Release of nucleosides from canine and human hearts as an index of prior ischemia. During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.


Effects of intraaortic balloon counterpulsation on regional myocardial function during acute coronary occlusion in the dog. The effects of intraaortic counterpulsation on regional myocardial function were studied using ultrasonic dimension gauges in 24 open chest dogs. Pairs of ultrasonic crystals were implanted in the subendocardium of the left ventricle in control, marginally ischemic and ischemic segments. After coronary arterial occlusion, the end-diastolic length of all three segments was increased. Segment shortening was rapidly replaced by systolic expansion in the ischemic segment. In the marginal segment, active shortening decreased by 53% and, in the control segment, shortening was augmented by compensatory operation of the Frank-Starling mechanism. Balloon pumping initiated 10 minutes after coronary occlusion resulted in an increase in mean aortic diastolic pressure from 103 to 115 mm Hg without any significant change in peak systolic pressure. In the marginal segment, end-diastolic length decreased by 3%, and previously reduced shortening increased to 82% of control value, deteriorating again with discontinuation of counterpulsation. Balloon pumping produced no change in the dyskinetic motion of the ischemic segment but caused compensatory augmentation of shortening of the control segment. Thus, counterpulsation selectively improved segment function of the marginally ischemic segment, presumably as a result of a regional increase in myocardial blood flow and in availability of oxygen due to augmented perfusion pressure. The systolic unloading effect was counterbalanced by improved cardiac performance.


Evaluation of persistent coarctation of aorta after surgery with blood pressure measurement and exercise testing. In 16 patients with coarctation of the aorta blood pressure in the arms and legs was measured before and after exercise using a treadmill and the Bruce protocol to achieve a standardized level of exercise. Three patients had had no previous operation; 13 had had a previous surgical repair of the coarctation. Three patients were studied both before and after operation. Two of the 13 patients studied postoperatively were found to have significant residual coarctation on the basis of a postexercise arm to leg pressure gradient that had not been appreciated on routine postoperative examination, and one of these patients was found to have residual coarctation after his second operation. One patient not operated on was believed to have mild coarctation of no clinical significance. Eleven of the 13 patients previously operated on (85%) were found to have had a satisfactory repair. A postexercise arm to leg systolic blood pressure gradient of more than 35 mm Hg after repair of coarctation of the aorta is suggested as an indication for recatheterization.


Effect of furosemide on hemodynamics and lung water in acute pulmonary edema secondary to myocardial infarction. Hemodynamic studies were carried out in 19 patients with left ventricular failure complicating acute myocardial infarction. Fourteen patients were studied before and after the intravenous administration of 0.5 mg/kg of furosemide, and five patients served as a control group. Serial measurements included intracardiac pressures, cardiac output and lung water by a double isotope technique. A significant reduction was noted in right atrial (P less than 0.005), pulmonary arterial (P less than 0.0005) and pulmonary wedge pressures (P less than 0.0005) after administration of furosemide. Only the change in right atrial pressure was significantly different from that in the control group (P less than 0.05). Lung water was not changed in 4 patients studied 2 hours after administration of furosemide but was significantly changed in the remaining 10 patients studied 4 to 24 hours after furosemide (P = 0.0001). This change was also significantly different from values in the control group (P less than 0.05). The patients with no reduction in excess lung water also had a smaller reduction in pulmonary wedge pressure and a lower pretreatment stroke work index than the other patients. The mobilization of excess lung water in patients with acute myocardial infarction complicated by left ventricular failure has several features. Despite a prompt diuresis, the reduction in lung water is delayed for at least several hours after the administration of furosemide and may be related to the degree of left ventricular dysfunction. Venodilation may be a major result of treatment with furosemide.


Safety and efficacy of procainamide infusions. Thirty-four patients who were resistant to conventional doses of lidocaine received procainamide intravenously according to a pharmacokinetically designed two infusion technique. A mean peak serum concentration of 7.1 mg/liter was achieved with an average loading dose of 989 mg administered over 1 hour. A mean steady state serum concentration of procainamide of 6.5 mg/liter was achieved with a mean dose of 64.4 mg/kg body weight for the first 24 hours of treatment. Dose, renal impairment, the degree of congestive heart failure and acetylator status influenced the steady state serum concentration of procainamide. Dangerous ventricular arrhythmias were abolished in 74% of the patients at a steady state level of 6.9 +/- 3.7  mg/liter (mean +/- standard deviation). Nonresponders to procainamide had a mean steady state serum concentration of procainamide of 4.2 +/- 2.1 mg/liter (P less than 0.05). Systolic and diastolic blood pressures decreased moderately (10 and 8%, respectively), and heart rate decreased 11%. The infusion was interrupted in one patient because of hypotension. The duration of electrocardiographic conduction intervals was increased slightly in some patients. It is concluded that procainamide administered by this two infusion method is effective and well tolerated by most patients.


Structured educational program for staff development. The development of a mandatory continuing education program for the pharmacy staff of a 675-bed hospital with 10 decentralized pharmacy satellites is described. The therapeutic topics selected for presentation were antibiotics, immunology and adverse drug reactions, diabetes mellitus and acid-base disorders. The format for each subject included a pretest of basic knowledge, a comprehensive lecture, a tape recording, supplemental handout material and readings, and a posttest. Posttests were scheduled three to four weeks following lectures to allow preparation time. Questionnaires were used to evaluate acceptance of the program. Posttest scores for each of the four topics were significantly better than pretest scores (p less than or equal to 0.0001). Questionnaire responses indicated that 97% of the participants believed the program to be worthwhile, and 94% voted to continue the series. The success and acceptance of this approach to continuing education support its application to a comprehensive program of staff development.


Comprehensive pharmaceutical services in the emergency room. A decentralized pharmaceutical service functioning in a hospital emergency room from 4 p.m. to midnight daily is described. Start-up costs were determined to be less than $2,200 for the system which includes a mobile medication cart stocked with a limited inventory of prepackaged medications. Approximately 94% of the prescriptions originating from the emergency room from 4 p.m. to 8 a.m. can be filled from the cart. Results of a nine-month survey indicated that an average of 20.6 prescriptions were filled on the 4 p.m. to midnight shift each day, producing an average daily profit over drug expense of $60.51, which was more than the salary expense of the pharmacists providing the service. The time required to provide traditional prescription services has not interfered with the provision of clinical services or opportunities for educating undergraduate pharmacy students who rotate through the area. Implementation of clinical pharmaceutical services with a traditional component is suggested as a cost-effective method of providing such services.


Comparison of two methods of observing work areas in a hospital pharmacy. Two methods of observing the work area within a pharmacy of an acute care, 140-bed hospital were compared. A work activity recording form was developed from the literature and from discussion with the pharmacy staff. The instrument was coded, tested, and refined in a pilot study. One hospital pharmacy department work area was personally observed for a period of time equal to an entire work week. A time-motion camera was placed in the pharmacy which recorded the activities in the same pharmacy work area for a second work week. The results indicated that the two methods of observation were approximately equivalent for observing the work activities of the nonpharmacists but not for the work activities of the pharmacists. The camera method of observing work areas of a hospital pharmacy appeared to be reliable and inexpensive, but it lacked the precision obtained with the personal observation mode. Further use of time-motion cameras within the hospital pharmacy setting are indicated.


Reliability of theophylline clearance in determining chronic oral dosage regimens. Predicted and approximated mean serum theophylline concentrations were compared to assess the feasibility of using theophylline clearance, calculated from the intravenous steady-state serum theophylline concentration, to determine appropriate oral dosage requirements. Ten patients with reversible airway disease (age 7 to 64 years) received theophylline (as Aminophylline USP) by constant i.v. infusion. Theophylline clearance was calculated for each patient from steady-state serum theophylline concentrations determined from blood samples obtained after a least 48 hours of constant theophylline infusion. Aminophylline USP tablets were then adminstered orally. Blood levels measured at peak and trough times following oral theophylline administration were used to calculate an approximate mean serum theophylline concentration. The relationship between predicted and approximated mean serum theophylline concentrations was calculated and analyzed by orthogonal least square regression line. Serum theophylline concentrations ranged from 5.1 microgram/ml to 20.1 microgram/ml, and clearances ranged from 0.03 liter/kg/hr to 0.09 liter/kg/hr. During oral therapy, the maximum concentration ranged from 10.4 microgram/ml to 23.8 microgram/ml, while the minimum ranged from 6.5 microgram/ml to 15.2 microgram/ml. The difference between predicted and approximated mean serum concentrations was within +/-1.6 micrograms/ml in all cases. The study indicates that the theophylline clearance calculated from i.v. infusion data can be used to determine appropriate oral dosage requirements.


Comparison of natriuretic and diuretic effects of single and divided doses of furosemide. The natriuretic and diuretic effectiveness of once-daily and twice-daily furosemide administration schedules was compared in a two-way crossover study using six normal subjects. Urine was collected for 24hours before and after administration of the first dose of furosemide. Patients received one 40-mg dose or two 20-mg doses of the drug administered six hours apart. Sodium and potassium urine concentrations were measured through flame emission photometry using lithium as an internal standard. Chloride urine concentrations were determined using colorimetric measurement with mercuric thiocyanate. Results were statistically evaluated by a one-way analysis of variance. Results showed no statistically significant differences (p greater than 0.7) between the two regimens in the cumulative 24-hour excretion of sodium, potassium, chloride or water. The average 24-hour sodium excretion following a single 40-mg furosemide dose was 268.9 mEq, while that following administration of the two 20-mg doses was 294.2 mEq. Differences during various intervals within the 24-hour collection period were consistent with the relative sizes of doses administered. It would appear that single daily dose administration regimens would be a logical beginning for furosemide therapy, particularly when lower doses are being considered.


