Search

OBJECTIVE Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. DESIGN The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. SETTING Three university hospitals and one private primary care facility. PATIENTS A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. INTERVENTION The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. MAIN OUTCOME MEASURE The use of arteriographic changes as a predictor of subsequent clinical coronary events. RESULTS Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). CONCLUSIONS Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality.

To the Editor: Dr Nicholls and colleagues found that treatment with statins was associated with regression of coronary atherosclerosis (assessed by intravascular ultrasonography) when low-density lipoprotein cholesterol (LDL-C) was substantially reduced and high-density lipoprotein cholesterol (HDL-C) was increased by more than 7.5%. The authors state that it remains to be determined whether these changes translate to improved clinical outcomes because the small increases in HDL-C observed during statin therapy have never been shown to correlate with clinical outcome. However, in a post hoc analysis of the secondary coronary heart disease prevention Greek Atorvastatin Coronary Heart Disease Evaluation (GREACE) Study, the composite end point of all vascular events was found to be partly determined by the extent of atorvastatin-induced HDL-C increase in the structured care group compared with usual care. This was in the setting of achieving an LDL-C level of 100 mg/dL (2.59 mmol/L) in 95% of patients in the structured care group (a 46% decrease in LDL-C from baseline values). After multiple regression analysis, the beneficial effect associated with HDL-C increase was independent of the LDL-C reduction (hazard ratio for each 4 mg/dL [0.10 mmol/L] increase in HDL-C, 0.85; 95% confidence interval, 0.76-0.94; P=.002). A relatively small increase in HDL-C (mean, 7%) observed during 3 years of statin treatment was associated with clinical event reduction, supporting the findings of Nicholls et al.

We found a recent article by Sramek et al 1 on the usefulness of patient interview in identifying bleeding disorders to be quite interesting. Using the patient's interview as a medical or laboratory test in terms of odds ratio can give us an important tool to help us decide when there is enough reduction in diagnostic uncertainty. In our laboratory we omit the bleeding time in the routine preoperative screen, as do many authors, 2-4 using instead the patient interview to identify which patients should undergo the bleeding time test. This approach is also in agreement with the conclusions of Sramek and colleagues, with two exceptions: very young people and children. In fact, the probability of bleeding disorders to develop is directly proportional to the age of the subjects. Some of the clinical events considered are very improbable or even impossible during childhood. Perhaps an age classification in some groups

Background: Do-not-resuscitate (DNR) orders are often inaccurately communicated between physicians and nurses or residents. Structured, procedure-specific DNR order forms have been suggested to improve communication, but no data exist to support this impression. Methods: The level of agreement between attending physicians and nurses or residents in their understanding of the DNR orders of critically ill patients was measured before and after instituting a structured DNR order form. Caregivers were asked (1) about the clinical events to which the DNR order applied, (2) whether the DNR order withheld all elements of cardiopulmonary resuscitation, and (3) whether other treatments were to be with-held. Results were reported as κ±SE. Results: Nurses (n=41) and residents (n=34) showed only fair to moderate agreement with attending physicians (n=53) for the 76 evaluable patients before initiation of the DNR order form. After initiation of the structured DNR order form, nurses showed higher levels of agreement for the second (0.67±0.14) and third (0.69±0.13) components but not the first (0.39±0.15) component of the DNR order. Residents showed higher levels of agreement for the second (0.90±0.10) and third components (0.81±0.13) but not the first (0.57±0.17) component. Nurses compared with residents had lower levels of agreement with attending physicians for most aspects of the DNR order. Conclusion: A structured DNR order form improves agreement in understanding of some but not all components of the DNR order. (Arch Intern Med. 1996;156:793-797)

Objective. —To investigate the costs and effects of long-term oral anticoagulant treatment after myocardial infarction. Design. —Cost-effectiveness analysis, based on a randomized, double-blind, placebo-controlled trial. Setting. —Sixty Dutch hospitals. Patients. —A total of 3404 hospital survivors of acute myocardial infarction randomized within a median period of 4 days after discharge to either oral anticoagulant treatment or placebo. The mean follow-up was 37 months. Intervention. —Oral anticoagulant treatment aimed at a target international normalized ratio of 2.8 to 4.8. Main Outcome Measurements. —Costs of hospital stay during readmissions, costs related to major cardiologic interventions, and costs of oral anticoagulant treatment. Results. —The costs of oral anticoagulant treatment were estimated at 394 Dutch guilders (Dfl) per patient-year (Dfl1=US $0.58). Placebo patients stayed 18 830 days in the hospital compared with 15 083 days for anticoagulation patients. Average costs per patient of medical care during follow-up were estimated at Dfl 10784 for placebo patients and Dfl 9878 for anticoagulation patients. Conclusions. —Costs of long-term anticoagulant treatment are outweighed by the costs of prevented clinical events. ( JAMA . 1995;273:925-928)

