Double heterozygosity for hemoglobin Camden (beta 131 Gln yields Glu) and hemoglobin S in an American negro. A hemoglobin variant with the slightly fast mobility associated with K hemoglobins was found, together with hemoglobin S, in an apparently healthy 3-year-old Negro girl from Washington, D.C. Her father had the same variant, along with hemoglobin A, and her mother had hemoglobins A plus S. Respective proportions of hemoglobins K and S in the propositus were 66-34. The K variant now has been found to have the structural change Gln yields Glu at position beta-131 (beta-H9); therefore it apparently is identical to hemoglobin Camden reported in trait form in a Negro subject by YATES, BELLINGHAM and HUEHNS (Nature 243: 467-468, 1973).


Agglutination kinetics. A method for quantitative red cell antigen assays. A simple, sensitive and highly reproducible method is described using a particle counting procedure for the study of agglutination percentage of red cells as a function of time. The method may advantageously be used for the current study of zygosity and other antigenic variations especially in family investigation.


Over 95 per cent sensitization against allogeneic leukocytes following single massive blood transfusion. The development and persistence of leukoagglutinating and lymphocytotoxic alloantibodies were systematically studied in 54 patients who had received single massive blood transfusions because of open-heart surgery. Of these patients over 95% were sensitized when tested for both leukoagglutinins and lymphocytotoxins, whereas 74% were found to be immunized when searched for cytotoxic antibodies only. The optimal time for detecting antibodies was 2 weeks after blood transfusions.


Antibody to vaccinia. II. Prevalence in blood donors. 3.6% of sera from random blood donors were found to contain antibody to vaccinia antigen(s) when screened by IEOP. Antibodies of the strength previously suggested as suitable for use in the preparation of anti-vaccinia immune globulin (titre 2 or more) were only found in revaccinated donors, especially but not exclusively those bled within about 3 months of last vaccination.


Incidence of hepatitis associated antigen HAA and homologous antibody in patients with rheumatoid arthritis. The authors have studied the incidence of hepatitis associated antigen (HAA) and the homologous antibody in sera of patients with rheumatoid arthritis on the basis of (1) arthritis sometimes associated with viral hepatitis, (2) the possible infectious etiology of rheumatoid arthritis, and (3) observation on the possible pathogenetic role of HAA in some cases of polyarteritis nodosa. The presence of HAA and antibody titer gave constantly negative results in all subjects examined with the exception of one case which showed no signs of serological or histological hepatic involvement. On the basis of the results obtained, the negligible role of HAA in the etiopathogenesis of rheumatoid arthritis is underlined. However, the authors emphasize as suggestive the hypothesis that the characteristic histopathological alterations of rheumatoid arthritis may be mediated by an immunological reaction toward an infectious agent other than HAA, but operating through mechanisms similar to those of HAA in polyarteritis nodosa.


Reactions of erythrocyte glycoproteins and their degradation products with various anti-I sera. Three fractions of erythrocyte glycoproteins obtained from Sepharose 4-B chromatography were tested for I activity with ten serologically differentiated anti-I sera. The most active was fraction I, eluted at the void volume and containing the lowest amount of alkali-labile oligosaccharide chains. The desialization of glycoproteins increased their activity toward anti-I-s and anti-I-D sera, and did not change or decreased the activity toward anti-I-F sera. The most abundant fraction II (major sialoglycoprotein of erythrocyte membranes) showed no or only a very weak I activity, but I-active glycopeptides were isolated from products of digestion of fraction II with trypsin. The major product of digestion, sialoglycopeptide IIT-2 showed I activity only after alkaline elimination of alkali-labile oligosaccharide chains. The results indicate  that I receptors are present in hindered form on apparently I-inactive components of erythrocyte membrane.


Separable anti-Hut which is specific for class II of the Miltenberger complex. Two examples of anti-Hut which is specific for cell class II of the Miltenberger complex were found by simple absorption test of previously called 'anti-Mi-a'.


Studies on the Miltenberger complex frequency in Thailand and family studies. In studies of Thai blood donors, 243 of 2,500 subjects (9.7%) were Mi-a positive. All but two were of class Mi -II. Family studies established that Mi III is probably inherited as an autosomal dominant character and usually accompanies the Ms gene complex of the MNSs blood group system.


Removal of leucocytes from whole blood and erythrocyte suspensions by filtration through cotton wool. IV. Immunization studies in rabbits. Hetero-immunization experiments in rabbits were performed to evaluate the quantity of leucocyte antigens present in red cell suspensions prepared by the filtration method of DIEPENHORST et al., in which no intact leucocytes could be detected. It was found that the quantity of leucocyte antigens is smallest in blood filtered immediately after taking. More leucocyte-antigenic material seems to be present in blood that is filtered after storage and in frozen-thawed red cell suspensions. Evidence was obtained that granulocyte-specific antigens are more strongly immunogenic in the rabbit than lymphocyte-specific antigens or antigens common to both cells.


Alternatives to freeze-drying for the removal of ethanol from plasma proteins. II. Gel filtration of albumin. Removal of ethanol from highly concentrated solutions of human albumin (Cohn fraction V) by gel filtration on Sephadex G-25 is hindered by the contraction of the gel in ethanolic solution, by incomplete retardation of ethanol compared with other low MW solutes, and by restricted diffusion of ethanol from the albumin zone. Despite these obstacles, the hourly capacity of such gel filtration columns, for approximately 100-fold reduction of ethanol concentration, may exceed 0.06 kg albumin per litre of column volume. The gel can be used safely at 5 degrees C for several years. The ethanol content of the final product is higher than that achieved by vacuum distillation, and it may be desirable to operate the two techniques sequentially.


Evaluation before thoracotomy.

Evaluation before thoracotomy. When a thoracotomy is being considered, the physician must first determine whether the lesion is potentially resectable. However, an equally important decision is whether the patient can tolerate pulmonary resection if there are other serious underlying medical problems. In any patient with signs or symptoms of pulmonary disease, a spirogram, arterial blood gas study and electrocardiogram should be done as part of the routine preoperative evaluation. The detection of abnormal pulmonary function should prompt preoperative institution of respiratory care to optimize maximally a patient's cardiorespiratory status before operation. If any of several indicators of a high risk of postoperative cardiopulmonary problems are found, split pulmonary function studies should be done to determine whether the lung remaining after resection will have adequate ventilation and perfusion. Xenon radiospirometry is preferable to bronchospirometry and right heart catheterization because of its noninvasiveness. Resection should not be undertaken in the presence of a predicted postoperative forced expiratory volume in one second (FEV(1)) less than 0.8 liter, an arterial carbon dioxide partial pressure (PaCO(2)) greater than 45 mm of mercury or Xenon scans which show poor ventilation/perfusion ( V/ Q) matchup in what would be the remaining lung after resection. A case is reported which shows the value of this approach to preoperative evaluation in determining the risk of postoperative problems.


Flexible fiberoptic bronchoscopy. Anesthesia, technique and results. During a period of three years, 256 diagnostic bronchoscopies were done with flexible fiberoptic bronchoscopes at a Veterans Administration hospital. In all of these procedures, topical cocaine hydrochloride anesthesia was used, and it proved satisfactory and free of any undesirable side effects. The peroral route using an endotracheal tube is preferred for flexible bronchofiberscopy. Fluoroscopic guidance is essential in examining peripheral lung lesions. A 70 percent positive yield was obtained for patients with peripheral carcinoma of the lung as contrasted to a 47 percent yield when the tissue specimens were obtained blindly.


Screening for skin cancer at a county fair. Six skin cancer detection clinics were held at a county fair booth in Turlock, California during August, 1973. Examination of sun-exposed skin areas in 605 people showed potential skin cancer in 28.6 percent of people 25 years of age or older. Of the people examined, 135 were referred to their own physicians for follow-up diagnosis and treatment of skin lesions.


Introduced schistosomiasis. Evaluation as a public health hazard. Schistosomiasis was found in many agricultural workers from Yemen who are residing in the San Joaquin Valley, and a study was done to evaluate the public health hazard of this imported disease. If the necessary intermediate hosts are present, a local focus of infection could be established. Numerous Biomphalaria obstructa snails collected in the vicinity of the Avenue 82 irrigation canal near Oasis, Riverside County, showed no evidence of natural schistosome infection. Laboratory-reared offspring of these snails were exposed to miracidia of Schistosoma mansoni originating from Yemen immigrants and to miracidia from a standard laboratory strain of Puerto Rican origin obtained from the National Institutes of Health. All exposures of California B. obstructa were made with a laboratory stock of highly susceptible B. glabrata snails also obtained from NIH as controls. Although miracidia penetrated California snails no evidence of infection was detected whereas the B. glabrata controls showed normal, mature infections with numerous cercariae.There appears little likelihood that B. obstructa can serve as intermediate host for schistosomiasis.


Health hazard appraisal in patient counseling. A program of annual health examinations was expanded to include counseling based on a computerized appraisal of individual patients' specific health hazard factors. Data obtained from a specially designed questionnaire, laboratory tests and a physical examination yielded a printout showing a number of weighted risk factors and their relation to ten leading causes of death as determined for that patient. From all of this information, a risk ("apparent") age was developed for the patient. The results were reviewed with each patient, and methods of correcting health hazards were stressed. A total of 488 persons were appraised, and 107 were randomly reappraised in less than a year, with the finding that the net risk age was reduced by 1.4 years. Such a reduction in risk age is significant; it indicates that appraisal-based counseling is an effective method of altering priorities of health practices.


Diagnosis of carcinoma and benign cysts of the breast. The value of needle aspiration. Diagnosis of solid breast masses by needle aspiration with cytological examination of the aspirate has been practiced for some time in several centers in this country and abroad. It has been proposed as an alternative to the conventional excisional biopsy for the diagnosis of carcinoma of the breast. At the same time, simple needle aspiration of benign cysts as an office procedure has gained new favor as a means of proving the presence of benign disease at the first office visit and thus avoiding the loss of time, and the expense and worry of surgical excision in a hospital. From a review of the reliability and practical usefulness of both methods, it is concluded that aspiration biopsy for the diagnosis of carcinoma is less reliable than conventional excisional biopsy and offers very little practical advantage. Simple aspiration of cysts, on the other hand, appears to offer a true saving of time, expense and worry, and to be a reliable method, if used properly.