Pharmacy inspections: constitutional without a warrant? The implications of the 1978 U.S. Supreme Court decision in Marshall vs. Barlow's, Inc., regarding warrantless inspections of pharmacies are discussed. Reviewed are the Fourth Amendment to the U.S. Constitution, related U.S. Supreme Court decisions (Camera vs. Municipal Court and See vs. City of Seattle), new "probable cause" standards, and exceptions to the requirement of warrants for inspections. The effect of the Barlow's case with specific reference to FDA, DEA and state board of pharmacy inspections is discussed. Although the Barlow's case has provided further case law in the area of administrative inspections, each case still requires individual resolution. DEA inspections are well delineated by statute and regulation. Under the "licensing exceptions," warrantless pharmacy inspections by the FDA and by boards of pharmacy are probably permissible.


Use of cholestyramine resin in the treatment of digitoxin toxicity. Two case reports describing the treatment of digitoxin toxicity with cholestyramine resin are presented. Both female patients were receiving 100 microgram/day of digitoxin when toxicity occurred. In both patients, digitoxin was discontinued and hypokalemia was corrected. In patient 1, lidocaine hydrochloride and phenytoin sodium also were administered. Serum digitoxin levels were decreased from 43 ng/ml to 21.8 ng/ml and from 42 ng/ml to 29 ng/ml in patients 1 and 2, respectively, following administration of three 4-g doses of cholestyramine resin over a one-day period. Previous studies on the treatment of digitoxin intoxication with potassium chloride, phenytoin sodium, lidocaine hydrochloride, digitoxin-specific antibodies, colestipol hydrochloride and cholestyramine resin are discussed. Ion-exchange resins may be valuable adjuncts in the treatment of digitoxin intoxication but further studies of their utility are needed.


Erikson's concept of inner space: a data-based reevaluation. An analytical critique is presented of Erikson's theory that physical differences between the sexes produce differences in spatial organization, and of the experiment cited in support of that theory. Results of a new experiment are reported, which run counter to the original findings and suggest that the theory of "inner space" be reevaluated.


A time-referenced Q-sort technique for evaluating behavioral change. The behavior of children in residential and day treatment centers alters over time in ways that can be documented objectively. This paper describes a method, field tested with 50 subjects in five agencies, in which observations of behavior are converted into quantitative indices of adjustment to yield a profile of change for each subject.


The preventive reduction of psychological risk in asymptomatic adolescents. To explore the preventive efficacy of training in coping and social skills, 121 high school students were assigned to four risk classifications, assessed by measures of psychological vulnerability and environmental adversity; within each group, subjects were randomly assigned to a preventive intervention or assessment-only control condition. Findings suggest that group behavioral training can be a beneficial and economical preventive approach with symptom-free high school students, and that training in social skills may benefit those with behavior problems that presage maladjustment.


Manic-depressive illness: psychodynamic features of multigenerational families. Psychodynamic features of families with multigenerational bipolar manic-depressive illness are described. Repetitive maladaptive patterns, including avoidance of affect, unrealistic standards of conformity, absence of intimate relationships apart from family, displaced parental low self-esteem, and fears related to illness heritability, may influence the maintenance of family pathology.


A stepfamily in formation.

A stepfamily in formation. The increasing incidence of stepparenthood requires that mental health clinicians develop skills for helping members of two families form a viable new family unit. This paper conceptualizes stages in the development of the reconstituted family. Case material describes a scapegoated child as the focus of conflict in one family's progression through these stages.


Paraverbal therapy in pediatric cases with emotional complications. Children often respond to hospitalization with severe anxiety and depression, frequently manifested by withdrawal or hyperactive and aggressive or hostile behavior. The use of paraverbal therapy, a specialized therapeutic approach, is described in the short-term treatment of patients exhibiting emotional disturbances secondary to illness or trauma.


Some evidence of race bias in the diagnosis and treatment of the juvenile offender. Clinical and epidemiological evidence is presented indicating that many more black delinquent children and their families fail to receive needed psychiatric and medical services than do white delinquents. Explanations and implications of the reluctance or inability of white mental health professionals to diagnose serious psychopathology in the black delinquent population are explored.


Beyond the mainstream: the special needs of the chronic child patient. Born of civil rights legislation and promoted by a desire for simple, rapid means of modifying behavior, Public Law 90-142 represents an effort at normalizing behaviorally disturbed children through "mainstreaming." This paper argues that a simplistic insistence on equality through mainstreaming violates the rights and needs of some behaviorally disturbed children to be different.


Primary prevention from a neighborhood base: a working model. A neighborhood development project is described, in which citizens were organized to work with mental health professionals in the area of primary prevention. Emphasis is given to methods for mobilizing citizen involvement, methods used by citizens to identify high risk populations, the working relationship between volunteers and professionals in designing and implementing services, the types of services developed, and an assessment of the project's impact.


Preventing unwanted adolescent pregnancy: a cognitive-behavioral approach. Teenage pregnancy is a growing social problem in the United States. Past interventive failures and current research suggest new directions for primary prevention. A comprehensive prevention program is outlined, and training techniques based on a cognitive-behavioral approach are proposed to help adolescents acquire skills necessary to avoid unwanted pregnancies.


Racial attitudes in young children as a function of interracial contact in the public schools. The relative effects of integrated and segregated schooling on racial attitudes were studied in a comparison of young children attending all-black, all-white, and integrated schools. Results of this photo-choice study suggest that segregated classes discourage realistic perceptions of the excluded race and promote a preference for whites among whites and blacks, whereas interracial schooling contributes to acceptance of blacks by all students and has especially profound and complex effects on black children.


Psychotherapy of the medically ill.

Psychotherapy of the medically ill. The author assesses the current status of psychotherapy with medically ill patients. He reviews the special problems of psychological treatment for this population; the respective rationales for the utilization of various psychotherapeutic approaches including psychoanalysis, dynamic psychotherapy, and family and group therapy; and the results of case reports and research studies. The author identifies specific areas of future investigation and research, elucidates some specific implications for clinical practice, and recommends more critical exploration of the role of psychotherapy in the treatment of the medically ill.


Primary prevention in perspective.

Primary prevention in perspective. Discussion of primary prevention has been made difficult by lack of clarity of underlying concepts and assumptions. Is the purpose to prevent diagnosable mental illness or to prevent unhappiness and social incompetence? What are the implications of the assumption that societal stress causes mental illness? Is there a clear distinction made between major and minor mental illness? Except for a few specific conditions there is little evidence that primary prevention has been effective. The authors feel that research and program evaluation in prevention is sorely needed but should be funded separately and with discretion. Scarce mental health funds should not be diverted from direct treatment for this purpose.


The changing role of psychiatrists in community mental health centers. The community mental health center (CMHC) movement, largely conceived by psychiatrists to improve standards of mental health care nationally, appears to be going through an evolutionary phase in which there is decreasing utilization of psychiatrists and increasing utilization of other mental health professionals. The author discusses some factors that may have influenced this trend. In order to counter it CMHCs must become a recognized, essential, and respectable part of a pluralistic system of mental health care, and psychiatrists must be willing to assume their responsibility for involvement in all segments of mental health care, including the private and public sectors, in both leadership and clinical positions.


Differential bonding: toward a psychophysiological theory of stereotyping. The author uses the concept of affiliative-affectionate bonding and the concept of differentiative-aggressive bonding to answer questions regarding the human tendency to stereotype. He states that the human processes of affiliation, introjection, identification, and affection appear to be psychophysiological elaborations of approach-seeking physiology and that differentiation, projection, and aggression appear to be psychophysiological elaborations of withdrawal-avoidance physiology. He also points out that some measure of stereotyping and paranoia may be necessary because differential bonding appears to be essential for adaptation.


Use of the Research Diagnostic Criteria and the Schedule for Affective Disorders and Schizophrenia to study affective disorders. In a pilot study of 150 manic or depressive patients, the authors used the Research Diagnostic Criteria (RDC) and the Schedule for Affective Disorders and schizophrenia (SADS) to perform preliminary analysis of symptom pictures of the index episode of different diagnostic groups, joint diagnostic classification of the different subtypes of major depressive disorder, and differential outcome by diagnostic groups. The results suggest that schizophrenic symptoms in affective disorders do have diagnostic and prognostic significance, that the term "psychotic depression" should be limited to impaired reality testing without reference to degree of incapacitation, that situational-nonsituational and endogenous-nonendogenous classifications are separate depressive subtypes, and that it may not be true that patients with endogenous major depressive disorder have a better prognosis than patients with nonendogenous depression.


Neurotic depressions: a systematic analysis of multiple criteria and meanings. Neurotic depression, the most commonly used psychiatric diagnosis, has multiple meanings that are often used interchangeably in clinical practice. The authors identify six different meanings of neurotic depression and present data from a study of 90 depressed inpatients to determine how many patients met several different criteria; 16 patients met four sets of criteria. The overlap that exists between the different meanings is higher than chance alone but not sufficiently high to allow complete interchangeability. Until new diagnostic classes are developed, the authors recommend that the term "neurotic depression" no longer be used clinically because of its vagueness.


Secondary depression: familial, clinical, and research perspectives. The authors evaluate the clinical and research significance of the diagnosis of secondary depression by comparing 48 cases of primary and 26 cases of secondary depression. The patients with secondary depression have a higher familial prevalence of alcoholism, affective disorder, and drug abuse. The groups differ somewhat on a few sociodemographic, behavioral, and attitudinal variables but are similar in symptomatology, sex ratio, onset and duration of symptoms, treatment received, and response to treatment. These results suggest that the distinction between primary and secondary depression should be retained in research that examines neurochemistry or genetics. Primary and secondary depression appear to be identical from the persepctive of clinical care. Management of these patients should emphasize the diagnosis of depression rather than antecedent diagnoses.


Personality attributes and affective disorders. To determine the personality characteristics associated with affective disorders the authors administered a battery of self-report personality inventories to a sample of hospitalized affective patients when their manifest symptoms had abated. Patients were instructed to answer according to their premorbid personalities. The personality characteristics assessed in the 73 depressive and 24 manic patients included neuroticism and extraversion from the Maudsley Personality Inventory, obsessional pattern, hysterical pattern, and oral pattern from the Lazare-Klerman-Armor Personality Inventory, obsessional state and trait from the Leyton Obsessionality Inventory, and solidity, stability, and validity from the Marke-Nyman Temperament Survey. Depressive patients demonstrated more neuroticism, introversion, and obsessionality than manic patients or normal individuals. The manic patients differed from normal persons only on obsessionality.


