Preventing heart disease: is treating the high risk sufficient?

Monte Carlo simulation was used to assess the effects of several intervention strategies on coronary heart disease mortality rates in a Finnish and a North American cohort. Lowering total serum cholesterol by 4%, smoking by 15%, and diastolic blood pressure by 3% for the whole cohort would be expected to reduce the incidence of non-fatal myocardial infarction by at least 13% and coronary heart disease deaths by at least 18%. Lowering serum cholesterol by 34%, diastolic blood pressure to 90 mmHg, and reducing smoking by 20% in the subset of the population with all three risk factors in the highest quartile would result in a 6-8% reduction in non-fatal myocardial infarction and a 2-9% reduction in deaths from coronary heart disease in these cohorts. These data demonstrate that in populations with a relatively high incidence of heart disease, treating the entire population will produce larger effects than focusing only on high-risk populations.     

Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Network analytic methods for epidemiological risk assessment

The authors measure the efficacy of three methods for predicting the time to infection for susceptible individuals in a population undergoing an HIV epidemic. The methods differ in whether they require detailed information of the contact network and whether they require knowledge of the initial source of infection. Efficacy is evaluated using simulations for 20 different contact patterns. Only the risk score that uses both kinds of information accounts for more than 15 per cent of individual variability. The efficacy of this score ranges from 10 per cent in very unstructured populations to 60 per cent for spatially localized contact networks. This improved performance may be explained by the larger fraction of the total variability not due to the disease dynamics. When all variables are dichotomized, the two poorer methods produce odds ratios between 1.4 and 2.3. The odds ratio for the risk score with full information ranges from 2.5 to 17. Risk assessment protocols and intervention programmes are encouraged to assess contact patterns and detect sources of infection.     

Pneumothorax and other lung diseases: effect of altered resolution and edge enhancement on diagnosis with digitized radiographs

Prior studies have shown that pneumothorax is one of the more difficult entities to diagnose with digitized radiography. This study was designed to test whether increasing resolution from 1.25 to 2.5 line pairs per millimeter (lp/mm) and image processing (edge enhancement from unsharp masking) would increase accuracy and confidence in the diagnosis of pneumothorax, as well as normal cases and other forms of lung disease. Conventional radiographs were digitized with use of a laser reader and then reformatted as film hard copy. Eleven observers read 35 cases reformatted in three different ways (1.25 lp/mm, 2.5 lp/mm, 1.25 lp/mm unsharp mask). The images with finer resolution (2.5 lp/mm) and unsharp mask images were superior to those with coarser resolution (1.25 lp/mm) for the diagnosis of pneumothorax. There was no difference in diagnostic accuracy for normal patients. For abnormalities other than pneumothorax, the unsharp mask images were significantly worse. Confidence in the diagnosis of pneumothorax and other abnormalities was highest with the finest resolution (2.5 lp/mm).     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Inhibition of 2-nitropropane-induced rat liver DNA and RNA damage by benzyl selenocyanate

We observed that pretreatment of male F344 rats with benzyl selenocyanate, a versatile organoselenium chemopreventive agent in several animal model systems, decreases the levels of DNA and RNA modifications produced in the liver by the hepatocarcinogen 2- nitropropane. To clarify the mechanisms involved, we pretreated male F344 rats with either benzyl selenocyanate, its sulfur analog benzyl thiocyanate, phenobarbital or cobalt protoporphyrin IX; the latter is a depletor of P450. We then determined (1) the ability of liver microsomes to denitrify 2-nitropropane, (2) effects on 2-nitropropane- induced liver DNA and RNA modifications and (3) amount of nitrate excreted in rat urine following administration of the carcinogen. Pretreatment with benzyl selenocyanate or phenobarbital increased the denitrification activity of liver microsomes by 217 and 765%, respectively, increased liver P4502B1 by 31- and 435-fold, respectively, decreased the levels of 2-nitropropane-induced modifications in liver DNA (29-70% and 17-30%, respectively) and RNA (67-85% and 30-50%, respectively), and increased the 24-h urinary excretion of nitrate by 157 and 209%, respectively. Pretreatment with benzyl thiocyanate had no significant effect on any of these parameters. Pretreatment with cobalt protoporphyrin IX decreased liver P4502B 1 by 87%, decreased the denitrification activity of liver microsomes by 76%, decreased the 24 h urinary excretion of nitrate by 88.5%, but increased the extent of 2-nitropropane-induced liver nucleic acid modifications by 17-67%. These results indicate that the metabolic sequence from 2-nitropropane to the reactive species causing DNA and RNA modifications does not involve the removal of the nitro group. Moreover, they suggest that benzyl selenocyanate inhibits 2-NP-induced liver nucleic acid modifications in part by increasing its detoxication through induction of denitrification, although it is evident that other mechanisms must also be involved.      

Using serum cholesterol to identify high risk and stimulate behavior change: will it work?

If the measurement of serum cholesterol is to be used to identify a sub-population at high risk of subsequent disease and to stimulate behavior change in this group to lower serum cholesterol, the test must be able to both discriminate and motivate the group. The ability of the test to motivate has been documented in a randomized trial. This paper therefore tests, in a cohort of United States men ages 40-59 at entry, the ability of serum cholesterol to discriminate between individuals who would and would not die from coronary heart disease. While risk of death increased with increasing serum cholesterol, the values for men who developed coronary heart disease overlapped the values of the men who did not develop the disease. Overall test accuracy declined from 92% correctly classified when 5% of the population was defined as "at high risk" to 55% when 50% of the population was defined as "at high risk". On a receiver operating curve, defining 5% of the men as "high risk" yielded a false positive rate of 5% and a true positive rate of 8%. Increasing the proportion of men defined as "at high risk" to 50% increased the true positive rate to 75% but also increased the false positive rate to over 50%. Monte Carlo simulation demonstrated that lowering mean serum cholesterol 0.78 mmol/l in the entire population would lower deaths from coronary heart disease by 28%. The same effect could be achieved by lowering the serum cholesterol of all people in the top 20% of the distribution to 4.66 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)