Drinking practices and cognitive functioning. The relationships between drinking practices and cognitive functioning were examined in a non-patient sample. Neither the amount of alcohol consumed over a lifetime nor current frequency of drinking occasions was significantly (ps greater than .05) correlated with cognitive test scores. However, the quantity of alcohol consumed per drinking occasion was inversely related to performance on tests of abstraction, adaptive abilities and concept formation. The results suggest that social drinking may have deleterious effects on cognitive processes.


The dipsogenic effect of alcohol and the loss of control phenomenon. A counterbalanced within-subjects design was employed to assess the acute effects of alcohol ingestion on thirst and fluid intake and to relate these effects to the dehydration known to result from acute ingestion of alcohol. Fourteen male nonalcoholic social drinkers between the ages of 18 and 30 consumed 0.8 gm of alcohol/kg body weight during one experimental session and a placebo (0.05 gm/kg) of equal volume during the other. During the 90-minute drinking period and for one hour both before and afterward, urine specimens were collected. After the drinking period, blood alcohol levels and unobstrusive measures of ad lib drinking were recorded. In addition, subjects rated their degree of thirst three times during each session. Analyses of variance indicated that alcohol significantly increased both fluid intake and urine output, and decreased urine specific gravity. Moreover, thirst ratings were also significantly greater after alcohol than after placebo and fluid intake after alcohol was significantly correlated with prior measures of fluid balance, mean urine specific gravity, peak blood alcohol level and thirst. The implications of these results for the loss of control in alcoholism are discussed and a new theoretical account of the phenomenon is proposed.


Assessing the alcoholic's disposition to drink. Reliable and valid techniques for assessing the alcoholic's disposition to drink would allow researchers to address many issues of clinical significance. This paper reviews some basic issues in behavioral assessment techniques, proposes several criteria for a reasonably general technique for assessing disposition to drink, and presents evidence relevant to the validity of one behavioral measure of disposition to drink. A study is presented which focuses on distinguishing good from poor treatment outcome subjects on the basis of their response patterns for alcohol during a simulated drinking binge. Alcoholic subjects were assigned to one of two treatment outcome groups based on treatment success evaluated at follow-up two months after hospital discharge. An analysis of the alcoholic's response patterns for alcohol during a simulated drinking binge revealed that good outcome subjects showed decreases in disposition to drink as their blood alcohol levels (BAL) rose, while poor outcome subjects showed increases in disposition to drink as their BAL increased. These results indicate that individual differences in behavioral response to alcoholization and withdrawal can index the alcoholic's potential for readdiction and relapse subsequent to hospital treatment and illustrate the role which behavioral assessment techniques can play in developing and refining models of human alcohol abuse.


On the possibility that opiate and ethanol actions are mediated by similar mechanisms. Opiates and alcohol modify neuronal electrical activity in many sites of the nervous system. Both act as depressants or stimulants of cell firing depending upon the type of cell studied. Alcohol seems to act upon some nerves by changing their membrane ionic conductance, while opiates seem to affect synaptic events. However, all of the known neural actions of these substances involve calcium-dependent mechanisms. A hypothesis is proposed to account for these facts.


A comparative analysis of the effects of narcotics, alcohol and the barbiturates on the hypothalamic-pituitary-gonadal axis. The purpose of this paper is to provide an overview of our current state of knowledge regarding the effects of alcohol, the narcotics and the barbiturates on the hypothalamic-pituitary-gonadal axis in the male. Three facets of this problem will be considered: acute drug effects; chronic effects, particularly with respect to the development of tolerance and physical dependence; and, finally, an attempt will be made to indicate the way in which these three substances of abuse are similar and/or dissimilar in their effects on this system. The effects of acute and chronic treatment with narcotics, alcohol and the barbiturates will be discussed first and then an attempt will be made, in a General Discussion, to summarize the data, make general comparisons between the drugs and suggest future lines of research.


Human cathepsin D.

Human cathepsin D. Cathepsin D was purified from human liver by a procedure involving autolysis, acetone fractionation, and chromatography on ion-exchange media and organomercurial-sepharose. Multiple forms of the enzyme were then separated by preparative isoelectric focusing. The molecular weight of the protein was found to be 43,000. Its amino acid composition was determined and it was shown to be a glycoprotein. When treated with sodium dodecyl sulphate or chaotropic agents (without reduction) all forms of the enzyme tested gave components of about 28,000 and 14,000 molecular weight. Specific antisera were raised against the enzyme, and the characteristics of immunoinhibition were investigated. Immuno-inhibition of rabbit cathepsin D within living macrophages was shown to interfere with degradation of some proteins endocytosed by the cells. The antisera against human and rabbit cathepsin D were used in immunofluorescent localization of the enzyme in sites of tissue damage in which cathepsin D might be implicated. The characteristics of inhibition of human cathepsin D by pepstatin were established. At pH values below 5, KD values of 5 x 10(-10)M were determined and pepstatin was shown to be an excellent titrant for cathepsin D. In the range pH 5-6.4 DK increased steeply and it was concluded that the binding site for substrate and inhibitor was abolished by a conformational change in the enzyme molecule in which three protons are lost.


Unique biochemical and biological features of cathepsin D in rodent lymphoid tissues. Cathepsin D, an enzyme consistently found to be lysosomal in many cells, has an unusual localization in rat thoracic duct lymphocytes (TDL). After fractionation of homogenates of rat TDL, most of the enzyme activity, as measured at pH 3.6 on denatured bovine hemoglobin, is distributed differently from the other lysosomal enzymes. The enzyme also has some unique properties: it is not inhibited by an antiserum inhibitory for rat liver cathepsin D; it exists in two molecular weight forms (approximately 45,000 and approximately 95,000) both of which have a higher specific activity than rat liver cathepsin D, as determined by studies using the irreversible inhibitor, sodium pepstatin; the high molecular weight form converts to the low molecular weight form after treatment with beta-mercaptoethanol without any loss in activity. These enzymes appear to be restricted to rodent lymphoid tissues. Reasons for considering them to be a type of cathepsin D are given in the text.


Specificity and biological role of cathepsin D. The purity of cathepsin D has been increased from 150 units/mg to over 200 units/mg. Peptides such as Ala-Phe-NH2, His-Phe-NH2 and Phe-Phe were split by impure enzyme and activity was blocked by pepstatin and diazoacetylnorleucine methyl ester. Pure preparations no longer digested these peptides. This points to the presence of a second peptidase activity similar to cathepsin D in specificity and inhibition properties, but distinct from it . Cathepsin D splits the peptides Leu-Phe-NH2, Leu-Tyr-NH2, Ac-Phe-TyrI2, and Ala-Leu-Tyr-Leu upon overnight incubation. More rapid splitting is found with phenyl sulfite, Glu-Ala-Leu-Tyr-Leu-Val, and Bz-Arg-Gly-Phe-Phe-Leu-4-methoxy-beta-naphthylamide. Digestion of bovine hemoglobin and human serum albumin by ruptured rat liver tritosomes was studied over the pH range 2.5-6.5. The combined action of cathepsin D and thiol proteinases accounted for most of the digestion. Cathepsin D accounted for 75% of the  hemoglobin digestion at pH 3 and 45% at pH 5. Thiol proteinase accounted for 85% of the albumin digestion at pH 5. The role of cathepsin D in the development of embryonic limbs and skin, in uterine involution, and in cartilage degradation was reviewed. The activity of cathepsin D on cartilage matrix proteoglycans is limited to acid pH values. Human articular cartilage also contains metalloproteases active at pH 4.5 and 5.7.


The crystal structure of an acid protease from Rhizopus chinensis at 2.5 A resolution. This paper contains a preliminary report of the crystal structure of the acid protease from Rhizopus chinensis at 2.5 A resolution. The molecule is bilobal with a large cleft between the lobes. Pepstatin binds in the cleft near the catalytically active Asp-35. The overall folding of the molecule consists primarily of antiparallel beta-strands, there being only four small helices.


Gastrointestinal disorders in old age.

Gastrointestinal disorders in old age. 399 elderly patients were studied in order to establish the frequency of different gastrointestinal diseases and to see to what extent gastrointestinal problems influenced the clinical picture and the final outcome. 276 patients were hospitalized because of medical emergencies. 123 patients were chronically ill. In the first group, 26.8% (74) had major gastrointestinal problems. In 42% of the remaining patients, important functional or organic gastrointestinal disorders were present. In the second group, 46% of the patients had gastrointestinal diseases. Lesions of the digestive system are an important cause of morbidity and mortality in the aged.


A longitudinal study of falls in an elderly population: I. Incidence and morbidity. Falls among the elderly, although associated with substantial morbidity and mortality, have not been previously the subject of a longitudinal study. This five-year prospective study of an active ambulatory institutionalized population over 65 years of age, revealed an annual fall rate of 668 incidents per 1000, with a rising frequency in successive age groups after age 75. Forty-five per cent of all subjects suffered at least one fall during the study period. Women had a higher fall rate in all age groups and the severity of their injuries appeared to increase with age. Injuries severe enough to be brought ordinarily to the immediate attention of a physician occurred in 17.5% of falls. Among subjects who ultimately died after suffering many falls, there appeared in some to be a 'clustering' of falls prior to death.


A longitudinal study of falls in an elderly population II. Some circumstances of falling. Some of the circumstances surrounding 651 falls which occurred in elderly residents of a standard care unit in a home for the aged are described. Falls occurred as frequently at night as during the day-time, and there was no significant variation by day of the week or by season. The great majority occurred inside the home, mainly in the resident's own suite. The subsequent morbidity varied according to the place of occurrence, the percentage of severe injuries being lower in falls occurring in toilets and elevators, and to a lesser extent hallways, compared with those occurring in other inside locations and outside. The commonest activity associated with falling was going to or returning from the toilet. However, one-third of day-time falls occurred when the resident was sitting in a chair. The severity of injury did not vary with associated activity. Possible explanations for these findings are discussed, particularly from the preventive viewpoint.


A study of exercise performance and heart rate: the response to exercise of a small group of manual workers before and after retirement. Measurements of walking pattern, exercise performance, heart rate response to exercise and body composition have been made in 13 male manual workers at retirement and again one and two years later. The exercise consisted of walking, in accordance with standard instructions; heart rate and footfall signals were recorded on magnetic tape during the test using body-borne tape recorders. After the first year highly significant reductions in walking speed were found but no significant changes in walking pattern, heart rate response or body composition. When the measurements made at the end of one year of retirement were compared with those made at the end of two years no significant changes were found.


