632
a negative or weakly positive catalase reaction, and lack of growth in 5% sodium chloride medium.2 S mucilaginosus is usually isolated from the sputum of patients with chronic respiratory diseases such as cystic fibrosis.3 More recently, this bacterium has been found to be associated with systemic infections such as bacteraemias, endocarditis, and peritonitis complicating chronic ambulatory peritoneal dialysis. Infection has also been reported in immunocompromised hosts/,2,4 although not to our knowledge in patients who are HIV positive. S mucilaginosus is usually sensitive to a wide range of antibiotics apart from macrolides (20-40% of all strains are resistant). Up to 80% of strains are amoxycillin-sensitive. Like R equi and B bronchiseptica, S mucilaginosus seems to be a new opportunistic pathogen in patients with AIDS.
Safety of triazolam
agar,
Infectious and Tropical Diseases Clinic, Hôpital de Villeneuve-Saint-Georges, 94195 Villeneuve St Georges Cedex, France
O. PATEY J. E. MALKIN A. COUTAUX N. LEFLOUR CH. LAFAIX
Microbiology Laboratory, Hôpital de Villeneuve-Saint-Georges
J. PH. EMOND A. DUBLANCHET
Magee JT, Burner IA, Hingmarch JM, Spencer RC. Micrococcus and Stomatococcus mucilaginosus from human infections. J Hosp Infect 1990; 16: 67-73. 2. Mitchell PS, Huston BJ, Jones RN, Holcomb L, Koontz FP. Stomatococcus mucilaginosus bacteremias: typical case presentations, simplified diagnostic criteria, and a literature review. Diagn Microbiol Infect Dis 1990; 13: 521-25. 3. Chomarat M, Rochette A. Signification de l’isolement de Stomatococcus mucilaginosus. 1.
Presse Med
1988; 17: 537-38. 4. Lemozy J, Maestre Ph, Huguet F, Chomarat M, Dabemat H, Lareng MB. Source of infection in Stomatococcus mucilaginosus septicemia. Lancet 1990; 335: 416.
Cold
sores
and safer sex
SIR,--0ver the past three months we have seen 18 cases of primary acute herpetic vulvovaginitis, 15 due to herpes simplex virus (HSV) type 1. 11 couples admitted to orogenital contact and in 7 this took place in the presence of orolabial "cold sores" in the partner. In a further 5 of the 15 couples, the man had a history of orolabial cold sores but none had been present at the time of contact. 3 patients were especially distressed since they had used condoms for "safer sex". Over a twenty-year period, the ratio of HSV-1 to HSV-2 among female genital isolates in Edinburgh has been steady at 30 to 70.1 However, in the past five years the proportion of HSV-1isolates has risen to 42%. The high HSV-1 isolation rate from our newly diagnosed patients with acute herpetic vulvovaginitis probably reflects an increase in orogenital contact.2 More worrying is the apparent failure of the lay public to appreciate that oral cold sores are HSV lesions that can transmit virus to an unsuspecting partner, and that transmission can take place even in the absence of overt clinical lesions, presumably through symptomless viral shedding. Safer sex campaigns concentrate on condoms but do not address themselves to foreplay. Health education campaigns should cover all aspects of HSV infectivity. 30% or so of the population have recurrent cold sores.3 Safer sex campaigns should highlight the need for great care in people with recurrent HSV lesions; not only is there a risk of infection from symptomless viral shedding but there may also be a facilitatory role for HSV ulceration in the transmission of HIV.4 Genitourinary Medicine Unit, Department of Medicine, University of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW, UK
A. MCMILLAN A. BLAKELY
Department of Medical Microbiology, University of Edinburgh
I. W. SMITH
products". Addressing
the "demands" your contributors make is
a moot