The letters from Reisfeld and Wilson and Lockman both favor the hypothesis that the linear or dermatomal pattern of lichenoid chronic graft-vs-host disease (GVHD) corresponds to Blaschko's lines rather than a relationship to herpes zoster virus infection as proposed in our article.1 While both of these hypotheses remain unproven, there are several points that favor the relationship to herpes zoster virus infection. The basic argument Dr Reisfeld is raising is that mosaicism within the skin causes differences in minor antigen expression that are recognized by donor lymphocytes resulting in GVHD in a linear distribution. If this were the only explanation, several clinical events would have been expected: (1) acute GVHD should have at least started in the same linear distribution before becoming confluent, and (2) chronic GVHD should have at least started in the same linear distribution. Neither of the above was true for the patients reported, 1 including the

HYPERTENSION CONTINUES to be one of the most common conditions treated by physicians. Ongoing research has better defined the mechanisms and clinical characteristics of this condition and enlarged the scope of therapeutic options. It is increasingly clear that high blood pressure, although an independent risk factor for adverse clinical events, frequently exists as part of a syndrome of cardiovascular, neuroendocrine, and metabolic abnormalities. 1-3 Prognosis and appropriate treatment for the individual patient must, therefore, be based on considerations that go beyond blood pressure itself. The Joint National Committee (JNC) on the Detection, Evaluation, and Treatment of High Blood Pressure has given opinions on the management of hypertension at 4-year intervals for almost 20 years. The recently published fifth report of the JNC (JNC V) concerning high blood pressure, presented as two separate and lengthy articles, 4,5 offers detailed commentary on newer developments in the diagnosis and managementof hypertension, especially as

To the Editor. —I have often read "Correspondence" in which researchers bristle when other researchers fail to replicate prior work or draw different conclusions about the same clinical events, and honest men do disagree. I have not with-stood the temptation to view such correspondence as defensive, petty, whiny, and self-serving. I apologize for my own hypocrisies. The report by Kalenak et al 1 in the May 1991 issue of theArchivespurportedly demonstrating no association between anterior ischemic optic neuropathy (AION) and elevated intraocular pressure (IOP) troubles me for several reasons. I believe such a conclusion is not warranted on the basis of the data reported. I am troubled by the criteria Kalenak et al used for diagnosing AION; although a combination of criteria was used, it is not clear if all patients fulfilled all criteria; the implication is that not all patients fulfilled all criteria. I am troubled with

In Reply.— The Cholesterol Lowering Atherosclerosis Study (CLAS) was designed to test lipid-lowering therapy by studying changes in the angiographic anatomy of the coronary arteries and was not designed to test effects on clinical events. It enrolled 188 subjects, an adequate number for a coronary angiographic end point but an insufficient number to evaluate treatment effects on clinical coronary events. The CLAS showed statistically strong and consistent treatment benefit to coronary anatomy after 2 years of treatment 1 and again after 4 years of treatment, as reported in our study. Other studies designed to test lipid-lowering effects on clinical coronary event rates have shown clear evidence for benefit. The Lipid Research Clinics Primary Prevention Trial (3806 randomized subjects) 2 and the Helsinki Heart Study (4801 randomized subjects) 3 both demonstrated a statistically significant reduction in clinical coronary events with lipid-lowering therapy. The Coronary Drug Project (2789 placebo, 1119 niacin-treated subjects)

The clinical events surrounding cerebral embolism have received scant attention from neurologists. Although various aspects of experimentally produced cerebral embolism have been pursued, most studies dealing with the clinical event in man have been written by cardiologists primarily interested in the origin of the embolus itself or by pathologists predominantly concerned with its end state. This situation has developed no doubt because the pathophysiology of the disorder appears obvious; i.e., a solid fragment is broken away, usually from a thrombus in the left auricle of the heart, passes into a cerebral vessel, obstructs blood flow through that vessel, and results in infarction of the region distal to the point of occlusion. The difficulty which neuropathologists have encountered in trying to explain why some of these infarcts are pale and some hemorrhagic reveals that the matter is not always so clear-cut. A more detailed clinical study of these patients reveals, likewise

Three-channel cassette electroencephalographic (EEG) recording for up to 24 hours was obtained from 37 neonates with clinically diagnosed or suspected seizures but no seizure activity on routine EEG. EEG seizures were recorded in seven patients, five of whom had experienced clinical seizures in the 24 hours prior to cassette EEG recording. EEG seizures were detected in only one of nine neonates with recurring clinical episodes believed unlikely to be seizures and in only one of 18 without recent clinical events. Cassette EEG can enhance the detection and differentiation of seizures in neonates with persistent clinical episodes but is of low yield otherwise.

