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M H Collins

Publications and source records attributed to M H Collins.

At least 37 records · Page 2Linked to original sources

Matrix metalloproteinase-9 (MMP-9) expression in childhood osseous osteosarcoma.

BACKGROUND: Over 80% of patients with osteosarcoma treated with excision alone develop pulmonary metastases, suggesting that the majority of patients with this disease harbor "micrometastases" at diagnosis. There are no histologic or molecular variables which can predict the presence or absence of micrometastasis. Matrix metalloproteinases (MMPs) are a class of matrix- and basement membrane-degrading enzymes whose expression is associated with tumor cell invasive and metastatic behavior. One of these enzymes, MMP-9 or gelatinase B, is expressed in developing and remodeling bone and in osteosarcoma cell lines. We speculated that MMP-9 expression might be associated with the micrometastatic behavior of osteosarcoma. PROCEDURE: We examined a series of pediatric primary osseous osteosarcomas and metastases for the expression of MMP-9, using a monoclonal antibody. RESULTS: We found intense MMP-9 immunostaining in most tumor cells in all samples of pretreatment osteosarcomas. In all postchemotherapy resection samples, tumor cells stained similarly, but there were fewer positively staining cells overall. In 4 of 5 metastastic lesions examined, intense immunostaining for MMP-9 was detected. CONCLUSIONS: These results suggest that MMP-9 expression is common in osteosarcoma, and that further study of the role of MMP-9 in pediatric osteosarcoma behavior is warranted.

Bone Neoplasms↗

Increased pulmonary blood flow produces endothelial cell dysfunction in neonatal swine.

BACKGROUND: The mechanisms by which increased pulmonary blood flow results in pulmonary hypertension have not been determined. METHODS: To determine if increased pulmonary blood flow produces endothelial dysfunction that precedes vascular remodeling and smooth muscle proliferation, neonatal swine (n = 12) (age, 6.1+/-0.5 days) underwent ligation of the left pulmonary artery (LPA) to increase blood flow to the right lung. At 12 weeks of age, endothelium-dependent vasodilatation was assessed by acetylcholine infusion and endothelium-independent vasodilatation by inhaled nitric oxide (NO) in the LPA group and age-matched controls (CON) (n = 11). RESULTS: Mean pulmonary artery pressure was 24.1+/-3.0 mm Hg in the LPA group and 20.8+/-1.9 mm Hg in the CON group (p < 0.1). Pulmonary vascular resistance was 13.2+/-2.2 Wood units in the LPA group and 5.8+/-0.8 Wood units in the CON group (p = 0.001). Acute occlusion of the left pulmonary artery in the CON group increased pulmonary vascular resistance to 6.9+/-3.9 Wood units (p = 0.04). Administration of acetylcholine in the CON group after preconstriction with the thromboxane A2 analogue U46619 resulted in a 30.6%+/-5.4% decrease in pulmonary vascular resistance. In the LPA group, acetylcholine produced paradoxical vasoconstriction and a 15.4%+/-4.1% increase in pulmonary vascular resistance (p < 0.001 versus CON) indicating loss of endothelium-dependent vasodilatation. Nitric oxide decreased pulmonary vascular resistance by 41.9%+/-3.3% in the CON group and 30.8%+/-2.7% in the LPA group (p = 0.04 versus CON), indicating preserved endothelium-independent vasodilatation in both groups. Morphometric analysis was performed in 4 animals from each group. Medial wall thickness as percent of external diameter of small arteries (<100 microm) was the same in both groups (6.4%+/-0.4% in the LPA group versus 6.6% +/-0.4% in the CON animals; p > 0.1). CONCLUSIONS: Increased pulmonary blood flow in immature animals produces endothelial cell dysfunction with loss of endothelium-dependent vasodilatation before the onset of pulmonary vascular remodeling. Subsequent smooth muscle proliferation may be mediated by endothelium-derived factors.

Animals↗

Adenovirus infection in the lung results in graft failure after lung transplantation.