point, since the clinical trial data they ask to be shared with regulatory authorities had already (before publication of your Aug 24 issue) been voluntarily provided by Upjohn to the Medicines Controls Agency in the UK and to the Food and Drug Administration in the USA. Upjohn is voluntarily taking steps to notify agencies in other countries about these data. Over a hundred studies form the basis of regulatory approval of halcion around the world. We recently became aware of a clerical error from one study done nearly twenty years ago. The transcription error has no bearing on the safety and efficacy of halcion under the approved use and dosing regimen. Upjohn does not knowingly withhold required information from regulatory authorities. The company has been dedicated to serving the medical needs of people for more than a century. We are proud of the excellent reputation we have among physicians, pharmacists, regulatory authorities, and patients around the world. We did not earn this reputation by suppressing information or by putting patients at risk. We have done hundreds of clinical trials to help us learn more about halcion. We have willingly shared this information with regulatory authorities, which have reviewed the data and agreed that halcion is a safe and effective medication when used as recommended. Your contributors imply that the clinical data in question have an impact on the health of patients who take halcion. In our opinion, data contained in the protocol referred to in The Lancet do not affect the risk-benefit assessment of triazolam under the approved use and
dosing regimen. We agree that investigating claims and determining safety and efficacy of pharmaceutical products is the role of the medical and pharmaceutical establishment and, we would add, of regulatory authorities. That is why Upjohn has, throughout its history, cooperated fully with regulatory authorities in labelling and marketing its products. That is why we make every effort to inform doctors about the appropriate use of our products. It is also stated that investigation of claims about medicines should not be left to chance litigation. We agree. This is the responsibility of regulatory authorities. We prefer to have the medical and scientific discussions about our products conducted by unbiased, scientific bodies unencumbered by the emotional component of civil jury trials. Speculation in the British press has been rife lately about Upjohn’s motivation in resolving litigation before trial. Such
resolution in no way intimates that halcion is unsafe or that it is causally related to any alleged event. Under the American system, out-of-court settlement does not represent any sort of implied fault on the part of the defendant-and certainly in cases involving pharmaceutical products such settlements do not represent a judgment on the safety or efficacy of the product involved. We have full confidence in the safety and efficacy of halcion as described in the labelling, and we welcome any opportunity to discuss the profile of this drug with any scientific or regulatory
body. J. G. MCKENNA
Smith IW, Peutherer JP. Immunological diagnosis of Herpes simplex virus. In: Young H, McMillan A, eds. Immunological diagnosis in sexually transmitted diseases. New York: Marcel Dekker, 1986. 2. Scoular A, Leask BGS, Carrington D. Changing trends in genital herpes due to Herpes simplex virus type 1 in Glasgow, 1985-88. Genitourin Med 1990; 66: 226. 3. Whitley RJ. Herpes simplex virus. In: Fields BN, Knipe DM, eds. Fields Virology, 2 ed. New York: Raven Press, 1990. 4. Holmberg SD, Stewart JA, Gerber R, et al. Prior herpes simplex virus type 2 infection as a risk factor for HIV infection. JAMA 1988; 259: 1048-50. 1.
SIR,-As managing director of Upjohn Limited, I am responding to Professor Oswald’s letter (p 516) and Mrs Brahams’ commentary (p 502) in your issue of Aug 24 on Upjohn’s product ’Halcion’ tablets (triazolam). As Mrs Brahams observes, Upjohn does indeed "welcome the opportunity to clear both its name and its
Upjohn Limited, Crawley RH10 2NJ, UK
KEITH T. KRZYWICKI, Managing director
Torsades de pointes and terodiline SIR,-Dr Connolly and colleagues (Aug 10, p 344) describe 5 patients taking terodiline who had torsades de pointes ventricular tachycardia and comment that this drug has a long half-life that is increased in elderly people and which results in high plasma concentrations. On admission, 1 of their 5 cases had a plasma terodiline concentration of 2946 pg/1 (therapeutic range 400-600 J..lg/l); plasma concentrations of the drug are not given for the other 4 patients.
