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Biomedical subjects

D Mayer

Publications and source records attributed to D Mayer.

At least 19 recordsLinked to original sources

Field-effect sensors with charged macromolecules: characterisation by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods.

Field-effect-based capacitive electrolyte-insulator-semiconductor (EIS) sensors have been utilised for the deoxyribonucleic acid (DNA) immobilisation and hybridisation detection as well as for monitoring the layer-by-layer adsorption of polyelectrolytes (anionic poly(sodium 4-styrene sulfonate) (PSS) and cationic poly(allylamine hydrochloride) (PAH)). The EIS sensors with charged macromolecules have been systematically characterised by capacitance-voltage, constant-capacitance, impedance spectroscopy and atomic-force microscopy methods. The effect of the number and polarity of the polyelectrolyte layers on the shift of the capacitance-voltage curves has been investigated. Alternating potential shifts of about 30-90 mV have been observed after the adsorption of each polyanion and polycation layer, respectively. The DNA immobilisation and hybridisation signals were 35-55 and 24-33 mV, respectively. The possible mechanisms for the sensor responses are discussed.

DNA↗

Delayed diagnosis and lower resection rate of adenocarcinoma of the distal duodenum.

BACKGROUND: Carcinoma of the duodenum is a rare disease that can present with varied symptoms and is often misdiagnosed. Prolonged survival following resection of the primary tumour is possible, whilst irresectable disease has a very poor prognosis. The factors determining resectability of the primary tumour have not been addressed. AIMS: We reviewed 45 consecutive cases of duodenal carcinoma to investigate factors which influence the operative outcome of patients with this condition. PATIENTS AND METHODS: Details of symptoms, diagnoses, surgical procedures and pathology were retrieved from patient records. There were 29 male and 16 female patients aged 24-79 years (median = 64 years). RESULTS: The frequency of tumours in the proximal and distal duodenum was 27 and 18. Failure to diagnose the tumours at endoscopy occurred in 10 of 27 tumours of the proximal duodenum and 15 of 18 tumours of the distal duodenum. The duration of symptoms prior to diagnosis was correspondingly longer for tumours in the distal duodenum (20 weeks) than the proximal duodenum (12 weeks). Of 27 patients with tumours in the proximal duodenum, 18 underwent a potentially curative resection, whereas only 6 of the 18 tumours in the distal duodenum were resectable with curative intent. The reasons for irresectability of lesions in the distal duodenum included malignant lymphadenopathy affecting the small bowel mesentery in ten cases, which was not noted in any patient with adenocarcinoma of the proximal duodenum. CONCLUSIONS: Our results suggest that lesions of the distal duodenum are inadequately investigated by endoscopy, and that distal duodenal tumours are less curable by resectional surgery due to invasion of the small bowel mesentery.

Adenocarcinoma↗

Gender-specific expression of liver organic anion transporters in rat.

BACKGROUND: Sex differences in drug pharmacokinetics have been well recognized and gender has been considered a risk factor for adverse events to medications. The aim of this study was to investigate the effect of gender on the expression of hepatocellular transport proteins involved in uptake and secretion of organic anions in rat. MATERIALS AND METHODS: Expression of the rat liver organic anion transporting polypeptides (Oatps) and multidrug resistance proteins (Mrps) was analysed by reverse transcription polymerase chain reaction (RT-PCR), immunoblot analysis and immunofluorescence microscopy in male and female rats. Regulation of these transport proteins in response to the steroid dehydroepiandrosterone (DHEA) was investigated. RESULTS: In untreated rats, protein expression significantly differed between genders being higher (Mrp2, Mrp3), comparable [Oatp1a1 (Oatp1); Oatp1b2 (Oatp4)] or lower [Oatp1a4 (Oatp2)] in female than in male rat. DHEA treatment over 3 days (100 mg d(-1)) led to a further increase in Mrp3 expression only in female rats. Mrp2 expression was not influenced by DHEA treatment. Oatp1a1 and Oatp1b2 were significantly down-regulated after DHEA treatment in both male and female rats. In contrast, Oatp1a4 was down-regulated in male rats only. CONCLUSIONS: In rat, liver transport proteins of the Oatp and Mrp family are expressed and regulated in a gender-specific manner according to sexual differences in the hepatic metabolism of steroids and drugs. These findings may partly explain the well-known sex differences in hepatic handling of organic anions.

