Showing papers in "The New England Journal of Medicine in 1983"

Hemorrhagic colitis associated with a rare Escherichia coli serotype

Abstract: We investigated two outbreaks of an unusual gastrointestinal illness that affected at least 47 people in Oregon and Michigan in February through March and May through June 1982. The illness was characterized by severe crampy abdominal pain, initially watery diarrhea followed by grossly bloody diarrhea, and little or no fever. It was associated with eating at restaurants belonging to the same fast-food restaurant chain in Oregon (P less than 0.005) and Michigan (P = 0.0005) and with eating any of three sandwiches containing three ingredients in common (beef patty, rehydrated onions, and pickles). Stool cultures did not yield previously recognized pathogens. However, a rare Escherichia coli serotype, O157:H7, that was not invasive or toxigenic by standard tests was isolated from 9 of 12 stools collected within four days of onset of illness in both outbreaks combined, and from a beef patty from a suspected lot of meat in Michigan. The only known previous isolation of this serotype was from a sporadic case of hemorrhagic colitis in 1975. This report describes a clinically distinctive gastrointestinal illness associated with E. coli O157:H7, apparently transmitted by undercooked meat.

A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer.

Abstract: The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.

Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study.

Abstract: We conducted a multicenter, double-blind, placebo-controlled randomized trial of aspirin treatment (324 mg in buffered solution daily) for 12 weeks in 1266 men with unstable angina (625 taking aspirin and 641 placebo). The principal end points were death and acute myocardial infarction diagnosed by the presence of creatine kinase MB or pathologic Q-wave changes on electrocardiograms. The incidence of death or acute myocardial infarction was 51 per cent lower in the aspirin group than in the placebo group: 31 patients (5.0 per cent) as compared with 65 (10.1 per cent); P = 0.0005. Nonfatal acute myocardial infarction was 51 per cent lower in the aspirin group: 21 patients (3.4 per cent) as compared with 44 (6.9 per cent); P = 0.005. The reduction in mortality in the aspirin group was also 51 per cent--10 patients (1.6 per cent) as compared with 21 (3.3 per cent)--although it was not statistically significant; P = 0.054. There was no difference in gastrointestinal symptoms or evidence of blood loss between the treatment and control groups. Our data show that aspirin has a protective effect against acute myocardial infarction in men with unstable angina, and they suggest a similar effect on mortality.

Risk Stratification and Survival after Myocardial Infarction

Abstract: We assessed the role of physiologic measurements of heart function in predicting mortality after myocardial infarction. Most of the 866 patients enrolled in our multicenter study underwent 24-hour Holter monitoring and determination of the resting radionuclide ventricular ejection fraction before discharge. Univariate analyses showed a progressive increase in cardiac mortality during one year as the ejection fraction fell below 0.40 and as the number of ventricular ectopic depolarizations exceeded one per hour. Only four risk factors among eight prespecified variables were independent predictors of mortality: an ejection fraction below 0.40, ventricular ectopy of 10 or more depolarizations per hour, advanced New York Heart Association functional class before infarction, and rales heard in the upper two thirds of the lung fields while the patient was in the coronary-care unit. Various combinations of these four factors identified five risk subgroups with two-year mortality rates ranging from 3 per cent (no factors) to 60 per cent (all four factors).

Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome.

Abstract: We studied B-lymphocyte function in 12 homosexual male patients with the acquired immunodeficiency syndrome, 5 healthy homosexual men, and 12 heterosexual controls. In comparison with the heterosexual controls, the patients were found to have elevated numbers of cells spontaneously secreting immunoglobulin, decreased B-cell proliferative responses to T-cell-independent B-cell mitogens, and qualitatively deficient helper T cells. The hyperactive spontaneous B-cell responses as well as the refractoriness to signals for T-cell-independent B-cell activation were highly suggestive of an in vivo polyclonal activation of B cells and may have been responsible for the manifestations of B-cell hyperreactivity, such as hypergammaglobulinemia, seen in these patients. We conclude that the scope of immune dysfunction in the acquired immunodeficiency syndrome involves B cells as well as T cells.

