147 in this system is associated with the
phenotype
known
as
with Yates’s correction leads to a result O.1O>p>O.05 one-tail test. However, the expected trequency in the upper left cell of the table is 2-5, so the X. test is scarcely appropriate. Fisher’s exact test yields a one-tail probability P=0.073. We conclude that it is premature to suggest an association between heterozygosity for the Z allele of alpha-1-antitrypsin and classical or definite rheumatoid arthritis.
x2
Che-
diak-Higashi syndrome.
on a
This research was made possible through a grant from the National Foundation-March of Dimes and National Institute of Health training grant, 5 T01 GMO 1918-07. Department of Medicine, HINDS
KRISTIN B. SHANNON DANES
Cornell University Medical College, New
York, N.Y. 10021, U.S.A.
Arthritis and Rheumatism Council Epidemiology Research Unit, Stopford Building (University of Manchester), Manchester M13 9PT
DIAGNOSIS OF PYOGENIC MENINGITIS
SIR,-Commenting on the usefulness of countercurrentimmunoelectrophoresis (C.I.E.) in bacterial meningitis’ you state that "previous antibiotic treatment has little effect on the success-rate ofc.f.E.—an important advantage over culture." What is the evidence for such a claim? Though there have been isolated examples2-4 of positive C.I.E. in pretreated pyogenic meningitis with negative bacteriology, our experience with this test has not been encouraging in the occasional diagnostic problems of partially treated bacterial meningitis-a problem that tends to be overemphasised, as you pointed out earlier.s In a study6 of 62 patients admitted to this unit with bacterial meningitis, 23 (37%) of whom had received pre-diagnosis antibiotic therapy, positive bacteriological diagnosis could be achieved in 73% of the partially treated group as opposed to 97% in the previously untreated group, characteristic cerebrospinal fluid (c.s.F.) changes sufficient for diagnostic purpose being present in all but 1 case. The C.S.F. was examined for bacterial antigen by C.I.E. in 11 patients and was positive in 5, all of whom also had positive bacteriology. In all 6 cases, where the conventional bacteriology was negative, the C.LE. also proved negative. 5 patients in this latter group were judged to have meningococcal infections on the basis of the characteristic rash or serology. In my limited experience, a few low oral doses of the commonly used antibiotics rarely cause diagnostic problems in pneumococcal or "H. influenzal" meningitis and in the post-neonatal age-group, I agree with Christie’ that the "negative" cases can generally be regarded as partially treated cases of meningococcal meningitis. Thus far, there is little evidence to indicate a definite advantage of C.I.E. over conventional bacteriology in these problematic cases. Regional Department Monsall Hospital,
of Infectious Diseases
B. K. MANDAL
Manchester 10
HYPERTENSION NO LONGER A DISEASE?
SIR,-Brown et al-argue convincingly that essential hypertension is the expression of a process present to a greater or lesser extent in all of us. The Framingham study2 links increasing morbidity and mortality just as closely with increasing blood-pressure for groups conventionally regarded "normotensive" as for those conventionally "hypertensive". Is it not time for the 80-year-old disease status of hypertension to be ended? In his Hunterian Society lecture of 1895,3 Sir Clifford Allbutt used the term arterial "hyperpiesis", the forerunner of hypertension, to denote patients who, in the absence of renal disease, were found to have a hard pulse. In their presentation, the 5 patients described had, in fact, little else in common: 2 experienced depression, 2 nervousness, and 2 did eventually have fatal heart-failure. However, all 5 responded symptomatically and with coincident blood-pressure reduction to dietary modification, oral administration of mercurials, potassium iodine, and spa water-observations which would nowadays face value. Although he took many sphygthese recordings in favour of a clinical estimate of the state of the pulse; but there is little doubt that a contemporaneous description of the first practical sphygmomanometer by Riva-Rocci4 was also responsible for be hard
to
accept
mograms, Allbutt
at
rejected
promoting widespread diagnosis of hypertension. The pulse-rate, cardiac output, and other quantitative clinical characteristics are not regarded as disease criteria. Sphygmomanometer readings, too, might be better regarded objectively; in the simple assessment of prognosis and in monitoring response to therapeutic measures. Attempting to reduce (treat) a risk factor hardly necessitates according it the status of a disease. of Health and Social London SE1 6TE
Department
RHEUMATOID ARTHRITIS AND ALPHA-1-ANTITRYPSIN
Security,
RAYMOND CARLISLE
CORTICOSTEROID SUSPENSIONS FOR INIECTION -
SIR,-Cox and Hubers claim
R. T. BENN PHILIP H. N. WOOD
significant association between the alpha-1-antitrypsin Pi type Z allele and rheumatoid arthritis in adults, with a p value of
phenotype
known
as
with Yates’s correction leads to a result O.1O>p>O.05 one-tail test. However, the expected trequency in the upper left cell of the table is 2-5, so the X. test is scarcely appropriate. Fisher’s exact test yields a one-tail probability P=0.073. We conclude that it is premature to suggest an association between heterozygosity for the Z allele of alpha-1-antitrypsin and classical or definite rheumatoid arthritis.
