Primitive neuroectodermal tumours of the cerebrum

Summary Eighteen cases of cerebral tumour composed partly or totally of primitive embryonal cells are reported. These lesions comprise 2.8% of all primary cerebral hemisphere tumours in the histopathology files of The Royal Marsden Hospital between 1971 and 1980 inclusive. Most exhibited some degree of differentiation towards neuronal or glial elements and, as more than one type of differentiation was often present in the same lesion, we agree with others that the term primitive neuroectodermal tumour (PNET) is more appropriate to describe these lesions than terms based on histogenesis. The extent of the primitive component varied, but usually accounted for more than 80% of the tumour. Although the tumours bear some similarities to posterior fossa medulloblastomas, they exhibit important differences in histology, immunohistology, natural history and response to treatment. Nearly all PNETs examined expressed some glial fibrillary acidic (GFAP) both in primitive areas and zones of astrocytic differentiation. GFAP staining may thus be of value in distinguishing PNETs from undifferentiated non-neurogenic tumours. Of 14 patients referred for radiotherapy, the survival rate at 3 years was 29% (\414) and 5 years 25% (\312). Patients with tumours in which at least 90% of the tissue was undifferentiated exhibited an extremely poor prognosis with none of 9 patients still alive at 3 years in contrast to 3 of 5 patients (60%) with tumours showing less than 90% undifferentiation. Radical tumour removal, where feasible, followed by irradiation of the whole cerebrospinal axis is recommended. Adjuvant chemotherapy with such agents as CCNU and Vincristine may be of value: the 3 long term survivors in the present series (7–11 years), including one who presented disseminated intracranial disease, received such adjuvant treatment.     

Reference values for radial bone width and mineral content using single photon absorptiometry in healthy children aged 4 to 10 years

Bone width and mineral content were measured in 420 healthy Cambridge children aged 4 to 10 years using single photon absorptiometry. The results are expressed first in the form of standard centile charts, with additional prediction charts which provide body-size-adjusted estimates for the measurements, and interpretation centiles for comparing these estimates with the actual measurements. The values obtained are similar to those reported for American children aged five to six years after adjusting for body-size differences. We suggest that appropriate application of these prediction charts will facilitate the use of single photon absorptiometry in monitoring and treating children who have disorders of bone growth and mineralization.     

Resurgence of Acanthamoeba keratitis in Auckland,New Zealand: a 7‐year review of presentation and outcomes

Purpose: To investigate the presentation, clinical characteristics and outcomes of Acanthamoeba keratitis (AK) in Auckland, New Zealand over a 7‐year period. Methods: Retrospective analysis of all cases of AK treated by the tertiary corneal service at Auckland City Hospital/ University of Auckland Department of Ophthalmology (August 2001 to May 2008). Data were collected regarding age, gender, contact lens history, presenting signs and symptoms, diagnosis at first presentation, time to final diagnosis, identifiable risk factors, presenting and final visual acuity, results of microbiological testing, medical treatment, surgical interventions, recurrence of disease and length of follow up. All photographs and in vivo confocal microscopy images were reviewed. Results: Twenty‐five eyes of 25 patients were identified with a diagnosis of AK (mean age 40 ± 13 years). Ninety‐six per cent were contact lens wearers. Mean time to diagnosis was 41 ± 49 days (range 0–181 days, median 21 days). Fourteen patients (56%) had been treated with topical corticosteroids prior to the diagnosis. Early diagnosis of AK (<21 days) was associated with significantly better final visual acuity and did not require any surgical intervention compared with those diagnosed at a later stage. Six patients, all in the late diagnosis group, required surgical intervention. Conclusions: AK has become significantly more common in New Zealand in the current decade. This study highlights the fundamental importance of early diagnosis and appropriate management in ensuring favourable outcomes. Practitioners should maintain a clinical suspicion of AK, especially as 96% of the subjects in this study were contact lens wearers.     

