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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 55 records · Page 3Linked to original sources

The pathogenesis and control of diarrhoea and breech soiling in adult Merino sheep.

Diarrhoea and soiling of the breech with faeces ('winter scours') is a serious problem in adult Merino sheep grazing improved pastures in south-eastern Australia during winter and spring. This occurs even on farms where gastro-intestinal nematodes are effectively controlled. It was shown that winter scours was associated with the ingestion of trichostrongylid larvae, and that host factors were important in determining susceptibility to this syndrome. No differences were detected in the protective immune response of affected and unaffected sheep to gut nematodes. However, affected sheep had a hypersensitive inflammatory reaction in the pylorus and upper jejunum, characterised by the infiltration of significantly more eosinophils and changed lymphocyte populations. The changes in the lymphocyte populations included a reduced number of CD8+ cells, increased CD4+:CD8+ T-cell ratio, and significantly reduced numbers of cells reacting to interferon-gamma. High doses of infective larvae (20,000/week of Ostertagia circumcincta and Trichostrongylus vitrinus) did not induce diarrhoea in sheep not susceptible to winter scours. In contrast, only low doses (2000/week) initiated scouring in sheep selected as being susceptible to winter scours. Therefore, even considerably improved worm control programmes, including the selection of sheep with increased resistance to gut nematodes, will not prevent winter scours. Rather, phenotypic culling and genetic selection, to remove sheep susceptible to the hypersensitivity inflammatory response, is proposed as the most suitable long-term control strategy.

Animal Husbandry↗

Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene.

In this study the detection rates of bacterial infection of hip prostheses by culture and nonculture methods were compared for 120 patients with total hip revision surgery. By use of strict anaerobic bacteriological practice during the processing of samples and without enrichment, the incidence of infection by culture of material dislodged from retrieved prostheses after ultrasonication (sonicate) was 22%. Bacteria were observed by immunofluorescence microscopy in 63% of sonicate samples with a monoclonal antibody specific for Propionibacterium acnes and polyclonal antiserum specific for Staphylococcus spp. The bacteria were present either as single cells or in aggregates of up to 300 bacterial cells. These aggregates were not observed without sonication to dislodge the biofilm. Bacteria were observed in all of the culture-positive samples, and in some cases in which only one type of bacterium was identified by culture, both coccoid and coryneform bacteria were observed by immunofluorescence microscopy. Bacteria from skin-flake contamination were readily distinguishable from infecting bacteria by immunofluorescence microscopy. Examination of skin scrapings did not reveal large aggregates of bacteria but did reveal skin cells. These were not observed in the sonicates. Bacterial DNA was detected in 72% of sonicate samples by PCR amplification of a region of the bacterial 16S rRNA gene with universal primers. All of the culture-positive samples were also positive for bacterial DNA. Evidence of high-level infiltration either of neutrophils or of lymphocytes or macrophages into associated tissue was observed in 73% of patients. Our results indicate that the incidence of prosthetic joint infection is grossly underestimated by current culture detection methods. It is therefore imperative that current clinical practice with regard to the detection and subsequent treatment of prosthetic joint infection be reassessed in the light of these results.

Animals↗

Use of alcohol fixed cytospins protected by 10% polyethylene glycol in immunocytology external quality assurance.

AIMS: To provide cytospins as a means of external quality assurance (EQA), while maintaining antigen expression integrity and achieving uniformity of material for all participating laboratories. METHODS: Cells were collected from two adenocarcinoma and one reactive pleural effusion specimens. Lymphoid cells were also collected through aspiration of a resected tonsil specimen. All cells were collected in Hanks balanced salt solution (HBSS); cytospins were made and fixed in methanol or acetone alone or protected using a layer of 10% polyethylene glycol (PEG) in 50% methanol. Two laboratories participated (RGHT and UCL). RESULTS: Cytokeratin expression detected using either CAM5.2 or AE1/AE3 antibodies was sensitive to temperature. Without PEG, unacceptable or negative staining was seen within six weeks of preparation. LCA was not sensitive to temperature, with good staining scores being achieved after eight weeks following preparation. CONCLUSIONS: It is possible to send alcohol fixed, air dried cytospins to laboratories participating as part of an EQA scheme for immunocytology. Some antigens will require protection from temperature variations during transit. A layer of 10% PEG in 50% methanol, allowed to air dry, is suitable for this purpose. Participating laboratories will only have to remove this layer using methanol before their localisation technique for assessment.

