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J B Anderson

Publications and source records attributed to J B Anderson.

At least 37 records · Page 2Linked to original sources

Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup.

PURPOSE: Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration. MATERIALS AND METHODS: Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio. RESULTS: A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup. CONCLUSIONS: Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Androgen Antagonists↗

Pharmacodynamics of a long acting depot preparation of avorelin in patients with prostate cancer. Avorelin Study Group.

PURPOSE: We evaluate the pharmacodynamics, pharmacokinetics and tolerability of a sustained release depot formulation of avorelin, a new potent super agonist of luteinizing hormone-releasing hormone receptors, in patients with prostate cancer. MATERIALS AND METHODS: A total of 60 patients were randomized to receive a 10 mg. (31) or 15 mg. (29) avorelin subcutaneous depot. Serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and plasma avorelin were measured regularly until depot exhaustion. RESULTS: Of the 10 mg. group patients 3 withdrew from the study after 31 to 35 weeks due to disease progression. Of the 15 mg. group patients 1 did not complete the study for logistical reasons. After the expected flare in serum testosterone, LH and FSH during week 1, medical castration (testosterone concentration less than 1.735 nmol./l.) was achieved within 4 weeks of depot injection. Median duration of testosterone suppression was 40 weeks in the 10 mg. (95% confidence interval 35 to 42) and 39 in the 15 mg. (37 to 43) group. The reduction in serum LH was similar to that of testosterone, while that of FSH was less pronounced. Plasma avorelin was proportional to the dose and correlated with serum testosterone. Normalization of serum prostate specific (4 ng./ml. or less) at 6 months was achieved in 80 and 88% of the 10 and 15 mg. groups, respectively. During the (7 to 20-month) observation period 94 and 86% of the 10 and 15 mg. groups, respectively, complained of adverse events mainly related to androgen suppression (hot flushes, decreased libido and impotence) or the nature of the disease (skeletal pain). In each group 3 patients had serious adverse events requiring hospitalization for reasons unrelated to avorelin treatment. The depot was well tolerated locally. CONCLUSIONS: Subcutaneous depot formulations of avorelin were well tolerated and had protracted inhibitory effects on pituitary gonadotropin secretion in patients with prostate cancer. Testosterone suppression was maintained for more than 6 months in all patients. Avorelin depots could be the first luteinizing hormone-releasing hormone agonist formulation to be administered at 6-month intervals.

Adult↗

A pilot study for a randomized controlled trial comparing the efficacy, safety and cost-effectiveness of surgical treatments of the prostate.

OBJECTIVE: To assess the numbers of men in outpatients and subsequently undergoing transurethral resection of the prostate (TURP) who were referred during 1993-94 and 1996-97, thereby assessing the feasibility of a subsequent study of treatment efficacy in men with bladder outlet obstruction secondary to benign prostatic hyperplasia, prospectively randomized to the surgical treatment options, i.e. TURP, laser ablation of the prostate, transurethral needle ablation and T3 thermotherapy, to investigate treatment outcome, cost-efficacy and cost-benefit. PATIENTS AND METHODS: All patients considered and consenting for prostate surgery were reviewed prospectively with a view to inclusion in the proposed trial. The diagnosis was based on two estimates of flow rate from voids of >150 mL and from symptoms assessed using the International Prostate Symptom Score. All patients had TURP explained by a urological surgeon and nursing staff, and subsequently had further consultation with research staff. RESULTS: Patients seen in clinic as new referrals increased by 11% between the periods assessed, although the numbers undergoing TURP decreased by 19%. Of the 383 patients screened, who were on the waiting list for TURP, only 13 elected to enter the trial. Of the 383 men, 267 (67%) ultimately had prostate surgery, with 39 (10%) electing to continue with watchful waiting and 34 (9%) continuing with pharmacotherapy. CONCLUSION: Although more men with benign prostatic disease and lower urinary tract symptoms are being seen in clinics, the reduced proportion of patients continuing to surgical intervention will lead to increasing difficulty in carrying out randomized controlled clinical trials assessing surgical options. With ever more therapeutic options available, patients find it difficult to make decisions in both the clinical situation and when asked to enter a trial. Fully informed decisions by both the surgeon and the patient will only be possible when objective data are available from trials that investigate outcome, cost-efficacy and cost-benefit. This study suggests that when presented with more information and counselling, fewer men decide to undergo prostate surgery for symptomatic BPH.

Adult↗

Multilocus genotypes and DNA fingerprints Do not predict variation in azole resistance among clinical isolates of Candida albicans.

