Michael Skinner | University of Texas Southwestern Medical Center at Dallas (original) (raw)

Papers by Michael Skinner

Research paper thumbnail of Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A

The New England journal of medicine, Jan 15, 2005

Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine... more Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN-2A) or type 2B or familial medullary thyroid carcinoma. We sought to determine whether total thyroidectomy in asymptomatic young members of kindreds with MEN-2A who had a mutated allele of the RET proto-oncogene could prevent or cure medullary thyroid carcinoma. A total of 50 patients 19 years of age or younger who were consecutively identified through a genetic screening program as carriers of a RET mutation characteristic of MEN-2A underwent total thyroidectomy. Five to 10 years after the surgery, each patient was evaluated by physical examination and by determination of plasma calcitonin levels after stimulation with provocative agents. In 44 of the 50 patients, basal and stimulated plasma calcitonin levels were at or below the limits of detection of the assay (proportion, 0.88; 95 percent confidence interval, 0.76 to 0.95). Two patients had basal and sti...

Research paper thumbnail of Fine Mapping of Wilms’ Tumors With 16q Loss of Heterozygosity Localizes the Putative Tumor Suppressor Gene to a Region of 6.7 Megabases

The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in... more The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in Wilms' tumors and to examine the expression of putative tumor suppressor.

Research paper thumbnail of Primary neonatal cricopharyngeal achalasia: A case report and Review of the literature

Journal of Pediatric Surgery, 1992

Primary cricopharyngeal achalasia is a rare cause of dysphagia in the pediatric population. In a ... more Primary cricopharyngeal achalasia is a rare cause of dysphagia in the pediatric population. In a review of the literature, only 11 well-documented cases were discovered. We report the case of a newborn with cricopharyngeal achalasia who was successfully treated with a myotomy of the upper esophageal sphincter. A review of the literature is presented and treatment options are discussed.

Research paper thumbnail of Routine insertion of a Silastic® spring-loaded silo for infants with gastroschisis

Journal of Pediatric Surgery, 2000

Background/Purpose: Gastroschisis traditionally is managed by emergency operating room closure (E... more Background/Purpose: Gastroschisis traditionally is managed by emergency operating room closure (EC), with a silo reserved for cases that cannot be closed primarily. The authors recently began using routine insertion of a SILASTIC (Dow Corning, Midland, MI) spring-loaded silo (SLS), followed by elective closure.

Research paper thumbnail of Transanal one-stage soave procedure for infants with Hirschsprung's disease

Journal of Pediatric Surgery, 1999

Research paper thumbnail of Experience with procedural sedation in a pediatric burn center

Journal of Pediatric Surgery, 1999

Research paper thumbnail of One-stage versus two-tage Soave pull-through for Hirschsprung's disease in the first year of life

Journal of Pediatric Surgery, 1996

Research paper thumbnail of Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B

Journal of Pediatric Surgery, 1996

Research paper thumbnail of Decreased E-cadherin expression correlates with higher stage of Wilms' tumors