Current status and future prospects for cultured limbal tissue transplants in Australia and New Zealand

Cultured limbal tissue transplants have become widely used over the last decade as a treatment for limbal stem cell deficiency (LSCD). While the number of patients afflicted with LSCD in Australia and New Zealand is considered to be relatively low, the impact of this disease on quality of life is so severe that the potential efficacy of cultured transplants has necessitated investigation. We presently review the basic biology and experimental strategies associated with the use of cultured limbal tissue transplants in Australia and New Zealand. In doing so, we aim to encourage informed discussion on the issues required to advance the use of cultured limbal transplants in Australia and New Zealand. Moreover, we propose that a collaborative network could be established to maintain access to the technology in conjunction with a number of other existing and emerging treatments for eye diseases.     

Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene

Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.      

Atrial septal defects: Magnetic resonance and computed tomography appearances

Atrial septal defects are associated with significant morbidity and mortality. Echocardiography is the first‐line imaging modality, but MR and CT imaging can provide complimentary information, especially for the detection of associated anomalies and for assessing changes in the pulmonary vasculature. The aim of this pictorial essay is to review the spectrum of atrial septal defects, with particular reference to their cross‐sectional imaging appearances and issues pertaining to management.     

Introductory comment

Objectives Injectable poly‐l ‐lactic acid (PLLA; Sculptra^®) is widely used throughout Europe and the USA to restore volume in depressed areas of the face by stimulating neocollagenesis. Injectable PLLA was previously marketed as New‐Fill™, which was often injected incorrectly and at too high a concentration, resulting in some physicians losing confidence in this product. Today, Sculptra^® is still regarded with a degree of scepticism by some physicians, due to direct or indirect experience with New‐Fill. Sculptra^®, both in formulation and use, is vastly superior to New‐Fill and clinical experience with this product dispels the myths associated with the earlier types of injectable PLLA. Results PLLA is a very safe, biodegradable compound that has been used in a wide range of medical devices for the last 30 years. In injectable form a good safety profile has been proven; however, when the device is overconcentrated, localized overstimulation of the fibroblasts can result in the formation of small lumps (subcutaneous papules), which are non‐pathological but nevertheless palpable by the patient. Physicians must also be trained in the injection of this device, as incorrect injection technique can cause device‐related adverse events. Conclusion New product guidelines have ensured that problems with PLLA concentration have been countered, and tried and tested injection techniques have been shown to ameliorate device‐related adverse events, both of which are dispelling the myths associated with modern injectable PLLA.     

The distribution of porcine pancreatic beta-cells at ages 5, 12 and 24 weeks

Jay TR, Heald KA, Carless NJ, Topham DE, Downing R. The distribution of porcine pancreatic beta-cells at ages 5, 12 and 24 weeks. Xenotransplantation 1999; 6: 131-140. ©Munksgaard, Copenhagen Islet transplantation is a potential treatment for diabetes mellitus and porcine pancreata may provide a readily available source of islets. The size, number and distribution of islets within the pancreas may influence the choice of age of donor for xenotransplantation. Samples (n = 3 per age group) from the dorsal and ventral pancreas of 5-, 12- and 24-week-old hybrid pigs were fixed in formal saline, processed in paraffin wax and stained with an avidin/biotin immunohistochemical kit for insulin, glucagon, somatostatin and pancreatic polypeptide. The arrangement of endocrine cells within the pancreata were studied and mean diameter of β-cell groups were measured (from insulin stained sections) in 1 mm² grid areas (n = 10 per section) and collated into groups according to size. Percentage volume density of β-cells in relation to the whole pancreas was calculated and also the distribution of β-cell groups, according to their size, within the total β-cell mass. There were differences in the frequency and arrangement of endocrine cells within islets at the different ages studied. β-Cell groups < 50 µm in diameter occupied 70 to 80% of the total β-cell mass at 5 weeks but, as the age of the pig increased, larger cell groups were more abundant. However, the percentage volume density of β-cells within the total pancreas did not change as the pancreas matured.This study shows that the endocrine porcine pancreas was maturing and its structure changed between the ages of 5 and 24 weeks. The relevance of these findings may have implications on the isolation and function of islets if young pigs are to be used as donors for transplantation as a treatment for diabetes mellitus.