1195 Publication of the code has spawned numerous committees, of them associated with scientific bodies, but as yet there has been no authoritative statement of criticism. The Royal College of Pathologists, properly a guardian of professional standards, is gathering views, but as yet has made no public pronouncement other than to advise its members of the legal consequences of a failure to implement the code in its entirety, and the implication is that it regards it as a set of orders which must be obeyed. Where I ask is the storm of protest? Have all British consultant microbiologists become frightened sheep? Are we prepared to accept any edict, provided it is printed on official paper? Those who believe that it would be wrong to implement the code’s proposals now as a package have a duty to say so. Furthermore, we should all obtain the latest Health and Safety Executive draft regulations’ and comment upon them too. I fear that the greatest danger in clinical laboratories could be a willingness on the part of those who run them to accept science by decree. some
flushing and six non-flushing subjects, the skin overlylateral part of the zygomatic process was gently punctured with the tip of a hypodermic needle introduced through a drop of either DAMME solution (1-7 mmol/1) or saline. In no case was there significantly more local cutaneous vasodilatation with DAMME solution than with saline. These findings support the view that the locus of action of the enkephalin induced flush is central rather than peripheral. The localisation of the flush suggests central activation of an anatomically specific vasodilator pathway or inhibition of tonic vasoconstriction. Alternatively, a peripheral effector may be released which is localised to or effective at specific sites. The prolonged duration of the flush suggests either some slowly removed effector or some slowly "recharged" tonemaintaining mechanism. Some of these alternative mechanisms.are being investigated. In six
ing the
Unit for Metabolic Medicine,
D. B. JEFFERYS
Department of Medicine, Guy’s Hospital Medical School,
C. R. STRAKOSCH H. KEEN
London SE1 9RT
Guy’s Hospital,
N. A. SIMMONS
London SE1
FACIAL FLUSHING IN DIABETES al.reported the special characteristics of the flushing provoked by alcohol in a large proportion of non-insulin-dependent diabetics (NIDD) receiving chlorpropamide treatment. A much smaller proportion (about 10%) of non-diabetics and of insulin-dependent diabetics showed the same response. NIDD patients who flushed were found to be different as a group from those who did not, in respect of family history of diabetes,2 and frequency and severity of retinopathy.3 Further work revealed that those who flushed on chlorpropamide/alcohol testing also did so (and showed a confirmatory greater rise in facial skin temperature) when given the metenkephalin analogue DAMME intravenously. From this evidence arose the hypothesis that both the flush and the diabetes might be due to increased sensitivity to enkephalin with a possible locus of action in the brain and produced by way of mechanisms akin to the experimental (piqure) diabetes of Claude Bernard,4,5 though a peripheral action of DAMME could not be excluded. The vasodilatation of the chlorpropamide/alcohol flush involves the conjunctival vessels, causing distinct reddening of the eye. We wondered whether, in proven flushers compared with non-flus hers, direct application of DAMME to the conjunctival sac as eyedrops might produce a peripheral vasodilatory effect of the enkephalin analogue and if so whether this might be a simpler way of identifying flushers and nonflushers. Sixteen NIDD, eight of them proven flushers and eight of them non-flushers, were selected from the diabetic clinic outpatients along with six non-diabetic, non-flushing normal controls. All of them were fully informed of the nature of the experiment and consented to it. One drop of DAMME at a concentration of 1/10 (0-17 mmol/1) was instilled into one eye and drop of the diluent (saline) into the other. A neutral observer was asked to judge and grade the vasodilator response in the conjunctivae. Very slight pinkening was seen in the DAMME treated eye in eight cases, as often in non-flushers as flushers. We concluded that, at the concentrations tested, there was no difference in the local conjunctival response between flushers and non-flushers and that it was trivial and non-
S!R,—Leslie
et
facial
specific. 1. Leslie
RDG, Pyke DA. Chlorpropamide-alcohol flushing: a dominantly intrait associated with diabetes. Br Med J 1978; ii: 1519. 2. Pyke DA, Leslie RDG. Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin dependent diabetes. Br Med J 1978; ii: 1521. 3. Leslie RDG, Barnet AH, Pyke DA. Chlorpropamide alcohol flushing and diabetic retinopathy. Lancer 1979; i: 997. 4. Leslie RDG, Pyke DA, Stubbs WA. Sensitivity to enkephalin as a cause of non-insulin dependent diabetes. Lancet 1979; i: 341. 5. Pyke DA. Claude Bernard lecture on Diabetes: the genetic connections, given at 10th International Diabetes Federation Congress, Vienna, 1979. herited
CHROMOSOMES, LEUKÆMIA, AND OCCUPATIONAL EXPOSURE TO LEUKÆMOGENIC AGENTS
retrospective study of 56 patients with acute nonleukaemia (ANLL) we found some striking chromosomal differences between patients occupationally exposed to potentially mutagenic/carcinogenic agents and patients with no history of occupational exposure to such agents.’ In the non-exposed group only 24% of the patients had clonal chromosomal aberrations in their bone-marrow cells, whereas 83% of patients exposed-to chemical solvents, insecticides, or petroleum products had clonal chromosomal changes. Using a similar approach, Lawler et al. were unable to demonstrate a correlation between exposure at work and chromosomal findings in 67 patients treated at the Royal Marsden Hospital. Data from an extended collaborative study confirm our previous results. The two series now comprise 156 patients with ANLL treated in Lund or in Rome. The records of all patients were reviewed and the occupations were categorised, without knowledge of the chromosomal findings, using the same criteria as in our previous study.’ Only clonal chromosomal abnormalities were recorded. SIR,-In
