[Iron supplement to blood donors. II. Effect of continuous iron supply]. Seventeen conscripts gave blood every second month, the amount representing an average iron loss of 3.5 mg daily. Seven of them were given 20 mg and ten 100 mg iron as ferrous carbonate once daily throughout the study. Before the first and after the fourth and sixth blood donations they were examined with regard to packed red cell volume, serum iron, total iron-binding capacity and stainable bone marrow iron, and a diagnostic iron absoprtion test was performed. Ten conscripts receiving no iron and giving no blood but comparable to those in the test groups with regard to age, exercise and diet served as controls. The stainable bone marrow iron was found to become stabilized at a level with reduced but still perceptible amounts when 20 mg iron was given, and at a level with somewhat greater amounts when the daily dose was 100 mg. Both levels were lower than before blood donation in most subjects, and the negative iron balance was also reflected in the diagnostic iron absorption test. When a healthy person loses 3.5 mg iron daily, supplementation with a 100 mg tablet per day is therefore insufficient to maintain the iron stores at their previous level. The decrease in storage iron is not progressive, however. When the storage iron is reduced, iron absorption seems to be stimulated sufficiently to establish a balance at a reduced storage iron level.


Intrauterine death and circulating anticoagulant ("antithromboplastin"). A report is presented of a young, otherwise apparently healthy, woman who had three pregnancies which for some unknown reason terminated in intrauterine death (macerated foetuses). During the third pregnancy a coagulation defect was diagnosed, which was characterized by prolonged coagulation times and prolonged one-stage prothrombin time. This defect disappeared after the end of the pregnancy, but returned during the fourth pregnancy. This time a circulating anticoagulant was found, which inhibited the action of thromboplastin. The values found for the various coagulation factors were normal. The anticoagulant titre rose during the pregnancy from 1/2 to 1/10. Leucocyte agglutinating as well as lymphocytotoxic antibodies directed against the husband's cells were demonstrated in the patient during the pregnancy. In this case, by passage of cell fragments and thromboplastic substances to the mother, the foetus had probably induced the development of antibodies against the foetal tissues. The foetus may  be regarded as an incompatible transplant. The fourth pregnancy was terminated by caesarean section in the 34th week. The child weighed 1440 g and, after three exchanges of blood, did very well. The placenta was severely infarcted. It is postulated that the development of antithromboplastin during pregnancy may be a contributory cause of intrauterine death.


Deaths from ischaemic heart disease in Helsinki in the years 1959-1968. Vital statistics and medico-legally autopsied sudden deaths. According to the official vital statistics, altogether 10910 deaths from ischaemic heart disease (IHD) occurred in persons resident in Helsinki during the 10-year period 1959-68. A significant increase was found in the incidence of IHD deaths in both sexes even though changes in the structure of the population were taken into account. The increase in the age-dependent incidence of IHD deaths was most conspicuous at middle age in both sexes and in young males. Altogether 3044 IHD deaths occurring unwitnessed or within 24 hours of the onset of the fatal attack were autopsied medico-legally during the 10-year period of the study. The medico-legally autopsied cases obviously represented a high proportion of sudden IHD deaths occurring outside hospitals in Helsinki. A clear male preponderance was found in the autopsy material as compared with all IHD deaths. The prevalence of cases of acute myocardial infarction varied in different years from 27 to 49 percent at medico-legal autopsies. No significant change occurred during the 10-year period in the distribution of the medico-legally autopsied IHD deaths into social groups, in the suddenness or place of death. The home was the most common place of death. From 1963 onwards the patients dying from an ischaemic heart attack during transportation to hospital or in an outpatient department constituted 6-7 percent of all annual IHD deaths.


Heme catabolism, carbon monoxide production and red cell survival in anemia. Total heme catabolism has been studied through measurement of the endogenous production of carbon monoxide (VCO) in 8 patients with hemolysis, 7 with hypoproliferative anemia, 10 with refractory anemia and hypercellular bone marrow and 7 with splenomegaly, 6 of whom had myeloid metaplasia. Simultaneously, catabolism of circulating red cell hemoglobin heme (Vheme-c) was measured through labelling of the red cells with 51Cr, and the VCA/Vheme-c ratio was calculated for each patient. From a control group it was calculated that this ratio should vary around 1.5. Since no isotope studies were performed in the control group, no range could be defined. Among patients with hemolysis the VCO/Vheme-c ratio was found to vary between 1.3 and 1.8 except in 2 cases of paroxysmal nocturnal hemoglobinuria (PNH) and PNH?, respectively, in whom the ratios were found to be 0.6 and 0.7 suggesting some heme catabolism without corresponding CO formation. In the hypoproliferative group the ratio varied between 1.2 and 1.8 except in one patient treated with androgens, in whom the ratio was found to be 2.9, suggesting increased extraerythrocytic heme turnover. In patients with myeloid metaplasia the ratio varied between 1.3 and 1.8. On the other hand, the ratio varied getween 2.4 and 3.0 among patients with refractory anemia and hypercellular bone marrow, thus confirming earlier findings that in this type of anemia turnover of bone marrow heme is markedly increased. A significant correlation was found between VCO and initial morning COHb%(r equals 0.84). The conclusions drawn are (a) that Vheme-c sometimes represents less than 50% of total heme turnover and (b) that COHb and/or VCO reflect total heme turnover except in patients with blood loss or intravascular hemolysis with hemoglobinuria.


Nicotinic acid and the endogenous production of carbon monoxide. The endogenous production of carbon monoxide (VCO) has been followed with the aid of a rebreathing system for 3 hours in four healthy volunteers after i.v. injection of 50 mg nicotinic acid (NA). After an initial slight decrease for 15-30 min in the CO hemoglobin per cent saturation (COHb), a rapid increase was registered for 120 min, whereafter the VCO returned to the normal preinjection level. The amount of "extra" CO produced varied between 4.1 and 2.2 ml, corresponding to 2.9 and 1.6 g Hb or 182 and 98 mumol heme,respectively. These figures are 3-5 times higher than those reported in the literature, calculated from increases in serum iron, bilirubin and COHb (without the use of a rebreathing system). When related to the total body heme (TBH) estimated with the CO dilution technique, the amount of "extra" heme metabolized after NA corresponded to 0.30% (range 0.26-0.32) of the TBH (a fourth of the total daily heme turnover or a third of the daily HB heme catabolism.


Deaths from ischemic heart disease in persons aged 65 or younger in Helsinki in 1970 with special reference to patho-anatomic findings in hearts.?211. Deaths from ischemic heart disease(IHD) occurring during a period of one year in Helsinki in persons aged 65 years or younger have been investigated by the Ischaemic Heart Disease Register. Altogether 526 fatalities were registered. Autopsy data were collected in 432 cases, the autopsy rate being 82 percent. The results are presented separately for persons autopsied in the pathologic departments, representing mostly delayed deaths in hospitals, and for medico-legally autopsied persons representing sudden deaths outside hospitals. The diagnosis of IHD death was either based on the positive patho-anatomic or clinical evidence of an acute heart attack or supported by a history of clinical IHD in 92 percent of all registered fatal cases. In the remaining fatalities the possibility of other causes of death had been more or less definitely excluced. All persons with an acute attack of IHD and all autopsied cases showed a division into four socio-economic groups very similar to that of the population of Helsinki. Men belonging to the lowest social group were over-represented among medico-legally autopsied cases. A history of a previous heart disease, visits to a doctor and the use of digitalis were less common in persons autopsied medico-legally than in those autopsied in the pathologic departments. In the former an acute infarction was most often located in the posterior wall and in the latter in the anterior wall of the left ventricle. The prevalence of an occlusion was highest in the right coronary artery in the former and in the left anterior descending coronary artery in the latter; In medico-legally autopsied cases in which a recent myocardial infarction was observed the interventricular septum was involved in 81 percent, but in cases with an old infarction the septum was involved in only 52 percent. No difference in the size of the hearts, the frequency of an old infarction or the prevalence of coronary occlusions was found between persons autopsied in the pathologic and forensic departments. Although a previous angina was about equally common in both sexes, old infarctions were more common in men. The increase in heart weight had occurred proportionally to the same extent in both sexes.


Oxygen uptake and cardiac output during submaximal and maximal exercise in adult subjects with totally corrected tetralogy of fallot. Ten female and eight male adults with tetralogy of Fallot, the majority totally corrected at adult age, have been studied at rest and during submaximal and maximal exercise on a bicycle ergometer. Oxygen uptake was determined by the Douglas bag technique and cardiac output by the dye-dilution method. Maximal oxygen uptake was reduced about 30-40% from normal. Thus a complete normalization of the aerobic working capacity was not achieved in spite of an intracardiac repair that was considered surgically satisfactory. Cardiac output response to exercise was subnormal, mainly due to small stroke volumes and partly because of low heart rates. A fall in stroke volume of more than 10 ml was found in 8 of the patients during exercise. No correlation was found between stroke volume during maximal excercise, on the one hand, and the presence of a particular residual defect, anatomy of the right ventricular outflow tract prior to operation and the use of a right ventricular outflow patch on the other. However, too few patients were studied to allow any definite conclusions as to the possible influence of these variables. It remains to be shown whether the haemodynamic abnormalities will be less and the aerobic work capacity better if total correction is undertaken at an early age.


