Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.

Background: Pancreatic cancer remains highly lethal. Previous attempts with neoadjuvant therapy in this disease have been inconclusive, but a potential for benefit exists. We conducted a phase II trial of dose-intense docetaxel and gemcitabine followed by twice-weekly gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma.

Quantification of the effects of melittin on liposome structure.

An optical technique, dual-polarization interferometry, has been used to examine lipid structures at the solid/liquid interface. Changes in the lipid structures, in real time, were examined as a consequence of challenging them with a peptide (melittin) that is known to induce liposome rupture. This work suggests that it should be possible to obtain a better understanding of the detail of the melittin rupture process.

Neonatal diabetes mellitus: Insulin pump as an alternative management strategy.

Neonatal diabetes mellitus (hyperglycaemia within the first month of life, with an insulin requirement) may be transient or permanent. Management is complex, due to lack of subcutaneous fat and the need for small doses of insulin, and may be complicated by additional medical problems. Three cases are presented, the first of which was treated with conventional insulin therapy.

Regulation of an insect cytochrome P450 monooxygenase gene (CYP6B1) by aryl hydrocarbon and xanthotoxin response cascades.

Many organisms respond to toxic compounds in their environment by inducing regulatory networks controlling the expression and activity of cytochrome P450 monooxygenase (P450s) detoxificative enzymes. In particular, black swallowtail (Papilio polyxenes) caterpillars respond to xanthotoxin, a toxic phytochemical in their hostplants, by activating transcription of the CYP6B1 promoter via several regions located within 150 nt of the transcription initiation site. One such element is the xenobiotic response element to xanthotoxin (XRE-Xan) that lies upstream of consensus XRE-AhR (xenobiotic response element to the aryl hydrocarbon receptor) and OCT-1 (octamer-1 binding site) element known to be utilized in mammalian aryl hydrocarbon response cascades.

Diabetic ketoacidosis, hyperosmolarity and hypernatremia: are high-carbohydrate drinks worsening initial presentation?

The case of five pediatric patients who presented to the Royal Children's Hospital, Melbourne with newly diagnosed diabetes mellitus between January 2001 and September 2003 is reported. Each case was complicated by hyperosmolarity and hypernatremia and required intensive therapy. Fluid intake prior to admission in each case was documented and consisted of between 5 and 12 L of carbonated carbohydrate beverages and 'isotonic' sports drinks.

A novel approach to continuous glucose analysis utilizing glycemic variation.

Background: Various methodologies have been proposed for analysis of continuous glucose measurements. These methods have mainly focused on the proportion of low or high glucose readings and have not attempted to analyze other dimensions of the data obtained. This study proposes an algorithm for analysis of continuous glucose data including a novel method of assessing glycemic variability.

A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.

Purpose: Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and topotecan have separately demonstrated activity against gliomas. We conducted a Phase II trial of these agents in combination with filgrastim (G-CSF) in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.

"Is this a dagger I see before me?"--an audit of stabbings and gunshot wounds in Limerick.

Background: According to a recent study in Cardiff, the incidence of stab wounds is 14 per 100,000 population per annum. No such figures are available for Ireland.

Aim: To evaluate the incidence, type of injury, medical consequences and outcome of patients with stab or gunshot wounds presenting to the Mid-Western Regional Hospital, Limerick, over a 12 month period.

Conserved regulatory elements in the promoters of two allelochemical-inducible cytochrome P450 genes differentially regulate transcription.

CYP6B4, a cytochrome P450 gene from the tiger swallowtail Papilio glaucus, is transcriptionally induced in the midgut by dietary furanocoumarins, plant allelochemicals that can crosslink DNA in their UV-activated form. The CYP6B4 promoter contains an overlapping EcRE/ARE/XRE-xan element similar to that used for basal and xanthotoxin-inducible expression of the CYP6B1 promoter from the black swallowtail Papilio polyxenes. Transfection of the CYP6B4 promoter:CAT reporter construct into Sf9 cells demonstrates that the basal and xanthotoxin-inducible expression levels observed reflect the relative expression levels of this gene in the midguts of tiger swallowtail larvae.

K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma.

Objective: Germline mutations in succinate dehydrogenase (SDH)B, SDHC and SDHD, encoding three of the four subunits of mitochondrial complex II, have been implicated in the tumourigenesis of familial paragangliomas and phaeochromocytomas. Twenty-three SDHB mutations have been identified to date.

Patients: We present a novel missense SDHB exon 2 mutation (c.

Primary adrenal insufficiency in childhood and adolescence: advances in diagnosis and management.

Objectives: Primary adrenal insufficiency occurring in childhood and adolescence is due to abnormalities of gland development, gland responsiveness, and steroid biosynthesis or target organ response. Causes include autoimmune Addison's disease, tuberculosis, HIV, adrenoleukodystrophy, adrenal hypoplasia congenita and syndromes including triple A and IMAGe. We aimed to define the causes of adrenal insufficiency for a cohort of children in Melbourne.

Conformational effects on glycoside reactivity: study of the high reactive conformer of glucose.

