Showing papers in "The New England Journal of Medicine in 1987"
TL;DR: Results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.
Abstract: In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.
3,697 citations
TL;DR: It is concluded that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area.
Abstract: Whether human coronary arteries undergo compensatory enlargement in the presence of coronary disease has not been clarified. We studied histologic sections of the left main coronary artery in 136 hearts obtained at autopsy to determine whether atherosclerotic human coronary arteries enlarge in relation to plaque (lesion) area and to assess whether such enlargement preserves the cross-sectional area of the lumen. The area circumscribed by the internal elastic lamina (internal elastic lamina area) was taken as a measure of the area of the arterial lumen if no plaque had been present. The internal elastic lamina area correlated directly with the area of the lesion (r = 0.44, P less than 0.001), suggesting that coronary arteries enlarge as lesion area increases. Regression analysis yielded the following equation: Internal elastic lamina area = 9.26 + 0.88 (lesion area) + 0.026 (age) + 0.005 (heart weight). The correlation coefficient for the lesion area was significant (P less than 0.001), whereas the correlation coefficients for age and heart weight were not. The lumen area did not decrease in relation to the percentage of stenosis (lesion area/internal elastic lamina area X 100) for values between zero and 40 percent but did diminish markedly and in close relation to the percentage of stenosis for values above 40 percent (r = -0.73, P less than 0.001). We conclude that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area. The preservation of a nearly normal lumen cross-sectional area despite the presence of a large plaque should be taken into account in evaluating atherosclerotic disease with use of coronary angiography.
3,631 citations
TL;DR: It is demonstrated that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.
Abstract: We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.
3,062 citations
TL;DR: This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present, and determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.
Abstract: We studied the effects of adoptive immunotherapy with lymphokine-activated killer (LAK) cells plus interleukin-2 or therapy with high-dose interleukin-2 alone in 157 patients with metastatic cancer for whom standard therapy had proved ineffective or no standard effective treatment was available. One hundred eight patients were treated with 127 courses of LAK cells plus interleukin-2, and 49 patients were treated with 53 courses of high-dose interleukin-2 alone. Of 106 evaluable patients receiving LAK cells plus interleukin-2, 8 had complete responses, 15 had partial responses, and 10 had minor responses. The median duration of response was 10 months among those with complete responses and 6 months among those with partial responses; the patient with the longest complete response was still in remission 22 months after treatment. Of 46 evaluable patients treated with high-dose interleukin-2 alone, 1 had a complete response (remission greater than 4 months), 5 had partial responses (2, greater than 3, greater than 5, 7, and greater than 11 months), and 1 had a minor response. Seven of the total of nine complete responses still remain in remission. Hypotension, weight gain, oliguria, and elevation of bilirubin and creatinine levels were common, but these side effects resolved promptly after interleukin-2 administration was stopped. There have been four treatment-related deaths among these 157 patients. This immunotherapeutic approach can result in marked tumor regression in some patients for whom no other effective therapy is available at present. Determining its ultimate role in cancer therapy awaits further attempts to increase the therapeutic efficacy of treatment and decrease its toxicity and complexity.
2,762 citations
2,670 citations
TL;DR: It is concluded that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.
Abstract: We assessed oral 5-aminosalicylic acid (5-ASA) prepared with a pH-sensitive polymer coating in 87 patients with mildly to moderately active ulcerative colitis in a double-blind, placebo-controlled trial. Patients were randomly assigned to receive 5-ASA at a dosage of either 4.8 or 1.6 g per day or placebo for six weeks. The outcome was monitored by flexible proctosigmoidoscopic examinations and physicians' assessments at three-week intervals and by patients' recordings of daily symptoms. Results showed 24 percent complete and 50 percent partial responses in those receiving 4.8 g of 5-ASA per day as compared with 5 percent complete and 13 percent partial responses in those receiving placebo (P less than 0.0001, rank-sum test). At a dosage of 1.6 g per day, the response was twice as good as with placebo, but the difference did not reach statistical significance (P = 0.51). Age, sex, duration of disease, duration of active symptoms, or extent of disease did not affect the clinical outcome. We conclude that oral 5-ASA administered in a dosage of 4.8 g per day is effective therapy, at least in the short term, for mildly to moderately active ulcerative colitis.
2,438 citations
TL;DR: Results provide preliminary evidence that essential hypertension is an insulin-resistant state and insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.
Abstract: High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.
2,271 citations
TL;DR: PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy, however, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.
