Primary cardiomyopathy in identical twins. Seventeen year old identical twin brothers with no family history of cardiopathy began experiencing palpitations almost simultaneously. In both, examination revealed marked cardiomegaly and hypokinesia of the ventricular walls, and clinical and radiologic signs of progressive cardiac failure developed a few days later. Both boys died suddenly, 49 days and 5 months, respectively, after the initial examination. Electrocardiographic and vectorcardiographic studies revealed a severe intraventricular conduction disturbance that coincided with histologic changes in the myocardial tissue, including profuse interstitial fibrosis, hypertrophy and degeneration of the myocardial fibers, aberrant arrangement of the muscular fibers and considerable alteration of the structure of cardiac tissue. In the absence of hereditary and chromosomal factors, and excluding possible viral intervention during fetal life, it is believed that a teratogenic factor can produce the structural alterations of the tissue and derangement of the fibers observed in these hearts. The irregular contractions of the heart at the level of the net-like meshwork, disarrangement of myocardial fibers, and adaptative mechanisms of the heart inherent in the destruction of the contractile tissue contributed to the functional cardiac disorders that resulted in congestive heart failure and sudden death in these twins.


Objective criteria for evaluating occupational health programs. An objective scoring system is proposed as a single and flexible method of evaluating occupational health programs to appraise the extent to which existing programs approach a basic standard of excellence as defined by a theoretical model based on published and professionally acceptable guidelines and standards. This proposed system emphasizes the importance of an interdependent relationship between four program components: (1) guiding philosophy and policy; (2) organizational structure; (3) resources; (4) occupational health services, and it stresses the importance of long range health commitments to employee health status in contrasts to short range health commitments aimed primarily at an economic payoff to a sponsoring agency, institution, or company. The proposed evaluation scheme should enable self-evaluation by individual programs. Additionally, programs can utilize this evaluative tool to examine their influence on such important questions as employee hospital utilization and other specific elements of employee health in an objective, relatively simple manner.


Program planning, evaluation, and the problem of alcoholism. Rational program planning and evaluation has been suggested as a necessary skill. First, a conceptual framework for planning and evaluation was presented and discussed, using the example of preventing alcoholism and providing services and rehabilitation for alcoholics. Second, a case study was presented, which is similar to that used by many professionals in their efforts to plan programs. Finally, some of the marked limitations of the case study were pointed out, when it was projected upon the conceptual framework.


Decontamination procedures for skin exposed to phenolic substances. Spraying or swabbing with a mixture of polyethylene glycol 300/industrial methylated spirits (PEG-300/IMS) (2:1 by volume) has been shown to substantially reduce mortality, systemic effects, and skin burns resulting from skin contamination by phenol, cumene hydroperoxide, or phenol/acetone cleavage product. The skin-damaging potentials of sodium hydroxide and sulfuric acid have also been investigated. PEG-300/IMS(2:1 by volume) mixture was found, in rats, to be slightly less effective than water as means of decontamination. The PEG-300/IMS mixture has been shown not to cause eye irritation, and so should not present a hazard where this mixture is used as a decontaminant spray.


Moderate hypoxia exposure and fetal development. Exposure of rabbits to 15.5% oxygen during pregnancy resulted in a 17% decrease of birth weight and a neonatal mortality of 19% as opposed to 1% in the control groups, just corresponding to the effects obtained previously by moderate exposure of pregnant rabbits to carbon monoxide. Since additive effects of hypoxia exposure and carbon monoxide exposure are supposed to occur, it is concluded that women living at a high altitude should be warned particularly about the risk of delivering small babies if they have been smoking during their pregnancy.


A syndrome of multiple congenital anomalies associated with teratogenic exposure. A study of 19 patients with multiple congenital anomalies described by the acronym VACTERL (Vertebral, Anal, Cardiac, Tracheoesophageal, Renal, and Limb) revealed exposure at the vulnerable period of embryogenesis to a progestogen/estrogen compound or a progestogen alone in 13 patients. These hormones were taken as a "pregnancy test," and for a variety of other reasons. Comparison of VACTERL patients with paired and matched controls, one group with chromosomal anomalies (other than Down syndrome) and another group with functional murmurs, revealed a significant difference with respect to exposure to hormonal contraceptives. The multiple anomalies of skeletal, cardiovascular, and gastrointestinal structures recapitulate the systems involved in the thalidomide syndrome, but present a variation of the pattern. Until more definitive data are available it would be prudent to emphasize the need to verify the absence of pregnancy before initiation of oral contraception and to discontinue hormonal agents as tests for pregnancy.


Short-term inhalation toxicity of halogenated hydrocarbons: effects on fasting rats. Male rats, fasted overnight (18 hours), and exposed to various materials in inhalation were more sensitive to the hepatotoxic effects of carbon tetrachloride, 2-chlorobutadiene, 1,1-dibromoethylene, and 1,1-dichloroethylene (DCE). Vinyl chloride monomer and 1,1-difluoroethylene were not acutely hepatotoxic in fed or fasted rats at any concentration tested. Vinyl chloride monomer when administered simultaneously with DCE prevented the injury associated with DCE inhalation in fasted rats. This prevention of injury may be a result of a competitive interaction since the effect was concentration dependent.


Hexachlorophene in mice. Effects after long-term percutaneous applications. The toxicity and carcinogenicity of life-time applications of hexachlorophene on the skin of Swiss mice were studied. Twice weekly applications of 0.02 ml of a 50% or 25% solution produced necrosis and ulceration of the skin as well as neurological symptoms and a mortality of up to 22% within two weeks. At autopsy, edema and cystic lesions were seen in the white matter of the central nervous system. The neurological symptoms were reversible, though a proportion of the cystic lesions persisted. Only one skin tumor was seen and the number of tumors of other organs, lymphomas, lung adenomas, liver hemangiomas, and other tumors, was not higher than in the controls. It is concluded from this study that percutaneous application of hexachlorophene has toxic local and systemic effects in mice, but no carcinogenic effects.


Effects of ozone and brief exercise on specific airway conductance in man. Four normal male subjects were exposed to 0.9 ppm ozone with exercise for five minutes. Specific airway conductance (Gaw/Vtg) was increased by exercise and decreased by inhalation of ozone in most subjects, but these effects were small. Ozone inhalation with exercise resulted in a highly significant decrease of Gaw/Vtg. It would seem that a peak concentration of 0.9 ppm of ozone for five minutes produces adverse effects when the subject undertakes exxercise in it.


Ozone and human blood.

Ozone and human blood. Statistically significant changes (P less than .05) were observed in erythrocytes (RBC) and sera of young adult human males following a single short-term exposure to 0.50 ppm ozone (O3) for 2 3/4 hours. The RBC membrane fragility, glucose-6-phosphate dehydrogenase (G-6-PDH) and lactate dehydrogenase (LDH) enzyme activities were increased, while RBC acetylcholinesterase (AcChase) activity and reduced glutathione (GSH) levels were decreased. The RBC glutathione reductase (GSSRase) activities were not significantly altered. Serum GSSRase activity, however, was significantly decreased while serum vitamin E, and lipid peroxidation levels were significantly increased. These alterations tend to disappear gradually, but were still detectable two weeks following exposure.


Hexachlorobenzene contamination: its effects in a Louisiana population. Plasma hexachlorobenzene (HCB) residues in a Louisiana population exposed through the transportation and disposal of chemical waste containing HCB averaged 3.6 plus or minus 4.3 parts per billion (ppb) in a sample of 86 people. The highest level was 345 ppb in a waste disposal facility worker while the highest level in the general population was 23 ppb. There was no evidence of cutaneous porphyria by history or skin examination. Males had significantly higher residues than females (4.71 vs. 2.79 ppb) but there were no age differences. A possible association between HCB residues and coproporphyrin and lactic dehydrogenase was found. Only 2 of 48 meals sampled were positive for HCB. There was a correlation between HCB levels in household dust and plasma levels. Perchloroethylene and carbon tetrachloride production workers had plasma HCB levels of up to 233 ppb.


Pesticide containers: their contribution to poisoning. Pesticide containers play an important role in the epidemiology of pesticide poisonings. Investigations of short-term exposures have shown that difficulty in disposal  of used containers, inappropriate pesticide paskaging, and lack of safety containers for household products contribute to morbidity. Remedies for some of the container-associated hazards could be achieved under existing laws.


Percutaneous penetration and disposition of triclocarban in man: body showering. The percutaneous penetration and metabolic disposition of 14C-3-4,4'-trichlorocarbanilide (triclocarban, TCC) after body showering has been determined in man. Single intravenous doses of trace amounts 14C-triclocarban were given to subjects to determine the pharmacologic disposition of the compound before conducting the shower study. Radioactivity was rapidly cleared from blood after intravenous administrations of 14C-triclocarban in propylene glycol with a blood clearance half-life of 8.6 hours. About 54% of the dose was excreted in the feces and 21% of the dose in the urine with a urinary elimination half-life of ten hours. No radioactivity was detected in the saliva. Subjects took a single shower employing a whole body lather with approximately 7 gm of soap containing 2% 14C-triclocarban on a soap basis. Special blood withdrawal and urinary/fecal collection techniques were utilized that minimized contamination of samples by extraneous 14C-triclocarban. About 0.23% of the applied radioactive dose was recovered in the feces after six days and 0.16% of the dose in the urine after two days. At all sampling times blood levels of radioactivity were below the detection limit of the method (10 part per billion).


Afferents to prefrontal cortex from the thalamic mediodorsal nucleus in the rhesus monkey. Thalamic afferents to Macaque prefrontal cortex from the mediodorsal nucleus were examined by techniques specific for anterograde degeneration and axoplasmic transport. The sampling procedure employed permits establishing the extent of topographic projections to cortex from subcortical foci for the same brain which was surveyed subsequently in tracing specific neuronal connections by electron microscopy. Topographic and general laminar distribution of thalamic terminals are presented in terms of 3 subareas of prefrontal cortex. The dorsolateral and ventral (orbital) surfaces of prefrontal cortex receive respectively projections from the lateral and medial subdivision of the mediodorsal nucleus. In addition, the medial wall of the frontal lobe, including the dorsomedial part of the lateral convexity, heretofore regarded as athalamic, receives input from the caudal-dorsomedial aspect of the mediodorsal nucleus. Preliminary evidence suggests that axons from the mediodorsal nucleus terminate in the head of caudate nucleus, as Sachs-81 described 65 years ago in the first orthograde study of thalamo-prefrontal cortex connections.


