- Email: [email protected]
BEHIND THE MASK
197
for cell function.6,13 For technical reasons, a gene to be transferred from one tissue to another is usually spliced to carrier DNA, often of viral origin.4,5 The possible influence of such extraneous DNA in the host cell gives further cause for concern.
Thus the expectation of immediate success for most attempts at gene therapy seems low in relation to possible attendant risks. The most promising circumstances for genetic engineering will be found in those conditions in which the illeffects can be attributed directly to deficiency or excess of a defined chemical substance throughout the body fluids, where maternal metabolism compensates for the abnormality during intrauterine development, and where the level of the substance in question does not need to be maintained within very strict limits for health. In such cases one can envisage the construction of a "genetic bypass" rather than "total correction". In other words, the gene to be inserted need not be very closely related to the one which normally subserves the defective function, nor need it be implanted in the tissue in which the normal one would have been expressed. All that will be required is synthesis and release of the missing substance in adequate quantity or, in conditions where a toxic compound is circulating, generation of a detoxifying enzyme. Phenylketonuria is one example of a condition for which such an approach may prove feasible. Another is hyperargininaemia, a rare disorder which has the distinction of being the first human disease for which gene therapy has actually been attempted.14.16 In that instance it was hoped that arginase from the Shope papilloma virus would be active in host tissues after inoculation of patients with the agent. There was some evidence from work in animals as well as indirect data from man both to justify the hope and to suggest that the risk to health from the virus itself would be very small. In the event, for reasons which remain unclear, the therapeutic trial was a failure and seems not to have been repeated.
(3° thalassaemia, the target of more recent attempts at gene therapy, presents problems of a different order. For a successful outcome it is essential that the replacement gene should generate, with absolute precision, large amounts of the normal human globin (3 chain, that it should do so exclusively within erythropoietic cells, and that it should be expressed in a substantial proportion of such cells. The actual procedures included in-vitro culture of patients’ bone marrow to enrich the tissue for haemopoietic stem cells, exposure of the cultures to cloned fragments of human DNA containing the structural sequence coding for (3 globin (and probably some of the relevant control elements), exposure also to a gene for the enzyme thymidine kinase (derived from herpes simplex virus), and reimplantation of the genetically "transformed" marrow cells into the original donors. It was intended that the viral thymidine kinase would give the treated cells a proliferative advantage over the original marrow population so that the former would overgrow the latter. Space for expansion of the reimplanted cell population was provided by clearing the marrow cavity of one femur by irradiation.
13 Williamson B. Reintroduction of genetically transformed bone marrow cells into mice. Nature 1980; 284: 397-98. 14 Rogers S. Genetic engineering In: De Grouchy J, Eblung FJG, Henderson IW, eds. Human genetics Amsterdam: Excerrpta Medien; 1972 36-40. 15. Neufeld EF, Sweeley CC, Rogers R, Friedmann J, Roblin R. Gene therapy for human genetic disease? Science 1972; 178: 648-49. 16 Terheggen HG, Lowenthal A, Lawinha F, Colombo JP, Rogers S. Unsuccessful trial of gene replacement in arginase deficiency. Z Kinderheilk 1975; 119: 1-3.
it has not yet been established by tissue work in animals that a (3 globin gene can become stably integrated into a host cell in such a way that adequate quantities of normal haemoglobin will be synthesised.6,’-20 Nor do we know that expression of herpes simplex thymidine kinase will confer upon human cells an appreciable selective advantage for growth. Small wonder that the two patients who participated in the experiment were forewarned that "the likelihood of it working was very small". 10
Unfortunately
culture
or
There is
serious ethical objection’to the development of genetic engineering for therapeutic purposes. (Alarmist reactions to progress in this sphere have been dealt with elsewhere.21) Fame, if not fortune, undoubtedly awaits the team that first achieves genetic cure of a genetic disease. This does not, however, justify the subjection of human beings to procedures which have not been fully evaluated in animals. The obstacles to successful gene therapy for (3° thalassaemia are unlikely to be overcome in a single stride. Thalassaemia-like disease can be geneated in animals,22,23 and such models, together with tissue culture studies, seem to offer scope for further development of the technology. Any giant leap for mankind which may be forthcoming will be no less impressive if preceded by a few more small steps for a no
mouse.
