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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 37 records · Page 2Linked to original sources

Trichostrongylid infections in sheep after rainfall during summer in southern Australia.

OBJECTIVE: To relate trichostrongylid infections acquired by sheep during summer to prevailing weather conditions. PROCEDURE: Groups of worm-free 'tracer' sheep were put onto pastures, previously contaminated with trichostrongylid eggs, for successive periods of 2 weeks from December to March. After grazing the sheep were housed for 6 weeks. Weekly worm egg counts and worm counts were used to estimate the numbers of worms acquired and related to weather conditions during the grazing period. RESULTS: No worm eggs were detected in the faeces of sheep that grazed at the end of January when only 7 mm of rainfall was recorded. At other times rainfall between 12 and 24 mm occurred and strongyle egg counts were generally either < 50 or > 150 eggs per g (epg). Mean counts of 1,100 Ostertagia and Trichostrongylus adults gave rise to mean counts of about 350 epg whereas about 6,000 Nematodirus spp were associated with mean egg counts of about 200 Nematodirus spp epg. CONCLUSIONS: Rainfall events during summer determine the numbers of trichostrongylid larvae acquired by sheep in summer but further studies are necessary before the implications for strategic control programs in southern Australia can be fully assessed.

Animal Husbandry↗

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Aged↗

Boron isotope effect in superconducting MgB2.

We report the preparation method of and boron isotope effect for MgB2, a new binary intermetallic superconductor with a remarkably high superconducting transition temperature T(c)(10B) = 40.2 K. Measurements of both temperature dependent magnetization and specific heat reveal a 1.0 K shift in T(c) between Mg11B2 and Mg10B2. Whereas such a high transition temperature might imply exotic coupling mechanisms, the boron isotope effect in MgB2 is consistent with the material being a phonon-mediated BCS superconductor.

Journal Article↗

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival.

The quantitative assessment of apoptotic index (AI) and mitotic index (MI) and the immunoreactivity of p53, bcl-2, p21, and mdm2 were examined in tumour and adjacent normal tissue samples from 30 patients with colonic and 22 with rectal adenocarcinoma. Individual features and combined profiles were correlated with clinicopathological parameters and patient survival data to assess their prognostic value. Increased AI was significantly associated with increased bcl-2 expression (p<0.008) and the immunoprofiles that included bcl-2, but not with MI, p53, p21 or mdm2. AI was significantly associated with increased Dukes' stage from A, B to C (p<0.02) but not D, while MI showed a significant association with all Dukes' stages (p<0.05). No significant association was found between either AI or MI and prognosis. p53, p21, mdm2, and bcl-2 positivity were detected in 65.4%, 53.8%, 65.4%, and 34.6% of cases, respectively. mdm2 was significantly associated with p53 (p<0.03) and p21 (p<0.04) expression and p53 immunoreactivity was more prevalent in rectal tumours (p<0.008). In univariate survival analysis, bcl-2 overexpression was associated with more favourable patient survival (p<0.03). Positive combined patterns p53+/p21+/bcl-2+ and p21+/mdm2+/bcl-2+ (p<0.005); p53+/bcl-2+, p21+/bcl-2+, and mdm2+/bcl-2+ (p<0.01); and p53+/p21+ (p<0.02) were also associated with favourable clinical outcome. In multivariate Cox survival analysis, bcl-2 (p<0.016) and Dukes' stage (p<0.0001) were the only significant independent prognostic indicators. In conclusion, bcl-2 immunoreactivity was associated with apoptosis and could be used in combination with Dukes' stage as a means of predicting prognosis in colorectal cancer.

Adenocarcinoma↗

Primary leiomyosarcoma of the breast: diagnosis, management and outcome. A report of a new case and review of literature.

