1380 BARORECEPTORS AND HIGH BLOOD-PRESSURE
Sir,-In your June 16 editorial you cite
an article by and Lumley in support of the statement: "The increase in arterial distensibility which followed endarterectomy caused a rise in the electrical output from the sinus nerve and an early postoperative decrease in blood-pressure". However, these workers reported a reduction in arterial distensi-
Angell-James
bility following endarterectomy. Lutheran Medical Center, Brookly, N.Y. 11220, U.S.A.
diagnosis
of
acute
EPIDEMIOLOGY OF NON-A, NON-B HEPATITIS
SIR,-Dr Farrow and colleagues (Aug. 11, p. 300) reported "sporadic" non-A, non-B hepatitis in 4.3% of hepatitis patients in West London. We have looked for serological markers of hepatitis A and B viruses (Abbott tests) in 243 patients admitted to hospital with viral hepatitis in the year ended Sept. 1, 1979 (see table). 50.6% were positive for HBsAg; and 2 others were positive for HBcAb only, showing that they too had type B hepatitis (HBsAb was detected during recovery). In 30-5% of cases hepatitis A was diagnosed (see below). EpsteinBarr virus and
cytomegalovirus hepatitis were excluded in the by immunofluorescence and complement fixation tests, respectively. This left 44 cases (18.1%) considered to be non-A, non-B hepatitis. cases
HEPATITIS TYPES IN MILAN INPATIENTS
Of the 44 cases of non-A, non-B hepatitis 20 were associated with transfusion, 14 with drug abuse, 2 with contact, and 1 with shellfish; in 7 cases no possible source for the hepatitis could be identified. Thus most cases of non-A, non-B hepatitis (7%) had a history of parenteral exposure. However, in the other 23% the hepatitis seems to have been transmitted by a
non-parenteral route. On Farrow’s criteria 3.3% (8 out of 243) of our inpatients hepatitis had the sporadic non-A, non-B variety. 2 cases a gave history of contact with hepatitis but it has not been possible to screen the index cases. Since the commercial HAAb diagnostic test (’HAVAB’; Abbott) was much discussed in your correspondence columns earlier this year we would like to record in greater detail our experience of this test in our inpatient series. After a first run with undiluted sera, positive cases were verified at serial dilutions. In 50 cases (68%) a fourfold rise in antibody titres permit-
type-A hepatitis
recovery. In all
cases
counts/min is
DOREEN KNOPMACHER
ty.-ED.L.
with
a
patient’s
between titre and titration.
***Angell-James and Lumley reported that the carotid sinus diameter at equivalent pressure was greater after endarterectomy in 7 of 11 patients, which might be interpreted as an increase in distensibility. They did report a decrease in distensibility when measurements of pressure and diameter change were taken over the prevailing pulse pressures. However, the pressure-volume relation is curvilinear; it is difficult to compare stiffness of vessels at different starting diameters. Had the vessels been examined at different pressures and/or volume ranges, the calculated "stiffness" might have been quite different. What Angell-James and Lumley have really shown is that after endarterectomy the vessels were bigger and operating then at the plateau of their pressure-volume curve. They were measuring volume distensibility not absolute distensibili-
remaining
to be made before the there was a significant rise in HAAb titre between acute and convalescent (8 week) sera. In the absence of an IgM-specific antibody test we think that the HAVAB test is useful for diagnostic purposes and we find that only three titres (1:64, 1:128, and 1:256) are necessary to demonstrate a significant increase in antibody levels. We agree with other correspondents that the inverse proportionality
ted
Infectious Diseases Clinic, University of Milan, L. Sacco Hospital, 20157 Milan, Italy
too
crude
to
replace detailed
F. CAREDDA A. D’ARMINIO MONFORTE S. LOPEZ D. CULRARO M. MORONI
ISOLATION OF TRANSMISSIBLE CYTOPATHIC AGENT FROM BONE-MARROW OF PATIENT WITH MULTIPLE SCLEROSIS
!iR,—That a transmissible agent is present in multiple sclerosis (MS) bone-marrow has aroused a lot of interest.1-5 Using the exact procedure described by Mitchell et al.’ we have examined seven MS marrow biopsy specimens, 3 MS marrow specimens obtained at necropsy, and 2 marrow biopsy specimens from patients with motor neurone disease and from 2 non-neurological controls. All the MS patients fulfilled the accepted criteria for the disease.6 When inoculated on to either Vero, HEp2, human embryonic lung (HEL), or pig-kidney (PK15) cells both untreated and lysolecithin-treated samples from all sources produced rounding up of some cells within 24 h, and this effect became more pronounced during the next 4 days. Serial transmission of each