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1.
Surg Obes Relat Dis ; 14(7): 882-901, 2018 07.
Article in English | MEDLINE | ID: mdl-30077361

ABSTRACT

The American Society for Metabolic and Bariatric Surgery Pediatric Committee updated their evidence-based guidelines published in 2012, performing a comprehensive literature search (2009-2017) with 1387 articles and other supporting evidence through February 2018. The significant increase in data supporting the use of metabolic and bariatric surgery (MBS) in adolescents since 2012 strengthens these guidelines from prior reports. Obesity is recognized as a disease; treatment of severe obesity requires a life-long multidisciplinary approach with combinations of lifestyle changes, nutrition, medications, and MBS. We recommend using modern definitions of severe obesity in children with the Centers for Disease Control and Prevention age- and sex-matched growth charts defining class II obesity as 120% of the 95th percentile and class III obesity as 140% of the 95th percentile. Adolescents with class II obesity and a co-morbidity (listed in the guidelines), or with class III obesity should be considered for MBS. Adolescents with cognitive disabilities, a history of mental illness or eating disorders that are treated, immature bone growth, or low Tanner stage should not be denied treatment. MBS is safe and effective in adolescents; given the higher risk of adult obesity that develops in childhood, MBS should not be withheld from adolescents when severe co-morbidities, such as depressed health-related quality of life score, type 2 diabetes, obstructive sleep apnea, and nonalcoholic steatohepatitis exist. Early intervention can reduce the risk of persistent obesity as well as end organ damage from long standing co-morbidities.


Subject(s)
Bariatric Surgery/standards , Metabolic Syndrome/surgery , Obesity, Morbid/surgery , Pediatric Obesity/epidemiology , Pediatric Obesity/surgery , Societies, Medical/standards , Humans , Metabolic Syndrome/diagnosis , Metabolic Syndrome/epidemiology , Obesity, Morbid/diagnosis , Obesity, Morbid/epidemiology , Pediatric Obesity/diagnosis , Practice Guidelines as Topic , Prognosis , Risk Assessment , Treatment Outcome , United States/epidemiology
2.
J Pediatr Gastroenterol Nutr ; 63(3): 352-6, 2016 09.
Article in English | MEDLINE | ID: mdl-27377833

ABSTRACT

OBJECTIVES: Infliximab (IFX) has become a mainstay of therapy for children with Crohn disease (CD). Despite medical advances, many children with CD, however, still require operative interventions. The risk of complications following resection in children treated with IFX remains largely unknown. We compare surgical outcomes stratified by IFX therapy in a cohort of children with CD who require bowel resection. METHODS: We reviewed the postoperative complications in 123 children with CD who underwent bowel resection with primary anastomosis at our institution between 1977 and 2011. Demographics, medications, types of operations, and inpatient courses were analyzed. Complications and length of stay were compared based on medical therapy. RESULTS: Overall, the postoperative complication rate was 13%. Of the 123 surgical cases, 24 children had received IFX before their operation. In the children treated with IFX, we identified 3 major complications, including anastomotic leak, acute renal failure, and intraabdominal abscess. There were 9 major complications in the non-IFX group, including infections (2), intraabdominal abscesses (2), bowel obstruction, shock, supraventricular tachycardia, phlegmon, and anastomotic stricture. No significant differences in complication rates or postoperative lengths of stay were identified between those who did or did not receive IFX. CONCLUSIONS: In this cohort, surgical procedures in children and young adults treated with IFX were not associated with an increased number of complications or prolonged length of stay. Given that postoperative complications are infrequent in children, larger multicenter studies may be required to determine whether IFX therapy increases the risk of surgical complications in pediatric CD.