Abstract: To compare the clinical usefulness of the serum markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), we measured them by radioimmunoassay in 2200 serum samples from 699 patients, 378 of whom had prostatic cancer. PSA was elevated in 122 of 127 patients with newly diagnosed, untreated prostatic cancer, including 7 of 12 patients with unsuspected early disease and all of 115 with more advanced disease. The PSA level increased with advancing clinical stage and was proportional to the estimated volume of the tumor. The PAP concentration was elevated in only 57 of the patients with cancer and correlated less closely with tumor volume. PSA was increased in 86 percent and PAP in 14 percent of the patients with benign prostatic hyperplasia. After radical prostatectomy for cancer, PSA routinely fell to undetectable levels, with a half-life of 2.2 days. If initially elevated, PAP fell to normal levels within 24 hours but always remained detectable. In six patients followed postoperatively by means of repeated measurements, PSA--but not PAP--appeared to be useful in detecting residual and early recurrence of tumor and in monitoring responses to radiation therapy. Prostate massage increased the levels of both PSA and PAP approximately 1.5 to 2 times. Needle biopsy and transurethral resection increased both considerably. We conclude that PSA is more sensitive than PAP in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific.
2,188 citations
TL;DR: An alternative concept of equipoise is suggested, which would be based on present or imminent controversy in the clinical community over the preferred treatment, which is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferredreatment.
Abstract: The ethics of clinical research requires equipoise--a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial. Should the investigator discover that one treatment is of superior therapeutic merit, he or she is ethically obliged to offer that treatment. The current understanding of this requirement, which entails that the investigator have no "treatment preference" throughout the course of the trial, presents nearly insuperable obstacles to the ethical commencement or completion of a controlled trial and may also contribute to the termination of trials because of the failure to enroll enough patients. I suggest an alternative concept of equipoise, which would be based on present or imminent controversy in the clinical community over the preferred treatment. According to this concept of "clinical equipoise," the requirement is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferred treatment.
2,088 citations
TL;DR: It is demonstrated that recombinant human erythropoietin is effective, can eliminate the need for transfusions with their risks of immunologic sensitization, infection, and iron overload, and can restore the hematocrit to normal in many patients with the anemia of end-stage renal disease.
Abstract: We administered recombinant human erythropoietin to 25 anemic patients with end-stage renal disease who were undergoing hemodialysis. The recombinant human erythropoietin was given intravenously three times weekly after dialysis, and transfusion requirements, hematocrit, ferrokinetics, and reticulocyte responses were monitored. Over a range of doses between 15 and 500 units per kilogram of body weight, dose-dependent increases in effective erythropoiesis were noted. At 500 units per kilogram, changes in the hematocrit of as much as 10 percentage points were seen within three weeks, and increases in ferrokinetics of three to four times basal values, as measured by erythron transferrin uptake, were observed. Of 18 patients receiving effective doses of recombinant human erythropoietin, 12 who had required transfusions no longer needed them, and in 11 the hematocrit increased to 35 percent or more. Along with the rise in hematocrit, four patients had an increase in blood pressure, and a majority had ...
1,958 citations
TL;DR: Mise a jour: anatomopathologie, anomalies immunologiques et pathogenese, tests de laboratoire, manifestations cliniques et troubles associes, evolution, traitement.
Abstract: Mise a jour: anatomopathologie, anomalies immunologiques et pathogenese, tests de laboratoire, manifestations cliniques et troubles associes, evolution, traitement
TL;DR: Experiments in animals showed complete intimal coverage within weeks and no late thrombosis during a follow-up period of up to one year, and preliminary experience suggests that this vascular endoprosthesis may offer a useful way to prevent occlusion and restenosis after transluminal angioplasty.
Abstract: Occlusion and restenosis are the most common reasons that transluminal balloon angioplasty may fail to provide long-term benefit. An intravascular mechanical support was therefore developed with the aim of preventing restenosis and sudden closure of diseased arteries after angioplasty. The endoprosthesis consists of a self-expandable stainless-steel mesh that can be implanted nonsurgically in the coronary or peripheral arteries. Experiments in animals showed complete intimal coverage within weeks and no late thrombosis during a follow-up period of up to one year. We performed 10 implantations in 6 patients for iliac or femoral arterial disease; 24 coronary-artery stents were implanted in 19 patients who presented with coronary-artery restenoses (n = 17) or abrupt closure (n = 4) after transluminal angioplasty or deterioration of coronary-bypass grafts (n = 3). We observed three complications in the group with coronary disease. One thrombotic occlusion of a stent resulted in asymptomatic closure, a second acute thrombosis was managed successfully with thrombolysis, and one patient died after bypass surgery for a suspected but unfound occlusion. Follow-up in the patients has continued for nine months without evidence of any further restenoses within the stented segments. Our preliminary experience suggests that this vascular endoprosthesis may offer a useful way to prevent occlusion and restenosis after transluminal angioplasty. Long-term follow-up will be required to validate the early success of this procedure.
