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Biomedical subjects

M A Jenkins

Publications and source records attributed to M A Jenkins.

At least 19 recordsLinked to original sources
PubMed2006

Estimating glomerular filtration rate in diabetes: a comparison of cystatin-C- and creatinine-based methods.

AIMS/HYPOTHESIS: We compared the predictive performance of a GFR based on serum cystatin C levels with commonly used creatinine-based methods in subjects with diabetes. SUBJECTS, MATERIALS AND METHODS: In a cross-sectional study of 251 consecutive clinic patients, the mean reference (plasma clearance of (99m)Tc-diethylene-triamine-penta-acetic acid) GFR (iGFR) was 88+/-2 ml min(-1) 1.73 m(-2). A regression equation describing the relationship between iGFR and 1/cystatin C levels was derived from a test population (n=125) to allow for the estimation of GFR by cystatin C (eGFR-cystatin C). The predictive performance of eGFR-cystatin C, the Modification of Diet in Renal Disease 4 variable formula (MDRD-4) and Cockcroft-Gault (C-G) formulas were then compared in a validation population (n=126). RESULTS: There was no difference in renal function (ml min(-1) 1.73 m(-2)) as measured by iGFR (89.2+/-3.0), eGFR-cystatin C (86.8+/-2.5), MDRD-4 (87.0+/-2.8) or C-G (92.3+/-3.5). All three estimates of renal function had similar precision and accuracy. CONCLUSIONS/INTERPRETATION: Estimates of GFR based solely on serum cystatin C levels had the same predictive potential when compared with the MDRD-4 and C-G formulas.

Adult↗
PubMed2006

Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry.

The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population.

Adolescent↗
PubMed2006

Parity and decreased use of oral contraceptives as predictors of asthma in young women.

BACKGROUND: Asthma is more prevalent among males in childhood, but females report higher rates in adulthood. The reasons are unknown; although it has been hypothesized that hormonal factors may explain this sex-dependent risk of adult-onset asthma. OBJECTIVE: To determine whether a woman's reproductive history or use of oral contraceptives is associated with adult-onset asthma. METHODS: In 1991-1993, we surveyed 681 women aged 29-32 years randomly sampled from participants first surveyed at age 7 years by the 1968 Tasmanian Asthma Survey, a study of all children born in 1961 and attending school. Current asthma was defined as reporting asthma or wheezy breathing in the past 12 months. RESULTS: In women who did not have asthma or wheezy breathing by age 7 years, 13% had current asthma. The risk of current asthma in these who were parous increased with the number of births (odds ratio (OR) 1.50 per birth, 95% confidence interval (CI) 1.01-2.23 P=0.04) while women with one birth were at a lower risk than nulliparous women (OR 0.46 95% CI 0.2-1.06, P=0.07). Independent of parity, the risk decreased by 7% (95% CI 0-13%) per year of oral contraceptive pill use in all women. In women who did have asthma or wheezy breathing by age 7 years, neither reproductive history nor oral contraceptive pill use predicted current asthma. CONCLUSION: Our observation that parity and decreased oral contraceptive use predict asthma in women, is consistent with the hypothesis that the asthma that develops after childhood is in part a response to endogenous and exogenous female hormones. This may be due to alterations of cytokine responses by the pregnant state, triggering adult-onset asthma in women.

Adult↗
PubMed2006

Risk-reducing surgery, screening and chemoprevention practices of BRCA1 and BRCA2 mutation carriers: a prospective cohort study.

This study prospectively evaluated the utilization of cancer risk management strategies in a multi-institutional cohort of BRCA1 and BRCA2 mutation carriers using a self-report questionnaire. Of 142 unaffected female mutation carriers, 70 (49%) had elected to receive their mutation result. Of those who knew their mutation result, 11% underwent bilateral mastectomy (BM), 29% had bilateral oophorectomy (BO), 78% performed regular breast self-examination (BSE), and 80%, 89%, 67%, and 0% had at least annual clinical breast examination (CBE), mammography, transvaginal ultrasound (TVU), and CA125, respectively. A further 20%, 7%, 0%, 21%, and 75%, respectively, reported never having had these tests. For women who elected not to receive their mutation result, 0% underwent BM, 6% underwent BO, and 77%, 42%, 56%, 7%, and 0% had regular BSE, CBE, mammography, TVU, and CA125, respectively. Only one woman used chemoprevention outside a clinical trial. Uptake of prophylactic surgery and screening was associated with knowing one's mutation status (for all behaviors except BSE), age (for BO and CBE) and residence (for mammography). In this cohort, the minority of mutation carriers utilized risk-reducing surgery or chemoprevention and a substantial minority were not undergoing regular cancer-screening tests.

