Transfer from extero-to interoceptive reinforcement in the course of instrumental conditioning in rats. The possibility of maintaining an ingestive instrumental reflex following the transfer from oral food reinforcement to different kinds of intragastric reinforcements (liquid food, water, hypertonic NaCl and morphine) was investigated. The experiment carried out on male hooded rats with previously implanted nasopharyngeal gastric tube showed that in all but the morphine reinforced group the performance gradually decreased showing a pattern of extinction similar to nonreinforced control group. Instrumental response was maintained in morphine reinforced rats although they were not drug addicted. The results obtained contradict the possibility of instrumental conditioning of ingestive reflexes reinforced interoceptively. They also question the drive-reduction hypothesis of instrumental conditioning, supplying further evidence in favor of the hedonistic view.


The role of paraprofessional: an administrative dilemma. Changing a paraprofessional's title will do little to improve his or her position. If they are to compete successfully in the status and power sweepstakes, paraprofessionals must continue their education. Administrators should make career development opportunities available if they hire paraprofessionals.


The characteristics of administrators and the effectiveness of community mental health centers. Using a methodology developed for industry, the personality traits, abilities, and motivations of CMHC administrators are assessed. The characteristics of these administrators do not appear to be significantly related to the effectiveness of their organization. This finding differs from those in other organizations and may be caused by the uniqueness of the CMHC.


Incomplete technology and the organizational dynamics of a state mental hospital. Inadequate clinical knowledge has a profound effect on the organization and administration of a state mental hospital. The official goal of active treatment is displaced by the operative goal of custody and there is a reliance upon hierarchy rather than expertise as the source of authority.


Standards and quality control: problems and pitfalls. The proliferation of standards and quality assurance programs is posing a major problem for mental health administrators. The authors review some of these problems and emphasize the differences between cost and quality controls. They propose that quality controls be judged on their ability to improve patient care and suggest that administrators consider the establishment of quality control offices.


Demographic data and mental health planning. The use of readily available demographic data in mental health planning is discussed and illustrated. Four indices are identified as important in setting priorities for mental health services: social class, family organization, population mobility, and population heterogeneity.


Cash planning in community mental health agencies. Community mental health agencies often receive funds from a number of different sources with varying restrictions. Cash planning can help them manage these funds properly and avoid serious problems. The use of a projected cash flow statement may even help produce additional income for them.


Fiscal resource development for state mental health agencies. As funds for human service programs grow scarcer, state mental health departments must become more aggressive in seeking out new funding sources. The development of a fiscal resource development unit at the state level is proposed as one approach to the problem.


How accurate are client reports?

How accurate are client reports? Information reported by clients on their previous contacts with community agencies is not accurate. A study of hospital and clinic records indicates that these reports contain omissions significant enough to jeopardize continuity of care.


Mental health training for the middle manager. Training in administration for middle managers is an important but much neglected area. While middle mangers such as unit chiefs, supervisors, and team leaders have significant administrative responsibilities along with their clinical work, they are seldom trained in administration. The authors describe a program to train full and part time students for middle management positions.


Aerobic exercise as a therapeutic modality in the relief of stress. This paper reviews the pathophysiologic influences of 20th century emotional stress. The physiologic consequences of cardiovascular conditioning by aerobic techniques are also reviewed. It would appear that cardiovascular conditioning has physiologic characteristics which would counterbalance those induced by such stress. Accordingly, it appears logical that cardiovascular conditioning by aerobic exercise techniques is an effective therapeutic and prophylactic tool. Future investigative efforts must take two directions. First, the extent to which exercise may be used in ameliorating the pathologic consequences of chronic stress must be scientifically documented. Secondly, in those instances where exercise is undertaken imprudently, evidence must be gathered as to the extent that physical activity precipitates maladaptive responses in humans.


Gastric secretory and motor inhibition induced by certain methyl analogues of prostaglandin E2 in healthy male volunteers and in patients with duodenal ulcer disease. The present investigation shows that the 15(S)-15-methyl and 16,16-dimethyl analogues of PGE2 given orally are potent inhibitors of gastric acid secretion. The inhibition of acid output is mainly due to a reduction in volume output. The effect on acid secretion was shown to be less pronounced in a group of duodenal ulcer patients than among healthy volunteers. Only the 15-methyl analogue gave any significant secretory inhibition following intestinal administration. The results from the experiments in dogs indicate that a local action on the oxyntic glands could be the main reason for secretory inhibition following oral administration. The results from the studies on motor activity show that the prostaglandins inhibit both antral and duodenal pressure activity. However, with our experimental design, only with doses exceeding those required for secretory inhibition.


Renal prostaglandin synthesis in experimental renal clip hypertension in the rat. 1. The hypothesis that suppression of prostaglandin E (PGE) synthesis by indomethacin exacerbates renal clip hypertension in the rat was investigated. 2. Indomethacin exacerbated hypertension in renal clip rats. 3. In vitro PGE synthesis determined by gas liquid chromatography (GLC) was suppressed in medullary tissue from the hypertensive animals irrespective of indomethacin treatment. 4. The findings support the concept that PGs participate in blood pressure regulation in experimental renal hypertension.


Synthesis and metabolism of prostaglandins in rat placenta, uterus, and ovary during various stages of pregnancy. 1. In the rat, during days 8 to 21 of pregnancy there exists distinct patterns for prostaglandin synthesis and metabolism in the placenta, uterus, and ovaries. These patterns are different in each of the organs. 2. The ratios between PGF and PGF2alpha synthesized or metabolized changes for each of the reproductive tissues studied. 3. Day 11 of gestation represents a critical period as reflected by a highly elevated synthesis and metabolism of prostaglandins. 4. Uterine prostaglandin synthesis increases progressively during the last trimester of pregnancy being maximal on the day of parturition.


The effect of infusions with two analogues of prostaglandin F2alpha on corpus luteum function. With the exception of one volunteer given the prostaglandin during ovulation, a transient decline in progesterone during the infusion was observed with both compounds. It is likely that the marked declines that were observed cannot be attributed solely to diurnal variation. Although the menstrual cycle was shortened in some cases after the infusion, this was not well-correlated with the acute effects seen at the time of infusion. Under the experimental conditions of this study, neither analogue appeared to be luteolytic. However, infusions with both compounds did alter serum progesterone transiently. It seems likely that both compounds do exert a potent effect on the corpus luteum and may in fact be luteolytic when given at some other time in the menstrual cycle.


Intrauterine prostaglandin E2 as an postconceptional abortifacient. 1. Thirty-eight pregnant women, 2 to 33 days overdue with a menstrual period, were treated with a single intrauterine injection of PGE2. 2. Abortion occurred in 7 of 12 patients (58.3%) treated with PGE2 100 mug and in 22 of 26 patients (84.6%) given PGE2 500 mug. 3. The only side effect was uterine pain requiring analgesia in four of the former and 15 of the latter. Four patients required curettage to control bleeding.


Platelet prostaglandin production and its implications. Both aspirin and indomethacin abolish platelet shape change and aggregation induced by arachidonic acid, indicating that these effects are due to prostaglandin production. An unstable prostaglandin endoperoxide (PGG2 or PGH2) is probably the mediator of the arachidonic acid effects, and they can be mimicked by the stable synthetic prostaglandin, 11-deoxy-15-methyl-15RS-PGE2 (Wy-17, 186). All three of these prostaglandins induce platelet aggregation in the presence of aspirin. Neither aspirin nor indomethacin inhibits shape change or primary aggregation induced by ADP, which indicates that these effects are not due to prostaglandin production. Arachidonic acid, Wy-17, 186, and ADP require fibrinogen as a cofactor in order to aggregate washed human platelets. However, the combination of ADP and arachidonic acid or of ADP and Wy-17, 186 is synergistic and will aggregate washed human platelets in the absence of added fibrinogen. No synergism is observed between arachidonic acnd and Wy-17, 186. During platelet degranulation (i.e., the platelet-release reaction) induced by collagen both ADP and prostaglandin endoperoxides are made available, and collagen can induce the aggregation of washed human platelets in the absence of added fibrinogen. Prostaglandin endoperoxides, ADP, and fibrinogen probably act in concert to aggregate platelets in normal hemostasis since the absence of any one of these principles usually has an effect on the bleeding time.


Benign esophageal strictures.

Benign esophageal strictures. For the treatment of esophageal strictures caused by reflux, dilation alone is rarely curative, as a reflux is not prevented. Standard antireflux repairs are the 1st procedures to be used whenever possible. If esophageal damage and shortening is more severe, the Collis gastroplasty operation coupled with an antireflux repair is effective, but the selection of patients is important. The gastroplasty should not be used if the stricture cannot be dilated easily or if several previous operations have been performed at the cardia. If the Thal fundic patch operation is used, a skin graft and full fundoplication should be employed as well. The results from a fundoplication left in the chest are encouraging from initial reports. Further follow-up of all 3 of these approaches is required. For patients with the most difficult strictures, especially following multiple previous failed operations, resection of the stricture and intestinal interposition is the operation of choice.


Development of humoral immunity system of the small bowel. The study was performed in 24 children aged 2 months to 6 years, without intestinal or immunological diseases. Intestinal biopsies were obtained by a Crosby's capsule, pediatric size. The number of immunoglobulin forming cells of lamina propria was measured by planimetry. Under 12 months of age there are increased levels of IgM forming cells and a low IgA forming cells/IgM forming cells quotient, but over 1 year the difference disappears. This suggests that the maturity process is very rapid. There are no correlation between serum IgA, IgM, and IgG levels and its respective forming cells number of lamina propria. It seems to support that the participation of intestinal lymphoid tissue in serum pool of immunoglobulin is very poor and that systemic and intestinal immunity maturation are completely independent.


