The Development of a National Paediatric Psycho-Oncology Service.

Aims To investigate the psychological care provided to children and young adolescents with cancer and their families within the National Children's Cancer Service (NCCS), Ireland, in respect of the national and international standards of care. Methods A retrospective audit of 316 referrals made over 32 months by the NCCS to the psychology service in malignant haematology and oncology was performed. Results The audit revealed that out of 316 patients, a yearly average of 189 (50%) of urgently referred patients received psychological support within the NCCS between January 2013 and August 2016. Furthermore only 20 (22%) undergoing haematopoietic stem cell transplantation (HSCT), 14 (22%) referred to the paediatric palliative care team, and 84 (62%) of teenage patients received psychological input during this timeframe. Conclusion The audit revealed that the current psychology service provision is failing to meet the international standards of care. Due to the data provided by this audit, in conjunction with a clinical risk assessment of the service, funds for the post of principal psychologist have been secured. Further psychology posts (HSCT, late-effects and neuropsychology), and development of the psycho-oncology model of care are required to ensure equality of access and evidence-based psychological care for all children with cancer.

Proton therapy in paediatric oncology: an Irish perspective.

BACKGROUND: Proton therapy (PT) is a radiotherapy treatment modality that uses protons, rather than conventional photons. PT is often used in paediatric oncology due to its reported capability to reduce acute and late adverse treatment effects. As PT is unavailable in Ireland, patients are referred abroad for treatment. AIMS: To: (1) produce a descriptive study of Irish children referred abroad for PT, and (2) discuss the case for PT in general. METHODS: A retrospective review of all children referred for PT before October 2015 was performed. Information was gathered regarding demographics, diagnosis, referral timeline, adverse effects attributable to PT, current status and cost. A review of the relevant literature was performed. RESULTS: Seventeen children treated in Ireland have been referred abroad for PT. The largest number was in the 0-4 year old group. At initial diagnosis the median age was 4.8 years. The average cost per child was €37,312. Two patients suffered disease relapse. Four have encountered PT-related adverse effects. CONCLUSION: Despite the fact that >100,000 patients worldwide have been treated with PT, the level of published evidence to support superiority over conventional treatment remains low. It is debated that randomised control trials in this area would be inconsistent with the principle of clinical equipoise. In contrast, there is a call for level 1 evidence to justify drastic changes in patient care, particularly in light of recent reports of unexpected toxicities. In time, careful evaluation, follow-up and clinical trials will likely support the preferential use of PT in children.

Melanotic neuroectodermal tumour of infancy: surgical and chemotherapeutic management.

Melanotic neuroectodermal tumour of infancy (MNTI) is a rare pigmented neoplasm of neural crest origin. It usually presents in the first year of life in the maxilla as a fast growing lesion. We describe the case of a 3-month-old boy who presented with an enlarging swelling of left maxillary alveolus. He was treated with combined surgical and chemotherapy modalities. MNTI is complicated by high recurrence rate, local invasion and malignancy has been reported. This report describes the diagnosis, treatment and follow-up of recurrent MNTI.

Measuring the change in CBV upon cortical activation with high temporal resolution using look-locker EPI and Gd-DTPA.

A method of simultaneously measuring the changes in cerebral blood volume (CBV) and T(*) (2) that occur on brain activation with high temporal resolution was developed. The method involves measuring the change in the longitudinal relaxation time (T(1)) that occurs following a bolus injection of Gd-DTPA and converting this measurement to a change in blood volume assuming fast exchange. The sequence was optimized for the measurement of changes in CBV with high temporal resolution. A change in CBV of 27 +/- 4% on activation of the primary visual cortex (V1) was measured across four subjects. The time course of changes in T(*) (2) showed a poststimulus undershoot (P = 0.008) corresponding approximately to a period over which CBV was still elevated above baseline, but falling (P = 0.01). The effects of perfusion, nonfulfillment of the assumption of fast exchange and of intrinsic T(1) changes on activation on the model used to calculate the change in CBV are discussed.

Investigating the BOLD effect during infusion of Gd-DTPA using rapid T2* mapping.

This work aimed to investigate the effects of administering Gd-DTPA on the BOLD effect, and to determine the feasibility of using this approach to measure fractional changes in blood volume and blood oxygenation on neuronal activation during a visual paradigm. A linear relationship between cortical R(2)(*) and the intravascular concentration of Gd-DTPA was demonstrated. The change in R(2)(*) in the visual cortex on activation at 3 T (in the absence of Gd-DTPA) was found to be 1.38 +/- 0.31 s(-1) (N = 4). The fractional change in total blood volume during visual activation was calculated to be 28% +/- 7% (N = 4). The absolute increase in venous blood oxygenation on activation (DeltaY) was estimated to be 21% +/- 4% (N = 4) (assuming HCT = 0.4, resting blood oxygenation = 60%, fraction of volume change that was venous = 36%, and the resting venous fraction of the blood volume = 70%). Simulations showed that the estimated change in venous blood oxygenation was sensitive to the assumed venous blood fraction, and that the estimated fractional change in blood oxygenation was insensitive to whether the change in blood volume occurred in the arterial or venous network.

Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.

Rosuvastatin is a new, synthetic, orally active statin, with marked low-density lipoprotein (LDL) cholesterol-lowering activity. We conducted 2 dose-ranging studies. In the first study, after a 6-week dietary run-in, 142 moderately hypercholesterolemic patients were randomized equally to receive double-blind placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg or open-label atorvastatin 10 or 80 mg once daily for 6 weeks; in the second study, conducted to extend the rosuvastatin dose range, 64 patients were randomized to double-blind, once-daily placebo or rosuvastatin 40 or 80 mg (1:1:2 ratio) for 6 weeks. Data from both studies were combined for analysis of lipid effects. No statistical comparison of atorvastatin arms with placebo or rosuvastatin was performed. Rosuvastatin was associated with highly significant dose-dependent reductions in LDL cholesterol compared with placebo (p <0.001); decreases ranged from 34% (1 mg) to 65% (80 mg). Linear regression analysis indicated an additional 4.5% LDL cholesterol reduction for each doubling of the rosuvastatin dose. Across the dose range, approximately 90% of LDL cholesterol reduction occurred within the first 2 weeks of treatment. Significant, dose-dependent reductions in total cholesterol and apolipoprotein B with rosuvastatin were also observed (p <0.001). High-density lipoprotein cholesterol increases and triglyceride reductions were consistently observed and statistically significant at some dose levels. All lipid ratios were significantly reduced at all rosuvastatin dose levels (p <0.001). Adverse events were similar across placebo and active treatments. No significant increases in alanine aminotransferase or creatine kinase were seen in any patient. Over 6 weeks, rosuvastatin produced large, rapid, dose-dependent LDL cholesterol reductions and was well tolerated in hypercholesterolemic patients.

Use of 24 h ambulatory ECG recordings in the assessment of new chemical entities in healthy volunteers.

1. Ambulatory (24 h) cardiac monitoring (ACM) is frequently used to screen healthy volunteers before inclusion in trials of new chemical entities in man. We analysed 156 consecutive ACM recordings in 'healthy' volunteers (on no medication). 2. Only 20 (13%) of the recordings showed normal sinus rhythm throughout. 3. Supraventricular ectopics were the commonest abnormality (83%). Ventricular ectopics occurred in 11%; ventricular tachycardia (unsustained) in 2% and sinus pauses in 6.5%. One volunteer was found to be in atrial fibrillation throughout. 4. The data indicate that when ACM recordings are performed in the assessment of the effects of experimental drugs, guidelines are needed to assess 'normality' to suggest when cardiological investigation is needed and to assign causality of the arrhythmia to the new chemical entity. 5. Proposed guidelines are presented.

Glucose-6-phosphatase in normal adult human intestinal mucosa.

1. The existence of specific glucose-6-phosphatase activity in human intestinal mucosa has been somewhat controversial. 2. We have demonstrated the presence of low levels of specific glucose-6-phosphatase activity in normal human adult intestinal mucosa. Activity was found in oesophagus, stomach, duodenum and colon. 3. Immunoblot analysis using antibodies monospecific for the 36.5 kDa liver glucose-6-phosphatase catalytic subunit demonstrated that intestinal mucosa contains low levels of the glucose-6-phosphatase enzyme protein. 4. The low levels of activity together with problems of proteolysis make human intestinal biopsies unsuitable for use in the diagnosis of type 1 glycogen-storage disease.

Audit of the quality of hospital discharge data.

An audit of the quality of computerised hospital discharge data, in General Medicine and Paediatrics in Dundee, showed that the national data set was often inaccurate. Structured discharge summaries checked by senior medical staff are recommended.

Amnesics have a disproportionately severe memory deficit for interactive context.

Two experiments were used to compare the recognition memory of amnesic and normal subjects for intentionally encoded words (targets) and for incidentally encoded words that were meaningfully related to the targets and presented at the same time (interactive context). In both experiments the target recognition of the two groups was matched at a high level by presenting the amnesics with much shorter lists of words to remember. Experiment 1 compared 20 amnesics and their matched controls and showed that whereas the amnesics' recognition of the target words did not benefit significantly when they were presented together with their interactive context words (relative to their recognition when the target words were presented alone), that of the controls did. Experiment 2 compared 14 amnesics and their matched controls and showed that when patients and their controls were matched on their target word recognition in isolation, then the patients still showed worse recognition for the interactive context words. These effects were not found only in Korsakoff patients, and their size did not correlate with behavioural measures of frontal-lobe damage. It is concluded that amnesics may be more impaired at recognizing incidentally encoded interactive context than they are at recognizing target material, and this deficit may be an essential feature of the syndrome.

A case of skin hyperpigmentation due to alpha-MSH hypersecretion.

