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Biomedical subjects

H Irving

Publications and source records attributed to H Irving.

13 recordsLinked to original sources

Retroperitoneal paraganglioma in a child: resection and vena caval reconstruction.

Retroperitoneal paragangliomas (PG) are tumors of neuroectodermal origin rarely seen in children. A 10-year-old boy presented with back pain and a palpable mass secondary to a large right-sided retrocaval PG inferomedial to the kidney. Preoperative chemotherapy and perioperative embolisation were instigated to reduce tumor vascularity. En-bloc resection of the inferior vena cava below the left renal vein and above the caval bifurcation was achieved. Caval reconstruction was completed using a complex autograft of anterior uninvolved vena cava and right renal vein. At 4-year follow-up, the child remains tumor-free with normal caval flow and patency.

Child↗

Retinoid-induced differentiation of neuroblastoma: comparison between LG69, an RXR-selective analogue and 9-cis retinoic acid.

The aim of this study was to investigate in vitro the effects of all-trans retinoic acid (RA), 9-cis RA and the RXR-selective analogue, LG69, on the morphological differentiation, proliferation and gene expression of neuroblastoma cells. Three different cell lines were cultured with the retinoid for either 9 continuous days or for 5 days followed by 4 days without the retinoid and morphological differentiation was assessed both qualitatively and quantitatively. SH SY 5Y cell proliferation was examined by measuring cell numbers after exposure to the retinoids and RAR-beta gene expression was examined by Northern blot analysis. Morphological differentiation was more effectively induced by all-trans and 9-cis RA than by LG69. SH SY 5Y cells, when treated with 9-cis RA for only 5 of the 9 days of culture, underwent apoptosis, but this was not seen with 9 days continuous exposure nor with LG69. Inhibition of SH SY 5Y cell proliferation by all-trans or 9-cis RA was dose-dependent, but LG69 had little effect. Conversely, LG69 induced higher expression of RAR-beta than all-trans RA, but less than that produced by 9-cis RA. These data suggest that 9-cis RA as a single agent is the most effective modulator of neuroblastoma behaviour and may be the most appropriate therapeutic agent.

Antineoplastic Agents↗

Apoptosis of N-type neuroblastoma cells after differentiation with 9-cis-retinoic acid and subsequent washout.

BACKGROUND: The overall survival rate for patients with neuroblastoma has improved over the past two decades, but long-term survival for the subgroup of patients with high-risk disease remains low. In recent years, there has been interest in the potential clinical use of drugs able to induce differentiation of neuroblastoma cells. Since 9-cis-retinoic acid induces better and more sustained differentiation of neuroblastoma in vitro than other retinoic acid isomers, this may be a more appropriate retinoid for use in neuroblastoma therapy. PURPOSE: The purpose of this work was to compare the long-term effects of all-trans- and 9-cis-retinoic acid on neuroblastoma differentiation using an N-type (neuroblastic) cell line, SH SY 5Y, as an in vitro model. In addition, we wanted to find out whether 9-cis-retinoic acid would induce programmed cell death (apoptosis) in these N-type neuroblastoma cells and to determine whether the effects of either 9-cis- or all-trans-retinoic acid are dependent on their continued presence in the culture medium. METHODS: SH SY 5Y cells were incubated in either the continued presence of all-trans- or 9-cis-retinoic acid or for 5 days with retinoic acid followed by culture in the absence of retinoid for up to 13 days. Morphologic changes were observed using phase-contrast and scanning electron microscopy. Apoptosis was determined by flow cytometry of propidium iodide-stained cells and by using terminal deoxynucleotidyl transferase to end-label DNA fragments in situ in apoptotic cells. RESULTS: Culture of SH SY 5Y cells with all-trans- or 9-cis retinoic acid for 5 days induced morphologic differentiation and inhibited cell growth. These effects were maintained in the continuous presence of each retinoic acid isomer but were more profound in cells treated with 9-cis-retinoic acid. The differentiation of cells treated with all-trans-retinoic acid was reversible once retinoic acid was removed from the medium. Conversely, apoptosis was induced in cells treated with 9-cis-retinoic acid for 5 days and cultured for 9 days (4 days after washout) but not in cells cultured in the continuous presence of 9-cis-retinoic acid. This effect was specific to 9-cis-retinoic acid. CONCLUSIONS: Previous studies have demonstrated differential responses to all-trans-retinoic acid in N- and S-type (substrate-adherent or Schwann-like) neuroblastoma cells: Apoptosis is induced in S-type cells, whereas differentiation occurs in N-type cells. The present results show that, unlike all-trans-retinoic acid, 9-cis-retinoic acid induces both differentiation and apoptosis in N-type SH SY 5Y neuroblastoma cells. However, apoptosis was dependent on removal of 9-cis-retinoic acid from the culture medium. IMPLICATIONS: Since both differentiation and apoptosis are involved in tumor regression, 9-cis-retinoic acid may be a more appropriate retinoid for clinical trials in neuroblastoma. The dependence of apoptosis on treatment and subsequent removal of 9-cis-retinoic acid implies that drug scheduling may be an important parameter affecting therapeutic efficacy.

Alitretinoin↗

Retinoids in neuroblastoma therapy: distinct biological properties of 9-cis- and all-trans-retinoic acid.

