New Q waves after bypass grafting: correlations between graft patency, ventriculogram and surgical venting technique. New Q waves were observed in 35 (11%) of 321 patients undergoing saphenous vein bypass grafting with an overall mortality rate of 1.1%. Twenty-eight (80%) had postoperative arteriograms and ventriculograms and are reported. Ventricular venting was used intra-operatively in 17 patients and atrial venting in 11. The incidence of new Q wave was 22% in patients with ventricular venting and 5.5% in those with atrial venting (p less than 0.05). Complete or incomplete revascularization did not affect the incidence of new Q waves. New Q waves appeared in a zone of myocardium supplied by a grafted artery in all except two patients with ventricular venting in whom Q waves occurred within the zone of myocardium supplied by diseased ungrafted vessels. In the ventricular venting group, seven (41%) demonstrated an improved or unchanged postoperative ventriculogram and ten (59%) had deteriorated ventriculograms. In 11 patients with atrial venting, nine (82%) showed improved or unchanged postoperative ventriculograms and two (18%) had deteriorated ventriculograms. Ventricular venting patients with improved or unchanged postoperative ventriculograms had 7% graft closure as compared to 5% of those with atrial venting (pNS). Graft closure rate was 44% in ventricular venting and 20% (pNS) of patients with atrial venting who had deteriorated left ventriculograms. These findings indicate poor correlation between new Q waves and graft closure. Improved postoperative ventriculograms corrleated well with graft patency despite new Q waves. The etiology of new post bypass graft Q waves are varied. They include ventricular trauma and conduction delays resulting from surgery or venting, as well as infarction. This may be due to compromised arterial inflow either in nonoperated vessels or in the vessels distal to the anastomosis with patent grafts, or due to occluded grafts.


The effects of growth hormone treatment of thyroid-deficient pregnant rats on maternal and fetal carbohydrate metabolism. Maternal hypothyroidism in rats has been shown previously to result in alterations of maternal, placental, and fetal metabolism. Maternal treatment with 2 IU GH/day for three days prior to autopsy (on the 22nd day of pregnancy) corrected many of the observed alterations of carbohydrate metabolism in hypothyroidism. The maternal and fetal liver glycogen concentrations and the fetal serum glucose levels of the hypothyroid animals were elevated significantly by the GH treatment. In most cases, the utilization of a [1-14C]glucose tracer dose was returned to normal by GH treatment. These results suggest that the impairment of fetal metabolism occurring in maternal hypothyroidism may be due in part to insufficient maternal GH secretion. However, GH alone in the absence of sufficient thyroid hormones did not totally correct all of the observed fetal abnormalities.


History strikes again: two 20th-century reform ventures. There are striking parallels between the rise and decline of the health center movement of the early decades of this century and the community mental health center movement of the sixties. Four ideas that dominated the early health center movement--district location, preventive care, community participation, and bureaucratic organization--were also important in the development of community mental health centers. Both movements initially were expressions of the reform spirit of the times and later were undermined by the shift to conservative domestic politics.


Direct evidence of estrogen modulation of pituitary sensitivity to luteinizing hormone-releasing factor during the menstrual cycle. To delineate the role of estradiol in the augmented pituitary gonadotropin responsiveness to synthetic luteinizing hormone releasing factor (LRF) seen during high-estrogen phases of the ovulatory cycles (late follicular and midluteal phases), the anti-estrogenic effect of clomiphene citrate (Clomid) on pituitary response to LRF was evaluated during different phases of the ovulatory cycle. Clomid administration (100 mg/day times 5 days) completely negates the augmented gonadotropin responses to LRF (150 mug) during late follicular and midluteal phases observed during the control studies. Thus, a quantitatively and qualitatively similar pituitary sensitivity to LRF during three distinct phases of the menstrual cycle was induced by Clomid treatment that resembles the LRF responsiveness of themale pituitary. The present study demonstrates the pituitary component of the estrogen-induced changes in the sensitivity to LRF. From this and previous data, we conclude that the increases of estradiol secretion associated with the follicular maturation and corpus luteum formation represent a major component of the feedback signal in the modulation of cyclic gonadotropin release occasioned in a large measure by the augmented pituitary sensitivity to LRF.


Partial characterization and purification of a rabbit granulocyte factor that increases permeability of Escherichia coli. Recently we reported that rapid killing of Escherichia coli by granulocytes or granulocyte fractions is accompanied by an equally rapid and discrete increase in permeability of the microbial envelope (Beckerdite, Mooney, Weiss, Franson, and Elsbach. 1974. J. Exp. Med. 140: 396-409). Most of this permeability-increasing activity (PI) is found in a crude granule preparation. PI is quantitatively recovered in a 23,000-g supernatant fraction (Sup II) after sulfuric acid extraction of granulocyte homogenates prepared in water. PI is nondialyzable, destroyed by pronase and trypsin, stable at 4degreesC for at least 2 mo, and destroyed by heating at 94degreesC. Anionic substances, such as heparin sulfate and isolated E. coli lipopolysaccharide, bind to and inhibit PI. PI has been purified up to 1,000-fold from homogenate in a yield of 50percent by acid extraction and carboxymethyl-Sephadex chromatography. Such purified fractions have bactericidal activity that equals that of disrupted granulocytes and Sup II, are similarly enriched with respect to granule-associated phospholipase, and protease activities. Whereas E. coli, sensitive to PI, binds or inactivates solubilized PI, a resistant strain of Serratia marcescens does not. Binding of PI to sensitive microorganisms seems to be necessary for expression of its biological activity since both the apparent binding to and the biological effect of PI on E. coli are completely blocked by 10-20 mM Mg2+ or Ca2+. Mg2+ or Ca2+ can reverse the effect on E. coli permeability produced by Sup II or the carboxymethyl-Sephadex fraction but not that produced by granulocyte homogenate. The close association of bactericidal, phospholipase A2, and permeability-increasing activities towards several gram-negative bacterial species suggests that they may be related.


Human lymphocyte surface immunoglobulin capping. Normal characteristics and anomalous behavior of chronic lymphocytic leukemic lymphocytes. The phenomenon of redistribution of surface membrane immunoglobulin (Ig) components (capping) has been well described in mouse lymphoid cells. The characteristics of this process in human lymphocytes are less clear. This study characterizes the phenomenon of surface membrane Ig redistribution of normal and chronic lymphocytic leukemia (CLL) lymphocytes with the use of fluoroscein-labeled anti-Ig sera. Normal lymphocytes underwent rapid cap formation after incubation with anti-Ig serum in the cold and subsequent rewarming. The morphology was characteristic with aggregation over the pole of the cell opposite the nucleus and over the uropod when present. The process was energy dependent but independent of protein synthesis, and could be inhibited by vincristine, vinblastine, and colchicine but not by cytochalasin B. CLL cells, on the other hand, though showing fluorescent complex aggregation on the surface, rarely demonstrated unidirectional movement of these aggregates to form a cap. Cap formation in these cells could not be stimulated by supplementing the energy source or protein concentration of the medium nor by adding glutamic acid which could partially reverse the vincristine and vinblastine inhibition of normal capping. The failure of agents which inhibit motility to inhibit capping of the normal lymphocytes suggests that active locomotion is not a direct prerequisite for capping. The results also suggest the involvement of microtubules in normal capping and the possibility that abnormal membrane structure or microtubular function could explain the failure of CLL cells to behave normally in this regard. The role of this cellular defect in the immune deficiencies exhibited by many patients with CLL, however, is not established.


Continuing dental education: reasonable answers to unreasonable questions. Increasing government involvement in health care, interest in consumerism, and improved instructional technology have raised new challenges for continuing dental education. Arguments from educational research and evaluation theory are used to show the potential dangers involved in compulsory, mass-media continuing education with pre- and posttest measures of success.


Technetium-99m radionuclide bone imaging for evaluating mandibular osseous allografts. Sequential interpretation of osseous repair, more sensitive than with conventional radiography, is possible with a noninvasive, nondestructive radio-nuclide method. The method was used in the evaluation of the progress of osteogenic activity in mandibular bone grafts in 24 beagle dogs.


Sjögren's syndrome.

Sjögren's syndrome. The diagnosis of Sjögren's syndrome, a multi-systemic disease, is often difficult. Sialography is useful; however, biopsy of labial salivary glands is a simple procedure that aids significantly in arriving at a positive diagnosis. Treatment of the disease is usually on the basis of symptoms.


Efficacy of an antihypertensive agent. Comparison of methyldopa and hydrochlorothiazide in combination and singly. In a double-blind evaluation, the efficacy of a combination of methyldopa with hydrochlorothiazide was compared with that of its components, methyldopa and hydrochlorothiazide. The combination was found to be more efficacious than either of its components. It reduced the arithmetic mean of the pressures of all patients from 170/116 to 133/95 mm Hg in four weeks. Despite the greater effect of the combination, side effects were mild.


Genetic regulation: the Lac control region. The nucleotide sequence of the lac promoter-operator region has been determined. The 122 base pairs comprising this region include the recognition sites for RNA polymerase, the positive regulatory protein, CAP, and the negative regulatory protein, the repressor. Identification of mutant variants of the sequence combined with the in vitro biochemical studies of others has allowed us to tentatively identify the recognition site for each of these proteins, and to suggest how CAP might act at a distance to affect the interaction of RNA polymerase with the promoter.


Mitosis in Tilia americana endosperm.

Mitosis in Tilia americana endosperm. The endosperm cells of the American basswood Tilia americana are favorable experimental material for investigating the birefringence of living plant spindles and anaphase movement of chromosomes. The behavior of the chromosomes in anaphase and the formation of the phragmoplast are unique. The numerous (3 n equals 123), small chromosomes move in precise, parallel rows until midanaphase when they bow away from the poles. Such a pattern of anaphase chromosome distribution has been described once before, but was ascribed to fusion of the chromosomes. The bowing of chromosome rows in Tilia is explainable quantitatively by the constant poleward velocity of the chromosomes during anaphase. Peripheral chromosomes are moving both relative to the spindle axis and laterally closer to the axis, whereas chromosomes lying on the spindle axis possess no lateral component in their motion, and thus at uniform velocity progress more rapidly than peripheral chromosomes relative to the spindle axis. The chromosomes are moved poleward initially by pole-to-pole elongation of the spindle, then moved farther apart by shortening of the kinetochore fibers. In contrast to other plant cells where the phragmoplast forms in telophase, the phragmoplast in Tilia endosperm is formed before midanaphase and the cell during midanaphase, while the chromosomes are still in poleward transit.