TL;DR: The body of scientific evidence regarding the mechanisms and effects of nociceptive activity in newborn infants has not been addressed directly and the pervasive view of neonatal pain is that newborns are frequently not given analgesic or anesthetic agents during invasive procedures, including surgery.
Abstract: THE evaluation of pain in the human fetus and neonate is difficult because pain is generally defined as a subjective phenomenon.1 Early studies of neurologic development concluded that neonatal responses to painful stimuli were decorticate in nature and that perception or localization of pain was not present.2 Furthermore, because neonates may not have memories of painful experiences, they were not thought capable of interpreting pain in a manner similar to that of adults.3 4 5 On a theoretical basis, it was also argued that a high threshold of painful stimuli may be adaptive in protecting infants from pain during birth.6 These traditional . . .
TL;DR: The metabolic impact of infectious and neoplastic disease states has long been known to clinicians and may provoke a severe wasting diathesis, in which negative calorie and nitrogen balance lead to death despite the absence of a large parasite or tumor burden.
Abstract: THE metabolic impact of infectious and neoplastic disease states has long been known to clinicians.1 2 3 4 Invasive diseases may disrupt normal homeo-static mechanisms, both locally and systemically. For example, acute gram-negative infections frequently lead to profound metabolic acidosis and to biphasic changes in plasma glucose concentration, both seen in the context of hypotension, disseminated intravascular coagulation, and widespread tissue injury.5 6 7 8 9 10 11 12 Chronic infectious diseases, as well as neoplastic diseases, may provoke a severe wasting diathesis, in which negative calorie and nitrogen balance lead to death despite the absence of a large parasite or tumor burden. It was once widely believed that invasive . . .
TL;DR: It is concluded that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.
Abstract: The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.
TL;DR: Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex as mentioned in this paper.
Abstract: Congenital adrenal hyperplasia is a group of autosomal recessive disorders resulting from the deficiency of one of the enzymes required for cortisol synthesis in the adrenal cortex. The most freque...
TL;DR: It is concluded that an urgent need exists for improved methods in literature searching, quality evaluation of trials, and synthesizing of the results.
Abstract: A new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. We found 86 meta-analyses of reports of randomized controlled trials in the English-language literature. We evaluated the quality of these meta-analyses, using a scoring method that considered 23 items in six major areas--study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Only 24 meta-analyses (28 percent) addressed all six areas, 31 (36 percent) addressed five, 25 (29 percent) addressed four, 5 (6 percent) addressed three, and 1 (1 percent) addressed two. Of the 23 individual items, between 1 and 14 were addressed satisfactorily (mean +/- SD, 7.7 +/- 2.7). We conclude that an urgent need exists for improved methods in literature searching, quality evaluation of trials, and synthesizing of the results.
TL;DR: The administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.
Abstract: Adoptive immunotherapy involving bolus-dose recombinant interleukin-2 (rIL-2) has been reported to induce tumor regression in some patients with cancer, but has been associated with severe fluid retention and cardiopulmonary stress. In an effort to preserve the efficacy but reduce the toxicity of this treatment, we used escalating doses of rIL-2 as a constant infusion rather than as a bolus dose. Forty-eight patients with advanced cancer received rIL-2 as a 24-hour infusion in five-day cycles separated by five-day periods of rest and leukapheresis. Eight patients were removed from the study before receiving cells activated in vitro. In the 40 who could be evaluated for their response, there were 13 partial responses (32.5 percent) and 2 minor responses. Partial responses were observed in Hodgkin's disease (one of one), non-Hodgkin's lymphoma (one of one), lung cancer (one of five), ovarian cancer (one of one), parotid cancer (one of two), renal cancer (three of six), and melanoma (five of ten). Responses were associated with a good performance status, a base-line lymphocyte count above 1400 per cubic millimeter, and an rIL-2-induced lymphocyte count of at least 6000. Optimal lymphocytosis required a priming dose of rIL-2 of 3 X 10(6) U per square meter of body-surface area per day, and 15 of 28 patients receiving this priming dose responded to treatment. A weight gain of more than 10 percent of total body weight (five patients) and dyspnea at rest (six patients) were unusual events restricted to patients with poorer pretreatment performance. We conclude that the administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.
