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Biomedical subjects

J D Phillips

Publications and source records attributed to J D Phillips.

At least 55 records · Page 3Linked to original sources
PubMed1991

Alterations in gastrointestinal motility during postoperative acute corticosteroid withdrawal.

Patients receiving exogenous corticosteroids may develop iatrogenic adrenal insufficiency, with resultant nausea, emesis, and abdominal distension if perioperative "stress steroid" dosages are inadequate. To investigate these gastrointestinal disturbances, motility measurements were obtained using perfused catheters in 10 dogs before steroid treatment (control), during administration of high-dose corticosteroids, and daily during 5 days of abrupt withdrawal. Withdrawal was characterized by a significant disruption in normal antral, duodenal, and jejunal motility with a prolongation of the migrating motor complex (MMC) and phases I and II, but not III (I = quiescence, II = irregular activity, and III = regular activity). Retrograde giant contractions (RGCs), giant migrating contractions (GMCs), and/or "intestinal fibrillation" were also observed during the first two withdrawal days. Adrenal weights and morphology did not change. We conclude: (1) high-dose corticosteroids can induce profound adrenal suppression in dogs without morphologic changes within 3 weeks; (2) high-dose steroid administration enhances gastrointestinal motility; and (3) acute withdrawal causes disappearance or shortening of MMC and the development of RGCs and GMCs with associated emesis.

Adrenal Insufficiency↗
PubMed1991

An improved model of experimental gastroschisis in fetal rabbits.

Previous animal models of gastroschisis have been associated with high mortality and variable degrees of intestinal evisceration. Using current fetal surgical techniques, an improved model of gastroschisis in fetal rabbits was developed. Twenty-eight time-mated New Zealand white rabbits underwent hysterotomies and fetal exposure on gestational day 25 (33-day gestation). Control fetuses (C) underwent fetal manipulation only. Gastroschisis fetuses (GS) had creation of right midabdominal wall defects. Twenty-five of 28 does (89%), 9 of 13 C fetuses (69%), and 18 of 22 GS fetuses (82%) survived. At the time of cesarean delivery 5 days later, GS fetuses had significantly lower body weights, intestinal lengths, and mucosa/submucosa height ratios (a measure of bowel wall edema), and significantly greater intestinal densities when compared with C fetuses (P less than .05, t test). This study demonstrates that (1) gastroschisis abdominal wall defects can be created in fetal rabbits with high survival rates; (2) experimental gastroschisis is associated with a profound decrease in fetal weight; and (3) eviscerated intestine is heavier, shorter, and thickened compared with normal control intestine, mimicking the clinical situation.

Abdominal Muscles↗
PubMed1991

Pulmonary edema and fluid mobilization as determinants of the duration of ECMO support.

The physiological variables that govern recovery of pulmonary function during neonatal extracorporeal membrane oxygenation (ECMO) remain poorly understood. We hypothesized that pulmonary hypertension (PHN) resolves soon after starting ECMO and that neonatal weight gain, pulmonary edema, and fluid mobilization are major determinants of recovery of pulmonary function and the ability to decrease ECMO support. To evaluate this, 17 consecutive neonates requiring ECMO for severe respiratory failure were reviewed. PHN was studied by daily echocardiography to assess the direction of ductal shunting. To evaluate fluid flux, pulmonary function, and edema during ECMO, we measured body weight, urine output, and ECMO flow every 12 hours. To evaluate pulmonary edema, serial chest radiographs obtained every 12 hours were randomly reviewed and scored by two radiologists with a semiquantitative chest radiograph index score (CRIS). By 25% of bypass time, PHN had resolved in all patients. However, at that time, weight had increased to 9.16% +/- 1.78% above birth weight, and the CRIS was 44% worse than the value just prior to ECMO. From 25% time on bypass, as urine output increased, patient weight and CRIS progressively decreased, allowing ECMO support to be weaned. At the time of discontinuation of ECMO support, weight had decreased to 2.0% +/- 1.3% above birth weight, and urine output remained steady at 3.0 +/- 0.3 mL/kg/h. Within 24 hours of stopping ECMO, the CRIS showed a 58% improvement compared to maximal scores during ECMO. We conclude that PHN decreases early in ECMO and that edema and its mobilization are important determinants of the improvement in pulmonary function and duration of ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Fluids↗
PubMed1991

Uptake and distribution of continuously infused intraamniotic nutrients in fetal rabbits.