Hypnotic treatment of smoking: the single-treatment method revisited. The authors replicated Spiegel's single-treatment method by treating 40 self-referred patients in a one-hour hypnosis session for smoking. Their results, a 6-month total abstinence rate of about 25%, were comparable with Spiegel's experience. They recommend future studies that include nontreatment control groups to validate the effects of the hypnotic treatment method of smoking.


MMPI diagnosis of black psychiatric patients. Black-white differences in MMPI norms may lead to significant misclassification of black psychiatric patients, which can compound diagnostic errors from other sources. The authors suggest that clinicians who use MMPI results in evaluations of black patients interpret test reports carefully, keeping in mind the possibility of spuriously elevated scores and paying careful attention to areas of potential "false positives."


Behavior therapy as a test of psychoanalytic theory. The author describes 4 patients in whom radically new symptoms appeared after intensive behavior therapy. He suggests that fresh symptoms are most likely to develop in a small minority of patients who are unable to learn more adaptive psychological defense mechanisms during or after behavior therapy and that psychoanalytic theory may help predict the nature of such symptoms.


Emergency room patients in concurrent therapy: a neglected clinical phenomenon. The authors found that more than one-third of emergency room patients were participating in concurrent psychiatric treatment. Exploration of the relationship between patient and therapist proved to be a valuable tool in formulating consultation and in ensuring continuity of care.


The fiscal crisis in New York City: effects on the mental health care of minority populations. The author describes the effect that severe budget cuts accompanied by guidelines stipulating that direct services be given priority over primary preventive services had on a community mental health center in New York City. He focuses his discussion on the effect these guidelines had on the mental health care services provided the minority populations served by the center. Before the budget cuts, 1 out of every 4 staff members was a nonprofessional indigenous worker. After the cutback, 2 out of every 3 of the people laid off were nonprofessionals. The author provides a number of recommendations to help government agencies plan budget reductions without sacrificing primary prevention efforts.


Mood and affect: a semantic confusion.

Mood and affect: a semantic confusion. Although semantic clarity is a cornerstone of scientific psychiatry, psychiatrists often use technical words with the false assumption that their meanings are clear. The common use of the terms "mood" and "affect" illustrates this point. The authors attempt to show how unclear definitions of these words have led to confusion and how they could be more clearly understood by careful semantic and phenomenologic analysis.


Origin of the adrenergic nerve fibers in the subdiaphragmatic vagus in the dog. The vagi at the subdiaphragmatic level were studied by the Hillarp-Falck technic in combination with a nerve crush procedure in three normal dogs and in eight dogs that had undergone previous surgical excision of the superior cervical ganglion and/or the stellate ganglia. Unilateral ganglionectomies were performed so that the contralateral vagus served as a control. Based on these results, it is concluded that: (1) the subdiaphragmatic canine vagus contains numerous adrenergic nerve fibers; (2) the main portion of these vagal adrenergic fibers arises from the stellate ganglia; and (3) removal of both the stellate and the superior cervical ganglia results in nearly  complete adrenergic denervation of the abdominal vagus.


The natural history of pancreatic pseudocysts: a unified concept of management. Between 1971 and 1976, ninety-three patients with a clinical diagnosis of pseudocyst confirmed by ultrasonography were identified from a group of 923 patients admitted for pancreatic disease. Uncertainties in diagnosis and/or rapid progression of underlying pancreatitis led to urgent laparotomy and drainage in eleven of the ninety-three patients. Another twenty-eight patients underwent elective drainage of the pseudocyst. The remaining fifty-four constituted the study group and were followed with serial clinical and sonographic examinations until either spontaneous resolution occurred, complications developed, or the patients did not return. Complications arising during the period of observation in the untreated patients (rupture, abscess, jaundice, and hemorrhage) occurred more than twice as commonly as spontaneous resolution (41 per cent versus 20 per cent), and led directly to death in seven cases (14 per cent). No deaths occurred in the group of patients undergoing elective surgical drainage (p less than 0.05). The interval between presumed formation of the pseudocyst and the development of a complication averaged 13.5 +/- 6 weeks. Prolonged observation of pancreatic pseudocysts in the expectation of spontaneous resolution exposed the patient to an unwarranted risk, which, after seven weeks, greatly exceeded the mortality of elective surgery.


Surgical management of familial polyposis and Gardner's syndrome. Twenty-six patients with documented familial polyposis or Gardner's syndrome were followed up to twenty-eight years after total colectomy with ileorectal anastomosis. All patients were followed a minimum of five years. Patients were subjected to periodic proctosigmoidoscopies, and rectal polyps were electrocoagulated when found. In no patient in this series did an adenocarcinoma of the rectum develop during the follow-up period. Total abdominal colectomy with ileorectal anastomosis is the treatment of choice in patients with familial polyposis and Gardner's syndrome, provided adequate follow-up is assured and polyps are destroyed when encountered.


Systemic absorption of bacitracin after peritoneal lavage. Nine patients underwent intraoperative peritoneal lavage with a solution containing 50,000 units of bacitracin in 200 ml of 0.9 per cent sodium chloride. The solution was removed by suction at 2 or 5 minutes, and venous blood samples were obtained at 15 minute intervals for 2 hours after lavage. Concentrations of bacitracin in serum were determined by agar diffusion assay. In the majority of patients, peak concentrations of bacitracin in serum occurred by 15 minutes post lavage. The mean peak serum concentration was 3.8 units/ml, which exceeds peak concentrations after intramuscular injection of 50,000 units. Due to potential nephrotoxicity, bacitracin should be used cautiously in peritoneal lavage solutions and should be abandoned in patients who have renal impairment in whom prolonged elevated serum concentrations could develop.


Effect of glucagon and insulin upon biliary lipid secretion. The choleretic hormones, glucagon and insulin, were studied to determine whether they influence biliary lipid secretion in the dog. Glucagon was found to decrease biliary cholesterol and phospholipid secretion. These findings provide further support for a canalicular action of glucagon.


The physiologic properties and therapeutic potential of coherin. Coherin, a peptide isolated from the bovine neurohypophysis, has been shown to be an effective therapeutic agent in post-gastric surgery physiologic obstruction and regional ileitis. Of twenty-four patients with post-gastric surgery physiologic obstruction, coherin relieved symptoms in twenty-three, a 96 per cent efficacy rate. The efficacy of coherin with ileitis was based on the fact that ten of twenty-seven patients treated have required coherin on a continuing basis to stay functional. These patients have requested coherin treatment for an average of five years each, and have each on multiple occasions tried to discontinue coherin treatment with prompt return of symptoms and cessation of symptoms when coherin was reinstituted. All of the ileitis patients had previously failed to respond to standard and usual medical treatment.


Neural control of the canine pylorus.

Neural control of the canine pylorus. After atropine administration the anesthetized dog exhibits significant spontaneous pyloric contractile activity and an inhibition-relaxation response upon electrical vagal stimulation. This inhibition-relaxation response was completely blocked by tetrodotoxin administration and by transection of the intraabdominal vagal nerves. In addition, tetrodotoxin administration caused a dramatic increase in spontaneous pyloric motor activity. The histaminergic receptor antagonists diphenhydramine and cimetidine did not block the inhibition-relaxation response. The octapeptide of cholecystokinin (CCK-OP) caused a dose-dependent increase in antral and pyloric motor activity which was significantly decreased by atropine administration. Therefore, histamine and CCK do not appear to play a significant role in the vagally mediated inhibition-relaxation response of the canine pylorus or in the atropine-resistant spontaneous pyloric motor activity.


Multifactorial probit analysis of mortality in burned patients. Burn mortality statistics may be misleading unless they account properly for the many factors which may influence outcome. In reviewing such factors in our patients, we identified age, total burn area, third degree burn area, prior bronchopulmonary disease, abnormal Pao2, and airway edema as the factors present on admission which best distinguished survivors from nonsurvivors. Using multifactorial probit analysis, we then calculated the contribution of each to the probability of fatal outcome. The resultant six-factor model significantly improved estimation of the probability of fatal outcome when compared to probit analysis based only on the traditional factors of age and total burn area. It also revealed a spectrum of mortality probabilities varying with the additional factors present. Although crucial in comparing different approaches to burn care, consideration of such prognostic factors will not eliminate the need for randomized treatment trials, because other factors, some of which are obscure, may also influence mortality rates in burned patients.


Expanded polytetrafluoroethylene graft fistula for chronic hemodialysis. In a retrospective study of 66 PTFE arteriovenous fistulae and 71 BCH arteriovenous fistulae for dialysis access, PTFE had a higher patency rate than BCH at 12 months (62.4 versus 32.5%). PTFE was easier to work with and easier to handle in the face of infection. The lateral upper arm approach to placement of the PTFE graft is desirable in patients who have had multiple previous access procedures because this area is usually free from scarring, is distant from neurovascular structures, and provides a greater length of graft for needle punctures.


Relationship of obesity to bile lithogenicity in man. Gallbladder bile was aspirated and analyzed for content of bile salts, cholesterol, and phospholipids in 97 patients undergoing jejunoileal bypass. Lithogenic indices (LI) (mole % cholesterol in sample/mole % cholesterol at saturation) were correlated with age, sex, lipid levels and hepatic fatty metamorphosis. The overall incidence of gallstones in the group was 43%(N = 121). Cholelithogenesis was unrelated to age, serum lipid concentrations, LI, or hepatic morphology. A significant relationship was noted between cholelithogenesis and female sex (p less than .03). The incidence of gallstones was greater in patients weighing more than 270% of ideal body weight and the LI greater in those weighing more than 230%. The mean LI of bile was greater than 1.0 (supersaturated) in all patients except nongallstone forming diabetics. The lithogenic index in diabetics without gallstones was 0.88 +/- 0.11, while in nondiabetics without gallstones, the LI was 1.49 +/- 0.10 (p less than 0.001). These observations indicate that grossly obese patients have an increased incidence of cholelithiasis, probably related to supersaturation of bile with cholesterol. In addition, female patients are especially at risk, while other parameters had little or no detectable influence on cholelithogenesis in this group of patients.