Radionuclides and the patient with coronary artery disease. The emergence in the past 20 years of nuclear medicine as a distinct diagnostic discipline has been a major clinical advance. The relatively rapid evolution from the small laboratory limited primarily to the study of thyroid disease to the large unit in which radioactive tracers (radionuclides) are utilized to evaluate structure and function of most organ systems has been accelerated by major advances in instrumentation, new radioactive tracers and application of computer techniques. Application of these radionuclide techniques to the study of coronary artery disease has been quite recent, and has in part been limited by the need for a coordinated effort between the cardiologist and the specialist in nuclear medicine. However, realization of the potential usefulness of these techniques has fostered an increasingly productive liaison between the two specialties. The potential advantages of these radionuclides in evaluating patients with cardiovascular disease is twofold: first, they may permit the noninvasive or atraumatic acquisition of data that might otherwise be obtained only at the time of cardiac catheterization; second, and perhaps more important, they may permit the acquisition of physiologic measurements or observations not attainable by more conventional modes of study. Functionally, these techniques can be divided into those that evaluate cardiac performance and those that evaluate coronary blood flow, regional myocardial perfusion and myocardial viability.


Cardiovascular investigations and fuzzy sets theory. Examining the circumstances that often lead modern, mechanistic cardiovascular research into areas devoid of practical significance, we suggest that our approaches, instead of our technology, are inadequate. A method for processing information, built on the concept of "fuzzy sets," is described as a potential way out of this dilemma. This system deserves application to clinical problems, perhaps together with more classic quantitative methods, because of its practical consequences and the conceptual revitalization it may bring.


Myocardial blood flow response to isometric (handgrip) and treadmill exercise in coronary artery disease. Thirty patients undergoing coronary cineangiography for diagnosis or evaluation of coronary artery disease had myocardial blood flow studies pre and post handgrip (isometric) exercise just prior to cineangiography. The handgrip was maintained at one-third maximum effort for three minutes. The patients also had treadmill exercise testing a day or two prior to the study. Treadmill testing was carried out until angina or positive ST-segment changes occurred or the patient attained 90% of predicted maximal heart rate. Of the 30 patients, seven had no coronary artery disease and 23 had significant disease, i.e., greater than 75% occlusion of at least one major coronary artery. Six of the 23 patients (26%) with disease had angina with handgrip and demonstrated a decreased myocardial blood flow, a significantly different response from the patients without agina (P less than 0.001). For the group without angina, the blood flow response was not significantly different from the normal group. Treadmill tests were positive in 19 of the 23 patients with coronary disease (83%). The arterial systolic and diastolic pressure rise was almost identical with the two stresses. The heart rate response, however, was significantly different (P less than 0.001), the rate increase being greater with treadmill exercise. The myocardial blood flow data demonstrate the relative insensitivity of handgrip exercise for the diagnosis of coronary artery disease. In terms of the supply demand ratio (diastolic pressure time/systolic pressure time) concept for subendocardial perfusion, it is possible that the difference between handgrip and treadmill stress may be due to the different heart rate response, more rapid heart rates having a relatively greater effect on diastolic than on systolic time indices, all other factors being equal.


Changes in monoamine oxidase and monoamines with human development and aging. A series of studies of monoamines and their metabolism in a variety of human tissues indicate that there are aging effects that may alter neurotransmitter substances. Monoamine oxidase (MAO) activity has a significant positive correlation with age in plasma and blood platelets of normal subjects and patients suffering from depressive disorders. Monoamine oxidase and age correlate positively in hindbrain and in eight separate ares of human brains from patients who died from a variety of causes. Hindbrain norepinephrine concentration progressively decreases with advancing age (r equals -0.44, P less than 0.01) while no changes were noted for serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). Hindbrain norepinephrine concentration has a significant negative correlation with MAO (r equals -0.41, P less than 0.025) and hindbrain 5-HIAA has a significant positive correlation with MAO (r equals +0.66, P equals less than 0.05). These studies suggest that aging processes may significantly affect monoamine mechanisms and be a predisposing factor to the development of clinical diseases in man such as depression, parkinsonism and other disorders of central nervous system homeostasis.


Towards a theory of development.

Towards a theory of development. A theory of development would effectively enable one to compute the adult organism from the genetic information in the egg. The problem may be approached by viewing the egg as containing a program for development, and considering the logical nature of the program by treating cells as automata and ignoring the details of molecular mechanisms. It is suggested that development is essentially a simple process, the cells having a limited repertoire of overt activities and interacting with each other by means of simple signals, and that general principles may be discerned. The complexity lies in the specification of the internal state which may be described in terms of a gene-switching network. Pattern formation is a central feature in development; it is the process whereby states are assigned to the cells according to their position. such that the appropriate type of cytodifferentiation is selected from the repertoire. The morphogenesis of the chick limb is briefly discussed. Genetic networks that account for such features as memory, competence and interpretation of positional information are given. The question of how these component parts are organized into a complete control system for development is posed as a problem for future study.


Growth and death of diploid and transformed human fibroblasts. Three possible explanations are presented for the differences in growth potential between human diploid fibroblasts of finite life-span and permanent transformed lines: 1) Only diploid cells have a molecular clock mechanism which counts cell divisions prior to senescence. Two hypothetical examples of such mechanisms are described; however, the available evidence argues against a clock mechanism for aging in fibroblasts. 2) Cells become committed with a given probability to a slow buildup in protein errors, which leads after many divisions to a lethal error catastrophe. It can be shown that speeding up the rate at which the error catastrophe develops, as may occur in transformed cells, can convert a population of finite life-span to one with infinite growth. 3) The growth rate of diploid cells may not depend on the limiting concentration of any one protein. If so, cells with a low level of errors will not have a reduced generation time, and there will be no selection against them. On the other hand the uncontrolled growth of transformed cells may be reduced in rate by the presence of faulty proteins, so that there is continuous selection for those with the fewest errors. Finally, the analogous problem of the mortality of somatic cells and the immortality of the germ line is also briefly discussed.


Pathological implications of cell aging in vitro. The replicative capacity of cultured human fibroblasts is discussed in relation to three areas, diabetes mellitus, expression of HL-A antigens, and interactions with polymerizing fibrin. The replicative capacity of cells is dimished in diabetes mellitus and certain related disorders such as progeria and Werner's syndrome, all of which feature accelerated aging. Expression of HL-A antigens is reduced in progeria fibroblasts compared to normal cultures at corresponding stages of passage. Normal cells show more subtle alteration during aging in vitro probably related to clonal heterogeneity and/or selection within mass cultures. Early-passage fibroblasts interact rapidly with polymerizing fibrin to form a mature clot which is then retracted by a process dependent on cellular integrity and active metabolism. Late-passage cultures are less active in both parameters as are fibroblasts from a subject with progeria. These observations, in total, may relate to altered self-recognition and certain autoimmune concomitants of aging in vivo. They may also help to explain impaired wound healing and increased predisposition to atherothrombosis in aging and diabetic individuals. This system of cultured human fibroblasts should serve as an excellent model to investigate the cellular and molecular basis of diabetes mellitus, aging and related pathology.


Hayflick's hypothesis: an approach to in vivo testing. The experimental evidence relating to the hypothesis of finite cellular life is reviewed. It is emphasized that even if somatic cell production were limited its total potential would have to be vast to provide for extensive cellular regeneration. The actual limit of reproductive cell life would therefore not likely be reached in a normal life-span. It is proposed to test the hypothesis by deliberate exhaustion of stem-cell reserve, and iron-55 cytocide is described as an experimental system that might be applicable.


Current theories of biological aging.

Current theories of biological aging. Several lines of evidence have led to the notion that biological aging occurs as a result of changes in the information-containing molecules either at the genetic or epigenetic level. The error theory, the redundant message theory, the codon restriction theory, and the transcriptional event theory represent the major current conceptualizations of biological aging as held by most gerontologists. The finding that cultured normal human and animal cells undergo a finite number of population doublings in vitro has provided new insights into age changes at the cellular level. The number of mitotic events that cultured normal animal cells can undergo appears to be inversely related to the age of the donor. A direct proportionality exists, however, between the mean maximum life-span of a species and the number of population doublings that their cultured embryonic cells will undergo. The several biochemical decrements known to occur prior to the cessation of mitotic activity in vitro are thought to herald those manifestations of senescence seen in the whole animal. Yet to be explained is how those cell classes such as the germ plasm and continuously propagable cancer cells escape from the inevitability of biological aging.


Haloperidol parenterally for treatment of vomiting and nausea from gastrointestinal disorders in a group of geriatric patients: double-blind, placebo-controlled study. Twenty-eight geriatric residents of a nursing home participated in a double-blind study to compare the 12-hour therapeutic effectiveness of a single intramuscular injection (1.0 mg) of haloperidol with that of placebo for the relief of vomiting and nausea due to gastrointestinal disorders. Significantly fewer episodes of vomiting occurred in the haloperidol group than in the placebo group. Nausea also was less frequent in the haloperidol group. After four hours, symptoms recurred much more often in the placebo group. Global evaluations showed that a significantly greater number of haloperidol patients improved markedly than did those given placebo. There were no clinically significant changes in vital signs throughout the study in the haloperidol group. In 1 placebo patient the pulse rate was significantly increased; otherwise no adverse reactions were reported for this group. Thus, in a nursing-home population of geriatric patients who experienced vomiting and nausea due to gastrointestinal disorders, haloperidol administered parenterally proved to be a safe and highly effective antiemetic agent.