BEHIND THE MASK
MASK-WEARING, to prevent contamination of wounds with mouth bacteria, is thought to have been introduced into surgery by Mikulicz-Radecki in 1896.1 The practice was extended to obstetrics when the throat was seen to be a potential source of Streptococcus pyogenes in puerperal infection; and during the 1940s mask-wearing was widely adopted for dressing of wounds, probably as a result of a Medical Research Council report2 stressing the importance of mouth organisms in wound infections.
Nowadays face masks are worn for many and various clinical procedures. How far do they contribute to prevention of infection? During quiet talking and breathing there is little or no expulsion of bacteria-laden particles,3-5 and in these circumstances Staphylococcus aureus from nasal carriers is thought to be transferred most commonly via the hands and fomites;3,4 some say that the wearing of gloves may be more 17
Mulligan RC, Howard BH, Berg P. Synthesis of rabbit &bgr;-globin in cultured monkey kidney cells following infection with a SV40 &bgr;-globin recombinant genome. Nature
1979; 277: 108-14. DH, Smith KD, Boyer SH, Leder P. SV40 recombinants carrying Rabbit &bgr;-globin gene coding sequences Cell 1979; 17: 725-35 19. Mantel N, Boll W, Weissmann C. Rabbit &bgr;-globin mRNA production in mouse L cells transformed with cloned rabbit &bgr;-globin chromosomal DNA Nature 1979, 281: 18. Hamer
40-46. 20. Anderson WF, Killos L, Sanders-Haigh L, Kretschmer PJ, Diacumakos EG. Replication and expression of thymidine kinase and human globin genes. Proc Nat Acad Sci U.S.A. 1980, 77: 5399-403 21. Davis BD. Prospects for genetic intervention in man Science 1970; 170: 1279-83 22 Popp RA, Stratton LP, Hawley DK, Effron K. Hemoglobin of mice with radiation induced mutations at the hemoglobin loci. J Mol Biol 1979; 127: 141-48. 23. Whitney JB, Russell ES. Linkage of genes for adult X-globin and embryonic &agr;-like globin chains. Proc Nat Acad Sci U.S.A 1980; 77: 1087-90. 1. Walter CW The aseptic treatment of wounds New York Macmillan Co., 1948: 20 2 Medical Research Council. The prevention of "hospital infection" of wounds Medical Research Council War Wounds Committee and Committee of London Sector Pathologists (M R.C. War Memorandum No 6) London H.M. Stationery Office, 1941. 3. Duguid JP, Wallace AT Air infection with dust liberated from clothing Lancet 1948, ii 845-49. 4. Hare R, Thomas CGA The transmission of Staphylococcus aureus Br Med J 1956, ii 840-44 5. Shooter RA, Smith MA, Hunter CJW A study of surgical masks Br J Surg 1959, 47: 246-49.