a
lymphocytic
ASSOCIATION BETWEEN CHROMOSOMAL ABNORMALITY IN ANLL AND OCCUPATIONAL EXPOSURE TO POTENTIALLY LEUKAMOGENIC
AGENTS
*p
flushing and six non-flushing subjects, the skin overlylateral part of the zygomatic process was gently punctured with the tip of a hypodermic needle introduced through a drop of either DAMME solution (1-7 mmol/1) or saline. In no case was there significantly more local cutaneous vasodilatation with DAMME solution than with saline. These findings support the view that the locus of action of the enkephalin induced flush is central rather than peripheral. The localisation of the flush suggests central activation of an anatomically specific vasodilator pathway or inhibition of tonic vasoconstriction. Alternatively, a peripheral effector may be released which is localised to or effective at specific sites. The prolonged duration of the flush suggests either some slowly removed effector or some slowly "recharged" tonemaintaining mechanism. Some of these alternative mechanisms.are being investigated. In six
ing the
Unit for Metabolic Medicine,
D. B. JEFFERYS
Department of Medicine, Guy’s Hospital Medical School,
C. R. STRAKOSCH H. KEEN
London SE1 9RT
Guy’s Hospital,
N. A. SIMMONS
London SE1
FACIAL FLUSHING IN DIABETES al.reported the special characteristics of the flushing provoked by alcohol in a large proportion of non-insulin-dependent diabetics (NIDD) receiving chlorpropamide treatment. A much smaller proportion (about 10%) of non-diabetics and of insulin-dependent diabetics showed the same response. NIDD patients who flushed were found to be different as a group from those who did not, in respect of family history of diabetes,2 and frequency and severity of retinopathy.3 Further work revealed that those who flushed on chlorpropamide/alcohol testing also did so (and showed a confirmatory greater rise in facial skin temperature) when given the metenkephalin analogue DAMME intravenously. From this evidence arose the hypothesis that both the flush and the diabetes might be due to increased sensitivity to enkephalin with a possible locus of action in the brain and produced by way of mechanisms akin to the experimental (piqure) diabetes of Claude Bernard,4,5 though a peripheral action of DAMME could not be excluded. The vasodilatation of the chlorpropamide/alcohol flush involves the conjunctival vessels, causing distinct reddening of the eye. We wondered whether, in proven flushers compared with non-flus hers, direct application of DAMME to the conjunctival sac as eyedrops might produce a peripheral vasodilatory effect of the enkephalin analogue and if so whether this might be a simpler way of identifying flushers and nonflushers. Sixteen NIDD, eight of them proven flushers and eight of them non-flushers, were selected from the diabetic clinic outpatients along with six non-diabetic, non-flushing normal controls. All of them were fully informed of the nature of the experiment and consented to it. One drop of DAMME at a concentration of 1/10 (0-17 mmol/1) was instilled into one eye and drop of the diluent (saline) into the other. A neutral observer was asked to judge and grade the vasodilator response in the conjunctivae. Very slight pinkening was seen in the DAMME treated eye in eight cases, as often in non-flushers as flushers. We concluded that, at the concentrations tested, there was no difference in the local conjunctival response between flushers and non-flushers and that it was trivial and non-
S!R,—Leslie
et
facial
specific. 1. Leslie
RDG, Pyke DA. Chlorpropamide-alcohol flushing: a dominantly intrait associated with diabetes. Br Med J 1978; ii: 1519. 2. Pyke DA, Leslie RDG. Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin dependent diabetes. Br Med J 1978; ii: 1521. 3. Leslie RDG, Barnet AH, Pyke DA. Chlorpropamide alcohol flushing and diabetic retinopathy. Lancer 1979; i: 997. 4. Leslie RDG, Pyke DA, Stubbs WA. Sensitivity to enkephalin as a cause of non-insulin dependent diabetes. Lancet 1979; i: 341. 5. Pyke DA. Claude Bernard lecture on Diabetes: the genetic connections, given at 10th International Diabetes Federation Congress, Vienna, 1979. herited
CHROMOSOMES, LEUKÆMIA, AND OCCUPATIONAL EXPOSURE TO LEUKÆMOGENIC AGENTS
retrospective study of 56 patients with acute nonleukaemia (ANLL) we found some striking chromosomal differences between patients occupationally exposed to potentially mutagenic/carcinogenic agents and patients with no history of occupational exposure to such agents.’ In the non-exposed group only 24% of the patients had clonal chromosomal aberrations in their bone-marrow cells, whereas 83% of patients exposed-to chemical solvents, insecticides, or petroleum products had clonal chromosomal changes. Using a similar approach, Lawler et al. were unable to demonstrate a correlation between exposure at work and chromosomal findings in 67 patients treated at the Royal Marsden Hospital. Data from an extended collaborative study confirm our previous results. The two series now comprise 156 patients with ANLL treated in Lund or in Rome. The records of all patients were reviewed and the occupations were categorised, without knowledge of the chromosomal findings, using the same criteria as in our previous study.’ Only clonal chromosomal abnormalities were recorded. SIR,-In
a
lymphocytic
ASSOCIATION BETWEEN CHROMOSOMAL ABNORMALITY IN ANLL AND OCCUPATIONAL EXPOSURE TO POTENTIALLY LEUKAMOGENIC
AGENTS
*p
