- Email: [email protected]
Low-molecular-weight heparin during instability in coronary artery disease
France, where the period of prescription of oral morphine for one form was increased in 1992 from 7 to 14 days (and in 1995 to 28 days), a survey found that 76% of primary of medical oncologists were care physicians and 50% reluctant to prescribe morphine for cancer pain mainly because of their fear of side-effects; the constraints of the prescription forms were cited with other secondary reasons.4 Similar studies on attitudes towards pain control in the USA and in Japan show that there are common barriers to adequate pain management4,5 in countries with different opioid prescription laws. The most frequent causes of underof cancer-related treatment pain are:4,5 inadequate knowledge due to inadequate training at undergraduate and postgraduate levels; difficulties in recognising and evaluating the severity of pain; reluctance to prescribe opioid analgesics for fear of addiction, tolerance and side-effects; failure to accept that analgesia is integrated to the treatment of cancer, both for those with advanced disease and for those whose life expectancy is longer and who are still undergoing specific treatment. In addition, analgesics are often costly, not reimbursable and not even available in many countries. All these causes have a common base-the lack of culture and sensibility towards a problem which affects 74% of patients with advanced cancer. The elimination of bureaucratic obstacles to prescription of morphine can alleviate the problem, but only in a population of physicians, pharmacists, social workers, and relatives of patients that is aware of the problem and willing to do something about it. We disagree with Simini’s proposal to change the denomination of morphine. This shows how strongly the problem is of a cultural nature. What shall we then do with terms like "cancer", "pain", or "death"-do we also have to change these? *Carla Ripamonti, Franco De Conno, Heidi Blumhuber, Vittorio Ventafridda Therapy and Palliative Care Division, National Cancer Institute, Milano, Italy; European Association for Palliative Care, INT, Milano; and WHO, Cancer Pain Relief Programme, Geneva, Switzerland *Pain
1 Simini B. Prescribing morphine for pain relief is unduly difficult in Italy. Lancet 1996; 347: 753. 2 Zenz M, Willweber-Strumpf A. Opiophobia and cancer pain in Europe. Lancet 1993; 341: 1075-76. 3 Zylicz Z. Opiophobia and cancer pain. Lancet 1993; 341: 1473-74. 4 Larue F, Zolleau SM, Fontaine A, Brasseur L. Oncologists and primary care physicians’ attitude toward pain control and morphine prescribing in France. Cancer 1995; 76: 2375-82. 5 Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994; 330: 592-96.
Low-molecular-weight heparin during instability in coronary artery disease SIR-The FRISC study group (March 2, p 561)’ cites four papers, two of which were published before the start of its study, showing that the combination of heparin and aspirin in the acute phase of unstable coronary artery disease is more effective than aspirin alone in preventing myocardial infarction or death. Despite this, the FRISC study compared dalteparin and aspirin with aspirin plus placebo. This does a disservice both to trial participants suffering as a consequence of inadequate treatment, and to clinicians denied information comparing a new treatment with one they currently use. There is an urgent need for the medical scientific community, the pharmaceutical industry, and
drug-regulating authorities internationally to agree criteria whereby a new treatment may be licensed after demonstration of an equivalent effect, within predefined
confidence intervals, to the current standard treatment. Research ethics committees should firmly reject proposals for any placebo-controlled trial where a beneficial treatment already exists.
Roger H Jay Department
of
Geriatrics, South Tyneside District Hospital, South Shields
NE34 0PL, UK
1
Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet
1996; 347: 561-68.
New Austrian mutation in BRCA1 gene detected in three unrelated HBOC families SiR-Germline
mutations
in
the
BRCAl gene confer and ovarian cancer mutations have been mutations that each account for about 11 % of all mutations (Breast Cancer Information Core, http://www.nchgr.nih.gov/intramural_ research/Lab_transfer/bic): the 185delAG mutation found in approximately 1 % of Ashkenazi Jewish people and the mutation 5382insC, often found in families with ovarian cancer. These results suggest that distinct populations may be characterised by a high frequency of certain mutations in BRCA and that these mutations may have been present in the population for many generations. We characterised genes of Austrian families with hereditary breast cancer. We found a mutation in three unrelated Austrian HBOC families. The families had 11 cases of breast cancer and one ovarian cancer. The average age of onset was from 36 to 40 years. The protein truncation test (PTT) indicated a stop codon in exon 11 of the BRCAgene.3 Cycle sequencing of PCR products of exon 11 showed a deletion of AAAG at position 2795 not so far reported. This mutation results in a BRCA1 protein truncated by 866 aminoacids with 106 new aminoacids at the C-terminus, the longest false reading frame reported to date. This mutation was detected in all three families, and was present in all patients with cancer. Some healthy people, including three women aged 24-30, carried the mutation. After inquiring about the family histories, we found out that the great-grandparents of two of the families lived in the same small village north of Vienna. The other family lives in Vienna, but their origin remains unclear. This "Austrian" mutation in the BRCA1gene may have come from the village north of Vienna and may be a mutation typical for this region of Austria. The establishment of regional, typical BRCA1 mutations may be of great help in the search for mutations in HBOC families.
susceptibility to hereditary breast (HBOC).’ More than 100 germline detected, although there are two
This work was supported by a grant of the ’Kommission Onkologie’, Medical Faculty, University of Vienna. We thank the families who participated in this study.
