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Biomedical subjects

D A Hill

Publications and source records attributed to D A Hill.

At least 19 recordsLinked to original sources
PubMed2001

Neonatal alveolar rhabdomyosarcoma with skin and brain metastases.

BACKGROUND: Approximately 5-10% of patients with rhabdomyosarcomas (RMS) are diagnosed during the first year of life, and their clinical characteristics have been well documented. However, because RMS rarely occurs during the neonatal period, little is known about neonatal RMS. METHODS: Four patients with neonatal RMS were treated at St. Jude Children's Research Hospital between 1962 and 1999. The authors report the results of a review of these patients and of cases described in the literature. Clinical, radiologic, and pathologic features of these patients and their outcomes were evaluated. RESULTS: One patient with embryonal RMS was treated successfully with a combination of systemic chemotherapy and local control measures. The other three patients had alveolar RMS. Two of them had multiple skin and subcutaneous metastatic nodules at the time of diagnosis and developed brain metastases early in their course. In one of these patients, the PAX3-FKHR fusion transcript was detected. Three other similar cases of neonatal alveolar RMS with metastases to the skin and brain have been reported in the literature. CONCLUSIONS: A distinct syndrome of neonatal RMS is described. This syndrome is characterized by alveolar histology, multiple skin and subcutaneous metastases, and fatal outcome as the result of early brain metastasis.

Brain Neoplasms↗
PubMed2001

Secondary ovarian neoplasms in children: imaging features with histopathologic correlation.

BACKGROUND: Although the pathologic features and imaging appearance of childhood primary ovarian neoplasms have been well described, little information is available about the malignancies that may secondarily involve the ovary. OBJECTIVE: To determine the relationship between the imaging features and the histopathology of secondary ovarian neoplasms in children treated at our institution. MATERIALS AND METHODS: We searched our institutional database for codes indicating metastatic ovarian disease. Of the 35 patients with such codes, 18 had pathologically proven secondary ovarian disease. From their medical records we recorded demographic data, presenting symptoms, and evidence of endocrine dysfunction. We reviewed the pre-oophorectomy imaging and the subsequent pathologic specimens. RESULTS: One-third of the patients had bilateral pelvic masses; another third had large masses indistinguishable from the ovaries. Twelve (67%) had either ascites, peritoneal implants, matted bowel, adenopathy, pleural effusions, or some combination of these. Five (28%) had other metastatic disease. Primary tumors included colon adenocarcinoma (9), Burkitt's lymphoma (3), alveolar rhabdomyosarcoma (3), Wilms' tumor (1), neuroblastoma (1), and retinoblastoma (1). CONCLUSION: Although rare, secondary ovarian tumors should be considered in the differential diagnosis of children with ovarian masses. Bilateral ovarian masses or large masses indistinguishable from the ovaries, particularly in the presence of other metastatic foci, may help distinguish primary from secondary ovarian malignancies.

Adenocarcinoma↗
PubMed2001

Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumor (IMT) is a rare, but distinctive mesenchymal neoplasm composed of fascicles of bland myofibroblasts admixed with a prominent inflammatory component. Genetic studies of IMTs have demonstrated chromosomal abnormalities of 2p23 and rearrangement of the anaplastic lymphoma kinase (ALK) gene locus. In a subset of IMTs, the ALK C-terminal kinase domain is fused with a tropomyosin N-terminal coiled-coil domain. In the current study, fusion of ALK with the clathrin heavy chain (CTLC) gene localized to 17q23 was detected in two cases of IMT. One of these cases exhibited a 2;17 translocation in addition to other karyotypic anomalies [46,XX,t(2;17)(p23;q23),add(16)(q24)].

Adult↗
PubMed2001

Prevalence of antibodies to hepatitis C virus, HIV and human T-cell leukaemia/lymphoma viruses in injecting drug users in Tayside, Scotland, 1993-7.

