Ascaris lumbricoides and Ascaris suum vary in their larval burden in a mouse model.

Ascariasis is a neglected tropical disease, caused by Ascaris lumbricoides, affecting 800 million people worldwide. Studies focused on the early stage of parasite infection, occurring in the gut, liver and lungs, require the use of a mouse model. In these models, the porcine ascarid, Ascaris suum, is often used. The results obtained from these studies are then used to draw conclusions about A. lumbricoides infections in humans. In the present study, we sought to compare larval migration of A. suum and A. lumbricoides in mouse models. We used a previously developed mouse model of ascariasis, which consists of two mouse strains, where one mouse strain - C57BL/6J - is a model for relative susceptibility and the other - CBA/Ca - for relative resistance. Mice of both strains were infected with either A. suum or A. lumbricoides. The larval burden was assessed in two key organs, the liver and lungs, starting at 6 h post infection (p.i.) and ending on day 8 p.i. Additionally, we measured the larval size of each species (µm) at days 6, 7 and 8 p.i. in the lungs. We found that larval burden in the liver is significantly higher for A. lumbricoides than for A. suum. However, the inverse is true in the lungs. Additionally, our results showed a reduced larval size for A. lumbricoides compared to A. suum.

Widespread hybridization within mound-building wood ants in Southern Finland results in cytonuclear mismatches and potential for sex-specific hybrid breakdown.

Hybridization and gene flow between diverging lineages are increasingly recognized as common evolutionary processes, and their consequences can vary from hybrid breakdown to adaptive introgression. We have previously found a population of wood ant hybrids between Formica aquilonia and F. polyctena that shows antagonistic effects of hybridization: females with introgressed alleles show hybrid vigour, whereas males with the same alleles show hybrid breakdown. Here, we investigate whether hybridization is a general phenomenon in this species pair and analyse 647 worker samples from 16 localities in Finland using microsatellite markers and a 1200-bp mitochondrial sequence. Our results show that 27 sampled nests contained parental-like gene pools (six putative F. polyctena and 21 putative F. aquilonia) and all remaining nests (69), from nine localities, contained hybrids of varying degrees. Patterns of genetic variation suggest these hybrids arise from several hybridization events or, instead, have backcrossed to the parental gene pools to varying extents. In contrast to expectations, the mitochondrial haplotypes of the parental species were not randomly distributed among the hybrids. Instead, nests that were closer to parental-like F. aquilonia for nuclear markers preferentially had F. polyctena's mitochondria and vice versa. This systematic pattern suggests there may be underlying selection favouring cytonuclear mismatch and hybridization. We also found a new hybrid locality with strong genetic differences between the sexes similar to those predicted under antagonistic selection on male and female hybrids. Further studies are needed to determine the selective forces that act on male and female genomes in these newly discovered hybrids.

IGF-I does not affect the proliferation or early osteogenic differentiation of human marrow stromal cells.

The ability of insulin-like growth factor-I (IGF-I) to regulate the proliferation and differentiation of primitive osteogenic precursors (CFU-F) has been investigated in cultures of bone marrow stromal cells (BMSC) derived from a large cohort of adult human donors. Treatment with IGF-I (0.1-20 ng/mL, days 0-28) had no consistent effect on the number or size of colonies that formed or the proportion of colonies that expressed the developmental marker alkaline phosphatase (AP). At the end of primary culture, similar numbers of cells were harvested from the control and IGF-I-treated groups and there was no detectable difference in the expression of AP (activity or percentage of positive cells) or the developmental marker STRO-1. This was found to be the case whether IGF-I was added alone or in combination with 10 nM dexamethasone (Dx), a known inducer of osteogenic differentiation in this cell culture system. In contrast, cells derived from the same cohort of donors responded to treatment with fibroblast growth factor-2 (FGF-2) with an increase in the number and size of the colonies that formed, in proliferation and in the number of cells recovered in STRO-1(+)/AP(+) (osteoprogenitor) fraction. Further analysis revealed that the majority of BMSC expressed the alpha and beta subunits of the type 1 receptor for IGF-I (IGF-IR), in the expected 1:1 ratio. Treatment with Dx did not affect the expression of these receptor subunits (percentage of positive cells or number of sites per cell) but did increase the proportion of cells present in the IGF-I(+)/AP(+) fraction. The results of this investigation suggest that the beneficial effects of IGF-I on the skeleton are not mediated primarily via an effect on osteoprogenitor fraction and are thus consistent with the hypothesis that the effects of IGF-I are differentiation dependent and restricted largely to the more mature cells of the osteoblast lineage.