TM U Wagner, R H Breiteneder
Möslinger,
*C Zielinski, O Scheiner,
Sections of Special Gynaecology, Department of Obstetrics and Gynaecology, *Medical Experimental Oncology, University Hospital, and Department of General and Experimental Pathology, University of Vienna, 1090 Vienna, Austria
1
2
3
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium. Risks of cancer in BRCA1mutation carriers. Lancet 1994; 343: 692-95. Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genet 1995; 11: 198-200. Hogervorst FBL, Cornelis RS, Bout M, et al. Rapid detection of BRCA1 mutations by the Protein Truncation Test. Nature Genet 1995; 10: 208-12.
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1 Simini B. Prescribing morphine for pain relief is unduly difficult in Italy. Lancet 1996; 347: 753. 2 Zenz M, Willweber-Strumpf A. Opiophobia and cancer pain in Europe. Lancet 1993; 341: 1075-76. 3 Zylicz Z. Opiophobia and cancer pain. Lancet 1993; 341: 1473-74. 4 Larue F, Zolleau SM, Fontaine A, Brasseur L. Oncologists and primary care physicians’ attitude toward pain control and morphine prescribing in France. Cancer 1995; 76: 2375-82. 5 Cleeland CS, Gonin R, Hatfield AK, et al. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994; 330: 592-96.
Low-molecular-weight heparin during instability in coronary artery disease SIR-The FRISC study group (March 2, p 561)’ cites four papers, two of which were published before the start of its study, showing that the combination of heparin and aspirin in the acute phase of unstable coronary artery disease is more effective than aspirin alone in preventing myocardial infarction or death. Despite this, the FRISC study compared dalteparin and aspirin with aspirin plus placebo. This does a disservice both to trial participants suffering as a consequence of inadequate treatment, and to clinicians denied information comparing a new treatment with one they currently use. There is an urgent need for the medical scientific community, the pharmaceutical industry, and
drug-regulating authorities internationally to agree criteria whereby a new treatment may be licensed after demonstration of an equivalent effect, within predefined
confidence intervals, to the current standard treatment. Research ethics committees should firmly reject proposals for any placebo-controlled trial where a beneficial treatment already exists.
Roger H Jay Department
of
Geriatrics, South Tyneside District Hospital, South Shields
NE34 0PL, UK
1
Fragmin during Instability in Coronary Artery Disease (FRISC) Study Group. Low-molecular-weight heparin during instability in coronary artery disease. Lancet
1996; 347: 561-68.
New Austrian mutation in BRCA1 gene detected in three unrelated HBOC families SiR-Germline
mutations
in
the
BRCAl gene confer and ovarian cancer mutations have been mutations that each account for about 11 % of all mutations (Breast Cancer Information Core, http://www.nchgr.nih.gov/intramural_ research/Lab_transfer/bic): the 185delAG mutation found in approximately 1 % of Ashkenazi Jewish people and the mutation 5382insC, often found in families with ovarian cancer. These results suggest that distinct populations may be characterised by a high frequency of certain mutations in BRCA and that these mutations may have been present in the population for many generations. We characterised genes of Austrian families with hereditary breast cancer. We found a mutation in three unrelated Austrian HBOC families. The families had 11 cases of breast cancer and one ovarian cancer. The average age of onset was from 36 to 40 years. The protein truncation test (PTT) indicated a stop codon in exon 11 of the BRCAgene.3 Cycle sequencing of PCR products of exon 11 showed a deletion of AAAG at position 2795 not so far reported. This mutation results in a BRCA1 protein truncated by 866 aminoacids with 106 new aminoacids at the C-terminus, the longest false reading frame reported to date. This mutation was detected in all three families, and was present in all patients with cancer. Some healthy people, including three women aged 24-30, carried the mutation. After inquiring about the family histories, we found out that the great-grandparents of two of the families lived in the same small village north of Vienna. The other family lives in Vienna, but their origin remains unclear. This "Austrian" mutation in the BRCA1gene may have come from the village north of Vienna and may be a mutation typical for this region of Austria. The establishment of regional, typical BRCA1 mutations may be of great help in the search for mutations in HBOC families.
susceptibility to hereditary breast (HBOC).’ More than 100 germline detected, although there are two
This work was supported by a grant of the ’Kommission Onkologie’, Medical Faculty, University of Vienna. We thank the families who participated in this study.
TM U Wagner, R H Breiteneder
Möslinger,
*C Zielinski, O Scheiner,
Sections of Special Gynaecology, Department of Obstetrics and Gynaecology, *Medical Experimental Oncology, University Hospital, and Department of General and Experimental Pathology, University of Vienna, 1090 Vienna, Austria
1
2
3
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, and the Breast Cancer Linkage Consortium. Risks of cancer in BRCA1mutation carriers. Lancet 1994; 343: 692-95. Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nature Genet 1995; 11: 198-200. Hogervorst FBL, Cornelis RS, Bout M, et al. Rapid detection of BRCA1 mutations by the Protein Truncation Test. Nature Genet 1995; 10: 208-12.
1263