anti-rabies vaccine

1
890 pot with a small hole (4 mm. x 2 mm.) in one side, connecting the agar-gel phase only with the same agar-electrolyte in a neighbouring pot. On top of this agar was placed a large brass " stapes " weighing about 2 g. A symmetrical system with electrodes was made on the other side of the " stapes " cell, but this system contained only saline solution and had no resin. A hearing-aid earpiece was held to the stapes and the elec- trodes were connected either to an oscilloscope or to the input of a tape recorder. All connections were made rigid, and care was taken to avoid earthing or other adventitious potentials. Tuning forks, one at a time, or together, could be recorded both on the oscilloscope and on the tape recorder, when the forks were held about 1 in. in the air above the hearing-aid microphone. When the electrodes in the resin side were con- nected up there was recording, but not when the saline solu- tion side only was in circuit. We have also recorded the human voice, counting 1 to 10, with a quality of reproduction approaching that of a carbon microphone, distinctive timbre being clearly heard. Similar results, but of much poorer quality, were obtained, for tuning forks only by means of a piece of filter paper appro- priately treated with resin-electrolyte. This system fatigued quickly and was accompanied by much adventitious noise. We do not claim that the transduction of acoustic energy to electrical potential in the scala media must be of this nature, but we have shown that an ion-exchange resin system (which maintains by its physico-chemical nature a permanent junction potential) can respond as accurately as a carbon microphone to acoustic vibration and is a possible mode of action in the tectorial membrane. It is relevant here to quote Hallowell Davis.2 " We have sought with the electron microscope for some structure ... that looks as though it might perform the job that we have assigned to it, which is really the job of being a resistance microphone like a carbon-type microphone of a telephone or hearing-aid. So far nothing helpful has been found. The electrical mechanism must be of molecular dimensions ...". The model we have made employs a molecular mechanism, and we derived our idea of it from the analysis of the tectorial membrane. We suggest that this type of transduction should be given serious consideration as a possible mode of con- version of acoustic to electrical energy in the receptor-organ of the cochlea. L. NAFTALIN A. STEPHENS. Biochemistry Laboratory, St. George’s Hospital, Lincoln. ANTI-RABIES VACCINE SIR,-Recently I attended a patient with neuroparalysis following a second course of anti-rabies vaccine (10 injections of carbolised fixed virus vaccine, M.R.I. Colombo no. 1062). The first course had been given three years previously. Despite treatment with cortisone and vitamin B}2} and resort to a respirator, the patient died on the fifth day of the illness. The dog survived. This is the first reported case of its sort in Ceylon, where dog- bites are a recognised hazard for planters and estate workers. In view of the fact that, on religious grounds, com- pulsory immunisation or extermination of stray dogs can- not be applied here, would it not be advisable to make available the duck embryo vaccine (non-nervous tissue),3 which does not give rise to these neuroparalytic accidents ? Such accidents only occur with carbol fixed virus vaccine, when used for second or subsequent courses. One course of the carbol vaccine can be given harmlessly. World figures for these accidents show a most unsatis- 2. Davis, H. in Neural Mechanisms of the Auditory and Vestibular Systems (edited by G. L. Rasmussen, W. F. Windle); p. 35. Spring- field, 1960. 3. W.H.O. Expert Committee on Rabies: Fourth Report. Tech. Rep. Wld Hlth Org. 1960, no. 201. factory picture for the carbol vaccine used in a second o: subsequent course: between 1 in 860 and 1 in 8000 0 vaccinated persons have been found to become paralysed and about 30% of those affected die.4 Thus the need for: vaccine without neurotoxic properties seems to be great My thanks are due to the director of the Medical Researc Institute, Ceylon, and Dr. J. Hay Arthur, Estates Health Servia Cevlon. for their kind help. J. T. DIXON. Colombo, Ceylon, BROAD-SPECTRUM REDEFINED J. R. ARCHER Manager of Medical Services J. A. L. GORRINGE Director of Clinical Investigation. Parke Davis & Company, Hounslow, Middlesex. G. EVERARD HEWSON. SiR,—Your leading article of Oct. 5 stated: "In urinary infections, its [chloramphenicol’s] undoubted activity against many of the common causal organisms is cancelled by the fact that it appears in the urine mainly as an inactive metabolite." It is true that a relatively large fraction of the administered dose of chloramphenicol is converted to forms not active against bacteria, but, in spite of this, urine concentrations of the active compound are high and peak levels of the antibiotic exceeding 200 g. per ml. have been recorded after a single 1-5 g. oral dose." This is not the whole story, however. It is generally agreed that infection of the urinary tract is primarily in tissue and the objective of therapy is to deliver to the site of infection amounts of a drug that are either bacteri- cidal or bacteriostatic .6 With chloramphenicol, the great- est tissue concentration of the drug is observed in the kidney,5 and so, in large part, this objective is achieved. Furthermore, if susceptible bacteria are shed into the urine, the urinary concentration of active drug is more than sufficient to prevent their multiplication providing adequate dosage is given. SiR,—Your editorial of Oct. 5 stated, when speaking of chloramphenicol, that " it may still find a place ... in topical treatment of some ocular and aural infections ". This dangerous drug continues to be an important antibiotic in treating some cases of intraocular infection, and your emphasis on topical treatment of eye infection should not be construed as indicating that systemic chloramphenicol has no place in the treatment of infection within t’1P put- JAUNDICE ASSOCIATED WITH HALOPERIDOL SIR,-I wish to report a case of jaundice in a patient undergoing treatment with haloperidol (’ Serenace ’). A man of 71 admitted to hospital on July 17, 1963, for a manic illness was found to have signs of chronic bronchitis and emphysema. On July 22 there were signs of an acute exacerba- tion of the chronic bronchitis. Treatment was instituted with oxytetracycline (’Terramycin’) 250 mg. 6-hourly. The patient’s haemoglobin was 12-3 g. per 100 ml. and the white- cell count was 5750 per c.mm. On July 25 treatment with haloperidol 1-5 mg. t.d.s. was begun and the dose was increased to 1-5 mg. q.d.s. on July 30. Next day the patient became excessively drowsy, and the pulse-rate increased to 160 per minute-at first irregular but reverting later to regular rhythm. Early cor pulmonale was suspected despite absence of raised jugular venous pressure. X-ray of chest confirmed early cor pulmonale, showing considerable pulmonary hilar congestion. Digoxin 0-25 mg. was given 4-hourly and the dose of oxytetra- 4. McFadzean, A. J. S. Trans. R. Soc. trop. Med. Hyg. 1952/53, 47, 372. Smith, G., Wells, C. W. Bulletin 8, Institute of Medical Research Federation of Malaya. Laha, P. N. Brit. med. J. 1957, i, 148. 5. Glazko, A. J., Wolf, L. M., Dill, W. A., Bratton, A. C., Jr. J. Pharmacol exp. Ther. 1949, 96, 445. 6. Antibiot. Chemother. 1961, 11, 681.