Prospective evaluation of angiography in the diagnosis and management of patients suspected of having pancreatic cancer. One hundred three patients suspected of having pancreatic cancer underwent celiac and superior mesenteric arteriography which was reported 'blind.' Final diagnosis, operative findings, and resectability of pancreatic cancers were correlated with angiography reports. Forty patients had pancreatic cancer. Thirty-seven of these underwent laparotomy, and 14 (37%) had resectable lesions. Sensitivity and specificity of arteriogrphy for pancreatic cancer were 72% (29/40) and 71% (45/63) respectively. Resectability was unrelated to the angiographic diagnosis. Nonresectability was related to an angiographic finding of definite tumor vessel (4/4), large-vessel encasement (14/7), and major venous pathology (8/11). Only the first of these was unique to pancreatic cancer. Hepatic metastases were detected in only six of 13 patients. Small-artery encasement, arterial occlusion, vessel displacement, and gallbladder distention were not indicators of diagnosis or extent of disease. Major anatomic anomaly of foregut vasulature was revealed in 25% of angiographic studies. Prior knowledge of such anomalies has important bearing on the operative approach to pancreatic resection. We conclude that angiography should be performed prior to laparotomy whenever a resectable pancreatic cancer is suspected from other investigations. When used prospectively, angiography is not a reliable diagnostic or prognostic tool for pancreatic cancer.


Cutaneous melanoma of the breast.

Cutaneous melanoma of the breast. A series of 21 patients treated surgically for primary melanoma of the skin of the breast has been studied. Melanomas in this location accounted for 1.8% of a total of 1,140 patients with primary clinical Stage I and Stage II melanomas treated during a 28 year period. Wide excision with axillary lymph node dissection in selected instances has resulted in no mortality and no local recurrence to date. This approach allowed the preservation of a major portion of the breast in eight female patients. It is emphasized that melanoma is a cutaneous lesion and considerations applying to lymphatic dissemination of parenchymal disease of the breast need not apply.


Effects of aspirin and dextran on patency of bovine heterografts in the venous system. The effect of short-term treatment with aspirin or dextran on the patency of bovine heterografts in the venous system was investigated. Animals treated preoperatively and for three days postoperatively with either aspirin (600 mgm BID) or low molecular weight dextran (500 cc/day) had statistically significant increased graft patency as compared to controls during the treatment interval. Significance was lost, however, after cessation of therapy. These results suggest that either aspirin or low molecular weight dextran would be useful adjuvants to venous reconstruction. If used in the venous system, bovine heterografts might be expected to yield better short term patency with adjuvant therapy employing either dextran or aspirin.


Several standard elective operations for duodenal ulcer: ten to 16 year clinical results. A survey was undertaken of 558 men with duodenal ulcer who had been treated ten to 16 years previously by truncal vagotomy and drainage, truncal vagotomy and antrectomy and subtotal gastrectomy. Of the 558, 65 had died and 111, presumed living, could not be traced, leaving 382 available for assessment. Between 75 and 85% of the traced patients were considered to have an excellent or very good result, which is a slight improvement on the previously published results in this same group of patients at five to eight years follow-up. Some of the side effects of operation had diminished slightly in frequency and there had been no significant increase in the incidence of recurrent ulceration since the previous survey. Anemia was an uncommon finding. As between the various forms of operation, truncal vagotomy and antrectomy and subtotal gastrectomy demonstrated significantly better protection against proven recurrent ulcer than did truncal vagotomy and pyloroplasty (p less than 0.05). Compared with truncal vagotomy and gastroenterostomy, however, the results of both resection operations, though better, did not achieve statistical significance at p - 0.5 level (p less than 0.1). In regard to Visick gradings the resection procedures had better scores, but the differences were not significant at the p - 0.05 level, except for vagotomy and antractomy as compared with vagotomy and pyloroplasty. But it is stressed that in formulating a policy of surgical therapy for duodenal ulcer the greater inherent immediate risks of resection operations need to be borne in mind.


Phleborheographic diagnosis of venous obstruction. Between February 1977 and May 1978, phleborheograms were done on 328 extremities. Interpretable tracings were obtained in 322 (98.2%). Results were positive for 102 extremities, negative for 220 extremities, and equivocal or uninterpretable for six extremities. Phlebograms as well as phleborheograms were done in 64 extremities. Phlebograms were positive in 41 and negative in 23. The overall agreement between the interpretations of the phlebograms and phleborheograms was 95.3%. The phleborheogram was positive in each case in which the phlebogram was positive. In three cases with negative phlebograms the phleborheogram was positive. Thus, the sensitivity was 100%, and the specificity was 87%. Phelborheography is a useful ajunct to the diagnosis of venous obstruction. It has a high degree of sensitivity (100% in our experience). Clinical correlation is necessary to determine the most likely cause of venous obstruction in individual cases.


Computed tomography in the diagnosis of intra-abdominal abscesses. The diagnosis of intra-abdominal abscess by radiographic means often relies on combining the results of several different imaging modalities. Computed tomography (CT) has been shown to be a safe, accurate and rapid diagnostic method of diagnosing these abscesses. Five patients with a variety of intra-abdominal abscesses are presented in whom the CT scan alone provided the correct diagnosis. The various imaging modalities available for the radiologic diagnosis of intra-abdominal abscess are described and are compared to CT diagnosis regarding their pitfalls.


Carcinoembryonic antigen (CEA) in gastric juice or feces as an aid in the diagnosis of gastrointestinal cancer. Carcinoembryonic antigen (CEA) levels in the feces and serum were evaluated in 22 colorectal cancer patients and 20 healthy volunteers; in CEA levels gastric juice and serum were also evaluated in 28 gastric cancer patients and 14 peptic ulcer patients. Fecal CEA was found in all of 22 colorectal cancer patients as well as in the 20 healthy volunteers. Elevated fecal CEA levels were observed in the colorectal cancer patients, as compared to the healthy volunteers. The feces of 15 of the 22 colorectal cancer patients contained CEA at concentrations higher than the mean value plus twice the standard deviation of the healthy volunteers. The fecal CEA levels did not correlate directly either with Dukes' stage or serum CEA levels. CEA in gastric juice was elevated significantly in 26 of gastric cancer patients, with the exception of two patients with early gastric cancer. On the other hand, serum CEA was elevated in only nine of the 28 gastric cancer patients. These results point out the distinct value of assaying CEA in the feces or gastric juice as an aid in the diagnosis of colorectal or gastric cancer.


Massive unifocal cyst of the liver in a drug abuser: case report and review of the literature. A 20-year-old white male presented, complaining of abdominal fullness. His previous history was unremarkable except for the use of intravenous illicit drugs. Physical examination disclosed a mass filling the upper and lower right quadrants. We evaluated this mass through the  use of barium contrast x-ray, sonography and angiography, and made the preoperative diagnosis of hepatic cystic disease. On operative exploration, a large thin-walled cyst was found on the right lobe of the liver and was shown to be free of communication with the biliary tree; 3,000 cc of chocolate colored fluid were aspirated from the cyst. Total removal of the cyst was achieved with careful dissection. The cavity was filled with omentum and closed with drainage. After a benign immediate postoperative course, the patient remains asymptomatic one year later. Although most reports from the literature describe unexpected intraoperative findings, we stress that symptomatic patients can and should be diagnosed prior to laparotomy, and that a thorough search be made for concomitant polycystic disease. Total extirpation of the cyst is the most desirable of the discussed treatments, when tempered by the age and physical condition of the patient. Thorough preoperative evaluation and awareness of different modalities of therapy allow for the correct choice of treatment.


Ocular pneumoplethysmography: detection of carotid occlusive disease. To determine the accuracy of ocular pneumoplethysmography (OPG-Gee) in detecting carotid arterial occlusive disease, 350 patients were tested by OPG-Gee. Sixty-three patients underwent angiography and the findings were correlated with the results of OPG-Gee tracings. Testing without carotid compression averaged three minutes and was easily performed by a physician or technician. There were no significant complications. Hypertension did not affect evaluation. There were two false-negative tests and no false-positive tests. Without carotid compression the overall accuracy for testing for significant arterial stenosis was 97%. When a carotid compression test was added, the two missed lesions were detected.


The significance of mammary skin edema in noninflammatory breast cancer. Mammary skin edema has been quantitated in 205 cases of T1, T2 and T3 breast cancer by mammographic measurement, and its prognostic significance assessed. Edema was present in 70% of patients and the incidence was directly related to tumor size. Edema was seen on occasions in all quadrants of the breast, but the inner and lower quadrants were the most frequent sites of edema irrespective of the site of tumor. Histology showed the skin thickening located in the reticular dermis; the papillary dermis and epidermis showed no change. It was shown that neither dermal lymphatic involvement nor lymphatic obstruction by regional node involvement was of primary etiological significance. Skin edema correlates with prognosis since there is an increased likelihood of both systemic and local recurrence if skin edema exceeds 0.5 mm. Further investigation and longer follow-up is necessary to show whether skin edema represents a parameter which carries prognostic significance independent of the more usual clinical indications.


Clinical aspects of nonsurgical percutaneous transhepatic bile drainage in obstructive lesions of the extrahepatic bile ducts. Percutaneous transhepatic cholangiography (PTC) with subsequent external bile drainage by nonsurgically established percutaneous transhepatic intubation of bile ducts was performed in 105 patients with obstructive jaundice. Recovery of liver function and improvement in the patients' general condition prior to radical or palliative surgery, nonsurgical palliation in advanced cases of malignancy as well as relief of postoperative leakage from a biliodigestive anastomosis are the indications for the bile drainage technique used in the present study. Clinical aspects such as optimal period of preoperative drainage, frequency of catheter dislodgement, and rate of complications such as cholangitis, bile leakage to the abdominal cavity and risk for peritoneal hemorrhage are discussed. Two deaths occurred within this series.


