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Biomedical subjects

A MacMillan

Publications and source records attributed to A MacMillan.

At least 19 recordsLinked to original sources
PubMed2006

Expression of a pertussis toxin S1 fragment by inducible promoters in oral Streptococcus and the induction of immune responses during oral colonization in mice.

Previous work aimed at developing a live oral vaccine expressing pertussis toxin S1 fragment on the surface of the bacterium Streptococcus gordonii elicited a lower than expected antibody response, perhaps because of low antigen expression. In this study, in-frame promoter fusions were constructed to investigate whether an increase in antigen production by the streptococcal vaccine strain results in a better antibody response. The promoters tested were (i) the Streptococcus mutans sucrose-inducible fructosyltransferase (ftf) promoter and (ii) the Bacillus subtilis/Escherichia coli chimeric tetracycline-inducible xyl/tetO promoter. Each of these two promoters was placed upstream of the spaP/s1 fusion gene to drive its expression. The constructs were introduced into S. gordonii DL1 and S. mutans 834. The inducibility of the promoters was confirmed through the determination of SpaP/S1 production via Western blottings. Induced production of SpaP/S1 was observed in S. gordonii and S. mutans with each of the promoters, but the level of expression was the highest in S. mutans, using the xyl/tetO promoter. Thus, S. mutans carrying the xyl/tetO/spaP/s1 construct (S. mutans PM14) was used in oral colonization studies in BALB/c mice. Streptococccus mutans PM14 was able to colonize the animals for the 14-week duration of experimentation. A mucosal IgA response was observed in all the treatment groups but was highest in mice receiving tetracycline induction. In the mouse model of Bordetella pertussis respiratory infection, animals colonized with S. mutans PM14 showed a decreased in B. pertussis lung colony count (P = 0.03) on day 3 compared with control mice colonized by the parent S. mutans 834.

Administration, Oral↗
PubMed2004

A quantitative risk assessment for the importation of brucellosis-infected breeding cattle into Great Britain from selected European countries.

Great Britain (GB) has been "Officially Brucellosis Free" (OBF) since 1991; because this disease has both public-health and international-trade implications, it is in the country's interest to maintain this freedom. A quantitative risk-assessment model was developed to determine the annual risk of importing brucellosis-infected breeding cattle into GB from Northern Ireland and the Republic of Ireland. (These countries exported the largest number of cattle into GB and were not brucellosis free during the development of the assessment in 2000.) We predicted that we can expect to import brucellosis from Northern Ireland every 2.63 years (1.89, 4.17) and from the Republic of Ireland, every 3.23 years (2.13, 5.88). The estimates of risk are sensitive to the assumed proportion of animals missed during routine surveillance that originate from OBF herds and the uncertainty associated with the surveillance test sensitivities. As a result of the assessment, the Department for Environment, Food and Rural Affairs (Defra) introduced post-calving testing for all cattle imported into British herds.

Animals↗
PubMed2004

A simulation model of brucellosis spread in British cattle under several testing regimes.

Brucellosis is a widespread, economically devastating and highly infectious zoonosis. In cattle, infection predominantly is caused by Brucella abortus, and is usually detected in pregnant females through abortions. Great Britain (GB) has been declared free from brucellosis (officially brucellosis free (OBF)) since 1993 and as such is required by European Union (EU) regulations to test > or =20% of both beef and dairy cattle >24 months old routinely. Currently, however, GB serologically tests more cattle than required and the issue of reducing the level of testing has come under consideration. We developed a simulation model to determine the rate of spread of brucellosis under a variety of testing regimes. For dairy herds, we found that reducing the level of testing would have a major effect on the rate of spread of infection, should it be imported. For beef herds, reducing the level of testing would have much less effect. We also found that abortion notification is a very-important additional means of surveillance. As a result of our predictions, policy-makers decided not to reduce the level of testing and actively to promote abortion notification.

