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Biomedical subjects

G W Shaw

Publications and source records attributed to G W Shaw.

11 recordsLinked to original sources

Responses and calibration of amperometric glucose sensors implanted in the subcutaneous tissue of man.

Glucose sensors based on immobilized glucose oxidase and hydrogen peroxide detection at a platinum base electrode were constructed and studied before, during and after implantation into the subcutaneous tissue of 11 non-diabetic subjects. A 75-g oral glucose load was given to elevate the blood glucose concentration. Seven of 14 sensors responded to the oral glucose administration with an increase in current and the output of the remainder was unchanged by the glucose load. Apparent subcutaneous glucose levels calculated from the pre-implantation calibration were a mean 58% of the plasma glucose values at baseline. A two-point in vivo calibration using paired current and glucose readings at baseline and at the maximum glucose and current after glucose ingestion showed a significantly reduced sensitivity in vivo compared with pre-implantation values (mean +/- SEM 52 +/- 21.5 vs 369 +/- 127 pA/mmol-1 per litre, P = 0.003). Recalibration of the subcutaneous glucose concentrations using the in vivo calibration sensitivity and extrapolated background current (I0) gave values similar to those in plasma. The sensitivity of five sensors recalibrated in vitro after explantation was also reduced compared with pre-implantation levels and not significantly different from the in vivo characteristics. Responding and non-responding sensors did not differ with respect to preimplantation I0, sensitivity or response time. However, provisional examination of some explanted sensors by scanning electron microscopy showed coating by cellular and other amorphous material in the non-functioning electrodes. We conclude that the sensitivity of glucose sensors of this design is markedly reduced, sometimes to zero, on implantation in the subcutaneous tissue of humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro testing of a simply constructed, highly stable glucose sensor suitable for implantation in diabetic patients.

We have constructed and tested in vitro a potentially implantable, needle-type amperometric enzyme electrode which is suitable for continuous monitoring of glucose concentrations in diabetic patients. The major requirements of stability during operation and ease of manufacture have been met with a sensor design which involves a simple dip-coating procedure for applying to a platinum base electrode an inner membrane of glucose oxidase immobilised in polyhydroxyethyl methacrylate (pHEMA), and an outer membrane composed of a pHEMA/polyurethane mixture. Sensors were operated at 700 mV for detection of hydrogen peroxide. Calibration curves for the sensor were linear to at least 20 mM glucose and were unaffected by a reduction in PO2 from 20 to 5 kPa. During continuous operation in 5 mM buffered glucose solutions in vitro, sensors suffered no significant loss of response over periods of up to 60 h. Such electrodes are, therefore, useful for development as in vivo glucose sensors.

Biosensing Techniques↗

In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer.

Miniature, amperometric glucose sensors were constructed for implantation in the subcutaneous tissue of normal and insulin-dependent diabetic subjects. To minimise dependence on fluctuating tissue oxygen tension, we employed the technology of mediated electron transfer, with 1,1'-dimethylferrocene acting as the redox shuttle between immobilized glucose oxidase and a platinum base electrode. In 6 normal subjects, the subcutaneous sensor responses mirrored the simultaneously-measured changes in blood glucose concentration after a 75 g oral glucose load and after intravenous injection of 0.15 U/kg short-acting insulin, though increases and decreases in the sensor output were slower than the glycaemic changes. The mean peak delay in sensor response after the oral glucose was 40 min (range 0-45 min) and the delay in the hypoglycaemic nadir was 4 min (range 0-15 min). In 5 insulin-dependent diabetic subjects, spontaneous and induced hypoglycaemia was detectable by the implanted sensor. In addition, marked and frequent oscillations in the sensor current occurred in several normal and diabetic individuals as the blood glucose fell below about 1.9 mmol/l. These oscillations were present in a diabetic subject who had lost adrenergic warning symptoms to hypoglycaemia. Continuous metabolic monitoring in diabetes, particularly the detection of hypoglycaemia, may be possible with implanted sensors based on this technology.

Adult↗

Potentially-implantable, amperometric glucose sensors with mediated electron transfer: improving the operating stability.

The major problems with existing amperometric enzyme electrodes for glucose sensing are oxygen sensitivity and output drift. The recently described miniature glucose sensors using immobilised ferrocene (dicyclopentadienyl iron) to mediate electron transfer from glucose oxidase to a base electrode are oxygen-independent but are often unstable. In this study, we test the hypothesis that the stability of ferrocene-based sensors can be markedly improved by better retention of the enzyme at the electrode. Sensors with graphite foil as the base electrode, dimethylferrocene as the mediator and carbodiimide/glutaraldehyde for enzyme immobilisation lost most of their activity when calibration curves were compared before and after 18 h operation in vitro at 37 degrees C (mean current decrease at 20 mmol/litre glucose was 91%). This sensor type with a covering cellulose membrane also lost activity (mean current decrease of 40% after 18 h). Electrodes in which the base sensor was platinum and the enzyme was covalently attached to agarose lost no activity when operated either at 700 mV without mediator (as a hydrogen peroxide detector) or at 160 mV with mediator. We conclude that both ferrocene-mediated and hydrogen peroxide-detecting amperometric glucose sensors with a high density of covalently-linked enzyme have an operating stability in vitro which may render them suitable for clinical use as, for example, an overnight hypoglycaemia alarm.