TL;DR: Data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease, and this increase appears to be prevented by estrogen-replacement therapy.
Abstract: To determine the relation of menopause to the risk of coronary heart disease, we analyzed data on a prospective cohort of 121,700 U.S. women 30 to 55 years old who were followed from 1976 to 1982. Information on menopausal status, the type of menopause, and other risk factors was obtained in 1976 and updated every two years by mailing questionnaires. Through 1982, the follow-up rate was 98.3 percent for mortality and 95.4 percent for nonfatal events. After we controlled for age and cigarette smoking, women who had had a natural menopause and who had never taken replacement estrogen had no appreciable increase in the risk of coronary heart disease, as compared with premenopausal women (adjusted rate ratio, 1.2; 95 percent confidence limits, 0.8 and 1.8). Again compared with premenopausal women, the occurrence of a natural menopause together with the use of estrogens did not affect the risk (rate ratio, 0.8, 95 percent confidence limits, 0.4 and 1.3). Women who had undergone bilateral oophorectomy and who had never taken estrogens after menopause had an increased risk (rate ratio, 2.2; 95 percent confidence limits, 1.2 and 4.2). However, the use of estrogens in the postmenopausal period appeared to eliminate this increased risk among these women as compared with premenopausal women (rate ratio, 0.9; 95 percent confidence limits, 0.6 and 1.6). These data suggest that, in contrast to a natural menopause, bilateral oophorectomy increases the risk of coronary heart disease. This increase appears to be prevented by estrogen-replacement therapy.
TL;DR: Findings on the epidemiology of post-traumatic stress disorder in 2493 participants examined as part of a nationwide general-population survey of psychiatric disorders show Behavioral problems before the age of 15 predicted adult exposure to physical attack and (among Vietnam veterans) to combat, as well as the development ofPost- traumatic stress disorder among those so exposed.
Abstract: There have been numerous studies of post-traumatic stress disorder in trauma victims, war veterans, and residents of communities exposed to disaster. Epidemiologic studies of this syndrome in the general population are rare but add an important perspective to our understanding of it. We report findings on the epidemiology of post-traumatic stress disorder in 2493 participants examined as part of a nationwide general-population survey of psychiatric disorders. The prevalence of a history of post-traumatic stress disorder was 1 percent in the total population, about 3.5 percent in civilians exposed to physical attack and in Vietnam veterans who were not wounded, and 20 percent in veterans wounded in Vietnam. Post-traumatic stress disorder was associated with a variety of other adult psychiatric disorders. Behavioral problems before the age of 15 predicted adult exposure to physical attack and (among Vietnam veterans) to combat, as well as the development of post-traumatic stress disorder among those so exposed. Although some symptoms of post-traumatic stress disorder, such as hyperalertness and sleep disturbances, occurred commonly in the general population, the full syndrome as defined by the Diagnostic and Statistical Manual of Mental Disorders, third edition, was common only among veterans wounded in Vietnam.
TL;DR: It is concluded that etoposide with cisplatin and bleomycin is superior to vinblastine with cisPlatin and Bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.
Abstract: Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.
TL;DR: This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.
Abstract: Systemically disseminated cutaneous T-cell lymphoma is generally resistant to chemotherapy and radiotherapy. We tested a treatment involving the extracorporeal photoactivation of biologically inert methoxsalen (8-methoxypsoralen) by ultraviolet A energy to a form that covalently cross-links DNA. After oral administration of methoxsalen, a lymphocyte-enriched blood fraction was exposed to ultraviolet A (1 to 2 J per square centimeter) and then returned to the patient. The combination of ultraviolet A and methoxsalen caused an 88 +/- 5 percent loss of viability of target lymphocytes, whereas the drug alone was inactive. Twenty-seven of 37 patients with otherwise resistant cutaneous T-cell lymphoma responded to the treatment, with an average 64 percent decrease in cutaneous involvement after 22 +/- 10 weeks (mean +/- SD). The responding group included 8 of 10 patients with lymph-node involvement, 24 of 29 with exfoliative erythroderma, and 20 of 28 whose disease was resistant to standard chemotherapy. Side effects that often occur with standard chemotherapy, such as bone marrow suppression, gastrointestinal erosions, and hair loss, did not occur. Although the mechanism of the beneficial effect is uncertain, an immune reaction to the infused damaged cells may have restricted the activity of the abnormal T cells. This preliminary study suggests that extracorporeal photochemotherapy is a promising treatment for widespread cutaneous T-cell lymphoma.