OBJECTIVES: Our goal was to examine the relationship between viral pneumonia and outcome in pediatric patients undergoing lung or heart-lung transplantation. METHODS: Prospective surveillance for common respiratory viruses of childhood was performed in all patients undergoing lung or heart-lung transplantation. Specimens were examined for the presence of replicating virus (by culture), viral genome (by polymerase chain reaction), and viral antigen (by immunofluorescence and immunohistochemical staining). The relationship between viral infection and outcome was examined. RESULTS: Sixteen patients underwent 19 transplants during the study period, with follow-up of 1 to 26 months. Virus was identified in the transplanted lung in 29 instances; adenovirus was identified most commonly (8/16 patients) and had the greatest impact on outcome. In 2 patients with early, fulminant infection, adenovirus was also identified in the donor. Adenovirus was significantly associated with respiratory failure leading to death or graft loss and with the histologic diagnosis of obliterative bronchiolitis (P < or = .002 in each case). CONCLUSIONS: Adenovirus infection in the transplanted lung is significantly associated with graft failure, histologic obliterative bronchiolitis, and death. Health care personnel and families must be vigilant in preventing exposure of transplant recipients to this virus. Availability of a rapid and reliable test for adenovirus in donors and recipients would have an impact on management and could improve outcome for pediatric lung recipients.

Adenovirus Infections, Human↗

Vertical lines in distal esophageal mucosa (VLEM): a true endoscopic manifestation of esophagitis in children?

BACKGROUND: We observed an endoscopic abnormally in a group of children with histological esophagitis. We termed this finding "vertical lines in esophageal mucosa" (VLEM). We examined the relationship between the presence of VLEM and significant histologic changes in esophageal mucosal biopsies. METHODS: Between January 1, 1992, and August 31, 1994, the senior author (JFF) performed 255 esophageal biopsies. The procedure reports, available endoscopic photographs, and histology reports were reviewed to establish the endoscopic and histologic appearance of the esophageal mucosa. Intraepithelial cells were counted in a blind review of 42 randomly selected biopsies. RESULTS: The esophageal mucosa had a normal appearance on 160 endoscopic studies (Group 1) and VLEM were the only mucosal abnormalities in 41 endoscopies (Group 2). Histology was normal in 92 of 160 biopsies (57.5%) from Group 1, and 1 of 41 biopsies (2.4%) from Group 2. Most patients in Group 2 had eosinophilic esophagitis (34 of 41, 83%, specificity 0.85, sensitivity 0.5, p > 0.001) which was of moderate to severe intensity (31 of 34, 91.2%, specificity 0.88, sensitivity 0.73, p < 0.001). CONCLUSIONS: Histology usually demonstrated moderate to severe inflammation when VLEM were present. VLEM may be a highly specific endoscopic feature of esophagitis in children.

Adolescent↗

Histology of rat small bowel transplants: cyclosporine A ameliorates features of rejection including apoptosis and ganglion cell reduction.

The histology of rat small bowel transplants (SBT) was examined in orthotopic isografts and allografts with and without immunosuppression. Lewis to Lewis isografts were examined 7 days after transplant, and LBNF1 to Lewis allografts were examined 2, 4, 7, and 10 days after transplant; one group received cyclosporine A (CyA), and their allografts were examined 7 days after transplant. Compared with similar intestinal segments from unoperated animals, allografts at 4, 7, and 10 days after surgery showed progressive inflammation, cryptitis, villous atrophy, and transmural necrosis. In contrast, SBT in animals given CyA did not significantly differ from normal in any histological parameter. The number of apoptotic structures per 100 crypts in SBT at day 4 (58.25 +/- 32.98) and day 7 (31.86 +/- 27.63) after transplant were significantly increased compared with unoperated bowel (5.23 +/- 13.41) (P < .05); the number in CyA-treated allografts (11.57 +/- 29.56) did not differ significantly from normal. The number of intermyenteric ganglion cells was significantly reduced (P< .05) in allografts 7 and 10 days after transplant (mean and [range] = 31 [18 to 38] and 25 [23 to 27], respectively) but the number in allografts from CyA-treated animals (47 [24 to 72]) did not differ from unoperated bowels (52 [30 to 88]). We conclude that CyA treatment significantly reduces the histological abnormalities associated with transplant rejection including adverse effects on epithelial and ganglion cells; therefore, the absorptive capacity and motility characteristics of the CyA-treated SBT should be preserved compared with untreated allograft controls.