A case is presented of generalized skin hyperpigmentation due to alpha-MSH hypersecretion from the pituitary that was most marked in the light-exposed areas. The patient also had secondary adrenal dysfunction, peripheral lymphadenopathy, streptococcal glomerulonephritis and malabsorption. Analysis of this patient's alpha-MSH using high-pressure liquid chromatography (HPLC) showed a novel acetylation profile compared to normal individuals and to patients with Cushing's disease and Nelson's syndrome. Glucocorticoid replacement therapy resulted in suppression of alpha-MSH hypersecretion and complete resolution of the illness.

Glycogen storage disease diagnosed in adults.

Glycogen storage diseases are usually identified in childhood. We present the clinical, biochemical and histological features of 10 patients first diagnosed in adult life. Five had glycogen storage disease type 1a, one type 1c, two type IX, and in two patients there were previously unreported abnormalities of hepatic glucose-6-phosphatase system activity. Of the latter, one patient had an inhibitor of liver glucose-6-phosphatase (pseudo-1b glycogen storage disease) the other having abnormal glucose-6-phosphatase activity and microsomal pyrophosphate transport. A glucagon test is suggested as a useful screening procedure. Glycogen storage disease should be considered in adults with symptoms suggesting hypoglycaemia.

Reactive hypoglycaemia in association with disordered islet function and abnormal hepatic glucose-6-phosphatase activity: response to diazoxide.

Severe reactive hypoglycaemia was confirmed in a non-diabetic male patient by a counter-regulatory hormone (GH, cortisol and catecholamine) response to profound hypoglycaemia induced by an intravenous glucose load. There was also evidence of disordered pancreatic islet cell paracrine regulation with hyperinsulinaemia and absent glucagon response to hypoglycaemia. A defect in the patient's hepatic glucose-6-phosphatase enzyme system was documented. Because of severe symptoms, dietary control was insufficient, but the patient responded clinically and biochemically to 18 months of oral diazoxide therapy. He also showed good biochemical response to a single dose (100 micrograms IM) of the somatostatin analogue octreotide.

Long-term weight changes in treated hyperthyroid and hypothyroid patients.

To compare the effect of three treatments for thyrotoxicosis on subsequent body weight, a retrospective survey of 65 patients was performed. The effect of thyroxine replacement on body weight in 25 patients with primary hypothyroidism was also examined. In one year after starting therapy 21 patients treated with carbimazole gained a mean of 5.4kg (95% confidence interval 3.6 to 7.2kg); 20 patients after thyroidectomy gained a mean of 6.3kg (95% c.i. 3.4 to 9.2kg); and 24 patients given radioiodine gained a mean of 7.4kg (95% c.i. 5.2 to 9.6kg), p less than 0.001 in all three groups. The weight gain in the three groups was not significantly different. 54-67% of the weight gain occurred in the first three months. The patients treated for hypothyroidism had lost an insignificant amount of weight 12 months after starting therapy--mean change was -0.6kg (95% c.i. -2.2 to +1.1kg) p greater than 0.1. This data suggests that all patients treated for thyrotoxicosis will gain body weight irrespective of the treatment used, but patients treated for primary hypothyroidism will not lose an appreciable amount of weight. Therefore dietary advice should be given, where appropriate, at the onset of any treatment of thyroid dysfunction.

Benign intracranial hypertension associated with danazol.

We describe a case of benign intracranial hypertension (BIH) whose onset coincided with treatment of danazol for menorrhagia. No other causative factors were identified. Headache and visual symptoms occurring in patients treated with danazol therefore require careful assessment, so that visual failure from advanced BIH can be avoided by appropriate treatment.

Amiloride activation of hepatic microsomal glucose-6-phosphatase; activation of T1?

The mechanism of activation of hepatic microsomal glucose-6-phosphatase (EC 3.1.3.9) in vitro by amiloride has been investigated in both intact and fully disrupted microsomes. The major effect of amiloride is a 4.5-fold reduction in the Km of glucose-6-phosphatase activity in intact diabetic rat liver microsomes. Amiloride also decreased the Km of glucose-6-phosphatase activity in intact liver microsomes isolated from starved rats 2.5-fold. Kinetic calculations, direct enzyme assays and direct transport assays all demonstrated that the site of amiloride action was T1, the hepatic microsomal glucose 6-phosphate transport protein. This is, to our knowledge, the first report of an activation of any of the proteins of the multimeric hepatic microsomal glucose-6-phosphatase complex.

Protracted systemic illness and interstitial nephritis due to minocycline.

A severe hypersensitivity-like illness with acute renal failure, lymphadenopathy and skin rash is reported following minocycline treatment in a 16 year old male. Following haemodialysis and steroid therapy his illness remitted, only to recur on withdrawal of the steroids. With further steroid treatment he recovered completely. Lymphocyte function tests, performed in an attempt to positively incriminate minocycline, were inconclusive due to a general suppression of the patient's lymphocytes to in vitro stimulation. Hypersensitivity reactions attributed to minocycline include skin rashes, lymphadenopathy and one previous case of acute interstitial nephritis.