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Showing papers in "The New England Journal of Medicine in 1988"


Journal ArticleDOI
TL;DR: It is found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas, which are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumors.
Abstract: Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.

6,309 citations


Journal ArticleDOI
TL;DR: It is concluded that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling.
Abstract: To study risk factors for falling, we conducted a one-year prospective investigation, using a sample of 336 persons at least 75 years of age who were living in the community. All subjects underwent detailed clinical evaluation, including standardized measures of mental status, strength, reflexes, balance, and gait; in addition, we inspected their homes for environmental hazards. Falls and their circumstances were identified during bimonthly telephone calls. During one year of follow-up, 108 subjects (32 percent) fell at least once; 24 percent of those who fell had serious injuries and 6 percent had fractures. Predisposing factors for falls were identified in linear-logistic models. The adjusted odds ratio for sedative use was 28.3; for cognitive impairment, 5.0; for disability of the lower extremities, 3.8; for palmomental reflex, 3.0; for abnormalities of balance and gait, 1.9; and for foot problems, 1.8; the lower bounds of the 95 percent confidence intervals were 1 or more for all variables. The risk of falling increased linearly with the number of risk factors, from 8 percent with none to 78 percent with four or more risk factors (P less than 0.0001). About 10 percent of the falls occurred during acute illness, 5 percent during hazardous activity, and 44 percent in the presence of environmental hazards. We conclude that falls among older persons living in the community are common and that a simple clinical assessment can identify the elderly persons who are at the greatest risk of falling.

6,197 citations


Journal ArticleDOI
TL;DR: This seminar reviews recent studies suggesting that the central pathologic features of diabetic complications are caused by the hyperglycemia-accelerated formation of nonenzymatic advanced gly...
Abstract: IN this seminar we review recent studies suggesting that the central pathologic features of diabetic complications are caused by the hyperglycemia-accelerated formation of nonenzymatic advanced gly...

2,556 citations


Journal ArticleDOI
TL;DR: It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells.
Abstract: Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients had received a single intravenous dose of cyclophosphamide. Objective regression of the cancer was observed in 9 of 15 patients (60 percent) who had not previously been treated with interleukin-2 and in 2 of 5 patients (40 percent) in whom previous therapy with interleukin-2 had failed. Regression of cancer occurred in the lungs, liver, bone, skin, and subcutaneous sites and lasted from 2 to more than 13 months. Toxic effects of interleukin-2 occurred, although the treatment course was short (five days); these side effects were reversible. It appears that in patients with metastatic melanoma, this experimental treatment regimen can produce higher response rates than those achieved with interleukin-2 administered alone or with lymphokine-activated killer cells. It is too early to determine whether this new form of immunotherapy can improve survival, but further trials seem warranted.

2,206 citations


Journal ArticleDOI
TL;DR: The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent and most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.
Abstract: We studied the risk of early loss of pregnancy by collecting daily urine specimens from 221 healthy women who were attempting to conceive. Urinary concentrations of human chorionic gonadotropin (hCG) were measured for a total of 707 menstrual cycles with use of an immunoradiometric assay that is able to detect hCG levels as low as 0.01 ng per milliliter, with virtually 100 percent specificity for hCG in the presence of luteinizing hormone. Our criterion for early pregnancy--an hCG level above 0.025 ng per milliliter on three consecutive days--was determined after we compared the hCG levels in the study group with the levels in a comparable group of 28 women who had undergone sterilization by tubal ligation. We identified 198 pregnancies by an increase in the hCG level near the expected time of implantation. Of these, 22 percent ended before pregnancy was detected clinically. Most of these early pregnancy losses would not have been detectable by the less sensitive assays for hCG used in earlier studies. The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent. Most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.

1,926 citations


Journal ArticleDOI
TL;DR: It is proposed that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits are less marked or restricted to discrete functions only.
Abstract: Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.