If variation in azole resistance is due to inherent differences in strains of Candida albicans, as a predominantly clonal organism, then correlation between multilocus genotypes and drug resistance would be expected. A sample of 81 clinical isolates from patients infected with human immunodeficiency virus in Toronto, Canada, plus 3 reference isolates were genotyped at 16 loci, distributed on all linkage groups, by means of oligonucleotide hybridizations specific for each of the alleles at each locus. These multilocus genotypes were significantly correlated with DNA fingerprints obtained with the species-specific probe 27A, indicating widespread linkage disequilibrium in the genome. There were 64 multilocus diploid genotypes and 77 DNA fingerprint types delineated in this sample. Neither the multilocus genotyping nor DNA fingerprinting alone identified all of the 81 types identified by the combination of these two methods. Multilocus genotypes were not predictive of fluconazole resistance, suggesting that resistance is gained or lost too quickly to be predicted by linkage with neutral markers.

Antifungal Agents↗

Spontaneous subcapsular renal haemorrhage presenting with pleuritic chest pain.

We present an unusual case of spontaneous renal subcapsular haematoma in a normal kidney presenting with pleuritic chest pain and mimicking pulmonary embolism. The literature suggests that the majority of these cases occur in association with renal tumours and that the diagnosis can best be made by computed tomographic scanning. Treatment is expectant but because of the high incidence of tumours, nephrectomy is usually necessary.

Aged↗

Early versus deferred hormone therapy.

Although hormone therapy is widely used in the management of prostate cancer, the optimal timing of its initiation remains a matter of debate. Immediate hormone treatment has been compared with deferred treatment in randomized studies conducted by the Veterans Administration Cooperative Urological Research Group, the South Sweden Prostate Cancer Study Group and the Medical Research Council. Despite criticism of the design of these studies, the results indicate that early treatment may be associated with advantages in time to progression and survival. It is anticipated that ongoing studies, such as the European Organization for Research and Treatment of Cancer protocols 30846 and 30891, will provide further information on the optimal timing of endocrine treatment. Prognostic and quality of life factors also have an impact on the treatment decision. On the basis of available evidence, early hormone therapy is recommended for younger men with poorly differentiated tumours or advanced disease and for those who are seen infrequently by their physician. Deferred treatment using a strategy of watchful waiting is probably the best option for older men with well differentiated, low volume prostate cancer.

Antineoplastic Agents, Hormonal↗

mtDNA recombination in a natural population.

Variation in mtDNA has been used extensively to draw inferences in phylogenetics and population biology. In the majority of eukaryotes investigated, transmission of mtDNA is uniparental and clonal, with genotypic diversity arising from mutation alone. In other eukaryotes, the transmission of mtDNA is biparental or primarily uniparental with the possibility of "leakage" from the minority parent. In these cases, heteroplasmy carries the potential for recombination between mtDNAs of different descent. In fungi, such mtDNA recombination has long been documented but only in laboratory experiments and only under conditions in which heteroplasmy is ensured. Despite this experimental evidence, mtDNA recombination has not been to our knowledge documented in a natural population. Because evidence from natural populations is prerequisite to understanding the evolutionary impact of mtDNA recombination, we investigated the possibility of mtDNA recombination in an organism with the demonstrated potential for heteroplasmy in laboratory matings. Using nucleotide sequence data, we report here that the genotypic structure of mtDNA in a natural population of the basidiomycete fungus Armillaria gallica is inconsistent with purely clonal mtDNA evolution and is fully consistent with mtDNA recombination.

Basidiomycota↗

Casodex (bicalutamide) 150-mg monotherapy compared with castration in patients with previously untreated nonmetastatic prostate cancer: results from two multicenter randomized trials at a median follow-up of 4 years.

OBJECTIVES: To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer. METHODS: A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis. RESULTS: In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated. CONCLUSIONS: Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Aged↗

A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer.

OBJECTIVES: To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer. METHODS: A total of 1,453 patients with either confirmed metastatic disease (M1), or T3/T4 non-metastatic disease with elevated prostate-specific antigen (M0) were recruited into one of two identical, multicentre, randomised studies to compare 'Casodex' 150 mg/day with castration. The protocols allowed for combined analysis. RESULTS: At a median follow-up period of approximately 100 weeks for both studies, 'Casodex' 150 mg was found to be less effective than castration in patients with metastatic disease (M1) at entry (hazard ratio of 1.30 for time to death) with a difference in median survival of 6 weeks. In symptomatic M1 patients, 'Casodex' was associated with a statistically significant improvement in subjective response (70%) compared with castration (58%). Analysis of a validated quality-of-life questionnaire proved an advantage for 'Casodex' in sexual interest and physical capacity. 'Casodex' had a substantially lower incidence of hot flushes compared to castration (6-13% compared with 39-44%) and the most commonly reported adverse events were those expected for a potent antiandrogen. However, in patients with M0 disease at entry, the data are still immature with only 13% of M0 patients having died. An initial analysis of this immature data has suggested that the results in these patients may be different to those obtained in patients with M1 disease. A further survival analysis in patients with M0 disease is therefore planned when the data are more mature. CONCLUSIONS: 'Casodex' 150 mg is less effective than castration in patients with M1 disease. However, 'Casodex' has shown a benefit in terms of quality of life and subjective response when compared to castration and has an acceptable tolerability profile. Thus 'Casodex' 150 mg monotherapy is an option for patients with M1 prostate cancer for whom surgical or medical castration is not indicated or is not acceptable.

