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Biomedical subjects

I Brown

Publications and source records attributed to I Brown.

At least 37 records · Page 2Linked to original sources

Biological control agents for white grubs (Coleoptera: Scarabaeidae) in anticipation of the establishment of the Japanese beetle in California.

We tested biological control agents for the control of 3rd-instar scarab turfgrass pests, both for the masked chafer Cyclocephala hirta LeConte and the Japanese beetle, Popillia japonica Newman. The former species is endemic in California whereas the latter, although not yet established, constitutes a permanent serious threat to agriculture and horticulture in California. We conducted experiments using C. hirta in California and P. japonica in New Jersey. A field trial conducted in 2 different California turfgrass sites compared the field persistence in the absence of hosts of Bacillus thuringiensis Berliner subspecies japonensis Buibui strain, the milky disease bacterium, Paenibacillus (=Bacillus) popilliae (Dutky), and the entomopathogenic nematodes Steinernema kushidai Mamiya and Heterorhabditis bacteriophora Poinar to that of the organophosphate diazinon. Soil samples taken 0-70 d after applications were bio-assayed with P. japonica. Only diazinon and the entomopathogenic nematode S. kushidai caused substantial mortality and S. kushidai activity persisted significantly longer than diazinon activity. In greenhouse experiments, combinations of entomopathogenic nematode species usually resulted in additive mortality of scarab larvae. Combinations of S. kushidai and diazinon also resulted in additive mortality. In field trials, the efficacy of H. bacteriophora and especially S. kushidai and S. glaseri, was comparable to that of diazinon over 14-18 d. However, it is likely that at least S. kushidai would have outperformed diazinon over an extended period because of its longer persistence and potential for recycling in the hosts. S. kushidai, should it become commercially available, deserves further examination as an alternative to chemical white grub control especially as a highly compatible component of sustainable turfgrass management.

Animals↗

211At-alpha-dose dependence of poly-ADP-ribosylation of human glioblastoma cells in vitro. Suitability in cancer therapy?

AIM: It was intended to test the biological response (poly-ADP-ribosylation of cellular proteins) of alpha-particles from extracellular 211At for enhanced damage to human glioblastoma cells in vitro and to discuss its suitability for potential application in therapy of high-grade gliomas. MATERIALS AND METHODS: Confluent cultures of human glioblastoma cells were exposed to different doses of alpha-radiations from homogeneously distributed extracellular 211At. Cellular poly-ADP-ribosylation of all proteins including histones was monitored since it is an indirect but sensitive indicator of chromatin damage and putative repair in both normal and malignant mammalian cells. RESULTS: A significant diminution (average 85.6%) in poly-ADP-ribosylation of total cellular proteins relative to that for non-irradiated glioblastoma cells was observed following 0.025 to 1.0 Gy alpha-radiations. In the dose range of 0.0025 to 0.01 Gy there was an increase with a maximum value of approximately 119.0% at 0.0025 Gy. Below 0.0025 Gy no change in poly-ADP-ribosylation was observed. CONCLUSIONS: Level of cellular poly-ADP-ribosylation of proteins at 0.025 to 1.0 Gy of alpha-radiation dose from 211At appears to cause enhanced damage by creating molecular conditions which are not conducive to repair of DNA damages in human glioblastoma cells in vitro. Therefore, it is assumed that clinical application of 211At at least in this dose range might enhance clinical efficacy in radiotherapy of cancer.

Alpha Particles↗

Extraosseous osteogenic sarcoma--a rare pediatric malignancy: case report and review of the literature.

BACKGROUND: Osteogenic sarcoma rarely occurs in soft tissues and generally affects individuals beyond the second decade of life. METHODS: The authors report a rare case of an extra osseous osteogenic sarcoma arising in the retroperitoneum of an adolescent, review the literature, and outline the diagnostic and therapeutic dilemmas. The role of adjuvant chemotherapy, using drugs used in managing bony osteosarcomas, is discussed. CONCLUSIONS: Retroperitoneal sarcomas may simulate ovarian teratomas. Careful consideration of the differential diagnosis of large cystic abdominal masses in adolescent females when size precludes adequate assessment of tumor mobility and imaging fails to demonstrate the ovaries is essential if these rare tumors are to be managed effectively.