Cancer of the stomach. Review of consecutive ten year intervals. Records were reviewed for all patients who underwent primary treatment for adenocarcinoma of the stomach at two UCLA hospitals between 1956 and 1975. Division of the data into two, ten-year time periods reveals a pattern of unchanging presentation and pathologic characteristics which probably accounts for the unaltered response to operative therapy. The consistency of certain prognostic findings justifies a surgical approach in which extensive resections are only selectively employed.


Moist bacterial strike-through of surgical materials: confirmatory tests. New tests consisting of modifications of the inverted Mason jar test confirm our previously reported studies which showed that woven and nonwoven surgical materials vary greatly in their ability to serve as barriers against moist bacterial strike-through. Among the woven materials, only tightly woven Pima cloth or materials treated with Quarpel waterproofing process or with polythene layer lamination was invariably resistant. However, tight-woven Pima cloth, which had been treated with Quarpel became permeable after 100 washing-sterilizing cycles. Of the nonwoven materials, single-layer nonwoven materials tended to unevenly permeable to moist bacterial strike-through. Only the front and sleeves of nonwoven gowns reinforced with polyethelene layer were invariably resistant to moist contamination.


Acute cholecystitis complicating trauma. Twelve patients developed acute cholecystitis complicating trauma. Acute acalculus cholecystitis was present in 11 patients. Nine patients died. A review of 20 reports comprising 98 patients shows 86.7% had acute acalculus cholelithiasis, and 61.1% had necrosis, gangrene, and/or perforation of the gallbladder. The overall mortality was 33.3% and only 16.1% of patients treated by cholecystectomy died. The etiology of acute cholecystitis complicating trauma is multifactorial. Gallstones are present infrequently whereas shock, increased bile pigment load, drugs, surgery, and (other) trauma are common precursors. Diagnosis is difficult and depends upon clinical suspicion and the physical examination. Immediate surgical intervention is required. Cholecystectomy is the procedure of choice. We recommend cholecystectomy at initial laparotomy whenever there is evidence of trauma to the gallbladder, or if the right or common hepatic artery is ligated for hepatic bleeding.


Hand-held toy squeaker during carotid endarterectomy in the awake patient. A toy squeaker held by the patient in the contralateral hand is used to monitor cerebral circulation during carotid endarterectomy. Regional anesthesia--cervical plexus block--allowed the patient to cooperate and give useful information, especially during the crucial period of test clamping. In a series of 300 cases, during a period of five years, it was instrumental in avoiding brain damage in 6% of the cases.


Removal of a distal common bile duct stone through percutaneous transhepatic catheterization. A residual distal common bile duct stone was successfully advanced into the duodenum after percutaneous transhepatic catheterization of the biliary tract. Nonsurgical retrieval of retained biliary duct stones through surgically created T-tube tracts has been shown to be a practical procedure with high reported success rates. Reoperation has been necessary in cases where no drainage tube was introduced at surgery or when stones have formed after the fistula closed. Transhepatic catheterization techniques may provide a way to manipulate residual biliary tract stones when no other access is available.


Ultrasound demonstration of wandering spleen. The correct preoperative diagnosis of a wandering spleen is infrequently made either clinically or with conventional radiologic studies. Since ultrasound can readily identify the spleen, it may assist in making this diagnosis. We describe three patients to illustrate the advantages and usefulness of ultrasound. In one postmastectomy patient, the suspected abdominal metastasis was shown to be a displaced spleen, thus obviating the necessity for an exploratory laparotomy. In the other two patients, ultrasound diagnosis was helpful in clinical treatment by localizing the wandering spleen. Ultrasound evaluation is particularly suited for patients with obscure abdominal masses because it is safe, simple, and fast.


Anatomy and osteotomy of the greater trochanter. Eleven human cadaver hips were dissected to define exactly the musculofascial anatomy of the greater trochanter and the supportive structures around it. A readily identifiable plane was defined that permitted osteotomy of the greater trochanter from an anterior approach leaving the vastus lateralis attached to it so that the trochanter could be folded posteriorly and then replaced securely. The osteotomy has been used in difficult total hip replacements at Waterbury (Conn) Hospital and found to be very satisfactory with no wire or bolt fixation necessary to maintain trochanter stability after surgery. Until a large series of these osteotomies has been reviewed, however, additional fixation may be advisable.


Netilmicin. A new aminoglycoside in the treatment of septic burn patients. Netilmicin sulfate, a new aminoglycoside antibiotic, was administered to ten patients with thermal burns who were suffering from septic complications, usually burn wound sepsis. There were seven survivors. Eighty-three percent of all clinical isolates recovered showed sensitivity to the drug. No renal or auditory side effects were noted in any of the patients.


Malignant melanoma. Delayed hypersensitivity skin testing. One hundred eighty-two patients undergoing initial surgical therapy for primary malignant melanoma were evaluated for delayed hypersensitivity using a battery of recall antigens prior to surgery. Fifty-six patients were also sensitized with 2, 4-dinitrochlorobenzene. All tumors were classified by Clark-Mihm levels and the patients were clinically staged. They were followed up for an average period of 55 months. There was no significant difference in the ability of patients with varied Clark-Mihm level lesions to mount a delayed hypersensitivity response to the recall battery or to 2, 4-dinitrochlorobenzene. Thirteen stage I melanoma patients in whom recurrence developed at a distant site exhibited no difference in immune responsiveness when compared to 148 patients in whom recurrence did not develop when both groups were tested with recall antigens. No difference was noted in patients with stage II disease in whom recurrence developed, as measured by reaction to these same antigens. Twelve patients demonstrated anergy to recall antigens, in none of whom has recurrence developed to date. Fifty-six patients who were tested with 2, 4-dinitrochlorobenzene showed no difference in reactivity with tumors classified at any of the Clark-Mihm levels. Anergy demonstrated by delayed hypersensitivity skin testing appears to reflect increasing tumor burden, rather than a preexisting deficiency that can be used to predict patients at high risk for the development of recurrent disease.


Treatment outcome in recurrent head and neck cancer. One hundred cases of recurrent oral, pharyngeal, or laryngeal squamous cancer were reviewed to determine the contribution of retreatment of such lesions to overall survival. Thirty percent (8/27) of locally recurrent T1-2 primary lesions and 4% (1/28) of recurrent T3-4 lesions were cured by retreatment. Forty-five percent (5/11) of patients with conversion of N0 necks were salvaged, while no cures of neck recurrence after an earlier elective (four) or therapeutic (22) neck dissection were seen. Three of eight patients with isolated lung recurrence were salvaged. Patients benefiting most from retreatment were those with local recurrence of small primary lesions, conversion of a previously N0 neck, or isolated lung disease. Those with other types of recurrence were helped much less.


Gastroesophageal fundoplication for reflux following repair of esophageal atresia. Experience with nine patients. Esophageal dysmotility and gastroesophageal reflux (GER) are common sequelae that may persist for many years in infants and children who have undergone repair of esophageal atresia and tracheoesophageal fistula (TEF). The slow clearance of refluxed gastric contents appears to cause a high incidence of aspiration, a high incidence of esophageal anastomotic stricture or leak, and a slow response to dilation of esophageal anastomotic strictures. Nissen transabdominal gastroesophageal fundoplication was performed in nine children (seven who were less than 4 months of age) subsequent to repair of esophageal atresia because of recurrent severe symptoms due to regurgitation. On the basis of this favorable experience with nine infants and children, we believe that an aggressive surgical approach should be taken in the management of symptomatic GER in patients at a young age following repair of esophageal atresia and TEF who fail to respond to an adequate trial of medical treatment.


Preoperative carcinoembryonic antigen levels in colorectal carcinoma. The records of 145 patients with colorectal carcinoma who had preoperative carcinoembryonic antigen (CEA) levels measured were evaluated. Preoperative CEA levels were correlated with pathological stage and tumor locations. Increasing levels of CEA were found with advanced stage of disease. Metastatic tumors could be accurately predicted in large percentage of cases. Right-sided colon tumors had lower levels of CEA, compared to left-sided lesions.


Surgical diagnosis of mediastinal lymphoma of childhood. Lymphoma was found in 40 of 72 children with a mediastinal mass who had had an intrathoracic or extrathoracic biopsy or excision of the tumor performed at the Yale-New Haven (Conn) Medical Center between 1964 and 1977. The lymphomas were typically located in the anterior or middle compartment in children 2 years of age or older, and they were usually accompanied by fever, nocturnal sweating, weight loss, or pruritus. Thirty (75%) of the children with lymphoma had enlarged supraclavicular or cervical lymph nodes available for biopsy, whereas the other ten without palpable lymphadenopathy required a limited anterior thoractomy to obtain tissue for diagnosis. Careful preoperative selection makes extensive thoracotomy or attempts at excision of mediastinal lymphoma unnecessary. The findings in this retrospective study also emphasize the prevalence of lymphoma among mediastinal tumors seen in children older than 2 years of age.


Prosthetic aortic valves. Indications for and results of reoperation. During a 15-year period from January 1962 through December 1976, 42 patients who had undergone a previous aortic valve replacement underwent reoperation. The mean interval between operations was 4.4 years. The indications for reoperation were aortic regurgitation resulting from mechanical malfunction (12 patients), ball variance (15 patients), perivalvular leaks (five patients), prosthetic stenosis (eight patients), anemia (one patient), and recurrent emboli (one patient). The indications were characteristic of a specific valve series. The most common reoperation was aortic valve replacement (29/42), which had a 10.3% operative mortality. Poppet change (10/42) carried a 10% operative mortality and no operative deaths followed suture closure of perivalvular leaks. Eighty-eight percent of patients alive six months after reoperation were New York Heart Association functional class 1 or 2. At last follow-up, 95% of surviving patients were still functional class 1 or 2, with a mean cumulative survival of 4.7 years after reoperation. This experience demonstrates that those patients surviving long enough to undergo reoperation can expect a reasonable operative risk, long-term survival, and excellent clinical improvement.


