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Biomedical subjects

D E Wesson

Publications and source records attributed to D E Wesson.

At least 55 records · Page 3Linked to original sources

Combined K+ and Cl- repletion corrects augmented H+ secretion by distal tubules in chronic alkalosis.

NaCl administration enhances HCO3 secretion in the distal tubule of animals with chronic metabolic alkalosis but does not correct the augmented H+ secretion characteristic of this disorder. The present studies used in vivo microperfusion micropuncture to investigate whether combined repletion of K+ and Cl- corrected the augmented H+ secretion in the distal tubule of rats with chronic furosemide-induced metabolic alkalosis. Correction of alkalosis was induced in one group of animals with NaCl and in another group with a similar amount of Cl- as NaCl + KCl for 24 h; each group was compared with animals with maintained alkalosis. Total 24-h urine HCO3 excretion by each Cl(-)-repleted group comprised > or = 70% of the calculated HCO3 loss necessary to induce the respective decrease in plasma total CO2. Alkalotic animals given NaCl+KCl had significantly lower H+ secretion in the distal tubule compared with animals with maintained alkalosis (15.5 +/- 1.2 vs. 34.6 +/- 1.8 pmol.mm-1.min-1, P < 0.01) but those given only NaCl did not (28.3 +/- 1.5 pmol.mm-1.min-1, P = 0.14). H+ secretion was not different among control animals given similar amounts of Na+, K+, and Cl-. These studies demonstrate that Cl- repletion corrects chronic furosemide-induced metabolic alkalosis predominantly by a renal mechanism and that combined administration of K+ and Cl-, but not of Cl- alone, corrects the augmented H+ secretion in the distal tubule in this model of chronic alkalosis.

Alkalosis↗

Xanthine oxidase inhibits transmembrane signal transduction in vascular endothelial cells.

The effect of xanthine oxidase (XO)-mediated oxidant stress on endothelial cell signal transduction was determined in bradykinin-stimulated cells loaded with the Ca+(+)-sensitive probe fura-2. Calf pulmonary artery endothelial cells were incubated with a reaction mixture containing XO (50 mU/ml) and its substrate, hypoxanthine (HX) (0.5 mM), for periods of 0.5 to 2.0 hr. HX/XO time dependently increased basal cytosolic free Ca++ ([Ca++]i) and decreased the response of [Ca++]i to bradykinin, so that incubation of cells with HX/XO for 1.5 hr or longer eliminated responsiveness to agonist. In presence of XO, HX dose dependently increased basal [Ca++]i (EC50 approximately 3 x 10(-5) M) and decreased the response of [Ca++]i to bradykinin. Sequential application of bradykinin and Ca++ to cells suspended in Ca+(+)-free/EGTA buffer was performed to characterize the effects of HX/XO on receptor-activated Ca++ entry and release of Ca++ from internal stores. HX/XO attenuated internal store Ca++ release and inhibited the bradykinin-stimulated Ca++ influx pathway in a time-dependent manner. When the HX dose was decreased by an order of magnitude, HX/XO selectively inhibited the agonist-stimulated influx pathway with little effect on internal store Ca++ release. Coincubation with superoxide dismutase tended to potentiate the effects of HX/XO, whereas catalase provided almost complete protection. Similar results to HX/XO-induced alterations in Ca++ signaling were observed when glucose-glucose oxidase (G/GO) was used as the oxidant-generating system. Inhibition of Ca++ signaling by HX/XO and G/GO occurred in the absence of decreased cell viability. Together, these results suggest that HX/XO-induced inhibition of signal transduction in endothelial cells is a function of H2O2-mediated oxidant stress and represents an early dysfunction in the process of oxidant injury.

Animals↗

Risk factors for extended disruption of family function after severe injury to a child.

OBJECTIVE: To identify risk factors for long-lasting disruption of family function following pediatric trauma that can be measured at the time of trauma. DESIGN: Prospective, exploratory study. Personal interviews were conducted at the time of admission and 6 months and 1 year after discharge. SETTING: Level I regional pediatric trauma centre. PARTICIPANTS: One hundred and five families (86% of those eligible) with a child admitted to hospital for severe trauma with an Abbreviated Injury Scale (AIS) score of 4 or higher or with two or more injuries in different body parts and AIS scores of 2 or higher were recruited; 13 families were lost to follow-up at 6 months or 1 year, so their data were not included in the analyses. MAIN OUTCOME MEASURES: Family function status (normal or abnormal compared with function before the injury), demographic characteristics of the parents and child, injury severity, presence of maternal psychologic disorder, presence of child behaviour abnormality and functional status of the child. MAIN RESULTS: At 6 months and at 1 year 41 families (45%) and 21 families (23%) respectively reported that their family lives had not returned to normal. The relative odds for disruption of family life were about five times higher (95% confidence limits [CL] 1.4 and 19.7) and four times higher (95% CL 1.1 and 14.0) for single-parent families than for families with married parents living together at 6 months and 1 year respectively. The presence of maternal psychologic disorders at admission and increased age of the injured child were also significantly associated with extended disruption of family function. Injury severity and functional status at discharge were not good predictors of family function. CONCLUSIONS: Severe injury to a child places a heavy strain on normal family function. In particular, single parents and parents experiencing mental or emotional problems at the acute stage of the injury need help in coping with their reactions to the trauma and may benefit from individual or group counseling.

