Combination therapy with tacrolimus and anti-thymocyte globulin for the treatment of steroid-resistant acute graft-versus-host disease developing during cyclosporine prophylaxis

We report our experience with the combination of anti-thymocyte globulin (ATGAM) and tacrolimus in the treatment of 20 patients with steroid refractory and dependent acute graft-versus-host disease (GVHD) transplanted between August 1996 and February 2000. All patients received cyclosporine-based GVHD prophylaxis. Thirteen patients developed a maximum of grade TV, five grade III and two grade II acute GVHD, with 15 patients being refractory to steroids and five dependent on steroids. Patients were treated with ATGAM (15 mg/kg for 5 d) and tacrolimus (0.025-0.1 mg/kg/d) in addition to continuation of their high-dose steroids and cessation of their cyclosporine. Within 28 d of treatment, we observed eight complete responses (CR), six partial responses (PR) and six with no response. Overall response (CR + PR) was predicted by GVHD severity. Infectious complications occurred in 80% of patients. The median survival was 86.5 d (range, 21-1081 d) with 35% of patients remaining alive, Survival following combination therapy was significantly more likely in men (P < 0.001), skin-only GVHD (P = 0.027), less severe GVHD (P = 0.048), and in responders to tacrolimus and ATGAM (P< 0.001). In conclusion, concurrent introduction of ATGAM and tacrolimus is a promising therapeutic combination for GVHD refractory to steroids and cyclosporine.

Granulocyte-colony-stimulating factor (G-CSF)-primed allogeneic bone marrow: significantly less graft-versus-host disease and comparable engraftment to G-CSF-mobilized peripheral blood stem cells

Prospective studies have shown rapid engraftment using granulocyte-colony-stimulating factor-mobilized peripheral blood stem cells (G-PBSCs) for allogeneic transplantation, though the risks for graft-versus-host disease (GVHD) may be increased. It was hypothesized that the use of G-CSF to prime bone marrow (GBM) would allow rapid engraftment without increased risk for GVHD compared with G-PBSC. Patients were randomized to receive G-BM or G-PBSCs for allogeneic stem cell transplantation. The study was designed (beta < .8) to detect a difference in the incidence of chronic GVHD of 33% ( < .05). The plan was to recruit 100 patients and to conduct an interim analysis when the 6-month follow-up point was reached for the first 50 patients. Fifty-seven consecutive patients were recruited (G-BM, n = 28; G-PBSC, n = 29). Patients in the G-PBSC group received 3-fold more CD34(+) and 9-fold more CD3(+) cells. Median times to neutrophil (G-BM, 16 days; G-PBSC, 14 days; P < .1) and platelet engraftment (G-BM, 14 days; G-PBSC, 12 days; P < .1) were similar. The use of G-PBSC was associated with steroid refractory acute GVHD (G-BM, 0%; G-PBSC, 32%; P < .001), chronic GVHD (G-BM, 22%; G-PBSC, 80%; P < .02), and prolonged requirement for immunosuppressive therapy (G-BM, 173 days; G-PBSC, 680 days; P < .009). Survival was similar for the 2 groups. Compared with G-PBSC the use of G-BM resulted in comparable engraftment, reduced severity of acute GVHD, and less subsequent chronic GVHD. (Blood. 2001;98:3186-3191) (C) 2001 by The American Society of Hematology.

Response of a scleractinian coral, Stylophora pistillata, to iron and nitrate enrichment

The purpose of this study was to determine whether the addition of iron alone or in combination with nitrate affects growth and photosynthesis of the scleractinian coral, Stylophora pistillata, and its symbiotic dinoflagellates. For this purpose, we used three series of two tanks for a 3-week enrichment with iron (Fe), nitrate (N) and nitrate + iron (NFe). Two other tanks were kept as a control (C). Stock solutions of FeCl3 and NaNO3 were diluted to final concentrations of 6 nM Fe and 2 muM N and continuously pumped from batch tanks into the experimental tanks with a peristaltic pump. Results obtained showed that iron addition induced a significant increase in the areal density of zooxanthellae (ANOVA, p = 0.0013; change from 6.3 +/- 0.7 x 10(5) in the control to 8.5 +/- 0.6 x 10(5) with iron). Maximal gross photosynthetic rates normalized per surface area also significantly increased following iron enrichment (ANOVA, p = 0.02; change from 1.23 +/- 0.08 for the control colonies to 1.81 +/- 0.24 mu mol O-2 cm(-2) h(-1) for the iron-enriched colonies). There was, however, no significant difference in the photosynthesis normalized on a per cell basis. Nitrate enrichment alone (2 muM) did not significantly change the zooxanthellae density or the rates of photosynthesis. Nutrient addition (both iron and nitrogen) increased the cell-specific density of the algae (CSD) compared to the control (G-test, p = 0.3 x 10(-9)), with an increase in the number of doublets and triplets. CSD was equal to 1.70 +/- 0.04 in the Fe-enriched colonies, 1.54 +/- 0.12 in the N- and NFe-enriched colonies and 1.37 +/- 0.02 in the control. Growth rates measured after 3 weeks in colonies enriched with Fe, N and NFe were 23%, 34% and 40% lower than those obtained in control colonies (ANOVA. p = 0.011). (C) 2001 Elsevier Science B.V. All rights reserved.