Abdominal Neoplasms↗

A protective role for common p21WAF1/Cip1 polymorphisms in human ovarian cancer.

The objective of this study was to compare the frequency of two common p21WAF1/Cip1 gene polymorphisms in ovarian cancer patients with that in age-matched controls, from a population originating from Eastern Scotland. Both polymorphisms were found significantly less frequently in both the constitutive and tumour tissue DNA of ovarian cancer patients (3/65; 4.6%), than in that from geographically and age-matched controls (25/186; 13.4%) (p=0.0495, chi2). Furthermore, we found no p21WAF1/Cip1 gene mutations in any of the tumours, reflected by a relatively low degree of loss of heterozygosity (LOH) at the chromosomal region where the gene maps, providing further evidence that the p21WAF1/Cip1 gene is not mutated in ovarian cancer. The data suggest however, that there may potentially be a protective function for the two p21WAF1/Cip1 gene polymorphisms in the population under study.

Alleles↗

The development of a [211AT]-astatinated endoradiotherapeutic drug: part IV--late radiation effects.

PURPOSE: 6-[211At]-astato-MNDP is a high-LET endoradiotherapeutic drug that selectively targets to an oncogenically associated alkaline phosphatase isoenzyme expressed by certain tumors. A detailed histopathological study of the late tissue effects of its endogenous alpha-particle emissions has been carried out in a murine tumor model. MATERIALS AND METHODS: Thyroid-blocked male C57BI/10 mice bearing a s.c. transplanted rectal adenocarcinoma were treated with a single i.p. injection of 10-750 kBq 6-[211At]-astato-MNDP. Cured mice (131) were studied. Detailed autopsies and histological examinations were performed on all mice. The study was concluded after 756 days. RESULTS: Lymphoma, plasmacytoma, and intercurrent infections secondary to chronic pulmonary fibrosis were the most commonly found late manifestations of alpha-radiation exposure. Low grade B-cell non-Hodgkin's lymphoma occurred in 19 (24.7%) of 77 mice, 13-17 months after receiving 3.5-185 kBq 6-[211At]-astato-MNDP. The incidence of lymphoma alone and its latency was similar to that of the control population (23.3%). Treatment doses exceeding 200 kBq 6-[211At]-astato-MNDP, were associated with the development of soft tissue plasmacytoma in 7 (13%) of 54 mice, after 17-22 months. Generalized debilitation and nonspecific infections supervening pulmonary fibrosis significantly contributed to the late morbidity and mortality observed in mice treated with 300-750 kBq 6-[211At]-astato-MNDP. Dosimetry has afforded LD50/360 and LD50/420 estimates of 12-14 and 10-12 Cobalt-Gray equivalent (CGyE), respectively, for chronic lung damage. There was no histological evidence of chronic radiation damage to other critical healthy tissues. Normal thyroid morphology was preserved. CONCLUSIONS: Dose activities of 6-[211At]-astato-MNDP exceeding 300 kBq, were associated an increased risk of tumor induction and development of varying degrees of chronic pulmonary fibrosis implicated in the onset of terminal intercurrent infections. Within the therapeutic dose range 55-300 kBq 6-[211At]-astato-MNDP, mortality associated with the incidence of significant late radiation damage in critical normal tissues and latent carcinogenesis was less than 15%. Data from this murine model suggest that clinically relevant activities of 6-[211At]-astato-MNDP may be given without unacceptable toxicity.

Animals↗

Epstein-Barr virus and Hodgkin's disease: further evidence for the three disease hypothesis.

The epidemiology of Hodgkin's disease suggests that it is a heterogeneous condition comprising more than one disease entity. The Epstein-Barr virus (EBV) is present in the Reed-Sternberg cells of a proportion of cases and is likely to play a role in the pathogenesis of these cases. In this study we show that EBV association rates vary with age at diagnosis. We suggest that Hodgkin's disease can be divided into three disease entities on the basis of EBV association and age, thereby providing biological support for the multiple aetiology hypothesis proposed by MacMahon (Cancer Res 1966; 26: 1189-1290).

Adolescent↗

Potential of limited day 21 post-chemotherapy CT scan in predicting need for post-chemotherapy surgery in nonseminomatous testicular germ cell cancer.

