CANCER GENETICS

1060

symptoms before his

with the infected the possibility that the surgeon surgeon. Ironically, the infection from this patient have acquired might was never discussed. Perhaps the most widely publicised report of HIV transmission from a health care worker is the case of the Florida dentist who was suspected of infecting some of his patients. Molecular studies of HIV sequences suggest that he may have infected 5 of 8 HIV-seropositive patients he had treatedY Nevertheless, the molecular data were based on analysis of a small highly variable region of the HIV genome and the validity of the conclusions drawn has been questioned.i2 The UK Department of Health lately concluded that there is no justification for routine testing of health care workers for HIV but that all such professionals have an ethical duty to seek advice if they have been exposed to HIV infection. Moreover, infected workers should not, according to these guidelines, perform invasive procedures that carry even a remote risk of exposing patients to the virus. This guidance also emphasised the importance of informing all patients on whom an invasive procedure had been done by a infected health care worker. In 1987 there was another outburst of public concern about HIV-infected doctors that culminated in a legal injunction imposed on the publication of confidential information. At that time we commentedl3 "guidance must be weighted toward over-caution in excluding doctors from any contact that could, in a very remote possibility, endanger patients". The judgment in that case was that "confidentiality was of paramount importance to such [HIV-infected] patients, including doctors who were patients".14 In 1993, those opinions still prevail. Yet the calls for routine testing of patients in some areas of known high HIV prevalence are bound to increase, despite the well-rehearsed arguments against such a policy, including infringement of human rights, cost, and the fact that a negative result cannot guarantee absence of infection. Clinical staff and management must be committed to infection control policies; there is enormous room for improvement, even in obvious areas such as prevention of needlestick injuries. is Ultimately, however, as Covello et all’ point out, health care workers in certain settings will have to adjust their expectations about the mortality risks associated with their occupational choices. contact

The Lancet Departments. AIDS-HIV infected health care workers: practical guidance on notifying patients. London: Department of Health, 1993. 2. Editorial. Needlestick transmission of HTLV-III from a patient infected 1. UK Health

in Africa. Lancet 1984; ii: 1376-77. 3. Kabukoba JJ, Young P. Midwifery and body fluid contamination. BMJ 1992; 305: 226. 4. Geberding JL, Littell C, Tarkington A, Brown A, Schecter WP. Risk of exposure of surgical personnel to patients’ blood during surgery at San Francisco General Hospital. N Engl J Med 1990; 322: 1788-93. 5. Leentvaar-Kuijpers A, Dekker MM, Coutinho RA, Dekker EE, Keeman JN, Ansink-Schipper MC. Needlestick injuries, surgeons, and HIV risks. Lancet 1990; 335: 546-47.

Joint Working Party of the Hospital Infection Society and the Surgical Infection Study Group. Risks to surgeons and patients from HIV and hepatitis: guidelines on precautions and management of exposure to blood or body fluids. BMJ 1992; 305: 1337-43. 7. Henderson DK, Fahey BJ, Willy M, et al. Risk for occupational transmission of human immunodeficiency virus type-1 (HIV-1) 6.

associated with clinical exposures. Ann Intern Med 1990; 113: 740-46. 8. Covello VT, Brandt-Rauf PW, Bendixen HH. The occupational risk of death from HIV transmission in health care workers—an assessment by extrapolation. Med Sci Res 1992; 20: 689—90. 9. Porter JD, Cruickshank JG, Gentle PH, Robinson RG, Gill ON. Management of patients treated by surgeon with HIV infection. Lancet 1990; 335: 113-14. 10. Mishu B, Schaffner W, Horan JN, Wood LH, Hutcheson RH, McNabb PC. A surgeon with AIDS: lack of evidence of transmission to patients. JAMA 1990; 264:467-70. 11. Ou C-Y, Ciesielski CA, Myers G, et al. Molecular epidemiology of HIV transmission in a dental practice. Science 1992; 256: 1165-71. 12. De Bry RW, Abele LG, Weiss SH, et al. Dental HIV transmission? Nature 1993; 361: 691. 13. Editorial. HIV infection: confidentiality for doctors. Lancet 1987; ii: 1188. 14. Brahams D. Confidentiality for doctors who are HIV positive. Lancet 1987; ii: 1221-22. 15. Editorial. Needlesticks: preaching to the seroconverted? Lancet 1992; 340: 640-42.