Journal of Pediatric Surgery, 2005

Purpose: The aim of this study was to examine the association between E-cadherin expression and m... more Purpose: The aim of this study was to examine the association between E-cadherin expression and markers of Wilms' tumor aggression, including metastasis and recurrence. Methods: Forty Wilms' tumor samples from the National Wilms' Tumor Study Group underwent immunohistochemical staining for E-cadherin. Tumor stage at diagnosis, recurrence, and loss of heterozygosity at 16q status was known for each of the tumor samples. E-Cadherin cell staining was defined as high (N33%) or low (b33%), and values were assigned by a pathologist blinded to the tumor characteristics. Five stage IV tumors were ineligible for assay because of lack of a tubular component. To identify a mechanism of downregulation, we screened tumor DNA for genetic mutations in exons 1-16 using a combination of WAVE and sequence analysis. To assess the functional significance of the identified mutations, the authors compared amino acid homology across multiple species. Finally, they performed reverse transcriptase-polymerase chain reaction for those tumors with intronic single nucleotide polymorphisms (SNPs) to evaluate for mRNA splice variants. Results: Wilms' tumors presenting with metastatic (stage IV) disease demonstrated decreased levels of Ecadherin expression compared with localized tumors (stage I) (Fisher's Exact test, P b .01). In a search for the mechanism of the downregulation of E-cadherin, we identified 5 different mutations in 7 high stage tumors (7/15) and 1 mutation in a low stage tumor (1/20). The mutations occurred in amino acids that were conserved across multiple species. Additionally, 11 of 15 high stage tumors contained an intronic SNP located within 6 bp of the 5V intronic splice junction immediately downstream of exon 1. However, examination of 5 of these tumors using reverse transcriptase-polymerase chain reaction showed that this intronic SNP does not appear to disrupt the assembly of full-length E-cadherin transcripts. Lastly, no correlation was identified between E-cadherin expression and recurrence of disease. Conclusions: In this study, the authors have found an association between decreased E-cadherin expression and metastatic Wilms' tumor. Mutations identified may help identify a mechanism for downregulation. The functional significance of these mutations is supported by the conserved nature of the 0022-3468/05/4002-0010$30.00/0 D 2005 Elsevier Inc. All rights reserved.

Research paper thumbnail of A study of 11,003 patients with hypertrophic pyloric stenosis and the association between surgeon and hospital volume and outcomes

Journal of Pediatric Surgery, 2005

Aim: The availability of large clinical databases allows for careful evaluation of surgical pract... more Aim: The availability of large clinical databases allows for careful evaluation of surgical practices, indicators of quality improvement, and cost. We used a large clinical database to compare the effect of surgeon and hospital volume for the care of children with hypertrophic pyloric stenosis (HPS). Methods: Patients with International Classification of Diseases-9 codes for HPS and pyloromyotomy were selected from the 1994 to 2000 National Inpatient Samples database. Multiple and logistic regression models were used to evaluate the risk-adjusted association between provider volume and outcomes. Results: Postoperative complications occurred in 2.71% of patients. Patients operated on by low-and intermediate-volume surgeons were more likely to have complications compared with those operated on by high-volume surgeons (95% confidence interval [CI], 1.25-3.78 and 95% CI, 1.25-2.69, respectively). Patients operated at low-volume hospitals were 1.6 times more likely to have complications compared with those operated at intermediate-or high-volume hospitals (95% CI, 1. 19-2.20). Procedures performed at high-volume hospitals were less expensive than those at intermediate-volume hospitals by a margin of 910(95910 (95% CI, 910(95443-$1377). Conclusions: These data represent the largest study to date on the epidemiology, complication rate, and cost for care for HPS. Patients treated by both high-volume surgeons and at high-volume hospitals have improved outcomes at less cost. D 2005 Elsevier Inc. All rights reserved.

Research paper thumbnail of Resection of hepatocellular adenoma in patients with glycogen storage disease type Ia

Journal of Hepatology, 2007

Background/Aims: Because dietary modifications have prolonged the life expectancy of patients wit... more Background/Aims: Because dietary modifications have prolonged the life expectancy of patients with glycogen storage disease type Ia (GSD Ia), the incidence of hepatocellular adenoma (HCA) to carcinoma (HCC) transformation is increasing. The objective of this retrospective study is to assess the safety and effectiveness of HCA resection in GSD Ia patients.

Research paper thumbnail of Combined Thymus and Parathyroid Allotransplantation in Complete DiGeorge Anomaly

Journal of Allergy and Clinical Immunology, 2008

Research paper thumbnail of Complete DiGeorge syndrome: Development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases

Journal of Allergy and Clinical Immunology, 2004

Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy ... more Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. The purpose of this study was to determine whether the patients had significant immunodeficiency. Research testing of peripheral blood included immunoscope evaluation of T-cell receptor beta variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). The patients were classified as having DiGeorge syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells (<50/mm(3)) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. Patients with DiGeorge syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor beta variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.