Adolescent↗

Fatal bicycle accidents in children: a plea for prevention.

We reviewed the coroner's records of all fatal bicycle accidents occurring in children (aged 0 to 15 years) in Ontario (pediatric population, 2,007,230) between January 1, 1985 and December 31, 1989. The injuries sustained were documented and scored with anatomical injury scores (Abbreviated Injury Score 1985 and Injury Severity Score) and categorized as unsurvivable or survivable. The causes and circumstances were documented from police accident reports. Eighty-one deaths resulted from bicycle accidents, an annual mortality rate of 1.44 deaths per 100,000 children per year. In 74 (91%) of these cases the injuries were deemed unsurvivable, 89% of which were head injuries. Seventy-eight (96%) of the deaths resulted from collisions with motor vehicles. No victim was wearing a helmet at the time of injury. In 70% of the deaths, the cyclist was considered to have caused the collision, either because of a violation of a road traffic law or poor road sense. These findings suggest that more emphasis should be placed on primary and secondary injury prevention by such methods as bicycle safety education for children and the promotion of bike helmet use. In addition, in view of the high incidence of unsurvivable head injury, the introduction of legislation requiring the use of protective helmets should be considered.

Abbreviated Injury Scale↗

Enhanced HCO3 secretion by distal tubule contributes to NaCl-induced correction of chronic alkalosis.

Free-flow micropuncture studies show depressed net HCO3 reabsorption in the surface distal tubule of rats undergoing correction of chronic metabolic alkalosis induced by NaCl infusion. The present studies used in vivo microperfusion of the rat distal tubule to investigate whether the described reduction in net HCO3 reabsorption was due to decreased luminal H+ secretion or to increased HCO3 secretion. Animals with correcting alkalosis had higher HCO3 secretion in this nephron segment than did animals with maintained alkalosis regardless of whether the perfusing solution was initially Cl free (-27.6 vs. -16.6 pmol.mm-1.min-1, P < 0.01) or contained 40 mM Cl (-31.5 vs. -23.0 pmol.mm-1.min-1, P < 0.01); H+ secretion was not different between animals with correcting and maintained alkalosis. Animals without alkalosis (control) demonstrated no differences in H+ or HCO3 secretion in response to NaCl infusion. These studies demonstrate that enhanced HCO3 secretion mediates the depressed net HCO3 reabsorption observed in the distal tubule of rats undergoing NaCl-induced correction of chronic metabolic alkalosis.

Absorption↗

Evaluation of a promotional strategy to increase bicycle helmet use by children.

Bicycle-related head injuries are an important cause of death and disability, despite the availability of helmets. The objective of this study was to evaluate the effectiveness of a school-based bicycle helmet promotion program in increasing helmet use by children while controlling for secular trends. Two high-income and two low-income schools in an urban Canadian community were selected to receive a bicycle helmet promotion intervention, with the remaining 18 schools serving as controls. Approximately 1800 observations of bicycling children were made at randomly selected observational sites 2 to 5 months after the intervention to assess changes in behavior. Helmet use at all observation sites tripled from 3.4% (1990, preintervention) to 16% (1991, postintervention). In the high-income intervention area, observed helmet use rose dramatically from 4% to 36% in contrast to the more modest increase in the high-income control area from 4% to 15%. In the low-income intervention area, there was a modest increase from 1% to 7%, but it did not differ from the increase in the low-income control area from 3% to 13%. The program was highly successful in children of high-income families but not in children of low-income families. Developing strategies for low-income families remains a priority.

Accident Prevention↗

Juvenile hemangiomas involving the thoracic trachea in children: report of two cases.

Two 3-month-old girls presented with posterior mediastinal juvenile hemangioma (JH), a benign tumor rarely found in the mediastinum. Incomplete resections were performed. Over 4 and 7 months, respectively, the hemangiomas recurred and grew through the tracheal wall into the tracheal lumina, reducing the airway by 90% in one case and 70% in the other. The recurrences were resected, including five tracheal rings in the first case and four in the second. In case 1 the tumor recurred in the trachea 2 months later. A tracheostomy was performed, and corticosteroids were administered for 6 months. The tumor involuted and the patient was decannulated after 18 months; she is doing well 7 years later. The patient in case 2 has been well in the 18 months since her second operation. Airway obstructions can be treated by tracheal resection when conservative management fails.