The Spirochetal Etiology of Lyme Disease

Abstract: We recovered a newly recognized spirochete from the blood, skin lesions (erythema chronicum migrans [ECM]), or cerebrospinal fluid of 3 of 56 patients with Lyme disease and from 21 of 110 nymphal or adult lxodes dammini ticks in Connecticut. These isolates and the original one from l. dammini appeared to have the same morphologic and immunologic features. In patients, specific IgM antibody titers usually reached a peak between the third and sixth week after the onset of disease; specific IgG antibody titers rose slowly and were generally highest months later when arthritis was present. Among 40 patients who had early disease only (ECM alone), 90 per cent had an elevated IgM titer (greater than or equal to 1:128) between the ECM phase and convalescence. Among 95 patients with later manifestations (involvement of the nervous system, heart, or joints), 94 per cent had elevated titers of IgG (greater than or equal to 1:128). In contrast, none of 80 control subjects had elevated IgG titers, and only three control patients with infectious mononucleosis had elevated IgM titers. We conclude that the I. dammini spirochete is the causative agent of Lyme disease.

Epidemic Listeriosis — Evidence for Transmission by Food

Abstract: The bacterium Listeria monocytogenes is a motile, gram-positive coccobacillus that can frequently be isolated from soil, water, and vegetation. It is a common cause of meningoencephalitis and abort...

Cerebral Arterial Spasm – A Controlled Trial of Nimodipine in Patients with Subarachnoid Hemorrhage

Abstract: We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.

Cytotoxic T-cell immunity to influenza.

Abstract: In a study designed to determine whether cytotoxic T lymphocytes contribute to immunity against influenza virus infection, we inoculated 63 volunteers intranasally with live unattenuated influenza A/Munich/1/79 virus. Over the next seven days clinical observations were made, and the amount of virus shed was measured. The protective effects of preinfection serum antibody and of cytotoxic T-cell immunity against influenza A virus were assessed for each participant. All subjects with demonstrable T-cell responses cleared virus effectively. This response was observed in volunteers in all age groups, including those born after 1956, who did not have specific antibody and hence had probably not been exposed to this subtype of influenza A virus before. Cytotoxic T cells show cross-reactivity in their recognition of the different subtypes of influenza A virus, in contrast to the antibody response that is specific for each virus subtype. We conclude that cytotoxic T cells play a part in recovery from influenza virus infection.

Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH.

Abstract: Fifty-eight patients with severe, progressive multiple sclerosis were prospectively randomized to one of three treatments: 20 received intravenous ACTH, 20 received high-dose intravenous cyclophosphamide plus ACTH, and 18 were placed on a regimen consisting of plasma exchange, low-dose oral cyclophosphamide, and ACTH. The three groups were similar in age, sex, duration and type of disease, and degree of disability. Before treatment and six months and one year after treatment, a disability-status score, ambulation index, and functional-status score were determined, and a quantitative neurologic examination was performed. In the ACTH group, the number of patients stabilized or improved was 8 of 20 at six months and 4 of 20 at one year; in the cyclophosphamide-ACTH group, 18 of 20 at six months and 16 of 20 at one year; and in the plasma exchange group, 11 of 18 at six months and 9 of 18 at one year. High-dose cyclophosphamide plus ACTH was most effective in halting progression of the disease at bot...

Survival after Cardiopulmonary Resuscitation in the Hospital

Abstract: Little is known about prognostic factors that determine outcomes after in-hospital cardiopulmonary resuscitation. We studied prospectively 294 consecutive patients who were resuscitated in a university teaching hospital. Forty-one patients (14 per cent) were discharged from the hospital; three quarters of them were still alive six months later. A multivariate analysis revealed that pneumonia, hypotension, renal failure, cancer, and a homebound life style before hospitalization were significantly associated with in-hospital mortality (P less than 0.05). None of the 58 patients with pneumonia and none of the 179 in whom resuscitation took longer than 30 minutes survived to be discharged. On the other hand, fully 42 per cent of the patients who survived for 24 hours after resuscitation left the hospital. At the time of discharge from the hospital and again six months later, 93 per cent of the survivors were mentally intact. Although depression was generally present at the time of discharge, it tended to resolve subsequently. However, all patients reported some decrease in functional capacity, often attributed to fear. This persisted at six months after discharge. Age alone did not appear to influence the prognosis for survival after cardiopulmonary resuscitation or the adjustment to chronic illness after discharge from the hospital.

