113
Even if the price of xenon were to be reduced, anaesthetists would evidence of this agent’s comparative efficacy and safety. A long series of detailed controlled studies would be required to bring the work on xenon up to the current standards of anaesthetic research which have advanced so much over the years. want much more solid
Division of Anaesthesia, Clinical Research Centre, Harrow HA1 3UJ, UK
J. F. NUNN M. J. HALSEY
1. Barton F, Nunn JF. Totally closed circuit nitrous oxide/oxygen anaesthesia. Br J Anaesth 1975; 47: 350-57. 2. Spence AA. Environmental pollution by inhalational anaesthetics. Br J Anaesth 1987; 59: 96-103. 3. Nunn JF. Clinical aspects of the interaction between nitrous oxide and vitamin B12. Br J Anaesth 1987; 59: 3-13.
Obstacle to early diagnosis of herpes simplex encephalitis via CSF SIR,—The notoriously difficult non-invasive, early diagnosis of herpes simplex virus (HSV) encephalitis has been addressed by Rowley et al,l who used the polymerase chain reaction (PCR) technique to detect HSV nucleic acid in the CSF. They reported positive results from four specimens obtained 6 days or more after onset of neurological symptoms, and suggested that PCR might permit accurate non-invasive diagnosis of herpes simplex encephalitis 2-3 days after onset of illness. We present central nervous system necropsy data from three cases of herpes simplex encephalitis where ependymal and choroid plexus cells were uninfected despite widespread HSV infection in other parts of the brain. It seems that an early, sensitive, non-invasive CSF assay for
rapid diagnosis of HSV may remain elusive because of intrinsic HSV resistance in ependymal and choroid plexus cells, hampering the transfer of HSV antigen from the central nervous system and blood vessels to CSF. Brain material routinely fixed in formalin and embedded in paraffin was studied. To detect HSV antigen we used peroxidase labelled monoclonal antibodies to HSV-1 and HSV-2 (Chemicon International, El Segundo, California) and an avidin biotin peroxidase immunohistochemical staining kit (’ABC Kit’; Vector Laboratories, Burlingame, California). The diagnosis was confirmed in all cases by post-mortem virus culture. The virus isolated at necropsy in case 1 wasHSV-2 and in caseitwasHSV-1 as confirmed by a direct monoclonal antibody immunofluorescent assay (’MicroTrak’; Syva, Palo Alto, California). The virus in case 3 was not typed but was later confirmed as HSV-1 in tissue by the immunoperoxidase monoclonal antibody stain. The neonatal infection in case 1 converted the brain to a semiliquid necrotic mass but even after infection for 11 days, with virtual destruction of the brain, ependyma and choroid plexus remained intact and unaffected, without immunocytochemical evidence of HSV antigen in the ependymal cells. In cases 2 and 3 there was less necrosis and inflammation than in case 1. Immunohistochemical staining for HSV was positive in cerebral parenchyma but choroid plexus and ependymal were negative. CSF taken on day 5 from case 1 was virus-culture negative; CSF virus culture was not attempted in cases 2 and 3. In cases 1 and 3 extensive inflammatory infiltrates were found at the leptomeningeal surface of the brain. There was positive immunoperoxidase staining for HSV in cortical neurons and their processes. The HSV immunoperoxidase findings suggest that the virus could have been shed into the CSF once inflammation interrupted the pial-glial border of the brain. We do not know when this inflammation begins; these patients died on days 11,15, and 14. These observations suggest that in cerebral HSV infection the virus will enter the CSF only when inflammation at the surface of the brain breaches the pial-glial border; this is in keeping with negative CSF HSV antigen assays in herpes simplex encephalitis 6 days after the onset of neurological symptoms.2 We propose that the ependymal and choroid plexus cells form an HSV-resistant barrier early in the disease, preventing the virus from reaching the CSF and thus precluding early diagnosis via CSF, despite the application of sensitive techniques such as PCR.