[Diagnostic problems in the sinus node syndrome]. The sick sinus syndrome includes numerous arrhythmias due to various functional disorders of the sinus node, the atria and the A-V junctional tissue. These disturbances of impulse formation and conduction involve many diagnostic problems. If clinical methods as ECG monitoring are of no help, provocative tests are indicated. The best indirect test of the sinus node activity is the measurement of the sinus node recovery time after overdrive suppression. In addition, the sinu-atrial conduction time, the conduction velocity within the right atrium, the A-V node and the His-Purkinje system can be measured. In patients with the sick sinus syndrome abnormalities of conduction in the specialized cardiac tissue are common in addition to sinus node dysfunction. The results of the provocative tests are important for drug therapy or pacemaker implantation.


[Atrioventricular conduction in the Lown-Ganong-Levine syndrome]. In 18 patients with LGL-syndrome His bundle electrography and atrial pacing were performed. In all cases the atrial conduction time was normal, the H-V interval within the lower limit (36 msec). The A-H interval was significantly shortened (58 msec). During rapid atrial pacing four different patterns of reaction could be distinguished: 1) A-H interval unchanged (1 case). 2) Sudden prolongation of the A-H interval at a critical rate (4 cases). 3) Continuous prolongation of the A-H time according to the driving frequency (9 cases). 4) Marked delay and block (4 cases). Verapamil had only little or no effect on the A-H interval in these patients. The results indicate, that only in a few cases with LGL-syndrome the shortened A-H time is due to a James bundle bypassing completely the A-V node.


[Significance of atrial stimulation in the diagnosis and therapy of rhythm and latent conduction disorders of the heart]. Temporary atrial pacings were carried out at several sorts of heart blocks on diagnostic and curing purpose. The proceedings can be useful to detect the latent blocks with different etiology and to set up the indication of permanent pacemaker implantation.


[Pathogenesis of acquired coronary anomalies. Case report]. The heart of a 44 years old man who died of a severe calcifying endocarditis of the aortic valves and the aortic root demonstrated a rare anomaly of the coronary arteries. The ostium and the stem of the left coronary artery were missing. In the left aortic sinus there was a small dimple covered by calcified tissue. Using histological serial sections a small vessel was detected that was completely obliterated by organized thrombotic tissue running between the small dimple in the aortic sinus and the main branches of the left coronary artery. This vessel was supposed to be the remaining stem of the left coronary artery. The regular branches of the left coronary artery were supplied by an anastomosis between the proximal part of the right coronary artery and the descending branch of the left coronary artery running within the upper interventricular septum. It has been suggested that this rare anomaly was caused by a gradual obliteration of the ostium and the stem of the left coronary artery during the course of the calcifying rheumatic endocarditis of the aortic valves.


[Ultrasonic cardiographic studies of heart size in atrial septal defect, combined mitral and aortic valve disease]. 27 patients with following diagnoses were examined by ultrasound: ASD; Aortic valve disease; Mitral valve disease with predominant insufficiency; Mitral stenosis; right heart failure; patients without evidence of cardiac disease. The right ventricular dimension (RVD Index) was assessed representing the distance between the right ventricular epicardial echoes and echoes from the right side of the interventricular septum divided by the patient's body surface area, analogue measurements were done to obtain the left ventricular dimension (LVD Index). The ratio from LVD to RVD was calculated. The motion of the interventricular septum was classified as Normal, Abnormal A and Abnormal B, according to known criteria. Three groups of patients could be differentiated: Patients without cardiac disease; Patients with right ventricular enlargement and ASD; Patients with left ventricular enlargement with aortic and mitral valve disease. In patients with cardiac enlargement, echocardiography provides better information concerning the ratio of the left ventricular to the right ventricular diameter compared to a routine chest X ray.


Pituitary necrosis following major heart surgery. Five cases of acute adenohypophysial necrosis were detected among 33 patients who underwent major cardiac operation and died within 10 days. This finding indicates an increased incidence of pituitary necrosis in heart surgery patients compared with unselected autopsy material. Histologically, the lesions which closely resemble those associated most frequently with obstetric shock, elevated intracranial pressure and diabetes mellitus, are coagulative infarcts, due to suppression of adenohypophysial blood flow. The cause of circulatory arrest to the adenohypophysis remains obscure.


[Clinical aspects and hemodynamics of idiopathic dilatation of pulmonary artery]. 1. The following clinical findings were seen with increased frequency in patients with idiopathic pulmonary artery dilatation: pulmonary ejection click, systolic ejection murmur in the pulmonic area and abnormally wide splitting of second heart sound. 2. Hemodynamically these patients present often a pressure gradient on the pulmonic valve of minor degree and a slightly elevated cardiac index. A congenitally increased elasticity of the tissue of the common pulmonary artery has to be considered as the possible etiology of this lesion. 3. The diagnosis of idiopathic dilatation of the pulmonary artery can be established by non invasive methods, excluding pulmonary valvular stenosis, pulmonary hypertension and left-to-right shunts.


[Registration and evaluation of blood pressure curves of the pulmonary artery with reference to various causes of error]. In about 250 experiments with male and female anesthetized mongrel dogs, measurements of right ventricle and pulmonary artery pressure were carried out. We used Goodale-Lubin-, micro- and Swan-Ganz-catheters. The pressure registration was done by usual equipment. The investigation was performed to evaluate the reason and the extent of disturbances, which affect the real and formal pressure curve in the arteria pulmonalis. The following results could be obtained: 1. The disturbances can lead to fluctuations of such extent, that a correct demarcation of normal and pathological values is impossible. 2. Of great influence on the results of measurements are preparation and registration (warm-up-time, amplification, closeness of pressure-system, unhurt catheters), factors relating to equipment and methods (air-bubbles in pressure-system, damping by filters, continuous infusion of the micro-catheter, level of zero-pressure), factors which occur during intravital measurement (pressure-drop along the arteria pulmonalis, influence of normal breathing, great intrapleural pressure changes, pressure damping in the catheter by thrombosis and external disturbances) and last not least positive and negative acceleration forces, which influence the diastolic and systolic pulmonary artery pressure. 3. Most of the defects and disturbances also occur, when the physical conditions of the equipment are correct. When the preparation and registration is conducted very carefully, all disturbances can be recognized, eliminated and corrected during the registration. 4. The main problems are caused by influence of normal and pathological intrapleural breathing pressures. By reasons of comparison it is necessary to select the pressure values to be used from a great number of real and formal correct pressure values. Besides it is necessary to have always in mind the transmural pressure in the evaluation of pulmonary artery pressures. 5. By consideration of these results it is possible to mark off the normal pressure zone of pulmonary artery pressure from the low pathological zone.


[Systemic error during measurement of dp/dt using conventional heart catheters and their correction]. The influence of 4 different types of conventional cardiac catheter on the systemic error during measurements of dp/dt was investigated by testing the frequency response. This was done by coupling on end of the fluid-filled catheters to a newly developed sine wave pressure generator (0-100 Hz), and the other end ot a pressure transducer (Statham 23 Db). The obtained electrical signal was preamplified and differentiated by means of a differentiation amplifier (linear rise up to 20 Hz). Also investigated was to what extent the dp/dt registration (UV-Oscilloscope) could be improved by damping the signal by means of electrical low pass filters.


A fine structural study of asexual stages of the murine coccidium Eimeria ferrisi Levine and Ivens 1965. The schizogony of Eimeria ferrisi was studied in experimentally infected Mus musculus. Developmental stages occurred in epithelial cells of the cecum and colon. During transformation of invasive stages into schizonts the inner membrane complex of the pellicle, the conoid, subpellicular microtubules and micronemes gradually disappeared. The micropore, however, seemed to persist. Dividing nuclei had eccentric intranuclear spindles consisting of microtubules which extended between 2 centrocones, in close relationship with centrioles. During the last nuclear division anlagen of merozoites appeared as extensions on the surface of schizonts. The outer single membrane of the schizont became the outer membrane of the merozoite pellicle. Cytoplasmic organelles, typical of eimerian merozoites were incorporated into the developing merozoites. Finally the merozoite became detached leaving behind a residual cytoplasm. Fully developed merozoites had a 3-layered pellicle, the outer single unit membrane was continuous around the merozoite with the inner complex having interruptions at the anterior and posterior poles and at the micropores. Thirty-two subpellicular microtubules, originating at the anterior polar ring extended to the posterior region of each merozoite. The apical complex consisted of a conoid, preceded by 2 rings and surrounded by a polar ring. Two rhoptries were present having club-shaped terminal ends and slender ductules in the conoid region. Some merozoites had enlarged rhoptries, with the distal vesical appearing dense and osmiophilic. The Golgi complex, endoplasmic reticulum, mitochondria, polysaccharide granules were similar to those seen in other eimerian merozoites.


Tricarboxylic acid cycle enzymes in the plerocercoid of Ligula intestinalis (Cestoda: Pseudophyllidea). All enzymes of the tricarboxylic acid cycle are present in subcellular fractions of the plerocercoid of Ligula intestinalis but the low activity of aconitase and malate dehydrogenase in the forward direction suggests that the complete cycle may be of questionable importance to the parasite. As in other helminths and intertidal molluscs, succinate, formed via a partial reversal of the tricarboxylic acid cycle, is a major end-product of anaerobic glucose degradation.


Sexual reproduction in the monogenean Diclidophora merlangi: tissue penetration by sperms. Copulation between pairs of adult Diclidophora merlangi detached from the host was frequently observed. The spined penis of one animal always attaches to a second worm at a latero-ventral position posterior to the genital openings. There is no vagina. The sperms travel between the cells of the recipient to reach the seminal receptacle. The ultrastructure of the sperm is described. Positions of adult D. merlangi on the gills of the host would facilitate pairing for sperm transfer.