culture after freeze-thawing, however, revealed only one sample (MS1, biopsy) capable of reproducing the cytopathic effect regularly. This sample did occasionally fail to produce the expected cellular changes. This sample produced the cytopathic effect most frequently in Vero cells. All of the other samples produced cytopathic effects only intermittently and this was never sustained beyond the third serial passage. We failed to isolate myocoplasma-like organisms from MS1 infected cells using agar plates which supported the growth of Mycoplasma hyorhinis and M. laidlawii. Furthermore Vero cells infected and damaged by MS 1 produced no immunofluorescence with either M. hyorhinis or M. laidlawii antisera in indirect immunofluorescence tests. The appearance of the cytopathic effect in Vero cells is shown in fig. (a) and uninfected cells are shown in fig. (b). Electronmicroscopy of parallel cultures revealed dense bodies approximately 200-400 nm in diameter and of indeterminate length, on the outside surfaces of cells or being pinocytosed (fig. c) and in the spaces between contiguous cells (fig. d). Also occasionally visible were bodies with the membrane and DNA structures characteristic of mycoplasma. The tubular structures observed in HEp2 cells by Mitchell et al.’ were not found in our Vero cultures but are often found in uninfected HEp2 cells. Using Millipore membrane filters we found that the transmissible agent at the fifth serial passage readily passed 1. Mitchell DN, Porterfield JS, Micheletti R, et al. Isolation of an infectious agent from bone-marrows of patients with multiple sclerosis. Lancet 1978; ii: 387-90. 2. Tyrrell DAJ, Perry RP, Crow TJ, et al. Possible virus in schizophrenia and some neurological disorders. Lancet 1979; i: 839-41. 3. Mitchell DN, Goswami KKA, Taylor P, et al. Failure to isolate a transmissible agent from the bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 415-16. 4. Wallen WC, Sever JL, McFarlin DE, et al. Attempt to isolate infectious agent from bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 414-15. 5. Huddlestone JR, Sipe J, Braheny S, et al. Failure to isolate a transmissible agent from the bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 415. 6. McDonald WI, Halliday AM. Diagnosis and classification of multiple sclerosis. Br Med Bull 1977; 33: no. 1: 4-8.
Sir,-In your June 16 editorial you cite
an article by and Lumley in support of the statement: "The increase in arterial distensibility which followed endarterectomy caused a rise in the electrical output from the sinus nerve and an early postoperative decrease in blood-pressure". However, these workers reported a reduction in arterial distensi-
Angell-James
bility following endarterectomy. Lutheran Medical Center, Brookly, N.Y. 11220, U.S.A.
diagnosis
of
acute
EPIDEMIOLOGY OF NON-A, NON-B HEPATITIS
SIR,-Dr Farrow and colleagues (Aug. 11, p. 300) reported "sporadic" non-A, non-B hepatitis in 4.3% of hepatitis patients in West London. We have looked for serological markers of hepatitis A and B viruses (Abbott tests) in 243 patients admitted to hospital with viral hepatitis in the year ended Sept. 1, 1979 (see table). 50.6% were positive for HBsAg; and 2 others were positive for HBcAb only, showing that they too had type B hepatitis (HBsAb was detected during recovery). In 30-5% of cases hepatitis A was diagnosed (see below). EpsteinBarr virus and
cytomegalovirus hepatitis were excluded in the by immunofluorescence and complement fixation tests, respectively. This left 44 cases (18.1%) considered to be non-A, non-B hepatitis. cases
HEPATITIS TYPES IN MILAN INPATIENTS
Of the 44 cases of non-A, non-B hepatitis 20 were associated with transfusion, 14 with drug abuse, 2 with contact, and 1 with shellfish; in 7 cases no possible source for the hepatitis could be identified. Thus most cases of non-A, non-B hepatitis (7%) had a history of parenteral exposure. However, in the other 23% the hepatitis seems to have been transmitted by a
non-parenteral route. On Farrow’s criteria 3.3% (8 out of 243) of our inpatients hepatitis had the sporadic non-A, non-B variety. 2 cases a gave history of contact with hepatitis but it has not been possible to screen the index cases. Since the commercial HAAb diagnostic test (’HAVAB’; Abbott) was much discussed in your correspondence columns earlier this year we would like to record in greater detail our experience of this test in our inpatient series. After a first run with undiluted sera, positive cases were verified at serial dilutions. In 50 cases (68%) a fourfold rise in antibody titres permit-
type-A hepatitis
recovery. In all
cases
counts/min is
DOREEN KNOPMACHER
ty.-ED.L.
with
a
patient’s
between titre and titration.
