Fetal brain activity demonstrated by functional magnetic resonance imaging.
Functional magnetic resonance imaging was used to study fetal brain activity. This activity was in response to an auditory stimulus.
Acoustic Stimulation↗
Biomedical subjects
P Baker
Publications and source records attributed to P Baker.
Role of accurate mass measurement (+/- 10 ppm) in protein identification strategies employing MS or MS/MS and database searching.
We describe the impact of advances in mass measurement accuracy, +/- 10 ppm (internally calibrated), on protein identification experiments. This capability was brought about by delayed extraction techniques used in conjunction with matrix-assisted laser desorption ionization (MALDI) on a reflectron time-of-flight (TOF) mass spectrometer. This work explores the advantage of using accurate mass measurement (and thus constraint on the possible elemental composition of components in a protein digest) in strategies for searching protein, gene, and EST databases that employ (a) mass values alone, (b) fragment-ion tagging derived from MS/MS spectra, and (c) de novo interpretation of MS/MS spectra. Significant improvement in the discriminating power of database searches has been found using only molecular weight values (i.e., measured mass) of > 10 peptide masses. When MALDI-TOF instruments are able to achieve the +/- 0.5-5 ppm mass accuracy necessary to distinguish peptide elemental compositions, it is possible to match homologous proteins having > 70% sequence identity to the protein being analyzed. The combination of a +/- 10 ppm measured parent mass of a single tryptic peptide and the near-complete amino acid (AA) composition information from immonium ions generated by MS/MS is capable of tagging a peptide in a database because only a few sequence permutations > 11 AA's in length for an AA composition can ever be found in a proteome. De novo interpretation of peptide MS/MS spectra may be accomplished by altering our MS-Tag program to replace an entire database with calculation of only the sequence permutations possible from the accurate parent mass and immonium ion limited AA compositions. A hybrid strategy is employed using de novo MS/MS interpretation followed by text-based sequence similarity searching of a database.
Animals↗
Moderately differentiated neuroendocrine carcinoma in the floor of the mouth: a case report.
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Carcinoma, Neuroendocrine↗
D-dimer for the exclusion of venous thromboembolism: comparison of a new automated latex particle immunoassay (MDA D-dimer) with an established enzyme-linked fluorescent assay (VIDAS D-dimer).
The use of D-dimer tests to exclude venous thromboembolism is an important advance in clinical practice and also has economic benefits. Ideally the test should be objective and a test that could be run on the routine coagulometer would obviate the need for additional investment in alternative hardware. A new automated latex particle immunoassay (MDA D-dimer) that can be run on a routine coagulometer was compared with a well established enzyme linked fluorescent assay (VIDAS D-dimer) on the basis of their ability to exclude venous thromboembolism. The assays were compared in 49 patients presenting to the emergency department with clinically suspected deep vein thrombosis or pulmonary embolism. After objective diagnostic imaging, 20 patients were confirmed to have venous thromboembolism. There was strong agreement between the assays in individual patients. Using a cut-off of 500 micrograms/l, both tests had a sensitivity of 100% and therefore a negative predictive value of 100%, however the MDA test would have spared more patients (20% vs. 12%) from further testing if a negative D-dimer was used to rule-out the diagnosis. It was concluded that a rapid, objective latex D-dimer test run on a routine coagulometer (MDA D-dimer) can be used to exclude the diagnosis of venous thromboembolism.
Enzyme-Linked Immunosorbent Assay↗
Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary thromboembolic disease using an improved method for factor VLeiden detection.
Activated protein C resistance caused by factor VLeiden mutation is the most common inherited predisposing cause of venous thromboembolism, including pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is higher among patients with PE evident at autopsy than in the general population. Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed pulmonary thromboembolic disease during a 4-year period were collected for DNA extraction. Extraction and molecular analysis of the DNA was performed with an improved technique with an internal control to determine the presence of factor VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no homozygotes for factor VLeiden mutation were identified. This yielded a positive rate of 6% overall and 7% among white patients, which is similar to the incidence of heterozygotes in the white population. This study indicates that routine determination of factor VLeiden mutation is not warranted for patients with PE diagnosed at autopsy.
