Surviving the 'heartsink' experience

The authors describe a pilot workshop designed to help doctorsachieve a greater understanding of and ability to cope withtheir ‘heartsink’ patients. Participants were askedto list their personal objectives in attending and a numberof cases were discussed in the group. A ‘heartsink survivalkit’ was provided which consisted of skills and strategieswhich are useful in difficult consultations and an approachto reassessing the goals of the relationship which might promotea more realistic understanding. The workshop was videotapedand two scenarios are presented. The implications for furthertraining are discussed.     

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.      

Occupational exposure to cis-1,3-dichloropropene: biological effect monitoring of kidney and liver function

OBJECTIVES—To investigate the possible effects of occupational exposure to the nematocide cis-1,3-dichloropropene (cis-DCP) on function of the kidney and liver in the starch potato growing region in The Netherlands.
METHODS—The study involved 13 commercial application workers exposed to cis-DCP for 117 days, and 22 matched control workers. The inhalatory exposure of the application workers was estimated from biological monitoring data. All workers collected urine and serum samples before, during, and after the fumigation season for monitoring of variables for kidney and liver function. Renal effect variables were alanine aminopeptidase (AAP), N-acetyl-β-D-glucosaminidase (NAG), retinol binding protein (RBP), and albumin (ALB) in urine, and β₂-microglobulin (β₂M-S) and creatinine in serum (Creat-S). Liver variables were alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltranspeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) in serum and the urinary ratio of 6-β-hydroxycortisol to free cortisol (βOHC/COR).
RESULTS—The geometric mean exposure of the application workers was 2.7 mg/m³ (8 hour time weighted average (8 hour TWA)); range 0.1-9.5 mg/m³. No differences were found between the values of the renal effect variables or the liver variables of the exposed group and the control group, except a lower urinary ratio of βOHC/COR in the exposed group. This was not considered to be related to the exposure to cis-DCP. No dose-effect relations were found between the exposure indices and the effect variables.
CONCLUSIONS—The present study does not provide evidence that occupational exposure to cis-DCP in the starch potato growing region causes adverse effects on the kidney or liver at 8 hour TWA exposure concentrations below 9.5 mg/m³ (2 ppm).


Keywords: cis-1,3-dichloropropene; occupational exposure; kidney; liver     

Rapid brain penetration of interleukin-1 receptor antagonist in rat cerebral ischaemia: pharmacokinetics,distribution, protection

Background and purpose:

Limited data on the brain penetration of potential stroke treatments have been cited as a major weakness contributing to numerous failed clinical trials. Thus, we tested whether interleukin-1 receptor antagonist (IL-1RA), established as a potent inhibitor of brain injury in animals and currently in clinical development, reaches the brain via a clinically relevant administration route, in experimental stroke.

Experimental approach:

Male, Sprague-Dawley rats [either naïve or exposed to middle cerebral artery occlusion (MCAo)] were given a single s.c. dose of IL-1RA (100 mg·kg⁻¹). The pharmacokinetic profile of IL-1RA was assessed in plasma and CSF up to 24 h post-administration. Brain tissue distribution of administered IL-1RA was assessed using immunohistochemistry. In a separate experiment, the neuroprotective effect of the single s.c. dose of IL-1RA in MCAo was assessed versus a placebo control group.

Key results:

A single s.c. dose of IL-1RA reduced damage caused by MCAo by 33%. This dose resulted in sustained, high concentrations in plasma and CSF, penetrated brain tissue exclusively in areas of blood–brain barrier breakdown and co-localized with morphologically viable neurones. CSF concentrations did not reflect massive parenchymal infiltration of IL-1RA in MCAo animals compared to naïve.

Conclusions and implications:

These data are the first to show that a potential treatment for stroke, IL-1RA, rapidly reaches salvageable brain tissue via an administration route that is clinically relevant. This allows confidence that IL-1RA, as a candidate for further clinical development, is able to confer its protective actions both peripherally and centrally.