Oxygen uptake arterial blood gases and blood lactate concentration during submaximal and maximal exercise in adult subjects with shunt-operated tetralogy of fallot. Ten female and six male adult subjects with shunt-operated tetralogy of Fallot have been studied at rest and during submaximal and maximal exercise on an average 20 years after the palliative operation. There was a considerable reduction in the aerobic work capacity, maximal oxygen uptake (VO2) being 1.00 1/min STPD. Though ventilation (VE) was out of proportion to VO2 as indicated by an abnormally high ventilation equivalent (52.1), values for VEmax were low (50.81/min BTPS) and of approximately the same order as in a comparable group of totally corrected TOF patients. In spite of increased VE in relation VO2 the PaCO2 increased from 30 mmHg at rest to 49 mmHg during maximal exercise, while PaCO2 decreased from 60 mmHg at rest to 44 mmHg during submaximal exercise I. During heavier exercise no further fall was noted. Base excess decreased from -2.9 to -9.8 mEq/l. Thus a combined respiratory and metabolic acidosis was at hand during exercise, the metabolic component, however, being normal. Maximal blood lactate concentrations were low (5.8 mmol/l) and contrasted with the high intramuscular lactate concentrations earlier reported in some of the patients. The low values found for VO2 max indicate that a palliative operative procedure in TOF is no alternative to an intracardiac repair in the long-term course. The two main factors limiting exercise tolerance were acidosis and accumulation of lactate within the muscle cell.


The frequency of secondary hypertension. In a series comprising 482 patients with hypertension requiring treatment 79 percent had to be classified as essential hypertension. Bilateral renal disease was found in 9 percent, unilateral renal disease in 3.3 percent, but only one patient underwent surgery. Renal artery stenosis was found in 24 patients (5 percent), but only 5 (1 percent) were operated on. Two cases of primary hyperaldosteronism and one of phaeochromocytoma were found; in all three surgical intervention was successful. Oral contraceptives had caused the elevated BP in 7 patients (1.5 percent). It is emphasized that the frequency of curable hypertension is still very low and this should be taken into account when routine examination of patients with hypertension requiring treatment is discussed.


Haemodynamic effect of atrail triggered versus fixed rate pacing at rest and during exercise in complete heart block. The central haemodynamics at rest and during exercise have been studied in 25 patients with complete AV block who were treated with fixed rate (FRP) and atrial triggered pacemakers (ATP). The aim of the investigation has been to study the effect of a synchronized atrial contraction for the filling of the ventricles and for the cardiac output (Q). Pressures and Q have been determined during heart catheterization. The P wave for triggering the atrial synchronized pacemaker has been obtained with an electrode in close contact with the atria, introduced by means of mediastinoscopy. The study consists of two series. In the first series (12 patients) the central haemodynamics were recorded with each patient connected first the FRP (about 70 impulses/min) and later to the ATP. Most patients were studied both at rest and during exercise, the work loads being identical with both types of pacemakers. Q at rest is 10% higher with ATP (p less than 0.02) than with FRP and during exercise 20% higher with ATP (p less than 0.01). Stroke volume (SV) at rest is equal with both types of pacemakers, but significantly larger with FRP during work (p less 0.001). The left ventricular (LV) filling pressure is significantly lower (p less than 0.01) with ATP at rest, but not during exercise (p less than 0.8). In the second series 13 patients were studied at rest and during exercise. The recordings of pressures and Q were first performed with the patient on ATP. After 30 min rest an identical study was performed with the patient connected to FRP, the rate of which was matched (FRPm) to that previously recorded with ATP. Q at rest is 18% higher (p less than 0.01) with ATP than with FRPm and during work 8% higher (p less than 0.05) with ATP. SV at rest is significantly larger (p less than 0.01) with ATP than with FRPm, whereas during exercise no significant difference is observed between the two types of pacemakers. LV filling pressure at rest is significantly lower on the 5% level with ATP; during exercise no significant difference is observed. The investigation shows that in many patients, especially younger ones, treatment with ATP makes it possible to obtain a larger Q during exercise, and thus to increase the oxygen transporting capacity of the circulation. This benefical effect may be more pronounced in patients with low compliance of the ventricular myocardium.


The thyroid in ulverative colitis and Crohn's disease. II. Thyroid enlargement and hyperthyroidism in ulcerative colitis. The frequency of thyroid disease has been surveyed in 300 patients with ulcerative colitis (UC) and 600 controls. The controls were drawn from visitors to the general medical wards of the Radcliffe Infirmary and were matched for age and sex with the UC patients. Two observers independently assessed all these subjects for thyroid enlargement of the simple goitre type. Although there were minor variations between the results obtained by the two observers, they found simple goitre in 8.7-6.3 percent among the UC patients compared with 4.3-3.3% percent among the controls; a difference which is significant. A history of thyrotoxicosis was obtained in 3.7 percent of the UC patients compared with 0.8 percent of the controls (p greater than 0.01). In more than half of the UC patients with a history of hyperthyroidism, the hyperthyroidism occurred years before the onset of the colitis. It is therefore highly unlikely that hyperthyroidism is a complication of the colitismpossible reasons for the association of the two diseases are discussed but it is concluded that no satisfactory explanation exists at present.


Initial serum potassium level in relation to early complications and prognosis in patients with acute myocardial infarction. During two years 450 patients with AMI have been treated in the CCU at Serafimerlasarettet. Serum potassium level was determined in 444 patients on admission. Hyperkalaemia was a rare finding associated with a bad state on admission and a poor prognosis. Hypokalaemia was recorded in 15% of the patients and was associated with previous diuretic treatment, supraventricular bradycardia as well as atrial flutter and fibrillation during the first 24 hours in the CCU. Ventricular ectopic beats and venticular tachycardia were also seen more frequently in hypokalaemic than in other patients.


Incidence and presentation of myocardial infarction in North Karelia, Finland. A myocardial infarction (mi) register was started on May 1, 1972 in the county of North Karelia in Eastern Finland as a part of the North Karelia project. Information about all cases with a suspected acute MI among the North Karelian population are collected by the register. The principles of the register follow the recommendations of the WHO expert working group. Altogether 713 cases were registered between May 1, and Dec. 31,1972. The distribution of them into diagnostic categories was: "definite" 57%, "possible" 30%, "no acute MI" 8% and "insufficient information" 5%. Patients with no acute MI have been excluded in the results. About 47% of the male patients below 65 years had a history of previous MI. Most of the patients in the group had been heavy cigarette smokers, eating mainly butter as the fat in their diet. Overweight was rare among the male patients but not among the females. During the years preceding the attack, most of the patients had visited a physician and a pathological ECG had been recorded. The average time delay before hospital treatment was internationally relatively short. The 4 week fatality rate among patients below 65 years was 37% for males and 35% for females. These rates were slightly lower than those in the register material in Helsinki. The annual incidence rate per thousand for the age group 30-64 in North Karelia was 13.8 among males and 2.6 among females. The incidence rate increased continuously with age among males,among females it increased markedly only after the age of 60. The risk ratio between North Karelia and Helsinki for the age standardized incidence rates of males in the age group 30-64 was 1.38, and for respective mortality rates 1.21. Within North Karelia the highest incidence rate for males aged 30-64 was recorded in the rural area of Ilomantsi-Tuupovaara in the East.


Substrate incorporation into hepatic lipids and proteins in vitro in patients with pre-beta hyperlipoproteinemia. Fifty-three patients operated on for uncomplicated gallstone disease have been studied concerning the hepatic synthesis rate in vitro of glycerides and proteins. Thirteen of the patients had pre-beta hyperlipoproteinemia. Five of them and four normolipoproteinemic patients were fed a sucrose-enriched diet for two weeks prior to the operation. In the non-sucrose-fed hyperlipoproteinemic patients the liver concentration of triglycerides (TG) and the incorporation rate of precursors into TG were increased. A significant correlation was found between the synthesis rate of TG in liver tissue and the plasma TG concentration in these hyperlipoproteinemic patients. After sucrose feeding of patients with hyperlipoproteinemia the concentration of phosphoglycerides  (PG) the incorporation rate of labelled precursors in PG were significantly lower than in normolipoproteinemic patients and in hyperlipoproteinemic patients on an ordinary diet. The incorporation rate of leucine into hepatic proteins and the hepatic protein concentration were the same in non-sucrose-fed controls, sucrose-fed, and non-sucrose-fed hyperlipoproteinemic patients. The results indicate an increased vulnerability of the hepatic PG and protein metabolism for dietary sucrose in patients with pre-beta hyperlipoproteinemia.


Antibody titre changes and skin reactivity in patients with liver cirrhosis undergoing portocaval shunt operation. Ten patients with liver cirrhosis undergoing portocaval shunt operation have been followed immunologically during their postoperative course regarding antibody titres to various antigens, viral as well as bacterial. The antibody determinations included rubella, vaccinia and cytomagalo viruses, diptheria toxoid, Candida albicans, streptolysin O, typhoid and paratyphoid O and H and the syphilis reactions: Kahn, Wassermann and Meinicke. Twenty-one blood donors served as controls. Skin test reactions to diptheria, Candida albicans, streptokinase and tuberculin were performed on the same patients. Eight patients submitted to cholecystectomy served as controls for pre-and postoperative skin tests and antibody titres. The liver cirrhosis group before operation had a significantly higher number of elevated antibody titres concomitant with a significantly reduced skin test reactivity to diphtheria toxoid and streptokinase. An increase in the number of elevated antibody titres was seen after portocaval shunt operation. In no case was a higher antibody titre associated with an increase in skin reactivity to the corresponding antigen. A number of significant titre changes to viral antigens were seen in the postoperative course without clinical evidence of the corresponding viral disease. Thes findings indicate that under certain circumstances antibody titre changes should be interpreted with caution.


Goal-setting as compensation for fear-of-success. Stories written in response to an academic achievement cue by junior high girls were scored for imagery that reflected fear of success. Fifty-four percent contained fear-of success themes, less than previously reported for college girls. The subjects subsequently worked in a group setting as they identified mistakes in a set of pictures. Each subject kept tally of her own progress as she proceeded with the task. Fifty-eight subjects were encouraged to set goals as they worked through the pictures and found significantly more mistakes from first picture to last than the 37 subjects who received control instructions. Task response was compared to interpretation of the story cue. The subjects who wrote positive stories and received control instructions for the picture mistake task found significantly more mistakes as they progressed through the task than the subjects who wrote fear-of-success stories. No significant difference in mistake indentification was found when goal-setting instructions were given between those who had written positive stories and those who had written fear-of-success stories. Goal-setting instructions appeared to compensate for the effects of fear-of-success that many girls exhibited.


