Interaction of inflammatory cells and oral microorganisms. III. Modulation of rabbit polymorphonuclear leukocyte hydrolase release response to Actinomyces viscosus and Streptococcus mutans by immunoglobulins and complement. In the absence of antiserum, rabbit polymorphonuclear leukocytes (PMNs) released lysosomal enzymes in response to Actinomyces viscosus (19246) but not to Streptococcus mutans (6715). Antibodies had a marked modulating influence on these reactions. PMN hydrolase release was significantly enhanced to both organisms when specific rabbit  antiserum and isolated immunoglobulin G (IgG) were included in the incubations. Immune complex F(ab')2 fragments of IgG directed against S. mutans agglutinated bacteria. Immune complexes consisting of S. mutans and F(ab')2 fragments of IgG directed against this organism were not effective as bacteria-IgG complexes in stimulating PMN release. The intensity of the release response to bacteria-IgG complexes was also diminished when PMNs were preincubated with isolated Fc fragments derived from IgG. Fresh serum as a source of complement components had no demonstrable effect on PMN release either alone or in conjuction with antiserum in these experiments. These data may be relevant to the mechanisms and consequences of the interaction of PMNs and plaque bacteria in the pathogenesis of periodontal disease.


Lung weight parallels disease severity in experimental coccidioidomycosis. Evidence provided by histopathological study of lesions is a valuable adjunct for evaluating chemotherapeutic efficacy in experimental animal models, In addition, this should be correlated with a measure of disease severity in the same animal. The latter could be obtained by homogenization of infected organs and quantitative enumeration of viable cells of the etiological agent, but this would preclude histopathological studies in the same animal. Progression of disease in pulmonary infection is associated with replacement of air space by fluid, cells, and cellular debris. Therefore, an increase in lung weight should reflect severity of disease. Results with the murine model of coccidioidomycosis demonstrate that increasing lung weight parallels the increasing census of fungus cells in the lungs of both treated and nontreated infected mice. This was supported with evidence obtained from microscopic studies of lesions indicating that specific chemotherapy limited spread of the infection and inhibited multiplication of the fungus in the lung. Therefore, lung weight can be used as a measure of disease severity in the murine model of coccidioidomycosis.


Lack of effect of azathioprine on phytohemagglutinin-induced lymphocyte transformation and established delayed cutaneous hypersensitivity. The effect of experimental long-term azathioprine administration on pre-existing in vitro and in vivo manifestations of delayed hypersensitivity was examined. Adult ewes were administered 3 mg/kg/day azathioprine for periods of up to 28 days. Neither phytohemagglutinin (PHA)-induced nor tuberculin-induced lymphocyte transformation was affected. Similarly, pre-existing skin test positivity to tuberculin showed no observable change following drug therapy. These results agree with the majority of those involving clinical situations and indicate that immunosuppression with azathiprine cannot be effectively monitored by either the lymphocyte transformation response to PHA or by changes in the in vivo or in vitro manifestations of pre-existing delayed cutaneous hypersensitivity.


Evaluation of tobacco hypersensitivity responses in the mouse. A potential animal model for critical study of tobacco allergy. CFW female mice immunized with tobacco leaf extract developed type 1 skin and mast cell sensitivities that could be quantitated. The presence of both IgG1- and IgE-tobacco-mast-cell-sensitizing antibodies was detected by 2 and 48 h. PCA test. On the basis of these findings, it is suggested that mice can surve as good animal models for critical investigation of tobacco hypersensitivity in the laboratory.


Preparation of an infectious mononucleosis receptor from sheep erythrocyte stroma. A method is described for the isolation and purification of infectious mononucleosis receptor (IMR) in high yield from sheep erythrocyte stroma. The procedure involves extraction of the stroma successively with boiling acetone, 100, 75 and 50% ethanol which removes approximately 40% non-infectious mononucleosis-active material. Subsequent phenol/buffered saline extraction of the residue from the organic extraction yields a highly active IMR preparation in the aqueous phases. This material was further purified by ethanol precipitation and gel filtration chromatography. The yield was 0.2% of the stroma. Approximately 0.1 mug/ml of the purified IMR inhibits 4 agglutinating units of infectious mononucleosis (IM) serum. The material is a glycoprotein containing N-acetyl- and N-glycolylneuraminic acids, hexose, hexosamine and approximately 46% protein. It gives one band in immunoelectrophoresis with IM serum and loses IM specificity upon treatment with neuraminidase.


Cytotoxic effector capacity of bone marrow mononuclear cells. Purified mononuclear cells from guinea pig bone marrow possess highly efficient cytotoxic effector cell capabilities in the phytohemagglutinin-induced cellular cytotoxity and antibody-dependent cellular cytotoxicity and antibody-dependent cellular cytotoxicity assays against chicken red blood cell targets. This cytotoxic activity is not removed by depletion of adherent cells by passage through rayon wool columns. Thus bone marrow lymphocytes themselves, depleted of adherent monocytes, possess this killer cell capacity. These effector cells may either arise de novo within the bone marrow parenchyma or arrive there as part of the recirculating lymphocyte pool. These studies lend further understanding of the development of functional capabilities of bone marrow lymphoid cells.