Adenocarcinoma↗

Disseminating the results of participant-focused research.

Participant-focused research (PFR) includes the "subjects" as full partners in the research process. As such, participants share in the products or outcomes of research. PFR goes beyond the traditional research approach of disseminating findings to other scientists and clinicians and includes participants and community residents in sharing the skills, knowledge, and resources of the study with the objective of empowering the participants. This article demonstrates the use of PFR in disseminating the results or products of study to the participants through two examples of long-term research projects conducted in Los Angeles. The first example is a community-based study of HIV prevention with low-income Latina women. The second example is an ethnographic study of health concerns and risks among adolescents in juvenile detention. These examples provide two approaches to dissemination of research findings and benefits to the participants and the community.

Adolescent↗

Perceived factors influencing the initiation of drug and alcohol use among homeless women and reported consequences of use.

A qualitative research approach was used to explore the factors that influence the initiation of drug and alcohol use among homeless women and the health and social consequences of drug and alcohol use. The sample consisted of 238 women; of whom 209 women reported drug and/or alcohol use in the past month and 29 women reported no history of drug or alcohol use. Findings of the study revealed homeless women who currently used drugs and alcohol, homeless women who currently used drugs only, and to a lesser extent current alcohol users only, had suffered traumatic childhood events and family dysfunction and had to cope with low self-esteem, emotional distress, and poor physical health. The initiation of drug and/or alcohol use was strongly affected by the social influence of other users. In comparison, homeless women who did not use drugs or alcohol reported a positive self-image, few traumatic events, and chose partners who did not use drugs or alcohol. Common among current drug and/or alcohol users were the reported social benefits of drug use. Quantitative analyses revealed homeless women who were current drug users were significantly more likely to have experienced childhood and adult victimization as compared with women in the other groups. Thus, the need for social interventions and positive social support early in the lives of these women are strongly implicated in these findings.

Adult↗

A dose-escalation phase II clinical trial of infusional mitomycin C for 7 days in patients with advanced measurable colorectal cancer refractory or resistant to 5-fluorouracil.

Chemotherapy for 5-fluorouracil (5-FU)-resistant colorectal cancer is largely ineffective with new and innovative therapeutic strategies needed to benefit patients developing progressive disease while receiving 5-FU or 5-FU-based programs. The tumor antibiotic mitomycin C is an alkylating agent with a broad range of clinical activity in a variety of gastrointestinal malignancies and is therefore a reasonable agent to test for clinical activity in the setting of 5-FU-resistant or -refractory colorectal cancer. The principal goal of this study is to investigate the logistical feasibility and clinical efficacy of a 7-day infusion of mitomycin C, delivering an equitoxic dose to the standard bolus delivery in patients with progressive disease while receiving 5-FU-based chemotherapy. Twenty-five patients with advanced measurable colorectal cancer, resistant or refractory to 5-FU-based chemotherapy, were treated with a 7-day intravenous infusion of mitomycin C. Doses ranged between 1.5 and 3.0 mg/M2/day for total cumulative mitomycin C, ranging between 10.5 and 21.0 mg/M2 per chemotherapy cycle. Forty-four courses of infusional mitomycin C were delivered to 25 patients via surgically implanted venous access devices. The median age of all patients was 63 years (range, 27-83); there were 11 men and 14 women. Eleven patients had received two or more prior chemotherapy combinations, with the average number of prior therapies before mitomycin C being 1.6. The median number of cycles of mitomycin C administered was two (range, one to six). Thirty-seven of 44 cycles were administered at the dose range of 2.0-3.0 mg/M2/day. Hematologic toxicity was mild, with only three courses associated with grade III thrombocytopenia and one course with grade III neutropenia. No extrahematologic toxicities were observed. No patient had a complete response; two patients (8%) showed partial responses that lasted for 145 and 190 days. One patient had stable disease for 180 days. Twenty-two of 25 patients (88%) developed progressive disease during mitomycin C administration. Infusional mitomycin C for 7 days, cycled every 42 days, is logistically feasible and associated with minimal clinical toxicity. Used on this schedule and with these doses in 5-FU-resistant/refractory colorectal cancer, however, there is no meaningful clinical activity for this agent, and it cannot be recommended as a salvage or second-line therapy in the treatment of metastatic colorectal cancer.

