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D E Wesson

Publications and source records attributed to D E Wesson.

107 records · Page 6Linked to original sources

Internephron heterogeneity for carbonic anhydrase-independent bicarbonate reabsorption in the rat.

The present experiments were designed to localize the sites of carbonic anhydrase-independent bicarbonate reabsorption in the rat kidney and to examine some of its mechanisms. Young Munich-Wistar rats were studied using standard cortical and papillary free-flow micropuncture techniques. Total CO2 (tCO2) was determined using microcalorimetry. In control rats both superficial and juxtamedullary proximal nephrons reabsorbed approximately 95% of the filtered load of bicarbonate. The administration of acetazolamide (20 mg/kg body weight [bw]/h) decreased proximal reabsorption to 65.6% of the filtered load in superficial nephrons (32% was reabsorbed by the proximal convoluted tubule while 31.7% was reabsorbed by the loop segment), and to 38.4% in juxtamedullary nephrons. Absolute reabsorption of bicarbonate was also significantly higher in superficial than in juxtamedullary nephrons after administration of acetazolamide (727 +/- 82 vs. 346 +/- 126 pmol/min; P less than 0.05). The infusion of amiloride (2.5 mg/kg bw/h) to acetazolamide-treated rats increased the fractional excretion of bicarbonate as compared with animals treated with acetazolamide alone (34.9 +/- 1.9 vs. 42.9 +/- 2.1%; P less than 0.01), and induced net addition of bicarbonate between the superficial early distal tubule and the final urine (34.8 +/- 3.0 vs. 42.9 +/- 2.1%; P less than 0.05). Amiloride at this dose did not affect proximal water or bicarbonate transport; our studies localize its site of action to the terminal nephron. Vasa recta (VR) plasma and loop of Henle (LH) tubular fluid tCO2 were determined in control and acetazolamide-treated rats in order to identify possible driving forces for carbonic anhydrase-independent bicarbonate reabsorption in the rat papilla. Control animals showed a tCO2 gradient favoring secretion (LH tCO2, 7.4 +/- 1.7 mM vs. VR tCO2, 19.1 +/- 2.3 mM; P less than 0.005). Acetazolamide administration reversed this chemical concentration gradient, inducing a driving force favoring reabsorption of bicarbonate (LH tCO2, 27.0 +/- 1.4 mM vs. VR tCO2, 20.4 +/- 1.0 mM; P less than 0.005). Our study shows that in addition to the superficial proximal convoluted tubule, the loop segment and the collecting duct show acetazolamide-insensitive bicarbonate reabsorption. No internephron heterogeneity for bicarbonate transport was found in controls. The infusion of acetazolamide, however, induced significant internephron heterogeneity for bicarbonate reabsorption, with superficial nephrons reabsorbing a higher fractional and absolute load of bicarbonate than juxtamedullary nephrons. We think that the net addition of bicarbonate induced by amiloride is secondary to inhibition of voltage-dependent, carbonic anhydrase-independent bicarbonate reabsorption at the level of the collecting duct, which uncovers a greater delivery of carbonate from deeper nephrons to the collecting duct. Finally, our results suggest that carbonic anhydrase-independent bicarbonate reabsorption is partly passive, driven by favorable chemical gradients in the papillary tubular structures, and partly voltage-dependent, in the collecting duct.

Absorption↗

Abdominal injuries in children.

The problem of abdominal trauma in children is briefly reviewed to show how the etiology, diagnosis and treatment differ from those in adults. Although in many ways management is the same in both groups, certain problems more commonly affect children, and the approach to diagnosis and treatment must be adapted to their needs. The importance of frequent clinical assessment and the rather limited role of peritoneal lavage in children with abdominal trauma are stressed. Experience with splenic injuries in 63 patients treated between 1974 and 1979 is reviewed to provide guidelines for conservative management to assist surgeons who seldom treat children. Since splenectomy in pediatric patients carries a risk of overwhelming infection, distinguishing those whose spleens can be salvaged is extremely important.

Abdominal Injuries↗

Results of bowel resection for Crohn's disease in the young.

Thirty patients (21 boys and 9 girls) underwent bowel resections for Crohn's disease from 1965 to 1979. They ranged in age from 6 to 18 yr. The follow-up period varied from 3 mo to 14 yr. There were no deaths. Seventeen developed clinical or radiologic evidence of recurrent Crohn's disease. Seven of these required reoperation and six are now well without sign of further recurrence. Eleven of 18 achieved catch-up growth in weight; 10 of 15 achieved catch-up growth in height. At the time of follow-up four had active disease, seven had evidence of recurrence but were generally well, and 19 were well without any evidence of recurrence.

Adolescent↗

Ruptured spleen--when to operate?