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Page 1: ANTI-RABIES VACCINE

890

pot with a small hole (4 mm. x 2 mm.) in one side, connectingthe agar-gel phase only with the same agar-electrolyte in aneighbouring pot. On top of this agar was placed a largebrass " stapes " weighing about 2 g. A symmetrical systemwith electrodes was made on the other side of the " stapes "cell, but this system contained only saline solution and hadno resin. -

A hearing-aid earpiece was held to the stapes and the elec-trodes were connected either to an oscilloscope or to the inputof a tape recorder. All connections were made rigid, and carewas taken to avoid earthing or other adventitious potentials.Tuning forks, one at a time, or together, could be recorded

both on the oscilloscope and on the tape recorder, when theforks were held about 1 in. in the air above the hearing-aidmicrophone. When the electrodes in the resin side were con-nected up there was recording, but not when the saline solu-tion side only was in circuit. We have also recorded thehuman voice, counting 1 to 10, with a quality of reproductionapproaching that of a carbon microphone, distinctive timbrebeing clearly heard.

Similar results, but of much poorer quality, were obtained,for tuning forks only by means of a piece of filter paper appro-priately treated with resin-electrolyte. This system fatiguedquickly and was accompanied by much adventitious noise.We do not claim that the transduction of acoustic energy to

electrical potential in the scala media must be of this nature,but we have shown that an ion-exchange resin system (whichmaintains by its physico-chemical nature a permanent junctionpotential) can respond as accurately as a carbon microphoneto acoustic vibration and is a possible mode of action in thetectorial membrane. It is relevant here to quote HallowellDavis.2 " We have sought with the electron microscope forsome structure ... that looks as though it might perform thejob that we have assigned to it, which is really the job of beinga resistance microphone like a carbon-type microphone of atelephone or hearing-aid. So far nothing helpful has beenfound. The electrical mechanism must be of moleculardimensions ...".The model we have made employs a molecular mechanism,

and we derived our idea of it from the analysis of the tectorialmembrane. We suggest that this type of transduction shouldbe given serious consideration as a possible mode of con-version of acoustic to electrical energy in the receptor-organof the cochlea.

L. NAFTALINA. STEPHENS.

Biochemistry Laboratory,St. George’s Hospital,

Lincoln.