Abortion, Veterinary↗
PubMed2000

Vaccines for preventing hepatitis B in health-care workers.

BACKGROUND: Hepatitis B causes acute and chronic liver disease and may be prevented by vaccination. OBJECTIVES: To assess the effectiveness and safety of plasma-derived vaccines against acute and chronic hepatitis B in health-care workers in protecting them from hepatitis B infection and its consequences. SEARCH STRATEGY: MEDLINE and Excerpta Medica Database (EMBASE) search using standard Cochrane strategy, Cochrane Library, full text searching of the journal "Vaccine", bibliography of retrieved studies and correspondence with authors, researchers and manufacturers. SELECTION CRITERIA: All original prospective randomised comparisons of yeast-derived vaccines and plasma-derived vaccines against no intervention, placebo, or vaccines against other disease (control vaccines). Assessment of trial quality was made according to: 1. generation of allocation schedule 2. measure(s) taken to conceal treatment allocation 3. drop-out of allocated health-care worker participants from the analysis of trial results 4. measures taken to implement double blinding Trial reports were blinded by removal of authors and their affiliation, journal reference, introduction, results, and discussion. DATA COLLECTION AND ANALYSIS: To assess efficacy the incidence rates of acute hepatitis B were observed in the surveillance of the vaccinated and control groups of the trials included in the review. Safety was assessed from side-effect rates, classified as systemic (malaise, nausea, fever, arthralgias, rash, headache) or local (induration and soreness at the site of the inoculation). MAIN RESULTS: Four trials fulfilling the criteria were identified and the data synthesised. All trials compared plasma-derived vaccines versus placebo. Differences in the settings (and level of incidence) between three of the trial settings and Dienstag's led us to stratify our comparison grouping the three trials performed in dialysis units together. After our stratification, the Desmyter, Smuzness and Crosnier group appears to be homogeneous (Chi-square = 0.11, degrees of freedom = 2). Our estimates of effectiveness and safety in the high risk group favour treatment, the OR for cases of HB being 0.34; 95% CI (0.21, 0.55). The analysis also revealed a non-significant trend towards benefit in the lower risk health-care workers (Dienstag trial, OR 0.26 (0.05, 1.30). Overall the evidence strongly favours vaccination (OR=0.33; 95% CI (0.21, 0.53)). There was no difference in the incidence and severity of side-effects between the two arms of the trials. We calculated that it was necessary to vaccinate between 145 (assuming a baseline rate of 10 cases/1000/year) and 7 (for a baseline rate of 200/1000/year) health-care workers with plasma-derived vaccines to avoid one case of hepatitis B. Completeness of trial reporting was not good with all four trials failing to report titre results on antibodies against hepatitis B surface antigen and hepatitis B core antigen in the placebo arms (correspondence with two of the four authors failed to shed light on the reasons for such an omission). All four trials achieved low scores in the four quality dimensions assessed (generation of allocation schedule, measure(s) taken to conceal treatment allocation, exclusion of allocated participants from the analysis of the trial and measures taken to implement and protect double blinding). Mean length of follow-up was 14.5 months. REVIEWER'S CONCLUSIONS: Plasma-derived vaccines appear to be efficacious and safe for use in high risk health-care workers, such as staff of renal dialysis and transplant units. There is some uncertainty concerning the effectiveness of the vaccine in lower risk health-care workers, although the trend is towards benefit. We found no evidence of a long-term protective effect due to the short follow-up time of the four trials included in this review. We found relatively poor standard of trial reporting, possibly related to the age of the trials.

Health Personnel↗
PubMed2000

ESHAP and G-CSF is a superior blood stem cell mobilizing regimen compared to cyclophosphamide 1.5 g m(-2) and G-CSF for pre-treated lymphoma patients: a matched pairs analysis of 78 patients.

