144
with glucose-6-phosphate dehydrogenase deficiency, and possibly in alcoholics. Even when patients with an SFG rickettsiosis present with the typical triad, the condition may be confused with diseases such as meningococcal septicaemia, measles, rubella, typhoid, infectious mononucleosis, secondary syphilis, and leptospirosis. Timely confirmation of a clinical diagnosis may not be easy: the Weil-Felix reaction is neither sensitive nor specific enough, and probably should be withdrawn. Serological assay for specific antibodies to SFG rickettsioses is useful only during convalescence. Isolation of rickettsiae likewise takes time and is done in only a few reference laboratories. In the acute phase the diagnosis can be achieved by immunofluorescence staining of rickettsiae in cutaneous biopsy specimens taken from rash or eschar. If the patient does not have a rash yet clinical suspicion is strong, empirical therapy should not be withheld. The polymerase chain reaction was lately used to detect rickettsiae in a patient with typhus,22 by use of a primer pair derived from the 17-kD antigen sequence of R rickettsii. This method offers hope for the rapid diagnosis of rickettsial spotted fever. 1. Raoult D, Walker DH. Rickettsia rickettsii and other spotted fever group rickettsiae. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone,
1990; 1465-71. 2. Centers for Disease Control. Rickettsial disease surveillance report 2.
Summary 1979. Atlanta, Georgia: CDC, 1981. 3. Harden VA. Rocky Mountain spotted fever: history of a twentiethcentury disease. Baltimore: Johns Hopkins University Press, 1990 Pp 375. ISBN 0-80183905X. £28.50. 4. Wilfert CM, McCormack JN, Kleeman K, et al. Epidemiology of Rocky Mountain spotted fever as determined by active surveillance. J Infect Dis 1984; 150: 469-79. 5. Mansueto S, Tringali G, Walker DH. Widespread simultaneous increase in the incidence of spotted fever group rickettsiosis. J Infect Dis 1986; 154: 539-40. 6. McDonald JC, MacLean JD, McDade JE. Imported rickettsial disease: clinical and epidemiologic features. Am J Med 1988; 85: 799-805. 7. Arenas EE, Font-Creus B, Bella Cueto F, Segura Porta F. Climatic factors in resurgence of Mediterranean spotted fever. Lancet 1986; i: 1333. 8. Fan MY, Walker DH, Yu SR, et al. The epidemiology and ecology of rickettsial diseases in the People’s Republic of China. Rev Infect Dis 1987; 9: 823-40. 9. Fan MY, Walker DH, Liu QH, et al. Rickettsial and serologic evidence for prevalent spotted fever rickettsiosis in inner Mongolia. Am J Trop Med Hyg 1987; 36: 615-20. 10. Sexton DJ, King G, Dwyer B. Fatal Queensland tick typhus. J Infect Dis 1990; 162: 779-80. 11. Okada T, Tange Y, Kobayashi Y. Causative agent of spotted fever group rickettsiosis in Japan. Infect Immun 1990; 58: 887-92. 12. Stephenson R. Rickettsia in the regiment. JR Army Med Corps 1989; 135: 21-24. 13. Bryceson A. Imported fevers. In: Pounder RE, Chiodini PL, eds. Advanced medicine 23. London: Baillière Tindall, 1987: 336-43. 14. Grove DI. African tick typhus in Australian travellers. Australas J Dermatol 1988; 29: 141-45. 15. Marmion BP. Rickettsial diseases of man and animals. In: Parker MT,
Collier LH, eds. Topley & Wilson’s principles of bacteriology, virology and immunity, vol 3: 673-89. 16. Tenenbaum MJ, Markowitz SM. Rocky Mountain spotted fever: diagnostic dilemma of the atypical presentation. South Med J 1980; 73: 1527. 17. Walker DH, Henderson FW, Hutchins GM. Abdominal pain in Rocky Mountain spotted fever: mimicry of appendicitis or acute surgical abdomen? Am J Dis Child 1986; 140: 742-44. 18. Hattwick MAW, O’Brien RJ, Hauson BF. Rocky Mountain spotted fever: epidemiology of an increasing problem. Ann Intern Med 1976; 84: 732-39.
