Biomedical subjects
Publications and source records attributed to J Williamson.
High energy photon beams traversing large iatrogenic air cavities can lead to surface underdosage and overdosage because of high exit dose. A water bag bolus in such external cavities is a remarkably simple and reproducible means of producing dosage homogeneity.
Daunorubicin is a highly potent trypanocide in vitro but lacks significant in vivo activity. Distribution in the drug in the blood components and in trypanosomes from mice infected with Trypanosoma rhodesiense was therefore examined. Drug is accumulated in the trypanosomes in a similar manner to, but to a greater extent than, its accumulation in platelets; it is, however, taken up by erythrocytes to a much smaller extent, Drug concentrations in trypanosomes, platelets and erythrocytes declined with its decline in plasma whereas in white blood cells the drug was retained at a constant level. Daunorubicin concentrations in plasma were several orders of magnitude higher than in vitro trypanocidal concentration. Fluorescence microscopy showed that although daunorubicin reaches the trypanosome nucleus, its concentration decreases rapidly so that adequate levels of drug may not be sustained in the bloodstream form of the organism for a sufficient length of time to give a trypanocidal effect in vivo.
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The possibilities of trypanocidal drug synergy have been examined in vitro and in vivo using a monomorphic laboratory strain of Trypanosoma rhodesiense. Twenty-seven different drug pair combinations were chosen from among 12 representative trypanocides on the basis of surmized or reported synergy, evidence of collateral sensitivity in resistant strains, and known differences in modes of action or in field use. In vitro synergy test were made with a transfer plate technique which allows direct isobol determination by microtest tray superimposition. All pairs showing synergy in vitro were tested further in mice. Statistically significant synergy was shown only by suramin and tryparsamide, suramin and Puromycin, and suramin and Berenil. Although six other pairs, of which three contained suramin, showed higher than addictive cure rates, these rates fell short of statistical significance.
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The practice of preadmission home visiting of patients referred to geriatric medicine units has in recent years been criticised as being unnecessary on the grounds that if there is no waiting list there is no need for allocation of priority for admission; as being wasteful of doctors' time; as being resented by general practitioners; and as failing to provide adequate clinical information. The geriatric medicine department at the City Hospital with no waiting list for patients referred by general practitioners has retained home visits for most referrals because of the advantages in terms of acceptability to general practitioners (98-100%); the quantity and quality of information obtained; the usefulness of this information in deciding appropriate management and in planning discharge from hospital; and the provision of a unique teaching opportunity, which is highly valued by students and teachers alike.
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The architecture and distribution of surface mucins were studied qualitatively and quantitatively by transmission electron microscopy in ruthenium red stained biopsies of the human conjunctiva. Six control specimens were compared with three from early keratoconjunctivitis sicca (KCS) and with three specimens from severe KCS cases. The area of the ruthenium red/OsO4/mucin reaction product on the conjunctival epithelial surface was measured by image analysis and the values were expressed in micron2 per micron length of epithelium. The total area of surface mucins was differentiated from the narrow zone of mucins in close contact with the microplicae. The value for total mucins in two cases of early KCS was higher (0.4 micron2/micron) than the control range (0.1-0.3 micron2/micron) due to the presence of large clumps of mucins on the surface. The values for microplical mucins in early and severe KCS were within the control range, but were an overestimate owing to the presence of abnormal structures, e.g. vesicles, and abnormal clumps on the surface. This morphometric technique has limitations, but with appropriate material it might be a useful tool for the identification of conjunctival surface mucins.
A compact inexpensive semi-automated continuous cultivation system for Plasmodium falciparum is described. The system is simple to operate and allows cultures to proceed unattended for several days. A particularly useful feature is a portable cultivation module that is freely transferable from the incubator to a tissue culture cabinet for manual operations such as sampling or addition of red cells. Each cultivation module holds plastic flasks which can give a combined culture surface area of up to 500 cm2. Parasitaemias of 12% are attained routinely at red cell densities of 1 to 7 x 10(8) per ml, if the medium is changed daily.
Phosphatase activity in Trypanosoma rhodesiense has been examined histochemically by light and electron microscopy and by enzymatic assay in homogenate fractions. Using a method with lead as capture ion, acid phosphatase was found in lysosome-like vesicles and in the flagellar pocket. No alkaline adenosine triphosphatase (ATPase) was detectable by this method. Direct assay of p-nitrophenylphosphatase activity in homogenate fractions showed that acid phosphatase activity was strongly membrane-bound, but that activity at pH 9 was minimal in both soluble and particulate fractions. "Endogenous" ATPase activity was localized specifically and reproducibly in the mitochondrial membranes and under the plasma membrane of he flagellum. This nonenzymic reaction product could not be eradicated by glycerol extraction or glucose depletion. Unlike the membrane staining, which was manifest only after lead treatment, heat-resistant electron-dense material was found in the matrix of lysosomal vesicles in trypanosomes fixed in glutaraldehyde only and not subjected to further treatment with heavy metal reagents. X-ray emission analysis showed the presence of calcium and phosphorus, indicating that the matrix might have a phosphate storage function.
