923
2 patients subsequently died after of severe refractory heart failure in 1 and pulmonary embolism in the other. Our patients had resistant oedema from severe congestive cardiac failure. All responded to the addition of bendrofluazide therapy by diuresis and resolution of the oedema. Unlike Kiyingi et al, we did not start with a low dose of thiazide-like diuretic but chose 10 mg of bendrofluazide in 9 and 5 mg in 1. This was not associated with profound or dangerous electrolyte disturbances. It is important to avoid overdiuresis in such patients since this causes a fall in cardiac output with subsequent prerenal failure. Treatment should be monitored by daily measurements of weight and serum creatinine, urea, and electrolytes. Metolazone is more than fifteen times more expensive than bendrofluazide, and our data suggest that it offers little advantage.
bendrofluazide therapy. recurrence
Cardiology Department, Royal Hallamshire Hospital,
KEVIN S. CHANNER MICHAEL RICHARDSON
Sheffield S10 2JF, UK
ROB CROOK
Cardiology Department, Bristol Royal Infirmary
JOHN V. JONES
1. Gunstone
RF, Wing AJ, Shani HGP, Njemo D, Sabuka EMW. Clinical experience with metolazone in 52 African patients: synergy with furosemide. Postgrad Med J 1971; 47: 789-93.
Effects of coronary risk reduction
on
vascular deaths in the placebo group and 461/4295 (10-7%) in the aspirin group. The reduction in mortality was greatest in patients treated within 4 h of symptom onset. The early use of aspirin in AMI is thus of demonstrated value and further randomised placebo-controlled trial seems unnecessary. Cardiac Department, London Chest Hospital, London E2 9JX, UK
STEPHEN J. D. BRECKER
1. ISIS-2 Collaborative
Group. Randomised trial of intravenous streptokinase, oral neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; ii: 349-60. aspirin, both,
or
B*This letter has been shown follows.-ED. L.
to
Dr
Elwood, whose reply
SIR,-In ISIS-2 the use of aspirin in hospital patients with acute myocardial infarction was clearly shown to be of benefit. The suggestion I had commented on was that a single dose of aspirin taken at the onset of chest pain would be beneficial. However, extrapolation from the one situation to the other is probably not unreasonable. MRC Epidemiology Unit (South Wales), 4 Richmond Road, Cardiff CF2 3AS, UK
P. C. ELWOOD
Why more keloids on back than on front of
mortality
earlobe
SIR,-On the basis of the observed relation between cholesterol concentrations and mortality in the Whitehall study, Professor Rose and Mr Shipley (Feb 3, p 275) predict substantial decreases in
SIR,-Keloid scarring is a common,",2 potentially severe cosmetic problem associated with surgical or accidental trauma. Despite advances in knowledge of the biochemistry and histology of keloids,
deaths from all causes for men in whom cholesterol concentrations are lowered by intervention in which cholesterol lowering has been achieved. These intervention trials, like the predictions of Rose and Shipley, apply to high risk, middleaged men. They reflect over 100 000 man-years of observation in eight studies and have been remarkably consistent in their findings-non-fatal coronary heart disease events are diminished in the experimental groups, deaths from heart disease are less clearly affected, and overall mortality is
unchanged. Even if cholesterol lowering does reduce mortality and if these studies have failed to demonstrate this advantage because they are not of sufficient duration, the findings still cast doubt on Rose and Shipley’s predictions. The intervention studies have lasted for up to 11 years and show no favourable mortality trends for the treated group.