Research paper thumbnail of Sa.103. Parathyroid and Thymus Transplantation in DiGeorge Syndrome

Clinical Immunology, 2006

bulinemia. Results: CBC was normal. Absolute lymphocyte count was 3620/Al. Lymphocyte subpopulati... more bulinemia. Results: CBC was normal. Absolute lymphocyte count was 3620/Al. Lymphocyte subpopulation analysis showed mildly low levels of B-cells (110/Al) with normal CD8+ T-and NK-cells. [CD3+ cells: 3150 /Al, CD4+ cells: 1950 /Al]. IgG and IgA was very low (96 and 9 mg/dl; respectively). IgG1 and IgG2 mg/dl were also low (122 and 26 mg/dl). IgM, IgE, total protein, albumin and CH50 were all normal. Despite prior 3 conjugate pneumococcal vaccinations, antibody responses to 14 pneumococcal serotypes were low. Conclusion: This case may help understand the immune system involvement and the mechanism of hypogammaglobulinemia in this disease.

Research paper thumbnail of Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

BMC Physiology, 2009

Background: Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studie... more Background: Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure.

Research paper thumbnail of Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants

Blood, 2007

The purpose of this study was to characterize a large group of infants with complete DiGeorge ano... more The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events de-veloping after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants. (Blood. 2007; 109:4539-4547)

Research paper thumbnail of Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A

New England Journal …, 2005

Original Article from The New England Journal of Medicine — Prophylactic Thyroidectomy in Multipl... more Original Article from The New England Journal of Medicine — Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A.

Research paper thumbnail of Results of a Pilot Trial Comparing Prolonged Intravenous Antibiotics With Sequential Intravenous/Oral Antibiotics for Children With Perforated Appendicitis

Archives of Surgery, 2001

For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) an... more For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) antibiotics is equivalent to a short course of i.v. antibiotics followed by sequential conversion to oral (PO) antibiotics. Prospective, randomized, clinical trial. Multicenter study in tertiary children&#39;s hospitals. Children (aged 5-18 years) with perforated appendicitis found at laparotomy. Children were randomized after appendectomy either to a 10-day course of a combination of i.v. ampicillin, gentamicin sulfate, and clindamycin (n = 10); or to a short course of a combination of i.v. ampicillin, gentamicin, and clindamycin, followed by conversion to a combination of p.o. amoxicillin and clavulanate potassium plus metronidazole (n = 16). The primary outcome measure was clinical success, which was rated as complete, partial, or failure. Secondary outcome measures included return of oral intake, duration of fever, return of normal white blood cell count, and patient charges. Treatment equivalence was determined using confidence interval analysis. We found treatment equivalence between the i.v. and i.v./p.o. groups, with 6 (60%) complete and 4 (40%) partial successes for the 10 patients in the i.v. group and 15 (94%) complete and 1 (6%) partial successes for the 16 patients in the i.v./p.o. group (P&lt; or =.05). There was no difference in return of oral intake, duration of fever, or return of normal white blood cell count between the groups. Conversion to oral therapy results in savings of approximately $1500 per case. There is treatment equivalence between prolonged i.v. therapy and i.v. therapy followed by conversion to oral antibiotic therapy in children with perforated appendicitis.

Research paper thumbnail of Incidence and Reversibility of Organ Failure in the Course of Sterile or Infected Necrotizing Pancreatitis

