Showing papers in "The New England Journal of Medicine in 1977"
TL;DR: If validated by prospective application, the multifactorial index may allow preoperative estimation of cardiac risk independent of direct surgical risk.
Abstract: To determine which preoperative factors might affect the development of cardiac complications after major noncardiac operations, we prospectively studied 1001 patients over 40 years of age. By multivariate discriminant analysis, we identified nine independent significant correlates of life-threatening and fatal cardiac complications: preoperative third heart sound or jugular venous distention; myocardial infarction in the preceding six months; more than five premature ventricular contractions per minute documented at any time before operation; rhythm other than sinus or presence of premature atrial contractions on preoperative electrocardiogram; age over 70 years; intraperitoneal, intrathoracic or aortic operation; emergency operation; important valvular aortic stenosis; and poor general medical condition. Patients could be separated into four classes of significantly different risk. Ten of the 19 postoperative cardiac fatalities occurred in the 18 patients at highest risk. If validated by prospective application, the multifactorial index may allow preoperative estimation of cardiac risk independent of direct surgical risk.
2,476 citations
TL;DR: The semiquantitative technic distinguishes infection (greater than or equal to 15 colonies) from contamination and is more specific in diagnosis of catheter-related septicemia than culture of the catheter in broth.
Abstract: We evaluated a semiquantitative culture technic for identifying infection due to intravenous catheters: rolling the catheter segment across blood agar. This method was compared to broth culture. Of 250 catheters studied, 225 (90%) had low-density colonization on semiquantitative culture (less than 15 colonies on the plate) although 49 (19.6%) of these grew some organisms in broth or on the plate. None of these catheters led to septicemia. Twenty-five catheters (10%) grew greater than or equal to 15 colonies by the semiquantitative technic; most gave confluent growth. Septicemia originated from four of these catheters (P = 0.008). Of 37 catheters exposed to bacteremias from distant foci of infection, four yielded matching growth in broth, whereas none were concordant with the blood isolate on semiquantitative culture. Local inflammation was associated with high-density colonization semiquantitative culture (P less than 0.001). The semiquantitative technic distinguishes infection (greater than or equal to 15 colonies) from contamination and is more specific in diagnosis of catheter-related septicemia than culture of the catheter in broth.
1,960 citations
Abstract: Limits on health-care resources mandate that resource-allocation decisions be guided by considerations of cost in relation to expected benefits. In cost-effectiveness analysis, the ratio of net health-care costs to net health benefits provides an index by which priorities may be set. Quality-of-life concerns, including both adverse and beneficial effects of therapy, may be incorporated in the calculation of health benefits as adjustments to life expectancy. The timing of future benefits and costs may be accounted for by the appropriate use of discounting. Current decisions must inevitably be based on imperfect information, but sensitivity analysis can increase the level of confidence in some decisions while suggesting areas where further research may be valuable in guiding others. Analyses should be adaptable to the needs of various health-care decision makers, including planners, administrators and providers.
1,855 citations
TL;DR: An explosive, common-source outbreak of pneumonia caused by a previously unrecognized bacterium affected primarily persons attending an American Legion convention in Philadelphia in July, 1976, killing 29 people, and epidemiologic analysis suggested that exposure may have occurred in the lobby of the headquarters hotel or in the area immediately surrounding the hotel.
Abstract: An explosive, common-source outbreak of pneumonia caused by a previously unrecognized bacterium affected primarily persons attending an American Legion convention in Philadelphia in July, 1976. Twenty-nine of 182 cases were fatal. Spread of the bacterium appeared to be air borne. The source of the bacterium was not found, but epidemiologic analysis suggested that exposure may have occurred in the lobby of the headquarters hotel or in the area immediately surrounding the hotel. Person-to-person spread seemed not to have occurred. Many hotel employees appeared to be immune, suggesting that the agent may have been present in the vicinity, perhaps intermittently, for two or more years.
1,468 citations
TL;DR: It is concluded that Legionnaires' disease is caused by a gram-negative bacterium that may be responsible for widespread infection.