19. Raoult D, Zuchelli P, Weiller PJ, et al. Incidence, clinical observations and risk factors m the severe form of Mediterranean spotted fever among patients admitted to hospitals to Marseilles 1983-1984. J Infect 1986; 12: 111-16. 20. Cohen MAH, Li PKT, Cheng AFB, et al. A fatal case of rickettsial spotted fever in Hong Kong—Lion rock fever. J HK Med Assoc 1989; 41: 185-86. 21. Christie AB. Rickettsial disease: typhus. In: Infectious diseases: epidemiology and clinical practice. Edinburgh: Churchill Livingstone, 1987: 1086. 22. Carl M, Tibbs CW, Dobson ME, et al. Diagnosis of acute typhus infection using the polymerase chain reaction. J Infect Dis 1990; 161: 791-93.
More thought for food—Richmond II The microbiological safety of food comes high on the public health agenda world wide; many of the underlying issues were aired in our foodborne illness
series (September-December, 1990). Numerically, salmonellosis and campylobacteriosis continue to top the list and there is little sign of an end to the Salmonella enteritidis PT4 outbreak. By contrast, the frequency of listeriosis has been considerably reduced. Other pathogens (bacteria, viruses, and protozoa) remain important causes of foodbome infection. The ability of microbes to evolve and adapt often reveals weaknesses in hygienic control of the food chain at any level from production of raw materials to retailing and catering. Consumers must likewise be vigilant in the storage, preparation, and cooking of food in the home. No one scientific, industrial, or public health agency has provided an overall analysis of the microbiological safety of food that will command the respect of governments and their health agencies, agricultural organisations, the food industry, local authorities, and the general public. However, in the UK, the reports of the Committee on the Microbiological Safety of Food chaired by Sir Mark Richmond attempt to do just that. Sir Mark’s Committee have undertaken a daunting task-probably the most detailed overview of food hygiene and safety yet attempted in any country. Part I of the report,l,2 published in February last year, covered public health matters (the incidence of foodbome illness, human and food surveillance, outbreak management) as well as poultry meat production, manufacturing processes, and food
processing by small enterprises. The rapidly evolving background to the UK legislative framework was also included. Part 113 and the Government’s response issued this week. Though interim and therefore patchy in coverage, part I generated sixty specific recommendations that were largely endorsed by the Government. On the crucial issue of licensing versus registration of food businesses the Committee strongly advocated licensing as the best means of control whereas the Government decided on a combination of registration in advance and new powers of enforcement, with licensing reserved for especially risky processes. Moreover, with respect to the sale of unpasteurised milk for direct consumption in England and Wales, were
145
the Committee’s support for ministers’ proposal of a ban was not endorsed by the public response during consultation which was overwhelmingly in favour of freedom of choice. Nevertheless, tighter regulations have been introduced on the labelling, testing, and sale of unpasteurised milk. Much has happened subsequently: (a) the Food Safety Act 1990, with stronger powers to protect the public, was passed by Parliament; (b) the Food Hygiene Regulations have been amended to tighten temperature control; (c) the Communicable Disease Surveillance Centre, together with the Medical Research Council and the London School of Hygiene, is conducting a pilot study to determine the frequency of intestinal disease in the community; (d) an even more rigorous slaughter policy for poultry flocks has been instituted; (e) the Department of Health/ Ministry of Agriculture, Fisheries and Food education and public information programme on food hygiene has been stepped up; (f) use-by rather than sell-by dates were introduced for highly perishable
goods from Jan 1, 1991. There are also numerous signs of positive action by industry, with the preparation of additional guidelines and codes of practice. Perhaps the greatest impact of part I was to secure the creation of a new dual committee structure for the microbiological safety of food-a Government steering group plus an independent advisory committee. That there can be no room for complacency was underlined by the publication last June of the Audit Commission report4 based on a survey of 5000 food premises by the Institution of Environmental Health Officers. This report emphasised the poor hygienic conditions in food and many catering manufacturing establishments. What do
