127
NAC twice a day should result in an average total NAC concentration of 20 µmol/1. Furthermore, in samples used for Lp(a) determinations by Gavish and Breslow, taken 10-12 h after the drug was given, intact reduced NAC was unmeasurable and the concentration of the major NAC metabolite cysteine was not significantly different from that in control plasma. Thus the plasma levels of NAC in the patients described by Gavish and Breslow were unlikely ever to have been high enough to alter Lp(a)
properties can be produced. One such a material, developed originally for use in urological surgery, is a composite of vicryl mesh and collagen film.6 The material is leak proof, readily degraded and replaced by host tissue, and non-antigenic. This membrane is now being used for dura mater replacement, and preliminary results in the UK and in France indicate that it is a very useful and acceptable biocompatible prosthetic material for use in this area of surgery.
immunoreactivity .
Department of Urology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK
Rockefeller University, New York, NY 10021 USA
JAN L. BRESLOW NEAL AZROLAN ANDREW BOSTOM
1. Penar 1 Gavish D, Breslow JL. Lipoprotein(a) reduction by N-acetylcysteine. Lancet 1991, 337: 203-04 2. Stalenhoef AFH, Kroon AA, Demacker PNM. N-acetylcysteine and lipoprotein. Lancet 1991, 337: 491. 3. Scanu AM N-acetylcysteine and immunoreactivity of lipoprotein(a). Lancet 1991; 337: 1159. 4. Kostner GM, Gavish D, Leopold B, Bolzano K, Weintraub MS, Breslow JL. HMG-CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels. Circulation 1988; 80: 1313-19. 5. Olsson B, Johansson M, Gabnelsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 1988; 34: 77-82. 6 Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration Eur J Clin Pharmacol 1989; 36: 127-31. 7. North DS, Peterson RG, Krenzelok EP. Effect of activated charcoal administration on acetylcysteine serum levels in humans. Am J Hosp Pharm 1981; 38: 1022-24.
Dural prostheses, where do we go from here? SIR,- The withdrawal of lyophilised cadaveric human dura from use in the UK
leaves a dearth of prosthetic materials for dural repair. The cadaveric material had proved an excellent substitute for the past two decades, but the disturbing reports of the transmission of viral disease has, quite rightly, necessitated abandonment.1 The main advantage of ’Lyodura’ was biodegradability; non-degradable materials, such as ’Silastic’ and Dacron’, carry the risk of and potentially persistent infectionThe use of permanent materials in the subdural space is far from ideal. Autologous tissue is now probably the best alternative but galea and fascia lata, though well established, are not always readily available. So what is the prosthetic material of choice
encapsulation, secondary haemorrhage,
today? Since the 1970s synthetic water-soluble polymers have revolutionised sutures. Polymers of polyglycolic acid (’Dexon’), co-polymers of glycolic and lactic acids (’Vicryl’), and polydioxone (’PDS’) have predictable rates of resorption in vivo and excellent tissue tolerance. These polymers can be woven to form meshes in which the tightness of the weave controls their physical properties and porosity. Vicryl mesh has been used experimentally for dural repair and it allows the growth of a fibrous layer over its surface. Initial reports of cerebrospinal fluid leakage were discouraging, but a finer weave has proved to be leak proof in laboratory animals3. In these experiments the mesh was replaced by a layer of collagen resembling dura mater. However, in the animal model, soft tissue was placed directly over the craniectomy site (from which the bone had been removed) and in immediate contact with the prosthesis, and it is well established that a similar layer of collagen will form if no prosthesis is used and soft tissue is applied directly over a dural defect.’ The efficacy of synthetic, water-soluble, polymer meshes alone as dural prostheses is therefore not proven. There has been a resurgence in the use of collagen films for repair of dural defects.’ Such films are prepared from reconstituted bovine dermis or tendon collagen. With carefully controlled sources and accredited herds the possibility of collagen being derived from an animal that may have had bovine spongiform encephalopathy can be eliminated. Collagen film alone, however, has certain practical surgical disadvantages with respect to its handling and ability to hold sutures-properties that are of prime importance when a watertight seal is needed. There is now a new generation of composite materials under development. By combining synthetic degradable meshes with reconstituted collagen, materials with a range of biological
R. N. MEDDINGS R. SCOTT J. F. BUCKLEY
PL, Prichard JW Jakob Creutzfeldt disease associated with cadaveric dura.
J Neurosurg 1987; 67: 149-50. 2 Simpson D, Robson A. Recurrent subarachnoid haemorrhage m association with a dural substitute. J Neurosurg 1984; 60: 408-09. 3. Nussbaum CE, Maurer PK, McDonald JV Vicryl (polyglactin 910) mesh as a dural substitute in the presence of pia arachnoid injury. J Neurosurg 1989; 1971: 124-27. 4. Keener EB. An experimental model of the reactions of the dura mater to wounding and loss of substance. Neurosurg 1959, 16: 424-27. J 5 Collins RLL, Christiansen D, Zazanis GA, et al. Use of collagen film as a dural substitute: preliminary animal studies. J Biomed Materials Res 1991; 25: 267-76. 6. Scott R, Gorham SD, Aitcheson M, et al. First clinical report of a new biodegradable membrane for use in urological surgery. Br J Urol 1991; 68: 421-24.
