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Biomedical subjects

J R Casley-Smith

Publications and source records attributed to J R Casley-Smith.

At least 19 recordsLinked to original sources
PubMed1992

Complex physical therapy for the lymphoedematous arm.

Complex physical therapy was used in 78 patients with post-mastectomy lymphoedema (17 with grade 1 and 61 with grade 2). This involves: skin hygiene, a special lymphatic massage, compression bandaging and garments, and special exercises which supplement the massage. Two courses of treatment were given, lasting four weeks each, with a year between them. There was a highly significant decrease in the oedema in both grades, with more than 50% removed in the first course of treatment and 50% of the remainder in the second. There was even a small, but very significant decrease during the interval between the two courses.

Adult↗
PubMed1992

Modern treatment of lymphoedema. I. Complex physical therapy: the first 200 Australian limbs.

Complex Physical Therapy (CPT) is discussed and its principles outlined. CPT involves: 1. skin care, 2. a special lymphatic massage, 3. compression bandaging and (later) garments, 4. special exercises which supplement the massage. CPT was used on 78 patients with postmastectomy lymphoedema (17 with Grade 1 and 61 with Grade 2). There were significant differences between the Grades. In the first four-week course the mean Grade 1 was reduced from 121% of normal to 107% (the mean change in the oedema was 103% of its initial value), and Grade 2 from 153% to 123% (with a mean change in oedema of 60%). All these were very highly significant. Over the next year there was a small, but very significant, decrease in the percentage of oedema. A further four-week course resulted in significant, and similar, reductions in the residual oedema. CPT was used to treat 128 lymphoedematous legs; 22 were Grade 1 lymphoedema, 84 were Grade 2 and 19 were elephantitic (Grade 3). After the first course of CPT the mean losses were: 1.1, 1.3 and 3.7 litres, respectively (all very significant). Over the next 11 months there were significant further reductions for all legs and in the amount of oedema of the unilateral legs. Some patients had a second course of CPT with similar reductions in the remaining oedema to that after the first course.

Arm↗
PubMed1992

Modern treatment of lymphoedema. II. The benzopyrones.

The benzo-pyrones reduce all high-protein oedemas, including lymphoedema and elephantiasis, by increasing the numbers of macrophages and their normal proteolysis. Thus they remove the excess protein, and thereby the oedema which is caused by it. They also remove the stimulus it provides for chronic inflammation and fibrosis, and its action as a culture medium for bacteria. Coumarin (5,6 benzo-[alpha]-pyrone, 56 BaP) and oxerutins (HR, O(beta-hydroxy-ethyl)-rutosides) have been used in many clinical trials on a variety of high-protein oedemas. Four such trials are summarised here: on lymphoedema and elephantiasis (from many causes in Australia, and filaritic in India and China). The drugs reduced these much more slowly than adequate physical therapy, but they did reduce them. About half the excess volume was removed over six months in the Australian trials. In India and China similar rates were achieved with lymphoedema, but elephantiasis reduced at a slower rate. The benzo-pyrones convert a slowly worsening condition into a slowly improving one. No compression garments are necessary. In addition, the drugs considerably reduce the number of attacks of secondary acute infection, reduce the deformities of elephantiasis and considerably improve the patients' comfort and mobility. They may be taken orally, or applied topically, have very low toxicities and only few, minor side-effects. They are useful in many other forms of high-protein oedema, and improve the results of physical therapy for lymphoedema.

Administration, Cutaneous↗
PubMed1990

The effects of O-(beta-hydroxy-ethyl)-rutosides (HR) on acute lymphoedema in rats' thighs, with and without macrophages.

The effect of O-(beta-hydroxy-ethyl)-rutosides (HR), injected subcutaneously, was investigated on experimental acute lymphoedema in rat thighs. The oedema was reduced from a 30% increase over the normal weight, to one of 13%. When the macrophages were destroyed by the intraperitoneal injection of silica (for eight days before the initiation of lymphoedema) the oedema of the thigh increased to 41% - thus showing the importance of these cells in limiting high-protein oedemas. When HR was given to animals treated with silica the oedema was no longer reduced (42%). Thus HR reduces a high-protein oedema substantially via the macrophages.

Animals↗
PubMed1989

The effects of 5,6 benzo-[a]-pyrone (coumarin) and DEC on filaritic lymphoedema and elephantiasis in India. Preliminary results.