ATP Binding Cassette Transporter, Subfamily B↗

Depth of word processing in Alzheimer patients and normal controls: a magnetoencephalographic (MEG) study.

Effects related to depth of verbal information processing were investigated in probable Alzheimer's disease patients (AD) and age matched controls. During word encoding sessions 10 patients and 10 controls had either to decide whether the letter "s" appeared in visually presented words (alphabetical decision, shallow encoding), or whether the meaning of each presented word was animate or inanimate (lexical decision, deep encoding). These encoding sessions were followed by test sessions during which all previously encoded words were presented again together with the same number of new words. The task was then to discriminate between repeated and new words. Magnetic field changes related to brain activity were recorded with a whole cortex MEG.5 probable AD patients showed recognition performances above chance level related to both depths of information processing. Those patients and 5 age matched controls were then further analysed. Recognition performance was poorer in probable AD patients compared to controls for both levels of processing. However, in both groups deep encoding led to a higher recognition performance than shallow encoding. We therefore conclude that the performance reduction in the patient group was independent of depth of processing. Reaction times related to false alarms differed between patients and controls after deep encoding which perhaps could already be used for supporting an early diagnosis. The analysis of the physiological data revealed significant differences between correctly recognised repetitions and correctly classified new words (old/new-effect) in the control group which were missing in the patient group after deep encoding. The lack of such an effect in the patient group is interpreted as being due to the respective neuropathology related to probable AD. The present results demonstrate that magnetic field recordings represent a useful tool to physiologically distinguish between probable AD and age matched controls.

Aged↗

Living arrangements and place of death of older people with cancer in England and Wales: a record linkage study.

The main objectives of the study were to (1) see whether the household circumstances of people aged 50 years and over with cancer, and trends in these, differ from those of the rest of the population and (2) whether living arrangements and presence and health status of a primary coresident are associated with place of death among older people dying of cancer and those dying from other causes. The design included prospective record linkage study of people aged 50 years and over included in a 1% sample of the population of England and Wales (the Office for National Statistics Longitudinal Study). The main outcome measures comprised family and household type, and death at home. The household circumstances of older people with cancer were very similar to those of the rest of the population of the same age and both showed a large increase in living alone, and decrease in living with relatives, between 1981 and 1991. The primary coresident of cancer sufferers who did not live alone was in most cases a spouse, with much smaller proportions living with a child, sibling or other person. In all, 30% of spouse, and 23% of other, primary coresidents had a limiting long-term illness. Compared with people who lived alone in 1991, odds of a home death among those dying of cancer between 1991 and 1995 were highest for those who lived with a spouse who had no limiting long-term illness (odds ratio (OR) 2.52, 95% confidence interval (CI) 2.15-2.97) and raised for those living with a spouse with a long-term illness (OR 2.14, CI 1.79-2.56) and those living with someone else who was free of long-term illness (OR 2.13, CI 1.69-2.68). Higher socioeconomic status, both individual and area, was positively associated with increased chance of a home death, while older age reduced the chance of dying at home. The changing living arrangements of older people have important implications for planning and provision of care and treatment for cancer sufferers.

Aged↗

Labelfree fully electronic nucleic acid detection system based on a field-effect transistor device.

The labelfree detection of nucleic acid sequences is one of the modern attempts to develop quick, cheap and miniaturised hand-held devices for the future genetic testing in biotechnology and medical diagnostics. We present an approach to detect the hybridisation of DNA sequences using electrolyte-oxide-semiconductor field-effect transistors (EOSFETs) with micrometer dimensions. These semiconductor devices are sensitive to electrical charge variations that occur at the surface/electrolyte interface, i.e. upon hybridisation of oligonucleotides with complementary single-stranded (ss) oligonucleotides, which are immobilised on the oxide surface of the transistor gate. This method allows direct, time-resolved and in situ detection of specific nucleic acid binding events without any labelling. We focus on the detection mechanism of our sensors by using oppositely charged polyelectrolytes (PAH and PSS) subsequently attached to the transistor structures. Our results indicate that the sensor output is charge sensitive and distance dependent from the gate surface, which pinpoints the need for very defined surface chemistry at the device surface. The hybridisation of natural 19 base-pair sequences has been successfully detected with the sensors. In combination with nano-transistors a PCR free detection system might be feasible in future.