A continuing medical education course was developed to improve the care of patients with chronic bronchitis and emphysema (COPD); 44 primary care physicians completed the course. The physicians were randomly assigned to experimental and control groups, with 3 of the 4 experimental groups assisting in the selection of topics for the programs and/or receiving feedback on tests given during the course. The course's impact was assessed using written tests to measure knowledge and simulated patient visits to observe physician performance. Experimental groups retained significantly greater amounts of information 9 months after completing the program and used more program material during patient visits than did the control group (p < 0.05). The test scores and patient visits of the 3 experimental groups involved in determining the audiovisual topics and/or receiving feedback were not significantly different from one another nor from the fourth experimental group.
Clobetasone butyrate eye drops comprise a new steroid preparation which has been investigated in two comparable, double-blind, multicentre clinical trials in patients with ocular inflammation. One study compared clobetasone butyrate with betamethasone phosphate eye drops (205 patients) and the other study compared corresponding preparations containing neomycin (169 patients). There was no difference between the responses to clobetasone butyrate and betamethasone. An excellent or good response was obtained in 73 per cent of patients treated with clobetasone butyrate, 75 per cent with betamethasone, 69 per cent with clobetasone butyrate formulated with neomycin, and 76 per cent with betamethasone formulated with neomycin. Patients who were known to react with a rise of intraocular pressure (IOP) to steroids were treated with clobetasone butyrate eye drops in one eye and either prednisolone eye drops (6 patients) or hydrocortisone eye drops (4 patients) in the other eye. The doses were continued for 6 weeks, or less if the IOP rose more than 10 mm Hg in one eye. All patients experienced a greater intraocular pressure rise in the eye treated with prednisolone or hydrocortisone. The mean changes in IOP were 9 mm Hg for prednisolone compared to 2 mm Hg for clobetasone butyrate (P less than 0.05 Wilcoxon signed ranks test) and 16 mm Hg for hydrocortisone compared to 2 mm Hg for clobetasone butyrate.
This paper reviews briefly the advantages of in vitro methods for predictive drug sensitivity testing and then summarizes the present situation. Clear evidence of variation in chemosensitivity at the cellular level is now available, the value of the test for predicting in vivo resistance is confirmed, and some evidence that treatment of advanced carcinoma of the ovary on the basis of a predictive test prolongs survival is presented. Ways in which the laboratory test might be improved are suggested and outstanding clinical problems, in particular the need for a very large number of patients in any prospective trial designed to detect a small improvement in treatment, are discussed.
Laboratory tests indicate that methylated spirits, widely espoused as a first-aid treatment for jellyfish stings, causes massive discharge of nematocysts in living tentacles of the box-jellyfish, Chironex fleckeri. This action, together with demonstrated hazards of flammability and intoxication, casts doubt on this substance as a treatment for Chironex stings. In an attempt to find a substitute which will be effective in inactivating unfired nematocysts in the tentacles adhering to sting victims, a number of substances were tested in the laboratory. Weak solutions of acetic acid, as well as commerical vinegar, were found to inactivate the penetrating nematocysts of Chironex rapidly and completely. Most other substances tested proved less effective, and some actually stimulated the firing of nematocysts.
Of 1998 patients consecutively admitted to Geriatric Medicine Departments in England, Wales and Scotland in 1975--6, 81.3% were receiving prescribed drugs at time of admission. Adverse reactions were noted in 248 patients, representing 15.3% of prescribed drug takers. In 209 of these patients, it was thought that an adverse reaction had contributed to the need for admission to hospital. Full recovery from adverse reactions and sequelae occurred in 68% of those with such reactions. Hypotensive drugs, antiparkinsonian drugs and psychotropics carried the greatest risk of adverse reactions although the largest single number of adverse reactions (60) were due to diuretics which were by far the most commonly prescribed drugs (37.4% of sample).
A pilot study for a scheme of augmented home care for elderly patients with acute or sub-acute illnesses is described. General practitioner care was supplemented by the services of a geriatrician. Home Help and District Nursing Services were involved where appropriate. Functional recovery was assessed using a new index based on the individual patient's pre-morbid function. Of 37 patients treated at home, six required admission to hospital and three died. The remainder made satisfactory functional recovery. Preliminary evidence suggests that in patients with comparable illness, recovery of function in terms of the Activities of Daily Living is more rapid at home than in hospital. This augmented home-care scheme proved practicable and acceptable to patients and participants and suggests that further controlled studies should be carried out.
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