Bacteriuria in geriatric hospital patients its correlates and management. Significant bacteriuria is associated with dementia, incontinence of faeces and of urine in long-stay hospital patients. Bacteriuria in these patients is a fluctuating condition: it occurred in 47% of an initially sterile control group during the course of a year. Management with urinary antiseptics and an initial course of antibiotics is more successful than antibiotics on demand. However, since the condition is so fluctuating, it is doubtful if any treatment is usually needed other than the prevention of faecal incontinence.


Radiography of the pelvis in a series of 200 elderly patients. Review of the findings of routine radiography of the pelvis in a series of 200 elderly patients admitted to a geriatric department shows that a great number of abnormalities are detected. It is suggested that this procedure is of equal value to routine chest radiography.


Mean cerebral transit time in demented and normal elderly persons. The mean cerebral transit time (MCTT) was measured in 31 elderly subjects, approximately half of whom suffered from chronic dementing illness. The results indicated a significant correlation between the MCTT and arm-to-head circulation time. Both times increased significantly with age. There was no difference in MCTT between demented and non-demented patients.


Prejudices in pharmacology and pharmacotherapy. The so-called anticholinergic effect of antidepressants. Imipramine and similarly acting compounds provoke a number of undesired reactions usually classified as so-called anticholinergic effects. Instances of dry mouth, disturbance of micturition and tachycardia are regularly quoted in the literature. It is contended that these effects are not necessarily due to inhibition of the vagal system, but preferentially attributable to increased activity of the sympathetic system, predominantly mediated by the beta- or the alpha-adrenergic receptors, depending on the organ affected. This hypothesis is not only theoretically interesting, but also of practical clinical significance with regard to possible remedies.


Inhibitory effect of enkephalins on contractions of the guinea-pig ileum elicited by PGE1. Methionine-enkephalin and leucine-enkephalin (m-enk and 1-enk) as well as D-Ala2-methionine-enkephalin amide have been shown to antagonize contractions of the isolated guinea-pig intestine elicited by PGE1, the last mentioned being the most potent of the three. The inhibitory effect of these pentapeptides is abolished by naloxone.


Prostaglandin release from macrophages: an assay system for anti-inflammatory drugs in vitro. It is the intention of this communication to present a simple and reliable in vitro system for the evaluation of anti-inflammatory drugs. The system described appears to combine the advantages of two established procedures, i.e. measurement of the inhibition of prostaglandin (PG) synthesis in vitro using microsomal enzyme preparations and the measurement of the inhibitory effects of drugs on PG synthesis in vivo avoiding major limitations. We propose to measure the effect of drugs on the PG release from mouse peritoneal macrophages in vitro. The influence of culture conditions, phagocytosis and drugs on the PG release from these cells is described. We found that antibody-coated erythrocytes are especially suitable triggers of PG release, and that the release can be inhibited by steroidal and non-steroidal anti-inflammatory drugs in concentrations resembling their effective doses in vivo.


Studies on the potency of various antitussive agents. Several antitussive agents were assessed for their cough-suppressant activity. Cough responses were obtained by electrically stimulating the lower brainstem, in cats lightly anesthetized with sodium pentobarbital or in unanesthetized midcollicular decerebrate preparations. Cough sounds were recorded with the aid of a microphone. The cough reactive region was concentrated in an area dorsomedial to the trigeminal tract and nucleus. The potency of these antitussive agents (dextromethorphan, RO 21-4790-001, codeine, clonazepam, diazepam and caramiphen) were determined by studying their effect on the centrally induced cough responses. Each of these agents was administered in graded doses intravenously to determine the minimal effective doses for suppressing the cough responses. They are 0.57, 2.55, 1.71, 0.048, 0.28 and 3.18 mg/kg for the above listed drugs. The results indicate that clonazepam was found to be the most potent antitussive among these agents, the mean effective dose being about 1/35 of that of codeine. The antitussive potency of benzodiazepines is not well correlated with their muscle relaxant activity. For instance, clonazepam and diazepam have the same potency in depressing polysynaptic spinal reflexes, whereas the former is six times more potent than diazepam as an antitussive. This finding indicates that clonazepam has a high specificity as an antitussive.


Toxicological evaluation of imipramine in combination with adriamycin and strophanthin. Chronic oral administration of imipramine to rats caused characteristic changes of the electrocardiogram (ECG), i.e. prolongation of the PR interval, widening of the QRS complex, and increase in T-wave voltage. The cardiotoxic anthracycline antibiotic adriamycin induced dose-dependent widening of the QRS complex. This effect on intraventricular conduction was not enhanced in rats receiving both drugs. The high adriamycin dose (5 x 4 mg/kg) abolished imipramine-induced prolongation of the PR interval and T-wave elevation. This was not seen with the low adriamycin dose (20 x 1 mg/kg). Imipramine prolonged survival time of rats treated with toxic doses of adriamycin, but enhanced growth retardation in animals receiving the low adriamycin dose. Chronic treatment with increasing doses of strophanthin induced significant flattening of the T wave in rats with and without imipramine therapy, but did not influence the changes of the ECG or body weight gain caused by imipramine. It is concluded that the combined use of imipramine and adriamycin or strophanthin did not lead to a serious enhancement of the toxicity of the tricyclic antidepressant.


Procedures for routine clinical electroretinography (ERG) in dogs. Following pupillary dilatation and immobilization of the dog with a cataleptic drug (l-Polamivet, Hoechst) the electroretinogram (ERG) was performed with the technique of Ganzfeld stimulation. The head of the dog was kept within a sphere of 60 cm diameter, the white inner surface of which could be indirectly illuminated with a stroboscope producing light flashes of 10 musec duration. The ERG was recorded oscillographically by means of modified contact lenses. Dogs were tested for rod and cone function with luminance curves including white, blue and red stimuli and with trains of repetitive photic stimuli. Tests were performed under dark and light adaptation. The ERG of the dark-adapted dog, an indicator for the electrical activity of the rod system, was similar with that of man with respect to configuration and other characteristics. The electrical activity of the cone system was different from that of man by having a 10-fold lower sensitivity and a reduced capability for discrimination of red versus blue or white stimuli.


One-dose and multiple-dose kinetics of minocycline in patients with renal disease. Kinetic analysis of minocycline concentrations in plasma and urine resulted in the following findings: In normal subjects the biological half-life is about 17 hours after the first dose and 21 hours after repeated administration. The renal drug clearance is only about 8% of the overall plasma clearance which is independent of renal function with a mean value of 47 ml/min. The fraction of the absorbed dose eliminated unchanged in the urine is only 9--19%. As a consequence the elimination rate of the drug is practically independent of renal function and decreases only 9--19% in anuric patients. The renal drug clearance depends linearly on renal function. The gastro-intestinal bio-availability of minocycline from the coated tablet preparation is incomplete. The cumulative behaviour of the drug corresponds to the kinetic parameters determined after repeated administration. It is suggested that the usual dosage regimen should be used in patients with renal disease.


Comparative studies of the protein binding of digoxin and its metabolites. The protein binding of Digoxin (D), Dihydrodigoxin (DH), Digoxigenin Bisdigitoxoside (DB) and Digoxigenin Monodigitoxoside (DM) was concentration independent and unaltered by the presence of high concentrations of the analogous compounds. The respective percentage of protein binding for D, DH, DB and DM were 22%, 22%, 23% and 27%.


Regional differences in the responsiveness of isolated arteries from cattle, dog and man. Changes in tension of spiral strips from basilar, external carotid, temporal and muscle arteries from cattle, dog and man were monitored isometrically. Dose-response curves for 5-HT, noradrenaline and ergotamine indicated a variation in responsiveness between different arteries of the same species as well as between the same arteries of different species. When tested against 5-HT ergotamine consistently acted as non-competitive dualist but it antagonized responses to to noradrenaline only in peripheral arteries from dog and man. In all arteries from the carotid vasculature and in bovine muscle arteries the vasoconstrictor effects of ergotamine and noradrenaline were independent additive. It is suggested that the therapeutic value of ergotamine in the treatment of migraine headache is due to its selective vasoconstrictor activity in the external carotid vasculature mediated through independent additive vasoconstrictor effects of ergotamine and noradrenaline.


Adsorption and structural studies on activated carbons. The porous structure of activated carbon is examined from the point of view of gas adsorption, and in relation to classical methods such as X-ray diffraction and electron microscopy. It is suggested that the different approaches to the problem of microporosity should provide complementary information, which can be useful for a better understanding of static and dynamic adsorption processes in activated carbons.


Morphology of the pineal complex in seven species of lanternfishes (Pisces: Myctophidae). The morphology of the pineal complex was compared in seven species of lanternfishes (family Myctophidae) using both light and electron microscopes. On the basis of compactness of the pineal end-vesicle and presence or absence of a dorsal sac, the species in this study were divided into two groups. This grouping seems to correlate well with current views on the phylogenetic relationships among these fishes. Receptor cells and supportive cells are described in the pineals of all species examined. The deepest-dwelling of the forms studied, Parvilux ingens, showed a significant increase in the mean number of lamellar membranes in the outer segments of the receptor cells and a higher convergence ratio of receptor cells to ganglion cells as compared to the shallow-dwelling form Tarletonbeania crenularis. Accordingly it is suggested that the pineal of P. ingens is more photosensitive. Additional differences among species were found in the ultrastructure of the supportive cells. Dorsal sacs were absent in the three shallowest-occurring myctophids studied. In those species with a dorsal sac, its close association with the pineal-end-vesicle suggests a functional relationship between the two structures.


Evidence of a specific nidation site in ruminants. The site of umbilical cord attachment in ruminants indicates the limited segment of the uterus where the blastocyst attachment occurs and could have potential significance for locating presumptive nidation sites. Measurements of the site of cord attachment were made on impala (Aepyceros melampus) and common duiker (Sylvicapra grimmia) at several stages of gestation. Both implant only in the right uterine horn although they ovulate from either ovary. Relative to uterine length, cord attachment in impala is somewhat closer to the cervix than it is in common duiker. As pregnancy advances in common duiker, the relative position of cord attachment becomes closer to the tubal end. This relationship was not seen in impala and may perhaps to be attributed inadequate data. Upon extrapolation of the data from common duiker, a presumptive attachment area is suggested for this species. This region is located at about 41% of the distance from the internal cervical os to the uterotubal junction. Similar cord attachment data could be used in any ruminant species to indicate the existence and location of a specific nidation site.