Reexamination of the force relationship of cortical cell discharge patterns with conditioned wrist movements. Single unit recordings were obtained from 103 precentral cortical cells whose activity was related to an alternate wrist flexion-extension task in monkeys. Although the task was carried out under different loads only a weak relationship between cortical cell firing rates and static force levels was observed for force in one direction. A large change in firing rate occurred, however, when direction of force shifted as a result of a change in the predominant activity between extensor and flexor muscles. The firing patterns of the observed cortical cells suggest that the motor cortex is involved in specifying the muscles to be activated for a given movement and not the level of force to be produced by these muscles. During the dynamic phase of the movement little change in cortical cell firing pattern was observed for large changes in the rate of change of force. Motor cortex cell firing patterns appear to be unrelated to the large values of rate of change of force seen in this experiment.


Postnatal maturation of the cochlear neclei in the cat: a neurophysiological study. The study of the postnatal maturation of the ventral cochlear nuclei (VCN) and the dorsal cochlear nuclei (DCN) was carried out on the cat by means of recordings of the extra-cellular neuronal activity. At birth it is already possible to obtain toneburst responses in the VCN and DCN. At this age the responses are characterised by a small number of spikes grouped in three bursts when the tone-bursts lasted 500 msec. Subsequently, the number of bursts increases until, from 9 or 10 days onwards the responses become sustained. These responses do not acquire their adult characteristics until more than a month after birth. During postnatal maturation of the cochlear nuclei, the VCN is distinguishable from the DCN by the greater number of units revealing spontaneous activity. Another criterion, such as latency, differentiates the VCN from the DCN from the point of view of the kinetics of maturation.


The effect of undernutrition in early life on cell generation in the rat brain. In undernourished rats aged up to 21 days, the DNA synthesis period in dividing cells of the subependymal and external granular layers is consistently and markedly prolonged, while rates of cell production from these layers are only slightly altered. Cell cycle times are unchanged up to the end of the first week of life and prolonged from day 12. The G1 phase is markedly shortened at 1, 6 and 12 days of age. It would appear that, in comparison with controls, disappearance of the external granular layer is delayed, and cell numbers in both germinal layers may be reduced.


Motor co-ordination and cerebellar size in adult rats undernourished in early life. The male progeny of mother rats which had been undernourished during most of gestation and all of lactation were divided into two groups when weaned at 25 days. One group was nutritionally rehabilitated (G-L-) while the other was underfed for a further 9 weeks (G-L-W-) before nutritional rehabilitation. Despite this further undernutrition the G-L-W- rats eventually caught up in both body and brain weight with the G-L- group. Compared with control rats of the same age that had been well fed throughout life, the G-L- and G-L-W- animals had permanent deficits in body and regional brain weights. At 36 weeks rats were given two tests of motor co-ordination. They were required (a) to run backwards on a revolving drum and (b) to cross a chasm bridged by a ladder or parallel rods for a food reward. Both previously undernourished groups did consistently worse than controls of the same age or of similar body weight on two measures of co-ordination: falls from the revolving drum and stumbles on the bridge-crossing test. It is postulated that these differences indicate impaired cerebellar function in the prevously undernourished rats.


Histamine synthesis in the developing rat brain: evidence for a multiple compartmentation. Subcellular fractionation techniques, radio-labeling by the 3H-precursor and pharmacological approach applied to the developing rat indicate the presence of at least two types of histamine-containing cells in brain. The presence of the histamine synthesizing enzyme in neurons is suggested by its developmental pattern: there is a 4- to 5-fold increase in enzyme activity from birth to adulthood, with a time-course paralleling the synaptogenesis in whole brain as well as in the 4 regions studied (medulla-pons, midbrain, hypothalamus and forebrain). As is the case for different transmitter synthesizing enzymes such as tyrosine hydroxylase, there is a shift in the subcellular distribution of histidine decarboxylase (H.D.) activity from the soluble fraction at birth to the synaptosomal fraction in the adult brain. On the other hand, several lines of evidence indicates that a portion of histamine is localized, at least in the noenatal rat brain, in mast cells: (a) the high level of histamine in the neonatal rat brain is, like in peripheral mast-cells, associated with a low enzyme activity; (b) the half-life of [3H]histidine injected s.c. at birth was about 4 days, a value close to that found in skin (a tissue rich in mast cells), but contrasting with that in adult brain (less than 1 h); (c) after subcellular fractionation, the endogenously formed [3H]histamine was recovered in the crude nuclear fraction as was the amine from peritoneal mast cells added to the brain homogenate; (d) the mast cell degranulators, compound 48/80 and polymyxin B, induce a small but significant release of the amine from incubated neonatal brain slices. Thus it appears that cerebral histamine is localized in at least two cell types. Its presence in neurons is compatible with a neurotransmitter function and its release from mast cells might represent some primitive form of cell-to-cell communication.


Effects of low temperatures on microtubules in the non-myelinated axons of post-ganglionic sympathetic nerves. The effect of temperature changes on the number of microtubules in non-myelinated axons has been studied in cat inferior mesenteric ganglion/hypogastric nerve preparations incubated at various temperatures in Eagles minimal essential tissue culture medium in vitro. At 37 degrees C the non-myelinated axons contained 28.4 plus or minus 0.8 S.E.M. (54) microtubules per axon. After incubation at 0 degrees C for 4 h this number fell to 2.3 plus or minus 0.1 S.E.M. (41) but returned to normal levels when the nerves were rewarmed. This loss of microtubules on cooling the nerves and their reappearance on rewarming was a rapid process; it was independent of the influence of the nueronal cell body and of protein synthesis within the axon. The preservation of the microtubules was improved when D2O was present in the incubation medium. Reformed microtubules appeared to function normally with respect to their possible role in the transport of noradrenaline storage vesicles along the axons.


Effect of steroid competition and time on the uptake of (3H)corticosterone in the rat brain; an autoradiographic study. The localization of [3H]corticosterone in the brain and pituitary of the adrenalectomized rat was studied by autoradiography. Corticosterone was concentrated preferentially by neurons in the hippocampus, septum, amygdala, and neocortex, with the hippocampal and septal neurons having the greatest concentration. [3H]-Corticosterone localization was significantly greater in neurons from adrenalectomized animals. Administration of unlabeled corticosterone (3 mg) 30 min before injection with [3H]corticosterone significantly decreased cellular localization of the labeled corticosterone, whereas [3H]corticosterone localization was not affected by progesterone pretreatment. Animals were sacrificed 15, 30 and 120 min after the injection of [3H]corticosterone to study the distribution of the hormone over the cytoplasm and nuclei. Silver grains were localized primarily over the cytoplasm of the concentrating neurons 15 min after injection; however, by 30 min after injection they were evenly distributed over both nuclei and cytoplasm.


Differential effects of the optical isomers of amphetamine on neuronal activity in the reticular formation and caudate nucleus of the rat. The activity of neurons in the caudate nucleus and reticular formation was recorded following intraperitoneal injection of the optical isomers of amphetamine. In general, D-amphetamine sulfate (2.0 mg/kg) produced an initial increase in firing rate of neurons in the caudate nucleus approximately 8-10 min following intraperitoneal injection, and a subsequent depression of firing rat which lasted for a period of time of from 70 to 120 min. Similar injections of L-amphetamine sulfate produced only a depression of activity in the caudate nucleus which was less marked and of lesser duration. Mephentermine sulfate (6.0 mg/kg), a peripheral sympathomimetic, did not produce these effects. Both D-amphetamine and L-amphetamine sulfate at the same dose produced an increase in firing rate of neurons in the reticular formation, although that produced by the L-isomer was less marked and of lesser duration. Mephentermine sulfate also produced an increase in reticular formation neuronal activity comparable to that produced by L-amphetamine sulfate. In some cases, neuronal activity was held for prolonged periods of time following injection. In the caudate nucleus, a rebound increase in firing rate was observed following the marked depression produced by both isomers of amphetamine. A rebound depression of activity was observed in the reticular formation following the initial increase in neuronal activity produced by these drugs. The results are discussed in terms of the known biochemical and behavioral effects of the stereoisomers of amphetamine.


Synaptosomal plasma membrane glycoproteins: fractionation by affinity chromatography on concanavalin A. Synaptosomal plasma membrane glycoproteins were solubilized in 0.08% sodium dodecyl sulfate (SDS) and separated by affinity chromatography on concanavalin A-Sepharose. Three fractions were obtained. Fraction CO (unadsorbed) contained 63% of the protein, but only 23% of the sugar and was rich in fucose, galactose and N-acetyl-neuraminic acid (NANA) relative to the other sugars. Many proteins were detected in this fraction by polyacrylamide gel electrophoresis, but only on band stained well for carbohydrate. Fraction CR (retarded) contained glycoproteins which reacted weakly with concanavalin A and stained poorly with periodic acid-Schiff reagent (PAS). There was no enrichment in total sugar/mg protein relative to the original fraction, but there was a marked enrichment in N-acetyl-glucosamine and NANA relative to the other sugars. The protein profile of this faction was complex, but only one major PAS-positive band was detected. However, most, if not all, the proteins seemed to be weakly PAS-positive. Fraction C1 (adsorbed) was markedly enriched (5-fold) in sugar/mg protein, particularly in mannose and N-acetyl-glucosamine. It had a relatively simple protein profile, and most of the protwin bands stained well with the PAS reaction. Glucose was detected in the initial fraction, and in all the subfractions, but it could not be shown definitely to be either a contaminant or an intrinsic constituent of synaptosomal plasma membrane (SPM) glycoproteins. Minor sugars, if present, could, at most, account for less than 0.25% of the carbohydrate.