find in Richmond part II? The introductory chapters review progress, or in some cases the lack of it, since publication of part I and give an overview of the causes of foodborne infection. The Committee note that changes in agricultural practice, in the pattern of food consumption, in the way food is processed and handled, and in lifestyles of consumers have contributed to the increase in foodborne illness. There is little coverage of eggs; the Committee maintain that, since the comprehensive range of measures introduced to deal with salmonella has only lately taken effect, it is premature to assess their impact. This task, it is argued, should be a matter for ongoing review by the newly formed steering group. BSE is excluded since expert advice on this topic is the remit of the Tyrrell Committee. Waterborne disease, we
especially cryptosporidiosis, has been the subject of a recent separate report by Sir John Badenoch’s Committee on Cryptosporidium in Water Supplies.5 Although the Committee recognise the public health arrangements peculiar to Scotland and Northern Ireland, they appeal for harmonisation of reporting across the UK so that comparable statistics
can
be assembled. With respect to red meat, the issue
of European Community regulations on slaughter houses is highlighted, along with the question of training and career structures for meat inspectors and veterinary surgeons working in meat plants. On milk and milk products, it emerges that the tightly regulated dairy industry is well structured to deal with microbiological hazards. Examination of outbreak data firmly implicates the consumption of unpasteurised milk as the main hazard and the striking effect of the ban in Scotland in 1983 is evident. The Committee take this opportunity to reiterate their firm views on the subject. There is strongly worded advice on the care required in cheese making with respect to listeriosis. However, Public Health Laboratory Service outbreak data analysed in the report reveal that very few outbreaks of foodbome illness in the UK have been linked to the consumption of cheese. Contamination of shellfish beds and the failure of depuration to remove enteric viruses explain the continuing problem of foodbome viral disease; the Committee believe that work in this area is urgently needed. The section on fish also identifies measures required to avoid hazards, especially Clostridium botulinum contamination, in the production of prepacked smoked fish-eg, the lack of oxygen in vacuum packs will inhibit spoilage but will not prevent growth of this anaerobe. The committee break new ground in attempting to analyse the complexities of retail operations-from supermarkets to doorstep deliveries-in terms of microbiological quality of supplies, storage, refrigeration and temperature control, design of premises, training and awareness, and operating practices. The same analytical approach is applied to catering. In both instances recommendations focus on the need for guidelines and codes and for ensuring enforcement of Government regulations; proper planning of premises and design of equipment are emphasised. Consumers are given much sensible advice, especially about refrigeration, microwave ovens, labelling, and kitchen design.
Continuing themes of the report are (a) the implementation of the Hazard Analysis Critical Control Point system across the whole industry; (b) the importance of impending European Community measures; and (c) education and training. Education applies to everyone involved in the food chain. The Committee address how food hygiene can best be taught in schools and colleges, and note that the training of foodhandlers by employers is patchy. The broad remit of enforcement officers means that many are overburdened; the introduction of specialist food technicians to help them (recommended in Richmond part I and reiterated in II) is surely overdue. The Committee believe that the teaching of Consultants in Communicable Disease Control must be kept under review, and that veterinary surgeons should be aware of the public health issues pertaining to their practice.
146
The Government largely agree with the Committee’s advice. A prominent exception is the licensing issue. Whereas the Committee reiterate the need for the licensing of premises in which meat is butchered and processed, and of all catering establishments, the Government have not shifted from their view that the Food Safety Act already provides ample controls. Sir Mark and his team have voiced their dismay at this response. The signposts of Richmond do not signal the end of the road-we hope that the creation of the Single European Market by 1993 will enhance existing UK controls. microbiological safety of food. Part I. Report of the Committee on the Microbiological Safety of Food. London: HM Stationery Office, 1990. 2. Anon. Safer food. Lancet 1990; 335: 531. 3. The microbiological safety of food. Part II. Report of the Committee on the Microbiological Safety of Food. London: HM Stationery Office, 1. The
1991. £19. 4. Environmental health survey of food premises. Audit Commission for Local Authorities for England and Wales. London: HM Stationery Office, 1990. 5. Cryptosporidium in water supplies. Report of the group of experts. London: HM Stationery Office, 1990.