Archives of Surgery, 2001

Multiple organ failure (MOF) and infected necrosis are both considered severe adverse events duri... more Multiple organ failure (MOF) and infected necrosis are both considered severe adverse events during the course of necrotizing pancreatitis. The incidence of MOF and its reversibility in patients with necrotizing pancreatitis are influenced by the presence or absence of infected necrosis. Case series. Intensive care, university teaching hospital. Forty-three patients with necrotizing pancreatitis and failure of at least 1 organ were prospectively included. Organ failure defined according to the Goris classification; MOF defined by the simultaneous occurrence of 3 organ failures and graded with an MOF score. Microbial status of necrosis was assessed by percutaneous or intraoperative sampling. Surgical drainage was performed in patients with infected necrosis, whereas sterile necrosis was managed conservatively. Infected necrosis occurred in 27 patients (63%). The mean (+/-SEM) number of organ failures was greater in cases of infection (3.6 +/- 1.1 vs 2.6 +/- 1.5; P =.02). Multiple organ failure occurred more frequently in cases of infected necrosis (23/27 vs 7/16; P&lt;.01) and was responsible for an increased mortality in this subgroup (33% vs 6%; P =.1). The severity of MOF graded by the MOF score was related to the bacteriologic status of necrosis. The higher mortality commonly attributed to MOF in patients with infected necrosis appears to be due to a higher frequency and an increased severity of MOF. Conservative management in patients with severe necrotizing pancreatitis and sterile necrosis complicated by MOF is supported by the high reversibility rate of MOF and the low mortality rate observed in this series.

Research paper thumbnail of Mediastinal tumors in children: Experience with 196 cases

Annals of Surgical Oncology, 1994

Background: Mediastinal masses are relatively common in infants and children. These lesions are o... more Background: Mediastinal masses are relatively common in infants and children. These lesions are often neoplastic in origin and have a high risk of malignancy.

Research paper thumbnail of Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A

The New England journal of medicine, Jan 15, 2005

Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine... more Medullary thyroid carcinoma is the most common cause of death in patients with multiple endocrine neoplasia (MEN) type 2A (MEN-2A) or type 2B or familial medullary thyroid carcinoma. We sought to determine whether total thyroidectomy in asymptomatic young members of kindreds with MEN-2A who had a mutated allele of the RET proto-oncogene could prevent or cure medullary thyroid carcinoma. A total of 50 patients 19 years of age or younger who were consecutively identified through a genetic screening program as carriers of a RET mutation characteristic of MEN-2A underwent total thyroidectomy. Five to 10 years after the surgery, each patient was evaluated by physical examination and by determination of plasma calcitonin levels after stimulation with provocative agents. In 44 of the 50 patients, basal and stimulated plasma calcitonin levels were at or below the limits of detection of the assay (proportion, 0.88; 95 percent confidence interval, 0.76 to 0.95). Two patients had basal and sti...

Research paper thumbnail of Fine Mapping of Wilms’ Tumors With 16q Loss of Heterozygosity Localizes the Putative Tumor Suppressor Gene to a Region of 6.7 Megabases

The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in... more The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in Wilms' tumors and to examine the expression of putative tumor suppressor.

Research paper thumbnail of Primary neonatal cricopharyngeal achalasia: A case report and Review of the literature

Journal of Pediatric Surgery, 1992

Primary cricopharyngeal achalasia is a rare cause of dysphagia in the pediatric population. In a ... more Primary cricopharyngeal achalasia is a rare cause of dysphagia in the pediatric population. In a review of the literature, only 11 well-documented cases were discovered. We report the case of a newborn with cricopharyngeal achalasia who was successfully treated with a myotomy of the upper esophageal sphincter. A review of the literature is presented and treatment options are discussed.

Research paper thumbnail of Routine insertion of a Silastic® spring-loaded silo for infants with gastroschisis

Journal of Pediatric Surgery, 2000

Background/Purpose: Gastroschisis traditionally is managed by emergency operating room closure (E... more Background/Purpose: Gastroschisis traditionally is managed by emergency operating room closure (EC), with a silo reserved for cases that cannot be closed primarily. The authors recently began using routine insertion of a SILASTIC (Dow Corning, Midland, MI) spring-loaded silo (SLS), followed by elective closure.