Biosensing Techniques↗

Endobronchial tuberculosis in the acquired immunodeficiency syndrome.

Although many of the pulmonary manifestations of tuberculosis in the acquired immunodeficiency syndrome (AIDS) are well known, endobronchial involvement has not been previously described. We report the clinical, roentgenographic, and bronchoscopic features of three patients with endobronchial tuberculosis and AIDS. All of the patients had nonspecific symptoms of fever and cough; however, none exhibited the classic findings of dyspnea, wheezing, or hemoptysis. Smears of sputum were nondiagnostic. The chest x-ray film revealed mediastinal adenopathy in two patients and a lower lobe consolidation in the third; all had small ipsilateral pleural effusions. Endobronchial lesions were white or pink exophytic masses obstructing the airways, mimicking bronchogenic carcinoma. Areas of "classic" primary tuberculosis were seen in two of the patients. Despite ongoing clinical and roentgenographic deterioration, all patients responded well to antituberculosis medications. Given the frequency of tuberculosis in patients with AIDS and AIDS-related complex, one should maintain a high index of suspicion for involvement of the tracheobronchial tree, so as to avoid a delay in diagnosis and resultant increased morbidity and mortality.

AIDS-Related Complex↗

An automated microcomputer-based system for determining canine paw pressure quantitatively in the dog synovitis model.

The automated system for measuring canine paw pressure is a very useful tool for the evaluation of nonsteroid antiinflammatory drugs such as indomethacin and ibuprofen in the dog synovitis model. The apparatus has been designed to give the operator control over the dog's posture while measuring hind-paw pressure. The stability of the measuring platform permits reproducible measurement of paw pressures. The software package performs direct data recording and data reduction and eliminates tedious manual calculations. Subsequently, the software produces a printout summarizing the experimental results in tabular and graphic form.

Animals↗

Nonparametric joint estimators for disease resistance and survival functions in survival/sacrifice experiments.

The nonparametric estimators proposed in this paper simultaneously estimate the disease resistance function, S(t), for the distribution of time to occurrence of disease, and the survival function, P(t), for the distribution of time to death caused by the disease. The estimators are applicable to animal survival data when the disease of interest is irreversible and the cause of death of each animal can be determined. Diseases need not be classified as universally lethal or universally nonlethal, and time to occurrence of the disease of interest need not be observable directly. It is shown that the proposed estimators are maximum likelihood estimators under the condition that S(t)/P(t) is monotonically decreasing. Application of the derived estimators is illustrated with experimental survival/sacrifice data, and results of a simulation study of the estimators' performance are reported.

Animals↗

Biologic and morphologic characteristics of urinary bladder neoplasms induced in BALB/c female mice with 2-acetylaminofluorene.

2-Acetylaminofluorene (2-AAF) induced transitional cell carcinomas, transitional cell carcinomas with squamous metaplasia, squamous cell carcinomas and undifferentiated carcinomas in the urinary bladders of BALB/c female mice. The transitional cell carcinoma was the most common, but was less aggressive and infiltrative than the other three types. The carcinomas were most likely to occur in the vertex of the bladder. A positive correlation existed between dose and length of administration of 2-AAF and the incidence, type, depth of invasion, and the location of the bladder carcinoma.

2-Acetylaminofluorene↗

Dose and time responses models for the incidence of bladder and liver neoplasms in mice fed 2-acetylaminofluorene continuously.

The incidence of bladder and liver neoplasms developed in mice continuously fed 2-acetylaminofluorene (2-AAF) in a multidisciplined study conducted at the National Center for Toxicological Research (NCTR) is represented using a probit model. The estimated incidences are made from time intervals using both sacrificed and dead and moribund mice. A probit log dose model is fit for each type of neoplasm at each time interval where the incidence permits. A probit log time model is fit for each of the neoplastic types for each dose level where the incidence permits. Finally, the response of liver neoplasms to 2-AAF is represented in the dose time plane using a probit plane model. 2-AAF appears to be an early acting bladder carcinogen and a late acting liver carcinogen. The bladders seem to be much more uniform in their response to the carcinogen than the livers and the uniformity of neither response appears to be age dependent. Although the time to appearence of both liver and bladder neoplasms is dose related, the increment in incidence of liver neoplasms with respect to time is not dose related while that of the bladder neoplasms is dose related. The data for bladder neoplasms do not contradict the "no threshold" theory of carcinogenesis while the liver data strongly support it.

2-Acetylaminofluorene↗

Implantable glucose sensors: choosing the appropriate sensing strategy.

The special requirements for implantable glucose sensors which differ from laboratory analysers and in vitro probes include continuous operation without drift, compatibility with in vivo body conditions, electrical and toxicological safety and patient acceptability. We have studied the effect of oxygen tension, operating temperature and pH, and the stability of various potentially implantable amperometric glucose sensors so as to aid the choice of the technologies most suitable for in vivo application.

Biosensing Techniques↗