Effect of postmortem tissue fixation on tooth mobility and pocket depth in human beings. With the exception of dry skulls, postmortem human material is rarely used in the study of periodontal disease. If the relationship between clinical periodontal measurements, such as mobility and pocket depth, were known antemortem versus postmortem, a new source of information would be available. In this study, such measurements were performed on a patient whose mandible was resected because of a malignant condition. Mobility was found to have decreased; pocket depths initially increased, and then returned to nearly preoperative levels.


The cooling, analgesic, and rewarming effects of ice massage on localized skin. The study was designed to produce objective data on the rate of local cooling following the ice massage technique of cold application and the rate of rewarming following termination of the ice application. More importantly, the onset of skin analgesia and its duration were evaluated. Sixteen normal subjects participated in four testing sessions, two of which were control session. A thermistor unit with probes monitored skin temperature and a standardized pain-evoking stimulus was used to verify analgesia. Analgesia was elicited by the ice massage only after the localized region had been cooled to, and maintained below, 13.6 degrees Celsius. The rate of cooling for the localized skin was more rapid than the rate of rewarming. The ten-minute ice massage was an effective procedure in achieving analgesia and, thus, may be sufficient to permit therapeutic exercise of selective painful conditions during, and for approximately three minutes immediately following, application.


Effect of alterations in extracellular fluid volume on segmental sodium transport. This review focuses on the segmental handling of sodium during alterations in extracellular fluid volume. There is abundant evidence that proximal tubular sodium reabsorption is inhibited by Ringer loading but there are also unequivocal data demonstrating that inhibition of a more distal nephron segment is required for a maximal natriuretic response. From the evidence at hand presently, it would seem that, of the distal nephron segments, only the collecting duct is inhibited by expansion of the extracellular volume per se.


Control of the ductus arteriosus.

Control of the ductus arteriosus. In the fetus the major function of the ductus arteriosus is to divert flow away from the lungs toward the placenta, therby avoiding unnecessary circulation through the lungs and reducing the work load of the heart. Constriction of the ductus arteriosus is produced by several mechanisms that may interact with one another in producing normal postnatal closure of the ductus arteriosus. The major mechanism is the constrictor effect of an increased O2 environment. This may directly affect the ductus arteriosus muscle or may work through the release of an intermediary substance. Other vasoactive substance circulating in the blood after birth may also play some role in constriction of the ductus arteriosus. There are major species differences in the degree and type of response to the various stimuli and the exact mechanisms ultimately responsible for closure are not yet fully understood.


Physiology of chemotaxis and random motility. The following aspects of random and directional migration of leukocytes have been considered: (1) basic cellular mechanisms involved in leukocyte locomotion; (2) the mechanisms of formation and the nature of various factors such as cytotaxins, cytotaxin-inactivators and inhibitors participating in the regulation of the chemotactic response, and (3) the relationship between chemotaxis and leukocyte emigration. The need for adequate techniques for measuring chemotaxis has been emphasized with special reference to clinical investigation.


Homotransplant renal artery stenosis.

Homotransplant renal artery stenosis. Transplant renal artery stenosis occurred in 12 of 101 consecutive kidney transplants. Stenoses were all located in the renal artery distal to the anastomosis. Two separate forms of stenosis are recognized: angulation and segmental. All transplant patients with severe diastolic hypertension, refractory to medical management, and an audible abdominal bruit should undergo angiography. Surgical correction of the stenosis was accomplished in nine of 12 patients with cure of their hypertension.


Current status of the treatment of syphilis. Penicillin remains the treatment of choice for syphilis, with sustained low blood levels curing virtually all patients having early syphilis and halting disease progression in most patients with symptomatic syphilis. Tetracycline, erythromycin or cephalothin yields similar cure rates for patients with early syphilis who are allergic to penicillin. The efficacy of non-penicillin regimens for the treatment of late syphilis is uncertain. Results of Venereal Disease Research Laboratory (VDRL) or other reagin tests should become negative or remain at very low titer following adequate therapy, although results of Treponema pallidum immobilization (TPI) and fluorescent treponemal antibody-absorbed (FTA-ABS) tests often remain positive.


The role of the kidney in spontaneous hypertension. There is direct and indirect evidence that the kidneys are involved in the onset of hypertension in spontaneously hypertensive animals. In the Dahl strain, rather convincing evidence exists for a primary, inherent renal defect that is worsened by high dietary salt. In the Okamoto and New Zealand strains, an intrinsic defect may be provoked by increased sympathetic nerve activity. Similarities between all of these strains and Goldblatt hypertension suggest a fluid volume abnormality, but the gradual onset of elevated pressure and continuing growth during development of hypertension may obscure critical volume changes. Theoretically, arterial pressure, somewhat independent of intermediate steps, will reach the level which is dictated by renal function as being necessary for the maintenance of salt and water homeostasis. While widespread use of different spontaneously hypertensive strains may currently be complicating our understanding of the intermediate steps, studies of dissimilar strains should, in time, enhance our understanding of the many different facets of long-term blood pressure control.


Interesting aspects of geriatric cardiology. Geriatric cardiology requires special knowledge and experience. It is not possible to extrapolate directly experience obtained with young patients to old people. Because of the multiple illnesses, many serious, in the elderly cardiac patients, it is imperative for the cardiologist to be, first of all, a master internist at all times. Old patients with their multiple illnesses are also sensitive to drugs, including digitalis and diuretics. There is a need to train more physicians in geriatric cardiology in order to offer the old patient the best of care since so many old people are living today. There is also a need to learn the effects of the aging process itself on the human heart. Such studies should command priorities in financial and other forms of support.


Use of chromium-adenosine triphosphate and lyxose to elucidate the kinetic mechanism and coordination state of the nucleotide substrate for yeast hexokinase. When initial velocities are measured with yeast hexokinase at pH 7, 17 degrees, the inert coordination complex chromium-ATP is competitive vs. MgATP and noncompetitive with glucose, with a dissociation constant of 4-6 muM in either the presence or absence of glucose. These patterns confirm a random kinetic mechanism for this enzyme. With CrATP present, however, the reaction slows down over the first several minutes to a much slower rate, suggesting tighter binding of CrATP with time. When CrATP, MgATP, and D-lyxose are preincubated with the enzyme for 10 min and the reaction started by addition of excess glucose, the dissociation constand of CrATP in now 0.13 muM and the reaction is linear with time. When glucose, CrATP, and enzyme are incubated together and then placed on a Sephadex column, 1 mol each of CrATP and glucose per active center is tightly bound to the enzyme, thus providing a simple and precise method of determining the concentration of active sites. This tight complex, after denaturation with acid, releases 25% free glucose and 75% of a chromium complex containing both ADP and sugar-6-P. CrADP-glucose-6-P is also slowly released from the enzyme during incubation, so that CrATP is actually a very slow substrate. Binding of CrATP with the formation of CrADP-sugar-6-P complexes is also induced by mannose, fructose, glucosamine, 2,5-anhydro-D-glucitol, 2,5-anhydro-D-mannose, and 2,5-anhydro-D-mannitol, while glucose-6-P, 6-deoxyglucose, and lyxose also induce tight binding of CrATP. With excess enzyme, only 25% of CrATP is bound, and the rest does not inhibit the hexokinase reaction. Since bidentate Cr(NH3)4ATP and monodentate CrADP also display inhibition which is tighter with time, but since bidentate CrADP is a poor inhibitor, the actural substrates in the hexokinase reaction appear to be beta, gamma-bidentate MgATP and beta-monodentate MgADP. Tighter inhibition by Cr-8-BrATP than by CrATP suggests that ATP ASSUMES THE SYN CONFORMATION ON THE ENZYME. The substrate inhibition by MgATP induced by the presence of lyxose is shown to be competitive vs. glucose and partial, and, together with other data available, to suggest a kinetic mechanism that is random, but where (1) the rate constant for release of glucose from E-glucose is equal to Vmax, and that for release of glucose from central complexes is less than Vmas; (2) the majority of the reaction flux when both substrates are present at Km levels goes through the path with glucose adding before MgATP, but where at physiological levels the flux through the two paths is more equal. Contd.


Past presidents I have known.

Past presidents I have known. This paper is an account of the accomplishments of some of the early past presidents of the Medical Library Association known personally to the author in his career as a medical librarian. It demonstrates the qualities that made these librarians leaders of our profession and also indicates their personal attributes that contributed to the advancement of medical librarianship. It is hoped that the historical presentation of some of the giants of our profession will inspire present and future presidents and other medical librarians with an understanding of some of the qualities necessary to the continuing success of our profession. Sir William Osler, who was a great believer in libraries and librarians and himself a Past President of MLA, summed up four qualities in his advice to medical students equally applicable to past and present leadership in the library profession-(1) the art of detachment, (2) the virtue of method, (3) the quality of thoroughness, (4) the grace of humility (Osler, Sir William. Teacher and Student. In his Aequanimitas: with Other Addresses to Medical Students. 3d ed. Philadelphia, Blakiston Company, 1904. p. 27-31.). It is thought that our past presidents possessed all of these qualities.


Death in amphetamine users: causes and rates. The world medical literature contains 43 reports of deaths associated with amphetamines in a 35-year period. These included seven cerebrovascular accidents, six sudden cardiac deaths, three cases of hyperpyrexia, eight poisonings of uncertain mechanism and seven cases of medical complications of intravenous injection; the remainder were of uncertain cause. In contrast, in Ontario alone, in 1972 and 1973 there were 26 deaths in amphetamine users, of which 16 were due to accident suicide or homicide. Of the remaining cases, two were cardiac, two hepatic and the rest were mixed drug overdose. Pulmonary granulomata, subacute hepatitis and other lesions resulting from intravenous drug use were common findings at autopsy. On the basis of the estimated number of regular users of intravenous amphetamine in Ontario, the mortality rate in such users is at least four times as high as in the general population of the same age, and is comparable to that in alcoholics and heroin addicts. However, the absolute number of alcohol-related deaths is far greater than the number of deaths in amphetamine or heroin users.