The application of computer touch-screen technology in screening for psychosocial distress in an ambulatory oncology setting.

The objective of the study was to evaluate the acceptability and feasibility of computer touch-screen technology as a method for patients to report psychosocial functioning in an ambulatory cancer clinic. Patients participating in a randomized trial evaluating the use of self-reported psychosocial information in the clinical encounter were surveyed. The patients completed the Cancer Needs Questionnaire (CNQ), European Organization for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the Beck Depression Inventory - Short Form (BDI) using a touch-screen computer. The time taken to complete the questionnaires was recorded electronically. Patients completed a seven-item pen and paper survey to assess acceptability of the process. Of the 450 patients, 244 (54%) were 60 years or older. Although over half the patients had no prior computer experience, nearly all found the touch screen easy to use and the instructions easy to understand. Each question was answered by at least 447 (99.3%) patients. The average time to complete the CNQ was 9.1 min, EORTC QLQ-C30 4.0 min and BDI 3.1 min. Factors influencing time to completion were prior use of computers, physical condition, education and overall level of needs. The study found that the use of computer touch-screen technology is an acceptable and efficient method for obtaining self-reported information on quality of life, cancer needs and psychological distress.

Uptake of psychosocial referrals in an outpatient cancer setting: improving service accessibility via the referral process.

The object of this study was to identify factors which influence the uptake of psychosocial services in an ambulatory cancer setting and to identify potential barriers to the access of support services in the referral process. To this end, 202 individuals attending outpatient clinics of a cancer hospital were randomised to the intervention arm of a study to assess the impact of providing co-ordinated, targeted psychosocial referrals and interventions. Qualitative and quantitative analysis of the reasons for failure to offer services and for nonacceptance of services was undertaken. Individuals accepted 22% of offered services, refused 38% of offered services, indicated that services were in place in 31% of cases, and were not offered 9% of identified services. The major response from patients refusing services was "not now". Female patients ( P < 0.01), and individuals with a moderate to high level of depression ( P = 0.02), were more likely to accept services. A variety of factors impact on decisions on utilisation of support services. Recommendations on how individuals' access to these services might be improved are offered, based on an analysis of the reasons given by patients for refusal.

Methotrexate in the treatment of rheumatoid arthritis. I. In vitro effects on cells of the osteoblast lineage.

OBJECTIVE: Low-dose methotrexate (MTX) is often used in the treatment of rheumatoid arthritis (RA). To be effective, treatment must be long-term, and there are concerns that MTX may impair bone formation in a population already predisposed to osteoporosis. The purpose of this investigation was to determine the direct effects of MTX at clinically relevant doses on the growth and differentiation of human cells of the osteoblast (bone-forming) lineage. METHODS: Cells derived from the marrow stroma (BMSC) and trabecular surfaces [human bone-derived cells (HBDC)] of adult ribs were cultured in the absence or presence of MTX (1-1000 nM). To promote the differentiation and further maturation of cells of the osteoblast lineage, one half of the cultures were treated additionally with 10 nM dexamethasone (Dx). RESULTS: In cultures of BMSC, treatment with MTX (+/-Dx) did not affect the total number of colonies that formed or the expression of the developmental markers STRO-1 and alkaline phosphatase (AP). At concentrations > or =10 nM, however, there was a statistically significant reduction in the number of cells harvested at the end of primary culture. In cultures of HBDC, treatment with MTX (in the presence of Dx) did not affect cell number or the expression of AP. CONCLUSIONS: At concentrations > or =10 nM, treatment with MTX inhibits the proliferation of primitive marrow stromal cells, but not their ability to undergo osteogenic differentiation. The proliferation and further maturation of cells of the osteoblast lineage is not affected by treatment with MTX. These findings are reassuring for clinicians using MTX in the treatment of RA.

Methotrexate in the treatment of rheumatoid arthritis. II. In vivo effects on bone mineral density.

