Search PubMed⌕ Search

Biomedical subjects

A Green

Publications and source records attributed to A Green.

At least 109 records · Page 6Linked to original sources
PubMed2000

T cell-depleted unrelated donor bone marrow transplantation for acute myeloid leukemia.

The outcome for 39 patients with acute myeloid leukemia (AML) in remission who had CAMPATH 1M T cell-depleted unrelated donor bone marrow transplantations (BMTs) is described. Conditioning was mainly with cyclophosphamide (120 mg/kg) and total body irradiation (TBI) (14.4 Gy), but 5 patients received busulfan in place of TBI and 200 mg/kg cyclophosphamide. All patients received cyclosporin, and short-course methotrexate was given to recipients of mismatched grafts. The patient population was predominantly pediatric (median age, 10 years), but one third of the patients was aged 15 years or above. Twenty-five patients were in second complete remission (CR2), and 14 had high-risk CR1 disease (primarily failed remission induction or antecedent myelodysplastic syndrome, often with complex cytogenetic abnormalities). Both recipient and donor were cytomegalovirus seronegative in 15 of 37 cases (38%); 51% of patients were matched for HLA class I and II. Grade II to IV acute graft-versus-host disease (GVHD) occurred in 24% of patients; chronic GVHD occurred in 5 of 31 evaluable patients (16%), 4 extensive and 1 limited. Relapse occurred in 5 cases (13%); 1 of these 5 patients survives, 24 months after a second unrelated donor transplantation. Two of these relapses were associated with secondary graft failure (incidence rate, 5%). All patients engrafted primarily. Severe viral infection was the major transplant-associated complication, with 12 episodes in 9 patients, 5 of them lethal. Twenty-five patients survive at a median follow-up of 44 months (range, 2-102 months), with estimated actuarial overall and disease-free survival rates at 44 months of 61% (SE 8%) and 57% (SE 8%), respectively. Nineteen patients are more than 2 years post-BMT and may be cured. The functional status of long-term survivors is excellent, with 19 of 21 patients who survive 6 months or more in full-time employment or full-time students. These encouraging results suggest that in patients lacking a sibling donor, unrelated donor BMT for AML in remission achieves survival figures as good as or better than those reported on patients with autologous stem cell transplantation, and that T-cell depletion of grafts is associated with a low relapse rate and an excellent functional status. However, only a randomized study comparing unrelated donor BMT and auto-grafting will resolve which of these treatment strategies is better for patients with AML.

Acute Disease↗
PubMed2000

Cellular responses of mammary carcinomas to aromatase inhibitors: effects of vorozole.

Vorozole (Vz) is a competitive non-steroidal inhibitor of aromatase, which has been used to treat breast cancer in postmenopausal women and in various chemoprevention pre-clinical studies. Recently, we assessed the inhibitory effect of Vz on MNU-induced mammary carcinogenesis (Lubet et al., 1994), as well as on the progression of mammary tumors (Lubet et al., 1998). In this study we evaluated the effects of Vz on tumor growth, serum estradiol, cell proliferation, apoptotic and non-apoptotic cell death to determine whether any of these 'surrogate' markers might reflect the efficacy of various doses of Vz. Vz at doses of 2.5 (Hi), 0.32 (Md), and 0.08 (Lo) mg/kg body weight induced complete (100%), 60%, and 20% regression of mammary tumors, respectively. Vz at Hi and Md doses caused a decrease in serum estradiol within the first two days of treatment, and the estradiol values remained low with additional treatment for 4 and 10 days. When Vz was administered to animals bearing palpable tumors a time and dose-dependent decrease in the proliferating cells (BrdU-L1) was observed. The percentage of apoptotic cells (A1) sharply increased 2 days after initiation of Vz treatment and then decreased followed by an increase in non-apoptotic dead cells. Interestingly even the Lo dose of Vz, which was only moderately effective in suppressing tumor growth, decreased cell proliferation and increased cell death in the peripheral tumor areas at 4 and 10 days after initiation of treatment. The time- and dose-dependent alterations in various cell parameters suggest two different phases of Vz-induced cellular responses: (1) an early phase (2-4 days of treatment) with a sharp increase in apoptotic cells and decrease in proliferating cells, and (2) a later phase (10 days) with disintegration of tumor parenchyma, increase in non-apoptotic dead cells, and decrease in apoptotic cells. The dose-dependent decrease in proliferating cells and increase in apoptotic and non-apoptotic cell death in Vz-treated animals suggest that these biomarkers might be used as potential surrogate endpoints for efficacy in breast cancer chemoprevention and therapy studies with aromatase inhibitors.