Surface immunoglobulin positive lymphocytes in human breast cancer tissue and homolateral axillary lymph nodes. Surface immunoglobulins were determined on human lymph node lymphocytes by the use of immunofluorescence technique in 59 breast cancer patients undergoing radical mastectomy. In 10 of these cases, lymphocyte surface immunoglobulins were also studied on lymphocytes infiltrating the primary cancer mass. The most outstanding finding was a difference between the IgM lymphocyte populations in the lymph nodes of patients with and without lymph node metastases. When cancer tissue was present in one or more lymph nodes, the tumor-free as well as the tumor-positive nodes showed a higher percentage of IgM positive lymphocytes than did lymph nodes from patients without nodal metastases. The greatest difference was found when IgM lymphocytes from tumor-bearing lymph nodes were compared with those from the lymph nodes of patients without nodal metastases (p is less than .005). The lymphocyte populations infiltrating 5 of the 10 primary cancer masses studied showed no surface immunoglobulins; in the remainder, both IgG and IgM positive lymphocytes were found but in variable proportions. While  the findings are not definitive, this is the first study dealing with the quantitation of immunoglobulin specific lymphocytes in the lymph nodes and tumor tissue of patients with breast cancer.


Nodular lymphoma: an ultrastructural study of its relationship to germinal centers and a correlation of light and electron microscopic findings. This study describes the ultrastructural findings in 16 cases of nodular lymphoma, and compares these with normal germinal centers in order to determine the possible germinal center origin of the lymphomas. Long branching desmosome-associated dendritic reticulum cells, characteristic of germinal centers, were found in all 16 cases of nodular lymphoma. Desmosomes were observed only between dendritic cells and not between lymphoid cells, and they were seen in only 1 of 7 cases of diffuse lymphoma. Cells comprising the nodular lymphomas share cytologic features, such as nuclear blebs and marked nuclear indentations, with germinal center cells. It appears that nodular lymphomas have a close anatomical relationship to germinal centers, although their actual origin from these sites is not established by this study. They are composed of lymphoid cells; we have no evidence to confirm the view that nodular lymphomas are derived from dendritic cells. Light and electron microscopic findings have been compared in order to establish the nature of large "histiocyte-like" cells in the nodular lymphomas. Many of these cells appear to represent transformed lymphocytes rather than histiocytes. They are more numerous in so-called mixed "histiocytic" lymphocytic lymphomas than in poorly differentiated lymphocytic lymphomas, which otherwise are ultrastructurally similar. This study casts doubt upon the existence of a mixed lymphocytic and histiocytic lymphoma within the spectrum of the nodular lymphomas, and indicates that a cytologic continuum exists between cells interpreted as poorly differentiated lymphocytes and those heretofore identified as histiocytes.


Aggressive growth and neoplastic potential of odontogenic cysts: with special reference to central epidermoid and mucoepidermoid carcinomas. An aggressive form of odontogenic cyst known as the keratocyst has been reviewed with a report on the findings of 70 new instances. Recurrence after 2 years of followup was found to be 20%. From both a review of the literature and original cases, carcinomatous and ameloblastomatous transformation in odontogenic keratocysts seems to be an extremely rare phenomenon. Alternatively, epidermoid carcinoma and mucoepidermoid carcinoma arising centrally within the jaws are often associated with other types of dental cycts. Review of 36 instances of central epidermoid carcinoma has disclosed that 75% were associated with a cyst lining; the 2-year survival rate was found to be 53%. Central mucoepidermoid carcinoma was associated with a dental cyst or impacted tooth in 48% of the cases, and enjoyed a 100% 2-year and 5-year survival; however, 2 patients were recorded alive with disease at 4 months and 10 years, whereas another patient succumbed to disease 14 years postoperatively.


Techniques for inhibiting tumor metastases. Of the four major biological mechanisms of cancer spread, hematogenous dissemination is perhaps the most significant, as it usually heralds a fatal outcome for the patient. Recent experimental approaches have shown ways of altering the metastatic process and even totally inhibiting it in some animal models. It appears that these models may be applicable to certain human cancers. To prevent hematogenous metastasis formation the process must be inhibited at any one of four levels: 1) growth of the primary; 2) invasion of vessel walls; 3) release of viable tumor cells; or 4) entrapment and growth in distant organs. Judicious handling of the primary can decrease metastasis by minimizing the shedding of tumor cells. New experimental agents prevent the release of tumor cells from the primary by normalizing the blood vessels of the tumor. Warfarin, heparin, and fibrinolytic agents inhibit the entrapment of circulating tumor cells, presumably by their effect on coagulative mechanisms. A better understanding of the benefits of combined approaches to cancer using chemotherapy, irradiation, and immunotherapy, alone and as adjuncts to surgery, offers new opportunity to study methods of controlling metastatic disease.


Combined modality therapy of gynecologic cancer. In the treatment of gynecologic malignancies, various combinations of surgery, drugs, and radiation therapy are used with increasing frequency. An examination is made of data dealing with combined modalities in the treatment of tumors of the cervix, endometrium, and ovary. Although the efficacy of such treatments has not been established, they are increasingly popular. Newer studies now being conducted, together with newer drugs employed in combination with radiation therapy and surgery, can result in the benefits which to date have not been realized.


Preoperative irradiation and surgery for certain cancers. Failure to cure cancer by surgery is caused by inability to remove all local extensions of the lesion or from prior or synchronous dissemination of tumor cells. Laboratory evidence has suggested that preoperative irradiation of the primary tumor can increase cure rates. In the clinical realm, the efficacy of preoperative irradiation appears to vary with specific tumors. Lung cancer shows no improvement in survival. Cancers of the bladder and breast may show enhancement of cure rate. Data indicate that cancer of the rectosigmoid does benefit from preoperative therapy. Adherence to important factors of dosage and timing of operation is necessary to prevent undesirable complications. Randomized clinical trials are needed to establish the efficacy of this combined modality treatment system. This is particularly true since both these modalities can be applied on a wide-scale basis if beneficial effects are conclusively demonstrated.


Immune inhibition of allogeneic lymphoma cells in the peritoneal cavity of mice. Mice were sensitized with cells of normal spleen, transplantable syngeneic lymphomas, or allogeneic lymphomas differing for alloantigens specified by the major histocompatibility complex. From three to eleven days later, the allograft reactivity of these sensitized and appropriate control mice was evaluated in the peritoneal cavity by the disappearance of injected lymphoma cells or the inhibition of DNA synthesis. For the disappearance test, target cells were labeled with [125-I]-5-ido-2'-deoxyuridine before transfer. For the inhibition test, unlabeled target cells were transferred, but these cells were subsequently exposed to the DNA precursor [125-I]-5-iodo-2'-deoxyuridine. In both procedures, cells were recovered from the peritoneal cavity without killing the hosts to measure retained radioactivity. Both tests were immunogenetically specific in detecting secondary allograft reactions, but the disappearance test was less sensitive. By inhibition of DNA synthesis, it was possible to detect primary and secondary reactions, the latter three to eight days after sensitization. Alloantigens associated with the H-2K-Ir regions of Murine Linkage Group IX were more immunogenic than those associated with the Ss-H-2D-Tla regions in eliciting antilymphoma reactions, and female mice responded better than males. It was concluded that the peritoneal inhibition test is sensitive enough to monitor transplantation immunity in vivo and could be applied to animals bearing tumors in sites other than the peritoneum and undergoing chemotherapy.


Stimulation of hemolysin plaque-forming cells by idoxuridine. 5-Iodo-2'-deoxyuridine markedly stimulates the production of hemolysin plaque-forming cells (HPFC) to sheep red blood cells in C3HeB/FeJ and A/J male and female mice. The degree of stimulation is dose dependent over a range of 50 to 200 mg/kg. Stimulation is observed when drug is given on the day of antigen administration, or up to 3 days thereafter, but not when given before antigen administration or 4 days thereafter. The stimulatory effect of IUdR given on day 2 after antigen is still noted on Day 15, but the time of HPFC production is not prolonged beyond that in controls. Both 19S and 7S HPFC are increased, although the effect on the latter is less pronounced. In addition to stimulating production of HPFC in immunized animals, 5-iodo-2'-deoxyuridine increases background HPFC production in nonimmunized mice by 250% when assayed on the day after treatment.


Etiological factors, stages, and the role of the foreign body in foreign body tumorigenesis: a review. Attempts were made to analyze the process of foreign body (FB) tumorigenesis and to identify etiologically significant factors by correlating information in the literature and recent experimental data from our labroatory. It appears that the process of FB tumorigenesis is dependent on sequence of specific conditions as expressed by the following criteria: (a) cellular proliferation and tissue infiltration during acute FB reaction; (b) fibrosis of the tissue capsule surrounding the FB; (c) quiescence of the tissue reaction, i. e., dormancy and phagocytic inactivity of FB-attached macrophages; and (d) availability of a FB surface for direct contact with clonal preneoplastic cells. There is no indication that the initial acquisition of neoplastic potential and the determination of specific tumor characteristics are based on direct physical or chemical reaction between cells and the FB. These etiological key events occur presumably in mesenchymal stem cells associated with the microvasculature no later than during the acute stage of FB reaction and certainly long before clonal descendants of these cells are first found in contact with the FB surface. In fact, there is no reason to assume that cells with neoplastic determination may be present in normal tissue prior to the introduction of a FB and that the FB would only create the conditions required for stepwise preneoplastic maturation.


LH-RH-containing neural elements in the rat hypothalamus. With the use of rabbit anti-LH-RH serum, a system of delicate nerve fibers and terminals which contain immunoreactive LH-RH can be demonstrated in the median eminence of the rat, corresponding exactly to the tubero-infundibular tract as described earlier with the aid of classical neurophistological methods. The delicate fiber system can be traced to the region of the rectrochiasmatic area and especially to that of the arcuate nucleus but not farther. Nerve cells do not show any immunopositive reaction for LH-RH in the experimental conditions studied. LH-RH positive nerve fibers terminate on or in the immediate vicinity of the capillary loops penetrating the median eminence.