Ependymal and
choroid plexus cells may resist HSV infection because of lack of cellular HSV receptors, a block of viral penetration, uncoating, or immediate early HSV protein synthesis.3 This is not a general antiviral feature of ependymal cells, for ependymal cells have been reported to be selectively susceptible to mumps virus.4 Department of Pathology, Faculty of Medicine, University of British Columbia Vancouver, Canada V6H 3V5
EVA E. THOMAS MARGARET G. NORMAN
Vancouver General
KENNETH BERRY
and British Columbia’s Children’s
Hospital,
Hospital
1. Rowley AM, Whitley RJ, Lakeman FD, Solinsky SM. Rapid detection of herpes-simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet 1990; 335: 440-41 2. Lakeman FD. Antigen detection in cerebrospinal fluid of patients with herpes simplex encephalitis. In: Lopez C, Roizman B, eds. Human herpes virus infections. New York: Raven Press, 1986: 235-44. 3. Roizman B, Sears AE. An inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol 1987; 41: 543-71 4. Johnson RT, Johnson KP. Hydrocephalus following viral infection: the pathology of aqueductal stenosis developing after experimental mumps virus infection. J Neuropathol Exp Neurol 1968; 27: 591-606.
Dangers of nebulisers
in
nursing and
residential homes SIR,-Bronchodilator drugs are often given by nebuliser. In frail elderly dyspnoeic patients these drugs are often prescribed for symptomatic relief. We report two cases highlighting the need for clear instructions with respect to methods of nebulising drugs. An elderly nursing home resident with chronic obstructive airways disease was prescribed salbutamol 2-5 mg, nebulised thrice daily. The nursing home matron commented to a visiting doctor that the patient became drowsy during administration, and furthermore each dose took about 30 min to deliver. Inquiry revealed that pure oxygen was being used to nebulise the salbutamol. The use of an air compressor to drive the nebuliser corrected the "dose drowsiness" and the dose was given in less than 10 min. A man in a residential home was thought to be using excessive amounts of oxygen, via his nebuliser. However, baseline blood gases showed a normal PCOZ and a P02 of 8-5 kPa. Following the use of a nebuliser driven with pure oxygen, the PC02 remained normal and P02 rose to 10-2 kPa. The results vindicated the use of oxygen, showing clinical relief from dyspnoea. The general practitioner reassured the matron about the safety of oxygen consumption in this
patient. In
our
first
patient
transient
CO2
narcosis is
suggested. The
second, clearly, had hypoxic respiratory failure. Two hospitalbased studies have shown the potential dangers of inappropriate gas mixtures to drive nebulisers.12 It was suggested that baseline blood gas measurements should be done in all patients before a home nebuliser is recommended, and that such patients should have medical follow-up. In nursing and residential homes oxygen cylinders and compressed air nebulisers seem to be very common and their use is largely unmonitored. Increasingly patients with chronic illness are being managed in private-care homes. Hospitals usually have clear policies for the administration of drugs such as nebulised bronchodilators, together with regular medical review. But these policies are not universal3 in private-care units; the prescribing doctor should therefore ensure that nebulised drugs are given appropriately. Weston General Hospital, Weston Super Mare, Avon BS23 4TQ, UK
M. K. DOSHI H. L. BHAKRI C. E. BOWMAN
PE, Renowden SA, Ward MJ. Audit of nebuliser use. Postgraduate Med J 1985; 61: 1055-56.
1. Williams
2. Gunawardena KA, Patel IA, Macdonald JB, Smith AP. Oxygen as a driving gas for nebulisers: safe or dangerous? Br Med J 1984; 288: 272-73. 3. Hepple J, Bowler I, Bowman CE. A survey of nursing home residents m Weston Super Mare. Age Ageing 1989; 18: 61-63.