Structure and mode of function of the organelles associated with nutrition of the macrogametes of Eimeria acervulina. The macrogamete of Eimeria acervulina, lay and developed within the host cell in a parasitophorous vacuole. The cytoplasmic membrane of the host cell bordering the vacuole was not smooth, but it had numerous folds extending into the vacuole. These "intravacuolar folds" varied in depth and number in different sections. In some, the majority of the folds were disconnected from the host cell. Once disconnected, they evidently disintegrated forming the amorphous, particulate material present in the parasitophorous vacuole. The pellicle of the young macrogamete consisted of a single unit membrane with an osmiophilic material representing the second membrane. Two unit membranes were apparent at a later stage of development when the wall-forming bodies had been formed and amylopectin granules deposited. Two kinds of organelles were present on the surface of the macrogamete, typical micropores and invaginations of the pellicle. The micropores arose from an invagination of the outer membrane, which continued through the invagination without interruption. Irrespective of whether an inner membrane was present in the pellicle or not, a thickened cylindrical wall around the inner portion of the invagination was always present. Micropores appeared in large numbers in both micro- and macrogametocytes. As many as three micropores were seen in a surface area of 2 mu2. Invaginations arose in a similar manner by infolding of the pellicle. They differed from micropores in that the thickened cylindrical wall present around the inner portion of the micropore was absent, and also in that invaginations had no uniform appearance. They were of varying shapes, and lengths, varying from very short V-shaped to long and narrow. Micropores and invaginations take in nutrients in the form of particulate matter present in the parasitophorous vacuole, this material having been derived from the host-cell membranous "intravacuolar folds". The micropores function as cytostomes and the invaginations take in material by means of pinocytosis. Large numbers of intravacuolar tubules were seen at the surface of the macrogamete. They were present only at certain areas of the macrogamete and in groups and were connecting the parasite with the host cell. They were about 80-110 nm in diameter, and were seen to attain a length of up to 6 mu. Evidence was obtained indicating that the tubules transport free ribosomes from the host cell to the parasite. The ribosomes were seen to accumulate in "pockets" within the cytoplasm of the host cell, at the area where the tubules were connected.


[Benign tumors of the stomach].

[Benign tumors of the stomach]. The authors report their surgical experience of benign gastric tumors between 1947 and 1972: 19 cases (18 patients) were operated, which represent 3, 5% of the operated malignant tumors. Distribution was as follows: 6 polyps, 4 schwannomas, 4 accessory pancreases, 4 leiomyomas, 1 lipoma plus one leiomyoma of the ampula of Vater. The authors recall the symptomatology and roentgenological aspect of these tumors. They point out the growing importance of fibroscopy. They insist on the connexion between these tumors and carcinomas: this is clear for schwannomas and polyps where volume is a determining feature. Resection can be limited where there is no danger of malignant change. Though unquestionalbe, the malignancy of polyps is less than that of classical carcinomas.


[Reflexions on carcinomas of the extra-hepatic bile ducts]. The authors present 12 cases of true malignant ampulloma and 23 cases of carcinoma of the biliary tract (MBT). They analyze frequency, symptomatology, pathology, radiology, treatment and results. They stress that decreasing malignancy is in the following order: cancer of the MBT, cancer of the gallbladder, and ampulloma. The latter is the least lethal with the most long-term cures. As to cancer of the MBT no cure is to be expected, but palliative surgery (resection or tumor by-pass) will bring temporary cure; consequently this should always be tried when possible despite the high operative mortality.


[Psychological implications of esthetic surgery. Apropos of a study of 68 cases]. The candidate to cosmetic surgery is not, contrary to a too common idea, a frivolous creature trying to become more beautiful. He is generally a person with a physical disgrace that induces a frustrating sense of inferiority. The role of the surgeon is to help by removal of the disgrace. The operative indication is thus only psychologic and in some extreme cases, difficult to establish, because the surgeon is badly prepared to this role. A study was performed to understand better the motives and psychologic results of cosmetic operations. Sixty-eight candidates were chosen by the surgeon who considered their disgrace operable. All accepted a psychologic analysis. Following this they were divided into 3 groups: "adapted" (39), "worried" (21) and "perturbated" (8), according to the increasing importance of their emotional disturbances. None of these patients was really psychotic. In the great majority of cases (83%), the interviews with the psychologist disclosed parental difficulties during childhood, followed by a sensation of frustration and of insecurity. Of the 64 operated patients, 62 were reviewed by the psychologist. Fifty-four (87%) were satisfied with the result, among which 45 felt improvement in their psychologic state. Eight were disappointed. Among these, 7 had been classified as "worried" or "distressed". Only 2 patients had reasons to be dissappointed, the others focussed a depressive tendency on a minor and temporary unperfection. Cosmetic surgery thus produces the best psychologic results in "adapted" patients, but is also justified in "worried" or "distressed" patients as the majority will benefit from the operation. In these a careful psychologic contact with the surgeon is mandatory to diminish the postoperative emotional disturbances.


Cancer of the breast. A study of prognostic factors as a guide in selecting cases for conservative treatment. We have analysed 2.649 observations of cancer of the breast in order to study factors influencing the prognosis. We have found a definitive relationship between the extend of the primary tumor, the condition of the regional lymph nodes and the presence or absence of metastases. A careful clinical examination remains of the utmost importance to assess the characteristics of tumor and nodes. This associated with systematic search for bone and pulmonary metastases, are the basic elements of a sound prognosis. The systematic removal of the internal and external mammary node chains in the surgical cases are indispensable to complete the clinical data. So defined the stage of the disease at the time of the first treatment is by far the most important factor in assessing the prognosis. Concerning the treatment, we have obtained better results with surgery associated with radiotherapy than with surgery alone. Therefore in early cases, that is to say cancer confined to the breast, we feel justified to apply conservative surgery associated with radiotherapy.


[Use of lande-edwards membrane oxygenators as artificial lungs]. Lande-Edwards membrane oxygenators were tested as artificial lungs in 6 dogs: the right heart directly perfused the oxygenators during an apneusis of one hour. During such a pulmonary by-pass right ventricular pressure doubles compared to initial value, with a moderate decrease in cardiac output; mean PO-2 rises from 40 to 67 mm Hg and PCO-2 decreases from 54 to 49 mm Hg through the oxygenator.


[On frozen vena saphena magna as an allograft in peripheral vascular surgery. Report of a case]. The case of a 75 year old white male, with severe ischemia of the left lower limb and gangrene of its fifth digit, is presented. Because of early post-operative thrombosis after insertion of an autogenous composite femoro-popliteal venous by-pass graft and recurrence of symptoms, a fresh frozen human varicose vein allograft procedure was performed. A pseudo-aneurism which occurred along the graft on the 13th postoperative day was successfully treated by segmental excision with "end-to-end" reconstruction of the allograft itself. This was followed by plastic reconstruction of his foot with primary healing and complete disappearance of symptoms. The patient is now eight months post- op with excellent functional result. Only twenty two similar cases were gathered from the literature. All problems associated with allograft transplantation of fresh and frozen veins are discussed. This case further supports the facts that bloodgroup incompatibility is not a major problem and that reinterventions on such grafts are feasable.


A reassessment of the distribution of multiple sclerosis. As difined in the first part of these papers, the distribution of MS does not really correlate well with broad geoclimatic factors. Specifically there is little evidence for a direct correlation with latitude, and such correlations, to be meaningful, need to consider longitude as well. At latitude 40 degrees north, for example, MS is high frequency in America, medium in Europe, and low in Asia. Accordingly the world-wide distribution of MS is best regarded as comprising three bands or zones of high medium, and low risk or frequency as delineated here. All the high and medium regions are at present found in Europe or in areas colonized by Europeans. It seems likely then that MS originated in western Europe and has spread from there to the United States and Canada as well as to New Zealand and Australia. The disorder may well have "taken" also in South Africa and Hawaii, but at considerably lower levels. Further attention to the character and timing of the depresion of this disease may well provide clues vital to determining its cause.


Palmar hyperhidrosis. Long-term results following high thoracic sympathectomy. Fourteen men and 22 wemon, with an average of 23 years (range 14-36 years) were operated on for hyperhidrosis of the upper extremity during the period from 1955 to 1970. Twenty-eight had had symptoms for more than 10 years. Resection of the 2nd and 3rd thoracic ganglia and the connecting sympathetic chain was carried out using a posterior approach; in 33 cases the operation was bilateral, and in three unilateral. Thirty-five patients were followed up after an average of 7.8 years (range 2-17 years). In one patient unilateral reoperation was carried out four months after the first operation. Since the first operation 34 patients had suffered from neither palmar nor axillary sweating. However 20 had permanent compensatory hyperhidrosis, and 15 suffered from gustatory facial sweating, which had usually started within six months of operation. Four, in whom two spinal thoracic nerves had also been resected, reported marked dysaesthesia over the front of the chest and in the axilla, lasting for several years.


Studies on the clustering of multiple sclerosis in Finland I: Comparison between the domiciles and places of birth in selected subpopulations. Further studies pm yjr rofr,op;phu pg ,i;yo;r dv;rtpdod (MS) IN Finland were carried out in three different types of geographical unit: in counties, combined clerical districts, and single clerical district. For longitudinal studies, the prevalence of MS by present domicile was compared to that by place of birth, and also to the number of MS cases in relation to the number of births. The analysis was based on 1,866 living MS patients. The highest prevalence by present domicile was recorded in the southwestern county of Turku and Pori (52.3 cases per 100,000 inhabitants). It was 39.6 for the whole country. Two separate clusters were found at the level of combined and single clerical districts: one in the western county of Vaasa, and another in the southwestern county of Turku and Pori. The highest prevalences by present comicile were found in two clerical districts of Vaasa (83.5 and 79.7). They also had very high prevalences by place of birth. They lie close to each other, but are not immediate neighbours. Another high-risk focus was revealed in an area of the neighbouring districts of Turku and Pori. In fact, the two highest prevalences by place of birth were found in this region (123.1 and 95.0). The focus extended from the coastal area to the more central region of the county, and further to the western districts of the otherwise medium-risk county of Hme. Thus, two separate foci were found in Finland: one in the western and another in the southwestern part of the country. The clustering became even more pronounced when the prevalences by place of birth were analysed. Considering that the Finnish population still largely originates from genetic isolates of varying degrees, gene enrichment explains the clustering at least partly.