Presence and characterization of lymphokines in mouse ascites tumor fluids. Considerable skin-reactive and macrophage-disappearance-inducing activities were detected in cell-free fluids of 2 mouse ascites tumors (Ehrlich ascites tumor, leukemia L 1210). Fractionation of the supernatants by ammonium sulfate precipitation, gel filtration on Sephadex G-200, and DEAE-Sephadex A-50 column chromatography resulted in characterization of the proteinaceous substance which accounts for skin-reactive activity. The factor responsible bears a close physicochemical and biological resemblance to the skin-reactive factor of lymphocytic origin which is known to be generated by specific or nonspecific stimulation of lymphocytes in vitro, or to be produced spontaneously by lymphoblastoid cell lines. The biological significance of the findings is discussed.


Motivation, capacity, learning and age.

Motivation, capacity, learning and age. Performance and ability to learn in old age seem to depend not only upon physical and mental capacities, but upon willingness to use these capacities fully. This paper outlines a possible model of such a process, in terms of two known principles of motivation: first, that willingness to undertake action is a function of some difference or ratio between expected result and the effort, whether physical or mental, required to attain it; and second that what is achieved is valued more highly if the effort required has been relatively great. These principles seem capable of tying together many seemingly disparate facts about age changes in learning and in adaptation to developments at work, and also in everyday interests and pursuits and in the acceptance of rehabilitative procedures. They also have implications for human relationships in old age. These are discussed with reference to loneliness, which is regarded as arising when personality characteristics make communications from and to other people unrewarding.


Test anxiety in elderly and young adults. Test anxiety in elderly and young adult college students was measured by the Anxiety Achievement Test following a free-recall memory experiment. As expected, the elderly had higher levels of debilitating test anxiety than the younger adults. A large proportion of older persons showed behavioural manifestations of test anxiety either by refusing to participate in the study, or by their reactions during the testing. Test anxiety was related to memory performance among both age groups, suggesting than an older person's performance on a cognitive task may be influenced by affective reactions to the testing situation itself.


Trends in anthropological gerontology: from Simmons to the seventies. An analysis of the major trends and findings of socio-cultural studies of the aged in various cultures, as carried out by anthropologists or by other social scientists using anthropological methodology. The paper discusses the present state of our knowledge concerning comparative gerontological phenomena and gives suggestions for further research.


Personal and social value concerns of Scandinavian elderly: a multivariate study. This study is a descriptive account of the results obtained by a set of three attitudes scales, as part of a larger study on the value concerns of two samples of Scandinavian elderly, one Danish and the other Norwegian. The measuring instruments were the Cantril Self Anchoring Scale, the Life Satisfaction Index-A and Rosencranz-McNevin's Semantic Differential. The results indicate that both samples are equally preoccupied with personal security rather than economic concerns. The Danish sample perceives greater congruence between life goals and achievements than the Norwegians. The Norwegians see their young as deviant from the modal ideology of the adult world, while the Danes perceive the young as drifters, but functionally efficient. No correlation was found between personal life satisfaction and acceptance of youth, a finding at variance with results obtained by the authors among previous U.S. Samples of aged.


Learning to live in a therapeutic community: a study of elderly inpatients. Fifty-two elderly mental patients in a state hospital were transferred to a new milieu ward. In order to evaluate patient success in the unit, three outcome categories were defined nine months after the unit opened: discharge to the community, adjustment to the setting, and return to the previous ward. Despite the unit's emphasis on performance criteria for success, staff evaluations of the patients' personality rather than the patients' achievement of the behavioural criteria, accounted for success in the setting.


Concrete and formal operational thought processes in young adulthood and old age. A study was conducted to examine the role of concrete and formal operations in a young and old population. In addition, the present study explored the relation between operational thought and Cattell's concept of fluid and crystallized intelligence, as well as the role of differential living arrangements in maintaining operational thought. Eighty females from three age groups (18-20 years, 60-70 years and 70-80 years of age) were tested on a series of Piagetian tasks and indices of fluid and crystallized intelligence. The findings supported the notion that age-related performance differences occur in the area of formal operational thought prior to the time they occur in concrete operational thought. Except for the young sample, the operational tasks were found to be unrelated to fluid intelligence at the age levels represented in this study. Living independently as opposed to living in an old age home did not appear to be a significant factor in maintaining operational thought. Discussion focused on the necessity of identifying those factors which influence the developmental course of formal operational thought across the life span.


Toward a metatheoretical model of cognitive development. Recently Piaget's model of cognitive development has been seriously questioned. This questioning was due partially to the inadequacy of the model in explaining creative, scientific and mature thought in adulthood. Various proposals have suggested the existence of a fifth stage in cognitive to represent adult thought. A second tradition has focused on the Piagetian model as a competence model. This has initiated a search for an appropriate performance model to describe the processes by which knowledge is actively constructed and applied. The present work reviews the theoretical positions and the research relevant to issue and proposes a synthesis through which cognitive development can be viewed as being both product and process, competence and performance, structure and function simultaneously.


Implementing an income strategy for the elderly: studies in organizational change. The organizational dimensions of the shift in aging policy from a services strategy to an income strategy are examined. With data from the first year of a longitudinal study of the impact of the new Supplemental Security Income program in the United States, hypotheses about the local-level effect of federally mandated changes in the relationships between organizations and in the adaptation of focal organization staff are tested. Domain consensus, differential prestige and complementarity of function are identified as important factors in the implementation of change.


