(FAB01_091) Book reviews

Leon Battista Alberti, 'On the Art of Building in Ten Books' Translated by Joseph Rykwert, Neil Leach and Robert Tavemor L. A. Zhadova (ed.), 'Tatlin' (Budapest 1984). English translation Helen Ross, 'Just For Living, Aboriginal Perceptions of Housing in North West Australia' Tony Fry, 'Design History Australia: A Source Text in Methods and Resources' Phillip Cox and David Moore, 'The Australian Functional Tradition' Lenore Coltheart and Don Fraser (eds.), 'Lamdmarks in Public Works, Engineers and Their Works in New South Wales 1884-1914' Peter Bridges and Don MacDonald, 'James Barnet, Colonial Architect' Don Watson and Judith McKay, 'A Directory of Queensland Architects to 1940' Russell Walden, 'Voices of Silence: New Zealand's Chapel of Futuna' Jeremy Salmond, 'Old New Zealand Houses 1800-1940' Victoria Middleton, 'The Legend of Green Valley' Dyranda Prevost and Ann Rado, 'Living Places' Mark Jackson and Mark Stiles (directors), 'Universal Provider' Lars Lerup, 'Planned Assaults'

Bioimpedance spectrometry in the determination of body water compartments: Accuracy and clinical significance

Bioelectrical impedance analysis (BIA) offers the potential for a simple, portable and relatively inexpensive technique for the in vivo measurement of total body water (TBW). The potential of BIA as a technique of body composition analysis is even greater when one considers that body water can be used as a surrogate measure of lean body mass. However, BIA has not found universal acceptance even with the introduction of multi-frequency BIA (MFBIA) which, potentially, may improve the predictive accuracy of the measurement. There are a number of reasons for this lack of acceptance, although perhaps the major reason is that no single algorithm has been developed which can be applied to all subject groups. This may be due, in part, to the commonly used wrist-to-ankle protocol which is not indicated by the basic theory of bioimpedance, where the body is considered as five interconnecting cylinders. Several workers have suggested the use of segmental BIA measurements to provide a protocol more in keeping with basic theory. However, there are other difficulties associated with the application of BIA, such as effects of hydration and ion status, posture and fluid distribution. A further putative advantage of MFBIA is the independent assessment not only of TBW but also of the extracellular fluid volume (ECW), hence heralding the possibility of,being able to assess the fluid distribution between these compartments. Results of studies in this area have been, to date, mixed. Whereas strong relationships of impedance values at low frequencies with ECW, and at high frequencies with TBW, have been reported, changes in impedance are not always well correlated with changes in the size of the fluid compartments (assessed by alternative and more direct means) in pathological conditions. Furthermore, the theoretical advantages of Cole-Cole modelling over selected frequency prediction have not always been apparent. This review will consider the principles, methodology and applications of BIA. The principles and methodology will,be considered in relation to the basic theory of BIA and difficulties experienced in its application. The relative merits of single and multiple frequency BIA will be addressed, with particular attention to the latter's role in the assessment of compartmental fluid volumes. (C) 1998 Elsevier Science Ltd. All rights reserved.

Localisation of gelatinase activity in epidermal hoof lamellae by in situ zymography

In situ gelatin zymography is a technique, which utilises a gelatin-based emulsion overlay to detect and, more importantly, localise the gelatinase activity in underlying tissue. Gelatinase A [matrix metalloproteinase-2 (MMP-2)] and gelatinase B [matrix metalloproteinase-9 (MMP-9)] are present in equine hoof homogenates and supernatants from cultured hoof explants by SDS-PAGE gelatin zymography, and it has been assumed that the enzymes are derived solely from matrix and epithelia and not from other sources such as leucocytes. Using in situ zymography, gelatinases are shown to be localised within the equine epidermal hoof lamellae and, more specifically, are apparently produced by epidermal basal and/or parabasal cells. The pattern of expression correlates with that expected based on the progression of pathological changes observed during the onset of laminitis, thus providing further evidence that laminitis pathology probably arises as a result of inadequate local MMP regulation.