Biosensing Techniques↗

Chemical and biological integration of a mouldable bioactive ceramic material capable of forming apatite in vivo in teeth.

Chemically bonded ceramics have several advantages compared with conventional ceramics to be used as biomaterials. Especially the possibilities to harden the material at room temperature and to control the rheology are very beneficial. This paper investigates the interface formed in vivo between a calcium aluminate based dental filling material and teeth. Class 1 occlusal fillings were made in wisdom teeth and extracted after up to four weeks. Polished cross-sections of the teeth were studied with scanning electron microscopy (SEM), focused ion beam microscopy (FIB) and transmission electron microscopy (TEM). In order to analyse the distribution of elements at the interface elemental mapping was performed using STEM and EDX. The results showed that a tight bond forms between the filling material and tooth and no gap could be found even at high magnification. A 100-200 nm wide zone with an increase in oxygen was detected in the enamel next to the filling. The zone was denser than the rest of the enamel. Elemental mapping indicated an increase of silicon and a decrease of Ca at the interface. Dark field imaging and EDX mapping showed that the calcium aluminate system formed apatite in situ during hardening through precipitation.

Aluminum Compounds↗

In vivo 2D J-resolved magnetic resonance spectroscopy of rat brain with a 3-T clinical human scanner.

A clinical 3-T scanner equipped with a custom-made transmit/receive birdcage coil was used to collect 2D J-resolved single-voxel spectroscopy in vivo of rat brain. Four adult Wistar rats were scanned twice each, with a 2-week interval. Voxel size was approximately 5 x 10 x 5 mm(3). Total spectroscopic acquisition time was 14 min for collection of two 4:20 min water-suppressed acquisitions and one 4:20 min acquisition acquired in the absence of water suppression. The unsuppressed water data were used in post-processing to reduce residual water side bands, as well as for metabolite signal normalization to account for variations in coil loading and voxel size. Peak areas were estimated for resonances from N-acetyl aspartate (NAA), creatine, choline, taurine, glutamate, and combined glutamate and glutamine. T(2)-relaxation times were estimated for NAA and creatine. The average deviation from the mean of repeated measures for glutamate, combined glutamate and glutamine, and taurine ranged from 7.6% to 18.3%, while for NAA, creatine, and choline, the deviation was less than 3%. The estimated T(2) values for NAA (mean +/- SD = 330 +/- 57 ms) and creatine (174 +/- 27 ms) were similar to those reported previously for rat brain and for human gray and white matter. These results indicate that reliable, small animal brain MR spectroscopy can be performed on a human clinical 3-T scanner.

Anesthesia↗

[Conservative therapy adapted to findings of superficial chronic venous ulcers].

A successful treatment of venous ulcers represents a special clinical challenge. The following conservative wound management of a high-risk patient presents an alternative to primary surgical treatment. A patient of 79 years in reduced general state with multiple underlying concomitant diseases is hospitalized with superinfected, necrotic and painful ulcers. Due to the severe morbidity of the patient the regular therapy of the underlying venous insufficiency consisting of stripping of great saphenous vein and ligation of perforator veins, is contraindicated. After interdisciplinary discussion conservative therapy is carried on. The conservative therapy includes initial local debridement, moist wound-healing dressings, compression therapy, systemic antibiotic and analgesic therapy, completed by stabilization of patient's general state. In regular intervals a photographic documentation of the wound is carried out. The period of treatment and observation is 63 days. Due to conservative wound management a clear improvement of the wound condition and of the patient's general state is observed. The period needed for change of wound dressing can be reduced from 2 hours to 30 minutes. The painscore is reduced from 8/10 to 4/10 as well as the analgesic need. The photographic documentation shows a clear progress of healing within 9 weeks. Under antibiotic therapy and conservative wound management the increased inflammation parameters are declining. By choosing a conservative therapeutical regime adapted to clinical findings superinfected, chronic venous ulcers are turned into a stable condition.