Adult↗

Case-based prediction of survival in colorectal cancer patients.

OBJECTIVE: To develop an approach to the prediction of survival in patients with colorectal cancer using nearest neighbor analysis and case-based reasoning. STUDY DESIGN: A total of 216 patients with full clinicopathologic records and five-year follow-up were the subjects of this study. They were divided into a core database of 162 cases and a test group of 54 cases, with follow-up on all patients. When the patient was still alive at the end of the follow-up period, censored survival time was used. For each of the test cases, the four closest neighbors from the database were retrieved and their median survival time recorded and used as the predicted estimate of survival. Case matching was based on a Euclidean multivariate distance measure for the three best predictor variables: patient age, Dukes stage and tubule configuration. Cases with the smallest distance from the test case were considered to be the most similar. The predicted survival times for the test cases were compared with the actual, observed survival in the test cases to determine the success of this approach. RESULTS: The results showed reasonable concordance between observed and predicted survival figures, although there was a large degree of spread. Classification of cases into < or = 60 and > 60 months' survival showed a correct classification rate of 63%. For the prediction of survival time, the distribution of differences between observed and predicted survival times for the uncensored test cases had a median value of--5 months but also showed a wide dispersion of values. Correlation of observed and predicted survival times, while not reaching statistical significance at P < .05, did show a strong positive association. CONCLUSION: Case-based approaches to the prediction of survival times in cancer patients are important. The results of the current study illustrate the difficulties in applying this approach to survival data and highlight the complexity of patient information and the inability to accurately predict patient outcome on a small subset of clinicopathologic features. While extensive work needs to be carried out to improve prediction power, this study illustrates the potential for case-based analyses. The ability to retrieve feature-matched cases from hospital patient databases has clear, independent advantages in patient management, but the ability to provide reliable, targeted prognostic estimates on individual cases should be a common goal in medical research.

Adult↗

Identifying inflorescence phytoliths from selected species of wheat (Triticum monococcum, T. dicoccon, T. dicoccoides, and T. aestivum) and barley (Hordeum vulgare and H. spontaneum) (Gramineae).

Analysis of microfossil silica phytoliths is becoming an increasingly important research tool for taxonomists, archaeobotanists, and paleoecologists. Expanded use of phytolith analysis by researchers is dependent upon development of phytolith systematics. In this study phytoliths produced by the inflorescence bracts from four species of wheat, Triticum monoccocum, T. dicoccon, T. dicoccoides, and T. aestivum, and two species of barley, Hordeum vulgare, and H. spontaneum, were analyzed using computer-assisted image and statistical analysis with the intent to develop taxonomic tools to distinguish among the taxa. A classification key based on significant differences among the mean morphometries of the inflorescence phytoliths produced by each species was created and tested. Discriminant analysis of the morphometries of several morphotypes of phytoliths was also conducted to determine whether this computer-assisted statistical procedure could be used as another method to classify the taxa and to determine which morphotypes have measurements that can best be used in discriminant functions. Test results indicated that, at the genus level, both the classification key and discriminant analysis of certain morphotypes of phytoliths were relatively reliable tools for distinguishing among phytoliths produced in the inflorescence bracts of the taxa considered. For distinguishing among the taxa at the species level, the classification key was most reliable. Of the discriminant analyses tested, that based on all the phytolith morphotypes combined was more reliable than those based on only one morphotype.

Journal Article↗

Public health response for the 1996 Olympic Games.

Extensive planning and preparation by public health agencies were required for the provision of public health services during the 1996 Centennial Olympic Games, which brought together more than 10000 athletes from 197 countries and more than 2 million visitors. Public health activities included the development and use of an augmented surveillance system to monitor health conditions and detect disease outbreaks; creation and implementation of 6 environmental health regulations; establishment of a central Public Health Command Center and response teams to coordinate response to public health emergencies; planning for potential mass casualties and the provision of emergency medical services; implementation of strategies for the prevention of heat-related illness; and distribution of health promotion and disease prevention information. Public health agencies should take the lead in organizing and implementing a system for preventing and managing public health issues at future large-scale public events such as the Olympics.

Anniversaries and Special Events↗

Agreement between survey and interview measures of weight control practices in adolescents.