Immunologic aspects of malignancy. II. Host immunocompetence and relationship to the clinical stage in patients with prostatic cancer. As knowledge of the stage and grade of tumour are essential to the selection of the appropriate therapeutic modality and subsequent management of the patient, the patient's immunological competence is equally significant. In the present communication a broad spectrum of cellular and humorally-mediated parameters of immunologic responsiveness reflecting more or less general immunocompetence rather than tumour-specific immunity were evaluated in 28 patients with the prostatic cancer. The immunocompetence of these patient's was then "immunostaged" independently without prior knowledge of their clinical stage, and the correlation and significance of these determinations evaluated. In this present preliminary report, a statistically significant correlation (P less than 0.05) was observed between the patients' "immunostage" and clinical stage.


Vertigo.

Vertigo. Vertigo, with or without nystagmus, may accompany many diseases. Most causes are transient and benign. A systematic approach saves valuable time. Nonrotational dizziness must be distinguished from true vertigo in which a sensation of motion is involved. Careful evaluation of nystagmus is essential, as is a complete cardiovascular examination. Meniere's syndrome, while common, is overdiagnosed.


Intramyocardial small-vessel disease in chronic alcoholism. A morphologic study of the small (50 to 200 micron) intramyocardial coronary arteries was performed. The cases chosen for study were selected from a relatively young group of patients without clinical evidence of alcoholic cardiomyopathy or pathologic evidence of large coronary artery disease, in order to evaluate alterations in the small vessels which could possibly be attributed to the chronic alcoholic state. Five basic vascular abnormalities were described. The most common alteration found in all nine cases was vascular wall edema (48 per cent), followed by perivascular fibrosis (42 per cent), vascular sclerosis (36 per cent), subendothelial humps (13 per cent), and vascular wall inflammation (11 per cent). The significance and pathogenesis of these changes were discussed. Primary endothelial cell damage was proposed as a common pathogenic mechanism for all five types of vascular abnormality. It was suggested that following endothelial damage, fluid and macromolecules penetrate into the vessel wall or into the perivascular space where, by incompletely understood processes, they induce vascular wall myocytes to produce collagen, elastin, and basement membrane-like substances. Evidence supporting this mechanism was derived from the common observation of vascular wall edema, from the occasional presence of erythrocytes and leukocytes within the vessel wall, and from experimental data in the literature. Several possible etiologic agents were implicated in the pathogenesis of endothelial and vessel wall injury. These included alcohol itself, acetaldehyde, biogenic amines, and magnesium deficiency. It is probable, however, that there are multiple etiologic factors which affect the small cardiac vessels of the chronic alcoholic. Finally, the proposal was advanced that the nonspecific pathology of the myocardium in chronic alcoholism may be a result of ischemia secondary to disease of the small intramyocardial coronary ateries.


Elevated arterial pressure and postexertional ST-segment depression in middle-aged women. Of ten healthy women, 43 to 61 years of age, four exhibited 1 mm. or more of upsloping ST-segment depression after maximal exercise, using the Bruce multistage treadmill protocol; the other six did not. Cardiac output (direct Fick) was not different in the two groups, wither at rest or during exercise. The women with ST-positive responses were older (56 vs. 51 years) and heavier (relative weights 109 per cent vs. 102 per cent), and their resting mean systemic pressures were higher. Their systemic and pulmonary mean arterial pressures during the last five minutes of upright exercise were significantly higher (P less than 0.001) than those in the ST-negative group. Although the ratio of systemic to pulmonary mean arterial pressures was higher at rest, it progressively fell during exercise in the ST-positive group. Polarcardiographic display of the Frank ECG during the first 3 minutes of recovery after maximal exercise showed significant differences between the ST and T of the two groups. At initial recovery, MS-phi greatly exceeded 10.6 mV. which is sensitive PCG ischemic exercise criterion in the ST-positive group. Although the number of observations is limited, it is concluded that greater hemodynamic stress imposed on the subendocardium by elevated pressures, rather than by any significant functional evidence of restriction in coronary blood flow, probably explains much of the postexertional ST-segment depression after maximal exercise.


Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion. In anesthetized dogs the circumflex and/or the anterior descending coronary artery were briefly occluded (10 to 90 seconds) and ectopic beats occurring during the occlusion or for 60 seconds following release were counted. Control occlusions were alternated with occlusions performed during complete, reversible, unilateral blockade of either the right or the left stellate ganglion. This was achieved with thermodes through which coolant was circulated. In this way the shortcomings associated with stellectomy, which is irreversible, are avoided. Blockade of the right stellate ganglion increased the number of ectopic beats associated with coronary occlusion. The occurrence of episodes of ventricular tachycardia and fibrillation was also greater. By contrast, blockade of the left stellate ganglion reduced or abolished occlusion-induced arrhythmias. These effects are independent of changes in heart rate or vegal activity; they depend solely upon unilateral alteration in sympathetic tone, and are not demonstrable when such tone is low. We suggest that the right and left cardiac sympathetic nerves have a different influence upon cardiac excitability.


The effect of acute hypoxia on the viscoelastic properties of the myocardium. The viscoelastic properties of the isolated rabbit papillary muscle were studied by constructing a semilogarithmic length-tension curve before and after it had undergone 5 minutes of stress relaxation before, during, and after exposure to a solution aerated with 95 per cent nitrogen and 5 per cent carbon dioxide. Stress relaxation was accomplished in each treatment group by a reduction in the tension intercept of the log length-tension curve without significant change in its slope. There was no significant change in either of these parameters between the control, hypoxia, and recovery groups. These findings lead to the conclusions that: (1) the loss of muscle tension during stress relaxation is not due to a change in the elastic properties of the myocardium and (2) hypoxia does not increase the fundamental stiffness characteristics of the cardiac muscle.


Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs. A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.


Spontaneous cardiac tamponade due to sternotomy wire suture. The first case of spontaneous cardiac tamponade caused by wire suture for sternotomy closure is presented. The proper analysis of bloody pericardial fluid, including simultaneous aspirate and venous hematocrit, oxygen content, and coagulation studies, is emphasized. In addition, the causes of acute hemopericardium are reviewed. Spontaneous cardiac tamponade as a potential late complication of cardiac surgery should be considered in the postoperative patient who presents with pericarditis or a sudden change in cardiac status.


A comparison of two impact noise measurement techniques. An impact noise analyzer has been tested to determine its accuracy and precision. Results showed that peak estimation when corrected by a suitable correction factor were good and the confidence limits on the corrected peak determination were less than +/- 1.0 dB. Determination of pulse duration with the meter proved to be poor. At present it is useful for making only general estimations of duration. For exact pulse duration measurements, it appears that development of a small, portable oscilloscope holds the most promise for a field instrument with the necessary accuracy and precision.


Chrome alloy welding fume study.

Chrome alloy welding fume study. Breathing zone samples obtained at a production arc welding operation employing approximately 90 welders demonstrated excessive exposure to chromium from the welding of high chromium alloy steel. Breathing zone samples were collected inside welding helmets. Methods considered for reducing employee exposure included local exhaust ventilation and the use of air-supplied helmets. Air-supplied helmets were chosen as best suited for the production scheme and suitable devices were subsequently developed that reduced breathing zone contaminant levels well below applicable standards.


Personal sampler for nitrogen dioxide.

Personal sampler for nitrogen dioxide. A new type of personal sampler for gases in air, originally reported from this laboratory, has been adapted to measurement of NO2. The sampler depends on the transfer of NO2 by diffusion to a triethanolamine coated collector at the sealed end of a tube; the open end of the tube is exposed to the test environment. The devices are accurate, light, simple to use and have very good shelf life before and after sampling.


The effects of anemia on heme synthesis parameters during lead exposure. The effects of anemia during lead exposures were studied using an infant baboon animal model. When the hemoglobin concentration was reduced to less than 70% of normal, a marked blood lead increase was observed and the free erythrocyte porphyrin value, aminolevulinic acid dehydratase activity and reticulocyte counts increased. Special emphasis should be placed on nutritional effects in lead exposures.


Development of an air purifier for personnel cubicles. An air purifier was developed for tunnel, toll and garage booths or cubicles. Catalytic oxidation, activated carbon and a HEPA filter are used to scrub out CO, hydrocarbons, NO2 and particulates. Tunnel tests showed these air impurities were adequately removed.


Methods of measuring and rating hearing protector performance. This paper reviews various methods that have been used to measure and rate the performance characteristics of hearing protectors. Subjective and objective measurements methods will be discussed with respect to test method, environment and stimuli. A variety of methods for relating protector attenuation data to the requirements of a specific environment will be presented and discussed. The paper includes suggestions for use of this information with environmental data developed from octave band analysis or sound pressure level measured in dBA.


The benzenediols: catechol, resorcinol and hydroquinone--a review of the industrial toxicology and current industrial exposure limits. A review of the published industrial toxicology for the benzenediols, catechol, resorcinol and hydroquinone was made to evaluate their proposed or established occupational exposure levels. Acute animal toxicity data for catecholand resorcinol are presented, along with that for phenol because of its analogous signs of illness and intoxication. The comparative acute toxicity data for catechol and phenol are anomalous, but suggest a TLV for catechol similar to that of phenol. The comparative acute toxicity data for resorcinol and phenol clearly show that resorcinol is significantly less toxic than phenol which has a 5 ppm TLV. These data, along with production plant exposures as high as 9.6 ppm without reported effects, suggest an industrial exposure level (TLV) for resorcinol of at least 10 ppm, perhaps 20 ppm or higher. The established 2 mg/M3 TLV for hydroquinone appears to be proper.


Cardiac amyloidosis, contrictive pericarditis and restrictive cardiomyopathy. Cardiac amyloidosis is not characterized by a single hemodynamic pattern. Some of the cases present the clinical findings of restrictive cardiomyopathy and in these differentiation from constrictive pericarditis remains difficult in spite of the introduction of techniques designed to assess myocardial contractility and ventricular diastolic compliance. The clinical features and the demonstration of left ventricular diastolic pressure greater than right remain the most useful means of distinguishing restrictive cardiomyopathy from constrictive pericarditis. In other cases of cardiac amyloidosis the diastolic pressure is elevated throughout diastole and ventricular ejectile ability is lost. These cases do not simulate constrictive pericarditis and should not be classified as restrictive cardiomyopathy.