Even if the price of xenon were to be reduced, anaesthetists would evidence of this agent’s comparative efficacy and safety. A long series of detailed controlled studies would be required to bring the work on xenon up to the current standards of anaesthetic research which have advanced so much over the years. want much more solid
Division of Anaesthesia, Clinical Research Centre, Harrow HA1 3UJ, UK
J. F. NUNN M. J. HALSEY
1. Barton F, Nunn JF. Totally closed circuit nitrous oxide/oxygen anaesthesia. Br J Anaesth 1975; 47: 350-57. 2. Spence AA. Environmental pollution by inhalational anaesthetics. Br J Anaesth 1987; 59: 96-103. 3. Nunn JF. Clinical aspects of the interaction between nitrous oxide and vitamin B12. Br J Anaesth 1987; 59: 3-13.
Obstacle to early diagnosis of herpes simplex encephalitis via CSF SIR,—The notoriously difficult non-invasive, early diagnosis of herpes simplex virus (HSV) encephalitis has been addressed by Rowley et al,l who used the polymerase chain reaction (PCR) technique to detect HSV nucleic acid in the CSF. They reported positive results from four specimens obtained 6 days or more after onset of neurological symptoms, and suggested that PCR might permit accurate non-invasive diagnosis of herpes simplex encephalitis 2-3 days after onset of illness. We present central nervous system necropsy data from three cases of herpes simplex encephalitis where ependymal and choroid plexus cells were uninfected despite widespread HSV infection in other parts of the brain. It seems that an early, sensitive, non-invasive CSF assay for
rapid diagnosis of HSV may remain elusive because of intrinsic HSV resistance in ependymal and choroid plexus cells, hampering the transfer of HSV antigen from the central nervous system and blood vessels to CSF. Brain material routinely fixed in formalin and embedded in paraffin was studied. To detect HSV antigen we used peroxidase labelled monoclonal antibodies to HSV-1 and HSV-2 (Chemicon International, El Segundo, California) and an avidin biotin peroxidase immunohistochemical staining kit (’ABC Kit’; Vector Laboratories, Burlingame, California). The diagnosis was confirmed in all cases by post-mortem virus culture. The virus isolated at necropsy in case 1 wasHSV-2 and in caseitwasHSV-1 as confirmed by a direct monoclonal antibody immunofluorescent assay (’MicroTrak’; Syva, Palo Alto, California). The virus in case 3 was not typed but was later confirmed as HSV-1 in tissue by the immunoperoxidase monoclonal antibody stain. The neonatal infection in case 1 converted the brain to a semiliquid necrotic mass but even after infection for 11 days, with virtual destruction of the brain, ependyma and choroid plexus remained intact and unaffected, without immunocytochemical evidence of HSV antigen in the ependymal cells. In cases 2 and 3 there was less necrosis and inflammation than in case 1. Immunohistochemical staining for HSV was positive in cerebral parenchyma but choroid plexus and ependymal were negative. CSF taken on day 5 from case 1 was virus-culture negative; CSF virus culture was not attempted in cases 2 and 3. In cases 1 and 3 extensive inflammatory infiltrates were found at the leptomeningeal surface of the brain. There was positive immunoperoxidase staining for HSV in cortical neurons and their processes. The HSV immunoperoxidase findings suggest that the virus could have been shed into the CSF once inflammation interrupted the pial-glial border of the brain. We do not know when this inflammation begins; these patients died on days 11,15, and 14. These observations suggest that in cerebral HSV infection the virus will enter the CSF only when inflammation at the surface of the brain breaches the pial-glial border; this is in keeping with negative CSF HSV antigen assays in herpes simplex encephalitis 6 days after the onset of neurological symptoms.2 We propose that the ependymal and choroid plexus cells form an HSV-resistant barrier early in the disease, preventing the virus from reaching the CSF and thus precluding early diagnosis via CSF, despite the application of sensitive techniques such as PCR.