Why the intervention studies have failed to demonstrate the effect mortality that would be predicted from cholesterol/mortality relations, such as those seen in the Whitehall study, remains debatable. Such studies are, nevertheless, most pertinent to predictions of the effects cholesterol lowering and need to be considered when such predictions are made. on
Medical Service, New York VA Medical Center, New York, NY 10010, USA
Early aspirin
NORTON SPRITZ
in
myocardial infarction
SiR,—Dr Elwood (Feb 24, p 486) suggests that there is insufficient evidence to justify the early use of aspirin in acute myocardial infarction (AMI) and he asks for a randomised controlled trial. The Second International Study of Infarct Survival (ISIS-2)1 was designed to evaluate the separate and combined effects of intravenous streptokinase and oral aspirin in patients presenting with suspected AMI. 4300 patients were treated with placebo infusion and tablets and 4295 patients with aspirin and placebo infusion. During the first 5 weeks there were 568/4300 (13-2%)
little is known of what will prevent keloid formation. Our knowledge has been greatly hindered by the fact that the only animal model available consists of athymic mice carrying transplanted human keloid cells. 3,4 Although results with this model clearly implicate abnormal fibroblasts in the maintenance of keloid tissue, they do not tell us much about the pathogenesis. I report a "natural experiment" that raises questions about the primary fibroblast-transforming event in keloids. In a predominantly Puerto Rican, Dominican, and AfroAmerican population in New York City, I have noted that earlobe keloids secondary to ear piercing occur more commonly on the back than on the front of the earlobe. I confirmed this impression by a brief review of surgical records. Fourteen consecutive patients had 19 keloids. Of 16 keloids in which the position was specified, only 1 was anterior. Assuming random placement, this should occur less than 1 % of the time. If one thinks of the two sides of the earlobe as matched-pair wound sites this observation is puzzling. Clearly host factors such as genetic make-up and age are identical. There is no tension or motion of the skin at either site. Presumably the frequency of infection is much the same since the wound sites are close and there is little, if any, barrier between them. What local factor induces the posterior keloid? Alternatively, what factor allows anterior lobe wounding without scar formation in patients with a keloid diathesis proven by the keloid on the posterior aspect? One explanation for the observation is that there is a difference in biochemical milieu between the anterior and posterior earlobe, resulting from peculiarities of the structure or ultrastructure of the organ. For obvious reasons the anatomy of the earlobe has not been explored in great detail; however, such a study might prove worthwhile. Another possibility is that preferential exposure to sun, soap, make-up, or other environmental factor protects the anterior aspect. A third possibility is that the mechanism of trauma is the differentiating factor. The wounds from earlobe piercing are produced, in the USA, by driving a sharp gold-plated hollow peg in an anterior to posterior direction with a mechanical punch. The peg is then held in place with a posterior fastener. Such a mechanism implies that the anterior wound occurs in the superficial to deep direction whereas the reverse is true for the posterior wound. We could speculate that a factor from the deep dermis must be brought
2 patients subsequently died after of severe refractory heart failure in 1 and pulmonary embolism in the other. Our patients had resistant oedema from severe congestive cardiac failure. All responded to the addition of bendrofluazide therapy by diuresis and resolution of the oedema. Unlike Kiyingi et al, we did not start with a low dose of thiazide-like diuretic but chose 10 mg of bendrofluazide in 9 and 5 mg in 1. This was not associated with profound or dangerous electrolyte disturbances. It is important to avoid overdiuresis in such patients since this causes a fall in cardiac output with subsequent prerenal failure. Treatment should be monitored by daily measurements of weight and serum creatinine, urea, and electrolytes. Metolazone is more than fifteen times more expensive than bendrofluazide, and our data suggest that it offers little advantage.
bendrofluazide therapy. recurrence
Cardiology Department, Royal Hallamshire Hospital,
KEVIN S. CHANNER MICHAEL RICHARDSON
Sheffield S10 2JF, UK
ROB CROOK
Cardiology Department, Bristol Royal Infirmary
JOHN V. JONES
1. Gunstone
RF, Wing AJ, Shani HGP, Njemo D, Sabuka EMW. Clinical experience with metolazone in 52 African patients: synergy with furosemide. Postgrad Med J 1971; 47: 789-93.
Effects of coronary risk reduction
on
vascular deaths in the placebo group and 461/4295 (10-7%) in the aspirin group. The reduction in mortality was greatest in patients treated within 4 h of symptom onset. The early use of aspirin in AMI is thus of demonstrated value and further randomised placebo-controlled trial seems unnecessary. Cardiac Department, London Chest Hospital, London E2 9JX, UK
STEPHEN J. D. BRECKER
1. ISIS-2 Collaborative
Group. Randomised trial of intravenous streptokinase, oral neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; ii: 349-60. aspirin, both,
or
B*This letter has been shown follows.-ED. L.