Primary leiomyosarcoma of the breast is very rare and represents a diagnostic challenge. Only 16 cases have been reported in the English language literature. We report another new case and have analysed reports of the previous cases aiming to present a simple evidence-based approach to the clinical, radiological and pathological diagnosis of this rare tumour. The average age of presentation is 56 years. All neoplasms have been limited to the breast at the time of diagnosis. The usual presentation is a slowly growing mass, but in the current case report the patient present with mastalgia. There is always a possibility of local recurrence or distant spread, which can occur many years after primary surgery. Leiomyosarcoma must be histologically distinguished from leiomyoma and the presence of >3 mitoses per 10 high-power fields is usually indicative of malignancy. Immunohistochemistry is helpful to confirm diagnosis. As this is a slow-growing malignant tumour with a propensity for local recurrence, total mastectomy is the treatment of choice. The tumour is not hormone-dependent and hormone manipulation is not a treatment option.

Journal Article↗

A polymorphism within the interleukin 1 receptor antagonist (IL-1Ra) gene is associated with ankylosing spondylitis.

OBJECTIVE: Genetic factors that predispose individuals to ankylosing spondylitis (AS) are not fully understood, but are unlikely to be restricted to HLA-B27. Proinflammatory cytokines are implicated in the development of sacroiliitis. We have examined the allele frequencies of three polymorphic sites in the interleukin (IL)-1 genes in AS patients to investigate whether genetic regulation of IL-1 production could be implicated in AS pathogenesis. METHODS: DNA from 188 AS patients, 115 healthy controls and 81 HLA-B27-positive healthy controls, all from the West of Scotland, were examined with the polymerase chain reaction in a case-controlled study. Polymorphic sites in genes of the IL-1 family were examined, including the 86-base pair variable number tandem repeat within intron 2 of the IL-1Ra gene, and the restriction fragment length polymorphisms at positions -889 in the IL-1alpha gene and -511 in the IL-1beta gene. RESULTS: No significant differences were seen at the polymorphic alleles in the IL-1alpha and IL-1beta genes, but there was a significant increase in the carriage of allele 2 in the IL-1Ra in the AS patients compared with local controls (16 vs 8%, odds ratio 2.3, 95% confidence interval 1.2-4.4, P=0.01). CONCLUSION: This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.

Adolescent↗

Antisense Bcl-2 oligonucleotide uptake in human transitional cell carcinoma.

OBJECTIVES: Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in: (1) the RT4 bladder tumour cell line; (2) normal pig urothelium, and (3) human superficial bladder tumours. METHODS: In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4-hour intervals over 24 h. Uptake of FITC-AO was assessed in normal pig urothelium by flow cytometry after FITC-AO was infused for 1 h. Uptake of FITC AO was assessed in samples from 14 human superficial bladder tumours which were maintained in an ex vivo model. In samples from 6 tumours, uptake at 4 h was assessed using fluorescence microscopy. In samples from 8 separate tumours uptake every 4 h within the first 24-hour incubation period was assessed by flow cytometry. RESULTS: In the RT4 cell line the FITC-AO, FITC-scrambled and FITC-sense oligonucleotide uptake was similar. Disaggregated cells from the normal urothelium of the 3 pigs exhibited 33, 46 and 51% of cells staining positively for FITC-AO as determined by flow cytometry. All 6 tumour samples had detectable intracellular FITC-AO by fluorescence microscopy at 4 h. In the 8 tumours examined over the 24-hour incubation period, there was a range of percentages of positively staining cells. However, most tumours had a monotonic increase in intracellular fluorescence intensity that plateaued 16 h post-infusion. CONCLUSION: Antisense Bcl-2 oligonucleotides were readily taken up by superficial bladder cancer cells but the heterogeneous uptake in tumour samples needs to be considered when assessing the bioavailability of these drugs.

Animals↗

An epidemic of corneal destruction caused by plasma gas sterilization. The Toxic Cell Destruction Syndrome Investigative Team.