Spontaneous abortion and exposure to vinyl chloride SIR,-Certain studies have suggested that the exposure to vinyl a reproductive hazard (spontaneous abortions, congenital malformations). 1-4 In one of these studies2 the frequency chloride may be
of spontaneous abortions amongst the wives of workers exposed to vinyl chloride was significantly raised but this result was contested.5 To provide more data we have done a similar study, in two chemical plants that synthesise and polymerise vinyl chloride. The wives of all men who worked in these factories and who were under 45 on Jan 1, 1984, completed a questionnaire on their obstetric history. The response rate was 76%. Women who had had three or more miscarriages were excluded from the study. To assess occupational exposure occupational physicians at the plants (F. D., A. P., and A. R.) compiled work records and associated risks. Workers exposed to benzene, mercury, dichloroethane, hydrazine, or oxodiazone were excluded from the study. When a worker had been exposed to vinyl chloride for at least 3 months before the date of conception, the pregnancies were said to be "exposed"; when the workers had not been exposed to vinyl chloride before their spouses’ pregnancies, these pregnancies were "unexposed". The study was done on 534 workers, 82 of them having been exposed to vinyl chloride at some time, and the number of exposed and unexposed pregnancies were, respectively, 90 and 1027. Rates of spontaneous abortions (number of spontaneous abortions divided by number of pregnancies) were compared, potentially confounding factors (age at conception, parity, smoking, time elapsed since conception6) were taken into account by conditional logistic regression. The crude rates of spontaneous abortion in exposed and unexposed pregnancies were 8-9% and 8-8%, respectively, and adjustment for confounders did not suggest a significant relation between spontaneous abortion and paternal exposure to vinyl chloride (odds ratio 0.94; 95% CI - 0-44-2-03):
Exposed Unexposed No of pregnancies
Parity Time
90
1027
2-0(1-1)
1-8(11)
p ..
elapsed since pregnancy
(yr) 9-7(4-4) 13-2(6-1) Age of mother at pregnancy (yr) 25 8 (3-7) 25-0 (4-3) Age of father at.pregnancy (yr) 28-4(38) 26.9(4-1) Smoking during pregnancy 31 2 25-4 (mother) (%) 0 Length of exposure (mo) 56-5(37-0) No of abortions (%) 8(8-9%) 90(88%) Results
as mean
(SE),
statistical
NAC twice a day should result in an average total NAC concentration of 20 µmol/1. Furthermore, in samples used for Lp(a) determinations by Gavish and Breslow, taken 10-12 h after the drug was given, intact reduced NAC was unmeasurable and the concentration of the major NAC metabolite cysteine was not significantly different from that in control plasma. Thus the plasma levels of NAC in the patients described by Gavish and Breslow were unlikely ever to have been high enough to alter Lp(a)
properties can be produced. One such a material, developed originally for use in urological surgery, is a composite of vicryl mesh and collagen film.6 The material is leak proof, readily degraded and replaced by host tissue, and non-antigenic. This membrane is now being used for dura mater replacement, and preliminary results in the UK and in France indicate that it is a very useful and acceptable biocompatible prosthetic material for use in this area of surgery.
immunoreactivity .
Department of Urology, Glasgow Royal Infirmary, Glasgow G4 0SF, UK
Rockefeller University, New York, NY 10021 USA
JAN L. BRESLOW NEAL AZROLAN ANDREW BOSTOM
1. Penar 1 Gavish D, Breslow JL. Lipoprotein(a) reduction by N-acetylcysteine. Lancet 1991, 337: 203-04 2. Stalenhoef AFH, Kroon AA, Demacker PNM. N-acetylcysteine and lipoprotein. Lancet 1991, 337: 491. 3. Scanu AM N-acetylcysteine and immunoreactivity of lipoprotein(a). Lancet 1991; 337: 1159. 4. Kostner GM, Gavish D, Leopold B, Bolzano K, Weintraub MS, Breslow JL. HMG-CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels. Circulation 1988; 80: 1313-19. 5. Olsson B, Johansson M, Gabnelsson J, Bolme P. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol 1988; 34: 77-82. 6 Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration Eur J Clin Pharmacol 1989; 36: 127-31. 7. North DS, Peterson RG, Krenzelok EP. Effect of activated charcoal administration on acetylcysteine serum levels in humans. Am J Hosp Pharm 1981; 38: 1022-24.
