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Biomedical subjects

N McMillan

Publications and source records attributed to N McMillan.

At least 19 recordsLinked to original sources

Evaluation of the effect of uterine artery embolisation on menstrual blood loss and uterine volume.

OBJECTIVE: To evaluate the effect of uterine artery embolisation (UAE) on menstrual blood loss (MBL) and uterine volume in women with symptomatic uterine fibroids. DESIGN: Prospective observational study. SETTING: West of Scotland gynaecology and radiology departments. POPULATION: Fifty women (mean age 43 years) with symptomatic fibroids undergoing UAE between January 1999 and June 2003. METHODS: Women collected sanitary protection from one menses pre-embolisation and at regular intervals thereafter. This allowed objective measurement of MBL using the alkaline haematin technique. Uterine volume was calculated using magnetic resonance imaging (MRI) before and six months following embolisation. Interventional radiologists performed bilateral UAE. The Wilcoxon's signed rank test was used for statistical analysis of data. MAIN OUTCOME MEASURES: Post-embolisation MBL and uterine volume changes. RESULTS: Median pretreatment MBL was 162 mL (mean 234, range 9-1339). The median MBL decreased to 60 mL at 3 months (n= 34, range 0-767, P < 0.001), 70 mL at 6-9 months (n= 34, range 0-1283, P < 0.001), 37 mL at 12-24 months (n= 25, range 0-265, P < 0.001), 18 mL at 24-36 months (n= 17, range 0-205, P < 0.001) and 41 mL at 36-48 months (n= 6, range 0-66, P < 0.05). The median reduction in uterine volume was 40% (n= 46, 95% CI 33.0-49.7, P < 0.001). CONCLUSIONS: UAE causes a statistically significant reduction in objectively measured MBL. UAE is also associated with a statistically significant reduction in uterine volume at six months. There was no relationship between the changes in uterine volume and MBL.

Adult↗

Don't wait for a sensory level--listen to the symptoms: a prospective audit of the delays in diagnosis of malignant cord compression.

AIM: To report details concerning symptoms (especially pain) preceding the development of malignant cord compression (MCC); delays between onset/reporting of symptoms and confirmed diagnosis of MCC; accuracy of investigations carried out. METHODS: A prospective observational study examined the diagnosis, management and outcome of 319 patients diagnosed with MCC at three Scottish cancer centres between January 1998-April 1999. The process was considered from the perspectives of the patient, the GP and the hospital doctor. RESULTS: At diagnosis, most patients (82%) were either unable to walk or only able to do so with help. Pain was reported by nearly all patients interviewed (94%) and had been present for approximately 3 months (median=90 days). It was severe in 84% of cases, with the distribution and characteristics of nerve root pain in 79%. The site of pain did not correspond to the site of compression. Where reported, weakness and/or sensory problems had been noticed by the patient for some time before diagnosis (median intervals 20 and 12 days, respectively). Most patients reported early symptoms to their General Practitioner (GP) and diagnosis was established, following referral and investigation, approximately 2 months (median=66 days) later. CONCLUSION: Patients who develop spinal metastases are at risk of irreversible spinal cord damage. Weakness and sensory abnormalities are reported late and identified even later, despite patients having reported pain for a considerable time. Patients with cancer who describe severe back or spinal nerve root pain need urgent assessment on the basis of their symptoms, as signs may occur too late. Plain films and bone scans requested for patients in this audit predicted accurately the level of compression in only 21% and 19% of cases, respectively. The only accurate investigation to establish the presence and site of a compressive lesion is magnetic resonance imaging (MRI). A referral guideline based on suspicious symptoms in addition to suspicious signs is suggested.

Aged↗

Efficiency of delivery of DNA to cells by bovine papillomavirus type-1 L1/L2 pseudovirions.