Adult↗
PubMed2005

Molecular characterization and cancer risk associated with BRCA1 and BRCA2 splice site variants identified in multiple-case breast cancer families.

Genetic screening of women from multiple-case breast cancer families and other research-based endeavors have identified an extensive collection of germline variations of BRCA1 and BRCA2 that can be classified as deleterious and have clinical relevance. For some variants, such as those in the conserved intronic splice site regions which are highly likely to alter splicing, it is not possible to classify them based on the identified DNA sequence variation alone. We studied 11 multiple-case breast cancer families carrying seven distinct splice site region genetic alterations in BRCA1 or BRCA2 (BRCA1, c.IVS6-2delA, c.IVS9-2A>C, c.IVS4-1G>T, c.IVS20+1G>A and BRCA2, c.IVS17-1G>C, c.IVS20+1G>A, c.IVS7-1G>A) and applied SpliceSiteFinder to predict possible changes in efficiency of splice donor and acceptor sites, characterized the transcripts, and estimated the average age-specific cumulative risk (penetrance) using a modified segregation analysis. SpliceSiteFinder predicted and we identified transcipts that illustrated that all variants caused exon skipping, and all but two led to frameshifts. The risks of breast cancer to age 70 yrs, averaged over all variants, over BRCA1 variants alone, and over BRCA2 variants alone, were 73% (95% confidence interval 47-93), 64% (95%CI 28-96) and 79% (95%CI 48-98) respectively (all P<0.0001). Therefore five of these seven consensus splice site variants of BRCA1 and BRCA2 produce a transcript similar to that of other previously described deleterious exonic variants and are associated with similar high lifetime risks.

Alternative Splicing↗
PubMed2003

A specific GFP expression assay, penetrance estimate, and histological assessment for a putative splice site mutation in BRCA1.

Genetic testing for cancer predisposing mutations in BRCA1 and BRCA2 has been of benefit to many individuals from breast and ovarian cancer-prone kindreds. However, a function has not been assigned to many of the domains that make up these complex proteins and hence, the significance of many sequence variants, including missense mutations, splice-site mutations, and in-frame deletions/insertions, remains unclear. We identified a putative splice site mutation (IVS6-2delA) in BRCA1 in a family attending a Familial Cancer Centre that had a significant history of both breast and ovarian cancer. This sequence variant was not novel but the exact effect on mRNA splicing and hence the biological impact of this sequence variation was unclear and therefore the finding was unable to be used in genetic counseling of the family. Via the construction of novel GFP-based expression fusion constructs, we demonstrated that this sequence variation prevented normal splicing of the BRCA1 transcript. By combining these data with an assessment of the histopathological features of the breast carcinomas in this family and mutation penetrance estimate we were able to conclude that this BRCA1 variant conveyed an increased risk of breast cancer.

Adult↗
PubMed2001

Multiple sclerosis: use of light-chain typing to assist diagnosis.

Although the presence of oligoclonal IgG with abnormal kappa/lambda light-chain ratio in multiple sclerosis (MS) has been known for many years, this finding has not been put to diagnostic use in most routine clinical laboratories. In a retrospective study we report differences in the oligoclonal banding patterns between multiple sclerosis and non-MS patients. We had sufficient cerebrospinal fluid (CSF) on 36 from 71 patients with oligoclonal bands for immunofixation for kappa and lambda light chains, and for free kappa and free lambda. Thirteen out of 14 patients with clinically confirmed MS had predominantly IgG (kappa) banding. In contrast, in seven out of eight patients with diagnoses other than MS the IgG was linked to both kappa and lambda light chains in approximately equal proportions. Nine out of 14 patients with probable/possible/suspected MS showed predominantly IgG (kappa) banding; five others in this group had both IgG (kappa) and IgG (lambda) and free lambda light chains. The finding of IgG (kappa) bands in CSF samples with oligoclonal bands supports a diagnosis of MS.

Humans↗
PubMed2000

Variability of standard clinical protein assays in the analysis of a model urine solution of fragmented albumin.