Pineal methoxyindoles: new evidence concerning their function in the control of pineal-mediated changes in the reproductive physiology of male golden hamsters. Maintaining adult male golden hamsters in short daily photoperiods (1hr of light and 23hr of darkness daily; LD 1.23) for 12 weeks caused the tests and accessory sex organs to atrophy and also led to significant depressions in pituitary LH and prolactin levels. If hamsters that were kept in LD 1.23 CYCLES RECEIVED WEEKLy subcutanceous implants of either a melanioninbeeswax or a 5-methoxtrypotophol-beeswax pellet (1 mgindole in 24 mg beeswax) the testes and accessory sex organs failed to involute and pituitary LH levels did not drop. Both treatments also retarded the depression in hypophyseal prolactin retarded the depression in hypophyseal prolactin levels. Treatment (twice daily on weekdays and once daily on weekends) with 1.5 mug injections of synthetic LRH (in 0.2 ml 8% gelatin) did not prevent gonadal or accessory organ atrophy while it further depressed hypophyseal LRH treatment, plasma LH titers were significantly elevated. The reproductive organs of hamsters that were moved from short (LD1;I 23) to long (LD 14;10) daily photoperiods regenerated within 8 weeks. This light-induced restoration of the gonads was not prevented or retarded by the weekly implantation of either melantonin-beeswax or 5-methoxytrptophol-beeswax pellets. The results suggest that in the male golden hamster neither melatonin nor 5-methoxtryptophol accounts for the antigonadotrophic activity of the pineal gland.


Direct action of prostaglandins on the rat pituitary. The purpose of this study is to ascertain whether or not prostaglandins (PGs) act directly on the pituitary. In the first experiment, the plasma LH levels were sharply decreased 24 hr after the production of hypothalamic lesions in ovariectomized mature rats. Ten min after the iv injection of PGE1, PGE2 or PGF2alpha, the plasma LH levels increased significantly as compared with the vehicle control. Also, the plasma LH levels were elevated following the iv injection of LH-releasing hormone (LH-RH). In the second experiment, after pretreatment of ovariectomized mature rats with estrogen and progesterone, animals received a SC injection of indomethacin, 2 mg in 0.2 ml of gelatin for 3 days. Twenty-four hr after the last injection, 100 ng of LH-RH were injected into the jugular vein. The response of the pituitary to the LH-RH was significantly lower in the indomethacin-treated rats than in the vehicle control rats. In the 3rd experiment, we tested several PGs for stimulatory effects on LH secretion by injecting them into the anterior pituitary. Following direct microinjection of PGE1 or PGE2 (50 or 100 mug/mul) into the rat pituitary, plasma LH was increased at 10 and 45 min after the injection. However, PGF2alpha at both 50 and 100 mug/5mul, failed to increase the plasma LH levels. In the last experiment, the effect of PGE1, PGE2 or PGF2alpha on in vitro rat anterior pituitary LH release was studied. Addition of PGE1, (2 or 20 mug), PGE2 (0.002 or 0.02 mug) or PGF2alpha (200 mug) to the incubation medium produced a significant increase in LH release into the incubation medium. These observations indicate that sufficient dosages of PGs can also stimulate LH secretion by acting directly on the pituitary.


Cirrhosis associated with partial deficiency of alpha-1-antitrypsin: a clinical and autopsy study. A 63 year old woman with cryptogenic cirrhosis, ascites, portal hypertension, and intermediate levels of alpha-1-antitrypsin of protease inhibitor SZ phenotype who died of esophageal variceal hemorrhage is described. The partial deficiency of alpha-1-antitrypsin and the diagnosis of cirrhosis were suspected one year prior to death because a needle biopsy of liver showed PAS positive, diastase resistant cytoplasmic bodies within hepatocytes. This report illustrates three previously undescribed features: (1) Heterozygous protease inhibitor SZ phenotype may be associated with coarsely nodular cirrhosis in the older adult. (2) The large intracytoplasmic glycoprotein droplets that are distinctive by light microscopy are probably formalin induced aggregates of submicroscopic flocculent material. (3) In the older patients with aberrant alpha-1-antitrypsin the flocculent material is present not only in the granular endoplasmic reticulum but also in smooth endoplasmic reticulum vesicles and cytolysosomes.


Coxsackie viral infection of human myocardium. The myocardiu m of a young patient who had clinically established cardiomyopathy and suspected Coxsackie virus B4 infection was studied. Coxsackie B4 viral antigen was found in the ventricular and atrial myocardium by specific immunofluorescent antibody staining. Histologic examination revealed varying degrees of myocardial damage. Interstitial fibrosis and edema, swelling and deterioration of hypertrophic muscle fibers, connective tissue proliferation, stasis of small coronary blood vessels, atrophy of myocardial fibers with pyknosis of nuclei, and lytic deterioration were observed. Electron microscopic examination showed portions of the Z bands to be either widened or displaced into the sarcomere. Adjacent cell membranes in the region of the intercalated disc in the myocardium of both the ventricle and the atrium were separated, forming large gaps. Morphologic changes were most pronounced in the atrium adjacent to the mitral valve, in which the mitochondria were grossly swollen, and large vesicles were present in the sarcoplasm. The pathologic changes found in the myocardium of all chambers of the heart apparently were due to Coxsackie B4 viral infection.


Inflammatory bowel disease: the surgical pathology of Crohn's disease and ulcerative colitis. Ulcerative colitis and granulomatous colitis are distinct entities, but up to 10 per cent of colectomy specimens remain unclassified. Ulcerative colitis is primarily a mucosal disease, and other changes appear to be secondary to this process. By contrast, Crohn's disease, or granulomatous colitis, involves the whole thickness of the bowel wall. About 20 per cent of the cases of Crohn's disease involve the small and large bowel, while another 20 per cent are restricted to the large bowel. Since granulomatous colitis is a patchy disease, and many of the changes are deep within the bowel wall, rectal biopsy may not be as helpful as in ulcerative colitis. Fully developed granulomas are present in only a small minority of cases, and a diagnostic report of granulomatous colitis may be given in the absence of granulomas. In biopsy material, the differentiation of inflammatory bowel disease from ischemic colitis and pseudomembranous colitis may be difficult. In the absence of specific demonstration of an organism it may also be impossible on rectal biopsy to distinguish amebic or bacillary dysentery from ulcerative colitis. Even by colectomy, 29 of 300 specimens were sufficiently atypical so as not to warrant a label of Crohn's disease, or ulcerative colitis. Cancer of the colon, which is common in ulcerative colitis, is rare in Crohn's disease, but may also represent a definite complication in the latter. Immunologic studies are still confusing, but it is suggested that patients with ulcerative colitis and Crohn's disease may have a state of altered immunologic reactivity.


Microcirculation in diabetes mellitus: a study of gingival biopsies. Gingival biopsy specimens from 24 diabetic patients, six obese persons, and six controls were studied statistically and morphologically to detect vascular basement membrane changes using a proposed classification of microvessels. Statistically significant basement membrane thickening is seen in all diabetic groups in most true capillaries and vessels proximal to them, especially in terminal arterioles and metarterioles, although the degree and extent of the changes vary among different clinical groups and vessel types. The basement membrane thickening is characterized by increased amorphous, granular, and fibrillary material with occasional scattered collagenous fibrils. Although nonspecific, basement membrane thickening in microvessels at, and especially proximal to, the level of true capillaries is intimately related to diabetes. Gingival biopsy may possibly be used as an adjunct in the diagnosis of diabetes.


Growth and transplantation of organ-cultured corneas. Calf corneal buttons were grown in medium M199 supplemented with newborn calf serum (xenogeneic to the recipient) or rabbit serum (allongeneic to the recipient) and implanted interlamellarly into rabbit recipients. Implantation of buttons, grown in medium containing calf serum were rejected sooner than noncultured buttons. The rejection was quicker as the grafts were kept longer in culture. However, corneal buttons grown in medium containing rabbit serum showed, in general, a slower rejection process.


Ciliary ganglion stimulation. I. Effects on aqueous humor inflow and outflow. Stimulation of the ciliary ganglion in an enucleated, arterially perfused cat eye preparation produced a sustained increase in aqueous humor formation and an increase in the rate of aqueous humor outflow. The increased aqueous humor formation induced by ciliary ganglion stimulation has been found to be pressure-dependent and therefore suggests that ultrafiltration may be the underlying mechanism of action. No change in capillary permeability of the ciliary body could be demonstrated.


Marijuana smoking and reduced pressure in human eyes: drug action or epiphenomenon? Normal pressure within the human eye was reduced after smoking a socially relevant dose of marijuana (12 mg. delta9-9-tetrahydrocannabinol), but only for light to moderate users who experienced a substantial "high" and a state of peaceful relaxation from the experimental dose. Analysis suggests an indirect effect of the drug associated with relaxation-a psychophysiologic state that can be produced by drug and nondrug  means.


Improved corneal storage for penetrating keratoplasties in man. Twenty-six of 28 human corneas stored for up to seven days in a simple tissue culture medium (dextran dissolved in tissue culture medium with streptomycin-penicillin mixture) remained clear and thin after keratoplasty. Temperature reversal phenomenon and electron microscopy demonstrated high quality of such tissue after storage. The method is inexpensive, requires limited technical assistance, and provides the surgeon with excellent tissue at regular operation hours.


Transvitreal chorioretinal biopsy in the rabbit. Transvitreal chorioretinal biopsy was performed in nine Dutch rabbits by introducing a biopsy instrument through a small eye wall incision, passing the instrument across the eye through the vitreous to the biopsy site, and by trephinating and removing from the eye a 1.6-mm diameter specimen of the posterior eye wall. Biopsy was carried out under stereotaxic control by using a micromanipulator especially designed for ophthalmic surgery. Hemostasis was achieved by circumferential mechanical pressure around the biopsy site. The eye wall defect was sealed by a preplaced explant and repaired by fibrovascular ingrowth from the surrounding choroid and episclera. The normal histologic features of the biopsy specimen were preserved, except for separation of the neurosensory retina from the pigmented epithelium. Complications of the procedure included hemorrhage from the incision site, transvitreal strand formation, and lens abrasion. In no instance, however, did these complications result in significant opacification of the optical media. The biopsy technique has potential use as a clinical procedure in the diagnosis of choroidal tumors and other selected disorders of the choroid and retina and as a technique in investigational animal studies.