1,909 citations


Journal ArticleDOI
TL;DR: It is concluded that the response to endotoxin is associated with a brief pulse of circulating tumor necrosis factor and that the resultant responses are effected through the cyclooxygenase pathway.
Abstract: Cytokines, products of stimulated macrophages, are thought to mediate many host responses to bacterial infection, but increased circulating cytokine concentrations have not been detected consistently in infected patients. We measured plasma concentrations of circulating tumor necrosis factor alpha (cachectin), interleukin-1β, and gamma interferon, together with physiologic and hormonal responses, in 13 healthy men after intravenous administration of Escherichia coli endotoxin (4 ng per kilogram of body weight) and during a control period of saline administration. Eight additional subjects received ibuprofen before receiving endotoxin or saline. Plasma levels of tumor necrosis factor were generally less than 35 pg per milliliter throughout the control period, but increased 90 to 180 minutes after endotoxin administration to mean peak concentrations of 240±70 pg per milliliter, as compared with 35±5 pg per milliliter after saline administration. Host responses were temporally associated with the in...

1,671 citations


Journal ArticleDOI
TL;DR: The results suggest that because of the high prevalence of clinically latent venous thrombosis, paradoxical embolism through a patent foramen ovale may be responsible for stroke more often than is usually suspected.
Abstract: The cause of ischemic stroke in younger adults is undefined in as many as 35 percent of patients. We studied the prevalence of patent foramen ovale as detected by contrast echocardiography in a population of 60 adults under 55 years old with ischemic stroke and a normal cardiac examination. We compared the results with those in a control group of 100 patients. The prevalence of patent foramen ovale was significantly higher in the patients with stroke (40 percent) than in the control group (10 percent, P less than 0.001). Among the patients with stroke, the prevalence of patent foramen ovale was 21 percent in 19 patients with an identifiable cause of their stroke, 40 percent in 15 patients with no identifiable cause but a risk factor for stroke, such as mitral valve prolapse, migraine, or use of contraceptive agents, and 54 percent in 26 patients with no identifiable cause (P less than 0.10). These results suggest that because of the high prevalence of clinically latent venous thrombosis, paradoxical embolism through a patent foramen ovale may be responsible for stroke more often than is usually suspected.

1,536 citations


Journal ArticleDOI
TL;DR: The goal is to provide a clear picture of the individual components of the immune system and provide a strategy for individualized treatment of these components according to their Kesslerian importance.
Abstract: WITH neither the time nor the resources available to prevent, detect, or treat every disorder in every patient, which preventive, diagnostic, or therapeutic interventions should take priority? When

1,524 citations


Journal ArticleDOI
TL;DR: Findings indicate that right ventricular cardiomyopathy, the cause of which is still unknown, may be more frequent than previously thought and may represent an important cause of sudden death among young people in the Veneto Region of northeastern Italy.
Abstract: From 1979 to 1986, we conducted postmortem studies of 60 persons under 35 years of age who had died suddenly in the Veneto Region of northeastern Italy. Unexpectedly, we found that 12 subjects — 7 males and 5 females ranging in age from 13 to 30 years — had morphologic features of right ventricular cardiomyopathy. This disorder had not been diagnosed or suspected before the subjects died. In five cases, sudden death was the first sign of disease; the remaining seven subjects had a history of palpitations, syncopal episodes, or both, and in five of those seven, ventricular arrhythmias had previously been recorded on electrocardiographic examination. Ten of the subjects had died during exertion. At autopsy, the subjects' heart weights were normal or moderately increased. Two main histologic patterns were identified — a lipomatous transformation or a fibrolipomatous transformation of the right ventricular free wall (6 cases each); in all cases, the left ventricle was substantially spared. Signs of m...

1,474 citations


Journal ArticleDOI
TL;DR: The glycopeptide antibiotic agents vancomycin and teicoplanin are useful in the treatment of severe infections due to gram-positive bacteria.
Abstract: THE glycopeptide antibiotic agents vancomycin and teicoplanin are useful in the treatment of severe infections due to gram-positive bacteria.1 2 3 Staphylococci, streptococci, and enterococci are a...