Research paper thumbnail of Transanal one-stage soave procedure for infants with Hirschsprung's disease

Journal of Pediatric Surgery, 1999

Research paper thumbnail of Experience with procedural sedation in a pediatric burn center

Journal of Pediatric Surgery, 1999

Research paper thumbnail of One-stage versus two-tage Soave pull-through for Hirschsprung's disease in the first year of life

Journal of Pediatric Surgery, 1996

Research paper thumbnail of Medullary thyroid carcinoma in children with multiple endocrine neoplasia types 2A and 2B

Journal of Pediatric Surgery, 1996

Research paper thumbnail of Decreased E-cadherin expression correlates with higher stage of Wilms' tumors

Journal of Pediatric Surgery, 2005

Purpose: The aim of this study was to examine the association between E-cadherin expression and m... more Purpose: The aim of this study was to examine the association between E-cadherin expression and markers of Wilms' tumor aggression, including metastasis and recurrence. Methods: Forty Wilms' tumor samples from the National Wilms' Tumor Study Group underwent immunohistochemical staining for E-cadherin. Tumor stage at diagnosis, recurrence, and loss of heterozygosity at 16q status was known for each of the tumor samples. E-Cadherin cell staining was defined as high (N33%) or low (b33%), and values were assigned by a pathologist blinded to the tumor characteristics. Five stage IV tumors were ineligible for assay because of lack of a tubular component. To identify a mechanism of downregulation, we screened tumor DNA for genetic mutations in exons 1-16 using a combination of WAVE and sequence analysis. To assess the functional significance of the identified mutations, the authors compared amino acid homology across multiple species. Finally, they performed reverse transcriptase-polymerase chain reaction for those tumors with intronic single nucleotide polymorphisms (SNPs) to evaluate for mRNA splice variants. Results: Wilms' tumors presenting with metastatic (stage IV) disease demonstrated decreased levels of Ecadherin expression compared with localized tumors (stage I) (Fisher's Exact test, P b .01). In a search for the mechanism of the downregulation of E-cadherin, we identified 5 different mutations in 7 high stage tumors (7/15) and 1 mutation in a low stage tumor (1/20). The mutations occurred in amino acids that were conserved across multiple species. Additionally, 11 of 15 high stage tumors contained an intronic SNP located within 6 bp of the 5V intronic splice junction immediately downstream of exon 1. However, examination of 5 of these tumors using reverse transcriptase-polymerase chain reaction showed that this intronic SNP does not appear to disrupt the assembly of full-length E-cadherin transcripts. Lastly, no correlation was identified between E-cadherin expression and recurrence of disease. Conclusions: In this study, the authors have found an association between decreased E-cadherin expression and metastatic Wilms' tumor. Mutations identified may help identify a mechanism for downregulation. The functional significance of these mutations is supported by the conserved nature of the 0022-3468/05/4002-0010$30.00/0 D 2005 Elsevier Inc. All rights reserved.

Research paper thumbnail of A study of 11,003 patients with hypertrophic pyloric stenosis and the association between surgeon and hospital volume and outcomes

Journal of Pediatric Surgery, 2005

Aim: The availability of large clinical databases allows for careful evaluation of surgical pract... more Aim: The availability of large clinical databases allows for careful evaluation of surgical practices, indicators of quality improvement, and cost. We used a large clinical database to compare the effect of surgeon and hospital volume for the care of children with hypertrophic pyloric stenosis (HPS). Methods: Patients with International Classification of Diseases-9 codes for HPS and pyloromyotomy were selected from the 1994 to 2000 National Inpatient Samples database. Multiple and logistic regression models were used to evaluate the risk-adjusted association between provider volume and outcomes. Results: Postoperative complications occurred in 2.71% of patients. Patients operated on by low-and intermediate-volume surgeons were more likely to have complications compared with those operated on by high-volume surgeons (95% confidence interval [CI], 1.25-3.78 and 95% CI, 1.25-2.69, respectively). Patients operated at low-volume hospitals were 1.6 times more likely to have complications compared with those operated at intermediate-or high-volume hospitals (95% CI, 1. 19-2.20). Procedures performed at high-volume hospitals were less expensive than those at intermediate-volume hospitals by a margin of 910(95910 (95% CI, 910(95443-$1377). Conclusions: These data represent the largest study to date on the epidemiology, complication rate, and cost for care for HPS. Patients treated by both high-volume surgeons and at high-volume hospitals have improved outcomes at less cost. D 2005 Elsevier Inc. All rights reserved.