Postmortem findings in three patients treated with intravenous fat emulsions. Three patients died of intercurrent illness in relation to intravenous nutrition with fat emulsions (20% Intralipid). In two cases, postmortem findings showed milky white, shiny, clotted lumps in the heart, with a fatty acid composition resembling that of fat emulsions. In vitro investigations make it likely that fibrin deposits in hyperlipemic plasma composed the lumps. In two cases, 30- to 50-mu Sudan-positive accumulations were found in the small vessels of the lungs, the cerebrum, and the kidneys.


Salivary gland heterotopia in the lower part of the neck. Heterotopic salivary gland tissue in branchial cleft cysts in the upper part of the neck reputedly differentiates from the epithelial lining of the cyst. We describe a patient with salivary gland tissue found in the lower part of the neck. How salivary gland tissue finds its way to the lower neck is obscure. It is conceivable that the tissue originated from a precervical sinus or cervical vesicle, a distinct embryologic structure that forms in the lower part of the neck between the second branchial arch and the upper thoracic wall, but that normally disappears by the time of birth. The epithelial lining of the cervical vesicle is thought to be associated with the early development of the glossopharyngeal and vagus nerves. Salivary gland tissue may differentiate from the epithelial lining of cervical vesicles and nurture the growing nerves by nerve growth factor elaboration.


Stewart-Treves syndrome. A lethal complication of postmastectomy lymphedema and regional immune deficiency. Lymphangiosarcoma is a fatal complication of postmastectomy lymphedema. The pathogenesis of lymphangiosarcoma in chronic lymphedema is a combination of two factors. First, the edematous region responds in a manner similar to "immunologically privileged sites." Second, because of its anatomic and physiologic properties, it is a favorable site for the development of mutant cell populations for reasons that are not fully understood. As a result, these mutant cells, with their genetically nonidentical antigens, escape recognition by the host's impaired immune surveillance mechanism. The failure to promote a sufficient immune response allows unrestricted tumor growth to take place, resulting in the ultimate death of the patient. Available therapeutic measures are equally unsatisfactory. Emphasis is placed on periodic examination of the lymphedematous extremity, aggressive treatment of established lymphedema and infections, and surgical preservation of lymphatic channels during breast cancer surgery.


Obstructing phytobezoar of an intrahepatic bile duct. Drainage of a choledochal cyst with a cystogastrostomy allowed food to reflux into the liver, where it obstructed a major right hepatic duct and produced recurrent cholangitis. Partial hepatectomy was necessary for relief. Drainage of choledochal cysts with a long Roux-en-Y loop seems advisable.


Phantom breast syndrome.

Phantom breast syndrome. In this study of 41 women who underwent mastectomy, over half (54%) experienced phantom breast syndrome (PBS). Of these, 80% had phantom breast pain. The majority of women (58%) did not report their symptoms to their physicians, despite the considerable interference in their lives from these symptoms. Six variables were found to differentiate the women who had phantom breast syndrome from those who did not. All of these factors were closely related to the psychological aspects of mastectomy. Significant among these was that women who experienced PBS perceived both that they did not receive much emotional support from their surgeons, and that most of their emotional problems were secondary to the mastectomy. In these respects, they differed from women not reporting PBS. By early evaluation of each patient who is to undergo mastectomy, it should be possible to identify those at risk, to develop means to prevent the development of the syndrome, and to treat those women in whom the preventive attempts are unsuccessful.


Management of nonmagnetic intraocular foreign bodies: a new approach with the aid of diagnostic x-ray spectrometry. A new approach is suggested for the management of nonmagnetic intraocular foreign bodies. This approach is based on diagnostic x-ray spectrometry, which is capable of detecting noninvasively the dissolution of metallic intraocular foreign bodies. As long as no copper dissolution is observed, foreign bodies of reasonable size are left in the eye and extraction is recommended whenever a persisting copper dissolution is detected. Of the 32 patients examined and followed up, 23 did not show any copper dissolution. The majority of these patients, one of whom has retained a foreign body for 28 years, have satisfactory visual functions. Of the nine patients in whom copper dissolution was observed, five were operated on. In three of the remaining four patients, the operation was delayed and the dissolution was found to be temporary. These patients retained good visual functions.


Photocoagulation of malignant melanoma.

Photocoagulation of malignant melanoma. A 59-year-old woman developed a pigmented, expanding posterior pole choroidal lesion nasally that was clinically consistent with malignant melanoma. She refused enucleation, but agreed to a trial of photocoagulation therapy. Four weeks after photocoagulation, a reaccumulation of pigmentation and apparent elevation prompted a second photocoagulation treatment. During the second photocoagulation episode corneal edema occurred, and thereafter the fundus view was poor. Again, four weeks after the second treatment there appeared to be increasing pigmentation and possible elevation in the lesion centrally. Because of apparent continued growth of the tumor, the globe was enucleated 82 days after the initial photocoagulation. Serial section histopathologic examination of the lesion revealed only rare neoplastic cells along the base of the lesion. However, myriad pigment-laden macrophages were present around a central area of necrosis. Pigment accumulation within macrophages had simulated tumor growth clinically.


Lipoma of the frontal bone.

Lipoma of the frontal bone. A 61-hear-old man was followed up for more than 17 years with what was thought to be fibrous dysplasia of the frontal bone. Postmortem microscopic examination of the lesion showed an intraosseous lipoma with myxomatous foci and bony metaplasia involving the frontal and orbital portions of the frontal bone.


Spindle cell lipoma of the orbit.

Spindle cell lipoma of the orbit. A 42-year-old woman had an orbital mass lesion removed surgically that proved histologically to be a spindle cell lipoma. To our knowledge, this is the first reported case of a spindle cell lipoma arising in the orbit. This specific type of lipoma occurs chiefly in male patients and is believed to affect the shoulder and posterior neck regions almost exclusively. Spindle cell lipomas, while having unusual features histologically, are benign and should not be mistaken for liposarcomas or other spindle cell soft-tissue tumors.


Posterior subcapsular cataracts: histopathologic study of steroid-associated cataracts. Long-term steroid therapy is associated with production of a posterior subcapsular cataract (PSC). Five steroid-associated cataractous lenses were studied, using light, scanning, and transmission electron microscopy. Anterior, equatorial, and posterior regions were examined. Findings were compared with five age-matched senile PSCs and five nuclear cataractous lenses with no cortical opacities. The posterior polar region of steroid-associated cataractous lenses consists of (1) a superficial zone of liquefaction and (2) a deep zone of segmentally swollen lens fibers. Nucleated lens fibers are present in posterior cortical regions. Cytoplasm at knob and socket junctions had become lucent and plasma membranes were disappearing, leaving empty spaces. Laminated membranous configurations were seen. Although the same basic histopathologic abnormalities were found in steroid-associated cataracts and in nonsteroid senile PSCs, it is their organization and localization that may be the distinguishing characteristics of the steroid-associated cataract.


Albumin-bound bilirubin in subchoroidal fluid. The most unique property of subchoroidal fluid was found to be the high bilirubin level. One distinct yellow band in the same position as albumin was observed when it was subjected to electrophoresis on agarose film. The yellow compound was very soluble in chloroform. Its identity to bilirubin was confirmed by its absorption maximum at 445 nm, and a positive reaction with Ehrlich's diazo reagent. Subretinal fluid and liquid vitreous often had a yellowish appearance after ocular hemorrhage. However, their bilirubin level was not elevated above that of serum. Our data indicated that the degradation of RBCs may be an important causative factor of persistant detachment.


Dextran 40-containing infusion fluids and corneal swelling: a specular microscopic study. We studied the effect of dextran 40 on corneal swelling with a specular microscope. The corneas were stressed by the addition of 10(-5)M ouabain to the infusion fluids for various time intervals. Dextran 40 inhibited swelling of functionally impaired corneas. However, when the dextran 40 was removed from the solution, the corneas swelled rapidly to reach the level of those incubated in ouabain without dextran 40. When the corneas were stressed in ouabain for a short period, dextran 40 had a protective effect that lasted even after its removal from the solution.


Dextran 40-containing incubation media: effect on lens electrolyte and water balance. The effect of dextran 40 on lens swelling and electrolyte balance in lenses stressed by incubation in Ca++-free media was studied. Dextran 40 substantially inhibited lens swelling, Na+ gain, and K+ loss caused by six-hour incubation in Ca++-free media. After an additional 12-hour incubation in Ca++-enriched media, the water and electrolyte balance in the dextran 40-incubated group was essentially the same as that of lenses that were never exposed to a Ca++-free media. Those lenses that were not incubated in dextran 40 demonstrated significant residual lens swelling and electrolyte imbalance. It is concluded that dextran 40, by virtue of its oncotic effect, inhibits colloidal osmotic swelling and exerts a protective effect on lens function under a stress situation.


Visual resolution in a patient exhibiting a visual fatigue or saturation-like effect: probable multiple sclerosis. A rapid visual resolution test conducted on available equipment reveals the presence of rapid falloff in acuity in a case of probable multiple sclerosis. Intense large field illumination was used, and grating acuity was tested using laser red light. The effect is so large that minor anomalies (not subjectively appreciated) or the residuum of earlier minor attacks of retrobulbar optic neuritis can be readily detected. A related "visual fatigue or saturation-like syndrome" was described earlier. In bright environments these patients' vision fades. Briefly closing the eyes restores visual sensitivity. Providing filters or lowering the light level tends to maintain vision. This test must be studied intensively. It offers a noninvasive simple means of showing underlying anomalies in neural conduction of the visual signal. Such anomalies can be prognostic and previously have been revealed only with sophisticated electrophysiological techniques.