Cyclophosphamide 1.5 g m(-2) followed by granulocyte colony-stimulating factor (G-CSF) is an effective peripheral blood stem cell (PBSC) mobilizing regimen, but has limited anti-lymphoma activity. We therefore assessed the mobilizing potential of ESHAP (etoposide, ara-C, methylprednisolone and cisplatin), a potent second-line lymphoma regimen followed by G-CSF. The results were compared in 78 patients with relapsed or resistant lymphomas with the use of cyclophosphamide 1.5 g m(-2) followed by G-CSF in a matched pairs analysis, matching the ESHAP recipients (for predetermined prognostic factors) from a cohort of 178 lymphoma patients mobilized with cyclophosphamide and G-CSF. The total numbers of mononuclear cells collected at apheresis was similar with both regimens but ESHAP plus G-CSF resulted in a significantly higher percentage of CD34+ cells, absolute number of CD34+ cells and GM-CFC (all with P-values < 0.001). The number of patients requiring only one apheresis harvest to achieve a CD34+ cell yield of > 2.0 x 10(6) kg(-1) was greatly increased in the ESHAP recipients (56/78 vs 17/78, P < 0.001). The total number of progenitor cells collected was not significantly different with the two mobilization regimens because of this higher number of apheresis in the cyclophosphamide group. The proportion of patients who failed to achieve a minimum CD34+ cell target of 1 x 10(6) kg(-1) with the pooled harvests was less in the ESHAP arm (four patients vs nine patients) despite an increased number of aphereses in the cyclophosphamide recipients. ESHAP plus G-CSF is well tolerated and is an excellent mobilization regimen in patients with pre treated lymphoma.

Adult↗
PubMed2000

Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory.

The Neuropsychiatric Inventory (NPI) is a validated clinical instrument for evaluating psychopathology in dementia. The authors developed a brief questionnaire form of the NPI (NPI-Q), intended for use in routine clinical practice, and cross-validated it with the NPI in 60 Alzheimer's patients. Test-retest reliability of the NPI-Q was acceptable. The prevalence of analogous symptoms reported on the NPI and NPI-Q differed on average by 5%; moderate or severe symptom ratings differed by less than 2%. The NPI-Q provides a brief, reliable, informant-based assessment of neuropsychiatric symptoms and associated caregiver distress that may be suitable for use in general clinical practice.

Aged↗
PubMed1998

Inflicted esophageal perforation.

Esophageal perforation in children is uncommon. A 2 1/2-year-old girl presented with multiple soft tissue injuries of various chronological ages. Initial lateral cervical spine films showed the presence of a prevertebral air collection with soft tissue swelling. Enhanced computerized tomography confirmed the presence of proximal esophageal rupture and a retropharyngeal abscess. External drainage of the abscess and intravenous antibiotics led to resolution of the perforation in 13 days. Discrepancies in the history and the constellation of injuries pointed to an inflicted etiology (through child abuse). Since 1984, 21 case studies have described inflicted esophageal perforation. Common mechanisms of injury include foreign body ingestion and blunt or penetrating external trauma. Early diagnosis of these injuries reduces both acute and long-term morbidity and mortality. Pediatric surgeons must be aware of inflicted injury as an etiology of esophageal and hypopharyngeal perforation.

Child Abuse↗
PubMed1998

A case of EBV-associated lymphoproliferative disease following high-dose therapy and CD34-purified autologous peripheral blood progenitor cell transplantation.

A fatal case of EBV-associated lymphoproliferative disorder arising after a CD34-selected autologous peripheral blood stem cell transplant is reported in a patient with multiple myeloma in first plateau phase. It is suggested that this is likely to be a consequence of the accessory cell depletion associated with the CD34+ cell purification and it is recommended that a source of autologous T cells is stored before transplantation to be used if a severe opportunistic infection or EBV lymphoma arises post-transplantation.

Antigens, CD34↗
PubMed1998

Assessing the impact of neuropsychiatric symptoms in Alzheimer's disease: the Neuropsychiatric Inventory Caregiver Distress Scale.