Research paper thumbnail of Resection of hepatocellular adenoma in patients with glycogen storage disease type Ia

Journal of Hepatology, 2007

Background/Aims: Because dietary modifications have prolonged the life expectancy of patients wit... more Background/Aims: Because dietary modifications have prolonged the life expectancy of patients with glycogen storage disease type Ia (GSD Ia), the incidence of hepatocellular adenoma (HCA) to carcinoma (HCC) transformation is increasing. The objective of this retrospective study is to assess the safety and effectiveness of HCA resection in GSD Ia patients.

Research paper thumbnail of Combined Thymus and Parathyroid Allotransplantation in Complete DiGeorge Anomaly

Journal of Allergy and Clinical Immunology, 2008

Research paper thumbnail of Complete DiGeorge syndrome: Development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases

Journal of Allergy and Clinical Immunology, 2004

Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy ... more Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. The purpose of this study was to determine whether the patients had significant immunodeficiency. Research testing of peripheral blood included immunoscope evaluation of T-cell receptor beta variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). The patients were classified as having DiGeorge syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50/mm(3)) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. Patients with DiGeorge syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor beta variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.

Research paper thumbnail of Sa.103. Parathyroid and Thymus Transplantation in DiGeorge Syndrome

Clinical Immunology, 2006

bulinemia. Results: CBC was normal. Absolute lymphocyte count was 3620/Al. Lymphocyte subpopulati... more bulinemia. Results: CBC was normal. Absolute lymphocyte count was 3620/Al. Lymphocyte subpopulation analysis showed mildly low levels of B-cells (110/Al) with normal CD8+ T-and NK-cells. [CD3+ cells: 3150 /Al, CD4+ cells: 1950 /Al]. IgG and IgA was very low (96 and 9 mg/dl; respectively). IgG1 and IgG2 mg/dl were also low (122 and 26 mg/dl). IgM, IgE, total protein, albumin and CH50 were all normal. Despite prior 3 conjugate pneumococcal vaccinations, antibody responses to 14 pneumococcal serotypes were low. Conclusion: This case may help understand the immune system involvement and the mechanism of hypogammaglobulinemia in this disease.

Research paper thumbnail of Transcriptional profile of isoproterenol-induced cardiomyopathy and comparison to exercise-induced cardiac hypertrophy and human cardiac failure

BMC Physiology, 2009

Background: Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studie... more Background: Isoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response of the heart in this model to other animal models of heart failure, as well as to the transcriptional response of human hearts suffering heart failure.

Research paper thumbnail of Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants

Blood, 2007

The purpose of this study was to characterize a large group of infants with complete DiGeorge ano... more The purpose of this study was to characterize a large group of infants with complete DiGeorge anomaly and to evaluate the ability of thymus transplantation to reconstitute immune function in these infants. DiGeorge anomaly is characterized by varying defects of the heart, thymus, and parathyroid glands. Complete DiGeorge anomaly refers to the subgroup that is athymic (< 1%). The characteristics of 54 subjects at presentation and results from 44 consecutive thymus transplantations are reported. Remarkably, only 52% had 22q11 hemizygosity and only 57% had congenital heart disease requiring surgery. Thirty-one percent developed an atypical phenotype with rash and lymphadenopathy. To date, 33 of 44 subjects who received a transplant survive (75%) with post-transplantation follow-up as long as 13 years. All deaths occurred within 12 months of transplantation. All 25 subjects who were tested 1 year after transplantation had developed polyclonal T-cell repertoires and proliferative responses to mitogens. Adverse events de-veloping after transplantation included hypothyroidism in 5 subjects and enteritis in 1 subject. In summary, diagnosis of complete DiGeorge anomaly is challenging because of the variability of presentation. Thymus transplantation was well tolerated and resulted in stable immunoreconstitution in these infants. (Blood. 2007; 109:4539-4547)

Research paper thumbnail of Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A

New England Journal …, 2005

Original Article from The New England Journal of Medicine — Prophylactic Thyroidectomy in Multipl... more Original Article from The New England Journal of Medicine — Prophylactic Thyroidectomy in Multiple Endocrine Neoplasia Type 2A.