Abstract: To identify the etiologic agent of Legionnaire's disease, we examined patients' serum and tissue specimens in a search for toxins, bacteria, fungi, chlamydiae, rickettsiae and viruses. From the lungs of four of six patients we isolated a gram-negative, non-acid-fast bacillus in guinea pigs. The bacillus could be transferred to yolk sacs of embryonated eggs. Classification of this organism is incomplete. We used yolk-sac cultures of the bacillus as antigen to survey suspected serum specimens, employing antihuman-globulin fluorescent antibody. When compared to controls, specimens from 101 to 111 patients meeting clinical criteria of Legionnaires' disease showed diagnostic increases in antibody titers. Diagnostic increases were also found in 54 recent sporadic cases of severe pneumonia and, retrospectively, in stored serum from most patients in two other previously unsolved outbreaks of respiratory disease. We conclude that Legionnaires' disease is caused by a gram-negative bacterium that may be responsible for widespread infection.
1,173 citations
TL;DR: Acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis.
Abstract: During hemodialysis, cardiopulmonary decompensation may appear in uremic patients, possibly caused by plugging of pulmonary vessels by leukocytes In 34 patients we noted leukopenia (20% of initial levels) during hemodialysis that in 15 was associated with impaired pulmonary function When we infused autologous plasma, incubated with dialyzer cellophane, into rabbits and sheep, sudden leukopenia and hypoxia occurred, with doubling of pulmonary-artery pressures and quintupling of pulmonary-lymph effluent Histologic examination showed severe pulmonary-vessel-leukostasis and interstitial edema The syndrome was prevented by preinactivation of complement but was reproduced by infusions of plasma in which complement was activated by zymosan Thus, acute pulmonary dysfunction from complement-mediated leukostasis may play a major part in the acute cardiopulmonary complications of cellophane-membrane hemodialysis
951 citations
TL;DR: The findings strongly suggest that regular use of three or more drinks of alcohol per day is a risk factor for hypertension.
Abstract: We studied blood pressure in relation to known drinking habits of 83,947 men and women of three races (83.5 per cent white). Using health-check-up questionnaire responses, we classified persons as nondrinkers or according to usual daily number of drinks: two or fewer per day, three to five per day, or six or more per day. As compared to nondrinkers blood pressures of men taking two or fewer drinks per day were similar. Women who took two or fewer drinks per day had slightly lower pressures. Men and women who took three or more drinks per day had higher systolic pressures (P less than 10(-24) in white men, and less than 10(-12) in white women), higher diastolic pressures (P less than 10(-24) in white men, and less than 10(-6) in white women), and substantially higher prevalence of pressures greater than or equal to 160/95 mm Hg. The associations of blood pressure and drinking were independent of age, sex, race, smoking, coffee use, former "heavy" drinking, educational attainment and adiposity. The findings strongly suggest that regular use of three or more drinks of alcohol per day is a risk factor for hypertension.
848 citations
TL;DR: In this paper, the authors developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise.
Abstract: Although coronary angiography defines regions of potential ischemia in patients with coronary-artery disease, accurate assessment of the presence and functional importance of ischemia requires appraisal of regional and global left ventricular function during stress. To perform such assessment, we developed a noninvasive real-time radionuclide cineangiographic procedure permitting continuous monitoring and analysis of left ventricular function during exercise. In 11 patients with coronary disease who had normal regional and global ventricular function at rest, new regions of dysfunction developed during exercise (P less than 0.001), and in 10, global ejection fraction dropped 7 to 47 per cent. Fourteen age-matched normal subjects were studied; during exercise none had regional dysfunction, and each increased global ejection fraction (average increase, 23 +/- 3 per cent [+/-S.E.], P less than 0.001 as compared with patients with coronary disease). Radionuclide cineangiography during exercise permits accurate assessment of the presence and functional severity of ischemic heart disease.
719 citations
TL;DR: These studies emphasize in importance of control of activation in regulation collagenase activity, it is likely that rheumatoid synovium produces both latent collagenase and plasminogen activator; plAsmin is activated from its zymogen, plasmineogen, present in inflamed tissues, and in turn activates collagenase.
