- Email: [email protected]
ANTIMICROBIAL PROPHYLAXIS IN COLORECTAL SURGERY
145
aonalty causes a defect in collagen formation in the fetus it is necessary to postulate an action other than copper depletion. Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ
J. M. WALSHE
ANTIMICROBIAL PROPHYLAXIS IN COLORECTAL SURGERY
SIR,-Keighley et aLl stated that the aim of their study was compare the effects of oral and systemic antibacterial prophylaxis, as if the route of administration was the sole predictor of drug distribution in the body. Oral administration of drugs such as metronidazole2 or tetracyclines, which are readily absorbed by the intestine results in a systemic distribution while drugs which are secreted in the bile, such as metronidazole,3 enter the intestine even when they have been given intravenously. Metronidazole levels in the colon in Keighley’s study were the same with either regimen (table iv). Incidentally, parenteral administration does not guarantee systemic distribution. Intravenous injection of substances such as mannitol or i indocyanin-green, which are confined to the extracellular , space, is hardly more systemic than is administration of oral i kanamycin. I The results obtained with kanamycin (tables in and iv), assuming that metronidazole did not directly or indirectly ; affect aerobes, show that preoperative reduction of colonic flora with kanamycin and injections of antimicrobial metronidazole given by mouth does indeed allow more sepsis than do peroperative and postoperative agents to suppress bacteria disseminated from colonic contents. With metronidazole, on the other hand, the results are ambiguous. If kanamycin has no direct or indirect effect on anaerobes, it does not really seem to matter whether metronidazole was given preoperatively or during i I and after surgery (table VI), except, perhaps, for the occurrence of toxin-producing clostridia with the preoperative regimen. This finding suggests that addition of metronidazole to an aminoglycoside might not enhance prophylaxis against sepsis: a trial of an anticlostridial cephalosporin with and without metronidazole could be even more profitable. I am intrigued by estimates such as a bacterial count of 2’8+3.4 (log counts/ml) or a serum drug level of I - 2 + 2.3 mg/1 (tables it and iv). These values indicate that some patients must have had negative bacterial counts and negative serumkanamycin levels. Clearly, these data are not normally distributed, and cannot be analysed by distribution-dependent tests. Medians or mid-ranges and quantiles or ranges might be better to
_
’
’
The 80 mrem dose in question (recently revised to 83 mrem) represents, not the average radiation dose to the population within 5 miles but, as Secretary Califano correctly stated, the highest cumulative offsite dose (offsite refers to locations beyond the exclusion area of 2000 ft [600 m] from the reactor site) that an individual located 0-5mile (800 m) east-northeast of the reactor site would have received had such an individual remained outdoors at that location from the onset of the accident on March 28 until April 7. In other words, the 83 mrem dose represents the highest cumulative gamma-radiation dose identified at a populated offsite location and not the average dose to the population within 5 miles (8 km). There were two other offsite dosimeters, both located on an unpopulated island, Kohr Island, in the Susquehanna River just outside the exclusion area of the Three Mile Island reactor, at 0.4 mile (640 m) north-northwest, that recorded higher cumulative gamma-radiation exposures for the period March 28 to April 7. One individual.was present on a nearby island (Hill Island, located 1-11 miles [1770 m] north-northwest of the reactor site) for 10 h, during March 28 and 29, who may have received a cumulative dose of approximately 37 mrem. This value is projected from dosimeter readings onsite and on Kohr Island. Though not included in its May 10 report the Ad Hoc Population Dose Assessment Group has estimated the collective dose that the population within 5 miles would have received from March 28 to April 7 to be about 500 person-rem. Dividing 500 person-rem by the population within 5 miles of the reactor site, 28 821 people (a 1980 census projection from the Metropolitan Edison Company’s Final Safety Analysis Report: Three Mile Island Nuclear Station-Unit 2), yields an average cumulative individual dose to people within 5 miles of about 17 mrem. This value does not take into account the fact that many of the people within 5 miles left the area for several days after the accident, and it assumes that all individuals in the 5 mile area remained outdoors continuously from March 28 to
April 7. Center for Disease Control, U.S. Public Health Service, Atlanta, Georgia 30333, U.S.A. Bureau of Radiologic Health, Food and Drug Administration,
Rockville, Maryland
MARK NELSON, MARVIN ROSENSTEIN, Members of the Ad Hoc Population Dose Assessment Group
*** With their letter Dr Nelson and Dr Rosenstein kindly
sent
copy of the Ad Hoc Group’s report, and appears on p. 161.-ED.L.
this
a
a note on
for such skewed distributions. 866 Adams Street,
Denver, Colorado 80206, U.S.A.
