1194 Case 2
Fig. 1-Continuous BP recordings. Recordings ran from 7 P.M. to 7 P.M. Arrows-indicate hypertensive attacks perceived and signalled by the patient. (A) Case 1; (B) case 2. attack values were 5811 pg/ml for noradrenaline and 1040 pg/ml for adrenaline. Because the attacks were so brief continuous BP recording via a radial artery was started with an Oxford recorder. The patient pressed a marker when an attack began and ended. For 24 h no "typical" episode was reported, but during the next 24 h the patient reported two episodes. In both, BP had dramatically increased (fig. 1A). When the tracings were displayed at higher speed simultaneously with BP integration, heart-rate, and ECG the heart-rate was seen to have increased at the start of the episode with premature ventricular beats and bursts of ventricular tachycardia (fig. 2). The patient’s signals corresponded to the heart-rate irregularities; early and late BP increases not associated with arrhythmias
one
were not
perceived.
Catheterisation of the inferior vena cava and plasma catecholamine measurement at different sites revealed increased concentrations at the level of the left adrenal veins, and at operation a multinodular mass of chromaffin cells was found in the left adrenal gland. After left adrenalectomy the symptoms
disappeared.
This 48-year-old man with known hypertension and frequent 3-S min episodes of flushing, throbbing headache, and dizziness was also admitted to our unit in March, 1979. His BP was 190/120 mm Hg, and there were signs of target organ damage in the optic fundi and ECG and radiographic evidence of left-ventricular hypertrophy. An intravenous pyelogram was normal. During the first week in hospital the patient reported daily attacks but catecholamine studies were equivocal. During 24 h continuous BP recording the patient reported three typical episodes, in all of which the BP rose dramatically above the already high values (fig. 1B). The polygraph tracings revealed that BP had risen many other times when the patient had perceived no symptoms. Catheterisation studies pointed to a left-side phaeochromocytoma and surgery was successful. In these two cases where diagnosis of hypertensive crises due to phaeochromocytoma was hampered by the brevity of the attacks continuous BP recording gave valuable diagnostic information. The BP, heart-rate, and ECG traces revealed that in patient 1 the crises were accompanied by severe life-threatening arrhythmias. The continuous recordings, by providing direct evidence of the magnitude of the paroxysmal hypertension and of its cardiac complications, suggested the need for prompt treatment (with labetalol) in both cases. We thank Dr G. B. Picotti for the catecholamine radioimmunoassays.
Institute of Cardiovascular Research, Medical Pathology I, Cardiovascular Research Centre CNR,
University of Milan, 20122 Milan, Italy
GIUSEPPE MANCIA ALBERTO FERRARI LUISA GREGORINI GIANFRANCO PARATI GUIDO POMIDOSSI ALBERTO ZANCHETTI
DANGEROUS PATHOGENS AND SAFETY AT WORK
SIR,-I warmly welcome your editorial (Nov. 10, p. 1004) the Health and Safety Executive’s draft regulations and guidance, notesl-an editorial which should alert consultant microbiologists to the danger of the introduction of even more ill-conceived safety regulations. However, I fear that your warning will not be heeded. If the recent past is any guide, the profession’s response could be sadly apathetic: that certainly seems to have been the case with the Howie report2 which was
on
published in March, 1979.
Fig. 2-Display
at
higher speed
of
hypertensive
attack in pa-
I have discussed the Howie report with well over a hundred consultant microbiologists and virtually all of them regard it with disfavour. Its meaning in places is not clear; it is inconsistent and some passages are contradictory; some of the measures proposed to prevent or reduce infection are out of date, some have little or no basis in scientific fact, some are regarded as excessive, and others, if implemented, would be positively harmful. That is the view of most British clinical microbiologists. All are in agreement with some of the code’s commandments-and they are commandments, not recommendations-but they are opposed to its inflexibility. Full implementation will cost millions of pounds, may do little good, and possibly some harm, yet some individuals who are well aware of the code’s limitations have seized upon it gleefully and are using it in attempts to extract money from hardpressed authorities. The effects of such action may well be quite different from those desired, and if departments which do not conform are not improved but closed, the joy will rapidly be converted to dismay which will evoke little sympathy.
tient 1.
ABP=arterial
blood
MAP=mean arterial pressure; /ABP=consecutive periods of blood pressure integration; HR=heartrate. Arrows indicate beginning and end of attacks as sensed by patient. pressure;
Dangerous pathogens: draft regulations and draft guidance notes. Obtainable from Health and Safety Executive, Baynards House, I Chepstow Place, London W2 4TF. 2. Code of practice for the prevention of infection in clinical laboratories and post mortem rooms. HM Stationery Office, 1978.