x2
Che-
diak-Higashi syndrome.
on a
This research was made possible through a grant from the National Foundation-March of Dimes and National Institute of Health training grant, 5 T01 GMO 1918-07. Department of Medicine, HINDS
KRISTIN B. SHANNON DANES
Cornell University Medical College, New
York, N.Y. 10021, U.S.A.
Arthritis and Rheumatism Council Epidemiology Research Unit, Stopford Building (University of Manchester), Manchester M13 9PT
DIAGNOSIS OF PYOGENIC MENINGITIS
SIR,-Commenting on the usefulness of countercurrentimmunoelectrophoresis (C.I.E.) in bacterial meningitis’ you state that "previous antibiotic treatment has little effect on the success-rate ofc.f.E.—an important advantage over culture." What is the evidence for such a claim? Though there have been isolated examples2-4 of positive C.I.E. in pretreated pyogenic meningitis with negative bacteriology, our experience with this test has not been encouraging in the occasional diagnostic problems of partially treated bacterial meningitis-a problem that tends to be overemphasised, as you pointed out earlier.s In a study6 of 62 patients admitted to this unit with bacterial meningitis, 23 (37%) of whom had received pre-diagnosis antibiotic therapy, positive bacteriological diagnosis could be achieved in 73% of the partially treated group as opposed to 97% in the previously untreated group, characteristic cerebrospinal fluid (c.s.F.) changes sufficient for diagnostic purpose being present in all but 1 case. The C.S.F. was examined for bacterial antigen by C.I.E. in 11 patients and was positive in 5, all of whom also had positive bacteriology. In all 6 cases, where the conventional bacteriology was negative, the C.LE. also proved negative. 5 patients in this latter group were judged to have meningococcal infections on the basis of the characteristic rash or serology. In my limited experience, a few low oral doses of the commonly used antibiotics rarely cause diagnostic problems in pneumococcal or "H. influenzal" meningitis and in the post-neonatal age-group, I agree with Christie’ that the "negative" cases can generally be regarded as partially treated cases of meningococcal meningitis. Thus far, there is little evidence to indicate a definite advantage of C.I.E. over conventional bacteriology in these problematic cases. Regional Department Monsall Hospital,
of Infectious Diseases
B. K. MANDAL
Manchester 10
HYPERTENSION NO LONGER A DISEASE?
SIR,-Brown et al-argue convincingly that essential hypertension is the expression of a process present to a greater or lesser extent in all of us. The Framingham study2 links increasing morbidity and mortality just as closely with increasing blood-pressure for groups conventionally regarded "normotensive" as for those conventionally "hypertensive". Is it not time for the 80-year-old disease status of hypertension to be ended? In his Hunterian Society lecture of 1895,3 Sir Clifford Allbutt used the term arterial "hyperpiesis", the forerunner of hypertension, to denote patients who, in the absence of renal disease, were found to have a hard pulse. In their presentation, the 5 patients described had, in fact, little else in common: 2 experienced depression, 2 nervousness, and 2 did eventually have fatal heart-failure. However, all 5 responded symptomatically and with coincident blood-pressure reduction to dietary modification, oral administration of mercurials, potassium iodine, and spa water-observations which would nowadays face value. Although he took many sphygthese recordings in favour of a clinical estimate of the state of the pulse; but there is little doubt that a contemporaneous description of the first practical sphygmomanometer by Riva-Rocci4 was also responsible for be hard
to
accept
mograms, Allbutt
at
rejected
promoting widespread diagnosis of hypertension. The pulse-rate, cardiac output, and other quantitative clinical characteristics are not regarded as disease criteria. Sphygmomanometer readings, too, might be better regarded objectively; in the simple assessment of prognosis and in monitoring response to therapeutic measures. Attempting to reduce (treat) a risk factor hardly necessitates according it the status of a disease. of Health and Social London SE1 6TE
Department
RHEUMATOID ARTHRITIS AND ALPHA-1-ANTITRYPSIN
Security,
RAYMOND CARLISLE
CORTICOSTEROID SUSPENSIONS FOR INIECTION -
SIR,-Cox and Hubers claim
R. T. BENN PHILIP H. N. WOOD
significant association between the alpha-1-antitrypsin Pi type Z allele and rheumatoid arthritis in adults, with a p value of
