- Email: [email protected]
ANTIBIOTIC-ASSOCIATED COLITIS
1058 We agree with Stanford
al. that a single estimation of alone is unlikely to help the clinician to determine the cause of the effusion. However, by determining both C.E.A. and lysozyme, the clinician is able to distinguish many malignant from tuberculous or empyematous effusions with a high degree of certainty.
plasma and pleural-fluid
et
C.E.A.
Department of Medicine IV, Helsinki University Central Hospital; and Department of Immunology and Bacteriology,
University of Helsinki, Finland; Mjöbolsta Hospital, Finland, and Uttran’s Hospital, Sweden
M. KLOCKARS
J. LINDGREN T. PETTERSSON P.-E. HELLSTROM Å. NORHAGEN
FLURBIPROFEN AND FLUDROCORTISONE IN SEVERE AUTONOMIC NEUROPATHY
SiR,—The long-term treatment of idiopathic orthostatic hypotension (i.o.H.) has been largely unsatisfactory and has included wrapping the legs, fludrocortisone to expand plasma volume,’ and vasoconstrictors such as ephedrine and tyramine, alone
in combination with monoamine-oxidase inhibitors or P-adrenergic blockade. Kochar and Itskovitz2 found indomethacin of value in patients with orthostatic hypotension. This compound is thought to exert its effect by inhibition of prostaglandin synthesis, and it may be that in t.o.H. there is a relative or absolute overproduction of potentially vasodilating prostaglandins. Unfortunately indomethacin used longterm may have undesirable central side-effects, and these have led to its replacement by compounds of the propionic-acid group (e.g., in the treatment of Bartter’s syndrome 3). The most effective inhibitor of prostaglandin synthesis in vitro in this class of drugs is flurbiprofen. Our patient is an 18-year-old schoolgirl who presented with a 2-year history of frontal headaches and recent onset of postural syncope. Blood-pressure was 95/70 mm Hg lying, 60/40 mm Hg sitting, and was unrecordable in the upright position; no abnormal neurological signs were noted. Tilting test, Valsalva manoeuvre, and negative pressure applied to the neck produced results compatible with sympathetic nervous dysfunction but indicated that the efferent vagus was intact. When transferred to our care she was unable to sit upright in bed because of severe postural hypotension. Tests of reflex vasodilatation and sweating demonstrated a widespread but patchy autonomic neuropathy. Peripheral-nerve conduction studies on the arms and legs were normal. Plasma-renin-activity with the patient recumbent was 4.75 ng/ml/h (near the upper limit of normal in our laboratory), 24 h urinary catecholamines were normal. The patient was put on increasing doses of fludrocortisone. Little symptomatic or objective improvement was noted on 0.4 mg daily. Sustained-release indomethacin, 75 mg twice daily, was added, and within 48 h symptomatic and objective improvement was recorded but at the expense of severe generalised headache which the patient found intolerable. Despite reduction of the dose to 25 mg twice daily the headache persisted until indomethacin was discontinued. Hypotensive symptoms returned, despite continued fludrocortisone, so flurbiprofen (50 mg twice daily) was given with good control of blood-pressure and no headache. After 3 months of this combined therapy the patient was symptom-free and leading a normal life. Blood-pressures were 100/60 mm Hg recumbent, 90/60 mm Hg standing for 30 s, and 88/60 mm Hg after standing for 2 min. Large doses of fludrocortisone may control LO.H., but there is a definite morbidity due to oedema, cardiac failure, and hypokalsEmia. The prostaglandin-synthetase inhibitors share, as a group, the side-effects of gastrointestinal ulceration, or
eight
Bannister, R. G., Ardill, L., Fentem, P. Q. Jl Med. 1969, 28, 377. Kochar, M. S., Itskovitz, H. D. Lancet, 1978, i, 1011. 3. Littlewood, J. M., Lee, M. R., Meadow, S. R. Archs Dis. Childh. 1978, 53, 1. 2.
43.
cedema, and interference with platelet function; in addition indomethacin may produce severe headache (as in our patient), vertigo, hallucinations, mental confusion, depression, and psychosis. Published experience of flurbiprofen is limited but these side-effects seem to be less common. In a condition like I.O.H., where therapy must be continuous, it is important that drugs be well tolerated with few side-effects. We suggest that the combination of flurbiprofen and fludrocortisone in low dosage should receive further evaluation. We thank Dr S. M. Rajah who referred this patient, Dr S. Kappathe studies of blood-pressure and autonomic function, Dr D. Taverner for the electromyographic studies, and Dr W. J. Cunliffe and his staff for the tests of reflex vasodilatation and sweating.