OBJECTIVES: This study investigates the sensitivity of various standard clinical techniques in the detection of albumin fragments. The significance of this work is in the detection of urinary proteins, such as albumin, which has recently been discovered to be excreted as mainly peptide fragments as a result of filtered albumin undergoing degradation during renal passage. All filtered proteins undergo a similar degradation process. DESIGN AND METHODS: Albumin digested with trypsin was used as a model urine solution. The solution was assayed for albumin concentration by various methods including the biuret assay that is known to detect urinary albumin fragments. The digest solution was also analyzed by various clinically used chromagen assays, electrophoretic and chromatographic methods to determine whether they are able to detect the fragmented protein. RESULTS: The benzethonium chloride, Coomassie blue, and pyrogallol red assays for urine protein, the immunoassay for human albumin and sodium dodecyl sulfate polyacrylamide gel electrophoresis with Coomassie blue staining were unable to detect the albumin fragments. Capillary electrophoresis was sensitive to the fragments but with low resolution. High-performance liquid chromatography gave the best results. CONCLUSIONS: Many techniques utilized to assay patient urine samples are unable to detect fragmented albumin and, hence, will severely underestimate albumin and protein excretion.

Albuminuria↗
PubMed2000

Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia.

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.

Aged↗
PubMed2000

Attentional dysfunction associated with posttraumatic stress disorder among rape survivors.

Posttraumatic stress disorder (PTSD) is characterized by subjective reports of decreased concentration and an inability to sustain attention. Some empirical validation of these symptoms has been demonstrated via reduced performance on attentional tests among war veterans with PTSD. However, the significance of such findings is unclear given high co-morbidity with other psychiatric, neurologic, and substance abuse disorders among veterans. The present study examined neuropsychological functioning among rape survivors with PTSD, a patient population with comparatively low rates of psychiatric co-morbidity. Rape survivors with PTSD (PTSD+; n = 15) were compared to rape survivors without PTSD (PTSD-; n = 16) and age- and education-matched nontraumatized controls (CTRL; n = 16) on tests of attention. Performance of the PTSD+ group was significantly worse than the other groups on measures of sustained and divided attention, but not on shifting of visuospatial selective attention. Performance differences were not attributable to co-morbid psychiatric disorders or substance abuse. The implications of these findings regarding the effects of trauma on attentional functions are discussed.

Adult↗
PubMed2000

Evidence for genetic associations between asthma, atopy, and bronchial hyperresponsiveness: a study of 8- to 18-yr-old twins.

We measured asthma in the last 12 mo, diagnosed by a respiratory physician at interview; atopy, defined by a positive skin prick test to any of eight common allergens; and bronchial hyperresponsiveness (BHR) to hypertonic saline, in 381 twin pairs aged 8 to 18 yr selected from the Australian Twin Registry-183 monozygous (MZ) and 198 dizygous (DZ). The associations between twins, as measured by an odds ratio, were greater in MZ pairs compared with DZ pairs for asthma: 25.6 (95% confidence interval 11.3- 57.8) versus 1.9 (1.0-3. 5); atopy: 14.6 (7.1-30.1) versus 2.5 (1.4- 4.5); and BHR: 14.1 (6. 4-31.0) versus 4.2 (2.1-8.6) (all p < 0.002). The associations between each pair of traits within an individual were slightly greater than the association between one trait in a twin and the other trait in the cotwin (cross-trait cross-pair) in MZ pairs. Further, the associations in MZ pairs were greater than in DZ pairs (p < 0.05). Under the assumptions of the classic twin model, these data suggest that the strong cross-sectional associations between these three traits are due to an overlap between the genetic factors involved in each of these three traits.

Adolescent↗
PubMed2000

Measurement of iohexol by capillary electrophoresis: minimizing practical problems encountered.

Iohexol is a non-ionic contrast agent, which has been widely described in recent literature as an accurate marker for the measurement of glomerular filtration rate (GFR). Our aim was to establish a capillary electrophoresis assay, based on a previously described method, that had adequate reproducibility to be used as part of a clinical trial. In this paper, we examine the practical aspects, pitfalls and steps we took to achieve a precise and reproducible assay. To minimize laboratory variation, we examined properties such as the use of an internal standard in a capillary electrophoresis separation, alternative deproteinization methods for serum, the most suitable matrix for the dilution of standards and the implementation of suitable quality control material to ensure that run-to-run variability was minimized. The optimized capillary electrophoretic assay of iohexol was found to be robust, with over 860 runs from the one capillary over a 9-month period. Excluding capital costs of the instrument, the consumable cost of the assay is less than A$0.25 per test, with a run time of 5.25 min and a coefficient of variation (CV) of 4.3% at 80 mg/L. The GFR, calculated from the plasma clearance, had a reproducibility of 5.47%.