Blindness secondary to steroid injections into the nasal turbinates. Two cases of inadvertent intra-arterial injection into the anterior turbinates for treatment of allergic rhinitis resulted in retrograde flow of methylprednisolone acetate in the ophthalmic artery. Both patients demonstrated embolization of the retinal circulation, and one of the choroidal circulation as well. Visual outcome was favorable, although one patient showed a permanent paracentral scotoma. Fundus photographs clearly showed intra-arterial obstruction of arterioles that cleared within several days. Precautions can be taken for the prevention of this complication.


Peripheral retinal neovascularization in rheumatic fever. During a two-year period, a 15-year-old boy had three major manifestations of rheumatic fever, ie, chorea, rash, and carditis. Following the acute carditis, peripheral retinal neovascularization appeared in the left eye. Associated transient hemiparesis suggests that emboli may account for the retinal vascular occlusion. Rheumatic fever should be considered in the medical survey of patients who have retinal new vessels of obscure origin.


Cilioretinal arteries and retinal arterial occlusion. A series of 187 cases of retinal artery occlusion was reviewed. 107 of which were central retinal artery occlusions (CRAO). Of the 107 cases, 28 (26%) showed some degree of macular sparing owing to a patent cilioretinalartery. The patients with cilioretinal sparing regained variable degrees of visual acuity, depending on the amount of the pipillomacular bundle supplied by the patent vessel. The patients with CRAO without cilioretinal sparing rarely regained any useful vision. To our knowledge, this is the first large series documenting the degree of visual return in such cases. From this data, guidelines for counseling patients with CRAO with cilioretinal sparing are presented.


Monofixational intermittent exotropia.

Monofixational intermittent exotropia. The surgical correction of intermittent exotropia occasionally results in a monofixational sensory pattern. Stereopsis as a measure of bifixation was studied preoperatively and postoperatively in 39 cases of intermittent exotropia. Of 26 patients with bifixation, 25 remained so after surgery. Of 13 patients with monofixation, 11 remained unchanged by surgery, one improved, and one lost all binocularity. The presence of preoperative monofixational intermittent exotropia, to explain a monofixation result from intermittent exotropia surgery, is proposed.


Articular manifestations of mixed connective tissue disease. All but one of 28 patients with mixed connective tissue disease (MCTD) who were studied prospectively had arthralgia, and 15 of them had noticed joint swelling. Arthralgia was the first symptom in 14 patients and one of the first two symptoms in 24. Arthralgia was pauciaticular in 4 and polyarticular in 23. Presence of morning stiffness in 15 patients, symmetrical joint swelling in 16, joint deformity in 6, marginal erosions in roentgenograms of the hands of 12, rheumatoid factor in 25, and subcutaneous nodules in 5 caused 24 of the 28 patients with MCTD to fulfill criteria for definite or classic rheumatoid arthritis. All patients, however, also had prominent signs or symptoms of scleroderma, systemic lupus eruthematosus, or polymyositis.


Effects of estrogen on cartilage and experimentally induced osteoarthritis. Estradiol valerate did not ameliorate experimentally induced osteoarthritis in the rabbit. Both normal and osteoarthritic cartilage were susceptible to estradiol suppression of proteoglycan synthesis. Protoeglycan concentration was not diminished with estradiol, suggesting estradiol suppression of proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased proteoglycan catabolism. The severity of osteoarthritis was unchanged despite markedly decreased protoeglycan synthesis in the estrogen treated animals. Osteophyte proteoglycan metabolism differed from other osteoarthritic lesions. Differences in the metabolism of femoral and tibial articular cartilage were observed.


PHA-induced cellular cytotoxicity. Inhibition by a nonimmunoglobulin factor present in sera from patients with active systemic lupus erythematosus. Phytohemagglutinin-induced cellular cytotoxicity by normal mononuclear cells (MNC) is inhibited by serum of patients with active untreated systemic lupus erythematosus (SLE) but not by that of patients with untreated inactive SLE or rheumatoid arthritis. Three-hour preincubation of normal MNC with SLE sera suffices to inhibit throughout the assay. Preincubation with phytohemagglutinin (PHA) before addition of sera does not prevent the inhibition. DEAE-cellulose chromatography, Sephadex G-200 fractionation and immunoelectrophoretic analysis have shown the nonimmunoglobulin nature of this factor. It is thermostable and not affected by deoxyribonuclease or ribonuclease treatment. The mitogen-induced cellular cytotoxicity-inhibiting factor seems to be independent of other serum factors capable of blocking PHA-induced blastogenic transformation.


Coexistent gout and rheumatoid arthritis. Case report and literature review. A 73-year-old woman with Felty's syndrome and arthritis mutilans of long duration presented with tophaceous gout. The 7 previously reported cases of coexistent gout and rheumatoid arthritis (RA) are critically reviewed. Possible explanations for the rare coexistence of RA and gout are discussed: if uric acid is an inhibitor of the immune response, then hyperuricemia and gout could protect against development of RA. Conversely, crystalline protein binding may be a critical factor in the pathogenesis of gout, and the presence of abnormal proteins in RA could protect against gout.


Breast-cancer incidence and mortality rates in different countries in relation to known risk factors and dietary practices. Breast-cancer incidence and mortality rates in different countries were found to be correlated with height, weight and age at menarche, all of which have been identified as risk factors in cohort or case-control studies of breast cancer. There were, however, correlations with total fat and animal protein consumption per capita even after controlling for the 3 anthropometric variables. This suggests that, while some of the effects of diet on breast-cancer rates may be mediated through effects on these known risk factors, there may be more direct effects as well.


Thromboplastic and fibrinolytic activities of cultured human cancer cell lines. Thromboplastic and fibrinolytic activities of 14 lines of cultured human cancer cells were estimated by modified Astrup's methods. High tissue thromboplastic activity was found in one line of urinary-bladder cancer, 2 lines of gastric cancer and one line of lung cancer, but no activity was found in 6 lines of lung cancer. High fibrinolytic activity was noted in one line of gastric cancer and 2 lines of lung cancer, but no activity was seen in 6 lines of lung cancer and one line of gastric cancer. No plasmin activity was found. The tumour cell lines could be classified into 3 groups on the basis of the 2 activities. Cancer cell lines could also be classified into 2 groups: with high or low release of thromboplastin into culture media. Fibrinolytic activity was found in the culture media of all cell lines with high fibrinolytic activity. Fibrinolytic activity, but not thromboplastic activity, seemed to be influenced by the constituents of culture media. No definite correlation was found between the 2 activities and the histological types of the parent tumours of the cultured cells.


Photodynamic effect of haematoporphyrin throughout the cell cycle of the human cell line NHIK 3025 cultivated in vitro. Cells from the established cell line NHIK 3025 were synchronized by repeated mitotic selections. Survival of the synchronized cells after treatment with haematoporphyrin and near-UV light was measured by testing the capacity of the cells to form macroscopic colonies. The sensitivity to photodynamic inactivation was small in early G1, late S and G2. The sensitivity increased throughout late G1 and early S to a maximum in mid S. More than a 100-fold variation is found in the survival after 20 min irradiation in the presence of 4 X 10(-4)M haematoporphyrin.


Two-stage malignant transformation in hamster embryo cells. Transformation of primary hamster embryo cells was investigated using 3-methylcholanthrene (MCA), a combination of MCA and 12-O-tetradecanoylphorbol-13-acetate (TPA), and initiation with MCA or dibenz(a,h)anthracene (DBA) followed by promotion with TPA. Evidence for transformation was (a) abnormal cellular morphology, (b) increased lifespan, (c) growth in soft agar, and (d) tumour induction by s.c. inoculation into suckling hamsters.Cells treated with either MCA or MCA+TPA showed the same latent period to morphological transformation, although their tumorigenic potential varied. Cells did not form tumours when TPA was administered 7 days after treatment with either MCA or DBA. However, when administration of TPA was delayed to 27 days after treatment with a transforming dose of MCA or a subthreshold dose of DBA, the cells transformed and produced tumours in hamsters.Our results show that TPA may act as an inhibitor or promoter, depending on the length of time between treatment of the hamster embryo cells with the carcinogen and administration of the TPA. It appears that treatment of cells with TPA before the initiating event is complete inhibits or delays the development of their ability to induce tumours in animals or grow in soft agar. However, with a sufficient interval between the application of the initiating carcinogen and the promoter, transformation occurs, and the ability of cells treated with subthreshold doses of DBA to form tumours is enhanced.


The fluorescence decay kinetics of in vivo chlorophyll measured using low intensity excitation. We report fluorescence lifetimes for in vivo chlorophyll a using a time-correlated single-photon counting technique with tunable dye laser excitation. The fluorescence decay of dark-adapted chlorella is almost exponential with a lifetime of 490 ps, which is independent of excitation from 570 nm to 640 nm. Chloroplasts show a two-component decay of 410 ps and approximately 1.4 ns, the proportion of long component depending upon the fluorescence state of the chloroplasts. The fluorescence lifetime of Photosystem I was determined to be 110 ps from measurements on fragments enriched in Photosystem I prepared from chloroplasts with digitonin.


The light-harvesting chlorophyll a/b-protein complex from barley thylakoid membranes. Polypeptide composition and characterization of an oligomer. Electrophoretic analysis by sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis showed that the light-harvesting chlorophyll a/b-protein complex of barley thylakoids contains only one polypeptide of apparent molecular weight 26 000. The barley mutant, deficient in chlorophyll b and this light-harvesting complex, lacks this polypeptide. The addition of a nonionic detergent, Triton X-100, to the sodium dodecyl solubilization buffer prior to SDS polyacrylamide tube gel electrophoresis, allowed separation of a relatively stable complex, characterized as an oligomeric form of the light-harvesting complex. The oligomer also contained a polypeptide with an apparent molecular weight of 26 000. The absorption and fluorescence spectral properties of the oligomer are similar to those of the monomer. It is suggested that the oligomer of the light-harvesting chlorophyll a/b-protein is closer to the in vivo form rather than the monomer.


