The New England Journal of Medicine

,

doi: 10.1056/NEJM199105023241801pmid: 2014035

AbstractBackground.Abnormalities of cellular calcium homeostasis have been implicated in the pathophysiology of postischemic encephalopathy. Calcium-entry—blocking drugs inhibit the influx of calcium into cells and have been shown to mitigate postischemic encephalopathy in animal models.Methods.Five hundred twenty patients with cardiac arrest who remained comatose after the restoration of spontaneous circulation were randomly assigned to receive three doses of lidoflazine, an experimental calcium-entry blocker, or a placebo and were followed for six months. Four patients were lost to follow-up. Treated patients received an intravenous loading dose (1 mg per kilogram of body weight) of lidoflazine and two subsequent doses (0.25 mg per kilogram) 8 and 16 hours after resuscitation. The investigators were blinded to treatment assignment.Results.There was no statistically significant difference between the lidoflazine group (n = 259) and the placebo group (n = 257) in the proportion of patients who died during the six-month follow-up (82 vs. 83 percent), who survived with good cerebral recovery (15 vs. 13 percent), or who survived with severe neurologic deficit (1.2 vs. 1.9 percent). Analysis of the best level of recovery achieved at any time during follow-up also did not show a difference between the treatment groups: 24 percent of those given lidoflazine and 23 percent of those given placebo recovered good cerebral function (normal or only moderately disabled cerebral performance) at some time.Conclusions.The administration of lidoflazine after cardiac arrest was not found to be beneficial. Our data do not support the routine use of this calcium-entry—blocking drug in comatose survivors of cardiac arrest. (N Engl J Med 1991;324:1225–31.)

Okano, Yoshiyuki; Eisensmith, Randy C.; Güttler, Flemming; Lichter-Konecki, Uta; Konecki, David S.; Trefz, Friedrich K.; Dasovich, Mary; Wang, Tao; Henriksen, Karen; Lou, Hans; Woo, Savio L.C.

doi: 10.1056/NEJM199105023241802

Lee, Thomas H.; Juarez, Gregory; Cook, E. Francis; Weisberg, Monica C.; Rouan, Gregory W.; Brand, Donald A.; Goldman, Lee

doi: 10.1056/NEJM199105023241803pmid: 2014037

AbstractBackground.Although previous investigations have suggested that 24 hours is required to exclude acute myocardial infarction in patients who are admitted to a coronary care unit for the evaluation of acute chest pain, we hypothesized that a 12-hour period might be adequate for patients with a low probability of infarction at the time of admission.Methods.Using a Bayesian model, we developed a strategy to identify candidates for a shorter period of observation from an analysis of a derivation set of 976 patients with acute chest pain who were admitted to three teaching and four community hospitals. In the derivation set, patients whose clinical characteristics in the emergency room predicted a low (≤7 percent) probability of myocardial infarction had only a 0.4 percent risk of infarction if they had neither abnormal levels of cardiac enzymes nor recurrent ischemic pain during the first 12 hours of hospitalization. In an independent testing set of 2684 patients from the seven hospitals, 957 admitted patients (36 percent) were classified as candidates for this 12-hour period of observation according to a previously published multivariate algorithm. Few of these patients were actually transferred from a monitored setting at 12 hours.Results.Of the 771 candidates for a 12-hour period of observation who did not have enzyme abnormalities or recurrent pain during the first 12 hours, 4 (0.5 percent) were subsequently found to have acute myocardial infarction, and only 3 (0.4 percent) died after primary cardiac arrests, all of which occurred three to five days after admission. Rates of other major cardiovascular complications were low in the patients who might have been transferred from the coronary care unit after 12 hours with this strategy. In patients with a higher initial risk of infarction, the standard strategy of 24-hour observation identified all but 11 of 739 acute myocardial infarctions (1 percent).Conclusions.Emergency room clinical data can be used to identify a large subgroup of patients for whom a 12-hour period of observation is normally sufficient to exclude acute myocardial infarction. Patient-specific evaluation and treatment can then proceed without the restrictions imposed by "rule-out" protocols for myocardial infarction. (N Engl J Med 1991; 324:1239–46.)

Brown, Zane A.; Benedetti, Jacqueline; Ashley, Rhoda; Burchett, Sandra; Selke, Stacy; Berry, Sylvia; Vontver, Louis A.; Corey, Lawrence

doi: 10.1056/NEJM199105023241804pmid: 1849612

AbstractBackground and Methods.To define the risk factors associated with neonatal acquisition of herpes simplex virus (HSV) infection, we prospectively obtained HSV cultures from the cervix and external genitalia of 15,923 pregnant women in early labor who were without symptoms or signs of genital HSV infection. Follow-up of the women with positive cultures for HSV and their HSV-exposed infants included serologic tests and serial cultures for HSV.Results.HSV was isolated from 56 of the women (0.35 percent), 18 of whom (35 percent) had serologic evidence of a recently acquired, subclinical first episode of genital HSV infection, and 34 of whom (65 percent) had reactivation of HSV. Neonatal HSV developed in 6 of 18 infants (33 percent) born to the women with a first episode of genital HSV, and in 1 of 34 infants (3 percent) born to the women with reactivation of HSV (P<0.01); neonatal HSV also occurred in three of the infants born to the 15,867 women with negative cultures. Neonatal HSV-2 occurred in 1 of 4 infants born to mothers seronegative at delivery for both HSV-1 and HSV-2, in 4 of 12 infants exposed to HSV-2 whose mothers had only HSV-1 antibodies at delivery, and in none of the infants born to 31 women who were HSV-2-seropositive. An increased risk of neonatal HSV was associated with exposure to viral shedding from the cervix and the use of fetal-scalp electrodes.Conclusions.Of the asymptomatic women who shed HSV in early labor, about a third have recently acquired genital HSV, and their infants are 10 times more likely to have neonatal HSV than those of women with asymptomatic reactivation of HSV. The presence of maternal antibodies specific to HSV-2 but not HSV-1 appears to reduce the neonatal transmission of HSV-2. Further studies are necessary to determine whether screening and prophylactic treatment are warranted for infants of HSV-2-seronegative mothers who shed HSV-1 or HSV-2 in early labor. (N Engl J Med 1991; 324:1247–52.)

