Showing papers in "The New England Journal of Medicine in 1975"

Polymyositis and dermatomyositis (first of two parts)

Abstract: Laboratory Features Elevation of sarcoplasmic enzymes in serum (creatine phosphokinase, aldolase, transaminases and lactic dehydrogenase) is valuable both for diagnosis and for following the clinic...

Primer on Certain Elements of Medical Decision Making

Abstract: The value of a diagnostic test lies in its ability to detect patients with disease (its sensitivity) and to exclude patients without disease (its specificity). For tests with binary outcomes, these measures are fixed. For tests with a continuous scale of values, various cutoff points can be selected to adjust the sensitivity and specificity of the test to conform with the physician's goals. Principles of statistical decision theory and information theory suggest technics for objectively determining these cutoff points, depending upon whether the physician is concerned with health costs, with financial costs, or with the information content of the test.

Optimum End-Expiratory Airway Pressure in Patients with Acute Pulmonary Failure

Abstract: To determine whether in the management of pulmonary failure, the maximum compliance produced by positive end-expiratory pressure coincides with optimum lung function, 15 normovolemic patients requiring mechanical ventilation for acute pulmonary failure were studied. The end-expiratory pressure resulting in maximum oxygen transport (cardiac output times arterial oxygen content) and the lowest dead-space fraction both resulted in the greatest total static compliance. This end-expiratory pressure varied between 0 and 15 cm of water and correlated inversely with functional residual capacity at zero end-expiratory pressure (r equal -0.72, p less than or equal to 0.005). Mixed venous oxygen tension increased between zero end-expiratory pressure and the end-expiratory pressure resulting in maximum oxygen transport, but then decreased at higher end-expiratory pressures. When measurements of cardiac output or of true mixed venous blood are not available, compliance may be used to indicate the end-expiratory pressure likely to result in optimum cardiopulmonary function.

Vertical transmission of hepatitis B antigen in Taiwan.

Abstract: To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.

Increased risk of endometrial carcinoma among users of conjugated estrogens.

Abstract: The possibility that the use of conjugated estrogens increases the risk of endometrial carcinoma was investigated in patients and a twofold age-matched control series from the same population. Conjugated estrogens (principally sodium estrone sulfate) use was recorded for 57 per cent of 94 patients with endometrial carcinoma, and for 15 per cent of controls. The corresponding point estimate of the (instantaneous) risk ratio was 7.6 with a one-sided 95 per cent lower confidence limit of 4.7. The risk-ratio estimate increased with duration of exposure: from 5.6 for 1 to 4.9 years exposure to 13.9 for seven or more years. The estimated proportion of cases related to conjugated estrogens, the etiologic fraction, was 50 per cent with a one-sided 95 per cent lower confidence limit of 41 per cent. These data suggest that conjugated estrogens have an etiologic role in endometrial carcinoma.

Association of exogenous estrogen and endometrial carcinoma.

Abstract: To determine the association between the incidence of endometrial cancer and the use of estrogen in menopausal and post-menopausal women, we retrospectively compared 317 patients with adenocarcinoma of the endometrium with an equal number of matched controls having other gynecologic neoplasms; 152 patients used estrogen, as compared to 54 of 317 controls. Thus, the risk of endometrial cancer was 4.5 times greater among women exposed to estrogen therapy. When estrogen use was adjusted for concomitant variables such as obesity, hypertension, diabetes, parity, referral pattern, age at diagnosis, year of diagnosis and other gynecologic neoplasms, the magnitude of the increased relative risk was associated with several of these variables, and was highest in patients without obesity and hypertension. Exogenous estrogen therapy is associated with an increased risk of endometrial carcinoma, but this increased relative risk is less apparent in patients with physiologic characteristics previously associated with an increased risk.

1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer. A report of early findings.

Abstract: Prolonged 1-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial. Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01). A statistically significant difference (p = 0.02) existed in favor of L-PAM relative to disease-free interval. In premenopausal women, the difference with respect to disease-free interval of treated and control groups was highly significant (p = 0.008). A treatment failure occurred in 30 per cent of premenopausal patients receiving placebo and 3 per cent of those treated with L-PAM (p = 0.008). Whereas a similar trend was observed in postmenopausal patients, the difference is not statistically significant. Thus, L-PAM has been demonstrated to be effective in the treatment of women with primary breast cancer, particularly those who are premenopausal. Results were achieved with minimal undesirable side effects.