198
important than masking.6 Larger particles may be expelled during coughing, sneezing, and particularly snorting, and the main function of the mask is then to deflect rather than filter bacteria. Since incoming air inevitably gets round the edges of such masks they provide little or no protection to the wearer. Thus, when the patient presents a high risk he or she must be nursed in a plastic isolator-or, alternatively, the attendants must wear protective garments, plus a full face mask with a bacteria-proof filter or a helmet with an independent air supply. The ability of masks to protect the patient varies widely; in one laboratory study,7 11 of 12 masks of the type normally worn in operating theatres were deemed satisfactory, but only 1 of 6 paper masks prevented the passage of most nasal and mouth organisms during forcible expulsion of air. Even with the better masks, room air is contaminated by expired air and the count of airborne organisms in an operating theatre is not influenced by the wearing of masks. This may be of no great moment in modern operating theatres with forced ventilation, which rapidly reduces the airborne count of bacteria to acceptable levels. But this facility is lacking in wards and some dressing rooms, and it is here that the less effective paper masks tend to be worn, often in a suboptimal way such as under the nose-and subsequent manipulation into the correct position simply serves to transfer nasal organisms to the fingers. There are few reports of the effect of mask-wearing on infection rates in patients. Ayliffe et a.,9 in an isolation unit with positive pressure ventilation where masks were not worn, found no evidence of transfer of Staph. aureus from staff to patients, other than on the hands of nurses. Likewise in baby units, the wearing of masks by staff did not reduce the rate at which babies became nasal carriers of Staph. aureus.l0,11In these situations, yet again, transfer on the hands and garments was deemed the main mode of spread. Where the need for protective isolation of patients is paramount, conventional face masks clearly do not adequately control airborne spread of infection; more elaborate measures are required, such as nursing the patient in a plastic isolator, or at least full barrier nursing by experienced staff in a room with positive pressure ventilation. In surgical operations and in the care of patients with burns or other large wounds, the wearing of efficient masks is a reasonable procedure, when allied to good aseptic techniques. In less demanding circumstances the evidence, such as it is, suggests that routine use of the less efficient masks may be no more than an expensive ritual.
from necrotic tumour cells (increasing the osmotic pressure), or erosion of local blood vessels inducing haemorrhage. Pleural effusions can also be due to transdiaphragmatic lymphatic drainage of ascitic fluid or obstruction of mediastinal lymphatics. The initial stage in management is to confirm the cause of the effusion by a search for malignant cells in the fluid. The distressing symptoms of fluid in the pleural or peritoneal cavities can recur rapidly after simple drainage, and at this point in the illness the patient may have some time to live: in one series’ the average survival with malignant effusion was 6 - 3 months, and patients with malignant lymphoma or carcinoma of the breast survived con. siderably longer. In general, when a tumour responds to systemic treatment with cytotoxic or endocrine therapy, so too does the effusion, though some patients have a temporary exacerbation. In patients with a tumour refractory to systemic treatment various approaches have been tried. Surgical pleurectomy is effective2 but carries a considerable morbidity in these patients with short expectation of life. Radiosensitive tumours can be treated by external irradiation or intracavitary instillation of radioactive isotopes such as 32P and 198 AU.1-3 Another approach is to induce pleural sclerosis by instillation of talc, quinacrine, or alkylating agents such as mustine and thiotepa after complete drainage. This controls the reaccumulation of fluid in some cases.2 Lately, several groups have reported the efficacy of tetracycline in the majority of patients with malignant effusion; although it causes local pain it has the advantage over quinacrine ofbeing given as a single dose rather than over 3-5 days. Bleomycin likewise controls effusions in most patients 7,8 although a possible drug-related deathS suggests that the dose should not be greater than 40 mg/m2 in elderly patients. One difficulty in assessing the various reports on management of malignant effusion has been the varying criteria used to assess response. Another has been that a substantial proportion of patients were on other therapy at the time of local treatment for their effusion. Keffort et awl. have reported a randomised comparison of doxorubicin, nitrogen mustard, and tetracycline after drainage of the effusion. Responses were seen with all three treatments, so doxorubicin is a further useful agent (controlling 12 out of 15 effusions). Further randomised studies are needed to determine the best way of treating malignant effusions. At present the least toxic choice seems to be tetracycline or bleomycin. If these prove to be equally effective (in a series bigger than the only randomised investigation so far reported6) then in terms of cost and complication rate tetracycline will be preferable.
TREATMENT OF MALIGNANT EFFUSIONS MALIGNANT
pleural or peritoneal effusion, a complication
of many forms of cancer, may result from local obstruction of lymphatics, release of irritant substances which increase the permeability of the serosal surfaces, accumulation of protein 6. Hare R. To mask or not to mask? Nurs Times 1962; 59: 715. 7. Rogers KB. An investigation into the efficiency of disposable face masks. J Clin Path
1980; 33: 1086-91. MA, Eitzen H, French MLV, Hart JB The operating
8. Ritter
affected by people and the surgical face mask. Clin
room environment as
Orthopaed Rel Res 1975; 111:
147-50. 9. 10.
