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Biomedical subjects

H Griffiths

Publications and source records attributed to H Griffiths.

At least 109 records · Page 6Linked to original sources
PubMed1987

A modified pharmacokinetic model for platinum disposition in ovarian cancer patients receiving cisplatin.

We have fitted a first-order multicompartment pharmacokinetic model to plasma platinum concentrations measured in nine ovarian cancer patients who received intravenous infusions of cisplatin for 6 h. The time-course of ultrafilterable plasma platinum was similar in all patients studied, and was fitted by a single compartment within the limits of experimental detection. However, the time-course of protein-bound platinum showed marked differences between patients, the differences being explained by distribution to two peripheral compartments. The wide inter-patient variation observed in protein-bound plasma platinum concentrations supports the view that pharmacokinetic modelling should be carried out separately for each patient, since averaging plasma concentrations would have obscured some individual pharmacokinetic characteristics.

Cisplatin↗
PubMed1987

Serum creatine kinase-BB levels and cerebral cortical creatine kinase activity in senile dementia of the Alzheimer type.

A rise in serum creatine kinase-BB (CK-BB) levels has been reported previously in cases of dementia. In the present study the levels of serum CK-BB have been measured in patients clinically assessed to have senile dementia of the Alzheimer's type (SDAT) and in cognitively intact individuals, matched for age, by a specific two-site monoclonal immunoradiometric assay. No significant difference was found between the 2 groups. Total creatine kinase activity in temporal cortex (Brodmann area 21 and 22) was also found to be similar in brains from SDAT or control cases, obtained at autopsy. These results suggest no major change in the permeability of the blood-brain barrier to this enzyme in SDAT patients.

Alzheimer Disease↗
PubMed1987

Immunogenic and antigenic epitopes of immunoglobulin--XX. Denaturation of human IgG3 by free radicals.

It has previously been demonstrated that exposure of polyclonal IgG to free radicals results in denaturation evidenced by aggregation, auto-fluorescence and destruction of cysteine, proline and aromatic amino acids. In the present study we have used a panel of monoclonal antibodies (McAb) to epitopes expressed on the IgG3 heavy chain to detect changes in antigenicity. When IgG3 was exposed to u.v. irradiation, as a source of free radicals, subclass specific epitopes were rapidly lost whilst other epitopes were unaffected. Prolonged exposure resulted in further denaturation and a progressive loss of expression of further epitopes. The IgG3 subclass specific McAb are specific to epitopes localized to the hinge region of IgG3. Thus, this exposed cysteine and proline rich region is shown to be particularly vulnerable to free radical attack; however, prolonged exposure results in structural alterations throughout the heavy chain.

Chromatography, High Pressure Liquid↗
PubMed1987

The importance of phase measurement in electrical impedance tomography.

A method is described for reconstructing images of electrical conductivity and relative permittivity in electrical impedance tomography (applied potential tomography). The method relies on measurement of both the amplitude and the phase of the surface electric potential profile. The principle is demonstrated using a computer model to simulate measurements. The reconstructed images, referenced to homogeneous saline, agree qualitatively with the values of conductivity and permittivity used in the computer model. In addition, by displaying the imaginary part of the logarithm of the complex electrical conductivity, certain tissues, e.g. liver and kidney, are emphasised on the image. When the same parameter is displayed for simulated dual-frequency measurements, in which 150 kHz values are referenced against 100 kHz, liver and pancreas are emphasised. These results suggest the possibility of distinguishing between different types of soft tissue more effectively than if only signal amplitudes are measured. The phase changes in the simulated signals, on which the formation of such images depends, have a mean value of 13.3 degrees for the saline-referenced simulation but only 1.6 degrees for the dual-frequency simulation requiring accurate measurement in practice.

Computer Simulation↗
PubMed1987

A dual-frequency applied potential tomography technique: computer simulations.

Applied potential tomography has been discussed in relation to both static and dynamic imaging. We have investigated the feasibility of obtaining static images by measuring profiles at two frequencies of drive current to exploit the differing gradients of electrical conductivity with frequency for different tissues. This method has the advantages that no profile for the homogeneous medium is then needed, and the electrodes can be coupled directly to the skin. To demonstrate the principle, computer simulations have been carried out using published electrical parameters for mammalian tissues at frequencies of 100 and 150 kHz. The distribution of complex electric potentials was calculated by the successive over-relaxation method in two dimensions for an abdominal cross-section with 16 electrodes equally spaced around the surface. From the computed electrode potentials, images were reconstructed using a back-projection method (neglecting phase information). Liver and kidney appeared most distinctly on the image because of their comparatively large conductivity gradients. The perturbations in the electrode potential differences between the two frequencies had a mean value of 5%, requiring accurate measurement in a practical system, compared with 150% when the 100 kHz values were related to a simulation of homogeneous saline equal in conductivity to muscle. The perturbations could be increased by widening the separation of the frequencies. Static imaging using a dual-frequency technique appears to be feasible, but a more detailed consideration of the electrical properties of tissues is needed to determine the optimum choice of frequencies.