Aged↗

Survival from breast cancer among South Asian and non-South Asian women resident in South East England.

Ethnic differences in breast cancer survival have been observed in the USA but have not been examined in Britain. We aimed to investigate such differences between South Asian (i.e. those with family roots in the Indian subcontinent) and non-South Asian (essentially British-native) women in England. Primary breast cancer cases incident in 1986 -1993 and resident in South East England were ascertained through the Thames Cancer and Registry and followed up to the end of 1997. Cases of South Asian ethnicity were identified on the basis of their names by using a previously validated computer algorithm. A total of 1037 South Asian and 50 201 non-South Asian breast cancer cases were included in the analysis; 30% of the South Asian (n=312) and 44% (n=22 201) of the non-South Asian cases died during follow-up. South Asian cases had a higher relative survival than non-South Asians throughout the follow-up period. The 10-year relative survival rates were 72.6% (95% confidence interval: 69.0, 75.9%) and 65.2% (64.5, 65.8%) for South Asians and non-South Asians, respectively. The excess mortality rates experienced by South Asians were 82% (72, 94%) of those experienced by non-South Asians (P=0.004). The magnitude of this effect was slightly reduced with adjustment for differences in age at diagnosis, but was strengthened with further adjustment for differences in stage at presentation and socioeconomic deprivation (excess mortality rates in South Asians relative to non-South Asians=72% (63, 82%), P&<0.001). These findings indicate that the higher survival from breast cancer in the first 10 years after diagnosis among South Asian was not due to differences in age at diagnosis, socioeconomic deprivation or disease stage at presentation.

Adult↗

Improved artificial neural networks in prediction of malignancy of lesions in contrast-enhanced MR-mammography.

The aim of this study was to evaluate the capability of improved artificial neural networks (ANN) and additional novel training methods in distinguishing between benign and malignant breast lesions in contrast-enhanced magnetic resonance-mammography (MRM). A total of 604 histologically proven cases of contrast-enhanced lesions of the female breast at MRI were analyzed. Morphological, dynamic and clinical parameters were collected and stored in a database. The data set was divided into several groups using random or experimental methods [Training & Testing (T&T) algorithm] to train and test different ANNs. An additional novel computer program for input variable selection was applied. Sensitivity and specificity were calculated and compared with a statistical method and an expert radiologist. After optimization of the distribution of cases among the training and testing sets by the T & T algorithm and the reduction of input variables by the Input Selection procedure a highly sophisticated ANN achieved a sensitivity of 93.6% and a specificity of 91.9% in predicting malignancy of lesions within an independent prediction sample set. The best statistical method reached a sensitivity of 90.5% and a specificity of 68.9%. An expert radiologist performed better than the statistical method but worse than the ANN (sensitivity 92.1%, specificity 85.6%). Features extracted out of dynamic contrast-enhanced MRM and additional clinical data can be successfully analyzed by advanced ANNs. The quality of the resulting network strongly depends on the training methods, which are improved by the use of novel training tools. The best results of an improved ANN outperform expert radiologists.

Algorithms↗

Progress in treatment and outcome for children with neonatal haemochromatosis.