a negative or weakly positive catalase reaction, and lack of growth in 5% sodium chloride medium.2 S mucilaginosus is usually isolated from the sputum of patients with chronic respiratory diseases such as cystic fibrosis.3 More recently, this bacterium has been found to be associated with systemic infections such as bacteraemias, endocarditis, and peritonitis complicating chronic ambulatory peritoneal dialysis. Infection has also been reported in immunocompromised hosts/,2,4 although not to our knowledge in patients who are HIV positive. S mucilaginosus is usually sensitive to a wide range of antibiotics apart from macrolides (20-40% of all strains are resistant). Up to 80% of strains are amoxycillin-sensitive. Like R equi and B bronchiseptica, S mucilaginosus seems to be a new opportunistic pathogen in patients with AIDS.
Safety of triazolam
agar,
Infectious and Tropical Diseases Clinic, Hôpital de Villeneuve-Saint-Georges, 94195 Villeneuve St Georges Cedex, France
O. PATEY J. E. MALKIN A. COUTAUX N. LEFLOUR CH. LAFAIX
Microbiology Laboratory, Hôpital de Villeneuve-Saint-Georges
J. PH. EMOND A. DUBLANCHET
Magee JT, Burner IA, Hingmarch JM, Spencer RC. Micrococcus and Stomatococcus mucilaginosus from human infections. J Hosp Infect 1990; 16: 67-73. 2. Mitchell PS, Huston BJ, Jones RN, Holcomb L, Koontz FP. Stomatococcus mucilaginosus bacteremias: typical case presentations, simplified diagnostic criteria, and a literature review. Diagn Microbiol Infect Dis 1990; 13: 521-25. 3. Chomarat M, Rochette A. Signification de l’isolement de Stomatococcus mucilaginosus. 1.
Presse Med
1988; 17: 537-38. 4. Lemozy J, Maestre Ph, Huguet F, Chomarat M, Dabemat H, Lareng MB. Source of infection in Stomatococcus mucilaginosus septicemia. Lancet 1990; 335: 416.
Cold
sores
and safer sex
SIR,--0ver the past three months we have seen 18 cases of primary acute herpetic vulvovaginitis, 15 due to herpes simplex virus (HSV) type 1. 11 couples admitted to orogenital contact and in 7 this took place in the presence of orolabial "cold sores" in the partner. In a further 5 of the 15 couples, the man had a history of orolabial cold sores but none had been present at the time of contact. 3 patients were especially distressed since they had used condoms for "safer sex". Over a twenty-year period, the ratio of HSV-1 to HSV-2 among female genital isolates in Edinburgh has been steady at 30 to 70.1 However, in the past five years the proportion of HSV-1isolates has risen to 42%. The high HSV-1 isolation rate from our newly diagnosed patients with acute herpetic vulvovaginitis probably reflects an increase in orogenital contact.2 More worrying is the apparent failure of the lay public to appreciate that oral cold sores are HSV lesions that can transmit virus to an unsuspecting partner, and that transmission can take place even in the absence of overt clinical lesions, presumably through symptomless viral shedding. Safer sex campaigns concentrate on condoms but do not address themselves to foreplay. Health education campaigns should cover all aspects of HSV infectivity. 30% or so of the population have recurrent cold sores.3 Safer sex campaigns should highlight the need for great care in people with recurrent HSV lesions; not only is there a risk of infection from symptomless viral shedding but there may also be a facilitatory role for HSV ulceration in the transmission of HIV.4 Genitourinary Medicine Unit, Department of Medicine, University of Edinburgh, Royal Infirmary, Edinburgh EH3 9YW, UK
A. MCMILLAN A. BLAKELY
Department of Medical Microbiology, University of Edinburgh
I. W. SMITH
products". Addressing
the "demands" your contributors make is
a moot