BACKGROUND: Toxic endothelial cell destruction (TECD) syndrome after intraocular ophthalmic surgery is rare and can result from exposure to a variety of toxins. During January 8 to 14, 1998, 6 patients developed TECD with corneal edema associated with unreactive or dilated pupils at Hospital A. METHODS: A case patient was any Hospital A patient with TECD within 24 hours after surgery during January 5 to 14, 1998 (epidemic period). A control was any hospital A ophthalmic surgery patient without TECD during the epidemic period. The medical records of hospital A ophthalmology surgery patients during the pre-epidemic (ie, September 1, 1997-January 4, 1998) and epidemic periods were reviewed. Inductively coupled plasma atomic emission spectrometry was used to detect trace inorganic elements on sterilized surgical instruments. Cannulated surgical instruments and laboratory rinsates were perfused directly to the corneal endothelium of isolated rabbit and human corneas. Corneal endothelial ultrastructure and swelling were assessed. RESULTS: The rate of TECD at hospital A was higher during the epidemic than pre-epidemic period (6/12 vs 0/118, P<.001). The only change during the periods was the introduction, on November 5, 1997, of a new sterilization method, AbTox Plazlyte, for sterilization of ophthalmic surgery instruments. Findings from spectrometry revealed that copper and zinc residues were higher in instruments sterilized with Plazlyte than in those sterilized with ethylene oxide (median copper value, 7.64 mg/L vs 0.14 mg/L, respectively, P =.02; median zinc value, 5.90 mg/L vs 1.35 mg/L, respectively, P =.2). Corneal endothelial perfusion of Plazlyte sterilized-instrument rinsates or laboratory solution with copper and zinc produced irreversible damage, similar to toxic corneal endothelial destruction, to rabbit and human corneas. CONCLUSION: A new sterilization method degraded brass to copper and zinc on cannulated surgical instruments resulting in TECD of the cornea. Arch Ophthalmol. 2000;118:1167-1176

Adult↗

Gambling involvement and drug use among adolescents.

The literature on youth gambling often notes the relationship of gambling involvement to drug use. The extent of this association and its importance toward advancing knowledge about the origins and course of adolescent gambling are discussed. The authors contend that (a) adolescent gambling, like drug use, may be a normal part of adolescence from a statistical perspective, (b) claims that the prevalence rate of problem/pathological gambling is comparable or higher than the rate of substance use disorders are not supportable at this time given the weaker methodological studies in the gambling area, (c) while research suggests that similar risk factors may be important determinants for both behavior domains, prospective studies of adolescent development are needed to further clarify which factors are unique and common to adolescent gambling, and (d) greater documentation of the harm associated with adolescent gambling is a major barrier to garnering more prevention and treatment resources for this issue.

Journal Article↗

Development of a district Cord Blood Bank: a model for cord blood banking in the National Health Service.

The Bristol Cord Blood Bank was established as a pilot project within existing health services to establish cost-effective recruitment, collection and processing suitable for use in the NHS should cord blood become a routine source of haemopoietic stem cells for transplantation in the UK. An important aim of the project was to evaluate the feasibility of establishing a midwifery-based collection network, thus utilising expertise already in place. Collection was performed on the delivery suite immediately after the placenta was delivered. The clinical experience of the midwife collector/counsellors allowed rapid pre-collection assessment of the condition of the cord and placenta. This prevented collection attempts from diseased or otherwise damaged placentas, leading to conservation of resources by preventing collection of most small volume donations. The bank was established within the National Blood Service, Bristol Centre to achieve Good Manufacturing Practice standards and ensure that processing was subject to the same stringency required for other sources of haemopoietic stem cells. Cord blood is an expensive resource. By utilising existing expertise in district Obstetric and National Blood Services, the Bristol Cord Blood Bank may serve as a model for health economic evaluation of cord blood banking of volunteer donations within the NHS.

Blood Banks↗

The relationship between the rate of intake of trichostrongylid larvae and the occurrence of diarrhoea and breech soiling in adult merino sheep.