goda for
University of Leeds Department Leeds General Infirmary, Leeds LS1 3EX
of Medicine,
C. M. PERKINS M. R. LEE
ANTIBIOTIC-ASSOCIATED COLITIS
SIR,-When discussing the underlying mechanisms of antibiotic-associated colitis, Dr Toffler and colleagues (Sept. 30, p. 707) do not consider the possible action of bacterial toxins, whose strong affinity for sympathetic nervous tissue offers an explanation for the ischaemic nature of the lesions they describe. Staphylococcus aureus, which is associated with pseudomembranous colitis, produces a very powerful vasoconstrictor toxin, thus offering a ready explanation for ischaemic lesions of the colon in the presence of this organism. Negative stool cultures do not exclude toxins; after antibiotic therapy gramnegative enteropathogens are destroyed, releasing endotoxin with equally strong sympathetic affinity. Their presence in the bowel could produce the local vasoconstriction and patchy destruction of bowel mucosa as well as the motor disturbances, colicky pain, and diarrhoea which Toffler et al. describe. 11 Chelsea Embankment, London SW3 4LE
D. A. BUXTON HOPKIN
AIRWAYS IN RHEUMATOID DISEASE
SiR,—Your editorial of July 22 does not mention one likely of airways disease in rheumatoid arthritis (R.A.)-
cause
involvement of tracheobronchial exocrine glands, as a component of SjSgren’s syndrome. 12 We have found bronchitis sicca in 17% of patients with Sjogren’s syndrome.’ Its pathological substratum in mucus glands of the respiratory tract is akin to that in lacrimal and salivary glands, and was described by Sjogren himself.3 Like airways disease, Sjogren’s syndrome may be either subclinical or symptomatic in R.A., and we have found evidence of it in 90 of 100 patients with R.A. studied with a battery of tests of lacrimal and salivary-gland involvement (unpublished) like the battery used to detect such involvement in systemic lupus
namely,
erythematosus.4 The atrophy of the tracheobronchial secreting apparatus found in Sjogren’s syndrome may cause recurrent pulmonary infections’5 apparently due to airway plugging by inspissated mucus. Subclinical exocrine-gland involvement of the mucussecreting glands of the respiratory tract may account for both the airways disease and the increased frequency of clinical chest infections in R.A. that you mention. Department of Immunology and Rheumatology; Instituto Nacional de la Nutrición, Mexico 22, Mexico DONATO ALARCÓN-SEGOVIA
Alarcón-Segovia, D., Divertie, M. B., Brown, A. L., Jr. Arthritis Rheum. 1965, 8, 427. 2. Strimlan, C. V., Rosenow, E. C., III, Divertie, M. B., Harrison, E. G. Jr. Chest, 1976, 70, 354. 3. Sjögren, H. Acta ophthalmol. 1933, 11, suppl. 2. 1. 4. Alarcdn-Segovia, D., Ibañez, G., Velázquez-Forero, F., Hernández-Ortïz, J., González-Jiménez, Y. Ann. intern. Med. 1974, 81, 577. 5. Ellman, P., Weber, F. P. Br. med. J. 1949, i, 304. 1.
al. that a single estimation of alone is unlikely to help the clinician to determine the cause of the effusion. However, by determining both C.E.A. and lysozyme, the clinician is able to distinguish many malignant from tuberculous or empyematous effusions with a high degree of certainty.
plasma and pleural-fluid
et
C.E.A.
Department of Medicine IV, Helsinki University Central Hospital; and Department of Immunology and Bacteriology,
University of Helsinki, Finland; Mjöbolsta Hospital, Finland, and Uttran’s Hospital, Sweden
M. KLOCKARS
J. LINDGREN T. PETTERSSON P.-E. HELLSTROM Å. NORHAGEN
FLURBIPROFEN AND FLUDROCORTISONE IN SEVERE AUTONOMIC NEUROPATHY
SiR,—The long-term treatment of idiopathic orthostatic hypotension (i.o.H.) has been largely unsatisfactory and has included wrapping the legs, fludrocortisone to expand plasma volume,’ and vasoconstrictors such as ephedrine and tyramine, alone
in combination with monoamine-oxidase inhibitors or P-adrenergic blockade. Kochar and Itskovitz2 found indomethacin of value in patients with orthostatic hypotension. This compound is thought to exert its effect by inhibition of prostaglandin synthesis, and it may be that in t.o.H. there is a relative or absolute overproduction of potentially vasodilating prostaglandins. Unfortunately indomethacin used longterm may have undesirable central side-effects, and these have led to its replacement by compounds of the propionic-acid group (e.g., in the treatment of Bartter’s syndrome 3). The most effective inhibitor of prostaglandin synthesis in vitro in this class of drugs is flurbiprofen. Our patient is an 18-year-old schoolgirl who presented with a 2-year history of frontal headaches and recent onset of postural syncope. Blood-pressure was 95/70 mm Hg lying, 60/40 mm Hg sitting, and was unrecordable in the upright position; no abnormal neurological signs were noted. Tilting test, Valsalva manoeuvre, and negative pressure applied to the neck produced results compatible with sympathetic nervous dysfunction but indicated that the efferent vagus was intact. When transferred to our care she was unable to sit upright in bed because of severe postural hypotension. Tests of reflex vasodilatation and sweating demonstrated a widespread but patchy autonomic neuropathy. Peripheral-nerve conduction studies on the arms and legs were normal. Plasma-renin-activity with the patient recumbent was 4.75 ng/ml/h (near the upper limit of normal in our laboratory), 24 h urinary catecholamines were normal. The patient was put on increasing doses of fludrocortisone. Little symptomatic or objective improvement was noted on 0.4 mg daily. Sustained-release indomethacin, 75 mg twice daily, was added, and within 48 h symptomatic and objective improvement was recorded but at the expense of severe generalised headache which the patient found intolerable. Despite reduction of the dose to 25 mg twice daily the headache persisted until indomethacin was discontinued. Hypotensive symptoms returned, despite continued fludrocortisone, so flurbiprofen (50 mg twice daily) was given with good control of blood-pressure and no headache. After 3 months of this combined therapy the patient was symptom-free and leading a normal life. Blood-pressures were 100/60 mm Hg recumbent, 90/60 mm Hg standing for 30 s, and 88/60 mm Hg after standing for 2 min. Large doses of fludrocortisone may control LO.H., but there is a definite morbidity due to oedema, cardiac failure, and hypokalsEmia. The prostaglandin-synthetase inhibitors share, as a group, the side-effects of gastrointestinal ulceration, or
eight
Bannister, R. G., Ardill, L., Fentem, P. Q. Jl Med. 1969, 28, 377. Kochar, M. S., Itskovitz, H. D. Lancet, 1978, i, 1011. 3. Littlewood, J. M., Lee, M. R., Meadow, S. R. Archs Dis. Childh. 1978, 53, 1. 2.