Long-term risk of first recurrent stroke in the Perth Community Stroke Study

Background and Purpose-Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke. This study aimed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population-based series of people with first-ever stroke in Perth, Western Australia. Methods-Between February 1989 and August 1990, all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results-Three hundred seventy patients with a first-ever stroke were registered, of whom 351 survived >2 days. Data were available for 98% of the cohort at 5 years, by which time 199 patients (58%) had died and 52 (15%) had experienced a recurrent stroke, 12 (23%) of which were fatal within 28 days. The 5-year cumulative risk of first recurrent stroke was 22.5% (95% confidence limits [CL], 16.8%, 28.1%). The risk of recurrent stroke was greatest in the first 6 months after stroke, at 8.8% (95% CL, 5.4%, 12.1%). After adjustment for age and sex, the prognostic factors for recurrent stroke were advanced, but not extreme, age (75 to 84 years) (hazard ratio [HR], 2.6; 95% CL, 1.1, 6.2), hemorrhagic index stroke (HR, 2.1; 95% CL, 0.98, 4.4), and diabetes mellitus (HR, 2.1; 95% CL, 0.95, 4.4). Conclusions-Approximately 1 in 6 survivors (15%) of a first-ever stroke experience a recurrent stroke over the next 5 years, of which 25% are fatal within 28 days. The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88% of cases. The predictors of first recurrent stroke in this study were advanced age, hemorrhagic index stroke, and diabetes mellitus, but numbers of recurrent events were modest. Because the risk of recurrent stroke is highest (8.8%) in the first 6 months after stroke, strategies for secondary prevention should be initiated as soon as possible after the index event.

Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice

Previously we described activating mutations of h beta(c), the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, h beta(c)FI Delta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the h beta(c)FI Delta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in h beta(c) may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic h beta(c) activation has the potential to contribute to pathological events in the central nervous system.

Placental growth hormone (GH), GH-binding protein, and insulin-like growth factor axis in normal, growth-retarded, and diabetic pregnancies: Correlations with fetal growth

We previously described significant changes in GH-binding protein (GHBP) in pathological human pregnancy. There was a substantial elevation of GHBP in cases of noninsulin-dependent diabetes mellitus and a reduction in insulin-dependent diabetes mellitus. GHBP has the potential to modulate the proportion of free placental GH (PGH) and hence the impact on the maternal GH/insulin-like growth factor I (IGF-I) axis, fetal growth, and maternal glycemic status. The present study was undertaken to investigate the relationship among glycemia, GHBP, and PGH during pregnancy and to assess the impact of GHBP on the concentration of free PGH. We have extended the analysis of specimens to include measurements of GHBP, PGH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), IGFSP-2, and IGFBP-3 and have related these to maternal characteristics, fetal growth, and glycemia. The simultaneous measurement of GHBP and PGH has for the first time allowed calculation of the free component of PGH and correlation of the free component to indexes of fetal growth and other endocrine markers. PGH, free PGH, IGF-I, and IGF-II were substantially decreased in IUGR at 28-30 weeks gestation (K28) and 36-38 weeks gestation (K36). The mean concentration (+/-SEM) of total PGH increased significantly from K28 to K36 (30.0 +/- 2.2 to 50.7 +/- 6.2 ng/mL; n = 40), as did the concentration of free PGH (23.4 +/- 2.3 to 43.7 +/- 6.0 ng/mL; n = 38). The mean percentage of free PGH was significantly less in IUGR than in normal subjects (67% vs. 79%; P < 0.01). Macrosomia was associated with an increase in these parameters that did not reach statistical significance. Multiple regression analysis revealed that PGH/IGF-I and IGFBP-5 account for 40% of the variance in birth weight. IGFBP-3 showed a significant correlation with IGF-I, IGF-II, and free and total PGK at K28 and K36. Noninsulin-dependent diabetes mellitus patients had a lower mean percentage of free PGH (65%; P < 0.01), and insulin-dependent diabetics had a higher mean percentage of free PGH (87%; P < 0.01) than normal subjects. Mean postprandial glucose at K28 correlated positively with PGH and free PGH (consistent with the hyperglycemic action of GH). GHBP correlated negatively with both postprandial and fasting glucose. Although GHBP correlated negatively with PGH (r = -0.52; P

Glutamate-mediated transmission, alcohol, and alcoholism

Glutamate-mediated neurotransmission may be involved in the range of adaptive changes in brain which occur after ethanol administration in laboratory animals, and in chronic alcoholism in human cases. Excitatory amino acid transmission is modulated by a complex system of receptors and other effecters, the efficacy of which can be profoundly affected by altered gene or protein expression. Local variations in receptor composition may underlie intrinsic regional variations in susceptibility to pathological change. Equally, ethanol use and abuse may bring about alterations in receptor subunit expression as the essence of the adaptive response. Such considerations may underlie the regional localization characteristic of the pathogenesis of alcoholic brain damage, or they may form part of the homeostatic change that constitutes the neural substrate for alcohol dependence. (C) 2000 Elsevier Science Ltd. All rights reserved.