Ocular reticulum cell sarcoma.

Ocular reticulum cell sarcoma. In four of eight cases of reticulum cell sarcoma with ocular involvement diagnosis was made by craniotomy when the signs of a brain tumor developed. A fifth case had an isolated intraocular tumor. Of the other three, two were diagnosed by vitreous aspiration and one by cerebrospinal fluid cytology. Ocular reticulum cell sarcoma frequently accompanies or precedes brain involvement. In this form of the disease the ocular lesion is usually a tumor cell infiltrate of the retina. The associated retinochoroiditis leads to marked vitreous clouding and eventual retinal detachment and glaucoma may occur. On the other hand, when intraocular reticulum cell sarcoma occurs in association with the systemic lymph node visceral form of the disease, choroidal involvement is the rule. Vitreous aspiration may confirm the diagnosis at an early stage when clinical and laboratory evaluation reveal no disease outside the globe. The retinal tumor foci are radiosensitive and local radiation, although not curative, may restore visual acuity. Immunosuppressive therapy given in low doses for anti-inflammatory effect may exacerbate the disease.


Neutropenia and salmonellosis in hospitalized horses. Colitis due to salmonellae was diagnosed in 9 horses following hospitalization for various reasons at the University of Missouri Veterinary Teaching Hospital, from May, 1971, to April, 1972. Diarrhea, fever, and either a neutrophil count of less than or equal to 3,600/cmm or a rapid decline in neutrophil numbers were specific for salmonellosis. The value of hematologic survelillance in hospitalized Equidae was demonstrated in another group of 9 horses with neutropenia, each of which was promptly treated and did not develop colitis. Bacteriologic culturing of fecal samples from 28 clinically normal horses yielded only 2 salmonella isolations, S manhattan in each case. The serotyped salmonellae isolated from the patients with colitis were all S typhimurium, with similar antibiotic resistance patterns.


Generalized mastocytosis in a foal, resembling urticaria pigmentosa of man. A newborn foal with multiple, nodular, cutaneous lesions containing mast cells and with mast cell accumulations in bone marrow was observed for 1 year. Cutaneous nodules grew to several centimeters in size, ulcerated, and regressed. Only a few healed nodules remained when the foal was 1 year old. The disease was considered to be similar to urticaria pigmentosa of man.


Distribution of red and white blood cells in alveolar walls. Dog lungs were perfused with blood and rapidly frozen with liquid Freon gas at various pulmonary artery and venous pressures. The numbers of red and white blood cells per mm-2 of alveolar wall were counted in lung sections and, in addition, the proportion (by area) of the wall occupied by the cells was measured by point counting. The number and proportional area of the red blood cells rapidly increased as perfusing pressure was raised. These findings are consistent with earlier observations of capillary recruitment and distension. An unexpected observation was the large number of leukocytes in the capillaries especially at low perfusing pressures. For example when arterial exceeded alveolar pressure by 5 cmH2O (as occurs near the apex of the upright human lung), there were about 5,000 red cells and 4,000 white cells per mm-2 of alveolar wall. As perfusing pressure was increased, the number of leukocytes paradoxically decreased in zone 3 but remained constant in zone 2. Most of the white cells were mononuclear cells. These results suggest that the lung behaves as a mechanical sieve for large cells and that the number of trapped cells depends on the capillary pressure.


Expiratory reserve volume and vital capacity of the lungs during immersion in water. The effects of immersion by 5-cm increments on the expiratory reserve volume of the lungs (ERV) and on the vital capacity were studied in the sitting and supine positions. These effects were compared to those produced by continuous negative-pressure breathing when the subjects were in air and were counteracted by positive pressure breathing during immersion. The depth of immersion was also related to definable anatomic landmarks. In the sitting position about one-fourth of the decrease in the ERV was accounted for by the hydrostatic pressure of the water on the abdomen and the remainder by the pressure on the thorax. Immersion to the level of the spinous process of the seventh cervical vertebra was equivalent to 28 cmH2o continuous negative pressure breathing in air. In the supine position, a comparable value was 8 cmH2o. These observations agree well with those of others if differences in the levels of immersion are accounted for.


Scanning electron microscopy of cavity margins finished with ultra-speed instruments. The quality of the margins of the box portions of Class II cavities finished with rotating instruments at ultraspeed was assessed. In a closed row of teeth, an adequate finish was obtained at the embrasure margin where the burs rotated toward the tooth surface and into the cavity. The finish of the opposite embrasure margin and of the gingival margin was imperfect, regardless of the instrument used.


Effect of temperature and humidity on the adhesive strength of orthodontic direct bonding materials. The effects of temperature and humidity on the adhesive strength of two direct bonding orthodontic materials were investigated. Tensile testing showed that the adhesive bond was much stronger than the polycarbonate brackets. There is a significant increase in tensile and shearlike strength after 15-, 22-, and 30-day incubation at 37 C and 100% humidity, as compared with initial strength (after 30 minutes) at room temperature.


Persistent individual differences in the bacterial flora of the skin of the forehead: numbers of propionibacteria. The bacterial flora of the central area of the forehead of 48 adults was examined by a standardized swabbing procedure to determine the extent of individual variation. Propionibacteria were the most abundant organisms on most subjects. Their numbers per cm-2 of skin ranged from fewer than 6 to 1,100,000. Seventeen subjects had more than 100,000 and 16 subjects yielded fewer than 10,000. Six had fewer than 1,000. Differences with respect to sex and age were not statistically significant. Coagulase-negative cocci numbered from 25 to 75,000 per cm-2. There was no statistically significant correlation between numbers of propionibacteria and numbers of cocci. In order to distinguish trivial or transient individual differences from those of a more fundamental nature, 16 subjects were examined four times at intervals of several months with a total elapsed time of from 329 days to 523 dyas and a median of 385 days. Eight subjects were representative of the upper third and 8 the lower third of the population with respect to numbers of propionibacteria in the initial survey. Geometric mean values for propionibacteria per cm-2 of skin in the measurements of subjects with a rich population ranged from 152,686 to 280,867. Corresponding figures for the subjects with a sparse population were 1,215 to 3,639. Comparing geometric means by the t-test yielded p values of less than .001 in the second and fourth measurements and less than .01 in the third. It is concluded that a rich or a sparse population of propionibacteria is a stable individual characteristic of the skin of the forehead.


Radioautographic evaluation of changes induced in the rat incisor by high-speed cavity preparation. Rat incisors were evaluated radioautographically for metabolic changes induced by high-speed cavity preparation. Label uptake was reduced substantially in those odontoblasts whose processes had been cut; labeling also was diminished in all other areas of the pulp, especially in that area immediately adjacent to the cavity preparation.


Serum complement and immunity in experimental simian malaria. I. Cyclical alterations in C4 related to schizont rupture. Previous studies indicated that the level of whole serum complement (C') falls during malaria, and that the fall in C' is linked to schizont rupture and the appearance of humoral antibody. For a more detailed study of the role of C' in malaria, levels of C4 were monitored in rhesus monkeys infected with Plasmodium coatneyi. After one to two weeks of infection, significant and abrupt declines in C4 levels occurred, and these were temporally related to the process of schizont rupture. The level of C4 began to fall within a few hours after the onset of schizont rupture and fell to values as low as 2% of prerupture levels. Over the next 24-36 hr, C4 returned to normal levels, and fell again during the next cycle of schizont rupture. In general, the decline in C4 levels was positively correlated with the onset of immune response (functional and serologic) and degree of parasitemia. This marked cyclincal depletion of C4 indicates tremendous turnover of C' in primates with malaria.


Mouth lesions in iron-deficient anemia: relationship to Candida albicans in saliva and to impairment of lymphocyte transformation. The atrophic glossitis and angular chilosis in patients with iron-deficient anemia are associated with infection of the mouth by Candida albicans. Saliva from these patients contained more Candida and supported the growth of Candida better than did saliva from a control group. The possibility that growth of Candida may be due to impaired lymphocyte function was investigated by measuring transformation of lymphocytes stimulated with phytohemagglutinin. Transformation was depressed in iron-deficient subjects and returned to normal after correction of their iron status. The lymphocyte count in the peripheral blood was also depressed and corrected by additional iron. Impaired lymphocyte function did not explain the mouth lesions and growth of Candida in saliva since lymphocyte transformation was equally depressed in patients with and without mouth lesions. A local factor, such as an effect of lack of iron on the resident vacterial flora of the mouth, may be important.


The relation of K-antigen to virulence of Escherichia coli. The content of K-antigen was determined for 100 strains of Escherichia coli isolated from the blood of patients with bacteremia. 30 strains isolated from urine cultures, and 30 strains isolated from the feces of patients recently admitted to the hospital. The K-antigen content of urinary isolates of E. coli was significantly greater than that of strains isolated from feces, as noted by other workers. In contrast, the amount of K-antigen of blood culture isolates was not significantly greater than that of fecal isolates and was significantly lower than that of urinary E. coli isolates. No correlation could be detected between the K-antigen content of blood culture isolates and the severity and outcome of the bacteremia.


Demonstration during life of rabies antigen in humans. In three cases of human rabies, in which the diagnosis was proved postmortem, rabies antigen was detected by direct immunofluorescence of frozen sections of facial skin. The antigen was thought to be in nerve fibers in association with hair follicles. Development of this technique might enable the establishment of a method for the diagnosis of human rabies during life.