Abstract: To elucidate the mechanism of synovial damage in rheumatoid arthritis, we studied the activation of latent collagenases released from adherent rheumatoid synovial cells in culture. Latent enzyme was not complexed with α2 macroglobulin, the principal proteinase inhibitor in serum, and could be activated by trypsin in the presence of α2, macroglobulin if sufficient proteinase was added to saturate inhibitor. Latent collagenase bound half as effectively to collagen fibrils as active enzyme. Plasmin was a threefold better activator of latent enzyme than trypsin and could be generated by addition of plasminogen to synovial-cell cultures. Production of both collagenase and plasminogen activator was inhibited by dexamethasone (10–9 M). These studies emphasize the importance of control of activation in regulating collagenase activity. It is likely that rheumatoid synovium produces both latent collagenase and plasminogen activator; plasmin is activated from its zymogen, plasminogen, present in inflamed ti...
687 citations
TL;DR: The work load imposed upon the right ventricle by elevation of pulmonary vascular resistance may be a factor limiting survival in severe acute respiratory failure.
Abstract: We repeatedly assessed pulmonary and systemic hemodynamics in 30 patients undergoing therapy for severe acute respiratory failure of diverse causes. Pulmonary-artery hypertension and elevated pulmonar vascular resistance were observed in all patients after correction of systemic hypoxemia. Increasing pulmonary blood flow by isoproterenol infusion or decreasing pulmonary blood flow by partial bypass of the right side of the heart minimally altered pulmonary-artery pressure. Although neither elevated pulmonary vascular resistance nor low cardiac index reliably predicted death, survivors had preogressive decreases of pulmonary vascular resistance with time, whereas nonsurvivors tended to maintain or increase pulmonary vascular resistance. Right ventricular stroke-work index was markedly elevated in all patients. The work load imposed upon the right ventricle by elevation of pulmonary vascular resistance may be a factor limiting survival in severe acute respiratory failure.
682 citations
TL;DR: Adenine arabinoside (vidarabine) was used for treatment of Type 1 herpes simplex encephalitis in a placebo-controlled study as mentioned in this paper, which reduced mortality from 70 to 28 per cent (P = 0.03).
Abstract: We evaluated adenine arabinoside (vidarabine) for treatment of herpes simplex encephalitis in a placebo-controlled study. In 28 cases proved by isolation of Type 1 virus from brain biopsy, treatment reduced mortality from 70 to 28 per cent (P = 0.03), and over 50 per cent of treated survivors had no or only moderately debilitating neurologic sequelae. This improvement was achieved without evidence of acute drug toxicity. Thus, adenine arabinoside has a good therapeutic index (efficacy/toxicity) for the treatment of Type 1 herpes simplex encephalitis. However, the drug must be given early in the course of infection before the advent of coma to have a beneficial effect. Moreover, it should be coupled with brain biopsy for specific diagnosis to avoid unnecessary treatment of nonresponsive encephalitides that can mimic herpes simplex. (N Engl J Med 297:289–294, 1977)
TL;DR: The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis and oral candidiasis was the only adverse effect ecountered from trimethoprim-sulfamethoxazole administration.
Abstract: In a randomized, double-blind, placebo-controlled study to evaluate the efficacy of trimethoprim–sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patie...
TL;DR: Analyses of survival taking into account other important prognostic variables establish that the presence of complex premature beats in the monitoring hour is associated with a risk of sudden coronary death three times that of the men free of complex ventricular premature beats.
Abstract: To assess the role of ventricular premature beats in influencing mortality of coronary patients, 1739 men with prior myocardial infarction were monitored for ectopic activity for one hour at a standard base-line examination, and followed for mortality for periods up to four years (average, 24.4 months). Analyses of survival taking into account other important prognostic variables establish that the presence of complex premature beats (R on T, runs of 2 or more, multiform or bigeminal premature beats) in the monitoring hour is associated with a risk of sudden coronary death three times that of the men free of complex ventricular premature beats. The corresponding risk of death from any cause is twice that of men without such complex beats in the hour. These arrhythmias make an independent contribution to increased risk of death that persists over the length of this observation period. (N Engl J Med 297:750–757, 1977)
TL;DR: In this paper, the authors show that liver and hepatomas are freely permeable to glucose; thus, the activity and concentration of competing enzyme systems (in the presence of competing enzymes) can be increased.
Abstract: Carbohydrate Metabolism — Imbalance in Cancer Cells (Fig. 5) Liver and hepatomas are freely permeable to glucose; thus, the activity and concentration of competing enzyme systems (in the presence o...
TL;DR: Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.
Abstract: From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.