Preservation of peripheral nerve function in severe uremia during treatment with low protein high calorie diet and surplus of essential amino acids. Twelve patients with severe chronic renal failure (serum creatinine 7.0-27 mg %), and marked uremic symptoms on a 40 g protein diet, were treated with a caloric-rich diet containing 16-20 g protein, supplemented with the 8 essential amino acids (1.1-2.2 g N) and histidine (0.23-0.45 g N)in the form of tablets for periods between 3 and 34 months. During the treatment the serum urea-N fell, and the uremic symptoms subsided or diminished without the patient exhibiting signs of malnutrition. The nerve function was followed with quantitative and semiquantitative neurological tests (among others, determination of vibratory perception thresholds and nerve conduction times). Initially all patients but 2 had signs of neuropathy as measured by these methods. During the course of treatment no deterioration of peripheral nerve function was recorded in any of the patients, several of whom had had serum creatinine conceptrations above 15 mg % for long periods. We conclude that conservative treatment with N-poor diet in far advanced chronic renal failure may prevent the further development of peripheral neuropathy provided that adequatecaloried and essential amino acids (2-3 times the minimal requirements) are supplied. The results suggest that, in addition to uremic toxines, malnutrition is a factor of importance for the developments of  of uremic neuropathy.


Gastric aspirate analysis in the newborn. The value of gastric aspirate analysis in screening for perinatal infection is disputed. We have studied the cellularity and bacterial content of 231 aspirates from 105 normal, infected and asphyxiated infants, with the following conclusions: (1) A positive culture has no pathological significance. (2). Aspirate cellularity does not correlate with bacterial culture results. (3) An excess of polymorphonuclear leucocytes (PMNL) in aspirates collected at birth is a pathological but non-specific stress response. (4) After birth there is a physiological rise and fall in the aspirate PMNL content parallel to that in the peripheral blood. Aspirate cellularity and bacterial culture are therefore of limited value in the diagnosis of neonatal pneumonia.


Blood glucose and plasma insulin and glucagon response during intravenous glucose tolerance test in newborn infants affected by erythroblastosis foetalis. Intravenous glucose injection (1 g/kg b.w.) was performed in eight newborn infants affected by erythroblastosis foetalis (IEF) and in seven controls during the first day of life in order to study insulin and glucagon response. The IEF infants were affected by mild or moderate hemolytic disease and their blood glucose values and plasma insulin concentrations before and throughout the test did not differ significantly from those of the controls. After the glucose injection the plasma glucagon concentrations showed great variations in both groups. The control infants did not show any significant changes; in the IEF infants, significant decreases were seen at 3 and 20 min of the test. These data seem to indicate that the alpha-cell sensitivity to glucose is greater in IEF than in normal infants and is not dependent on the development of the glucose-mediated insulin release mechanism.


Biochemical diagnosis of cystinosis using leukocytes. A simple method for the biochemical diagnosis of cystinosis involves incubating leukocytes from a small volume of blood with 35S-cystine. Non-protein 35S-labelled compounds are then extracted from the leucocytes and separated by thin-layer chromatography. The excessive incorporation of 35S-cystine into the increased cystine pool of cystine cells is easily detected in autoradiographs of the chromatograms.


Wolff-Parkinson-White syndrome. A fatal case in a girl with no other heart disease. A fatal case of the pre-excitation syndrome in a 3 10/12 years old girl with no other heart disease is presented. Her death is thought to be the consequence of ventricular fibrillation. This observation is in contrast to the reported benign course in infants and children with the Wolff-Parkinson-White syndrome without other heart disease.


Oxidation of glucose and D-B-OH-butyrate by the early human fetal brain. The isolated brains of 12 previable human fetuses obtained at 12 to 21 weeks' gestation, were perfused through the interval carotid artery with glucose (3 mM) and/or DL-B-OH-butyrate (DL-BOHB), 4.5 MM, plus tracer quantities of either glucose-6-14C (G6-14C) or beta-OH-butyrate-3-14C (BOHB3-14C). Oxidative metabolism was demonstrated by serial collection of gaseous 14CO2 from the closed perfusion system, and from the recirculating medium. Glucose and BOHB were utilized at physiological rates as indicated (mean plus or minus SEM): G6-14C at 0.10 plus or minus 0.01 mumoles/min g brain (n equal 7) or 17.5 plus or minus 1.9 mumoles/min kg fetus; and BOHB3-14C at 0.16 plus or minus 0.05 mumoles/min g (n equal to 5) or 27.3 plus or minus 7.4 mumoles/min kg. Based on fetal weight, glucose metabolism by brain apparently accounted for about 1/3 of basal glucose utilization in the fetus. On a molar basis BOHB3-14C was taken up at 1.47 times the rate of G6-14C. Both BOHB3-14C and G6 14C were converted to 14CO2. The rate of BOHB3-14C conversion to 14CO2 was equal to its rate of consumption, and exceeded the conversion of glucose to CO2 because 45% of the G6-14C was incorporated into lactate-14C. Accordingly, both substrates support oxidative metabolism by brain; and BOHB is a major potential alternate fuel which can replace glucose early in human development.


Value of brain scanning in pediatric subdural collections. Piepsz, A., Bormans, J., Segers, A., Noterman, J. and Decostre, P. (Departments of Paediatrics, Radioisotopes and Neurosurgery, University Hospital, Brussels, Belgium). Value of brain scanning in pediatric subdural collections. Acta Paediatr Scand, 64:2, 1965. Eighteen children with subdural collections were submitted to brain scintigraphy. By this method, idopathic and post-traumatic hematomas were detected in 40% of the cases, and subdural effusions in 70% of the cases. No false-negative results were noted in the 3 cases of empyema. Several false-positive images were recorded, most of them following purulent meningitis, without any satisfactory explanation. Neither the technique of scintigraphy used in the department, the dimensions of the skull, the age of hematoma, nor the presence of membranes seemed to affect the accuracy of the method. Compared with the other easily performed examinations (eye fundus, EEG, Echo), scintigraphy still remains important in the diagnosis of subdural collections in children.


Prenatal diagnosis of methylmalonic aciduria. Prenatal diagnosis using amniocentesis was sought in two midtrimester pregnancies, each at risk for a different type of inherited methylmalonic aciduria. In one pregnancy a normal fetus was diagnosed from studies of cultured amniotic fluid cells and the diagnosis confirmed after the baby was born. In the second pregnancy a fetus with a methylmalonyl-CoA mutase apo enzyme defect was found. The diagnosis was based on cultured cell studies and supported by an elevation of methylmalonate in both amniotic fluid and maternal urine. Confirmatory studies were obtained using cultured cells from the aborted fetus. At the present time, assays of cultured amniotic fluid cells are imperative for firm diagnosis. With more experience, quantities of amniotic fluid and maternal urine methylmalonate may prove sufficient if differentiation among the various types of methylmalonic aciduria is not required.


Method for determination of pulmonary gas exchange in connection with birth. An apparatus built on the "open" system for determination of pulmonary gas exchange in the newborn infant after birth is described. At four-minute intervals diluted expired air (5-7 1/min) was collected in bags. The oxygen and carbon dioxide fraction in the bags were analysed with a Nyons Diaferometer (working on the principle of thermoconductivity). In calibration experiments using a gas-mixing technique a high degree of linearity was found, both in the determination of the fraction of oxygen and carbon dioxide (r equal to 0.9996). Reproducibility from duplicate readings was also good (for oxygen determination 0.9% and for carbon dioxide determination 0.8%). Duplicate determinations performed on infants with the same degree of motor activity resulted in an estimated error of the method of 5.8% for VO2 and 7.8% for VCO2 respectively. A metabolic chamber was used to control environmental temperature. The air temperature and wall temperature in the chamber were regulated by water from a thermostatically controlled waterbath and were kept equal within 0.5 degrees C. As the method for determination of the fraction of oxygen and carbon dioxide is not specific, other gaseous materials exhaled by the infants influence the measurements and nitrous oxide was found to interfere with the determinations, and made VO2 and VCO2 determinations in these patients impossible. Experience from more than 50 investigations on newborn infants has shown that the method is well suited to this particular type of study.


Lung expansion and the formation of the alveolar lining layer in the fullterm newborn rabbit. Light and electron microscopic studies of lungs from fullterm newborn rabbits, 0-24 hours after birth, revealed a patchy alveolar air expansion during the first few hours of extra-uterine life. Fairly uniform aeration of alveoli was noted 6-24 hours after birth but minor "unexpanded" areas were still present after 24 hours. In the fetal pulmonary fluid as well as in the alveolar lining layer formed after the onset of breathing there are multiple large phospholipid complexes, and a discontinuous  multilamellar surface film can be demonstrated in some alveoli from 2 hours after birth. Apparently, the neonatal adaptation of the rabbit lung is a protracted process, not even complete at the age of 24 hours.


Electrical polarization of rectal mucosa and excretion of tetrahydroaldosterone in patients with cystic fibrosis of pancreas and in normal subjects. The electrical potential difference (PD) across the rectal wall was measured in 26 patients with cystic fibrosis of pancreas (CFP) and in 18 healthy subjects. The PDs obtained in normal children were identical to those previously obtained in normal adults. A significantly greater dispersion of the values was observed in CFP. When the patients were divided into groups according to metachromasia in fibroblast cultures, the mean PD was increased only in the ametachromatic group. True enough, this observation suggests a difference between various forms of CFP, distinguished by metachromasia, and thus is a further indication of the heterogeneity of the disease. The greater abnormalities in metachromasia negative patients may, however, be due solely to the fact that these patients are more severely affected by the disease. The urinary excretion of tetrahydroaldosterone in patients was within the ranges obtained in controls, which excludes the possibility of secondary hyperaldosteronism as the source of increased PD. No evidence was provided in favour of a basic defect in the intestinal transport of Na+ or Cl minus, but K+ concentrations in faecal fluids of patients were significantly lower than in controls. The equilibrium concentration of K+ could be accounted for by simple passive diffusion, suggesting that the epithelium behaved inertly with respect to this ion in CFP.


Single injection polyfructosan clearance in normal and asphyxiated neonates. The postnatal development of the glomerular filtration rate in 36 neonates has been evaluated by the single injection polyfructosan clearance method (GFRPfr) by studies performed at 0-1, 2-4 and 5-7 weeks of postnatal age. During the first weeks of life there is a rapid postnatal increase of GFRPfr of almost the same magnitude in term and preterm healthy infants. Thus the postnatal development of glomerular filtration rate is more closely related to extra-uterine excretory needs than to the maturatinal stage and gestational age at birth. In the asphyxiated neonates studied the GFRPfr was significantly lowered in the immediate postasphyxial stage while the infants were still hypoxemic. However the postnatal rise of GFRPfr in the time period following the postasphyxial stage was of the same order as in the non-asphyxiated healthy neonates.