Magnetic resonance imaging (MRI) and diseases of the liver and biliary tract. Part 1. Basic principles, MRI in the assessment of diffuse and focal hepatic disease

Magnetic resonance imaging (MRI) relies on the physical properties of unpaired protons in tissues to generate images. Unpaired protons behave like tiny bar magnets and will align themselves in a magnetic field. Radiofrequency pulses will excite these aligned protons to higher energy states. As they return to their original state, they will release this energy as radio waves. The frequency of the radio waves depends on the local magnetic field and by varying this over a subject, it is possible to build the images we are familiar with. In general, MRI has not been sufficiently sensitive or specific in the assessment of diffuse liver disease for clinical use. However, because of the specific characteristics of fat and iron, it may be useful in the assessment of hepatic steatosis and iron overload. Magnetic resonance imaging is useful in the assessment of focal liver disease, particularly in conjunction with contrast agents. Haemangiomas have a characteristic bright appearance on T-2 weighted images because of the slow flowing blood in dilated sinusoids. Focal nodular hyperplasia (FNH) has a homogenous appearance, and enhances early in the arterial phase after gadolinium injection, while the central scar typically enhances late. Hepatic adenomas have a more heterogenous appearance and also enhance in the arterial phase, but less briskly than FNH. Hepatocellular carcinoma is similar to an adenoma, but typically occurs in a cirrhotic liver and has earlier washout of contrast. The appearance of metastases depends on the underlying primary malignancy. Overall, MRI appears more sensitive and specific than computed tomography with contrast for the detection and evaluation of malignant lesions. (C) 2000 Blackwell Science Asia Pty Ltd.

Is there a role for axillary dissection for patients with operable breast cancer in this era of conservatism?

Background: The trend in breast cancer surgery is toward more conservative operative procedures. The new staging technique of sentinel node biopsy facilitates the identification of pathological node-negative patients in whom axillary dissection may be avoided. However, patients with a positive sentinel node biopsy would require a thorough examination of their nodal status. An axillary dissection provides good local control, and accurate staging and prognostic information to inform decisions about adjuvant therapy. In addition, the survival benefit of axillary treatment is still debated. The objectives of the present study were to examine the pattern of lymph node metastases in the axilla, and evaluate the merits of a level III axillary dissection. Methods : Between June 1997 and May 2000, 308 patients underwent a total of 320 level III dissections as part of their treatment for operable invasive breast cancer. The three axillary levels were marked intraoperatively, and the contents in each level were submitted and examined separately. The patterns of axillary lymph node (ALN) metastases were examined, and factors associated with 4 positive nodes, and level III ALN metastases were evaluated by univariate and multivariate analyses. Results: An average of 25 lymph nodes were examined per case (range: 8-54), and using strict anatomical criteria, the mean numbers of ALN found in levels I, II and III were 18 (range: 2-43), 4 (range: 0 19), and 3 ( range: 0-11), respectively. Axillary lymph node involvement was found in 45% of the cases (143/320). Of the 143 cases, 78% (n = 111) had involvement of level I nodes only, and 21% (n = 30) had positive ALN in levels II and, or, III, in addition to level I. Involvement of lymph nodes in level II or III without a level I metastasis was found in two cases only (0.6%). By including level II, in addition to level I, in the dissection, four cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.64). By the inclusion of level III to a level I and II dissection, three cases (1%) were converted from one to three positive nodes to 4 positive nodes (P = 0.74). Involvement of lymph nodes in level III was found in 22 cases (7%), and 51 cases (16%) had 4 positive nodes. Palpability of ALN, pathological tumour size, and lymphovascular invasion (LVI), were significantly associated with level III involvement and 4 positive nodes by univariate and multivariate analyses. The frequencies of level III involvement and 4 positive nodes in patients with palpable ALN were 22% and 42%, respectively. The corresponding frequencies in patients with a clinically negative axilla, and a primary tumour which was >20 mm and LVI positive, were over 14% and 31%, respectively. Conclusion: Level III axillary dissection is appropriate for patients with palpable ALN, and in those with a tumour which is >20 mm and LVI positive, principally to reduce the risk of axillary recurrence. Staging accuracy is achieved with a level II dissection, or even a level I dissection alone based on strict anatomical criteria. Sentinel node biopsy is a promising technique in identifying pathological node-positive patients in whom an axillary clearance provides optimal local control and staging information.

Identification of "pathologs" (disease-related genes) from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

Background: A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term patholog to mean a homolog of a human disease-related gene encoding a product ( transcript, anti-sense or protein) potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. Results: Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity ( 70 - 85% identity) to known human-disease genes. Using a newly developed biological information extraction and annotation tool ( FACTS) in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic ( 53%), hereditary ( 24%), immunological ( 5%), cardio-vascular (4%), or other (14%), disorders. Conclusions: Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

Attentional modulation of visual cortex activity following right parietal damage in humans

Pathological inattention following parietal damage causes perceptual impairments for visual stimuli in the contralesional hemifield. Here we used functional magnetic resonance imaging (fMRI) to examine visual cortex activity in parietal patients as they performed a spatial attention task. Righthemisphere patients and healthy controls viewed counterphasing checkerboards in which coloured targets appeared briefly within the contralesional and ipsilesional hemifields. In separate fMRI runs participants focused their attention covertiy on the left or right hemifield, or on both hemifields concurrentiy. They were required to detect coloured targets that appeared briefly within the attended hemifield(s), and to withhold responses to distractor stimuli. Neural activit}' was significantly attenuated in early visual areas within the damaged hemisphere. Crucially, although attention significantiy modulated early visual activit}' within the intact (left) hemisphere, there was relatively littie modulation of activity within the affected hemisphere. Our findings suggest that parietal lesions alter early cortical responses to contralesional visual inputs.