JEAN SICÉ VIRUS-LIKE AGENTS, IgA, AND SCHIZOPHRENIA
RADIATION DOSES AFTER THREE MILE ISLAND ACCIDENT
SIR,-Your April 28 editorial about the Three Mile Island nuclear power-plant accident states that: "The average dose of radiation to people within 5 miles of the accident was said by Mr Joseph Califano, Secretary of Health, Education, and Welfare to be 80 mrem from the accident (natural background is about 100 mrem a year)." As Dr McLean pointed out in his letter of May 12 (p. 1039), your editorial was wrong on this
point. Arabi Y, Alexander-Williams J, Young D, Burden DW. Comparison between systemic and oral antimicrobial prophylaxis in colorectal surgery. Lancet 1979,i:894-7. 2 Welling PG, Monro AM. The pharmacokinetics of metronidazole and tinidazole in man. Arzneimittel Forsch 1972;22:2128-32. Lykkegaard Nielsen M, Justesen T. Excretion of metronidazole in human
1 Keighley MRB,
bile
Scand J Gastroenterol 1977;12:1003-8.
SIR,-The finding of Dr Crow and his colleagues (April 21,
842) of a possible association between increased serum-IgA concentrations and presence of a virus-like agent (VLA) in cerebrospinal fiuid of schizophrenics may explain contradictory findings on serum-IgA levels in schizophrenia. 1,2 Crow et al. found a greater mean serum-IgA in VLA-positive than in VLA-negative schizophrenics. 3 of the 18 VLA-positive schizophrenics had high serum-IgA levels, whereas 5 of the 29 VLAnegative patients had low serum-IgA levels. These findings suggest that schizophrenic patients with high serum-IgA may represent a subpopulation of patients in whom the illness is associated with the presence of a VLA. The findings of Crow et al. of a possible association between VLA with female sex and poor outcome is compatible with the
p.
1. Strahilevitz M, Davis SD. Lancet 1970; ii: 370. 2. Domino EF, Krause RR, Thiessen MM, Batsakis
1975; 32: 717.
JG. Archs
Gen
Psychiat
aonalty causes a defect in collagen formation in the fetus it is necessary to postulate an action other than copper depletion. Department of Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ
J. M. WALSHE
ANTIMICROBIAL PROPHYLAXIS IN COLORECTAL SURGERY
SIR,-Keighley et aLl stated that the aim of their study was compare the effects of oral and systemic antibacterial prophylaxis, as if the route of administration was the sole predictor of drug distribution in the body. Oral administration of drugs such as metronidazole2 or tetracyclines, which are readily absorbed by the intestine results in a systemic distribution while drugs which are secreted in the bile, such as metronidazole,3 enter the intestine even when they have been given intravenously. Metronidazole levels in the colon in Keighley’s study were the same with either regimen (table iv). Incidentally, parenteral administration does not guarantee systemic distribution. Intravenous injection of substances such as mannitol or i indocyanin-green, which are confined to the extracellular , space, is hardly more systemic than is administration of oral i kanamycin. I The results obtained with kanamycin (tables in and iv), assuming that metronidazole did not directly or indirectly ; affect aerobes, show that preoperative reduction of colonic flora with kanamycin and injections of antimicrobial metronidazole given by mouth does indeed allow more sepsis than do peroperative and postoperative agents to suppress bacteria disseminated from colonic contents. With metronidazole, on the other hand, the results are ambiguous. If kanamycin has no direct or indirect effect on anaerobes, it does not really seem to matter whether metronidazole was given preoperatively or during i I and after surgery (table VI), except, perhaps, for the occurrence of toxin-producing clostridia with the preoperative regimen. This finding suggests that addition of metronidazole to an aminoglycoside might not enhance prophylaxis against sepsis: a trial of an anticlostridial cephalosporin with and without metronidazole could be even more profitable. I am intrigued by estimates such as a bacterial count of 2’8+3.4 (log counts/ml) or a serum drug level of I - 2 + 2.3 mg/1 (tables it and iv). These values indicate that some patients must have had negative bacterial counts and negative serumkanamycin levels. Clearly, these data are not normally distributed, and cannot be analysed by distribution-dependent tests. Medians or mid-ranges and quantiles or ranges might be better to
_
’
’