Incidence of right ventricular asynergy in patients with coronary artery disease. The effects of coronary artery disease on patterns of left ventricular contractility have been thoroughly investigated. In contrast, little is known about the incidence of right ventricular dysfunction induced by this disease. To evaluate the frequency of right ventricular asynergy, biplane right ventricular cineangiograms were obtained in 26 patients. Seven segmental axes of shortening were analyzed in each end-systolic and end-diastolic frame and normalized as percent decrease (or increase) in axis from end-diastolic length. Of 26 patients, 8 (Group I) served as normal (control) subjects. The remaining 18 patients had significant coronary artery disease; 6 of these (Group II) had no significant disease of the right coronary artery, whereas 12 (Group III) had significant obstruction of this artery. Four patients in Group II had a previous anteroseptal myocardial infarction, and six in Group III had a previous inferior myocardial infarction. There was a progressive decrease in segmental axes of shortening from Group I to II and from Group II to II, but the decrease was not significant at the level P less than 0.01. Only one patient in Group II had frank dyskinetic segmental motion of the interventricular septum (this patient had had a previous anteroseptal myocardial infarction), whereas two patients in Group III had dyskinetic segmental motion of the free right ventricular wall (both had previous inferior myocardial infarction). Therefore, coronary artery disease seldom produces significant right ventricular asynergy. Abnormal septal motion is associated with previous anteroseptal myocardial infarction; however, dyskinetic motion of the free right ventricular wall occurs only in patients with a right coronary arterial lesion and previous inferior myocardial infarction.


Afterload reduction therapy with nitroprusside in severe aortic regurgitation: improved cardiac performance and reduced regurgitant volume. To assess the hemodynamic effects of afterload reduction in severe aortic regurgitation, nitroprusside was infused at cardiac catheterization in 12 patients with aortic regurgitation. Cardiac hemodynamics, angiographic variables and regurgitant volumes were quantified during control periods, and nitroprusside was infused to reduce systemic systolic pressure to 110 to 125 mm Hg. The following were reduced by the drug: systolic arterial pressure (from 154 +/- 6.4 to 115 +/- 2.3 mm Hg, P less than 0.001); left ventricular end-diastolic pressure (from 23 +/- 2.2 to 11 +/- 1.0 mm Hg, P less than 0.001); systemic vascular resistance (from 1,782 +/- 133 to 1,148 +/- 94 dynes sec cm-5, P less than 0.001); left ventricular end-diastolic volume (from 242 +/- 25 to 196 +/- 19 ml, P less than 0.001); aortic regurgitant fraction (from 0.53 +/- 0.05 to 0.44 +/- 0.06, P less than 0.01); and aortic regurgitant minute volume (from 5.5 +/- 0.10 to 4.3 +/- 0.09 liters/min, P less than 0.01). Effective cardiac index increased (from 2.49 +/- 0.19 to 3.10 +/- 0.24 liters/min per m2, P less than 0.01), and left ventricular ejection fraction rose (from 0.55 +/- 0.03 to 0.61 +/- 0.03, P less than 0.005). These data indicate that afterload reduction with nitroprusside in severe aortic regurgitation improves cardiac performance, greatly decreases left ventricular preload and reduces aortic regurgitant volume. Thus, nitroprusside therapy has special value in severe aortic regurgitation that is of particular benefit in critical clinical conditions.


Vectorcardiographic diagnosis of diaphragmatic myocardial infarction. Vectorcardiograms of 31 patients with arteriographic evidence of complete occlusion of the right coronary artery were analyzed in order to evaluate and attempt to improve the vectorcardiographic criteria for the diagnosis of an old diaphragmatic myocardial infarction. The electrocardiogram showed no evidence of a diaphragmatic infarction in 48 percent of these patients. This was advantageous, since the intent of the study was to develop vectorcardiographic criteria that exceeded the capability of the electrocardiogram. The criteria that appeared optimal were: (1) an instantaneous 0.02 second QRS vector equal or superior to 315 degrees (-45 degrees) in the sagittal plane, or (2) ratio of voltages of 0 to left x-intercept to maximal QRS vector greater than 0.22 in the frontal plane. These criteria identified a diaphragmatic infarction in 77 percent of patients (24 of 31) with complete occlusion of the right coronary artery. There were no false positive findings in 40 normal subjects. A group of criteria previously defined by others, based upon rotation, contour of initial forces, duration of superior forces relative to the contour, magnitude of 0 to left x-intercept, and maximal QRS vecotr, was equally sensitive. Other previously defined criteria were less sensitive. The criteria developed in this study, when tested in 22 patients with prominent Q waves indicative of an old diaphragmatic infarction, properly diagnosed the infarction in all 22 patients. All previous criteria also successfully detected infarction in these patients. However, the new criteria identified a greater number of patients without electrocardiographic evidence of diaphragmatic infarction than were identified with previously defined vectorcardiographic criteria unless the latter were complex.


Correlation of electrocardiogram and vectorcardiogram with coronary occlusion and myocardial contraction abnormality. Electrocardiograms and Frank vectorcardiograms were recorded in 156 consecutive patients with total occlusion of at least one coronary artery (on arteriography) and associated left ventricular contraction abnormality (on ventriculography). The angiograms and cardiograms were independently reviewed. In the presence of single vessel occlusion, appropriate vectorcardiographic diagnosis of myocardial infarction was determined in 118 of 156 cases (76 percent) compared with a lower electrocardiographic detection rate in 77 of 156 cases (49 percent). Findings diagnostic of two coexisting infarctions were observed in 71 percent of vectorcardiograms and 37 percent of electrocardiograms in 51 patients with double vessel occlusion and two areas of left ventricular dyskinesia. The vectorcardiographic detection rate was similarly superior to the electrocardiographic rate in the presence of subtotal coronary occlusion and myocardial asynergy in single (73 percent versus 53 percent) and double (53 percent versus 28 percent) vessel disease. The incidence rate of false positive diagnoses was 3 percent for electrocardiography and 4 percent for vectorcardiography. It is concluded that the vectorcardiogram is superior to the electrocardiogram in the diagnosis of obstructive coronary artery disease and left ventricular contraction abnormality.


Dermatoglyphic patterns in patients with mitral valve prolapse: a clue to pathogenesis. Fingerprints were obtained from 100 patients with mitral valve prolapse and compared with those of 100 control subjects matched for sex and race. Arches were found in 16.8 percent of all digital patterns in patients with mitral valve prolapse but in only 2.5 percent of all digits in the control group. Whereas no patient in the control group had four or more arches, 19 percent of patients with mitral valve prolapse had this finding. In addition, arches were found on 16 and 9 percent, respectively, of digits IV and V in patients with mitral valve prolapse but were not found on these digits in the control group. The finding of four or more arches or arches on digits IV or V may be important supportive evidence of mitral valve prolapse when evaluating patients with atypical chest pain and palpitations. Antenatal factors may be involved in the pathogenesis of mitral valve prolapse since it is possible that a genetic or environmental factor that interferes with the development of the mitral valve may also influence epidermal ridge patterns.


Coronary arterial reperfusion. III. Early and late effects on regional myocardial function and dimensions in conscious dogs. Regional myocardial function was studied in five conscious chronically instrumented dogs for 4 weeks after coronary reperfusion following a 2 hour period of occlusion of the left circumflex coronary artery. A cuff and flowmeter were placed around the left circumflex coronary artery, and a micromanometer and three pairs of ultrasonic crystals were implanted 1 cm apart subendocardially in control, marginal and ischemic segments of the left ventricle. Control normal segments showed progressive increases in end-diastolic length and extent of active shortening. Ischemic segments tended to show slight improvement early after reperfusion, but in succeeding weeks, despite some improvement in shortening, they showed progressive decreases in end-diastolic length compatible with subendocardial tissue loss. In marginally ischemic segments, shortening initially remained depressed after reperfusion, but showed late recovery so that shortening and end-diastolic length were not different from control values by 4 weeks. These results contrasted with findings in five similarly studied dogs subjected to permanent coronary occlusion; in that group the data suggested greater tissue loss and less recovery of function in marginal and ischemic segments. The late return of segmental function and reduced loss of subendocardial tissue several weeks after coronary reperfusion suggest that substantial time periods may be required to assess the ultimate effect of therapeutic interventions. The findings further indicate that in this experimental model the usual time constraints for occurrence of irreversible tissue damage do not apply to all of the myocardium within the ischemic zone.


Rechargeable silver-modified mercuric oxide-zinc cell for cardiac pacemakers. Tests were conducted on rechargeable mercury-zinc pacemaker batteries under simulated and actual biologic conditions, using a variety of discharge rates and charging schedules. In tests on 96 cells at a 6.4 milliampere (ma) discharge, recharging once every 15 months of simulated pacing at a 25 microampere (mua) drain, the earliest cell failure occurred after an equivalent of 50 years of pacing. The mean pacing equivalent for all 96 cells was more than 140 years. In 6.4 ma discharge tests on 24 cells, recharging once every 8 days of simulated pacing, only 1 cell in 24 failed after an equivalent of more than 500 years of pacing (actual time 2 years). In tests on 13 cells pacing at a 200 mua drain without recharging, the simulated mean duration of pacing before total discharge was 4.8 years. Seven other cells at a 200 mua drain with periodic recharging continue to function normally after more than 7 years of actual time, simulating 56 years of pacing at a 25 mua drain. Cardiac pacemakers using the rechargeable mercury-zinc cell have been implanted in animals for more than 2 1/2 years and in patients for more than 1 year with all units continuing to function satisfactorily. It has been demonstrated unequivocally that a rechargeable mercury-zinc pacemaker will function continuously for more than 4 years without recharging and that periodic recharging will extend pacing life far beyond that predicted for lithium and nuclear primary power sources.