Diurnal changes in the photochemical efficiency of the symbiotic dinoflagellates (Dinophyceae) of corals: photoprotection, photoinactivation and the relationship to coral bleaching

The photochemical efficiency of symbiotic dinoflagellates within the tissues of two reef-building corals in response to normal and excess irradiance at wafer temperatures < 30 C were investigated using pulse amplitude modulated (PAM) chlorophyll fluorescence techniques, Dark-adapted F-v/F-m showed clear diurnal changes, decreasing to a low at solar noon and increasing in the afternoon. However, F-v/F-m also drifted downwards at night or in prolonged darkness, and increased rapidly during the early morning twilight. This parameter also increased when the oxygen concentration of the wafer holding the corals was increased. Such changes have not been described previously, and most probably reflect state transition's associated with PQ pool reduction via chlororespiration. These unusual characteristics may be a feature of an endosymbiotic environment, reflective of the well-documented night-time tissue hypoxia that occurs in corals. F-v/F-m decreased to 0.25 in response to full sunlight in shade-acclimated (shade) colonies of Stylophora pistillata, which is considerably lower than in light-acclimated (sun) colonies. In sun colonies, the reversible decrease in F-v/F-m was caused by a lowering of F-m and F-o suggesting photoprotection and no lasting damage. The decrease in F-v/F-m, however, was caused by a decrease in F-m and an increase in F-o in shade colonies suggesting photoinactivation and long-term cumulative photoinhibition. Shade colonies rapidly lost their symbiotic algae (bleached) during exposure to full sunlight. This study is consistent with the hypothesis that excess light leads to chronic damage of symbiotic dinoflagellates and their eventual removal from reef-building corals. It is significant that this can occur with high light conditions alone.

Effects of phosphonate and salicylic acid treatments on anthracnose disease development and ripening of 'Kensington Pride' mango fruit

This study investigated treatment of mango (Mangifera indica L.) fruit with 2 host defence-promoting compounds for suppression of anthracnose disease (Colletotrichum gloeosporioides). Cultivar 'Kensington Pride' fruit were treated at concentrations of up to 1000 mg/L with either potassium phosphonate or salicylic acid. Applications were by various combinations of pre- and postharvest dips and vacuum infiltration. Postharvest treatments at up to 2000 mg/L salicylic acid were evaluated in a second fruiting season. Fruit were either uninoculated or inoculated with the fungal pathogen. Colour, firmness and disease-severity were assessed during shelf life at 23 degreesC. There were no significant (P>0.05) effects of potassium phosphonate or salicylic acid on anthracnose disease severity in the first season. Moreover, phosphonate or salicylic acid treatment did not significantly affect fruit colour or firmness changes. There were significant (P

Influence of fungal pathogens and environmental conditions on disease severity, flower fall and desiccation of harvested Geraldton waxflower - 2. Studies with commercial packages

Relationships were examined between environmental conditions mediated by packaging and handling and the deterioration of harvested Geraldton waxflower cv. 'Fortune Cookie'. Disease severity plus flower and leaf drop caused by inoculation with Botrytis cinerea were reduced by lowering handling temperatures to 0, 5 or 5/20 degreesC alternated daily, versus 20 degreesC. They were also reduced by inhibition of ethylene action with a silver thiosulfate pulse pretreatment. Additionally, treatments that enhanced water loss, such as packing dry, keeping forced air-cooling holes open and strategic placement of extra ventilation holes may also reduce disease severity and flower plus leaf fall. Inclusion of KMnO4-based Bloomfresh ethylene scrubbing sachets in packages did not reduce disease severity or lessen flower plus leaf fall. Thus, deterioration of waxflower packaged in commercial cartons can be minimised by keeping temperatures low, packing plant material dry, use of cartons with strategically placed ventilation holes and/or pretreatment with silver thiosulfate.

Characterisation of New Zealand isolates of infectious bursal disease virus

Isolates of infectious bursal disease virus (IBDV) were obtained from domestic poultry in New Zealand in 1997 and 1998. An in-vivo pathogenicity study carried out in specific pathogen free (SPF) chickens demonstrated the low virulence of one of the virus isolates. The nucleotide sequences of the hypervariable region of the VP2 gene of two isolates were determined and compared with published sequences of strains from other countries. The deduced amino acid sequence of the two New Zealand IBDV isolates showed 100% identity with each other, suggesting that little genetic drift had occurred. Phylogenetic analysis showed that the New Zealand isolates were more closely related to two attenuated IBDV strains (Cu1 and PBG98) than to classical (STC and 52/70), very virulent (DV86), variant (variant E) or Australian (002-73) strains. The results support the hypothesis that an attenuated strain of the virus was inadvertently introduced into the NZ poultry population in 1993.