Sixty-three patients with splenic injuries were treated during a 5-yr period from 1974-1979. The decision to operate was based on the patient's clinical course, not on the presence of splenic injury alone. Those who were stable on admission or after initial resuscitation were treated nonoperatively. This consisted of strict bed rest, nasogastric suction, and i.v. fluids--including blood--as required. Those who bled massively were operated on promptly. At operation, the spleen was repaired if possible or excised if damaged beyond repair. Forty patients were treated nonoperatively. Sixteen of these required blood transfusions (mean 31.2 +/- 5.3 ml/kg). One patient in this group developed a large defect on spleen scan at 3 wk post injury. There was no other morbidity and no mortality following nonoperative treatment. Nineteen required operation all within 16 hr of admission. Fifteen underwent splenectomy, 2 partial splenectomy, and 1 splenorrhaphy. In 1 the bleeding had stopped. All required blood before operation (mean 80.4 +/- 10.1 ml/kg). Seven in this group died (6 from head injuries and 1 from bleeding). Thus surgery was avoided in 2 out of 3 and the spleen saved in 3 out of 4 patients with documented splenic injuries. We believe that where adequate facilities exist nonoperative treatment of splenic injuries is both safe and effective. When bleeding is massive from the beginning or replacement requirements exceed 40 ml/kg, operation is indicated.

Adolescent↗

Intraoperative autotransfusion in blunt abdominal trauma.

We have used intraoperative autotransfusion in three cases of massive intraabdominal hemorrhage following blunt trauma. Based on this experience we recommend that: (1) To prevent sudden collapse the abdomen should be decompressed slowly through a small incision while blood is collected into the autotransfusion reservoir; (2) A skilled person is required to operate the autotransfusor; and (3) To prevent consumption coagulopathy, autotransfusion must be supplemented by the use of blood components, especially fresh frozen plasma.

Abdominal Injuries↗

A novel hemoglobin-adenosine-glutathione based blood substitute: evaluation of its effects on human blood ex vivo.

Chemically modified hemoglobin (Hb) solutions are under current investigation as potential red cell substitutes. Researchers at Texas Tech University have developed a novel free Hb based blood substitute product. This blood substitute is composed of purified bovine Hb cross-linked intramolecularly with o-adenosine-5'-triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione (GSH). In this study, we compared the effects of our novel blood substitute and unmodified (U) Hb, by using allogenic plasma as the control, on human blood components: red blood cells (RBCs), platelets, monocytes (Mo), and low-density lipoproteins (LDLs). The pro-oxidant potential of both Hb solutions on RBCs was examined by the measurement of osmotic and mechanical fragility, conjugated dienes (CD), lipid hydroperoxides (LOOH), thiobarbituric acid reactants (TBAR-S), isoprostanes (8-iso PGF2alpha) and intracellular GSH. The oxidative modification of LDLs was assessed by CD, LOOH, and TBAR-S, and the degree of apolipoprotein (apo) B cross-linking. The effects of Hb on platelets have been studied by monitoring their responses to the aggregation agonists: collagen, ADP, epinephrine, and arachidonic acid. Monocytes were cultured with Hb solutions or plasma and tested for TNF-alpha and IL-1beta release, then examined by electron microscopy. Results indicate that native UHb initiates oxidative stress of many blood components and aggravates inflammatory responses of Mo. It also caused an increase in RBC osmotic and mechanical fragility (p < 0.001). While the level of GSH was slightly changed, the lipid peroxidation of RBC increased (p < 0.001). UHb was found to be a stimulator of 8-iso PGF2alpha synthesis, a potent modulator of LDLs, and an effective potentiator of agonist induced platelet aggregation. Contrarily, our novel blood substitute did not seem to induce oxidative stress nor to increase Mo inflammatory reactions. The osmotic and mechanical fragility of RBCs was similar to that of the control. Such modified Hb failed to alter LDLs, increase the production of 8-iso PGF2alpha, but markedly inhibited platelet aggregation. The effect of this novel blood substitute can be linked with the cytoprotective and anti-inflammatory properties of adenosine, which is used as a cross-linker and surface modifier, and a modification procedure that lowers the hemoglobin pro-oxidant potential.

Adenosine↗

Evaluation of a new catheter for total parenteral nutrition.