Adolescent↗
Stemming the tide: reducing cardiovascular disease and renal failure in Australian Aborigines.
An epidemic of cardiovascular disease (CVD) and end stage renal disease (ESRD) has developed among Aborigines in the Northern Territory; CVD deaths increased over the 1980s (tripling among women!), and are now more than five times those of non-Aboriginal people, while ESRD rates are increasing more than 20-fold and are doubling every three to four years. Dialysis costs (>$75,000 per person/year) pose a crisis for health care budgets, but premature mortality is the greater human catastrophe. Health services are not meeting the challenge of timely diagnosis, prevention and containment. We screened 90% of adults (20+ years) in one community, with CVD mortality among the highest in Australia, and ESRD rates increased 60-fold. Seventy-five per cent of persons were smokers. Central obesity was common, but BMIs only modestly increased by Caucasian standards, 23% had hypertension (>140/90), 29% had diabetes or impaired glucose tolerance (IGT) (peaking at 65% of persons aged 40-49 years), high triglyceride and insulin levels were common, and 55% had albuminuria (albumin/creatinine ratio (ACR), >3.4 gm/moL). Progressive albuminuria predicted renal failure. ACR was correlated with age, BMI, blood pressure, lipid, glucose and insulin levels, heavy drinking and past and current skin infections, and, inversely with birth weight. ACR correlated strongly with a composite CV risk score, and in a two to five year follow-up, microalbuminuria (ACR 3.4-33) and overt albuminuria (ACR 34+) have both predicted increased rate of premature death from natural causes of lower ACRs. Thus albuminuria marks CV risk/disease. This implies that renal and CV disease share common risk factors, and should respond to the same interventions, and that this response might be monitored through ACR levels. Robust public health programmes could reduce all these reversible risk factors, lowering disease rates over the intermediate term, however, few such programmes are in place. Modification of disease in persons already afflicted is a parallel responsibility. To this end, in November 1995, we introduced a treatment programme with Coversyl (perindopril, Servier) for all persons in the study community with hypertension (>140/90), for all diabetics with ACR 3.4+ and for all nondiabetic, non-hypertensive persons with progressive overt albuminuria (ACR 34+). One-quarter of all adults, or 224 persons have enrolled; 162 have reached one year of treatment and 100 have passed two years. Compliance is reasonable and enthusiasm high. Average SBP has fallen 12 mmHg (24 mmHg in hypertensive persons), while average ACR and estimated glomerular filtration rate (GFR) have stabilised. This contrasts favourably with the pretreatment course (average 2.7 years) in the same persons, when SBP had increased by 3 mmHg, ACR had increased by 15% and GFR had decreased by 3.5 mL/min each year. Cautious estimates suggest a >50% fall in ESRD, and a reduction in all-cause and CV deaths, even at this early stage, although more extended observation is needed. These data predict a dramatic and rapid fall in morbidity, premature deaths and health care costs if these basic principles of medical care are extended to all Aboriginal people. A national, concerted, multi-disciplinary effort to implement a coherent, effective strategy to this end is of great urgency.
Adult↗
Giving evidence in court appearances.
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Australia↗
Significance of fatty acids in pregnancy-induced immunosuppression.