The fine structure of the melanocytes of the adult mouse hair follicle during their amelanotic phase (telogen and early anagen). Melanocyte-precursor cells have been described previously in telogen and early anagen hair germs by observation of Epon sections using light microscopy. The existence of these precursor cells has not been generally accepted due to lack of ultrastructural evidence. It is our purpose to describe these cells using transmission electron microscopy. We studied hair germs of the dorsal skin of adult mice in the appropriate stages of the hair cycle prior to melanogenesis. Telogen melanocytes are distinguishable from adjacent keratocytes by their lack of desmosomes, lack of coarse clumps of microfilaments, sparsity of ribosomes, unusually few nuclear pores and presence of dendrites. Melanocytes in early anagen show extensive growth with abundant polysomes, elaborate RER and Golgi zones. They still differ from keratocytes in their lack of desmosomes and clumps of microfilament, and also in the occasional presence of premelanosomes.


A radioautographic study of chondrocytic proliferation in nasal septal cartilage of the newborn rat. Growth sites within the newborn cartilaginous nasal septum have been identified by monitoring chondrocytic proliferation radioautographically. Tritiated thymidine was the labeling agent used. The results were tabulated and charted graphically; they showed the overall septum to be relatively active mitotically, yielding an average of 3.54 labeled cells per microscopic field counted. However, certain areas showed greater activity than others, namely the anterior tip (4.51 labeled cells/field), the midportion (3.98 labeled cells/field) and the posterior section of the presphenoidal tail (4.24 labeled cells/field).


Endoscopic electrosurgical polypectomies of the upper gastrointestinal tract. The electrosurgical removal of polypoid lesions from the upper gastrointestinal tract with the esophagogastroduodenoscope has proven to be safe, effective and relatively inexpensive procedure. Thirty polypectomies performed on 26 different patients are presented. Polyps were removed from the distal esophagus, stomach, duodenum and jejunum. There were no significant complications.


Paraduodenal hernias.

Paraduodenal hernias. Paraduodenal hernias comprise approximately 50% of all internal hernias. The clinical diagnosis of this condition is analyzed. Two cases are presented and two theories for the embryological development of these malformations and their surgical management are discussed.


The effect of portacaval shunting in the alcoholic cirrhotic on serum cholesterol concentration. A retrospective study. Preoperative and postoperative cholesterol levels were obtained by retrospective analysis of 28 patients subjected to successful portalsystemic decompression. The average cholesterol values showed a statistically significant decline from 189-161 mg.%.


Hepatic amebiasis-analysis of 56 cases. II. Laboratory and chest x-ray findings. Laboratory and chest x-ray findings in 56 cases of hepatic amebiasis previously reported are described. Anemia and an  elevated E.S.R., frequently without an elevated leucocyte count, were the most frequent hematologic findings. Abnormalities of liver function tests were mild and nonspecific. The most frequent abnormalities seen in chest x-ray were an elevated right hemidiaphragm whose motility on fluoroscopy was reduced or abolished. The abnormalities may be of great help in diagnosis in endemic areas were more sophisticated facilities may not be available.


Polypoid villous adenoma of the stomach. A case report. Clinical symptoms, endoscopic findings and radiographic features of a polypoid villous adenoma of the stomach are described. A working classificaiton of gastric epithelial polyps and a table of differential diagnoses are presented. The clinical significance of this lesion is discussed.


Clinical significance of preoperative liver scintigraphy in gastric cancer. The surgical and liver scintigraphic findings were compared for evaluation of preoperative diagnostic value in 146 cases of gastric carcinoma. Correct diagnosis was found in 95% with a false negative rate of 2.7% and a false positive rate of 27%. In all the false negative cases, the size of all space-occupying lesions within the liver was less than 3 cm. in diameter. In view of the high percentage of correct diagnosis (95%), we believe that the preoperative liver scintigraphy is very useful clinically. Furthermore, we documented that liver metastasis is a late complication of gastric cancer and suggest that new diagnostic tools are needed to assess the presence of nodal metastasis, serosal infiltration and peritoneal dissemination.


Celiac disease with jejunal ulceration.

Celiac disease with jejunal ulceration. A patient with celiac disease with ulceration of the jejunum, an infrequent association, is reported. Patient underwent surgery for resection of the ulcerated segment. The frequency of such an association, possible complications and an approach to therapy is reviewed.


Duodenal Hodgkin's disease.

Duodenal Hodgkin's disease. An unusual case of primary extranodal Hodgkin's disease, localized to the duodenum is reported and illustrated. A review of the literature stressing the incidence, clinical presentation, radiographic appearance and prognosis of primary gastrointestinal Hodgkin's disease is presented. It is pointed out that although the majority of the lesions are infiltrating in type, intestinal Hodgkin's may present as a solitary ulceration or as a polypoid lesion indistinguishable from other forms lymphoma.


Determination of antiplatelet antibody activity in sera cytotoxic for human lymphocytes. Pooled serum aliquots obtained from sensitized potential renal allograft recipients on chronic hemodialysis were evaluated for their lymphocytotoxicity titers against the lymphocytes and then for alloantibodies against the platelets of 7 random donors by 5 methods. Platelet donor specific lymphocytotoxicity was present in 93% of 42 combinations. Of the positive combinations, 57% had a positive test for antiplatelet activity by the 14C serotonin release assay, 16% by the platelet aggregation method, and 19% as judged by acid phosphatase availability on the platelet membrane. No serum tested released beta-glucoronidase or lactic dehydrogenase. No correlation of the height of the titer of antiplatelet activity with that for lymphocytoxicity was detected. Thus, even in sera demonstrating significant activity against donor lymphocyte antigens, detection of associated platelet antibody activity is not uniform. Thus, a positive lymphocytoxic titer does not necessarily predict detectable antiplatelet activity. Therefore, additional tests for detection of antiplatelet activity should also be considered. This study shows that of the tests evaluated, the 14C serotonin release assay is the most sensitive for detection of antiplatelet antibodies.


Successful transfusion of platelets "mismatched" for HLA antigens to alloimmunized thrombocytopenic patients. A critical factor limiting the availability of histocompatible platelet transfusions for alloimmunized, thrombocytopenic patients is the large pool of HLA-typed donors needed to procure platelets perfectly matched for HLA antigens. We have, therefore, investigated the effectiveness of platelets obtained from donors having lesser degrees of histocompatibility. In 421 transfusions administered to 59 alloimmunized patients who were refractory to "random donor" platelets, it was found that platelets mismatched for 1 or 2 "cross-reactive" HLA antigens were in most instances as effective in increasing circulating platelet levels as perfectly matched platelets. A significant number of patients also responded to platelets from donors selectively mismatched for non-cross-reactive HLA antigens. The latter group had a significantly reduced frequency of the antigen HLA-A2 (13%) in comparison to the total patient population (49%). Use of donors whose HLA antigens are serologically cross-reactive with those of alloimmunized patients provides approximately 10 times as many prospective donors as does selection based on matching for HLA and simplifies the procurement of hemostatically effective platelets for such patients.


Comparative ultrastructure of late rabbit-embryo erythroid cells in liver and peripheral blood. A morphological study of hemoglobin biosynthesis activity in rabbit-embryo liver and peripheral blood was comparatively developed. Orthochromatic erythroblasts and reticulocytes of the same maturing degree were analysed through thin sections, as to their organellar constitution and behaviour regarding iron incorporation. It was found that peripheral blood erythroid cells contain mainly hemosomes, organelles taken as sites of final hemoglobin molecule biosynthesis. The ratio between the mean number of hemosomes in blood erythroid cell sections and that in liver erythroid cell sections reaches a little more than 6:1. Inversely, late liver erythroid cells are predominantly constituted by mitochondria that directly or indirectly participate in hemosome formation. The ratio between the mean number of mitochondria in blood erythroid cell sections and that in liver erythroid cell sections reaches 1:11. Besides this, the iron incorporation activity is higher in peripheral blood erythroid cells than in liver erythroblasts and reticulocytes. It is apparent that erythroid cells in the liver accumulate heme, given the ratio of the means of iron incorporation activity per cell to hemosome per cell (3.67), while blood erythroid cells, with a 1.08 ratio, synthesize heme, which is immediately afterwards integrated into the globin chains. The sudden increase in the formation of hemosomes when liver orthochromatic erythroblasts and reticulocytes enter the peripheral blood, reflecting an enhancement of hemoglobin synthesis, agrees with biochemical findings of other authors.


Production paroxysmal nocturnal hemoglobinuria-like red blood cells by tea. Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria-like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement-dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement-dependent hemolysis in teaincubated red cells was inhibited by antisera to C3 and C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement-dependent hemolysis of red cells incubated with tea. Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.


A plasma inhibitor of ristocetin-induced platelet aggregation in patients with sickle hemoglobinopathies. Because of the high prevalence of thrombotic complications in patients with sickle cell anemia (SCA), we investigated platelet function in patients with sickle hemoglobinopathies. Platelet aggregation induced by epinephrine, ADP, and collagen, except for absent secondary wave in 3 of 10 patients with SCA, was qualitatively normal. However, ristocetin-induced platelet aggregation (RIPA) with a final concentration 1.12 mg/ml was markedly abnormal-absent or virtually absent in 9 of 10 patients with SCA, 3 of 3 patients with hemoglobin S-C disease, and 2 of 3 patients with sickle trait. All 8 controls used in these experiments repeatedly demonstrated normal RIPA. Addition of normal plasma failed to correct abnormal RIPA in sickle hemoglobinopathy patients. All patients demonstrated normal RIPA with a ristocetin dose of 2.24 mg/ml and aggregated with bovine fibrinogen. Recombinant mixing experiments demonstrated that washed SCA platelets support RIPA (1.12 mg/ml) when resuspended in normal plasma or high dilutions of SCA plasma, but not in undiluted SCA plasma. Washed normal platelets do not support RIPA (1.12 mg/ml) when resuspended in SCA plasma. These findings suggest the presence of a plasma inhibitor of RIPA in patients with sickle hemoglobinopathies.