Ayliffe GA, Babb JR, Taylor L, Wise R. A unit for source and protective isolation in a general hospital. Br Med J 1979; ii. 461-65. Cook J, Parrish JA, Shooter RA Acquisition of Staphylococcus aureus by newborn babies in a hospital maternity department. Br Med J 1958; i: 74-76. JO, MacCabe AF. Masking and gowning in nurseries for the newborn infant: effect on staphylococcal carriage and infection. Br Med J 1958; i. 76-79
11. Forfar
1. Ariel IM, Orupeza R, Pack GT. Intracavitary administration of radioactive isotopes in the control of effusions due to cancer. Cancer 1966; 19: 1096-1102. 2. Friedman MA, Slater E Malignant pleural effusions Cancer Treatment Rev 1978, 5: 49-66 3. Croll MN, Brady LW. Intracavitary use of colloids. Semin Nucl Med 1979; 9: 108-13 4 Wallach HW Intrapleural tetracycline for malignant effusions. Chest 1975; 68: 510-12. 5. Bayly TC, Kisner DL, Sybert A, MacDonald JS, Tsou E, Schein PS Tetracycline and quinacrine in the control of malignant pleural effusions Cancer 1978; 41: 1188-92. 6. Gupta N, Opfell RW, Padova J, Margileth D, Souadjian J. Intrapleural bleomycin versus tetracycline for control of malignant pleural effusion: a randomised study. Proc Am Assoc Clin Oncol 1980; 21: abstr C-189 7 Paladine W, Cunningham TJ, Sponzo R, Donavan M, Olson K, Horton J Intracavitary bleomycin in the management of malignant effusions. Cancer 1976. 38: 1903-08. 8. Trotter JM, Stuart JEB, McBeath F, McVie JG, Calman KC The management of malignant effusions with bleomycin. Br J Cancer 1979; 40: 316. 9 Keffort RF, Woods RL, Fox RM, Tattersall MHN Intracavitary adriamycin, nitrogen mustard and tetracycline in the control of malignant effusions Med J Aust 1980; ii 447-48.
for cell function.6,13 For technical reasons, a gene to be transferred from one tissue to another is usually spliced to carrier DNA, often of viral origin.4,5 The possible influence of such extraneous DNA in the host cell gives further cause for concern.
Thus the expectation of immediate success for most attempts at gene therapy seems low in relation to possible attendant risks. The most promising circumstances for genetic engineering will be found in those conditions in which the illeffects can be attributed directly to deficiency or excess of a defined chemical substance throughout the body fluids, where maternal metabolism compensates for the abnormality during intrauterine development, and where the level of the substance in question does not need to be maintained within very strict limits for health. In such cases one can envisage the construction of a "genetic bypass" rather than "total correction". In other words, the gene to be inserted need not be very closely related to the one which normally subserves the defective function, nor need it be implanted in the tissue in which the normal one would have been expressed. All that will be required is synthesis and release of the missing substance in adequate quantity or, in conditions where a toxic compound is circulating, generation of a detoxifying enzyme. Phenylketonuria is one example of a condition for which such an approach may prove feasible. Another is hyperargininaemia, a rare disorder which has the distinction of being the first human disease for which gene therapy has actually been attempted.14.16 In that instance it was hoped that arginase from the Shope papilloma virus would be active in host tissues after inoculation of patients with the agent. There was some evidence from work in animals as well as indirect data from man both to justify the hope and to suggest that the risk to health from the virus itself would be very small. In the event, for reasons which remain unclear, the therapeutic trial was a failure and seems not to have been repeated.
(3° thalassaemia, the target of more recent attempts at gene therapy, presents problems of a different order. For a successful outcome it is essential that the replacement gene should generate, with absolute precision, large amounts of the normal human globin (3 chain, that it should do so exclusively within erythropoietic cells, and that it should be expressed in a substantial proportion of such cells. The actual procedures included in-vitro culture of patients’ bone marrow to enrich the tissue for haemopoietic stem cells, exposure of the cultures to cloned fragments of human DNA containing the structural sequence coding for (3 globin (and probably some of the relevant control elements), exposure also to a gene for the enzyme thymidine kinase (derived from herpes simplex virus), and reimplantation of the genetically "transformed" marrow cells into the original donors. It was intended that the viral thymidine kinase would give the treated cells a proliferative advantage over the original marrow population so that the former would overgrow the latter. Space for expansion of the reimplanted cell population was provided by clearing the marrow cavity of one femur by irradiation.