Improving Drug-Therapy Decisions through Educational Outreach

Abstract: Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain healthcare costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed "unadvertisements" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The eff...

Bias in Treatment Assignment in Controlled Clinical Trials

Abstract: Controlled clinical trials of the treatment of acute myocardial infarction offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment. A group of 145 papers was divided into those in which the randomization process was blinded (57 papers), those in which it may have been unblinded (45 papers), and those in which the controls were selected by a nonrandom process (43 papers). At least one prognostic variable was maldistributed (P less than 0.05) in 14.0 per cent of the blinded-randomization studies, in 26.7 per cent of the unblinded-randomization studies, and in 58.1 per cent of the nonrandomized studies. Differences in case-fatality rates between treatment and control groups (P less than 0.05) were found in 8.8 per cent of the blinded-randomization studies, 24.4 per cent of the unblinded-randomization studies, and 58.1 per cent of the nonrandomized studies. These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration.

Active life expectancy

Abstract: This study was designed to demonstrate the feasibility of forecasting functional health for the elderly. Using life-table techniques, we analyzed the expected remaining years of functional well-being, in terms of the activities of daily living, for noninstitutionalized elderly people living in Massachusetts in 1974. The expected years, or active life expectancy, showed a decrease, from 10 years for those aged 65 to 70 years to 2.9 for those 85 or older. Active life expectancy was shorter for the poor than for others, and women had a longer average duration of expected dependence than men. The measure of active life expectancy provides important information about health at a given population level, in terms other than death. This information can be used for actuarial purposes in planning and policy making. It is also useful in identifying high-risk populations for which preventive health care and medical care can compress morbidity during the last years of life.

Marrow Transplantation for Acute Nonlymphocytic Leukemia after Treatment with Busulfan and Cyclophosphamide

Abstract: Fifty-one patients with acute nonlymphocytic leukemia (16 with end-stage disease, 17 in second or third remission or in early relapse, and 18 in first remission) were given infusions of HL...

Western Washington Randomized Trial of Intracoronary Streptokinase in Acute Myocardial Infarction

Abstract: Two hundred fifty patients were enrolled in a multicenter, community-based study of the efficacy of intracoronary streptokinase thrombolysis in acute myocardial infarction; 134 were randomly assigned to streptokinase therapy and 116 were controls. All patients underwent left ventricular angiography and coronary arteriography before the random assignment. The mean time from the onset of symptoms to hospitalization was 134 +/- 144 minutes (S.D), and the mean time to random assignment was 276 +/- 185 minutes. Coronary reperfusion was achieved in 68 per cent of the streptokinase-treated group. The overall 30-day mortality was 18 (7.2 per cent); there were five deaths in the streptokinase-treated group (3.7 per cent) and 13 in the control group (11.2 per cent, P less than 0.02). Fifteen of the 18 deaths occurred in patients with anterior infarction. Intracoronary streptokinase therapy resulted in a nearly threefold reduction in the 30-day mortality after hospitalization for acute myocardial infarction.

Somatostatin (First of two parts)

Abstract: Phylogenie de la somatostatine. Biosynthese, manipulation et transport. Fonction dans la regulation hypophysaire

The value of the autopsy in three medical eras.