Left ventricular function by echocardiography in children with fixed aortic stenosis. Left ventricular function was evaluated echocardiographically within 24 hours of cardiac catheterization in 45 children with fixed aortic stenosis. Left ventricular systolic time intervals, mean velocity of circumferential fiber shortening, left ventricular end-diastolic volume and shortening fraction were evaluated. Some patients with severe aortic stenosis had a shortened preejection period, prolonged ejection time and increased mean velocity of circumferential fiber shortening in comparison with normal subjects, but these findings were not consistent within the group with severe aortic stenosis or apparent in patients with mild or moderate aortic stenosis. Left ventricular end-diastolic volume was smaller in children with severe obstruction than in normal children. Evaluation of the shortening fraction provided good separation of patients with significant obstruction from those with mild disease. Further, there was a linear correlation between the shortening fraction and the left ventricular-aortic gradient demonstrated at cardiac catheterization. This correlation was also of use in evaluating the response of patients to surgical relief of obstruction. Pre- and postoperative echocardiographic evaluation of the shortening fraction appears to provide a readily available noninvasive method of assessing the course and severity of obstruction in fixed aortic stenosis in children.


The binding of calcium within the Golgi saccules of the rat odontoblast. Odontoblasts of developing rat molar teeth were treated with OsO4-pyroantimonate to ascertain the localization of calcium. In addition, some tooth germs were incubated in solutions which were intended to allow for the escape of diffusible ions prior to fixation in OsO4-pyroantimonate. In tissues treated directly with OsO4-pyroantimonate, antimonate reaction product was found chiefly in abacus bodies and secretory granules of the Golgi region and in secretory granules in the distal pole of the cell. Lesser amounts of reaction product were found in the extracellular space, mitochondria, nucleus and generally throughout the cell. Tissues pre treated to allow for the escape of diffusible ions showed reaction product, identified as containing calcium, only in the abacus bodies and secretory granules. These results are considered to reflect the binding of calcium within the Golgi apparatus of the odontoblast. Moreover, since it has been shown by others that the abacus bodies and secretory granules contain collagen precursor, it is suggested that the collagen precursor is being seeded with calcium within the Golgi apparatus and that this intracellular calcium binding will play a role in facilitating the major wave of extracellular mineralization of the dentin which is to follow.


Tight and gap junctions in a vertebrate inner ear. The auditory organ of the alligator lizard has been investigated with the transmission electron microscope using methods which distinguish between tight and gap junctions. There is a continuous zone of tight junctions located near the endolymphatic surface of the organ forming a boundary between the endolymph in scala media and the interstitial spaces between the cells. No such tight junctions were observed between the perilymph of scala tympani and the interstitial fluid within the organ. Small gap junctions occur between hair cells and supporting cells and large gap junctions occur between adjacent supporting cells. The locations of the tight junctions suggest that the composition of the intercellular fluid in the receptor organ is probably more like perilymph than like endolymph. The presence of gap junctions between hair cells and supporting cells provides a possible morphological basis for the occurrence of intracellular responses to sound in supporting cells, and for elctric coupling of receptor cells.


Specific response of ovarian and uterine veins of mice to sex hormones. Pellets of glass (control), progesterone (P), testosterone (T), and estradiol-17beta (E) were placed on the mesentery or subcutaneously in the flank in ovariectomized (O) and ovariectomized-hysterectomized (OH) mice, insuring that all or most of the hormone would pass through the superior mesinteric or circumflex iliac veins. After 21 days the diameters of these and of the ovarian, uterine, and femoral veins and inferior vena cava were measured at autopsy. T and E caused significant enlargement of the uteri; E was also responsible for bladder distention. The ovarian and uterine veins enlarged significantly in mice treated with T and E as compared to the controls. All other veins failed to respond to P, T, and E. The evidence demonstrates a specific response of ovarian and uterine veins in O and OH mice to T and E.


The fine structure of the digital corpuscle of the mouse toe pad, with special reference to nerve fibers. Digital corpuscles in the dermal papillae of the mouse toe pad have been studied using light and electron microscopy of serial thick and thin sections, and silver impregnations of frozen sections. These corpuscles are ellipsoid in shape and approximately 10-30 mum in diameter. They consist of one to three lamellar cells, nerve fibers and a capsule. These digital corpuscles are regarded as small Meissner corpuscles. The capsule is perineural epithelium. One or two myelinated nerve fibers and occasionally an unmyelinated nerve fiber enter the corpuscle. The axon terminals contain many mitochondria and a variable population of vesicular profiles. These terminals are ellipsoid or discoid in shape with the long axis parallel to the skin surface. The cytoplasmic plates (or lamellae) of the lamellar cells are arranged parallel to the skin surface, as is the cleft between the bilaterally symmetrical stacks of lamellae. Small processes extend from the expanded terminal of the neurite into the cleft between the lamellae. The relationship of the neurite terminal and associated lamellar cells resembles in some respects the organization of the inner core of Pacinian corpuscles. Intraepidermal fibers derived from myelinated neurites of the corpuscle may extend to the superficial epidermis. Intraepidermal fibers derived from unmyelinated neurites usually terminate in the basal regions of the epidermis.


Dissociation of epithelial cells from rabbit trachea and small intestine with demonstration of APUD endocrine cells. In this study the entire epithelial lining of tracheas and a 15-cm segments of small intestine were dissociated into individual cell components after 45-minute incubation with 1% pronase. Light and electron microscopy of isolated cells confirmed good morphologic preservation of various epithelial cell types dissociated from the trachea and small intestinal mucosa. Of particular interest was the recovery and preservation of APUD endocrine cells, which are known to be widely dispersed amongst various non-endocrine epithelial cells in both the trachea and small intestine. The APUD cells were demonstrated in dissociated cell preparations by a formaldehyde-induced fluorescence method, Grimelius' silver nitrate stain, and electron microscopy. The isolated APUD cells retained their characteristic features, e.g., amine-handling properties, argyrophilia and cytoplasmic dense-core vesicles. The cell dissociation method described in this report provides high yields of viable epithelial cells in single cell suspensions which are suitable for further cell separation into homogeneous populations of single kinds of cells, including the APUD endocrine cells. Availability of methods for isolation of tracheal and intestinal APUD cells will facilitate further studies, in vitro, on secretory, metabolic and functional aspects of these cells.


Secretion by parafollicular cells beginning at birth: ultrastructural evidence from developing canine thyroid. The ultrastructure of developing canine parafollicular cells has been examined. The hypothesis that secretion is relatively inactive prior to birth but very active at and following birth was tested. Parafollicular cells develop and accumulate characteristic secretory granules prior to birth. However, there is little or no evidence of exocytosis at this time. At birth and during the neonatal period, but not in adult thyroids, signs of exocytosis of granular contents by parafollicular cells are abundant. Just prior to the expected date of birth and before evidence of exocytosis appears, parafollicular cells accumulate intracisternal granules within rough endoplasmic reticulum. These observations are consistent with the view that parafollicular cells first become actively secretory around the time of birth and are more active at this time than in early fetal or later adult life.


Effect of puromycin on the ultrastructure of keratohyalin granules. Keratohyalin granules (KHG) from control and puromycin-treated hamster cheek pouch epithelium were studied by electron microscopy. The animals were killed 1-4 hours after injection with 75-100 microgram puromycin per gram body weight; controls were injected with saline. The KHG from control animals were round or oval and consisted of a finely granular background matrix containing many small, round, homogeneous electron-dense deposits. The KHG from puromycin-treated animals showed marked variation in morphology and size. They consisted of a coarse granular or speckled matrix and round, club-shaped or comma-shaped electron-dense deposits. Since puromycin is known to inhibit protein synthesis, alterations in KHG structure support previous reports suggesting the protein nature of KHG.


Isoantigen ABH in cervical intraepithelial neoplasia. The purpose of the study was to examine the relationship between the histologic findings and the presence or absence of ABH isoantigens in intraepithelial neoplasia of the cervix. After the lesions were graded by four pathologists, the Red Cell Adherence (RCA) test was done to demonstrate the ABH antigens, and the results of the two were compared. The correlation between the morphologic diagnosis and the results of the RCA test was limited. The percentages of tissues giving positive (+) or positive-negative (+/-) reactions were very similar in intraepithelial neoplsia (59.2%) and normal squamous epithelium (58.4%). The relationship of the RCA test results and behavior of the lesion was not studied.


Carcinoma of the cervix. Clinicopathologic correlation of 196 cases. One hundred ninety-six cases of patients with invasive squamous carcinoma of the cervix treated at the Mayo Clinic from 1960 to 1970 were evaluated for survival. All patients had been followed for at least five years; treatment was surgical, irradiation, or a combination of the two. The probability of survival was compared with grade and histologic type, with clinical staging taken into consideration. No significant difference in prognoses was found between grades or histologic type of tumors within any stage. As expected, advanced stages were associated with poorer survival rates than localized disease. Within patients who had Stage 1 disease, metastatically involved lymph nodes did not significantly diminish the probability of survival.


Two cases of enteric myiasis in man. Pseudomyiasis and true intestinal myiasis. Dipterous larvae were found in the appendices from two postmortem examinations. The single maggot in the first case was not immediately identified in the sections. However, when the posterior end of the larva was recovered from the unsectioned portion of the appendix, it was identified as a maggot of the genus Sarcophaga. The first case was believed to be a case of "pseudomyiasis,+ i.e., the accidental entrapment of a swallowed larva passing through the digestive tract. In the second case, the appendix contained numerous larvae with great variation in sizes and stages of development of the mouth hooks, pharyngeal sclerites, and spiracular breathing plates. Such development was considered to have occurred within the intestinal tract, which indicated that this was a case of true intestinal myiasis.