Subject(s)
Crohn Disease/drug therapy , Crohn Disease/surgery , Gastrointestinal Agents/therapeutic use , Ileum/surgery , Infliximab/therapeutic use , Postoperative Complications/epidemiology , Adolescent , Adult , Child , Female , Humans , Laparoscopy , Length of Stay/statistics & numerical data , Male , Odds Ratio , Retrospective Studies , Young Adult
3.
Obes Res Clin Pract ; 9(3): 274-80, 2015.
Article in English | MEDLINE | ID: mdl-25458372

ABSTRACT

BACKGROUND: During Roux-en-Y gastric bypasses (RYGB), some surgeons elect to perform a vagotomy to reduce symptoms of gastro-oesophageal reflux (GER). Routine vagotomy during RYGB may independently affect weight loss and metabolic outcomes following bariatric surgery. We aimed to determine whether vagotomy augments percent excess weight loss in obese patients after RYGB. METHODS: We examined the effect of vagotomy in 1278 patients undergoing RYGB at our institution from 2003 to 2009. Weight and percent excess weight loss (%EWL) were modelled at three months and annually up to five years using a longitudinal linear mixed model controlling for differences in age, gender, initial body mass index (BMI), ideal body weight, and presence of vagotomy. RESULTS: Vagotomy was performed on 40.3% of our cohort. Vagotomy patients had significantly lower initial BMI (46.4±6.2 vs. 48.3±7.7kg/m(2), p<0.001), but there were no other significant differences at baseline. The strongest predictor of %EWL over time was initial BMI, with lower BMI patients exhibiting greater %EWL (p<0.001). Age and gender effects were also significant, with younger patients (p<0.04) and males (p<0.002) attaining greater %EWL. Vagotomy had no effect on %EWL in either simple or multiple regression models. CONCLUSION: Our series suggest that vagotomy does not augment %EWL when performed with RYGB.


Subject(s)
Gastric Bypass , Obesity, Morbid/surgery , Vagotomy, Proximal Gastric , Adult , Age Factors , Body Mass Index , Cohort Studies , Diet, Reducing , Electronic Health Records , Female , Gastric Bypass/adverse effects , Humans , Lost to Follow-Up , Male , Middle Aged , Obesity, Morbid/prevention & control , Recurrence , Reoperation/adverse effects , Retrospective Studies , Sex Characteristics , United States , Vagotomy, Proximal Gastric/adverse effects , Weight Loss
4.
J Nutr Metab ; 2014: 850820, 2014.
Article in English | MEDLINE | ID: mdl-25210625

ABSTRACT

Background. A common site for neonatal intestinal obstruction is the duodenum. Delayed establishment of enteral nutritional autonomy continues to challenge surgeons and, since early institution of nutritional support is critical in postoperative newborns, identification of patients likely to require alternative nutritional support may improve their outcomes. Therefore, we aimed to investigate risk factors leading to delayed establishment of full enteral nutrition in these patients. Methods. 87 patients who were surgically treated for intrinsic duodenal obstructions from 1998 to 2012 were reviewed. Variables were tested as potential risk factors. Median time to full enteral nutrition was estimated using the Kaplan-Meier method. Independent risk factors of delayed transition were identified using the multivariate Cox proportional hazards regression model. Results. Median time to transition to full enteral nutrition was 12 days (interquartile range: 9-17 days). Multivariate Cox analysis identified three significant risk factors for delayed enteral nutrition: gestational age (GA) ≤ 35 weeks (P < .001), congenital heart disease (CHD) (P = .02), and malrotation (P = .03). Conclusions. CHD and Prematurity are most commonly associated with delayed transition to full enteral nutrition. Thus, in these patients, supportive nutrition should strongly be considered pending enteral nutritional autonomy.