Quantative analysis of the vectorcardiogram in obesity. The effects of weight reduction. Vectorcardiograms (VCG) recorded in 37 subjects with marked chronic EXOGENOUS OBESITY (AVERAGE WEIGHT: 285 LBS.) WERE COMPARED before and after a significant weight reduction (average weight loss: 86 lbs). They were also compared with the VCGs of 293 age and sex matched controls with normal body weight. The SVEC III corrected orthogonal lead system was used, and out of several hundred vectorcardiographic measurements obtained by computer processing, 59 measurements representing various scalar, planar and spatial voltage and angular measurements were selected for study and comparisons. No significant differences were found between the measurements of obese subjects and those of the controls. Of 59 VCG measurements, 13 showed significant differences after weight reduction (paired t test) although they remained within the range of normal controls. There was a trend toward decrease of P and QRS amplitudes after weight reduction. There were no significant changes in the angular measurements. Although they are statistically significant these changes in voltage are too small to be detected in clinical vectorcardiography. The possible decrease of a preexisting myocardial hypertrophy superimposed onto the changes in the anatomy of the thorax might explain the effects of weight reduction. In general the reproducibility of VCG measurements obtained by the SVEC III system was greater than that reported in day-to-day operation with the Frank system in normal subjects.


Junctional reciprocating tachycardias. The permanent and paroxysmal forms of A-V nodal reciprocating tachycardias. Stimulation technics have demonstrated a reciprocating mechanism in many supraventricular tachycardias previously classified from a purely morphologic point of view. Three conditions are required for the creation of a circus movement: a potential circuit pathway, undirectional block in this curcuit, and slowed conduction. While all three conditions are readily apparent in reciprocating tachycardias of the WPW syndrome, two or even all of these factors may be concealed in the others forms. Paroxysmal reciprocating tachycardias are characterized by prolongation of the P-R interval in the beat immediately preceding the tachycardia, and are generally accepted as being related to longitudinal dissociation of the A-V node, though the possibility of unidirectional (anterograde) block of an extra-nodal accessory pathway should be appreciated. Permanent reciprocating tachycardias start after a normal P-R interval when the sinus cycle reaches a critical value. Both paroxysmal and permanent forms of reciprocating tachycardia must be differentiated from tachycardias located in the atria: one of the most reliable features of reciprocating tachycardia is the existence of a 1:1 A-V relationship which cannot be altered without interrupting the tachycardia. Study of capture phenomena during the tachycardia, and the modes of termination not only permit the demonstration of the reentry mechanism but may also determine more precisely the actual location of the circus movement.


Somatotopic representation of hindlimb skin in cat dorsal horn. Single-unit exploration of the dorsal horn of segments L4-S2 of unanesthetized cats with the neuraxis transected at lower thoracic levels reveals a somototopic organization in the horizontal plane. The dorsal horn dermatomes correspond closely to the dermatomes of the corresponding dorsal roots, and the ML gradient is equally well described by two different projection schemes: a distoproximal gradient and a ventrodorsal one (5, 33). There is no evidence of segmental discontinuity of the map. As is the case in other nuclear regions of the CNS, the relative area devoted to projections from the foot is disproportionately large relative to the area devoted to skin regions of similar size which are located more proximally on the limb. From our data, and from the close correspondence to anatomical data obtained by others, we suggest that at least some cutaneous afferent fibers from a given skin area project directly to any dorsal horn region where that skin area is represented. This assumption, together with the organization of the dorsal horn map, yields a model which predicts a precise somatotopic organization of presynaptic neuropil in the substantia gelatinosa.


Follow-up comparison of hydrocephalus with and without myelomeningocele. A series of 454 hydrocephalic patients with and without myelomeningocele and with and without treatment is reviewed. The survival rates for hydrocephalus alone and for hydrocephalus with myelodysplasia are comparable. The authors reach the conclusion that treatment of the hycrocephalic process and its complications is the most critical therapeutic consideration. Mental retardation is the major unalterable cause for failure to develop independence; some lesser emotional causes can be modified by encouragement. Repeated reassessment of the patient's condition and adjustment are important. Before treatment is started parents or guardians should be fully informed of the child's future potential for independent life and mental development.


A comparison of 111In with 52Fe and 99mTc-sulfur colloid for bone marrow scanning. Under most circumstances 52Fe, 111In, and colloid show a similar distribution of marrow. The lesser uptake of 111In by liver and spleen may occasionally be of value in permitting visualization of that portion of the spinal marrow obscured by these organs in the colloid scan. However, in red cell aplasia, when there is dissociation between phagocytic and erythropoietic functions, scanning with 111In gives no information about erythropoietic tissue distribution. Therefore, indium cannot be used as an analog for iron in the study of the hematopoietic system.


The medical ethics of bone marrow transplantation in childhood. Bone marrow transplantation has been utilized for the treatment of severe aplastic anemia in a program at The Children's Hospital Medical Center. A protocol has been developed to help ensure that the interests and rightful claims of all involved parties will be taken into account. Three cases are presented. In one case all involved parties concurred with the plan for bone marrow transplantation. In a second case the prospective donor was deemed mentally incompetent to give truly informed consent for the procedure. In a third case the parents were unwilling to have their child undergo transplantation. The ethical issues raised in these cases suggest the need for further development of a moral technology to enhance decision-making competence and to aid in the recognition and application of the rights of children without impeding the advancement of pediatric medicine.


Mesangiocapillary glomerulonephritis: changes in glomerular morphology with long-term alternate-day prednisone therapy. In all of eight patients with mesangiocapillary glomerulonephritis who received prednisone in an alternate-day schedule for 3 to 9 hr, the glomerule showed a marked reduction in mesangial cellularity and complete regression of mesangial interposition. Subendothelial deposits disappeared but intramembranous dense deposits, when present previously, persisted. Repair was incomplete in that a few mesangial deposits were still present, immunoflourescence was unchanged, and several of the patients developed focal mesangial scarring and increased numbers of global bodies. Functional glomerule and glomerular tuft segments, however, showed greatly improved morphology. There was no evidence of deterioration of renal function over a follow-up period of 5 to 11.5 yr.


Clinical observations following root amputation in maxillary molar teeth. Thirty-four maxillary molar teeth were evaluated from 11 to 84 months after root amputation. The most consistent finding was that although 24 were neither splinted nor supported in any way, only three developed mobility. Two of these were used as abutments for partial dentures. One other tooth was extracted due to recurrent lateral abscesses and subsequent involvement of the mesial furca.


Development of dental plaque on epoxy resin crowns in man. A light and electron microscopic study. A method was presented to fabricate epoxy resin crowns to be worn by human subjects requiring full crown restorations. These crowns were utilized in six young adults to study the internal structure of plaque after plaque formation periods of 1 and 3 days, 1 and 3 weeks and 2 months. This study confirmed previous findings that early plaque contains primarily coccal forms, with a shift to predominantly filamentous forms by 3 weeks. Early plaque growth seems to occur by the formation of columnar microcolonies which coalesce and grow by cell division within the colony in a direction perpendicular to the crown surface. Filamentous microorganisms appear in large numbers by 1 week. They appear to colonize the surface of the predominantly coccal plaque, eventually growing into it and replacing the coccal forms. The subgingival, mature plaque contains many motile forms including bacteria with unusual cell wall ultrastructures. Certain bacteria combine into distinctive bacterial aggregations resembling "corn cobs" and "test tube brushes," the latter occurring exclusively in subgingival plaque. Spirochetes appear to grow preferentially on the external surface of subgingival plaque in close contact to the gingival tissue of the deepened sulcus. Their high concentration in the external layer of subgingival plaque suggests that because of their strategic location they may play an important role in the etiology of periodontal disease. Studies of well preserved plaque, possibly combined with the use of serological markers, can serve a useful role in identifying certain microorganisms in dental plaque. Because of their numbers and/or location in relation to periodontal tissues, some of these bacteria may warrant further studies as potential etiologic agents of certain forms of periodontal disease.


Mating, ovulation and corpus luteum function in the vole, Microtus agrestis. A study of the relationship between the mating vehaviour of the vole and the induction of ovulation and CL function is described. A single intromission or an injection of LH-RF constitute stimuli which induce ovulation, but normally give rise to CL that degenerate soon after formation. More prolonged mating, or mechanical stimulation of the vagina and cervix given after a separate ovulatory stimulus, result in the maintenance of the CL. Mechanical genital stimulation is effective in inducing CL MAINTENANCE WHEN GIVEN UP TO 48 HR AFTER AN LH-RF injection. Similarities, therefore, are apparent between the vole, an induced oculator, and spontaneous ovulator, and spontaneous ovulators such as the rat, mouse and hamster.


Scanning electron microscopy of the luminal epithelium of the mouse uterus. Four methods of manipulating mouse uterine tissue during fixation, preparatory to examination of the luminal epithelium by scanning electron microscopy (S.E.M.), are described and the results assessed. The appearance of the epithelium varies according to the technique used, the choice of method depending on the type of information required from the S.E.M. study. Surface topography is preserved in a condition most closely resembling that of fresh tissue by opening the uterus and fixing the tissue flat. Critical examination of cellular and subcellular surface detail, however, depends on adequate spreading of the epithelial layer during fixation by distension of the uterine lumen under positive pressure. The method of tissue manipulation has a more profound effect on the appearance of the sample than any of the dehydration techniques which follow. For routine S.E.M. examinations at medium magnifications (smaller than X10,000), specimens which were air dried from alcohol, acetone or ether, or freeze dried, gave satisfactory results. Air drying from amyl acetate, and CO2 critical-point drying gave superior results at higher magnifications (greater than X10,000) with better preservation of individual microvilli.


Neuroendocrine mechanisms responsible for gonadotropin release. Regulation of the ovulatory cycle involves the interdependence of the adenohypophysis, the ovaries, the CNS, and the external environment. Several distinctions in brain functions and the overlapping control of several neuro-endocrine systems are pointed out. Important neuro-anatomical relationships between basomedial hypothalamus and other brain regions are noted. The anatomical structure is correlated with the control of gonadotropin secretion. Reflexive ovulation is considered as a special instance of external environmental influence. Data suggests that both lower mammals and human primates may show reflexive as well as spontaneous ovulation.


Cesarean section in the massively obese. A series of 24 abdominal sections were performed on patients weighing 114 Kg or over. A detailed analysis of the indications, vital statistics, and medical, surgical, and post operative complications were made. There were no serious complications. The authors conclude that reluctance to perform abdominal section because of obesity is not warranted.


The immature HPO axis.