Journal ArticleDOI
TL;DR: The presence of the same serologic marker in patients with kidney-limited and arteritis-associated necrotizing and crescentic glomerulonephritis, including Wegener's granulomatosis and polyarteritis nodosa, suggests that these clinically diverse diseases may have a similar pathogenesis, initiated by autoantibody-mediated activation of neutrophils.
Abstract: Anti-neutrophil cytoplasmic autoantibodies have been found in patients with systemic arteritis and glomerulonephritis We studied the disease distribution and antigen specificity of these autoantibodies Anti-neutrophil cytoplasmic autoantibodies were identified by indirect immunofluorescence microscopy in 27 of 35 patients with idiopathic necrotizing and crescentic glomerulonephritis, in whom the manifestations of disease ranged from injury limited to the kidney to systemic arteritis The incidence and titers of the autoantibodies did not differ between patients with disease limited to the kidney and those with systemic disease Anti-neutrophil immunostaining was detected in 5 of 11 patients with lupus nephritis, 4 of 71 patients with other renal diseases, and none of 50 normal controls This distribution of autoantibodies was confirmed by an enzyme-linked immunosorbent assay (ELISA) using neutrophil lysate as antigen According to ELISA, anti-neutrophil cytoplasmic autoantibodies were found to be specific for constituents of primary granules Two types of autoantibodies were identified; one with reactivity with myeloperoxidase on ELISA produced an artifactual perinuclear immunostaining of alcohol-fixed neutrophils, and another with no reactivity with myeloperoxidase on ELISA produced diffuse cytoplasmic immunostaining The presence of the same serologic marker in patients with kidney-limited and arteritis-associated necrotizing and crescentic glomerulonephritis, including Wegener's granulomatosis and polyarteritis nodosa, suggests that these clinically diverse diseases may have a similar pathogenesis, initiated by autoantibody-mediated activation of neutrophils

Journal ArticleDOI
TL;DR: Most deep-vein thromboses are subclinical and resolve completely when mobility is restored, although some do produce permanent valvular damage and chronic venous insufficiency, and a few, however, may travel to the lungs and, depending on how much of the pulmonary circulation is.
Abstract: DURING prolonged general anesthesia and any period of limited mobility following surgery, thrombus formation may be initiated in the deep veins of the legs. Studies employing Radio-labeled fibrinogen or venography have revealed deep-vein thrombosis in 20 to 30 percent of patients who have undergone general surgery and in an even larger proportion of patients who have had orthopedic surgery.1 2 3 Most such thromboses are subclinical and resolve completely when mobility is restored, although some do produce permanent valvular damage and chronic venous insufficiency. A few, however, may travel to the lungs and, depending on how much of the pulmonary circulation is . . .

Journal ArticleDOI
TL;DR: It is concluded that a low rate of energy expenditure may contribute to the aggregation of obesity in families.
Abstract: The contribution of reduced energy expenditure to the development of obesity has been a point of controversy. We measured 24-hour energy expenditure (adjusted for body composition, age, and sex), in a respiratory chamber, in 95 southwestern American Indians. Energy expenditure correlated with the rate of change in body weight over a two-year follow-up period (r = -0.39, P less than 0.001). The estimated risk of gaining more than 7.5 kg in body weight was increased fourfold in persons with a low adjusted 24-hour energy expenditure (200 kcal per day below predicted values) as compared with persons with a high 24-hour energy expenditure (200 kcal per day above predicted values; P less than 0.01). In another 126 subjects, the adjusted metabolic rate at rest at the initial visit was also found to predict the gain in body weight over a four-year follow-up period. When the 15 subjects who gained more than 10 kg were compared with the remaining 111 subjects, the initial mean (+/- SD) adjusted metabolic rate at rest was lower in those who gained weight (1694 +/- 103 vs. 1764 +/- 109 kcal per day; P less than 0.02) and increased to 1813 +/- 134 kcal per day (P less than 0.01) after a mean weight gain of 15.7 +/- 5.7 kg. In a group of 94 siblings from 36 families, values for adjusted 24-hour energy expenditure aggregated in families (intraclass correlation = 0.48). We conclude that a low rate of energy expenditure may contribute to the aggregation of obesity in families.