OBJECTIVE: To determine the effect of methotrexate (MTX) on bone mineral density (BMD) in rheumatoid arthritis (RA). METHODS: One hundred and sixteen non-steroid-treated RA subjects (90 women) were studied in a prospective, longitudinal, non-randomized study. Subjects started MTX (n=36) or sulphasalazine (n=23) or continued long-term (>5 yr) treatment with MTX (n=28) or other disease-modifying anti-rheumatic drugs (n=29). BMD was estimated at entry and after 1 yr. Markers of bone turnover were measured at entry and at 1 yr, and additionally at 3 and 6 months in those starting treatment. Bone biopsies were taken before and after MTX treatment in four subjects. The primary outcome was change in BMD Z score and secondary outcomes were changes in bone turnover markers and bone formation by histomorphometry. RESULTS: Univariate analysis of covariance found that MTX at baseline was associated with reduced BMD at the femoral neck. However, femoral neck BMD was also associated with radiological damage score for the hand. Multivariate analysis and discriminant analysis of the subset of post-menopausal women showed that reduced bone density associated with MTX was due to confounders such as disease activity. There was no adverse effect of MTX on bone turnover markers or on measures of bone formation in biopsies. CONCLUSIONS: No adverse effect of low-dose MTX (mean 10 mg/week) on bone formation in RA was found.

Randomized trial of coordinated psychosocial interventions based on patient self-assessments versus standard care to improve the psychosocial functioning of patients with cancer.

PURPOSE: To determine whether making patient-reported cancer needs, quality-of-life (QOL), and psychosocial information available to the health care team, allowing coordinated specifically targeted psychosocial interventions, resulted in reduced cancer needs, improved QOL, and increased satisfaction with care received. METHODS: Self-reported cancer needs, QOL, and psychosocial information was collected from 450 people with cancer, using standardized questionnaires via a touch-screen computer. For a randomly chosen two thirds, this information was made available to the health care team who coordinated targeted psychosocial interventions. Information from the remaining one third was not seen. Patients were assessed 2 and 6 months after randomization for changes in their cancer needs, QOL, and psychosocial functioning and satisfaction with overall care received. RESULTS: There were no significant differences between the two arms with respect to changes in cancer needs, QOL, or psychosocial functioning between the baseline and follow-up assessments, nor with respect to satisfaction with care. However, for the subgroup of patients who were moderately or severely depressed at baseline, there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment (P =.001). CONCLUSION: Making patient-reported cancer needs, QOL, and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL, psychosocial functioning, or satisfaction with the care received. However, identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression.

Comparison of refractive state and circumferential morphology of retina, choroid, and sclera in chick models of experimentally induced ametropia.

PURPOSE: Simultaneous comparisons of the circumferential morphological tissue profiles and final refractions from form-deprivation myopia (FDM), defocus-induced myopia (DIM), and defocus-induced hyperopia (DIH) models of ametropia have been made to test the hypothesis that changes in the thickness profiles of the three coats of the eye, and particularly that of the choroid, can be predicted from the degree of induced refractive error. METHODS: Hatchling chickens (n = 23) were raised for 2 weeks wearing either a monocular translucent diffuser (FDM, n = 8), monocular -10.00 D lens goggle (DIM, n = 7), monocular +10.00 D lens goggle (DIH, n = 7), or nothing (Norm, n = 1). All animals were refracted using retinoscopy and were then sacrificed, and whole eyes were processed for scanning electron microscopy. Retinal, choroidal, and cartilaginous sclera (CS) thickness measurements were made from photographic collages of the entire circumference of the globe. Of the 23 chickens, complete morphological profile data were available for both eyes of 10 animals (nine treated and one normal). The contralateral fellow eyes (FEyes) of all nine experimental chickens were used as experimental controls as paired comparisons for statistical analyses. RESULTS: Morphological profiles of control and experimental eyes revealed significant systematic regional variations in tissue thickness. This variation was related to nasal or temporal eccentricity with the nasal side generally thinner than the temporal. Retinal, choroidal, and CS tissue from FDM and DIM eyes showed very similar anatomical responses despite significantly different degrees of refractive change. DIH eyes showed significant increases in choroidal thickness but none in retinal or CS thickness. Analysis of fellow control eyes indicated that in both myopia models (FDM and DIM), significant changes in all tissues of the untreated fellow eyes occur whereas only the choroid of the fellow eye was affected in the hyperopic (DIH) model. CONCLUSIONS: The morphological similarity observed in the circumferential profiles of the retina, choroid, and cartilaginous sclera of the FDM and DIM eyes despite approximately 20 D difference in final refraction suggests that choroidal thickness is not a good predictor of final refractive error across models. Similarly, the final refractive difference of approximately 20 D between the DIM and the DIH eyes did not receive a major contribution from the final difference in choroidal thickness (with its implied effect on vitreous chamber length).