In the June 13 issue ofThe Journal, M. Robert-Guroff et al1reported antibody prevalences of 9% for human T-cell lymphotropic virus (HTLV) type I, 18% for HTLV-II, and 41% for HTLV-III in drug abusers in New York. Of concern is the known association of HTLV-I and adult T-cell leukemia (ATL), raising the possibility that this report of serological findings may be the forewarning of serious clinical events yet to come. Although HTLV-I is endemic in some areas of Japan, the Caribbean, and Africa, both HTLV-I infection and ATL are rare in the United States.2,3In Kyushu, an endemic area in Japan, a recent study revealed that 100% of 18 patients with ATL had HTLV-I antibodies, compared with 16% HTLV-I seropositivity in 604 apparently healthy adults.2Other studies of healthy populations in Japan indicate that high rates of HTLV-I infection are restricted geographically, with prevalences ranging from

It has been clearly demonstrated that temperature increases of only a few degrees greater than normal induce profound cellular changes and even cell death. The first beneficial effects of these phenomena were recorded more than a century ago by Busch, 1 who observed the disappearance of a sarcoma after high fever in a patient with erysipelas. In 1893, Coley 2 noted the same clinical event and then deliberately induced erysipelas as a form of treatment for patients with malignancies. He described disease-free survival from one to seven years in ten of 34 patients with inoperable carcinomas or sarcomas, but was undecided whether to attribute these remissions to the fever induced or to some effect of bacterial toxins. Later, the use of local heat and of pyrogenic bacterial toxins was also evaluated in patients with tumors. Occasional successes then prompted the induction of fever therapy for infectious diseases (syphilis and gonorrhea)

To the Editor.— Intravenous anesthetic agents and muscle paralyzing drugs can occasionally cause anaphylaxis or anaphylactoid reactions, and we were interested to note that Keenan and Boyan 1 observed no such cases in their large study of cardiac arrest due to anesthesia. In order to provide information on the frequency of allergic events occurring in the operating room, we examined data collected from 1977 until 1981 by the Boston Collaborative Drug Surveillance Program encompassing 4,395 administrations of general anesthesia in five surgical units in the United States, New Zealand, and Scotland. 2 Among other observations, all clinical events occurring in the operating room were recorded and described. We examined data on all patients recorded as having suffered anaphylaxis, rash, or bronchospasm in the operating room after the induction of anesthesia. A total of 20 patients suffered at least one of these events of which only one was thought to be

Some patients with renal disease accrue 6,000 to 8,000 individual data items relating to symptoms, signs, laboratory information, and treatment in one year. To deal with the problem of handling so many data items, the following steps were taken: (1) a dictionary of terms peculiar to nephrology was created; (2) manual time-oriented records for nephrology were constructed; and (3) an on-line data processing system, using a PDP-11/70 computer and remote teleprocessing terminal, was developed. On the terminal screen, up to 11 consecutive patient visits can be displayed horizontally, with 18 data items displayed vertically. Up to 30 of the most recent patient visits are easily accessible. For patient treatment, a special feature allows a rearrangement and instantaneous display of any combination of data, thus permitting review of essential feedback relationships between clinical events and treatment. ( Arch Intern Med 137:446-456, 1977)

Parenteral prophylactic cephalosporins used in surgery were compared in 17 published studies. Examination of these studies reveals little justification for preference of one cephalosporin over another. For gastrointestinal, obstetrical-gynecologic, or cardiac operations, newer cephalosporins did not result in substantial decreases in adverse postoperative clinical events (eg, wound infections, intra-abdominal and pelvic infections, and endocarditis) when compared with older cephalosporins. There is no evidence that second- or third-generation cephalosporins result in postoperative infection rates lower than with first-generation cephalosporins. ( JAMA 1984;252:3277-3279)

Toxic epidermal necrolysis is a dramatic, easily recognized clinical event in which sheets of the upper layer of the epidermis slide off the lower layers of the skin. This sign developed in a 70-year-old man in association with a rapidly fatal staphylococcal septicemia. Although recognized in children, this association has been reported only rarely in adults. Inoculation of the isolated bacterium into newborn mice produced characteristic wrinkling. Development of this epidermolysis requires immediate antibiotic therapy. (JAMA229:425-427, 1974)

THE importance of nitrous fumes as a cause of pulmonary tissue damage gained universal recognition with the demonstration that these were the mysterious toxic gases evolved in silos during the first week after ensilage. 1,2 Two types of pulmonary chemical injuries have been described: (1) pulmonary edema may occur within 24 hours of a prolonged or concentrated exposure; (2) a more subtle bronchiolar injury may cause life-threatening bronchiolar obstruction during the repair phase, one to four weeks after a brief encounter with the toxic gases. 3 There are simple and accurate descriptions of man's experience with the fumes of nitric acid, but there is none more vivid than the first recording 175 years ago. To give this classical description wider reading and its due historical prominence, an edited translation of the story of a man and his dog is presented here. 4 The clinical events are discussed in terms of