Acetonitriles↗
PubMed2000

Clinical applications of capillary electrophoresis. Status at the new millennium.

Capillary electrophoresis (CE) is an extremely sensitive technique, which has been used in the clinical laboratory for almost 10 yr. The components of CE instrumentation are described, as are injection modes, buffers, and effects of electroosmotic flow. The modes of separation used in CE, namely, capillary zone electrophoresis, capillary isoelectric focusing, capillary isotachophoresis, and micellar electrokinetic capillary chromatography, are explained. References for 26 different clinical applications of CE are included, among them assays that are used routinely as well as niche assays for specialized applications of CE. Verification of CE assays, current instrumentation, and future development of CE in the clinical laboratory are addressed.

Blood Chemical Analysis↗
PubMed1999

Impairments of attention after cingulotomy.

BACKGROUND: Outcome studies have generally not indicated significant cognitive disturbances after cingulotomy. There is now considerable evidence that the cingulate may play an important role in emotional behavior and attention. OBJECTIVE: To characterize impairments of attention associated with bilateral lesions of the anterior cingulate cortex produced by cingulotomy. METHODS: Twelve patients who underwent cingulotomy for treatment of intractable pain were administered tests of attention, executive functions, response intention and production, and a broad range of other neurocognitive functions before surgery and again 3 and 12 months after surgery. Data from this within-subjects repeated-measures design were analyzed by multivariate analysis of variance procedures. RESULTS: After cingulotomy, patients initially had executive and attentional impairments. By 12 months, these had resolved into more circumscribed deficits, with greatest impairments on tasks requiring intention and spontaneous response production, and milder impairments of focused and sustained attention. Other aspects of attention and other cognitive functions were generally unaffected. CONCLUSION: The anterior cingulate cortex modulates response intention and focused attention.

Adult↗
PubMed1999

Five unusual serum protein presentations found by capillary electrophoresis in the clinical laboratory.

Capillary electrophoresis (CE) has been used in our teaching hospital clinical laboratory to assay approximately 13 000 specimens for serum protein electrophoresis (SPE) in 4 1/2 years. During that period we have found several unusual samples, five of which are discussed here. These samples are from separate patients with IgD myeloma, IgG heavy chain disease, a triple IgG(Kappa) monoclonal band, a rapidly changing abnormal/monoclonal band and a mixed type-11 cryoglobulinaemia. Albumin has been used to calibrate the 50-microm fused silica capillary, the quantity of the monoclonal bands being calculated by the software of either the Applied Biosystems 270A-HT or BioFocus instrument. We have found CE for the initial SPE to be a robust, labour-saving, cost effective technique, which is able to determine less than 1 g/l of monoclonal protein. However, because of the expense and time required for immunosubtraction, we prefer isoelectric focusing (IEF) for typing of paraproteins. The only samples which need care in handling are serum containing large amounts of cryoglobulin protein.

Aged↗
PubMed1999

Capillary isoelectric focusing of haemoglobin variants in the clinical laboratory.

For capillary isoelectric focusing (CIEF) to be accepted in the clinical laboratory, it must be reproducible and cost effective. The advent of polyAAEE coated capillaries (Bio-Rad Laboratories, Hercules, CA, USA) has provided the means of obtaining over 100 runs per capillary, something which previously had not always been possible with coated capillaries. Using the Clinical Data Management computer program on the BioFocus 2000 Capillary Electrophoresis System (Bio-Rad Laboratories), we have used a one-step salt mobilization to achieve focusing of haemoglobin variants. Washed red cells are diluted, haemolyzed and separated in the capillary at 8 kV using 1.3% Pharmalyte ampholytes (pH 6.6-7.7/pH 6-8 2:1) in 0.40% methylcellulose. The separated haemoglobins were detected by adsorption at 280 nm. Using published values of haemoglobin variants, we investigated the use of pI markers to confirm the pI of haemoglobin variants detected. CIEF, though more expensive than capillary electrophoretic separations of haemoglobin variants, has greater resolution due to the fact that the separation of variants from pI 6.95 to 7.42 occurs over 4 min, whereas the electrophoretic separation is over 60 s. CIEF is quicker than gel IEF, and shows real-time results as the sample is being processed. The potential for CIEF in the clinical laboratory is not limited to haemoglobin variants, and the technique should become increasingly popular in the near future.

Calibration↗
PubMed1999

BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer.

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% CI 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.

Adult↗