Pregnancy can exert suppressive effects on chronic inflammatory conditions. We have previously demonstrated a depression in polymorphonuclear leukocyte (PMN) respiratory burst during pregnancy which could explain this amelioration. To elucidate the biochemical mechanism, we have examined PMN phospholipase A2 (PLA2) activity and its relationship to cellular and circulating fatty acids in pregnant women (30 to 34 weeks) and nonpregnant controls. PMN PLA2 activity was determined by arachidonic acid (AA) and leukotriene B4 (LTB4) release, respiratory burst activity was determined by lucigenin-enhanced chemiluminescence, and total serum and PMN fatty acid levels were determined by gas-liquid chromatography. AA release was significantly reduced for pregnancy PMNs in response to N-formyl-met-leu-phe (fMLP) under unprimed and tumor necrosis factor alpha (TNF-alpha)- or interleukin 8-primed conditions. Similarly, LTB4 liberation was significantly reduced in response to fMLP and phorbol myristate acetate in unprimed and TNF-alpha-primed pregnancy PMNs. All major fatty acid classes were altered in the pregnant state. Of these differences in PMNs, oleic acid and alpha-linolenic acid showed a significant increase (13 and 26%, respectively) and stearic acid and AA showed a significant decrease (8 and 30%, respectively). The stearic acid, oleic acid, and AA compositions of all cells analyzed correlated with their corresponding changes in serum fatty acid levels. Crossover serum incubations modified both fatty acid profiles and the PMN respiratory burst accordingly, while individual fatty acid incorporation studies highlighted the importance of polyunsaturated fatty acids for NADPH oxidase efficiency. These findings indicate that the attenuation of PMN function in pregnancy may originate from a reduction in the available pool of cellular fatty acids. Furthermore, this reduction arises as a direct result of a pregnancy-induced shift in circulating fatty acids from polyunsaturated to monounsaturated forms.
Adolescent↗
Lymphatic and hematopoietic cancer in teachers.
A recent study found high rates of leukemia and related disorders among teachers. This finding may be related to exposure to childhood infections. Therefore, epidemiologic studies on the risk of lymphatic and hematopoietic cancer among teachers were systematically reviewed. Altogether 26 relevant investigations were identified, most from ad hoc publications rather than from scientific journals. Elevated risks of leukemia, lymphoma, and multiple myeloma were found in studies using proportional mortality or mortality odds ratios as outcome measures. However, these observations may reflect low overall mortality and do not necessarily indicate high death rates from the cancers of interest. In studies deriving standardized mortality or incidence ratios, the risk estimates were generally lower. The most striking finding was for non-Hodgkin's lymphoma (approximate summary relative risk 1.36, 95% confidence interval 1.13-1.62), but it was likely to have been exaggerated by publication bias. In conclusion, no compelling epidemiologic evidence exists for a hazard of leukemia or related diseases among teachers.
Adolescent↗
VEGF via VEGF receptor-1 (Flt-1) mimics preeclamptic plasma in inhibiting uterine blood vessel relaxation in pregnancy: implications in the pathogenesis of preeclampsia.
Preeclampsia is a multisystem disorder characterized by hypertension and proteinuria. There is accumulating evidence that this is a disease of the endothelium, with an as-yet unidentified circulating factor, or factors, causing the observed alteration in vascular function. We previously reported that the function of myometrial vessels is altered on exposure to plasma from women with preeclampsia. Vascular endothelial growth factor (VEGF) is an angiogenic growth factor that acts via two high-affinity receptors (KDR and Flt-1), and its production is increased in preeclampsia. Here we report that VEGF and its Flt-1 receptor may play a pivotal role in the altered vascular function of preeclampsia. Myometrial resistance vessels were obtained at the time of cesarean section. Using the Mulvany wire myograph, the endothelium-dependent behavior of these vessels was studied. Incubation of vessels from pregnant women with VEGF resulted in a reduction of endothelium-dependent relaxation that mimicked the reduction induced by plasma from women with preeclampsia. The altered function that occurred upon exposure of vessels to VEGF or plasma from women with preeclampsia did not occur when plasma was incubated with antibodies to VEGF before vessel incubation. The presence of an anti-KDR receptor antibody had no effect on VEGF response. However, in the presence of an anti-Flt-1 receptor antibody, VEGF or plasma from women with preeclampsia no longer attenuated the endothelium-dependent relaxation (p < 0.05). The changes observed with VEGF and plasma from women with preeclampsia and their subsequent blockade with anti-VEGF antibody and anti-Flt-1 receptor antibody strongly suggest that VEGF acting through the Flt-1 receptor is pivotal in the pathogenesis of this disease.