Lymphomatoid granulomatosis of the lung, associated with a long history of benign lymphoepithelial lesions of the salivary glands and lymphoid interstitial pneumonitis. Report of a case. A case of a man who had bilateral benign lymphoepithelial lesions of major salivary glands, subsequently had lymphoid interstitial pneumonitis at the age of 26 years, and progressed to lymphomatoid granulomatosis of the lung at the age of 42 years is reported, A labial gland biopsy was consistent with Sjögren's syndrome, which the patient was clinically suspected of having although his disease lacked many of the classic clinical features of that disorder. There was no evidence of malignant lymphoma of lymph nodes. Immunoglobulin distribances were minor, limited to slightly elevated IgG.


Pulmonary cytopathology of former asbestos workers. Report of the first year. Five hundred fifty-four workers, 84% of whom are chronic cigarette smokers, have been examined during the past year with emphasis on the role of sputum cytopathology in the early detection and diagnosis of lung cancer. Of the 554, 232 (42%) have shown squamous metaplasia, 44 (8%), mild to moderate atypias, 18 (3.2%), severe atypias, and two (0.4%), squamous carcinoma. Both of the carcinomas were in x-ray negative, cytopathology-positive elderly cigarette smokers. Ferruginous bodies have been found in the sputa of 187 (33%) workers. Ferruginous bodies in the sputum do not appear to be a marker for severe atypias; rather, their presence correlates best with duration and extent of industrial exposure to asbestos.


Ultraviolet spectrophotometric analysis of barbiturates. Current assessment as an emergency screening procedure. Several laboratory methods are currently available for the detection of barbiturates, but few are suitable for emergency use, The  authors evaluated use of an ultraviolet spectrophotometric method as a screening procedure and compared the results with results obtained by other barbiturate methods (colorimetric, gas-liquid chromatographic, and immunochemical), Procedure time was approximately 40 minutes, sensitivity 0.2 mg/dl, precision (coefficient of variation) 5.4%, recovery 97.8% for phenobarbital, and there was good correlation with results obtained by gas-liquid chromatography and the EMIT system for phenobarbital. The authors recommend ultraviolet spectrophotometry as an excellent screening procedure for assessing the severity of barbiturate intoxication.


Levels of immunoreactive glycine-conjugated bile acids in health and hepatobiliary disease. A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.


A quality control program for the radioimmunoassay laboratory. The major problems in applying quality control to radioimmunoassay measurements are (a) nonlinearity of the dose-response curve, and (b) nonuniformity of the residual variance. A logit-log transformation of the dose-response variables combined with an iterative weighted regression analysis appears to overcome most of the difficulties. This technic is particularly helpful when applied to substandard runs where extraneous standard points tend to distort assay results. The authors describe a quality control program that involves recording control values on calendar and histogram formats, monitoring assay variables by charting, and comparing the computer-calculated slope with the graphic plot to reveal "outliers." This program is useful in guiding technologists to locate possible causes for "out-of-limits" runs.


Radioisotopic assay of vitamin B12 in tissues. The present study delineates the application of the radioisotopic competitive-inhibition assay for the measurement of vitamin B12 in tissues. The extraction of endogenous B12 from tissues was shown to be simple and complete. Proportional dilution studies suggest that tissue factors do not interfere with the assay. Although some variability exists when multiple areas of an organ are sampled, the differences between B12 levels in tissues obtained from normal individuals and B12-deprived individuals are so wide that individual intra-organ variability is trivial, As this tissue B12 assay is similar to the widely utilized radioisotopic assays for serum B12, it is applicable for routine use.


Routine erythrocyte measurements in diagnosis of iron-deficiency anemia and thalassemia minor. A study was made of the routine electronic measurements of erythrocyte size and hemoglobin concentration in blood samples from 122 patients with decreased transferrin saturation and 66 patients with elevated levels of hemoglobin A2 or F. The medical histories of these patients were reviewed to identify 52 cases of uncomplicated iron-deficiency anemia and 39 cases of uncomplicated thalassemia minor. Four decision functions were compared for separating these two disorders. The functions evaluated were: D.F'. = MCV--[5 X Hb]-RBC; ratio MCV/RBC; ratio MCH/RBC, and RBC. The rules performed better in the uncomplicated cases than in the routine laboratory defined cases. Only minor differences in the performances of the various decision functions were observed. None was sufficiently accurate for final diagnosis, but they should have value in screening patients and in determining which additional test should be considered.


Effects of hemoglobin F levels, KCN, and storage on the isopropanol precipitation test for unstable hemoglobins. Although the isopropanol precipitation test is a commonly used and sensitive test for detecting unstable hemoglobins, false-positive reactions are frequently observed. In this study, the storage temperature of the test samples, type of stored sample amount of fetal hemoglobin (Hb F) in the sample, and presence of potassium cyanide (KCN) in the hemolysate preparation all affected the accuracy of the test. The addition of 2% KCN to samples before testing eliminated or greatly reduced false-positive reactions. Hb F levels greater than 4% caused false-positive results. When specimens with Hb F levels less than 4% were stored at 4C and as whole blood, they showed no false-positive reaction for as long as two weeks. However, duplicate specimens stored as whole blood but unrefrigerated and those stored as hemolysates showed false-positive reactions after three days.


An evaluation of the Haema-Count MK-40 blood counting system. The Haema-Count MK-40, a semiautomated blood counting system, determines hemoglobin, erthrocyte count, leukocyte count, and hematocrit values of blood cell suspensions prepared with a small automatic pipetter-diluter. It is similar to the MK-3, which the authors previously evaluated, but has automatic coincidence correlation and a modified prime and rinse cycle. Its performance was compared with those of standard methods, i.e., the single-channel Coulter Counter and manual cyanmethemoglobin and microhematocrit methods. Precisions for hemoglobin determinations and for leukocyte and erythrocyte counts were equal to those of the reference (comparative) methods. Patients comparisons for those determinations had only small intermethod variability and small clinically insignificant biases. The hematocrit channel was the least precise. With a modified method of calibration, the authors obtained patient comparisons without statistically significant bias from the microhematocrit. Calibration was stable for all channels during the course of the study.


Progress report: the activated coagulation time of whole blood (ACT). The activated coagulation time of whole blood (ACT) has, in the nearly ten years since its first description in the literature, proven itself one of the best laboratory tests for the control of heparin therapy, both for patients undergoing treatment for thromboembolic disease and for those on extracorporeal circulation. It is simple, largely free from subjective variation, precise, and quick. Prolongation of the ACT in the heparinized individual is directly proportional to the concentration of heparin in the blood, and the test accurately reflects the semilogarithmic disappearance of the anticoagulant effect in most patients. In addition, the test serves well as a bedside screening test for deficiencies of the intrinsic coagulation mechanism. The author summarizes the sutdies that have been carried out on this technic since its original description, and briefly presents three protocols for heparinization of patients who have thromboembolic disease.


A modified leukocyte nitroblue tetrazolium test in acute bacterial infection. The increased ability to leukocytes to reduce nitroblue tetrazolium (NBT) has been used to detect the presence of systemic bacterial infection. This test has been utilized to evaluate infections and leukocyte dysfunction in children, but has not been extensively applied to traumatized patients or infected volunteers. Moreover, the technic as originally described presented methodologic difficulties. In this study of 889 such patients, a modified NBT test provided excellent differentiation of 63 systemic bacterial infections (NBT score greater than or equal to 10%) from non-infectious fevers, local enteric diseases, and certain viral and plasmodial infections (NBT score less than or equal to 9%). Splenectomy was associated with a transient false-positive score and clinical typhoid fever with a false-negative response


Haemophilus paraphrophilus endocarditis in a prolapsed mitral valve. A case of Haemophilus paraphrophilus endocarditis successfully treated with ampicillin is described. The patient, a 24-year-old woman, had a prolapsed mitral valve. The organism was initally misidentified as H. parainfluenzae, which it closely resembles. H. paraphrophilus is distinguished by its requirement of 10% CO2 for growth on NaCl-free medium and its inability to ferment xylose.


Sudden infant death syndrome. A prospective study. One hundred twenty-five sudden infant death syndrome (SIDS) victims followed up since birth from a large prospective study were compared with matched controls. Some of the future SIDS victims showed evidences of neonatal brain dysfunction including abnormalities in respiration, feeding, temperature regulation, and specific neurologic tests. These abnormalities could not be ralated to events in labor or delivery. A greater proportion of the future victims were mildly underweight for gestational age. The gestations that produced the SIDS victims were characterized by a greater frequency of mothers who smoked cigarettes and had anemia. The demographic profile of SIDS families proved to be indentical to the profile for families with excessive perinatal mortality. Many of the SIDS victims showed a retardation in postnatal growth prior to death.


Screening for cell-mediated immunity in children. Skin testing and in vitro lymphocyte blastogenesis with Monilia and tetanus toxoid were examined as methods of screening cell-mediated immunity (CMI) in infants and children. With increasing age, all assays were more likely to be positive. Tetanus toxoid was a better single screening antigen than Monilia, particularly for young infants. Combining all assays, at least one was positive in 88% of children over 6 weeks of age. Combining the two skin tests, at least one was positive in 73% of children in the same age range. Results for the blastogenic assays indicated that this in vitro test is more sensitive than the in vivo skin test for demonstrating CMI to these two antigens. Infants with documented histories for Monilia diaper rash had a significantly higher probability of having a positive skin or blastogenic reaction with Monilia.


Radionuclide imaging of airway obstruction following assisted ventilation. Radioaerosol lung scintigraphy was performed in five infants in whom obstructive airway complications developed following assisted ventilation. These studies suggest that a primary functional defect was obstruction to airflow at the level of the major airways, which occurred during expiration. Perfusion lung scintigraphy showed areas of diminished or redistributed pulmonary blood flow, which, like the results of the radioaerosol scintigraphic studies, are findings often associated with adult chronic obstructive pulmonary disease.