Airway Obstruction↗

The physical, psychological, and socioeconomic costs of pediatric trauma.

This prospective study examined the physical, psychological, and socioeconomic effects of injuries on children and their immediate families. Ninety-two injured children admitted with minor (ISS less than 16) or major (ISS greater than or equal to 16) injuries were compared with a control group of 59 children admitted during the same period with acute appendicitis. The two populations were similar in mean age, sex ratio, parental age and work status, and number of siblings. The parents of the injured children had a lower level of education than those of the controls. Fifty-four percent of the minor injury patients and 71% of the major injury patients had persistent physical limitations at 12 months in contrast to none of the controls. Thirty-eight percent of minor injury patients had pre-existing behavioral disturbances compared with 14% of major injury patients and 10% of controls. Behavioral disturbances among major trauma patients showed a sharp rise to 41% at 12 months and tended to persist in cases with continuing physical limitations. The major injury patients and those with significant head injuries exhibited a decrease in academic performance; minor injury patients and those without head injury showed no change. Maternal malaise rose sharply to about 40% in both injury groups in contrast to 7% in the controls and was more common in the presence of persistent physical limitations. Only 73% of families in the major injury group had returned to normal family life compared with 87% of the minor injury group and 100% of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Achievement↗

Field triage--help or hindrance?

Field triage protocols have potential benefits in urban trauma systems, but for optimal effect they must be tailored to local needs and tested in each system for sensitivity and specificity. They should be implemented only by experienced physicians and surgeons who can monitor and adjust the protocol when necessary.

Canada↗

Current status of pancreatectomy for persistent idiopathic neonatal hypoglycemia due to islet cell dysplasia.

A series of 18 children suffering from persistent idiopathic neonatal hypoglycemia (PINH) is reported. Medical and surgical managements are described in detail. All patients subjected to surgery had failed medical treatment. These patients were divided into two groups: 1) 85% pancreatectomy leaving the uncinate process in situ, and 2) 95% pancreatectomy leaving a small rim of pancreatic tissue along the duodenum and the common bile duct. The spleen was preserved in all cases. Two out of 5 children of group 1 required further resection of the pancreas for persistent hypoglycemia and were converted to 95% pancreatectomy. Since 1981 95% pancreatectomy was exclusively employed. Only one patient required insulin for 3 weeks postoperatively. Histopathology and immunohistochemistry revealed islet cell dysplasia and islet cell nuclear hypertrophy in the majority of cases, 35% of the patients had focal adenomatosis. Better control of hypoglycemia is achieved by primary 95% pancreatectomy and, thus, 95% pancreatectomy is recommended as the initial procedure in the treatment of PINH.

Female↗

Factors influencing postoperative recurrence of Crohn's disease in childhood.

We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn's disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). The mean height velocity of patients with growth potential increased from 2.4 (2.3) cm per year preoperatively to 8.1 (3.4) cm per year in the first postoperative year (p=0.0001). These results support an early approach to surgery in the management of ileal Crohn's disease with or without caecal or right colonic involvement, especially when complicated by persistent growth failure. The higher recurrence rates in more diffuse ileocolonic disease emphasise the need for alternative treatment strategies in these children.

Adolescent↗

Augmented bidirectional HCO3 transport by rat distal tubules in chronic alkalosis.

Free-flow micropuncture studies show both augmented net HCO3 reabsorption in the distal tubule of rats with chronic metabolic alkalosis and higher HCO3 delivery to this nephron segment. The present studies in rats used in vivo microperfusion of surface distal tubules to investigate whether the augmented net reabsorption 1) was due to decreased HCO3 secretion and/or to increased proton secretion or 2) depended on the higher HCO3 delivery to the distal tubule. Artificial perfusates were designed to simulate in situ deliveries of HCO3 to the distal tubules of both alkalotic and control animals and to represent extremes of in situ Cl deliveries. Rather than being decreased, both measured and calculated HCO3 secretion were higher in the alkalotic animals for each perfusate used. Similarly, calculated proton secretion (difference between net HCO3 reabsorption and calculated HCO3 secretion) was higher for the alkalotic animals using each HCO3-containing perfusate. Augmented net HCO3 reabsorption by alkalotic animals was more clearly demonstrated using higher HCO3 deliveries and Cl-free perfusates. These studies demonstrate that both the reabsorptive and secretory components of net HCO3 transport are increased in the distal tubule of animals with chronic metabolic alkalosis.