Spinal Epidural Abscess

Abstract: Thirty-nine patients with spinal epidural abscess were evaluated at the Massachusetts General Hospital between 1947 and 1974. Twenty had acute symptoms, and purulent epidural collections were present; 19 had prolonged courses, and epidural granulation tissue was observed at operation. Staphylococcus aureus was the most common etiologic agent (57 per cent), followed by streptococci (18 per cent) and gram-negative bacilli (13 per cent). The source of infection was osteomyelitis in 38 per cent of cases and bacteremia in 26 per cent. In 16 per cent epidural abscess was due to postoperative infection. The progression from spinal ache to root pain to weakness followed by paralysis continues to be characteristic of spinal epidural abscess. Although the disease is uncommon, the complications are so serious that prompt diagnosis and treatment are of paramount importance. The combination of back pain with fewer and local tenderness is an indication for cerebrospinal-fluid examination and, depending on the results, immediate performance of myelography.

Methotrexate: Distribution in Cerebrospinal Fluid after Intravenous, Ventricular and Lumbar Injections

Abstract: The kinetics and distribution of methotrexate in intraventricular and intrathecal cerebrospinal-fluid spaces were studied in patients with meningeal leukemia and meningeal carcinomatosis after drug administration by intravenous infusion, indwelling intraventricular subcutaneous reservoir (Ommaya), or standard lumbar puncture. Negligible ventricular concentrations followed a single intravenous dose. During an intravenous infusion (500 mg per square meter for 24 hours) the ventricular cerebrospinal-fluid concentration rose to 6 X 10–7 M. Methotrexate administered by Ommaya reservoir, at a dose of 6.25 mg per square meter, rapidly distributed in the subarachnoid space; the peak ventricular concentration of 2 X 10–4 M declined exponentially over 48 hours. Lumbar cerebrospinal-fluid concentration reached a maximum of 5 X 10–5 M four hours after injection and then fell exponentially. Administration by lumbar puncture occasionally produced epidural and subdural leakage; even with successful lumbar punct...

Immunoblastic lymphadenopathy. A hyperimmune entity resembling Hodgkin's disease.

Abstract: Immunoblastic lymphadenopathy, although it resembles Hodgkin's disease, is a distinct, hyperimmune disorder apparently of the B-cell system. In 32 cases, it was characterized by a morphologic triad: proliferation of arborizing small vessels; prominent immunoblastic proliferations; and amorphous acidophilic interstitial material. Clinically, it is manifested by fever, sweats, weight loss, occasionally a rash, generalized lymphadenopathy and often hepatosplenomegaly. There is a consistent polyclonal hyperglobulinemia and often hemolytic anemia. The course of the disease is usually progressive, with a median survival of 15 months in 18 fatal cases. The cellular proliferation appears benign morphologically in the pretherapy biopsies and in 10 of 12 available autopsy cases. In three cases the process evolved into a lymphoma of immunoblasts, immunoblastic sarcoma. The basic process appears to be a non-neoplastic hyperimmune proliferation of the B-cell system involving an exaggeration of lymphocyte transformation to immunoblasts and plasma cells that may be triggered by a hypersensitivity reaction to therapeutic agents.

The Reliability of Clinical Methods, Data and Judgments

Abstract: SKILLED physicians examining a patient may disagree regarding the findings. Such disagreements reflect the imperfect reliability of clinical methods and data. A decade ago, Fletcher1 urged physicia...

Work activity and coronary heart mortality.

Abstract: To appraise the role of physical activity in reducing coronary mortality among longshoremen, 6351 men, 35 to 74 years old upon entry, were followed for 22 years or to death or to the age of 75. Their longshoring experience was computed in terms of work-years according to categories of high, medium and low caloric output. Individual work assignments were reclassified annually to allow for effect of job transfers. The age-adjusted coronary death rate for the high-activity category was 26.9 per 10,000 work-years, and the medium and low catgories had rates of 46.3 and 49.0 which were little different from each other. This protective "threshold" effect was seen especially for the sudden-death syndrome, in which the death rate for heavy workers was 5.6, as contrasted with 19.9 for moderate and 15.7 for light workers. We conclude that repeated bursts of high energy output established a plateau of protection against coronary mortality, and that several different mechanisms may explain this finding.

Active and passive euthanasia.