A randomized double-blind, placebo-controlled, trial of 5,6 benzo-[alpha]-pyrone (coumarin, '56 BaP') and of diethylcarbamazine (DEC) is being performed on patients with filaritic lymphoedema and elephantiasis over two years, using matched groups. In 169 patients there were significant (1% level) reductions in the amounts of oedema for the patients taking 56 BaP. The excess limb volumes were reduced from 40 to 25% over two years. A similar, but less significant (5% level), improvement was found for the circumference measurements. The rate of reduction was increased when the initial amount of oedema was greater. This therapy, while much slower than many other methods of treatment, does convert a slowly worsening condition into a slowly improving one. There were no significant reductions in the amount of oedema following DEC treatment.

Analysis of Variance↗
PubMed1989

Drainage of the prelymphatics of the brain via the adventitia of the vertebral artery.

Carbon particles injected into the cortex of the cerebellum of the rat were found in the Virchow-Robin spaces of the adjacent capillaries, and in the adventitia of the cerebellar artery, basilar artery and vertebral artery--both inside and outside the skull. They were also found in some portions of the deeper cervical lymph nodes. However, while tracers injected into the cerebral hemispheres are drained via the tissue channels in the adventitia of the internal carotid arteries, tracers injected into the cerebellar hemispheres are drained via those of the vertebral arteries.

Animals↗
PubMed1989

The fine structure of the amphibian lymph heart.

The fine structure of an amphibian lymph heart is described. There was an overlapping, flattened endothelial lining on the inner aspect of the tunica intima. This was usually thin with irregular processes on both luminal and abluminal surfaces, especially on the afferent ostium. Most of the intercellular junctions had a number of adhesion devices and were often convoluted. Very few open junctions were seen. The basement membrane was usually absent, but on occasion was prominent. The abluminal cytoplasmic projections of the endothelial lining often bordered on dense elastic and collagenous fibers. The surrounding media was thick and was mainly composed of smooth muscle cells and interstitial tissue with occasional fibroblasts.

Animals↗
PubMed1989

The fine structure of the amphibian lymph sac.

The fine structure of lymph sacs in the amphibian was observed by transmission electron microscopy. The wall was lined by endothelial cells which were similar to those of the endothelium of lymph capillaries in mammals, but with many more abluminal projections and a much more prominent basement membrane--especially centrally, near the lymph hearts. There were four types of intercellular junctions: open, overlapping, end-to-end, and interdigitating or complex. Specialized complexes were seen in 50% of the junctions. The cytoplasm frequently projected from the lumen and abluminal surfaces. Many thin filaments anchored the abluminal endothelial wall to the surrounding connective tissue. There were numerous small vesicles in the cells and opening onto both surfaces.

Animals↗
PubMed1988

Expressing stereological results 'per cm3' is not enough.

Stereological results are usually expressed as volumes, areas, lengths, or numbers per cm3 of tissue. This has led to wildly incorrect conclusions about tissues when they have been distorted (and effectively 'diluted') by oedema. Similar problems occur whenever the reference parameters (volume, area, weight, etc.) differ between one group and another. In tissues which occur in layers (e.g., the subcutaneous tissue), the mean depth of the tissue superficial to the deep fascia may be used to multiply these estimates, thus giving results expressed per cm2 of deep fascia. Depth measurements incorrect by an angle of 25 degrees to the perpendicular cause only a 10 per cent error. Such results are independent of the effects of oedema. A similar technique can be used in organs, multiplying the estimates by the volume of the organ, and expressing the results per organ. This presentation can be extended by then dividing these by the animal's body weight and expressing the results per kg. This last is useful for localized disease processes but not for generalized ones, or normal growth.

Animals↗
PubMed1988

A double-blind, cross-over trial of O-(beta-hydroxyethyl)-rutosides (benzo-pyrones) in the treatment of lymphoedema of the arms and legs.

A randomised, double-blind, cross-over trial was performed on 26 patients with postmastectomy lymphoedema of the arm, and 14 with lymphoedema of the leg. For 6 months, patients took 0-(beta-hydroxyethyl)-rutosides (oxerutin; "Paroven", "Venoruton", Zyma) in doses of 3 g/day, or the placebos; then they took the reverse. Measurements (volume, circumferences, tonometry and skin temperature) were made monthly. The active drug reduced the volumes of the limbs (p less than 0.05 to 0.01) and their circumferences (p less than 0.05 to 0.001). It increased the softness of the limbs, as shown by the increases in the tonometry values (p less than 0.01 to 0.001). There was a lowering of the elevated skin temperatures (p less than 0.05 to 0.001). Patients reported increased comfort and freedom of movement, a lessening of their bursting pains, heaviness and tension (p less than 0.05 to 0.01), and an increased mobility of their limbs (p less than 0.0001). Most patients (70%) preferred the active drug (p less than 0.0001). An increase in general well-being was reported by 97% of patients when taking the active drug compared with 4% for placebo (p less than 0.0001).

