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Biomedical subjects

M A Jenkins

Publications and source records attributed to M A Jenkins.

At least 37 records · Page 2Linked to original sources

Design and analysis issues in a population-based, case-control-family study of the genetic epidemiology of breast cancer and the Co-operative Family Registry for Breast Cancer Studies (CFRBCS).

BACKGROUND: Historically, studies of the "genetic epidemiology" of cancer have used nonsystematically sampled kindreds with numerous cases of cancer across multiple generations. From the epidemiologic viewpoint, it is difficult to extrapolate findings to the population because of the ad hoc ascertainment of these atypical, ill-defined families. Since 1992, we have been conducting a population-based, case-control-family study of breast cancer. METHODS: Families are identified through a single, population-sampled proband, who is either affected or unaffected, making adjustment for ascertainment straightforward. Administered questionnaires and blood samples are sought from cases, controls, and specified sets of relatives. From 1996 through 1999, a further 1200 case families have been recruited as part of the Co-operative Family Registry for Breast Cancer Studies (CFRBCS). Issues relevant to the study design and analysis are discussed. RESULTS: Epidemiologic and genetic findings published to date are summarized. In particular, this population-based study has shown that the so-called "high-risk" families containing multiple cases of breast cancer are not typical of families in the general population in which BRCA1 or BRCA2 mutations are segregating. Most "hereditary" cancers are "sporadic." CONCLUSION: The collection of DNA, as well as data on disease status and risk factors, from population-sampled sets of relatives provides a powerful resource for addressing genetic and environmental determinants of cancer. A population-based multicenter, multidisciplinary enterprise, such as has been developed by the CFRBCS, may become a model for future research in cancer epidemiology, allowing genetic and environmental risk factors to be put into a proper population perspective.

Breast Neoplasms↗

Alteration of intention and self-initiated action associated with bilateral anterior cingulotomy.

Neuropsychological manifestations of bilateral anterior cingulate cortex lesions were studied in patients treated with cingulotomy for chronic intractable pain. Cingulotomy patients more than 1 year postsurgery were contrasted with nonsurgical chronic pain patients. Patients were assessed on a neuropsychological battery, including measures of response intention, initiation, generation, and persistence. Cingulotomy patients were intact across most cognitive domains, but they showed deficits of focused and sustained attention as well as mild executive dysfunction. Self-initiated responding--including spontaneous verbal utterances and unstructured design fluency--was most impaired. Results indicate that the greatest impact of cingulotomy lesions is on response intention and self-initiated behavior, with reduced behavioral spontaneity.

Adult↗

An unusual alkaline phosphatase isoenzyme associated with gastric carcinoma.

We describe a 50-year-old man with a diagnosis of gastric carcinoma made on gastroscopy after X-rays of the thoracolumbar spine had revealed multiple lytic metastases. A bone marrow aspirate showed adenocarcinoma cells. Polyacrylamide gel electrophoresis incorporating wheat germ lectin was used to separate the serum alkaline phosphatase isoenzymes. Isoenzyme separation showed a markedly increased amount of bone isoenzyme, a normal amount of liver isoenzyme and a considerable amount of an intestinal-like isoenzyme running cathodic to the bone isoenzyme. There was also some immunoglobulin-complexed alkaline phosphatase, which, when digested, showed more of the intestinal-like isoenzyme. This was a variant alkaline phosphatase isoenzyme found in a patient with a gastric carcinoma with a super bone scan. There have been two previous reports of patients with a variant alkaline phosphatase isoenzyme and a super bone-scan.

Alkaline Phosphatase↗

Three methods of capillary electrophoresis compared with high-resolution agarose gel electrophoresis for serum protein electrophoresis.