Abstract: The distinction between active and passive euthanasia is thought to be crucial for medical ethics. The idea is that it is permissible, at least in some cases, to withhold treatment and allow a patient to die, but it is never permissible to take any direct action designed to kill the patient. This doctrine seems to be accepted by most doctors, and is endorsed in a statement adopted by the House of Delegates of the American Medical Association on December 4, 1973: The intentional termination of the life of one human being by another—mercy killing—is contrary to that for which the medical profession stands and is contrary to the policy of the American Medical Association. The cessation of the employment of extraordinary means to prolong the life of the body when there is irrefutable evidence that biological death is imminent is the decision of the patient and/or his immediate family. The advice and judgment of the physician should be freely available to the patient and/or his immediate family.

High blood acetaldehyde levels after ethanol administration. Difference between alcoholic and nonalcoholic subjects.

Abstract: Blood acetaldehyde and ethanol levels were measured in 11 subjects, six with chronic alcoholism and five nonalcoholic controls, after alcohol had been given intravenously. Despite a progressive fall in blood ethanol over a range of 54 to 33 mM, acetaldehyde did not decrease in any of the 11 subjects. The mean acetaldehyde plateau level was significantly (p < 0.001) higher in alcoholic (42.7 ± 1.2 μM) than in nonalcoholic (26.5 ± 1.5 μM) subjects. When the mean blood ethanol concentration reached 24 mM, the acetaldehyde plateau ended abruptly in each subject. The ethanol concentration at which this fall of blood acetaldehyde occurred suggests desaturation of an ethanol oxidizing system other than alcohol dehydrogenase and indicates that at high ethanol blood levels, such a system contributes to ethanol oxidation. The higher acetaldehyde levels in alcoholism may result from both greater activity of this system and mitochondrial damage, and could contribute to the neurologic, hepatic and cardiac com...

Transfusion-associated hepatitis not due to viral hepatitis type A or B.

Abstract: Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.

Measurement of Delayed Skin-Test Responses

Abstract: Measurement of delayed skin-test responses is a basic clinical procedure, originally used for identification of infection with microbial agents. More recently, skin testing with a battery of antige...

A simple test for the diagnosis of absorptive, resorptive and renal hypercalciurias

Abstract: A test was developed to diagnose various forms of hypercalciuria. A two-hour urine sample after an overnight fast and a four-hour urine sample after 1 g of calcium by mouth were tested for calcium, cyclic AMP and creatinine. The 24 patients with absorptive hypercalciuria had normocalcemia and normal fasting urinary calcium (less than 0.11 mg per milligram of urinary creatnine). Urinary calcium was high (greater than or equal to 0.2 mg per milligram of creatinine) after a calcium load. Of the 28 patients with primary hyperparathyroidism (resorptive hypercalciuria), 25 had hypercalcemia and 21 had high fasting urinary calcium. Urinary cyclic AMP, elevated in 30 per cent of fasting patients, was high (greater than 4.60 mu moles per gram of creatinine) in 82 per cent of cases after calcium load. Six patients with renal hypercalciuria had normocalcemia, high fasting urinary calcium, and high (greater than 6.86 mu moles per gram of creatinine) or high-normal fasting urinary cyclic AMP was normal. This simple test should facilitate the differentiation of various causes of hypercalciuria.

Platelet Physiology and Abnormalities of Platelet Function

Abstract: (First of Two Parts) THE blood platelets, approximately 2 μm in diameter and numbering 200,000 to 400,000 per cubic millimeter, are produced in the megakaryocytes of the bone marrow by the coalescence of cytoplasmic membranes formed by invaginations of the megakaryocyte surface.1 Under normal circumstances, platelets circulate in the blood for 10 days as smooth, disk-shaped cells that are nonadherent to each other and to normal vascular endothelium. Their unique biologic properties are the changes that occur when the endothelium is broken or when disruption of the vessel allows the blood to come into contact with elements of the vessel . . .

Therapeutic decision making: a cost-benefit analysis.

Abstract: To help the physician decide whether or not to treat a patient who may or may not have a disease, a method has been developed for calculating a therapeutic threshold. If the probability of disease in a given patient exceeds the threshold, the preferable course of action is to treat; if the probability is below the threshold, the preferable course of action is to withhold treatment. This method is applicable in many medical and surgical settings in which some diagnostic uncertainty exists after all appropriate studies have been carried out. The technic not only exposes some of the basic principles of therapeutic decision making in the face of diagnostic uncertainty but also forms a convenient framework for analyzing the impact of "soft" clinical data on the decision-making process. (N Engl J Med 293:229–234, 1975)

Polymicrobial etiology of acute pelvic inflammatory disease.