ANTI-RABIES VACCINE

SIR,-Recently I attended a patient with neuroparalysisfollowing a second course of anti-rabies vaccine (10injections of carbolised fixed virus vaccine, M.R.I.Colombo no. 1062). The first course had been giventhree years previously. Despite treatment with cortisoneand vitamin B}2} and resort to a respirator, the patient diedon the fifth day of the illness. The dog survived. This isthe first reported case of its sort in Ceylon, where dog-bites are a recognised hazard for planters and estate

workers.In view of the fact that, on religious grounds, com-

pulsory immunisation or extermination of stray dogs can-not be applied here, would it not be advisable to makeavailable the duck embryo vaccine (non-nervous tissue),3which does not give rise to these neuroparalytic accidents ?Such accidents only occur with carbol fixed virus vaccine,when used for second or subsequent courses. One courseof the carbol vaccine can be given harmlessly.World figures for these accidents show a most unsatis-

2. Davis, H. in Neural Mechanisms of the Auditory and VestibularSystems (edited by G. L. Rasmussen, W. F. Windle); p. 35. Spring-field, 1960.

3. W.H.O. Expert Committee on Rabies: Fourth Report. Tech. Rep. WldHlth Org. 1960, no. 201.

factory picture for the carbol vaccine used in a second o:subsequent course: between 1 in 860 and 1 in 8000 0vaccinated persons have been found to become paralysedand about 30% of those affected die.4 Thus the need for:vaccine without neurotoxic properties seems to be greatMy thanks are due to the director of the Medical Researc

Institute, Ceylon, and Dr. J. Hay Arthur, Estates Health ServiaCevlon. for their kind help.

J. T. DIXON.Colombo, Ceylon,

BROAD-SPECTRUM REDEFINED

J. R. ARCHERManager of Medical Services

J. A. L. GORRINGEDirector of Clinical Investigation.

Parke Davis & Company,Hounslow, Middlesex.

G. EVERARD HEWSON.

SiR,—Your leading article of Oct. 5 stated: "In urinaryinfections, its [chloramphenicol’s] undoubted activityagainst many of the common causal organisms is cancelledby the fact that it appears in the urine mainly as aninactive metabolite." It is true that a relatively largefraction of the administered dose of chloramphenicol isconverted to forms not active against bacteria, but, in spiteof this, urine concentrations of the active compound arehigh and peak levels of the antibiotic exceeding 200 g.per ml. have been recorded after a single 1-5 g. oral dose."

This is not the whole story, however. It is generallyagreed that infection of the urinary tract is primarily intissue and the objective of therapy is to deliver to thesite of infection amounts of a drug that are either bacteri-cidal or bacteriostatic .6 With chloramphenicol, the great-est tissue concentration of the drug is observed in thekidney,5 and so, in large part, this objective is achieved.Furthermore, if susceptible bacteria are shed into theurine, the urinary concentration of active drug is morethan sufficient to prevent their multiplication providingadequate dosage is given.

SiR,—Your editorial of Oct. 5 stated, when speaking ofchloramphenicol, that " it may still find a place ... intopical treatment of some ocular and aural infections ".

This dangerous drug continues to be an importantantibiotic in treating some cases of intraocular infection,and your emphasis on topical treatment of eye infectionshould not be construed as indicating that systemicchloramphenicol has no place in the treatment of infectionwithin t’1P put-

JAUNDICE ASSOCIATED WITH HALOPERIDOL

SIR,-I wish to report a case of jaundice in a patientundergoing treatment with haloperidol (’ Serenace ’).A man of 71 admitted to hospital on July 17, 1963, for a

manic illness was found to have signs of chronic bronchitis andemphysema. On July 22 there were signs of an acute exacerba-tion of the chronic bronchitis. Treatment was instituted withoxytetracycline (’Terramycin’) 250 mg. 6-hourly. The

patient’s haemoglobin was 12-3 g. per 100 ml. and the white-cell count was 5750 per c.mm. On July 25 treatment withhaloperidol 1-5 mg. t.d.s. was begun and the dose was increasedto 1-5 mg. q.d.s. on July 30. Next day the patient becameexcessively drowsy, and the pulse-rate increased to 160 perminute-at first irregular but reverting later to regular rhythm.Early cor pulmonale was suspected despite absence of raisedjugular venous pressure. X-ray of chest confirmed early corpulmonale, showing considerable pulmonary hilar congestion.Digoxin 0-25 mg. was given 4-hourly and the dose of oxytetra-4. McFadzean, A. J. S. Trans. R. Soc. trop. Med. Hyg. 1952/53, 47, 372.

Smith, G., Wells, C. W. Bulletin 8, Institute of Medical ResearchFederation of Malaya. Laha, P. N. Brit. med. J. 1957, i, 148.

5. Glazko, A. J., Wolf, L. M., Dill, W. A., Bratton, A. C., Jr. J. Pharmacolexp. Ther. 1949, 96, 445.

6. Antibiot. Chemother. 1961, 11, 681.