13 Williamson B. Reintroduction of genetically transformed bone marrow cells into mice. Nature 1980; 284: 397-98. 14 Rogers S. Genetic engineering In: De Grouchy J, Eblung FJG, Henderson IW, eds. Human genetics Amsterdam: Excerrpta Medien; 1972 36-40. 15. Neufeld EF, Sweeley CC, Rogers R, Friedmann J, Roblin R. Gene therapy for human genetic disease? Science 1972; 178: 648-49. 16 Terheggen HG, Lowenthal A, Lawinha F, Colombo JP, Rogers S. Unsuccessful trial of gene replacement in arginase deficiency. Z Kinderheilk 1975; 119: 1-3.
it has not yet been established by tissue work in animals that a (3 globin gene can become stably integrated into a host cell in such a way that adequate quantities of normal haemoglobin will be synthesised.6,’-20 Nor do we know that expression of herpes simplex thymidine kinase will confer upon human cells an appreciable selective advantage for growth. Small wonder that the two patients who participated in the experiment were forewarned that "the likelihood of it working was very small". 10
Unfortunately
culture
or
There is
serious ethical objection’to the development of genetic engineering for therapeutic purposes. (Alarmist reactions to progress in this sphere have been dealt with elsewhere.21) Fame, if not fortune, undoubtedly awaits the team that first achieves genetic cure of a genetic disease. This does not, however, justify the subjection of human beings to procedures which have not been fully evaluated in animals. The obstacles to successful gene therapy for (3° thalassaemia are unlikely to be overcome in a single stride. Thalassaemia-like disease can be geneated in animals,22,23 and such models, together with tissue culture studies, seem to offer scope for further development of the technology. Any giant leap for mankind which may be forthcoming will be no less impressive if preceded by a few more small steps for a no
mouse.
BEHIND THE MASK
MASK-WEARING, to prevent contamination of wounds with mouth bacteria, is thought to have been introduced into surgery by Mikulicz-Radecki in 1896.1 The practice was extended to obstetrics when the throat was seen to be a potential source of Streptococcus pyogenes in puerperal infection; and during the 1940s mask-wearing was widely adopted for dressing of wounds, probably as a result of a Medical Research Council report2 stressing the importance of mouth organisms in wound infections.
Nowadays face masks are worn for many and various clinical procedures. How far do they contribute to prevention of infection? During quiet talking and breathing there is little or no expulsion of bacteria-laden particles,3-5 and in these circumstances Staphylococcus aureus from nasal carriers is thought to be transferred most commonly via the hands and fomites;3,4 some say that the wearing of gloves may be more 17
Mulligan RC, Howard BH, Berg P. Synthesis of rabbit &bgr;-globin in cultured monkey kidney cells following infection with a SV40 &bgr;-globin recombinant genome. Nature
1979; 277: 108-14. DH, Smith KD, Boyer SH, Leder P. SV40 recombinants carrying Rabbit &bgr;-globin gene coding sequences Cell 1979; 17: 725-35 19. Mantel N, Boll W, Weissmann C. Rabbit &bgr;-globin mRNA production in mouse L cells transformed with cloned rabbit &bgr;-globin chromosomal DNA Nature 1979, 281: 18. Hamer
40-46. 20. Anderson WF, Killos L, Sanders-Haigh L, Kretschmer PJ, Diacumakos EG. Replication and expression of thymidine kinase and human globin genes. Proc Nat Acad Sci U.S.A. 1980, 77: 5399-403 21. Davis BD. Prospects for genetic intervention in man Science 1970; 170: 1279-83 22 Popp RA, Stratton LP, Hawley DK, Effron K. Hemoglobin of mice with radiation induced mutations at the hemoglobin loci. J Mol Biol 1979; 127: 141-48. 23. Whitney JB, Russell ES. Linkage of genes for adult X-globin and embryonic &agr;-like globin chains. Proc Nat Acad Sci U.S.A 1980; 77: 1087-90. 1. Walter CW The aseptic treatment of wounds New York Macmillan Co., 1948: 20 2 Medical Research Council. The prevention of "hospital infection" of wounds Medical Research Council War Wounds Committee and Committee of London Sector Pathologists (M R.C. War Memorandum No 6) London H.M. Stationery Office, 1941. 3. Duguid JP, Wallace AT Air infection with dust liberated from clothing Lancet 1948, ii 845-49. 4. Hare R, Thomas CGA The transmission of Staphylococcus aureus Br Med J 1956, ii 840-44 5. Shooter RA, Smith MA, Hunter CJW A study of surgical masks Br J Surg 1959, 47: 246-49.