Absorption↗

Maximal proton secretory rate of rat distal tubules is higher during chronic metabolic alkalosis.

In vivo microperfusion studies show augmented proton secretion in the distal tubule of rats with chronic metabolic alkalosis. The present studies used the same technique to determine whether this augmented proton secretion is due predominantly to an increase in substrate affinity or alternatively to a predominant increase in the maximal proton secretory rate. Surface distal tubules of alkalotic and control rats were microperfused in vivo with solutions containing increasing concentrations of HCO3. Proton secretion was determined as the difference between measured net HCO3 reabsorption and passive HCO3 transport calculated by use of the permeability derived from perfusing with a HCO3-free solution. Proton secretion was expressed as a function of the initial luminal HCO3 concentration and was assumed to follow saturable Michaelis-Menten kinetics. Alkalotic animals had a significantly higher Km (33.9 vs. 21.6 mM, P less than 0.03) and Vmax (223.8 vs. 99.1 pmol.mm-1.min-1, P less than 0.001) compared with control. These data are consistent with the augmented proton secretion in the distal tubule of alkalotic animals as predominantly due to an increased maximal proton secretory rate rather than to increased substrate affinity.

Alkalosis↗

Complications of gastroesophageal antireflux surgery in neurologically impaired versus neurologically normal children.

Antireflux surgery was performed in 234 children over a 5-year period; 153 were neurologically impaired (NI) and 81 were neurologically normal (NN). Initial presentation, demographic data, and type of antireflux operation were similar in the two groups. Eighty-six percent of the NI group versus 30% of the NN group had gastrostomy tubes placed. The incidence of late postoperative complications was 26% in the NI group and 12% in the NN group (P less than .01). During the late postoperative period, NI children underwent reoperation four times as frequently as NN children (19% v 5%, respectively; P less than .01). Wrap herniation accounted for 38% of complications and 59% of reoperations in the late postoperative period. Mortality due to aspiration occurred in 9% of the NI group versus 1% of the NN group. Combined failure rate (reoperation plus aspiration-induced deaths) was 28% in NI and 6% in NN (P less than .01). We conclude that neurological status is the major predictor of operative success and that wrap herniation due to crural disruption is the most common cause of operative failure.

Adolescent↗

Dietary bicarbonate reduces rat distal nephron acidification evaluated in situ.

Whether altered reabsorption of bicarbonate by the superficial distal nephron contributes to the renal response to a chronic dietary bicarbonate challenge is not known. These micropuncture studies were done in control, NaHCO3-loaded, and NaCl-loaded Munich-Wistar rats to determine whether this dietary maneuver altered acidification in this nephron segment as evaluated in situ. Urinary bicarbonate excretion of NaHCO3-loaded animals was higher than control for each day of a 7-day study period, but bicarbonate excretion for animals identically loaded with NaCl was not sustained above control. Bicarbonate transport by the superficial distal nephron was assessed using paired collections from this segment. Net bicarbonate reabsorption was observed in all three groups. Reabsorption was lower in NaHCO3-loaded vs. control (11 vs. 25 pmol/min, P less than 0.01) but that for NaCl-loaded animals was not. The data indicate that reduced reabsorption of bicarbonate by the superficial distal nephron of rats contributes to the renal response to a chronic dietary bicarbonate challenge as evaluated in situ.

Acid-Base Equilibrium↗

Depressed distal tubule acidification corrects chloride-deplete alkalosis in rats.

We investigated the relative contributions made by the proximal and distal tubule to the correction of Cl-deplete metabolic alkalosis induced by systemic administration of NaCl. Free-flow micropuncture was used to examine net bicarbonate reabsorption in superficial proximal and distal tubules of anesthetized Munich-Wistar rats during maintenance and correction of chronic furosemide-induced Cl-deplete metabolic alkalosis. The distal tubule of animals with correcting vs. maintained alkalosis had a lower fractional reabsorption of bicarbonate (38 vs. 75%, P less than 0.001) and a lower slope of the linear regression comparing absorption to delivered load (0.48 vs. 0.99, P less than 0.02). By contrast, proximal tubule of animals with correcting vs. maintained alkalosis had fractional reabsorption (85 vs. 90%, P = 0.07) and slopes of the regression comparing reabsorption to filtered load (1.09 vs. 0.98, P = 0.48) that were not different. The data indicate that correction of Cl-deplete metabolic alkalosis induced by NaCl administration involves a qualitative decreased in bicarbonate reabsorption in distal tubule with maintenance of the same load-dependent relationship for bicarbonate reabsorption in proximal tubule.

Absorption↗