Aged↗

Human papillomavirus and bladder cancer.

Bladder cancer remains an important cause of oncological morbidity and mortality in women. Known etiological agents include smoking and exposure to certain industrial chemical compounds, though the origin of the majority of cases remains unknown. Human papillomavirus infection is also common in women and has been closely linked to the development of carcinoma of the cervix. It has been suggested that infection with HPV may also be an important factor in the subsequent development of bladder cancer. A number of studies using various techniques of molecular biology have looked at the relationship between HPV infection and bladder cancer. Although the results are somewhat conflicting, the overall picture would suggest little involvement of HPV in the evolution of bladder cancer, except possibly in a small group of patients who are immunocompromised.

Aged↗

Mitochondrial Haplotype Influences Mycelial Growth of Agaricus bisporus Heterokaryons.

We evaluated the influence of mitochondrial haplotype on growth of the common button mushroom Agaricus bisporus. Ten pairs of heterokaryon strains, each pair having the same nuclear genome but different mitochondrial genomes, were produced by controlled crosses among a group of homokaryons of both wild and commercial origins. Seven genetically distinct mitochondrial DNA (mtDNA) haplotypes were evaluated in different nuclear backgrounds. The growth of heterokaryon pairs differing only in their mtDNA haplotypes was compared by measuring mycelial radial growth rate on solid complete yeast medium (CYM) and compost extract medium and by measuring mycelial dry weight accumulation in liquid CYM. All A. bisporus strains were incubated at temperatures similar to those utilized in commercial production facilities (18, 22, and 26(deg)C). Statistically significant differences were detected in 8 of the 10 heterokaryon pairs evaluated for one or two of the three growth parameters measured. Some heterokaryon pairs showed differences in a single growth parameter at all three temperatures of incubation, suggesting a temperature-independent difference. Others showed differences at only a single temperature, suggesting a temperature-dependent difference. The influence of some mtDNA haplotypes on growth was dependent on the nuclear genetic background. Our results show that mtDNA haplotype can influence growth of A. bisporus heterokaryons in some nuclear backgrounds. These observations demonstrate the importance of including a number of mitochondrial genotypes and evaluating different nuclear-mitochondrial combinations of A. bisporus in strain improvement programs.

Journal Article↗

The aetiological significance of human papillomavirus in bladder cancer.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA types 6, 11 and 16 in histological sections of human bladder cancer. MATERIALS AND METHODS: Fifty-five formalin-fixed, paraffin-embedded bladder tumour specimens were analysed for the presence of HPV infection using Southern blotting DNA hybridization and radiolabelled probes for HPV DNA types 6/11 and 16. RESULTS: Despite the detection of HPV DNA type 6, 11 and 16 in positive control samples and the successful detection of HPV DNA in anogenital cancer using the same technique, no HPV DNA was found in any of the bladder tumour specimens examined. CONCLUSIONS: Using a technique with proven efficacy in the detection of HPV DNA from histological specimens, no HPV DNA was present in any of the bladder tumours examined. This finding is in agreement with most recently published studies suggesting that HPV has no significant role in the development of human bladder cancer.

Adult↗

Genetic exchange and recombination in populations of the root-infecting fungus Armillaria gallica.

Genetic individuals, or genets, of Armillaria and other root-infecting basidiomycetes are usually found in discrete patches that often include the root systems of several adjacent trees. Each diploid individual is thought to arise in an unique mating event and then grow vegetatively in an expanding territory over a long period of time. Our objective in this study was to describe the population from which such genetic individuals are drawn. In a sample including 274 collections representing 121 genetic individuals of A. gallica (synonym A. bulbosa) from two sites in each of four regions of eastern North America, genotype frequencies at seven nuclear loci were not significantly different from Hardy-Weinberg expectations. Furthermore, allele frequencies at the seven loci were not significantly different between regions. Additional allelic data from four non-contiguous regions of mitochondrial DNA showed little or no population subdivision over the four regions. Analysis of the distribution of multilocus mtDNA haplotypes revealed some clonal transmission of mtDNAs between genets and nonrandom mating within sites. Despite the sharing of mtDNA types by some individuals, the overall sample contained a high level of genotypic diversity. The apparent linkage equilibrium between some pairs of loci and the high level of phylogenetic inconsistency among all four loci suggest the occurrence heteroplasmy and recombination among mtDNAs of A. gallica in nature. In laboratory matings of two haploid strains with different mtDNA types, a low frequency of recombination in mtDNA was detected.