A study of the dynamic relations between the mitral valve echogram and phasic mitral flow. Echocardiographically recorded mitral valve motion was compared with phasic transmitral flow in 17 open chest dogs. The normal mitral valve opening started with the onset of mitral flow and reached its full excursion while flow was still accelerating. Complete valve opening occurred .044 sec (plus or minus .002 sem) before peak flow, during which time an average of 17.6 percent of total mitral filling volume had passed through the valve. In contrast to the opening movement, the closing motion of the anterior mitral valve cusp lagged behind the deceleration of mitral flow. The E-F phase of the mitral valve echogram started while mitral flow was still increasing and resulted from a combined posterior motion of the cusp and the ring. The E-F slope of the normal valve was found to decrease with reduced cardiac output. The amplitude of the anterior cusp excursion did not reflect the amount of mitral flow. Prolonged P-R interval may induce a mid-diastolic reversal of mitral flow which, in turn, may be accompanied by partial or complete valve closure, occurring before the onset of ventricular contraction. Such premature closure of the mitral valve may be accompanied by a certain amount of regurgitant flow.


Systolic time intervals by echocardiography. Technical difficulties in recording phonocardiogram or indirect carotid pulse occasionally preclude determination of the systolic time intervals. Accordingly, an alternative method was tested in 52 patients, using high-speed strip chart recording of the aortic valve echocardiogram. Satisfactory records were obtained in 36. The interval from opening to closing of the aortic valve (ejection time) was subtracted from the interval between the Q wave of the electrocardiogram and the closing of the aortic valve (total electromechanical systole) to provide the pre-ejection period. When these intervals and the pre-ejection period/ejection time ratio were compared to corresponding values obtained by conventional methods from the simultaneously recorded phonocardiograms and indirect carotid pulses, a high degree of correlation (r greater than 0.97) was found. Differences between the two methods for each interval were insignificant, being greatest in the case of the ejection time but never exceeding 16 msec. These findings indicate that the echocardiogram of the aortic valve provides an alternative, noninvasive method for determination of the systolic time intervals whenever the usual methods fail.


Prognosis in coronary artery disease. Angiographic, hemodynamic, and clinical factors. Evaluation of the results of surgery for coronary artery disease requires a knowledge of the clinical course of patients not having this mode of treatment. To obtain such information we performed a retrospective analysis of the fate of 266 patients with arteriographically documented significant stenosis following from one to ten years. For the entire group the five year survival was 73%. Subdivided into single, double or triple vessel disease categories the percent five year survival rates were respectively 92, 65 and 55. A history of angina pectoris or myocardial infarction prior to angiography did not affect survival. However, hypertension, congestive heart failure, abnormal hemodynamics or left ventricular asynergy were all associated with a diminished five year survival, the values being respectively 61%, 38%, 62% and 58%. These results should be of VALUE IN ASSESSING THE PROGNOSIS OF NONSURGICALLY TREATED PATIENTS WITH CORONARY ARTERY DISEASE.


Mechanism of normal splitting of the second heart sound. The mode of inspiratory augmentation (1A) of the A2-P2 interval was investigated in seven normal volunteers (group 1) and six patients with pulmonary hypertension of diverse etiology (group 2) using catheter-tip micromanometers. In group 1 subjects, inspiratory widening of this interval was found to average 27.2 msec, of which 7.6 plus or minus 2.7 msec (1 sd) or 27 plus or minus 7% was due to a decrease in the Q-A2 interval. The major contribution of Q-P2 interval prolongation was divided into two components: a) Q-O was measured from the onset of the QRS to the onset of the rapid descent of the right ventricular (RV) negative dp/dt, which was felt to reflect the duration of RV electromechanical systole, b) O-P2 or Q-P2 - Q-O. Increase in the Q-O interval accounted for only 7.7 plus or minus 5.0 msec or 28 plus or minus 12% of the total IA. The major single component of IA was the increase in O-P2 which averaged 11.9 plus or minus 3.0 msec. Five of six group 2 patients demonstrated significant respiratory change in Q-P2 intervals. In contrast to group 1 subjects, however, this was accomplished primarily via increases in the duration of RV electromechanical systole. The O-P2 interval is felt to primarily reflect the impedance characteristics of the pulmonary vascular bed. It is concluded that physiologic splitting of the second heart sound in normal subjects is most probably due to an inspiratory decrease in impedance of the pulmonary bed rather than the traditional explanation of prolongation of RV systole secondary to an increase in venous return. When the normal impedance characteristics of this bed are lost, as in pulmonary hypertension, IA must occur primarily via increases in the duration of RV systole. The inspiratory delay from the conclusion of RV systole to the occurrence of P2 is attributed to the inertiance of the RV stroke mass.


Postural changes in left ventricular and mitral valvular dynamics in the systolic click - late systolic murmur syndrome. Marked changes in the auscultatory pattern with posture have been noted in patients with mid-systolic clicks and/or late systolic murmurs (MSC-LSM). MSC tend to move earlier in systole and LSM become longer and often louder when patients assume upright posture. Systolic prolapse of the mitral leaflets with mild regurgitation account for MSC-LSM; earlier and greater prolapse with more and prolonged regurgitation associated with a reduced left ventricular volume (LVV) in the upright position would explain the auscultatory changes. Twenty-two patients with MSC-LSM were studied supine and at 45 degrees head-up tilt, recording intracardiac pressures, cardiac outputs, systolic time intervals, and performing LV cineangiography. Systolic prolapse of one or both mitral leaflets was demonstrated in all patients. Left ventricular end-diastolic and end-systolic volumes both decreased significantly at 45 degrees in all sixteen technically satisfactory studies. Greater mitral prolapse was noted upright in 12 of 14 studies with enough sinus beats to judge. The amount of mitral regurgitation was mild in all, and changes in amount from supine to upright posture could not be discerned angiographically. THE FINDINGS, SUGGEST THAT THE AUSCULTATORY CHANGES OCCURRING WITH UPRIGHT POSTURE IN PATIENTS WITH MSC-LSM are related to greater prolapse of the mitral leaflets which is associated with a small LVV in the upright position.


Bacterial endocarditis in subjects 60 years of age and older. Forty-two cases of bacterial endocarditis with pathologic confirmation are reviewed. Infection was restricted to one or both left-sided valves in 31 cases, right-sided valves in five cases, and valves in both sides of the heart in six cases. In those specimens available for review, underlying valvular disease was identifiable in 24 of 38 cases (63%). The common underlying diseases, in order of decreasing frequency, were calcified or otherwise deformed aortic valves (11 cases) and rheumatic fibrosis of the mitral valve (eight cases). The floppy mitral valve was the underlying condition in two cases and amyloid infiltration of the tricuspid valve in one. Among the 34 cases from which a specific organism was identified, the dominant organisms were Staphylococcus (14 cases) and various types of Streptococci(ten cases). Fungi were the causative organisms in two cases. The clinical suspicion for the presence of bacterial endocarditis was low (40% of 40 cases with adequate data). In those cases with adequate data, murmurs were present in 68% and fever in 93%. Of those patients with fever, clinical diagnosis was made or suspected in only 38%. When a murmur was present, the clinical diagnosis was made or suspected in 54% of the cases, while when a murmur was absent the disease was suspected in only 9% of the cases. The clinical diagnosis of bacterial endocarditis in older subjects depends upon 1) knowledge that the disease may occur in such subjects and 2) recognition that, although fever is commonly present, murmurs may be absent.


Visualization and measurement of the main bronchi by tomography as an objective indicator of thoracic situs in congenital heart disease. When investigating complex congenital heart disease, determination of atrial situs is essential. Pathological studies have demonstrated that the best predictor of atrial situs is thoracic situs. To assess thoracic situs, bronchial tomography was performed in 92 patients with congenital heart disease. Sixty-four of these, without abnormalities of situs or cardiac position, formed 'normal' controls. The lengths of the left and right main bronchi were measured. When these were related to age, and the results analyzed statistically, linear discriminant equations resulted giving a chance of only 0.09% of misclassifying a bronchus of unknown morphology. The lowest ratio between bronchial lengths (BLR) in any individual was 1.71:1. These results were then used to assess thoracic situs in 17 patients with abnormal situs or CARDIAC POSITION. In 7 (2 with situs inversus), abdominal and thoracic situs agreed. Of 6 patients with bilateral left lung, 3 had an interrupted inferior vena cava. Of 4 patients with presumptive asplenia, 2 had bilateral right lung, but two had thoracic lateralization, one solitus and one inversus. The highest BLR in thoracic isomerism was 1.4:1. This emphasizes the complex interrelation of splenic status, thoracic, and abdominal situs, but demonstrates the value of bronchial measurement particularly in apparent situs indeterminatus.


Return of normal conduction after paroxysmal heart block. Report of a case with major discordance of electrophysiological and pathological findings. This report describes a 52-year-old male with paroxysmal heart block as well as left and right bundle branch block, resulting in Stokes-Adams attacks. The patient experienced a return to 1:1 atrioventricular (A-V) conduction with narrow QRS within 48 hours of the attacks and heart block never recurred. Electrophysiological studies three weeks later revealed a narrow QRS, a normal H-V interval (36 msec), 1:1 A-V conduction up to an atrial paced rate of 210 beats/min, and normal refractory periods with atrial extrastimulus techniques (His-Purkinje system refractory periods less than 370 msec). The patient died from a cerebral embolus incurred during diagnostic left heart catheterization two days after electrophysiological studies. Postmortem examination revealed calcific aortic stenosis with calcific impingement upon the pars membranacea resulting in compression of the distal His bundle and marked disruption of the proximal portions of both bundle branches. This report documents a major limitation of electrophysiological studies, this limitation being that these studies may be totally normal on one occasion in a patient with pathologically significant chronic conduction disease, which may become clinically manifest on another occasion.