***Angell-James and Lumley reported that the carotid sinus diameter at equivalent pressure was greater after endarterectomy in 7 of 11 patients, which might be interpreted as an increase in distensibility. They did report a decrease in distensibility when measurements of pressure and diameter change were taken over the prevailing pulse pressures. However, the pressure-volume relation is curvilinear; it is difficult to compare stiffness of vessels at different starting diameters. Had the vessels been examined at different pressures and/or volume ranges, the calculated "stiffness" might have been quite different. What Angell-James and Lumley have really shown is that after endarterectomy the vessels were bigger and operating then at the plateau of their pressure-volume curve. They were measuring volume distensibility not absolute distensibili-
remaining
to be made before the there was a significant rise in HAAb titre between acute and convalescent (8 week) sera. In the absence of an IgM-specific antibody test we think that the HAVAB test is useful for diagnostic purposes and we find that only three titres (1:64, 1:128, and 1:256) are necessary to demonstrate a significant increase in antibody levels. We agree with other correspondents that the inverse proportionality
ted
Infectious Diseases Clinic, University of Milan, L. Sacco Hospital, 20157 Milan, Italy
too
crude
to
replace detailed
F. CAREDDA A. D’ARMINIO MONFORTE S. LOPEZ D. CULRARO M. MORONI
ISOLATION OF TRANSMISSIBLE CYTOPATHIC AGENT FROM BONE-MARROW OF PATIENT WITH MULTIPLE SCLEROSIS
!iR,—That a transmissible agent is present in multiple sclerosis (MS) bone-marrow has aroused a lot of interest.1-5 Using the exact procedure described by Mitchell et al.’ we have examined seven MS marrow biopsy specimens, 3 MS marrow specimens obtained at necropsy, and 2 marrow biopsy specimens from patients with motor neurone disease and from 2 non-neurological controls. All the MS patients fulfilled the accepted criteria for the disease.6 When inoculated on to either Vero, HEp2, human embryonic lung (HEL), or pig-kidney (PK15) cells both untreated and lysolecithin-treated samples from all sources produced rounding up of some cells within 24 h, and this effect became more pronounced during the next 4 days. Serial transmission of each culture after freeze-thawing, however, revealed only one sample (MS1, biopsy) capable of reproducing the cytopathic effect regularly. This sample did occasionally fail to produce the expected cellular changes. This sample produced the cytopathic effect most frequently in Vero cells. All of the other samples produced cytopathic effects only intermittently and this was never sustained beyond the third serial passage. We failed to isolate myocoplasma-like organisms from MS1 infected cells using agar plates which supported the growth of Mycoplasma hyorhinis and M. laidlawii. Furthermore Vero cells infected and damaged by MS 1 produced no immunofluorescence with either M. hyorhinis or M. laidlawii antisera in indirect immunofluorescence tests. The appearance of the cytopathic effect in Vero cells is shown in fig. (a) and uninfected cells are shown in fig. (b). Electronmicroscopy of parallel cultures revealed dense bodies approximately 200-400 nm in diameter and of indeterminate length, on the outside surfaces of cells or being pinocytosed (fig. c) and in the spaces between contiguous cells (fig. d). Also occasionally visible were bodies with the membrane and DNA structures characteristic of mycoplasma. The tubular structures observed in HEp2 cells by Mitchell et al.’ were not found in our Vero cultures but are often found in uninfected HEp2 cells. Using Millipore membrane filters we found that the transmissible agent at the fifth serial passage readily passed 1. Mitchell DN, Porterfield JS, Micheletti R, et al. Isolation of an infectious agent from bone-marrows of patients with multiple sclerosis. Lancet 1978; ii: 387-90. 2. Tyrrell DAJ, Perry RP, Crow TJ, et al. Possible virus in schizophrenia and some neurological disorders. Lancet 1979; i: 839-41. 3. Mitchell DN, Goswami KKA, Taylor P, et al. Failure to isolate a transmissible agent from the bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 415-16. 4. Wallen WC, Sever JL, McFarlin DE, et al. Attempt to isolate infectious agent from bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 414-15. 5. Huddlestone JR, Sipe J, Braheny S, et al. Failure to isolate a transmissible agent from the bone-marrow of patients with multiple sclerosis. Lancet 1979; ii: 415. 6. McDonald WI, Halliday AM. Diagnosis and classification of multiple sclerosis. Br Med Bull 1977; 33: no. 1: 4-8.