Laron dwarfism Human growth depends on pulsatile release of growth hormone (GH) from the anterior pituitary gland. Metabolic actions of GH are mediated through the liver, which releases insulin-like growth factor 1 (IGF-1, somatomedin C) in response to the binding of GH to its receptor. Congenital GH deficiency leading to short stature may be an autosomal recessive, X-linked, or dominantly inherited condition. Serum GH concentration is usually low and does not rise above 20 mU/1 in response to an insulin-tolerance test. Laron dwarfism, an autosomal recessive trait, was first reported in 1966.1 Patients have a characteristic physical appearance-small facies and mandibles, prominent forehead, saddle nose, discoloured and delayed dentition, slow and sparse hair growth, and small hands and feet. Serum GH concentration is increased but IGF-1 is low. There are two possible explanations: (a) an IGF-1 defect, which has been excluded,or (b) impaired interaction of GH with its receptor. The early findings of reduced binding capacity of GH to hepatic cell membranes suggested a receptor defect, and the report of a single nucleotide substitution (thymidine to cytosine) in the GHreceptor gene, which causes a phenylalanine to serine switch at position 96 in the extracellular GH-binding domain of the receptor, supported this hypothesis.3 That the amino terminal of this domain is identical to part of the high-affinity GH-binding protein suggests that the binding protein is a circulating fragment of the receptor. Binding protein concentration is also reduced in Laron dwarfism. However, although a gene defect has been shown, this mutation was found in only one of two families studied3 and the polymorphisms probably differ between such families. The abnormal extracellular
protein domain of the GH receptor, synthesised from a plasmid in Escherichia coli, bound GH with identical affinity to the wild-type GH-binding protein also expressed in E COli.4 Furthermore, the study of an isolated, inbred population with a low plasma GHbinding protein, as in Laron dwarfism, has revealed clinical features that differ from typical descriptionseg, female preponderance, less frequent dental abnormalities, and preserved intellect.s The true explanation of this probably heterogeneous condition may be that the clinical variations in phenotype are matched by a molecular diversity of gene defects, not necessarily confined to the GH-receptor gene. 1. Laron
2.
Z, Pertzelan A, Mannheimer S. Genetic pituitary dwarfism with high serum concentration of growth hormone—a new inborn error of metabolism? Isr J Med Soc 1966; 2: 152-55. Laron Z, Klinger B, Erster B, Anin S. Effect of acute administration of insulin-like growth factor 1 in patients with Laron-type dwarfism.
Lancet 1988; ii: 1170-72. 3. Amselem S, Dequesnoy P, Attree O, et al. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 1989; 321: 989-95. 4. Bass S, Wells J. Growth hormone-receptor gene in Laron dwarfism. N Engl J Med 1990; 322: 854-55. 5. Rosenbloom AL, Agruirre JG, Rosenfeld RG, Fielder PJ. The little women of Loja—growth hormone-receptor deficiency in an inbred population of southern Ecuador. N Engl J Med 1990; 323: 1367-74.
PTHrP: endocrine and autocrine regulator of calcium
Parathyroid-hormone-related protein (PTHrP) isolated and cloned in 1987,1 and we now know that this previously unrecognised hormone can reproduce all the essential features of the syndrome of humoral hypercalcaemia of malignancy (HHM). PTHrP and parathyroid hormone are homologous in that eight of the first thirteen aminoacid residues are identical; this homology allows PTHrP to act via the parathyroid hormone receptor. HHM, like is characterised by hyperparathyroidism, and increased hypercalcaemia, hypophosphataemia, urinary cyclic AMP. That PTHrP, and not parathyroid hormone, is the mediator of HHM is beyond doubt. PTHrP can be detected in the circulation of patients with HHM and antibodies to N-terminal regions of PTHrP can reduce the hypercalcaemia and prevent the bone abnormalities in was