Erythrocyte survival in children as studied by labeling with stable 50Cr. The survival of 50Cr- and 51Cr-labeled autologous and/or homologous erythrocytes was compared simultaneously in eight pediatric patients and one adult. 50Cr, a stable, nonradioactive nuclide, had values comparable to those of standard radioactive 51Cr labeling. The data also demonstrated the capability of 50Cr-51Cr labeling to reveal differences in survival between two populations of erythrocytes monitored simultaneously in the same individual. The technique permitted the use of the nonradioactive isotope in volumes of blood that are appropriate for the pediatric age group.


The 2p partial trisomy syndrome. Duplication of region 2p23 leads to 2pter in two members of a t(2;7) translocation kindred. Strikingly similar abnormalities were present in two severely retarded children, an 8-year-old boy and a 12-year-old girl, who were first cousins once removed. Dysmorphic features included high bulging forehead with frontal upsweep of hair, flat, wide glabella and nasal bridge, maxillary hypoplasia, ptosis, dacryostenosis, dolichostenomelia, hyperextensible fingers with subluxation in proximal interphalangeal joints, hypoplastic external genitalia, and overconstriction of the shafts of all long bones. Both patients had unbalanced karyotypes, with duplication of the distal third of the short arm of chromosome 2, resulting from the same balanced reciprocal translocation prestne in both mothers: der (2), t(2;7)(p23;q36)mat. Seven additional translocation carriers were identified in four generations of this kindred.


Heat stroke in infancy.

Heat stroke in infancy. We observed a 16-month-old infant with residual brain damage following a heat stroke from being left in a parked automobile. In contrast with adults, in whom heat stroke usually follows strenuous exercise, the condition in infants usually results from excessive environmental temperature and/or dehydration. Early recognition of the illness is imperative. Three cardinal freatures are hot, dry skin, central nervous system disturbance, and hyperpyrexia. Immediate treatment should be aimed at improving circulation with volume expanders and rapid cooling. Other supportive measures may be necessary to control seizures, renal failure, hematologic abnormalities, or hepatic involvement.


Malignant pheochromocytoma in childhood. A child had malignant pheochromocytoma. Her tumor originally was thought to be a benign one, but persistent elevation of catecholamine values in the post operative period, and consequent appearance of lytic bone lesions, proved her disease to be metastatic. Malignancy is rare in this tumor, and difficult to diagnose even with sophisticated biochemical radiologic techniques. Treatment with chemotherapy and radiation failed to halt the spread and growth of this patient's tumor.


Gastroesophageal reflux with protein-losing enteropathy and finger clubbing. Finger clubbing, protein-losing enteropathy, and iron deficiency were documented in three children with severe gastroesophageal reflux. One patient had Sandifer syndrome and the other two had the rumination syndrome. In each case, surgical repair of the gastroesophageal reflux resulted in immediate clearing of signs of the Sandifer syndrome, gastroesophageal reflux, and anemia and the return of serum protein levels to normal. There was definite regression of the finger clubbing during the ensuing year. It is suggested that finger clubbing, protein-losing enteropathy, Sandifer syndrome, and rumination be viewed as parts of an extended syndrome of unusual presentations of gastroesophageal reflux.


Calcified right ventricular fibroma causing outflow obstruction. Report of a case with successful excision. A 5-year-old boy with clinical findings of pulmonic stenosis was found to have a large calcified mass in the right ventricular outflow region and a gradient of 120 mm Hg between the right ventricle and the pulmonary artery. At surgery, an ovalshaped tumor attached to the interventricular septum and obstructing the right ventricular outflow tract was removed. The child survived and is doing well. Histologically, the tumor had the characteristics of fibroma. A hemodynamic study three months after surgery showed almost complete abolishment of the gradient. To our knowledge this is the fifth reported case of calcified right ventricular fibroma with successful operation. In childhood intracardiac calcifications, together with obstruction, are highly suggestive of this lesion.


Myelopathy in infancy complicating congenital atlantoaxial dislocation. Two infants had congenital atlantoaxial dislocation associated with myelopathy. One of them, a 3-month-old girl, showed anterior dislocation of the atlas on the axis, and had extreme weakness of the extremities. Another patient, an 8-month-old boy, showed tetraplegia, and posterior dislocation with absent odontoid process was demonstrated radiologically. These cases add another cause to the varied etiologies of floppiness in early infancy.


Symptomatic gastroesophageal reflux: incidence and precipitating factors. The incidence and precipitating factors associated with symptomatic gastroesophageal reflux were evaluated by a questionnaire in 446 hospitalized and 558 nonhospitalized subjects. Of 385 control subjects 7% experienced heartburn daily, 14% noted heartburn weekly, and 15% experienced it once a month, giving a total of 36% of subjects having heartburn at least monthly. Daily heartburn occurred at a significantly greater (P less than 0.05) rate for 246 medical inpatients (14%) and for 121 patients seen in outpatient gastroenterological clinic (15%). Pregnant women seen in uncomplicated obstetrical clinic had symptoms of significantly greater (P less than 0.01) incidence: daily (25%) and at least once monthly (52%). Age, sex, or hospitalization did not significantly affect incidence. Fried foods, "spicy" foods, and alcohol were the most common precipitating factors.


Sugar absorption by small bowel biopsy samples from patients with primary lactase deficiency and with adult celiac disease. The present study was undertaken to compare the 3-O-methyl-D-glucose (3MG) absorption by jejunal biopsies from normal human subjects (N = 3) with that by the jejunum of the rat (N = 8) and of the hamster (N = 8), and to examine whether jejunal biopsies from normal subjects (N = 3), patients with primary lactase deficiency (N = 5) and from patients with celiac sprue (N = 5) follow the same pattern of sugar absorption as usually observed in vivo. The results indicate that under the conditions of our experiments the estimated affinity of carrier for 3MG (ie, apparent Km) in the biopsies from normal subjects did not differ significantly from that in rat or hamster jejunum. The estimated capacity of carriers for 3MG absorption (ie, Vmax) appeared to be similar in biopsies from normal subjects and in hamster jejunum, but significantly lower in rat jejunum. There was no difference in apparent Km between the biopsies from normal subjects and those from the patients with lactase deficiency. Although the Vmax for the lactase deficient patients was substantially higher than that for the normal subjects, the difference was not statistically significant. The absorption of 3MG by the biopsies from patients with celiac sprue did not follow Michaelis-Menten kinetics and was compatible with that of passive diffusion or low saturation conditions. Since the intracellular concentration of 3MG in all biopsies from celiac patients exceeded the concentration of the media, sugar transport could not have occurred by diffusion, and it is concluded that the absence of Michaelis-Menten kinetics was the result of low saturation conditions. This active transport with low saturation kinetics in patients with celiac disease suggests that in these patients not only the number of functioning carrier molecules is diminished but also the affinity of the existing carrier for sugar molecule is reduced. This situation, at least in some patients, seems to improve after treatment with gluten-free diet.


The effects of VIP on intestinal motility: study on ex vivo perfused isolated canine jejunal loops. The effects of VIP on intestinal motility were studied on isolated canine jejunal loops ex vivo perfused at normothermia, under pulsatile flow with heparinized, oxygenated and nonrecirculated canine whole blood, by means of an intraluminal balloon. VIP was administered intraarterially either by 1 min injections or by long-time infusions. The results showed that for arterial concentrations of the polypeptide ranging between 25 pg/ml and 300-500 pg/ml a fast but short-lasting relaxant effect was observed. For higher concentrations VIP usually produced a biphasic response: The relaxant effect is followed by an increase of the basal muscular tone often accompanied, for concentrations higher than about 25 ng/ml, by a marked and transient increase in amplitude of the intestinal rhythmic contractions. During long-time infusions a biphasic response was also observed but both effects were of short duration. A cholingeric origin of the secondary contracting phase was expected but could not be demonstrated because, at blood concentrations at which atropine affected the biphasic response, not only was the contractile effect abolished but also the initial relaxing phase. It is suggested that the secondary contraction may be a "rebound excitation" of myogenic nature or a result of noncholingeric excitatory fiber stimulations. The short-lasting relaxant effect observed under the present experimental conditions, even during long-time infusion of the polypeptide, fails to argue for an important physiological role of VIP as an hormonal inhibitor of intestinal motility. The biphasic response, however, might have a physiological significance in so far as the aboral propulsion of the intestinal content requires a muscular inhibition which rapidly changes to contraction.


Effect of nicotine on serum secretin and exocrine pancreatic secretion. The effect of nicotine (100 mug/kg hr-1) on serum secretin and pancreatic secretions was studied in dogs with chronic pancreatic fistulas. Release of immunoreactive secretin (IRS) was stimulated by intraduodenal infusion of HCl (9.6 mEq/30 min). Pancreatic flow rate and bicarbonate and protein secretions were stimulated either by intestinal acidification or infusion of exogenous secretin (1.0 IU/kg hr-1). It was found that nicotine delayed the appearance of peak IRS concentrations in response to intraduodenal HCl by about 20 min. However, nicotine had no effect on the total amount of IRS released nor was this delay accompanied by a similar delay in the appearance of peak bicarbonate output. Furthermore, nicotine did not affect pancreatic secretory function stimulated by either HCl or exogenous secretin. These data do not support the thesis that nicotine plays an important role in the pathogenesis of duodenal ulcers in smokers by inhibiting the pancreatic secretion of bicarbonate.


Acinar pancreatic tumor with metastatic fat necrosis: report of a case and review of rheumatic manifestations. This report deals with a pancreatic tumor associated with metastatic fat necrosis. Our patient displayed the full gamut of nodular panniculitis, polyarthritis, fever, eosinophilia, hyperlipasemia, lytic bones lesions, and marrow fat necrosis. The rheumatologic features are reviewed. Elevated serum lipase is a most helpful laboratory confirmation. The tumor in our patient presented a difficult problem in classification. Although the appearance under light microscopy was most compatible with islet cell carcinoma or islet cell carcinoid, the ultrastructural characteristics were those of acinar carcinoma.