Central venous catheters play an important role in the management of children with a variety of disorders. Desirable characteristics of such catheters include ease and reliability of placement, secure fixation, low rates of complication, and ease of removal. We describe our experience with a new form of catheter that displays all of these characteristics. One hundred twenty-nine catheters were inserted in 111 patients over a 2-year period for a total of 5,729 treatment days. This catheter is made of silicone rubber and is positioned by using P-wave changes seen during intraoperative electrocardiography. x-Ray confirmation is not routinely necessary. The catheter is fixed in position by use of a grommet, which is sutured in the neck at the site of the venotomy. This form of fixation allows the catheter to be easily removed by nonsurgical means while keeping it securely in position for the duration of use. Our experience with this catheter has been associated with a low incidence of septic (1.1-4.2 septic episodes per 1,000 patient days) and mechanical (2.3 episodes per 1,000 patient days) complications in a setting that includes both in-hospital and home total parenteral nutrition patients. It is felt that this new form of catheter and catheter fixation offers several advantages over other types of central venous catheters currently in use.

Adolescent↗

Feeding gastrostomy in neurologically impaired children: is an antireflux procedure necessary?

Some authors recommend a routine "protective" antireflux procedure (ARP) in neurologically impaired children undergoing feeding gastrostomy (FG). Over 4 years, we performed FG in 107 neurologically impaired children aged 1 month to 16 years. Ninety-eight had preoperative radiological assessment for gastroesophageal reflux (GER), which was documented in 44, of whom 33 had FG plus ARP and 11 had FG alone. Seven of the 11 subsequently developed symptomatic GER and 5 of them had a secondary ARP. Of the 54 children with no demonstrable GER preoperatively, 3 children underwent FG plus ARP. The remaining 51 had FG alone. There was one postoperative death. Of the 50 surviving patients, 22 developed symptomatic GER and 17 of these had a subsequent ARP. Mean follow-up of 20.0 months showed that the risk of developing GER after FG alone was not influenced by age, sex, indication for FG, underlying diagnosis, or method of gastrostomy. There was no significant difference in mortality and early morbidity between patients undergoing FG alone and those having FG with simultaneous or subsequent ARP. Only 44% of our patients in whom GER was not demonstrated initially developed symptomatic GER followed FG alone. This incidence does not justify a routine "protective" ARP.

Adolescent↗

Evaluating the accuracy of nutritional assessment techniques applied to hospitalized patients: methodology and comparisons.

Herein we describe a methodology which can be used to evaluate the predictive accuracy of nutritional assessment techniques. We use this methodology to compare seven techniques of nutritional assessment in terms of their ability to predict one nutrition associated hospital complication (infection) by dividing a sample of 59 surgical patients into high risk and low risk groups. One technique was subjective global assessment (SGA) of the patient's nutritional status on admission to hospital. Five techniques were single objective measurements (albumin, transferrin, delayed cutaneous hypersensitivity, anthropometry, and creatinine-height index). The 7th technique was the prognostic nutritional index. The best combination of sensitivity (0.82) and specificity (0.72) was found with SGA. The second best combination (0.88 and 0.45) was found by using either the prognostic nutritional index or creatinine-height index. We also found that combining the five objective measurements with SGA into a single index did not increase the discriminatory (or predictive) power over that of SGA alone in a clinically significant way. We conclude that a larger study comparing these approaches should be undertaken to confirm these findings and to develop methods which improve the predictive properties of SGA.

Anthropometry↗

Artificial beta-cell promotes positive nitrogen balance and whole body protein synthesis in insulin-dependent diabetic subjects.

To assess the effects of artificial beta-cell-directed insulin therapy on protein metabolism in patients with diabetes mellitus, nitrogen balance, urea production, and whole body protein turnover were determined in five type I insulin-dependent subjects and five age- and sex-matched controls. Each diabetic participant was studied over two 4-day periods while receiving conventional insulin therapy (one or two daily injections of short and intermediate acting insulin) or insulin delivered by the artificial beta-cell. While the diabetic participants received conventional insulin therapy, nitrogen balance, urea production, whole body protein turnover, and protein synthesis and breakdown rates did not differ significantly from the control group. However, when the same subjects were on artificial beta-cell-directed insulin therapy, they manifested a significant net positive nitrogen balance of over 2 g/day. This change in nitrogen balance was largely due to a fall in urea nitrogen production from 174 +/- 6 to 140 +/- 13 mg/kg body weight per day (p less than 0.05). In addition, while artificial beta-cell therapy did not affect whole body protein turnover or breakdown rates, a significant rise (2.1 +/- 0.2 to 2.4 +/- 0.1 g/kg per day) in whole body protein synthesis was observed (p less than 0.05). Thus when compared to conventional insulin treatment, artificial beta-cell-directed insulin therapy was associated with a 14% increase in the rate of protein synthesis and a decrease of 20% in urea nitrogen production, leading to a net positive nitrogen balance.

Adult↗

Fatal and non-fatal childhood injuries in Metropolitan Toronto, 1986-1991.