The prevalence of blood-borne viruses in injecting drug users (IDUs) in Tayside, Scotland was determined by testing serum samples from IDUs who underwent attributable HIV antibody testing during 1993-7. The prevalence of antibodies to HIV was 29/802, (3.6%); to hepatitis C virus (HCV) 451/691, (65.3%); and to human T-cell leukaemia/lymphoma viruses type 1 and 2 (HTLV) 0/679, (0.0%). The prevalence of HIV and HCV antibodies were higher in subjects over the age of 25 (P = 0.03 and P = 0.001, respectively). During 1993-7 the prevalence of HCV fell only in younger female IDUs (P < 0.01). HIV prevalence has declined dramatically since 1985, when a rate of 40% was recorded in similar populations. Harm reduction measures have failed to control HCV the spread of infection among IDUs in Tayside, as indicated by the high proportion of antibody positive IDUs, particularly males under the age of 25. Future studies should address the nature and effective reduction of continuing risk taking among IDUs in Tayside.

Adolescent↗
PubMed2001

A role for fluorescence in situ hybridization detection of chromosome 22q dosage in distinguishing atypical teratoid/rhabdoid tumors from medulloblastoma/central primitive neuroectodermal tumors.

It has been postulated that infants with medulloblastomas/central primitive neuroectodermal tumors (MB/PNET) may fare worse than older patients because some of them harbor unrecognized atypical teratoid/rhabdoid tumors (AT/RT), rare intracranial neoplasms that are typically unresponsive to therapy and rapidly fatal. Although small primitive cells are common to both entities, chromosome 22q11.2 deletions are common only in AT/RTs. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded biopsy tissue with commercially available probes to 22q11.2, the region associated with RTs, we studied 8 cases of AT/RT, 12 cases of MB/PNET, and 4 cases of primitive central nervous system (CNS) neoplasms, which were difficult to classify. 22q Deletions were identified in 6 of 8 (75%) conventional AT/RTs and 0 of 12 (0%) children with classic MB/PNET. Of the 4 originally "difficult to classify" cases, 3 had deletions of 22q. In light of the FISH results, review of the morphology and immunophenotype resulted in 3 tumors being reclassified as AT/RTs and 1 as a large cell MB. These 4 cases highlight the potential diagnostic use of FISH for selected cases of primitive CNS malignancies in children and substantiate the notion that misdiagnosed AT/RTs may, in part account for the worse prognosis associated with "MB/PNET" in children younger than 2 years of age.

Adolescent↗
PubMed2001

Molecular genetic aspects of solid tumors in childhood.

Advances in molecular genetic research in the past 2 decades have led to an increased understanding of the genetic events in the pathogenesis and progression of human malignancies, including those of childhood. A number of pediatric malignancies have served as models for the molecular genetic approach to patients with cancer. These have highlighted the utility of molecular analysis for a variety of purposes including diagnosis, risk stratification and treatment planning, understanding of syndromes associated with cancer and genetic screening, genetic counseling and prophylactic treatment including surgery. It is likely that there soon will be individualized treatment regimens based on the molecular biologic profile of a patient's tumor. In addition, molecular profiling will lead to new drug development designed to induce differentiation of tumor cells, block dysregulated growth pathways, or reactivate silenced apoptotic pathways. This review discusses the molecular genetic aspects of some of the more common pediatric tumors as well as tumors whose pathogenetic mechanisms are particularly instructive.

Child↗
PubMed2001

Metastatic osteosarcoma to the liver after treatment for synovial sarcoma: a case report.