Animals↗
PubMed2000

Characterization of [(3)H]-CGP54626A binding to heterodimeric GABA(B) receptors stably expressed in mammalian cells.

Functional human GABA(B(1a,2)) and GABA(B(1b,2)) receptors have been stably expressed in mammalian CHO K1 cells. Detailed characterization of GABA(B) ligand binding at each of the receptors has been compared using [(3)H]-CGP54626A. In cell membranes fractions, [(3)H]-CGP54626A bound to a single site with a K(D) of 1. 51+/-1.12 nM, B(max) of 2.02+/-0.17 pmoles mg protein(-1) and 0. 86+/-0.20 nM, B(max) of 5.19+/-0.57 pmoles mg protein(-1) for GABA(B(1a,2)) and GABA(B(1b,2)) respectively. In competition binding assays the rank order was identical for both GABA(B) receptors. For known GABA(B) agonists the rank order was CGP27492>SKF97541=CGP46381>GABA>Baclofen and for GABA(B) antagonists the rank order was CGP54262A>CGP55845>CGP52432>SCH 50911>CGP51176>CGP36742=CGP35348 > or =2-OH Saclofen > or =ABPA. The allosteric effect of calcium cations was also investigated. The effect of removal of CaCl(2) from the binding assay conditions was ligand dependent to either cause a decrease in ligand affinity or to have no significant effect. However, these effects were similar for both GABA(B) receptors. A whole cell, scintillation proximity binding assay was used to determine agonist affinity at exclusively heterodimeric GABA(B) receptors. In competition assays, the rank order was the same for both GABA(B(1a,2)) and GABA(B(1b,2)) and consistent with that seen with cell membrane fractions. These data suggest that, in terms of ligand binding, the currently identified isoforms of the GABA(B) receptor are pharmacologically indistinguishable.

Animals↗
PubMed2000

N-acetylcysteine replenishes glutathione in HIV infection.

BACKGROUND: Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. DESIGN: Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks. SUBJECTS: HIV-infected, low GSH, CD4 T cells < 500 micro L(-1), no active opportunistic infections or other debilitation; n = 81. Study conducted prior to introduction of protease inhibitors. RESULTS: Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P = 0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and beta2-microglobulin levels, also increased in the NAC-treated subjects (P = 0.04). Adverse effects were minimal and not significantly associated with NAC ingestion. CONCLUSION: NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.

Acetylcysteine↗
PubMed2000

Geographical differences within Finland in the frequency of HLA-DQ genotypes associated with type 1 diabetes susceptibility. The Childhood Diabetes in Finland Study Group.

Geographical variations in the HLA-DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south-west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA-DQB1 genotypes between south-western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, chi2 test). These differences reflected the allele frequencies in newborn cohorts in which HLA-DQB1*02 and DQB1*0301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national 'Childhood Diabetes in Finland' (DiMe) study between the years 1986-1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study.

Adolescent↗
PubMed2000

Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT).

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. OBJECTIVE: To estimate (i) the prevalence of PAVM, and (ii) the occurrence of neurological symptoms in a geographical well-defined population of HHT patients. METHODS: HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for pulmonary arteriovenous malformations and neurological evaluation. Two groups served as controls: (i) first-degree relatives without any signs of HHT; and (ii) age- and gender-matched controls. SETTING: Odense University Hospital. SUBJECTS: HHT patients identified in a cross-sectional family survey carried out in the County of Fyn, Denmark. RESULTS: Included in the study were 169 HHT family members representing 24 families. They included both HHT patients and their first-degree relatives. The criteria of HHT were fulfilled in 75 participants; of these, 59 had a screening procedure performed, and PAVMs were demonstrated at pulmonary angiography (PA) in 18. Seven of the HHT patients had a history of cerebral stroke, compared with none of their healthy first-degree relatives. CONCLUSION: The prevalence of PAVM was 24% amongst HHT patients. The study confirmed an increased prevalence of neurological symptoms amongst HHT patients; the odds ratio was estimated to be 7.6. In order to enable prevention of these complications, screening for PAVM should become an integral part of the medical care for HHT patients.

