- Email: [email protected]
RAPID INFLUENZA DIAGNOSIS
1193 EFFECT OF CENTRIFUGE SPEED ON VIRUS CLUMPING
versely proportional to the gravitational force (table). Frequently these clumps are larger than the bacteria in the sample. Thus even at modest g forces a substantial proportion of the total virus is lost in the pellet. At the higher g forces routinely used to clarify fsecal suspensions most of the virus remaining in the supernatant will be seen as single particles or in twos and threes. Routine preparation of grids from this material by pelleting in the ultracentrifuge followed by dipping the grids in the resuspended pellet for examination in the electronmicroscope would fail to indicate the pre-existence of clumped virus; and furthermore any counting technique based on the method would grossly underestimate the true particle count. Immune electronmicroscopy has proved a useful technique for typing viruses, particularly from tissue culture,5 but it requires that the virus exists as single particles in suspension and that agglutination occurs when specific antisera is added. There is no reason to suppose that our observations are restricted to the properties of a single strain of rotavirus since the specimens examined were collected from different outbreaks and from sporadic cases, over a season. Public Health Laboratory, Institute of Pathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
in contrast to the more lasting action on serum alkaline phosphatase,2,3 is not a promising trend. The opposite changes are seen after calcitonin withdrawal .4 Osteolytic or not, Paget’s disease will always be a controversial indication for mithramycin because of toxicity. We,5 and many others, have noticed transient signs of hepatotoxicity. Although permanent liver dysfunction has not been observed, we cannot be sure that this will not happen in the sensitive patient. To our knowledge, liver biopsy before and after courses of mithramycin have not been done. A 25 g/kg infusion given intraperitoneally every other day for 2 months to a growing rabbit produces hepatic central lobular necrosis in every case, and renal proximal tubular degeneration.6 In man, mithramycin has been given at the same concentration twice weekly for up to 5 months.’ Nephrotoxicity is the other serious problem, since 5 % of the cases show transient signs of deterioration of renal function, with persistent impairment in 2% of cases.’ This is. not acceptable, when alternative treatments are available. Calcitonin is expensive. However, to the cost of mithramycin must be added the cost of monitoring the patient during the perfusions, of checking liver and kidney function, and of complete blood counts so that the perfusions can be halted or postponed in time to prevent side-effects. Furthermore, the number of patients who really need calcitonin for Paget’s disease is small. C. NAGANT de DEUXCHAISNES
hydroxyproline excretion,
C. ROMBOUTS-LINDEMANS
Rheumatology Unit and Departments of Medicine and Radiology, Louvain University in Brussels, St-Luc University Hospital, B-1200 Brussels, Belgium
J. P. HUAUX J. P. DEVOGELAER J. MALGHEM B. MALDAGUE
H. K. NARANG A. A. CODD RAPID INFLUENZA DIAGNOSIS
CALCITONIN OR MITHRAMYCIN FOR PAGET’S DISEASE
SIR,-Dr Russell (April 19, p. 884) criticises us for favouring (Feb. 16, p. 374) calcitonin rather than mithramycin as the most rational therapeutic approach in Paget’s disease, pointing out that mithramycin is cheaper, effective in relieving pain, and relatively safe. He has misread our letter; we proposed calthe agent of choice in osteolytic Paget’s disease. If is to be useful in this condition it should, as we stressed, induce a positive focal bone balance as seen on X-rays of the affected bones, This was noticed in only 2 out of 150 patients so treated by Ryan,’ but we are not told in how many patients this was looked for nor how many of them lent themselves to such an analysis. We have achieved a positive total bone balance in all 10 patients given calcitonin. Pain is one problem in Paget’s disease, but bone strength should also be taken into consideration, as should the possibility of arresting an osteolytic advancing front progressing towards a joint space or petrous bone. If pain can be relieved while the bone is strengthened and the disease process is being controlled, this does represent a distinct advantage. We are not saying that mithramycin cannot achieve this-merely that it has not yet been proved to do so. The transitory effect of mithramycin on
citonin
as
a treatment
5.
Narang HK, Codd AA. Enterovirus typing by immune electron microscopy using low-speed centrifugation. J Clin Pathol 1980; 33: 191-94. 1. Ryan WG. Treatment of Paget’s disease of bone with mithramycin. Clin Orthop 1977; 127: 106-10.