point, since the clinical trial data they ask to be shared with regulatory authorities had already (before publication of your Aug 24 issue) been voluntarily provided by Upjohn to the Medicines Controls Agency in the UK and to the Food and Drug Administration in the USA. Upjohn is voluntarily taking steps to notify agencies in other countries about these data. Over a hundred studies form the basis of regulatory approval of halcion around the world. We recently became aware of a clerical error from one study done nearly twenty years ago. The transcription error has no bearing on the safety and efficacy of halcion under the approved use and dosing regimen. Upjohn does not knowingly withhold required information from regulatory authorities. The company has been dedicated to serving the medical needs of people for more than a century. We are proud of the excellent reputation we have among physicians, pharmacists, regulatory authorities, and patients around the world. We did not earn this reputation by suppressing information or by putting patients at risk. We have done hundreds of clinical trials to help us learn more about halcion. We have willingly shared this information with regulatory authorities, which have reviewed the data and agreed that halcion is a safe and effective medication when used as recommended. Your contributors imply that the clinical data in question have an impact on the health of patients who take halcion. In our opinion, data contained in the protocol referred to in The Lancet do not affect the risk-benefit assessment of triazolam under the approved use and
dosing regimen. We agree that investigating claims and determining safety and efficacy of pharmaceutical products is the role of the medical and pharmaceutical establishment and, we would add, of regulatory authorities. That is why Upjohn has, throughout its history, cooperated fully with regulatory authorities in labelling and marketing its products. That is why we make every effort to inform doctors about the appropriate use of our products. It is also stated that investigation of claims about medicines should not be left to chance litigation. We agree. This is the responsibility of regulatory authorities. We prefer to have the medical and scientific discussions about our products conducted by unbiased, scientific bodies unencumbered by the emotional component of civil jury trials. Speculation in the British press has been rife lately about Upjohn’s motivation in resolving litigation before trial. Such
resolution in no way intimates that halcion is unsafe or that it is causally related to any alleged event. Under the American system, out-of-court settlement does not represent any sort of implied fault on the part of the defendant-and certainly in cases involving pharmaceutical products such settlements do not represent a judgment on the safety or efficacy of the product involved. We have full confidence in the safety and efficacy of halcion as described in the labelling, and we welcome any opportunity to discuss the profile of this drug with any scientific or regulatory
body. J. G. MCKENNA
Smith IW, Peutherer JP. Immunological diagnosis of Herpes simplex virus. In: Young H, McMillan A, eds. Immunological diagnosis in sexually transmitted diseases. New York: Marcel Dekker, 1986. 2. Scoular A, Leask BGS, Carrington D. Changing trends in genital herpes due to Herpes simplex virus type 1 in Glasgow, 1985-88. Genitourin Med 1990; 66: 226. 3. Whitley RJ. Herpes simplex virus. In: Fields BN, Knipe DM, eds. Fields Virology, 2 ed. New York: Raven Press, 1990. 4. Holmberg SD, Stewart JA, Gerber R, et al. Prior herpes simplex virus type 2 infection as a risk factor for HIV infection. JAMA 1988; 259: 1048-50. 1.
SIR,-As managing director of Upjohn Limited, I am responding to Professor Oswald’s letter (p 516) and Mrs Brahams’ commentary (p 502) in your issue of Aug 24 on Upjohn’s product ’Halcion’ tablets (triazolam). As Mrs Brahams observes, Upjohn does indeed "welcome the opportunity to clear both its name and its
Upjohn Limited, Crawley RH10 2NJ, UK
KEITH T. KRZYWICKI, Managing director
Torsades de pointes and terodiline SIR,-Dr Connolly and colleagues (Aug 10, p 344) describe 5 patients taking terodiline who had torsades de pointes ventricular tachycardia and comment that this drug has a long half-life that is increased in elderly people and which results in high plasma concentrations. On admission, 1 of their 5 cases had a plasma terodiline concentration of 2946 pg/1 (therapeutic range 400-600 J..lg/l); plasma concentrations of the drug are not given for the other 4 patients.