The effect of hearing impairment on the vocal characteristics of older people

Measures of vocal intensity, frequency and harshness were compared for 19 hearing-impaired and 21 normal-hearing people over 60 years of age. Significantly greater comfortable intensity levels were found in the hearing-impaired group, but the other measures of frequency and harshness were not significantly different. A large proportion of the subjects in both groups reported a history of gastro-oesophageal reflux (GER), a condition associated with vocal fold pathology and hoarseness. Comparison of the GER and non-GER subjects on the measures of vocal function showed that the female GER speaker exhibited lower frequency on the vowel /u/ than the non-GER subjects. Clinicians need to be aware of the effect of highly prevalent disorders such as hearing impairment and GER on the voices of elderly speakers.

Helminth parasite communities of the water-rat, Hydromys chrysogaster, from Queensland

The helminth fauna from 124 water-rats, Hydromys chrysogaster, collected from 33 localities in Queensland was analysed. A total of 45 species of helminths was found, comprising 2 acanthocephalans, 2 cestodes, 13 nematodes and 28 trematodes. The helminth community of the water-rats in the region north of latitude 18 degrees (far north) was different from that of water-rats south of 18 degrees (central); Sorensen's Index 45.8% similarity, whereas Holmes and Podesta's Index gave 32.1% similarity. Comparisons with data from water-rats from southern and Tasmanian regions showed that they were different from each other and from both Queensland regions. The helminth communities were characterised by high diversity, dominated by trematodes in the central and Tasmanian regions, but with nematodes becoming more prominent in the far northern and southern regions. No core or secondary species were found in the Queensland helminth communities, the southern community was suggestive of a bimodal distribution and the Tasmanian had two core species. A checklist of helminth species occurring in water-rats from eastern Australia is provided.

Features of colorectal cancers with high-level microsatellite instability occurring in familial and sporadic settings

High-level microsatellite instability (AISI-H) is demonstrated in 10 to 15% of sporadic colorectal cancers and in most cancers presenting In the inherited condition hereditary nonpolyposis colorectal cancer (HNPCC). Distinction between these categories of MSI-H cancer is of clinical importance and the aim of this study was to assess clinical, pathological, and molecular features that might he discriminatory. One hundred and twelve MSI-H colorectal cancers from families fulfilling the Bethesda criteria were compared with 57 sporadic MSI-H colorectal cancers. HNPCC cancers presented at a lower age (P < 0.001) with no sporadic MSI-H cancer being diagnosed before the age of 57 years. MSI was less extensive in HNPCC cancers with 72% microsatellite markers showing band shifts compared with 87% in sporadic tumors (P < 0.001). Absent immunostaining for hMSH2 was only found in HNPCC tumors. Methylation of bMLH1 was observed in 87% of sporadic cancers but also in 55% of HNPCC tumors that showed loss of expression of hMLH1 (P = 0.02). HNPCC cancers were more frequently characterized by aberrant beta -catenin immunostaining as evidenced by nuclear positivity (P < 0.001). Aberrant p53 immunostaining was infrequent in both groups. There were no differences with respect to 5q loss of heterozygosity or codon 12 K-ras mutation, which were infrequent in both groups. Sporadic MSI-H cancers were more frequently heterogeneous (P < 0.001), poorly differentiated (P = 0.02), mucinous (P = 0.02), and proximally located (P = 0.04) than RNPCC tumors. In sporadic MSI-H cancers, contiguous adenomas were likely to be serrated whereas traditional adenomas were dominant in HNPCC. Lymphocytic infiltration was more pronounced in HNPCC but the results did not reach statistical significance. Overall, HNPCC cancers were more like common colorectal cancer in terms of morphology and expression of beta -catenin whereas sporadic MSI-H cancers displayed features consistent with a different morphogenesis. No individual feature was discriminatory for all RN-PCC cancers. However, a model based on four features was able to classify 94.5% of tumors as sporadic or HNPCC. The finding of multiple differences between sporadic and familial MSI-H colorectal cancer with respect to both genotype and phenotype is consistent with tumorigenesis through parallel evolutionary pathways and emphasizes the importance of studying the two groups separately.