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Biomedical subjects

W H Weintraub

Publications and source records attributed to W H Weintraub.

At least 19 recordsLinked to original sources

Successful splenorenal shunt for emergent control of variceal bleeding in a small child.

A 8.6-kg, 10-month-old boy with idiopathic cavernous transformation of the portal vein developed variceal hemorrhage refractory to nonoperative management. A distal splenorenal shunt was performed while the bleeding was controlled with balloon tamponade. Hemorrhage was successfully controlled with no recurrent bleeding and the shunt remains patent at 1 year of follow-up.

Esophageal and Gastric Varices

Calcium signaling in endothelia: cellular heterogeneity and receptor internalization.

The vasoactive factors thrombin, bradykinin (BK), and ATP are released in response to tissue damage and inflammation and act on endothelium to modulate vascular perfusion. We have investigated the second messenger response of endothelium activated by these agonists and, in particular, the mechanism of desensitization to BK. Fura-2 fluorescence ratio imaging of calf pulmonary artery endothelial cells (CPAE) revealed 5- to 10-fold increases on intracellular Ca (Cai) in response to these agents. Maximal doses caused Cai to increase from 52 to 248 nM (thrombin), 556 nM (BK), and 643 nM (ATP). Agonists elicited a rapid (within 30 s) increase of Cai due to release of Ca from intracellular stores followed by a secondary elevation of Cai dependent on entry of external Ca. The temporal characteristics of the Cai responses to all agonists were heterogeneous from cell to cell, and, interestingly, repeated stimulation gave identical signature responses from individual cells, although the amplitude of the Cai response decreased to thrombin and especially bradykinin but not for ATP. This decrease was agonist specific because ATP elicited large increases of Cai after thrombin or BK desensitization. Maximal desensitization was obtained with BK applied for 5-10 min followed by a rest of < 10 min before restimulation. Although desensitization primarily reduced the elevation of Cai due to the release of the internal store, entry of extracellular Ca was also reduced. Cells responded heterogeneously to desensitization in that those with prominent extracellular Ca entry responded most strongly upon a second stimulation with BK. Because desensitized cells still responded to ATP with an increase of Cai, the desensitization was controlled at a step prior to the activation of phospholipase C. Desensitization occurred by a reduction of BK receptor number; a 10-min BK pretreatment reduced [3H]BK binding to receptors by 70% (from 14,600 receptors/cell, Km = 5 nM, to 5,300). As surface receptor numbers decreased, internalized receptors increased as assayed by an acetic acid wash. The time course of the receptor internalization was similar to the decrease in Cai response to BK. We conclude that the vasoactive agonists thrombin, BK, and ATP increase the second messenger Cai in endothelial cells and that a desensitized Cai response occurs with BK, but not with ATP, due to downregulation and endocytosis of the BK receptor.

Adenosine Triphosphate

Intravenous digital subtraction angiography: its use in evaluating vascular injuries in children.

Angiography is often essential in the evaluation of patients with suspected vascular injuries. However, arterial cannulation has a significant inherent complication rate, especially in small patients. Therefore, a less invasive method of evaluating children with such injuries is desirable. We report nine children (age range, 9 months to 16 years; median, 7 years) in whom intravenous digital subtraction angiography (IV-DSA) was used to evaluate suspected vascular injuries. IV-DSA showed a false aneurysm in two children, one managed by ligation alone and the other by resection with primary anastomosis. One child was found to have an arteriovenous fistula, which was treated by ligation. An iliac occlusion, following an arteriogram to evaluate a liver tumor, was documented by IV-DSA and successfully managed with aggressive anticoagulant therapy. Demonstration of a normal vascular tree avoided exploration in four children. A planned skin flap was abandoned in a child who suffered an electrical injury when IV-DSA showed lack of adequate vascular supply. In all nine cases, the IV-DSA obviated the need for intraarterial angiography. In addition to avoiding arterial cannulation, IV-DSA required significantly less radiation and less time to perform than conventional arteriography. Motion artifact, vessel overlap, and some loss of minute detail are some of its potential shortcomings. IV-DSA is an effective method of screening children with suspected vascular injuries. In addition, our experience has shown that IV-DSA can be the definitive diagnostic procedure, although intraarterial angiography may be necessary in selected cases.

