1
507 Dr. Peter Davey leans towards an M.n.c.r. (PATH.) and then dismisses it as a vain hope. Since Sir Ernest Finch wrote 1 it has been generally agreed that diplomas are not badges of suitability for training as consultants. Despite public sugges- tions 2 and informal conversations, the Royal College of Physicians so far appears to have done nothing ; but perhaps Dr. Peter Davey’s hope of an M.B.c.r. (PATH.) is not, in the long run, as vain as it appears now : it is less unlikely than the alternatives. The adulation of Dr. Peter Davey’s last three paragraphs distresses me. Of course, if he is one of the ruling class in the world of pathology, it is understandable : there never was an oligarchy yet which did not believe its rule to be for the best in the best of all possible worlds. Dr. Peter Davey calls it aristarchy. The Oxford English Dictionary defines an aristarchy as a body of severe critics : I am not sure that it is an appro- priate title for my pathological professorial acquaintances. If aristarchy were intended to mean government by the elite -largely self-appointed and self-named-I can only cry A bas les aristos! A la lanterne ! ! " It would be needless to bedevil these exchanges with personalities. Perhaps some may seek to knock me off my self-allotted perch and I will crave your permission to sign myself HUMPTY-DTJMPTY. 1. Lancet, 1952, i, 1. 2. Jordan, A. Ibid, p. 156. 3. Laguesse, E. Arch. Biol., Paris, 1921, 31, 173. 4. Day, T. D. Lancet, 1947, ii, 945. 5. Day, T. D., Eaves, G. Biochim. biophys. Acta, 1953, 10, 203. 6. Day, T. D. J. Physiol. 1952, 117, 1. 7. Day, T. D. Ibid, 1949, 109, 380. LOCALISATION OF ACUTE INFLAMMATORY SWELLING SIR,-Acute inflammatory swelling in its early stages is manifestly due to local excess of a fluid exudate rather than to cellular aggregation. It is not obvious, however, why this fluid should not disperse into the surrounding tissue rather than localise as it usually does. The following observation suggests that one reason for this localisation may lie in the peculiar properties and arrangement of connective tissue. Experiments with mice showed that unrestricted subcuta- neous injection of water at pressures in the region of 10 cm. water always resulted in a localised bleb at the injection site. But when small quantities (2 c.mm. or so) were injected, using a fine glass needle loosely packed with minute glass spheres (ballotini), the water diffused away evenly and rapidly for a distance of 1-2 em. without any tendency to bleb formation. But even in these circumstances continued infusion did not increase the area of spread. Thus while small quantities of water disperse to some extent, larger quantities merely accumulate at the point of injection. It appears as though wetting of the tissue provides a barrier against the further passage of water. Previous work affords some explanation of this phenomenon. Connective tissue has been considered to have an essentially lamellar constitution.3-5 The lamellae offer considerable resistance to the passage of water across them,6 so that water may be expected to find its way between rather than through the layers. Further it has been shown that at hydrogen-ion and salt levels such as exist in living tissues, the substance of the lamellse is intensely hydrophilic. 7 Free water must therefore pass through interstices which are bounded by hydrophilic material. It is easy to see that such an arrange- ment might allow the rapid passage of small amounts of free water while blocking the passage of larger quantities completely. In-vitro studies have drawn attention to a dynamic equilibrium between chemical forces which promote the taking up of free water by connective tissue and mechanical forces which lead to its extrusion. It may be conjectured that ordinarily the equilibrium may allow the presence of a little free water, but injection experiments show that the addition of only a few cubic millimetres at pressures such as obtain in blood-capillaries is enough to bring the localising mechanism postulated into play. Since there is nothing in the composition of inflammatory exudates in general which is likely to lessen the affinity of connective tissue for water, it is probable that the same mechanism operates in the early stages of all acute inflammatory processes in which interstitial connective tissue is involved. T. D. DAY. Department of Experimental Pathology and Cancer Research, University of Leeds. SCLERODERMA TREATED BY VERATRUM ALKALOIDS SiR,-Assuming that in scleroderma the vascular changes are an important factor in the progress of the disability, and that the gradual diminution of blood- supply to the peripheral tissues is the cause of the muscular weakness particularly in the hands, I have treated three cases of generalised scleroderma with vera- trum alkaloids in the form of V eriloid.’ CASE 1.-A married woman, aged 54, gave a history of Raynaud’s disease since 1933. This had been getting worse, and she had trophic ulceration on the fingers of both hands in the winter months. In 1949 she had undergone bilateral cervical and lumbar sympathectomy, which improved the peripheral circulation especially in the legs. Despite the circulatory improvement she still had trophic ulcers on the fingers in cold weather and had become progressively less able to use her fingers for fine work such as sewing. It was realised that she had generalised scleroderma involving the face, bib area, and both arms and hands. In December, 1951, she was started on tab. veriloid 1 mg. t.d.s., which was increased gradually to 3 mg. t.d.s. She has continued this dose steadily ever since. Improvement started quite soon ; her fingers became more supple, and by 1953 she could sew and knit again. She has had no trophic ulcers during the past two years despite the hard winters. She can now grip quite strongly. The only other medicinal treatment which she has had is tab. phenobarb. gr. 1/2 at night, prescribed because she complained that her nerves were bad, she was not sleeping, and she felt sick in the mornings. CASE 2.-A married woman, aged 52, was seen in February, 1952, with generalised scleroderma involving the face, bib area, both arms and hands, and the legs. She had noticed stiffness and gradual loss of power in the hands for about two years, and increasing stiffness and tightness of the skin of the face for about a year. She was unable to dress herself, carry on her housework and cook, or look after her family. She was started on veriloid 1 mg. t.d.s., which was gradually increased to 3 mg. t.d.s. Within two months there was definite improvement of the condition of the skin and increasing power of movement in the hands and fingers. For some time now she has been able to do everything for herself, has done her cooking and housework, and has walked and got about normally. Since the early part of this year the dose of veriloid has been increased to 4 mg. t.d.s., and this has hastened the improvement, particularly in the hands. CASE 3.-A married woman, aged 45, who was seen on Dec. 8, 1955, three years ago had been operated on for repair of the pelvic floor. Since then her hands and feet had been intermittently purple and stiff. She had never had trouble with her circulation when she was younger. During the past six months she had had dysphagia ; her hands and arms had become puffy and swollen, and she had difficulty in holding things as she was unable to close her hands properly and grip. On examination the patient had typical generalised sclero- derma involving the face, neck, bib area, arms, and hands, combined with a Raynaud’s condition involving the arms and legs. Treatment was started with 1 mg. of veriloid three times a day. On Dec. 22 the dose was increased to 2 mg. three times a day. By Jan. 26 there was much improvement in swallow- ing, and dysphagia was noticed only in the evenings. There was also noticeable improvement in the appearance of the skin of the forearms and hands. By Feb. 23 the oedema of the hands had considerably diminished and the patient could grip normally despite the very cold weather. Her arms were quite warm down to the wrists ; although the hands were still bluish they were not unduly cold. The dose of veriloid was increased to 3 mg. three times a day. Of these three cases two have been treated with veriloid for four years. In both cases improvement has