COMMENTARY

CANCER GENETICS

Gene for familial breast and ovarian

cancer

Breast cancer aggregates in certain families, often in association with ovarian cancer. In 1990, linkage studies localised an inherited susceptibility gene for these cancers to chromosome 17q. The gene, called BRCA1, is thought to be a tumour suppressor gene.3,4 The prevailing notion is that cancer-predisposing mutations in the BRCA1 gene are heritable, and can also be acquired within somatic cells during neoplastic transformation. Easton and colleagues,s using polymorphic markers in the region of the BRCA1 gene, have now reported the pooled results of linkage analysis of 214 breast cancer families. Additional data on one of these families are provided by Narod and colleagues in this issue (p 1101). The collection and examination of pedigree data and blood specimens represents a massive effort of thirteen groups in the Breast Cancer Linkage Consortium. Evidence for linkage was found for all 57 families with both breast and ovarian cancers, and for about half of the remaining breast cancer families. The figures suggest that germline BRCA1 mutations contribute to the development of several thousand breast and ovarian cancers annually in the US and UK. The families in Easton’s study, though highly selected, also provide additional data on penetrance-the probability of developing cancer among carriers of an altered gene. The calculations show that a woman with an inherited BRCA1 mutation has a nearly 60% likelihood of getting breast or ovarian cancer by age 50. In the general population, the risk of these cancers by age 50 is 2%. Identification of the BRCA1 gene is now a matter of time and hard work. Cloning the gene will provide a blood test that can identify carriers of BRCA1 mutations before cancer appears. In preparation for clinical application of the new technology, we need to develop guidelines for the of candidates for selection testing.6 Important considerations include the prevalence of carriers within population subgroups and the sensitivity and specificity of

1061

the assay. Among appropriate candidates for testing, the decision to proceed should rest solely with the individual. Counselling and other support services should be provided during the testing process and thereafter. Experience with presymptomatic testing for other hereditary disorders has shown the potential for both beneficial and harmful effects of learning one’s genotype.6 How should female carriers of BRCA1 mutations be managed? No single approach will suffice; each woman should have an active role in all decisions. A reasonable recommendation is intensive surveillance for early cancer. Additional interventions might include chemoprophylaxis with agents such as tamoxifen, or prophylactic bilateral mastectomy with or without oophorectomy. Unfortunately, effects of these and other interventions, including lifestyle changes, are unknown in BCRA1 carriers. Large cooperative studies will be needed to identify services that yield a net benefit, and the appropriate circumstances for their use. Frederick P. Li Judy E. Garber 1. Hall JM, Lee MK, Newman B, et al. Linkage analysis of familial breast cancer to chromosome 17q21. Science

early-onset

1990; 250: 1684-89. 2. Narod SA, Feunteun J, Lynch HT, et al. Familial breast-ovarian cancer locus on chromosome 17q12-23. Lancet 1991; 338: 82-83. 3. Sato T, Akiyama F, Sakamoto G, Kasumi F, Nakamura Y. Accumulation of genetic alterations and progression of primary breast cancer. Cancer Res 1991; 51: 5794-99. 4. Weinberg RA. Tumor suppressor genes. Science 1991; 254: 1138-46. 5. Easton DF, Bishop DT, Ford D, Crockford GP, the Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer-results from 214 families. Am J Hum Genet 1993; 52: 678-701. 6. Li FP, Garber JE, Friend SH, et al. Recommendations on predictive testing for germ line p53 mutations among cancer-prone individuals. J Natl Cancer Inst 1992; 84: 1156-60.