The immature HPO axis. One cause or anovulation may be an immature hypothalamic-pituitary-ovarian axis. The fact that initial menstrual cycles are usually irregular and often anovulatory implies that a maturation process is taking place in the HPO axis and that cyclic ovulatory menstruation begins only when adequate maturation occurs. Moreover, the external appearance of the ovary of a severely oligomenorrheic or amenorrheic female frequently is similar to that of a prepubertal female--this is, the ovary appears normal in size of slightly smaller, has a smooth, glistening surface without convolutions, and its capsule-like outer surface reveals few, if any, underlying follicles. A reasonable assumption is that there is inadequate gonadotropin stimulation of these ovaries possibly as a result of an immature HPO axis. The studies by radioimmunoassay of FSH and LH levels in prepubertal and pubertal  females offer no statistical data by which to measure the maturity of the HPO axis, although consistently low FSH and LH levels may prove meaningful. Studies of FSH and LH in patients exhibiting gonadal dysgenesis neither support or disprove the immature HPO axis theory, but studies of idiopathic sexual precocity tend to support it. Studies using LH-RF in prepubertal and pubertal females indicate a pattern of response which may give useful information in the area.


Field trials of a gonococcal vaccine.

Field trials of a gonococcal vaccine. Several small, well controlled field trials with a gonococcus vaccine have been initiated. The results to date indicate that the vaccine elicits only mild reactions in humans, and that it will produce antibodies of possible significance in over 90 per cent of vaccines. Its value in preventing gonorrhea has yet to be established. Studies towards this end are now being considered.


Release of sediment-bound fecal coliforms by dredging. Fecal coliform concentrations increased significantly (F test) in the immediate vicinity of a maintenance dredging operation in the Mississippi River navigation channel. Increased counts were attributed to the disturbance and relocation of bottom sediments by dredging and a concomitant release of sediment-bound fecal coliforms.


Medium-scale production of citrinin by Penicillium citrinum in a semisynthetic medium. A convenient method is described for the production of up to 1.75 g of citrinin per liter by Penicillium citrinum growing in stationary culture in a 5-gallon (18.925 liters) carboy containing 4 liters of 4% sucrose and 2% yeast extract medium.


Evaluation of a medium for the rapid recovery of Escherichia coli from shellfish. A medium (A-1) which shortens the time necessary to identify and enumerate Escherichia coli found in estuarine water was evaluated for use for recovery of E. coli found in shellfish. Productivity of E. coli by this medium was comparable to that of the lengthier American Public Health Association method, and the occurrence of false positives was substantially reduced.


Irradiation of Escherichia coli in the visible spectrum with a tunable organic-dye laser energy source. Pulsed laser energy was shown to be effective in inhibiting the growth of Escherichia coli. The irradiation source was derived from a tunable organic-dye laser utilizing rhodamine 6G (590 plus or minus 5 nm) solutions as lasing media. The organisms, suspended in nutrient broth, were irradiated both with and without an exogenous photosensitizer. One photosensitizer (toluidine blue) did not appreciably alter the inhibitory effect observed. In the presence of acridine orange, however, some additional growth occurred.


Evaluation of a muscle relaxant: dantrolene sodium (Dantrium). Dantrolene sodium (Dantrium) is a skeletal muscle relaxant, unique in that it acts on the muscle itself. It should be considered for use in patients with skeletal muscle spasticity who are in a stable neurological state. After careful adjustment of the dose, a substantial number of such patients will experience one or more of the following benefits: (1) a reduction in pain, (2) an increased ability to make use of residual motor function, (3) a reduction in the level of nursing care required, (4) an increased ability to utilize devices, and (5) an increased ability to participate in rehabilitation. The drug should not be used when reduced spasticity will decrease functional ability. The adverse effects generally are transient; some are the result of central nervous system depression.


Complexities of smoking education.

Complexities of smoking education. Cigarette smoking is a many-headed Hydra, which grows new smokers' heads as fast as they are lopped off. Efforts to change smokers' behavior usually reach a  point of diminishing returns, as evidenced by experiences in smoking withdrawal clinics and in public anti-smoking education campaigns. Obviously, many smokers are refactory to anti-smoking education, a situation which has generated a great deal of pharmacological, neurochemical, psychological, and sociological research. The National Clearinghouse for Smoking and Health in the U.S.A. has used a "gradualist" or permissive approach in anti-smoking messages, aimed at less hazardous smoking "if you must smoke," rather than at complete cessation, and found this approach to be useful. U.S.A. school-children are exposed to anti-smoking education in lower grades than formerly, when it was offered in high school. Thus a population of as yet non-smoking children is being educated. Perhaps the adult non-smokers should be enlisted in an effort to create a social climate wherein smoking is not an acceptable behavior-an approach reflecting the concept of smoking as a social disease. Health education addressed to the receptive non-smoker would circumvent the refractory smoker. A theme with appeal to non-smokers is the protest against environmental pollution by smokers. It is possible that if a movement by non-smokers against smoking would gather momentum, it could turn the present accepting social climate into one rejecting smoking, thus striking at the regeneration of the Hydra: the incessant recruitment of smokers among ex-smokers and non-smokers. With recruitment below replacement level, the Hydra would in time wither away.


Continuous sutures in replacement of mitral and tricuspid valves with prostheses. Four years' experience with 363 patients, in whom 360 mitral and 65 tricuspid prosthetic valves have been implanted with single continuous sutures, is presented. The occurrence of prosthetic valve detachment is particularly discussed. There were 4 cases of detachment of the prosthetic mitral valve and no cases of tricupsid dehiscence. All 4 patients with detached valves required reoperation. Calcifications that penetrate into the annulus and myxomatous degeneration of the valve are considered more important factors in the production of prosthetic cases so long as a uniform distribution of stitches is maintained (not too close to each other) and excessive tension in the suture line is avoided.


Surgical considerations in patients undergoing repeat median sternotomy. A retrospective review of 122 repeat median sternotomy incisions in 100 consecutive patients was made to evaluate complications and management. Eighty-one patients had one repeat sternotomy, )6 had two repeat sternotomies, and 3 had three repeat sternotomies. All had valve procedures in the past and were reoperated upon for progressive rheumatic valvular disease or for complications related to the prostheses. Complications included operative hemorrhage in 8 patients, postoperative hemorrhage in 2, seroma in 4, and dehiscence, wound infection, and hematoma in 1 patient each. The most serious complication was hemorrhage and was the cause of the only operative death. Seven other patients survived hemorrhage encountered during repeat sternotomy. Control of massive hemorrhage during repeat sternotomy has been possible due to an organized approach to the patient with adhesions from previous surgery.


Selective sputum cultures. A bronchial culture technique using a modified nasotracheal suction catheter with a sterile, inner telescoping cannula. The contamination of expectorated or catheter-aspirated sputum specimens by pathogenic microorganisms which have colonized the nose and oropharynx remains a formidable obstacle to the accurate interpretation of sputum cultures. This problem is encountered in all forms of acute and chronic bronchopulmonary infection. A standard suctioning technique via a nasotracheal catheter has been modified with a telescoping sterile inner cannula to obtain uncontaminated bronchopulmonary secretions for culture. Bacteriologic results of selective bronchial cultures obtained in 18 patients following major chest surgery have provided important considerations concerning the prophylactic use of antibiotics. The telescoping cannula method is a simple, safe, and practical means of selectively monitoring the bacteriologic flora of the lower respiratory tract.


Sociobehavioral determinants of compliance with health and medical care recommendations. Over the past two decades, hundreds of articles, editorials, and commentaries have been published describing the considerable disruptive effects on quality of care of individuals noncompliance with health and medical advice. While much research has been directed at determining factors responsible for poor compliance, past studies have tended to focus upon easily measured characteristics of the patients, regimen, or illness which, unfortunately, are usually neither predictive nor alterable. This paper systematically reviews the literature on patient acceptance of recommended health behaviors, attempting to find social-psychological and related variables which have proven to be consistent predictors of compliance. The review suggests that certain health beliefs (especailly personal estimates of vulnerability to, and seriousness of, the disease, and faith in the efficacy of care), health-related motivations, perceptions of psychological and other costs of the recommended action, various aspects of the doctor-patient relationship, and social influence are the most productive dimensions for present intervention and further exploration. Building upon an earlier formulation, an hypothesized model is presented which combines these elements for explaining and predicting compliance behavior. Further research should, with standardized questionnaires and analysis techniques, employ prospective, experimental designs for a variety of population groups, settings, and regimens, to evaluate the ability of practical attempts to modify the model variables and thus enhance compliance.


Metabolic factors in the control of energy stores. We have examined some of the factors involved in the control of food intake and integrated the data using methods of systems analysis from biomedical engineering. The central hypothesis is that energy stored in the body is a regulated variable. Alterations in the quantity of stored calories initiates changes designed to restore the store of calories to its original level. These responses are both short-term and long-term in nature. They involve integrating data on the quantities of protein, carbohydrate, and lipid stores in the body, probably through such feedback signals as amino acids, glucose, glycerol, and free fatty acids.


Effects of corticosteroid therapy on human monocyte function. Since high-dose corticosteroid therapy appears to impair cellular defense mechanisms, this study examined its effect on human monocyte function. Fifteen normal volunteers were studied before and after a three-day course of prednisone therapy (50 mg every 12 hours for six doses). A transient period of monocytopenia occurred during the first few hours of therapy. Monocyte killing of Staphylococcus aureus was reduced in nine subjects from 5.6 plus or minus 0.2 (plus or minus S.E.) X 10-6 organisms before to 1.3 plus or minus 0.4 x 10-6 organisms at completion of therapy (p less than 0.01). Similary, killing of Candida tropicalis four subjects fell from 9.3 plus or minus 0.6 to 0.6 plus or minus 0.3 x 10-6 organisma (p less than 0.01). Bactericidal activity returned to normal levels 48 hours after the last dose of prednisone. These same monocyte preparations had normal or increased chemotactic response, phagocytic rate of cryptococci, hexosemonophosphate-shunt response to phagocytosis and ultrastructural characteristics. This impairment of bactericidal and fungicidal activity during prednisone therapy may contribute to the infectious complications seen in patients receiving comparable doses of corticosteroids.