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IMPORTANCE OF PREOPERATIVE ANTIBIOTIC PROPHYLAXIS FOR PATIENTS UNDERGOING ACUTE APPENDICECTOMY
1279 VIRUSES AND ORAL "HAIRY" LEUCOPLAKIA
SIR,-I read the paper by Deborah Greenspan and her colleagues (Oct 13, p 831) with great interest and I am sure their conclusion that both papillomaviruses and herpesviruses may be involved in oral "hairy" leucoplakia is correct. The results of the work this group has in hand will help to establish both the relative importance of these viruses and their identities. However, I am not happy about their interpretation of the electronmicrographs in fig 4. Two kinds of intranuclear object are shown in fig 4A, the larger of which (solid arrows) look typical of unenveloped herpesvirus capsids. They have a roughly hexagonal outline, are consistent in size, lack envelopes (as would intranuclear capsids), and several contain irregular "nucleoids" (a common finding by both thin section and negative contrast electron
immunofluorescence and DNA hybridisation done in collaboration with Dr Evelyn Lenette and Dr Karl Freeze, Dr Lutz Gissman, and Prof H. zur Hausen, identify the herpes-type virus. These results will be published elsewhere. Divisions of Oral Biology, and Oral Medicine, School of Dentistry, University of California, San Francisco, San Francisco, California 94143, USA 1.
the nuclei of herpes-infected cells in culture but they are reported to be about 30 nm in diameter. Those in fig 4A are ill-defined but are clearly larger. Their relation to the herpesvirus is uncertain but they do not resemble papillomaviruses whose outlines are usually very well defined in thin section. If my interpretation is correct, the 500 nm scale bar is about 50% too short. Herpesvirus capsids are very constant in size at 100 nm in diameter, and this discrepancy suggests either that the electron microscope had not been calibrated at the magnification at which the pictures were taken (manufacturers’ figures are often wrong) or a miscalculation. A 500 nm scale bar 25 mm long would also be consistent with the desmosome in fig 4B. If a proportionately similar error in calculating the length of the scale bar in fig 4B is assumed, the intercellular virions appear to be 100 nm naked nucleocapsids. The apparent lack of an envelope on virus released from cells is surprising. Since the presence of an envelope is associated with infectivity, it may prove difficult to isolate any virus. Even so, it may still be possible to identify the member of the herpes group using in-situ hybridisation with a radiolabelled DNA probe. Herpes simplex virus (Herpesvirus hominis type 1) is often isolated from the nasopharynx of children, most of whom have no overt lesions, and is the most likely member of the group to be involved. If so the situation is very similar to one of those proposed by zur Hausen2for the induction of cervical cancer in women.
DEBORAH GREENSPAN
G. Partial purification and electronmicroscopy of virus in the EB-3 cell line derived from a Burkitt lymphoma. Science 1966; 151: 1084-85.
Toplin I, Schidlovsky
IMPORTANCE OF PREOPERATIVE ANTIBIOTIC PROPHYLAXIS FOR PATIENTS UNDERGOING ACUTE
APPENDICECTOMY
microscopy). The smaller, granular particles (hollow arrows) do not resemble herpes nucleocapsids at all. Granular structures have been found in
JOHN S. GREENSPAN
SIR,-Infective complications after appendicectomy are reported be reduced as a result of antibiotic administration 14 and since December, 1982, the following routine preoperative antibiotic prophylaxis and postoperative antibiotic regimens have been used in this department:
to
patients referred for appendicectomy, body weight as a single intravenous dose 112-1 hour
all
Preoperatively.-For metromdazole 7’ 5 mg/kg before the operation.
Postoperattvely.-In patients with a gangrenous or perforated appendix or appendiceal abscess, co-trimoxazele 0’4 ml/kg body weight daily and metronidazole 22 - 5 mg/kg daily divided into two intravenous doses (orally when the patient starts oral feeding) over 7 days.
Formerly postoperative antibiotic treatment with cefoxitin was only when the surgeon found a gangrenous or a perforated appendix or an appendiceal abscess. The frequency of postoperative infective complications fell significantly after the institution of routine antibiotic prophylaxis chi-squared test) to less than 0-5% (table). To our (p<0-001, knowledge this is the lowest rate of infectious complications reported after appendicectomy.
used
INFECTIOUS COMPLICATIONS OF APPENDICECTOMY BEFORE
(1980-82) AND AFTER (1983-84) THE START OF ROUTINE ANTIBIOTIC PROPHYLAXIS
Department of Virology, University of Newcastle upon Tyne, Victoria Infirmary, Newcastle upon Tyne NE1 4LP
Royal
C. R. MADELEY
K Mechanism of intranuclear crystal formation of herpes simplex virus as revealed by the negative staining of thin sections J Virol 1971; 8: 534-50. 2 zur Hausen H. Human genital cancer: Synergism between the viral infections or synergism between a virus infection and initiating events Lancet 1982, ii: 1370-72.