Adolescent

pH regulation in hepatoma cells: roles for Na-H exchange, Cl-HCO3 exchange, and Na-HCO3 cotransport.

Regulation of intracellular pH (pHi) was studied in Fu5, a rat hepatoma cell line that maintains a variety of differentiated functions. Microspectrofluorimetry of the pH-sensitive dye 2',7'-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) was used to measure pHi in 10-15 cells growing on cover glasses that were mounted in a flow-through chamber on the stage of a microscope. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions, pHi was 7.14, and intrinsic buffer capacity was inversely related to pHi. Amiloride (0.1 mM) caused pHi to decrease by 0.33 pH units in 4 min. Recovery from an acid load (using either NH4 prepulse technique or Na-free solutions) was completely blocked by amiloride. In HCO3-CO2-buffered solutions, pHi was 7.15, and buffer capacity was relatively insensitive to pHi between pHi of 6.6 and 7.2. Amiloride caused pHi to decrease by only 0.09 units. Recovery from an acid load was Na dependent, occurred in Cl-free solutions, and was totally blocked by the combination of amiloride plus 0.5 mM dihydro-4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (H2DIDS); recovery occurred when either amiloride or H2DIDS was removed. Removal of external Cl caused a rapid, H2DIDS-blockable alkalinization that was faster in HCO3-CO2 than in HEPES. The apparent Km for Clout for relaxation of Cl-free alkalinization was 4.5 mM. Rate of HCO3 transport during Cl-free treatment increased at alkaline resting pHi. It is concluded that Fu5 cells have two Na-dependent base-loading mechanisms and an acid-loading Cl-HCO3 exchanger. In solutions containing HCO3-CO2, the Na-H exchanger accounts for approximately 40% of recovery from an acid load, and a Na-HCO3 cotransporter accounts for the remainder. Recovery from an alkaline load appears to occur through the activity of the Cl-HCO3 exchanger.

Amiloride

Intracellular pH regulation in IEC-6 cells, a cryptlike intestinal cell line.

Regulation of intracellular pH, pHi, was studied using microspectrofluorimetry of the pH-sensitive, fluorescent dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the rat intestinal crypt cell line, IEC-6. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solutions with pHi 7.25, treatment with a pulse of NH4Cl caused cells to acidify and then recover to control level. Because recovery was Na dependent, blocked by 1 mM amiloride, and unaffected by the presence and absence of Cl, it was likely because of a Na+-H+ exchanger. Cells were also acid loaded by changing from HEPES to HCO3-CO2-buffered solutions. pHi again recovered, but 1 mM amiloride reduced the rate of H+ efflux by only 47%. This HCO3-dependent, amiloride-insensitive H efflux required Na+ but not Cl- and was completely blocked by 200 microM [H2] 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). We conclude that a Na+-HCO3- cotransporter was operative. Cl-free solutions caused pHi to increase from 7.19 to 7.41; this effect required the presence of exogenous HCO3-CO2 but not Na and was blocked by 200 microM [H2]DIDS. A Cl- -HCO3- exchanger is the most likely explanation for these data. All the pHi regulatory mechanisms are operative in NaCl-HCO3-CO2-buffered solutions. The Na+-H+ and Na+-HCO3- mechanisms are acid extruders, whereas the Cl- -HCO3- exchanger is an acid loader. These transporters may be important for generating HCO3 secretion by intestinal crypt cells.

Acids

Glucocorticoids confer normal serum/growth factor-dependent growth regulation to Fu5 rat hepatoma cells in vitro. Sequential expression of cell cycle-regulated genes without changes in intracellular calcium or pH.