We assessed the BioFocus 2000 capillary electrophoresis instrument for use in a routine clinical laboratory. We examined 210 serum samples received for serum protein electrophoresis by four methods: (1) The Bio-Rad HR015EC high-resolution serum protein kit on the BioFocus; (2) the Jenkins-Guerin (JG) method on the Applied Biosystems 270A HT Capillary Electrophoresis System (JG-ABI); (3) the Jenkins-Guerin method using the BioFocus (JG-BF); and (4) the quantitation of monoclonal bands found in 76 of the 210 samples was assayed by Helena Titan Hi-Res agarose gel electrophoresis (HRAGE). The correlation coefficient between the three sets of capillary electrophoresis monoclonal band results and the Helena quantitation was 0.92 or better. Although the quantitative comparison of monoclonal bands by HR015EC was very good, the lack of sharpness of monoclonal bands using the HR015EC kit meant our preference was to use the JG method on either the ABI or on the Biofocus.

Blood Proteins↗

Learning and memory in rape victims with posttraumatic stress disorder.

OBJECTIVE: Studies have shown memory deficits among combat veterans with posttraumatic stress disorder (PTSD); however, high rates of comorbid conditions, including alcoholism, make it difficult to definitively associate these findings with the PTSD diagnosis. In this study the authors examined memory functioning among rape survivors without alcoholism or substance abuse but with PTSD. METHOD: Rape victims with (N = 15) and without (N = 16) PTSD were compared to age- and education-matched nontraumatized comparison subjects (N = 16) on measures of learning and memory. RESULTS: The subjects with PTSD performed significantly worse than the other groups on delayed free recall. The deficits were ameliorated by cueing and recognition testing. CONCLUSIONS: Recall deficits in noncombat PTSD patients strengthen the theory that memory deficits are associated with the PTSD diagnosis. The deficits were mild and were not attributable to comorbid depression, anxiety, or substance abuse.

Adult↗

Serum cytokine levels in infectious mononucleosis at diagnosis and convalescence.

Infection with the Epstein-Barr virus (EBV) is common worldwide. A significant number of infected individuals develop infectious mononucleosis (IM). IM is manifested in most patients as a benign disease with mild symptoms. However, serious complications may develop in a subset of patients. Because EBV-infected B lymphocytes produce various cytokines that may provide the cells with a proliferative advantage, cytokine concentrations in serum samples taken from IM patients were measured in order to identify the cytokines responsible for the clinical manifestations of the disease. The concentrations of interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), and lymphotoxin (LT) were measured using an enzyme-linked immunosorbent assay (ELISA) in serum obtained from 14 IM patients during the acute phase of the disease and during convalescence, 5 patients with identical clinical manifestations who did not have IM (sick controls), and 11 healthy volunteers. It was found that the serum levels of TNF-alpha and IL-6 were significantly high in patients with acute IM compared with the serum levels in healthy individuals (P = 0.008 and P < 0.001, respectively) but returned to normal at convalescence (P = 0.009 and P = 0.005 respectively). However, whereas TNF-alpha concentrations were significantly higher (P = 0.04) in patients with acute IM than in the sick controls, no significant difference in IL-6 concentrations was found between the two groups of patients. Changes in IL-10 concentration were not statistically significant, and IL-1beta, IL-2, IL-8, and LT were detected only sporadically. The data in this study suggest that TNF-alpha may have a specific role in causing the clinical manifestations of IM. Further studies should determine the clinical significance of TNF-alpha inhibition in IM.

Convalescence↗

Capillary electrophoresis procedures for serum protein analysis: comparison with established techniques.

Methods using automated capillary electrophoresis (CE) instrumentation are available for serum protein electrophoresis with monoclonal band quantitation, isoelectric focusing and sodium dodecyl sulphate-polyacrylamide gel electrophoresis separations. The advantages of CE over previous gel methods relate to the time and labour saved by the automated instrumentation. High pI monoclonal bands and cryoglobulin specimens can be successfully analysed by CE. However, if the CE application uses a standard company supplied kit, then the cost savings are often negated by the high cost of the kit. Improvements such as the inclusion of both a UV-Vis as well as a fluorescence detector as standard within the one commercial instrument, the production of coated IEF capillaries with a useful life of at least 100 samples, and the introduction of a capillary array into all commercial instrumentation would ensure greater use of CE within both the clinical and other protein laboratories.