Journal ArticleDOI
TL;DR: It is concluded that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoringHeparin over aspirin.
Abstract: We tested the usefulness of aspirin (325 mg twice daily), heparin (1000 units per hour by intravenous infusion), and a combination of the two in the early management of acute unstable angina pectoris in a double-blind, randomized, placebo-controlled trial involving 479 patients. The patients entered the study as soon as possible after hospital admission (at a mean [+/- SD] of 7.9 +/- 8.0 hours after the last episode of pain), and the study was ended after 6 +/- 3 days, when definitive therapy had been selected. Major end points--refractory angina, myocardial infarction, and death--occurred in 23, 12, and 1.7 percent of the 118 patients receiving placebo, respectively. Heparin was associated with a decrease in the occurrence of refractory angina (P = 0.002). The incidence of myocardial infarction was significantly reduced in the groups receiving aspirin (3 percent; P = 0.01), heparin (0.8 percent; P less than 0.001), and aspirin plus heparin (1.6 percent, P = 0.003), and no deaths occurred in these groups. There were too few deaths overall to permit evaluation of the effect of treatment on this end point. The combination of aspirin and heparin had no greater protective effect than heparin alone but was associated with slightly more serious bleeding (3.3 vs. 1.7 percent). We conclude that in the acute phase of unstable angina, either aspirin or heparin treatment is associated with a reduced incidence of myocardial infarction, and there is a trend favoring heparin over aspirin. Heparin treatment is also associated with a reduced incidence of refractory angina.

Journal ArticleDOI
TL;DR: It is concluded that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.
Abstract: Among 141 consecutive patients with neuro-psychiatric abnormalities due to cobalamin deficiency, we found that 40 (28 percent) had no anemia or macrocytosis. The hematocrit was normal in 34, the mean cell volume was normal in 25, and both tests were normal in 19. Characteristic features in such patients included paresthesia, sensory loss, ataxia, dementia, and psychiatric disorders; longstanding neurologic symptoms without anemia; normal white-cell and platelet counts and serum bilirubin and lactate dehydrogenase levels; and markedly elevated serum concentrations of methylmalonic acid and total homocysteine. Serum cobalamin levels were above 150 pmol per liter (200 pg per milliliter) in 2 patients, between 75 and 150 pmol per liter (100 and 200 pg per milliliter) in 16, and below 75 pmol per liter (100 pg per milliliter) in only 22. Except for one patient who died during the first week of treatment, every patient in this group benefited from cobalamin therapy. Responses included improvement in neuropsychiatric abnormalities (39 of 39), improvement (often within the normal range) in one or more hematologic findings (36 of 39), and a decrease of more than 50 percent in levels of serum methylmalonic acid, total homocysteine, or both (31 of 31). We conclude that neuropsychiatric disorders due to cobalamin deficiency occur commonly in the absence of anemia or an elevated mean cell volume and that measurements of serum methylmalonic acid and total homocysteine both before and after treatment are useful in the diagnosis of these patients.

Journal ArticleDOI
TL;DR: Effets preventifs et benefiques sur l'atherosclerose et l'infarctus, dans l'alimentation, sur les lipides plasmatiques, sur le metabolisme and the fonctions des eicosanoides.
Abstract: A detailed technical overview summarizes and discusses available evidence concerning the effects of fish oil n-3 polyunsaturated fatty acids (PUFA's) on reducing cardiovascular disease risks. Attention is given to: the characteristics and metabolism of n-6 and n-3 PUFA's and the effects of n-3 PUFA's on plasma lipid profiles; the role of n-3 PUFA's in reducing atherosclerosis risk; possible protection of n-3 PUFA's during myocardial infarction; the relative importance of eicosapentaenoic vs. docosahexaneoic acids; and appropriate intakes of n-3 PUFA's. The potential adverse health effects from ingesting fish oils also are discussed.(wz)