Adolescent↗
Clinical characteristics of sudden death victims in heritable (chromosome 1p1-1q1) conduction and myocardial disease.
OBJECTIVES: The purpose of this study was to identify the clinical characteristics of family members at risk of sudden death. BACKGROUND: The significance of sudden death in heritable cardiac disorders with delayed expression is incompletely understood. Additional insights come from a four-decade experience of seven generations of a family of German origin with autosomal dominant (chromosome 1p1-1q1) cardiac conduction and myocardial disease. METHODS AND RESULTS: A total of 38 family members (20 males; 18 females) were identified with sudden death. Twenty-eight family members (mean age 48+/-8 years) from earlier generations had no pacemaker at the time of sudden death. In this group, 15 subjects were asymptomatic prior to sudden death. Ten family members with sudden death, from later generations, had chronically implanted pacemakers for high grade atrioventricular block. This group was older (mean age 57+/-2 years), with decreased functional status (New York Heart Association class II to IV), enlarged left atria, dilated left ventricles with reduced systolic function and documented ventricular fibrillation in three members. Twenty-eight family members with sudden death were descendants of sib lineages 2 or 6; 21 family members with sudden death were offspring of a parent who also suffered sudden death. CONCLUSION: Sudden death is an important late outcome in heritable (chromosome 1p1-1q1) cardiac conduction and myocardial disease. Pacemaker therapy is important for the treatment of symptomatic bradycardia, but it does not prevent sudden death. Family members who are beyond the third decade of life with reduced functional capacity, left ventricular dysfunction, pacemakers and who are the offspring of a parent with sudden death appear to be at greatest risk
Adult↗
Case of the month: Institutional autopsy rates. Autopsy Committee of the College of American Pathologists.
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Acquired Immunodeficiency Syndrome↗
Effect of catheter tip length and position on lesion volume in temperature controlled RF ablation in canine tricuspid valve annulus.
BACKGROUND: Radiofrequency (RF) energy has been delivered to the tricuspid valve annulus (TVA) in humans with both 4 mm and 8 mm long catheter tip electrodes to treat atrial flutter. However, lesion volume with temperature controlled RF delivery systems has not been previously characterized. METHODS: In 10 anesthetized canines, a single pulse of temperature controlled RF energy at a 70 degrees C set point, 30 second duration was delivered with either a 7 Fr/4 mm tip or a 7 Fr/8 mm tip electrode in a position both anterolateral and posteroseptal to the tricuspid valve annulus (TVA). Surface echocardiogram was obtained prior and after ablation. The animals were sacrificed after ablation and the lesions underwent gross and histological examination. RESULTS: Lesion size, tip temperature and power were related to tip electrode surface area (SA). Eight mm tips (SA = 59 mm2) tended to create significantly larger lesions than 4 mm tips (SA = 29 mm2). Median lesion volume was 22 vs. 1.5 mm3, respectively. Eight mm tips were also associated with higher power requirements and lower temperatures than 4 mm tips. Posteroseptal TVA lesions tended to be larger than anterolateral lesions. No significant complications were noted. CONCLUSIONS: Using temperature controlled RF ablation, large lesions may be safely created on the canine TVA using 7 Fr catheters with 8 mm long tips.
Animals↗
Autism and tuberous sclerosis complex: prevalence and clinical features.