to
Dr
Elwood, whose reply
SIR,-In ISIS-2 the use of aspirin in hospital patients with acute myocardial infarction was clearly shown to be of benefit. The suggestion I had commented on was that a single dose of aspirin taken at the onset of chest pain would be beneficial. However, extrapolation from the one situation to the other is probably not unreasonable. MRC Epidemiology Unit (South Wales), 4 Richmond Road, Cardiff CF2 3AS, UK
P. C. ELWOOD
Why more keloids on back than on front of
mortality
earlobe
SIR,-On the basis of the observed relation between cholesterol concentrations and mortality in the Whitehall study, Professor Rose and Mr Shipley (Feb 3, p 275) predict substantial decreases in
SIR,-Keloid scarring is a common,",2 potentially severe cosmetic problem associated with surgical or accidental trauma. Despite advances in knowledge of the biochemistry and histology of keloids,
deaths from all causes for men in whom cholesterol concentrations are lowered by intervention in which cholesterol lowering has been achieved. These intervention trials, like the predictions of Rose and Shipley, apply to high risk, middleaged men. They reflect over 100 000 man-years of observation in eight studies and have been remarkably consistent in their findings-non-fatal coronary heart disease events are diminished in the experimental groups, deaths from heart disease are less clearly affected, and overall mortality is
unchanged. Even if cholesterol lowering does reduce mortality and if these studies have failed to demonstrate this advantage because they are not of sufficient duration, the findings still cast doubt on Rose and Shipley’s predictions. The intervention studies have lasted for up to 11 years and show no favourable mortality trends for the treated group.
Why the intervention studies have failed to demonstrate the effect mortality that would be predicted from cholesterol/mortality relations, such as those seen in the Whitehall study, remains debatable. Such studies are, nevertheless, most pertinent to predictions of the effects cholesterol lowering and need to be considered when such predictions are made. on
Medical Service, New York VA Medical Center, New York, NY 10010, USA
Early aspirin
NORTON SPRITZ
in
myocardial infarction
SiR,—Dr Elwood (Feb 24, p 486) suggests that there is insufficient evidence to justify the early use of aspirin in acute myocardial infarction (AMI) and he asks for a randomised controlled trial. The Second International Study of Infarct Survival (ISIS-2)1 was designed to evaluate the separate and combined effects of intravenous streptokinase and oral aspirin in patients presenting with suspected AMI. 4300 patients were treated with placebo infusion and tablets and 4295 patients with aspirin and placebo infusion. During the first 5 weeks there were 568/4300 (13-2%)
little is known of what will prevent keloid formation. Our knowledge has been greatly hindered by the fact that the only animal model available consists of athymic mice carrying transplanted human keloid cells. 3,4 Although results with this model clearly implicate abnormal fibroblasts in the maintenance of keloid tissue, they do not tell us much about the pathogenesis. I report a "natural experiment" that raises questions about the primary fibroblast-transforming event in keloids. In a predominantly Puerto Rican, Dominican, and AfroAmerican population in New York City, I have noted that earlobe keloids secondary to ear piercing occur more commonly on the back than on the front of the earlobe. I confirmed this impression by a brief review of surgical records. Fourteen consecutive patients had 19 keloids. Of 16 keloids in which the position was specified, only 1 was anterior. Assuming random placement, this should occur less than 1 % of the time. If one thinks of the two sides of the earlobe as matched-pair wound sites this observation is puzzling. Clearly host factors such as genetic make-up and age are identical. There is no tension or motion of the skin at either site. Presumably the frequency of infection is much the same since the wound sites are close and there is little, if any, barrier between them. What local factor induces the posterior keloid? Alternatively, what factor allows anterior lobe wounding without scar formation in patients with a keloid diathesis proven by the keloid on the posterior aspect? One explanation for the observation is that there is a difference in biochemical milieu between the anterior and posterior earlobe, resulting from peculiarities of the structure or ultrastructure of the organ. For obvious reasons the anatomy of the earlobe has not been explored in great detail; however, such a study might prove worthwhile. Another possibility is that preferential exposure to sun, soap, make-up, or other environmental factor protects the anterior aspect. A third possibility is that the mechanism of trauma is the differentiating factor. The wounds from earlobe piercing are produced, in the USA, by driving a sharp gold-plated hollow peg in an anterior to posterior direction with a mechanical punch. The peg is then held in place with a posterior fastener. Such a mechanism implies that the anterior wound occurs in the superficial to deep direction whereas the reverse is true for the posterior wound. We could speculate that a factor from the deep dermis must be brought