A note on the modifiability and reversibility of development and aging. Two major theories of biological development and aging are discussed: the mutation theory and the waste theory. The first relies on the instability of chromosomes and proposes that the aged organism, during his long life span, is more likely to have experienced damaging effects. Changes in irradiation have been introduced to manipulate longevity in the laboratory. The second theory relies on the accumulation of metabolic waste in cells and proposes, likewise, that the aged organism is more likely than the young to experience damaging effects. Recent developments in chemotherapy enable the removal of cellular waste material and, thus, the reversibility of aging processes. Some implications for the behavioral sciences are discussed.


Metabolism of calcium and magnesium in liver during acute thioacetamide intoxication. The metabolism of calcium and magnesium in liver of thioacetamide treated rats has been studied. A change in the semipermeability of the cell membrane to calcium, magnesium, sodium and potassium was observed. The variations in the concentration of extra- and intracellular cations indicates that an undiscriminated in- and outflux of those ions takes place at the time of highest calcium deposition. This change in the cell membrane permeability seems to be related to modifications in the phospholipid metabolism. An increased incorporation of 32P into the acidic phospholipids (phosphatidyl ethanolamine and phosphatidyl serine) suggests their involvement in the physiological changes of the cell membrane. The results also point out the existence of a hormonally determined susceptibility of the cell membrane to undergo those changes.


Pharmacokinetic study and bioavailability of three marketed compounds releasing p-chlorophenoxyisobutyric acid (CPIB) in volunteers. The bioavailability and the pharmacokinetics of three hypolipidemic marketed drugs: clofibride, clofibrate and basic aluminium salt of p-chlorophenoxyisobutyric acid (CPIB), releasing in vivo p-chlorophenoxyisobutyric acid (CPIB), the active metabolite, have been investigated in seven healthy male volunteers. The plasma and urinary concentrations of CPIB were determined by a gaschromatographic method, after oral ingestion of a single dose of each compound, releasing 1,3 g of CPIB, as a therapeutic dose, according to a crossover repetition design. The CPIB peak plasma level achieved by clofibride occurs earlier and is higher than this observed after clofibrate, but the CPIB bioavailability, measured by the areas under the plasma concentration-time curve released by clofibride and clofibrate, has be found similar. On the other hand, the CPIB released by the basic aluminium salt of CPIB is slowly absorbed as shown by the very low plasma levels and CPIB urinary excretion during this 24h study.


Effects of lidocaine on myocardial function and on isoprenaline-induced circulatory changes in man. 14 non-cardiac patients aged 42 to 71 years (mean 49 years) were studied. Part I 1 mg/kg or 2 mg/kg of lidocaine were administered i.v. on two consecutive days and systolic time intervals (STI) were obtained at one minute intervals for 30 minutes. No change in STI was observed after lidocaine injection. In Part II, a bolus of 5 mug of isoprenaline was given i.v. before and after an injection of 2 mg/kg of lidocaine. Isoprenaline caused a highly significant increase in the heart rate, shortening of the total electromechanical systole, pre-ejection period, electromechanical delay, isovolumic contraction time as well as PEP/LVET and ICT/QS1, indices (in all cases p less than 0.001). 2 mg/kg lidocaine had no blocking or potentiating action on the catecholamine-induced circulatory changes. In Part III, after the isoprenaline challenge, a dose of 2 mg/kg of lidocaine was administered and the bolus injection was followed by an infusion of 30 mug/kg/min. Lidocaine per se caused no change in STI in the course of the infusion over 90 minutes, and there was no difference between isoprenaline-induced changes in STI before and during lidocaine infusion. These results suggest that lidocaine has no negative inotropic effect in the therapeutic dose range in man. Lidocaine caused no change in the systolic time intervals, it had no blocking or potentiating action on the isoprenaline-induced circulatory changes, and it had no negative inotropic effect in therapeutic doses in man.


The effect of propranolol, prindolol, practolol and verapamil versus placebo on exercise induced tachycardia in patients with ventricular preexcitation. Propranolol, prindolol, practolol and verapamil have been given orally in a fixed dose to subjects with preexcitation syndrome in a cross over study. The effect on exercise induced tachycardia, prevention of tachyarrhythmias and normalization of heart rate after exercise was investigated. Propranolol, practolol and prindolol significantly (p less than 0.01-0.05) reduced the heart rate at rest and during exercise and favourably influenced the normalization of the heart rate after exercise. The effect on effort tolerance (work done till the submaximal heart rate was reached) was significantly better after propranolol (versus prindolol and verapamil) and practolol (versus verapamil) only. Verapamil showed a consistent effect only given intravenously in paroxysmal tachycardia while in the majority of patients there was no difference between oral verapamil and placebo.


The importance of individual pharmacokinetic data for treatment of epilepsy with carbamazepine. 4 patients with therapy-resistant psychomotor seizures had been treated with high doses of carbamazepine for 3-6 mo. The serum concentration, taken 2-hourly from 1600-0400 and at 0700 hr, showed the plasma half-life to be on the order of 10 hr, about one-third of that in normal volunteers. The half-life was about 5, 10, 10 and 20 hr. The findings showed that a therapeutic concentration of carbamazepine in serum can be maintained over 24 hr by 3 high doses per day. Single doses of up to 800 mg could be taken without serious side effects in patients treated for long periods with carbamazepine as sole medication.