5.
ISRN Obes ; 2014: 517694, 2014.
Article in English | MEDLINE | ID: mdl-24693463

ABSTRACT

Background. Obesity studies are often performed on population data. We sought to examine the incidence of obesity and its associated comorbidities in a single freestanding children's hospital. Methods. We performed a retrospective analysis of all visits to Boston Children's Hospital from 2000 to 2012. This was conducted to determine the incidence of obesity, morbid obesity, and associated comorbidities. Each comorbidity was modeled independently. Incidence rate ratios were calculated, as well as odds ratios. Results. A retrospective review of 3,185,658 person-years in nonobese, 26,404 person-years in obese, and 25,819 person-years in the morbidly obese was conducted. Annual rates of all major comorbidities were increased in all patients, as well as in our obese and morbidly obese counterparts. Incidence rate ratios (IRR) and odds ratios (OR) were also significantly increased across all conditions for both our obese and morbidly obese patients. Conclusions. These data illustrate the substantial increases in obesity and associated comorbid conditions. Study limitations include (1) single institution data, (2) retrospective design, and (3) administrative undercoding. Future treatment options need to address these threats to longevity and quality of life.

6.
Case Rep Endocrinol ; 2013: 671848, 2013.
Article in English | MEDLINE | ID: mdl-24198980

ABSTRACT

Obesity is commonplace, and surgical treatment usually includes Roux-en-Y gastric bypasses (RYGBs). RYGBs have the most documented side effects including vitamin deficiencies, rebound weight gain, and symptomatic hypoglycemia; fewer series exist describing hypoglycemia following other bariatric operations. We reviewed all patients undergoing laparoscopic adjustable gastric banding (LAGB) at our institution between 2008 and 2012. Three patients were identified to have symptomatic hypoglycemia following LAGB. Mean time from surgery was 33 months (range 14-45 months), and mean weight loss was 32.7 kg (range 15.9-43.1 kg). None of the patients had preexisting diabetes. Therefore, symptomatic hypoglycemia should be investigated irrespective of bariatric operation.

8.
J Pediatr Surg ; 48(10): 2027-31, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24094952

ABSTRACT

PURPOSE: Treatment of long-gap esophageal atresia challenges pediatric surgeons. Dr. Foker described utilization of external traction sutures to promote in-vivo growth through tension-induced lengthening, but reproducibility of this technique is difficult. We describe a safe and reproducible traction system using transduction of hydrostatic pressure as a surrogate for tension. METHODS: We conducted a multi-institutional review of patients treated with this system from 2005 to 2012. All children had sutures applied to both pouches with continuous measurement of associated hydrostatic pressures (tension). Main outcome measures were days to delayed primary repair and thoracotomies prior to primary repair. RESULTS: Seven children were included. Median time to delayed repair was 15 days (range: 6-47 days). Three patients required repeat thoracotomies owing to mechanical entrapment of a pouch, all identified early by this system. All required postoperative dilations. Three had self-limited postdilation leaks, and there was one operation-related leak. CONCLUSIONS: This system provides reproducible traction application, facilitating staged primary repair by preventing major failures through limiting excessive traction and guides re-exploration for trapped segments. Larger studies are needed to determine the optimal tension protocol, prevent postoperative leaks, while decreasing the need for dilations and time to enteral feeding.


Subject(s)
Esophageal Atresia/surgery , Esophagus/surgery , Preoperative Care/methods , Suture Techniques , Traction/methods , Anastomosis, Surgical , Anastomotic Leak , Biomechanical Phenomena , Female , Humans , Hydrostatic Pressure , Infant , Kaplan-Meier Estimate , Male , Reproducibility of Results , Retrospective Studies , Thoracotomy
9.
J Pediatr Surg ; 48(7): 1540-5, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23895969