Transposition of the great arteries. Results of treatment with early palliation and late intracardiac repair. A longitudinal study was made of 62 patients with dextro-transposition of the great arteries. The patients were managed with balloon atrial septostomy (BAS), palliative surgery if any operation was needed in the first year of life, and Mustard intra-atrial baffle repair after one year of age. Of the 47 patients with intact ventricular septum (IVS) treated in this manner, 41 (87 percent) were living at three months of age, 36 (77 percent) at one year, and 31 (66 percent) at two years of age. Survival rates were lower at each age for patients with associated ventricular septal defect (VSD). In relation to therapeutic interventions in the 62 patients, there were six medical deaths within one week of BAS, three deaths during palliative operations, and eight deaths associated with 31 Mustard procedures. Three patients with IVS and five with VSD developed pulmonary vascular obstructive disease, and two patients suffered strokes. In view of the relatively low mortality rate after the neonatal period and our good results with palliative surgery, we continue to defer the Mustard procedure to the second year of life. This is in contrast to the policy of some centers which now advocate elective intracardiac repair in the first year of life.


Problems in the recognition of conduction disturbances in the His bundle. Two cases with conduction disturbances in the His bundle are described. In each it was not possible to obtain both components, H and H', of the "split" His bundle potential at one time from a single bipolar electrode catheter with an interelectrode distance of 10 mm. Initial failure to record the proximal His component (H) let to the incorrect diagnosis of block located within the atrioventricular (A-V) node, of third degree, in patient A, and of first to second degree in patient B. However, careful withdrawal of the catheter resulted in the appearance of proximal components (H), accompanied by disappearance of the distal components (H') of the His bundle potential. Apparently the lesion in the His bundle and the recording electrodes were spatially related in such a way that the bipolar electrode could not override the lesion. In view of these findings it is advocated that in patients the A-V conduction disturbances the His bundle catheter should be withdrawn carefully, if the initial recording reveals His bundle potentials bearing a time relation to the ventricular complexes, or advanced carefully, if these His potentials are related to the atrial activations, in order to demonstrate the (co)existence of a lesion in the His bundle. Search for a proximal His potential by withdrawal of the catheter should be done, if possible, while the atrium is paced at a rate in excess of the spontaneous sinus rate since the H potential may be obscured by the atrial complex if the A-V nodal transmission time is short at the spontaneous rate, as was the case with patient A. In patient B the not yet described phenomenon of bradycardia-dependent block within the His bundle was observed.


Analysis of re-entry mechanisms in the three patients with concealed Wolff-Parkinson-White syndrome. Three patients with recurring attacks of supraventricular tachycardia and no electrocardiographic evidence of the Wolff-Parkinson-White syndrome (WPW syndrome) were studied using intracardiac recordings and atrial stimulation. The findings are interpreted as evidence of a concealed WPW syndrome. In all patients there was antegrade block of the anomalous atrioventricular (A-V) pathway while retrograde conduction was unimpaired and allowed the initiation of the observed reciprocating tachycardias. The diagnosis was based on the assumption that the ventricular myocardium was an essential link in the re-entry circuit. The three most important findings to support this assumption are: 1) retrograde conduction time, measured by the Q-A' interval (Q in ECG to atrial echo), and the rate of tachycardia were dependent on the mode of intraventricular conduction: 2) the first Q-A' interval of the tachycardia was independent of the A-H interval (initiation of atrial impulse to first activation of the His bundle) of the initiating premature atrial depolarization (PAD); 3) there was retrograde conduction following a ventricular premature beat during tachycardia at a time when the A-V node and/or the bundle of His would be refractory.


Echocardiographic analysis of mitral valve motion after acute myocardial infarction. To examine the effects of acute myocardial infarction on mitral valve diastolic velocity, echocardiograms were performed in 18 patients on admission, daily in the Coronary Care Unit, and at 3-day intervals during the remainder of hospitalization. These patients were divided into three groups based on the time interval between onset of symptoms and initial echocardiogram. Five of six patients admitted within 5 hours of onset of myocardial infarction had a triphasic response of mitral valve diastolic velocity with a transient  rise above initial values, followed by a fall to below initial values, and then a slow rise during recovery. Seven of eight patients admitted 1-2 days after onset of myocardial infarction had a biphasic response, i.e., a fall from initial values and then a slow rise. Four patients admitted later in the course of myocardial infarction had a monophasic response, i.e. low initial velocity followed by a slow recovery. We conclude that in patients with myocardial infarction the mitral valve diastolic velocity following myocardial infarction shows a triphasic response which may appear biphasic or monophasic depending on the interval between myocardial infarction and admission. The temporal pattern of mitral valve diastolic velocity changes may reflect the dynamic alterations of myocardial function and compliance that are occurring after acute myocardial infarction and during the recovery period.


The echocardiogram of the anterior leaflet of the mitral valve. Correlation with hemodynamic and cineroentgenographic studies in dogs. The echocardiogram of the anterior leaflet of the mitral valve (ECHO) was compared to hemodynamic and cineroentgenographic data to evaluate its accuracy in timing mitral valve (MV) opening and closure, and to validate it as an indicator of MV motion. The ECHO, high speed cineroentgenography at 250 frames/sec, and/or measurement of intracardiac pressures allowed accurate timing of the events of MV motion in dogs on right heart bypass. The intersection of left ventricular and left atrial pressures in early diastole preceded the onset of rapid anterior motion of ECHO (D' point) by 17 to 33 plus or minus 7.6 msec; r equals 0.98. The onset of left ventricular systole occurred before the termination of final rapid posterior motion of the ECHO in end diastole (Co point) by 25 plus or minus 10 msec; r equals 0.96. Radiopaque clips were attached to the free edges of both leaflets of the MV. Cineroentgenographically determined plots of clip distance from the ultrasound transducer were morphologically similar to the simultaneously recorded ECHO. A delay of 23 plus or minus 3 (0 to 40) msec was observed in the ECHO peaks of diastolic anterior excursion compared to clip motion. Contrast medium advances beyond the free edges of MV leaflets mixing with left ventricular blood 43 plus or minus 3 msec after initial separation. These cineroentgenographic studies elucidate nonuniformity of leaflet motion responsible for ECHO delays. Thus, ECHO D' and Co correlate well with hemodynamic indicators of MV opening and closure. However, ECHO motion, although qualitatively similar, is unpredictably delayed compared to cineroentgenography of clips on the MV free edge. Since the ECHO correlates well with hemodynamic indices of MV opening and closure, this noninvasive technique can be used as a reference in the timing of intracardiac events and in the determination of systolic and diastolic time intervals.


The echocardiographic determination of mitral valve opening and closure. Correlation with hemodynamic studies in man. The ability of the echocardiogram to define mitral valve opening and closure was assessed by simultaneously recording the echocardiogram of the anterior leaflet (ECHO) with intracardiac pressures, aortic second sound, and ECG on 38 occasions in 14 patients undergoing cardiac catheterization. Hemodynamic opening and closure were defined by intersection of the pulmonary wedge and left ventricular pressures and the onset of left ventricular systole. The onset of the most rapid anterior motion (D') in early diastole and termination of the last rapid posterior movement in end diastole (Co) were used as echocardiographic markers of mitral valve opening and closure. Intervals measured included: the isovolumic relaxation period (IRP) from A2 to either hemodynamic (IRPH) or echocardiographic (IRPE) opening; the Q to closure interval (QCI) from the Q wave to either hemodynamic (QCIH) or echocardiographic (QCIE) closure; and diastolic filling period (DFP), either hemodynamic (DFPH) or echocardiographic (DFPE). The following significant (P less than .01) regression equations resulted: IRPE equals (.97) IRPH plus 30 (sem plus or minus 8 msec) r equals .89; QCIE equals (.68) QCIH plus 37 (sem plus or minus 7 msec) r equals .71; DEPE equals (.98) DFPH plus 10 (sem plus or minus 18 msec) r equals .98. Thus hemodynamic markers of opening  and closure systematically precede echocardiographic markers of opening (D') and closure (Co) and the diastolic filling periods are equal within 10 msec. It is concluded that the echocardiogram of the anterior leaflet is a reliable indicator of hemodynamic markers of opening and closure of the mitral valve in man and is useful in the noninvasive determination of certain systolic and diastolic time intervals.


Procaine HCl (Gerovital H3): a weak, reversible, fully competitive inhibitor of monoamine oxidase. A specially stabilized form of procaine hydrochloride (Gerovital H3) has been shown to be a more potent inhibitor of monoamine oxidase than procaine HCl itself and a weaker inhibitor of this enzyme than iproniazid. This preparation was studied to determine its mode of interaction with monoamine oxidase using purified rat brain mitochondrial monoamine oxidase as the enzyme source. Reaction velocities were determined spectrophotometrically by quantitating the rate of appearance of 4-hydroxyquinoline from kynuramine. Dilutional studies comparing the mechanism of inhibition of monoamine oxidase produced by Gerovital H3 and by ipronizid demonstrated that Gerovital H3 was a reversible inhibitor of monoamine oxidase. Analysis of studies using Lineweaver-Burk and Dixon plots revealed that Gerovital H3 was a fully competitive inhibitor of monoamine oxidase. That Gerovital H3 is a weak, reversible, competitive inhibitor of monoamine oxidase may explain the absence of adverse reactions associated with the clinical use of Gerovital H3 as compared to the severe adverse reactions that have been associated with the use of irreversible monoamine oxidase inhibitors.


Restricted replicative life-span of diabetic fibroblasts in vitro: its relation to microangiopathy. The finding that diabetic microangiopathy is caused by accumulation of multiple layers of basal lamina and experiments in which similar basal lamina layering is produced when new cell generations repopulate preexisting basal lamina scaffolding (from which previous cell generations have shed) indicate, that the rates of cell death and cell replenishment are accelerated in diabetics. Because the lesions are focal and regional and develop at different ages and in different time sequences, we have proposed that the accelerated cell turnover is probably caused by increased vulnerability of diabetic cells to injury which in turn may represent the expression of a genetically transmitted defect. To test whether this aberration can be detected in vitro, we examined the replicative life-span of skin fibroblasts from three nondiabetics, three age- and sex-matched diabetics and one individual with acquired hyperglycemia due to pancreatitis. Cells of diabetics exhibited about half the number of population doublings as cells from nondiabetics (0.01 less than P less than 0.025). Cells of the individual with pancreatitis generated a normal number of cell doublings. The interpretation that fits best with all data is that decreased replicative life span of diabetic fibroblasts in vitro is also an expression of increased susceptibility of diabetics' cells to injury and dying.


