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Biomedical subjects

A C Baker

Publications and source records attributed to A C Baker.

At least 19 recordsLinked to original sources

A possible approach to the treatment of polycystic ovarian syndrome using focused ultrasound.

A new method of treatment for infertility caused by polycystic ovarian syndrome (PCOS) using thermal lesion formation by high intensity ultrasound has been suggested. Current options for PCOS therapy and the achievements of focused ultrasound surgery technique are reviewed and discussed. A prototype of a low-cost commercial device for the treatment of PCOS has been designed and tested to prove the feasibility of the method. A transducer with curvature radius of 36 mm and aperture diameter of 36 mm, operating at 0.97 MHz, was designed and tested. It provided a maximum acoustic power output of 180 W. Well-defined tissue damage was obtained within 10 s in a pig's liver in vitro at 3 cm depth within an area 5 mm in diameter and 12 mm in length without damaging the surrounding tissue. Evaluation of the size of the lesions produced at different frequencies, sonication times and output power has been carried out by visual inspection of the colour changes in cut tissue sections. Results demonstrate that a surgical tool based on the method suggested should be feasible and warrants further investigation.

Acoustics↗

A numerical study of the effect of drive level on the intensity loss from an ultrasonic beam.

Knowledge of the spatial distribution of intensity loss from an ultrasonic beam is vital to bioeffect predictions such as heating and streaming. A method for calculating the distribution of intensity loss over a finite-amplitude ultrasonic beam is described. The technique demonstrates that the location of peak intensity loss varies considerably with drive level for a plane circular source, as does the overall distribution of intensity loss across the beam. The effects are shown to be less pronounced but still significant for a focused source.

Acoustics↗

Nonlinear propagation applied to the improvement of resolution in diagnostic medical ultrasound.

Medical B-mode scanners operating under conditions typically encountered during clinical work produce ultrasonic wave fields that undergo nonlinear distortion. In general, the resulting harmonic beams are narrower and have lower sidelobe levels than the fundamental beam, making them ideal for imaging purposes. This work demonstrates the feasibility of nonlinear harmonic imaging in medical scanners using a simple broadband imaging arrangement in water. The ultrasonic system comprises a 2.25-MHz circular transducer with a diameter of 38 mm, a membrane hydrophone, also with a diameter of 38 mm, and a polymer lens with a focal length of 262 mm. These components are arranged coaxially giving an imaging geometry similar to that used in many commercial B-scanners, but with a receiver bandwidth sufficient to record the first four harmonics. A series of continuous wave and pulse-echo measurements are performed on a wire phantom to give 1-D transverse pressure profiles and 2-D B-mode images, respectively. The reflected beamwidths wn decrease as wn/W1 = 1/n0.78, where n is the harmonic number, and the reflected sidelobe levels fall off quickly with increasing n. In imaging terms, these effects correspond to a large improvement in lateral resolution and signal-to-clutter ratio for the higher harmonics.

Equipment Design↗

Choosing a powerful lithotriptor.

Clinicians have no yardstick to help them choose the most efficient lithotriptor. Their leading priority is a system allowing complete disintegration of the stone with the minimum number of shocks and a low re-treatment rate. One of the prerequisites of this system is a powerful shock wave generator. "Power" is as yet ill defined in lithotripsy. Therefore clinicians' choice depends upon other factors. Acoustic output measurements were recorded on 3 commercial lithotriptors representing the 3 main shock wave generating systems. These were the Dornier MPL 9000 (standard and X-155 electrodes), the Siemens (Lithostar, Lithostar Plus and System C) and the Wolf Piezolith 2300. The shock wave measurements were correlated to the capability of the lithotriptors to disintegrate standard stone models in vitro. Two factors were identified. The pulse intensity integral in the focus and the size of the focal zone proved to be the most important factors to assess and compare the efficacy or "power" of different lithotriptors. Together they can help clinicians to identify and choose the most efficient shock wave generating systems.

Acoustics↗

Presence of low amounts of "neuronal" antigens in cultured human skin fibroblasts.

To explore the utility of cultured skin fibroblasts in investigating diseases of the nervous system in which constituents characteristic of neurons are involved, sensitive immunochemical methods were used to test for the presence in skin fibroblasts of low amounts of proteins normally used as neuronal markers. The presence of each of the neurofilament triplet proteins and of neuron-specific enolase was demonstrated by immunoblotting and by immunocytochemistry, and of an 86-kDa synapsin-like material by immunoblotting. These observations agree with previous suggestions that readily available cultured fibroblasts may be useful in investigations of disorders in which molecules are involved which are typically associated with neurons in vivo, such as Alzheimer's disease.

Animals↗

Expression of 'Alzheimer antigens' in cultured skin fibroblasts.