Journal ArticleDOI
TL;DR: The right of patients to accept or refuse recommended treatment requires careful reassessment when their decision-making capacities are called into question, and the clinical examiner's proper role is to gather relevant information and decide whether an adjudication of incompetence is required.
Abstract: The right of patients to accept or refuse recommended treatment requires careful reassessment when their decision-making capacities are called into question. Patients must be informed appropriately about treatment decisions and be given an opportunity to demonstrate their highest level of mental functioning. The legal standards for competence include the four related skills of communicating a choice, understanding relevant information, appreciating the current situation and its consequences, and manipulating information rationally. Since competence is a legal concept and can be formally determined only in court, the clinical examiner's proper role is to gather relevant information and decide whether an adjudication of incompetence is required. Treatment for impairment of mental functioning can sometimes restore patients' capacities, making it unnecessary to deprive them of their decision-making powers.

Journal ArticleDOI
TL;DR: Low back pain is usually a self-limiting symptom, but it costs at least $16 billion each year and disables 5.4 million Americans, and the fact that a benign physical condition has such an importa...
Abstract: LOW back pain is usually a self-limiting symptom, but it costs at least $16 billion each year1 , 2 and disables 5.4 million Americans.3 The fact that a benign physical condition has such an importa...

Journal ArticleDOI
TL;DR: It is concluded that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serogroup 4b of the epidemic phagetype in Brand A Mexican-style cheese.
Abstract: In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.

Journal ArticleDOI
TL;DR: It is indicated that after anterior myocardial infarction, ventricular enlargement is progressive and that captopril may attenuate this process, reduce filling pressures, and improve exercise tolerance.
Abstract: We conducted a double-blind, placebo-controlled trial to determine whether ventricular dilatation continues during the late convalescent phase after myocardial infarction and whether therapy with captopril alters this process. Fifty-nine patients with a first anterior myocardial infarction and a radionuclide ejection fraction of 45 percent or less underwent cardiac catheterization 11 to 31 days after infarction, when they were not in overt congestive heart failure. They were randomly assigned to placebo or captopril and were followed for one year. A repeat catheterization was performed to evaluate interval changes in hemodynamic function and left ventricular volume. Thirty-eight male patients were evaluated with maximal-exercise treadmill tests every three months. No differences were detected at base line in clinical, hemodynamic, or quantitative ventriculographic variables. During one year of follow-up, the end-diastolic volume of the left ventricle increased by a mean [±SEM] of 21 ±8 ml (P<0.02...

Journal ArticleDOI
TL;DR: Whereas psychopharmacologic intervention may be required to resolve an active episode of major depression and to prevent recurrences, psychotherapy may be equally important to lessen the burden of stress imposed by intense inner conflict and counterproductive defenses.
Abstract: Thousands of studies have been conducted of the functioning of the many neurotransmitter systems in order to explore the biologic basis of major depressive disorder. Instead of reviewing this literature exhaustively, we have attempted to propose a model that accommodates the clinical observation that chronic stress early in life in vulnerable persons predisposes them to major depression with contemporary observations of the potential consequences of repeated central nervous system exposure to effectors of the stress response. This model accords with current clinical judgment that major depression is best treated with a combination of psychopharmacologic agents and psychotherapy. Accordingly, whereas psychopharmacologic intervention may be required to resolve an active episode of major depression and to prevent recurrences, psychotherapy may be equally important to lessen the burden of stress imposed by intense inner conflict and counterproductive defenses.

Journal ArticleDOI
TL;DR: In patients with autism, neocerebellar abnormality may directly impair cognitive functions that some investigators have attributed to the neoceebellum; may indirectly affect the development and functioning of one or more systems involved in cognitive, sensory, autonomic, and motor activities.
Abstract: Autism is a neurologic disorder that severely impairs social, language, and cognitive development. Whether autism involves maldevelopment of neuroanatomical structures is not known. The size of the cerebellar vermis in patients with autism was measured on magnetic resonance scans and compared with its size in controls. The neocerebellar vermal lobules VI and VII were found to be significantly smaller in the patients. This appeared to be a result of developmental hypoplasia rather than shrinkage or deterioration after full development had been achieved. In contrast, the adjacent vermal lobules I to V, which are ontogenetically, developmentally, and anatomically distinct from lobules VI and VII, were found to be of normal size. Maldevelopment of the vermal neocerebellum had occurred in both retarded and nonretarded patients with autism. This localized maldevelopment may serve as a temporal marker to identify the events that damage the brain in autism, as well as other neural structures that may be concomitantly damaged. Our findings suggest that in patients with autism, neocerebellar abnormality may directly impair cognitive functions that some investigators have attributed to the neocerebellum; may indirectly affect, through its connections to the brain stem, hypothalamus, and thalamus, the development and functioning of one or more systems involved in cognitive, sensory, autonomic, and motor activities; or may occur concomitantly with damage to other neural sites whose dysfunction directly underlies the cognitive deficits in autism.

