1
449 relation which these normal cups bear to the glaucoma I cup. In some cases of chronic glaucoma there is a cup which does not occupy the whole area of the disc I And yet is undoubtedly a glaucoma cup. This is a fact which, although it has not found its way into most text-books, is recognised by most ophthalmic surgeons. Mr. Pickard, in his paper, gives diagrams, taken at periods of several months apart from patients who did develop undoubted glaucoma, which strikingly illustrate the fact. In these cases the cause of the enlargement must have been the same as that which produces the typical cup of glaucoma- i.e., an abnormal increase of intra-ocular pressure. Mr. Pickard’s argument is that the increase in the size of the cup which he has observed in certain normal cases is also due to intra-ocular pressure, though it may be that this has never risen above the normal. Whilst, however, this may be so, it may also be the fact that in some of these cases, at any rate, an abnormally high intra-ocular pressure may be the cause of the phenomenon. He concludes, therefore, supporting in this what has already been put forward by other writers in the matter of unduly large cups, that the enlargement of the cup in adult life, without symptoms of glaucoma, must be regarded with suspicion, and that such cases require careful watching for the development of glaucoma: whether or not there is any particular type of cup which in the absence of any evidence of increase of size ought to be regarded with similar suspicion is a further point which might be investigated. A form of cup which Mr. Pickard terms " bulbous " is one with an over- hanging margin, so that the continuity of the vessels on the periphery of the disc with those lying at the base of the cup on the lamina cribrosa cannot be traced. It is rare for this to be the case round the whole margin of the disc, but it is extremely common for it to be the case as regards about half of it. This fact is hardly consistent with the common explanation of the physiological cup that it is merely the result of the separation of the nerve-fibres. It must either be the result of an anatomical peculiarity or of the intra-ocular pressure acting on the nerve-fibres between the lamina cribrosa and the superficial level of the disc. On the other hand, the appearance is far too common to suggest that there is any close connexion between it and the development of glaucoma. THE ORIGIN OF GALL-STONES. NUMEROUS circumstances and influences favour the development of gall-stones, but uncertainty exists as to which of them are contributory in character and which critical. With a view to the elucidation of this subject, Peyton Rous, P. D. McMaster, and G. 0. Broun, of the Rockefeller Institute, have made observations on dogs under strictly controlled experi- mental conditions.’- It is possible to join a rubber tube to the common bile-duct of a dog and collect the bile under sterile conditions for months. The gall-bladder should be removed at the time of intuba- tion. Dogs thus treated remained in excellent condition. Out of 12 dogs, calculi were found in 6, and in 3 of these the bile had been sterile. The calculi-to begin with multiple and discrete-were found only in the walls of the collecting system of rubber and glass, never in the ducts themselves. Nor did thev occur when the rubber or glass tubes remained clear of organic debris (dead cells and mucinoid matter). The early stages of the calculi I that had formed on the glass connexions were examined by the microscope. The stones consisted of calcium bilirubinate and calcium carbonate, with a scaffolding of organic material. Cholesterol was not demonstrable in them. The majority had a centre of calcium bilirubinate surrounded by an ,envelope of crystalline slightly pigmented carbonate ; but stones consisting almost wholly of one or other substance were found. The relation between these two salts in the gall-stones of the dog had similarities 1 Proc. Soc. for Expt. Biol. and Med., vol. xx., 1922. to that between calcium bilirubinate and cholesterol in human calculi. There is the same tendency in both instances for a nucleus of the pigment material to be overlaid with another substance. These observations seem to show that infection is not the essential factor of cholelithiasis. That it frequently plays the determining r6le is equally certain. This it would seem to do by damaging the duct wall, with result in desquamation-which the sterile cannula did in these experiments-and by lessening the ability of the bile channels to rid themselves of the cell debris. The debris induces or furthers the direct deposition of solids, and may catch and retain poten- tial nuclei for stone formation, in the shape of pigment particles from higher up in the biliary system, which would under ordinary circumstances be voided with the bile. ____ OCTO-CENTENARY OF ST. BARTHOLOMEW’S HOSPITAL. THE 800th anniversary of the foundation of St. Bartholomew’s Hospital is being celebrated from Tuesday, June 5th, to Thursday, June 7th. On Tuesday, after service at the Priory Church of St. Batholomew-the-Great, delegates will be entertained to luncheon by the governors and staff of the Medical College. In the afternoon the Prince of Wales, as President of the hospital, will receive addresses from the delegates, and in the evening old students of the school will dine together. On Wednesday afternoon a reception will be held at the Royal College of Surgeons of England, the Bartholomew Fair will take place within the hospital precincts, and a banquet will be given to the delegates in the evening. On Thursday, after service at St. Paul’s Cathedral, the hospital and medical college will be " at home." During the celebrations an exhibition of historical and scientific interest will be held within the hospital. The grati- fying announcement has just been made that the medical college authorities have acquired a block of modern premises in Giltspur-street to be devoted mainly to a new physiology department, which will then have separate laboratories for histology, chemical physiology, and experimental physiology, along with numerous research rooms. The size of the College necessitates and justifies this expansion, for there are at the present time in attendance 690 full-time and 88 part-time students, and the full and part-time entries which in October, 1920, amounted to 243, rose in 1921 to 266 and in 1922 to 286. SEASONAL PHYSIOLOGICAL PHENOMENA. THOUGH it is often tacitly admitted that the bodily functions are liable to suffer modifications with the change of the seasons, we have little precise knowledge of the incidence of such changes, and next to none regarding their causation. An example of seasonal variation often seen in the physiological laboratory is the failure of stimulus applied to the vago- sympathetic to arrest the frog’s heart during the summer months. This is due to overactivity of the sympathetic fibres in the trunk, and not to inaction of the vagus. The change from the winter to the summer type of response takes place at the mating season, and Cori considers that the response at different seasons has a relation to thyroid activity. It is interesting to note that Seidell and Fenger 2 found that in various mammals the iodine content of the thyroid during the months from June to November is three times as great as from December to May. Reid Hunt3 found that guinea-pigs were least resistant to the toxic effects of acetonitrile in the winter. It seems reasonable that any effect which the seasons may produce would be due to an effect of change either in the amount of light or in the mean temperature. That light may be an important factor is shown by some recent investiga- 1 Arch. f. exp. Path. u. Pharm., 1921, xci., 130. 2 Jour. Biol. Chem., 1913, xiii., 517. 3 Bull. 69, Hyg. Lab., U.S.P.H.S., 1910.