Nutrient delivery via the fetal gastrointestinal tract may be a potential prenatal treatment for intrauterine growth retardation. Uptake from continuous intraamniotic infusions with nutrient incorporation into developing fetal tissues has not previously been shown. To study this, ovarian-end fetuses of 18 time-mated rabbit does underwent amniotic cavity catheterization and either esophageal ligation (EL) or sham operation (SH) on gestational day 23 (term, 33 days). Saline plus 14C D-glucose and 3H proline were infused into the amniotic fluid for 4 days. Nutrients absorbed by the EL fetus represent only those taken up into the maternal circulation and subsequently redelivered hematogenously to the fetus. Radioactivity of fetal blood and organs was determined using a liquid scintillation counter. All infused does and 10 of 18 infused fetuses (56%) survived the entire study period. In SH fetuses, uptake of 14C per mg of tissue was highest in the lung and significantly greater in the stomach, jejunum, ileum, and lung than in fetal blood (P less than .05). Uptake of 3H per mg of tissue was also highest in the lung and significantly greater than fetal blood in the stomach, small intestine, lung, and liver (P less than .05). Each organ's 14C and 3H uptake was greater in SH than in EL fetuses (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Brief communication: magnesium absorption in human ileum.

A novel technique utilizing samples of human distal ileum removed at surgery was used to study magnesium (Mg) absorption. Specimens of isolated absorptive mucosa were obtained by careful dissection of the tissue to remove the muscle layers, and were mounted in flux chambers. Mean tissue Mg concentration in human isolated intestinal mucosa was found to be within the postulated normal range for human tissue. Mucosal to serosal Mg transport was unaffected by ouabain or 2,4-dinitrophenol and sodium fluoride. Overall, the data indicate Mg absorption in distal ileum to be passive in nature, although a minor active transcellular component cannot be excluded.

2,4-Dinitrophenol↗
PubMed1991

Pergolide mesylate treatment of cocaine withdrawal.

Side effects occasionally limit the use of bromocriptine for cocaine withdrawal. The recently released medication pergolide shares some pharmacologic properties with bromocriptine but differs in potency and dopamine receptor subtype specificity. The authors tested pergolide in the treatment of 21 patients experiencing cocaine withdrawal. Sixteen patients reported rapid improvement in sleep and decreased cocaine craving. Side effects were limited primarily to gastrointestinal complaints.

Adult↗
PubMed1990

Isolation and characterization of QCR9, a nuclear gene encoding the 7.3-kDa subunit 9 of the Saccharomyces cerevisiae ubiquinol-cytochrome c oxidoreductase complex. An intron-containing gene with a conserved sequence occurring in the intron of COX4.

A nuclear gene (QCR9) encoding the 7.3-kDa subunit 9 of the mitochondrial cytochrome bc1 complex from Saccharomyces cerevisiae has been isolated from a yeast genomic library by hybridization with a degenerate oligonucleotide corresponding to nine amino acids proximal to the N terminus of purified subunit 9. QCR9 includes a 195-base pair open reading frame capable of encoding a protein of 66 amino acids and having a predicted molecular weight of 7471. The N-terminal methionine of subunit 9 is removed posttranslationally because the N-terminal sequence of the purified protein begins with serine 2. The ATG triplet corresponding to the N-terminal methionine is separated from the open reading frame by an intron. The intron is 213 base pairs long and contains previously reported 5' donor, 3' acceptor, and TACTAAC sequences necessary for splicing. The splice junctions, as well as the 5' end of the message, were confirmed by isolation and sequencing of a cDNA copy of QCR9. In addition, the intron contains a nucleotide sequence in which 15 out of 18 nucleotides are identical with a sequence in the intron of COX4, the nuclear gene encoding cytochrome c oxidase subunit 4. The deduced amino acid sequence of the yeast subunit 9 is 39% identical with that of a protein of similar molecular weight from beef heart cytochrome bc1 complex. If conservative substitutions are allowed for, the two proteins are 56% similar. The predicted secondary structure of the 7.3-kDa protein revealed a single possible transmembrane helix, in which the amino acids conserved between beef heart and yeast are asymmetrically arranged along one face of the helix, implying that this domain of the protein is involved in a conserved interaction with another hydrophobic protein of the cytochrome bc1 complex. Two yeast strains, JDP1 and JDP2, were constructed in which QCR9 was deleted. Both strains grew very poorly, or not at all, on nonfermentable carbon sources and exhibited, at most, only 5% of wild-type ubiquinol-cytochrome c oxidoreductase activity. Optical spectra of mitochondrial membranes from the deletion strains revealed slightly reduced levels of cytochrome b. When JDP1 and JDP2 were complemented with a plasmid carrying QCR9, the resulting yeast grew normally on ethanol/glycerol and exhibited normal cytochrome c reductase activities and optical spectra. These results indicate that QCR9 encodes a 7.3-kDa subunit of the bc1 complex that is required for formation of a fully functional complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

Adaptive changes in ileal mucosal nutrient transport following colectomy and endorectal ileal pull-through with ileal reservoir.