Antibodies, Monoclonal↗

Regressive logistic modeling of familial aggregation for asthma in 7,394 population-based nuclear families.

The aim of this population-based study was to determine whether asthma aggregates in families, and if so, whether aggregation was consistent with environmental and/or genetic etiologies. Data were from 7,394 nuclear families (41,506 individuals) from the 1968 Tasmanian Asthma Survey, in which all Tasmanian schoolchildren born in 1961 were surveyed by respiratory questionnaire completed by their parents. Similar data were obtained for parents and siblings of probands. For a child, having ever had asthma was predicted by a parent or sibling having ever had asthma; odds ratio (OR) = 3.13 (95% confidence interval [CI] 2.82-3.48) for mother, 2.99 (2.69-3.32) for father, and 3.47 (3.23-3.72) for a sibling. Regressive logistic modeling showed that, in addition to parent-offspring effects, the data were consistent with the existence of an unmeasured factor shared by siblings, evident in 15% (SE 2%) of families and associated with a conditional OR of 9.68 (8.27-11.32). Familial aggregation was best described by a general oligogenic model with non-Mendelian transmission probabilities. Of the Mendelian models, a codominant model with an allele frequency of 16% (SE 0.3%) was preferred. Under a dominant model there was evidence for additional parent-offspring and sibling effects of similar magnitude. It is unlikely that there is one major loci influencing asthma susceptibility; the overall effects of asthma genes in the population are more likely to be inherited codominantly, at least for the majority of loci of major etiological importance. The role of environmental factors in explaining part of familial aggregation for asthma cannot be ruled out, as major triggers of asthma attacks are familial.

Asthma↗

Clinical application of capillary electrophoresis to unconcentrated human urine proteins.

Urine protein electrophoresis can be performed by capillary electrophoresis using spun unconcentrated urine diluted with running buffer. The separation which utilises the excellent sensitivity of capillary electrophoresis gives electropherograms similar to those obtained by diluting concentrated urine with buffer. A 72 cm x 50 microns internal diameter (ID) fused silica capillary was used for the analysis which took less than 15 min. Bence Jones protein can be detected from unconcentrated urine over urine protein concentrations ranging from 9.7 g/L to 0.04 g/L. Other clinical patterns, such as glomerular proteinuria, the presence of intact immunoglobulin and Tamm Horsfall protein can also be detected. The benefit of using unconcentrated urine is the time and cost saved by not concentrating the urine.

Adult↗

Neuropsychiatric factors in the illusion of visitors among geriatric patients: a case series.

The 'illusion of visitors' is a common phenomenon among geriatric patients presenting for psychiatric or neurologic evaluation and treatment. Although these illusory beliefs are etiologically diverse, patients may commonly have visual impairment and functional and/or structural disruption of frontal and right-hemisphere-mediated cognitive functioning. This article outlines eight cases of illusory beliefs among elderly patients, presenting psychiatric, neurologic, neuroimaging, and neuropsychological findings among these patients. Commonalities and differences among these cases are discussed, and a framework is provided for multidisciplinary assessment and treatment of patients presenting with illusory beliefs.

Aged↗

Capillary electrophoresis as a clinical tool.

Clinical laboratories must produce accurate results for patients with a minimum turn-around time. Automated commercial capillary electrophoresis instrumentation has been available to the clinical laboratory for the past five years. Our laboratory has utilised capillary electrophoresis (CE) to automate serum protein electrophoresis. We have used the technique of CE to produce clinical results for nearly two years. CE methods are also available for the quantitation of haemoglobin variants, by both isoelectric focusing and free solution techniques. Micellar electrokinetic separations by CE have been developed for some specialised drug assays and for B-group vitamin analysis, while gel-filled capillaries have the capability to separate DNA fragments, such as PCR products. Isoenzyme analysis has shown possibilities by CE, but quantitative results are needed to be clinically useful. Analysis of amino acids for newborn screening programs and as an arterial clotting indicator are being developed. The next five years should see a proliferation of clinical laboratory methods using automated CE.