OCTO-CENTENARY OF ST. BARTHOLOMEW'S HOSPITAL

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449

relation which these normal cups bear to the glaucoma Icup. In some cases of chronic glaucoma there is acup which does not occupy the whole area of the disc IAnd yet is undoubtedly a glaucoma cup. This is afact which, although it has not found its way intomost text-books, is recognised by most ophthalmicsurgeons. Mr. Pickard, in his paper, gives diagrams,taken at periods of several months apart from

patients who did develop undoubted glaucoma, whichstrikingly illustrate the fact. In these cases thecause of the enlargement must have been the same asthat which produces the typical cup of glaucoma-i.e., an abnormal increase of intra-ocular pressure.Mr. Pickard’s argument is that the increase in thesize of the cup which he has observed in certainnormal cases is also due to intra-ocular pressure,though it may be that this has never risen above thenormal. Whilst, however, this may be so, it mayalso be the fact that in some of these cases, at anyrate, an abnormally high intra-ocular pressure maybe the cause of the phenomenon. He concludes,therefore, supporting in this what has already been putforward by other writers in the matter of undulylarge cups, that the enlargement of the cup in adultlife, without symptoms of glaucoma, must be regardedwith suspicion, and that such cases require carefulwatching for the development of glaucoma: whetheror not there is any particular type of cup which in theabsence of any evidence of increase of size ought tobe regarded with similar suspicion is a further pointwhich might be investigated. A form of cup whichMr. Pickard terms " bulbous " is one with an over-hanging margin, so that the continuity of the vesselson the periphery of the disc with those lying at thebase of the cup on the lamina cribrosa cannot betraced. It is rare for this to be the case round thewhole margin of the disc, but it is extremely commonfor it to be the case as regards about half of it. Thisfact is hardly consistent with the common explanationof the physiological cup that it is merely the resultof the separation of the nerve-fibres. It must eitherbe the result of an anatomical peculiarity or of theintra-ocular pressure acting on the nerve-fibres betweenthe lamina cribrosa and the superficial level of thedisc. On the other hand, the appearance is far toocommon to suggest that there is any close connexionbetween it and the development of glaucoma.

THE ORIGIN OF GALL-STONES.