TL;DR: The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly, and in vitro platelet responsiveness to either adenosine diphosphate or epinephrine was lower.
Abstract: We have previously reported that the frequencies of myocardial infarction and of sudden cardiac death are highest during the period from 6 a.m. to noon. Since platelet aggregation may have a role in triggering these disorders, we measured platelet activity at 3-hour intervals for 24 hours in 15 healthy men. In vitro platelet responsiveness to either adenosine diphosphate (ADP) or epinephrine was lower at 6 a.m. (before the subjects arose) than at 9 a.m. (60 minutes after they arose). The lowest concentration of these agents required to produce biphasic platelet aggregation decreased (i.e., aggregability increased) from a mean ±SEM of 4.7±0.6 to 3.7±0.6 μM (P<0.01) for ADP and from 3.7±0.8 to 1.8±0.5 μM (P<0.01) for epinephrine. The period from 6 to 9 a.m. was the only interval in the 24-hour period during which platelet aggregability increased significantly. We subsequently studied 10 subjects on alternate mornings after they arose at the normal time and after delayed arising. The morning increas...
TL;DR: Aldose reductase inhibitors firmly link defects in myo-inositol metabolism to activation of the polyol pathway in diabetes; the resulting "sorbitol-myo- inositol hypothesis" has been extended from its application to the lenses and peripheral nerves to most of the tissues involved with diabetic complications.
Abstract: During the past decade, our appreciation of the original experiments with myo-inositol supplementation in diabetic rats has greatly expanded. The effects of myo-inositol on nerve conduction are now explained by concepts that were largely unappreciated in 1976, including the fundamental role of phosphoinositide metabolism in cell regulation and the importance of the activity of sodium-potassium-ATPase in nerve conduction. Aldose reductase inhibitors firmly link defects in myo-inositol metabolism to activation of the polyol pathway in diabetes; the resulting "sorbitol-myo-inositol hypothesis" has been extended from its application to the lenses and peripheral nerves to most of the tissues involved with diabetic complications. These biochemical mechanisms provide a new framework within which to explore the complex interactions between hyperglycemia and the vascular, genetic, and environmental variables in the pathogenesis of diabetic complications. It is anticipated that these endeavors will result in the appearance of new classes of therapeutic agents, the first of which--the aldose reductase inhibitors--has emerged from the laboratory and is now undergoing extensive clinical testing. These efforts are very likely to result in the appearance of new treatment methods that may dramatically lighten the burden of chronic complications in patients with diabetes.
TL;DR: It is concluded that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke, and routine anticoagulation may not be warranted.
Abstract: From 1950 to 1980, 3623 patients from Olmsted County, Minnesota, were found to have atrial fibrillation. Ninety-seven of these patients (2.7 percent), who were 60 years old or younger at diagnosis, had lone atrial fibrillation (atrial fibrillation in the absence of overt cardiovascular disease or precipitating illness), and their data were reviewed to determine the incidence of thromboemboli. Twenty of these patients (21 percent) had an isolated episode of atrial fibrillation, 56 (58 percent) had recurrent atrial fibrillation, and 21 (22 percent) had chronic atrial fibrillation. The total follow-up period was 1440 person-years, with a mean of 14.8 years per patient. The mean age at diagnosis was 44 years. Nineteen cardiovascular events occurred in 17 patients; 4 patients had strokes thought to be due to emboli from atrial fibrillation, and 4 had myocardial infarctions without overt evidence of previous coronary artery disease. The probability of survival at 15 years was 94 percent among the patients with lone atrial fibrillation. At 15 years, 1.3 percent of the patients had had a stroke on a cumulative actuarial basis. On an actuarial basis, there was no difference in survival or in survival free of stroke among the patients with the three types of lone atrial fibrillation (i.e., isolated, recurrent, and chronic). We conclude that lone atrial fibrillation in patients under the age of 60 at diagnosis is associated with a very low risk of stroke. This suggests that routine anticoagulation may not be warranted.
TL;DR: The hypothesis that the sedative and autonomic effects of psychotropic drugs increase the risk of falling and fractures in elderly persons is supported and the need for studies of this association in other populations is suggested.
Abstract: To assess the risk of hip fracture associated with the use of four classes of psychotropic drugs, we performed a case-control study of 1021 patients with hip fractures and 5606 controls among elderly Medicaid enrollees. Persons treated with hypnotics-anxiolytics having short (less than or equal to 24 hours) elimination half-lives had no increased risk of hip fracture. By contrast, a significantly increased risk was associated with current use of hypnotics-anxiolytics having long (greater than 24 hours) elimination half-lives (odds ratio, 1.8; 95 percent confidence interval, 1.3 to 2.4), tricyclic antidepressants (odds ratio, 1.9; 95 percent confidence interval, 1.3 to 2.8), and antipsychotics (odds ratio, 2.0; 95 percent confidence interval, 1.6 to 2.6). The risk increased in relation to the doses of drugs in these three classes. An analysis for possible confounding by dementia did not alter the results. Previous but noncurrent use of drugs in these classes conferred no increase in risk. Although a cause-and-effect relation was not proved, these data support the hypothesis that the sedative and autonomic effects of psychotropic drugs increase the risk of falling and fractures in elderly persons. The results suggest the need for studies of this association in other populations and for evaluation of newer psychotropic drugs with fewer undesirable sedative and autonomic effects.
TL;DR: It is concluded that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angiopLasty.
Abstract: We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.
TL;DR: HUMAN neutrophilic polymorphonuclear leukocytes (neutrophils) provide an effective host defense against bacterial and fungal infection, but they are also important in the pathogenesis of tissue damage in certain noninfectious diseases.
Abstract: HUMAN neutrophilic polymorphonuclear leukocytes (neutrophils) provide an effective host defense against bacterial and fungal infection, but they are also important in the pathogenesis of tissue damage in certain noninfectious diseases. Some important events in neutrophil function that will be discussed in this review are shown in Figure 1. Mild to moderate abnormalities of neutrophil function have been reported in many acquired and congenital diseases.1 2 3 4 5 In most of these disorders, the biochemical or morphologic basis of the defects is unknown and the relevance of the neutrophil defect to the manifestations of the disease is unclear. In contrast, persons with marked neutropenia6 or . . .
TL;DR: The data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.
Abstract: Corticosteroids are widely used as therapy for the adult respiratory distress syndrome (ARDS) without proof of efficacy. We conducted a prospective, randomized, double-blind, placebo-controlled trial of methylprednisolone therapy in 99 patients with refractory hypoxemia, diffuse bilateral infiltrates on chest radiography and absence of congestive heart failure documented by pulmonary-artery catheterization. The causes of ARDS included sepsis (27 percent), aspiration pneumonia (18 percent), pancreatitis (4 percent), shock (2 percent), fat emboli (1 percent), and miscellaneous causes or more than one cause (42 percent). Fifty patients received methylprednisolone (30 mg per kilogram of body weight every six hours for 24 hours), and 49 received placebo according to the same schedule. Serial measurements were made of pulmonary shunting, the ratio of partial pressure of arterial oxygen to partial pressure of alveolar oxygen, the chest radiograph severity score, total thoracic compliance, and pulmonary-artery pressure. We observed no statistical differences between groups in these characteristics upon entry or during the five days after entry. Forty-five days after entry there were no differences between the methylprednisolone and placebo groups in mortality (respectively, 30 of 50 [60 percent; 95 percent confidence interval, 46 to 74] and 31 of 49 [63 percent; 95 percent confidence interval, 49 to 77]; P = 0.74) or in the reversal of ARDS (18 of 50 [36 percent] vs. 19 of 49 [39 percent]; P = 0.77). However, the relatively wide confidence intervals in the mortality data make it impossible to exclude a small effect of treatment. Infectious complications were similar in the methylprednisolone group (8 of 50 [16 percent]) and the placebo group (5 of 49 [10 percent]; P = 0.60). Our data suggest that in patients with established ARDS due to sepsis, aspiration, or a mixed cause, high-dose methylprednisolone does not affect outcome.
TL;DR: Seconde partie d'une revue: interrelations entre mecanismes physiopathologiques et manifestations cliniques ; traitement medical; traitement chirurgical.
Abstract: Seconde partie d'une revue: interrelations entre mecanismes physiopathologiques et manifestations cliniques; traitement medical; traitement chirurgical