A social psychiatric investigation of a rural district in Northern Norway: a preliminary communication. The psychiatric morbidity of Berlevaag in Northern Norway (71 degrees North) was studied in 1944 by Bremer. A follow-up and a re-examination of the persons in the community was initiated in 1972. Preliminary data suggest that the prevalence of psychoses is practically the same in 1973 as in 1944. Various registers have provided a fairly complete count of psychoses even before the onset of an intensive field study. Only a minor part of the non-psychotic psychiatric disorders appears to have been identified.


Incidence of depressive syndromes in a Danish county. The Aarhus County investigation. On the basis of a material from a cumulative registration of the psychiatric morbidity in a geographically delimited population group - the County of Aarhus with approximately 175,000 inhabitants over the age of 15 years - the frequency of depressive syndromes in psychiatric and other medical services was investigated. The material fulfils the following criteria: During the calendar years 1960 to 1964, the patients 1) were residents in the County of Aarhus, 2) had attained the age of 15 years or more, 3) had contacted at least one of the services which systematically sent information to the psychiatric register; and 4) based on an evaluation of all available data, had a main diagnosis of manic-depressive psychosis, psychogenic depression or neurotic depression. An average yearly registration rate of 1.30 per 1,000 men and 3.28 per 1,000 women was found (males: manic-depressive psychosis 0.60, psychogenic depression 0.23 and neurotic depression 0.47; females: manic-depressive psychosis 1.00, psychogenic depression 0.88 and neurotic depression 1.40). The three diagnostic groups show differences in age distribution, geographical pattern and distribution by marital status.


A psychiatric-psychological study of XYY males found in a general male population. The psychological test results of five XYY males from in a population study showed an intellectual level within the normal range but with a mean full scale IQ and educational level lower than expected. The cognitive as well as emotional function was characterized by immaturity, manifested in passivity, unreflectiveness and emotional liability, in three resulting in uncontrolled aggressive outbursts. Conflict material also appeared immaturely resolved, centering around unfulfilled needs of contact and insecure masculine identification. The defense mechanisms used were generally rather weak, but only in one subject did the anxiety level seem to be excessively low. All five males differed to a certain extent from their siblings; three of them were hyperactive, restless, hot-tempered and impulsive at school and four of them had difficulties at school. Three learned a trade, but only one stayed in his trade, and one was applying for disablement pension on account of personality deviation. Two of the five had a criminal record. It is concluded that the presence and degree of the above-mentioned characteristics of XYY males varied. It is evident that environmental factors play as great a role for the development of personality and behaviour in males with karyotype 47, XYY as in males with a normal chromosome constitution.


Depression: influence on time estimation and time experience. Time studies are partly concerned with time estimation partly with time experience. In a study of depression both principles were applied. Depression did not influence time estimation, but, on the other hand, the patients did report a slowing down of time (change in time experience). An item analysis of Beck's and Hamilton's rating scales showed that the disturbance in time experience accompanies items referring mainly to mood changes, only to a small extent to somatic symptoms, and not at all to changes in the psychomotor activity.


Empirical investigations on the reliability and the value for differential diagnosis of 21 clinical symptoms of disturbed states of consciousness. Two groups of patients in disturbed states of consciousness (DSC's) were compared with three groups of patients in clear states of consciousness (CSC's): demented, schizophrenic, and non-psychotic patients. In each of the groups, 15 patients were evaluated for 21 "objective" symptoms; each patient was evaluated by two psychiatrists. In this way, reliable symptoms were sought out which could discriminate: 1) elderly patients in DSC's from elderly demented but clear patients; and 2) schizophrenic patients from patients in DSC's caused by either withdrawal states after abuse of alcohol or barbiturates, or psychogenic psychoses. Reliable and discriminating symptoms were found. However, different symptoms discriminated when patients in different diagnostic groups were compared. Three kinds of discriminating values of a symptom may be distinguished from one another: 1) only the presence of a symptom is informative; 2) only its absence is informative; 3) both presence and absence of the symptom are informative.


Plasmid dependent impermeability barrier to cadmium ions in Staphylococcus aureus. The nature of plasmid born resistance of Staphylococcus aureus to cadmium ions has been investigated. Plasmid harbouring strain was significantly more resistant than its plasmid negative variant, both in growth tests and in manometric experiments. Radioisotopic studies have revealed that the resistant organism did not take up 115mCdCl2 at concentrations 10-4M--10-6M, which were also harmless to its respiration. In contrast to this, plasmid negative variant was permeable to all concentrations used (10-3M--10-6M), and the uptake of 115mCd2+ ions always resulted in inhibition of respiration. These findings suggest that the cadmium resistance could be due to the impermeability barrier controlled by plasmid genes. This barrier, however, could be broken through, since at 10-3M some marked uptake of radioactive cadmium by resistant strain was observed, which was accompanied by partial inhibition of respiration. Binding of Cd2+ ions to the sensitive cells was irreversible and temperature dependent (took place at 37 degrees, but did not occur at 2-4 degrees). The bound molecules could not be removed either by extensive washing with water or by cysteine treatment, although cells pretreated with this amino acid were protected against the uptake of 115mCdCl2.


The 11alpha and 17alpha-progesterone hydroxylases of Rhizopus nigricans NRRL 1477. Differential induction of cultures of Rhizopus nigricans indicated that hydroxylation of progesterone at the 11alpha- and 17alpha-positions is due to two separate enzymes. This is supported by the finding that 11alpha- and 17alpha-hydroxylating activities are separated by differential centrigufation of cell-free extracts. The feasibility of introducing a hydroxyl group at the 11alpha- or 17alpha-position of hydroxylated progesterone derivatives was tested.


Rehabilitation in extremity fractures.

Rehabilitation in extremity fractures. General principles in the rehabilitation of a patient with an extremity fracture include: treat the patient, not the x-ray; move all joints not immobilized; prevent disuse atrophy; use gravity to assist in mobilizing a joint; stabilize proximal joints to avoid reverse action of biarticular muscles; permit early protected weight bearing until adequate joint mobility is achieved; appropriately instruct the patient in a home program, and avoid all stretching.


Current transfusion practices.

Current transfusion practices. Utilization of packed red blood cells (PRBC) and plasma components individually or in combination allows replacement of the precise blood element needed, while avoiding some of the potential hazards of whole blood transfusions. Transfusion of PRBC, rather than whole blood, reduces the risk of circulatory overload and nonhemolytic transfusion reactions. Frozen PRBC essentially eliminate leukocyte or platelet sensitization and transmission of hepatitis is extremely rare.


Reye's syndrome.

Reye's syndrome. Although frequently unrecognized, Reye's syndrome is a significant cause of serious illness and death in children. Erroneous diagnoses include gastroenteritis, meningoencephalitis, metabolic encephalopathy, drug overdose and primary psychiatric disease. No specific cure is known but early diagnosis and vigorous empirical treatment may increase chances of survival. Although the EEG may be a useful tool in prognosis, it cannot be relied upon in deciding when to initiate or abandon aggressive therapy.


Outpatient anorectal surgery.

Outpatient anorectal surgery. Fulguration of polyps, rectal biopsy and the Barron method of removing hemorrhoids require no anesthesia. Anal fissures, warts, small fistulas and hemorrhoids can be removed with a minimal amount of anesthesia. Pilonidal cysts or abscesses can also be incised and drained in this manner. Extensive fistulas, unusually large hemorrhoids with generalized prolapse of mucosa and disorders involving poor-risk patients should be managed in the hospital.


Hemodynamic changes during ventricular pacing in patients with complete heart block and aortic and mitral valvular heart disease. Increasing the heart rate to near normal in patients with complete heart block (CHB) and slow ventricular rates may lead to greater improvement in ventricular function than when the heart rate is increased from normal to more rapid heart rates. Improvement in ventricular function is usually manifested by a decrease in left ventricular end-diastolic pressure (LVEDP) and volume and by an increase in contractility. In patients with both CHB and valvular heart disease improvement in ventricular function during pacing may be modified by the nature of the valvular disease. Hemodynamic data from six patients with both valvular heart disease and CHB were compared with those from ten patients with CHB and normal cardiac valves. Hemodynamic studies were performed at slow or idioventricular rates and again after increasing the heart rate to more nearly normal levels by ventricular pacing. When obstruction to left ventricular inflow (mitral stenosis) co-existed with CHB, increasing the heart rate resulted in a reduction of an elevated LVEDP to normal. This resulted in only a small increase in left atrial pressure in spite of a striking increase in the mean left atrial-ventricular gradient. When obstruction to left ventricular outflow prevailed (aortic stenosis), improvement in cardiac function was manifested mainly by a decrease in LVEDP and was accompanied by a decrease in left ventricular stroke work. When a large regurgitant volume (aortic insufficiency) was added to a ventricle which has enlarged subsequent to CHB, there was striking elevation in ventricular filling pressures which returned to more nearly normal levels when the heart rate was increased. This was accompanied by a reduction in regurgitant stroke volume in the patient in whom it was measured. Thus, an increase in heart rate may be especially beneficial to those patients with CHB who also have valvular lesions which contribute to an increase in LVEDP and end-diastolic volume. Careful hemodynamic evaluation is helpful in determining appropriate therapy in these patients.


Preclinical abnormality of left ventricular function in diabetes mellitus. Abnormal cardiac muscle function has been reported in experimental diabetes mellitus from this laboratory. To examine left ventricular performance in diabetic patients without clinical evidence of myocardial ischemia or other cardiovascular disease, a noninvasive measurement of the systolic time intervals was carried out. Simultaneous recordings of the electrocardiogram, heart sounds, and carotid pulse were made in 25 diabetic subjects, 20 to 56 years of age, and compared with 37 normal subjects. The diabetic subjects had a shorter left ventricular ejection time, longer pre-ejection period, and a higher ratio of pre-ejection period/left ventricular ejection time (P less than 0.001). The isovolumic time was prolonged (P less than 0.001), while heart rate and arterial pressure were within normal limits. Abnormal function was independent of apparent duration and treatment by diet alone, insulin, or hypoglycemic agents. On the basis of available morphologic data in human and canine diabetes, an alteration of the myocardial interstitium may be the basis for this preclinical abnormality in diabetic patients.