NUMEROUS circumstances and influences favourthe development of gall-stones, but uncertainty existsas to which of them are contributory in characterand which critical. With a view to the elucidationof this subject, Peyton Rous, P. D. McMaster, andG. 0. Broun, of the Rockefeller Institute, have madeobservations on dogs under strictly controlled experi-mental conditions.’- It is possible to join a rubbertube to the common bile-duct of a dog and collectthe bile under sterile conditions for months. Thegall-bladder should be removed at the time of intuba-tion. Dogs thus treated remained in excellentcondition. Out of 12 dogs, calculi were found in 6,and in 3 of these the bile had been sterile. Thecalculi-to begin with multiple and discrete-werefound only in the walls of the collecting system ofrubber and glass, never in the ducts themselves.Nor did thev occur when the rubber or glass tubesremained clear of organic debris (dead cells andmucinoid matter). The early stages of the calculi Ithat had formed on the glass connexions wereexamined by the microscope. The stones consistedof calcium bilirubinate and calcium carbonate, witha scaffolding of organic material. Cholesterol wasnot demonstrable in them. The majority had acentre of calcium bilirubinate surrounded by an

,envelope of crystalline slightly pigmented carbonate ;but stones consisting almost wholly of one or othersubstance were found. The relation between thesetwo salts in the gall-stones of the dog had similarities

1 Proc. Soc. for Expt. Biol. and Med., vol. xx., 1922.

to that between calcium bilirubinate and cholesterolin human calculi. There is the same tendency inboth instances for a nucleus of the pigment materialto be overlaid with another substance. Theseobservations seem to show that infection is not theessential factor of cholelithiasis. That it frequentlyplays the determining r6le is equally certain. Thisit would seem to do by damaging the duct wall, withresult in desquamation-which the sterile cannuladid in these experiments-and by lessening theability of the bile channels to rid themselves of thecell debris. The debris induces or furthers the directdeposition of solids, and may catch and retain poten-tial nuclei for stone formation, in the shape of pigmentparticles from higher up in the biliary system, whichwould under ordinary circumstances be voided withthe bile.

____

OCTO-CENTENARY OF ST. BARTHOLOMEW’S

HOSPITAL.

THE 800th anniversary of the foundation of St.Bartholomew’s Hospital is being celebrated fromTuesday, June 5th, to Thursday, June 7th. OnTuesday, after service at the Priory Church of St.Batholomew-the-Great, delegates will be entertainedto luncheon by the governors and staff of the MedicalCollege. In the afternoon the Prince of Wales, asPresident of the hospital, will receive addresses fromthe delegates, and in the evening old students of theschool will dine together. On Wednesday afternoon areception will be held at the Royal College of Surgeonsof England, the Bartholomew Fair will take placewithin the hospital precincts, and a banquet will begiven to the delegates in the evening. On Thursday,after service at St. Paul’s Cathedral, the hospital andmedical college will be " at home." During thecelebrations an exhibition of historical and scientificinterest will be held within the hospital. The grati-fying announcement has just been made that themedical college authorities have acquired a block ofmodern premises in Giltspur-street to be devotedmainly to a new physiology department, which willthen have separate laboratories for histology, chemicalphysiology, and experimental physiology, along withnumerous research rooms. The size of the Collegenecessitates and justifies this expansion, for there areat the present time in attendance 690 full-time and88 part-time students, and the full and part-time

entries which in October, 1920, amounted to 243,rose in 1921 to 266 and in 1922 to 286.

SEASONAL PHYSIOLOGICAL PHENOMENA.

THOUGH it is often tacitly admitted that the bodilyfunctions are liable to suffer modifications with thechange of the seasons, we have little precise knowledgeof the incidence of such changes, and next to noneregarding their causation. An example of seasonalvariation often seen in the physiological laboratoryis the failure of stimulus applied to the vago-sympathetic to arrest the frog’s heart during thesummer months. This is due to overactivity ofthe sympathetic fibres in the trunk, and not toinaction of the vagus. The change from the winterto the summer type of response takes place at themating season, and Cori considers that the responseat different seasons has a relation to thyroid activity.It is interesting to note that Seidell and Fenger 2found that in various mammals the iodine contentof the thyroid during the months from June toNovember is three times as great as from Decemberto May. Reid Hunt3 found that guinea-pigs wereleast resistant to the toxic effects of acetonitrile inthe winter. It seems reasonable that any effect whichthe seasons may produce would be due to an effectof change either in the amount of light or inthe mean temperature. That light may be an

important factor is shown by some recent investiga-1 Arch. f. exp. Path. u. Pharm., 1921, xci., 130.

2 Jour. Biol. Chem., 1913, xiii., 517.3 Bull. 69, Hyg. Lab., U.S.P.H.S., 1910.