198
important than masking.6 Larger particles may be expelled during coughing, sneezing, and particularly snorting, and the main function of the mask is then to deflect rather than filter bacteria. Since incoming air inevitably gets round the edges of such masks they provide little or no protection to the wearer. Thus, when the patient presents a high risk he or she must be nursed in a plastic isolator-or, alternatively, the attendants must wear protective garments, plus a full face mask with a bacteria-proof filter or a helmet with an independent air supply. The ability of masks to protect the patient varies widely; in one laboratory study,7 11 of 12 masks of the type normally worn in operating theatres were deemed satisfactory, but only 1 of 6 paper masks prevented the passage of most nasal and mouth organisms during forcible expulsion of air. Even with the better masks, room air is contaminated by expired air and the count of airborne organisms in an operating theatre is not influenced by the wearing of masks. This may be of no great moment in modern operating theatres with forced ventilation, which rapidly reduces the airborne count of bacteria to acceptable levels. But this facility is lacking in wards and some dressing rooms, and it is here that the less effective paper masks tend to be worn, often in a suboptimal way such as under the nose-and subsequent manipulation into the correct position simply serves to transfer nasal organisms to the fingers. There are few reports of the effect of mask-wearing on infection rates in patients. Ayliffe et a.,9 in an isolation unit with positive pressure ventilation where masks were not worn, found no evidence of transfer of Staph. aureus from staff to patients, other than on the hands of nurses. Likewise in baby units, the wearing of masks by staff did not reduce the rate at which babies became nasal carriers of Staph. aureus.l0,11In these situations, yet again, transfer on the hands and garments was deemed the main mode of spread. Where the need for protective isolation of patients is paramount, conventional face masks clearly do not adequately control airborne spread of infection; more elaborate measures are required, such as nursing the patient in a plastic isolator, or at least full barrier nursing by experienced staff in a room with positive pressure ventilation. In surgical operations and in the care of patients with burns or other large wounds, the wearing of efficient masks is a reasonable procedure, when allied to good aseptic techniques. In less demanding circumstances the evidence, such as it is, suggests that routine use of the less efficient masks may be no more than an expensive ritual.