TL;DR: The results support the hypothesis that a congenital defect in the cilia and sperm tails will cause chronic respiratory-tract infections and male sterility--the immotile-cilia syndrome.
Abstract: We investigated six men and a woman suspected of suffering from congenital immotility of cilia. All had chronic airway infections, and the men had immotile spermatozoa. The woman and three men had Kartagener's syndrome. The investigations included measurements of the mucociliary transport in the lower airways and ultrastructural studies of the sperm tails or respiratory cilia (or both). Mucociliary transport was significantly delayed. Sperm tails lacked dynein arms in five patients. Respiratory cilia from the women and two men lacked dynein arms and were irregularly oriented. The results support the hypothesis that a congenital defect in the cilia and sperm tails will cause chronic respiratory-tract infections and male sterility--the immotile-cilia syndrome. In about half these patients there will also be a situs inversus--i.e., Kartagener's syndrome.
TL;DR: (Second of Two Parts)
Abstract: (First of Two Parts) A NOVEL sterol hormone that is undoubtedly a major physiologic regulator of mineral metabolism in man, 1α,25-dihydroxyvitamin D (1,25(OH)2D), is produced from vitamin D in response to situations of calcium and phosphorus need, with the final enzymatic reaction occurring in the kidney. A complex and elegant biochemical mechanism is thought to function at the pivotal kidney site to modulate the biosynthesis of this most active form of vitamin D. In concert with other calcitropic principles, such as parathyroid hormone (PTH) and calcitonin, the l,25-(OH)2D hormone mediates calcium and phosphorus metabolism at target . . .
TL;DR: Patients with high-renin hypertension, but not those with normal plasma renin activity, exhibited suppressed hostility, a behavioral pattern linked to increased sympathetic activity, which is neurogenic and possibly psychosomatic in origin.
Abstract: To determine whether the elevated plasma renin activity in some cases of mild essential hypertension expresses sympathetic-nervous-system over-activity, we compared indexes of sympathetic activity in 16 patients with mild high-renin essential hypertension, 15 hypertensive patients with normal plasma renin activity and 20 normal subjects. Patients with elevated activity exhibited a raised plasma norepinephrine concentration (P less than 0.05), a greater fall in cardiac output with cardiac beta-adrenergic blockade by intravenous propranolol (P less than 0.01), reduction in total peripheral vascular resistance with alpha-adrenergic blockade produced by intravenous phentolamine (P less than 0.01), and reduction to normal of blood pressure by "total" autonomic blockade (atropine, propranolol and phentolamine). On psychometric testing, patients with high-renin hypertension, but not those with normal plasma renin activity, exhibited suppressed hostility (P less than 0.01), a behavioral pattern linked to increased sympathetic activity. The hypertension in these patients with high renin activity is neurogenic and possibly psychosomatic in origin.
TL;DR: A glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.
Abstract: We examined the role of a prostaglandin producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182±60 per cent in 3H-thymidine incorporation versus a 44±18 per cent increase in 29 controls (mean ± S.D., P<0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48 per cent of that of control. With indomethacin it was 94 per cent of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P<0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80 per cent and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus,...
TL;DR: There was no statistically significant difference in survival, at a minimal follow-up interval of 21 months, between patients treated medically and those treated with saphenous-vein-bypass grafting.
Abstract: We evaluated the effect of saphenous-vein-bypass grafting on survival in patients with chronic stable angina by comparing medical and surgical treatment in a large-scale, prospective randomized study. Excluding patients with left-main-coronary-artery disease who have already been reported, a total of 596 patients were entered into this study; when randomized into a medical group (310 patients) and a surgical group (286 patients), entry clinical and angiographic base lines were comparable. Operative mortality at 30 days was 5.6 per cent. At an average of one year after operation, 69 per cent of all grafts were patent, and 88 per cent of the surgical patients had atleast one patent graft. There was no statistically significant difference in survival, at a minimal follow-up interval of 21 months, between patients treated medically and those treated with saphenous-vein-bypass grafting. At 36 months, 87 per cent of the medical group and 88 per cent of the surgical group were alive.
TL;DR: It is shown that surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea and amenorrhea often persisted after treatment, and thyrotropin-releasing hormone was most useful in identifying patients with pituitary tumors.