Dating patterns, sexual relationships and use of contraceptives of 700 unwed mothers during a two year period following delivery. Little has been systematically studied regarding the adjustment period following the birth of an illegitimate child and finalizing the decision to either raise or relinquish the child for adoption. In order to better understand the phenomenon it was decided to ask the UM herself regarding her experience. Seven hundred UMs were sent a questionnaire, each being randomly assigned to several time intervals varying from 3 to 18 months post decision time. The UMs were approximately 98% Caucasian, coming from primarily low and middle socioeconomic levels, and residing in the Upper Midwest. Questionnaires were returned by 79% of the UMs (n equals 550). Over 75% of thses had relinquished their child for adoption. The majority of the UMs reported they were dating (86%), with approximately one-half dating someone steadily at the time of the study. Those who relinquished reported a higher incidence of dating in general, however, those who kept their children were more linely to date and marry the alleged father (AF). Approximately one-half of the UMs had indicated having had sexual intercourse, and over 75% of these indicated that they were contracepting. However, of those not having had intercourse, approximately 10% were contracepting. These dating patterns and sexual relationships varied by age and the respective decision regarding the child. As other adjustment areas are examined in the total study it is hoped that a clearer understanding of the dyamics will be forthcoming.


Treating heroin overdose.

Treating heroin overdose. Immediate attention must be given to the respiratory system of the heroin abuser; then he should be given naloxone HCl. Search for evidence of use of additional drugs, which may compound problems. Pulmonary edema, aspiration pneumonia and pulmonary embolization are the most common complications. Infections, particularly endocarditis, and cardiac arrhythmia also occur with heroin overdose. Hepatitis is common. Treatment must include not only attention to the presenting symptoms but also referral to a rehabilitation center when possible.


Hemodialysis in the home.

Hemodialysis in the home. Hemodialysis can be performed safely and satisfactorily in the home. It is the method of choice for long-term maintence dialysis in properly selected patients and offers an excellent opportunity for porlonged survival and rehabilitation. Minimal criteria include the availability of an assistant, suitable physical facilities, appropriate age, adequate intellectual capacity and the potential for rehabilitation.


Psychohormonal treatment during the menopause. Today the physician who treats women with emotional problems during menopause cannot function solely as a psychotherapist; he must deal with both their soma and psyche. The interaction between the endocrine and emotional states has long been known. When the equilibrium of an essentially normal state--menopause--is disturbed, a multifaceted approach is essential to restore homeostasis. Hormone replacement, psychotherapy and psychotropic drugs may all be necessary. Serial vaginal smears are useful in monitoring therapy.


Natural history of S-T segment elevation after acute myocardial infarction. Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 per cent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation. We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.


Q waves and ventricular asynergy: predictive value and hemodynamic significance of anatomic localization. Two hundred sixteen consecutive patients were evaluated to determine the value of pathologic Q waves in predicting the presence and severity of ventricular asynergy. Of 64 patients with pathologic Q waves, 95 percent demonstrated asynergy. Q waves in the anterior leads denoted asynergy in 30 of 30 patients, anterior asynergy in 29 of 30 and an anterior aneurysm in 25. Q waves in the inferior leads indicated asynergy in 30 of 33 patients, inferior asynergy in 25 of 30 and an associated aneurysm in 19. Conversely, of 52 patients with an aneurysm, 44 also had pathologic Q waves. If Q waves were present, 72 percent of asynergic zones exhibited akinesis or dyskinesis; however, in the absence of Q waves an aneurysm was present in only 22 percent (P less than 0.0001). Hemodynamically, anterior asynergy, whether defined by Q waves or by ventriculography, was associated with more left ventricular dysfunction than was inferior asynergy (P less than 0.01). Of 21 patients with a cardiomyopathy, none had pathologic Q waves. The data indicate that pathologic Q waves can aid significantly in predicting the presence and location of a severely asynergic zone. Although their absence does not exclude the possibility of asynergy, the latter is much less likely and, if present, amy be of milder form.


Effects of changes in preload, afterload and inotropic state on ejection and isovolumic phase measures of contractility in the conscious dog. Despite much investigation, the usefulness of various indexes employed clinically for detecting alterations in ventricular contractility in the intact circulation remains controversial. The effects of acute preload, afterload and contractility changes on both ejection and isovolumic phase measures of left ventricular function were analyzed in normal, trained conscious dogs instrumented with micromanometers and endocardial ultrasonic diameter gauges. Rapid volume overload increased the excursion of the left ventricular diameter (delta LVD) by 7 percent above the control level, but mean velocity of circumferential shortening (VCF) did not change significantly; peak rate of left ventricular pressure rise (dP/dt) increased by 11 percent and (dP/dt)/DP40 (DP = developed pressure) was augmented by 10 percent, but maximal [(dP/dt)/LVP], or "Vpm," decreased by 20 percent. Pressure overload by phenylephrine infusion decreased delta LVD by 15 percent and mean VCF fell by 26 percent; peak dP/dt and (dP/dt)/DP40 remained unaltered, but VPM was reduced by 37 percent. Isoproterenol augmented peak dP/dt by 55 percent, and (dP/dt)/DP40, Vpm and mean VCF were increased comparably. Propranolol decreased these measures equally by about 16 percent. Therefore, in the conscious animal in the steady state, isovolumic phase indexes were mildly influenced by acute volume loading, wheras ejection phase indexes were not. Acute increases in aortic pressure markedly reduced ejection phase measures, whereas the isovolumic indexes were unaffected. All of the indexes studied were comparably sensitive to acute alterations in contractility, but we conclude that no single measure can always be used for defining an acute contractility change in the intact circulation.


Noninvasive assessment of clinical response to oral propranolol therapy. Nineteen patients with severe but stable angina pectoris entered a double blind controlled study to evaluate the effect of orally administered propranolol on exercise tolerance measured with a bicycle ergometer, and left ventricular function measured by echocardiography and systolic time intervals. In the group treated with propranolol the dose was increased from 80 to 320 mg/day. Studies including determination of propranolol blood levels were obtained before treatment and for each dose of propranolol. With propranolol, 80 mg/day, total work performance increased by 128 percent from 765 plus or minus 125 before treatment to 1,792 plus or minus 285 kilopond-meters (mean plus or minus standard error) (P less than 0.01). With 160 mg of propranolol daily, total work performance decreased, but remained higher than at control levels. In the group given propranolol, left ventricular function decreased progressively with increasing doses of the drug. As measured from the echocardiogram, maximal endocardial posterior wall velocity decreased 42 percent, from 72 plus or minus 7 to to 41 plus or minus 4 mm/sec (P less than 0.02); ejection fraction decreased 13 percent, from 0.68 plus or minus 0.01 to 0.59 plus or minus 0.01; and end-diastolic bolume increased 28 percent, from 79 plus or minus 11 to 102 plus or minus 9 ml/m2 (P less than 0.05). The preejection period and the ratio between preejection period and left ventricular ejection time significantly increased with progessive dose increments. There was no correlation between blood level of propranolol and improved work performance. Exercise tolerance was maximally improved with doses of 80 to 160 mg/day. At higher dose levels left ventricular function deteriorated and exercise work decreased. Noninvasive assessment of left ventricular function proved more valuable than determination of drug blood levels in managing patients with angina pectoris and provided a guide to optimal adjustment of dosage.


The use of practolol in supraventricular arrhythmias associated with acute illnesses. Supraventricular arrhythmias complicating acute illnesses were treated with intravenously administered practolol, a cardioselective beta adrenergic blocking agent. Slowing of atrioventricular conduction resulted in rapid control of ventricular rate in 23 of 33 episodes (70 percent) in 31 patients. Profound hypotension developed in two patients, presumably as a result of interference with adrenergic circulatory support. Serum levels from 19 patients showed no correlation with response to therapy and were much lower than levels previously reported necessary for slowing of tachycardias induced by isoproterenol and exercise. Response to practolol was maximum within 15 minutes and was not improved by additional dosage sufficient to raise serum levels. Practolol was a rapidly effective and safe antiarrhythmic agent in situations in which propranolol would be contraindicated and the risk of digitalis toxicity increased; it should be considered a primary drug for initiation of therapy for supraventricular tachyarrhythmias.


Inefficacy of "therapeutic" serum levels of digoxin in controlling the ventricular rate in atrial fibrillation. Although therapeutic and toxic serum concentrations of digoxin have been established, there is sparse information permitting correlation of drug level with clinical effect. This study was undertaken to assess the radioimmunoassay serum digoxin levels in 30 patients with acute atrial fibrillation (38 determinations) and 30 patients with chronic atrial fibrillation (54 determinations). Those with chronic fibrillation were subdivided into those in clinically stable condition (14 patients), and those seriously ill and in clinically unstable condition (16 patients). Slowing of ventricular rate in patients with stable, chronic atrial fibrillation was accomplished in 10 of 16 instances by "therapeutic" and "subtherapeutic" levels of digoxin (less than 2 ng/ml). Ventricular rate was "controlled" (65 to 95 beats/min) with therapeutic levels of serum digoxin in only five instances of acute atrial fibrillation and seven of unstable chronic atrial fibrillation. In 43 studies (23 of acute atrial fibrillation, 20 of chronic atrial fibrillation), a rapid ventricular rate (95 to 140 beats/min) persisted in the presence of "therapeutic" or high levels of digoxin. Thirty-nine of these were in patients who were seriously ill with conditions such as infection, hypoxia or recent thoracotomy. Slowing of the ventricular rate required "toxic" concentrations of digoxin (2.5 to 6 ng/ml) in 15 instances. We conclude that sufficient amounts of digoxin to achieve "therapeutic" serum concentrations may fall to lower the ventricular rate in atrial fibrillation to less than 100 beats/min, especially when a serious, complicating illness coexists.