The 80 mrem dose in question (recently revised to 83 mrem) represents, not the average radiation dose to the population within 5 miles but, as Secretary Califano correctly stated, the highest cumulative offsite dose (offsite refers to locations beyond the exclusion area of 2000 ft [600 m] from the reactor site) that an individual located 0-5mile (800 m) east-northeast of the reactor site would have received had such an individual remained outdoors at that location from the onset of the accident on March 28 until April 7. In other words, the 83 mrem dose represents the highest cumulative gamma-radiation dose identified at a populated offsite location and not the average dose to the population within 5 miles (8 km). There were two other offsite dosimeters, both located on an unpopulated island, Kohr Island, in the Susquehanna River just outside the exclusion area of the Three Mile Island reactor, at 0.4 mile (640 m) north-northwest, that recorded higher cumulative gamma-radiation exposures for the period March 28 to April 7. One individual.was present on a nearby island (Hill Island, located 1-11 miles [1770 m] north-northwest of the reactor site) for 10 h, during March 28 and 29, who may have received a cumulative dose of approximately 37 mrem. This value is projected from dosimeter readings onsite and on Kohr Island. Though not included in its May 10 report the Ad Hoc Population Dose Assessment Group has estimated the collective dose that the population within 5 miles would have received from March 28 to April 7 to be about 500 person-rem. Dividing 500 person-rem by the population within 5 miles of the reactor site, 28 821 people (a 1980 census projection from the Metropolitan Edison Company’s Final Safety Analysis Report: Three Mile Island Nuclear Station-Unit 2), yields an average cumulative individual dose to people within 5 miles of about 17 mrem. This value does not take into account the fact that many of the people within 5 miles left the area for several days after the accident, and it assumes that all individuals in the 5 mile area remained outdoors continuously from March 28 to
April 7. Center for Disease Control, U.S. Public Health Service, Atlanta, Georgia 30333, U.S.A. Bureau of Radiologic Health, Food and Drug Administration,
Rockville, Maryland
MARK NELSON, MARVIN ROSENSTEIN, Members of the Ad Hoc Population Dose Assessment Group
*** With their letter Dr Nelson and Dr Rosenstein kindly
sent
copy of the Ad Hoc Group’s report, and appears on p. 161.-ED.L.
this
a
a note on
for such skewed distributions. 866 Adams Street,
Denver, Colorado 80206, U.S.A.
JEAN SICÉ VIRUS-LIKE AGENTS, IgA, AND SCHIZOPHRENIA
RADIATION DOSES AFTER THREE MILE ISLAND ACCIDENT
SIR,-Your April 28 editorial about the Three Mile Island nuclear power-plant accident states that: "The average dose of radiation to people within 5 miles of the accident was said by Mr Joseph Califano, Secretary of Health, Education, and Welfare to be 80 mrem from the accident (natural background is about 100 mrem a year)." As Dr McLean pointed out in his letter of May 12 (p. 1039), your editorial was wrong on this
point. Arabi Y, Alexander-Williams J, Young D, Burden DW. Comparison between systemic and oral antimicrobial prophylaxis in colorectal surgery. Lancet 1979,i:894-7. 2 Welling PG, Monro AM. The pharmacokinetics of metronidazole and tinidazole in man. Arzneimittel Forsch 1972;22:2128-32. Lykkegaard Nielsen M, Justesen T. Excretion of metronidazole in human
1 Keighley MRB,
bile
Scand J Gastroenterol 1977;12:1003-8.
SIR,-The finding of Dr Crow and his colleagues (April 21,
842) of a possible association between increased serum-IgA concentrations and presence of a virus-like agent (VLA) in cerebrospinal fiuid of schizophrenics may explain contradictory findings on serum-IgA levels in schizophrenia. 1,2 Crow et al. found a greater mean serum-IgA in VLA-positive than in VLA-negative schizophrenics. 3 of the 18 VLA-positive schizophrenics had high serum-IgA levels, whereas 5 of the 29 VLAnegative patients had low serum-IgA levels. These findings suggest that schizophrenic patients with high serum-IgA may represent a subpopulation of patients in whom the illness is associated with the presence of a VLA. The findings of Crow et al. of a possible association between VLA with female sex and poor outcome is compatible with the
p.
1. Strahilevitz M, Davis SD. Lancet 1970; ii: 370. 2. Domino EF, Krause RR, Thiessen MM, Batsakis
1975; 32: 717.
JG. Archs
Gen
Psychiat