Age-related changes in the thermoregulatory capacity of tryptophan-deficient rats. From a larger study seeking to develop indexes of physiological aging, the present experiment was designed 1) to test thermoregulatory capacity in the aging and old rat subjected to 3 minutes of whole-body ice water immersion, and 2) using this index of physiological age, to determine whether tryptophan deficiency from time of weaning can retard the onset of senescence. Results indicate a progressive prolongation of temperature recovery time from young to middle age to old, and tryptophan-deficient animals restored to commercial diet at middle age show the thermoregulatory capacity of young adults. The implications of tryptophan deficiency with respect to brain development, serotonin metabolism, and temperature regulation are also discussed in terms of the possibility of intervening with the aging process.


Zinc deficiency and brain development in the rat. Effects of prenatal and postnatal zinc deficiency on the composition of the brain and on subsequent adult behavior were studied. Deficiency throughout the latter third of pregnancy resulted in decreased body and brain size without affecting total brain DNA, RNA, or protein. Adult males that had been subjected to intrauterine zinc deficiency displayed impaired shock avoidance. Zinc deficiency from birth until 21 days of age resulted in impaired growth, decreased brain size, diminished brain DNA, RNA and protein. Cerebellar lipid concentration was also diminished. Such male animals displayed impaired maze acquisition as adults.


Pituitary inhibitor of thyroxine.

Pituitary inhibitor of thyroxine. A description is given of a new pituitary function. It is suggested that the new function acts to decrease gradually the responsiveness of the peripheral tissues to thyroid hormones throughout life. It is suggested that the postulated relative hypothyroidism of older animals might contribute to their loss of viability.


Olfactory bulb connections with basal rhinencephalon in the ferret: an evoked potential and neuroanatomical study. The lateral olfactory tract (LOT) of the ferret has been shown to project to most of the pyriform lobe, as in the cat. Only a small medio-posterior region of the pyriform cortex (the angular cortex), which has a distinctly different appearance in Nissl stained sections, proves to be devoid of olfactory connections. Despite the fact that sub-areas can be recognized within olfactory cortex, there is an underlying constancy in design throughout. Latency measurements indicate that fine collateral branches of theLOT reach the posterior olfactory cortex, whereas mainly larger diameter (faster conducting) fibres comprise the contribution to anterior olfactory cortex. Thus in the present context it is sufficient to recognise just an anterior and posterior subdivisionof olfactory cortex, contingent on the above criterion and correlated with cytoarchitectural features, chiefly variations in cortical layers II and III of the regions concerned. Pyriform cortex directly in receipt of LOT fibres, and associated deeper cortical zones, generated potentials in the olfactory bulbs which can only be attributed to centrifugal input, thus further substantiating an olfactory role for this cortex. In addition, non-cortical regions in receipt of LOT fibres, namely the anterior olfactory nucleus, olfactory tubercle, cortical amygdaloid nucleus and nucleus of the lateral olfactory tract, also contribute centrifugal input to the bulbs. All these regions are thereby capable of providing a rather direct feedback on olfactory bulb activity. The exact pathways concerned have yet to be determined.


Retinogeniculate projections in the rabbits of the albino allelomorphic series1. Retinogeniculate pathways have been studied by fiber degeneration and autoradiographic methods in rabbits that are homozygous for alleles of the albino series of genes. It has been found that albino and Himalayan rabbits, which both lack all melanin pigment in the eye, have a similar abnormality of the retinogeniculate pathway. The number ofipsilateral optic fibers going to the lateral geniculate nucleus is reduced in these rabbits, the ipsilateral projection forms a discontinuous terminal zone instead of the normal continuous zone, and some of the ipsilateral axons terminate in an inappropriate part of the nucleus, so that regions receiving a crossed input in normal rabbits receive an uncrossed input in the abnormal rabbits. Chinchilla rabbits show a slightly reducedfur pigmentation but have a normal distribution of pigment in the retinal pigment epithelium and these rabbits have normal retinogeniculate pathways. In addition,the normalretinogeniculate pathway was studied. Autoradiographic methods show that the beta segment of the lateral geniculate nucleus receives a contralateral input. Hence, earlier views that this segment projects to the visual cortex but receives no retinal input, areuntenable. Further, in the autoradiographic material it was not possible to identify seperate ipsilateral laminae and it was concluded that in the normally pigmented rabbit the ipsilateral retinogeniculate projection forms one relatively continuous group.


The distribution of acetylcholinesterase in buds of the rat vallate papilla as determined by electron microscope histochemistry. The distribution of acetylcholinesterase (AChE) in the rat vallate papillary bud was investigated by histochemical electron microscopy. Previous reports of specific AChE activity around subgemmal and intragemmal nerves and between some taste bud cells have been confirmed. In addition we have consistently observed dense precipitation between microvilli in the taste pore. The studies suggest that the neurotransmitter, acetylcholine, may be involved in early events in the taste process which are believed to occur in the pore.


The autopsy in geriatrics.

The autopsy in geriatrics. The marked decline in the autopsy rate is a serious matter that is not receiving enough attention in the present medical system. Before 1940, a high rate of postmortem examinations was a mark of distinction for a hospital and the findings contributed greatly to our knowledge of disease. This should continue. In geriatrics, a valuable goal is the differentiation of pathologic processes from the process of aging. One outstanding factor in the neglect of the autopsy is the cost to the hospital or other institution; moreover, the cost is not reimbursable by third-party insurance payers. The Pathology Resource Center is proposed as a solution for the problem. Regional autopsy centers could serve the surrounding institutions with greater competence and economy. Medicine should no longer be restricted regarding the valuable contributions to knowledge provided by autopsy findings.


The pathologist and the geriatric autopsy. In the past forty years the autopsy rate in many large institutions has fallen drastically to a level of only 20-25 per cent. The large number of diagnostic errors revealed in autopsy records is in itself a cogent reason for a return to higher standards. The inhibitory effect of high cost would be modified by the use of central regional pathology services and by reimbursement from third-party insurance carriers. The end-result would be a higher quality of medical care for all patients, not excepting those in the geriatric age group.


Autopsy data and their total evaluation. The role of the autopsy is discussed in the study of the etiology of the current major causes of death (cardiovascular and neoplastic diseases) in developed countries. Evidence is accumulating for the importance of environmental factors in the etiology of these diseases. The study of regional differences in occurrence is described as a method of identifying specific factors. Maps are shown of mortality rates for all causes of death in Ontario counties for males aged 65-74 and 95+ during 1964-68. Some of the difficulties in obtaining data in this form, and in their analysis, are indicated. Regional mortality patterns can be interpreted by the use of associations with available regional socioeconomic measures, or by the use of regional data on trace-metal levels in autopsy samples of human lung, rib, vertebra, kidney and liver. The methodology and the difficulties involved in the determination of trace-metal levels in these tissues are discussed, as is the possible relevance of these levels to the study of degenerative diseases. All these considerations emphasize the valuable contributions of autopsy studies.


Progressive deterioration of glucose tolerance in the aged. This long-term study of the natural history of glucose tolerance in the aged is now in its eleventh year. Of 411 nondiabetic persons screened on admission to the Jewish Home for the Aged (J.H.A.) since 1968, 15 per cent had abnormally elevated levels of postglucose blood sugar (PGBS) as compared with 25 per cent in the period 1964-1968. Fewer positive reactors were discovered with annual screenings and with the glucose tolerance test (GTT). Although the proportion of positive reactors and of diabetic-type GTT curves was higher in subjects over age 80 than under age 80, there were 83 residents screened annually for five to nine years who retained normal glucose tolerance despite advancing age. The relatively lower rate of deterioration of glucose tolerance in the second period was attributable to: 1) the younger age of residents admitted since 1968, and 2) the diabetes-oriented diet plus emphasis on exercise and prevention of obesity. The reactive hypoglycemia found in 6 per cent of the residents was asymptomatic, whereas iatrogenic hypoglycemia was usually symptomatic and often severe. This led to a deliberate policy of undertreatment. Dietotherapy induced a lasting remission in about 60 per cent of newly diagnosed cases of diabetes, often to the point of normal glucose tolerance. Early diagnosis of chemical diabetes, by postponing or obviating the need for antidiabetic therapy, reduced the incidence of iatrogenic hypoglycemia. Diabetes-oriented measures are recommended for the aged in general, and for residents of homes for the aged in particular.


Surgical mortality in the elderly.

Surgical mortality in the elderly. Surgical mortality rates were reviewed for the four-year period 1970-1973, in a series of 2,186 operations. The majority of these operations were performed in patients aged 70 or older; of these, 116 were performed in patients of the 90+ age group. Predictably, the surgical mortality in the older groups was higher than in the younger groups. However, the overall mortality for patients aged 70 or older was 4.9 per cent as compared with 8 to 21 per cent for series reported in the literature. Gastrointestinal, biliary, and chest procedures carried a much higher mortality than did the other major categories. Minor surgical operations in the elderly should be approached with caution since they may be associated with a significant mortality rate. Nevertheless, elderly patients should not be denied surgical intervention, major or minor, on the basis of age alone when the operation can make their remaining years more comfortable.


Patterns of contacts for residents of age-segregated and age-integrated housing. It has been suggested that age-segregated housing for the elderly is undesirable because elderly need contact with, and stimulation from, the young. Research has shown that, even in age-integrated housing, intergenerational contact is normally limited and greater density of age peers will lead to more opportunities for contacts and friendships. Interviews with residents of six retirement facilities and with matched controls in age-integrated housing showed that test residents interacted less than their controls with their children, grandchildren, and other relatives, and fewer had friends younger than 40. Test residents had, relative to their controls, more new friends and visited more with neighbors and with age-peer friends. Very little test-control difference was found on sufficiency of contact. A 2-year follow-up interview showed substantially the same patterns. It was concluded that age-segregated housing does imply different spheres of contacts but that either situation can be satisfactory for person who has freely made the choice.