Action of drugs in patients early after cardiac surgery. I. Comparison of isoproterenol and dopamine. Dopamine and isoproterenol were each administered in two different doses to 12 patients with coronary artery disease in the period immediately after open heart surgery. The two doses of dopamine resulted in respective increases in cardiac output of 23 and 43 percent and reductions in systemic vascular resistance of 23 and 32 percent; neither dose significantly altered heart rate. The two doses of isoproterenol caused respective increases of 23 and 37 percent in cardiac output and 18 and 28 percent in heart rate and reductions in systemic vascular resistance of 22 and 29 percent. We conclude that lack of chronotropic effect of dopamine as compared with isoproterenol may make the former the agent of choice in patients requiring inotropic agents for their care in the early period after cardiac surgery.


Hyperkinetic heart in severe hypertension: a separate clinical hemodynamic entity. A long-term study of established hypertension helped identify a well defined group of 10 patients who differed both clinically and hemodynamically from 59 patients with the more frequent form of this disease. Their cardiac output was significantly increased (P less than 0.001) despite a severe elevation of arterial pressure (average 212/125 mm Hg plus or minus 13.5/7.3[standard error[). All had labile hypertension of long standing (16.2 years average) that was difficult to control and always symptomatic; in all, the diagnosis of pheochromocytoma had to be specifically excluded. Increased myocardial contractility was suggested by (1) significant elevation of the rate of rise of isovolumic pressure (P less than 0.001), and (2) high ratio of cardiac output to cardiopulmonary volume (P less than 0.005). Beta adrenergic blockade with propranolol helped to alleviate symptoms and to control tachycardia but failed by itself to reduce arterial pressure.


Atypical posterior leaflet motion in echocardiogram in mitral stenosis. The echocardiographic diagnosis of mitral stenosis is based on the finding of a decreased early diastolic slope of the anterior mitral leaflet. This finding is also seen in other conditions in which the rate of left ventricular filling is reduced by decreased compliance of the ventricular myocardium rather than by mitral valve obstruction. Patients with "true" mitral stenosis have been differentiated from those with decreased ventricular compliance resulting in "false" mitral stenosis by the direction of movement of the posterior mitral valve leaflet. This report describes a patient with mitral stenosis proved at cardiac catheterization whose echocardiogram showed posterior motion of thickened posterior mitral leaflet during diastole, a finding previously considered to exclude organic mitral stenosis. This false negative echocardiographic finding in proved mitral stenosis has not previously been reported.


Echocardiographic findings in isolated, surgically created tricuspid insufficiency. The effects of surgically created tricuspid insufficiency on the right ventricular dimension and the motion of the interventricular septum were determined by serial echocardiography in a patient with a hemodynamically normal heart who underwent tricuspid valvulectomy and later tricuspid valve replacement for medically intractable bacterial endocarditis. Initially, both the right ventricular dimension (1.8 cm) and motion of the interventricular septum were normal. After valvulectomy interventricular septal motion became distinctly paradoxical (pattern A, later pattern B), and the right ventricular dimension progressively increased to 3.5 cm. After successful tricuspid valve replacement interventricular septal motion promptly returned toward normal as did the right ventricular dimension (2.2 cm). The rapid changes in these echocardiographic variables with creation and relief of acute right ventricular volume overload correspond well with results of previous work in experimental animals but differ from findings in man with chronic right ventricular volume overload.


Transient Q waves in Prinzmetal's angina. Transient abnormal Q waves were seen in two patients with Prinzmetal's angina during episodes of chest pain. The Q waves appeared recurrently while the patients had chest pain and disappeared when it subsided, indicating that Q waves suggestive of myocardial infarction can be seen with severe myocardial ischemia without actual necrosis. We describe these two patients, the various conditions in which transient abnormal Q waves have been reported and the theories offered to explain this electrophysiologic finding.


Ventricular aneurysm with ventricular tachycardia. Report of a case with epicardial mapping and successful resection. A case of ventricular aneurysm with refractory ventricular tachycardia is presented. Epicardial mapping was used to localize the site of earliest epicardial activity to the margin of the aneurysm, and subsequent resection of this area abolished the rhythm disturbance.


Cardiovascular complications of pheochromocytoma crisis. Two patients with hypertensive crises due to pheochromocytoma presented with unusual features suggestive of cardiovascular disorders other than pheochromocytoma. These features included transient cortical blindness and other neurologic deficits, electrocardiographic changes indicative of transmural infarction and peripheral arterial spasm. In both patients the diagnosis of pheochromocytoma was made later; removal of the tumor was followed by ready reversal of the clinical and biochemical abnormalities. Management of such cases includes suspicion of the diagnosis in the presence of atypical features, early initiation of therapy with alpha and beta adrenergic blocking agents and a definitive surgical procedure before peripheral vascular changes become irreversible. When an apparent myocardial infarction occurs, the diagnosis of coronary artery disease cannot always be excluded, but rapid stabilization of the clinical and electrocardiographic changes after adrenergic blockade would favor the diagnosis of a catecholamine-induced myocarditis. The coexistence of coronary artery disease and uncontrollable arrhythmias presents an increased risk but, if pheochromocytoma is suspected, surgery may be necessary despite the increased risk.


Valve replacement--a perspective.

Valve replacement--a perspective. Several potential hazards in the evaluation of patients with valve replacement are emphasized. A more uniform method of analysis of data is urgently needed. In the symptomatically disabled patient aortic and mitral valve replacement have improved both the quality of life and the length of life, provided that the disease is not far advanced. Anticoagulation with sodium warfarin is still needed in patients with prosthetic valves. Many important questions, including those related to ventricular function and choice of prosthetic devices, remain unanswered. The cost-benefit ratio and a weighting of various complications of valve replacement should be assessed. Many factors have to be taken into account before considering valve replacement early in the course of the patient's disease.


Hemodynamic changes after valve replacement with Starr-Edwards prostheses. A brief review of the pathophysiology of aortic and mitral valve disease and the hemodynamic results of valve replacement with caged ball prostheses are described. In most patients intracardiac pressures and restored to normal at rest, although there are small pressure gradients across mechanical valves. Severe pulmonary hypertension, if present, usually will regress. With exercise, abnormalities of left atrial pressure or left ventricular function may be found after valve replacement. The causes of failure to achieve hemodynamic improvement with surgery and the late return of congestive failure are discussed.


Myocardial ultrastructure in patients with chronic aortic valve disease. Light and electron microscopic observations were made on left ventricular myocardium removed at operation from 16 patients with chronic aortic valve disease. In all 16 patients most cardiac muscle cells were hypertrophid, and surrounded by small amounts of fibrous tissue. In two of the six patients with pure aortic regurgitation and in four of the five patients with combined aortic stenosis and regurgitation, cardiac muscle cells with evidence of degeneration were present in addition to hypertrophied, nondegenerated cells. Degenerated cardiac muscle cells were not observed in the six patients with predominant aortic stenosis. Cardiac muscle cells with mild degeneration showed focal myofibrillar lysis, with preferential loss of thick myofilaments, and focal proliferation of tubules of sarcoplasmic reticulum. More severely degenerated muscle cells showed a marked decrease in the numbers of myofibrils and T tubules and proliferation of sarcoplasmic reticulum or mitochondria, or both. Severly degenerated cells usually were present in areas of marked fibrosis, often were atrophic, had thickened basement membranes and had lost their intercellular connections. These findings suggest that degenerated cardiac muscle cells have poor contractile function and may be responsible for impaired cardiac performance in some patients with chronic aortic valve disease.


Diet, growth and cultural food habits in Chinese-American infants. This study was composed of one hundred Chinese-American mothers and infants in the Chinatown district of San Francisco. The mothers were interviewed with regard to infants' dietary intakes and past dietary patterns, infant health, maternal pre-natal history and diet, cultural habits, and socio-economic status. Infants' growth patterns were recorded and compared to those of American and Chinese babies. Their growth patterns were noted to be dissimilar to both American and Chinese growth patterns, but to be very similar to infant growth patterns in underdeveloped countries. The cultural influences on the dietary intakes were commented upon.


Increase of pain threshold as a function of conditionsing electrical stimulation.  An experimental study with application to electro-acupuncture for pain suppression. Previous studies have shown that 2 Hz electrical conditioning stimulation of hands and cheeks increased the tooth pain threshold. In the present study the relation between strength of conditioning stimulation and amplitude of pain threshold increase is elucidated. Intense conditioning stimulation, giving subjective beating sensations and extensive muscles twitches, is required to obtain a substantial pain threshold increase. The results are discussed in relation to intensities used in electro-acupuncture and to interindividual variation of the effect. It is suggested that pain relief is obtained due to an inhibitory feed-back mechanism activated, not via low threshold afferents but via high threshold afferents.


Preliminary observations on the effect of acupuncture on immune responses in sensitized rabbits and guinea pigs. A preliminary report is presented on the possible effect of acupuncture on immune responses in rabbits injected with sheep RBC and in guinea pigs with an encephalitoenic antigen preparation. Results from acupuncturing experimental animals at four loci-Ta-Chu, Tsu-San-Li, Ch u-Chih-Shih-strongly suggest that acupuncture has an effect on the immune response.  If these observations can be substantiated by more refined methods in subsequent experiments, a new avenue will be opened for acupuncture research.