Animals↗

Empirically validated family interventions for pediatric psychology: sickle cell disease as an exemplar.

Prompted by the growth of managed care and the American Psychological Association's recent guidelines for treatment efficacy studies, we have struggled with the challenges associated with devising and implementing manualized family intervention programs for pediatric patients. This manuscript outlines the strengths and challenges of controlled manual-based family interventions for medically ill children, using pediatric sickle cell disease (SCD) as an example. A culturally and developmentally sensitive intervention program, designed for the researcher's subject population (African American, low SES, inner city) is discussed. Possible solutions to the challenges of conducting family-oriented intervention efficacy studies with pediatric populations are presented.

Adolescent↗

Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 25 tumors.

Lipoblastoma/lipoblastomatosis is an uncommon benign adipose tissue tumor of children. Since 1958, 25 of these tumors from 24 patients have been reviewed in the Department of Pathology at The Children's Hospital of Philadelphia. Tumors were resected from 19 boys (79%) and five girls, and 20 patients (84%) were < or =5 years of age at diagnosis. Twenty-three tumors presented as painless superficial soft-tissue masses; one tumor was retroperitoneal and was discovered because of vomiting; one hand tumor was present at birth. Tumors occurred in an extremity (n = 11 patients), the head and neck (n = 5), groin (n = 2), axilla (n = 2), back (n = 1), chest (n = 1), flank (n = 1), labia (n = 1), and retroperitoneum (n = 1). Thirteen tumors occurred on the left side, and five occurred on the right. Lesions measured 1.0-21.0 cm in greatest dimension; 15 of 25 (60%) measured < or =5.0 cm. The largest (retroperitoneal) tumor weighed 450 g. Eleven tumors were discrete lipoblastoma, and 14 had irregular margins (lipoblastomatosis). Microscopically, the tumors displayed adipocytes in different stages of maturation; lobules bordered by septae that were cellular in 11 cases; prominent blood vessels in 19 cases; and myxoid foci in 13 cases. Chart review of 22 patients showed that one tumor recurred 4 years after resection; one tumor recurred after 7 years as fibrolipoma; and one incompletely resected tumor enlarged and at second resection was lipoma. There were no metastases. Three patients also had hemangioma. Juvenile aponeurotic fibroma occurred in one patient near the site of resection of a lipoblastoma 4 years earlier. We conclude that lipoblastoma/lipoblastomatosis behaves benignly, occurs in both superficial and deep sites, occasionally attains large size, may mature, can recur, and may be associated with other benign soft-tissue lesions. Complete surgical excision is the treatment of choice.

Adolescent↗

Alpha-1-proteinase inhibitor prolongs small intestinal graft preservation and survival.

Organ preservation solutions currently used for cold storage of human donor organs are less effective in preserving small intestinal grafts than other organ grafts. The maximal safe period of cold preservation for human small intestinal graft is only about 6 hours. The pathology of preserved and reperfused small intestinal grafts is characterized by mucosal autolysis and sloughing. The authors speculated that the preservation/reperfusion injury results from a proteinase/proteinase-inhibitor imbalance in the graft that favors tissue degradation. This study evaluates whether the addition of an alpha-1-proteinase inhibitor (alpha-1-PI) to the preservation solution can improve graft survival after small bowel transplantation. Forty small intestinal grafts (20 cm long) were harvested from Lewis rats. The grafts were divided randomly into three groups and were preserved in one of the following solutions: normal saline (NS) (n = 10), alpha-1-PI (25 mg/mL; n = 20), or proteinase-free bovine serum albumin (BSA) (25 mg/mL; n = 10). After 12-hour cold storage in the respective solutions, the grafts were transplanted orthotopically into syngeneic recipients. Full-thickness graft biopsies were performed before and 1 hour after revascularization. The effectiveness of preservation was judged by graft histopathology and recipient survival. Histological studies showed that there was less mucosal autolysis and sloughing of the grafts in the alpha-1-Pl group than in the other two groups. All recipients in the NS and BSA groups died of graft failure within 7 days (NS: median, 4 days; range, 2 to 5 days; BSA: median, 6 days; range, 4 to 7). However, 60% (12 of 20) of the recipients in the alpha-1-PI group survived more than 90 days (median, > 90 days; range, 4 to > 90 days; P < .005 v NS or BSA groups, log-rank method). These data suggest that the inclusion of alpha-1-PI in the preservation solution may enhance graft integrity and improve the surgical outcome after small bowel transplantation.