Dural prostheses, where do we go from here? SIR,- The withdrawal of lyophilised cadaveric human dura from use in the UK
leaves a dearth of prosthetic materials for dural repair. The cadaveric material had proved an excellent substitute for the past two decades, but the disturbing reports of the transmission of viral disease has, quite rightly, necessitated abandonment.1 The main advantage of ’Lyodura’ was biodegradability; non-degradable materials, such as ’Silastic’ and Dacron’, carry the risk of and potentially persistent infectionThe use of permanent materials in the subdural space is far from ideal. Autologous tissue is now probably the best alternative but galea and fascia lata, though well established, are not always readily available. So what is the prosthetic material of choice
encapsulation, secondary haemorrhage,
today? Since the 1970s synthetic water-soluble polymers have revolutionised sutures. Polymers of polyglycolic acid (’Dexon’), co-polymers of glycolic and lactic acids (’Vicryl’), and polydioxone (’PDS’) have predictable rates of resorption in vivo and excellent tissue tolerance. These polymers can be woven to form meshes in which the tightness of the weave controls their physical properties and porosity. Vicryl mesh has been used experimentally for dural repair and it allows the growth of a fibrous layer over its surface. Initial reports of cerebrospinal fluid leakage were discouraging, but a finer weave has proved to be leak proof in laboratory animals3. In these experiments the mesh was replaced by a layer of collagen resembling dura mater. However, in the animal model, soft tissue was placed directly over the craniectomy site (from which the bone had been removed) and in immediate contact with the prosthesis, and it is well established that a similar layer of collagen will form if no prosthesis is used and soft tissue is applied directly over a dural defect.’ The efficacy of synthetic, water-soluble, polymer meshes alone as dural prostheses is therefore not proven. There has been a resurgence in the use of collagen films for repair of dural defects.’ Such films are prepared from reconstituted bovine dermis or tendon collagen. With carefully controlled sources and accredited herds the possibility of collagen being derived from an animal that may have had bovine spongiform encephalopathy can be eliminated. Collagen film alone, however, has certain practical surgical disadvantages with respect to its handling and ability to hold sutures-properties that are of prime importance when a watertight seal is needed. There is now a new generation of composite materials under development. By combining synthetic degradable meshes with reconstituted collagen, materials with a range of biological
R. N. MEDDINGS R. SCOTT J. F. BUCKLEY
PL, Prichard JW Jakob Creutzfeldt disease associated with cadaveric dura.
J Neurosurg 1987; 67: 149-50. 2 Simpson D, Robson A. Recurrent subarachnoid haemorrhage m association with a dural substitute. J Neurosurg 1984; 60: 408-09. 3. Nussbaum CE, Maurer PK, McDonald JV Vicryl (polyglactin 910) mesh as a dural substitute in the presence of pia arachnoid injury. J Neurosurg 1989; 1971: 124-27. 4. Keener EB. An experimental model of the reactions of the dura mater to wounding and loss of substance. Neurosurg 1959, 16: 424-27. J 5 Collins RLL, Christiansen D, Zazanis GA, et al. Use of collagen film as a dural substitute: preliminary animal studies. J Biomed Materials Res 1991; 25: 267-76. 6. Scott R, Gorham SD, Aitcheson M, et al. First clinical report of a new biodegradable membrane for use in urological surgery. Br J Urol 1991; 68: 421-24.
Spontaneous abortion and exposure to vinyl chloride SIR,-Certain studies have suggested that the exposure to vinyl a reproductive hazard (spontaneous abortions, congenital malformations). 1-4 In one of these studies2 the frequency chloride may be
of spontaneous abortions amongst the wives of workers exposed to vinyl chloride was significantly raised but this result was contested.5 To provide more data we have done a similar study, in two chemical plants that synthesise and polymerise vinyl chloride. The wives of all men who worked in these factories and who were under 45 on Jan 1, 1984, completed a questionnaire on their obstetric history. The response rate was 76%. Women who had had three or more miscarriages were excluded from the study. To assess occupational exposure occupational physicians at the plants (F. D., A. P., and A. R.) compiled work records and associated risks. Workers exposed to benzene, mercury, dichloroethane, hydrazine, or oxodiazone were excluded from the study. When a worker had been exposed to vinyl chloride for at least 3 months before the date of conception, the pregnancies were said to be "exposed"; when the workers had not been exposed to vinyl chloride before their spouses’ pregnancies, these pregnancies were "unexposed". The study was done on 534 workers, 82 of them having been exposed to vinyl chloride at some time, and the number of exposed and unexposed pregnancies were, respectively, 90 and 1027. Rates of spontaneous abortions (number of spontaneous abortions divided by number of pregnancies) were compared, potentially confounding factors (age at conception, parity, smoking, time elapsed since conception6) were taken into account by conditional logistic regression. The crude rates of spontaneous abortion in exposed and unexposed pregnancies were 8-9% and 8-8%, respectively, and adjustment for confounders did not suggest a significant relation between spontaneous abortion and paternal exposure to vinyl chloride (odds ratio 0.94; 95% CI - 0-44-2-03):
Exposed Unexposed No of pregnancies
Parity Time
90
1027
2-0(1-1)
1-8(11)
p ..
elapsed since pregnancy
(yr) 9-7(4-4) 13-2(6-1) Age of mother at pregnancy (yr) 25 8 (3-7) 25-0 (4-3) Age of father at.pregnancy (yr) 28-4(38) 26.9(4-1) Smoking during pregnancy 31 2 25-4 (mother) (%) 0 Length of exposure (mo) 56-5(37-0) No of abortions (%) 8(8-9%) 90(88%) Results
as mean
(SE),
statistical