Carbenicillin half-life in children with early diabetes mellitus. It has been shown earlier by the authors that the glomerular filtration rate (GFR) and the penicillin clearance are increased in short-term childhood diabetes. Recently, GFR and carbenicillin half-life (T/2) were determined in insulin-treated children with a diabetes duration of 1-5 years, and in a healthy control group. An inverse relationship, between carbenicillin T/2 and GFR was found in both groups. The GFR was significantly higher, and the carbeniciliin T/2 significantly lower in diabetic children than in healthy controls. There was no correlation to blood sugar levels. It is suggested that the accelerated elimination of penicillin and carbenicillin in early diabetes necessitates higher dosages of these drugs for an adequate therapeutic effect.


Reversal of the suppressed potassium excretion during treatment with combinations of antikaliuretic drugs (spironolactone, canrenone, triamterene, amiloride) in patients with liver cirrhosis. "Refractory" ascites was drained off by combinations of antialdosterone (spironolactone, canrenone) and pseudoantialdosterone (triamterene, amiloride) drugs inducing as high sodium excretion as 100 mEq per day in two patients with liver cirrhosis kept on a 9 mEq Na diet. Potentiation of the natriuretic effects of the two types of antikaliuretic drugs occurred by real synergism rather than addition. Although natriuretic acitivity showed a typical dose-related pattern, potassium excretion was unpredictable. Significant increase in potassium excretion (reversal of the suppression) occurred when 300 mg triamterene was combined with 200 mg canrenone in one of the two patients and when the dose of spironolactone or canrenone was increased from 200 mg to 600 mg within the combinations with 300 mg triamterene or 20 mg amiloride in the other. Parallel increase in sodium and potassium excretions might be caused by a proximal tubular effect or by inhibition of potassium reabsorption along with sodium in Henle's loop. The vasopressin (DDAVP) refractory distorsion of the relationship between osmolal clearance and free water reabsorpton (induced by pseudo-antialdosterone agents and potentiated by antialdosterone drugs) observed in all the 6 cases of the present patient material favoured the "loop hypothesis".


Interference of bencyclan with 11-hydroxycorticosteroids determinations. Falsely high fluorimetric readings were obtained in plasma and urine 11-hydroxycorticosteroids (mostly cortisol) assays during the administration of bencyclan to hypertensive patients. No valid conclusion can be drawn from 11-hydroxycorticosteroids assays in bencyclan treated patients.


[Hemostatic disorders with secretolytics? A contribution to drug safety]. Based on literature and on the results of this open clinical trial we conclude, that there is no connection between application of the above named group of drugs and the change in parameters of haemostasis function, which might lead to a manifest haemorrhagic diathesis. Within the period surveyed of 14 days no case of induced coagulopathy and particularly no thrombocytopenia was seen. The substances under consideration themselves did not exert any anticoagulatory effect nor did they potentiate or inhibit the effect of a concurrently given cumarin derivative.


Dopamine induced hypoxemia in patients with left heart failure. Previous studies in our laboratory have demonstrated that dopamine produces a significant decrease in arterial PO2 and a mild increase in arterial PCO2 in patients with left heart failure. The present investigations were designed to find out dopamine-induced effects impairing gas exchange. In patients with left heart failure and pulmonary congestion the true pulmonary shunt has been determined by O2-breathing. A statistically significant increase of true shunting could be evaluated. However, from calculations of the components composing AaDO2-air it can be demonstrated that most of dopamine-dependent increase of AaDO2-air is due to an elevated diffusion-distribution gradient. This dopamine effect on arterial PO2 does not limit dopamine application because oxygen administration will outrange the side effect. As changes of ventilation did not occur dopamine is assumed to open up pulmonary vessels producing blood flow in poorly ventilated parts of the lungs and causing an increased disturbance of ventilation/perfusion ratio. The increased true pulmonary shunt can be regarded as result of perfusion of totally unventilated lung areas when dopamine is infused. Haloperidol can attenuate dopamine-dependent decrease in arterial PO2. How haloperidol abolishes this dopamine effect on arterial oxygen tension remains unknown.


Deaths in connection with chlormethiazole (heminevrin) therapy. Six cases are described where death occurred in connection with chlormethiazole (Heminevrin) infusion. The close time relationship and indirect evidence strongly suggest that chlormethiazole had an important role in the fatal outcome of the patients, but definite proof of this way was not possible to obtain. Present or past alcohol abuse and respiratory, liver, cardiac or CNS diseases of different degrees seemed to be features in common for the patients possibly rendering them susceptible to the suggested detrimental effect of chlormethiazole therapy. Respiratory depression is supposed to be the primary pathogenetic mechanism of the death. Considering the relatively limited use of chlormethiazole in the department in which these cases were observed and the recommended dosage applied, the risk of serious complication during chlormethiazole infusions seems to be surprisingly high.


Use of antimicrobial drugs in medical wards. Antimicrobial usage patterns in 17,750 consecutive medical in-patients, monitored between 1966 and 1972 are described. 36.4% of all patients were exposed to one or more antimicrobials and about half of them received more than one antimicrobial agent. Penicillins accounted for 49% of all exposures and use of ampicillin rose steadily over the years. Concomitant receipt of more than one antimicrobial was common (22% of all exposed patients). Of 171 possible two-drug combinations involving 19 drugs, 126 were actually encountered. Apart from combinations, 60% of antimicrobial recipients received more than one agent at different times.