SIR,-We must welcome the development of new and more sensitive rapid diagnostic methods such as the new enzyme immunoassays reported by Dr Berg and his colleagues (April 19, p. 851). Unlike conventional fluorescent antibody tests, the new techniques promise the distinct advantage of being applicable to the type of respiratory specimen which can be readily collected from adults. Meantime, while outbreaks of influenza in geriatric units are of topical concern, it may be useful to remind clinicians that specific diagnosis of such outbreaks can usually be given within 24 h provided that adequately representative blood samples are sent to the laboratory from groups of patients with long and short periods of illness.I Department of Infectious Diseases, University of Glasgow, Ruchill Hospital, Glasgow G20 9NB
2. Condon JR, Reith SBM, Nassim JR, Millard Treatment of Paget’s disease of bone with
N. R. GRIST
FJC, Hilb A, Stainthorpe EM. mithramycin. Br J Med 1971;
i: 421-3. 3. Aitken JM, Lindsay R. Mithramycin in Paget’s disease. Lancet 1973; i: 1177-8. 4. Avramides A, Flores A, DeRose J, Wallach S. Paget’s disease of the bone: Observations after cessation of long-term synthetic salmon calcitonin treatment. J Clin Endocr Metab 1976; 42: 459-63. 5. Nagant de Deuxchaisnes C, Dercq JP, Devogelaer JP, Huaux JP, RomboutsLindemans C. Traitement de la maladie de Paget au moyen d’immunosuppresseurs et de mithramycine. In: Hioco DJ. La Maladie de Paget. Paris: Armour Montagu, 1974: 228-31. 6. Robins PR, Jowsey J. Effect of mithramycin on normal and abnormal bone turnover. J Lab Clin Med 1973; 82: 576-86. 7. Lebbin D, Ryan WG, Schwartz TB. Outpatient treatment of Paget’s disease of bone with mithramycin. Ann Intern Med 1974; 81: 635-37. 1. Gnst NR. Rapid serological diagnosis of outbreaks of influenza. Br Med J 1976; i: 581.
versely proportional to the gravitational force (table). Frequently these clumps are larger than the bacteria in the sample. Thus even at modest g forces a substantial proportion of the total virus is lost in the pellet. At the higher g forces routinely used to clarify fsecal suspensions most of the virus remaining in the supernatant will be seen as single particles or in twos and threes. Routine preparation of grids from this material by pelleting in the ultracentrifuge followed by dipping the grids in the resuspended pellet for examination in the electronmicroscope would fail to indicate the pre-existence of clumped virus; and furthermore any counting technique based on the method would grossly underestimate the true particle count. Immune electronmicroscopy has proved a useful technique for typing viruses, particularly from tissue culture,5 but it requires that the virus exists as single particles in suspension and that agglutination occurs when specific antisera is added. There is no reason to suppose that our observations are restricted to the properties of a single strain of rotavirus since the specimens examined were collected from different outbreaks and from sporadic cases, over a season. Public Health Laboratory, Institute of Pathology, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
in contrast to the more lasting action on serum alkaline phosphatase,2,3 is not a promising trend. The opposite changes are seen after calcitonin withdrawal .4 Osteolytic or not, Paget’s disease will always be a controversial indication for mithramycin because of toxicity. We,5 and many others, have noticed transient signs of hepatotoxicity. Although permanent liver dysfunction has not been observed, we cannot be sure that this will not happen in the sensitive patient. To our knowledge, liver biopsy before and after courses of mithramycin have not been done. A 25 g/kg infusion given intraperitoneally every other day for 2 months to a growing rabbit produces hepatic central lobular necrosis in every case, and renal proximal tubular degeneration.6 In man, mithramycin has been given at the same concentration twice weekly for up to 5 months.’ Nephrotoxicity is the other serious problem, since 5 % of the cases show transient signs of deterioration of renal function, with persistent impairment in 2% of cases.’ This is. not acceptable, when alternative treatments are available. Calcitonin is expensive. However, to the cost of mithramycin must be added the cost of monitoring the patient during the perfusions, of checking liver and kidney function, and of complete blood counts so that the perfusions can be halted or postponed in time to prevent side-effects. Furthermore, the number of patients who really need calcitonin for Paget’s disease is small. C. NAGANT de DEUXCHAISNES