Telehealth and the diagnosis and management of cardiac disease

The financial and personal burden of chronic cardiac disease is high. Costs are likely to increase over the next few decades. Promising applications of telehealth have appeared in the diagnosis and management of cardiac disease and there are indications that telehealth services can improve the management of chronic cardiac disease as well as extend services to remote and rural populations. Telehealth has been applied to the capture of symptoms of cardiac disease with electrocardiography and echocardiography, to the management and rehabilitation of recently discharged patients, and in peer-to-peer consultation where remote expertise can facilitate diagnosis. Telehealth promises cost reductions in service delivery, although there is a need for properly controlled cost-effectiveness trials to underpin telehealth with a firm evidence base.

Effect of propionyl-L-carnitine on exercise performance in peripheral arterial disease

Background: Supplementation with propionyl-L-carnitine (PLC) may be of use in improving the exercise capacity of people with peripheral arterial disease. Methods: After a 2-wk exercise familiarization phase, seven subjects displaying intermittent claudication were studied over a 12-wk period consisting of three 4-wk phases, baseline (B), supplementation (S), and placebo (P). PLC was supplemented at 2 g(.)d(-1), and subjects were blinded to the order of supplementation. Unilateral calf strength and endurance were assessed weekly. Walking performance was assessed at the end of each phase using an incremental protocol, during which respiratory gases were collected. Results: Although there was not a significant increase in maximal walking time (similar to 14%) in the whole group, walking time improved to a greater extent than the individual baseline coefficient of variation in four of the seven subjects. The changes in walking performance were correlated with changes in the respiratory exchange ratio both at steady state (r = 0.59) and maximal exercise (r = 0.79). Muscle strength increased significantly from 695 +/- 198 N to 812 +/- 249 N by the end of S. Changes in calf strength from B to S were modestly related to changes in walking performance (r = 0.56). No improvements in calf endurance were detected throughout the study. Conclusions: These preliminary data suggest that, in addition to walking performance, muscle strength can be increased in PAD patients after 4 wk of supplementation with propionyl-L-carnitine.

Alcoholic liver disease: A clinical series in an Australian private practice

Background and Aim: The published literature on alcoholic liver disease (ALD) in Australia lacks a large clinical series out of private practice as distinct from hospital-based hepatology referral units. This series describes the presentation and clinical features of ALD in a consecutive series out of metropolitan private practice in Australia. Methods: A retrospective descriptive study by case-note review found 297 cases of ALD at a Brisbane practice over 20 years. The main outcome measures were: clinical features and stage at presentation, reasons for referral, and the predictive value of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio. Results: Most patients (57.9%) had no symptoms of liver disease and 29 patients (9.8%) had neither symptoms nor signs. Cirrhosis was found in 41% of patients and hepatitis-fibrosis was found in 26% of patients. The male to female (M: F) ratio was 4.7:1. The AST/ALT ratio was not reliably predictive of ALD stage. The average reported daily alcohol intake was 131 g. Females drank less on average and presented a more vigorous clinical picture. Conclusions: This series presents the spectrum of ALD in a metropolitan Australian private practice. Many patients are asymptomatic on presentation. All heavy drinkers should be targeted for early investigation without waiting for volunteered symptoms or abnormal physical signs. The male to female ratio in ALD is higher than hitherto reported. The AST/ALT ratio is not generally applicable in the staging of ALD. The differences from hospital series data suggest the demography and epidemiology of ALD in Australia are incomplete, and further study is warranted. (C) 2001 Blackwell Science Asia Pty Ltd.

Familial Paget's disease of bone: Nonlinkage to the PDB1 and PDB2 loci on chromosomes 6p and 18q in a large pedigree

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis remains largely unknown. Susceptibility loci for Paget's disease of bone have been mapped to chromosome 6p21.3 (PDB1) and 18q121.1-q22 (PDB2) in different pedigrees, We have identified a large pedigree of over 250 individuals with 49 informative individuals affected with Paget's disease of bone; 31 of whom are available for genotypic analysis. The disease is inherited as an autosomal dominant trait in the pedigree with high penetrance by the sixth decade. Linkage analysis has been performed with markers at PDB1; these data show significant exclusion of linkage with log,, of the odds ratio (LOD) scores < -2 in this region. Linkage analysis of microsatellite markers from the PDB2 region has excluded linkage with this region, with a 30 cM exclusion region (LOD score < -2.0) centered on D18S42, These data confirm the genetic heterogeneity of Paget's disease of bone. Our hypothesis is that a novel susceptibility gene relevant to the pathogenesis of Paget's disease of bone lies elsewhere in the genome in the affected members of this pedigree and will be identified using a microsatellite genomewide scan followed by positional cloning.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system, While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation, Patients with negative washings had a DFS of 96'7e at 36 months compared with 67% for patients with positive washings (log-rank P < 0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.