Inadequacy of information about drugs.

Inadequacy of information about drugs. A questionary was sent back by 52 interns in three internal medicine services. It showed that approximately 60% of doctors lack "often" or "very often" pharmacological facts. Information about comparative efficacy is the most difficult to obtain.


Individual differences in the antidiuretic response induced by single doses of 1-deamino-8-D-arginine-vasopressin (DDAVP) in patients with pituitary diabetes insipidus. Marked interindividual differences were found in the height and duration of the antidiuretic action induced by increasing single intravenous doses (0.5 mug and 8 mug) of DDAVP in patients with pituitary diabetes insipidus. It was assumed that differences in the duration of action reflected individual variations in the rate of removal of vasopressin.


Comparison of the effects of atenolol and practolol on exercise tachycardia in normal subjects. The relationship between cumulative doses of practolol and atenolol and resultant decreases in exercise tachycardia has been examined in 4 healthy volunteers. Continuous intravenous infusions of practolol (0.4 mg/kg), atenolol (0.12 mg/kg) and saline were administered between 7 and 12 minutes of bicycle exercise. The mean (+/- S.E.M.) heart rate (HR) at 7 min. for practolol (133 +/- 5.1) and atenolol (132 +/- 2.8) were significantly (p less than .01) reduced to 115 +/- 2.3 and 104 +/- 2.9 beats/min. respectively. The pre-infusion HR in the saline study (132 +/- 1.2) was unchanged (133 +/- 4.6) at 12 min. The relationship between the log cumulative dose of each drug and the per cent fall in HR/min was linear for each subject. The log dose-response curve (mean of 4 subjects) for practolol (y = 9.6x + 18.1) was more horizontal than for atenolol (y = 18.4x + 38.6).


Combined simultaneous radiotherapy and chemotherapy for treatment of unresectable and/or metastatic cancer. The present program was started in 1971 and is being conducted as a probing study. We believe that the only conclusion that can be drawn thus far is that, by utilizing the conventional cobalt therapy and chemotherapy together, there has been no increase in morbidity or mortality. The patients appear to have tolerated this therapy well on an out-patient basis with hospitalization only being needed occasionally. By the time the radiotherapist and/or chemotherapist sees the patient, the cancer is usually systemic. Therefore, a combined approach should be seriously considered since we have found that the patients tolerate this program well. The authors also feel that there has been an improvement, thus far, in terms of completion and duration of response. Further studies are currently being carried out in order to arrive at a more satisfactory statistical conclusion.


[Isoelectric focusing of an alkylating 3H-cyclophosphamide derivative from human bladder urine]. 1) A stable polar 3H-cyclophosphamide metabolite capable of alkylating 4-(p-nitrobenzyl) pyridine and relatively high concentrated in human bladder urine was isolated. The compound has the pI value 9.06. It is a phosphoramide mustard conjugate. 2) Determination of the isoelectric point was accomplished by means of a new thin-layer isoelectric focusing technique applicable for characterizing loaded parts of low molecular weight substance mixtures.


On human biotransformation of some penicillins. Urinary excretion of ampicillin, amoxicillin and oxacillin was studied in five healthy volunteers. Determinations were carried out by chemical methods (PC, TLC, spectrophotometry). Beside the parent compounds and their penicilloic acids, an alphaamino-substituted derivative was demonstrated. The total recovery of amoxicillin was nearly complete, recovery of ampicillin and oxacillin was about 50%. The combination of aminopenicillins with oxacillin did not alter significantly the excretion of the individual compounds.


Effect of acebutolol, a new beta-receptor antagonist on heart rate and rate-pressure product in normal subjects. A study on the effect of acebutolol, a new beta receptor antagonist, on the resting and post-exercise heart rate and rate-pressure product was carried out in 8 normal volunteers. Intravenous administration of 10 and 20 mg acebutolol was compared with 10 and 20 mg practolol administered at weekly intervals. In the oral study, increasing doses of acebutolol were administered over a period of 20 days. The heart rate and blood pressure was recorded before and at the completion of 4-minute exercise period. The exercise was carried out on a bicycle ergometer at 150 watt per minute for 4 minutes. In a dose to dose comparison, the potencies of acebutolol and practolol administered intravenously were of the same order, in decreasing the resting and post-exercise heart rate and rate pressure product. Their duration of action was also similar. In the oral study, the peak effect was achieved at a dosage of 200 mg per day (100 mg twice daily) of acebutolol. Acebutolol decreased the resting as well as post-exercise rate-pressure product (cardiac work load). This may be the mechanism for the reported beneficial effect in angina pectoris. Acebutolol was well tolerated and no serious side-effects were observed.


Pharmacokinetics of azathioprine under haemodialysis. Due to the retarded elimination of azathioprine and its metabolites immunosuppressive therapy creates certain problems during acute or chronic renal failure. For this reason the pharmacokinetics of azathioprine and its metabolites were studied in patients with chronic renal failure. Elimination during eight hours of haemodialysis amounted to 45%, which is only slightly less than the elimination in the urine of normal persons over a period of 24 hours. The dialysance of azathioprine and its metabolites was similar to that for uric acid. Effective elimination through haemodialysis is therefore possible. We are of the opinion that the dose of azathioprine for effective immunosuppressive therapy can be maintained under simultaneous haemodialysis.


Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man. Elimination of the bacteriostatics tetracycline and doxycycline was compared in patients on long-term alcohol consumption to that in healthy controls. The half-life of doxycycline but not that of tetracycline was significantly shorter in alcoholics than in controls and in some patients the serum concentration of doxycycline decreased below the generally accepted minimum therapeutic concentration when dosed once daily. So, the dosing twice daily might be indicated especially if additional inducing drugs are used.


Distribution and elimination kinetics of intravenously and intramusculary administered tobramycin in man. The pharmacokinetic profile of Tobramycin, a new aminoglycoside antibiotic, has been determined in man following intravenous and intramuscular administration. The serum elimination of the antibiotic obeys two-compartment open model kinetics after intravenous injection. The fast (alpha) and slow (beta) disposition rate constants averaged 0.1169 min-1 and 0.0099 min-1 respectively. The volume of distribution at the steady-state averaged 0.123 liter kg-1 and the plasma clearance 0.8 ml min-1 kg-1. Calculation of the intrinsic absorption rate of an intramuscular dose according to the two-compartment open model indicates that absorption increases during the first 40 minutes, then decreases and is virtually complete 90 minutes after administration in all subjects. The absolute physiological availability of the intramuscular dose averaged 84.9%. A method of administration compatible with the kinetic properties of the drug is proposed.


Nephrectomy. A five-year material.

Nephrectomy. A five-year material. A review of 158 consecutive nephrectomies is presented. The pathological findings are listed and compared to other author's findings. In the present series a very low rate of nephrectomy necessitated by stone and infection is noted. Surprisingly, 14 normal kidneys were removed. The specific diagnostic problems in each case are discussed, and better diagnostic procedures in the future are mentioned.


The non-functioning kidney in renal tuberculosis. The authors have found a non-functioning kidney in 117 patients, constituting more than 24 per cent of 487 patients with bacteriologically and/or histologically confirmed renal tuberculosis, treated and followed up in the last ten years. In 2/3 of the patients with non-functioning kidney and renal tuberculosis, the conditions of non-functioning had been already present from the very beginning, at the time when renal tuberculosis was established. In the remaining 1/3 of the patients, one of the kidneys had ceased to function in the course of treatment. The authors found that the main causes for the failure of the kidney function in renal tuberculosis are strictures of the draining urinary pathways. Emphasis is laid upon the necessity of a careful observation of the patients with renal tuberculosis in the course of drug treatment in view of a timely detection and treatment ofthe strictures in the draining urinary pathways.


Magnesium deficiency in children with urolithiasis. In a group of 57 children with urolithiasis hypomagnesaemia was found in 15 cases (26.3%). All children but one with abnormally low serum magnesium levels had recurrent or bilateral nephrolithiasis or nephrocalcinosis. Prevalence of hyperoxaluria and hypercalciuria, marked severity of the clinical features, abnormality of Ca metabolism and its responsiveness to MgO treatment were demonstrable in Mg deficiency.


Urethral pressure profile measurements in children. After a brief representation of the physiological processes during micturition in the region of the bladder-urethra junction, the pathological changes in neurogenic micturition dysfunctions leading to an increase of the infravesical flow resistance are considered. A suitable procedure for determining exactly the dysfunction is the registration of a urethral pressure profile. The construction is based on pressure measurement by means of a catheter with a lateral eye, with constant slow perfusion. Measuring errors had to be determined in preliminary trials. Examples of investigations in children with various subvesical urinary dysfunctions demonstrates different points concerning this method.


Prognostic usefulness of serum lactic dehydrogenase and its fifth isoenzyme levels in carcinoma of the prostate. Antiandrogenic treatment with castration, intravenous diethylstibestrol diphosphate and oral estradiol benzoate was given to 51 patients with prostatic carcinoma. The interrelationship between the clinical response to this treatment and the changes of serum lactic dehydrogenase (SLDH) and SLDH isoenzyme V fraction (SLDH-V) level was studied. Pretreatment SLDH level is significant in regard to the 5-year survival rate. Response of SLDH and SLDH-V levels to antiandrogenic treatment has no significant influence on the 5-year survival rates. As regard the index of the 5-year survival rate in patients with prostatic carcinoma, SLDH-V was almost as specific as SLDH.


The effect of saline-induced extracellular volume expansion on the kidney function. The functional parameters of renal function of non-hydrated and hydrated dogs (saline-infused to an extent of 1-2% of the body weight) have been compared. The directly measured renal blood flow and the total renal vascular resistance were the same in the two groups. No difference has been found in glomerular filtration rate, the Cinulin was the same in the two groups. There was no important difference in the PAH clearance and PAH extraction. In the hypervolaemic group, the sodium and water excretion was about threefold that of the non-hydrated animals. The plasma protein concentration was significantly lower in the hydrated group. In our experiments we did not find glomerular factors responsible for the increase of sodium and water excretion. The decrease of tubular reabsorption is attributed partly to the decreased plasma protein concentration, partly to unknown (perhaps natriuretic) humoral factors.