Determination of zero reference level for left atrial pressure by echocardiography. This study compares the anterior chest wall to mid-left atrial distance (D) determined by echocardiography with three standard cardiac zero reference levels (ZRL); 5 cm. from the sternal angle, (2) 10 cm. from the back, (3) midchest. Echocardiography was performed on 50 subjects (16 normal subjects and 34 subjects with heart disease). Chest wall, aortic root, and left atrial echoes were obtained to measure D. The AP diameter of the chest (L) was measured using calipers. Thus, ZRL (2) equals (L-10) cm. from the front of the chest and ARL (3) equals L/2, respectively. The difference between the mean of D and ZRL 1, ZRL 2, and ZRL 3 is ø8 c.m, -0.9 cm., and -0.5 cm., respectively. (a) ZRL (1) is consistently in error; in 17 patients the difference was greater than 5.4 cm.; (b) there is no significant difference between D and ZRL (2) or ZRL (3), and hence they are valid reference systems, and (c) echocardiography can be used to accurately determine the zero reference level for left atrial pressure measurements.


Immediate cardiac response to exercise: physiologic investigation by systolic time intervals at graded work loads. Immediate cardiac responses to exercise were investigated in five normal male volunteer subjects by measuring heart rate and systolic intervals from rest through the onset of exertion at three different work loads. Recordings were continued for fifty beats and again at one minute with measurements plotted on a beat-to-beat basis and grouped for statistical analysis. During exercise, heart rate and corrected ejection time increased, pre-ejection period and PEP/LVET decreased, and pulse transmission time remained stable. The heart rate acceleration was sudden, occurring in the first few beats of exercise, a phenomenon also demonstrated by previous investigators. A significant new finding was the equally abrupt major change in each of the other parameters. The immediacy of all responses was independent of load and was consistent with experimental studies showing that changes in both neural activity and venous return at the onset of exercise are virtually instantaneous.


Normal variations in tricuspid valve attachments to the membranous ventricular septum: a clue to the etiology of left ventricle-to-right atrial communication. In 39 out of 95 normal specimens, there was either no commissure between the anterior and medial leaflets of the tricuspid valve, which resulted in an interrupted valve margin at the center of the membranous ventricular septum, or an incompletely formed commissure. It is suggested that one end of this spectrum of normal anatomic variations could have a direct relationship to VSD associated with left ventricle-to-right atrial communication.


Late hemodynamic results of fascia lata reconstruction of the right ventricular outlet. Eight patients were catheterized between 1.2 and 2.4 years after reconstruction of the right ventricular outflow tract with autologous fascia lata. Whereas the immediate post-bypass pressures had demonstrated a maximum gradient of 15 mm. Hg across the fascial valve at the time of recatheterization, this varied from 55 to 142 mm. Hg (mean 83 mm. Hg). Right ventricular systolic pressure varied between 80 and 160mm. Hg (mean 106 mm. Hg). All but one patient had clinical evidence of pulmonary incompetence. Selective angiography with injection into the right ventricle and pulmonary artery demonstrated shrunken, thickened, immobile valve cusps with an abrupt stenosis of the fascial tube or a diaphragm across it. Re-operation has been done in five patients. In each, the graft tube functioned satisfactorily, but at the site of the "valve," no leaflets were visible, and the orifice of the conduit narrowed abruptly to 6 to 10 mm. in diameter. It is concluded that autologous fascia lata is unsuitable for reconstruction of the right ventricular outflow tract.


Sustained accelerated idioventricular rhythm. A 73-year-old white man became easily fatigued and hypotensive six weeks after a documented acute inferior myocardial infarction. Continuous ECG monitoring showed a sustained tachycardia with a right bundle branch block pattern. A His bundle electrogram showed no His deflection prior to ventricular activation. The patient was successfully treated with intravenous procaine amide resulting in reversion to sinus rhythm, loss of symptoms, and return of blood pressure to normal levels. The unique aspects of this case and therapeutic considerations in the management of this problem are discussed.


Myocardial infarction in the newborn: a case report complicated by cardiogenic shock and associated with normal coronary arteries. Fatal myocardial infarction occurring in a neonate is reported. The patient presented with a clinical picture of cardiogenic shock simulating a hypoplastic left heart syndrome. Etiology of the myocardial infarction is uncertain for the coronary arteries were patent, anatomically and histologically normal, and there was no significant associated cardiac defect. The possible etiologies in relationship to myocardial infarction in the neonatal period are presented.


Electrophysiology and pharmacology of cardiac arrhythmias. III. The causes and treatment of cardiac arrhythmias. Part B. Studies on the electrophysiologic mechanisms responsible for disturbances of cardiac rate, rhythm, and conduction, and studies on the actions and mechanisms of action of antiarrhythmic and other drugs, permit the development of an apparently reasonable approach to treatment of cardiac arrhythmias. Some of the rules derived from an appreciation of cardiac electrophysiology are generally applicable. Others appear to require further testing. There are many discrepancies between what can be predicted or expected and what happens; these discrepancies result from many factors. It is likely that cardiac disease in humans has effects on the electrical activity of cardiac cells which have not been reproduced in the laboratory. It is likely, also, that disease modifies the response of cardiac cells to drugs in ways that have not yet been discovered. Nevertheless, some progress has been made and further experiment and thought may provide both better understanding and new and better therapeutic agents.


Calcific aortic insufficiency--a review of 26 patients. Twenty-six patients, 8.3 per cent of all patients with aortic valve disease, and 10.7 per cent of all patients with any degree of aortic insufficiency detected in our catheterization laboratory, had pure calcific aortic insufficiency (no associated stenosis). Nineteen (73 per cent) males and seven (27 per cent) females ranged in age from 25 to 75 years of age (mean 51). Twenty-three per cent were younger than 40. Sixteen (62 per cent) had rheumatic heart disease, one had luetic aortic valve disease, one had congenital bicuspid valve, and eight (31 per cent) had aortic insufficiency of undetermined etiology. Twenty-three patients (89 per cent) had an aortic systolic ejection murmur, and seven (28 per cent) had an aortic ejection click. Aortic valve calcification was detected by plain chest films in only four patients (16 per cent), and by routine image intensification fluoroscopy (before catheterization) in fifteen patients (68 per cent). The reamining 32 per cent had the calcification of the aortic valve detected during catheterization. Aortic valve calcification was severe in nine patients (35 per cent), moderate in eleven patients (42 per cent), and minimal in six patients (22 per cent). Aortic insufficiency was severe in twenty patients (77 per cent), moderate in five patients (19 per cent), and minimal in one patient (4 per cent). Nineteen patients (77 per cent) had reduced left ventricular contractility. Sixteen patients (67 per cent) had low cardiac index. Eighteen patients had obstructive coronary artery disease. Aortic stenosis was misdiagnosed as the predominant lesion in fourteen patients (54 per cent)--prior to catheterization. This series demonstrates that all patients with calcified aortic valve disease and with ejection murmurs do not necessarily have aortic stenosis. Pure calcific aortic insufficiency is a distinct entity, more common than previously suspected.


P-wave analysis in myocardial infarction, pulmonary edema, and embolism. In a retrospective study, the P-terminal force in Lead V1 (PTF-V1) was measured in three groups, each of 35 patients, with the respective diagnoses of acute myocardial infarction without pulmonary edema, acute pulmonary embolism, and acute pulmonary edema. In all but one of the patients with acute pulmonary edema, a highly negative PTF-V1 value was obtained, whereas by contrast, all the patients with pulmonary embolism had normal PTF-V1 values. Four of the patients with acute myocardial infarction had abnormal PTF-V1 values, although at the time there was no clinical or radiologic evidence of pulmonary edema. However, one of these patients did develop acute pulmonary edema a few hours later. Measurement of the PTF-V1 is a simple noninvasive test that may, therefore, be useful in separating patients with acute pulmonary embolism from those with acute or impending pulmonary edema.


Correlation of "critical" left coronary artery lesions with positive submaximal exercise tests in patients with chest pain. This study correlates the anatomic pathologic coronary anatomy found by arteriography in each of three groups of symptomatic patients, all with coronary artery disease, divided according to the magnitude of ST-segment depression after an adequate submaximal treadmill exercise test. Group I consists of 45 patients with ST-segement depression of 2 mm. or more, Group II of 31 patients with ST-segment depression between 1.0 and 1.9 mm., and Group III, 30 patients with 0 to 0.9 mm. ST-segment depression. Seventy-five per cent of the patients in Group I had critical lesions defined as (1) 75 per cent or greater narrowing of left main coronary artery (LMCA), (2) 75 per cent or greater obstructive left anterior descending and left circumflex coronary artery both proximal to any major branching, the so-called left main equivalent (LME) lesions, and (3) 90 per cent or more obstruction of the left anterior descending coronary proximal to any major branches. Of patients in Group I, 24 PER CENT Had LMCA lesions, 29 per cent had LAD lesions. Eight-two per cent of Group I patients had two- or three-vessel disease. All patients with LMCA lesions had 2 mm. or more ST-segment depression. Over 95 per cent of patients with "critical" lesions is less than 5 per cent in the presence of an adequate aubmaximal treadmill test that shows less than 1 mm. of ST-segment depression, it is concluded that in such patients with medically controllable angina, coronary arteriography is not necessary.


A His bundle electrocardiographic analysis of cardiac conduction in the pediatric and adolescent patient. Bipolar electrode catheter recordings of His bundle electrograms with three simultaneously recorded surface electrocardiographic leads were obtained from 30 pediatric and adolescent patients (aged 3 to 18 years). In 14 patients, cardiac murmurs were proved to be innocent by cardiac catheterization. The control conduction intervals were compared to those of 13 patients with congenital heart disease, and three with acquired heart disease (myocardiopathy, rheumatic valvular disease, and Friedreich's ataxia). P-R, intra-atrial (P-A), A-V nodal (A-H), and intraventricular (H-V) conduction intervals were measured to the nearest 5 msec. Conduction delays were analyzed in each of the three components of the P-R interval. These delays occurred both in single components of the system as well as in combined conduction delays and were not always demonstrable by surface electrocardiograms. The Wenckebach phenomenon induced by atrial pacing was localized to the A-V node as well as the His-Purkinje system. This technique of intracardiac electrogram recordings is safe, does not significantly prolong cardiac atheterization time, and often yields unique and useful data concerning A-V conduction.