Animals↗

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.

Acetylcholinesterase↗

Hepatic granulomas in children. A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma.

In a 15-year period at the Riley Hospital for Children, granulomas were found in 23 (4%) of a total of 521 liver biopsies. An etiology was identified in 87%: Histoplasma was diagnosed in 15 cases (65%) by polymerase chain reaction (PCR) on paraffin-embedded tissue, serology, and special stains; sarcoidosis was diagnosed in four cases; and schistosomiasis was diagnosed in one case. Serial liver biopsies were available from five patients; granulomas occurred in only one biopsy of the series from each patient. Extrahepatic tissue from six patients contained granulomas, and an etiology for the liver granulomas was identified in all six patients (four histoplasmosis, two sarcoidosis). The extrahepatic tissue from two patients with Histoplasma was diagnostic. We made the following conclusions: that PCR is applicable to archival material and greatly increases the yield of specific infectious diagnoses of liver granulomas compared with conventional diagnostic methods (65 versus 22%); that the infections causing liver granulomas are those that are endemic in a community (e.g., Histoplasma in Indiana); that Histoplasma can coexist with a wide variety of systemic and primary liver diseases; that the likelihood of identifying a cause of liver granulomas is increased if there are extrahepatic granulomas; and that hepatic granulomas may have a limited life span. Treatment of liver granulomas should be determined by the clinical setting and directed at the underlying cause.

Adolescent↗

Postnatal growth of lung parenchyma in the piglet: morphometry correlated with mechanics.

BACKGROUND: A previous study of piglet lung growth (Mansell et. al. 1989. J. Appl. Physiol., 67:1422-1427) showed transient stiffness to changes in shape and volume immediately after birth. Later, elastic recoil was found to increase as the lung grew in weight and volume. The present study uses morphometry to test possible structural correlates of these two mechanical changes. METHODS: Piglet lungs were fixed near full inflation via the airways during the immediate newborn period (6-12 hours, n = 3), at 3-5 days (n = 6), 25-30 days (n = 5), and 80-85 days (n = 3). Morphometry comprised arithmetic and harmonic mean thicknesses of alveolar septae and average mean surface curvature. Measurements of curvature and airspace volume were combined to differentiate alveolar expansion from septal proliferation as mechanisms for volumetric growth. RESULTS: The unique mechanical behavior of the newborn lungs was associated with relatively thick alveolar septae. Marked thinning of the septae and resolution of the stiffness to shape and volume change had occurred by 3-5 days. An increase in elastic recoil during the first postnatal month was found to be associated with simple airspace expansion. The second and third months were characterized by septal proliferation and increase in arithmetic mean septal thickness but elastic recoil did not increase further. Harmonic mean septal thickness and airspace volume per gram of lung tissue did not change over the course of the study. CONCLUSIONS: 1) A relative stiffness to shape and volume change in freshly newborn piglet lungs is associated with relatively thick alveolar septal walls; 2) postnatal development of piglet lung parenchyma involves septal lengthening and thinning followed by septal proliferation; 3) the initial phase of septal lengthening, rather than the later phase of septal proliferation, is associated with increase in parenchymal recoil.

Animals↗

Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Primary hepatic B-cell lymphoma in a child.

Lymphoma arising in the liver is uncommon in adults and rare in children. A 12-year-old boy with hepatomegaly and jaundice had a calcified intrahepatic large-cell lymphoma of B-cell origin that expressed bcl-2 protein and had near-tetraploid chromosome number with a t(8;14) (q24;q32) and a homogeneously staining region (HSR). This tumor, only the fourth example of primary hepatic lymphoma in a child, has the rare finding of an HSR before treatment and is the first human lymphoma with t(8;14) that expresses bcl-2 protein. In addition, the demonstration of extensive calcification in the tumor by computed tomography scan is highly unusual for lymphoma. Lymphoma must be considered in the differential diagnosis of primary liver tumors in children and adults, especially if the serum alpha-fetoprotein level is normal.

Child↗