from necrotic tumour cells (increasing the osmotic pressure), or erosion of local blood vessels inducing haemorrhage. Pleural effusions can also be due to transdiaphragmatic lymphatic drainage of ascitic fluid or obstruction of mediastinal lymphatics. The initial stage in management is to confirm the cause of the effusion by a search for malignant cells in the fluid. The distressing symptoms of fluid in the pleural or peritoneal cavities can recur rapidly after simple drainage, and at this point in the illness the patient may have some time to live: in one series’ the average survival with malignant effusion was 6 - 3 months, and patients with malignant lymphoma or carcinoma of the breast survived con. siderably longer. In general, when a tumour responds to systemic treatment with cytotoxic or endocrine therapy, so too does the effusion, though some patients have a temporary exacerbation. In patients with a tumour refractory to systemic treatment various approaches have been tried. Surgical pleurectomy is effective2 but carries a considerable morbidity in these patients with short expectation of life. Radiosensitive tumours can be treated by external irradiation or intracavitary instillation of radioactive isotopes such as 32P and 198 AU.1-3 Another approach is to induce pleural sclerosis by instillation of talc, quinacrine, or alkylating agents such as mustine and thiotepa after complete drainage. This controls the reaccumulation of fluid in some cases.2 Lately, several groups have reported the efficacy of tetracycline in the majority of patients with malignant effusion; although it causes local pain it has the advantage over quinacrine ofbeing given as a single dose rather than over 3-5 days. Bleomycin likewise controls effusions in most patients 7,8 although a possible drug-related deathS suggests that the dose should not be greater than 40 mg/m2 in elderly patients. One difficulty in assessing the various reports on management of malignant effusion has been the varying criteria used to assess response. Another has been that a substantial proportion of patients were on other therapy at the time of local treatment for their effusion. Keffort et awl. have reported a randomised comparison of doxorubicin, nitrogen mustard, and tetracycline after drainage of the effusion. Responses were seen with all three treatments, so doxorubicin is a further useful agent (controlling 12 out of 15 effusions). Further randomised studies are needed to determine the best way of treating malignant effusions. At present the least toxic choice seems to be tetracycline or bleomycin. If these prove to be equally effective (in a series bigger than the only randomised investigation so far reported6) then in terms of cost and complication rate tetracycline will be preferable.
TREATMENT OF MALIGNANT EFFUSIONS MALIGNANT
pleural or peritoneal effusion, a complication
of many forms of cancer, may result from local obstruction of lymphatics, release of irritant substances which increase the permeability of the serosal surfaces, accumulation of protein 6. Hare R. To mask or not to mask? Nurs Times 1962; 59: 715. 7. Rogers KB. An investigation into the efficiency of disposable face masks. J Clin Path
1980; 33: 1086-91. MA, Eitzen H, French MLV, Hart JB The operating
8. Ritter
affected by people and the surgical face mask. Clin
room environment as
Orthopaed Rel Res 1975; 111:
147-50. 9. 10.
Ayliffe GA, Babb JR, Taylor L, Wise R. A unit for source and protective isolation in a general hospital. Br Med J 1979; ii. 461-65. Cook J, Parrish JA, Shooter RA Acquisition of Staphylococcus aureus by newborn babies in a hospital maternity department. Br Med J 1958; i: 74-76. JO, MacCabe AF. Masking and gowning in nurseries for the newborn infant: effect on staphylococcal carriage and infection. Br Med J 1958; i. 76-79
11. Forfar
1. Ariel IM, Orupeza R, Pack GT. Intracavitary administration of radioactive isotopes in the control of effusions due to cancer. Cancer 1966; 19: 1096-1102. 2. Friedman MA, Slater E Malignant pleural effusions Cancer Treatment Rev 1978, 5: 49-66 3. Croll MN, Brady LW. Intracavitary use of colloids. Semin Nucl Med 1979; 9: 108-13 4 Wallach HW Intrapleural tetracycline for malignant effusions. Chest 1975; 68: 510-12. 5. Bayly TC, Kisner DL, Sybert A, MacDonald JS, Tsou E, Schein PS Tetracycline and quinacrine in the control of malignant pleural effusions Cancer 1978; 41: 1188-92. 6. Gupta N, Opfell RW, Padova J, Margileth D, Souadjian J. Intrapleural bleomycin versus tetracycline for control of malignant pleural effusion: a randomised study. Proc Am Assoc Clin Oncol 1980; 21: abstr C-189 7 Paladine W, Cunningham TJ, Sponzo R, Donavan M, Olson K, Horton J Intracavitary bleomycin in the management of malignant effusions. Cancer 1976. 38: 1903-08. 8. Trotter JM, Stuart JEB, McBeath F, McVie JG, Calman KC The management of malignant effusions with bleomycin. Br J Cancer 1979; 40: 316. 9 Keffort RF, Woods RL, Fox RM, Tattersall MHN Intracavitary adriamycin, nitrogen mustard and tetracycline in the control of malignant effusions Med J Aust 1980; ii 447-48.