When cultured skin fibroblasts were exposed to culture conditions designed to favor the expression of neuronal antigens, cells from each of 19 patients with Alzheimer's disease reacted immunocytochemically with antibodies to paired helical filaments, Alz-50, or both compared with only a small fraction of cells from 19 identically treated age-matched control cultures. Immunoblots confirmed the presence of soluble material reacting with Alz-50 antibody in the Alzheimer fibroblasts. Ultrastructurally, fascicles of 10-nm filaments were seen that occasionally twisted around each other, but no structures were seen that were identical to paired helical filaments. Thus, cultured skin fibroblasts from patients with Alzheimer's disease developed greater immunocytochemical reactivity with antibodies raised to paired helical filaments than did fibroblasts from control subjects, when cultured under the specified conditions.

Aged↗

Prediction of non-linear propagation in water due to diagnostic medical ultrasound equipment.

There is a well established requirement for making output measurements on medical ultrasound equipment, in particular for safety and calibration purposes. In addition there is a need for non-linear propagation models to allow predictions to be made for in vivo pressure fields of systems ranging from lithotripters to diagnostic imaging sets. In the past it has been shown that good agreement can be found between experiment and theory for transducers that behave as perfect pistons but little work has been published on comparisons for 'real' medical ultrasound systems. This paper compares experiment with theory for a medical ultrasound system operating in water. Pressure field measurements are presented for a Philips 3.5 MHz, 13 mm diameter, 'long internal focus' (LIF) transducer. The measurements were made using a membrane hydrophone in water. Initially the transducer was driven continuously with a function generator at low amplitude so that the effective aperture radius and focal length could be determined. The transducer was then driven by a Philips 'sono-Diagnost B' imaging system which produced a short finite amplitude pulse. The results are compared with a finite difference model based on the parabolic approximation to the non-linear wave equation. Reasonable agreement (typically 10-15%) is shown for spectral magnitudes although some difficulty was encountered in accurately characterizing the transducer in terms of its geometry and drive waveform.

Medical Laboratory Science↗

Measurement of lithotripsy pulses through biological media.

Lithotripsy is now the method of choice for the treatment of renal calculi. The mechanism of destruction is not clearly understood, and detailed knowledge of the shock-wave characteristics at the calculus would aid understanding of the phenomenon. Current methods of measuring the pressure pulse by observing it through a water path are not well characterized, and the results may not represent the actual pressure fluctuations produced in vivo. In order to determine the actual pressure pulse experienced at the site of the calculus, measurements have been made through a variety of biological media. The results show that there are considerable differences between measurements taken through a water path and through biological media. This paper describes the pressure fluctuations in the time domain. The implications of the results for lithotripsy are discussed.

Animals↗

Intrauterine pressures in labours induced by amniotomy and oxytocin or vaginal prostaglandin gel compared with spontaneous labour.

Uterine activity during the first stage of labour was measured by an intrauterine transducer in 22 women induced with intravaginal PGE2 gel, in 37 induced by amniotomy and intravenous oxytocin, and in nine women in spontaneous labour. The nulliparous women in the PGE2 gel group had a significantly longer pre-established phase of labour and a significantly shorter established phase than nulliparae induced by amniotomy and oxytocin. The mean levels of total uterine activity (kPas) during labour and the uterine activity integrals (kPas/15 min) were significantly lower in nulliparae induced with PGE2 gel than in those induced by amniotomy and oxytocin. These findings suggest that PGE2 gel has a positive, beneficial effect on cervical compliance during the pre-established phase, resulting in less myometrial effort during established labour. These effects were less evident in parous women, probably because of an innate lower cervical resistance due to their previous labours. Uterine activity patterns during the 4 h leading to full cervical dilatation in nulliparae were similar in labours induced with PGE2 gel and spontaneous labours, whereas labours induced by amniotomy and oxytocin exhibited a significantly different pattern. Expulsion of the fetus during normal labour is a function of both uterine contractions and a decrease in the cervical resistance and the data suggest that induction by PGE2 gel more closely mimics spontaneous labour, whereas the predominant effect of oxytocin is to stimulate myometrial activity.

Amnion↗

Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation.

Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects of carbonyl cyanide m-chlorophenylhydrazone, a hydrazone known to uncouple mitochondrial oxidative phosphorylation, were tested on the development of immunoreactivity with antibodies to "Alzheimer antigens" in cultured fibroblasts from cognitively intact subjects. The fibroblasts were exposed for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal differentiation in fetal brain cultures. The addition of a 10-microns concentration of carbonyl cyanide m-chlorophenylhydrazone to the DMd culture medium increased by more than 10-fold the proportion of cells reacting immunocytochemically with antibodies to paired helical filaments and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal antibody. These observations suggest that the oxidative abnormalities previously described in tissues from patients with Alzheimer's disease may contribute to the accumulation of abnormal cytoskeletal materials in this disorder.

Aged↗

Cultured cells as a screen for novel treatments of Alzheimer's disease.

Two easily measured abnormal properties of fibroblasts from patients with Alzheimer's disease have been utilized to develop an in vitro test system for screening novel therapeutic agents for Alzheimer's disease. The abnormal properties selected for study were increased isoproterenol-stimulated cyclic adenosine monophosphate production and decreased pH (measured by the weak-acid distribution method). L-Carnitine was tested as a potential therapeutic agent, since it has been used to treat a variety of experimental metabolic encephalopathies. The addition of L-carnitine normalized both of these properties in the Alzheimer cells. Tissue culture may aid as a preliminary screen for identifying novel approaches to the treatment of Alzheimer's disease.