BACKGROUND AND OBJECTIVE: A hypersensitive inflammatory response, associated with the ingestion of trichostrongylid larvae, is a major cause of diarrhoea and soiling of the breech with faeces in adult Merino sheep ('hypersensitivity scours'). This response is characterised by an infiltration of eosinophils and altered lymphocyte populations in the gut of affected sheep. The objective of this study was to investigate the numbers of Ostertagia circumcincta and Trichostrongylus vitrinus infective larvae that were needed to induce diarrhoea in adult Merino sheep grazing improved pastures. METHOD: Sheep from three farms were categorised as either being susceptible, or not susceptible, to hypersensitivity scours, then transported to an experimental farm and grazed on pastures with low numbers of trichostrongylid infective larvae. They were ranked by farm of origin and previous worm egg count, then systematically allocated to one of five dose-rate groups and infected with 0, 2, 4, 10 or 20 x 10(3) trichostrongylid infective larvae per week for 13 weeks. RESULTS: In sheep selected as being susceptible to hypersensitivity scours, the lowest dose rate of infective larvae (2000 per week) was as effective in inducing diarrhoea as the highest dose rate (20,000 per week). In contrast, even the highest larval dose did not induce diarrhoea in sheep selected as not susceptible to hypersensitivity scours. Sheep selected with an increased susceptibility to hypersensitivity scours also had a significantly higher amount of moisture in their faeces at all times except during summer. CONCLUSIONS: The apparent lack of a threshold dose of trichostrongylid infective larvae needed to induce hypersensitivity scours suggests that even improved worm control programs, which substantially decrease the ingestion of larvae, may not be able to reduce the prevalence of hypersensitivity scours or the severity of breech soiling. Controlled-release anthelmintic capsules will control breech soiling but are often not a cost-effective strategy. Thus, genetic selection of less susceptible sheep is probably the best long-term option for the control of hypersensitivity scours, and the assessment of faecal moisture may be a convenient marker of susceptibility to this syndrome.

Animals↗

Cognitive impairments after surgical repair of ruptured and unruptured aneurysms.

OBJECTIVES: To determine the frequency and severity of neuropsychological impairments associated with aneurysmal subarachnoid haemorrhage, and associated with repair of intracerebral aneurysms. METHODS: Two groups of patients who underwent repair of intracerebral aneurysms were studied: patients with unruptured aneurysms (n=20) and patients with ruptured aneurysms (n=27). All patients were administered a battery of standardised neuropsychological tests about 3 months after surgery. A subset of 12 patients with unruptured aneurysms were administered the battery both before and after elective repair of the aneurysm(s). A subset of six patients with ruptured aneurysms were given the test at both 3 months and 1 year after surgery. RESULTS: As previously reported for patients with ruptured aneurysms, patients with both ruptured and unruptured aneurysms performed, as a group, significantly below published norms on many of the neuropsychological tests after surgery. However, there were significant differences between preoperative and postoperative performance in the unruptured aneurysm group only on a few tests: measures of word fluency, verbal recall, and frontal lobe function. Performance of patients with ruptured aneurysms was significantly below that of patients with unruptured aneurysms only on a few tests of verbal and visual memory. In addition, group differences compared with published norms reflected severely impaired performance by a minority of patients, rather than moderately impaired performance in a majority of patients. CONCLUSIONS: Although patients who undergo repair of ruptured aneurysms perform, as a group, below published norms on many neuropsychological tests, significant impairments are seen in a minority of patients. Some of the impairments are associated with subarachnoid haemorrhage, whereas others (found in patients who underwent repair of unruptured aneurysms) are due to general effects of neurosurgery and perioperative management. Finally, some of the postoperative deficits are merely a reflection of premorbid weaknesses.

Adult↗

Bradykinin B(2) receptor antagonism attenuates blood pressure response to acute angiotensin-converting enzyme inhibition in normal men.

The physiological effects of angiotensin-converting enzyme (ACE) inhibition may be in part mediated by bradykinin. We investigated the effect of coadministration of the specific bradykinin B(2) receptor antagonist icatibant on hemodynamic and neurohormonal responses to acute intravenous ACE inhibition in normal men on a normal sodium diet. We performed a 4-phase, double-blind, double-dummy, placebo-controlled study in 12 male volunteers. The bradykinin antagonist icatibant (10 mg IV) was coadministered over the first 15 minutes of a 2-hour infusion of the ACE inhibitor perindoprilat (1.5 mg IV). Perindoprilat inhibited ACE activity and elicited the expected changes in active renin concentration and angiotensin peptides. Over the 3 hours after the start of drug infusion, perindoprilat lowered and icatibant increased mean arterial blood pressure (each P<0.0005 versus placebo). Coadministration of icatibant attenuated the mean arterial blood pressure response to perindoprilat (P<0.0005) but had no effect on neurohormonal responses to perindoprilat. Our study indicates that the bradykinin B(2) receptor antagonist icatibant attenuates the short-term blood pressure-lowering effect of acute ACE inhibition in normal men on a normal sodium diet. Bradykinin B(2) receptor antagonism alone increases resting blood pressure. Bradykinin may be involved in the control of blood pressure in the resting state in humans.