OBJECTIVES: To develop an adjunct scale to the Neuropsychiatric Inventory (NPI) for assessing the impact of neuropsychiatric symptoms in Alzheimer's disease (AD) patients on caregiver distress. DESIGN: Cross-sectional descriptive and correlational study. SETTING: University out-patient memory disorders clinics. PARTICIPANTS: Eighty-five AD subjects and their caregivers (54 spouses, 31 children). MEASUREMENTS: The NPI and NPI Caregiver Distress Scale (NPI-D) were used to assess neuropsychiatric symptoms in AD patients and related caregiver distress, respectively. Criterion validity of the NPI-D was examined (N = 69) by comparison with an abridged version of the Relatives' Stress Scale (RSS'), a general measure of caregiver stress, using item clusters that had previously been correlated to behavioral disturbances in demented patients. Test-retest (n = 20) and inter-rater reliability (n = 16) of the NPI-D were also assessed. RESULTS: Test-retest and interrater reliability of the NPI-D were both adequate. Overall, caregiver NPI-D distress ratings were correlated significantly with the RSS' (r = .60, P < .001). RSS' ratings correlated strongly with NPI scores (r = .64, P < .001), even after controlling for degree of cognitive impairment based on the Mini-Mental State Exam (MMSE) score (r = .61). MMSE scores showed a moderate correlation to RSS' ratings (-.30, P = .02), but this association was markedly attenuated when controlling for the degree of neuropsychiatric disturbance based on the NPI score (r = -. 14). NPI-D ratings for 9 of 10 NPI symptom domains correlated most strongly with either NPI symptom severity or total (frequency x severity) scores. Agitation, dysphoria, irritability, delusions, and apathy were the symptoms most often reported to be severely distressing to caregivers. CONCLUSIONS: The NPI-D provides a reliable and valid measure of subjective caregiver distress in relation to neuropsychiatric symptoms measured by the NPI. Neuropsychiatric alterations are more strongly associated than cognitive symptoms to caregiver distress. The NPI-D may be useful in both clinical and research settings for assessing the contribution to caregiver distress of neuropsychiatric symptoms in AD patients.

Aged↗
PubMed1998

Genetic implications of double primary cancers of the colorectum and endometrium.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition predisposing to cancers of the colorectum and endometrium. Endometrial cancer is the most commonly occurring extracolonic cancer in HNPCC. Estimates of the cumulative incidence of endometrial cancer in women with mutations in the HNPCC genes range from 22-43%. In order to determine how frequently double primary cancers of the colorectum and endometrium are the result of a hereditary factor, we conducted a registry based study in Ontario and Quebec, Canada. We obtained pedigrees on 80 women diagnosed with double primary cancers of the colorectum and endometrium at less than 70 years of age. Family histories of cancer were obtained for all first degree relatives of these women and cancer rates were compared with age standardised provincial incidence rates in order to estimate the relative risks. There was a total of 82 cancers observed in relatives below the age of 55, compared with 31.2 expected, giving a relative risk of 2.6 (95% confidence interval (CI) 2.1-3.3). The relative risk for colorectal cancer below 55 was 16.1 (95% CI 11.6-21.8). This risk decreased with increasing age of onset of cancers in probands. For probands with both colorectal and endometrial cancer diagnosed under the age of 55, the relative risk of colorectal cancer in relatives below the age of 55 was 30.5 (95% CI 18.8-46.6). Similar patterns were observed for endometrial and pancreatic cancer. There were non-significant increases in rates of cancer of the oesophagus, stomach, small intestine, and bladder. There was no increased risk of breast cancer. The risk of lung cancer was decreased, especially in older relatives. Our findings indicate the presence of a significant genetic component of cancer in women with double primary cancers of the colorectum and endometrium.

Adult↗
PubMed1997

A structure/function analysis of Rat7p/Nup159p, an essential nucleoporin of Saccharomyces cerevisiae.