Metastatic osteosarcoma most commonly affects the lungs and other bones. Hepatic metastasis at the time of diagnosis is extremely rare. A 14-year-old boy with synovial sarcoma of the left popliteal fossa was treated with surgical resection, radiotherapy for microscopic residual disease, and 1 year of chemotherapy (vincristine, cyclophosphamide, dactinomycin, and doxorubicin). Approximately 10 years after the initial diagnosis, a secondary osteosarcoma developed in the left proximal tibia. Computed tomography at presentation showed bilateral pulmonary metastases and large ossified nodules in the liver that demonstrated abnormal avidity on 99mTc MDP bone scan indicating hepatic metastasis. Despite chemotherapy (cisplatin, ifosfamide, high-dose methotrexate, and dacarbazine), the patient died of progressive disease 4 months after the diagnosis of the second cancer. Hepatic metastasis was found at the time of diagnosis of a secondary osteosarcoma and manifested as ossified nodules. The risk of radiation-induced osteosarcoma should always be considered in decisions about treatment for soft-tissue sarcoma.

Adolescent↗
PubMed2001

Patient-controlled analgesia for labour using remifentanil: a feasibility study.

We have investigated the efficacy and safety of remifentanil in a patient-controlled analgesia device for labour in 21 women. Remifentanil was available in increasing doses (bolus doses 0.25-1.0 microg x kg(-1)) with and without a background infusion (0.025-0.05 microg x kg(-1) x min(-1)). A lockout time of 2 min was used. Thirteen out of 21 (62%) women chose to continue using remifentanil up to and during delivery. Nineteen out of 21 (90%) achieved a reduction in pain score from baseline. Using a VAS of 0-10 cm the median maximum reduction in pain score was 3 cm (range 0-8 cm). There was a significant reduction (P<0.05) from baseline pain scores (median= 8 cm) to scores at bolus doses in the range 0.25-0.5 microg x kg(-1) (median=5 cm). There were no significant reductions in the fetal heart rate. Apgar scores and cord blood gas analyses remained within normal limits. We conclude that a remifentanil patient-controlled analgesia system (bolus doses 0.25-0.5 microg x kg(-1), without a background infusion) may safely provide worthwhile, although incomplete, analgesia for labour.

Adult↗
PubMed2001

Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study.

Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal neoplasm with a variable histologic appearance that may mimic other spindle cell processes, particularly nodular fasciitis, desmoid tumor, and in intra-abdominal locations, gastrointestinal stromal tumor. Recently, gene fusions involving ALK at chromosome 2p23 have been described in IMTs. The resultant ALK protein overexpression in the myofibroblastic component of these tumors is detectable by immunohistochemistry. We examined 73 IMTs, 20 cases of nodular fasciitis, 15 desmoid fibromatoses, and 15 gastrointestinal stromal tumors by immunohistochemistry using ALK-11, a rabbit polyclonal antibody that recognizes the C-terminus of the protein. ALK positivity was detected in 44 of 73 (60%) IMTs. All cases of nodular fasciitis, desmoid fibromatosis, and gastrointestinal stromal tumors were ALK negative (p < 0.001). These findings demonstrate that ALK positivity is common in IMTs, and immunohistochemistry using anti-ALK antibodies can be helpful in the differential diagnosis of these neoplasms. In addition, anti-ALK staining seems to correlate with those IMTs that have the typical tri-patterned histologic appearance and clinical presentation, providing additional support to the premise that IMT is a distinctive clinicopathologic entity within the broad category of inflammatory pseudotumors.

Adolescent↗
PubMed2001

Influence of linker histone H1 on chromatin remodeling.

Chromatin-remodeling complexes have been a central area of focus for research dealing with accessing cellular DNA sequestered in chromatin. Although the linker histone H1 plays a major role in promoting and maintaining higher-order chromatin structure, it has been noticeably absent from assays utilizing chromatin-remodeling enzymes. This review focuses on two ATP-dependent chromatin-remodeling complexes, Drosophila ISWI and mammalian SWI/SNF, that have been assayed using chromatin templates containing histone H1.

Acetyltransferases↗
PubMed2000

Human SWI/SNF nucleosome remodeling activity is partially inhibited by linker histone H1.