The effect of parabiosis on life-span of rats stressed by radiation. The life-spans of four series of NEDH rats were compared: (1) single control rats, (2) single rats irradiated with 1000 R, (3) control parabiont rats, (4) parabiont rats one of which had received 1000 R. The stress of radiation (1000 R) produced a median life shortening of 571 days in single rats. Parabiosis followed by irradiation (1000 R) of a member of the pair shortened life 132 days. Parabiosis alone produced a median life shortening of 62 days. Ninety percent of the older irradiated parabiont pairs died with one or more tumors present. Parabiosis largely protected animals from the gastrointestinal radiation syndrome.


Runwheel activity patterns of mature-young and senescent mice: the effect of constant lighting conditions. A group of 18 5-mo.-old young and a group of 16 27-mo.-old senescent mice of the C57BL/6J strain were adapted for wheel-running under standard LD 12 : 12 cyclic illumination, after which each group was divided into three subgroups. One old and one young subgroup remained in standard lighting conditions as controls, while the two experimental subgroups received constant light followed by constant dark or constant dark followed by constant light. Rhythmic runwheel activity patterns were compared using periodicity, activity-rest ratios, and amplitude as parameters (defined in text). As expected, senescent mice were less active than young mice, although they did not always spend less time in activity than did the young. Generally, young mice were more reactive to the initial experimental conditions than were the senescent mice, whereas the reverse was observed in the final experimental conditions.


Composition of liver histones in aging rat and mouse. In contrast to the earlier reports on the age-dependent reduction of the ratio of F3 plus F2al plus F2a2 / Fl plus F2b in rat liver histones and the reduction of arginine-rich histone (F3 or III) in beef thymus, the result obtained by high-resolution polyacrylamide gel electrophoresis of histones shows no apparent age-related change in the proportion of any histone fraction of mouse and rat liver chromatin.


Aging and the passage of L-tyrosine, L-DOPA, and inulin into mouse brain slices in vitro. The effect of age on active transport of catecholamine precursors was studied in a healthy population of mature (12-mo.-old) and senescent (30-mo.-old) C57BL/6J male mice. No age differences were observed in uptake of L-(3H)-tyrosine IN VITRO by slices of hypothalamus, brain stem, and striatum at external concentrations equal to or greater than blood levels. However, age-related reductions were observed intermittently in the hypothalamus, brain stem, and striatum at very low concentrations of tyrosine (less than 10 pg/ml). No age differences were observed in incorporation of L-(3H)-tyrosine into hypothalamic proteins when corrected for intracellular uptake of L-(3H)-tyrosine. No age differences were observed in uptake of L-(3H)-DOPA. The possible contribution of age-related changes in extra-cellular space to decreased uptake was determined to be negligible by wash-out studies of tyrosine and by the uptake of inulin. A significant age-related increase of inulin uptake IN VITRO was observed under ionic conditions which minimize tissue swelling.


Safety of administration of procaine hydrochloride-hematoporphyrin (KH3) to beagle dogs. Data were collected as to food consumption, body weight, coat condition, blood cells and chemical constituents, as well as physical and chemical characteristics of urine on 31 adult Beagle dogs (male and female) during a control period and later at monthly intervals during course of the study. After the control period, the dogs were divided into four groups and were given orally for 90 days either placebo, 0.5 gm. (one capsule), 1.5 gm., or 3 gm. of KH3 per day. At the end of the study, animals were necropsied and organs weighed. The coat appeared to be glossy and have luxurious growth. The other parameters studied showed no significant variations from control or normal ranges. Tissues revealed no gross or microscopic abnormalities which could be attributed to treatment. On the basis of this study, KH3 does not appear to have any deleterious effect on dogs at dose levels which are substantially higher than those recommended for animal or human usage.


Biological and psychological predictors of survival in a psychogeriatric population. Out of 206 geriatric subjects who had been assessed with respect to a number of biological and psychological features (Müller & Grad, 1974), it was possible to reach 180 (or 87%) for a 5-year follow-up. Associations of these previous data to six survival categories were examined in order to explore their prognostic value. Of the biological variables the amount of slow EEG activity showed the greatest predictive power concerning the chances of survival, with only a few subjects, who had shown a slow EEG originally, alive after 5 years. Several other biological variables also showed significant differences between survivors and nonsurvivors; the plasma cortisol levels which were determined after the EEG test were lower in the survivors. Diagnostic and predictive value of routine electroencephalographic examinations in geropsychiatric assessments is emphasized. The close relationship of psychological and biological factors is discussed in the context of a dynamic concept of organic brain syndromes.


Fluid and crystallized intelligence in young adulthood and old age. The theory of fluid and crystallized intelligence predicts that the relationship between these two abilities will decline systematically across the age span after young adulthood. In order to test this hypothesis in an elderly sample, the Raven Progressive Martices and the WAIS vocabulary subtest were administered to a sample of individuals (N=40), ranging in age from 60 to 79, and also, for purposes of comparison, to a sample of young adults (N=35). It was found that the correlation was significantly lower in the elderly sample (.386) than in the young adult sample (.672).


Mode of presentation, age, and short-term memory. Female volunteers, ranging in age from 19 to 78 years, viewed or listened to prose passages and sequences of unrelated digits in an evaluation of the effects of modality (visual vs. auditory) upon short-term memory. The data indicated that performance on the digit span task was better with the auditory than with the visual presentation mode, while the opposite effect (i.e., visual better than auditory) was found with the prose passages. Although there were age-related deficits with both types of materials, the modality effects were similar for all age levels.


Social indicators in black and white: some ethnic considerations in delivery of service to the elderly. A random sample of older persons who contacted the Central Intake Referral and Information Service (CIRIS) of the Houston Areawide Model Project for the Elderly responded to the Social Indicators Index for the Aged. The scores obtained from this instrument were analyzed with respect to ethnicity. Comparisons were made with data from an independent city-wide sample to which the same instrument was administered. When ethnicity was controlled, consistent differences emerged both between the two samples and within each sample. Significant differences found in the CIRIS sample on measures of income, health, and life satisfaction were combined with differences between the two samples to provide indications of cultural factors involved in utilization of services by the elderly. Our findings support other literature which has stressed the necessity of considering ethnic differences in developing theories on aging and in designing and delivering services to the aged--regardless of whether one is dealing with minority or majority individuals.


Aging and adaptation to illness.

Aging and adaptation to illness. The relation of age, adaptation to illness, and the severity of cerebral dysfunction was evaluated for persons having suffered cerebrovascular accidents (CVA). All (89) subjects (age range 38 to 84 years, mean 62) were interviewed at least 1 mo. following onset of illness. It was found that older persons were more likely to manifest mental impairment following a DVA but that measures of sensory and motor functions were not similarly affected. The association of age and psychological adaptation varied, depending on the severity of brain dysfunction. Among a minimally impaired group, older persons tended to be more depressed and to use less denial than younger subjects. While denial was increasingly manifested by all persons with severe degrees of cerebral dysfunction, this change was shown to a greater extent by older subjects. The findings suggest that the severity of cerebral dysfunction may be a more critical factor in determining adaptation to illness than chronological age.


Voluntary association participation and life satisfaction: a replication note. The results of a replication study carried out in Kansas City in 1973 are compared with the original study in Oberlin, Ohio, in 1970 to see if the relationship between participation in voluntary associations and life satisfaction of the aged holds up over time and in a different geographic region. In a confirmation of the original study, the data indicate that health and status characteristics are more potent predictors of life satisfaction than participation in voluntary associations, which shows a nonsignificant relationship to life satisfaction when controlling for the effects of health and status.


A retesting and modification of the Philadelphia Geriatric Center Morale Scale. The inter-item structuring of the questions in the Philadelphia Geriatric Center Morale Scale was analyzed for sample members of two studies being conducted by the Dept. of Social Gerontological Research of The Hebrew Rehabilitation Center for Aged (Boston) in an attempt to understand better the several components of the PGC battery first reported by Lawton. PGC items were subjected to principal component and Varimax factor analyses for both the original 22 items and also a reduced 17-item battery. In addition, using more recent findings of Lawton, further structural tests were performed in order to obtain the best possible configuration of items for the several reliable scale components found. The results of these cross SAMPLE ANALYSES INDICATE AN OVER-ALL LEVEL OF RELIABILITY FOR THREE OF THE ORIGINAL PGC components; and at the same time, indices of greater length and reliability resulted when these three PGC components were slightly restructured.


The Philadelphia Geriatric Center Morale Scale: a revision. The 22-item Philadelphia Geriatric Center (PGC) Morale Scale was subjected to a series of principal component analyses utilizing different item pools and rotating differing numbers of factors. Subjects were 1086 tenants of federally-assisted housing for the elderly and older people living in the community. Results were compared with analyses of the PGC Scale done by Morris and Sherwood. Consideration of factors defined by the analyses suggested three consistently reproduced factors: Agitation, Attitude Toward Own Aging, and Lonely Dissatisfaction, utilizing 17 of the original items. These results were compared with other multi-dimensional measures of morale: the Bradburn Affect Balance Scale, and morale scales reported by Pierce and Clark, and Schooler. In addition to the dimensions derived from the current study related domains of self-rated health, social accessibility, generalized attitude toward aging, and positive affect were suggested as worthy of further exploration as dimensions of morale.


Changes in size of lacunae during the life of osteocytes in osteons of compact bone. The cross-sectional areas of 739 lacunae from 31 osteons of gibbon femur, gibbon ulna, and human humerus were measured and compared on the basis of their distance from the osteon canal. There was great variation in size of lacunae at all distances, but the mean size of lacunae adjacent to the canal and of those in the periphery of the osteon were larger than the mean size of lacunae found intermediate in position. This was interpreted to mean that new osteocytes continue to form bone, thus decreasing the size of their lacunae, but later in their life cycle, enlarge their lacunae through bone absorption. The great variation in size was interpreted to be evidence for alteration of function of osteocytes.