INTENSIVE CARE

International standards for intensive

care

guidelines. As far as we are aware, no legal standards of care for intensive care units have been approved. Consequently, doctors will be held responsible according to specialty or national standards. Institutional standards in the USA2 dictate that "each special care unit be properly directed and staffed according to the nature of the special care needs anticipated and the scope of services offered. The director assures that the quality, safety, and appropriateness of patient care services provided within the unit are monitored and evaluated on a regular basis and that appropriate actions based on findings are taken. The director is responsible for implementing policies established by the medical staff for the continuing operation of the unit". In this manner, the US Joint Commission on Accreditation of Hospitals (1986) placed the responsibility and gave early directions as to possibilities of quality assurance in the unit, but did not attempt to set minimum standards. The lack of consensus regarding the monitoring standards in intensive care units is reflected in numerous articles about differences in standards between university and nonuniversity departments.3Recently, a document developed by the International Task Force on Safety in the Intensive Care Unit has appeared in international journals.4 A parallel free-standing body published similar guidelines for standards for a safe practice of anaesthesia.5 The article entitled "International Standards for Safety in the Intensive Care Unit" defines basic standards such as design features, staffing, services, drugs, and education, and makes recommendations about specific invasive and therapeutic procedures and control of infection. The target departments are tertiary referral or level 1 intensive care units. As stated in the preamble, the standards were developed to help avoid preventable mishaps or diminish the severity of their consequences. Two of the specialists involved were also on The International Task Force on Anaesthesia Safety where the standards were approved by the World Federation of Societies of Anaesthesiologists on June 13, 1992, and consequently the intensive care unit standards are expected to reach the same level of recognition. Michael E. Crawford

unit

Mogens Bredgaard Sørensen Jørgen B. Dahl

safety Intensive care medicine throughout the past thirty years has developed from several single medical specialties into a multidisciplinary subject. Advances in intensive care medicine are based on the availability of complex equipment, so management of individual patients requires knowledge of the function of this machinery. The most fundamental requirement for the care of critically ill and injured patients is on-site commitment of physicians, anaesthetists, and surgeons qualified to provide life-support management. Life-sustaining ventilatory support dates back to the late 1940s and was introduced in most major medical centres to treat patients with bulbar poliomyelitis. In the 1952 epidemic in Denmark, Lassen1 used conventional techniques such as endotracheal intubation and manual bag ventilation by medical students and nurses for this purpose. Since then progress especially in organ transplantation procedures has led to the introduction of specific guidelines for monitoring in recovery and intensive care units. Data retrieval systems have been refmed to generate severity of illness scores that can be used to

predict outcome.

Of course, the degree of expansion in the use of electronic devices and other equipment necessitates introduction of

1. Lassen HC. A

preliminary report on the 1952 epidemic of poliomyelitis in Copenhagen with special reference to the treatment of acute respiratory insufficiency. Lancet 1953; i: 37-41. 2. Joint Commission on Accreditation of Hospitals (USA) 1986. Standard 22.2. In: Shoemaker et al, eds. Textbook of critical care. 2nd ed. Philadelphia: WB Saunders, 1989. 3. Saarela E, Kari P, Nikki P, Rauhala V, Iisola E, Kaukinen L. The Finnish

4.

Intensive Care Study Group: Current practice regarding invasive monitoring in ICUs in Finland. Intensive Care Med 1991; 17: 264-72. International Task Force on Safety in the Intensive Care Unit. International standards for safety in the intensive care unit. Crit Care

Med 1993; 21: 453-56 and Intensive Care Med 1993; 19: 178-81. 5. International Task Force on Anaesthesia Safety: International standards for a safe practice of anaesthesia. Eur J Anaesthesiol 1993; 10 (suppl 7): 12.

PAIN RELIEF

Narcotic

drug

use

for

severe

pain

problem raised by Zenz and Willweber-Strumpf (p 1075) as a follow-up of the consensus conference on narcotic drug legislation in Europe and its impact on the cancer pain patient is very important. Seldom do conferences reach a complete agreement, as they did on this The