Exceptionally high serum erythropoietin activity in an anephric patient with severe anemia. An exceptionally high serum erythropoietin (EPO) activity was documented in an anephric patient with severe anemia who required transfusions every 4 weeks. The patient's serum EPO was comparable to normal human urinary EPO in the polycythemic mouse assay and was neutralized by an antiserum against EPO. The patient's serum inhibited EPO stimulated-heme synthesis by normal human marrow cells in vitro. This finding suggests that an inhibitor played an important role in causing the anemia of this uremic patient.


Identification of hemoglobins in single erythrocytes by electrophoresis. We present here a method for electrophoretic identification of hemoglobin variants in many individual erythrocytes simultaneously, which is made possible by instruments developed in our laboratory. The system spaces and aligns the erythrocytes along a common origin and prevents 'doubling' of cells. Unambiguous separation of different hemoglobins (Hbs) occurred from single erythrocytes, such as Hbs A, C, F. Staged micrographs showed that hemoglobins of differing mobility from a single cell arise from a single point source of hemoglobin. In principle this capability is applicable to other proteins and could facilitate investigation at a cellular level into a variety of questions pertaining to gene action.


Alpha-thalassemia.

Alpha-thalassemia. The current concepts of alpha-thalassemia including incidence, genetics, clinical spectrum and diagnosis are reviewed. Speculation concerning clinical application of the molecular biology of alpha-thalassemia is also presented.


Health care and hospital pharmacy in Sweden. Health care and hospital pharmacy in Sweden are discussed. The system of drug distribution in Sweden is reviewed, and the following functions of hospital pharmacies are discussed; drug and hygiene committees, inspection activities, drug information and educational services, radiopharmacy, and research activities. Pharmacy education, drug manufacturing, and Apoteksbolaget--The National Corporation of Swedish Pharmacies--are also discussed. Future developments in hospital pharmacy are expected to include increased sales to outpatients, a restructuring of the drug supply within outpatient care and recommendations from the hospital drug committees on outpatient care.


Drug therapy reviews: intravenous fluid therapy. The indications for use of large-volume parenteral solutions are reviewed, and the types of fluids administered and their potential hazards are described. The indications discussed are replacement therapy, maintenance therapy and emergency venous access. Hazards presented include thrombophlebitis, infection, volume overload, air embolism, particulate matter and chemical contamination. The indications for specific parenteral fluids, such as saline solutions, dextrose solution, fructose and alkaline solutions are discussed. Also reviewed are agents used to treat alkalosis, intravenous potassium therapy, calcium salts, magnesium salts and mixed solutions. Most clinical situations can be managed with judicious use of 0.9% saline and 5% dextrose with the addition of other electrolytes as determined by the needs of the individual patient.


Labeling and recording orders for intravenous solutions: the concept of total amounts of ingredients. A system of nomenclature for labeling and recording information on orders for parenteral solutions was developed using the concept of total amounts of ingredients. Compared with the traditional nomenclature, the new system is more useful for monitoring, is less ambiguous, saves time in recording and labeling, is easier to check, and is readily automated. An error study showed a significant decrease in "wrong solution" errors with the new system. No important problems occurred during the changeover from the traditional to the new nomenclature.


Saccharin sodium as a potential sweetener for antidotal charcoal. This study explored if saccharin sodium, as a sweetener in activated charcoal formulations, would be sufficiently available to provide sweetness while not severely reducing charcoal's adsorption capacity. In vitro tests showed that charcoal takes up 40wt% of saccharin at a 1 g/liter concentration of saccharin in the residual fluid; 29.3wt% at 0.1 g/liter. A saccharin level of 0.1 g/g of charcoal in a carboxymethylcellulose formulation gave enough residual flavor to be appealing. Sodium salicylate, 1 g/liter and 10 g/liter, was used to test whether the 0.1 g/g level of saccharin would interfere with charcoal's ability to adsorb a typical drug. By use of colorimetric assay, it was shown that a 2 g charcoal per gram of salicylate (initial salicylate concentration of 1 g/liter), the extent of drug adsorption was reduced from 70% to 64%, at a 10 g/liter initial concentration, the reduction was 87% to 82%. Under the conditions tested, the antidotal mixture should be pleasantly sweet at a saccharin level of 1 g/10g charcoal, and little effect would be produced on the adsorption of sodium salicylate and other drugs that are well adsorbed by charcoal.


Preparation of progesterone suppositories. The manufacture and assay of progesterone suppositories by a hospital pharmacy department are described. The compounding formula and procedures are presented. The product is used to treat luteal phase insufficiency.


Effect of large-dose ascorbic acid on the two-drop clinitest determination. A study was conducted to determine if high doses of ascorbic acid would affect the two-drop Clinitest determination for glucosuria in normal individuals. Numerous secondary literature sources indicate that large doses of ascorbic acid may cause a false positive Clinitest result. Three-gram and nine-gram doses of ascorbic acid following two dosing schedules (once daily and three times daily) were taken by nine normal individuals to determine if the renal excretion of large enough quantities of ascorbic acid or its metabolites would produce false positive results with the two-drop Clinitest procedure. Each dose was given for seven days in each schedule. There were only two (0.27%) trace positive Clinitest determinations reported out of 748 Clinitest determinations. High doses of ascorbic acid in normal individuals do not appear to affect the two-drop Clinitest determination for urinary glucose. The study indicates a need to be cautious about secondary literature references on drug-laboratory test interferences.


Implementation of clinical pharmacy services in a cardiac rehabilitation unit. The implementation of a comprehensive program for the rehabilitation of cardiac patients is discussed with primary emphasis on the clinical pharmacy services provided and the method of reimbursement for these clinical services. The three basic clinical pharmacy service objectives in the cardiac rehabilitation unit (CRU) are: (1) to provide drug information to the patient, his family and health-care team members; (2) to intensively monitor the drug therapy of all CRU patients, and (3) to evaluate the impact of pharmacy services being provided upon the quality of patient care and subsequent avoidable drug-related morbidity and mortality. The pharmacist is reimbursed for his clinical services from a percentage of the revenues gained from the higher room rate rather than from traditional dispensing functions and drug fees. It is concluded that the pharmacist is recognized as a necessary drug information source and an important member of the CRU team.


Agranulocytosis associated with procainamide therapy--report of a case. The case of a 69-year-old woman with procainamide-induced agranulocytosis is reported, and literature reports of 14 other such cases are reviewed. The patients was exposed to procainamide, prescribed for atrial fibrillation, for 26 days, with a daily dose of 1.5 to 4 g and a total dose of 57.5 g. She recovered from agranulocytosis after discontinuation of the drug and hospital treatment for 16 days. Among the reported cases of procainamide-induced agranulocytosis, the daily dosage ranged from 750 mg to 4.5 g; the total ingested dose before agranulocytosis was observed ranged from 36.5 to 316.3 g. Patients treated with procainamide should be instructed to report any soreness of the mouth, throat or gums; unexplained fever; or any symptoms of upper respiratory tract infection. If white blood cell counts indicate bone marrow depression, the drug should be withdrawn and appropriate evaluation begun at once.


Quantitative corneal endothelial evaluation in intraocular lens implantation and cataract surgery. We analyzed pre- and postoperative corneal endothelial photographs of 33 intraocular lens patients and found an average endothelial cell density loss of 14%. Twenty-six cataract patients, similarly examined, showed a 13% mean endothelial cell loss. In 14 of the intraocular lens patients, a second postoperative evaluation of the central endothelium, at a later date, revealed a trend toward continuing cell loss. Our results indicate fewer endothelial cells were lost after intraocular lens implantation than has been previously reported. This may be accounted for by our considering only patients with normal corneas for lens implantation, and by our constant maintenance of the anterior chamber with an air bubble during lens implant surgery.


A simple conjunctival biopsy.

A simple conjunctival biopsy. Biopsy of conjunctival goblet cells may be carried out by pressing a piece of Millipore filter on the conjunctival surface. This can then be stained with PAS and hematoxylin and observed under the microscope after the filter has been cleared with oil. Either spots of mucous corresponding to the openings of the goblet cells are seen, or the filter adheres to the surface and pulls off one or more layers of epithelial cells and goblet cells. The procedure can be carried out on the unanesthetized eye and does not cause discomfort.


External ophthalmomyiasis caused by Estrus ovis. External ophthalmomyiasis occurred in a 16-year-old white girl who was infected on Catalina Island, an endemic area for the sheep bot fly. With the patient under topical anesthesia, we isolated the larva, Estrus ovis, removed it with jewelers' forceps, and examined it with light and scanning electron microscopy. The patient responded well to a treatment regimen of corticosteroids and antibiotics.


Pityrosporum species associated with dacryoliths in obstructive dacryocystitis. Two dacryoliths removed from the obstructed and enlarged lacrimal sac of a 54-year-old woman during dacryocystorhinostomy were found to contain filamentous forms consistent with Pityrosporum orbiculare. To my knowledge, this fungus has not been observed before in a dacryolith or in dacryocystitis.


The effect of fibrinolytic inhibition in the resolution of experimental vitreous hemorrhage. Complete inhibition of vitreous fibrinolytic activity with 4-amino-methylcyclohexane carbonic acid was associated with significantly delayed resolution of vitreous hemorrhages in rabbits. However, polyacrylamide gel electrophoresis indicated but a slight delay in the removal of the fibrin component of vitreous clots, and most of the residual vitreous opacity comprised intact red blood cells. Fibrin degradation products may act as chemotactic agents, promoting the removal of red blood cells by leukocytes; hence, their absence in treated rabbits might explain in part the delayed red blood cell clearance.


Endophthalmitis after pars plana vitrectomy. In three cases of bacterial endophthalmitis following pars plana vitrectomy the important diagnostic findings included increased orbital pain, decreased visual acuity, and the presence of a hypopyon. Despite agressive antibiotic therapy, all three eyes became blind, and two progressed rapidly to phthisis.


Necrotic melanocytoma of iris with secondary glaucoma. A 23-year-old white man had a pigmented iris tumor that was not enlarging; it produced satellite iris lesions, diffuse pigmentation of the trabecular meshwork, and secondary glaucoma. Although enucleation was initially recommended, we chose to remove only the primary lesion with a sector iridectomy. Histologically, the lesion proved to be a benign melanocytoma that had undergone extensive necrosis. Postoperatively, the satellite lesions, pigmentation in the angle, and glaucoma all resolved.