ABSTRACT

PURPOSE: The primary purpose of this study was to investigate the relationship between Pediatric Ulcerative Colitis Activity Index (PUCAI) and operative management. We also specifically evaluated those patients receiving tacrolimus for their disease. METHODS: A retrospective review (1/06-1/11) identified ulcerative colitis patients (≤21 years old) undergoing restorative proctocolectomy with rectal mucosectomy and ileal pouch-anal anastomosis. Main outcomes included pre-operative PUCAI, combined versus staged procedure, and postoperative complications. Patients receiving tacrolimus within 3 months of surgical intervention were identified. PUCAI at tacrolimus induction and medication side effects were also noted. RESULTS: Sixty patients were identified. Forty-two (70%) underwent combined and 18 (30%) had staged procedures. Pre-operative PUCAI was lower for combined versus staged patients (p = < 0.001). Furthermore, a higher pre-operative PUCAI strongly correlated with the likelihood of undergoing a staged procedure (p < 0.001). Forty-four patients (73%) received tacrolimus. Significant improvement in their PUCAI was noted from induction to pre-operative evaluation (p < 0.001). Minor and reversible side effects occurred in 46% of patients receiving tacrolimus, but complication rates were not significantly different. CONCLUSIONS: There is a very strong correlation between the PUCAI and the likelihood of undergoing a staged procedure. A significant improvement in PUCAI occurs following preoperative tacrolimus therapy.


Subject(s)
Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/surgery , Adolescent , Child , Child, Preschool , Colitis, Ulcerative/drug therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Predictive Value of Tests , Retrospective Studies , Tacrolimus/therapeutic use , Young Adult
10.
J Pediatr Surg ; 48(7): 1546-50, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23895970

ABSTRACT

BACKGROUND: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000's. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC). METHODS: We retrospectively reviewed 68 laparoscopic-assisted TPCs and 39 open TPCs performed at our institution for UC between January 1997 and February 2011. Case duration, postoperative length of stay, and complications of the two groups were compared, and multivariable analysis was applied. RESULTS: The two groups were comparable with respect to gender, age, and postoperative length of stay. Total abdominal colectomy (TAC) duration was significantly longer in the laparoscopic-assisted group (P < .001). Complications were similar in the laparoscopic and open group, although small bowel obstruction (SBO) was significantly less frequent in the laparoscopic group (log-rank test = 8.88, P = .003). Kaplan-Meier estimated freedom from SBO at 1 year follow-up is 99% for patients treated laparoscopically (95% CI: 98%-100%) and 76% for those undergoing an open surgical approach (95% CI: 64%-88%). CONCLUSIONS: The significantly lower SBO rate, low complication rates, and equivalent length of stay favor use of the laparoscopic-assisted approach for TPC and IPAA in children.


Subject(s)
Anal Canal/surgery , Colitis, Ulcerative/surgery , Colonic Pouches , Laparoscopy , Proctocolectomy, Restorative/methods , Adolescent , Anastomosis, Surgical , Child , Female , Humans , Male , Retrospective Studies
12.
J Pediatr Surg ; 47(12): 2345-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23217903

ABSTRACT

BACKGROUND: Laparoscopic techniques have been applied to restorative proctocolectomy since the early 2000s. We have employed a technique for laparoscopic-assisted total proctocolectomy (TPC) and ileal pouch anal anastomosis (IPAA) for the treatment of children with ulcerative colitis (UC). METHODS: A total of 68 children underwent laparoscopic-assisted TPCs at our institution from June 2003 to February 2011. The patients ranged from 5 to 22 years of age. We progressively modified our surgical approach in positioning, equipment use, and operative technique. RESULTS: A total of 68 children underwent laparoscopic-assisted TPC within the 8-year time period. Two major complications occurred (2/68=3%) consisting of 1 duodenal injury and 1 small bowel injury. There were 6 minor complications (6/68=9%), including 5 stoma revisions and 1 port site hernia. There were no superficial wound infections. There were no reported cases of pouch fistulas, anastomotic breakdown, or neurovascular injuries. CONCLUSIONS: Our surgical technique is safe and effective in treating children with UC.