Abstract: An analysis of 235 patients with galactorrhea (5.5 per cent males) showed that 20 per cent of all patients, and 34 per cent of women with associated amenorrhea, had radiologically evident pituitary tumors; these patients had the highest serum prolactin concentrations. The largest single group (32 per cent) consisted of women with idiopathic galactorrhea without amenorrhea; prolactin was normal in 86 per cent of these cases. Five patients had the empty-sella syndrome. Prolactin response was tested in selected patients by thyrotropin-releasing hormone, chlorpromazine, L-dopa, 24-hour sampling and other means. Tests with thyrotropin-releasing hormone were most useful in identifying patients with pituitary tumors. Surgery and radiotherapy lowered prolactin to a similar degree in patients with tumor, but galactorrhea and amenorrhea often persisted after treatment. The ergot derivatives, bromergocryptine and lergotrile mesylate, lowered prolactin in all 18 patients with idiopathic hyperprolactinemia or...
TL;DR: There was a strong negative association between moderate alcohol consumption and the risk of nonfatal myocardial infarction and death from coronary heart disease in a cohort of Japanese men living in Hawaii during a six-year period.
Abstract: We examined the relation of coffee and alcohol consumption to the risk of coronary heart disease during a six-year period in a cohort of 7705 Japanese men living in Hawaii. The analysis was based on 294 new cases of coronary heart disease. There was a positive association between coffee intake and risk, but it became statistically insignificant when cigarette smoking was taken into account. There was a strong negative association between moderate alcohol consumption (up to 60 ml per day), mainly from beer, and the risk of nonfatal myocardial infarction and death from coronary heart disease. This association remained significant in multivariate analysis, taking into account smoking and other risk factors. The correlation of alcohol consumption with the level of alpha cholesterol (positive) and beta cholesterol (negative) may partly account for the observed negative association between alcohol and coronary heart disease.
TL;DR: The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 percent (23 of 939) as mentioned in this paper.
Abstract: The overall prevalence of congenital cytomegalovirus infection among the offspring of a highly immune young female population was 2.4 per cent (23 of 939). To ascertain whether the presence of anticytomegalovirus antibodies protects the developing fetus, we examined the offspring of 239 prospectively studied women. Despite substantial levels of preconceptional antibodies, intrauterine cytomegalovirus infection occured in seven of 208 (3.4 per cent) seroimmune women. Three neonates with congenital infection were born to 31 initially seronegative women. All the congenitally infected infants had subclinical involvement. Maternal humoral immunity may not protect the fetus against congenital cytomegalovirus infection. Neutralization kinetics and restriction enzyme analysis with endonucleases (EcoR-1 and HinD 111) demonstrated antigenic and genetic homology between viral strains isolated from two siblings consecutively infected in utero, indicating that repeat maternal infection with the same virus is transmissible to sequential products of conception.
TL;DR: The prevalence of S. bovis in fecal cultures from patients with carcinoma of the colon was significantly increased as compared to that in controls, and also to all other groups, although patients with inflammatory bowel disease were more frequently carriers.
Abstract: Two patients with colonic adenocarcinoma and Streptococcus bovis endocarditis suggested a possible association between the two. Non-enterococcal Group D streptococci were isolated from fecal cultures of 11 of 105 controls, 35 of 63 patients with carcinoma of the colon, seven of 25 with inflammatory bowel disease, four of 21 with non-colonic neoplasms and five of 37 with other gastrointestinal disorders. All such streptococci examined for lactose fermentation were S. bovis. The prevalence of S. bovis in fecal cultures from patients with carcinoma of the colon was significantly increased (P 0.05) although patients with inflammatory bowel disease were more frequently carriers. The carrier state was unrelated to age, hospitalization status, colonic stasis, gastrointestinal bleeding or recent barium-enema examination. The implications of this asso...
TL;DR: Findings indicate two forms of immunity for viral gastroenteritis, one of short and the other of long duration, and factors other than serum antibody appear important in immunity to Norwalk gastroEnteritis.