Abstract: We studied 204 women with acute pelvic inflammatory disease to delineate further the causes of that illness. Gonococci were recovered from 91. Gonococcal pili antibody rose or fell significantly in 12 of 18 patients with positive cultures and only two of 19 who had negative cultures and smears for Neisseria gonorrhaoea(P smaller than 0.005). N. gonorrhoeae was found in peritoneal exudate from eight of 21 patients with, and none of 33 without, cervical gonococcal infection. Among patients with severe disease, other bacteria were recovered from peritoneal exudates from five of 16 with, and 19 of 22 without, cervical gonococcal infection (P smaller than 0.025). Mixed anaerobic and aerobic bacterial peritoneal infection was common in nongonococcal pelvic disease. The most common species recovered were Bacteroides fragilis, peptostreptococci, and peptococci. Tuboperitoneal gonococcal infection probably causes pelvic inflammatory disease in most patients with cervical gonococcal infection, whereas polymicrobial tuboperitoneal infection probably causes most nongonococcal cases.

Quantitative determination of antibody in idiopathic thrombocytopenic purpura. Correlation of serum and platelet-bound antibody with clinical response.

Abstract: We studied the clinical applicability of a recently developed technic that determines antiplatelet antibody directly on the platelet surface or in serum. The technic is a quantitative complement lysis-inhibition assay. Normal platelets have less than 0.4 pg of surface IgG. All patients with idiopathic thrombocytopenic purpura who were studied had greater than that value. Surface IgG was increased in inverse proportion to the platelet count. Surface levels of greater than 1.1 pg correlated with failure to respond to prednisone therapy. Incubation of normal serums with normal platelets did not increase surface IgG of such platelets, but the incubation with thrombocytopenic serums increased their surface IgG 0.5 to 100 times. The degree of increase did not predict response to treatment. However, quantitation of surface IgG of thrombocytopenic platelets was useful in predicting response to treatment.

Actions and Interactions of Antithrombin and Heparin

Abstract: THE coagulation of blood occurs via two pathways in which activation of specific plasma proteins initiates a cascade of reactions that ultimately lead to a fibrin clot. In the first pathway, injury...

Prostaglandins as Mediators of Hypercalcemia Associated with Certain Types of Cancer

Abstract: We investigated the role of prostaglandins in the hypercalcemia associated with neoplasia. In patients with hypercalcemia and solid tumors the excretion of the major urinary metabolite of the E prostaglandins, 7 alpha-hydroxy-5, 11-diketotetranorprostane-1, 16-dioic acid (PGE-M), was significantly greater than normal, P LESS THAN 0.01 (median of 58.4 and 7.1 ng per milligram of creatinine respectively). Slightly elevated values were seen in normocalcemic patients with solid tumors (14.3 ng per milligram). The levels of the metabolite were normal in hypercalcemic patients with either hematologic neoplasia or primary hyperparathyroidism. Immunoreactive parathyroid hormone was undetectable in the plasma of all hypercalcemic patients with solid tumors. Inhibition of prostaglandin synthesis by aspirin or indomethacin reduced excretion of both the urinary metabolite and serum calcium in six hypercalcemic patients with solid tumors and elevated excretion of the metabolite. These findings support the concept that prostaglandins are mediators of the hypercalcemia caused by certain solid tumors.

Management of heparin therapy: Controlled prospective trial.

Abstract: Among 100 consecutive patients receiving heparin in therapeutic dosage, major bleeding occurred in 21, and minor bleeding in 16. Two patients died from bleeding, and two had recurrent pulmonary embolism. Major bleeding occurred in 21% when therapy was regulated with whole-blood clotting time and in 20% when heparin was given without clotting tests. In a subsequent prospective trial patients received heparin by intermittent intravenous injection with or without laboratory control according to the partial thromboplastin time or continuously by intravenous infusion. Recurrent thromboembolism occurred once in each group. Major bleeding was seven times more frequent with intermittent injection than with continuous infusion. Control with the partial thromboplastin time did not prevent major bleeding in patients receiving intermittent injections. With continuous infusion, one-fourth less heparin was required than with intermittent injections. Administration of heparin by continuous infusion appears safe...

Cardiovascular control mechanisms in the conscious state.

Abstract: CLINICIANS and clinical physiologists would prefer to base an understanding of the function and regulation of the cardiovascular system on observations carried out in man. However, both ethical considerations and limitations in instrumentation mandate the study of laboratory animals, in which appropriate controls and interventions can be introduced. Whereas extremely important hemodynamic information has been obtained from studies of man, most of the knowledge of cardiovascular physiology and pharmacology is based on findings obtained in animal experiments, which have been conducted most frequently on animals in the anesthetized state, often with an open chest. The conclusions derived from these experiments . . .