Clinical penetrance of C282Y homozygous HFE haemochromatosis.

The prevalence of the C282Y homozygous HFE genotype is high, approximately 1 in 200 in populations of Anglo-Celtic descent, and most authorities assumed this mutation would have a high clinical penetrance. Recent studies report the clinical penetrance of C282Y homozygous hereditary haemochromatosis is much lower than its prevalence, with possibly less than 5% developing clinical disease, although there is lack of consensus on a precise estimate. This review discusses reasons for this paradigm shift, including controversy on various definitions of clinical penetrance.

Case report: immune anti-D stimulated by transfusion of fresh frozen plasma.

FFP has occasionally been reported to generate an immune response to RBC antigens (e.g., anti-D and anti-Fya).

Australian multicentre comparison of subtyping methods for the investigation of Campylobacter infection.

In order to identify subtyping methods able to contribute to the surveillance or investigation of Australian Campylobacter infection, six genotypic and three phenotypic subtyping methods were evaluated on a collection of 84 clinical isolates collected over a 30-month period from one region in Australia. The aim was to compare the logistics of various subtyping methods and examine their ability to assist in finding outbreaks or common sources of sporadic infection. The genotypic subtyping methods used were sequencing of the short variable region of the flaA gene, two methods using restriction fragment length polymorphism (RFLP) of the flaA gene using either DdeI or EcoRI with PstI, automated ribotyping, pulsed field gel electrophoresis and multilocus sequence typing.

Folate levels and cancer morbidity and mortality: prospective cohort study from Busselton, Western Australia.

Purpose: To test a community population for the hypothesis that carcinogenesis is related to blood folate levels.

Methods: Prospective analysis of cancer mortality data for a cohort of 964 men (person-time follow up: 20,254 years) and 1024 women (person-time follow up: 24,970 years) and morbidity data for a subcohort, all of whom participated in the 1969 Busselton (Western Australia) Health survey. Outcome measures were adjusted hazard ratios according to baseline folate levels for total cancer mortality and morbidity and site specific mortality and morbidity for colorectal, lung, breast, and prostate cancers.

Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a joint consensus conference of the Growth Hormone Research Society and the Pituitary Society.

In April 2003, the Growth Hormone (GH) Research Society and The Pituitary Society developed a consensus statement to address the current status of both biochemical assessment and long-term monitoring in patients with acromegaly. They also highlighted the pitfalls of current GH and Insulin-like Growth Factor-1 (IGF-1) assay methodologies and the difficulties in defining target GH and IGF-1 levels in treated acromegaly.

Combination assay detecting both human immunodeficiency virus (HIV) p24 antigen and anti-HIV antibodies opens a second diagnostic window.

Fourth-generation human immunodeficiency virus (HIV) screening immunoassays reduce the diagnostic window between infection and diagnosis by the inclusion of HIV p24 antigen detection together with HIV antibody detection in the same test. We compared third- and fourth-generation HIV immunoassays and a dedicated HIV p24 antigen test for detection of a case of HIV seroconversion. This demonstrated a second diagnostic window using the fourth-generation assay due to a decline of HIV p24 antigen prior to the detection of HIV antibody.

Pathology reporting of breast cancer: trends in 1989-1999, following the introduction of mammographic screening in Western Australia.

Background: A survey of pathology reporting of breast cancer in Western Australia in 1989 highlighted the need for improvement. The current study documents (1) changes in pathology reporting from 1989 to 1999 and (2) changes in patterns of histopathological prognostic indicators for breast cancer following introduction of mammographic screening in 1989.

Methods: Data concerning all breast cancer cases reported in Western Australia in 1989, 1994 and 1999 were retrieved using the State Cancer Registry, Hospital Morbidity data system, and pathology laboratory records.

Can HPV DNA testing on FNA material determine anogenital origin in metastatic squamous cell carcinoma?

Aims: Currently there are no diagnostic techniques that can precisely determine the primary site of a metastatic squamous cell carcinoma (SCC). Anogenital SCC has a high prevalence of high-risk (HR) human papillomavirus (HPV) DNA, particularly in the cervix where the value approaches 100%, whereas non-anogenital SCC generally has a low prevalence. The aim of this study was to examine whether the finding of HR HPV DNA in a fine needle aspiration (FNA) of metastatic SCC could be used to determine a likely anogenital origin.

Multiplex nested PCR (MNP) assay for the detection of 15 high risk genotypes of human papillomavirus.

Background: Human papillomavirus (HPV) is now recognized as the causative agent in cervical cancer. The HPV genotypes that infect the genital region have been classified into high and low risk types according to their oncogenic potential. There is still uncertainty regarding rare HPV genotypes, however the types considered high risk in this study are: HPV-16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 70.

Gastrointestinal stromal tumours (GISTs): a clinicopathological and molecular study of 66 cases.

Aims: Predicting the clinical behaviour of gastrointestinal stromal tumours (GISTs) is difficult and criteria delineating benign from malignant cases are not firmly established. The aims of this study were to define the clinicopathological and molecular features of 66 GISTs, and to determine whether any specific parameters were associated with patient outcome.

Methods: Archival cases of GIST from two major teaching hospitals in Western Australia were studied.

Comparison of diagnostic laboratory methods for identification of Burkholderia pseudomallei.

Limited experience and a lack of validated diagnostic reagents make Burkholderia pseudomallei, the cause of melioidosis, difficult to recognize in the diagnostic microbiology laboratory. We compared three methods of confirming the identity of presumptive B. pseudomallei strains using a collection of Burkholderia species drawn from diverse geographic, clinical, and environmental sources.

Stromelysin-1 (MMP-3) gene 5A/6A promoter polymorphism is associated with blood pressure in a community population.