To investigate the efficiency of encapsidation of plasmid by papillomavirus virus-like particles (PV VLPs), and the infectivity of the resultant PV pseudovirions, Cos-1 cells were transfected with an 8-kb plasmid incorporating a green fluorescent protein (GFP) reporter gene (pGSV), and infected with bovine PV (BPV-1) L1/L2 recombinant vaccinia virus to produce BPV1 pseudovirions. Approximately 1 in 1.5 x 10(4) of dense (1.35 g/ml) PV pseudovirions and 0.3 in 10(4) of less-dense (1.29 g/ml) pseudovirions packaged an intact pGSV plasmid. The majority (>75%) of packaged plasmids contained deletions, and the deletions affected all tested genes. After exposure of Cos-1 cells to BPV-1 pseudovirions at an MOI of 40,000:1, 6% of cells expressed GFP, giving a calculated efficiency of delivery of the pGSV plasmid, by pseudovirions which had packaged an intact plasmid, of approximately 5%. Plasmid delivery was not effected by purified pGSV plasmid, was blocked by antiserum against BPV-1, and was not blocked by DNase treatment of pseudovirions, confirming that delivery was mediated by DNA within the pseudovirion. We conclude that a major limitation to the use of PV pseudovirions as a gene delivery system is that intact plasmid DNA is not efficiently selected for packaging by VLPs in cell-based pseudovirions production systems.

Animals↗

Multiple Symmetric Lipomatosis--MR appearances.

Multiple Symmetric Lipomatosis (MSL) is a rare disorder of lipid metabolism which is mainly seen in Mediterranean and eastern European populations, which results in massive fat accumulation mainly around the neck and back. The main differential diagnosis lies between MSL and the fat accumulation of Cushing's disease, and liposarcoma. This case demonstrates that MR imaging is a valuable aid to the diagnosis and treatment of this disease by giving excellent definition of soft tissue and vascular structures, allowing accurate assessment and preoperative planning of the disease.

Adult↗

Potential strategies utilised by papillomavirus to evade host immunity.

The co-evolution of papillomaviruses (PV) and their mammalian hosts has produced mechanisms by which PV might avoid specific and non-specific host immune responses. Low level expression of PV proteins in infected basal epithelial cells, together with an absence of inflammation and of virus-induced cell lysis, restricts the opportunity for effective PV protein presentation to immunocytes by dendritic cells. Additionally, PV early proteins, by a range of mechanisms, may restrict the efficacy of antigen presentation by these cells. Should an immune response be induced to PV antigens, resting keratinocytes (KC) appear resistant to interferon-gamma-enhanced mechanisms of cytotoxic T-lymphocyte (CTL)-mediated lysis, and expression of PV antigens by resting KC can tolerise PV-specific CTL. Thus, KC, in the absence of inflammation, may represent an immunologically privileged site for PV infection. Together, these mechanisms play a part in allowing persistence of PV-induced proliferative skin lesions for months to years, even in immunocompetent hosts.

Animals↗

Human PKR transfected into murine cells stimulates expression of genes under control of the HIV1 or HTLV-I LTR.

We have analyzed the effect of transfection into murine NIH/3T3 cells of the human dsRNA-activated kinase PKR on the expression of the beta-galactosidase reporter gene, placed under control of the HIV1 or the HTLV-I LTR. beta-Galactosidase expression is stimulated when the reporter plasmids are cotransfected with wild-type PKR but inhibited when cotransfected with a catalytically inactive mutant PKR. In the case of HIV1, beta-galactosidase expression was not stimulated when cotransfection was carried out with PKR harboring mutations in the dsRNA binding domains, indicating that stimulation depends on the classical mode of PKR activation through dsRNA binding. In contrast, the dsRNA binding mutants of PKR could still partially stimulate beta-galactosidase expression from the HTLV-I LTR, suggesting that PKR activation in this case may involve different/additional mechanisms. These results show that, in addition to the known down-regulation of protein synthesis through elF2 phosphorylation, PKR can also positively stimulate gene expression in vivo, most probably through phosphorylation of a substrate distinct from elF2.

3T3 Cells↗

Heterosexual behaviour and HIV risk in New Zealand: data from a national survey.

The pattern of any future major heterosexual epidemic of acquired immunodeficiency syndrome (AIDS) will depend partly on sexual behaviour and condom use among heterosexuals. This survey was designed to provide information on patterns of sexual behaviour in New Zealand. A national sample aged 18 to 54 was selected using a random method and telephone interviews were administered to 2361 people, using a questionnaire based on the protocol developed by the Global Program on AIDS of the World Health Organization. The reported mean lifetime number of partners increased with age up to 25 to 29 years for women and 30 to 34 years for men, and declined at older ages. Fifteen or more lifetime partners were reported by 17 per cent of men and 4 per cent of women. Multiple partnerships in the previous 12 months were commonest in those aged 20 to 24. In this age group, 32 per cent of men and 20 per cent of women reported two or more partners. Recent condom use for contraception was reported by 23 per cent of men and 19 per cent of women. Use was highest amongst those aged 18 to 24, and decreased sharply with age. The true proportion of the population with many sexual partners may be higher than reported. These data will be useful in modelling approaches to estimate the likelihood of future heterosexual spread of AIDS. The data on lifetime numbers of partners suggest that sexual decisions depend not just on age and sex but also on the era, and thus on changing social values about sexual behaviour.