The clinical events and findings by light and electron microscopy are presented of a patient with malignant melanoma, primary in the skin, widely metastasized, and terminally associated with diffuse melanosis and melanuria. A marked increase in pigment was found in epidermis and dermis. The most likely explanation for the dermal melanosis is that it represents pigment produced by distant malignant melanoma cells. This pigment is secondarily deposited in the skin via the circulation. Hyperpigmentation of the epidermis in this patient probably arose from a different mechanism such as by increased melanogenesis by epidermal melanocytes or by decreased epidermopoiesis.

In the preceding volumes of this exhaustive monograph the author presented disease-dysfunction-disintegration-organic alteration (pathologic change) as a problem from which the factor of environment is inseparable; in particular, that of meteorologic change. If this is decisive or at least of influence in the precipitation of the actual clinical event, it must be even more significant for the underlying fault, the pathogenesis. It is to be regretted that fundamental work in the relation of constitution and meteorologic environment to surgical conditions has been practically ignored in the English and the American literature. In a chapter devoted to ophthalmologic episodes one learns that the attention of the oculist has naturally been centered wholly on the eye and that the background of constitution, of phase fluctuations in the general organic status and in its adaptation to the environment, has been disregarded. A study of cases of intraocular hemorrhage, optic neuritis

The primary tuberculous complex of the skin, although rare in dermatologic experience, is a well established clinical entity. The literature on this subject has been adequately reviewed, by Stokes1in 1925, by Michelson2in 1935 and by O'Leary and Harrison3in 1941. As these papers are so complete, no attempt will be made to present the subject in detail. The purpose of this paper is to report the case of an elderly woman who presented the clinical picture of the primary tuberculous complex of the skin. While the literature already contains a sufficient number of cases which satisfactorily describe the clinical features of this type of inoculation tuberculosis, the case reported here is of such an unusual character as to be worthy of discussion. The primary tuberculous complex of the skin as summarized by Bruusgaard4consists of a series of clinical events which follow the

Many ill-defined but significant factors relating to the anesthetized patient enter into therapeutic and diagnostic decisions governing his care. These factors have not yet been reduced to structured statements or formulas to provide answers which the clinician can accept with confidence. However, a physiological communication network consisting of an automatic transducer system and a digital computer is now being used to accumulate and present accurate, timely physiological data to the surgical team for immediate use in clinical decision-making. These data are also stored in a format which allows easy retrieval for later study of clinical cause and effect. Modern concepts of mathematics, statistics, and technology are being used to reduce these data to computer-solvable, structured statements or models which relate clinical events to physiological variations. These models may be used for making decisions in the clinic and as tools for testing biological theories.

A review of the clinical course and complications of Hodgkin's disease stresses the recently acquired knowledge on its modes of spread with particular emphasis on lymphatic and vascular dissemination. The available data supporting these pathways of progression are correlated with the clinical events in the course of this disease. The manifestations related to the tumor involvement of different organs as well as those representing the remote effects of this malignant process on different systems are considered. The nonspecific clinical manifestations, as well as hematologic, metabolic, and endocrine-like complications are surveyed. Finally, the interrelationship of Hodgkin's disease with various conditions characterized by immunologic aberrations is discussed.

To the Editor:— With regard to your editorial "Immunity in Syphilis" (The Journal, August 23, p. 1485), may I call attention to my paper "Semantic Confusion and Resolution in the Concepts of Cure in Syphilis and of Reinfection With Syphilis," which was published in the American Journal of Syphilis, Gonorrhea and Venereal Diseases ( 30 :344 [July] 1946). This article covers much the same ground as your editorial and appeared in point of time between the paper of Moore and that of Urbach and Beerman, which you cite. My interpretations of the clinical events of syphilis and of allergic and immunologic theory as related to the disease are somewhat different from those of the writers cited. It may be of interest to readers to examine this version together with the references given.

In this study of 3,000 males the statistical association of coronary artherosclerotic heart disease (CAHD) and smoking habits was most striking under the age of 51. In this group 21 (11.7%) of 179 heavy cigarette smokers had CAHD, whereas 100 (6.5%) of 1,521 other individuals had CAHD. The ratio of myocardial infarcts to isolated angina pectoris was 1.3:1 in heavy smokers, and 0.5:1 in other categories. Heavy cigarette smoking was also associated with higher serum cholesterol levels. It was suggested not so much as a factor in atherogenesis, but as a factor in precipitating acute clinical events in individuals with advanced CAHD. Cigar, pipe, and light cigarette smoking did not appear to be related to the problem.