Characteristics of mentally-impaired aged profiting from individualized treatment. This study investigated subjects' characteristics which related to improvements from individualized treatment of mentally impaired aged. Project variables (158) were reduced to 12 Q-type factors. The excess disability (ED) criteria were partialled into experimental/control influences (EDe/c) and residual ED variance. Statistical regressions were run on the EDe/c criteria vs. age and the 12 Q-factors. Age significantly predicted post-treatment ED functioning in both conditions. Younger subjects (ages 65-82) profited most in both groups. After the statistical removal of age in the regression, Factor Q-3 still retained a significant relationship to EDe/c for the experimentals. The correlations indicate the importance of social capabilities, irrespective of age level, with regard to improvements due to ED treatments. For the control subjects, Q-12 and Q-5 showed significant independent relationships to the criteria. Subjects' competence appeared most important for EDe/c gains made without treatment.


Predictors of a dimension of well-being in the relocated healthy aged. One hundred twenty-two subjects aged 61 to 88 years were given a wide variety of tests around the time they moved to an apartment complex in which independent living and self-care was necessary. After living in their apartments approximately 15 mo., they were rated for how well they were faring in terms of a clinical dimension, from "played out" to "vital." Of 25 predictor variables, 14 were related to this dimension. Two were especially prominent--the WAIS Comprehension subtest and the Crossing-Off psychomotor task.


The paucity of course work in medical care evaluation. In view of the current emphasis on measurement of the quality of health care services, reflected in regulatory provisions and accreditation requirements, an inquiry was made as to the extent to which medical schools are presently offering formal training in the techniques of medical care evaluation. Of 118 medical schools surveyed, 24 responded with the information that they are actually providing such training. The training reported ranged from a one-hour lecture to five elective courses. The implications of the findings are discussed with reference to the need of physicians to become familiar with the principles and methods of scientific evaluation of medical care. Some of the areas that might be covered in courses on evaluation are discussed, and examples of two current programs are given.


An outreach program for a rural medical school. An outreach program for Dartmouth Medical School has been developed which utilizes rural communities in the education and training of medical students and residents in primary care. A correlated curricular track for primary care and a residency program have been established. The program is interdepartmental and administered by the dean, and services provided to patients are financed by fee-for-service. The cost incurred by the presence of residents and medical students is shared by the community and the medical school. The program is based on a close partnership between the medical school and the community in fulfilling their respective educational and service objectives.


Evaluation of review courses for the ECFMG examination. In this paper three review courses for the Educational Council for Foreign Medical Graduates (ECFMG) examination are described. A comparison of the pass rates on the January 1973 ECFMG examination for examinees taking the courses with those not taking the courses shows a statistically significant difference (47 percent passing for those taking the courses in contrast to 18 percent passing for those not taking the courses). Although the courses appear to be effective, the limitations of the ECFMG examination as a screening device for foreign medical graduates (FMGs) make it unwise to expand the number of such courses. The cramming of basic medical knowledge into students is not a useful solution to the problem of physician shortages. The focus of attention on the FMG in the health care system must shift from a search for expedient ways of providing for greater utilization of FMGs to the deleterious effects of this utilization on the quality of patient care.


Forecasting and medical education.

Forecasting and medical education. The ability to render more accurate predictions of the future will enable medical educators and administrators to make more advantageous policy and program decisions. Modern forecasting techniques and criteria to evaluate prognostic endeavors are described. Examples of how these methods can be applied to medical education are provided.


Paradigms in medicine: consequences for medical education. Paradigms play an important role in the natural sciences. Basic medical science has primary paradigms from which are derived secondary paradigms that allow the practice of medicine. Medical education consists in students acquiring this paradigm and in practitioners changing their paradigm in the light of medical research. Problem-solving plays an important role in the acquisition of this paradigm. Unless educators, especially basic scientists, are aware of their own paradigm, communicating with others who hold different paradigms can be difficult and cause serious misunderstanding.


An introduction to the study of medicine: phase I of the McMaster M.D. program. "Phase I" describes the initial 11 weeks of study in the M.D. training program offered by the Faculty of Medicine of McMaster University. This three-year program stresses the responsibility of students for their own education, encourages self-directed learning using realistic biomedical problems, and offers little didactic instruction. Students are assigned to tutorial groups, and much of the educational thrust of the program is built upon interactions within these groups. Phase I is designed to allow students to adapt to a less structured environment, and intensive faculty support is available. The successes and failures of Phase I of the program were examined using a combined questionnaire and interview at various stages during the 11-week period. Not all program goals were satisfactorily measured, but those that could be assessed appeared to have been attained by most students.


Absence of hexosaminidase A and B in a normal adult. In the course of screening for heterozygotes for beta-hexosaminidase deficiency, the serum and white cells of a clinically normal father of deficient children were found to have an apparent deficiency for both hexosaminidases A and B, assayed with an artificial substrate, 4-methylumbelliferyl-beta-glucosaminide. No inhibitor was present. Assayed with a natural substrate, n-acetylgalactosaminyl beta 1-4 galactosyl beta 1-4 glucosyl ceramide, which had been isolated from the brain of a patient with Tay--Sachs disease and labeled in the terminal n-acetyl-galactosamine, a value in the heterozygote range was found. It was concluded that the proband is probably a double heterozygote for two mutations; one is the classic Sandhoff type (lack of hexosaminidases A and B), giving rise to deficient offspring when combined with the same mutation borne by the wife. The other obscures any activity with the artificial substrate but allows an action on natural substrates, explaining the normal life of its carrier.


Abortion, euthanasia, and care of defective newborns. Growing use of abortion to prevent births of infants with unfavorable prenatal diagnoses raises ethical questions about active euthanasia for newborn infants with similar impairments. Two opposing ethical arguments are those of Paul Ramsey, who equates genetically indicated abortion with infanticide disapprovingly, and of Joseph Fletcher, who equates the morality of abortion with selective euthanasia approvingly. Though radically different, these arguments treat the ethical aspects of the prenatal and postnatal situations as essentially similar. There are, however, different moral features between the two situations, in that the postnatal situation is characterized by the independent physical existence of the infant, the possibility of treatment, and the formation of parental loyality to the infant. Thus, a decision for abortion after prenatal diagnosis does not necessarily commit parents to euthanasia in the management of a seriously damaged infant.


Active and passive euthanasia.

Active and passive euthanasia. The traditional distinction between active and passive euthanasia requires critical analysis. The conventional doctrine is that there is such an important moral difference between the two that, although the latter is sometimes permissible, the former is always forbidden. This doctrine may be challenged for several reasons. First of all, active euthanasia is in many cases more humane than passive euthanasia, Secondly, the conventional doctrine leads to decisions concerning life and death on irrelevant grounds. Thirdly, the doctrine rests on a distinction between killing and letting die that itself has no moral importance. Fourthly, the most common arguments in favor of the doctrine are invalid. I therefore suggest that the American Medical Association policy statement that endorses this doctrine is unsound.


Clinical approach to jaundice.

Clinical approach to jaundice. Jaundice, with and without hepatobiliary damage, has a wide spectrum of causes. In the initial evaluation, fractionation of the bilirubin facilitates differential diagnosis. Unconjugated hyperbilirubinemia most often is the result of pigment overload or Gilbert's disease. Most patients with jaundice seen by the clinician have underlying hepatobiliary disease. Liver biopsy usually establishes the etiology of hepatocellular forms of jaundice. In patients with cholestasis, visualization of the biliary tree by either transhepatic or endoscopic retrograde cholangiopancreatography provides the most direct means of differentiating mechanical biliary obstruction from intrahepatic cholestasis.


Gallstone disease.

Gallstone disease. Most gallstones are composed largely or entirely of cholesterol. The larger calculi are more often associated with acute cholecystitis than are smaller stones. Factors predisposing to gallstone formation include sex, age, race, child-bearing, and possibly diet and obesity. About half of all persons with cholelithiasis have symptoms referable to the biliary tract. The most important symptom in the diagnosis of gallstone disease is biliary colic. Biliary pain lasting longer than five or six hours is indicative of acute cholecystitis, with obstruction of the cystic duct by a calculus as the primary event in most instances. The reliability of cholecystography in detecting gallstones is at least 95 percent. In patients over age 60, cholecystectomy is indicated only in those with specific symptoms referable to the biliary tract. The effectiveness of chenodeoxycholic acid in dissolving radiolucent gallstones in asymptomatic patients has been confirmed in several clinical trials. Early operation in patients with acute cholecystitis is advocated.


Peptic ulcer disease.

Peptic ulcer disease. Smoking, heredity, aspirin ingestion, and various diseases are associated with increased prevalence of peptic ulcer disease. Significant pathophysiologic differences between ulcer patients and normal subjects have been shown to exist, but many of the observed abnormalities are still poorly understood and require further study. Prospective studies are also needed to quantitate the role of psychologic factors in the pathogenesis of ulcer disease. Ulcer disease is diagnosed by history, physical examination, upper gastrointestinal radiography, and endoscopy. In some patients measurements of serum gastrin levels and gastric acid secretion at rest and after stimulation give significant information. Antacids and anticholinergics remain the primary therapeutic agents; new therapeutic agents are currently under study.


Psychosomatic aspects of gastrointestinal disease. Gastrointestinal diseases are notoriously protean in their modes of expression. The patient's description of symptoms is particularly important, but psychologic, physiologic, and social factors can cause data-base unreliability. Many of the patients termed crocks have symptoms referable to the gastrointestinal system, and they are at considerable health risk, since they usually alienate health care personnel. Patients with pancreatitis usually have a history of heavy alcohol intake which also needs treatment. Behavioral disturbances are related to toxic psychosis. Pancreatic carcinoma has a higher incidence of associated psychiatric symptoms than other types of cancer. Biologic, psychologic, and environmental factors all interact dynamically to cause peptic ulcer disease. There is a high correlation between the severity of inflammatory bowel disease and degree of emotional disturbances.