Stimulation of renin secretion by various methods: optional results with hydrochlorothiazide. Serum renin concentration (SRC) was determined in 97 hypertensive patients under basal conditions and during stimulation of renin secretion. Renin secretion was stimulated by upright posture and by either of the following means: (a) diet containing 20 mEq Na/24 hours for 3 days; (b) 300 mg i.v. diazoxide injections; (c) oral ingestion of 80 mg furosemide; (d) oral hydrochlorothiazide (HCT), 25 mg twice daily for 3 days. HCT was used in 6 patients previously treated with daizoxide and in 8 patients previously treated with furosemide. Using pairs of basal and stimulated SRC determinations, the patients could be classified as high, normal, or low renin hypertensives. HCT proved to be the most convenient stimulus as far as efficacy, reliability and the patients' tolerance were concerned, and compared well with sodium restriction.


Hepatitis and its problems in a haemodialysis Unit. Current knowledge on the hazard of hepatitis in haemodialysis units is reviewed. Its routes of access and spread, and the possibilities of prevention are discussed. The preventive measures employed at the Haemodialysis Unit of the Department of Urology, University Medical School, Pécs, are outlined and the results reflecting three and a half years' experience are presented.


X-ray appearance and clinical significance of left atrial wall calcification. Ten patients with calcifications of the left atrium are reported with review of the literature. Calcification of the left atrium is frequently associated with history of rheumatic fever, longstanding congestive heart failure, atrial fibrillation, mural thrombus and embolization. Early recognition of such lesions is essential for the management of the patients, particularly when surgical intervention is contemplated. A practical classification of left atrial calcification is proposed according to the dominant lesion in each group: (a) Calcification of the left atrial appendage alone (Mitral stenosis). (b) cacification of all 3 component lesions of the left atrium, i.e., the left atrial appendage, the free wall, and the mitral valve (Severe mitral stenosis). (c) Calcification of the left atrium in MacCallum's patch alone (Mitral insufficiency).


Acute lobar collapse in canine lungs.

Acute lobar collapse in canine lungs. A series of experiments was carried out on 28 dogs in which the following aspects were investigated: in 9 dogs, the special configuration of acute lobar atelectasis; in 10 dogs, the pressure-volume characteristics of collapsed and non-collapsed diaphragmatic lobes; in 12 dogs, the wet-weight/dry-weight ratios of atelectatic contralateral lobes; in 6 dogs, the amount of blood sequestered in atelectatic diaphragmatic lobes was estimated. The relationships of an atelectic lobe closely resemble those described in man. Loss of apposition between visceral and parietal pleural surfaces was never observed. The W/D weight ratio of the collapsed lobe invariably was higher than that of the non-collapsed contralateral lobe indicating a slight increase in the volume of fluid in the atelectatic lobe. No pressure-volume differences were found between atelectatic and non-collapsed lobes.


Evaluation of various contrast agents for improved arthrography. In the canine knee joint the monomer methylglucamine iothalamate, the dimer methylglucamine iocarmate, and the nonionic contrast agent metrizamide were examined for use in arthrography. A total of 104 injections were performed with equal iodine concentrations (280-282 mg/ml) and volumes (4 ml) of the three contrast agents. These were evaluated using radiographic comparison and iodine estimations of the joint fluid at various times after injection. Radiographically the dimer was superior, followed by metrizamide and then the monomer. The greatest amount of total iodine within the joint fluid at various times after injection was found with the dimer. Iodine concentrations in the joint fluid were similar for the dimer and metrizamide, both greater than with the monomer.


Arthrography with Amipaque (metrizamide) and other contrast media. A roentgenographic and histologic evaluation in rabbits. Arthrography of the knee joint was performed in 30 rabbits for comparison of Amipaque (metrizamide) with Urografin 60% (meglumine-sodium diatrizoate), Isopaque Amin (meglumine-calcium metrizoate), Conray Meglumin 282 (meglumine iothalamate) and Dimer-X (meglumine iocarmate). Films taken at regular intervals show longer contrast duration, and less hydrarthrosis after injection of Amipaque. Minimal focal inflammatory reaction in the synovial membrane is found in many cases when the animals are sacrificed 1 day or 7 days after the injections. No significant difference can be found between the contrast media, and similar changes are also seen after injection of physiologic saline.


Skeletal demineralization and growth retardation in inflammatory bowel disease. Skeletal growth and mineralization in 54 adolescent and adult patients with inflammatory bowel disease have been analyzed comprehensively. Quantitative and qualitative radiologic techniques consisted of conventional roentgenography, photon absorptiometry, and radiographic morphometry. The data are correlated with the type, duration, and severity of disease, and with several modes of therapy. The results indicate the osteopenia and retardation of growth are common in patients with inflammatory bowel disease, particularly in adolescents, in whom the effects of corticosteroids on the skeleton are most deleterious.


Adenoviridae.

Adenoviridae. The elevation of the genus Adenovirus to a family named Adenoviridae is described. This family at the present stage contains two genera, mammalian adenoviruses--Mastadenovirus--and avian adenoviruses--Aviadenovirus. The two genera are separated primarily on the basis of difference in immunological properties of the virions.


Occurrence of a peculiar type of adenovirus 2 penton oligomer. Evidence was presented that in adenovirus type 2, a representative of Rosen's subgroup III, a preferential oligomer species of pentons, penton tetramers, could be detected in freshly purified penton preparations.