UNLABELLED: Nonseminomatous germ cell cancers (NSGCC) have a varied response to chemotherapy, some melting away with resultant cure, some have tumour stem cell necrosis and residual benign disease whilst others are resistant to treatment. The latter two require surgical excision in order to identify those needing high intensity chemotherapy. OBJECTIVE: The aim of this study was to investigate whether it was possible to give an earlier prediction of need for surgery after chemotherapy on the basis of a limited CT scan performed after the first course. MATERIALS AND METHODS: Twenty-three patients with metastatic NSGCC undergoing induction chemotherapy were studied. The site of the maximum disease was noted before treatment and only this area was rescanned at day 21. The change in disease bulk, measured as maximum transverse diameter (MTD), was compared with appearances on a CT scan immediately after chemotherapy and post-treatment response. RESULTS: Of those patients showing a poor response on the day 21 scan (i.e. no change, or less than 50% reduction in MTD), 70% required early surgical excision of residual disease, while none of the good responders (i.e. greater than 50% reduction in MTD), required immediate surgery (p < 0.001). CONCLUSION: It is concluded that a limited day 21 CT scan may represent an independent predictor of good and poor response to chemotherapy, thus enabling reduction in chemotherapy and its toxicity in good responders and early identification of those who may need surgical excision, thereby permitting easier scheduling of these often difficult surgical procedures.

Adult↗

Is incidental prophylactic oophorectomy an acceptable means to reduce the incidence of ovarian cancer?

BACKGROUND: According to previous reports, the lifetime risk of developing ovarian carcinoma is 1.4%. This figure varies with age from 6.6 per 100,000 among women aged 35 to 39 years up to 55.1 per 100,000 among women aged 75 to 79 years. Prophylactic oophorectomy remains a modality to decrease the incidence of ovarian cancer. What proportion of women diagnosed with an ovarian malignancy had a preceding laparotomy at which time a prophylactic oophorectomy could have been performed? METHODS: We reviewed the new ovarian cancer diagnoses seen in patients between August 1988 and August 1993 at the Ottawa Regional Cancer Foundation. Four hundred and four patients were identified. These patients were analyzed for preceding abdominal surgery, age, time to disease progression, time to death, time to death from other causes, and average follow-up. The previous abdominal surgeries were divided into: (1) major gynecological surgery; and (2) general surgery procedures, which were further divided into laparotomy and pelvic surgery (group A surgeries) and general surgery that included other abdominal surgeries (ie, appendectomy, cholecystectomy) where access to the pelvis could be more difficult (group B surgeries). RESULTS: A total of 270 abdominal surgeries was performed, prior to the diagnosis of ovarian cancer. The group was stratified according to the timing of the surgery (< or =40 years, 41 to 45 years, 46 to 50 years, >50 years). Based on these data, and on the grouping of general gynecologic surgeries plus the general surgical procedures of group A, 10.9% of ovarian cancers would have been prevented if prophylactic oophorectomy had been performed in patients who had surgery over 40 years of age; over 45 years this was 6.7%, over 50 years it was 4%. If one adds all major surgeries, including general surgery groups A and B, the results were 26.9% over 40 years of age, 20% over 45, and 16.6% over 50. CONCLUSION: We found that, depending on the age of the patient, prophylactic oophorectomy results in a 4% to 10.9% reduction in the incidence of ovarian carcinoma. This increases to 16.6% to 26.9% if one considers general surgery procedures in which access could be more difficult. Although we are not advocating the frequent use of this procedure, we recommend that surgeons routinely discuss this option before surgery with their postmenopausal female patients over 49 years of age. Given that the decision for prophylactic oophorectomy is multifaceted, we feel that a risk scoring for ovarian cancer and a discussion of the risk and benefit ratio should be undertaken. The ultimate goal is to heighten patient awareness of the risk factors to ensure that an informed decision is made concerning this consistently lethal disease.

Abdomen↗

Measuring the quality of life of older persons: a model with implications for community and public health nursing.

Measuring the quality of life (QOL) of older persons can assist health professionals in achieving a number of important objectives. These include assessing the effects of illness and treatment, identifying need for support services, and developing health enhancing environments. Most QOL models focus unduly on illness and disability, define QOL too narrowly, and do not consider aspects of personal control and potential opportunities for change. A new model of QOL with associated instrumentation, the Quality of Life Profile: Seniors Version (QOLPSV), is described. Administration of the QOLPSV to 205 older persons in Ontario, Canada found it to be reliable and valid. Limitations of the instrument are presented and potential uses explored.