This study employed a hierarchical assessment to detect the prevalence of autism in a clinic sample of individuals with tuberous sclerosis complex (TSC). After screening subjects with the Autism Behavior Checklist, subsequent evaluations with the Autism Diagnostic Interview, and direct clinical observation, the prevalence of autistic disorder in this sample of 20 subjects was conservatively estimated at 20%. Data suggest a possible association between both hypsarrythmia and TSC-related cardiac abnormalities with autism in this subgroup of TSC individuals. Implications of these findings for clinical practice and further research are discussed.
Adolescent↗
Upper limb disorder due to manual pipetting.
This case report describes the occurrence of non-specific upper limb symptoms, in a 47-year-old female scientific officer, associated, with manual pipetting. The discussion considers the difficulty of risk assessment and reduction for this common procedure.
Arm↗
Temperature controlled RF ablation in canine ventricle and coronary sinus using 7 Fr or 5 Fr ablation electrodes.
The safety and lesion volume of temperature controlled radiofrequency ablation (TCRFA) in the right ventricle (RV), left ventricle (LV), and coronary sinus (CS) comparing long 5 Fr to standard tip electrodes have not been previously reported. In 10 canines, TCRFA was delivered at a 70 degrees C set point for 30 seconds. Lateral and septal RV lesions were made with either a 5 Fr/5 mm or 7 Fr/4 mm tip. Lateral and septal LV lesions were made with either a 5 Fr/7 mm or 7 Fr/4 mm tip. Proximal and distal CS lesions were made with either a 7 Fr/4 mm, 5 Fr/5 mm or 5 Fr/7 mm tip. Gross and histologic examination of the lesions was completed. Lesion size, tip temperature and power required are related to electrode surface area (SA) when ablating in the RV, LV or CS. 5 Fr/7 mm tips (SA = 36 mm2) tended to create larger lesions than 7 Fr/4 mm tips (SA = 29 mm2) in the LV. 7 Fr4 mm tips tended to create larger lesions than 5 Fr/5 mm tips (SA = 26 mm2) in the RV. 7 Fr/4 LV lesions exceeded 7 Fr/4 mm RV lesions due to thicker LV walls. In the CS, 5 Fr/7 mm tips tended to create the largest lesions. In the RV, LV and CS, tips with larger SA tended to have lower temperatures and require higher power. No high temperature or high impedance shut-downs were observed. In conclusion, varying 5 Fr tip length can safely produce larger or smaller lesions compared to those created with 7 Fr/4 mm tips.
Animals↗
Glucose transport inhibitors protect against 1,2-cyclohexanedione-produced potassium loss from human red blood cells.
It has been suggested that the glucose transport system of human erythrocytes contains an arginine shield to prevent the leak of potassium through the transporter. To investigate this suggestion we treated human erythrocytes with the specific arginine reagent 1,2-cyclohexanedione. Under conditions which produce a covalent reaction between arginine and the reagent, a steady leak of potassium occurs. If glucose, maltose or the inhibitor phloretin are present during the reaction the extent of the leak is reduced. These findings support the view that arginines have a role in preventing potassium loss through the glucose transporter.
Arginine↗
A species-specific monoclonal antibody to Cynodon dactylon.
BACKGROUND: It is usually difficult to differentiate between the pollens of different grass species on the basis of their appearance under a microscope, as they often appear similar. Such distinctions are important when interpreting the clinical relevance of pollens in air samples as individuals can differ in their allergic responses to different grass species. As this allergenic distinction occurs at the level of presence and differences of epitopes on the allergens associated with different species, it could be anticipated that species-specific monoclonal antibodies could provide such distinctions between pollens. METHOD: Monoclonal antibodies raised against Cynodon dactylon were screened and characterised in ELISA assays and blotting, using a range of grass pollen extracts, to identify clones which were species specific. RESULTS: The most specific monoclonal raised to C. dactylon did not react at a level of greater than 1.2% to extracts of 10 other grass pollens in a direct ELISA assay and showed no detectable cross-reactivity in a particle blotting assay. CONCLUSION: It has been possible to produce a monoclonal antibody that is functionally species specific to C. dactylon.
Animals↗