Glucocorticoid hormones induced a stringent dependence on serum for the in vitro proliferation of Fu5 rat hepatoma cells by suppressing the growth rate and final quiescent cell density. Treatment of dexamethasone-suppressed quiescent Fu5 with serum plus insulin caused a rapid reinitiation of cellular proliferation and DNA synthesis that peaked at 16 h. RNA dot blot analysis of this time course showed that the transcript levels for the proto-oncogenes c-fos, c-myc, and c-rasKi peaked at 0.5, 2, and 4 h, respectively, while expression of c-rasHa and ornithine decarboxylase transcripts rose steadily during 16 h. Microspectrofluorimetric measurements of cytosolic calcium (Ca2+i) with fura-2 showed that insulin and serum, alone or in combination, elicited no changes in Ca2+i over a 50-min time course, although ATP, which is not a mitogen, induced large increases in Ca2+i. Cytosolic pH, pHi, was also measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Insulin and serum, alone or in combination, did not cause pHi to increase in either 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (pHi 7.17)- or HCO3/CO2 (pHi 7.19)- buffered media. Acid-loading of cells with NH4Cl indicated that both quiescent and proliferating Fu5 cells have equally active, amiloride-sensitive Na/H exchangers. Therefore, induction of DNA synthesis and proto-oncogene expression occurs in Fu5 epithelial tumor cells in the absence of any short term increases of pHi or Ca2+i.

Adenosine Triphosphate

Respiratory complications in cervical thymic cysts.

Thymic cysts are considered uncommon lesions in the differential diagnosis of pediatric neck masses. They have been described as asymptomatic and of little clinical consequence. Recent reports have stressed the possibility of respiratory compromise associated with these lesions. We reviewed our experience with cervical thymic cysts with emphasis on respiratory problems. Ten pediatric patients underwent surgery and were found to have cervical thymic cysts. Ages ranged from newborn to 14 years. There were four boys and six girls. Two were found to have the thymic cysts at time of neck exploration for Grave's disease and hyperparathyroidism. Of the remaining eight patients, all had mobile cystic masses, located anterior to but extending beneath the lower third of the sternocleidomastoid muscle. The size of the mass ranged from 3.0 to 8.5 cm. Preoperative diagnosis included cystic hygroma/branchial cleft cyst (five), lymphoma (one), teratoma (one), and thymic cyst (one). All had a history of rapidly developing neck mass. Seven of the eight gave a history of upper respiratory tract infection (URI) prior to the development of the mass. Five had imaging studies that showed tracheal compression. Three of these required airway management in the early postoperative period. All were excised through a neck incision, with two requiring sternal extension. Histology showed cholesterol crystals, Hassall's corpuscles, and giant cell reaction diagnosis of thymic cysts. There has been no recurrence and no permanent respiratory sequela in the ten patients. Cervical thymic cysts are benign lesions that may be more common than literature suggests.(ABSTRACT TRUNCATED AT 250 WORDS)

Child

Pyelonephritis following pediatric renal transplant: increased incidence with vesicoureteral reflux.

The association between pyelonephritis and vesicoureteral reflux (VUR) following pediatric renal transplantation is unclear. To understand the relationship of vesicoureteral reflux with urinary tract infection (UTI) and pyelonephritis, 67 patients were evaluated for reflux and pyelonephritis. Sixty-seven pediatric patients, aged 2 to 18 (39 males and 28 females) underwent renal transplantation. Beginning in 1982, all patients underwent voiding cystourethrography or radionuclide voiding studies 1 to 3 months postoperatively to assess the incidence of VUR. Techniques of ureteroneocystostomy (UNC) included the Leadbetter-Politano (L-p) in 39 cases, and two different modifications of the LICH (herein called LICH-1 and LICH-2) in 30 cases. Urinary cultures were performed routinely. Pyelonephritis was considered present in any patient with UTI and increased serum creatinine or fever greater than 38.5. VUR occurred in 36% of patients; highest in LICH-1 (79%), intermediate in L-P (22%), and lowest in LICH-2 (9%). VUR was not statistically significantly higher in females (43%) v males (31%). UTI occurred in 37% of patients. The difference in incidence between females (54%) and males (26%) was significant (P less than .05). The frequency of UTI in patients with VUR was 46% v 33% in patients without reflux (NS). However, pyelonephritis that occurred in 16% of cases overall was present in 82% of UTIs in patients with reflux v 14% of UTIs in patient without reflux (P less than .01). Pyelonephritis is significantly increased in pediatric renal transplant patients with UTI was have VUR. A nonrefluxing UNC is advocated in all patients. All renal transplant patients should have routine monitoring of urinary cultures and should be evaluated of VUR posttransplant.