Abstract: To determine whether advances in diagnostic procedures have reduced the value of autopsies, we analyzed 100 randomly selected autopsies from each of the academic years 1960, 1970, and 1980 at one university teaching hospital. In all three eras about 10 per cent of the autopsies revealed a major diagnosis that, if known before death, might have led to a change in therapy and prolonged survival; another 12 per cent showed a clinically missed major diagnosis for which treatment would not have been changed. Among 1980 autopsies, renal disease and pulmonary embolus were less common causes of death than before, but systemic bacterial, viral, and fungal infections increased significantly and were missed clinically 24 per cent of the time. The introduction of radionuclide scans, ultrasound, and computerized tomography as diagnostic procedures did not reduce the use of conventional tests in patients who subsequently died and were studied by autopsy. Over-reliance on these new procedures occasionally contributed directly to missed major diagnoses. We conclude that advances in diagnostic technology have not reduced the value of the autopsy, and that a goal-directed autopsy remains a vital component in the assurance of good medical care.

A Prospective Evaluation and Follow-up of Patients with Syncope

Abstract: We prospectively evaluated and followed 204 patients with syncope to determine how often a cause of syncope could be established and to define the prognosis of such patients. A cardiovascular cause was established in 53 patients and a noncardiovascular cause in 54. The cause remained unknown in 97 patients. At 12 months, the overall mortality was 14 +/- 2.5 per cent. The mortality rate (30 +/- 6.7 per cent) in patients with a cardiovascular cause of syncope was significantly higher than the rate (12 +/- 4.4 per cent) in patients with a noncardiovascular cause (P = 0.02) and the rate (6.4 +/- 2.8 per cent) in patients with syncope of unknown origin (P less than 0.0001). The incidence of sudden death was 24 +/- 6.6 per cent in patients with a cardiovascular cause, as compared with 4 +/- 2.7 per cent in patients with a noncardiovascular cause (P = 0.005) and 3 +/- 1.8 per cent in patients with syncope of unknown origin (P = 0.0002). Patients with syncope can be separated into diagnostic categories that have prognostic importance. Patients with a cardiovascular cause have a strikingly higher incidence of sudden death than patients with a noncardiovascular or unknown cause.

Spirochetes isolated from the blood of two patients with Lyme disease.

Abstract: We isolated spirochetes from the blood of 2 of 36 patients in Long Island and Westchester County, New York, who had signs and symptoms suggestive of Lyme disease. The spirochetes were morphologically similar and serologically identical to organisms recently found to infect lxodes dammini ticks, which are endemic to the area and have been epidemiologically implicated as vectors of Lyme disease. In both patients, there was a rise in specific antispirochetal antibodies in paired specimens of serum. We conclude that the l. dammini spirochete has an etiologic role in Lyme disease.

Use of Single Voided Urine Samples to Estimate Quantitative Proteinuria

Abstract: Quantitation of urinary protein excretion is used extensively for diagnostic and prognostic purposes and to assess the effects of therapy. The method most commonly used to measure urinary protein relies on 24-hour urine collections, which are time consuming, cumbersome, and often inaccurate. We reasoned that the urinary protein/creatinine ratio in a single voided urine sample should correlate well with the quantity of protein in timed urine collections. In a study of 46 specimens we found an excellent correlation between the protein content of a 24-hour urine collection and the protein/creatinine ratio in a single urine sample. The best correlation was found when samples were collected after the first voided morning specimen and before bedtime. We conclude that the determination of the protein/creatinine ratio in single urine samples obtained during normal daylight activity, when properly interpreted by taking into consideration the effect of different rates of creatinine excretion, can replace the 24-hour urine collection in the clinical quantitation of proteinuria. In the presence of stable renal function, a protein/creatinine ratio of more than 3.5 (mg/mg) can be taken to represent "nephrotic-range" proteinuria, and a ratio of less than 0.2 is within normal limits.

The pharmacology and clinical use of methotrexate

Abstract: METHOTREXATE, the most widely used antimetabolite in cancer chemotherapy, has an essential role in the treatment of such diverse diseases as acute lymphocytic leukemia, non-Hodgkin's lymphoma, oste...

Physiologic repair of aortic atresia-hypoplastic left heart syndrome.