Adult↗
PubMed2000

No association between birth weight and Type 1 diabetes mellitus--a twin-control study.

AIMS: To investigate, by means of a twin-control study, whether there is a relationship between birth weight and Type 1 diabetes mellitus. METHODS: In the youngest part (n = 20 888 pairs) of the Danish Twin Register, 95 twin pairs (26 monozygotic and 69 dizygotic) with Type 1 diabetes were identified. Information about birth weight and birth length, prematurity, maternal age and parity was obtained from midwives' records and from the Danish Medical Birth Registry and analysed using Student's two-sided t-test, Chi-square test and logistic regression. RESULTS: Birth data were available for 83 diabetic and 51 healthy twin individuals, altogether 67 twin pairs (20 monozygotic and 47 dizygotic). Mean birth weight was 2537 g and 2565 g (NS) in monozygotic and dizygotic pairs and the corresponding length at birth 47.6 cm and 48.2 cm (NS). In pairs discordant for diabetes, the mean birth weight was 2538 g in twins with diabetes and 2549 g in twins without diabetes (NS). Logistic regression in discordant pairs showed no relationship between diabetes status and birth weight, birth length, birth order, sex or prematurity. Logistic regression in concordant vs. discordant pairs showed no effect of mean birth weight and birth length, maternal age, parity or weeks of prematurity. CONCLUSIONS: There is no association between Type 1 diabetes mellitus and birth weight in this study. Furthermore, variables related to birth weight and length cannot explain why some pairs are concordant while other remain discordant.

Birth Weight↗
PubMed2000

High incidence and regression rates of solar keratoses in a queensland community.

The presence of solar keratoses on the skin is one of the major risk factors for basal cell and squamous cell carcinomas, which constitute a growing public health problem in today's white populations. In spite of this, little is known of the natural history of solar keratoses. We conducted follow-up studies to monitor the incidence, regression, and recurrence rates of solar keratoses in a random sample (N = 96) of the Nambour community in Queensland. At baseline, 43 participants (46%) were diagnosed with at least one solar keratosis [26 men (55%), 17 women (37%)] with a total count of 494 prevalent solar keratoses. The distribution of lesions per person was highly skewed, with 11 individuals (12%) having 65% of the total number of solar keratoses. During 12 mo of follow-up, 614 incident solar keratoses were diagnosed (549 in men and 65 in women); 526 solar keratoses regressed and 53 prevalent solar keratoses recurred, giving a net 45% increase in solar keratosis numbers in men (from 354 to 512 solar keratoses) and a net 44% reduction in women (from 114 to 64). Regression rates were higher in prevalent (74%) than incident (29%) solar keratoses. Solar keratosis prevalence increased with age in both sexes, and individuals with solar keratoses at baseline were over seven times more likely to develop additional solar keratoses in the next 12 mo than those without prevalent solar keratoses at baseline. These results show that the natural history of solar keratoses in the community is one of high turnover and that a small percentage of susceptible individuals carry the major burden of solar keratoses in the community.

Adult↗
PubMed2000

Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication.

BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs.

Adult↗
PubMed2000

Long-term mortality trends in patients with traumatic brain injury.

Comparison of long-term mortality rates between patients with traumatic brain injury (TBI) and the general population has not been adequately investigated. This project aimed to obtain information on the long-term mortality rate of patients with TBI. Using a rehabilitation database of a major teaching hospital, the search identified 476 patients, of whom 27 were deceased. This mortality rate (5.7%) was compared with the expected mortality rate for an equivalent population without TBI (1.5%) using Australian Life Table data. It was found that patients with TBI had a significantly higher mortality rate than the general population (chi2 = 12.2, p < 0.001). Possible reasons for this finding are discussed.