*Venfied
by direct palpation, plain abdominal X-ray, ultrasonography. tdemanding operative drainage.
computer
tomography,
or
1 Miyamoto
**This letter has been shown to the San Francisco team, whose reply follows.-ED. L. SIR,-The magnification in fig 4 was, it seems, inaccurate. We had calibrated the magnification of our electronmicroscope against that of a heavily used high-resolution instrument but even so, error crept in. The naked capsid of the virus which we described and illustrated measures 100 nm. The core or nucleoid within the naked capsid is difficult to measure but seems to be in the range 65-70 nm in diameter. These appearances and dimensions clearly qualify the virus as a member of the herpes group. Numerous particles, similar in appearance and size to the core or nucleoid but lacking its outer layer, were seen in the same cases. As Professor Madeley observes, these do not resemble papillomavirus particles, nor do they fit with the 30 nm diameter particles to which he alludes. The virus particles in fig 4b are 155-220 nm in diameter and are seen in large numbers in intercellular spaces. We take these appearances to be consistent with herpes-type enveloped virions. We have now examined twenty cases by electron microscopy and continue to find evidence of this herpes-type virus in almost all. We have now found particles in most cases which resemble single papillomavirus particles. Furthermore, indirect
significant difference between the proportion of (2207ol2lO7o), phlegmonous (47%/49%), gangrenous (14/0/11/0), or perforated (15%/17%) appendices or appendiceal abscesses (2%) found at operation during the two periods studied. We have noted no other changes in management that might have influenced the complication rates. No adverse reactions to the There normal
was no
antibiotics have been recorded. There was 1 wound infection despite the antibiotic prophylaxis, suggesting that not all the infectious complications during 1980-82 could have been avoided. However, our results strongly support the routine use of preoperative antibiotic prophylaxis in appendicectomy patients. Department of Paediatric Surgery, University of Lund,
E. ARNBJORNSSON C. MIKAELSSON
S-221 85 Lund, Sweden
1.
Gaffney
PR Wound infections
in
appendicitis
Effective
prophylaxis
World J
Surg
1984; 8: 287-92 2. McLean MD, Buick RG, Goston VE The influence of metronidazole prophylaxis and the method of closure on wound infection in non-perforating appendicitis in childhood Z Kinderchir 1983, 38: 283-85 3 Miholic J, Riezinger F, Wurnig P Metronidazole plus cefazolin versus cefazolin in gangrenous and perforated appendicitis in childhood: a prospective randomised trial Z Kinderchir 1983; 38: 159-62. 4 Sandusky WR. Use of prophylactic antibiotics in surgical patients Surg Clin N Am
1982; 60: 83-96
SIR,-I read the paper by Deborah Greenspan and her colleagues (Oct 13, p 831) with great interest and I am sure their conclusion that both papillomaviruses and herpesviruses may be involved in oral "hairy" leucoplakia is correct. The results of the work this group has in hand will help to establish both the relative importance of these viruses and their identities. However, I am not happy about their interpretation of the electronmicrographs in fig 4. Two kinds of intranuclear object are shown in fig 4A, the larger of which (solid arrows) look typical of unenveloped herpesvirus capsids. They have a roughly hexagonal outline, are consistent in size, lack envelopes (as would intranuclear capsids), and several contain irregular "nucleoids" (a common finding by both thin section and negative contrast electron
immunofluorescence and DNA hybridisation done in collaboration with Dr Evelyn Lenette and Dr Karl Freeze, Dr Lutz Gissman, and Prof H. zur Hausen, identify the herpes-type virus. These results will be published elsewhere. Divisions of Oral Biology, and Oral Medicine, School of Dentistry, University of California, San Francisco, San Francisco, California 94143, USA 1.
the nuclei of herpes-infected cells in culture but they are reported to be about 30 nm in diameter. Those in fig 4A are ill-defined but are clearly larger. Their relation to the herpesvirus is uncertain but they do not resemble papillomaviruses whose outlines are usually very well defined in thin section. If my interpretation is correct, the 500 nm scale bar is about 50% too short. Herpesvirus capsids are very constant in size at 100 nm in diameter, and this discrepancy suggests either that the electron microscope had not been calibrated at the magnification at which the pictures were taken (manufacturers’ figures are often wrong) or a miscalculation. A 500 nm scale bar 25 mm long would also be consistent with the desmosome in fig 4B. If a proportionately similar error in calculating the length of the scale bar in fig 4B is assumed, the intercellular virions appear to be 100 nm naked nucleocapsids. The apparent lack of an envelope on virus released from cells is surprising. Since the presence of an envelope is associated with infectivity, it may prove difficult to isolate any virus. Even so, it may still be possible to identify the member of the herpes group using in-situ hybridisation with a radiolabelled DNA probe. Herpes simplex virus (Herpesvirus hominis type 1) is often isolated from the nasopharynx of children, most of whom have no overt lesions, and is the most likely member of the group to be involved. If so the situation is very similar to one of those proposed by zur Hausen2for the induction of cervical cancer in women.