Alzheimer Disease↗

Comparison of two theoretical models for predicting non-linear propagation in medical ultrasound fields.

Non-linear propagation models are required to predict the fields from medical ultrasonic equipment, particularly diagnostic devices and lithotripters. This need arises because of the requirement to know the safety and effectiveness of these instruments. Several theoretical models have been developed to take account of non-linear propagation as well as diffraction, focusing and attenuation, but little work has been done to validate them. This paper compares two theoretical models with each other and with measurements in the field of a 3.5 MHz focused transducer. One model uses an approximation based on modelling the beam profile with a Gaussian function, whereas the other utilises a full three-dimensional finite difference method, using a uniform transducer excitation function. Comparisons are made in the time and frequency domain at the focus for four different source levels and in general the results agree to within about 10%. However, an important conclusion is that the finite amplitude field of a real transducer may differ significantly from that of an ideal piston source, particularly for the weakly focused beams used in diagnostic ultrasound.

Acoustics↗

Deficiency of pyruvate dehydrogenase complex (PDHC) in Leigh's disease fibroblasts: an abnormality in lipoamide dehydrogenase affecting PDHC activation.

Several groups have reported abnormalities of the pyruvate dehydrogenase complex (PDHC) in cultured cells or other tissues from patients with Leigh's disease (subacute necrotizing encephalomyelopathy). We therefore undertook studies to elucidate the molecular basis of the defect of PDHC in cultured skin fibroblasts from two patients with Leigh's disease. The deficit of total PDHC activity in homogenates of Leigh's disease fibroblasts could be restored by adding exogenous lipoamide dehydrogenase (LAD, E3), the third component of PDHC. The LAD in these Leigh's disease cells had a markedly reduced ability (less than 20% of normal LAD) to reconstitute with other PDHC components to form active enzyme complex. A polyclonal antibody to pig heart LAD inhibited LAD activity in control cells more efficiently than in Leigh's disease cells. Other mitochondrial enzyme activities and growth of these two Leigh's disease cells appeared normal. These results suggest that the deficiency of PDHC in these two patients with Leigh's disease was due to a structural abnormality of the LAD component of PDHC.

Brain Diseases, Metabolic↗

A comparison of oral prostaglandin E2 tablets with intravenous oxytocin for stimulation of labor after premature rupture of membranes at term.

Sixty-nine patients (48 primigravidae and 21 multigravidae) with 12 hours of spontaneous premature rupture of membranes (PROM) after 36 weeks gestation were randomly allocated to receive either prostaglandin E2 (PGE2) oral tablets or intravenous oxytocin to stimulate labor. The two treatments were compared regarding stimulation - delivery interval (SDI), analgesic requirements, maternal and fetal side effects, and patient acceptability. The mean SDI was shorter in the oxytocin group, but without statistical significance. Analgesic requirements and fetal side effects were similar in the two groups, but there was a higher incidence of nausea and vomiting in those patients receiving the maximum dose (1 mg hourly) of PGE2. On subjective assessment, clinicians considered oxytocin to be more effective (p less than 0.05), while midwives felt both regimes to be equally helpful. PGE2 oral tablets were significantly (p less than 0.05) more acceptable to the patients, who preferred the convenience of oral dosing, the absence of an i.v. line and the increased mobility. It is concluded that PGE2 tablets are a safe and effective method of stimulating labor following PROM, and highly acceptable to parturients. In those women in whom labor has not been established within 8 h of initiating PGE2 therapy, or in whom gastric side effects are troublesome, intravenous oxytocin should be substituted.

Adolescent↗

A double-blind comparative study of alprazolam and dothiepin hydrochloride in the treatment of anxiety associated with depression.

One hundred patients with mixed symptoms of anxiety and depression were enrolled into a prospective, multi-centre, randomized, double-blind study comparing the response to, and the side-effects of, alprazolam and dothiepin hydrochloride over 4 weeks of treatment. Mean daily doses were 2.33 mg alprazolam and 115 mg dothiepin. Data on 96 patients were evaluated for tolerance, and data for 85 patients were analyzed for therapeutic response. In each case, the groups were similar in numbers, mean ages and sex ratios. Both groups experienced satisfactory responses to therapy, with highly statistically significant changes (p less than 0.001) in the means of all efficacy measures within each group. No statistical difference was demonstrated in favour of either treatment group. Both dothiepin and alprazolam exhibited a similar profile of mild minor side-effects, but more patients suffered moderate to severe reactions to dothiepin, leading to a greater drop-out rate in the dothiepin-treated group. It is concluded that, as both treatments produced equally satisfactory responses in this study, alprazolam should be considered for the treatment of anxiety associated with depression in patients for whom tricyclic antidepressant drugs are either contra-indicated or poorly tolerated.

Adolescent↗