The treatment of headaches employing acupuncture. Thirty-three patients have been treated by acupuncture since July 8, 1974, using body loci, ear points and electrical stimulation. Of the 33 cases, 18 were female and 15 were male, ranging in age from 25 to 77 years. Sixteen patients suffered from migraines, 12 from tension headaches, 2 from cluster headaches, 1 from vascular headaches, and for 2 patients the etiology was uncertain. The duration of the headaches ranged from 3 months to 40 years. The patients received from 3 to 16 treatments. Of the 33 cases, 5 patients had only 3 treatments and 10 patients had 5 or less treatments. Eighteen patients had good results, i.e., no headache at all. Twelve patients had fair results, that is they sometimes had headaches, but they could be controlled with a few repetitions of treatment or by analgesics at a lesser dosage than they were taking at the beginning of treatments. Three patients had no response at all or poor results; however, these discontinued treatment before the author could evaluate whether they were actual absolute no-response cases. Of the 33 patients, 2 patients had a good response after only 2 treatments; 4 had a good response after 10 treatments. However, most of the patients had a good response after 6-8 treatments. A course of treatment usually requires 10 to 14 visits befor definite evaluation of the results can be made. It was observed that patients with fair or particularly poor results usually discontinued treatment too early and/or had concomitant conditions as well. Even though a longer period of time for follow-up is necessary before drawing any conclusions, results have already shown that acupuncture, perhaps, can be a valuable form of treatment for headaches.


The management of foreign affairs of the GI tract. The flexible fiberoptic endoscope has not been employed consistently in the removal of foreign bodies from the gastrointestinal tract due to size limitations of the forceps and biopsy channel. The following report describes a technique for extracting large irregular objects from the upper-gastrointestinal tract, employing the polypectomy snare. It is a safe and reproducible procedure for the careful extraction of impacted objects.


The influence of carbenoxolone on steroid-induced ulcer and mucus secretion in the rat. In rats, gastric mucus was decreased by starvation. The administration of carbenoxolone sodium, prednisolone, or their combination to starved rats brought the level of gastric mucus to that of nonstarved controls. Concomitant treatment with carbenoxolone sodium did not prevent prednisolone-induced ulceration of the glandular stomach in starved rats. The ulcerations of the prostomach (squamous spithelium)induced by starvation were prevented by carbenoxolone sodium, prednisolone, or the combination of the two.


Effects of meals and interruption of enterohepatic circulation on flow, lipid composition, and cholesterol saturation of bile in man after cholecystectomy. In 4 patients studied after cholecystectomy and common-duct exploration for cholesterol gallstones, bile salt (BS) and phospholipid (PL) output and bile flow increased significantly in response to breakfast, but cholesterol (Ch) output was unaltered. Simultaneously, Ch concentration decreased while PL and BS concentrations did not change. The degree of Ch saturation of bile, [BS PLUS PL]/[ch], decreased in each study, whether or not the original ratio indicated Ch supersaturation; in 3 of 5 studies, an initially super-saturated bile became unsaturated with Ch in response to breakfast. No significant changes were noted after lunch. During interruption of enterohepatic circulation (EHC), studies with radiolabeled bile acids indicated that the increased bile acid output in response to meals was secondary to increased recirculation of intestinal bile acids rather than to de novo bile acid synthesis. This mechanism may account for the adequate delivery of BS and for the decreased degree of Ch saturation of bile postprandially in cholecystectomized patients.


Cholinergic stimulation of the lower esophageal sphincter in patients with vagotomy and antrectomy. Recently cholinergic stimulation of the lower esophageal sphincter (LES) with bethanechol has been shown to be effective in the treatment of chronic gastroesophageal reflux. Since chronic reflux and esophagitis also occur in patients with vagotomy and antrectomy, we studied the effect of bethanechol on sphincter pressure in 10 patients who had had vagotomy and antrectomy. Both subcutaneous (0.08 mg/kg) and oral (25 mg) administration of bethanechol caused significant increases in LES pressure in these patients. In addition, both subcutaneous and oral administration of bethanechol elevated hypotensive sphincter pressures to normal levels. Orally administered bethanechol produced a sustained increase in LES pressure throughout a 90-min study period. These studies suggest that cholinergic stimulation of the LES with bethanechol may be of therapeutic benefit in vagotomized and antrectomized patients with gastroesophageal reflux.


Relationship between serum gastrin concentration and lower-esophageal sphincter pressure. Serum gastrin concentration [G] has been proposed as the major factor regulating resting lower-esophageal sphincter pressure (LESP). Available supporting evidence in man, however, is largely circumstantial. The present study directly compares measurements of LESP with concurrent levels of circulating serum gastrin in fasting human subjects. A direct correlation was not shown between [G] and resting LESP; rather, a trend existed toward an inverse relationship. The study results indicate that the concentration of serum immunoreactive gastrin is not a major determinant of lower-esophageal sphincter tone in humans.


The absorption and subsequent utilization of lecithin by the rat jejunum. Labeled lecithin (32P, 2-3H-glycerol, 1-14C-palmitate) was prepared for studying absorption of lecithin by rat intestine and its incorporation into microsomal and prechylomicron-chylomicron lecithin. Bile fistula rats were perfused intraduodenally with bile salts and lecithin plus a liquid diet. Intestinal samples were obtained after sacrifice and specific activities (DPM/mumol) of isotopes in lecithin were determined. Ratios of specific activities of isotopes were calculated and compared to respective ratios in the original perfusate lecithin. Radioactivity rapidly appeared in jejunal lecithin following perfusion. When specific activities of isotopes in prechylomicron-chylomicron lecithin were compared to those in microsomal lecithin, specific activities were always greater in prechylomicron-chylomicron lecithin. Analysis of ratios of specific activities of isotopes in jejunal lecithin showed that the ratios were nearly identical to those in perfusate phospholipid, indicating that the lysolecithin portion of luminal lecithin can be absorbed intact and can then be utilized for jejunal lecithin synthesis.


Clindamycin-associated colitis.

Clindamycin-associated colitis. Four cases of clindamycin-associated colitis have recently been observed at Kansas University Medical Center. There have been a few reports in the literature of colitis associated with this antibiotic, and our 4 cases are similar to those noted previously. All had the onset of diarrhea 7-14 days following the initiation of clindamycin therapy; the diarrhea persisted for weeks after the drug was discontinued. Mucosal changes ranged from focal ulceration to pseudomembrane formation. Diarrhea in a patient on clindamycin should alert the physician to the possibility of antibiotic induced colitis, a condition with significant morbidity and occasional mortality.


Adenocarcinoma of the bile ducts. Relationship of anatomic location to clinical features. Case histories of 23 patients with adenocarcinoma of the bile ducts presenting at the Cleveland Clinic from January 1960 through March 1974 were reviewed and a comparison was made between carcinoma in the hepatic duct system and carcinomas in the common bile ducts. There were 14 cases of hepatic duct carcinoma and 9 cases of carcinoma of the common bile ducts. It was found that age, sex, presenting symptoms, physical examination, and laboratory findings were similar regardless of the location of the carcinoma. Moreover, the location of the carcinoma did not influence whether the correct diagnosis was made at the initial operation. Percutaneous cholangiography, operative cholangiography, and endoscopic retrograde cholangio-pancreatography (ERCP) were successful in making the diagnosis in both locations. The tumors differed in pathology. The hepatic duct carcinomas were often scirrhous; the more distal carcinomas were adenocarcinomas of varied grades of differentiation. The location influenced the type of surgery; resection was more common in the distal common bile duct cases. The average survival rate was less than 2 years for both locations. Radiation and/or 5-fluorouracil therapy did not appear to increase this survival rate. Since the prognosis is so poor, attention must focus on means of earlier diagnosis.


The influence of food consumption and running activity on the activity-stress ulcer in the rat. Rats housed in activity cages and fed 1 hour daily died before the end of the 21-day experimental period and revealed extensive ulcers in the glandular stomach, whereas food-yoked control rats, not housed in activity cages, did not die and were ulcer-free. Rats demonstrating high running-activity levels under ad lib feeding conditions subsequently revealed a higher incidence of lesions as compared to low-activity rats. Attempts to attenuate activity and lesion incidence by reversing the light-dark cycle failed, but the higher mortality level in rats under the reversed light-dark condition was related to higher activity levels in these rats. Young rats with high activity levels died sooner and had ulcers when compared to older rats with low activity levels. These results suggested that running activity, and not reduced food intake, was critically involved in the development of the activity-stress ulcer.


An epidemiologic study of hepatitis B virus in Bangkok, Thailand. Residents of a randomly selected sample of households in a low-income housing project in Bangkok were studied between July 1971 and April 1972. Prevalence of hepatitis B antigen (HBs Ag) in July 1971 was 8.2% in 697 persons age one year and older and changed little with age. Prevalence of antibody to HBs Ag (anti-HBs) was much higher in all age groups and was 46% overall. The prevalence of HBs Ag was higher in males than females from ages 10-29 years and the prevalence of anti-HBs was higher in males up to age 60. The HBV (combined HBs Ag and anti-HBs) age prevalence distribution in July 1971 revealed that over 20% of the children 1-4 years of age had serologic evidence of infection and that the prevalence rose rapidly with age reaching a plateau between 60-70% after age 15. During the nine months of serologic surveillance 13% of individuals acquired either HBs Ag or anti-HBs and 7% lost serologic evidence of HBV infection. The study data suggest that most HBs Ag positive persons are long-term antigen carriers, that their numbers and spatial distribution may be sufficient to account for the wide-spread transmission of HBV in this population, that close person-to-person contact with carriers is probably the most important mode of HBV transmission, and that the susceptibility to becoming an HBs Ag carrier is probably genetically determined.


Determination of the site of oral rabies vaccination. Foxes developed serum neutralizing antibodies to rabies only after oral administration of an attenuated rabies vaccine, and not when a similar vaccine dose was introduced into the stomach. These results emphasize the need for a bait that assures delivery of a vaccine dose orally.