The high frequency electrocardiogram in coronary artery disease. The high-frequency ECG clearly contains information not available in the conventional ECG. Patients with angina pectoris could not be identified as statistically different from the normal group based on notching, although isolated examples existed. MI, on the other hand manifested abnormal notch counts in the presence of absence of abnormal Q-waves. We were unable to correlate the treadmill exercise test or the site of the arterial lesion with the high-frequency ECG. Pathophysiologic mechanisms are discussed.


Primary chylopericardium: a review of the literature and an illustrated case. A report of a case of chylous pericardium and a review of previously reported cases are given. The specific diagnosis can be made with pericardiocentesis and analysis of the fluid which is milky in appearance and contains fat droplets microscopically. Thoracic duct obstruction with failure of adequate collateral drainage and resultant reflux of chylous lymph through lymphatics draining the heart and pericardium is proposed as a mechanism of development of this entity. Thoracic duct ligation and partial pericardectomy remain the preferred treatment for chylopericardium.


Left-axis deviation: etiologic factors in one-hundred patients. Clinical and electrocardiographic findings were analyzed in 100 consecutive cases of LAD. Below the age of forty years, LAD was uncommon, but its incidence increased continuously thereafter. The most frequent primary clinical diagnosis was arteriosclerotic heart disease. The functional mechanism producing LAD most often was LAHB, responsible in about 40 per cent. Approximately half the instances of LAHB were associated with old myocardial infarction of septal, anterior, or lateral regions, but half were seen in the absence of infarction or clinical coronary sclerosis and are presumed due to primary degenerative processes within these specialized conducting fibers. Approximately one-sixth of the instances of LAD were due to loss of inferior forces following inferior myocardial infarction. Typical left ventricular hypertrophy was a distinctly uncommon cause of LAD. Last, in 24 patients with LAD the mechanism or cause was not evident initially, of which two were subsequently shown to represent a very mild degree of LAHB. Also it is suggested that asymmetric myocardial hypertrophy of the anterior wall may account for some instances of LAD not otherwise explained.


Transient ST-segment elevation with postmyocardial infarction angina: prognostic significance. Fifty-seven patients with acute myocardial infarction were observed for early postmyocardial infarction angina and associated transient ST-segment changes. Nine patients had postinfarction angina with transient ST-segment elevation (group 1), seventeen patients had postinfarction angina with ST-segment depression or no ST-segment changes (Group 2), and 31 patients had no postinfarction angina (Group 3). The patients in Group 1 had a statistically significant increased incidence of early reinfarction and death, when compared with the other two groups, singly or combined. There was no significant difference in the incidence of reinfarction and death when Group 2 is compared with Group 3. Patients with transient ST-segment elevation associated with early postmyocardial infarction angina may be an appropriate group in whom to consider newer, more aggressive modes of postinfarction management.


Blood levels of lidocaine after various infusion rates in patients with acute myocardial infarction. Blood levels of lidocaine were estimated following two different infusion rates in patients with acute myocardial infarction. Forty-one patients received lidocaine as a bolus injection of 75 mg. directly followed by an infusion. The infusion rate was, in 16 patients, 2 mg. per minute. Blood levels of lidocaine were determined at different times up to 180 minutes after the start of drug administration. The levels in the 2 mg. per minute group were lower than had been expected and the mean level plus or minus S.E. was, after three hours, only 1.1 mug per milliliter. Many of the 2 mg. per minute petients did not, during the time period observed, reach 1.2 mug per milliliter, which has been considered as the lowest effective therapeutic level. In the 4 mg. per minute group, mean level of lidocaine already at 15 minutes was significantly higher than in the 2 mg. per minute group (1,1 plus or minus 0.14 and 0.6 plus or minus 0.05, respectively; p less than 0.05). After three hours, the mean blood level in the 4 mg. per minute group was 2.6 mug per milliliter. Although the blood levels were not followed after three hours, a careful observation did not reveal any severe toxic effects in the 4 mg. per minute group during next 21 hours. In five cases, however, lidocaine side effects were probable. These symptoms disappeared rapidly after cessation of the infusion. In order to reach therapeutic blood levels of lidocaine within a reasonable time, the infusion rate of 4 mg. per minute is recommended at least for the first three hours.


Correlation between segmental early relaxation of the left ventricular wall and coronary occlusive disease. Fifty of 305 patients studied angiographically had segmental early relaxation phenomenon (SERP) of the anterolateral or apical left ventricular wall. Fourteen of the 50 patients had cardiac abnormality other than, or in addition to, coronary occlusive disease. Of the remaining 36 patients, 35 had significant lesions in the left anterior descending artery (LAD) and one had occlusion of the proximal left circumflex artery. SERP was noted in 35 (37.2 per cent) of 94 patients with LAD disease who did not have severe anteroapical contraction abnormality. SERP was found in none of 49 patients who had neither significant coronary occlusive disease nor other cardiac abnormality. Eight patients were restudied after bypass grafting of the LAD. Three patients with patent grafts no longer demonstrated SERP. Five had persistent SERP, but four of these had occluded LAD grafts or nongrafted disease in other vessels supplying the anterolateral wall. Myocardial ischemia appears to be one cause, but probably not the only cause, of SERP.


Vascular reactivity to norepinephrine and hemodynamic parameters in borderline hypertension. Pressor response to norepinephrine, cardiopulmonary blood volume, and hemodynamic parameters were studied in 41 borderline hypertensive patients in comparison with 42 permanent essential hypertensive patients and 28 normal subjects. Borderline hypertensive subjects had high cardiac index (p less than 0.0001), normal total peripheral resistance, and low total blood volume (p less than 0.005). The ratio between cardiopulmonary blood volume (CPBV) and total blood volume (TBV) was significantly higher in comparison with normal subjects (p less than 0.01) and permanent hypertensive subjects subjects (p less than 0.0001). The pressor dose of norepinephrine was elevated (p less than 0.0001) and was directly correlated with the basal values of the cardiac output (p less than 0.005), the cardiopulmonary blood volume (p less than 0.001), and the CPBV/TBV ratio (p less than 0.01). None of these results was observed in permanent hypertensive subjects: the only significant result was a negative correlation between the pressor dose of norepinephrine and the basal diastolic arterial pressure (p less than 0.0001). This study provides evidence that the cardiac output elevation in borderline hypertensive subjects was related to increased venous return and enhanced sympathetic venous tone.


Mechanism of immediate hemodynamic effects of chlorothiazide. The mechanism of the immediate hemodynamic effects of intravenous chlorothiazide (25 mg. per kilogram) was studied in 22 anesthetized open-chest dogs. Within 20 minutes after administration, cardiac output and stroke volume significantly fell; this was associated with decreased central venous and left ventricular end-diastolic pressures. That these hemodynamic effects were caused by, and dependent upon, volume loss through diuresis (eightfold increase in urine volume) was shown: by a return of these measurements to control levels when the volume loss (by diuresis) was corrected with 6 per cent Dextran; by prevention of the hemodynamic changes in chlorthiazide-treated dogs previously prepared with ureterocaval anastomosis; and by confirming these same hemodynamic effects by quantitatively equivalent hemorrhage. Thus, the immediate diuresis produced by chlorothiazide resulted in a contracted plasma volume (increased hematocrit and serum protein concentration) which, in turn, diminished cardiac venous return, central filling pressures, stroke volume, and cardiac output. There was no evidence demonstrated to indicate any direct myocardial effect or peripheral venodilation induced by thiazide.


Cardiac effect of diuretic drugs.

Cardiac effect of diuretic drugs. Triamterene, amiloride, ethacrynic acid, and furosemide were studied to determine whether they modified the digitalis-induced egress of myocardial potassium which is thought to facilitate the development of digitalis arrhythmias. In a control group of 15 dogs, potassium was measured in samples obtained simultaneously from the femoral artery (FA) and the coronary sinus (CS) in a control period and at intervals after the administration of 1 mg. of acetylstrophanthidin. Acetylstrophanthidin caused a significant increase in cardiac A-V difference in the potassium concentration (CS-FA) averaging 0.47 mEq. per liter. In a group of 10 dogs, when 175 mg. of triamterene was infused prior to the acetylstrophanthidin, the rise in A-V differnece was abolished and the arrhythmias often aborted. In contrast, the infusion of potent diuretics (40 mg. of furosemide in five dogs and 100 mg. of ethacrynic acid in another five dogs) prior to acetylstrophanthidin, caused a doubling of the maximal A-V potassium difference. This study suggests that the clinical administration of antikaliuretic drugs may prevent the arrhythmias of digitalis toxicity not only by reducing kaliuresis and subsequent hypokalemia, but by a myocardial effect which antagonized the digitalis-induced loss of myocardial potassium. Contrariwise, potent diuretics may facilitate digitalis arrhythmias through a myocardial action causing a greater egress of myocardial potassium, thus explaining the development of arrhythmias despite normal serum potassium levels. These potent diuretics should be used cautiously, especially when given intravenously to patients receiving digitalis.


Disorders of impulse conduction and impulse formation caused by hyperkalemia in man. In eight patients we have demonstrated manifold types of impairment of impulse conduction produced by hyperkalemia. These abnormalities of impulse conduction occurred either simultaneously or in sequence, and were located in the atria, in the A-V junction, in the fascicular distribution of the ventricular conduction system, or in the free ventricular walls. In association with the abnormalities of conduction, abnormal impulse formation was also frequently observed as manifested by acceleration of normal pacemakers or the emergence of ectopic pacemakers. In one patient hyperkalemia produced alteration in sinus and A-V junctional impulse formation which overshadowed conduction disorders. In all of the eight cases the hyperkalemia was considered to be noniatrogenic. Hyperkalemia appears to potentiate subclinical conduction abnormalities, especially in the His-Purkinje system. However, the presence of pre-existent intraventricular conduction defects such as a bifascicular block does not exclude the possibility that the site of an A-V conduction delay during hyperkalemia can be in the A-V node, as demonstrated by His bundle recording in one instance after development of second-degree (type I) A-V block.


