The use of topical fibrin glue at cannulation sites in neonates.

The application of fibrin glue to ECMO cannulation sites in neonates is described. Excellent hemostasis was obtained in all 11 patients which simplified hemodynamic management and significantly reduced blood product transfusions.

Securing broviac catheters in children.

Placement of a single suture in a strategic location helps to insure against inadvertent dislodgement of Broviac or Hickman catheters immediately after insertion. Indwelling Broviac and Hickman type catheters are gaining popularity for long-term venous access, particularly in children and infants. These silicone catheters were introduced in 1973, and many papers have been written since then documenting their efficacy and their incidence of complications. Inadvertent dislodgement of these catheters is rarely mentioned in these reports, but we have seen this complication in a number of patients; therefore, we have modified our insertion technique to prevent this unfortunate complication.

Mössbauer spectroscopic studies of hemoglobin and its isolated subunits.

Samples of 90% enriched 57Fe hemoglobin and its isolated subunits have been prepared. Mössbauer spectroscopic measurements have been made on three such samples. Sample one contained contributions of oxyhemoglobin, deoxyhemoglobin, and carbonmonoxyhemoglobin. This sample was studied from a temperature of 90 K down to 230 mK. Measurements were also made at 4.2 K using a small applied magnetic field of 1.0 T. In general, the measured quadrupole splittings and isomer shifts for each component agreed with previous measurements on single component samples in the literature, and thus demonstrated that chemically enriched hemoglobin has not been altered. The second and third samples were isolated alpha and beta subunits, respectively. We have found measurable Mössbauer spectral differences between the HbO2 sites in the alpha subunit sample and the beta subunit sample. The measured Mössbauer spectral areas indicate that the iron ion has the largest mean-square displacement at the deoxy Hb sites as compared to that at the oxy- and carbonmonoxy Hb sites. The mean-square displacement at the HbO2 sites is the smallest.

Virilizing hepatoblastoma: precocious sexual development and partial response of pulmonary metastases to cis-platinum.

A 42/3 year old boy with hepatoblastoma presented with precocious sexual development and an abdominal mass. During the course of disease, serial endocrinologic laboratory investigations were done, along with alpha-fetoprotein levels. A significant correlation is noted in these values at diagnosis, postsurgery, and later during a relapse. Ectopic production of chorionic gonadotropins by the tumor is evident. After extensive surgical resection, chemotherapy was started because of metastases. Although the primary tumor failed to respond, the pulmonary metastatic disease showed a greater than 50 percent response rate with cis-platinum.

Technique for continuous sampling of peritoneal fluid for prediction of intestinal gangrene.

The challenge presented to the surgeon by infants with NEC is to time an operation to coincide with the finite interval between infarction of gut and perforation. This study describes a new technique for continuous monitoring of peritoneal fluid in a rabbit model of intestinal ischemia to aid in predicting this interval. Color change to brown appears to be a reliable indicator of infarction. A sudden dramatic rise in the WBC of this fluid may also be an easily obtained, useful parameter. Further clinical studies of this method seem warranted to help improve the still dismal outcome of this disease.

The use of glucagon in the diagnosis and management of illeocolic intussusception.

Twenty-one of 25 episodes of ileocolic intussusception were successfully reduced by the barium enema hydrostatic technique supplemented by glucagon. No apparent serious complications occurred from the use of this drug. The comfort of the children and the ease of filling the colon and small bowel seemed enhanced by the glucagon.