Evaluation of mortality data for cervical cancer with special reference to mass screening programs, Denmark, 1961-1971. During the years 1961-1971, a total of 3696 women died in Denmark from cervical cancer. The annual mortality per 1000 was 0.23 and was constant in this period. The mortality was 0.30 in the Capital where a mass screening program has existed since 1968; in the Provinces, where screening was negligible, the rate was 0.21; the time trend was also constant. The mortality was low in youth, reaching a level of 0.30 around 45 years. Single women had the lowest mortality; among married women it was double, among widows 2-4 times higher, among divorcees 4 times. Within the marital groups, the Capital had higher or the same rates as the Provinces, except for divorcees in the Provinces who had higher rates. The lowest socioeconomic groups had the highest death rates at young ages. The effects of a total vs. an age-specific case-finding program have been estimated under three circumstances, namely that mass screening could reduce the cervical cancer mortality by 10%, by 50%, or by 100%. The impact on the public's health has been evaluated by relating the hypothetically prevented cervical cancer deaths to all cancer deaths and to deaths from all causes. The general population was subdivided by age, marital status and residence and ranked according to cervical cancer mortality. These data were used to design programs which would minimize the number of examinees and maximize the number of prvented deaths.


An epidemiologic study of renal failure. II. Acute renal failure. A total community study of acute renal failure (ARF) was carried out in Israel. The mean annual incidence was 4.8/100,000, the risk being 50% higher in males than in females. It was found that ARF is due primarily to a multiplicity of factors and rarely to a single cause; the high mortality associated with ARF is related to the patient's basic underlying condition. The epidemiology of ARF results from a compilation of the various conditions leading to it, and would, therefore, vary according to the differential distributions of these conditions in the population.


Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam, 1945-1972. I. Descriptive epidemiology. An overview of the epidemiologic studies of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) from 1945 through 1972 is presented. During this period 350 cases of ALS were documented. PD, which is apparently unique to the native Chamorro population, was not recognized during the early years of the study. A total of 213 PD patients have now been seen. The rates of both diseases have declined by approximately 50 per cent since 1965. In the early years incidence per 100,000 for ALS males approached 60; for females it was about 40. For PD males it was about 50; for females it was close to 20. The declines in both diseases have occurred in both sexes and at all age groups and no cohort phenomenon was observed. Marked geographic differences in the distribution of the diseases were observed with southern villages having the highest rates and western villages having the lowest rates; the remainder of the island was intermediate. Recent declines have been most marked in the southern high-rate villages. Chamorros living on the island of Rota have rates similar to those on Guam; those on Saipan have lower rates. A possible excess of ALS among Filipino residents ofGuam was noted; ALS has not been seen among other ethnic groups. Geographic mapping even in high incidence areas did not reveal true clusters or foci. Extensive case-control studies did not reveal any patterns of prior illness, life-style, or exposures distinguishing patients. A tendency for patients to be of somewhat lower socioeconomic level, have less education, eat more homegrown foods and raw meats, and more contact with animals was found. No Mendelian genetic patterns were observed; males were affected more frequently than female for both diseases. Cases did not occur before age 20, reached maximum frequency between ages 55 and 65 and there-after declined. Environmental factors associated with some aspects of the traditional way of life seem to be causally involved, but, since most aspects of the traditional life have changed in the past 50 years, the specific factors remain elusive.


Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam, 1945-1972. II. Familial and genetic studies. The extraordinarily high rate of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the Chamorro linguistic group on Guam suggested a genetic etiology for these diseases. Results of three studies are described. Two involved comparisons of the rates of disease in relatives and spouses of index patients and controls. In the third we examined offspring of doubly affected parents, 10 spouse pairs with ALS, 3 spouse pairs with PD and 13 spouse pairs in which 1 spouse had ALS and the other PD. Within the limitations of numbers and age of offspring, we found a tendency among siblings and offspring of ALS cases to have a higher risk than control relatives. Numbers were small and in no instance were significant differences encountered. Spouses of patients had at least as high risk of developing ALS or PD as any of the groups of blood relatives. A slightly higher age-specific rate of ALS and PD occurred in the offspring of doubly affected parents. The only group large enough for present analysis are 60 offspring of doubly affected ALS parents over the age of 20. Thus far only 3 have developed ALS. Within our entire patient population of 350 ALS cases and 219 PD cases there were 12 instances in which one parent of the patient was not Chamorro. In addition there is a consistent two- to threefold excess of affected males which could not be accounted for by competitive risks of death from other causes among females. While a familial tendency does exist these findings and observations are not compatible with any simple Mendelian form of inheritance. It is possible that genetic influences affect the occurrence of these diseases but our studies suggest that environmental factors play at least as important a role.


A method for estimating the prevalence of tuberculosis infection. The prevalence of tuberculous infection in a population is generally estimated from calculating the proportion of tested individuals who react with at least 10 mm of induration to 5 TU of PPD-S tuberculin. Reactions due to infection with atypical mycobacteria, however, may cause the prevalence to be overestimated. This paper is concerned with an alternative method of estimating the prevalence of infection with Mycobacterium tuberculosis. The method utilizes population distributions of reaction size by dividing study populations into two groups--individuals with and without known exposure to tuberculosis. The mathematical model developed here removes the effect of atypical infections and provides a truer picture of tuberculous infection. Data from a Navy recruit population demonstrate the use of the model with the result that among recruits with no known exposure to tuberculosis, the estimated prevalence is reduced by about one-half. Among recuits with known exposure to tuberculosis, there is essentially no difference between the two methods. Important advantages in using this method are that probabilities of true infection by induration size are generated, and that itis less sensitive to variations caused by differences in reading techniques and in tuberculin potencies. Furthermore, it is applicable to other diseases if the underlying assumptions are met.


Hereditary persistence of fetal hemoglobin, beta thalassemia, and the hemoglobin delta-beta locus: further family data and genetic interpretations. Three Negro kindreds with hereditary persistence of fetal hemoglobin (HPFH) alone and in combination with various other hemoglobin abnormalities including beta thalassemia are presented. Among 11 offspring of two women heterozygous for both HPFH and the delta chain mutation Hb B2, five inherited the HPFH gene and six inherited the Hb B2 gene. In another kindred, a man inferred to be heterozygous for both HPFH and Hb C had six children; three offsprivg obtained the Hb C gene and three the HPFH gene. Similarly, a woman heterozygous for both Hb S and HPFH transmitted the Hb S gene to one of her two children and the HPFH gene to the other. Thus among 19 offspring, no crossovers between the HPFH locus or the Hb delta-beta locus were observed. These and earlier data are compatible with deletion of the Hb beta and delta loci as the primary event to explain the genetic origin of HPFH. Genetic considerations indicate that the finding of a single person with a hematologically normal phenotype among offspring of heterozygotes for both the African type of HPFH and a Hb beta or Hb delta structural abnormality would invalidate the deletion model.


Observations of de novo clones of cytogentically aberrant cells in primary fibroblast cell strains from phenotypically normal women. In a recent study of chromosome breakage frequencies in 36 primary fibroblast cell strains derived from skin from 10 phenotypically normal women, we observed seven different clones of cells having consistent chromosomal abnormalities. Five of the stem lines were noted in cultures from "control" women and two in fibroblasts from women taking oral contraceptives. We observed aneuploid clones as well as stem lines bearing structural abnormalities (e.g., translocation, inversions). The various aberrant clones were found in cultures ranging in age from 41 to 144 days and comprised varying percentages of the cell populations ranging from 0.8% to virtually 100%. The possible evolution in culture of clones of cells having aberrant karyotypes should be considered in interpreting findings from fibroblast cultures initiated for clinical evaluation.


Screening for microcytemia in Italy: analysis of data collected in the past 30 years. Extensive population surveys begun in Italy in 1943 revealed a high incidence of mycrocytemia. Health authorities established a national organization to combat microcytemia which financed and directed activities throughout Italy from 1955 to 1971. The work performed by the microcytemia centers in screening and prophylaxis is described. The results of a screening program underway since 1967 involving 46,559 students of the University of Rome are presented in detail. A preliminary survey of 256 families revealed that the incidence of subsequent births after the births of a child affected by Cooley's anemia was generally low. Results obtained to date are encouraging and justify more extensive programs for the prevention and treatment of microcytemia.


Half chromatid mutations: transmission in humans? Attention is drawn to the possibility of half chromatid and early somatic mutations and to several implications of these mosaic-yielding events. There is suggestive evidence that spontaneous mutations can result in mosaics. A world-wide cooperative study of Lesch-Nyhan families could determine the extent of half chromatid mutation transmission and early somatic mutation in humans.


Haptoglobin-ABO interaction: a possible explanation for the excess of Hp 1 among offspring of ABO incompatible matings. The Hp1 frequency among ABO phenotypes varies in the Hutterite population as follows: O less than A less than B less than AB. Within group O, the Hp1 frequency is significantly lower than the Hp1 frequency among the other groups combined. The Hp1 frequencies among ABO genotypes, known by means of family pedigrees, vary as follows: OO less than AO less than BO less than AB less than AA less than BB. This holds for both main subjects of this isolate, although they have been reproductively isolated since World War I. The higher Hp1 frequency among type A, B, and AB individuals explains the observation of the higher Hp1 frequencies found among H-leut offspring who are incompatible with their mothers (mainly AO offspring of OO mothers) compared to offspring from the same matings who are compatible with their mothers.


Evidence for the inactivation of an X chromosome early in the development of the human female. Studies of somatic tissues and cultured cells, including fibroblast clones, from human embryos heterozygous for the electrophoretic variants of glucose-6-phosphate dehydrogenase confirm that one X chromosome is inactivated very early in embryonic development and indicate that X inactivation has occurred in the majority of cells from a variety of tissues at least by 5 weeks from conception.


Physician attitudes toward drug information resources. A survey of the drug information needs of physicians in western Washington State is discussed. Of 5006 questionnaires mailed to physicians, 1227 were returned completed. The results showed that physicians depended primarily on journals and texts for drug information. Pharmacists were seldom considered as sources of drug information which would directly affect patient therapy. Slightly more than a third of the respondents indicated a willingness to pay for drug information services


Regional drug information service benefits: free versus fee-for-service. Health providers in a four-state area who had utilized the Nebraska Regional Drug Information Service were surveyed to determine: (1) if providers would pay a fee for drug information services; and (2) if they would prefer a per-call fee or an annual subscription fee. Of 1,000 questionnaires mailed, approximately 500 were returned and analyzed. Results indicated that 52% of those responding felt that the drug information service provided direct benefits to patients. The service fee preferred most was $2.00 to $5.00 per call or $25.00 per year. Actual operating cost data showed that a per-call charge of $2.50 would not permit the service to break even. However, it was projected that the service would break even if it charged an annual fee of $25.00.