Computer Simulation↗
PubMed1987

Applied potential tomography for non-invasive temperature mapping in hyperthermia.

In the field of hyperthermia for cancer treatment, much effort is being put into the development of non-invasive temperature monitoring so that the trauma of implanting thermocouple or thermistor probes in the patient can be avoided. Preliminary studies investigating the use of applied potential tomography (APT) for this purpose have been reported. APT has the advantages over other tomographic methods that the instrumentation is inexpensive, transportable, and could easily be accommodated in a hyperthermia treatment environment. Moreover, the temperature coefficient of electrical conductivity is large (2% degrees C-1) compared, for example, with the corresponding quantity in CT, the x-ray attenuation coefficient, which changes by only 0.04% degrees C-1. In our experimental system, 16 electrodes were fixed around a cylindrical block of agar simulating a human thigh. The system was driven with 5 mA at 50 kHz. The agar was heated using the 13.56 MHz capacitive system currently in clinical use in this hospital. By relating data sets recorded at different times during heating to a set recorded before heating, images of the temperature change in the agar with time were computed and are presented. The experiment was then repeated in vivo on the thigh of a volunteer.

Agar↗
PubMed1986

Specific absorption rate and tissue temperature in local hyperthermia.

Specific absorption rate (SAR) and tissue temperature were measured for a total of 83 treatments in 33 patients who received local hyperthermia treatment for cancer. The patients were grouped into three categories according to tumor size. Hyperthermia was induced by 13.56 MHz electromagnetic energy applied using capacitive coupling. A method is described for evaluating SAR from the tissue temperature traces at any time in the treatment when a step change is made in applied power. The method is possible only if the temperature traces are free from interference and the total power delivered to the patient is monitored. Mean values of SAR ranged from 4.6 to 89 W kg-1 depending on the treatment site. Satisfactory heating was achieved for superficial tumors, with temperatures greater than 42 degrees C being recorded in 69% of treatments. For axillary nodes only 4% of treatments exceeded 42 degrees C. For cervix tumors an idealized tumor model was used to estimate tumor temperature from the temperature and SAR measured in the adjacent normal tissue. From the model it appears necessary either to raise the systemic temperature to 40 degrees C or to increase the SAR by at least a factor of 4 to obtain a temperature of 42 degrees C in a typical tumor. Measurements of SAR and temperature are essential for feedback control of computer models which, in principle, could provide a complete distribution of temperature during a hyperthermia treatment. Furthermore, measured SAR provides a direct comparison of the power deposition from different treatment machines in a clinical environment. The data presented form a basis for comparison with the clinical use of other heating systems.

Absorption↗
PubMed1985

Solitary rib lesions.

Solitary rib lesions are not uncommon. They are frequently asymptomatic and usually benign. Virtually all of the malignant tumors are associated with an obvious soft tissue mass which merits further investigation. However, should any of the benign appearing lesions either become symptomatic, change appearance or start growing then they too should be biopsied.

Adolescent↗
PubMed1984

The inhibition by etomidate of the 11 beta-hydroxylation of cortisol.

The effect of a sleep-dose of etomidate on the plasma concentrations of cortisol, 11-deoxycortisol and 17 alpha OH-progesterone was investigated in eight patients; two other patients received thiopentone. Blood samples were collected at 0, 15 and 30 min after etomidate or thiopentone when an injection of tetracosactrin was given and a final sample was collected at 60 min. The plasma cortisol response to tetracosactrin was depressed below normal in patients given etomidate, and the 11-deoxycortisol response was very high, ranging from 36.4 to 184.7 nmol/l. The two patients that received thiopentone had a normal response to all steroids. The identity of the plasma 11-deoxycortisol in two patients was confirmed by high-performance liquid chromatographic separation and quantification by both spectrophotometric and radioimmunoassay measurements. These results suggest that a single dose of etomidate inhibits 11 beta-hydroxylation of cortisol.

17-Hydroxycorticosteroids↗