Background And Objectives: Arterial remodelling contributes to the development of hypertension. Stromelysin-1 (MMP-3), a member of the matrix metalloproteinase family may contribute to this process. Stromelysin-1 gene expression is partly regulated by a common polymorphism in the promoter region of either five or six consecutive adenosine bases (5A/6A).

Hepatic iron loading in patients with compound heterozygous HFE mutations.

Aim: To assess the severity of hepatic iron loading in patients with a compound heterozygous C282Y/H63D HFE genotype.

Methods: A total of 246 patients were referred to the Hepatology Clinic at a tertiary hospital for HFE genotyping and further assessment of elevated serum transferrin saturation and/or ferritin results, either with or without abnormal liver function tests. Subjects of the study were 19 patients compound heterozygous for HFE who had liver biopsy, quantitative liver iron estimation and liver histopathology.

Preliminary report on the northern Australian melioidosis environmental surveillance project.

An environmental surveillance programme was developed to determine whether water supplies could be a source of Burkholderia pseudomallei as noted during previous melioidosis outbreak investigations. Water supplies to communities in the three northern Australian jurisdictions (Western Australia, Northern Territory and Queensland) were sampled periodically during 2001 and 2002. Water and soil samples were collected from communities known to have had recent culture-positive melioidosis cases and nearby communities where no cases had been diagnosed.

Expression of the HFE hemochromatosis gene in a community-based population of elderly women.

Background And Aim: Recent studies suggest that the clinical penetrance of associated hereditary hemochromatosis, defined as either the C282Y homozygote or compound heterozygote HFE genotype status, is much lower than previously thought.

Methods: We investigated the clinical penetrance and phenotypic expression of HFE-associated hereditary hemochromatosis in a community-based population of 1352 elderly female subjects with a mean age of 75 years. Serum transferrin saturation and ferritin levels were determined on all subjects bearing a C282Y mutation and a subset of wild-type C282Y subjects.

Perineurioma: a clinicopathological study of eight cases.

Aims: Perineuriomas (PN) are uncommon, benign neoplasms that mimic a number of benign and malignant soft tissue lesions. There are two main forms: a rare intraneural PN (IPN), and a relatively more common extraneural soft tissue PN (STPN) including a conventional form (STPNc), sclerosing (SPN), reticular and lipomatous variants. Their diagnosis requires immunohistochemical (IHC) and/or ultrastructural (US) confirmation of perineurial cell differentiation.

Reduced breast cancer risk with increasing serum folate in a case-control study of the C677T genotype of the methylenetetrahydrofolate reductase gene.

Breast cancer risk may be associated with folate status or the C677T genotype of the methylenetetrahydrofolate reductase (MTHFR) gene. We compared serum folate concentrations and C677T genotype in 141 breast cancer patients and 109 age-matched controls. Serum folate was significantly lower in cases compared to controls (geometric means, 5.

Quality assessment of interpretative commenting in clinical chemistry.

Background: Clinical interpretation of laboratory results is an integral part of clinical chemistry. However, the performance goals for assessing interpretative commenting in this discipline have not been as well established as for the quality of analytical requirements.

Methods: We present a review of the 10 case reports circulated in the 2002 Patient Report Comments Program by the Royal College of Pathologists of Australasia (RCPA) and the Australasian Association of Clinical Biochemists Chemical Pathology Group of RCPA-Quality Assurance Programs Pty Ltd.

The role of molecular studies in lymphoma diagnosis: a review.

Lymphoma classification is based on a multiparametric approach to diagnosis, in which clinical features, morphology, immunophenotype, karyotype and molecular characteristics are important to varying degrees. While in most cases, a diagnosis can be confidently established on the basis of morphology and immunophenotype alone, a small proportion of diagnostically difficult cases will rely on molecular studies to enable a definitive diagnosis. This review discusses the various molecular techniques available including Southern blotting (SB), polymerase chain reaction (PCR), fluorescence in situ hybridisation (FISH)--including multicolour-FISH/spectral karyotyping and comparative genomic hybridisation--and also gene expression profiling using cDNA microarray technology.

Paradoxical embolism secondary to ovarian carcinoma resulting in stroke.

A middle aged woman presented with a posterior fossa stroke after an elective ear nose and throat procedure. The occurrence of a paradoxical embolism was suspected. The evidence for this and a discussion about this condition are presented.

The value of HPV DNA typing in the distinction between adenocarcinoma of endocervical and endometrial origin.

Aims: Distinguishing between adenocarcinomas of endocervical and endometrial origin histologically can be difficult, particularly in small biopsies. Most endocervical adenocarcinomas contain human papillomavirus (HPV) deoxyribonucleic acid (DNA) of 'high-risk' (HR) types, whereas this has not been consistently demonstrated in endometrial adenocarcinomas. The aim of this study was to determine whether HPV DNA testing could aid in this differential diagnosis.

Real-time application of automated ribotyping and DNA macrorestriction analysis in the setting of a listeriosis outbreak.

A cluster of three cases of listeriosis cases occurred against a background of endemic listeriosis in Western Australia. Human and environmental isolates of Listeria monocytogenes obtained during the outbreak investigation were rapidly subtyped by automated ribotyping using an EcoRI protocol and a RiboPrinter. DNA macrorestriction analysis by pulsed-field gel electrophoresis (PFGE) was used to confirm the relatedness of isolates.

National atypical mycobacteria survey, 2000.

Infections with atypical mycobacteria in Australia during 2000 occurred at a rate of 1.8 cases per 100,000 population. The main sites of disease were the respiratory tract, soft tissue, and the lymphatics.

Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice.

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE).