- Email: [email protected]
EFFECT, COST, AND VALUE OF HOSPICE CARE
259
theoretically feasible, when it was first proposed about three years ago15-17 this molecular fishing expedition looked like a lot of work with no certainty of a worthwhile catch. However, it has already allowed a British group to obtain an RFLP linkage to the locus for Duchenne muscular dystrophy, 18 and a few weeks ago workers in the USA announced that they had discovered a very close linkage marker for the gene for Huntington’s chorea. 19 Finally, since it is now possible to construct short oligonucleotide probes that can identify single base mutations,2° it may soon be possible directly to identify many single gene disorders by gene mapping, once their molecular pathology has been determined.
EFFECT, COST, AND VALUE OF HOSPICE CARE THE treatment of dying patients continues to range from the superb to the unsympathetic dismissal. The desire to improve care brought about the development of hospices in Britain, a lead enthusiastically followed in North America where over a thousand hospice services have sprung up since 1974. But hospices need more than the initial inspiration and charitable funds to play their part. In Britain a recent report indicated that, after the exhilaration of obtaining funds to open local hospices, almost as much must be found each year to run them. In the United States public favour of the hospice movement has strengthened the demand for Federal financial support. Reasonably enough, an initial scheme for reimbursement through Medicare has been coupled with a requirement that the effectiveness of hospice care be tested and costed. Questions immediately arise about the criteria of good care and how the large but not limitless sums of money should be apportioned to treat patients. The editors of the 7ournal of Chronic Disease have devoted considerable space to airing the proposed methods of evaluating hospice care.2They have risked boring some readers with detail because the study is important, and its multicentre design will not easily be repeated. They are persuaded that early criticism and comments based on fuller information are preferable to delayed criticisms of a final report where the account of methods is so often curtailed. In the same journal Mount and Scott, who have conducted assessments in their own palliative care service in Montreal, contribute comments and criticisms of the proposed investigation while observing that hospices have already been 15. Kan
YW, Dozy
AM. Antenatal
diagnosis of sickle
cell anaemia
by
DNA
analysis of
amniotic-fluid cells. Lancet 1978; ii: 910. 16. Solomon E, Bodmer WF. Evolution of sickle variant gene. Lancet 1979; i: 923. 17. Botstein D. White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in Man using restriction length fragment polymorphisms. Am J Hum Genet 1980; 32: 314-31. 18. Murray JM, Davies KE, Harper PS, Meredith L, Mueller CR, Williamson R. Linkage relationship ofa cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature 1982, 300: 69-71. 19. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB. A polymorphic DNA marker genetically linked to Huntington’s chorea. Nature 1983; 306: 234-38. 20. Conner BJ, Reyes AA, Morin C, Itakura K, Teplitz RL, Wallace RB. Detection of sickle cell &bgr;s-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 1983; 80: 278-82. 1. Taylor H. The hospice movement in Britain, its role and its future. London: Centre for Policy on Ageing, 1983. 2. Greer DS, Mor V, Sherwood S, Morris JN, Birnbaum H. National hospice study analysis plan. J Chron Dis 1983; 36: 737-80. 3. Mount BM, Scott JF. Whither hospice evaluation? J Chron Dis 1983; 36: 731-36.
superior to conventional care in controlling pain and increasing mobility, and are probably better in terms of social shown
and psychological adjustment. They dispute some of the characteristics of hospices and their patients presented by Greer and others2 in the National Hospice Study Analysis Plan-eg, patient and family must know of the terminal illness. The plan uses the statements on hospice "philosophy" to form a conceptual framework from which to derive research questions, but an economic interest has slanted the theorising. For example, the conceptual framework has translated the hospice principle that family members, friends, and volunteers should take an active part in the support of the dying into a statement that non-paid people substitute for professional personnel. This is doubtful; hospice staff see non-professional caring as a beneficial contribution to all concerned, but not with an automatic reduction of the often sparse professional care. Likewise the hospice desire to increase home-based care is seen as an economic advantage; perhaps so ifincreased homebased care just means less time in expensive hospitals, but not necessarily if the intention is to improve the care at home. In fact in Britain Parkes4 has shown that provision ofa hospicebased home care team has so far tended to lengthen the patients’ time at home but eventually a similar proportion experience discomfort. The theoretical extrapolations of the National Hospice Study warrant criticism not because they invalidate the subsequent legitimate research questions on efficacy and cost, but lest they foster biased interpretation of the results. If the test of a hospice is that it saves professional time, it will have apparently failed if it takes as much or more professional effort to give good appropriate terminal care as it does to undertake the irrelevant investigations and incredible cures.
study is to evaluate quality of life and care. Spitzer et a Quality of Life Scale that can be used in terminal care, but Mount and Scott2 point to the scale’s limitations in respect of personal and spiritual values affecting individuals and families-important elements in hospice care. A sense of spiritual fulfilment may have a unique value hardly reflected in any total score of welfare. Subjective measures can not be wholly precise; even criteria regarding physical suffering are disputable. Can any numerical score validly equate so many hours of mild pain to so many minutes of severe pain? The proposed measures of pain and symptoms have generally given good guidance to the quality of symptom relief. The hypothesis, however, that because hospices emphasise the prevention of pain and other symptoms they will use more analgesics and tranquillisers is misleading. Too often the less skilled give intermittent large doses and, instead of comfort, produce fluctuation between The
al5 have patiently constructed and tested
distress and unconsciousness. The practical difficulties of assessment are not negligible. The data collector and the bereaved are not to be envied in their potentially turgid final interview scheduled to include questions on grief experience and the quality of the last three days of life and to cross-check the service records with the bills received and expenses incurred by the family. The investigation will produce data of varying quality, requiring careful interpretation. The authors lay open for inspection their proposed elaborate statistical techniques, including the allowances made since the "controls" cannot be perfect. Clearly, the statistical significance of data, often imprecise, 4. Parkes CM. Terminal
care evaluation of an advisory domiciliary service at St. Christopher’s Hospice. Postgrad Med J 1980; 56: 685-89. 5. Spitzer WO, Dobson AJ, Hall J, et al. Measuring the quality of life of cancer patients J
Chron Dis 1981; 34: 585-97.
260
be distinguished from clinical or moral significance in a sphere where individuality is so important. The description of how results will be analysed states at one point that "outliers are dropped"-valid enough, perhaps, in the statistical context but inconceivable to hospice workers who expend great effort to help the unusual person. The editors and authors are to be thanked for tackling and exposing the difficulties fully. The necessary refinement of thought and the conduct of the inquiry itself may well have lasting benefits. The results should yield much information on some aspects of what hospices do or do not achieve and the financial cost, but they will need cautious interpretation and cannnot say how much a State ought to spend in helping people to end their lives in reasonable physical and mental comfort. must
CEFTIZOXIME AND CEFTAZIDIME Two more parenteral cephalosporins, ceftizoxime and ceftazidime have come on the UK market. It is futile to ask whether we really need more agents of this kind (cephalosporins seldom being drugs of first choice); instead let us see how these new compounds compare with the other "3rd generation" cephalosporins and what might be the clinical indications for their use. Structurally, ceftizoxime is closely related to cefotaximei but differs in not being metabolised (desacetylated). The spectrum and degree of antibacterial activity is similar to that and of cefotaxime latamoxef, encompassing the Enterobacteriaceae and streptococci (but not enterococci), Haemophilus influenzae, and Neisseria species. The activity against Staphylococcus aureus is more modest and there is little useful activity against Pseudomonas aeruginosa; like most of the recently introduced cephalosporins ceftizoxime is resistant to destruction by a wide range of bacterial (3-lactamases,2 with the important exception of that produced by Bacteroides fragilis. Ceftazidime differs from ceftizoxime in being even less effective against S aureus4but in being highly active against Ps aeruginosa;5 9007o of strains are inhibited by 4 mg/1 or less, and after 1 g intravenously blood levels will exceed.4 mg/1 for about 8 h.6The two compounds differ a little in their pharmacokinetics, ceftizoxime having a 6 serum half-life of 1 h7 compared with ceftazidime’s 1 ’8 h.b Ceftizoxime should probably be given 3-4 times a day (despite the recommendations that it be given twice daily) and ceftazidime 2-3 times a day. Neither compound contains the N-methylthiotetrazole side-chain that is common to many in been has and implicated cephalosporins
1. Dunn GL. Ceftizoxime and other 3rd generation cephalosporins: structure-activity relationships. J Antimicrob Chemother 1982; 10 (suppl C): 1-10. 2. Greenwood D, Pearson N, Eley A, O’Grady F. Comparative in vitro activity of
cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency. Antimicrob Ag Chemother 1980; 17: 397-401. 3. Neu HC. Factors that affect the in vitro activity of cephalosporin antibiotics. J Antimicrob Chemother 1982; 10 (suppl C): 11-23. 4. Phillips I, Warren C, Shannon K, King A, Hanslo D. Ceftazidime: in vitro antibacterial activity and susceptibility to &bgr;-lactamases compared with that of cefotaxime, moxalactam and other &bgr;-lactam antibiotics. J Antimicrob Chemother 1981; 8 (suppl B): 23-31. 5. Acuna G, Johnston J, Young LS, Martin WJ. In vitro studies with Ceftazidime against aerobic Gram-negative bacilli and Bacteroides fragilis group. J Antimicrob Chemother 1981; 8 (suppl B): 83-89. 6. Wise R, Armstrong GC, Brown RM, Andrews JM. The pharmacokinetics and tissue penetration of ceftazidime and cefamandole in healthy volunteers. J Antimicrob Chemother 1981; 8 (suppl B): 277-82. 7. Quintiliani R, Nightingale CH. Comparative pharmacokinetics of ceftizoxime and other third-generation cephalosporins in humans. J Antimicrob Chemother 1982; 10
(suppl C): 99-104
hypoprothrombinaemia.8 Nor is there any information that these compounds are nephrotoxic. Ceftazidime does share a side-chain with cephaloridine, which certainly is nephrotoxic, but at a meeting Norrby9 suggested that nephrotoxicity was unlikely to arise with ceftazidime provided that the dose was monitored in patients with preexisting renal dysfunction. Ceftizoxime, being closely similar to earlier 3rd generation agents such as cefotaxime and latamoxef, cannot be said to have any particular clinical niche. It has been used for a wide range of infections of chest, urinary tract, and abdomen, in neutropenic patients (though not as a single agent), and in newborn babies.10 Ceftazidime, with its high antipseudomonal activity may well be useful in pseudomonas infections. It should be of particular use in the treatment of infections in neutropenic patients and newborn babies, possibly without an aminoglycoside in addition. Ceftazidime, at about 10/g or up to f60/day is twice the price of ceftizoxime and many similar agents, so it should be reserved for the treatment of such difficult patients. There is still further scope in cephalosporin development for synthesis of compounds of even broader spectrum. A cephalosporin that has good activity against staphylococci and Bacteroides fragilis, as well as high potency against the Enterobacteriaceae and Ps aeruginosa, must be the Holy Grail of the pharmaceutical industry at present.
WEGENER’S GRANULOMATOSIS WEGENER’S granulomatosis is part of the spectrum of disorders characterised by the presence of vasculitic lesions throughout the body. Although some overlap occurs, typical cases may be distinguished by a combination of clinical and pathological criteria from polyarteritis nodosa, relapsing polychondritis, and the Churg Strauss syndrome. The lungs1 and upper respiratory tract are nearly always involved early,’ so that patients tend to present with symptoms of sinusitis, otitis media, or chest infection. In addition, they may have virtually any of the clinical manifestations of polyarteritis except asthma. At presentation most (71% in one series’) have focal pulmonary infiltrates that tend to cavitate; later renal failure develops and, in the absence of treatment, this usually leads to death. Although more limited forms of disease are encountered, in predialysis days the mean survival time was only five months.2 The pathological hallmark is the co-existence of granulomas and vasculitis: this combination, observed most often in pulmonary tissue, may also be found in the upper
respiratory tract although non-specific inflammatory changes are at least as common in this site. Lately Pinching and colleagues from the Hammersmith Hospital3 have reported their experience with 18 patients with severe renal 8.
Lipsky JJ. N-Methyl-thio-tetrazole inhibition of gamma carboxylation of glutamic acid. possible mechanism for antibiotic associated hypoprothrombinaemia. Lancet 1983, ii: 192-93.
Norrby SR. Ceftazidime in clinical practice—a summary. J Antimicrob Chemother 1983; 12 (suppl A): 405-08. 10. Neu HC, Turck M, Phillips I, eds. Ceftizoxime, a broad spectrum &bgr;-lactamase stable cephalosporin. J Antimicrob Chemother 1982; 10: suppl C. 1. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 9.
1983; 98: 76-85. 2. Walton EW. Giant cell granuloma ofthe respiratory tract Br Med J 1958; ii: 265-70.
3.
(Wegener’s granulomatosis).
Lockwood CM, Pussell BA, Rees AJ, Sweny P, Evans DJ, Bowley N, Peters DK. Wegener’s granulomatosis: observations on 18 patients with severe renal disease. Quart J Med 1983; 52: 435-60.
Pinching AJ,
theoretically feasible, when it was first proposed about three years ago15-17 this molecular fishing expedition looked like a lot of work with no certainty of a worthwhile catch. However, it has already allowed a British group to obtain an RFLP linkage to the locus for Duchenne muscular dystrophy, 18 and a few weeks ago workers in the USA announced that they had discovered a very close linkage marker for the gene for Huntington’s chorea. 19 Finally, since it is now possible to construct short oligonucleotide probes that can identify single base mutations,2° it may soon be possible directly to identify many single gene disorders by gene mapping, once their molecular pathology has been determined.
EFFECT, COST, AND VALUE OF HOSPICE CARE THE treatment of dying patients continues to range from the superb to the unsympathetic dismissal. The desire to improve care brought about the development of hospices in Britain, a lead enthusiastically followed in North America where over a thousand hospice services have sprung up since 1974. But hospices need more than the initial inspiration and charitable funds to play their part. In Britain a recent report indicated that, after the exhilaration of obtaining funds to open local hospices, almost as much must be found each year to run them. In the United States public favour of the hospice movement has strengthened the demand for Federal financial support. Reasonably enough, an initial scheme for reimbursement through Medicare has been coupled with a requirement that the effectiveness of hospice care be tested and costed. Questions immediately arise about the criteria of good care and how the large but not limitless sums of money should be apportioned to treat patients. The editors of the 7ournal of Chronic Disease have devoted considerable space to airing the proposed methods of evaluating hospice care.2They have risked boring some readers with detail because the study is important, and its multicentre design will not easily be repeated. They are persuaded that early criticism and comments based on fuller information are preferable to delayed criticisms of a final report where the account of methods is so often curtailed. In the same journal Mount and Scott, who have conducted assessments in their own palliative care service in Montreal, contribute comments and criticisms of the proposed investigation while observing that hospices have already been 15. Kan
YW, Dozy
AM. Antenatal
diagnosis of sickle
cell anaemia
by
DNA
analysis of
amniotic-fluid cells. Lancet 1978; ii: 910. 16. Solomon E, Bodmer WF. Evolution of sickle variant gene. Lancet 1979; i: 923. 17. Botstein D. White RL, Skolnick M, Davis RW. Construction of a genetic linkage map in Man using restriction length fragment polymorphisms. Am J Hum Genet 1980; 32: 314-31. 18. Murray JM, Davies KE, Harper PS, Meredith L, Mueller CR, Williamson R. Linkage relationship ofa cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature 1982, 300: 69-71. 19. Gusella JF, Wexler NS, Conneally PM, Naylor SL, Anderson MA, Tanzi RE, Watkins PC, Ottina K, Wallace MR, Sakguchi AY, Young AB, Shoulson I, Bonilla E, Martin JB. A polymorphic DNA marker genetically linked to Huntington’s chorea. Nature 1983; 306: 234-38. 20. Conner BJ, Reyes AA, Morin C, Itakura K, Teplitz RL, Wallace RB. Detection of sickle cell &bgr;s-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 1983; 80: 278-82. 1. Taylor H. The hospice movement in Britain, its role and its future. London: Centre for Policy on Ageing, 1983. 2. Greer DS, Mor V, Sherwood S, Morris JN, Birnbaum H. National hospice study analysis plan. J Chron Dis 1983; 36: 737-80. 3. Mount BM, Scott JF. Whither hospice evaluation? J Chron Dis 1983; 36: 731-36.
superior to conventional care in controlling pain and increasing mobility, and are probably better in terms of social shown
and psychological adjustment. They dispute some of the characteristics of hospices and their patients presented by Greer and others2 in the National Hospice Study Analysis Plan-eg, patient and family must know of the terminal illness. The plan uses the statements on hospice "philosophy" to form a conceptual framework from which to derive research questions, but an economic interest has slanted the theorising. For example, the conceptual framework has translated the hospice principle that family members, friends, and volunteers should take an active part in the support of the dying into a statement that non-paid people substitute for professional personnel. This is doubtful; hospice staff see non-professional caring as a beneficial contribution to all concerned, but not with an automatic reduction of the often sparse professional care. Likewise the hospice desire to increase home-based care is seen as an economic advantage; perhaps so ifincreased homebased care just means less time in expensive hospitals, but not necessarily if the intention is to improve the care at home. In fact in Britain Parkes4 has shown that provision ofa hospicebased home care team has so far tended to lengthen the patients’ time at home but eventually a similar proportion experience discomfort. The theoretical extrapolations of the National Hospice Study warrant criticism not because they invalidate the subsequent legitimate research questions on efficacy and cost, but lest they foster biased interpretation of the results. If the test of a hospice is that it saves professional time, it will have apparently failed if it takes as much or more professional effort to give good appropriate terminal care as it does to undertake the irrelevant investigations and incredible cures.
study is to evaluate quality of life and care. Spitzer et a Quality of Life Scale that can be used in terminal care, but Mount and Scott2 point to the scale’s limitations in respect of personal and spiritual values affecting individuals and families-important elements in hospice care. A sense of spiritual fulfilment may have a unique value hardly reflected in any total score of welfare. Subjective measures can not be wholly precise; even criteria regarding physical suffering are disputable. Can any numerical score validly equate so many hours of mild pain to so many minutes of severe pain? The proposed measures of pain and symptoms have generally given good guidance to the quality of symptom relief. The hypothesis, however, that because hospices emphasise the prevention of pain and other symptoms they will use more analgesics and tranquillisers is misleading. Too often the less skilled give intermittent large doses and, instead of comfort, produce fluctuation between The
al5 have patiently constructed and tested
distress and unconsciousness. The practical difficulties of assessment are not negligible. The data collector and the bereaved are not to be envied in their potentially turgid final interview scheduled to include questions on grief experience and the quality of the last three days of life and to cross-check the service records with the bills received and expenses incurred by the family. The investigation will produce data of varying quality, requiring careful interpretation. The authors lay open for inspection their proposed elaborate statistical techniques, including the allowances made since the "controls" cannot be perfect. Clearly, the statistical significance of data, often imprecise, 4. Parkes CM. Terminal
care evaluation of an advisory domiciliary service at St. Christopher’s Hospice. Postgrad Med J 1980; 56: 685-89. 5. Spitzer WO, Dobson AJ, Hall J, et al. Measuring the quality of life of cancer patients J
Chron Dis 1981; 34: 585-97.
260
be distinguished from clinical or moral significance in a sphere where individuality is so important. The description of how results will be analysed states at one point that "outliers are dropped"-valid enough, perhaps, in the statistical context but inconceivable to hospice workers who expend great effort to help the unusual person. The editors and authors are to be thanked for tackling and exposing the difficulties fully. The necessary refinement of thought and the conduct of the inquiry itself may well have lasting benefits. The results should yield much information on some aspects of what hospices do or do not achieve and the financial cost, but they will need cautious interpretation and cannnot say how much a State ought to spend in helping people to end their lives in reasonable physical and mental comfort. must
CEFTIZOXIME AND CEFTAZIDIME Two more parenteral cephalosporins, ceftizoxime and ceftazidime have come on the UK market. It is futile to ask whether we really need more agents of this kind (cephalosporins seldom being drugs of first choice); instead let us see how these new compounds compare with the other "3rd generation" cephalosporins and what might be the clinical indications for their use. Structurally, ceftizoxime is closely related to cefotaximei but differs in not being metabolised (desacetylated). The spectrum and degree of antibacterial activity is similar to that and of cefotaxime latamoxef, encompassing the Enterobacteriaceae and streptococci (but not enterococci), Haemophilus influenzae, and Neisseria species. The activity against Staphylococcus aureus is more modest and there is little useful activity against Pseudomonas aeruginosa; like most of the recently introduced cephalosporins ceftizoxime is resistant to destruction by a wide range of bacterial (3-lactamases,2 with the important exception of that produced by Bacteroides fragilis. Ceftazidime differs from ceftizoxime in being even less effective against S aureus4but in being highly active against Ps aeruginosa;5 9007o of strains are inhibited by 4 mg/1 or less, and after 1 g intravenously blood levels will exceed.4 mg/1 for about 8 h.6The two compounds differ a little in their pharmacokinetics, ceftizoxime having a 6 serum half-life of 1 h7 compared with ceftazidime’s 1 ’8 h.b Ceftizoxime should probably be given 3-4 times a day (despite the recommendations that it be given twice daily) and ceftazidime 2-3 times a day. Neither compound contains the N-methylthiotetrazole side-chain that is common to many in been has and implicated cephalosporins
1. Dunn GL. Ceftizoxime and other 3rd generation cephalosporins: structure-activity relationships. J Antimicrob Chemother 1982; 10 (suppl C): 1-10. 2. Greenwood D, Pearson N, Eley A, O’Grady F. Comparative in vitro activity of
cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency. Antimicrob Ag Chemother 1980; 17: 397-401. 3. Neu HC. Factors that affect the in vitro activity of cephalosporin antibiotics. J Antimicrob Chemother 1982; 10 (suppl C): 11-23. 4. Phillips I, Warren C, Shannon K, King A, Hanslo D. Ceftazidime: in vitro antibacterial activity and susceptibility to &bgr;-lactamases compared with that of cefotaxime, moxalactam and other &bgr;-lactam antibiotics. J Antimicrob Chemother 1981; 8 (suppl B): 23-31. 5. Acuna G, Johnston J, Young LS, Martin WJ. In vitro studies with Ceftazidime against aerobic Gram-negative bacilli and Bacteroides fragilis group. J Antimicrob Chemother 1981; 8 (suppl B): 83-89. 6. Wise R, Armstrong GC, Brown RM, Andrews JM. The pharmacokinetics and tissue penetration of ceftazidime and cefamandole in healthy volunteers. J Antimicrob Chemother 1981; 8 (suppl B): 277-82. 7. Quintiliani R, Nightingale CH. Comparative pharmacokinetics of ceftizoxime and other third-generation cephalosporins in humans. J Antimicrob Chemother 1982; 10