Adult↗
PubMed2000

Neoplastic transformation of mammary epithelial cells in rats is associated with decreased apoptotic cell death.

Previous studies have shown that terminal end buds (TEBs) in the murine mammary gland have high proliferative activity and demonstrate apoptotic cell death (ACD). Since TEBs are considered the place of origin of most chemically induced mammary carcinomas, we hypothesized that the development of hyperplastic and premalignant (carcinoma in situ, CIS) lesions in TEBs is associated with either a further increase in cell proliferation and/or with a decrease in ACD. To test this hypothesis we used the N-methyl-N-nitorosourea (MNU) carcinogenesis model in rats, where the occurrence of mammary tumors is preceded by hyperplastic and premalignant lesions arising mostly in TEBs, as well as in ducts and alveoli. The percentage of proliferating cells, as evaluated by 5-bromodeoxyuridine labeling (BrdU-LI), was similar in TEBs to those in terminal endbud hyperplasia (TEBH), CIS, and carcinomas (CA), whereas the percentage of apoptotic cells (apoptotic index, AI) was relatively high in TEBs and decreased in TEBH, CIS, and CA. This indicates that neoplastic transformation of mammary epithelial cells in TEBs is not associated with an increase in cell proliferation, but with a decrease in ACD. In addition to TEBH, hyperplastic lesions developed in ductal branching areas (ductal hyperplasia, DH) and alveolar structures (alveolar hyperplasia, AH). However, BrdU-LI in both DH and AH was lower than in TEBH, whereas the AI values were similar, suggesting that TEBH has a higher potential for progression and malignant transformation than DH and AH. In mammary tumors apoptotic cells were rare in the peripheral, proliferative areas, but frequent close to the necrotic areas, suggesting that intratumoral factors may significantly affect ACD. Thus, it appears that dissociation between cell proliferation and apoptosis occurs in the hyperplastic stages of mammary carcinogenesis and that neoplastic transformation of mammary epithelial cells is associated with decreased ACD but not with increased cell proliferation.

Animals↗
PubMed2000

Beyond ovulation: oral contraceptives and epithelial ovarian cancer.

In a case-control study in three Australian states that included 794 women with epithelial ovarian cancer and 853 community controls for whom we had adequate contraceptive and reproductive histories, we examined the effects of oral contraceptive use after controlling for estimated number of ovulatory cycles. Other covariates included in the multiple logistic regression analysis were parity, smoking, and history of pelvic surgery. The protective effect of duration of oral contraceptive use appeared to be multiplicative, with a 7% decrease in relative risk per year [95% confidence interval (CI) = 4-9%], persisting beyond 15 years of exposure. Use for up to 1 year may have a greater effect than predicted (odds ratio = 0.57; 95% CI = 0.40-0.82), whereas use before the first pregnancy may be additionally beneficial (odds ratio = 0.95; 95% CI = 0.87-1.03, adjusted for overall duration of use). Better control for ovulatory life might attenuate these estimates somewhat. There was little evidence of waning protection with time since last exposure or of extra benefit with early commencement of oral contraceptive use. We found no convincing evidence of effect modification in any factor examined or differences in effect among the three main histologic cancer types or between borderline and malignant tumors. Oral contraceptives may act by both suppressing ovulation and altering the tumor-promoting milieu.

Adult↗
PubMed2000

Do forecasts of UV indexes influence people's outdoor behaviour?