Blood Protein Electrophoresis↗

Airway sealing pressures of the laryngeal mask airway in pediatric patients.

STUDY OBJECTIVES: To determine if the laryngeal mask airway (LMA) seal is maintained during surgery, to evaluate the safety of an LMA leak test, and to determine the time course of the increase in LMA cuff pressure in vivo in the presence of nitrous oxide (N2O). STUDY DESIGN: Descriptive clinical study. SETTING: University teaching hospital. PATIENTS: 78 ASA Physical Status I and II pediatric patients, aged 3 months to 17 years, undergoing general anesthesia with an LMA; 14 patients were studied on two occasions approximately 2 months apart. INTERVENTIONS: The airway pressure at which the LMA seal was broken (leak pressure) was determined immediately following insertion of the LMA and at the end of surgery. In 17 patients, the LMA cuff pressure was continuously measured during surgery, during which 67% N2O was administered. The mean duration of surgery was 29.5 minutes. MEASUREMENTS AND MAIN RESULTS: The LMA leak pressure was determined by closing the circuit popoff valve and recording the pressure at which gas was first heard to escape around the LMA at the mouth. The LMA cuff pressure was determined by connecting the check valve of the LMA pilot balloon to a sphygmomanometer. The elastance of the LMA was determined from the slopes of the regression lines of pressure versus volume for the various sized LMAs in vitro (Sizes 1-4) and in vivo (sizes 2 and 2 1/2). The initial LMA leak pressure was 25.9 cm H2O, and it increased to 31.2 cm H2O during surgery (p < 0.001). 146 leak tests were performed without causing gastric dilatation or LMA dislodgement. The mean LMA cuff pressure increased during surgery from 106.2 mmHg to 132.8 mmHg (p < 0.001), a pressure increase that corresponds to a volume increase of 1.4 ml. CONCLUSIONS: The LMA leak test can be safely performed. The airway seal provided by the LMA is well maintained during surgery. The increase in LMA cuff pressure during surgery in the presence of N2O is small and probably is not a cause for clinical concern. If positive pressure is to applied in the presence of an LMA, one should limit this pressure to below the LMA leak pressure so as to lower the risk of inflating the stomach with gas that may than leak around the LMA.

Adolescent↗

Validation of questionnaire and bronchial hyperresponsiveness against respiratory physician assessment in the diagnosis of asthma.

BACKGROUND: The Tasmanian Asthma survey (TAS) and the International Study of Asthma and Allergies in Childhood (ISAAC) have used questionnaires to measure the prevalence of asthma in adults and children. We have investigated the validity of these questionnaires by comparing response to questionnaire with a physician assessment of asthma status in the past 12 months. METHODS: Ninety-three adults were given the TAS questionnaire to complete and 361 children were given the ISAAC questionnaire. Ninety-one adults and 168 children completed bronchial challenge with hypertonic saline. A consultation with a respiratory physician blinded to the results of the questionnaire and bronchial challenge was given to all subjects. RESULTS: In both adults and children, questionnaires showed high agreement with respiratory physician diagnosis with respect to asthma symptoms in the past 12 months. For the TAS questionnaire the positive and negative predictive values (95% confidence limits) for physician diagnosis for adults were 0.89 (0.68-0.98) and 0.94 (0. 86-0.98) respectively. The instrument was also sensitive 0.80 (0. 58-0.93) and highly specific 0.97 (0.90-0.99). For the ISAAC questionnaire the positive and negative predictive vales for physician diagnosis of asthma in children were 0.61 (0.50-0.71) and 0.94 (0.88-0.98) respectively. Sensitivity and specificity were 0.85 (0.73-0.93) and 0.81 (0.76-0.86) respectively. Compared to the physician diagnosis, the sensitivity of bronchial hyperresponsiveness (BHR) for asthma was low for adults 0.39 (0.21-0. 61) and children 0.54 (0.48-0.67) as were the positive predictive values: 0.55 (0.31-0.79) for adults and 0.64 (0.449-0.77) for children. A definition of asthma requiring both a positive questionnaire response and BHR was highly specific but not sensitive for adults 0.37 (0.20-0.59) or children 0.47 (0.35-0.60). CONCLUSIONS: Both the TAS and ISAAC questionnaires are valid instruments for the determination of asthma symptoms in the past 12 months.

