- Email: [email protected]
GLOMERULONEPHRITIS AND ORGANIC SOLVENTS
566 or
previous operations), excluding patients if they exhibited physiological changes suggesting established bacteraemia. This procedure should have had a normalising effect on the study
(2) Exposure to organic solvents: a missing link in poststreptococcal glomerulonephritis? Acta Med Scand 1978; 203: 351-56. (3) Glomerulonephritis and exposure to organic solvents: a case-control study.
population with respect to the variables that Knaus is most worried
Acta Med Scand 1979; 205: 575-79.
about.
(4) Improvement
Moreover, the APS injury severity score is not the only factor that correlates with hospital mortality. More importantly, when dealing with gram-negative infections, a clear-cut relation was found as early as 1962 by McCabe and Jackson between the severity of preexisting disease (well balanced in our study) and outcome of infection. Furthermore, in a study like ours it was very important to look at the site of infection and the type of bacteria, two obviously critical factors for outcome. Thus, stratification of patients at randomisation ensured that the type and severity of surgery were comparable in the two groups, and criteria for outcome of infection were shown to be well balanced. Good evidence that risk factors were equally distributed is the fact that the deaths from causes not related to gram-negative shock were similar in the two groups. We therefore feel that it is legitimate to draw conclusions about the prophylactic efficacy of anti-endotoxin antibody in these patients. We question whether the p values of O. 017 and 0 - 006 in the abdominal surgery patients ought to be termed "marginal statistical differences", especially when they are corroborated by
logistic regression analysis. Dr Freeman and Dr Gould show that the presence of antibody to endotoxin was associated with a lower incidence of postoperative gram-negative urinary tract infections. We did not find a reduction of the incidence of focal gram-negative infections, but cannot comment on this difference between the two studies because Freeman and Gould do not provide information on the endotoxin antigens they used for measuring anti-endotoxin antibody. Antibodies against 0 antigens are expected to behave differently from antibody against core glycolipid. Dr Burden may have mistaken our explanatory study for a pragmatic trial. As Schwartz et al2 have pointed out, with a pragmatic approach the appropriate type of patient is determined in general terms by the population to which the results of the trial will be applied. With an explanatory approach, the type of patient may be specifically chosen to be that which will display a well-defined biological feature. Our study was undertaken to see if the beneficial effect of anti-endotoxin treatment in patients with established gramnegative bacteraemia3 could be seen in high-risk patients treated prophylactically, before bloodstream infection has developed. We showed that immune plasma did not prevent acquisition of gramnegative infection in the group as a whole but it improved the course of the gram-negative infections that did occur. Since patients died from conditions other than gram-negative infections protection would not be expected to be demonstrable in the entire group, but only in those with gram-negative infections. Such statistical considerations do not diminish the potential value of anti-coreglycolipid antibody in surgical patients at high risk of death from endotoxin shock. Division of Infectious Diseases, Department of Internal Medicine, CHU Vaudois, 1011 Lausanne, Switzerland Division of Infectious Diseases, University of California, San Diego, School of Medicine, San Diego, California, USA
JEAN DANIEL BAUMGARTNER MICHEL P. GLAUSER
ELISABETH J. ZIEGLER J. ALLEN MCCUTCHAN MELVILLE R. KLAUBER
1. McCabe WR, Jackson GG. Gram-negative bacteremia. I. Etiology and ecology. Arch Intern Med 1962; 110: 847-55 2. Schwartz D, Flamant R, Lellouch J. Clinical trials. London: Academic Press, 1980: 58. 3. Ziegler EJ, McCutchan JA, Fierer J, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 1982; 307: 1225-30.
exposure. Lancet
of
glomerulonephritis after discontinuation of
solvent
1979; i: 1194.
(5) Hydrocarbon exposure and glomerulonephritis: occupations. Lancet 1983; ii: 1214-16.
Evidence from patients’
(2)-(5) deal with organic solvents and glomerulonephritis. Dr Ravnskov was the main author of the publications but had coworkers in (1), (3), (4), and (5). (4) is a letter heralding a paper in the Quarterly Journal of Medicine and gives a summary of the abstract in that paper. This Q 7M paper was withdrawn in 1979 shortly before publication because of my discovery of serious faults in it. Simultaneously a similar paper sent to Läkartidningen (Swedish) was withdrawn. Data in case-records and exposure protocols have been reviewed the dean and vice-dean of the Medical Faculty, University of Lund, together with me and in the presence of Dr Ravnskov. The deans confirmed that there were many serious discrepancies between the statements in the Q,7M article and the facts. Discrepancies were found in the description of methods and in the work-up of the clinical material. The deans concluded that it was reasonable that I, as head of the department, had lost confidence in Dr Ravnskov. Some months later he resigned from my department. His 1983 paper (5) falsely gave the department of nephrology in Lund as the responsible institution.
by
Papers (1), (2), (3), and (5) have been scrutinised similarly and parts of the same patient material. The description of methods and patient selection deviates from the procedure used, many laboratory data are incorrect, and the case histories given do not always accord with the case records. These articles do not meet the usual standards required for publication in medical journals and I regret that they have been repeatedly cited in other publications on the same topics. cover
This letter has been Medical Faculty.
sent
after consultation with the dean of the
Department of Nephrology, University Hospital, S-221 85 Lund, Sweden
letter has been shown follows.-ED. L.