Adolescent

Retrieval of an umbilical artery catheter: a potential for misadventure.

We have described an infant in whom migration of a transected umbilical artery catheter resulted in sudden vascular ischemia of an extremity. Early operative retrieval was successful, but long-term effects of this complication were encountered. We have outlined an approach to the initial management of the complication. In addition, this case demonstrates the need for careful follow-up for identification and treatment of the long-term sequelae in the involved extremity.

Catheters, Indwelling

The central venous anatomy in infants.

A study of 21 consecutive autopsy specimens of infants less than one year of age and weighing less than 6 kilograms was performed to determine the topographic anatomy and regional relationships of the central venous anatomy. This anatomy was compared with 14 additional autopsies performed upon older children. There was no significant difference in diameter between the internal jugular and subclavian venous system, on either the right or left side. In the infant, the right and left subclavian veins entered the central system at an acute angle. The left innominate vein joined the right innominate vein at a right angle. These angulations become less acute after one year of age. This adult configuration may account for the relative ease of central venous cannulation through the percutaneous subclavian approach in the older patient. In contrast, the external and internal jugular veins entered centrally in almost a straight line even in the infant. The findings of this study suggest that the internal and external jugular veins should be considered as safe and reliable portals for percutaneous entry into the central venous system in infants. In the infant less than one year of age, the difficult patient (for example, those with thrombocytopenia or severe pulmonary failure) or when the surgeon is less familiar with the infraclavicular approach, the veins of the neck may, in fact, be the site of choice. Additionally, we believe that a surgeon should not hesitate to switch to the internal or external jugular site after unsuccessful attempts at percutaneous entry into the subclavian vein.

Brachiocephalic Veins

Intestinal perforation due to blunt trauma in children in an era of increased nonoperative treatment.

Over the past decade, nonoperative management of most pediatric blunt abdominal trauma has emerged as accepted practice. It is possible that treatment of associated hollow visceral disruption might be missed or delayed because of this nonoperative approach. In a review of all cases of intestinal perforation from blunt trauma seen over the past 6 years, we found 12 cases of intestinal disruption in more than 600 cases of significant blunt trauma. Child abuse caused eight cases and four were motor vehicle related (MVR). Seven of eight battered children had a delay of more than 48 hours from injury to hospital presentation. Three of four MVR patients had an 18-hour delay from injury to operation. Ten of 12 patients survived. The two children who succumbed were both battered and were moribund and unstable when first seen and failed to respond to aggressive stabilization and surgery. Serial physical examinations, contrast radiographic studies, and peritoneal lavage were the most helpful diagnostic modalities. There were no significant complications and no patient required more than one operation (except for ostomy closure). All surviving patients are well at followup and seven of ten have been followed for more than 3 years; two are not yet 1 year from surgery and one is lost to followup. Several principles have emerged from this review: 1) motor vehicle trauma and child abuse are the major etiologic factors in childhood blunt trauma; 2) accurate and rapid diagnosis of intestinal perforation in children is difficult; 3) recovery in the presence of stable vital signs can be expected, even with the long delays; and 4) abused children must be carefully evaluated for abdominal trauma.

Accidents, Traffic

Evaluation of absorbable polyglycolic acid mesh as a wound support.