1.
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
Fig. 1-Continuous BP recordings. Recordings ran from 7 P.M. to 7 P.M. Arrows-indicate hypertensive attacks perceived and signalled by the patient. (A) Case 1; (B) case 2. attack values were 5811 pg/ml for noradrenaline and 1040 pg/ml for adrenaline. Because the attacks were so brief continuous BP recording via a radial artery was started with an Oxford recorder. The patient pressed a marker when an attack began and ended. For 24 h no "typical" episode was reported, but during the next 24 h the patient reported two episodes. In both, BP had dramatically increased (fig. 1A). When the tracings were displayed at higher speed simultaneously with BP integration, heart-rate, and ECG the heart-rate was seen to have increased at the start of the episode with premature ventricular beats and bursts of ventricular tachycardia (fig. 2). The patient’s signals corresponded to the heart-rate irregularities; early and late BP increases not associated with arrhythmias
one
were not
perceived.
Catheterisation of the inferior vena cava and plasma catecholamine measurement at different sites revealed increased concentrations at the level of the left adrenal veins, and at operation a multinodular mass of chromaffin cells was found in the left adrenal gland. After left adrenalectomy the symptoms
disappeared.
This 48-year-old man with known hypertension and frequent 3-S min episodes of flushing, throbbing headache, and dizziness was also admitted to our unit in March, 1979. His BP was 190/120 mm Hg, and there were signs of target organ damage in the optic fundi and ECG and radiographic evidence of left-ventricular hypertrophy. An intravenous pyelogram was normal. During the first week in hospital the patient reported daily attacks but catecholamine studies were equivocal. During 24 h continuous BP recording the patient reported three typical episodes, in all of which the BP rose dramatically above the already high values (fig. 1B). The polygraph tracings revealed that BP had risen many other times when the patient had perceived no symptoms. Catheterisation studies pointed to a left-side phaeochromocytoma and surgery was successful. In these two cases where diagnosis of hypertensive crises due to phaeochromocytoma was hampered by the brevity of the attacks continuous BP recording gave valuable diagnostic information. The BP, heart-rate, and ECG traces revealed that in patient 1 the crises were accompanied by severe life-threatening arrhythmias. The continuous recordings, by providing direct evidence of the magnitude of the paroxysmal hypertension and of its cardiac complications, suggested the need for prompt treatment (with labetalol) in both cases. We thank Dr G. B. Picotti for the catecholamine radioimmunoassays.
Institute of Cardiovascular Research, Medical Pathology I, Cardiovascular Research Centre CNR,
University of Milan, 20122 Milan, Italy
GIUSEPPE MANCIA ALBERTO FERRARI LUISA GREGORINI GIANFRANCO PARATI GUIDO POMIDOSSI ALBERTO ZANCHETTI
DANGEROUS PATHOGENS AND SAFETY AT WORK
SIR,-I warmly welcome your editorial (Nov. 10, p. 1004) the Health and Safety Executive’s draft regulations and guidance, notesl-an editorial which should alert consultant microbiologists to the danger of the introduction of even more ill-conceived safety regulations. However, I fear that your warning will not be heeded. If the recent past is any guide, the profession’s response could be sadly apathetic: that certainly seems to have been the case with the Howie report2 which was
on
published in March, 1979.
Fig. 2-Display
at
higher speed
of
hypertensive
attack in pa-
I have discussed the Howie report with well over a hundred consultant microbiologists and virtually all of them regard it with disfavour. Its meaning in places is not clear; it is inconsistent and some passages are contradictory; some of the measures proposed to prevent or reduce infection are out of date, some have little or no basis in scientific fact, some are regarded as excessive, and others, if implemented, would be positively harmful. That is the view of most British clinical microbiologists. All are in agreement with some of the code’s commandments-and they are commandments, not recommendations-but they are opposed to its inflexibility. Full implementation will cost millions of pounds, may do little good, and possibly some harm, yet some individuals who are well aware of the code’s limitations have seized upon it gleefully and are using it in attempts to extract money from hardpressed authorities. The effects of such action may well be quite different from those desired, and if departments which do not conform are not improved but closed, the joy will rapidly be converted to dismay which will evoke little sympathy.
tient 1.
ABP=arterial
blood
MAP=mean arterial pressure; /ABP=consecutive periods of blood pressure integration; HR=heartrate. Arrows indicate beginning and end of attacks as sensed by patient. pressure;
Dangerous pathogens: draft regulations and draft guidance notes. Obtainable from Health and Safety Executive, Baynards House, I Chepstow Place, London W2 4TF. 2. Code of practice for the prevention of infection in clinical laboratories and post mortem rooms. HM Stationery Office, 1978.
1.
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