LOCALISATION OF ACUTE INFLAMMATORY SWELLING

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Page 1: LOCALISATION OF ACUTE INFLAMMATORY SWELLING

507

Dr. Peter Davey leans towards an M.n.c.r. (PATH.) and thendismisses it as a vain hope. Since Sir Ernest Finch wrote 1 ithas been generally agreed that diplomas are not badges ofsuitability for training as consultants. Despite public sugges-tions 2 and informal conversations, the Royal College of

Physicians so far appears to have done nothing ; but perhapsDr. Peter Davey’s hope of an M.B.c.r. (PATH.) is not, in thelong run, as vain as it appears now : it is less unlikely than thealternatives.The adulation of Dr. Peter Davey’s last three paragraphs

distresses me. Of course, if he is one of the ruling class in theworld of pathology, it is understandable : there never was an

oligarchy yet which did not believe its rule to be for the best inthe best of all possible worlds. Dr. Peter Davey calls it

aristarchy. The Oxford English Dictionary defines an aristarchyas a body of severe critics : I am not sure that it is an appro-priate title for my pathological professorial acquaintances. If

aristarchy were intended to mean government by the elite-largely self-appointed and self-named-I can only cryA bas les aristos! A la lanterne ! ! "

It would be needless to bedevil these exchanges withpersonalities. Perhaps some may seek to knock me offmy self-allotted perch and I will crave your permission tosign myself

HUMPTY-DTJMPTY.

1. Lancet, 1952, i, 1.2. Jordan, A. Ibid, p. 156. 3. Laguesse, E. Arch. Biol., Paris, 1921, 31, 173.4. Day, T. D. Lancet, 1947, ii, 945.5. Day, T. D., Eaves, G. Biochim. biophys. Acta, 1953, 10, 203.6. Day, T. D. J. Physiol. 1952, 117, 1.7. Day, T. D. Ibid, 1949, 109, 380.

LOCALISATION OF ACUTE INFLAMMATORYSWELLING

SIR,-Acute inflammatory swelling in its early stagesis manifestly due to local excess of a fluid exudate ratherthan to cellular aggregation. It is not obvious, however,why this fluid should not disperse into the surroundingtissue rather than localise as it usually does. The followingobservation suggests that one reason for this localisationmay lie in the peculiar properties and arrangement ofconnective tissue.

Experiments with mice showed that unrestricted subcuta-neous injection of water at pressures in the region of 10 cm.water always resulted in a localised bleb at the injection site.But when small quantities (2 c.mm. or so) were injected,using a fine glass needle loosely packed with minute glassspheres (ballotini), the water diffused away evenly and rapidlyfor a distance of 1-2 em. without any tendency to blebformation. But even in these circumstances continuedinfusion did not increase the area of spread. Thus while smallquantities of water disperse to some extent, larger quantitiesmerely accumulate at the point of injection. It appears asthough wetting of the tissue provides a barrier against thefurther passage of water.Previous work affords some explanation of this phenomenon.