Experience with a drug information services review committee. The efforts of a committee to review the performance of a formal drug information service were evaluated. The organization and functions of the committee are described, Among other duties, the committee rates the difficulty of a random selection of questions and the adequacy of the answers provided. These ratings were compared to the evaluations of the persons asking the questions. There appeared to be a correlation between the ratings of the review committee and the evaluation of users of the service.


The pharmacist's ability to use bioavailability data. The ability of the pharmacist to use analytical, dissolution, blood level, excretion and cost data in evaluating drug products was studied. A questionnaire asked respondents to evaluate four brands of an antibiotic based on the comparative data presented. The responses of 19 pharmacists were compared to those of an expert panel. The pharmacists performed adequately in evaluating all types of data except urinary excretion data.


Unit dose packaging of respiratory therapy solutions. A program of preparing respiratory therapy medications in a tamper-proof, disposable, unit dose package was developed and evaluated. Comparisons were made between the old system of dispensing respiratory therapy solutions and the new unit dose system. The evaluation indicated that: (1) personnel costs between the two systems were similar; (2) patient charges increased under the unit dose system by approximately 10 cents per dose; (3) packaging technique and controls improved under the unit dose system; and (4) medication errors were reduced.


Licorice-induced pseudoaldosteronism.

Licorice-induced pseudoaldosteronism. Licorice ingestion as a cause of pseudoaldosteronism is discussed. The mechanism whereby licorice, when consumed in large quantities, exhibits the physiologic properties of aldosterone, is reviewed. A case report of a 51-year-old male hospitalized with hypertension and hypokalemia is presented with reports of laboratory findings which lead to the diagnosis of pseudoaldosteronism.


Effect of intrarenal furosemide on renal function and intratenal hemodynamics in acute renal failure. The ability of short-term furosemide administration to alter intrarenal hemodynamics and to modify the clinical course of acute renal failure was assessed in six patients 2 to 9 days after the onset of acute renal failure. Following renal arterial catheterization, the intraarterial administration of furosemide at a dose of 9.6 mg/min for 30 minutes failed to improve renal function as assessed either by an increase in urine output or a decrease in serum creatinine during the 4 days after administration in the five oliguric patients. In a sixth patient with nonoliguric acute renal failure, urine volume increased with a gradual decrease in blood urea nitrogen and creatinine during the week after study. Furosemide failed to alter either mean renal blood flow or its intrarenal distribution as determined at intervals of 3 to 40 minutes after its infusion. These studies demonstrate that the short-term administration of furosemide in large doses does not improve renal hemodynamics or alter the clinical course of patients with established acute oliguric renal failure.


Studies in myasthenia gravis: early thymectomy. Electrophysiologic and pathologic correlations. Indications for thymectomy in myasthenia gravis have been recently expanded to include all cases with extraocular symptoms as a result of the minimal morbidity and negligible mortality of the transcervical approach. As increasing numbers of patients with myasthenia gravis, covering the entire spectrum of generalized disease, have been added to the thymectomy population, a more accurate evaluation of the effects of the operation is possible. Our experience with 353 patients who have undergone thymectomy indicates that early thymectomy, particularly in patients who do not have germinal centers, is followed by early remission of the disease. Delayed remission after thymectomy is related to the duration and severity of the disease, and to presence of thymic germinal centers. Germinal centers were found more frequently in patients with long duration of the disease and in patients in whom the disease had progressed to respiratory involvement. Marked improvement in electromyographic findings immediately after thymectomy was observed in the majority of patients who had had the disease for 1 year of less and where germinal centers were absent. The percentage of malignant thymomas was higher in patients who underwent thymectomy 1 year or more after the onset of symptoms of myasthenia gravis. These data indicate the importance of early thymectomy while the disease is still in the mild stages. Transcervical thymectomy is the treatment of choice as it is followed by a higher percentage of remissions and by less morbidity than other forms of treatment.


Pharmacokinetics of digoxin and digitoxin in patients undergoing hemodialysis. The pharmacokinetics of digoxin and digitoxin in patients undergoing long-term hemodialysis were examined to determine which is the preferred cardiac glycoside in this patient population. Absorption curves from 0 to 24 hours after an oral dose of digitoxin were similar in dialyzed patients and in control patients. Serum glycoside concentrations after an oral dose of digoxin were higher in dialyzed patients than in control patients, significantly so from 2 to 24 hours, reflecting the absence of the predominantly renal route of excretion of digoxin. When nine dialyzed patients were placed on a maintenance dose of digoxin, 0.125 mg 5 days a week, serum levels plateaued at 30 days at a mean concentration (plus or minus SE) of 0.84 plus or minus 0.05 ng/ml. Maintenance therapy with 0.1 mg digitoxin 5 days a week resulted in stabilization of serum levels within 30 days at a mean concentration of 19 plus or minus 1 ng/ml. Variability in the serum glycoside concentrations was determined after stabilization of levels during 2 to 19 week follow-up periods with each drug. Variability in serum levels was somewhat increased during maintenance therapy with digitoxin. On the basis of the parmacokinetic data obtained in this study, no clear cut preference for one glycoside over the other could be established.


Hemoglobin S-C disease presenting as acute pneumonitis with pulmonary angiographic findings in two patients. Acute illness characterized by fever, cough, chest pain and pulmonary infiltrates on chest film is characteristic of patients witb sickle cell anemia and with sickle-C disease. The underlying hemoglobinopathy is usually recognized in the former, but because patients with sickle-C disease as a rule have less severe anemia and fewer, less severe crises their abnormal hemoglobin may not be detected until adolescence or adulthood. Acute pulmonary illness in such patients may therefore present a diagnostic dilemma for the unwary. Two cases are presented to highlight this point. Pulmonary angiographic findings in patients with sickle cell states might add information about the pathogenesis of this disorder since vascular occlusion appears to play a major role. Pulmonary angiograms in the two patients we describe documented the presence of localized abnormalities of perfusion. In one, the presence of filling defects in medium-sized arteries suggests intravascular thromboembolism.


Hemoglobin S/C disease in a pregnant woman with crisis and fat embolization syndrome. The complications of painful crisis and megaloblastic anemia are hallmarks of the pregnant patient with hemoglobin S/C disease. We describe here the clinical course in a patient with hemoglobin S/C disease in whom painful crisis and the fat embolization syndrom developed postpartum with severe neurologic abnormalities. Response to exchange blood transfusion was dramatic, and the patient recovered without neurologic impairment.


Bullous photoreaction to nalidixic acid. Curtaneous blisters developed after exposure to the sun in two women who were taking nalidixic acid. Blisters continued to appear even after therapy was discontinued and there was no further exposure to the sun. Phototesting showed abnormal sensitivity to both short and long wavelength ultraviolet spectra in one patient. The low incidence of this phenomenon suggests a photoallergic mechanism, but features of both photoallergy and phototoxicity are present.


Pericardial tamponade. A presenting manifestation of procainamide-induced lupus erythematosus. Procainamide, a frequently sued antiarrhythmic agent, may produce a syndrome clinically indistinguishable from idiopathic lupus erythematosis. Pericarditis with or without effusion is occasionally a prominent manifestation of the disease, but cardiac tamponade is exceptional. The patient described had a clinically evident and laboratory confirmed drug-induced syndrome complicated by an unusually severe pericarditis with effusion and tamponade necessitating pericardiocentesis. Treatment with prednisone produced impressive amelioration of the pericarditis with no recurrence of the lupus erythematosis syndrome during a prolonged period of observation following cessation of corticosteroid therapy. Prompt initation of steroid treatment in drug-induced lupus erythematosus complicated by massive pericardial effusion is strongly suggested by this experience.


Refractory reentrant atrial tachycardia. Successful treatment with a permanent radio frequency triggered atrial pacemaker. This 68 year old man had recurrent episodes of paroxysmal atrial tachycardia, probably due to chronic pericarditis, persisting over a 7 year period. These episodes were resistant to all conventional medical therapy and at times produced ischemic chest pain. There was no evidence of Wolff-Parkinson-White syndrome either on the standard electrocardiogram or on the His bundle electrogram performed with atrial pacing. Rapid atrial pacing at a rate of 200/min was found to promptly terminate the tachycardia and restore normal sinus rhythm. Because of the refractoriness of the patient's tachycardia, in addition to the presence of ischemic chest pain during these episodes, a permanent radio frequency triggered atrial pacemaker was inserted which enables him to initiate rapid atrial pacing by pressing an external control. The patient has been maintained on antiarrhythmic medications in an attempt to decrease the frequency of these episodes; during an 8 month follow-up period, he has done well with approximately one episode of tachycardia each month requiring radio frequency atrial pacing for termination.


Glucose uptake in the brainstem of thiamine-deficient rats. Acute dietary deficiency of thiamine was produced in immature female rats. Uptake of glucose by brainstem nuclei was determined by autoradiographic examination of tissue concentrations of 14-C-3-O-methyl-d-glucose following a test dose, and compared with levels in normal and isocaloric control animals. The experiment showed that glucose uptake was depressed in the lesions of thiamine deficiency as compared with the controls, that the depression occurred with the occurrence of morphologic evidence of tissue edema, and that the depression was temporally independent of the breakdown of the blood-brain barrier to protein which is found in the late, necrotic lesions.