animal models of HHM.2 The gene for human PTHrP is far more complex than that for parathyroid hormone: 9 exons predict protein species of 139, 141, and 173 aminoacids in length, generated by alternate splicing events. The opportunity for tissue-specific expression as well as post-translational processing is enormous, and glucocorticoids, 1,25 dihydroxycholecalciferol, and cyclic AMP have all been shown to regulate gene expression. There is some evidence for tissue-specific processing, but the circulating forms of PTHrP in patients with cancer have not been characterised.3A
with glucose-6-phosphate dehydrogenase deficiency, and possibly in alcoholics. Even when patients with an SFG rickettsiosis present with the typical triad, the condition may be confused with diseases such as meningococcal septicaemia, measles, rubella, typhoid, infectious mononucleosis, secondary syphilis, and leptospirosis. Timely confirmation of a clinical diagnosis may not be easy: the Weil-Felix reaction is neither sensitive nor specific enough, and probably should be withdrawn. Serological assay for specific antibodies to SFG rickettsioses is useful only during convalescence. Isolation of rickettsiae likewise takes time and is done in only a few reference laboratories. In the acute phase the diagnosis can be achieved by immunofluorescence staining of rickettsiae in cutaneous biopsy specimens taken from rash or eschar. If the patient does not have a rash yet clinical suspicion is strong, empirical therapy should not be withheld. The polymerase chain reaction was lately used to detect rickettsiae in a patient with typhus,22 by use of a primer pair derived from the 17-kD antigen sequence of R rickettsii. This method offers hope for the rapid diagnosis of rickettsial spotted fever. 1. Raoult D, Walker DH. Rickettsia rickettsii and other spotted fever group rickettsiae. In: Mandell GL, Douglas RG, Bennett JE, eds. Principles and practice of infectious diseases. New York: Churchill Livingstone,
1990; 1465-71. 2. Centers for Disease Control. Rickettsial disease surveillance report 2.
Summary 1979. Atlanta, Georgia: CDC, 1981. 3. Harden VA. Rocky Mountain spotted fever: history of a twentiethcentury disease. Baltimore: Johns Hopkins University Press, 1990 Pp 375. ISBN 0-80183905X. £28.50. 4. Wilfert CM, McCormack JN, Kleeman K, et al. Epidemiology of Rocky Mountain spotted fever as determined by active surveillance. J Infect Dis 1984; 150: 469-79. 5. Mansueto S, Tringali G, Walker DH. Widespread simultaneous increase in the incidence of spotted fever group rickettsiosis. J Infect Dis 1986; 154: 539-40. 6. McDonald JC, MacLean JD, McDade JE. Imported rickettsial disease: clinical and epidemiologic features. Am J Med 1988; 85: 799-805. 7. Arenas EE, Font-Creus B, Bella Cueto F, Segura Porta F. Climatic factors in resurgence of Mediterranean spotted fever. Lancet 1986; i: 1333. 8. Fan MY, Walker DH, Yu SR, et al. The epidemiology and ecology of rickettsial diseases in the People’s Republic of China. Rev Infect Dis 1987; 9: 823-40. 9. Fan MY, Walker DH, Liu QH, et al. Rickettsial and serologic evidence for prevalent spotted fever rickettsiosis in inner Mongolia. Am J Trop Med Hyg 1987; 36: 615-20. 10. Sexton DJ, King G, Dwyer B. Fatal Queensland tick typhus. J Infect Dis 1990; 162: 779-80. 11. Okada T, Tange Y, Kobayashi Y. Causative agent of spotted fever group rickettsiosis in Japan. Infect Immun 1990; 58: 887-92. 12. Stephenson R. Rickettsia in the regiment. JR Army Med Corps 1989; 135: 21-24. 13. Bryceson A. Imported fevers. In: Pounder RE, Chiodini PL, eds. Advanced medicine 23. London: Baillière Tindall, 1987: 336-43. 14. Grove DI. African tick typhus in Australian travellers. Australas J Dermatol 1988; 29: 141-45. 15. Marmion BP. Rickettsial diseases of man and animals. In: Parker MT,
Collier LH, eds. Topley & Wilson’s principles of bacteriology, virology and immunity, vol 3: 673-89. 16. Tenenbaum MJ, Markowitz SM. Rocky Mountain spotted fever: diagnostic dilemma of the atypical presentation. South Med J 1980; 73: 1527. 17. Walker DH, Henderson FW, Hutchins GM. Abdominal pain in Rocky Mountain spotted fever: mimicry of appendicitis or acute surgical abdomen? Am J Dis Child 1986; 140: 742-44. 18. Hattwick MAW, O’Brien RJ, Hauson BF. Rocky Mountain spotted fever: epidemiology of an increasing problem. Ann Intern Med 1976; 84: 732-39.