The physical structure and the compact nature of the eukaryotic genome present a functional barrier for any cellular process that requires access to the DNA. The linker histone H1 is intrinsically involved in both the determination of and the stability of higher order chromatin structure. Because histone H1 plays a pivotal role in the structure of chromatin, we investigated the effect of histone H1 on the nucleosome remodeling activity of human SWI/SNF, an ATP-dependent chromatin remodeling complex. The results from both DNase I digestion and restriction endonuclease accessibility assays indicate that the presence of H1 partially inhibits the nucleosome remodeling activity of hSWI/SNF. Neither H1 bound to the nucleosome nor free H1 affected the ATPase activity of hSWI/SNF, suggesting that the observed inhibition of hSWI/SNF nucleosome remodeling activity depends on the structure formed by the addition of H1 to nucleosomes.

Animals↗
PubMed2000

Synergistic hepatotoxicity from coexposure to bacterial endotoxin and the pyrrolizidine alkaloid monocrotaline.

Individuals are commonly exposed to bacterial endotoxin (lipopolysaccharide [LPS]) through gram-negative bacterial infection and from its translocation from the gastrointestinal lumen into the circulation. Inasmuch as noninjurious doses of LPS augment the hepatotoxicity of certain xenobiotic agents, exposure to small amounts of LPS may be an important determinant of susceptibility to chemical intoxication. Monocrotaline (MCT) is a pyrrolizidine alkaloid phytotoxin that at large doses produces centrilobular liver lesions in rats. In the present study, MCT was coadministered with LPS to determine whether LPS would enhance its hepatotoxicity. Doses of MCT (100 mg/kg, ip) and LPS (7.4 x 10(6) EU/kg, iv), which were nonhepatotoxic when administered separately, produced significant liver injury in male, Sprague-Dawley rats when given in combination. Within 18 h after MCT administration, this cotreatment resulted in enhanced plasma alanine aminotransferase and aspartate aminotransferase activities, two markers of liver injury. Histologically, overt hemorrhage and necrosis appeared between 12 and 18 h. The lesions were centrilobular and midzonal and exhibited characteristics similar to lesions associated with larger doses of MCT and LPS, respectively. In the presence of LPS, the threshold for MCT toxicity was reduced to 13-33% of the dose required for toxicity with MCT alone. A study in isolated, hepatic parenchymal cells revealed no interaction between MCT and LPS in producing cytotoxicity. In summary, coexposure of rats to noninjurious doses of MCT and LPS resulted in pronounced liver injury. Results in vitro suggest that the enhanced toxicity does not result from a direct interaction of MCT and LPS with hepatic parenchymal cells. These results provide additional evidence that exposure to small amounts of LPS may be a determinant of susceptibility to food-borne hepatotoxins.

Animals↗
PubMed2000

Phosphoaminoglycosides inhibit SWI2/SNF2 family DNA-dependent molecular motor domains.

Members of the SWI2/SNF2 family of proteins participate in an array of nucleic acid metabolic functions, including chromatin remodeling and transcription. The present studies identify a novel strategy to specifically inhibit the functional DNA-dependent adenosinetriphosphatase (ATPase) motor domain common to SWI2/SNF2 family members. We have identified preparations of phosphoaminoglycosides, which are natural products of aminoglycoside-resistant bacteria, as inhibitors of the in vitro activities of three SWI2/SNF2 family members. These compounds inhibit the ATPase activity of the active DNA-dependent ATPase A domain (ADAAD) by competing with respect to DNA and thus have no effect on DNA-independent ATPases or on RNA-dependent ATPases. Within the superfamily of DNA-dependent ATPases, these compounds are most potent toward SWI2/SNF2 family members and less potent toward other DNA-dependent ATPases. We demonstrate that it is feasible to target DNA-dependent ATPases of a particular type without affecting the function of other ATPases. As the SWI2/SNF2 proteins have been proposed to function in all aspects of DNA metabolism, this paper provides an archetype for development of DNA metabolic inhibitors.

Adenosine Triphosphatases↗
PubMed2000

Fine-needle aspiration cytology of mesenchymal hamartoma of the chest wall.