Electrical spike potentials of the small bowel: a comparative study of recordings obtained from muscular implanted and intraluminal suction electrodes. Electrical spike potentials from the canine duodenum have been recorded from intramuscular implanted and intraluminal suction electrodes. There was a significantly greater amplitude of the spike potentials recorded from implanted electrodes, otherwise the potentials were identical in number, duration and time of onset. Thus spike potentials recorded from suction electrodes, as used in clinical motility studies, accurately represent the event within the muscular layer.


The effect of regression to the mean in epidemiologic and clinical studies. In this paper, we have noted the ways in which regression to the mean can affect the measurement of treatment effects in clinical and epidemiologic studies. It is apparent that regression can have a sizeable effect and may lead to erroneous conclusions concerning treatment effects. Thus, the procedures outlined here should be useful in taking regression into account at the planning stage as well as at the time of analysis.


The descriptive epidemiology of primary intracranial neoplasms: the Connecticut experience. The age-specific incidence pattern for tumors of the brain and cranial meninges in Connecticut over a 30-year period shows an early peak followed by a taller and sharper peak with a maximum in the 55-65 year age group. This overall curve reflects the pattern shown for glioblastoma, the tumor accounting for the majority of the histologically confirmed cases. The reported rates are probably underestimates of the actual rates. The various histologic types of brain tumors reveal sufficiently distinct epidemiologic patterns to be considered as separate diseases.


A statistical note on the association of colorectal cancer and lymphoma. Four patients are presented who were ascertained to have synchronous primary neoplasms-adenocarcinoma of the colon and lymphoma. The age-specific incidence of these lesions is used to compute the expected incidence of this joint occurrence in the aggregate. A hypothesis is proposed to explain the association between adenocarcinoma of the colon and lymphoma. The available data concerning the incidence of multiple primary malignancy of different organs is briefly discussed. It is suggested that data pertaining to multiple primary malignancies of different organs is confused as a result of pooling heterogeneous groups.


Cancer mortality and asbestos deposits.

Cancer mortality and asbestos deposits. Asbestos deposits are found in many parts of the United States. In this paper the question is asked: Is there an increase in risk from cancer associated with naturally-occurring asbestos? In an attempt to control for the urban effect, geographic gradient and socioeconomic class, each county in the United States with asbestos deposits was matched for percent of area that was urban and for median years in school with two nearby counties that did not have known asbestos deposits. The study of cancer mortality rates in these matched counties provides no evidence that naturally-occurring asbestos is a great hazard to the general population of counties with asbestos depostis.


Sex, birth order, and maternal age characteristics of infants with congenital heart defects. The records of the New England Regional Infant Cardiac Program, a service program covering all of New England, provide a useful source of information about the characteristics of children born with congenital heart defects. Data were analyzed on more than 2000 children born in New England who were diagnosed with a congenital heart defect before the first birthday. Children with arterio-venous fistula, aortic stenosis, transposition of the great arteries or hypoplastic left ventricle were predominantly male; children with persistent ductus arteriosus and endocardial cushion defect were predominantly female. Positive trends in risk with increasing birth order were present for pulmonic stenosis and transposition of the great arteries, and a negative trend was seen for persistent ductus arteriosus. What evidence there was for associations with maternal age was greatly reduced after controlling for confounding by birth order.


Comparative incidence of gonorrhea and nongonococcal urethritis in the United States Navy. The relative frequency of gonorrhea and nongonococcal urethritis was studied among all active duty US Navy and Marine Corps personnel. Between 1966 and 1974, the incidence of the two diseases increased in parallel fashion, reaching 80.2 cases of gonorrhea and 61.8 cases of nongonococcal urethritis per 1000 average strength in 1974. The 56,457 cases of gonorrhea and 43,538 cases of nongonococcal urethritis reported in 1974 were unevenly distributed geographically. In the United States that year, nongonococcal urethritis was the more commonly reported condition, with 32.9 cases per 1000 average strength per year compared to 28.6 for gonorrhea; and, for the last four years, the ratio of the two was 1.05 cases of nongonococcal urethritis for each case of gonorrhea. These findings imply that nongonococcal urethritis is a significantly greater problem than has been generally recognized.


The risk of meningitis among classroom contacts during an epidemic of meningococcal disease. During an epidemic of meningococcal disease in Belo Horizonte, Brazil, a retrospective survey was carried out to assess the risk of meningitis associated with exposure in a schoolroom. Forty-seven of 17,012 students reportedly had meningitis in August-November 1974, an incidence of 276 per 100,000. Four of 1356 students with classroom exposure to a case contracted meningitis (secondary attack rate, 295 per 100,000). The results indicate that in the population surveyed, 95% of whom were from 7 to 14 years of age, there is no significantly increased risk associated with classroom exposure to a student with meningitis. Antibiotic prophylaxis of classroom contacts is therefore not indicated and should be reserved for contacts known to be at increased risk, such as members of the patient's household or those having direct contact with the patient's oral secretions.


A longitudinal study of Mycoplasma pneumoniae: infections in Navy recruits by isolation and seroepidemiology. A longitudinal serologic study of M. pneumoniae infections in two recruit training centers with grossly different climates showed that the frequency of this infection peaks in the late summer-early fall and to a lesser degree in the spring at both training centers. Seroconversions (four-fold or greater increase in titer) were as high as 45-57% in some recruit companies during the late summer peak. M. pneumoniae isolations from men admitted to the dispensary or hospital with pneumonia during the major peak season were as high as 32%. While M. pneumoniae infections are not generally life-threatening, the high incidence of infections observed in personnel during recruit training is of major concern and warrants consideration of effective control measures.


Hemodialysis-associated hepatitis: report of an epidemic with further evidence on mechanisms of transmission. In the period January-September 1974, 50 cases of hepatitis B infection occurred among a nephrology center's hemodialysis patients and staff. The in-center patient population had an attack rate of 96%. Epidemiologic analysis of risk factors for patients revealed an association between the receipt of intravenous medication and the subsequent development of hepatitis, suggesting that parenteral inoculation was a mode of spread among patients (p equals .008). Nineteen per cent of the staff contracted hepatitis, and all of these personnel had had close contact with patients (p equals .005). The prevalence of hepatitis B infection in staff was related to the failure to use gloves (p less than .01), and accidental needle puncture was associated with the development of clinical hepatitis. These data suggested that disease was transmitted to staff by contact with contaminated blood or close personal contact with patients. Additional data showed that the presence of endogenous antibody protected both patients and staff from antigenemia (p equals .002). These data support the hypothesis that contact with blood is the primary mechanism of spread of hepatitis B in dialysis units, and suggest that, as preventive measures, gloves should be used and antibody-positive staff should dialyze antigen-positive patients.


Tables and formulas for extended use of the Ederer-Myers-Mantel disease-clustering procedure. The principles of the Ederer-Myers-Mantel procedure for seeking evidence of disease clustering are reviewed. The procedure is based on cumulative empirical clusters, i.e., the largest frequency in a single time period or in two successive time periods, and comparing that cumulation with the expected cumulation of largest frequencies under random occurrence. Original tabulations covered totals of up to 15 cases distributed among three, four or five time periods. Present tabulations of expectations and variances cover up to 500 cases distributed among two or three time periods and 200 cases distributed among four or five time periods. Asymptotic formulas are provided for the expectation and variance of the largest frequency in a single period when arbitrarily many cases are distributed at random among two, three, four or five time periods.


Arteriovenous shunts in the human spleen. The mission of this study was to determine whether or not arteriovenous connections, indicative of a "closed" type of circulation, existed in the human spleen. Spleens from four patients requiring therapeutic splenectomy were the basis for this report. Scanning electron microscopy of plastic corrosion casts, prepared from these four spleens, revealed direct vascular conduits between splenic pulp arteries or arterial capillaries and the venous sinuses in the red pulp. Also demonstrated were a few arteriovenous shunts between pulp arteries or arterial capillaries and pulp or trabecular veins. Inclusion of sized microspheres in low-viscosity perfusion plastic illustrated that some diameters of the connecting shunts were 7-10 mum, with other shunts even smaller. Not only do arteriovenous connections exist in human spleens, but their frequency, as revealed by methods accentuating three-dimensional aspects of the splenic microcirculation, justify future reconsiderations of the functional significance of this closed type of circulation. Examination of samples of the same intact spleens, prepared by freeze-fracture and conventional critical-point drying, also revealed an "open" type circulation structure, namely, pore-patterned sinus walls that could facilitate blood cell movement from pulp cords into venous sinuses. Scanning electron microscopy thus has provided direct evidence that human spleens have both "open" and "closed" circulatory pathways in their microvasculature.


The activities of uroporphyrinogen synthetase and cosynthetase in congenital erythropoietic porphyria (CEP). Normal or increased amounts of series III porphyrins with greater amounts of series I were observed on incubation of PBG in hemolysates of congenital erythropoietic porphyria vs. normal erythrocytes, human or bovine. Correlation with reticulocyte percentage was poor, in the aggregate a general trend toward increased values of both isomers I and III was noted with increasing reticulocytes. When the percent of type III was low the net amount was increased as compared with normal. Hemolysates of non-porphyric, reticulocyte-rich red cells (hemolytic or posthemorrhagic anemia) formed only minute amounts of type I porphyrin but at the same time no more, or even less type III than the porphyric hemolysates, although representing red cells of greater reticulocyte content. No evidence of deficient heme synthesis was observed in porphyric hemolysates incubayed with [14C]-porphobilinogen or 59Fe. Other studies of porphyric hemolysates incubated with and without added mouse spleen synthetase failed to reveal evidence of an absolute UPG-III cosynthetase (Co-S) deficiency. The large increases of type I porphyrin with normal or increased formation of type III, both in the disease and in the hemolysates, are believed due to a primary increase of ALA-S or UPG-S activity rather than a decrease of Co-S. Possible mutations which might be responsible for this increase are considered.