OBJECTIVE: The present study examined agreement between survey and interview measures of weight control practices in a nonclinical sample of adolescents. METHOD: Surveys were administered in three school health classes. Clinical interviews were conducted in a student subsample (N = 43). RESULTS: Survey-based prevalences for eating behaviors in the past month were: trying to lose weight, 44%; binge eating, 41%; vomiting, 4.7%; laxative use, 0%; and fasting, 14%. Interview-based prevalences were 30%, 11.6%, 0%, 0% and 0%, respectively. Sensitivity was high for all behaviors assessed. However, positive predictive values were low. DISCUSSION: Surveys may be useful as preliminary screening tools for prevention programs, but may yield inflated estimates of unhealthy weight control practices in nonclinical adolescent populations. Research is needed to examine whether adolescents overreport weight control practices on surveys or whether they are less willing to disclose such practices in a private interview.

Adolescent↗

Phase I-II trial of 14 day infusional 6-mercaptopurine in advanced colorectal cancer.

6-Mercaptopurine (6-MP) is a cycle specific antineoplastic agent with a short serum half-life following bolus administration, providing a rationale for continuous infusional administration of the parenteral formulation. 22 patients received 38 courses of 14 day 6-MP infusion. The maximum tolerated dose (MTD) was 35 mg/m2/day (total dose per 14 day cycle 490 mg/m2) with cycles repeated at 28 days. Toxicities included transient hyperbilirubinaemia, leucopenia and thrombocytopenia. 13 evaluable patients with advanced colon cancer resistant to 5-fluorouracil with or without leucovorin received infusional 6-MP at the MTD as part of the phase II study analysis, but no objective responses were observed. Phase II studies in previously untreated patients and longer infusion durations are being evaluated.

Adult↗

Paclitaxel, cisplatin, etoposide combination chemotherapy: a multifractionated bolus dose schedule for non-small cell lung cancer.

In this phase II study, paclitaxel was added to the combination of cisplatin and etoposide (TPE regimen), in 37 patients with advanced non-small cell lung cancer, using a multifractionated dosing schedule. The total dose of paclitaxel (175-200 mg/m2); cisplatin (75 mg/m2); and etoposide (175-200 mg/m2) was divided into five daily doses administered over 3 h with cycles repeated at 21-28 days. 15 patients had stage III A or B disease and 22 stage IV disease. 32 patients were evaluable for toxicity and 37 for response. Neutropenia was the most prominent toxicity. Grade 3 or grade 4 neutropenia was observed in 12 (38%) and 9 (25%) of the patients, respectively and 11 patients required hospitalisation. 3 patients died secondary to chemotherapy related sepsis. Diarrhoea (grade 3, 3 patients; grade 4, 2 patients) was the only other significant non-haematological acute toxicity. The optimal dose rate for this multifractionated regimen was paclitaxel 35 or 40 mg/m2/fraction; cisplatin 15 mg/m2/fraction; etoposide 35 or 40 mg/m2/fraction. Responses were observed in 28 of 37 evaluable patients (3 complete response; 25 partial responses [76%]. 22 patients are alive; 8 with stage III B disease received radiation or surgery (3 had minimal or no tumour in the pathology specimen). TPE is a highly active regimen for non-small cell lung cancer and multifractionated dose scheduling is a feasible and well tolerated system.

Adult↗

Paclitaxel, cisplatin and etoposide combination chemotherapy: a comparison of dose intensity in two multifractionated dose schemas.

66 patients with a variety of tumour types received the multifractionated TPE three drug regimen in a non-random allocation as a 5 day schedule (schedule A) or as a twice weekly schedule (schedule B). The dose per fraction for each component drug was 35, 40 or 50 mg/m2 for both paclitaxel and etoposide and for cisplatin, the dose per fraction was 15 mg/m2. The total paclitaxel and etoposide dose was 175, 200, 250 mg/m2 3 week cycle. For schedule A, grade 3 or 4 neutropenia was observed in 70/114 cycles (61%) with two treatment related deaths from 50 treated patients. For schedule B, grade 3 neutropenia was observed in 1 of 30 courses (3%) with one drug related death from 19 treated patients. Dose intensity was increased by 20% for both paclitaxel and etoposide with the twice weekly schedule and at all dose levels, with haematological toxicity substantially reduced relative to schedule A. Using multifractionated schedules, a twice weekly open ended schedule results in an approximately 20% greater dose intensity and less toxicity compared with a 5 day schedule repeated every 3 weeks. The recommended dose schedule for TPE is paclitaxel 40 mg/m2; cisplatin 15 mg/m2 and etoposide 40 mg/m2 twice weekly for 3 weeks repeated every 4 weeks.