Journal ArticleDOI
TL;DR: NICOTINE has been consumed in the form of tobacco and other plants for many hundreds of years and has become available as a pharmaceutical agent, marketed as a chewing gum to help people stop smoking.
Abstract: NICOTINE has been consumed in the form of tobacco and other plants for many hundreds of years. The compulsive use of tobacco has been observed in nearly every culture into which tobacco has been introduced. Nearly 30 percent of adult Americans smoke despite, in most cases, a desire to quit and despite common knowledge of the health hazards.1 Their failure to quit smoking is attributable in large part to the addictive properties of nicotine. Recently, nicotine has become available as a pharmaceutical agent, marketed as a chewing gum to help people stop smoking. In addition to its direct effect on . . .

Journal ArticleDOI
TL;DR: It is concluded that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion, and it may be superior when treatment is delayed.
Abstract: During the investigational use of oral N-acetylcysteine as an antidote for poisoning with acetaminophen, 11,195 cases of suspected acetaminophen overdose were reported. We describe the outcomes of 2540 patients with acetaminophen ingestions treated with a loading dose of 140 mg of oral N-acetylcysteine per kilogram of body weight, followed four hours later by 70 mg per kilogram given every four hours for an additional 17 doses. Patients were categorized for analysis on the basis of initial plasma acetaminophen concentrations and the interval between ingestion and treatment. Hepatotoxicity developed in 6.1 percent of patients at probable risk when N-acetylcysteine was started within 10 hours of acetaminophen ingestion and in 26.4 percent of such patients when therapy was begun 10 to 24 hours after ingestion. Among patients at high risk who were treated 16 to 24 hours after an acetaminophen overdose, hepatotoxicity developed in 41 percent--a rate lower than that among historical controls. When given within eight hours of acetaminophen ingestion, N-acetylcysteine was protective regardless of the initial plasma acetaminophen concentration. There was no difference in outcome whether N-acetylcysteine was started zero to four or four to eight hours after ingestion, but efficacy decreased with further delay. There were 11 deaths among the 2540 patients (0.43 percent); in the nine fatal cases in which aminotransferase was measured before treatment, values were elevated before N-acetylcysteine was started. No deaths were clearly caused by acetaminophen among patients in whom N-acetylcysteine therapy was begun within 16 hours. We conclude that N-acetylcysteine treatment should be started within eight hours of an acetaminophen overdose, but that treatment is still indicated at least as late as 24 hours after ingestion. On the basis of available data, the 72-hour regimen of oral N-acetylcysteine is as effective as the 20-hour intravenous regimen described previously, and it may be superior when treatment is delayed.