Arm↗
PubMed1988

A double-blind trial of calcium dobesilate in chronic venous insufficiency.

Calcium dobesilate was studied in a double-blind trial in 30 normal subjects and in 30 patients with chronic venous insufficiency (CVI). There were no significant alterations in the normal subjects. In patients with CVI the active drug gave significant improvements (p less than 0.01) in the measured volume of the foot and lower limb, in clinical tenderness (p less than 0.05), and in most of the symptoms (including feelings of heaviness, swelling, tiredness, and aching in the lower extremities). Even though the chronic venous insufficiency had existed for an average of fifteen years, a relatively short course of the drug caused considerable, and significant, improvements in a number of signs and symptoms of the disease.

Adult↗
PubMed1988

The pathophysiology of lymphedema and the action of benzo-pyrones in reducing it.

The pathogenesis of lymphedema is briefly reviewed. Swelling secondary to lymphostasis shares the common deleterious effects of other edemas, especially those of chronic high protein edema, namely chronic inflammation with excess tissue fibrosis. Benzo-pyrones are the only known drugs which reduce the excess protein in the tissues with high protein edema including lymphedema. Once excess tissue protein is resorbed, edema subsides and the fibrosis slowly resolves by remodeling. Two of these benzo-pyrone drugs have been shown to reduce postmastectomy and primary lymphedema in randomized, double-blind, cross-over, placebo-controlled trials. One of these drugs (which is also inexpensive) has also been shown to reduce filaritic lymphedema and elephantiasis in a similar trial in India. The bigger the leg initially, the more rapid is the reduction. In this extreme condition about a 20% lessening of the excess volume occurs each year. The benzo-pyrones do not work rapidly, but they do convert a rapidly worsening condition into a slowly improving one. In addition, they have extremely low toxicity and are effective orally. They also seem to reduce the incidence of secondary acute inflammation.

Clinical Trials as Topic↗
PubMed1987

The phylogeny of the fine structure of blood vessels and lymphatics: similarities and differences.

As animals increased in size, various modifications had to come into being to carry nutrients and waste around the body. Different phyla solved the various problems differently; sometimes there was convergent evolution. In invertebrates the endothelial cells are often widely separated from each other; permeability is limited by the pericyte layer; the reverse occurs in vertebrates. In primitive chordates small peripheral vessels often consist only of the basement membrane, and even this may be partly missing; the more centrally one looks, the more the endothelial cells become continuous. Fenestrae appeared first in the agnatha, but only become common in the elasmobranchs. Increased size and activity necessitated still larger blood hydrostatic pressure and increased blood colloidal osmotic pressures to balance this. Since the permeability of the vessels could not be reduced, much more protein (and fluid) had to leak to the tissues. So the lymphatic system had to evolve. This is first seen in the torpedoes and fully evolved in the bony fishes. However, the small venous vessels of the elasmobranchs have openable inter-endothelial junctions and other structures very similar to those of the initial lymphatics. Apart from the absence of fenestrae in lymphatics, or when this system is injected with a tracer, it is not always possible to tell them apart with the electron microscope. There are, however, various differences between them which will help to differentiate them.

Animals↗
PubMed1986

Benzo-pyrones in the treatment of chronic schizophrenic diseases.

Sixteen chronic schizophrenic subjects were treated for 3 months each with either a benzo-pyrone (Paroven/Venoruton, Zyma) or a placebo in a randomized, double-blind crossover trial. They continued to take their previous drug therapies. Therapeutic effects were measured by the Brief Psychiatric Rating Scale (BPRS), by self-assessment, and by assessment by a relative. Eleven patients completed the trial in relation to BPRS assessment. When on the active substance, as compared with the placebo, they showed a mean improvement of 27% (significant at the 1% level). Ten patients completed the trial in relation to the self and relative's assessments. There were improvements of 16% and 13%, respectively (significant at the 5% levels). Half the patients showed improvements on all the tests. Their improvements were 49%, 31%, and 21%, respectively. There was evidence that the active substance began to have an effect within 2 weeks. No side effects were observed with the active substance.

Adult↗