Aged↗

Health care resource utilization and antimicrobial use in elderly patients with community-acquired lower respiratory tract infection who develop Clostridium difficile-associated diarrhoea.

We conducted a prospective observational study on the medical management and health service resource utilization associated with the hospital care of patients with community-acquired lower respiratory tract infection. Between January 1994 and June 1995, 28 such patients developed Clostridium difficile-associated diarrhoea; these 28 patients were matched with 56 age-matched patients, who were used as a control group in a comparative study. Progress during the first week after admission was similar as measured by fever days and pathology or radiology use. The use of iv cephalosporins (g/day) during the first week was greater in the group who developed C. difficile-associated diarrhoea than in controls. The length of hospital stay was 36.4 +/- 21.6 days in patients with C. difficile-associated diarrhoea compared with 19.8 +/- 13.3 days in controls. Cases also required more pathological and radiological tests and greater use of antimicrobials and other drugs; however, if pathology and radiology use was calculated per day of patient stay there was no difference between the two groups. When antimicrobial use was compared, controlling for the time taken until found to be C. difficile toxin positive, patients with C. difficile infection received more iv cefuroxime as well as more total cephalosporins, beta-lactams and macrolides measured in g/day. Interestingly, in this study we could not show an increased mortality associated with C. difficile diarrhoea despite obvious evidence of morbidity. The development of C. difficile-associated diarrhoea substantially increases health care resource utilization for individual patients who are admitted to hospital with lower respiratory tract infection.

Aged↗

Fecal numbers of bifidobacteria are higher in pigs fed Bifidobacterium longum with a high amylose cornstarch than with a low amylose cornstarch.

Twelve young male pigs consumed a purified diet containing wheat bran as fiber source. Starch provided 50% of total daily energy either as a low amylose cornstarch or as a high amylose (amylomaize) starch. The pigs were given a supplement of a freeze-dried probiotic organism (Bifidobacterium longum CSCC 1941). A block crossover design was used so that at any one time two groups of three pigs consumed either the high or low amylose cornstarch without probiotic and a further two groups of three pigs consumed either high or low amylose cornstarch with probiotic. Neither food intake nor body weight gain was affected by diet. Fecal output was higher when pigs were fed the high amylose cornstarch, but moisture content was unaffected. Fecal concentrations and excretion of total volatile fatty acids were higher when pigs were fed the high amylose cornstarch. Concentrations of acetate were unaffected by dietary starch, but those of propionate and butyrate were higher when the high amylose cornstarch was consumed. Fecal excretion of all three acids was higher during high amylose cornstarch feeding. Bifidobacteria were detected in the feces only when pigs were fed Bifidobacterium longum. Fecal bifidobacteria counts (expressed per gram of wet feces) and their daily fecal excretion were higher when pigs were fed high amylose cornstarch. Feeding the probiotic did not alter fecal starch or volatile fatty acids. None of the variables studied was affected by the order of feeding of starch or probiotic. The data show that a high amylose starch acts as a prebiotic in promoting the fecal excretion of probiotic organisms.

Amylose↗

Basal expression of stress-inducible hsp70 mRNA detected in hippocampal and cortical neurons of normal rabbit brain.

In response to stresses, such as elevated temperature, cells increase synthesis of a group of highly conserved proteins known as heat shock proteins (hsps). Here, we report detection of basal expression of the stress-inducible hsp70 mRNA species in neurons of the normal rabbit brain. By regional Northern blot analysis, basal levels of hsp70 mRNA were observed in control hippocampus, cortical layers, thalamus, and kidney. Using radioactive in situ hybridization, similar patterns of expression were noted for constitutive hsc70 mRNA and hsp70 mRNA in the unstressed rabbit forebrain. Non-radioactive (DIG) in situ hybridization allowed localization of both heat shock mRNA species to hippocampal neurons. In addition, a dual in situ hybridization protocol, which allowed colocalization of two mRNAs to a single cell, demonstrated that hsp70 and hsc70 mRNAs are expressed in the same hippocampal and cortical neurons.

Animals↗