Rat7p/Nup159p is an essential nucleoporin of Sac-charomyces cerevisiae originally isolated in a genetic screen designed to identify yeast temperature-sensitive mutants defective in mRNA export. Here we describe a detailed structural-functional analysis of Rat7p/Nup159p. The mutation in the rat7-1 ts allele, isolated in the original genetic screen, was found to be a single base pair change that created a stop codon approximately 100 amino acids upstream of the actual stop codon of this 1,460 amino acid polypeptide, thus eliminating one of the two predicted coiled-coil regions located near the carboxyl terminus of the protein. These coiled-coil regions are essential since an allele lacking both coiled-coil regions was unable to support growth under any conditions. In contrast, no other region of the protein was absolutely required. The SAFG/PSFG repeat region in the central third of the protein was completely dispensable for growth at temperatures between 16 degrees C and 37 degrees C and cells expressing this mutant allele were indistinguishable from wild type. Deletion of the amino-terminal third of the protein, upstream from the repeat region, or the portion between the repeat region and the coiled-coils resulted in temperature-sensitivity, but the two alleles showed distinct phenotypes with respect to the behavior of nuclear pore complexes (NPCs). Taken together, our data suggest that Rat7p/Nup159p is anchored within the NPC through its coiled-coil region and adjacent sequences. In addition, we postulate that the N-terminal third of Rat7p/Nup159p plays an important role in mRNA export.

Alleles↗
PubMed1994

Primary prevention of child physical abuse and neglect: a critical review. Part I.

This paper (Part I) and its companion paper (Part II) provide an overview of the primary prevention of child maltreatment. Part I reviews the effectiveness of interventions aimed at the primary prevention of child physical abuse and neglect. Prospective controlled trials published between January 1979 and May 1993 were systematically identified. The quality of each study was determined using criteria which assessed methodological rigor. Interventions aimed at the prevention of physical abuse and neglect were classified into six main categories within the broad group of perinatal and early childhood programs. While many of these programs did not show a reduction in physical abuse or neglect, there is evidence that extended home visitation can prevent physical abuse and neglect among disadvantaged families.

Adolescent↗
PubMed1994

Primary prevention of child sexual abuse: a critical review. Part II.

This paper (Part II) and the previous paper (Part I) provide an overview of the primary prevention of child maltreatment. Part II focuses on the effectiveness of interventions aimed at the primary prevention of child sexual abuse. It includes prospective controlled trials published between January 1979 and May 1993. These studies were systematically identified and the quality of each trial was determined using criteria which assessed methodological rigor. Interventions aimed at the prevention of sexual abuse were classified into eight main categories based on the method of intervention. All programs had education as the primary focus. There is evidence that educational programs can improve safety skills and knowledge of children about sexual abuse but no study has produced data that education actually reduces the occurrence of sexual abuse.

Adolescent↗
PubMed1992

Evaluation of zones of iris hypoplasia in horses and ponies.

Mass-like lesions of the iris were evaluated in 15 horses or ponies of various ages and breeds. Breed or gender predilection was not found. These lesions were most often found in blue irides at the 12 o'clock region. Because the lesions transilluminated and changed shape rapidly with changes in pupillary size, they were hypothesized to be zones of iris hypoplasia. Histologic evaluation of one specimen supported this interpretation. The lesions were not associated with any other ocular or systemic abnormality.

Animals↗
PubMed1985

Malignant melanoma of the conjunctiva in a cat.

A conjunctival melanoma was diagnosed in an adult domestic cat. The neoplasm was excised without further complications. It is important to differentiate conjunctival melanoma from other types of pigmented ocular neoplasia. In man, conjunctival melanomas are often malignant tumors with potential for metastatic behavior. Although this neoplasm had histologic features of malignancy, no evidence of local recurrence or metastasis has been apparent during the 11-month follow-up period.

Animals↗