Adolescent↗

Ultrasonic evaluation of movement of the diaphragm after acute cerebral infarction.

Respiratory dysfunction is an important complication of acute stroke but its mechanisms are poorly understood. Previous indirect assessments suggest that paralysis of the diaphragm occurs contralateral to the cerebral lesion. Diaphragmatic excursion was studied with real time ultrasound during quiet and deep breathing in 50 patients within 72 hours of acute stroke and 40 controls. During quiet breathing, hemidiaphragmatic movements were not significantly different between right hemispheric stroke, left hemispheric stroke, and controls. During deep inspiration, there was a significant bilateral reduction in hemi-diaphragmatic excursion in patients with stroke, for both right hemispheric stroke and left hemispheric stroke when compared with controls (both P < 0.001). Thus isolated hemidiaphragmatic paresis does not occur but maximal excursion of the diaphragm is reduced bilaterally in patients with acute stroke. This is a likely contributor to the respiratory dysfunction after acute stroke.

Acute Disease↗

Ultrasonic assessment of hemidiaphragmatic movement: an indirect method of evaluating mediastinal invasion in non-small cell lung cancer.

This preliminary study aimed to assess the potential value of diaphragmatic ultrasound (DUS) in evaluating phrenic nerve involvement indirectly, in the non-invasive pre-operative staging of mediastinal invasion in non-small cell lung cancer (NSCLC). A prospective study of 30 patients with NSCLC comparing the findings of diaphragmatic ultrasound, chest radiograph, computed tomography (CT) thorax and mediastinoscopy was performed. In all cases adequate quantitiative assessment of hemidiaphragmatic excursion was obtained. There was discordance in four of 30 patients between DUS and chest radiograph. Three of nine patients with extensive mediastinal disease on CT had abnormal DUS, and two of eight patients with indeterminate mediastinal disease on CT had abnormal DUS and were later found to be non-resectable. No abnormal cases of DUS were found in those cases with normal mediastinal CT. There was no clear relationship between the site, size and side of the primary tumour on CT, or its pleural or diaphragmatic contiguity, and hemidiaphragmatic excursion. There was concordance between DUS and mediastinoscopy in 17 of 21 patients. Two patients had normal mediastinoscopy and abnormal DUS but were not resectable at thoracotomy. No patient with abnormal DUS was resectable. DUS may be of potential value in the pre-operative staging of NSCLC and is therefore worthy of further evaluation.

Aged↗

Effect of outdoor airborne particulate matter on daily death counts.

To investigate the possible relationship between airborne particulate matter and mortality, we developed regression models of daily mortality counts using meteorological covariates and measures of outdoor PM10. Our analyses included data from Cook County, Illinois, and Salt Lake County, Utah. We found no evidence that particulate matter < or = 10 microns (PM10) contributes to excess mortality in Salt Lake County, Utah. In Cook County, Illinois, we found evidence of a positive PM10 effect in spring and autumn, but not in winter and summer. We conclude that the reported effects of particulates on mortality are unconfirmed.

Air Pollutants↗

The New Zealand Partner Relations Survey: methodological results of a national telephone survey.

OBJECTIVE: To implement and evaluated a national survey of sexual behaviour using computer-assisted telephone interviewing (CATI). DESIGN: A two-stage stratified national sample survey in which households were selected by random digit-dialing (RDD), with a single eligible interviewee per selected household, followed by subsample surveys of non-contacts and refusals to determine eligibility. METHODS: A 15-minute questionnaire based on the Global Programme on AIDS (GPA)/World Health Organization (WHO) protocol was administered by telephone to a nationally representative sample of 2361 respondents in the 18-54-year age group. RESULTS: The overall response rate was 63%, but lower in the cities, in the 18-24 age group, and among men. Three-quarters of surveyed non-contacts, and a quarter of re-surveyed refusals, did not meet the eligibility criteria for the study. Less than 20% of refusals cited the subject matter of the survey as the reason for refusal. Item non-response (< 1%) increased with question sensitivity, and varied by respondent age, ethnicity and partnership status. Men reported twice as many adult lifetime partners as women. CONCLUSIONS: The GPA/WHO protocol can be successfully adapted to administration by telephone, with adequate response rates and exceptionally low levels of item non-response. CATI is a cost-effective method for collecting national information on sexual behaviour in countries where there is a high level of telephone ownership. Used in conjunction with RDD, it can overcome problems of sample design in settings where there is no comprehensive population-sampling frame. Checks on item sensitivity and partner estimates suggest that acceptable levels of reliability can also be achieved.