**This
ULLA BENGTSSON
to
Dr
Ravnskov, whose reply
SIR,-It is correct that a paper accepted for publication in the Quarterly Journal of Medicine in 1979 on glomerulonephritis and organic solvents had serious faults, and I am grateful to Professor Bengtsson for having discovered these faults. But all that I have published on this subject is correct, irrespective of her accusations. Professor Bengtsson has the view that the medical records of her department are her personal property. We found it proper to give the name of the institution where the main part of the studyl was done and where the records were kept. Our 1983 paper clearly states that none of the authors was affiliated to the department of nephrology in Lund at the time of publication. Professor Bengtsson does not mention that her consultation with ProfChrister Owman, the present dean of the Medical Faculty, was a failure. The dean found no reason to interfere in a scientific
disagreement. I invite Professor Bengtsson to participate in research on the causation of glomerulonephritis instead of spending her time on libel and personal persecution. For a start she could read the paper which she failed to stop.2 Olsh6gsv 14,
GLOMERULONEPHRITIS AND ORGANIC SOLVENTS
SIR,-I refer to the following publications on glomerulonephritis written
by Dr Uffe Ravnskov:
(1) Treatment of glomerulonephritis with drainage of the thoracic duct and plasmapheresis. Acta Med Scand 1977; 202: 489-94.
U. RAVNSKOV
S-223 60 Lund, Sweden
1 Ravnskov
U, Lundström S, Nordén A Hydrocarbon exposure and glomerulonephritis: Evidence from patients’ occupations. Lancet 1983; ii: 1214-16.
2. Ravnskov U. Possible
Nephrol 1985; 23:
mechanisms of hydrocarbon-associated glomerulonephritis Clin 284-98.
previous operations), excluding patients if they exhibited physiological changes suggesting established bacteraemia. This procedure should have had a normalising effect on the study
(2) Exposure to organic solvents: a missing link in poststreptococcal glomerulonephritis? Acta Med Scand 1978; 203: 351-56. (3) Glomerulonephritis and exposure to organic solvents: a case-control study.
population with respect to the variables that Knaus is most worried
Acta Med Scand 1979; 205: 575-79.
about.
(4) Improvement
Moreover, the APS injury severity score is not the only factor that correlates with hospital mortality. More importantly, when dealing with gram-negative infections, a clear-cut relation was found as early as 1962 by McCabe and Jackson between the severity of preexisting disease (well balanced in our study) and outcome of infection. Furthermore, in a study like ours it was very important to look at the site of infection and the type of bacteria, two obviously critical factors for outcome. Thus, stratification of patients at randomisation ensured that the type and severity of surgery were comparable in the two groups, and criteria for outcome of infection were shown to be well balanced. Good evidence that risk factors were equally distributed is the fact that the deaths from causes not related to gram-negative shock were similar in the two groups. We therefore feel that it is legitimate to draw conclusions about the prophylactic efficacy of anti-endotoxin antibody in these patients. We question whether the p values of O. 017 and 0 - 006 in the abdominal surgery patients ought to be termed "marginal statistical differences", especially when they are corroborated by
logistic regression analysis. Dr Freeman and Dr Gould show that the presence of antibody to endotoxin was associated with a lower incidence of postoperative gram-negative urinary tract infections. We did not find a reduction of the incidence of focal gram-negative infections, but cannot comment on this difference between the two studies because Freeman and Gould do not provide information on the endotoxin antigens they used for measuring anti-endotoxin antibody. Antibodies against 0 antigens are expected to behave differently from antibody against core glycolipid. Dr Burden may have mistaken our explanatory study for a pragmatic trial. As Schwartz et al2 have pointed out, with a pragmatic approach the appropriate type of patient is determined in general terms by the population to which the results of the trial will be applied. With an explanatory approach, the type of patient may be specifically chosen to be that which will display a well-defined biological feature. Our study was undertaken to see if the beneficial effect of anti-endotoxin treatment in patients with established gramnegative bacteraemia3 could be seen in high-risk patients treated prophylactically, before bloodstream infection has developed. We showed that immune plasma did not prevent acquisition of gramnegative infection in the group as a whole but it improved the course of the gram-negative infections that did occur. Since patients died from conditions other than gram-negative infections protection would not be expected to be demonstrable in the entire group, but only in those with gram-negative infections. Such statistical considerations do not diminish the potential value of anti-coreglycolipid antibody in surgical patients at high risk of death from endotoxin shock. Division of Infectious Diseases, Department of Internal Medicine, CHU Vaudois, 1011 Lausanne, Switzerland Division of Infectious Diseases, University of California, San Diego, School of Medicine, San Diego, California, USA
JEAN DANIEL BAUMGARTNER MICHEL P. GLAUSER
ELISABETH J. ZIEGLER J. ALLEN MCCUTCHAN MELVILLE R. KLAUBER
1. McCabe WR, Jackson GG. Gram-negative bacteremia. I. Etiology and ecology. Arch Intern Med 1962; 110: 847-55 2. Schwartz D, Flamant R, Lellouch J. Clinical trials. London: Academic Press, 1980: 58. 3. Ziegler EJ, McCutchan JA, Fierer J, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med 1982; 307: 1225-30.