Abstract: AORTIC-VALVE atresia associated with mitral atresia or stenosis, a diminutive or absent left ventricle, and severe hypoplasia of the ascending aorta and aortic arch make up a constellation of defects that was initially termed "hypoplasia of the aortic tract complexes" by Lev1 and later called "hypoplastic left heart syndrome" by Noonan and Nadas.2 The anatomic complexity of this cardiac malformation has been considered prohibitive of long survival, and generally, only supportive therapy has been recommended. Indeed, aortic atresia–hypoplastic left heart syndrome is uniformly fatal without surgical intervention, and prolonged survival after reparative surgery has not been reported. It is, however, . . .

Human cryptosporidiosis in immunocompetent and immunodeficient persons. Studies of an outbreak and experimental transmission.

Abstract: Infection with cryptosporidium occurred in 12 immunocompetent persons who had direct contact with the feces of infected calves during three unrelated outbreaks of calf cryptosporidiosis. Nine of the twelve subjects had diarrhea and abdominal cramps that lasted 1 to 10 days. Infections were diagnosed and monitored by detection of oocysts in feces, with a modified Sheather's flotation technique and phase-contrast microscopy. Oocysts of cryptosporidium were isolated from calves but not from other animals with which these subjects had been in contact. Oocysts of cryptosporidium were also detected during repeated examinations of feces from two immunodeficient patients with persistent cryptosporidiosis. An apparently identical infection was transmitted to calves and mice, using oocysts from infected calves and human beings. Oocysts from an immunodeficient person also produced infections in kittens, puppies, and goats. This study shows that cryptosporidium may produce a moderate self-limited illness in immunocompetent persons, which contrasts sharply with the prolonged severe diarrhea in immunocompromised patients who contract cryptosporidiosis. Calves with diarrhea should be considered a potential source of human infection, and immunocompromised persons should avoid contact with such animals.

Steroid-Induced Fractures and Bone Loss in Patients with Asthma

Abstract: To study the association between bone disease and long-term steroid administration in asthmatics, we reviewed the hospital records of 128 patients over 40 years of age who had taken daily or alternate-day adrenal corticosteroids for at least a year and compared them with the records of 54 other asthmatics of similar age who had not required long-term administration of steroids. We found evidence in the records of a total of 58 fractures of the ribs or vertebrae in 14 of the patients who had received long-term steroid treatment (11 per cent) and no evidence of fractures in the patients who had not received long-term treatment. We also prospectively studied 30 hospitalized asthmatic patients between 20 and 70 years of age who had been screened for medications (other than steroids) or complicating diseases known to affect bone mineralization. Eight of 19 asthmatic patients receiving long-term steroid therapy had rib or vertebral fractures, whereas none of 11 matched patients not receiving such therapy had fractures. Furthermore, bone-density measurements of the distal and proximal radius by photon absorptiometry revealed that the trabecular, but not the cortical, bone mass was below normal in the former group of patients but not in the latter. Within the long-term steroid group, there was no significant correlation between bone density and dose or duration of steroid treatment. We conclude that long-term steroid therapy in asthmatic patients is associated with decreased trabecular bone density and an increased prevalence of rib and vertebral fractures.

Does free care improve adults' health? Results from a randomized controlled trial.

Abstract: Does free medical care lead to better health than insurance plans that require the patient to shoulder part of the cost? In an effort to answer this question, we studied 3958 people between the ages of 14 and 61 who were free of disability that precluded work and had been randomly assigned to a set of insurance plans for three or five years. One plan provided free care; the others required enrollees to pay a share of their medical bills. As previously reported, patients in the latter group made approximately one-third fewer visits to a physician and were hospitalized about one-third less often. For persons with poor vision and for low-income persons with high blood pressure, free care brought an improvement (vision better by 0.2 Snellen lines, diastolic blood pressure lower by 3 mm Hg); better control of blood pressure reduced the calculated risk of early death among those at high risk. For the average participant, as well as for subgroups differing in income and initial health status, no significant effects were detected on eight other measures of health status and health habits. Confidence intervals for these eight measures were sufficiently narrow to rule out all but a minimal influence, favorable or adverse, of free care for the average participant. For some measures of health in subgroups of the population, however, the broader confidence intervals make this conclusion less certain.

Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). A mechanism for the increased degradation of muscle proteins during fever.

Abstract: To clarify the mechanisms underlying the loss of body protein during fever and sepsis, we incubated rat muscles with highly purified human leukocytic pyrogen. This polypeptide, which appears identical to interleukin-1, is released by leukocytes and signals the onset of fever in the hypothalamus. In muscles incubated at 37 degrees C, leukocytic pyrogen stimulated net protein degradation by 62 to 118 per cent (P less than 0.001). Proteolysis increased, but rates of muscle-protein synthesis did not change. The pyrogen also dramatically stimulated muscle synthesis of prostaglandin E2, which promotes protein breakdown in this tissue. Addition of indomethacin with leukocytic pyrogen prevented prostaglandin E2 synthesis and abolished the increase in proteolysis. The acceleration of protein breakdown induced by pyrogen was also blocked by Ep-475, an inhibitor of lysosomal thiol proteases. When muscles were incubated at 39 degrees C to mimic fever, protein breakdown increased, but addition of leukocytic pyrogen caused a further marked increase in proteolysis and prostaglandin E2 production. Thus, human leukocytic pyrogen can act on skeletal muscle to stimulate intralysosomal proteolysis by increasing the production of prostaglandin E2. These findings suggest that cyclooxygenase inhibitors may be useful in the treatment of negative nitrogen balance in fever. In addition, the release of prostaglandin E2 induced by leukocytic pyrogen may account for the myalgia that accompanies fever.

Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome.

Abstract: We describe seven adults who had ataxia and severe sensory-nervous-system dysfunction after daily high-level pyridoxine (vitamin B6) consumption Four were severely disabled; all improved after withdrawal Weakness was not a feature of this condition, and the central nervous system was clinically spared Although consumption of large doses of pyridoxine has gained wide public acceptance, this report indicates that it can cause sensory neuropathy or neuronopathy syndromes and that safe guidelines should be established for the use of this widely abused vitamin

Captopril-induced functional renal insufficiency in patients with bilateral renal-artery stenoses or renal-artery stenosis in a solitary kidney.

Abstract: ACUTE renal failure occasionally complicates therapy with the oral angiotensin-converting-enzyme inhibitor captopril.1 2 3 4 5 A variety of mechanisms have been postulated to account for captopril-...

Hypokalemia from beta2-receptor stimulation by circulating epinephrine.

Abstract: To determine whether epinephrine-induced hypokalemia is due to beta2-adrenoceptor stimulation, and whether hypokalemia can occur at physiologic concentrations of the agonist, epinephrine was infused into six normal volunteers at a rate of 0.1 microgram per kilogram of body weight per minute. The circulating epinephrine concentration was increased to 1.74 +/- 0.65 ng per milliliter, plasma potassium was reduced by 0.82 +/- 0.19 meq per liter, plasma insulin fell by 12 +/- 4 mU per liter, plasma renin activity was elevated, and tachycardia occurred. Isoproterenol infused at 0.02 micrograms per kilogram per minute caused similar tachycardia (25 beats per minute) and elevation in plasma renin activity (6.0 to 6.5 ng per milliliter per hour), but no hypokalemia. The difference in responses to the two catecholamines was ascribed to the relative beta2-selectivity of epinephrine. This hypothesis was tested in six subjects given infusions of epinephrine (0.05 micrograms per kilogram per minute) after administration of either 2.5 or 5 mg of ICI 118551--a selective beta2-receptor antagonist--or placebo. After placebo, epinephrine infusion elevated the circulating epinephrine concentration and reduced plasma potassium; hypokalemia was prevented by the beta2-antagonist. This drug only partially inhibited the rises in plasma renin and glucose and the shortening of systolic time intervals; there was no tachycardia. Fifteen-fold to 30-fold increases in circulating epinephrine concentration appear to cause hypokalemia by a specific beta2-receptor effect distinct from other actions of epinephrine. This phenomenon may be of physiologic importance after severe myocardial infarction, when similar increases in plasma epinephrine have occurred.