Biomed & Pharmacorher (1993) 47, 353-355 0 Elsevier, Paris

353

Notes

Cardiovascular disease in young men.

The risk of cardiovascular disease associated with serum cholesterol measured in middle-aged persons has been clearly established. The risk of clinically evident cardiovascular disease in midlife, associated with serum cholesterol levels assessed at younger ages, however, has not been determined.

A prospective study of 1017 young men (mean age, 22 years) followed for 27-42 years was used to charac- terize the risk of cardiovascular disease and total mor- tality associated with serum cholesterol levels. Mean serum cholesterol at entry, 192 mgldl (5.0 mg/dl), was well within the desirable range.

Over a median follow-up of 30.5 years, I25 cardio- vascular disease events, 97 of which were due to coro- nary heart disease, were observed. Serum cholesterol level was strongly associated with the incidence of coro- nary heart disease and cardiovascular disease, as well as total and cardiovascular disease mortality. Risks were similar whether coronary disease events occurred before or after 50. Even after taking into account age, body mass index, physical activity, coffee intake, and change in cigarette smoking status and the incidence of diabetes and hypertension over follow-up, the men in the highest quartile of serum cholesterol (2 209 mgldl) had an in- creased risk of cardiovascular disease (Relative Risk [RR], 95% CI: 3.56, I .78-7.1 I), coronary heart disease (RR 5.26, 2.21-12.53). and cardiovascular mortality (RR 9.63, I .20-77.15) compared to men in the lowest quartile (5 172 mgldl). Serum cholesterol was also sig- nificantly associated with an increased risk of total mor- tality before age 50.

These findings indicate a strong association of serum cholesterol, measured in young men, with disease in midlife.

MJ Klag (1) The Johns Hopkins University

School of Medicine, Baltimore, MD 21205. USA

Interleukin-8 and adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a catastrophic form of lung injury which occurs in some patients, often after a “latent period” of 2-3 days, fol- lowing conditions such as sepsis, multiple trauma and pancreatitis amongst many other conditions. It has a mortality of more than 50% and is responsible for a significant drain on intensive care unit resources. We were interested to examine the inflammatory events

very early in the latent period of patients at risk for ARDS in the hope of identifying key mechanistic events and improving the prognostic criteria. We examined pe- ripheral blood and bronchoalveolar lavage fluid from well-defined subgroups of patients at risk for ARDS. Most of the lavages were obtained within 2 h of the initiating insult. We found that the levels of interleukin- 8 in blood did not correlate with the subsequent development of ARDS, however there was a strong cor- relation between levels of interleukin-8 in the bronchoalve- alar lavage fluid and the subsequent development of ARDS. These data suggest that sampling the target organ in the at-risk period may be particularly valuable in predicting the likelihood of ARDS and, since inter- leukin-8 is an extremely powerful neutrophil chemoat- tractant and activator, these data support a role for neutrophil granulocytes in the very early pathogenetic stages of ARDS.

C Haslett (2) University of Edinburgh,

Edinburgh EHIO 5 SB, UK

Cigarette smoking and radiation.

This study investigated the influence of cigarette smoking during radiation therapy on the toxicity and efficacy of treatment in patients with locally advanced head and neck cancer. Patients were entered into a randomized trial of infusional 5-fluorburacil or placebo during the 1st and 3rd weeks of 6 I12 weeks of radiation. Infor-

mation on smoking and toxicity were obtained weekly for IO weeks from the beginning of treatment. Response to radiation was evaluated after I3 weeks of completion and all patients were followed until death.

There was no effect of smoking on weekly toxicity scores. There was a significant difference in the res- ponse to radiation between the patients smoking (45%) and not smoking (74%) during radiation (P - 0.008). At two years, 39% of patients in the smoking group were alive compared with 66% in the non-smoking group (P = 0.005). Factors hypothesized to be linked to sur- vival were examined, such as toxicity, comorbid con- ditions and unbalanced distribution of other prognostic factors, but these did not account for the survival differ- ence. Smoking during radiation therapy emerged as the only significant variable independently associated with survival.

The study suggests that smoking during treatment may contribute to reduced efficacy of radiation therapy in patients with locally advanced head and neck cancer.

(I) N Engl J Med (1993) 328, 313 (2) Lancer (1993) 341, 643

354

A dose-gradient effect of the amount of smoking during radiation is being investigated in a follow-up study.

G Browman (1) McMaster University,

Hamilton, ON L8N 325, Canada

Diltiazem and prevention of coronary artery disease in transplanted hearts.