hydroxyproline excretion,
C. ROMBOUTS-LINDEMANS
Rheumatology Unit and Departments of Medicine and Radiology, Louvain University in Brussels, St-Luc University Hospital, B-1200 Brussels, Belgium
J. P. HUAUX J. P. DEVOGELAER J. MALGHEM B. MALDAGUE
H. K. NARANG A. A. CODD RAPID INFLUENZA DIAGNOSIS
CALCITONIN OR MITHRAMYCIN FOR PAGET’S DISEASE
SIR,-Dr Russell (April 19, p. 884) criticises us for favouring (Feb. 16, p. 374) calcitonin rather than mithramycin as the most rational therapeutic approach in Paget’s disease, pointing out that mithramycin is cheaper, effective in relieving pain, and relatively safe. He has misread our letter; we proposed calthe agent of choice in osteolytic Paget’s disease. If is to be useful in this condition it should, as we stressed, induce a positive focal bone balance as seen on X-rays of the affected bones, This was noticed in only 2 out of 150 patients so treated by Ryan,’ but we are not told in how many patients this was looked for nor how many of them lent themselves to such an analysis. We have achieved a positive total bone balance in all 10 patients given calcitonin. Pain is one problem in Paget’s disease, but bone strength should also be taken into consideration, as should the possibility of arresting an osteolytic advancing front progressing towards a joint space or petrous bone. If pain can be relieved while the bone is strengthened and the disease process is being controlled, this does represent a distinct advantage. We are not saying that mithramycin cannot achieve this-merely that it has not yet been proved to do so. The transitory effect of mithramycin on
citonin
as
a treatment
5.
Narang HK, Codd AA. Enterovirus typing by immune electron microscopy using low-speed centrifugation. J Clin Pathol 1980; 33: 191-94. 1. Ryan WG. Treatment of Paget’s disease of bone with mithramycin. Clin Orthop 1977; 127: 106-10.
SIR,-We must welcome the development of new and more sensitive rapid diagnostic methods such as the new enzyme immunoassays reported by Dr Berg and his colleagues (April 19, p. 851). Unlike conventional fluorescent antibody tests, the new techniques promise the distinct advantage of being applicable to the type of respiratory specimen which can be readily collected from adults. Meantime, while outbreaks of influenza in geriatric units are of topical concern, it may be useful to remind clinicians that specific diagnosis of such outbreaks can usually be given within 24 h provided that adequately representative blood samples are sent to the laboratory from groups of patients with long and short periods of illness.I Department of Infectious Diseases, University of Glasgow, Ruchill Hospital, Glasgow G20 9NB
2. Condon JR, Reith SBM, Nassim JR, Millard Treatment of Paget’s disease of bone with
N. R. GRIST
FJC, Hilb A, Stainthorpe EM. mithramycin. Br J Med 1971;
i: 421-3. 3. Aitken JM, Lindsay R. Mithramycin in Paget’s disease. Lancet 1973; i: 1177-8. 4. Avramides A, Flores A, DeRose J, Wallach S. Paget’s disease of the bone: Observations after cessation of long-term synthetic salmon calcitonin treatment. J Clin Endocr Metab 1976; 42: 459-63. 5. Nagant de Deuxchaisnes C, Dercq JP, Devogelaer JP, Huaux JP, RomboutsLindemans C. Traitement de la maladie de Paget au moyen d’immunosuppresseurs et de mithramycine. In: Hioco DJ. La Maladie de Paget. Paris: Armour Montagu, 1974: 228-31. 6. Robins PR, Jowsey J. Effect of mithramycin on normal and abnormal bone turnover. J Lab Clin Med 1973; 82: 576-86. 7. Lebbin D, Ryan WG, Schwartz TB. Outpatient treatment of Paget’s disease of bone with mithramycin. Ann Intern Med 1974; 81: 635-37. 1. Gnst NR. Rapid serological diagnosis of outbreaks of influenza. Br Med J 1976; i: 581.