exposure. Lancet
of
glomerulonephritis after discontinuation of
solvent
1979; i: 1194.
(5) Hydrocarbon exposure and glomerulonephritis: occupations. Lancet 1983; ii: 1214-16.
Evidence from patients’
(2)-(5) deal with organic solvents and glomerulonephritis. Dr Ravnskov was the main author of the publications but had coworkers in (1), (3), (4), and (5). (4) is a letter heralding a paper in the Quarterly Journal of Medicine and gives a summary of the abstract in that paper. This Q 7M paper was withdrawn in 1979 shortly before publication because of my discovery of serious faults in it. Simultaneously a similar paper sent to Läkartidningen (Swedish) was withdrawn. Data in case-records and exposure protocols have been reviewed the dean and vice-dean of the Medical Faculty, University of Lund, together with me and in the presence of Dr Ravnskov. The deans confirmed that there were many serious discrepancies between the statements in the Q,7M article and the facts. Discrepancies were found in the description of methods and in the work-up of the clinical material. The deans concluded that it was reasonable that I, as head of the department, had lost confidence in Dr Ravnskov. Some months later he resigned from my department. His 1983 paper (5) falsely gave the department of nephrology in Lund as the responsible institution.
by
Papers (1), (2), (3), and (5) have been scrutinised similarly and parts of the same patient material. The description of methods and patient selection deviates from the procedure used, many laboratory data are incorrect, and the case histories given do not always accord with the case records. These articles do not meet the usual standards required for publication in medical journals and I regret that they have been repeatedly cited in other publications on the same topics. cover
This letter has been Medical Faculty.
sent
after consultation with the dean of the
Department of Nephrology, University Hospital, S-221 85 Lund, Sweden
letter has been shown follows.-ED. L.
**This
ULLA BENGTSSON
to
Dr
Ravnskov, whose reply
SIR,-It is correct that a paper accepted for publication in the Quarterly Journal of Medicine in 1979 on glomerulonephritis and organic solvents had serious faults, and I am grateful to Professor Bengtsson for having discovered these faults. But all that I have published on this subject is correct, irrespective of her accusations. Professor Bengtsson has the view that the medical records of her department are her personal property. We found it proper to give the name of the institution where the main part of the studyl was done and where the records were kept. Our 1983 paper clearly states that none of the authors was affiliated to the department of nephrology in Lund at the time of publication. Professor Bengtsson does not mention that her consultation with ProfChrister Owman, the present dean of the Medical Faculty, was a failure. The dean found no reason to interfere in a scientific
disagreement. I invite Professor Bengtsson to participate in research on the causation of glomerulonephritis instead of spending her time on libel and personal persecution. For a start she could read the paper which she failed to stop.2 Olsh6gsv 14,
GLOMERULONEPHRITIS AND ORGANIC SOLVENTS
SIR,-I refer to the following publications on glomerulonephritis written
by Dr Uffe Ravnskov:
(1) Treatment of glomerulonephritis with drainage of the thoracic duct and plasmapheresis. Acta Med Scand 1977; 202: 489-94.
U. RAVNSKOV
S-223 60 Lund, Sweden
1 Ravnskov
U, Lundström S, Nordén A Hydrocarbon exposure and glomerulonephritis: Evidence from patients’ occupations. Lancet 1983; ii: 1214-16.
2. Ravnskov U. Possible
Nephrol 1985; 23:
mechanisms of hydrocarbon-associated glomerulonephritis Clin 284-98.