(suppl C): 99-104
hypoprothrombinaemia.8 Nor is there any information that these compounds are nephrotoxic. Ceftazidime does share a side-chain with cephaloridine, which certainly is nephrotoxic, but at a meeting Norrby9 suggested that nephrotoxicity was unlikely to arise with ceftazidime provided that the dose was monitored in patients with preexisting renal dysfunction. Ceftizoxime, being closely similar to earlier 3rd generation agents such as cefotaxime and latamoxef, cannot be said to have any particular clinical niche. It has been used for a wide range of infections of chest, urinary tract, and abdomen, in neutropenic patients (though not as a single agent), and in newborn babies.10 Ceftazidime, with its high antipseudomonal activity may well be useful in pseudomonas infections. It should be of particular use in the treatment of infections in neutropenic patients and newborn babies, possibly without an aminoglycoside in addition. Ceftazidime, at about 10/g or up to f60/day is twice the price of ceftizoxime and many similar agents, so it should be reserved for the treatment of such difficult patients. There is still further scope in cephalosporin development for synthesis of compounds of even broader spectrum. A cephalosporin that has good activity against staphylococci and Bacteroides fragilis, as well as high potency against the Enterobacteriaceae and Ps aeruginosa, must be the Holy Grail of the pharmaceutical industry at present.
WEGENER’S GRANULOMATOSIS WEGENER’S granulomatosis is part of the spectrum of disorders characterised by the presence of vasculitic lesions throughout the body. Although some overlap occurs, typical cases may be distinguished by a combination of clinical and pathological criteria from polyarteritis nodosa, relapsing polychondritis, and the Churg Strauss syndrome. The lungs1 and upper respiratory tract are nearly always involved early,’ so that patients tend to present with symptoms of sinusitis, otitis media, or chest infection. In addition, they may have virtually any of the clinical manifestations of polyarteritis except asthma. At presentation most (71% in one series’) have focal pulmonary infiltrates that tend to cavitate; later renal failure develops and, in the absence of treatment, this usually leads to death. Although more limited forms of disease are encountered, in predialysis days the mean survival time was only five months.2 The pathological hallmark is the co-existence of granulomas and vasculitis: this combination, observed most often in pulmonary tissue, may also be found in the upper
respiratory tract although non-specific inflammatory changes are at least as common in this site. Lately Pinching and colleagues from the Hammersmith Hospital3 have reported their experience with 18 patients with severe renal 8.
Lipsky JJ. N-Methyl-thio-tetrazole inhibition of gamma carboxylation of glutamic acid. possible mechanism for antibiotic associated hypoprothrombinaemia. Lancet 1983, ii: 192-93.
Norrby SR. Ceftazidime in clinical practice—a summary. J Antimicrob Chemother 1983; 12 (suppl A): 405-08. 10. Neu HC, Turck M, Phillips I, eds. Ceftizoxime, a broad spectrum &bgr;-lactamase stable cephalosporin. J Antimicrob Chemother 1982; 10: suppl C. 1. Fauci AS, Haynes BF, Katz P, Wolff SM. Wegener’s granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med 9.
1983; 98: 76-85. 2. Walton EW. Giant cell granuloma ofthe respiratory tract Br Med J 1958; ii: 265-70.
3.
(Wegener’s granulomatosis).
Lockwood CM, Pussell BA, Rees AJ, Sweny P, Evans DJ, Bowley N, Peters DK. Wegener’s granulomatosis: observations on 18 patients with severe renal disease. Quart J Med 1983; 52: 435-60.
Pinching AJ,