Oculocutaneous albinism associated with Apert's syndrome. Five of nine patients with Apert's syndrome (acrocephalosyndactyly) showed an associated hypopigmentation of hair, skin, and eyes. The hair color of these five patients ranged from light brown to blond, the skin was pale, and the irides hazel or blue. Iris transillumination and hypopigmentation of the fundus were present and associated with absent or diffuse foveal reflexes. Unlike most forms of classic oculocutaneous albinism, however, there was good visual acuity and no pendular nystagmus. The evidence indicated that the lack of pigmentation associated with the characteristic skeletal anomalies of Apert's syndrome resulted from a disturbance of independent, genetically related, processes occurring at a common point in gestation.


Clinical trials with the Equator-Plus camera. The Equator-Plus camera can photograph a 148-degree view of the fundus, measured from the nodal point of the eye. We tested this instrument clinically more than 800 times on over 700 eyes. The large field, which is three to four times that of any conventional fundus camera, is achieved by using a special contact lens as the front element in the camera optics. Photographs taken with the Equator-Plus camera can resolve a lesion as small as one-eighth of a disk diameter, if the contrast is good. Protruding tumors, choroidal or retinal detachment, and extensive disease of the choroid and fundus show up well with this technique. We obtained good pictures in 87% of the clinical tests. We have not observed complications of any kind after photography with the Equator-Plus camera.


Evaluation of the teratogenicity of fluorescein sodium. Pregnant rabbits in their first and second "trimesters" of gestation were used in a controlled study to evaluate the teratogenicity of fluorescein sodium. Injections of the drug were given in doses comparable to those planned for human administration. No abortions or defects apparent at birth or as delayed manifestations were evident as a result of the drug therapy.


Clip-on eyeglass loupe as a writing aid for low-vision patients. To aid the partially sighted in writing on small areas, such as bank drafts, a clip-on eyeglass loupe (11 diopters, 3.5 inches, Bausch and Lomb) attached to a finepoint felt pen provides adequate vision.


Ocular effects of near ultraviolet radiation: literature review. The literature related to the effects on the eye of ultraviolet radiation in the wavelength range 300 to 400 nm is reviewed. Insufficient data are available to establish criteria for ocular protection. Exposure of the eye to sufficient quantities of near ultraviolet radiation can interfere with synthesis of crystalline lens protein, catalyze lens proteins, produce chromatic changes in the lens, and enhance formation of cataract.


Fixation disparity and stereopsis.

Fixation disparity and stereopsis. The magnitude of fixation disparity has been proposed to be uncorrelated with stereoscopic sensitivity. Studies on this relationship have been confined to the effects of vergence-induced fixation disparity on stereoacuity: some subjects exhibited decreased stereoacuity with induced fixation disparity. The present study was designed to determine whether prismatic correction of naturally occurring horizontal fixation disparity would result in increased stereoacuity. Five subjects with eso and 5 with exo fixation disparity had their fixation disparity curves and stereothresholds evaluated before and after wearing corrective lenses and prisms that neutralized the fixation disparity. Five subjects with no fixation disparity served as controls. After 1 month most subjects showed no change in their fixation disparity curves and stereothresholds.


Stereoscopic localization with the eyes asymmetrically converged. When the eyes fixate a point in the median plane of the head, the physical surface to which the stereoscopic disparities of "nearer" and "farther" points are referred is the so-called frontal plane horopter. When, however, a point is fixated with the eyes in asymmetrical convergence, the horopter is now rotated with respect to the objective normal plane--that is, the surface that is normal to the direction of gaze. This rotation is believed to pose a problem with veridical stereoscopic localization. It has, therefore, been postulated that in asymmetrical convergence some physiological compensation takes place in order to preserve accurate stereoscopic perception. Some experimental evidence apparently supports this view. The logic of the arguments and the experiments are critically assessed with the conclusion that there is little evidence of any visual modification, nor would any seem likely. A reinterpretation of the stereoscopic axes of reference does occur, but this can be accounted for purely by innervational factors, the visual aspects remaining unchanged.


Rapid measurement of contrast-sensitivity functions. We have developed a reliable and valid procedure for determining a person's contrast sensitivity function in approximately 6 min. This rapid procedure, which resembles that used in the Bekesy sweep-frequency audiometer, has potential as a clinical tool for diagnostic assessment.


Does refractive error change twice as fast as corneal power in orthokeratology? We analyzed data from 4 orthokeratology studies of refractive error change (deltaRE) and keratometer-reading change (deltaK). Instead of the reported deltaRE/deltaK ratio of 2:1, we calculated from linear-regression analysis a ratio (slope) of 2:3. The ordinate intercept of the straight line fitted to the data (N = 181 eyes) indicates that when deltaK = 0, deltaRE = 0.72. The correlation between deltaK and deltaRE is poor (+0.63). Causes and interpretations of these results are discussed.


Marginal aberrations of different bifocal-lens designs. Marginal astigmatism and longitudinal chromatic aberration were measured (with a modified Vertometer) for +2-D bifocal lenses of different designs, base curves, and major-lens powers. At a reading level 20 deg below the pole of the major lens, deterioration of the optical image occurred and was created by the interaction of marginal astigmatism (tangential error) and lateral chromatic aberration (prismatic dispersion). Suggestions for selecting an optimal bifocal-lens design for different types of refractice error are presented.


Comparison of accommodation with rigid and flexible contact lenses. Measurements were made of the amplitude of accommodation for myopes wearing spectacles, rigid contact lenses, and flexible contact lenses. Both forms of contact lenses placed greater accommodative requirements on the myope than did spectacle correction, but no significant difference was found between the 2 types of contact lenses in this respect.


Monocular fixation and acuity in amblyopic and normal eyes. We studied the relation between eccentricity of monocular fixation and the minimum angle of resolution invisually normal subjects and in both the amblyopic and dominant eyes of amblyopes. For the amblyopic and visually normal eyes, this relation was linear; resolution was poorer at the eccentrically fixating locus than at the corresponding region of the normal eye. The dominant eyes of the strabismic amblyopes had a nasal component of eccentric fixation that was less than that of the companion amblyopic eyes, but greater than the that found in the visually normal eyes. In terms of the eccentricity of monocular fixation, the domonant eyes of strabismic amblyopes were different from the normal eyes.


Computation of unwanted sphere and cylinder in the periphery of a spectacle lens. The author discusses practical issues relating to optometrists ordering and laboratories supplying ophthalmic lenses that meet the ANSI Z80. 1 Standard (1972) for minimizing unwanted spherical and cylindrical power in the periphery of lenses. He spells out the optical principles and formulas needed to develop a computer program that can be used by optometrists and opticians for designing lenses that meet the Z80. 1 Standard.


Tear-film dynamics and oxygen tension under a circular contact lens. The cornea requires a minimum level of oxygenation; this may be prevented by a contact lens, and corneal swelling and other undesirable effects may result. By employing thin-film lubrication theory, this study derives analytical solutions for tear-film velocity components and pressure under a circular contact lens. Oxygen-tension contours are then obtained for various values of squeeze action and parallel motion of the lens.


Do optical aberrations contribute to visual loss in strabismic amblyopia? If aberrations contribute significantly to the decreased visual function of strabismic amblyopic eyes, one would predict that (1) the pupil size for optimum resolution should be smaller in the amblyopic than in the normal eyes, (2) increasing target contrast by a constant ratio should not compensate for defocus of an amblyopic eye, and (3) the contrast sensitivity of the amblyopic eye should improve when tested with a stimulus that bypasses the eye's optics. We tested these predictions, using contrast sensitivity techniques, and found no evidence that aberrations contribute to the amblyope's abnormality.


Type-size variability for near-point acuity tests. We measured the sizes of the test forms (letters, digits, and symbols) on 19 different near-point acuity cards. The results are all expressed in the M notation (1 mm of letter height equals 0.7 M) and are tabled according to the acuity specification system used by the manufacturers--such as, the point-type system, Jaeger notation, equivalent 20-ft Snellen notation, and so on. Our results demonstrate that manufacturer's specifications on near-point acuity cards cannot be used to determine the sizes of test letters. The M system has sufficient advantages over other systems to warrant its universal use for specifying near-point visual acuity.


A new dark adaptometer.

A new dark adaptometer. A dark adaptometer that was designed for student-laboratory use is described and advocated for use in optometric practice because of its simplicity, accuracy, and low cost. Representative dark-adaptation results obtained from 2 naive and 2 sophisticated subjects are presented.


The effect of chronic hypoxemia on regional myocardial blood flow in the conscious dog after acute coronary artery occlusion. Chronic hypoxemia was produced in 16 dogs by surgical transposition of the caudal vena cava to the left atrium to determine if chronic hypoxemia would alter the response of the myocardium to acute ischemia. An electromagnetic aortic flow probe, left atrial tube, and occlusive cuff on the left circumflex coronary artery were permanently implanted in 11 hypoxemic and 26 normal control dogs. The animals were studied in the conscious state after recovery from the surgery. Dogs with hypoxemia had a blood hematocrit value of 54.3 +/- 1.0% (SE), arterial PO(2) of 43.2 +/- 1.4 mm Hg, and 80.2 +/- 1.6% oxygen saturation. There was no difference from control animals in the ratio of left ventricular weight to body weight, but the right ventricular weight was significantly decreased in the hypoxemic dogs. Cardiac output from the left ventricle was twice that of the right ventricle. Aortic blood flow was 3.68 +/- 0.22 liters/min in hypoxemic animals and 2.64 +/- 0.19 liters/min in normal dogs. Myocardial blood flow measured with 15-mu diameter tracer microspheres was increased from 79 +/- 10 and 59 +/- 8 ml/100 g/min in left ventricular endocardial and epicardial halves, respectively, in normal dogs to 212 +/- 48 and 172 +/- 39 in dogs with chronic hypoxemia. There were no deaths in 10 hypoxemic dogs within 24 hours after complete circumflex coronary artery occlusion; 7 of 26 (27%) normal dogs died after circumflex coronary artery occlusion during the conscious state. Gross infarct size was extremely variable in both groups. Median infarct size was smaller in dogs with hypoxemia and was directly correlated with arterial PO(2) in hypoxemic dogs. There was a mild, but statistically not significant, increase in the anastomotic index of hypoxemic dogs compared with that of normal animals, suggesting that a metabolic adaptive change rather than increased collateral circulation may have been responsible for the decreased mortality and smaller infarct size in hypoxemic dogs.