Agaricales↗

A group-I intron in the mitochondrial small subunit ribosomal RNA gene of Sclerotinia sclerotiorum.

A 1,380-bp intervening sequence within the mitochondrial small subunit ribosomal RNA (mt SSU rRNA) gene of the fungus Sclerotinia sclerotiorum has been sequenced and identified as a group-I intron. This is the first report of an intron in the mt SSU rRNA gene. The intron shows close similarity in secondary structure to the subgroup-IC2 introns from Podospora (ND3i1, ND5i2, and COIi5) and Neurospora (ND5i1). The intron has an open reading frame (ORF) that encodes a putative protein of 420 amino acids which contains two copies of the LAGLI-DADG motif. The ORF belongs to a family of ORFs identified in Podospora (ND3i1, ND4Li1, ND4Li2, ND5i2, and COIi5) and Neurospora (ND5i1). The putative 420-aa polypeptide is also similar to a site-specific endonuclease in the chloroplast large subunit ribosomal RNA (LSU rRNA) gene of the green alga Chlamydomonas eugametos. In each clone of S. sclerotiorum examined, including several clones which were sampled over a 3-year period from geographically separated sites, all isolates either had the intron or lacked the intron within the mt SSU rRNA gene. Screening by means of Southern hybridization and PCR amplification detected the intron in the mt SSU rRNA genes of S. minor, S. trifoliorum and Sclerotium cepivorum, but not in other members of the Sclerotiniaceae, such as Botrytis anamorphs of Botryotinia spp., or in other ascomycetous and basidiomycetous fungi.

Amino Acid Sequence↗

Bladder and erectile dysfunction before and after rectal surgery for cancer.

OBJECTIVE: To establish the incidence of bladder and erectile dysfunction after rectal surgery for cancer. PATIENTS AND METHODS: Twenty patients (16 men and four women, median age 66 years, range 36-78) with carcinoma of the rectum were prospectively studied immediately before and 4 months after operation by clinical assessment, uroflowmetry and video-cystometrography. All patients were catheterized routinely at the time of surgery. Those experiencing voiding difficulties after catheter removal were managed by intermittent self-catheterization or an indwelling urethral catheter. RESULTS: Before surgery, only six patients had completely normal bladder function and 13 of the 16 men were at least partially potent. Eight of the 19 patients who eventually had surgery developed identifiable bladder dysfunction, of whom three had urodynamic evidence of complete bladder denervation. Three men who were potent before became impotent after surgery. CONCLUSIONS: Bladder and erectile dysfunction are recognized complications of radical rectal surgery, although there is significant variation in the reported risk; much of this variability is related to the retrospective nature of most previous studies. This study demonstrates the importance of prospective urodynamic evaluation and confirms that the small but significant risk of permanent bladder dysfunction is likely to be related to pelvic nerve injury at the time of surgery.

Adult↗

A tool to assess the cognitively impaired elderly.

When elderly persons become cognitively impaired, decision-making and case management can be intensely frustrating for health care providers who must make provisions for both short-term and long-term care. Numerous barriers pose challenges to the case managers in addition to those that occur when health care terminology does not fit easily into the legal vocabulary of the judge who makes the ultimate decision naming a guardian or conservator. Ongoing research by the authors has been involved in identifying criteria to determine incompetency by both formal and informal caregivers of cognitively impaired elderly. A scale, currently consisting of 10 criteria, has been developed and continues to be refined by the authors.

Aged↗

Mitochondrial DNAs of the fungus Armillaria ostoyae: restriction map and length variation.

A restriction-enzyme-site map is presented for the 147-kb mtDNA of North American Armillaria ostoyae. The locations of five structural genes, atp6, atp8, coxI, coxIII, and cob, along with the location and orientation of the large and small ribosomal RNA genes, were determined through Southern hybridizations with cloned genes from other fungal mtDNAs. Based on this map, the variation in mtDNA suggested geographic structure at two different levels. On a large geographic scale, 17 mtDNA types from North America were distinct, with respect to both size and restriction maps, from three mtDNA types from Europe. At the local scale, identical mtDNA types were evident among several different genetic individuals located no more than 1 km apart at a site in Michigan. No mtDNA type occurred more than once among genetic individuals from different regions of North America, although the occurrence of similar mtDNAs in isolates from distant regions suggested that this may occur at a low frequency with large sample sizes. Among the North American mtDNA types, analysis of discrete length variants was inconsistent with the hypothesis that the mtDNA of A. ostoyae evolves as a clonal lineage in which each length mutation represents a unique event. The two remaining hypotheses, that similar mutational events have occurred independently and that genetic exchange and recombination occurs among mtDNAs in natural populations of this species, remain to be tested.

Agaricales↗