Woolhandler, Steffie; Himmelstein, David U.

doi: 10.1056/NEJM199105023241805pmid: 1901623

AbstractBackground and Methods.In 1983 the proportion of health care expenditures consumed by administration in the United States was 60 percent higher than in Canada and 97 percent higher than in Britain. To assess the effects of recent health policy initiatives on the administrative efficiency of health care, we examined four components of administrative costs in the United States and Canada for 1987: insurance overhead, hospital administration, nursing home administration, and physicians' billing and overhead expenses. Most data were provided by the two nations' federal health and statistics agencies, supplemented by state and provincial data and published sources. Because data on physicians' billing costs were limited, we estimated a range for these costs by two methods that rely on different sources of data. All figures are reported in 1987 U.S. dollars.Results.In 1987 health care administration cost between $96.8 billion and $120.4 billion in the United States, amounting to 19.3 to 24.1 percent of total spending on health care, or $400 to $497 per capita. In Canada, between 8.4 and 11.1 percent of health care spending ($117 to $156 per capita) was devoted to administration. Administrative costs in the United States increased 37 percent in real dollars between 1983 and 1987, whereas in Canada they declined. The proportion of health care spending consumed by administration is now at least 117 percent higher in the United States than in Canada and accounts for about half the total difference in health care spending between the two nations. If health care administration in the United States had been as efficient as in Canada, $69.0 billion to $83.2 billion would have been saved in 1987.Conclusions.The administrative structure of the U.S. health care system is increasingly inefficient as compared with that of Canada's national health program. Recent health policies with the avowed goal of improving the efficiency of care have imposed substantial new bureaucratic costs and burdens. (N Engl J Med 1991; 324:1253–8.)

Trunkey, Donald

doi: 10.1056/NEJM199105023241806pmid: 2014038

PATIENTS with life-threatening injuries make up approximately 10 to 15 percent of all patients hospitalized because of injuries.1 Some authors have defined patients with extensive trauma as those with injury severity scores (ISSs) higher than 15 (for an explanation of the ISS see the Appendix).2 3 4 That is an acceptable definition for purposes of triage, but in this discussion I shall define extensive trauma as indicated by an ISS above 25. Most patients in this category have multisystem trauma. Deforming and destructive injuries can be obvious, but the surgeon or physician who initially treats the patient must promptly conduct a systematic . . .

Lubs, Marie-Louise E.; Bauer, Mislen S.; Formas, Maria E.; Djokic, Borivoje

doi: 10.1056/NEJM199105023241807pmid: 1901624

Lisch nodules are melanocytic hamartomas that appear as well-defined, dome-shaped elevations projecting from the surface of the iris and are clear to yellow or brown. Multiple Lisch nodules appear to be found only in patients with peripheral neurofibromatosis (neurofibromatosis type 1, or von Recklinghausen's disease), an autosomal disorder with a prevalence of 1 in 3500.1,2 Although these nodules were first described by Waardenburg in 1918,3 the association between them and neurofibromatosis 1 was not fully appreciated until the report by Lisch in 1937,4 after whom they were then named. Lisch nodules are the most common clinical feature of neurofibromatosis 1 . . .

Smith, David B.; Pettit, Carolyn K.

doi: 10.1056/NEJM199105023241808pmid: 1901625

Presentation of Case A 70-year-old man with treated lymphoma was admitted to the hospital because of fever and weakness. The patient was well until 16 years earlier, when a periumbilical mass developed. Medical evaluation at another hospital, including a laparotomy, showed a diffuse, well-differentiated lymphocytic lymphoma and a paraproteinemia. A modified program of cyclophosphamide, vincristine, and prednisone (CVP) was administered during the following two years. The patient was then well until three years before admission, when cervical and axillary lymphadenopathy was found. A computed tomographic (CT) scan of the abdomen revealed two low-attenuation abnormalities in the right hepatic lobe, believed . . .

Plum, Fred

doi: 10.1056/NEJM199105023241809pmid: 2014039

The report in this issue of the Journal on the large international study by the Brain Resuscitation Clinical Trial II Study Group1 describing the ineffectiveness of the calcium-channel blocker lidoflazine in reducing either mortality or brain damage after cardiac arrest deserves attention with respect to several points. The analysis reemphasizes that with good will, moderate financing, and much effort, the potential effectiveness of costly new drugs can be evaluated relatively promptly and, on the whole, definitively. The essential step is to catalyze large groups of physicians and statisticians with complementary talents to attack an important common problem. Such efforts have . . .

Scriver, Charles R.

doi: 10.1056/NEJM199105023241810pmid: 2014040

Phenylketonuria contributes to our acceptance of a model of disease that relates the manifestations (phenotypes) of a disease to an underlying process (pathogenesis) that has its origin in a cause (which may include a variant genotype). Our knowledge of phenylketonuria1,2 has evolved in the context of that model. A new point of departure is clearly marked by the study by Okano et al. in this issue of the Journal,3 which correlates several mutations in the gene for phenylalanine hydroxylase with their effects on the activity of the enzyme and the severity of the associated clinical disease. The study could . . .