The ideal wound-support material would reinforce a wound early in the healing process when intrinsic wound strength is the weakest, yet disappear over time, preventing many of the untoward late effects seen with currently utilized nonabsorbable materials. This study was designed to evaluate the effectiveness of a newly designed absorbable material, polyglycolic acid mesh (Dexon), as a buttress for abdominal wounds closed under moderate tension. Young male rats (n = 211) were divided into three experimental groups. Animals in groups 1 (n = 96) and 2 (n = 95) had a 1.2 cm2 midline abdominal wall defect created and closely primarily. Animals in group 2 had a 2 X 5 cm piece of polyglycolic acid mesh sutured to the anterior abdominal wall overlying the closed abdominal defect. Animals in group 3 (n = 20) were unoperated controls. The animals in groups 1 and 2 were killed 1, 2, 3, 4, and 5 weeks after surgery. The entire anterior abdominal wall was removed and placed upon a bursting strength testing device. Bursting strength determinations of the supported and unsupported abdominal closures revealed that the strength of the wounds reinforced with polyglycolic acid mesh was significantly greater than unsupported wounds at 1, 2, and 3 weeks after surgery. Wounds supported with mesh had bursting strengths similar to unoperated abdomens by the first postoperative week. This study demonstrates that abdominal wall defects in rats closed primarily develop increased wound strength when the closure is supported by absorbable polyglycolic acid mesh. The use of an absorbable material may alleviate potential late complications associated with implantation of nonabsorbable materials. The clinical application of such a material remains to be determined.

Abdominal Muscles

Esophageal atresia. A 41-year experience.

Since the first attempted repair in 1935, a total of 365 infants have undergone treatment for esophageal atresia with or without tracheoesophageal fistula. To evaluate the improvement in our results, we have divided our patients into four, approximately equal, time periods. The overall late survival has indeed improved during each of the four decades from between 36% and 53% to 68% in the last ten years. During this past decade, the group A risk infants (35 patients) had a 3% mortality, the group B (20 patients) had a 5% mortality, but the group C babies (22 patients) had a 41% mortality due to associated anomalies or severe prematurity. Anastomotic leaks and recurrent fistulas were each encountered in approximately 5% of the cases in all decades. Postoperative stricture has been encountered in 20% of the entire series and no esophageal replacements have been required.

Abnormalities, Multiple

An evaluation of the modified endorectal procedure for Hirschsprung's disease.

During the past 4 yr, 60 patients with Hirschsprung's disease have been treated at our institution. Twenty-eight patients within this group have undergone a modified endorectal pull-through procedure. There are 18 males and 10 females in the series. There are 5 children with total colonic involvement, 3 patients with aganglionosis to the mid-transverse colon, and one child with Hirschsprung's disease extending to the distal jejunum. The associated anomalies have consisted of four cases of Down's syndrome, one of whom also has transposition of the great vessels. There has been no operative-related mortality or late mortality in our series. Two major complications (anastomotic leak following a colostomy closure and incorrect pathological diagnosis of aganglionic level) and five minor complications have occurred. The average follow-up period is 31.3 mo. The functional results postoperatively have been excellent. The 18 patients over the age of 3 yr are completely toilet-trained. The remaining patients are too young to be toilet-trained, but are continent in the sense that they do not soil between bowel movements. Because of the satisfying functional results in this series, we have now expanded our indications for this procedure to patients requiring total colectomy for ulcerative colitis and familial polyposis. During the past 2 yr, 8 patients with ulcerative colitis have undergone the endorectal pull-through together with a total colectomy.

Anal Canal

Crohn's disease in children and adolescents: is inadequate weight gain a valid indication for surgery?

Seventy children and adolescents hospitalized for Crohn's disease at the University of Michigan Medical Center between 1966 and 1976 are reviewed. Thirty-three of these children were managed medically and 37 underwent a total of 60 operative procedures. There were 33 bowel resections, 7 appendectomies, 4 abscess drainages, 3 bowel bypasses, and 13 miscellaneous operative procedures. The total operative mortality was 1.7%, and there were 10 complications, all of which were successfully managed. Among the 26 children undergoing bowel resections, 22 were below the third percentile for weight preoperatively. Nearly two-thirds of these gained weight to the 35th percentile following resection. The remainder of the children had a variety of growth and symptomatic responses to surgery. Resection aimed at complete removal of diseased bowel can be expected to yield substantial weight gain in children with Crohn's disease.

Adolescent