19. Raoult D, Zuchelli P, Weiller PJ, et al. Incidence, clinical observations and risk factors m the severe form of Mediterranean spotted fever among patients admitted to hospitals to Marseilles 1983-1984. J Infect 1986; 12: 111-16. 20. Cohen MAH, Li PKT, Cheng AFB, et al. A fatal case of rickettsial spotted fever in Hong Kong—Lion rock fever. J HK Med Assoc 1989; 41: 185-86. 21. Christie AB. Rickettsial disease: typhus. In: Infectious diseases: epidemiology and clinical practice. Edinburgh: Churchill Livingstone, 1987: 1086. 22. Carl M, Tibbs CW, Dobson ME, et al. Diagnosis of acute typhus infection using the polymerase chain reaction. J Infect Dis 1990; 161: 791-93.
More thought for food—Richmond II The microbiological safety of food comes high on the public health agenda world wide; many of the underlying issues were aired in our foodborne illness
series (September-December, 1990). Numerically, salmonellosis and campylobacteriosis continue to top the list and there is little sign of an end to the Salmonella enteritidis PT4 outbreak. By contrast, the frequency of listeriosis has been considerably reduced. Other pathogens (bacteria, viruses, and protozoa) remain important causes of foodbome infection. The ability of microbes to evolve and adapt often reveals weaknesses in hygienic control of the food chain at any level from production of raw materials to retailing and catering. Consumers must likewise be vigilant in the storage, preparation, and cooking of food in the home. No one scientific, industrial, or public health agency has provided an overall analysis of the microbiological safety of food that will command the respect of governments and their health agencies, agricultural organisations, the food industry, local authorities, and the general public. However, in the UK, the reports of the Committee on the Microbiological Safety of Food chaired by Sir Mark Richmond attempt to do just that. Sir Mark’s Committee have undertaken a daunting task-probably the most detailed overview of food hygiene and safety yet attempted in any country. Part I of the report,l,2 published in February last year, covered public health matters (the incidence of foodbome illness, human and food surveillance, outbreak management) as well as poultry meat production, manufacturing processes, and food
processing by small enterprises. The rapidly evolving background to the UK legislative framework was also included. Part 113 and the Government’s response issued this week. Though interim and therefore patchy in coverage, part I generated sixty specific recommendations that were largely endorsed by the Government. On the crucial issue of licensing versus registration of food businesses the Committee strongly advocated licensing as the best means of control whereas the Government decided on a combination of registration in advance and new powers of enforcement, with licensing reserved for especially risky processes. Moreover, with respect to the sale of unpasteurised milk for direct consumption in England and Wales, were
145
the Committee’s support for ministers’ proposal of a ban was not endorsed by the public response during consultation which was overwhelmingly in favour of freedom of choice. Nevertheless, tighter regulations have been introduced on the labelling, testing, and sale of unpasteurised milk. Much has happened subsequently: (a) the Food Safety Act 1990, with stronger powers to protect the public, was passed by Parliament; (b) the Food Hygiene Regulations have been amended to tighten temperature control; (c) the Communicable Disease Surveillance Centre, together with the Medical Research Council and the London School of Hygiene, is conducting a pilot study to determine the frequency of intestinal disease in the community; (d) an even more rigorous slaughter policy for poultry flocks has been instituted; (e) the Department of Health/ Ministry of Agriculture, Fisheries and Food education and public information programme on food hygiene has been stepped up; (f) use-by rather than sell-by dates were introduced for highly perishable
goods from Jan 1, 1991. There are also numerous signs of positive action by industry, with the preparation of additional guidelines and codes of practice. Perhaps the greatest impact of part I was to secure the creation of a new dual committee structure for the microbiological safety of food-a Government steering group plus an independent advisory committee. That there can be no room for complacency was underlined by the publication last June of the Audit Commission report4 based on a survey of 5000 food premises by the Institution of Environmental Health Officers. This report emphasised the poor hygienic conditions in food and many catering manufacturing establishments. What do