Age-associated glycopeptide pigment in human costal cartilage. Age-associated pigmentation of human costal cartilage is caused by the accumulation of a brown water-soluble substance which can be only be extracted after proteolytic disruption of the cartilage. After isolation by gel filtration and ion exchange chromatography, the compound was identified as an acid glycopeptide. In contrast to ochronotic pigment and an artificial pigment derived by oxidation of homogentistic acid in alkaline solution, the age-associated cartilage pigment was strongly fluorescent and did not form insoluble complexes with cetylpyridinium chloride. Moreover, age-associated cartilage pigment is alkali resistant, in contrast to the ochronotic pigment. The pigment differs from lipofuscin in being strongly hydrophilic and having no affinity for fat stains. The unidentified chromophore could not be separated from the glycopeptide molecule.


Diffuse alveolar damage in cats induced by nitrogen dioxide or feline calicivirus. The ultrastructural morphogenesis of pulmonary lesions was studied in cats exposed to either aerosols of feline calicivirus (FCV) or high concentrations of NO2. Both directly injured alveolar lining cells, particularly type I cells. Necrosis of pneumocytes attended by an acute exudative response in the air exchange tissues was evident from 0 through 24 hours after exposure of cats to NO2 and from 12 through 96 hours after infection with FCV. The reparative process following alveolar injury was characterized by regenerative hyperplasia of type II pneumocytes, proliferation of stromal cells, and infiltration of mononuclear cells. Differences in the lesions produced by NO2 and FCV also were encountered. Endothelial necrosis was detected only after NO2 injury, whereas a marked infiltration of neutrophils and immunocytes was observed only after FCV injury. The FCV/NO2 experimental system in cats is well suited for studies of diffuse alveolar damage of toxic and viral etiology.


Newcastle disease as a model for paramyxovirus-induced neurologic syndromes. II. Detailed characterization of the encephalitis. All chickens infected by intranasal and conjunctival routes with a neurovirulent strain of Newcastle disease virus (NDV) developed pneumonitis by 4 days after infection. This was followed 6 to 12 days later by the appearance of severe encephalitis in a significant number of survivors. Histologically, the encephalitis was characterized by neuronal degeneration and perivascular inflammation. In addition, a proliferative vasculitis in the molecular layer of the cerebellum was noted after 30 days, and this persisted for at least 200 days. Although CNS signs were absent during the pneumonic stage, significant amounts of virus were present in the brains of all birds at this time, and viral antigens were easily demonstrable in neurons, glial cells, and endothelial cells. However, when the CNS disease became apparent, viral antigens could not be detected in brains and NDV could regularly be recovered only by application of cocultivation techniques. At this time, the agent was selectively present in birds exhibiting neurologic signs. No evidence for immunopathologic processes was obtained, although hemagglutination inhibiting antibody levels to NDV were elevated in birds with CNS disease. Studies of an avirulent strain of NDV that replicated in the CNS but produced no disease provided evidence that the histologic lesions and the neurologic disease were related to virus multiplication in the brain parenchyma. A mechanism of the pathogenesis of NDV encephalitis is proposed and the disease is discussed relative to other paramyxovirus-induced encephalitic syndromes.


Reversible suppression of malignancy and differentiation of melanoma cells. Tumorigenicity is reversibly suppressed in mouse melanoma cells grown with 5-bromodeoxyuridine (BrdU). The nontumorigenic cells are immunogenic, and preinjection of these cells can protect mice against tumors inevitably formed when the parental, untreated melanoma cells are inoculated into inbred strain C57BL/6. A mixture of highly immunogenic clone, C(3)471, with malignant cells is also nontumorigenic. These effects are related to the host immune response since they occur only in immunocompetent mice. BrdU also reversibly suppresses functions related to pigment formation and plasminogen activation. These effects require incorporation of BrdU into DNA, emphasizing the value of the thymidine analog, BrdU as a tool to relate normal regulation of gene activity to perturbations of this regulation which produce malignant cells. This research can facilitate basic understanding of the malignant state and its relationship to host response as well as a method for immunizing melanoma patients after surgery to prevent tumor recurrence.


Reversal of the neoplastic state in plants. Crown-gall transformation involves the gradual and progressive activation of several biosynthetic capacities of the normal cell. These changes in cellular heredity, although extremely stable, are nonetheless potentially reversible and leave the cell totipotent. There is growing evidence that tumor-inducing principle is a self-replicating entity similar to a plasmid. Thus, it could be argued that tumor progression involves changes in the number or state of these entities in the cell. Studies of CDF habituation bear directly on this problem. Conversion of a cell division factor (CDF)-requiring normal cell to the CDF-autotrophic state is a key event in transformation. The fact that CDF habituation is progressive, occurs in the absence of agents of bacterial origin, and has an epigenetic basis indicates that it is not necessary to invoke either somatic mutation or the addition of foreign genes to account for tumor stability and progression in crown-gall. This conclusion provides further support for the hypothesis that, in the words of Braun,(78) "... the cancer problem is basically a problem of anomolous differentiation... Neoplastic growth, like developmental processes, stems from epigenetic modifications against a constant cellular genome."


Effect of dantrolene sodium on muscle contraction. The force of contraction of the adductor pollicis before and after dantrolene sodium was evaluated in 5 paraplegic patients. The muscle was indirectly stimulated through supramaximal stimulation of the ulnar nerve at the wrist, with single pulse and variable number of stimuli at frequency of 50 Hz. There was a marked and significant reduction (an average of 64%) of the single twitch response in all patients while on medication. When the muscle, however, was stimulated with tetanic frequency no significant difference was evident in the force of the sustained contraction with or without medication. The  amplitude of evoked electrical potentials, simultaneously recorded from the adductor pollicis remained unchanged irrespective of the status of medication. Decrement of the twitch response, with no effect on the electrical activity, tends to substantiate the distal effects of dantrolene on muscle contraction. The drug, however, does not seem to prevent the muscle from achieving its normal maximal tetanic force when activated with frequencies close to the physiological frequencies of maximal, voluntary effort (50 Hz.) These effects point to the usefulness and limitations of the drug in clinical situations.


Isolated membrane vesicles as tools for analysis of epithelial transport. In recent years a methodology has been developed to use vesicles of the isolated brush border and basolateral plasma membranes for intestinal transport studies. The methodology and information gained with the vesicle systems are discussed using the examples of nonelectrolyte transport. In particular, results are presented on the mechanisms of D-glucose and neutral amino acid translocation across both plasma membranes and the coupling of Na+ with sugar and amino acid transport in the brush-border membrane. Furthermore, the kinetic parameters of the Na+-dependent glucose transport system, determined with an equilibrium exchange procedure, and the effects of semistarvation on the transport properties of the brush border membrane are described.


Fetal fuels II: contributions of selected carbon fuels to oxidative metabolism in rat conceptus. The effects of fasting on the oxidative disposition of selective fuels in tissues of the rat conceptus were examined on day 20 of gestation. Placentas and portions of fetal liver and brain from fed and 48-h fasted mothers were incubated in vitro with artificial mixtures containing glucose, lactate, and beta-hydroxybutyrate in concentrations simulating those that obtain in fed or 48-h fasted animals in vivo. Oxidative contributions from individual components were evaluated by separate incubations in which only one of the three fuels was 14C-labeled. As judged by the evolution of 14CO2, rates of oxidation of individual fuels by tissues of the conceptus appeared to be conditioned by ambient fuel concentrations rather than the dietary status of the mother. Additional studies indicated that evolution of 14CO2 from glucose or lactate may be depressed directly by adding beta-hydroxybutyrate to the incubation medium. This substitutive property of beta-hydroxybutyrate may "spare" glucose and lactate within the placenta for transfer to the fetus and preserve glucose and lactate availability for biosynthetic rather than oxidative disposition within the fetus.


Gluconeogenesis from alanine in vivo by the ovine fetus and lamb. Gluconeogenesis from alanine was determined with an intravenous infusion of [U-14C]alanine and [6-3H]glucose or [U-14C]glucose in five fetal lambs (3.6 +/- 0.1 kg; 127 days of gestation) and four growing ewe lambs (37 +/- 2 kg). Conversion of alanine to glucose (mmol/h) was 0.40 +/- 0.12 and 0.51 +/- 0.10 and accounted for 7.3 and 25.6%  of the alanine turnover in fetal and growing lambs, respectively. Alanine contributed 2.3 and 1.1% of the glucose turnover and 22.3 and 1.1% of the lactate turnover in fetal and growing lambs, respectively. Lactate contributed 19.5% of the glucose turnover in growing lambs, and glucose synthesis from lactate accounted for 24.7% of the lactate turnover. Glucose turnover (mmol/h) was 10.2 and 25.1 in fetal and growing lambs, respectively. Results from these studies have shown that the fetal lamb at 127 days of gestation has a high rate of alanine turnover and conversion to glucose when compared with that of the growing lamb on a high plane of nutrition.


Storage telemetry of radionuclide tracers by implantable thermoluminescent dosimeters. A storage telemetrical method using thermoluminescent (TL) dosimeters for long-term measurements of incorporated radioactive substances in unrestrained rats has been developed. The system has been used in combination with radiotelemetrical registration of the circadian temperature rhythm. By sequential replacement of double TL dosimeters (60 mg, CaSO4:Dy) through an implanted silicon tube, the concentration of different radionuclides can be determined over long periods. The persistence of the circadian temperature rhythm indicates that the animals were unaffected by the experimental conditions. The relative uncertainty of the dosimeter system and the temperature transmitter is approximately +/- 2% (SD) at 5 mR exposures and +/- 0.05 degrees C, respectively. The weight of the system in total is 5.7 g. Disappearance studies (36-48 h) have been performed with the beta-emitters, 32P nad 42K, in subcutaneous tissues and tumor tissue. This TL method permits the repetition of an experiment on the same rat several times, and thereby avoids errors due to biological variations between animals.