Adolescent↗

Evaluation of serum protein separation by capillary electrophoresis: prospective analysis of 1000 specimens.

To critically assess the method of capillary electrophoresis (CE) we examined 1000 prospective serum samples submitted for protein electrophoresis by both high-resolution agarose gel electrophoresis (HRAGE) and CE. CE was performed using a 72 cm (50 cm to detector) x 50 microns I.D. fused-silica capillary with detection of absorbance at 200 nm. The 1000 samples examined contained 362 monoclonal paraproteins with concentrations ranging from 1 to 71 g/l. We evaluated the individual paraprotein correlations, the overall correlation between the two methods being 0.96. We found that HRAGE gave slightly higher values for the monoclonal bands than CE and the difference was statistically significant. We conclude that CE is a viable alternative to HRAGE for the determination of protein dyscrasias in a routine clinical laboratory.

Antibodies, Monoclonal↗

Increase in the self-reported prevalence of asthma and hay fever in adults over the last generation: a matched parent-offspring study.

The study compared current measures on a population-based cohort of adults with past measures on their parents to determine whether the prevalence of self-reported asthma and hay fever in adults increased between 1968 and the early 1990s. In 1968, 8585 cohort members (99 per cent of eligible Tasmanian 7-year-old school children born in 1961), 16,273 (95 per cent) of their parents (mean age 35 years) and 20,937 siblings completed a questionnaire about asthma and hay fever. In 1991-1993, 1494 members (75 per cent) of a stratified random sample of the cohort (aged 29 to 32 years), 75 per cent resident in Tasmania, were surveyed again. In 1968, the proportion of parents who reported having ever had asthma or attacks of wheezing like asthma was 10.9 per cent, independent of age and sex. In 1991-1993, the estimated adult prevalence of having ever suffered from attacks of asthma or wheezy breathing was 23.2 per cent. The proportion reporting at least one asthma attack within the previous 10 years, 5 years, 2 years, 12 months and 6 months was 17.6 per cent, 16.1 per cent, 14.5 per cent, 13.3 per cent and 10.3 per cent, respectively. For hay fever, the adult prevalence was 19.2 per cent in 1968, and 41.3 per cent in 1991-1993. The self-reported lifetime prevalence of asthma and hay fever among adults in the 1961 birth cohort of Tasmanians was twice as high in 1991-1993 as in their parents 25 years earlier.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quantification of serum proteins using capillary electrophoresis.

Capillary electrophoresis is a technique that can be automated for the separation of charged particles. By investigating suitable sample dilution and injection time and adhering to a strict washing procedure we have been able to quantify paraproteins in serum samples. This has enabled us to use the technique of capillary electrophoresis for the provision of serum protein electrophoresis in a routine clinical laboratory. We present our findings of 260 serum samples, which included 76 samples with paraproteins analysed by both capillary electrophoresis (EC) and high resolution agarose gel electrophoresis (HRAGE). CE was able to detect all the monoclonal bands detected by HRAGE, and in particular, better able to detect IgA monoclonal bands occurring in the beta region. The major advantages of CE over HRAGE relate to the automated nature of CE with the elimination of the need for a densitometer.

Blood Protein Electrophoresis↗

Endoscopic retrograde cholangiopancreatography and endobiliary stenting in the treatment of biliary injury resulting from liver trauma.

Two patients with the bile duct injury secondary to blunt liver trauma are presented. Endoscopic retrograde cholangiopancreatography (ERCP) proved to be a useful diagnostic and therapeutic modality in the treatment of these patients. This report advocates the use of ERCP and endobiliary stenting in the management of biliary injury resulting from liver trauma.

Adult↗