AIM: To evaluate the role of antioxidant treatment and liver transplantation in the management of neonatal haemochromatosis. METHODS: A retrospective review was performed of eight infants with acute liver failure and raised ferritin levels between 1990 and 1998. From 1994, treatment with an antioxidant cocktail (vitamin E, N-acetylcysteine, selenium, prostaglandin E1, and desferrioxamine) was begun once the diagnosis was suspected. Pathological and other findings were reviewed, and outcome before and after antioxidant treatment was evaluated. RESULTS: Median age at presentation was 4 days with median ferritin levels of 4180 micro g/l (range 1650-40 000 micro g/l; normal range 110-503 micro g/l). Three infants presented before 1994. One infant died before liver transplantation from acute liver failure and one from neurological damage after transplantation. The third patient underwent successful transplantation at day 13 and remains well on follow up 8 years later. From 1994, five patients received antioxidant treatment, of whom two responded: both responders started antioxidants earlier (by day 5) than non-responders and had lower peak ferritin levels (< 4200 micro g/l) and a milder phenotype. Treatment was continued until ferritin levels were < 500 micro g/l. Both children remain well with mean follow up of 42 months, with no recurrence of iron overload. One child showed a partial response to treatment and survived long enough for a liver transplant, but died from graft failure after the transplant. Two children did not respond to antioxidant treatment; both had multiorgan failure and were not listed for transplantation. Only three of the eight patients survived (37.5%) over this time period. CONCLUSION: Neonatal haemochromatosis can be a fatal disease with > 60% mortality. Early treatment with antioxidant cocktail is beneficial and may be curative in those who present with milder phenotype. Liver transplantation should always be considered at an early stage in non-responders and in children with more severe acute liver failure.

Antioxidants↗

Repair of abdominal aortic aneurysms with the Excluder bifurcated stent-graft.

The design of the Excluder, which is considered a 3rd generation device for endovascular repair of abdominal aortic aneurysms, is described. Based on a literature search, clinical short- to mid-term results are reviewed. So far, efficacy and safety of the Excluder for elective and emergent aneurysm repair have been demonstrated. In none of the studies perioperative conversion to open surgery or late aneurysm rupture has been reported. The cumulative 30-day-mortality rate was below 1%. Compared to the other commercial devices, aneurysm shrinkage is less marked after repair with the Excluder. Whether this is inconvenient remains to be proven on long-term follow-up.

Aortic Aneurysm, Abdominal↗

Radiological imaging as the basis for a simulation software of ventilation in the tracheo-bronchial tree.

The inhaled route is a promising new way for administering drugs to the human body. Flow and particle deposition in the human respiratory tract depends on the individual's anatomy as well as on the drug composition. A European Framework V Program supported project is currently developing a simulation tool for assessment of drug distribution and deposition. This tool relies heavily on the input of radiological data sets, which are obtained in humans. Both high temporal and spatial resolutions are required, and CT and MRI (including hyperpolarized helium-3 MRI) are applied. The radiological data are integrated into computation fluid dynamics software, which is capable of assessing air-flow profiles and compartmental behaviours. This is complemented by pharmacokinetic models, which should result in a simulation tool that will be of use for the theoretical design of new inhaled therapies. This article describes the special imaging requirements of each region of the respiratory tract and the feasibility of these sophisticated radiological techniques with a view of using these data in a simulation model of the lung.

Administration, Inhalation↗

A modified system to evaluate the potency of anti-oxidative compounds in different cell types in vitro.

Common assays for evaluation of antioxidative capacity of different compounds are usually performed in cell-free systems. By this approach, cell-specific regulatory mechanisms upon distinct stimuli are not taken into account. Therefore, there is a need to measure anti-oxidative capacity in a cellular setting. - We now developed a valid method that provides monitoring of anti-oxidative capacities of compounds in different cell types. Oxidative stress, induced by 100 microM H subset2O subset2 in human microvascular endothelial cells (HMEC-1), was quantified by the generation of oxidized, fluorescent C-DCF from C-H subset2DCF-DA/AM. As DCF-production could be almost completely blocked by diethyldithiocarbamate (DEDTC), which inhibits intracellular Cu/Zn superoxide dismutase (SOD), mainly intracellular production of C-DCF was assumed. Preincubation with alpha-tocopherol resulted in a dose-dependent reduction of both spontaneous and H subset2O subset2-induced C-DCF-production (maximal inhibition by 41.6% at 75 microM). A synergistic effect was observed with co-incubation with vitamin C (maximal inhibition 46.8% at 10 microM vitamin C and 50 microM alpha-tocopherol). In this way compounds with different modes of action and subcellular localization can be evaluated concomitantly in respect of their anti-oxidative capacities. As this method was established on 24- and 48-well plates in other cell lines (Caco-2, HFP-1), too, screening of a large array of antioxidative compounds in different cell lines can be performed.

Antioxidants↗