Diarrhea: pathogenesis and diagnostic techniques. Daily fecal weight is the feature most useful in defining diarrhea, as normal weights for various societies are known. Diarrhea is associated with increased fecal water excretion, with heightened sensitivity of the rectal mucosa, and with exudation of mucus. It occurs acutely, as in gastroenteritis, bacterial dysenteries, and parasitic infections, and chronically, as in functional disorders, malabsorption syndromes, and inflammatory bowel disease. Many seemingly unrelated diseases can also cause diarrhea. The patient's history as well as macroscopic, microscopic, and chemical analysis of stools will offer major clues to the cause of the ciarrhea.


Intestinal gas.

Intestinal gas. Patients with functional bowel disease commonly complain of abdominal pain, bloating, and excessive flatulence and eructation. Pain and bloating may be primarily caused by abnormal intestinal motility rather than by excessive intestinal gas. As yet there are no data available that prove excessive flatulence is actually caused by the presence of excessive intestinal gas. A study of the composition of intestinal gas provides insight into whether it is derived from swallowed air or from intraluminal metabolism. Therapy aims primarily at excluding the presence of organic disease as a cause and reassuring the patient that the disorder is functional in nature. Dietary manipulation, changing the habit of aerophagia, exercise, and pressure and heat applied to be abdominal area are all possibilities to be tried.


Recent advances in management of gastroesophageal reflux. Gastroesophageal reflux is not synonymous with sliding hiatus hernia. It should be approached as a condition dependent on the intrinsic strength of the lower esophageal sphincter rather than on the presence of a hiatus hernia. The patient's account of symptoms is probably the most important means of diagnosis, but in addition the patient's history should be supplemented by radiographic evaluation. Initially the treatment of gastroesophageal reflux is one of prevention. If this conservative approach proves ineffective, drugs that restore sphincter strength can be tried. Surgery should be resorted to only if medical treatment fails, and then one of the newer specific antireflux procedures should be the operation of choice.


Effects of therapeutic ultrasound on bone marrow in dogs. With a thermocouple in the medullary cavity of one dog's femur, the increases in bone marrow temperature were demonstrated at five different intensities of ultrasound. The right distal femurs of six dogs were treated ten times, three dogs at 1.5 w/cm2 and three dogs at 2.5 w/cm2 each for five minutes. At a later date, two of these dogs received an additional ten minutes of ultrasound at 2.5 w/cm2 for ten treatments. Histological and hematological studies gave presumptive evidence of bone marrow damage and regeneration. A marked increase in oil was also seen in the bone marrow smears.


Vibratory stimulation. Part II. Vibratory stimulation as an evaluation tool. Phasic neural mechanisms are heavily involved in volitional movements, where as tonic mechanisms support postural adjustments. Yet, the two systems are so intimately related that any disturbance in one will exert profound effects on the other. Whether one system or the other is involved preferentially in different neural disorders is not known; hence, tests are needed to evaluate phasic and tonic functions independently. In this article, the classical applications of the tendon jerk reflex and H-response for assessing phasic mechanisms are first reviewed. Following this review, the tonic stretch reflex and tonic vibration reflex (TVR) are analyzed and compared. The effects of experimentally ablating or stimulating precise brain regions are described as a means of revealing the role of supraspinal mechanisms in the TVR. Finally, the responses to vibratory stimulation in specific motor disorders are examined and discussed as to their usefulness in prognosis and diagnosis.


Methods of reducing environmental stress for the acute burn patient. All measures must be taken to enhance conservation of energy in patients with burns so that they can withstand the stresses imposed upon them. Many environmental factors can be regulated to decrease these stresses. Room temperature can be regulated to 29 degrees Celsius (84 degrees F) to decrease evaporative cooling and fluid loss. Humidity can be regulated to approximately 30 percent. Water temperature can be maintained between 35 and 37 degrees Celsius (95-98 degrees F) to encourage mobility and relaxation and to minimize shivering. Proper concentration of sodium can be used in the tank to minimize leaching to the electrolyte from the wound into the water. These measures for conserving energy help to provide the patient with the maximal metabolic efficiency necessary for wound healing and recovery.


Mortality and morbidity rates after inferior vena caval clipping. In 112 patients receiving inferior vena caval, serrated, Teflon clips over a 7 year period beginning Jan. 1, 1966, the operative mortality rate was 6 percent (seven patients) and the 1 to 12 month mortality rate was 9 percent (10 patients). Patients with severe heart disease accounted for eight of these 17 deaths. The mortaligy rate was zero in patients who were free of heart disease, malignancy, sepsis, or massive pulmonary embolism. Recurrent pulmonary embolism was suspected, but not lethal, in four patients and was proved in two. Patients who had leg swelling preoperatively were more likely to have swelling postoperatively than those who were initially free of swelling. Postoperative anticoagulation was ineffective in preventing edema and carried the risk of wound hemorrhage. Twelve months after operation, 12 of the 83 patients available for follow-up had severe lower extremity symptoms and 23 had milder, easily controlled edema. Late stasis changes, therefore, appeared at an acceptably low frequency and could reasonably be expected for patients with lower extremity phlebothrombosis. There was no instance of fatal pulmonary embolism in the follow-up period extending from 1 to 6 years.


The effect of Travase on heat-injured skin. When applied topically and compared to its placebo experimentally in guinea pigs, Travase was associated with no damage to the epithelium of normal skin, slight damage to that of mechanically injuried (donor-site) skin, and total destruction of all the epithelium in skin subjected to severe but otherwise reversible burn injury. While not preventing this destruction of heat-injured epithelium by Travase, simultaneous use of topical silver sulfadiazine cream did reduce the weight loss and purulence associated with Travase therapy of burns. To evaluate the safety of any form of topical burn therapy satisfactorily, preclinical testing should consider its effects on (1) uninjured skin, (2) skin reversibly injured by heat, and (3) skin immediately coagulated (irreversibly injured) by heat.


Accidents and complications in selective and proximal gastric vagotomy. In 3 years 266 consecutive patients were electively operated on for ulcer disease with either selective vagotomy (SV) with drainage (159) or proximal gastric vagotomy (PGV) without drainage (107). The total number of operative accidents was 15 (6 percent), similar to that of truncal vagotomy. Perforation of the stomach occurred in six SV and in one PGV. The perforation went unobserved in two patients, of whom one died. Esophageal perforations were not observed. Bleeding from the lesser omentum or from the spleen was seen in seven patients, requiring reoperation in one. Postoperative surgical complications were seen in 25 patients (9 percent): clinical gastric retention was observed in nine patients, five with SV and four with PGV, and 13 had wound abscesses or dehiscence. Fifty-nine patients had other complications, of which 52 were radiologically demonstrated atelectases, mostly without any clinical significance. The total mortality rate was 1.1 percent, similar to that of truncal vagotomy. The duration of the two operative procedures did not differ, and the greater care required for preservation of the nerve of Latarjet tended to diminish the number of operative accidents.


Liver regeneration after portacaval transportation in rats. General recognition of the presence of a specific hepatotrophic factor in portal blood that is necessary for liver regeneration was delayed by two major problems. First, there was a long period of confusion regarding liver atrophy, liver hypertrophy, and cellular hyperplasia. Second, because only exposure to other liver tissue destroys the hepatotrophic activity, all of the studies that were based on bypassing the portal blood into the systemic circulation merely diluted the active substance, which still was available to the hepatocytes by recirculation through the hepatic artery. These problems have been resolved by the development of more sophisticated methods by which to assay liver regeneration and by the introduction of the double liver model to study regeneration. During the time when liver weight alone was used to assess regeneration, the regenerative capacity of the liver was reported to be much greater after portacaval transposition than after end-to-side portacaval shunt, a finding that is inconsistent with current knowledge of the hepatotrophic portal blood factor. To re-evaluate the effect on liver regeneration of providing a compensatory systemic venous inflow after complete portal diversion, 40 partially hepatectomized inbred rats which had previously undergone either a sham operation and end-to-side portacaval shunt or a portacaval transposition were compared on the basis of six separate criteria of regeneration. All of the livers actively regenerated and no significant advantage of providing a substitute systemic venous inflow to the liver could be detected by any of the criteria.


Primary adenocarcinoma of the jejunum and coexisting primary adenocarcinoma of the vermiform appendix: a case report. An unusual case of primary adenocarcinoma of the proximal jejunum with coexisting primary adenocarcinoma of the appendix is presented. The symptomatology, diagnosis, surgical management, and prognosis are also presented. To our knowledge, this is the only such case reported in the medical literature of English-speaking countries.


Arterial embolectomy before and after the Fogarty catheter. Arterial emboli were extracted from 79 patients between 1955 and 1963 with polyethylene catheter suction systems and/or retrograde flushing and from 149 patients between 1963 and 1973 with Fogarty catheters. The Fogarty-era patients were older, had a greater incidence of ischemic heart disease, and presented with a greater degree of preoperative peripheral ischemia. The limb salvage rate of 87 percent after Fogarty catheter embolectomy was not statistically different from the salvage rate of 79 percent after suction catheter embolectomy, but the number of limbs with distal pulses postoperatively was significantly greater after Fogarty treatment, 64 vs. 42 percent. Delay in treatment and the presence of prior occlusive vascular disease adversely affected results in both eras. The in-hospital embolic recurrences occurred in 9 percent of the patients anticoagulated postoperatively and in 31 percent of those not anticoagulated. Heparin and warfarin were equally effective in preventing recurrences, but wound complications were seen in 33 percent of the heparinized patients, compared with 7 percent of those receiving warfarin and 4 percent of those not anticoagulated.


The role of vena caval interruption in the management of pulmonary embolism. Sixty patients with documented moderate-to-severe pulmonary embolism have been managed primarily with anticoagulant or lytic-anticoagulant therapy during the past 6 years. The in-hospital mortality rate from embolization was 5 percent. Recurrent embolization was documented in only two patients (3 percent). Three patients (5 percent) required caval ligation because of a profound heparin sensitivity, peptic ulcer bleeding, and recurrent embolization while adequately anticoagulated. The study suggests that adequate anticoagulation is sufficient therapy for most patients and is associated with a low incidence of recurrent embolism. In view of the significant mortality rate reported following caval interruption and especially of the associated long-term venous sequelae, it is concluded that inferior vena caval interruption is seldom indicated in the management of pulmonary embolism and should be performed only when firm indications are present.