First heart sound and ejection sounds. Echocardiographic and phonocardiographic correlation with valvular events. To provide additional information on the relation of valvular events to the principal components of the first heart sound (s1), combined echocardiograms and phonocardiograms were recorded in 49 subjects, chosen because of audible splitting of S1 or a combination of S1 and an ejection sound. The subjects included 14 normal persons, 16 patients with a variety of predominantly right-sided heart conditions, 7 with mitral stenosis, 3 with pulmonary stenosis and 9 with aortic valve disease or systemic hypertension. A precise relation was found between completion of closure of the atrioventricular (A-V) valves manifested in the echocardiogram and the high-frequency components of S1 (M1 and T1). The average time from the Q wave of the electrocardiogram to M1 was 0.06 plus or minus 0.003 second and the Q-T1 interval was 0.09 plus or minus 0.002 second. In mitral stenosis the Q-M1 interval was delayed to 0.10 plus or minus 0.005 second, resulting in some instances in reversed splitting of S1. In pulmonary stenosis, the ejection sound occurred 0.10 plus or minus 0.003 second from the Q wave. In 7 of the 16 patients with various right-sided abnormalities, but without valvular stenosis, an ejection sound of pulmonary origin occurred 0.18 plus or minus 0.012 second from the Q wave. In the nine patients with aortic valve disease or systemic hypertension, the time from the Q wave to the aortic ejection sound was 0.13 plus or minus 0.004 second. With only two exceptions the ejection sounds of aortic and plumonary origin coincided exactly with achievement of a fully opened position of the respective semilunar valve. Our findings support the postulate that M1, T1 and the ejection sounds occur in association with closing or opening of valves with consequent sudden deceleration or acceleration of a column of blood that, in turn, results in vibrations of the cardiohemic system and audible sounds.


Pericardial rub. Prospective, Multiple observer investigation of pericardial friction in 100 patients. A prospective, multiple observer ausculatory and phonocardiographic study of 100 patients with pericardial friction confirmed the dominant prevalence of triphasic pericardial rubs (56 percent of patients with sinus rhythm). In 9 of 33 patients with various biphasic rub patterns there was summation of the ventricular diastolic rub with the atrial systolic rub, concealing an additional 10 percent of potential triphasic friction. Fourteen of 15 monophasic rubs were audible or recordable only during ventricular systole. Rubs were best heard along the left sternal border in 84 percent of cases and tended to be louder during inspiration than during expiration; in 35 cases there was no respiratory predilection. Twenty-three rubs were palpable. Ten rubs occurred in patients with pericardial effusion, five of whom had tamponade. Extension of the neck did not have a dependable effect on rub intensity.


Prolapse of the posterior leaflet of the mitral valve associated with secundum atrial septal defect. The association of prolapse of the posterior leaflet of the mitral valve with secundum atrial septal defect has recently been reported but the prevalence and features of this association have not been defined. Analysis of left ventricular cineangiograms in 54 patients have secundum atrial septal defect revealed evidence of prolapse of the posterior leaflet of the mitral valve in 20 (37 percent). In 11 patients (20 percent) there was clinical evidence of a mitral valve lesion (pansystolic murmur in 9 patients and mid-systolic click in 2 patients, 1 of whom also had a late systolic murmur); the remaining 9 patients had no auscultatory evidence of a mitral valve lesion. Thus, the incidence of clinically silent prolapse in association with secundum atrial septal defect was 17 percent (9 of 54 patients). Analysis of the angiographic findings revealed that the prolapse was triscalloped in 4 patients, biscalloped in 11 and uniscalloped in 5. Mitral regurgitation was present in 12, including the 11 patients with clinical signs of a mitral lesion. Three patients with moderate or severe mitral regurgitation had triscalloped prolapse. The association of prolapse of the posterior leaflet of the mitral valve with secundum atrial septal defect is common and may be present in the absence of any clinical evidence of a mitral valve lesion.


Effect of digoxin on sinus nodal reentry in the dog. The effect of digoxin on sinus reentry was examined in 20 open chest mongrel dogs during infusion of digoxin at a rate of 2.5 mu g/kg per min. The extrinsic cardiac nerve supply was removed acutely in 10 dogs and was left intact in the remaining 10 dogs. Sinus nodal reentry was relatively unaffected by digoxin in 18 of 20 dogs. In these 18 dogs, digitalis toxicity developed before reentry was abolished and was manifested as increased atrial and ventricular automaticity in 14 and as advanced atrioventricular (A-V) block in four. In the remaining two dogs, sinus  nodal reentry was relatively sensitive to digoxin and was abolished before toxicity became manifest as advanced A-V block. The knowledge of the relative insensitivity of sinus nodal reentry to digoxin, at least in this experimental model, contrasts with the previously reported sensitivity of sinus nodal reentry to quinidine, and may be important in the management of sinus nodal reentry in man.


Detection of acute myocardial infarction by technetium-99m polyphosphate. Experimental work has shown that technetium-99m (99mTc) pyrophosphate accumulates in recently infarcted myocardium and can be detected by external imaging techniques. Twenty-two 99mTc polyphosphate myocardial studies were performed in 17 patients (in 3 after cardiac surgery) 3 to 20 days after myocardial infarction. Seventeen myocardial studies were performed in 17 control patients (in 6 after cardiac surgery). Twenty millicuries of 99mTc polyphosphate was injected intravenously 60 to 120 minutes prior to gamma camera imaging in several views. Myocardial images were processed by the Gamma-11 computer system using standardized background subtraction and contrast enhancement. Results of 16 myocardial studies performed 4 to 20 days after transmural myocardial infarction in 12 patients were positive in 13 instances and questionable in 1. The location of the myocardial infarction by imaging corresponded to location by standard electrocardiograhic criteria in 8 of the 10 patients with positive findings. In five patients with nontransmural myocardial infarction, results of myocardial imaging were positive in two, questionable in one and normal in one. In one patient with questionable findings results were normal when imaging was repeated 16 days after nontransmural myocardial infarction. Results of 17 control myocardial imaging studies were normal in 16 and questionable in 1. Therefore, 99mTc polyphosphate myocardial imaging appears promising in the detection and location of transmural myocardial infarction. Its accuracy in detecting nontransmural myocardial infarction may be increased with greater experience and development of sophisticated digital analysis techniques. The method may prove useful in clinical situations such as cardiac surgery in which standard diagnostic aids are difficult to interpret.


Late systolic murmur of rheumatic mitral insufficiency. Of 184 patients with acute rheumatic fever and associated mitral insufficiency encountered during a 15 year period, 34 manifested a mid-late systolic murmur or a nonejection click, or both, during the course of follow-up. The mid-late systolic murmur later disappeared in four patients whose condition is now considered normal. In one of the four, systolic prolapse of the mitral valve was demonstrated on an angiocardiogram obtained when the systolic murmur was present. Since disappearance of the murmur there has been no evidence of systolic prolapse on meticulous echocardiographic study of the mitral valve. In another child with angiographically demonstrated systolic prolapse of the mitral valve the systolic murmur has also disappeared, but systolic prolapse is still evident on echocardiographic study. None of the 34 patients with a mid-late systolic murmur manifested the T wave abnormalities commonly associated with the familial variety of mitral valve prolapse.


Tetralogy of Fallot: a morphometric and geometric study. Fourteen examples of tetralogy of Fallot were studied by morphometric and geometric methods, and the findings compared with results from 10 normal hearts. The data show that in Fallot's tetralogy the conal septum is deviated anteriorly. The infundibulum, although narrow, is similar to, or of greater length than, that of the normal heart. This finding is not in agreement with the recent observations suggesting that the anomaly represents lack of growth of the pulmonary conus. Our results further demonstrate that the aorta is dextroposed in Fallot's tetralogy and that in the majority of cases absorption of the right extremity of the conoventricular flange has led to aortic-tricuspid fibrous continuity. The overall findings indicate that conal rotation has occurred in addition to anterior deviation. The data are interpreted as supporting a hypothesis of "lack of conal inversion" and conal malseptation as the morphogenetic mechanisms in tetralogy of Fallot.


Potassium canrenoate in the treatment of long-term digoxin-induced arrhythmias in conscious dogs. The effects of potassium canrenoate on arrhythmias induced by long-term progressive digoxin toxicity were studied in eight conscious beagle dogs. Sinus bradycardia and sinoatrial block, as well as atrioventricular (A-V) conduction disturbances, were consistently alleviated by administration of potassium canrenoate. Premature supraventricular (including junctional) and ventricular depolarizations as well as ventricular tachycardias were also suppressed. Although potassium canrenoate always terminated the digitalis-induced arrhythmias, it usually converted the rhythm to sinus arrhythmia rather than to normal sinus rhythm. Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication. These data indicate that canrenoate, a diuretic agent with reported positive inotropic effects, may be useful in the treatment of digitalis-induced arrhythmias in man.


Loud first heart sound with long P-R intervals. A case of partial atrioventricular block with Wenckebach periods and a loud first heart sound (S1) associated with the longest P-R interval of the cardiac cycles is described. Although the surface electrocardiogram provided no clues to this paradoxical behavior, the intraatrial electrogram revealed that the long P-R interval with the loud S1 was accompanied by atrial echoes (reciprocal atrial beats). The loud S1 with a very long P-R interval was always caused by an atrial contraction synchronous with the QRS complex.


Traumatic right coronary arterial-right atrial fistula. A healthy 25 year old man presented with a machinery murmur and a history of a penetrating thoracic injury. Hemodynamic and angiographic evaluation demonstrated a fistula from the right coronary artery to the right atrium that was later successfully repaired. This case and similar reported cases indicate that fistula formation is a late complication of penetrating thoracic injuries. The onset of the murmur occurs with enlargement of the fistula and typically is delayed for several weeks to months after the initial injury.


Echocardiographic findings in right coronary arterial-right ventricular fistula. Report of a neonate with fatal congestive heart failure. Coronary arteriovenous fistula is a rare cause of congestive heart failure in the newborn. We describe a 2 day old infant with a large fistula between the right coronary artery and right ventricle that caused fatal congestive heart failure. An echocardiographic study revealed a large right ventricle, paradoxical motion of the interventicular septum and an enlarged aorta, suggesting an unusual location of a left to right shunt. The diagnosis was established at cardiac catheterization when a large left to right shunt was found at the ventricular level; the fistula was visualized by angiography.


Transmural myocardial infarction during pregnancy. Two young pregnant women with no known risk factors had a transmural myocardial infarction while they were lying in the supine position. Coronary arteriograms 3 1/2 and 4 months later, respectively, were normal. Coronary arterial spasm related to renin release from the transiently ischemic chorion is the proposed cause.