Ependymal and
choroid plexus cells may resist HSV infection because of lack of cellular HSV receptors, a block of viral penetration, uncoating, or immediate early HSV protein synthesis.3 This is not a general antiviral feature of ependymal cells, for ependymal cells have been reported to be selectively susceptible to mumps virus.4 Department of Pathology, Faculty of Medicine, University of British Columbia Vancouver, Canada V6H 3V5
EVA E. THOMAS MARGARET G. NORMAN
Vancouver General
KENNETH BERRY
and British Columbia’s Children’s
Hospital,
Hospital
1. Rowley AM, Whitley RJ, Lakeman FD, Solinsky SM. Rapid detection of herpes-simplex virus DNA in cerebrospinal fluid of patients with herpes simplex encephalitis. Lancet 1990; 335: 440-41 2. Lakeman FD. Antigen detection in cerebrospinal fluid of patients with herpes simplex encephalitis. In: Lopez C, Roizman B, eds. Human herpes virus infections. New York: Raven Press, 1986: 235-44. 3. Roizman B, Sears AE. An inquiry into the mechanisms of herpes simplex virus latency. Annu Rev Microbiol 1987; 41: 543-71 4. Johnson RT, Johnson KP. Hydrocephalus following viral infection: the pathology of aqueductal stenosis developing after experimental mumps virus infection. J Neuropathol Exp Neurol 1968; 27: 591-606.
Dangers of nebulisers
in
nursing and
residential homes SIR,-Bronchodilator drugs are often given by nebuliser. In frail elderly dyspnoeic patients these drugs are often prescribed for symptomatic relief. We report two cases highlighting the need for clear instructions with respect to methods of nebulising drugs. An elderly nursing home resident with chronic obstructive airways disease was prescribed salbutamol 2-5 mg, nebulised thrice daily. The nursing home matron commented to a visiting doctor that the patient became drowsy during administration, and furthermore each dose took about 30 min to deliver. Inquiry revealed that pure oxygen was being used to nebulise the salbutamol. The use of an air compressor to drive the nebuliser corrected the "dose drowsiness" and the dose was given in less than 10 min. A man in a residential home was thought to be using excessive amounts of oxygen, via his nebuliser. However, baseline blood gases showed a normal PCOZ and a P02 of 8-5 kPa. Following the use of a nebuliser driven with pure oxygen, the PC02 remained normal and P02 rose to 10-2 kPa. The results vindicated the use of oxygen, showing clinical relief from dyspnoea. The general practitioner reassured the matron about the safety of oxygen consumption in this
patient. In
our
first
patient
transient
CO2
narcosis is
suggested. The
second, clearly, had hypoxic respiratory failure. Two hospitalbased studies have shown the potential dangers of inappropriate gas mixtures to drive nebulisers.12 It was suggested that baseline blood gas measurements should be done in all patients before a home nebuliser is recommended, and that such patients should have medical follow-up. In nursing and residential homes oxygen cylinders and compressed air nebulisers seem to be very common and their use is largely unmonitored. Increasingly patients with chronic illness are being managed in private-care homes. Hospitals usually have clear policies for the administration of drugs such as nebulised bronchodilators, together with regular medical review. But these policies are not universal3 in private-care units; the prescribing doctor should therefore ensure that nebulised drugs are given appropriately. Weston General Hospital, Weston Super Mare, Avon BS23 4TQ, UK
M. K. DOSHI H. L. BHAKRI C. E. BOWMAN
PE, Renowden SA, Ward MJ. Audit of nebuliser use. Postgraduate Med J 1985; 61: 1055-56.
1. Williams
2. Gunawardena KA, Patel IA, Macdonald JB, Smith AP. Oxygen as a driving gas for nebulisers: safe or dangerous? Br Med J 1984; 288: 272-73. 3. Hepple J, Bowler I, Bowman CE. A survey of nursing home residents m Weston Super Mare. Age Ageing 1989; 18: 61-63.