High concentrations of dexamethasone suppress the proliferation but not the differentiation or further maturation of human osteoblast precursors in vitro: relevance to glucocorticoid-induced osteoporosis.

OBJECTIVE: The use of glucocorticoids (GCs) in the treatment of RA is a frequent cause of bone loss. In vitro, however, this same class of steroids has been shown to promote the recruitment and/or maturation of primitive osteogenic precursors present in the colony forming unit-fibroblastic (CFU-F) fraction of human bone and marrow. In an effort to reconcile these conflicting observations, we investigated the effects of the synthetic GC dexamethasone (Dx) on parameters of growth and osteogenic differentiation in cultures of bone marrow stromal cells derived from a large cohort of adult human donors (n=30). METHODS: Marrow suspensions were cultured in the absence and presence of Dx at concentrations between 10 pm and 1 microm. After 28 days we determined the number and diameter of colonies formed, the total number of cells, the surface expression of receptors for selected growth factors and extracellular matrix proteins and, based on the expression of the developmental markers alkaline phosphatase (AP) and the antigen recognized by the STRO-1 monoclonal antibody, the proportion of cells undergoing osteogenic differentiation and their extent of maturation. RESULTS: At a physiologically equivalent concentration, Dx had no effect on the adhesion of CFU-F or on their subsequent proliferation, but did promote their osteogenic differentiation and further maturation. These effects were independent of changes in the expression of the receptors for fibroblast growth factors, insulin-like growth factor 1, nerve growth factor, platelet-derived growth factors and parathyroid hormone/parathyroid hormone-related protein, but were associated with changes in the number of cells expressing the alpha(2) and alpha(4), but not beta(1), integrin subunits. At supraphysiological concentrations, the effects of Dx on the osteogenic recruitment and maturation of CFU-F and their progeny were maintained but at the expense of a decrease in cell number. CONCLUSIONS: A decrease in the proliferation of osteogenic precursors, but not in their differentiation or maturation, is likely to be a key factor in the genesis of GC-induced bone loss.

Patterns of integrin expression in a human mandibular explant model of osteoblast differentiation.

Cell-matrix interaction is crucial in regulating osteoblast differentiation and function. These interactions are themselves regulated, at least in part, by integrins. Although there are some data from mammalian models, few studies have compared integrin expression at different stages of the osteoblast lineage. Here, primary human mandibular osteoblast cultures were grown in the presence of epidermal growth factor (EGF), giving a proliferative, less differentiated phenotype, or of vitamin D(3) and hydrocortisone (D+Hc), giving a more differentiated phenotype. These cultures were compared with those of cells prepared in the absence of EGF or D+Hc by fluorescence-activated cell sorter using a panel of monoclonal antibodies to specific integrin heterodimers. To provide in vivo correlation, the same panel of antibodies was used to stain fresh-frozen, undemineralised sections of human mandibular bone. Under baseline conditions the alpha(3), alpha(5), alpha(v), alpha(v)beta(3), beta(3) and beta(1) integrin subunits were expressed strongly by the cells, with low-level expression of the alpha(1), alpha(2) and alpha(4) subunits. In the presence of EGF there was increased alpha(2) expression. With D+Hc, alpha(3) and alpha(5) expression was elevated. Immunohistochemical analysis demonstrated alpha(2), alpha(3), alpha(5), alpha(v)beta(3), beta(1) and beta(3) subunits in cells of the osteoblast lineage; alpha(2) staining was restricted to cells close to the bone surface whilst alpha(v)beta(3) and beta(3) were most frequently localised in the osteocytes. The results provide evidence that cells at successive stages of the osteoblast lineage show different patterns of integrin expression. These integrins may be important in cell-matrix interactions leading to osteoblast differentiation.

Expression of the developmental markers STRO-1 and alkaline phosphatase in cultures of human marrow stromal cells: regulation by fibroblast growth factor (FGF)-2 and relationship to the expression of FGF receptors 1-4.