Abstract: To examine immunity in viral gastroenteritis, we challenged and then rechallenged 12 volunteers with Norwalk agent and evaluated symptoms, jejunal biopsies and serum antibody. With the first challenge, gastroenteritis developed in six volunteers but not in the others. When rechallenged 27 to 42 months later, the six who became ill initially again had gastroenteritis with jejunal lesions; in the six previously immune volunteers illness or jejunal lesions did not develop. Four of five ill volunteers had increases in serum antibody to Norwalk agent after both challenges. Serum antibody did not increase in three immune volunteers after either challenge. Four volunteers who had twice become ill underwent a third challenge four to eight weeks after their second illness. In one gastroenteritis developed; in three, it did not. These findings indicate two forms of immunity for viral gastroenteritis, one of short and the other of long duration. Factors other than serum antibody appear important in immunity to Norwalk gastroenteritis.
TL;DR: The symptoms of cardiac failure are related to some combination of circulatory congestion and low cardiac output and therapy for cardiac failure has traditionally involved the Administration of an inotropic drug to increase the contractile force of the heart and the administration of a diuretic to increasing the renal excretion of salt and water.
Abstract: (First of Two Parts)* THE symptoms of cardiac failure are related to some combination of circulatory congestion (often referred to as "backward failure") and low cardiac output ("forward failure"). In simple pump-function terms these symptoms indicate that the heart is performing on a depressed Frank-Starling curve relating stroke volume (or cardiac output or stroke work) to ventricular diastolic filling (pressure or volume) (Fig. 1). Therapy for cardiac failure has traditionally involved the administration of an inotropic drug to increase the contractile force of the heart and the administration of a diuretic to increase the renal excretion of salt and water. . . .
TL;DR: Study of patients with Hodgkin's disease, treated at Stanford University Medical Center from July 1, 1968, through December 31, 1975, to determine the risk of development of hematologic neoplasia found no cases of leukemia in patients in clinical remission.
Abstract: We studied 680 patients with Hodgkin's disease, treated at Stanford University Medical Center from July 1, 1968, through December 31, 1975, to determine the risk of development of hematologic neoplasia. Six cases of leukemia occurred in patients in clinical remission, one 7 1/2 years after diagnosis. Two additional cases occurred in patients with active Hodgkin's disease. No cases were seen in 320 patients treated with radiotherapy alone or in 30 treated with chemotherapy alone. A single case of subacute leukemia occurred in a patient treated initially with radiation therapy and colloidal gold. The actuarial probability of development of leukemia at five and seven years is 1.5 and 2.0 per cent for the entire group and 2.9 and 3.9 per cent for the 330 patients treated with combined radiation and chemotherapy. The median survival after diagnosis is four months, with no patient living beyond six months. (N Engl J Med 297:1249–1252, 1977)
TL;DR: Two images of the cell membrane are presented — as a sea of lipid with islands of protein and as a matrix of protein with lakes of lipid, both of which suggest that zones of fluid lipid within the membrane form the environment for membrane proteins.
Abstract: Early in this century, colloid chemists debated about whether cells were bounded by a surface membrane. Today, they debate about the organization of molecules within that membrane. The research involved has led to two images of the cell membrane — as a sea of lipid with islands of protein and as a matrix of protein with lakes of lipid. Both concepts suggest that zones of fluid lipid within the membrane form the environment for membrane proteins. Much of this lipid is in the form of a bilamellar leaflet with hydrophilic portions that face the aqueous environment on either side and . . .
TL;DR: To estimate the leukemogenic potential of alkylating agents, 70 institutions using these drugs for the frequency of second cancers in patients with advanced ovarian cancer were surveyed.
Abstract: To estimate the leukemogenic potential of alkylating agents, we surveyed 70 institutions using these drugs for the frequency of second cancers in patients with advanced ovarian cancer. Thirteen cases of acute nonlymphocytic leukemia occurred among 5455 patients, as compared to 0.62 cases expected (relative risk = 21.0). All 13 had received alkylating agents. Nine also received radiotherapy. The relative risk for patients given chemotherapy was 36.1 and rose to 171.4 for those surviving for two years (rate = 13.75 per 1000 patients per year). To evaluate the role of therapy versus underlying disease, a historical control of 13,309 patients with ovarian cancer in the National Cancer Institute's End Results Program was analyzed. No excess of leukemia was noted in this group, even among 6596 women receiving radiation. The excess of acute nonlymphocytic leukemia, therefore, appears attribute to alkylating agents, although the effect may be enhanced by exposure to radiation, as previously suggested for Hodgkin's disease.