Adolescent↗

Computed tomographic findings in two patients with vascular hamartomas.

The clinical, computed tomographic (CT) and histological findings of two patients with vascular hamartomas are presented. The appearances on CT of the two lesions were markedly different. Although both lesions were histopathologically benign, one showed a more disorganized architecture on histology and clinically behaved in a more aggressive manner. The CT findings in this case reflected the histological picture and could have been interpreted as a malignant process if viewed in isolation. Review of the literature and the cases presented suggest that the CT appearances of vascular hamartomas can be diverse, and to avoid a misdiagnosis the radiological features should be considered in conjunction with the clinical and histopathological findings.

Adolescent↗

Magnetic resonance imaging of renal transplants: initial experience.

Magnetic resonance imaging (MRI) was used in 45 renal transplant investigations (38 patients) using a Picker 0.15 T resistive system and a localized surface coil. An attempt was made to define optimal sequences in the evaluation of both normal and pathological transplants. Three sequences were found to be of value; a T1 weighted sequence (IR2180/700/40) to assess corticomedullary differentiation and its loss in acute rejection and acute tubular necrosis, a T2 weighted sequence (SE2000/80) for assessment of renal vessels and disturbances in blood supply, and a STIR (short tau inversion recovery) sequence (IR800/100/40) to define further the distended collecting system in obstruction and the presence of any perirenal collection. Encouraging results have been obtained, particularly in cases of acute rejection. It is suggested that the MRI scan is a useful screening test in cases of clinical doubt and may even obviate biopsy in some cases.

Adult↗

A comparison between islet transplantation and parenteral insulin in the control of diabetes and prevention of renal complications in mice.

The control of diabetes and the prevention of renal complications were studied in mice that received different treatment regimes for six months. Transplantation of syngeneic cultured fetal pancreas completely reversed streptozotocin-induced diabetes (mean FBG 5.1 +/- 0.4 mmole/liter six months after transplantation, versus 5.8 +/- 0.2 mmole/liter in normal mice). The mean fasting blood glucose (FBG) level of insulin-treated mice was lower than the mean FBG level of untreated diabetic mice (9.0 +/- 1.2 mmole/liter versus 11.5 +/- 1.3 mmole/liter, P less than 0.05) but exceeded the FBG level of transplanted mice (P less than 0.001) or normal controls (P less than 0.001). There were no significant differences between the mean level of glycosylated hemoglobin (HbA1c) of normal (4.8 +/- 0.3%), transplanted (4.5 +/- 0.3%), or insulin-treated mice (5.3 +/- 0.4%), but the HbA1c level in the untreated diabetic group was increased (7.0 +/- 0.5%; P less than 0.001). Six months after transplantation, the thickness of the glomerular capillary basement membrane (GCBM) was not different in the transplanted group and normal controls (156.4 +/- 5.7 nm versus 157.3 +/- 12.6 nm); the GCBM was thicker in the insulin-treated mice than in the transplanted mice (179.8 +/- 4.2 nm versus 156.4 +/- 5.7 nm; P less than 0.02), but thinner than in untreated diabetic mice (179.8 +/- 4.2 nm versus 202.2 +/- 4.4 nm; P less than 0.001). It is concluded that islet transplantation, in contrast to good control as judged by normalization of HbA1c levels achieved with parenteral insulin, prevents GCBM thickening in experimental diabetes.

Animals↗

Haemophilia and the kidney: assessment after 11-year follow-up.

Radiological and biochemical investigations of renal function were performed in 57 patients with haemophilia, 27 of whom had been previously investigated in 1969. Although one-third of patients had a renal radiographic abnormality, only two had abnormalities persisting since 1969 and attributable to renal bleeding. Isotope renography was a sensitive indicator of renal abnormality whereas a history of haematuria was a poor discriminator for patients with abnormal intravenous urograms or impaired creatinine clearance. Haematuria was not associated with progressive loss of renal function and its natural history in haemophilia is probably benign.

Adolescent↗