The effect of conformation on glycoside reactivity was investigated by studying the hydrolysis of a selection of 3,6-anhydroglucosides as models for glucose in the highly reactive (1)C(4) conformation. Methyl 3,6-anhydro-beta-D-glucopyranoside was found to hydrolyze 200-400 times faster than methyl glucosides in the (4)C(1) conformation, while methyl 3,6-anhydro-beta-D-galactopyranoside, which is in the B(1,4) conformation, was less reactive than methyl beta-D-galactopyranoside. Methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranoside, methyl (3,6-anhydro-alpha-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D-glucopyranoside, and methyl (3,6-anhydro-beta-D-glucopyranosyl)-(1 --> 6)-alpha-D-glucopyranosyl-(1 --> 6)-alpha-D-glucopyranoside were prepared and found to react selectively at the anhydro residue.

A general synthesis of iminosugars.

1-Deoxynojirimycin, 1-deoxymannojirimycin, and 1-deoxygalactostatin have been synthesized by epoxidation of tri-O-acetyl-6-deoxyhex-5-enopyranosyl azides followed by methanolysis, deacetylation, and catalytic hydrogenation. 1,6-Dideoxygalactostatin was obtained by the reaction of 2,3,4-tri-O-acetyl-6-deoxy-beta-L-arabino-hex-5-enopyranosyl azide with NIS in methanol followed by deacetylation and catalytic hydrogenation. The overall yields were 4.

Improvement in efficacy of chemoradiotherapy by addition of an antiangiogenic agent in a murine tumor model.

Background: Chemoradiotherapy improves survival for some cancer patients. Methods of enhancing treatment response would further enhance survival rates. The effect of the addition of an antiangiogenic agent to a chemoradiotherapy regime has not previously been examined.

Carotid artery angioplasty for restenosis following endarterectomy.

Introduction: The higher complication rate associated with the surgical treatment of restenosis following carotid endarterectomy (CEA) has led several authors to advocate angioplasty as the treatment of choice in the management of restenosis. We describe our experience with internal carotid artery angioplasty for post-endarterectomy restenosis over 7 years.

Patients And Methods: From January 1994 to April 2001, all patients with a >90% restenosis following CEA were considered for angioplasty.

Laparoscopic repair of a strangulated Bochdalek hernia.

Background: Bochdalek herniae are rare. They are usually repaired by open abdominal surgery or by a thoracic video-assisted approach. When strangulated and in a compromised patient the options are fewer.

Adrenal cortical tumours: 25 years' experience at the Royal Children's Hospital, Melbourne.

Aims: Adrenal cortical tumours remain a rare entity with inconsistent consensus about treatment and follow up. This article reviews 25 years of experience in the Royal Children's Hospital, Melbourne, Australia.

Methods: All records with the diagnosis of adrenal adenoma or carcinoma between 1976 and 2001 were reviewed, excluding tumours of the adrenal medulla.

Effect of neoadjuvant chemoradiotherapy on angiogenesis in oesophageal cancer.

Background: Vascular endothelial growth factor (VEGF) levels are raised in the serum of patients with oesophageal carcinoma. The aim of this study was to evaluate the tumour microvasculature and the role of tumour-associated macrophages in VEGF production after neoadjuvant chemoradiotherapy and surgery for oesophageal cancer.

Methods: Sections from 92 consecutively resected oesophageal tumours were stained for VEGF, von Willebrand factor and CD68.

Elimination of alfentanil delivered by infusion is not altered by the chronic administration of atorvastatin.

Background And Objective: Statins are prescribed for patients with hypercholesterolemia. Atorvastatin is metabolized by cytochrome P4503A4 and inhibits P4503A4 activity in vitro. Alfentanil is a potent opioid used in clinical anaesthetic practice and is also metabolized by P4503A4.

A 3-year prospective study to assess uterine growth in girls with Turner's syndrome by pelvic ultrasound.

Objective: Adult women with Turner's syndrome who have used the donor ovum IVF programme are reported to have reduced pregnancy outcome with an increased risk for first trimester spontaneous abortion. This is considered to be related to a small uterine size and reduced endometrial thickness. This study examines whether adequate oestrogen replacement during the early adolescent years will result in normal adult uterine dimensions, with consequent reduction in these pregnancy risks.

Iodine deficiency and goitre in schoolchildren in Melbourne, 2001.

Objective: To assess iodine status and goitre prevalence in a sample of schoolchildren in Melbourne.

Design: Cross-sectional study of urinary iodine excretion and presence of goitre in a sample of schoolchildren from Years 5-12 attending two urban schools.

Participants: 607 children aged 11-18 years consented to thyroid gland palpation and 577 provided a urine sample on the day of examination in August 2001.

The effect of cholecystectomy on plasma cholecystokinin.

Objective: Gallbladder removal is associated with an increased incidence of gastroesophageal reflux, but the mechanism is unclear. Cholecystokinin (CCK) release, which causes gallbladder contraction, is inhibited by bile in the duodenum. This study investigates the effect of cholecystectomy on meal-stimulated CCK secretion.

Low dose intraarterial thrombolysis with tissue plasminogen activator: does it deliver as promised?

The widespread use of intraarterial thrombolytic therapy has been based on perceived benefits over operative treatment and the downgrading of the magnitude of subsequent surgery. Thirty-three patients who had thrombolysis for peripheral artery occlusion were retrospectively analyzed at St. James's Hospital from 1991 to 1997.