DEBORAH GREENSPAN
G. Partial purification and electronmicroscopy of virus in the EB-3 cell line derived from a Burkitt lymphoma. Science 1966; 151: 1084-85.
Toplin I, Schidlovsky
IMPORTANCE OF PREOPERATIVE ANTIBIOTIC PROPHYLAXIS FOR PATIENTS UNDERGOING ACUTE
APPENDICECTOMY
microscopy). The smaller, granular particles (hollow arrows) do not resemble herpes nucleocapsids at all. Granular structures have been found in
JOHN S. GREENSPAN
SIR,-Infective complications after appendicectomy are reported be reduced as a result of antibiotic administration 14 and since December, 1982, the following routine preoperative antibiotic prophylaxis and postoperative antibiotic regimens have been used in this department:
to
patients referred for appendicectomy, body weight as a single intravenous dose 112-1 hour
all
Preoperatively.-For metromdazole 7’ 5 mg/kg before the operation.
Postoperattvely.-In patients with a gangrenous or perforated appendix or appendiceal abscess, co-trimoxazele 0’4 ml/kg body weight daily and metronidazole 22 - 5 mg/kg daily divided into two intravenous doses (orally when the patient starts oral feeding) over 7 days.
Formerly postoperative antibiotic treatment with cefoxitin was only when the surgeon found a gangrenous or a perforated appendix or an appendiceal abscess. The frequency of postoperative infective complications fell significantly after the institution of routine antibiotic prophylaxis chi-squared test) to less than 0-5% (table). To our (p<0-001, knowledge this is the lowest rate of infectious complications reported after appendicectomy.
used
INFECTIOUS COMPLICATIONS OF APPENDICECTOMY BEFORE
(1980-82) AND AFTER (1983-84) THE START OF ROUTINE ANTIBIOTIC PROPHYLAXIS
Department of Virology, University of Newcastle upon Tyne, Victoria Infirmary, Newcastle upon Tyne NE1 4LP
Royal
C. R. MADELEY
K Mechanism of intranuclear crystal formation of herpes simplex virus as revealed by the negative staining of thin sections J Virol 1971; 8: 534-50. 2 zur Hausen H. Human genital cancer: Synergism between the viral infections or synergism between a virus infection and initiating events Lancet 1982, ii: 1370-72.
*Venfied
by direct palpation, plain abdominal X-ray, ultrasonography. tdemanding operative drainage.
computer
tomography,
or
1 Miyamoto
**This letter has been shown to the San Francisco team, whose reply follows.-ED. L. SIR,-The magnification in fig 4 was, it seems, inaccurate. We had calibrated the magnification of our electronmicroscope against that of a heavily used high-resolution instrument but even so, error crept in. The naked capsid of the virus which we described and illustrated measures 100 nm. The core or nucleoid within the naked capsid is difficult to measure but seems to be in the range 65-70 nm in diameter. These appearances and dimensions clearly qualify the virus as a member of the herpes group. Numerous particles, similar in appearance and size to the core or nucleoid but lacking its outer layer, were seen in the same cases. As Professor Madeley observes, these do not resemble papillomavirus particles, nor do they fit with the 30 nm diameter particles to which he alludes. The virus particles in fig 4b are 155-220 nm in diameter and are seen in large numbers in intercellular spaces. We take these appearances to be consistent with herpes-type enveloped virions. We have now examined twenty cases by electron microscopy and continue to find evidence of this herpes-type virus in almost all. We have now found particles in most cases which resemble single papillomavirus particles. Furthermore, indirect
significant difference between the proportion of (2207ol2lO7o), phlegmonous (47%/49%), gangrenous (14/0/11/0), or perforated (15%/17%) appendices or appendiceal abscesses (2%) found at operation during the two periods studied. We have noted no other changes in management that might have influenced the complication rates. No adverse reactions to the There normal
was no
antibiotics have been recorded. There was 1 wound infection despite the antibiotic prophylaxis, suggesting that not all the infectious complications during 1980-82 could have been avoided. However, our results strongly support the routine use of preoperative antibiotic prophylaxis in appendicectomy patients. Department of Paediatric Surgery, University of Lund,
E. ARNBJORNSSON C. MIKAELSSON
S-221 85 Lund, Sweden
1.
Gaffney
PR Wound infections
in
appendicitis
Effective
prophylaxis
World J
Surg
1984; 8: 287-92 2. McLean MD, Buick RG, Goston VE The influence of metronidazole prophylaxis and the method of closure on wound infection in non-perforating appendicitis in childhood Z Kinderchir 1983, 38: 283-85 3 Miholic J, Riezinger F, Wurnig P Metronidazole plus cefazolin versus cefazolin in gangrenous and perforated appendicitis in childhood: a prospective randomised trial Z Kinderchir 1983; 38: 159-62. 4 Sandusky WR. Use of prophylactic antibiotics in surgical patients Surg Clin N Am
1982; 60: 83-96