We investigated the potential for 9-cis-retinoic acid in the differentiation therapy of neuroblastoma using an N-type neuroblastoma cell line, SH SY 5Y, as an experimental model. In these cells, 9-cis-retinoic acid is more effective than other isomers at inducing the expression of RAR-beta. An RAR-alpha-specific antagonist inhibited the induction of RAR-beta in response to all-trans-but not to 9-cis-retinoic acid. This indicates that the mechanism of gene induction by 9-cis-retinoic acid differs markedly from all-trans-retinoic acid. 9-cis-retinoic acid is also better than all-trans at producing sustained morphological differentiation and inhibition of proliferation of SH SY 5Y cells. Although N-type neuroblastoma cells are not thought to undergo apoptosis in response to all-trans-retinoic acid, we observed a significant degree of apoptosis in SH SY 5Y cells treated with 9-cis-retinoic acid for 5 days and then cultured in the absence of retinoid, an effect not observed in cells treated with the all-trans isomer. These results suggest that 9-cis- and all-trans-retinoic acid have distinct biological properties and that 9-cis retinoic acid may be clinically effective in neuroblastoma by inducing both differentiation and apoptosis under an appropriate treatment regimen.

Alitretinoin↗

9-cis retinoic acid--a better retinoid for the modulation of differentiation, proliferation and gene expression in human neuroblastoma.

To date, the clinical success of 13-cis or all-trans retinoic acid in the treatment of neuroblastoma has been disappointing. In vivo, 13-cis will isomerise to both all-trans and 9-cis retinoic acid, believed to be the main biologically-active isomers. In vitro studies with an N-type neuroblastoma cell line, SH SY 5Y, show that 9-cis is better than other isomers at both inducing morphological differentiation and inhibiting proliferation. RAR-beta, a gene which may mediate retinoic acid responsiveness and be of prognostic significance, is also more-effectively induced by 9-cis retinoic acid. 9-cis and all-trans retinoic acid do not have synergistic effects on SH SY 5Y cell proliferation and gene expression. A retinoid X receptor (RXR)-specific analogue of 9-cis retinoic acid had similar effects on gene expression to 9-cis retinoic acid alone. In view of these results, 9-cis retinoic acid or stable analogues of this retinoid may have potential for the treatment of neuroblastoma.

Alitretinoin↗

Influence of intraperitoneal drains on subhepatic collections following cholecystectomy: a prospective clinical trial.

In this prospective randomized study, the influence of an intraperitoneal drain on the incidence and clinical significance of subhepatic collections occurring in patients after acute or elective cholecystectomy was assessed by ultrasound examination. A total of 112 patients entered the study, of whom 54 received a drain. There was no significant difference between the drainage and the non-drainage groups with respect to mean age or sex distribution, the number of patients in whom the gallbladder bed was formally closed (27 versus 21) nor in the number of acute cholecystectomies performed in either group (12 versus 13). Ultrasound detected 10 (18 per cent) collections in the drainage group and only one (1.8 per cent) in the non-drainage group (P less than 0.01, chi 2 test). None of the collections required any further treatment and no morbidity occurred that was directly attributable to the presence of the retained fluid. These results suggest that rather than preventing fluid collections, suction drains may predispose to the development of subhepatic collections after cholecystectomy.

Bile↗

Prospective comparison of three non-invasive tests for pancreatic disease.

Ultrasonography, computed tomography (CT), and an oral pancreatic function test were evaluated prospectively in 107 consecutive patients suspected of having pancreatic disease, the final diagnosis being made independently of these tests. Seventeen patients proved to have either chronic pancreatitis or a pancreatic neoplasm. Five had an unfused ventral pancreas and 10 had "minimal change" pancreatograms. Seventy five patients did not have pancreatic disease. Among the 17 patients with pancreatic disease the sensitivities of ultrasound, CT, and the pancreatic function test were 70%, 71%, and 76% respectively; among those without disease values of specificity of the three tests were 75%, 87%, and 72%. All three tests failed to detect most of the patients with unfused ventral pancreases or minimal change pancreatograms. The predictive values of a positive result for the three tests were 43%, 67%, and 34%. The predictive value of a negative result was greater than 90% for all the tests. Results improved when CT was combined with either of the two other tests. These findings show that CT is the most accurate of the three tests in diagnosing pancreatic disease but that a combination of ultrasound and the oral pancreatic function test offers a more widely applicable and almost as accurate alternative.

4-Aminobenzoic Acid↗

Krypton-81m ventilation scanning: acute respiratory disease.

From experience with 700 patients undergoing ventilation and perfusion lung scanning with krypton-81m/technetium-99m technique, 34 patients suffering from nonembolic acute respiratory disease were selected for review. In 16 patients with pneumonia, all had defects of ventilation corresponding to, or larger than, the radiologic consolidation. In 13 patients there were some preservation of perfusion in the consolidated region. In two of the three patients with matched defects, the pneumonia was of long standing. In seven patients with collapse or atelectasis and in 11 patients with acute reversible bronchial obstruction and normal volume lungs, a similar pattern of ventilation and perfusion was observed.

Adult↗

Values in radiology.

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Interprofessional Relations↗

The use of transdermal fentanyl in pediatric oncology palliative care.

Transdermal fentanyl offers a noninvasive approach to the management of patients with opioid dependent and stable, chronic cancer pain. The transdermal delivery system offers distinct advantages where oral administration of opioids is difficult as a consequence of progressive disease and in patients whose compliance with oral medications is poor. Thirteen patients ranging in age from three years and nine months to 18 years and seven months were treated with transdermal fentanyl for between six hours and 112 days. All had previously been receiving oral morphine prior to the commencement of fentanyl and were transferred to fentanyl because of oral opioid side effects and poor oral compliance. Fentanyl was well tolerated and provided effective pain relief for 11 of 13 patients. Overall, patients and parents experienced satisfaction with fentanyl, both in terms of pain relief and improvement in quality of life.

Administration, Cutaneous↗