Adult↗

The sensitivity and specificity of two methods for detecting Fasciola infections in cattle.

Counts of Fasciola spp. eggs in faeces and measurements of antibody concentration to the excretory/secretory antigens of Fasciola spp. by ELISA were related to the numbers of flukes in the livers of 92 cattle killed in the abattoirs of Hanoi City, Vietnam. In this population, about 22% of the cattle had no flukes, another 22% had between 1 and 10 flukes, 44% between 11 and 100 flukes and 12% had more than 100 flukes in their livers. Of the 14 animals less than 2 years of age, only three were infected. At 2 years of age the mean number of flukes per liver was 10 whereas at 3 years and older, the mean varied between 60 and 80 flukes. Prevalence of infection was 78.3%. No eggs of Fasciola spp. were detected in the faeces of one third of infected cattle and 60% of the counts were less than 100 eggs per gram. The sensitivity of the egg counting method was 66.7% and specificity 100%, overall accuracy was 73.9%. Corresponding values for the ELISA method were 86.1, 70 and 82.6%, respectively. The positive and negative predictive values for the egg counting method were 100 and 45.5% and for the ELISA method were 91.2 and 58.3%, respectively.

Animals↗

The multifractionated, twice-weekly dose schedule for a three-drug chemotherapy regimen: a phase I-II study of paclitaxel, cisplatin, and vinorelbine.

BACKGROUND: Paclitaxel, cisplatin, and vinorelbine are three important antineoplastic drugs with different mechanisms of cell kill. A combination of these three drugs potentially could have additive therapeutic effects. METHODS. The three-drug combination (designated TPN) was administered on a twice-weekly (Monday/Thursday; Tuesday/Friday) schedule for 3 weeks, with cycles repeated every 28 days. The Phase I design utilized a dose de-escalation schema in which the maximum tolerated dose was defined by a patient's ability to complete 6 doses (a full cycle) without interruption for hematologic Grade 3 or 4 toxicity. RESULTS: Twenty-seven patients received a total of 42 evaluable courses of the 3-drug regimen. The cisplatin dose was fixed at 15 mg/M2/fraction. The paclitaxel dose was first fixed at 50 mg/M2/fraction, and venorelbine was delivered at 3 dose levels per fraction: 10, 7.5, and 5 mg/M2. Paclitaxel then was de-escalated to 40 mg/M2/fraction, and the same 3 dose levels of vinorelbine were evaluated. The dose-limiting toxicity was neutropenia. Using fixed doses of paclitaxel at 40 mg/ M2/fraction and cisplatin at 15 mg/M2, the optimal dose fraction for vinorelbine was 7.5 mg/M2, defined as the dose that allowed > 67% of patients to complete 3 weeks (6 consecutive doses) of therapy. Using paclitaxel at 50 mg/M2/fraction (cisplatin at 15 mg/M2/fraction), the optimal dose of vinorelbine was 5 mg/M2/fraction. Tumor responses were observed in 13 patients: 2 with unknown primary, 1 with esophageal carcinoma, 6 with nonsmall cell lung carcinoma, and 3 with breast carcinoma. Grade 2 neurologic (sensory) toxicity was observed in 5 patients. CONCLUSIONS: TPN administered according to a twice-weekly dosing scheme can be delivered with acceptable toxicity. The dose intensity for paclitaxel (60-75 mg/M2/week), cisplatin (22 mg/M2/week), and vinorelbine (15 mg/M2/week) is > 50% of the single agent dose intensity for the component agent. Recommended Phase II or Phase III trials could utilize dose fractions of paclitaxel, cisplatin, and vinorelbine at either 50, 15, and 5 mg/M2/fraction or 40, 15, and 7.5 mg/M2/fraction in this twice-weekly, multifractionated dose schedule.

Adult↗