Clinical, hematologic and biosynthetic studies in sickle cell-betao-thalassemia: a comparison with sickle cell anemia. The diseases commonly confused with sickle cell anemia include sickle cell beta-thalassemia in which synthesis of betaA-chains are completely suppressed (HbS-betao-thalassemia). We obtained hematologic measurements and studied globin biosynthesis in five patients with this disorder and compared the results with those obtained in five patients with "mild" sickle cell anemia and seven individuals with sickle cell-beta-thalassemia having hemoglobin A levels of 20-30% (HbS-beta+-thalassemia). A distinction between HbS-betao-thalassemia and sickle cell anemia was not always possible on clinical, hematologic, or electrophoretic grounds. Thalassemia heterozygotes had hypochromia and microcytosis, not generally a feature of sickle cell anemia, although overlap of values did exist. The ratio of alpha to non-alpha, or alpha to betaS-chains in sickle cell anemia approximated unity, whereas patients with HbS-betao-thalassemia had a deficit of beta-chain production relative to that of the alpha-chain. The differentiation of HbS-betao-thalassemia and sickle cell anemia can be best made on the basis of family or biosynthetic study. We estimated the regional prevalence of HbS-betao-thalassemia to be 1:23,000 of the black population.


Zinc in the treatment of homozygous sickle cell anemia: studies in an animal model. We have studied the effects of zinc on the 51Cr survival of red blood cells (RBC) from patients with homozygous sickle cell anemia (SCA) using an animal model in which the RBC were transfused into specially prepared rats. The slope (lambdas) of a standard 51Cr RBC survival curve was used as a measure of the rate of RBC sequestration. The effects of intravenous zinc were of considerable therapeutic interest from the standpoint of setting guidelines for effective blood levels of zinc in patients. SCA RBC were transfused into rats whose plasma zinc levels had been raised 3-6 times above normal (300-600 mug/100 ml) by prior iv injection of zinc acetate; in three experiments the mean lambdas in zinc-treated animals breathing 15-16% oxygen was significantly lower (meaning lessened sequestration and greater survival) than saline-treated controls. A possible explanation for the requirement to lower ambient oxygen tension in order to see this zinc effect is discussed. We have further observed an increased mean lambdas for RBC from 10 SCA patients compared to 4 normal controls (0.134 vs 0.030; t = 2.8, p less than 0.01). The lambdas values are quite patient specific (4 patients studied; F = 18.2, P = 0.002). In vitro pretransfusion treatment of SCA RBC with 1.5 mM zinc resulted in a significant increase in hemoglobin oxygen affinity and a marked reduction in lambdas (0.073 vs 0.120; t = 4.5, p less than 0.01). The mean lambdas was not affected by in vitro 0.3 mM zinc treatment; this level did not change hemoglobin oxygen affinity. We conclude that systemic zinc therapy in the animal model described, at plasma levels only slightly higher than those presently obtained in patients, prolongs SCA RBC survival. This animal model is a sensitive measure of the sicklability of SCA RBC and is useful in the testing of in vitro and in vivo antisickling agents.


The effect of thrombin on the uptake and transformation of arachidonic acid by human platelets. Washed human platelets take up arachidonic acid from plasma and incorporate the fatty acid into the major classes of complex lipids. Thrombin impairs net incorporation. It activates endogenous phospholipases which liberate arachidonic acid from phospholipids. As a consequence of thrombin induced aggregation platelets release arachidonic acid intermediates formed by the action of platelet fatty acid cyclooxygenase and by platelet fatty acid lipoxygenase. Cyclooxygenase, but not lipoxygenase, is inhibited by aspirin and indomethicin. Analysis of the pathways of arachidonic acid metabolism may furnish new insight into platelet function and into disorders of primary hemostasis.


Effects of single and combined chemotherapeutic agents on hemopoietic stem cells in mice. Bone marrow cell responses to injections of nitrogen mustard, oncovin, procarbazine, hydrocortisone, and a regimen of all four drugs (MOPH) were evaluated in CRF1 and C57B1/6 mice by determining bone marrow cellularity and content of transplantable colony forming units (CFU) after treatment. The study was done to determine whether the combined regimen, which is widely used clinically in treatment of disseminated Hodgkin's disease, is more or less detrimental to the hemopoietic system than the same drugs used as single agents. Nitrogen mustard and procarbazine used clinically as single drugs are given in three and two times, respectively, greater doses than in the combined regimen. Hydrocortisone, given singly, was least toxic of the drugs, reducing the CFU/femur to 63% and 71% of control values. MOPH appeared slightly more toxic than hydrocortisone, resulting in 41% and 52% of the CFU/femur surviving, and was about equally as toxic as oncovin alone. Nitrogen mustard and procarbazine, administered as single drugs in high doses, were highly suppressive, resulting in only 10-19% survival of CFU/femur, whereas, reduced doses of the two drugs as used in the MOPH regimen spared 30-45% of the CFU/femur. Survival of CFU after MOPH treatment was three to four times greater than after high doses of nitrogen mustard or procarbazine alone. The component drugs of the combined regimen did not act on separate populations of stem cells to produce an additive effect but appeared to inactivate the same population of cells.


Platelet injury during phototherapy.

Platelet injury during phototherapy. Phototherapy with blue fluorescent light is widely employed for treatment of neonatal hyperbilirubinemia. Functional, biochemical, and morphologic changes produced by blue fluorescent light in human platelets were identified and characterized. Platelet-rich plasma was exposed for up to 170 min to amounts of light equivalent to that used in phototherapy of neonatal hyperbilirubinemia. Within 110 min of light exposure, platelets were essentially no longer aggregable by ADP and connective tissue suspension and were depleted of ADP, ATP, and glycogen. Electron photomicrographs revealed these platelets to be swollen, depleted of glycogen granules and organelles, and to have ill-defined membranes. Platelet injury could be accelerated by adding a photosensitizing agent, hematoporphyrin, to platelet samples before exposure. In contrast, control platelets kept in the dark for 170 min or nonirradiated platelets resuspended in irradiated plasma maintained their integrity. The results indicate that platelets are damaged in vitro when exposed to amounts of blue light used in phototherapy.


Estimation of age and rate of increase of rare variants. The problem considered is that of estimating the age or rate of increase of a variant on the basis of the present number of replicates observed in a population. In place of previous diffusion equation analyses of age probability distributions, the likelihood for the age is studied on the basis of a discrete branching process model. It is shown that variations inherent in the process of gene evolution in natural populations make it impossible to provide a reliable point estimate of the age of a specified variant, although the likelihood analysis provides a confidence interval which may place useful bounds on the period in which a variant originated. The observed distribution of numbers of several variants may also provide useful information. The problems of estimation are discussed with reference to rare variants arising in American Indian populations.


Analysis of genetic and environmental sources of variation in serum cholesterol in Tecumseh, Michigan. III. Identification of genetic effects using 12 polymorphic genetic blood marker systems. Four of 12 unlinked polymorphic marker systems were identified as predictors of normal serum cholesterol levels. Consistent effects between males and females and with other studies suggest that these marker loci are themselves involved in cholesterol determination or are closely linked to the involved loci. Two-locus combinations suggest that an 8-9 mg/100 ml difference in nonfasting serum cholesterol may be predicted between phenotypic classes which are not rare in frequency.


Specific chromosome aberrations in senescent fibroblast cell lines derived from human embryos. In senescent fibroblast cell lines derived from human embryos, the number of chromosome aberrations were found to increase rapidly. In addition to an increase in aneuploidy and polyploidy, a high frequency of dicentrics occurred, but the number of other chromosome abnormalities remained approximately constant. Banding revealed that many of the dicentrics appeared to be end-to-end fusions of whole chromosomes. The involvement of chromosomes was nonrandom. This "telomeric binding" may reflect a progressive decrease in the stability of telomeric sequences or associated enzymes which may also occur in vivo.


A new pyruvate kinase variant (PK Osaka) demonstrated by partial purification and condensation. A qualitative variant of erythrocyte and liver pyruvate kinases (PK Osaka) was detected in a family in which two siblings have extremely low PK activity by semipurification with DEAE cellulose chromatography and subsequent concentration of the enzyme solutions. This was previously reported to be a quantitative variant based on studies of crude tissue preparations. The molecular aberrations were characterized by slow mobility upon electrophoresis, abnormal kinetics for phosphoenolpyruvate, and low affinity for anti-human erythrocyte PK serum. The mutant PK L was similar both electrophoretically and immunologically to PK R.


The phenotypic range of hemophilia A carriers. We have described the study of a small kindred with X-linked hemophilia A. It was ascertained through a clinically affected female, the daughter of a man with moderately severe hemophilia. The pedigree and the proband's phenotype suggest that she may be a heterozygote in whom most of the normal alleles at the VIII-1 locus are not active. She has two sisters, also obligatory carriers. The three sisters exhibit the three phenotypes possible for heterozygous females: clinically affected, clinically normal but phenotypically abnormal as determined by laboratory tests, and clinically and phenotypically normal.


Variability of red cell phenotypes between and within individuals in an unbiased sample of 77 heterozygotes for G6PD deficiency in Sardinia. The distribution of G6PD red blood phenotypes in an unbiased sample of 77 Sardinian certain heterozygotes for the GdMediterranean mutant was found to be skewed in favor of the G6PD (+) cells. Four of these individuals exhibited the normal hemizygous phenotype in all of their cells, but two of them had a mosaic population of G6PD (+) and (-) red blood cells when reexamined after 1 year. These findings suggest that somatic selection may be the main factor determining the phenotype variability of individual somatic cells in highly differentiated tissues of heterozygotes at the G6PD locozygotes for the GdMediterranean mutant should not be used as a criterion for precise estimation of the embryonic or stem tissue cell pool at X inactivation.