Autologous marrow stromal cells have been proposed as an adjuvant in the treatment of bone defects and diseases. This will require the development of culture conditions that permit their rapid expansion ex vivo while retaining their potential for further differentiation. Fibroblast growth factor (FGF)-2 has been proposed as a candidate for the ex vivo expansion of cells with enhanced osteogenic potential, and we have explored this possibility further using cells obtained from a large cohort of adult human donors. Treatment with FGF-2 (0.001-2.5 ng/mL) had no detectable effect on colony formation, but markedly increased their proliferative potential and that of their immediate progeny, as shown by the increases in colony size and cell number. Based on the observed increase in the expression of the developmental markers STRO-1 and alkaline phosphatase (AP), a major target for the actions of FGF-2 appears to be the more primitive cells of the osteoblast lineage, and that, when added in combination with the synthetic glucocorticoid dexamethasone (Dx), it interacts positively to promote further cell maturation. The maintenance of adequate levels of ascorbate was shown to be a critical component in determining the nature of the effect of FGF-2 on AP expression. Variation in the response (predominantly in the magnitude and/or sensitivity) of the cultured cell populations to treatment with FGF-2 was apparent, but a preliminary analysis indicated that this was not due to differences in the age or gender of the donors used. The cultured cell populations were found to express multiple FGF receptors (FGFRs; 1-4) and the observed changes in the spectrum and abundance of FGFRs expressed in relation to that of STRO-1 and AP are consistent with their expression being developmentally regulated during the process of osteogenic differentiation. These results provide novel insights into the mechanism of action of FGF-2 on human cells of the osteoblast lineage and support the use of this factor, alone or in combination with Dx, for the rapid, ex vivo expansion of cell populations with enhanced osteogenic potential.

Squamous cell carcinoma of the lip: a retrospective review of the Peter MacCallum Cancer Institute experience 1979-88.

BACKGROUND: Squamous cell carcinoma (SCC) of the lower lip is a common malignancy in Australia. Surgical excision and/or radiotherapy are used in treatment, and are regarded as equally effective. METHODS: A retrospective review of 323 patients treated at the Peter MacCallum Cancer Institute with either surgical excision and/or radiotherapy, evaluated disease recurrence, cause-specific mortality, and the incidence of metachronous lesions. RESULTS: Recurrence-free survival at 10 years was estimated to be 92.5%, and cause-specific survival at 10 years was estimated to be 98.0%. Equivalent rates of local control were obtained with surgery and radiotherapy. Recurrence was related to tumour stage and differentiation. A high incidence of metachronous lesions was noted, 25 patients had a lesion prior to presentation and 33 patients developed second lip lesions during the study period. CONCLUSIONS: Squamous cell carcinoma of the lower lip is well treated with surgery or radiotherapy. The preferred treatment for most patients with SCC of the lower lip in the Australian population is surgical excision. This study has shown a significant incidence of metachronous lip neoplasia, except in those patients whose whole lip had been resurfaced.

Varicella-zoster infection after allogeneic bone marrow transplantation: incidence, risk factors and prevention with low-dose aciclovir and ganciclovir.

We examined the incidence of herpes varicella-zoster virus (VZV) infection in 151 patients undergoing allogeneic BMT between August 1990 and September 1997 and who survived at least 3 months. Median follow-up was 17 (range 3.3-80.7) months. Herpes simplex virus antibody positive (HSV+) patients received aciclovir 1200 mg p.o. daily or 750 mg i.v. daily, in divided doses from day 0 to engraftment. Ganciclovir (5 mg/kg i.v. three times per week) was given in CMV+ patients (or if the donor was CMV+) from engraftment to day 84. Ganciclovir was continued or recommenced if a dose of greater than 20 mg of prednisone was used for the treatment of GVHD otherwise aciclovir was recommenced. In HSV+ patients not receiving ganciclovir, aciclovir 600 mg p.o. daily in divided doses was given until at least 6 months after BMT. Thirty-two patients developed VZV infection from 4.1 to 28 months after transplant. The estimated cumulative incidence of VZV was 13% (95% confidence interval 6-19%) at 12 months, 32% (22-42%) at 24 months and 38% (27-50%) at 28 months, with no further cases beyond that time. No patient developed VZV whilst receiving aciclovir or ganciclovir (P < 0.0001). However, there was a rapid onset of VZV following cessation of antiviral therapy (33% (20-46%) at 1 year post cessation). The presence of GVHD and the prior duration of antiviral prophylaxis were significant and independent risk factors for the development of VZV. Age, underlying disease, conditioning therapy or donor type were not. We conclude that 3-6 months of low-dose aciclovir and ganciclovir are effective at delaying the onset of VZV after allogeneic BMT, but may not affect the overall incidence of infection. Prolonged prophylaxis may be warranted in patients at high risk of infection, for example those patients with GVHD.