Research paper thumbnail of Results of a Pilot Trial Comparing Prolonged Intravenous Antibiotics With Sequential Intravenous/Oral Antibiotics for Children With Perforated Appendicitis

Archives of Surgery, 2001

For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) an... more For children with perforated appendicitis, the use of a prolonged course of intravenous (i.v.) antibiotics is equivalent to a short course of i.v. antibiotics followed by sequential conversion to oral (PO) antibiotics. Prospective, randomized, clinical trial. Multicenter study in tertiary children&#39;s hospitals. Children (aged 5-18 years) with perforated appendicitis found at laparotomy. Children were randomized after appendectomy either to a 10-day course of a combination of i.v. ampicillin, gentamicin sulfate, and clindamycin (n = 10); or to a short course of a combination of i.v. ampicillin, gentamicin, and clindamycin, followed by conversion to a combination of p.o. amoxicillin and clavulanate potassium plus metronidazole (n = 16). The primary outcome measure was clinical success, which was rated as complete, partial, or failure. Secondary outcome measures included return of oral intake, duration of fever, return of normal white blood cell count, and patient charges. Treatment equivalence was determined using confidence interval analysis. We found treatment equivalence between the i.v. and i.v./p.o. groups, with 6 (60%) complete and 4 (40%) partial successes for the 10 patients in the i.v. group and 15 (94%) complete and 1 (6%) partial successes for the 16 patients in the i.v./p.o. group (P&lt; or =.05). There was no difference in return of oral intake, duration of fever, or return of normal white blood cell count between the groups. Conversion to oral therapy results in savings of approximately $1500 per case. There is treatment equivalence between prolonged i.v. therapy and i.v. therapy followed by conversion to oral antibiotic therapy in children with perforated appendicitis.

Research paper thumbnail of Incidence and Reversibility of Organ Failure in the Course of Sterile or Infected Necrotizing Pancreatitis

Archives of Surgery, 2001

Multiple organ failure (MOF) and infected necrosis are both considered severe adverse events duri... more Multiple organ failure (MOF) and infected necrosis are both considered severe adverse events during the course of necrotizing pancreatitis. The incidence of MOF and its reversibility in patients with necrotizing pancreatitis are influenced by the presence or absence of infected necrosis. Case series. Intensive care, university teaching hospital. Forty-three patients with necrotizing pancreatitis and failure of at least 1 organ were prospectively included. Organ failure defined according to the Goris classification; MOF defined by the simultaneous occurrence of 3 organ failures and graded with an MOF score. Microbial status of necrosis was assessed by percutaneous or intraoperative sampling. Surgical drainage was performed in patients with infected necrosis, whereas sterile necrosis was managed conservatively. Infected necrosis occurred in 27 patients (63%). The mean (+/-SEM) number of organ failures was greater in cases of infection (3.6 +/- 1.1 vs 2.6 +/- 1.5; P =.02). Multiple organ failure occurred more frequently in cases of infected necrosis (23/27 vs 7/16; P&lt;.01) and was responsible for an increased mortality in this subgroup (33% vs 6%; P =.1). The severity of MOF graded by the MOF score was related to the bacteriologic status of necrosis. The higher mortality commonly attributed to MOF in patients with infected necrosis appears to be due to a higher frequency and an increased severity of MOF. Conservative management in patients with severe necrotizing pancreatitis and sterile necrosis complicated by MOF is supported by the high reversibility rate of MOF and the low mortality rate observed in this series.

Research paper thumbnail of Mediastinal tumors in children: Experience with 196 cases

Annals of Surgical Oncology, 1994

Background: Mediastinal masses are relatively common in infants and children. These lesions are o... more Background: Mediastinal masses are relatively common in infants and children. These lesions are often neoplastic in origin and have a high risk of malignancy.