43.
cedema, and interference with platelet function; in addition indomethacin may produce severe headache (as in our patient), vertigo, hallucinations, mental confusion, depression, and psychosis. Published experience of flurbiprofen is limited but these side-effects seem to be less common. In a condition like I.O.H., where therapy must be continuous, it is important that drugs be well tolerated with few side-effects. We suggest that the combination of flurbiprofen and fludrocortisone in low dosage should receive further evaluation. We thank Dr S. M. Rajah who referred this patient, Dr S. Kappathe studies of blood-pressure and autonomic function, Dr D. Taverner for the electromyographic studies, and Dr W. J. Cunliffe and his staff for the tests of reflex vasodilatation and sweating.
goda for
University of Leeds Department Leeds General Infirmary, Leeds LS1 3EX
of Medicine,
C. M. PERKINS M. R. LEE
ANTIBIOTIC-ASSOCIATED COLITIS
SIR,-When discussing the underlying mechanisms of antibiotic-associated colitis, Dr Toffler and colleagues (Sept. 30, p. 707) do not consider the possible action of bacterial toxins, whose strong affinity for sympathetic nervous tissue offers an explanation for the ischaemic nature of the lesions they describe. Staphylococcus aureus, which is associated with pseudomembranous colitis, produces a very powerful vasoconstrictor toxin, thus offering a ready explanation for ischaemic lesions of the colon in the presence of this organism. Negative stool cultures do not exclude toxins; after antibiotic therapy gramnegative enteropathogens are destroyed, releasing endotoxin with equally strong sympathetic affinity. Their presence in the bowel could produce the local vasoconstriction and patchy destruction of bowel mucosa as well as the motor disturbances, colicky pain, and diarrhoea which Toffler et al. describe. 11 Chelsea Embankment, London SW3 4LE
D. A. BUXTON HOPKIN
AIRWAYS IN RHEUMATOID DISEASE
SiR,—Your editorial of July 22 does not mention one likely of airways disease in rheumatoid arthritis (R.A.)-
cause
involvement of tracheobronchial exocrine glands, as a component of SjSgren’s syndrome. 12 We have found bronchitis sicca in 17% of patients with Sjogren’s syndrome.’ Its pathological substratum in mucus glands of the respiratory tract is akin to that in lacrimal and salivary glands, and was described by Sjogren himself.3 Like airways disease, Sjogren’s syndrome may be either subclinical or symptomatic in R.A., and we have found evidence of it in 90 of 100 patients with R.A. studied with a battery of tests of lacrimal and salivary-gland involvement (unpublished) like the battery used to detect such involvement in systemic lupus
namely,
erythematosus.4 The atrophy of the tracheobronchial secreting apparatus found in Sjogren’s syndrome may cause recurrent pulmonary infections’5 apparently due to airway plugging by inspissated mucus. Subclinical exocrine-gland involvement of the mucussecreting glands of the respiratory tract may account for both the airways disease and the increased frequency of clinical chest infections in R.A. that you mention. Department of Immunology and Rheumatology; Instituto Nacional de la Nutrición, Mexico 22, Mexico DONATO ALARCÓN-SEGOVIA
Alarcón-Segovia, D., Divertie, M. B., Brown, A. L., Jr. Arthritis Rheum. 1965, 8, 427. 2. Strimlan, C. V., Rosenow, E. C., III, Divertie, M. B., Harrison, E. G. Jr. Chest, 1976, 70, 354. 3. Sjögren, H. Acta ophthalmol. 1933, 11, suppl. 2. 1. 4. Alarcdn-Segovia, D., Ibañez, G., Velázquez-Forero, F., Hernández-Ortïz, J., González-Jiménez, Y. Ann. intern. Med. 1974, 81, 577. 5. Ellman, P., Weber, F. P. Br. med. J. 1949, i, 304. 1.