Giant gastric ulcer: its natural history and outcome in the H2RA era.

OBJECTIVE: The aim of this paper is to study the natural history and outcome of medical treatment of giant gastric ulcer in the histamine H2-receptor antagonist era. METHODS: All patients with gastric ulcer were prospectively followed. We assessed the special features (in particular, demography and treatment outcome) in patients with giant gastric ulcer, defined as ulcers large enough to occupy at least one wall. RESULTS: Between 1976 and 1991, 537 patients with gastric ulcer were seen, of whom 129 (24%) had giant gastric ulcer. Giant gastric ulcer patients were significantly older (p < 0.05) than patients with smaller ulcers and had more aggressive disease, reflected by a higher incidence of bleeding, anorexia, weight loss, and emergency admission. More giant gastric ulcers were located in the body of the stomach and a higher proportion looked malignant. Four of 129 patients died immediately (bleed n = 3, unrelated cause n = 1), 15 had urgent surgery (bleed n = 11, perforation n = 2, suspected cancer n = 2) and 110 were treated medically, mainly with cimetidine 1 g daily. Healing occurred in 97 of 110 (88%), including 14 of 15 with refractory disease, i.e., healing took >3 months and/or needed cimetidine 2-3 g daily. Of the remaining 13 patients, six died (from unrelated causes), three had surgery for failed medical treatment, two defaulted, and two were still on treatment (one with refractory ulcer). Refractoriness was more common in patients with associated major medical illness (42% vs 12%, p < 0.01) or with giant gastric ulcers that looked malignant although they were benign (53% vs 21%, p < 0.01). Relapse off treatment was higher (13 of 26) than on maintenance treatment with cimetidine 0.4-2 g daily (14 of 70). Complications occurred in six patients: four off treatment and two on maintenance treatment. Only two giant gastric ulcers finally proved to be malignant. Of the 129 patients, 47 (36%) died, 14 within 3 months (two from bleeding, three postoperatively, nine from unrelated causes) and 33 later (two with gastric cancer and 31 from unrelated causes). CONCLUSIONS: Giant gastric ulcer is uncommon. Patients are more seriously ill than those with smaller ulcers. Most giant gastric ulcers heal with histamine H2-receptor antagonist treatment. The condition is a marker of poor general health, reflected by the high long term mortality.

Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukaemia.

We evaluated the outcome of allogeneic bone marrow transplantation (BMT) for advanced acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in 383 adult patients in nine Australian adult BMT centres between 1981 and 1997. The median overall survival for the group was 4.8 months, with an estimated 5-year survival of 18%. 28% of patients died of transplant-related toxicities within the first 100 d. Progressive disease was responsible for 48% of deaths. Multi-factor analysis demonstrated that AML (v ALL), disease status (second complete remission [CR2] v others), age (< 40 years) and duration of prior first complete remission (CR1) (> 6 months) were pre-transplant variables significantly associated with improved survival. Acute graft-versus-host disease (GVHD) of any grade reduced the rate of relapse in both AML and ALL, but only grades I-II were associated with improved survival. Both limited and extensive chronic GVHD were associated with increased survival. Only patients with AML in untreated first relapse or CR2, with a duration of CR1 > 6 months, or patients with T ALL, had a 5-year survival > 20%. Transplants for AML in induction failure or pre-B ALL in untreated first relapse or CR2 had an intermediate outcome, with 5-year survival of 10-20%. A 5-year survival of < 10% was observed for patients transplanted for ALL in induction failure or for pre-B ALL or AML in refractory first relapse or beyond CR2. These results suggest that for most adult patients with advanced acute leukaemia an allograft offers only a small chance of cure.

A technique for in vivo measurement of photoreceptor orientation in the chicken retina.

The aim of the current study was to develop a method for simultaneously assessing central and peripheral photoreceptor alignment in vivo in animal models. The stimulus apparatus consisted of nine light-emitting diodes (LED) positioned 7.5 degrees apart around an arc. The stimulus was viewed through a pinhole imaged into the entrance pupil of the eye using a telecentric lens system. Photodiodes placed over an array of the VERIS imaging system stimulated the electroretinogram. Data were obtained by positioning the pinhole at 0.25-mm intervals across the pupil and recording (Volk Optical, Mentor, OH, USA) at each location. Orientation assessed in normal chickens demonstrates that photoreceptors orientate towards a locus near the centre of the pupil and that there is a systematic change in peak location with eccentricity. This technique provides a valuable method for determining photoreceptor orientation properties in vivo and can be applied to animal models of pathology.