Cardiac transplant patients were randomly assigned to receive diltiazem 30-90 mg tid (n = 52) or no calcium channel blocker (n = 54) lo- I4 d after transplantation to assess the efficacy of diltiazem in preventing coronary artery disease post-transplantation which affects 50% of all patients by five years post-transplant. All patients were receiving cyclosporine, azathioprine, prednisone, and aspirin. Seventy-five patients completed I or 2 years of the study. Among patients who had three angio- grams, average coronary artery diameter decreased in the group not receiving diltiazem (P < 0.001 at I and 2 y), but changed very little in the group receiving dilti- azem (P < 0.001). New angiographic evidence of coro- nary artery disease developed in I4 patients not receiving diltiazem vs five who did receive the drug (P = 0.82); coronary stenoses of > 50% of the luminal diameter developed in seven and two patients, respec- tively. Death related to coronary artery disease or re- transplantation occurred in five patients not receiving diltiazem; no such deaths were noted in the diltiazem group. These findings suggest that diltiazem can prevent the intimal proliferation which occurs in response to im- mune injury as well as the lipid deposition. This obser- vation is consistent with the reports in non-transplant CAD that calcium channel blockers may prevent new atherosclerotic lesions, and therefore may have a pro- tective effect when used in patients for angina or hy- pertension.

JS Schroeder (2) Stanford University

School of Medicine, Stanford, CA 94305, USA

Side effects of cerebral angiography.

Cerebral arterial angiography is widely used to investi- gate cerebrovascular disease. A major problem with this technique is the incidence of neurological side-effects which include both focal symptoms such as stroke and more diffuse symptoms such as confusion. The patho- genesis of these side-effects is unclear; it has been sug- gested that air embolism may play a role.

Doppler ultrasound can be used to detect circulating air emboli. Air results in high intensity signals due to reflection of ultrasound at the air/blood interface. Re- cently, with the advent of transcranial Doppler ultra- sound (TCD) it has been possible to use this technique to monitor for air emboli in the cerebral circulation.

(1) N End/ J Med (1993) 328. 159 (2) N Engl J Med (1993) 328, 164

Using TCD, the middle cerebral arteries of seven patients were monitored during cerebral angiography. In all patients, signals consistent with air emboli were ob- served. These particularly occurred during injection of the non-ionic contrast medium. This phenomenon was studied further in a sheep model in which a major carotid branch was insonated transorbitally, while con- trast was injected into the proximal carotid artery. During all contrast injections, air embolic signals were observed. Allowing the contrast to stand prior to injec- tion, resulted in a marked reduction in air emboli; it is hypothesised that air is introduced when the viscous contrast medium is drawn up, and this diffuses out if the contrast is allowed to stand.

These results indicate that air is introduced during routine cerebral angiography. This may account for at least some of the neurological side-effects observed. Simple measures, such as allowing contrast to stand prior to injection, may allow the quantity of air em- bolism to be reduced.

HS Markus (3) St George’s Hospital

Medical School, London SW I7 ORE, UK

Leukaemia and eating disorders.

Eating disorders (anorexia nervosa and bulimia) are common diseases among young women in industrialized countries. These disorders often follow a chronic course. The authors observed three cases who developed leukaemia after a relatively long history of eating dis- orders. Case I (23 years-old) was diagnosed as having chronic myelocytic leukaemia after a history of con- siderable body weight fluctuation from the age of I6 and severe vomiting after the age of 20. She died of blastic crisis. Acute promyelocytic leukaemia (FAB classification M3 type) was diagnosed in case 2 (27 years-old) after a 5-year history of anorexia nervosa. Case 3 started dieting when she was I5 and lost 27 kg in two years. The habit of binging and vomiting then developed. At the age of 24, she was found to have acute myeloblastic leukaemia (FAB classification Ml type). Cases I and 2 are among 89 eating disorder patients who were referred to our clinic for research on eating disorders. Although the number of patients ob- served here is very small, the prevalence of leukaemia among eating disorder patients seems higher than that among the general population. We suggest that pro- tracted malnutrition, hypokalemia etc may affect general systems such as the immune system and make the patients vulnerable to the genesis of leukaemia rather than triggering a specific factor which may lead to one type of leukaemia.

A Nishizono-Maher (4) Keio University, Tokyo 160, Japan

(3) Lancer (1993) 341, 784 (4) BMJ (1993) 306. 830