Connective tissue has been considered to have an essentiallylamellar constitution.3-5 The lamellae offer considerableresistance to the passage of water across them,6 so that watermay be expected to find its way between rather than throughthe layers. Further it has been shown that at hydrogen-ionand salt levels such as exist in living tissues, the substanceof the lamellse is intensely hydrophilic. 7 Free water musttherefore pass through interstices which are bounded byhydrophilic material. It is easy to see that such an arrange-ment might allow the rapid passage of small amounts offree water while blocking the passage of larger quantitiescompletely.

In-vitro studies have drawn attention to a dynamicequilibrium between chemical forces which promote thetaking up of free water by connective tissue andmechanical forces which lead to its extrusion. It maybe conjectured that ordinarily the equilibrium mayallow the presence of a little free water, but injectionexperiments show that the addition of only a few cubicmillimetres at pressures such as obtain in blood-capillariesis enough to bring the localising mechanism postulated

into play. Since there is nothing in the composition ofinflammatory exudates in general which is likely tolessen the affinity of connective tissue for water, it is

probable that the same mechanism operates in the earlystages of all acute inflammatory processes in whichinterstitial connective tissue is involved.

T. D. DAY.Department of Experimental Pathologyand Cancer Research, University of Leeds.

SCLERODERMA TREATED BY VERATRUMALKALOIDS

SiR,-Assuming that in scleroderma the vascular

changes are an important factor in the progress of thedisability, and that the gradual diminution of blood-

supply to the peripheral tissues is the cause of themuscular weakness particularly in the hands, I havetreated three cases of generalised scleroderma with vera-trum alkaloids in the form of V eriloid.’

CASE 1.-A married woman, aged 54, gave a history ofRaynaud’s disease since 1933. This had been getting worse,and she had trophic ulceration on the fingers of both hands inthe winter months. In 1949 she had undergone bilateralcervical and lumbar sympathectomy, which improved theperipheral circulation especially in the legs. Despite thecirculatory improvement she still had trophic ulcers on thefingers in cold weather and had become progressively less ableto use her fingers for fine work such as sewing. It was realisedthat she had generalised scleroderma involving the face, bibarea, and both arms and hands.

In December, 1951, she was started on tab. veriloid 1 mg.t.d.s., which was increased gradually to 3 mg. t.d.s. She hascontinued this dose steadily ever since. Improvement startedquite soon ; her fingers became more supple, and by 1953 shecould sew and knit again. She has had no trophic ulcersduring the past two years despite the hard winters. She cannow grip quite strongly. The only other medicinal treatmentwhich she has had is tab. phenobarb. gr. 1/2 at night, prescribedbecause she complained that her nerves were bad, she was notsleeping, and she felt sick in the mornings.CASE 2.-A married woman, aged 52, was seen in February,

1952, with generalised scleroderma involving the face, bibarea, both arms and hands, and the legs. She had noticedstiffness and gradual loss of power in the hands for about twoyears, and increasing stiffness and tightness of the skin of theface for about a year. She was unable to dress herself, carryon her housework and cook, or look after her family.

She was started on veriloid 1 mg. t.d.s., which was

gradually increased to 3 mg. t.d.s. Within two months therewas definite improvement of the condition of the skin andincreasing power of movement in the hands and fingers. Forsome time now she has been able to do everything for herself,has done her cooking and housework, and has walked and gotabout normally. Since the early part of this year the doseof veriloid has been increased to 4 mg. t.d.s., and this hashastened the improvement, particularly in the hands.

CASE 3.-A married woman, aged 45, who was seen onDec. 8, 1955, three years ago had been operated on for repair ofthe pelvic floor. Since then her hands and feet had been

intermittently purple and stiff. She had never had troublewith her circulation when she was younger. During the pastsix months she had had dysphagia ; her hands and arms hadbecome puffy and swollen, and she had difficulty in holdingthings as she was unable to close her hands properly and grip.On examination the patient had typical generalised sclero-derma involving the face, neck, bib area, arms, and hands,combined with a Raynaud’s condition involving the arms andlegs.

Treatment was started with 1 mg. of veriloid three times a

day. On Dec. 22 the dose was increased to 2 mg. three timesa day. By Jan. 26 there was much improvement in swallow-ing, and dysphagia was noticed only in the evenings. Therewas also noticeable improvement in the appearance of theskin of the forearms and hands. By Feb. 23 the oedema ofthe hands had considerably diminished and the patient couldgrip normally despite the very cold weather. Her arms werequite warm down to the wrists ; although the hands were stillbluish they were not unduly cold. The dose of veriloid wasincreased to 3 mg. three times a day.

Of these three cases two have been treated withveriloid for four years. In both cases improvement has