To study ileal mucosal function when used in an ileal reservoir or ileostomy, eight dogs underwent colectomy and endorectal ileal pull-through with creation of a lateral ileal reservoir. Ileal mucosal biopsy specimens were obtained at the initial operation, from the ileostomy and dormant ileal reservoir at the time of ileostomy closure, and from the reservoir 3 months later. Rates of uptake for four different substrates were determined by radioactive absorption techniques. Absorption of carbohydrates, amino acids, and bile acids was markedly decreased and of short-chain fatty acid mildly reduced in ileal reservoir mucosa compared with normal ileum, largely owing to a decrease in reservoir absorptive surface area from flattened villi. Reservoir uptake of the substrates evaluated within 3 months after operation was similar to that for normal colonic mucosa. Uptake of all measured substrates from ileostomy mucosa approximated that of normal ileum. The use of short ileal reservoirs and the avoidance of stasis may favor reduced bacterial growth and increased nutrient absorption.

Adaptation, Physiological↗
PubMed1990

Acute ileus from steroid withdrawal simulating intestinal obstruction after surgery for ulcerative colitis.

Sixty of 127 prednisone-dependent patients with ulcerative colitis who underwent colectomy and endorectal ileal pull-through with ileal reservoir and subsequent laparotomy with ileostomy closure (254 operations) during a 4-year period developed 95 episodes of intestinal obstruction during the early post-operative period. Acute ileus due to steroid withdrawal caused symptoms of intestinal obstruction in 43 patients (76 episodes), whereas true mechanical small-bowel obstruction occurred in only 17 patients (19 episodes). Symptoms of both conditions were similar; however, hypoactive bowel sounds, acute onset of emotional depression, no evidence of obstruction on radiologic contrast stomatogram or enema, and prompt relief of symptoms within 4 hours after intravenous administration of hydrocortisone acetate distinguished acute steroid withdrawal. Since ileus from acute steroid withdrawal occurred four times as frequently as mechanical small-bowel obstruction, prompt recognition and treatment should appreciably reduce postoperative morbidity and hospital costs.

Adolescent↗
PubMed1990

Extracorporeal membrane oxygenation in the treatment of neonatal respiratory failure.

We report 18 consecutive neonates with severe respiratory failure due to pulmonary hypertension treated with extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation was begun at 52 +/- 36 hours of age with an arterial partial pressure of oxygen (PO2) of 36 +/- 14 mm Hg despite maximal pharmacologic and ventilator support (inspired fraction of oxygen [FiO2], 0.99 +/- 0.03; respiratory rate, 98 +/- 31/min; and positive inspiratory pressure, 54 +/- 11 cm of water). With initial flows of 130 +/- 17 mL/kg per minute, ventilator settings were reduced to the following: FiO2, 0.30; respiratory rates, 15/min; and positive inspiratory pressure, 24 cm of water. Support using extracorporeal membrane oxygenation was gradually reduced to 22% of initial flows and arterial blood samples showed pH 7.48 +/- .05, PO2 of 106 +/- 27 mm Hg, and PCO2 of 36 +/- 5 mm Hg just prior to decannulation. After 107 +/- 45 hours, extracorporeal membrane oxygenation was stopped and infants were extubated 61 +/- 53 hours (median, 46 hours) afterward. There was one death (94.4% survival rate); all survivors were discharged and underwent a follow-up examination at 1 to 27 months of age. Complications included two intracranial hemorrhages (one death and one asymptomatic), one patent ductus arteriosus requiring ligation on extracorporeal membrane oxygenation, and chronic lung disease in one patient. In selected neonates, extracorporeal membrane oxygenation allows for resolution of pulmonary hypertension, results in improved survival, and is associated with a low incidence of chronic lung disease. Extracorporeal membrane oxygenation should be considered in the treatment of severe respiratory failure.