We report on an uncommon entity, the so-called "chest wall chondromatous hamartoma" or "mesenchymal hamartoma of the chest wall" (MHCW), diagnosed by fine-needle aspiration (FNA) cytology in a 6-mo-old boy. Radiologic features were those of an aggressive lesion with rib expansion and destruction, that contrasted with aspirate smears showing bland cartilage and spindled mesenchymal elements. The clinicoradiographic features together with the FNA yield of mixed cellular elements aided in the correct diagnosis of MHCW.

Biopsy, Needle↗
PubMed2000

Adherence to postmenopausal hormone therapy during the year after the initial prescription: A population-based study.

OBJECTIVE: In randomized trials a higher proportion of women prescribed continuous combined hormone replacement therapy complete the full course of treatment compared with those prescribed sequential therapy. We sought to determine adherence to hormone therapy in a less-selected population. STUDY DESIGN: Women enrolled in a prepaid health plan participated in a telephone interview 12 to 15 months after newly initiating use of hormone replacement therapy. The interview elicited information on whether the women were still taking the hormones as first prescribed and reasons for switching or discontinuation. A computerized pharmacy database was used to determine initial doses, prescription renewal, and dates of switching or discontinuation. RESULTS: The proportion continuing the originally prescribed hormone regimen at 1 year was higher among continuous combined therapy users (68.9%, 62/90) than among sequential therapy users (54.4%, 62/114). Women who initiated continuous combined therapy were less likely to have switched regimens (10.0%) than were sequential users (20.2%; relative risk, 0.5; 95% confidence interval, 0.2-1.0) but only somewhat less likely to have discontinued use (21.2% vs 25.4%; relative risk, 0.7; 95% confidence interval, 0.4-1.3). Examined as a whole, women prescribed continuous combined therapy were less likely than those prescribed sequential therapy to quit or switch during the first year (relative risk, 0.6; 95% confidence interval, 0.4-1.0). CONCLUSION: Although adherence was higher among women prescribed continuous combined hormone replacement therapy than sequential therapy, the high level of nonadherence in both groups suggests room for improvement of menopausal therapies so that women find them acceptable for sustained use.

Aged↗
PubMed2000

Gliomatosis peritonei as a complication of a ventriculoperitoneal shunt: case report and review of the literature.

Gliomatosis peritonei, the implantation of neuroglial tissue upon the peritoneal surfaces, is a rare event most often associated with solid or immature teratomas of the ovary in young girls. The authors report a case of a 10-month-old girl with a ventriculoperitoneal shunt (VPS) who presented with bilateral inguinal hernias. Herniorrhaphy was uneventful. Microscopic examination of the hernia sacs showed exuberant mesothelial hyperplasia containing multiple nests of differentiated glial tissue. Subsequent computed tomography and laparoscopy disclosed normal ovaries with no evidence of intraabdominal or pelvic abnormalities. Gliomatosis peritonei in this case was attributed to transport of glial tissue from the cerebrospinal fluid into the peritoneal cavity via the shunt. With the exclusion of an ovarian germ cell neoplasm and in the presence of a VPS, the clinical course with regard to the glial implants in these children is uneventful. If it is appreciated that gliomatosis peritonei may be a complication of a VPS, an extensive clinical evaluation generally is unnecessary.

Choristoma↗
PubMed2000

Late-onset puerperal ovarian vein thrombophlebitis treated laparoscopically.

Puerperal ovarian vein thrombophlebitis is an uncommon condition that usually develops in the immediate postpartum period. Computed tomography, magnetic resonance imaging, Doppler ultrasound, and exploratory laparotomy may be performed to diagnose it. A woman developed worsening abdominal pain 6 weeks postpartum. Laparoscopic intervention allowed treatment of late-onset, left-sided puerperal ovarian vein thrombophlebitis. The disorder may develop much later after delivery than expected and can be successfully treated laparoscopically.

Adult↗