Subject(s)
Colitis, Ulcerative/surgery , Colonic Pouches , Laparoscopy/methods , Proctocolectomy, Restorative/methods , Academic Medical Centers , Adolescent , Anal Canal/surgery , Anastomosis, Surgical/methods , Boston , Child , Cohort Studies , Colitis, Ulcerative/diagnosis , Female , Follow-Up Studies , Humans , Laparoscopy/adverse effects , Male , Operative Time , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Proctocolectomy, Restorative/adverse effects , Retrospective Studies , Risk Assessment , Severity of Illness Index , Treatment Outcome
13.
J Pediatr Surg ; 47(8): 1555-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22901916

ABSTRACT

BACKGROUND: Negative pressure wound therapy (NPWT) is an established and effective tool in the management of complicated abdominal wounds. This management approach has been used in infants, but few large series reports exist in the literature. METHODS: The outcomes of infants with abdominal wounds receiving NPWT over the last 10 years at our institution were evaluated. Overall survival, time between initiation of NPWT, and discharge/death were examined. RESULTS: We identified 18 infants who had abdominal wounds treated with NPWT. Diagnoses were varied, as was the duration of therapy. The median NPWT duration of treatment was 34.0 ± 92.1 days. Forty-four percent of the infants had a stoma before application of NPWT, and 22% of the infants had enterocutaneous fistulas before use of NPWT. There were only 2 cases in which a new fistula developed during the use of NPWT, and both of these omphalopagus conjoined twins had undergone the Bianchi procedure. No additional NPWT-related complications were identified. Of 18 infants, 6 died in this cohort. CONCLUSION: Negative pressure wound therapy is an important therapeutic tool for the management of abdominal wounds in infants.


Subject(s)
Abdominal Injuries/therapy , Abdominal Wound Closure Techniques , Intraoperative Complications/therapy , Negative-Pressure Wound Therapy , Diseases in Twins , Enterocolitis, Necrotizing/surgery , Gastroschisis/surgery , Hernia, Umbilical/surgery , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/therapy , Intestinal Fistula/etiology , Intestinal Fistula/prevention & control , Intestinal Fistula/therapy , Laparotomy/adverse effects , Liver Transplantation , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/therapy , Retrospective Studies , Surgical Sponges , Twins, Conjoined/surgery , Wound Healing
14.
Pediatr Dev Pathol ; 14(3): 224-7, 2011.
Article in English | MEDLINE | ID: mdl-19995209

ABSTRACT

Juvenile granulosa cell tumor (JGCT) is an uncommon gonadal stromal tumor that occurs rarely in the testis. We report a newborn boy with bilateral intra-abdominal JGCT presenting with abdominal distention and respiratory distress at birth. He was taken to the operating room emergently, and 2 large masses connected by gubernacula to the inguinal canals were resected. Associated abnormalities included a constitutional chromosome 4 abnormality, polymicrogyria, and renal cysts. This report describes a rare presentation of JGCT with abdominal compression and expands the literature to include bilateral testicular involvement. Additionally, it is the 1st report of JGCT associated with a chromosome 4 abnormality, highlighting a genetic region that may be important in JGCT development.


Subject(s)
Chromosomes, Human, Pair 4/genetics , Granulosa Cell Tumor/congenital , Granulosa Cell Tumor/genetics , Testicular Neoplasms/congenital , Testicular Neoplasms/genetics , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Granulosa Cell Tumor/pathology , Humans , Infant, Newborn , Male , Testicular Neoplasms/pathology
15.
J Pediatr Surg ; 44(12): 2402-5, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20006037

ABSTRACT

Hypopharyngeal perforation secondary to blunt trauma is a rare injury. It can be managed operatively or expectantly without clear criteria for either approach. Here, we present a case of a 17-year-old adolescent boy who had a hypopharyngeal tear from direct blunt trauma to the anterior neck received during a high school football game. Physical examination demonstrated cervical crepitus, and neck radiograph revealed air in the retropharyngeal space. Rigid endoscopy diagnosed a 3-cm linear tear in the posterior hypopharynx. The tear was repaired transorally using laparoscopic instruments and visualized by a rigid endoscope, followed by anterior neck dissection and drain placement. Postoperatively, he was kept nil per os and received intravenous antibiotics. He was discharged home and returned to the football field the same fall.