Journal ArticleDOI
TL;DR: Moderate alcohol consumption among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.
Abstract: In 1980, 87,526 female nurses 34 to 59 years of age completed a dietary questionnaire that assessed their consumption of beer, wine, and liquor. By 1984, during 334,382 person-years of follow-up, we had documented 200 incident cases of severe coronary heart disease (164 nonfatal myocardial infarctions and 36 deaths due to coronary disease), 66 ischemic strokes, and 28 subarachnoid hemorrhages. Follow-up was 98 percent complete. As compared with nondrinkers, women who consumed 5 to 14 g of alcohol per day (three to nine drinks per week) had a relative risk of coronary disease of 0.6 (95 percent confidence interval, 0.4 to 0.9); for 15 to 24 g per day the relative risk was 0.6 (0.3 to 1.1), and for 25 g or more per day it was 0.4 (0.2 to 0.8), after adjustment for risk factors for coronary disease. Alcohol intake was also associated with a decreased risk of ischemic stroke. For 5 to 14 g of alcohol per day the relative risk was 0.3 (0.1 to 0.7), and for 15 g per day or more it was 0.5 (0.2 to 1.1). In contrast, although the number of cases of subarachnoid hemorrhage was small, alcohol intake tended to be associated with an increased risk of this disorder; for 5 to 14 g per day the relative risk was 3.7 (1.0 to 13.8). These prospective data suggest that among middle-aged women, moderate alcohol consumption decreases the risks of coronary heart disease and ischemic stroke but may increase the risk of subarachnoid hemorrhage.

Journal ArticleDOI
TL;DR: It is concluded that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic Acid in the diet.
Abstract: We studied the metabolic effects of stearic acid (18:0) on plasma lipoprotein levels in 11 subjects during three dietary periods of three weeks each. The three liquid-formula diets, which were used in random order, were high in palmitic acid (16:0), stearic acid, and oleic acid (18:1), respectively. Caloric intakes were the same during the three periods. As compared with the values observed when the subjects were on the high-palmitic-acid diet, plasma total cholesterol decreased by an average of 14 percent during consumption of the high-stearic-acid diet (P less than 0.005) and by 10 percent during consumption of the high-oleic-acid diet (P less than 0.02). Low-density lipoprotein cholesterol levels fell by 21 percent in subjects on the high-stearic-acid diet (P less than 0.005) and by 15 percent in subjects on the high-oleic-acid diet (P less than 0.005). No significant differences were observed in the plasma levels of triglycerides or high-density lipoprotein cholesterol among the three diets. Measurements of the intestinal absorption of palmitic, stearic, and oleic acids revealed essentially complete absorption of each during the three dietary periods. The oleic acid content of plasma triglycerides and cholesteryl esters increased significantly during the high-stearic-acid period, suggesting that stearic acid is rapidly converted to oleic acid. We conclude that stearic acid appears to be as effective as oleic acid in lowering plasma cholesterol levels when either replaces palmitic acid in the diet.

Journal ArticleDOI
TL;DR: This review attempts a reasoned psychiatric appraisal of the prototypical abused psyche in the context of cocaine use.
Abstract: SENSATIONALISM and shifting acceptance of drug use have influenced much of what has been written about cocaine. This review attempts a reasoned psychiatric appraisal of the prototypical abused psyc...

Journal ArticleDOI
TL;DR: It is demonstrated that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation and its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.
Abstract: We evaluated the ability of human recombinant granulocyte colony-stimulating factor (rhG-CSF) to prevent chemotherapy-induced neutropenia or to accelerate recovery from this complication and thus allow patients to receive full doses of antineoplastic agents on time, according to protocol design. Twenty-seven patients with transitional-cell carcinoma of the urothelium who were undergoing treatment with methotrexate, doxorubicin, vinblastine, and cisplatin were given rhG-CSF (up to 60 micrograms per kilogram of body weight per day) before their first cycle of combination chemotherapy, during the first cycle, or at both points. Treatment with rhG-CSF before chemotherapy resulted in a dose-dependent increase in the absolute neutrophil count. Treatment with rhG-CSF after chemotherapy significantly reduced the number of days (91 percent) per patient on which the absolute neutrophil count was 1000 per microliter or less (P = 0.0039), reduced the number of days (1 vs. 35) on which antibiotics were used to treat fever and neutropenia, and significantly increased the percentage (100 vs. 29 percent) of patients qualified to receive planned chemotherapy on day 14 of the treatment cycle (P = 0.0015). In addition, the incidence of mucositis was significantly decreased (11 vs. 44 percent, P = 0.041), as was its severity. These findings demonstrate that rhG-CSF is a potent stimulus of normal neutrophil proliferation and maturation. In addition, its administration can reduce both the hematopoietic and oral toxicity of chemotherapy.