The influence of the thylakoid membrane surface properties on the distribution of ions in chloroplasts. Thylakoid membranes isolated from peas have been subjected to ionic analyses using the technique of neutron activation. This has allowed the analyses of K+, Na+, Mg2+, Ca2+ and Cl- to be measured simultaneously on the same sample. By varying the ionic composition of the suspending medium it has been shown that these chloroplast membranes have no obvious chemical specificity for the inorganic cations studied and that the major controlling factor is the electrostatic neutralization of the surface negative charges. In agreement with the Gouy-Chapman theory and for the conditions used, divalent cations were preferentially attracted to the membrane surface. This finding, together with the ionic analysis of the unwashed thylakoids and of isolated intact chloroplasts, indicated that the major physiological surface cation is Mg2+ and that K+ is probably the main inorganic cation of the stroma. This conclusion is discussed in terms of counterion movement in response to light induced proton pumping at the thylakoid membrane.


A dynamic interaction between the bicarbonate ligand and photosystem II reaction center complexes in chloroplasts. The binding of HCO-3 to Photosystem II reaction center complexes in broken chloroplasts requires the presence of the oxidized form of the negative charge accumulator 'B'. HCO-3 which is already bound to the reaction center II complex can escape if chloroplasts are illuminated with saturating light in the presence of a Hill oxidant and high concentrations of sodium chloride and sodium formate. These observations are explained in terms of a cyclic dark binding of HCO-3 to the reaction center II complex and a subsequent release in the light.


Study of cytochromes c3 from Desulfovibrio vulgaris (Hildenborough) and Desulfovibrio desulfuricans (Norway) by differential pulse polarography and spectroelectrochemical method. (1) Cytochromes c3 from Desulfovibrio vulgaris (Hildenborough strain) and Desulfovibrio desulfuricans (Norway strain) have been studied by differential pulse polarography and spectroelectrochemical method. Both cytochromes exhibit two reduction potential values Eh approximately --0.25 and --0.34 V (D. vulgaris), Eh approximately --0.16 and --0.34 V (D. desulfuricans). (2) Titrations by dithionite and controlled potential electrolysis coupled with polarography and spectrophotometry suggest that in both cases electronic exchanges are rapid.


The isolation of coupled mitochondria from Physarum polycephalum and their response to Ca2+. A method for the isolation of coupled mitochondria from the acellular slime mould Physarum polycephalum is described. The mitochondria oxidize respiratory substrates at rates comparable to those of mitochondria from other microorganisms and show similar responses to respiratory inhibitors. ADP/O values approach similar values to those obtained with mitochondria from higher organisms: 3 with NAD-linked substrates, 2 with succinate, and 1 with ascorbate-TMPD. Mitochondria actively take up low concentrations of Ca2+ with stimulation of their respiration. With succinate or pyruvate-malate as substrates respiratory responses are depressed by Ca2+ concentrations in excess of 200 micron in the presence or absence of phosphate. Exogenous NADH is unique in supporting the uptake of large amounts of Ca2+ in the presence of phosphate and in showing an unusual 'uncoupled' response in the absence of phosphate. A sigmoidal relationship occurs between initial velocity of Ca2+ uptake and Ca2+ concentration with a maximum velocity of approx. 15 nmol/s per mg protein and half maximum velocity occurring at approx. 50 micron Ca2+.


Fusion of phosphatidic acid-phosphatidylcholine mixed lipid vesicles. Ca2+-induced transformation of phosphatidylcholine-phosphatidic acid vesicles to larger bilayer structures has been examined using nuclear magnetic resonance, electron microscopy, gel permeation and radioisotope tracer techniques. For concentrated vesicle preparations where phosphatidic acid content remains less than 50% of total lipid, transformation to larger well defined unilamellar structures can be induced. The size of the product formed is dependent on phosphatidic acid content and on Ca2+ content when Ca2+ levels are between 0.3 and 1.0 mol ratios with respect to phosphatidic acid. During transformation bilayer composition remains unchanged and internal contents are retained in the final structure. These properties are indicative of concerted two vesicle and multiple vesicle fusions. The controllable and concerted fusions make the phosphatidic acid system suitable for further mechanistic studies.


Biochemical studies of the excitable membrane of Paramecium tetraurelia. II. Phospholipids of ciliary and other membranes. The phospholipids of cilia and deciliated bodies of Paramecium tetraurelia were isolated and characterized. 1-alkyl-2-acyl-sn-glycero-3-(2'-aminoethyl) phosphonate (GAEPL), phosphatidylethanolamine, and 1-alkyl-2-acyl-sn-glycero-3-phosphorylcholine (GPC) were the major lipids of Paramecium, and the minor lipids included phosphatidylinositol, cardiolipin, ceramide-(2-aminoethyl) phosphonate (CAEP), ceramide phosphorylethanolamine (COPE) and four sphingolipids whose identity was not established. The deciliated bodies contained 4% cardiolipin, 15% GAEPL, 41% phosphatidylethanolamine, 30% GPC and 3% each of CAEP and phosphatidylinositol; the cilia contained no cardiolipin, 24% GAEPL, 37% phosphatidylethanolamine, 15% GPC, 15% CAEP, 3% phosphatidylinositol, 2% COPE and small amounts (approx. 1%) of the four uncharacterized sphingolipids. No alteration in phospholipid composition was found among cells harvested in the various stages of growth. The phospholipids of six Paramecium mutants of three distinct phenotypes (pawn, paranoiac and fast) were also examined. Only one significant difference was found on comparison of the whole cell, deciliated body and cilia fraction of the mutants with the analogous fractions from wild type cells: the fast mutant, fA 97, had two extra, minor phospholipids (approx. 2%) in the deciliated body fraction that were tentatively identified as 1,2-diacyl-sn-glycero-3-(2'-aminoethyl) phosphonate (AEPL) and 1-alkyl-2-acyl-sn-glycero-3-phosphorylethanolamine (GPE).


The permeability of bilayer lipid membranes on the incorporation of erythrocyte membrane extracts and the identification of the monosaccharide transport proteins. 1. Extracts of the human erythrocyte membrane have been prepared by five different procedures involving Triton X-100 solubilization and gel chromatography. 2. The extracts have been analysed by gel electrophoresis and incorporated asymmetrically into phosphatidylcholine-cholesterol-n-decane planar bilayers. 3. Removal of excess Triton X-100 from membrane extracts or prolonged storage facilities the proteolysis of membrane extracts with the partial or complete breakdown of band 3 polypeptides (notation of Fairbanks, G., Steck, T.L. and Wallach, D.F.H. (1971) Biochemistry 10, 2606--2616) and the appearance of an enhanced zone 4.5 and low molecular weight material. 4. Incorporation of zone 4.5 polypeptides into bilayer lipid membranes increases their permeability to D-glucose at 27 and 5 degrees C. 5. It is suggested that the components of the monosaccharide system are present in band 3 polypeptides but that they can undergo proteolysis with some retention of transport activity.


The binding of organic ions to phospholipid bilayers. The binding of organic anions and cations, mainly tetraphenylboride and tetraphenylarsonium, to phospholipid membranes has been studied using an NMR method. Binding is appreciable and is affected by cholesterol in the membrane and counterions in solution. The passage of the organic anions through the membrane has also been followed. These measurements indicate that it is naive to use organic anions to measure membrane potentials in a simple manner.


Photoaffinity labeling of procaine-binding sites in normal and sickle cell membranes. A photoaffinity probe, procaine azide, was employed to determine the sites of interaction of procaine in normal and sickle cell erythrocytes. Studies show that the number of binding sites and affinity of procaine to membranes derived from normal and sickled cell erythrocytes were similar, although procaine retards the in vitro formation of irreversibly sickled cells from cells, The results show that procaine azide, a photoaffinity analogue of procaine, is covalently incorporated into both protein (60--70%) and lipid (40--30%) components of the membrane. Sodium dodecyl sulfate-gel electrophoresis of the labeled ghosts show that procaine binds specifically to band 3 and periodic acid Schiff staining bands in membranes derived from labeled erythrocytes. Binding of procaine or covalent incorporation of procaine azide into membrane proteins does not affect the phosphate transport. Moreover, pre treatment of intact erythrocytes with 4,4-'diisothiocyano-2,2'-stilbene disulfonate, an anion transport inhibitor, did not affect either the binding or covalent incorporationof procaine azide into erythrocytes. These results indicate that the binding of procaine azide to Band 3 protein occurs at a locus different than that involved in anion translocation process.


The effect of copper on erythrocyte deformability: a possible mechanism of hemolysis in acute copper intoxication. Although the development of hemolytic anemia as a complication of acute copper intoxication is well documented, the precise mechanism by which copper produces accelerated erythrocyte destruction is unknown. Normal erythrocyte survival depends in part on the ability of the cell to deform and pass through narrow areas of microcirculation in the liver and especially in the spleen. In the present study, it is demonstrated that toxic concentrations of copper rapidly and markedly reduce erythrocyte deformability. This reduction in cell deformability is associated with a marked increase in membrane permeability and osmotic fragility of copper-treated cells. Further, the decrease in deformability occurs despite normal levels of cell ATP and the apparent absence of oxidative damage to the cell. These observations indicate that copper-mediated changes in the erythrocyte membrane may be responsible for reducing the flexibility of the cell. The loss of deformability could act to reduce erythrocyte survival and thus explain the hemolysis associated with copper intoxication in vivo.


The effects of suspending medium viscosity on erythrocyte deformation and haemolysis in vitro. Fresh adult human erythrocytes were suspended in isotonic pH adjusted solutions containing various concentrations of Dextran T.500. The cells were subjected to uniform hydrodynamic shear stress in a Ferranti Shirley Cone and Plate Viscosimeter. The amount of lysis incurred at any given combination of exposure parameters was markedly affected by the viscosity of the suspending medium. Optical diffraction patterns obtained whilst the cells were undergoing shear demonstrated that cellular deformation was also a function of viscosity. Consequently, the distorted shape of the stressed cell may play a crucial role in the haemolytic process.