Origin of migrating myoelectric complex in sheep. The electrical activity of the gastroduodenal junction was recorded in conscious sheep for 8 to 12 wk with chronically implanted electrodes. The flow of digesta was simultaneously recorded, and the duodenal bulb was isolated at the time of implantation. The mean slow-wave frequency of the antrum was 5.6 +/- 0.3/min with spike bursts randomly superimposed on about 60% of the slow waves. The activity of the duodenal bulb was characterized by an absence of slow-wave unpropagated spike bursts and by two types of propagated spike bursts. The first consisted of isolated bursts accompanied by a rapid movement of digesta through the entire duodenum and proximal jejunum. The second, an irregular series of 8-12 spike bursts was associated with total evacuation of the duodenal bulb, followed in turn by an inhibition of antral spiking activity and the development of a migrating myoelectric complex (MMC) in the distal duodenum. The results indicate that in sheep organization of the MMC is located at the duodenal level where the duodenal bulb has a reservoir function.


Intestinal Ca and phosphate transport: differential responses to vitamin D3 metabolites. The transport of Ca and inorganic phosphate (Pi) was studied in the absence of electrochemical gradients across rat intestine in vitro. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the active absorption of both Ca and Pi in all segments of the small intestine, with changes occurring only in absorptive fluxes, whereas secretory fluxes were unaffected. Active Ca absorption was greatest in the duodenum (greater than jejunum greater than ileum) and active Pi absorption was highest in jejunum (greater than duodenum greater than ileum), in agreement with earlier reports. 24R,25-dihydroxy-vitamin2D3 had similar effects on transport but was less potent. The ratios of Pi absorptive fluxes to Ca absorptive fluxes remained remarkably constant during 80-200% increases in absorption produced by 1,25(OH)2D3, suggesting coupled Ca-Pi transport or coordinate stimulation of Ca and Pi absorptive processes by hormonally active metabolites of vitamin D. The results seem most compatible with a differential distribution of vitamin D-responsive Ca and Pi absorptive cells with a predominance of cells with Ca absorptive sites occurring in duodenum, more Pi absorbing cells in jejunum, and a nearly equal ratio of each type in ileum.


Dominant-subordinate relationships in castrated male mice bearing testosterone implants. This study tested the hypothesis that subordination in male mice is directly related to reduced levels of circulating testosterone. Several measures of aggressiveness and submissiveness were quantified during or after daily encounters between pairs of intact males, castrated males, or castrated males bearing testosterone implants that were designed to maintain plasma testosterone titers at levels slightly above those of intact males. Behavioral measures included the total amount of fighting that resulted from daily pairing, the tendency for subordinates to fight back, and the relative frequency of urine marking. In all these regards, pairs of testosterone-implanted, castrated males formed dominant-subordinate relationships that involved apparently normal submissive behavior (compared to intact control pairs). Thus we found no evidence that submissive behavior was directly related to a reduction in circulating testosterone titers.


Glucose delivery: a modulator of glucose uptake in contracting skeletal muscle. To evaluate glucose delivery and neuromuscular activity as modulators of glucose uptake in skeletal muscle, rat hindlimbs from pentobarbital-anesthetized rats were perfused in the presence of electrically stimulated muscular contractions. Glucose delivery was varied by altering non-cyclic perfusate flow. When flow was increased from 3 to 12 ml/min glucose disappearance increased from 1.1 +/- 0.2 to 4.0 +/- 0.2 mumol/min per 100 g rat (P less than 0.001). When glucose delivery was held constant, glucose disappearance was unaltered during muscular contractions. Insulin enhanced glucose disappearance, and its effect was unaltered during muscular contractions. Muscular contractions increased oxygen disappearance by two- to 3.5-fold and lactate appearance by 4.5- to fivefold (P less than 0.02). It was concluded that glucose delivery and insulin modulate glucose disappearance in isolated perfused rat hindlimbs. Electrical stimulation of muscle enhances lactate appearance and oxygen disappearance but does not alter glucose disappearance when flow is held constant. Because blood flow to muscle increases during exercise in vivo, increased glucose delivery may be a modulator of the augmented muscle glucose consumption observed under these conditions.


Episodic growth hormone secretory patterns in sheep: relationship to gonadal steroid hormones. The influence of anabolic steroids on growth hormone (GH) secretion in ruminants remains unclear, perhaps because of the dynamic nature of GH secretion. In the present study, blood samples were obtained at 15-min intervals for 12 h from intact ram lambs, ram lambs castrated postpubertally, and castrated ram lambs treated with either testosterone propionate (TP) or diethylstilbestrol (DES). Intact rams exhibited GH secretory episodes of greater (P less than 0.01) amplitude than did castrated lambs. Similarly, mean base-line and mean overall GH concentrations were higher (P less than 0.01) in rams than in castrates. Treatment of castrates with either TP or DES resulted in increased base-line (P less than 0.05) and overall (P less than 0.05) GH concentrations compared to untreated castrates. Although amplitude of GH spikes was larger in TP and DES groups, this difference was not statistically significant (P greater than 0.05). Because numerous studies have demonstrated that intact rams and castrates treated with TP or DES grow faster than untreated castrates, the data in the present study support the hypothesis that the anabolic action of androgens and estrogens is due, at least in part, to their influence on GH secretion.


Maturation of diluting capacity in loop of Henle of rat superficial nephrons. The postnatal development of renal diluting capacity was studied by free-flow micropuncture and by microdissection of single superficial loops of Henle in rats kept on a high salt diet. Total renal filtration rate, sodium absorption, total solute excretion, and systemic arterial pressure were monitored during single nephron evaluation at two maturational stages (12-15 days and 27-35 days postnatal). Nephron filtration rates were identical when measured in early distal and late proximal segments of the same nephron. Absolute fluid absorption between these sites increased by a factor of 2.5, whereas loop fractional absorption of the volume load changed from 38.1 +/- 6.9 to 49.8 +/- 4.8% (SD), while proximal volume delivery to the loop increased from 4.33 +/- 1.12 to 7.14 +/- 0.65 nl/min. Simultaneously, the osmolarity of early distal fluid (8.8% of distal length) decreased significantly from 284 + 19.8 to 180.9 +/- 18.2 mosmol/liter during maturation. This study suggests that the ability of the loop of Henle to generate hypotonic fluid is attained only gradually during ontogeny. Volume absorption in the loop of Henle increases disproportionately to the loop volume load.


Transport characteristics of renal collecting tubules: influences of DOCA and diet. Isolated renal cortical collecting tubules from rabbits were studied at random (control) and from rabbits maintained on diets containing either high or low Na and K content or injected with DOCA for up to 31 days. In general, the values of transepithelial voltage (VT) and electrical resistance (RT) varied considerably between tubules. When rabbits were fed a high K, low Na diet or were injected with DOCA the values of VT increased. Of interest was the observation that tubules obtained from rabbits maintained on DOCA for 11-18 days or longer possessed markedly elevated values of VT (mean VT, -54 mV) and a marked increase in their ability to reabsorb Na and secrete K at rates well above the levels observed even at 3-6 days of treatment when it was expected that maximal transport rates would have been achieved. From the estimates of the conductances of Na, K, and Cl, the data could be interpreted to mean that DOCA caused a decrease in the conductance of Cl, perhaps via the shunt pathway, while elevating the conductances of Na and K, thereby enhancing active Na and especially K transport by this nephron segment.


Sodium retention and ascites formation in dogs with experimental portal cirrhosis. Experimental cirrhosis was produced in dogs by the sporadic feeding of dimethylnitrosamine for the purpose of studying the temporal relationships between urinary sodium retention, plasma volume expansion, and ascites formation. Sodium retention started about 16 days following the onset of cirrhosis and preceded ascites formation by about 10 days. Plasma volume increased by 9% (P less than 0.05) within 3-4 days of sodium retention and expanded further as ascites accumulated. Splanchnic plasma volume was greater by 161 ml in 10 cirrhotic dogs with ascites than in 14 normal dogs. Nonsplanchnic volume was greater by 96 ml (P less than 0.05). Thus, the "effective" as well as the splanchnic component of the vascular space was expanded. Paracentesis did not cause the re-formation of ascites in five dogs as long as dietary salt was denied. Refeeding permitted reaccumulation of ascites and further plasma volume expansion. Renal perfusion remained constant as dogs became progressively cirrhotic. We conclude that ascites formation depends on the prior retention of urinary sodium, and occurs as an "overflow" phenomenon. A contracted effective plasma volume does not appear to be necessary for continuing sodium retention.


Effects of surgery on plasma volume and salt and water excretion in rats. Surgical preparation of rats for micropuncture resulted in a marked decrease in sodium excretion (UNaV) compared to awake animals. Associated with surgery, hematocrit (Hct) rose. Studies were performed to determine whether the rise in Hct resulted from reduced plasma volume (PV) or increased red cell volume (RCV) and to explore the relation of such alterations to the fall in UNaV. PV and RCV were determined in the calm awake rat using 125I-albumin and 51Cr-labeled red blood cells. Micropuncture surgery was performed and RCV, PV, and Hct again measured. After anesthesia and femoral artery catheterization, Hct was not different from Hct in awake animals (42.9 +/- 2.8%). The Hct increased following surgery to 48.2 +/- 2.8% (P less than 0.001), accompanied by a large fall in PV (-18.9 +/- 2.3%, P less than 0.001) with no change in RCV. Plasma volume repletion to awake values restored UNaV toward levels appropriate for dietary intake in animals on a high salt diet. Althouth plasma repletion slightly increased UNaV above awake values in low salt diet rats, they continued to avidly retain salt with respect to total salt load.


Collection of urine from each kidney in the rabbit without ureteral cannulation. Collection of urine in rabbits by conventional methods such as catheterization of ureters or bladder with polyethylene tubing or Foley cannulas is hampered by the occurrence of hematuria or obstruction of urine flow, or both. These problems were solved by placing in the bladder a stainless steel device with a horizontal round disk attached to an eliptic vertical septum. The vertical septum divides the bladder into two compartments in such a way as to allow the collection of urine from each kidney. Studies show that this intrabladder devide can be satisfactorily used in acute experiments in anesthetized or conscious rabbits for periods up to 5-6 h.