OBJECTIVE: To investigate Australian adults' awareness of the ultraviolet (UV) indexes forecast in the media, and whether these UV forecasts influence their behaviour in the sun. METHODS: A self-administered questionnaire was used on two occasions in 1997 to ask about knowledge of UV indexes shown in the media and about possible influence on outdoor behaviour. SETTING AND PARTICIPANTS: Participants were 977 residents (423 men; 554 women) of Nambour originally randomly selected in 1986 from the electoral roll, who have been followed up subsequently. RESULTS: The majority of people--92% of men and 86% of women--reported having seen or heard the UV indexes forecast during summer. Of these, significantly fewer men (107; 28%) than women (209; 46%) reported that their outdoor behaviour was influenced by knowledge of the forecast (p = 0.001). Neither age nor skin type, nor history of sunburns or skin cancer, affected knowledge of UV forecasts or their influence on behaviour. CONCLUSIONS AND IMPLICATIONS: Although most people are aware of the forecasts of UV indexes in the media, the majority do not take them into account in their outdoor behaviour. Compared with women, men were more aware of, but less influenced by, forecasts of UV indexes. Better communication of the implications of the UV indexes is needed, particularly to men, if they are to adapt their outdoor behaviour to improve their sun protection.

Adult↗
PubMed2000

Fecal shedding of Campylobacter and Arcobacter spp. in dairy cattle.

Campylobacter jejuni, Campylobacter coli, and Arcobacter spp. were detected in feces of healthy dairy cows by highly specific multiplex-PCR assays. For C. jejuni, at this one-time sampling, cows from 80.6% of farm operations (n = 31) and 37.7% of individual dairy cattle fecal samples (n = 2,085) were positive. Farm management factors were correlated with prevalence in herds in which >25% of cows were positive for C. jejuni. Statistical significance was set at a P of 0.20. Using these criteria, application of manure with broadcast spreaders (P = 0.17), feeding of whole cottonseed or hulls (P = 0.17) or alfalfa (P = 0.15), and accessibility of feed to birds (P = 0.17) were identified as possible risk factors for C. jejuni infection. C. coli was detected in at least one animal in 19.4% of operations and 1.8% of individual cows (n = 2,085). At the herd level, use of broadcaster spreaders was not a risk factor for C. coli infection. For Arcobacter, cows from 71% of dairy operations (n = 31) and 14.3% of individual dairy cattle fecal samples (n = 1,682) were positive. At the herd level, for Arcobacter spp., feeding of alfalfa (P = 0.11) and use of individual waterers (P = 0.19) were protective. This is the first description of Arcobacter spp. in clinically healthy dairy cattle and the first attempt to correlate their presence with C. jejuni.

Animal Feed↗
PubMed2000

The 5-HT(3) receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinal c-fos expression in the anaesthetised rat.

BACKGROUND: Noxious intestinal distention elicits a reflex depressor response in the sodium pentobarbitone anaesthetised rat, which can be used as an index of visceral nociception. 5-HT(3) receptor antagonists inhibit this reflex. Repeated colorectal distention (CRD) induces Fos like immunoreactivity (Fos-LI) in the rat spinal cord. AIMS: To examine the effect of the 5-HT(3) receptor antagonist alosetron on the depressor response to CRD, and on Fos expression in the lumbosacral spinal cord. METHODS: Male rats were anaesthetised with sodium pentobarbitone, and mean arterial blood pressure monitored during repeated colorectal balloon inflation before and after treatment with alosetron or saline. Rats anaesthetised with urethane and treated with alosetron or saline underwent a repeated CRD paradigm, after which the lumbosacral spinal cord was removed and processed for visualisation of Fos-LI. RESULTS: CRD elicited reproducible, volume dependent falls in arterial blood pressure, and repeated distention-effect curves were constructed. Alosetron (1-100 microg/kg intravenously) inhibited the depressor response to CRD in a dose related manner, with an ID(50) value of 3.0 microg/kg. Following repeated CRD, numbers of Fos-LI neurones were significantly increased to 1246 (total in 12 sections at 120 microm intervals from L6 to S1) compared with 49 in sham distended animals. Pretreatment with alosetron (100 microg/kg) significantly reduced numbers of Fos-LI neurones to 479.8. CONCLUSION: The 5-HT(3) receptor antagonist alosetron inhibits the depressor response to CRD in a potent and dose dependent manner. It also inhibits CRD induced Fos-LI in the spinal cord. These results suggest that 5-HT(3) receptors are involved in visceral nociceptive transmission, perhaps located on primary afferent or spinal neurones.

Animals↗