Carbon Dioxide↗
PubMed1990

Fetal rabbit intestinal absorption: implications for transamniotic fetal feeding.

Delivery of nutrients to the fetus via the developing gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. Previous studies have demonstrated significant increases in fetal length and weight following continuous intraamniotic nutrient infusions in animals. The ideal composition of intraamniotic feedings has yet to be determined. Thirteen time-mated rabbit does underwent ceserean section between gestational days 27 and 33 to deliver 54 fetuses. The everted intestinal sleeve technique was used to measure radiolabeled carbohydrate and amino acid uptake rates from 1-cm segments of midjejunum. Uptake of galactose was more than double that of glucose and fructose. Active uptake of glucose, fructose, and galactose increased by 3.3-fold, 6.2-fold, and 2.1-fold, respectively, during the final 7 days of gestation when expressed as uptake per mg intestine. In contrast, uptake of the amino acids leucine, lysine, and proline decreased by 41%, 34%, and 17%, respectively, during the final 5 days of gestation. The demonstrated changes in intestinal absorption and nutrient delivery in the rabbit model, during the last days of gestation, suggest that certain substrates are absorbed more rapidly than others. Galactose may be the preferred intraamniotic carbohydrate for fetal growth.

Amino Acids↗
PubMed1990

Changes in mucosal nutrient transport in small and large ileal reservoirs after endorectal ileal pullthrough.

It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well-emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR.

Animals↗
PubMed1990

Nephrolithiasis and urine ion changes in ulcerative colitis patients undergoing colectomy and endorectal ileal pullthrough.

Nephrolithiasis occurs in 5 to 13% of patients with ulcerative colitis (UC) who undergo colectomy and abdominal ileostomy, presumably from chronic dehydration and urinary concentration. Whether endorectal ileal pullthrough with ileal reservoir (PTR) changes the incidence of stones (primarily calcium oxalate) after colectomy is not known. Urinary excretion of Na2+, K+, Ca2+, Mg2+, phosphate, urate, oxalate, and citrate was measured in a prospective study of 12 UC patients undergoing PTR with temporary end ileostomy. Twenty-four-hour urine samples were obtained before colectomy (t1), after colectomy but before ileostomy closure (t2), and 5 months after ileostomy closure (t3). Urine volumes decreased from 831 +/- 101 cc (mean +/- SE) at t1 to 715 +/- 101 cc at t2 and then increased to 1278 +/- 421 cc at t3 (significant, with P less than 0.01 by t test). Urinary excretions of Mg2+, oxalate, and citrate were low in UC patients compared to those in controls (15 healthy adult volunteers). Excretion of Ca2+ increased significantly following temporary ileostomy while excretion of Mg2+ fell. Excretion of Ca2+ fell and excretion of Mg2+ and citrate increased following PTR. We conclude that PTR patients have increased urine volumes and urinary ion changes known to decrease the risk of developing renal stones.

Adolescent↗
PubMed1990

Reconstruction of malfunctioning ileoanal pouch procedures as an alternative to permanent ileostomy.

During the past 13 years, 261 patients with ulcerative colitis and 29 with colonic polyposis underwent endorectal pullthrough (ERP) at UCLA Medical Center. Of the first 111 consecutive patients to undergo ERP, 5 returned to a permanent ileostomy because of persistent symptoms related to reservoir stasis. Transabdominal shortening of the reservoir was performed in 38 of the 111 patients; 24 experienced marked clinical improvement. Fourteen of the 38 patients had persistent stasis and required shortening of the ileal spout either transanally (5 patients) or via an abdominoperineal approach (9 patients). Eighteen of the initial 111 patients underwent one-stage abdominoperineal reservoir reconstruction. During the past 4 years, 8 of 149 consecutive patients with a primary lateral isoperistaltic reservoir underwent subsequent abdominoperineal reservoir reconstruction. Fourteen of 18 patients with a straight pullthrough with reservoir underwent reconstruction to a lateral isoperistaltic reservoir. An aggressive operative approach to the management of pouchitis and reservoir stasis (diarrhea, frequency, urgency, incomplete emptying) has resulted in only 4 of the last 246 consecutive patients returning to a permanent ileostomy. Several changes in the operative technique have evolved during the 13-year period. Important features for optimal pouch function appear to include: (1) a short rectal muscle cuff, (2) a small ileal reservoir, (3) a short ileal spout, (4) removal of all rectal mucosa, and (5) aggressive correction of rectal strictures.

Adenomatous Polyposis Coli↗