Further characterization of cells expressing STRO-1 in cultures of adult human bone marrow stromal cells.

Primitive cells of the osteoblast lineage are not well characterized but are known to be present within the STRO-1+ fraction of adult human bone and marrow. A survey of human osteosarcoma cell lines revealed that STRO-1 is expressed by MG-63 but not SaOS-2. Among murine cell lines tested, expression of STRO-1 was detected in the bipotential (adipocyte/osteoblast) line BMS-2 but not the committed osteoblast precursor MC3T3-E1. A proportion of cultured adult human bone marrow stromal cells (BMSCs) consistently expressed the STRO-1 antigen. The expression of a range of cell surface antigens was studied in relation to STRO-1 by flow cytometry and several, including the bone/liver/kidney isoform of alkaline phosphatase (ALP), were found to subtype the STRO-1+ population of BMSCs. Further, BMSCs dual-labeled with antibodies recognizing STRO-1 and ALP could be assigned to one of four fractions: STRO-1-/ALP-, STRO-1+/ALP-, STRO-1+/ALP+, and STRO-1-/ALP+. Cells from each fraction could be isolated in high purity and, when recultured, remained viable and exhibited a limited degree of phenotypic stability. Using reverse transcriptase-polymerase chain reaction, cells in the four fractions were found to express different levels of transcripts for the parathyroid hormone receptor (PTHr) and bone sialoprotein (BSP). The expression of transcripts for the nuclear transcription factor core-binding factor alpha 1/osteoblast-specific factor-2 (CBFA1/OSF2) was restricted to those fractions expressing STRO-1 and/or ALP. Treatment with 10 nM dexamethasone consistently increased the proportion of cells present in those fractions which expressed the highest levels of transcripts for PTHr and BSP (STRO-1+/ALP+ and STRO-1-/ALP+) while simultaneously decreasing the proportion present in the STRO-1+/ALP- fraction. In conclusion, the expression of STRO-1 in vitro remains a characteristic of less well differentiated cells of the osteoblast lineage; in cultures of BMSCs and in established human osteosarcoma cell lines, there is an inverse association between the expression of STRO-1 and ALP; dual labeling of BMSCs with monoclonal antibodies recognizing STRO-1 and ALP permits the identification and isolation of cells of the osteoblast lineage at different stages of differentiation.

Increased survival in patients diagnosed with Hodgkin's disease in Tasmania, 1972-1992.

BACKGROUND: It has been shown that in certain populations the prognosis of Hodgkin's disease (HD) has improved markedly since the late 1960s. This has not been formally demonstrated in an Australian population. AIMS: To review all patients in Tasmania diagnosed with HD between 1972 and 1992, and to ascertain whether variation in survival is evident in this group over this period. METHODS: Tasmanian patients with HD diagnosed from 1978 to 1992 were identified retrospectively from the Tasmanian Cancer Registry database. Identification of those diagnosed prior to 1978 was obtained from a previously published data set. To be valid for inclusion, subjects were required to have been diagnosed between January 1972 and December 1992, enabling a minimum four year follow up period. Survival was assessed by contacting patients' medical practitioners and by examining the most current electoral roll, medical records, and the register of births, deaths and marriages. Univariate and multivariate analyses were performed of the influence on prognosis of age, sex, histological subtype and epoch of diagnosis; information concerning stage of disease was not available. RESULTS: During the period of this study 206 patients were newly diagnosed as having HD. Comparisons of cases diagnosed in the successive seven-year epochs 1972-8, 1979-85 and 1986-92 revealed a significant increase in survival duration (p = 0.023), with ten year survival rates of 46%, 55% and 73% respectively. In a multivariate analysis adjusting for age, sex and histology, each successive epoch was associated with an estimated 28% reduction in the death rate relative to the preceding epoch (p = 0.022). CONCLUSIONS: There was a significant improvement in the survival duration of patients diagnosed with HD in Tasmania over the period 1972-92, which was possibly due to a combination of better diagnostic techniques and more effective treatments.