Glucagon inhibition of hepatic arterial responses to hepatic nerve stimulation. The hepatic arterial vascular bed of the chloaralose-urethan-anesthetized dog was perfused with blood from a cannulated femoral artery. Hepatic arterial blood flow and perfusion pressure were measured. The hepatic periarterial postganglionic sympathetic nerves were stimulated supramaximally at 0.1, 0.5, 1, 2, 5, 10, and 20 Hz; this caused frequency-dependent rises in the calculated hepatic arterial vascular resistance at all frequencies above the threshold of 0.1 or 0.5 Hz. Glucagon was infused intra-arterially in dosese from 0.25 to 10 microgram/min; glucagon antagonized both the vasoconstrictor effects of hepatic nerve stimulation and of intra-arterial injections of norepinephrine. The degree of antagonism of these responses was significantly correlated with the calculated hepatic arterial glucagon concentration. It is possible that glucagon released physiologically in stress and hypoglycemia may protect the hepatic arterial vasculature from the effects of increased sympathetic discharge.


Responses of canine endocardium to stimulation of the upper thoracic roots. In each of 10 mongrel dogs anesthetized with alpha chloralose, strain-gauge arches were sutured to five epicardial and three endocardial locations. Comparisons of contractile force responses during stimulation of the left and right roots of the same segmental level revealed several differences dependent upon the particular myocardial area observed. Of the three left ventricular endocardial areas studied, the interventricular septum was the most responsive, particularly during stimulation of the right roots. The basal free wall and posterior papillary muscle were more responsive to left-root than to right-root stimulations. Epicardial responses were consistent with those previously reported. Generally, all areas responded to the greatest degree during stimulation of the second roots with the third and first next in order of effectiveness. Although stimulation of each level of preganglionic outflow activated all epicardial and endocardial segments of the myocardium, the magnitude of the changes in contractile force were highly variable dependent upon the specific level of preganglionic outflow and the location of the strain-gauge arch.


Umbilical vascular compliance in sheep.

Umbilical vascular compliance in sheep. To explore the mechanical properties of umbilical vessels and to test for possible interactions between maternal and fetal circulations, we recorded pressure-volume curves from isolated in situ placentas of 17 sheep. We estimated static umbilical compliance by extrapolating to infinitely slow rates of volume change. We found that compliance averaged .231 +/- .014 SE ml/mmHg per kg fetal wt under control conditions, a value that increased 26.5% when maternal arterial pressure was lowered 85 mmHg (clamping the aorta), but did not change when venous pressure was raised 37 mmHg (clamping IVC). After replacing blood with kerosene which does not penetrate small vessels because of interfacial tension, we found arteries accounted for 22% and veins for 41% of total compliance, leaving 37% attributable to small placental vessels and surrounding tissue. We conclude that umbilical vessels are about one-half as compliant as adult vessels on a body-weight basis, but only slightly less compliant than vessels elsewhere in the fetal body. When maternal vessels expand they interact with surrounding placental tissue, displacing fetal blood and altering the apparent compliance of umbilical vessels.


Myocardial contracture and accumulation of mitochondrial calcium in ischemic rabbit heart. The relationship between myocardial contracture and cell calcium was studied in electrically paced, isolated perfused rabbit hearts. Isovolumic left ventricular dP/dt and end-diastolic pressure were utilized as indexes of contractility and ventricular stiffness. After 60 min of low flow (ischemia) without or with reperfusion at high flow for 10 min, calcium was measured in the mitochondrial fraction and used as an indicator of intracellular calcium. Low flow led to ventricular standstill and contracture, and reperfusion produced partial mechanical recovery with end-diastolic pressure remaining markedly elevated. Nifedipine (10(-7) M), an antagonist of myocardial calcium uptake, prevented contracture and permitted nearly complete mechanical recovery without elevation in diastolic pressure. Increases in mitochondrial calcium paralleled the severity of contracture and the lack of diastolic relaxation after reperfusion. Mitochondrial calcium did not increase in hearts protected by nifedipine. Results demonstrate a close relationship between mechanical changes induced by ischemia and accumulation of intracellular calcium.


Alterations of postural and Valsalva responses in coronary heart disease. Patients in congestive heart failure are known to have altered autonomic responses to circulatory stress. In this study, two different age groups of male coronary heart disease (CHD) patients, not in failure, as well as normal male subjects, underwent standard 20-min 70 degrees head-up tilt and Valsalva tests. Responses were monitored by noninvasive methods and cardiac output was estamated with a transthoracic impedance method. During tilt, the CHD patients and control subjects had similar heart rate and diastolic pressure responses. However, the CHD patients had a greater decline in pulse pressure during tilt, mainly due to a decrease in systolic pressure. CHD patients had lesser declines in stroke volume and cardiac index and lesser increases in total vascular resistance than did control subjects. In the Valsalva, the heart rate phase increments (and decrements) from control and rate increments (and decrements) between successive phases were less in the coronary patients. The results indicate that coronary patients, not in failure, have diminished circulatory responses to the tilt and Valsalva maneuver and suggest that these tests may be useful functional indices of cardiovascular capability in coronary disease.


Noninvasive analysis of regional myocardial wall motion: cardiokymography. The validity of a new noninvasive device, the cardiokymograph, was assessed as to its ability to detect regional myocardial wall motion by direct comparison of the analog tracing with that of an epicardial length gauge in 11 open-chest dogs. The correlation of the two methods was excellent both during control conditions and following changes induced by acute coronary occlusion. The average difference between the methods in timing of various cardiac events was only 6.2 +/- 1.9 ms at rest and 6.8 +/- 1.5 ms following ischemia (P = NS). Relative amplitude ratio correlations, determined for the four portions of the cardiac cyele (isovolumic systole, ejection, isovolumic relaxation, and diastole), were also excellent. The average correlation of the kymograph to the length gauge was r = 0.896 +/- 0.018 at rest (K = 0.977 LG + 0.033) and r = 0.932 +/- 0.013 following occlusion (K = 1.071 LG + 0.101). Thus, the cardiokymograph is a sensitive and accurate noninvasive method for detection of regional ischemic dysfunction and produces an analog tracing essentially identical to that of the epicardial length gauge.


Myocardial enzyme activities in guinea pigs during development. The activities of hexokinase, glucose-6-phosphate dehydrogenase, and glycolytic enzymes were higher in the fetal myocardium of the guinea pig than at birth and fell progressively during the 1st mo of life. The alphaHBDH/LDH ratio of H to M subunits of lactate dehydrogenase, was low in the fetus and continued to rise during the 1st mo after birth. The distinction between the left and right ventricular activities of lactate dehydrogenase, which is clear in adult guinea pigs, was absent in the fetus and appeared during postnatal development. Glycogen phosphorylase activity was low in the fetus and at birth. The activities of beta-hydroxyacylcoenzyme A dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and aspartate aminotransferase were low in the fetus, but had reached, or even temporarily exceeded, normal adult levels at birth. Palmitylcarnitine transferase activity was also low in the fetal heart compared with the newborn but continued to increase substantially during the first 2 wk after birth.


End-systolic force-length relationship of nonexcised canine papillary muscle. End-systolic force-length (F-L) relationships were studied in blood-perfused papillary muscles remining in the canine right ventricle. The muscles contracted spontaneously at a regular rate of 114 +/- 4 (SE, N = 31) beats/min at 37 degrees C. In each muscle, end-systolic F-L curves were obtained in different modes of contraction at different diastolic lengths between the unstressed length (9.4 +/- 0.7 mm) and 143 +/- 4% of it. At the latter length, muscles developed a peak isometric force of 46 +/- 4 g (5.1 +/- 0.5 g/mm2). The isotonic F-L curve was lower than the isometric F-L curves to various extents. An auxotonic F-L curve fell between the two curves. At identical end-systolic lengths peak isometric forces were greater than isotonic forces by 14.4 +/- 1.4% in the first transient beats after switching the contraction mode from isometric to isotonic. The difference increased to 28.5 +/- 3.5% in the steady-state beats. The reduced force in the first isotonic beat was suspected to be due to the uncoupling effect of shortening. The further reduction of isotonic force in the steady-state beats was caused by viscous properties (creep and stress relaxation) and by a gradual decrease in contractility.


End-diastolic and end-systolic ventricular volume clamper for isolated canine heart. We devised a servo-controlled pump system which can clamp both end-diastolic and end-systolic volumes of the left ventricle of an excised, supported canine heart at desirable values in the face of changing patterns of ejection and filling. The system consists of a Bellofram cylinder and a powerful electromagnetic shaker which is driven by a position servo circuit. A water-filled balloon placed in the ventricle was connected to the water housing of the cylinder. As the ECG triggered the system, a fixed amount of water reciprocated between the heart and the cylinder in a programmed manner. The onset, duration, and speed of ejection and those of filling can be programmed separately. The performance of this pump system was tested in experiments on 15 cross-circulated hearts and proved satisfactory for precise analysis of the instantaneous pressure-volume relation in the ventricle.


Creating permanent complete heart block by indirect cauterization without atriotomy. We created permanent complete heart block (CHB) in 11 dogs without atriotomy by means of indirect cauterization of the atrioventricular (A-V) bundle with a partially insulated wire placed through a small puncture in the atrial wall and guided by palpation. In six acute studies and five chronic studies, all dogs exhibited permanent CHB. To test the block, isoproterenol increased both atrial and ventricular rates 200%-400% without affecting the block. Atropine had no effect on ventricular rate or block.


The concurrent treatment of a multiple-personality woman and her son. A nine-year-old boy, unaware of his mother's three personalities, was referred for treatment because of difficulties in adjustment. The mother's two created personalities, despite antagonism toward each other, evidenced mutual dependency needs strong enough to preclude the integration necessary to resolve both her son's problems and her own.


Intensive psychotherapy for the psychiatrist's family. A series of intensive psychotherapy cases of wives and children of psychiatrists reveals that the special problems they present may be divided into those at the onset of treatment, those in the process of the treatment, and special countertransference problems. Paradoxically, early recognition and acceptance of psychotherapy are a foremost problem involving the psychiatrist as father or spouse. During therapy, narcissistic injuries to the psychiatrist father or spouse and loyalty problems in the patient emerge as special problems. Countertransference revolves around peer relationships and "psychopolitics," as well as referrals of other patients.


Psychotherapeutic options in the treatment of child and adolescent hydrocarbon inhalers. Preadolescent and adolescent hydrocarbon inhalation is a significant mental and physical health problem among low socioeconomic communities, particularly those with large concentrations of Mexican-Americans. For a variety of reasons to be discussed in this paper, those most in need of help are least likely to obtain it. The therapeutic approach should depend on the severity of the sniffing problem, and some preliminary guidelines are presented.