Subject(s)
Football/injuries , Hypopharynx/injuries , Hypopharynx/surgery , Lacerations/surgery , Neck Injuries/surgery , Wounds, Nonpenetrating/complications , Adolescent , Drainage , Humans , Lacerations/diagnostic imaging , Lacerations/etiology , Laparoscopy/methods , Male , Neck Injuries/complications , Radiography , Treatment Outcome
16.
J Laparoendosc Adv Surg Tech A ; 19 Suppl 1: S249-54, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19371150

ABSTRACT

BACKGROUND/PURPOSE: Aortopexy is an established treatment method for severe tracheomalacia. It can be performed by thoracotomy or thoracoscopically. The purpose of this study is to review our experience with thoracoscopic aortopexy. METHODS: Thoracoscopic aortopexy was performed for treatment of tracheomalacia in five patients. A left-sided approach with three ports was used. The aorta was sutured to the sternum with a series of transversely oriented simple interrupted Prolene sutures. Knots were tied subcutaneously. Pre- and postprocedure bronchoscopy was used to verify improvement in tracheal patency. The study protocol was approved by the Institutional Review Board. A retrospective chart review was performed and indications, perioperative course, and, where available, long-term results were noted. RESULTS: We treated four girls and one boy. Ages were between 6 weeks and 2 years. Weights were between 3.2 and 10 kg. Resolution of symptoms was achieved in all patients. There was no morbidity or mortality associated with the procedure. Length of hospital stay after aortopexy ranged between 4 and 59 days. Follow-up ranged between 34 and 5 months. CONCLUSIONS: Thoracoscopic aortopexy is an effective treatment for severe tracheomalacia not controlled by conservative measures. It can be safely performed even in small infants as long as equipment and skill for pediatric thoracoscopy are available. The authors believe that thoracoscopic exposure offers advantages over open technique and is cosmetically more pleasing to patients and their families. It may result in less pulmonary complications, shorter hospital stay, and less narcotic requirement compared to open thoracotomy.


Subject(s)
Thoracoscopy , Tracheomalacia/surgery , Aorta/surgery , Child, Preschool , Female , Follow-Up Studies , Humans , Infant , Male
17.
J Pediatr Surg ; 44(2): 459-63, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19231558

ABSTRACT

Osteosarcoma is the most common osseous malignancy of childhood. Vascular reconstruction during resection is uncommon. However, when required, thrombosis is a major cause of failed limb salvage surgery. A 19-year-old patient required complex vascular reconstruction in conjunction with lower extremity osteosarcoma resection. Preoperatively, his case was complicated by an ipsilateral popliteal deep vein thrombosis presenting during neoadjuvant chemotherapy. At the time of resection, to increase vascular graft flow, a distal arteriovenous fistula was created between the posterior tibial artery and the greater saphenous vein. This case illustrates a patient with a complex extirpation procedure requiring concomitant vascular reconstruction. This technique should be considered when limb salvage with vascular resection is being attempted in a high-risk patient.


Subject(s)
Arteriovenous Shunt, Surgical/methods , Femoral Neoplasms/surgery , Neoplasms, Multiple Primary/surgery , Osteosarcoma/surgery , Saphenous Vein/surgery , Soft Tissue Neoplasms/surgery , Tibial Arteries/surgery , Humans , Male , Risk Factors , Young Adult
19.
J Gastrointest Surg ; 7(6): 777-82, 2003.
Article in English | MEDLINE | ID: mdl-13129556