find in Richmond part II? The introductory chapters review progress, or in some cases the lack of it, since publication of part I and give an overview of the causes of foodborne infection. The Committee note that changes in agricultural practice, in the pattern of food consumption, in the way food is processed and handled, and in lifestyles of consumers have contributed to the increase in foodborne illness. There is little coverage of eggs; the Committee maintain that, since the comprehensive range of measures introduced to deal with salmonella has only lately taken effect, it is premature to assess their impact. This task, it is argued, should be a matter for ongoing review by the newly formed steering group. BSE is excluded since expert advice on this topic is the remit of the Tyrrell Committee. Waterborne disease, we
especially cryptosporidiosis, has been the subject of a recent separate report by Sir John Badenoch’s Committee on Cryptosporidium in Water Supplies.5 Although the Committee recognise the public health arrangements peculiar to Scotland and Northern Ireland, they appeal for harmonisation of reporting across the UK so that comparable statistics
can
be assembled. With respect to red meat, the issue
of European Community regulations on slaughter houses is highlighted, along with the question of training and career structures for meat inspectors and veterinary surgeons working in meat plants. On milk and milk products, it emerges that the tightly regulated dairy industry is well structured to deal with microbiological hazards. Examination of outbreak data firmly implicates the consumption of unpasteurised milk as the main hazard and the striking effect of the ban in Scotland in 1983 is evident. The Committee take this opportunity to reiterate their firm views on the subject. There is strongly worded advice on the care required in cheese making with respect to listeriosis. However, Public Health Laboratory Service outbreak data analysed in the report reveal that very few outbreaks of foodbome illness in the UK have been linked to the consumption of cheese. Contamination of shellfish beds and the failure of depuration to remove enteric viruses explain the continuing problem of foodbome viral disease; the Committee believe that work in this area is urgently needed. The section on fish also identifies measures required to avoid hazards, especially Clostridium botulinum contamination, in the production of prepacked smoked fish-eg, the lack of oxygen in vacuum packs will inhibit spoilage but will not prevent growth of this anaerobe. The committee break new ground in attempting to analyse the complexities of retail operations-from supermarkets to doorstep deliveries-in terms of microbiological quality of supplies, storage, refrigeration and temperature control, design of premises, training and awareness, and operating practices. The same analytical approach is applied to catering. In both instances recommendations focus on the need for guidelines and codes and for ensuring enforcement of Government regulations; proper planning of premises and design of equipment are emphasised. Consumers are given much sensible advice, especially about refrigeration, microwave ovens, labelling, and kitchen design.
Continuing themes of the report are (a) the implementation of the Hazard Analysis Critical Control Point system across the whole industry; (b) the importance of impending European Community measures; and (c) education and training. Education applies to everyone involved in the food chain. The Committee address how food hygiene can best be taught in schools and colleges, and note that the training of foodhandlers by employers is patchy. The broad remit of enforcement officers means that many are overburdened; the introduction of specialist food technicians to help them (recommended in Richmond part I and reiterated in II) is surely overdue. The Committee believe that the teaching of Consultants in Communicable Disease Control must be kept under review, and that veterinary surgeons should be aware of the public health issues pertaining to their practice.
146
The Government largely agree with the Committee’s advice. A prominent exception is the licensing issue. Whereas the Committee reiterate the need for the licensing of premises in which meat is butchered and processed, and of all catering establishments, the Government have not shifted from their view that the Food Safety Act already provides ample controls. Sir Mark and his team have voiced their dismay at this response. The signposts of Richmond do not signal the end of the road-we hope that the creation of the Single European Market by 1993 will enhance existing UK controls. microbiological safety of food. Part I. Report of the Committee on the Microbiological Safety of Food. London: HM Stationery Office, 1990. 2. Anon. Safer food. Lancet 1990; 335: 531. 3. The microbiological safety of food. Part II. Report of the Committee on the Microbiological Safety of Food. London: HM Stationery Office, 1. The
1991. £19. 4. Environmental health survey of food premises. Audit Commission for Local Authorities for England and Wales. London: HM Stationery Office, 1990. 5. Cryptosporidium in water supplies. Report of the group of experts. London: HM Stationery Office, 1990.