The distribution of the cause, rate and nature of fatal and major non-fatal injuries in children living in Metropolitan Toronto and their trends from 1986 to 1991 were systematically reviewed from hospital discharge records and coroner's records. A total of 11,024 non-fatal injuries, of which falls were the leading cause (45%), and 133 fatal injuries, of which intentional injury (21%) was the principal cause, occurred during the six-year study period. The non-fatal injury rate dropped 23%, from 567 to 436 per 100,000 children. Mortality rates also fell during the study period. However, injuries to motor vehicle occupants and drownings increased considerably. Fractures of various kinds were the most common clinical diagnosis. Protecting children in motor vehicles by promoting the use of proper restraints and preventing injuries caused by falls and drowning should be high priorities for childhood injury prevention in Metropolitan Toronto.

Adolescent↗

Current bicycle helmet ownership, use and related factors among school-aged children in metropolitan Toronto.

A random digit dialing telephone survey was conducted to examine bicycle helmet ownership, use and related factors among 707 children in Metropolitan Toronto. The ownership rate was 22% and use rate 12%. Although ownership was similarly distributed by age and sex, helmet use varied considerably across age strata among boys; only about one fifth of teenaged boys who owned a helmet wore it regularly. Both parental education and annual family income were significantly associated with ownership and use. Past bicycle injuries, although increasing helmet ownership, had no positive impact on use. The strength of a parental role model was reflected in the fact that when parents owned and used a helmet, 93% of their children had a helmet and more than 80% of them always wore it. Since about half of parents are cyclists themselves, helmet promotion activities are likely to maximize their effect if they target both parents and children.

Adolescent↗

Parental attitudes toward legislation for helmet use by child cyclists.

A random-digit dialing telephone survey was conducted in the second half of 1991 to examine parental attitudes toward legislation of helmet use by child cyclists. The surveyed population were 703 parents of at least one child aged 5-17 years who owned a bicycle and lived within Metropolitan Toronto. Five hundred sixty-eight (80.8%) responding parents were in favour of the suggested legislation, 81 (11.5%) were against, and 54 (7.7%) had no opinion on the issue. The 95% confidence interval for the support rate was 78.9-83.7%. Although there was some variation in the level of support, at least two thirds of the respondents in every subgroup, except parents with teenaged children (aged 15-17 years), were in favour of the legislation. Legislation requiring bicycle helmet use by all children has strong support from the public. Additional surveys should be directed at public attitudes to legislation of helmet use by adults.

Adolescent↗

Improved blood substitute: evaluation of its effects on human endothelial cells.

The authors have previously documented that appropriate chemical and pharmacologic modification of the hemoglobin molecule are required to attenuate certain pathophysiologic reactions of the reticuloendothelium. The current study further investigates the molecular responses of human coronary artery endothelial cells to a high concentration (0.4 mmol) of 1) unmodified bovine hemoglobin; and 2) an improved blood substitute that comprises hemoglobin cross-linked intramolecularly with o-adenosine triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione. In this study, the scavenging effect of hemoglobins toward nitric oxide (NO) was evaluated by the measurement of nitrite (NO2-) and nitrate (NO3-) formation. The pro-oxidant effect of hemoglobin on endothelial cells was examined by the measurement of intracellular reduced glutathione, and by monitoring the formation of lipid hydroperoxides and 8-iso prostaglandin F2alpha, a novel potent vasoconstrictor, which is produced by a noncyclooxygenase mechanism involving free radical catalyzed peroxidation of arachidonic acid. The inflammatory reactions of endothelial cells were evaluated by the expression of the adhesion molecule, intracellular adhesion molecule-1, and the activation of nuclear transcription factor, nuclear factor kappaB. In additional, endothelial cell responses were investigated by analysis of intracellular ionized calcium concentrations. Results indicate that unmodified hemoglobin in a concentration of 0.4 mmol/L can aggravate endothelial cell oxidative and inflammatory responses. This hemoglobin produced a significant (p < 0.01) depletion of reduced glutathione, acceleration of lipid peroxidation, and a greater influx of Ca2+. The formation of 8-iso prostaglandin F2alpha increased compared with the control cells (p < 0.01). Unmodified hemoglobin was found to be a potent scavenger of NO, great activator of nuclear factor kappaB, and a stimulator of intracellular adhesion molecule-1 expression. Contrarily, the improved blood substitute did not appear to induce oxidative stress nor to increase the intracellular Ca2+. The concentration of 8-iso prostaglandin F2alpha was similar to that in the control cells, whereas the formation of NO2-/NO3- was much lower (p < 0.05) than in the unmodified hemoglobin group. The effect of an improved blood substitute can be linked with the anti-inflammatory and cytoprotective properties of adenosine, which is used as a cross-linker and surface modifier, and the type of the chemical modification procedure that lowers hemoglobin pro-oxidant potential.

Arachidonic Acid↗