ABSTRACT

Because of the favorable anatomy of the left lateral segment of the liver, a totally laparoscopic approach to resection is feasible. Herein we describe a technique for laparoscopic stapled resection of the left lateral segment of the liver, including the necessary anatomic criteria for a safe operation and data on clinical outcome. Five patients at our center underwent laparoscopic exploration, ultrasound examination, and resection of segments II and III. After complete mobilization of the left lateral segment and minimal portal dissection, the totally laparoscopic resections were performed with two endoscopic staple loads (4.5 mm x 60 mm) applied sequentially across the portal pedicle and the left hepatic vein. The mean operative time was 182 minutes (range 130 to 240 minutes), blood loss was 41 ml (range 25 to 50 ml), and length of hospital stay was 2.2 days (range 1 to 3 days). All three patients with malignancy had negative surgical margins. All five patients returned to normal activity or work by 1 week postoperatively. There were no complications. Patients with isolated malignant and benign diseases of the left lateral segment of the liver are candidates for totally laparoscopic resection, if evaluation demonstrates a normal liver character and hepatic parenchymal thickness less than 3 cm overlying the ligamentum venosum groove. Such patients benefit from the minimally invasive approach, with no compromise in the surgical result as compared to the open approach.


Subject(s)
Hepatectomy/methods , Laparoscopy , Liver Diseases/surgery , Sutures , Adult , Aged , Aged, 80 and over , Female , Humans , Liver Diseases/diagnostic imaging , Male , Middle Aged , Treatment Outcome , Ultrasonography
20.
Am J Physiol Lung Cell Mol Physiol ; 285(6): L1354-61, 2003 Dec.
Article in English | MEDLINE | ID: mdl-12882761

ABSTRACT

To test the hypothesis that chronic intrauterine pulmonary hypertension (PHTN) compromises pulmonary artery (PA) smooth muscle cell (SMC) O2 sensing, fluorescence microscopy was used to study the effect of an acute increase in Po2 on the cytosolic Ca2+ concentration ([Ca2+]i) of chronically hypoxic subconfluent monolayers of PA SMC in primary culture. PA SMCs were derived from fetal lambs with PHTN due to intrauterine ligation of the ductus arteriosus. Acute normoxia decreased [Ca2+]i in control but not PHTN PA SMC. In control PA SMC, [Ca2+]i increased after Ca2+-sensitive (KCa) and voltage-sensitive (Kv) K+ channel blockade and decreased after diltiazem treatment. In PHTN PA SMC, KCa blockade had no effect, whereas Kv blockade and diltiazem increased [Ca2+]i. Inhibition of sarcoplasmic reticulum Ca2+ ATPase activity caused a greater increase in [Ca2+]i in controls compared with PHTN PA SMC. Conversely, ryanodine caused a greater increase of [Ca2+]i in PHTN compared with control PA SMC. KCa channel mRNA is decreased and Kv channel mRNA is unchanged in PHTN PA SMC compared with controls. We conclude that PHTN compromises PA SMC O2 sensing, alters intracellular Ca2+ homeostasis, and changes the predominant ion channel that determines basal [Ca2+]i from KCa to Kv.


Subject(s)
Fetal Diseases/physiopathology , Hypertension, Pulmonary/physiopathology , Muscle, Smooth, Vascular/physiology , Oxygen/pharmacology , Pulmonary Artery/physiology , Animals , Blood Proteins/pharmacology , Calcium/metabolism , Calcium-Transporting ATPases/antagonists & inhibitors , Cells, Cultured , Cytoplasm/metabolism , Enzyme Inhibitors/pharmacology , Female , Fetal Diseases/metabolism , Fetus , Hypertension, Pulmonary/metabolism , Hypoxia/metabolism , Hypoxia/physiopathology , Muscle, Smooth, Vascular/cytology , Peptides/pharmacology , Potassium/pharmacology , Potassium Channels/genetics , Potassium Channels/metabolism , Pregnancy , Pulmonary Artery/cytology , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Ryanodine/pharmacology , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Sheep , Thapsigargin/pharmacology
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