Adult↗

Carboplatin versus cisplatin in solid tumors: an analysis of the literature.

BACKGROUND: Introduced into clinical usage in 1992 as a platinum analogue with a distinctively different toxicity profile from cisplatin, carboplatin has become a commonly preferred agent over cisplatin. The comparative therapeutic efficacy of the two agents remains controversial however, prompting an analysis of the phase III trials in ovarian cancer and other tumors in which the two were compared. METHODS: Clinical trials comparing carboplatin with cisplatin, both as single agents and in combination with other agents, were analyzed within the tumors for which platinum has become a standard or commonly employed agent. A Medline search identifying the randomized trials and references from these reports were collated for analysis. RESULTS: The original clinical comparative trials as well as literature reviews and commentaries were reviewed. Five solid tumors were identified within which comparative trials had been conducted: ovary, 10 trials; lung, 2 trials; head and neck, 2 trials; germ cell tumors, 3 trials and 1 trial in bladder cancer. Depending upon the end point selected, cisplatin was superior or equivalent to carboplatin in therapeutic efficacy in all five tumors but was associated with an increased toxicity profile for gastrointestinal, renal and neurologic effects. CONCLUSIONS: For some tumors, cisplatin appears to be superior to carboplatin in terms of therapeutic effectiveness (germ cell tumors, bladder cancer, head and neck cancer), while for others, effectiveness is comparable (lung cancer, ovarian cancer). Toxicity profiles are distinctly different for the two analogues however, generally favoring carboplatin. The issue of potential carboplatin underdosing related to the lack of physiologic dose calculations (utilizing the AUC [area under the curve] method) in the comparative trials of cis- versus carboplatin is probably not clinically important since a dose response effect has not been established for carboplatin or for cisplatin. The selection of the optimal platinum analogue to be employed is dependent on the type of tumor, the treatment intention (palliative vs. curative) and the other component drugs being used in combination.

Antineoplastic Agents↗

Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1.

Few well-controlled diet studies have investigated the effects of reducing dietary saturated fatty acid (SFA) intake in premenopausal and postmenopausal women or in blacks. We conducted a multicenter, randomized, crossover-design trial of the effects of reducing dietary SFA on plasma lipids and lipoproteins in 103 healthy adults 22 to 67 years old. There were 46 men and 57 women, of whom 26 were black, 18 were postmenopausal women, and 16 were men > or =40 years old. All meals and snacks, except Saturday dinner, were prepared and served by the research centers. The study was designed to compare three diets: an average American diet (AAD), a Step 1 diet, and a low-SFA (Low-Sat) diet. Dietary cholesterol was constant. Diet composition was validated and monitored by a central laboratory. Each diet was consumed for 8 weeks, and blood samples were obtained during weeks 5 through 8. The compositions of the three diets were as follows: AAD, 34.3% kcal fat and 15.0% kcal SFA; Step 1, 28.6% kcal fat and 9.0% kcal SFA; and Low-Sat, 25.3% kcal fat and 6.1% kcal SFA. Each diet provided approximately 275 mg cholesterol/d. Compared with AAD, plasma total cholesterol in the whole group fell 5% on Step 1 and 9% on Low-Sat. LDL cholesterol was 7% lower on Step 1 and 11% lower on Low-Sat than on the AAD (both P<.01). Similar responses were seen in each subgroup. HDL cholesterol fell 7% on Step 1 and 11% on Low-Sat (both P<.01). Reductions in HDL cholesterol were seen in all subgroups except blacks and older men. Plasma triglyceride levels increased approximately 9% between AAD and Step 1 but did not increase further from Step 1 to Low-Sat. Changes in triglyceride levels were not significant in most subgroups. Surprisingly, plasma Lp(a) concentrations increased in a stepwise fashion as SFA was reduced. In a well-controlled feeding study, stepwise reductions in SFA resulted in parallel reductions in plasma total and LDL cholesterol levels. Diet effects were remarkably similar in several subgroups of men and women and in blacks. The reductions in total and LDL cholesterol achieved in these different subgroups indicate that diet can have a significant impact on risk for atherosclerotic cardiovascular disease in the total population.

Adult↗