Laron dwarfism Human growth depends on pulsatile release of growth hormone (GH) from the anterior pituitary gland. Metabolic actions of GH are mediated through the liver, which releases insulin-like growth factor 1 (IGF-1, somatomedin C) in response to the binding of GH to its receptor. Congenital GH deficiency leading to short stature may be an autosomal recessive, X-linked, or dominantly inherited condition. Serum GH concentration is usually low and does not rise above 20 mU/1 in response to an insulin-tolerance test. Laron dwarfism, an autosomal recessive trait, was first reported in 1966.1 Patients have a characteristic physical appearance-small facies and mandibles, prominent forehead, saddle nose, discoloured and delayed dentition, slow and sparse hair growth, and small hands and feet. Serum GH concentration is increased but IGF-1 is low. There are two possible explanations: (a) an IGF-1 defect, which has been excluded,or (b) impaired interaction of GH with its receptor. The early findings of reduced binding capacity of GH to hepatic cell membranes suggested a receptor defect, and the report of a single nucleotide substitution (thymidine to cytosine) in the GHreceptor gene, which causes a phenylalanine to serine switch at position 96 in the extracellular GH-binding domain of the receptor, supported this hypothesis.3 That the amino terminal of this domain is identical to part of the high-affinity GH-binding protein suggests that the binding protein is a circulating fragment of the receptor. Binding protein concentration is also reduced in Laron dwarfism. However, although a gene defect has been shown, this mutation was found in only one of two families studied3 and the polymorphisms probably differ between such families. The abnormal extracellular
protein domain of the GH receptor, synthesised from a plasmid in Escherichia coli, bound GH with identical affinity to the wild-type GH-binding protein also expressed in E COli.4 Furthermore, the study of an isolated, inbred population with a low plasma GHbinding protein, as in Laron dwarfism, has revealed clinical features that differ from typical descriptionseg, female preponderance, less frequent dental abnormalities, and preserved intellect.s The true explanation of this probably heterogeneous condition may be that the clinical variations in phenotype are matched by a molecular diversity of gene defects, not necessarily confined to the GH-receptor gene. 1. Laron
2.
Z, Pertzelan A, Mannheimer S. Genetic pituitary dwarfism with high serum concentration of growth hormone—a new inborn error of metabolism? Isr J Med Soc 1966; 2: 152-55. Laron Z, Klinger B, Erster B, Anin S. Effect of acute administration of insulin-like growth factor 1 in patients with Laron-type dwarfism.
Lancet 1988; ii: 1170-72. 3. Amselem S, Dequesnoy P, Attree O, et al. Laron dwarfism and mutations of the growth hormone-receptor gene. N Engl J Med 1989; 321: 989-95. 4. Bass S, Wells J. Growth hormone-receptor gene in Laron dwarfism. N Engl J Med 1990; 322: 854-55. 5. Rosenbloom AL, Agruirre JG, Rosenfeld RG, Fielder PJ. The little women of Loja—growth hormone-receptor deficiency in an inbred population of southern Ecuador. N Engl J Med 1990; 323: 1367-74.
PTHrP: endocrine and autocrine regulator of calcium
Parathyroid-hormone-related protein (PTHrP) isolated and cloned in 1987,1 and we now know that this previously unrecognised hormone can reproduce all the essential features of the syndrome of humoral hypercalcaemia of malignancy (HHM). PTHrP and parathyroid hormone are homologous in that eight of the first thirteen aminoacid residues are identical; this homology allows PTHrP to act via the parathyroid hormone receptor. HHM, like is characterised by hyperparathyroidism, and increased hypercalcaemia, hypophosphataemia, urinary cyclic AMP. That PTHrP, and not parathyroid hormone, is the mediator of HHM is beyond doubt. PTHrP can be detected in the circulation of patients with HHM and antibodies to N-terminal regions of PTHrP can reduce the hypercalcaemia and prevent the bone abnormalities in was
animal models of HHM.2 The gene for human PTHrP is far more complex than that for parathyroid hormone: 9 exons predict protein species of 139, 141, and 173 aminoacids in length, generated by alternate splicing events. The opportunity for tissue-specific expression as well as post-translational processing is enormous, and glucocorticoids, 1,25 dihydroxycholecalciferol, and cyclic AMP have all been shown to regulate gene expression. There is some evidence for tissue-specific processing, but the circulating forms of PTHrP in patients with cancer have not been characterised.3A