Intravascular fibrin deposits, hepatic infarcts and thrombocytopenia in parent/F mouse chimeras with host-versus-graft syndrome. Host-versus-graft (HVG) disease is the fatal result of the allogenic reaction which occurs in parental strain mice perinatally inoculated with F(1) hybrid spleen cells. The principal manifestations of the syndrome in RFM/(T(6) X RFM)F(1) mice are thrombocytopenia, intestinal hemorrhage, hepatic necrosis, lymphoproliferative disorders and renal disease due to immune complexes. The discovery of intravascular fibrin deposits in the present studies establishes disseminated intravascular coagulation (DIC) as an intermediary mechanism of HVG disease. It is suggested that the characteristic declines in blood platelet levels, intestinal hemorrhages and hepatic infarcts are triggered principally by immune complexes. Cellular infiltrates of the liver, granulocytosis and hypergammaglobulinemia are other abnormalities which are regularly found in HVG mice and which are also thought to predispose to DIC.


Restitution of aortic wall after sustained necrotizing transmural ligation injury. Role of blood cells and artery cells. Partial ligation of the rabbit abdominal aorta with fine silk suture for 48 hours produced a circular band of transmural necrosis. On release of the ligature, blood cells from the lumen and from adventitial vasa vasorum, as well as cells derived by mitosis from the adjacent surviving endothelium and media, participated in the restitution of a continuous endothelial lining and an intact media containing well-differentiated smooth muscle cells within normal medial lamellar units. Initial deposition of a layer of blood platelets on the fibrillar material coating the denuded lumenal surface was followed by ingress from the lumen of polymorphonuclear granulocytes and mononuclear cells. These changes preceded the appearance of mitoses in surviving endothelial and medial smooth muscle cells at the margin of injury. By 24 hours, poorly differentiated cells had accumulated in the central portion of the intima and inner media. Similar cells formed a more extensive, nearly complete lumenal layer which was eventually continuous with and indistinguishable from the adjacent uninjured endothelium. By 7 days, smooth muscle cells repopulated the media, and a collection of less differentiated cells persisted between the restored endothelium and media. By 28 days, the only deviation from normal arterial structure was the persistence at the point of ligature of intimal thickening, consisting of smooth muscle cells and collagen and elastin fibers. Though still present at 6 weeks, this zone became increasingly compact and layered. There was no evidence that fibrin thrombus formation was a consistent feature of the initial reaction or that it played a role in the healing process or in the formation of the intimal lesion. Despite complete circumferential necrosis at the site of ligature, there was no evidence of medial rupture or intramural hemorrhage.


Characterization of human platelets separated from blood by ADP-induced aggregation. Separation of platelets from plasma is achieved by adding ADP (final concentration 10-5 M) to platelet-rich plasma and allowing aggregates to form. Aggregates are removed quickly by brief, gentle centrifugation, washed two to three times with 0.9% NaCl (saline), and then incubated for 10 minutes in the presence of apyrase, albumin and calcium. Platelet aggregates deaggregate completely during this incubation period. The platelet suspension is then subjected to 1100g for 12 minutes, gently resuspended in a small volume of saline, and finally diluted with an appropriate medium to the desired concentration. The entire separation procedure requires approximately 30 minutes. Platelets obtained by this procedure are a) comparable in aggregability to the platelet preparations obtained by gel filtration, b) have normal intracellular amounts of ATP and ADP, and c) except for slight dilatation of the surface-connected canalicular system, have normal ultrastructural appearance. When suspended in an appropriate medium, these separated platelets take up serotonin 14-C and subsequently release it in nearly normal quantities when exposed to thrombin, collagen or ADP.


Marital therapy from a psychiatric perspective: an overview. The authors describe various methods of marital therapy in use today. Although absence of a unifying conceptual scheme in the past has hampered developments in this field, the increasing acknowledgment by psychiatrists of the important effect of the environmental system on thoughts, feelings, and behavior has facilitated a therapeutic approach stressing not only a person's intrapsychic conflicts but current environmental, family, and spouse-related phenomena. The authors discuss three dimensions of marital psychodynamics--power, intimacy, and marital boundary setting--and relate them to the marital life cycle and to four classifications of the marital relationship: 1) rules for defining power, 2) parental stage, 3) level of intimacy, and 4) personality style and psychiatric terminology. The paper includes a brief discussion of therapy techniques, sex counseling, the use of cotherapists, the future of marriage, and alternative lifestyles.


A comparison of biofeedback-mediated relaxation and group therapy in the treatment of chronic anxiety. The authors compared treatment of chronic anxiety with biofeedback-mediated electromyographic (EMG) relaxation to treatment with group psychotherapy in a control group. Feedback patients were given two weeks of EMG relaxation training followed by two weeks of self-practice. Significant decreases were found in the feedback group in electromyogram levels, mood distrubance, trait anxiety, and (to a lesser extent) state anxiety; no such decreases occurred in the control group. The authors suggest that EMG feedback can be an important adjunct therapy for chronic anxiety.


The impact of medical school on future psychiatrists. Although psychiatry and clinical medicine share ideals about what distinguishes a good practitioner, medical schools do not select students on the basis of these qualities. Moreover, they seem to discourage many interested students from choosing psychiatry. Part of the problem is that psychiatry is poorly taught. Research suggests that psychiatry can be better taught and that medical students will be receptive. However, the clash between the values of technological medicine and psychiatry has created discouragement, with the ironic result that medical students rate psychiatrists poorly because they embody the very qualities that distinguish the good clinician.


Methadone maintenance: some client opinions. The authors found similar attitudes toward methadone and methadone treatment programs in 75 detoxification and 115 methadone maintenance clients. Both groups expressed considerable ambivalence--although they viewed methadone as capable of helping them end their herioin addiction, they were concerned about possible methadone dependence and about side effects, both real and imagined. The authors stress the societal context of such concern and suggest that, althought they are not easily allayed, limiting the duration of methadone maintenace from the outset of treatment may be an ameliorative factor.


Is everyone depressed?

Is everyone depressed? The authors collected a large number of research interviews with relatives of patients from a psychiatric research clinic. Half of these patients were clinically depressed; their relatives as well as the rest of the relatives interviewed were therefore at high risk for depression. However, few of the relatives reported memorable dysphoria or any clustered episodes of other affective symptoms. The authors conclude from these data that, contrary to the opinions expressed by some, not everyone has episodes of depression. Everybody is not depressed.


Depression: schism in contemporary psychiatry. The author decribes an experience in his own family involving the initial unsuccessful treatment of a depressed patient. The patient failed to respond to psychotherapeutic and drug treatment on an outpatient basis and in three hospitals; in a fourth hospital he improved dramatically after a series of ECT treatments and remained without depressive symptoms. The author stresses the importance of psychiatrists keeping an open mind about various treatment approaches.


Electroconvulsive therapy for chronic pain associated with depression. Electroconvuslive therapy alleviated the symptoms of four out of six patients suffering from chronic pain and from depression as measured by the Hamiliton Depression Rating Scale. All of the patients had been unsuccessfully treated with tricyclic antidepressant medication. The author suggests that ECT may be the treatment of choice for some patients with this combination of symptoms.


The depressine Syndrome: a follow-up study of 130 professionals working overseas. A four-year follow-up of professional personnel who had been working overseas indicates that the depressive syndrome was the most common diagnosable psychiatric illness in this population. The study also shows that in this content the syndrome had a good prognosis. It therefore seems reasonable not to exclude persons with diagnosable depression from assignment abroad but, rather, to identify the syndrome and recommend necessary treatment.


Treatment of depression in alcoholics.

Treatment of depression in alcoholics. The authors compared two groups of depressed alcoholics given either placebo or chlordiazepoxide-imipramine in a double-blind study. Although depression decreased in both groups, there were no significant differences between them on any of three pre- and posttreament measures. The Zung scale showed that medication decreased depression significantly, however, this finding was not supported by the Beck Depression Inventory or by the Minnesota Multiphasic Personality Inventory, indicating the necessity for use of multiple assessment instruments.


The Iowa 500: suicide in mania , depression, and schizophrenia. Long-term (30-to 40-year) follow-up data for 76 manic patients, 182 depressives. 170 schizophrenics, and 109 controls showed that 10 per cent of the schizophrenics, 8.5 percent of the manics, and 10.6 percent of the depressives who were decreased had died by suicide. None of the controls had committed suicide. The authors suggest that suicide is a significant outcome factor in all three of these illnesses and is likely to occur at an earlier age in schizophrenia than in the other illnesses.


The relationship between hiatus hernia and tricyclic antidepressants: a report of five cases. Of five patients who were receiving tricyclic antidepressants, two experienced an aggravation of preexisting hiatus hernia, and three with previously normal gastrointestinal X rays developed hiatal herination. The author suggests that this group of drugs may exert an anticholinergic effect on the esophageal sphincter and reduce the tone of the esophagogastric sphincter, thus aggravating existing hiatus hernia or causing its development.


Evaluation of therapist candidates.

Evaluation of therapist candidates. The authors describe one phase of a four-step procedure designed to more fully evaluate candidates for psychotherapist positions. All applicants must conduct an interview with a patient, which is observed and evaluated by a team of staff members to assess diagnostic skills. This procedure has not only proved valuable in the program for which it was designed but has been extended to other programs and proposed for use in peer review.


Some guidelines for the training of foreign medical graduates: results of a special project. Since over one-third of the psychiatric residency positions in the United states are filled by foreign medical graduates, there is a need to identify and correct both the emotional and cognitive problems of these medical trainees. To meet this need the authors describe the findings and recommendations that resulted from a project involving two psychiatrists from a southweast Asian country who were given a specially planned year of training in Hawaii.


Intentional isoniazid overdosage among southwestern American Indians. A 30-month study explored the degree to which self-destructive behavior compromised tuberculosis therapy and prophylaxis among southwestern American Indians. The frequency of isoniazid (INH) overdosage paralleled the extent of INH usage in each tribe and the entent to which INH was perscribed for each tuberculosis category. The authors recommend the careful selection of patients for INH prophylaxis, the dispensing of small amounts at short intervals, the close monitoring of patient compliance with the prescribed drug regimen, and, possiblly, the dispensing of individually wrapped tablets to inhibit the impulsive ingestion of massive amounts of the drug.