A method for the study of regional ischemic dysfunction in the intact dog. Permanent endocardial markers and the pressure-length loop. A radiographic method for use in the closed-chest dog is described which allows the quantitation of segmental mechanical performance. Previous work has shown that the area of the pressure-length loop (an approximation of a stress-strain integral) is a useful measure of the mechanical work performed by a segment of myocardium. The position of radiopaque markers previously placed to define segments of myocardium is recorded by biplane cineradiography. From simultaneous measurements of left ventricular pressure the integral of pressure with respect to segment length during one cardiac cycle is calculated. An example illustrating the utility of this model for the study of regional myocardial ischemia is presented.


Mechanism of production of cardiac conduction abnormalities due to coronary arteriography in dogs. Left coronary arteriography and left coronary artery injections of Tyrode's solution and glucose solutions were performed in 12 anesthetized dogs. The contrast medium was found to prolong the conduction time through the AV junctional tissue and through the most distal part of the conduction network as verified by His-bundle electrogram and by surface ECG (lead II). The results indicate that for evaluation of the effects on conductivity of various media, it is most reliable to measure the altered conduction velocity in the AV nodal region. The prolongation of conduction time produced by contrast medium explains heart conduction blocks and may contribute to the genesis of ventricular fibrillation, frequent complications to coronary arteriography. The data suggest that anoxemia does not cause this delayed conduction. Hyperosmolarity contributes to the alterations of the conductivity, but the ionic composition and anion toxicity of the contrast medium also may be of importance.


Preliminary characterization of the nucleic acid of infantile gastroenteritis virus (orbivirus group). The nucleic acid of infantile gastroenteritis virus was partially characterized. It was found to be a double-stranded RNA having a buoyant density in CS2SO4 of 1.57 g/ml.


Cardiac function during coronary arteriography with calcium enriched diatrizoate and metrizamide. Calcium was added to diatrizoate (Renografin 76) and metrizamide (Amipaque) to concentrations from 2.5 to 50 mEq/1. The solutions were injected into the left coronary artery in dogs with either the chest opened or closed. In open chest experiments contractile force and aortic pressures were recorded. In closed chest dogs, left ventricular pressure, first derivative of that pressure and aortic pressure were registered. The calcium ion concentration was linearly, inversely related to the effect of the contrast solutions on the recorded parameters. In these experiments the optimal amount of calcium is suggested to 40 mEq/1 added to the diatrizoate solution but only 10 mEq/1 added to the metrizamide solution. No ECG changes due to calcium addition could be registered. The cardiac toxicity of these contrast media seem to be due to an interference with the calcium flux across the cell membrane. The effect on contractility can be recorded with the same reliability in either closed or open chest experiments.


Comparisons between X-ray photodensitometric and gamma-ray absorptiometric findings of bone mineral measurements, and the evidence of their convertibility. Fifty-two bone mineral measurements were made in chronic renal failure patients using two different radiologic techniques concurrently: gamma-ray absorptiometry; and x-ray photodensitometry. Although the sites of measurements of the cortical bone mineral mass in radius were different (distal vs. proximal) and different parameters were determined (in units of gm/cm vs. gm/cm2), a moderately good correlation was found between measurements by the two techniques (r = 0.61, p less than 0.001). Using external bone width, it was possible to calculate from photodensitometric measurements the bone mass per unit length (gm/cm). This conversion improved the correlation with absorptiometry values considerably (r = 0.78, p less than 0.001). A similar correlation was found between the trabecular bone mass in the distal radius, measured by absorptiometry, and the cortical bone mass in the proximal radius, determined by photodensitometry (r = 0.79, p less than 0.001), the correlation between the cortical and trabecular bone masses by absorptiometry being only slightly higher (r = 0.84, p less than 0.001). The residual variations not explained by the correlations between the absorptiometric and photodensitometric techniques may be largely due to the real differences of bone mineral masses at the two measuring sites and by the inherent methodological errors.


Slow response induced in canine Purkinje fiber by contrast medium. Cardiac toxicity of angiographic contrast medium has been documented at the cellular level by using the methods of micro-electrode electrophysiology. Canine Purkinje fibers exposed to contrast medium exhibit a "slow response." The increased automaticity and slowed conduction inherent in this "slow response" may cause the serious arrhythmias and other adverse effects recorded by electrocardiograms during coronary angiography. Hyperosmolarity plays only a minor role in the observed cellular toxicity. The unphysiologic concentrations of sodium, potassium, and calcium in the tested contrast medium were not responsible for the changes observed. Toxicity is probably an inherent chemical property of iodinated diatrizoate or meglumine ions.


Interaction of ligandin with radiographic contrast media. Ligandin (Y protein) is an abundant cytoplasmic glutathione transferase present in liver, kidney and gut in various animals and man. Its interaction with four radiologic contrast media (Telepaque, 3-(3 amino-2,4,6, triiodophenyl -2 ethylpropanoic acid, sodium salt; Hypaque, sodium -3, 5-diacetamido-2,4,6,-triiodobenzoate; Cholografin, N,N'adipyl-bis-(3-amino-2,4,6-triiodobenzoic acid) N-methyl-glucosamine; Diodrast, 3,5-Diiodo-4-pyridone-N-acetic acid, Diethanolamine Salt was investigated by observing inhibitory effects on the enzyme-catalyzed conjugation of glutathione with 1-chloro-2, 4-dinitrobenzene. Lineweaver-Burk plots of reciprocal initial velocity versus reciprocal inhibitor concentrations at fixed glutathione and chlorodinitrobenzene concentrations demonstrate non-competitive inhibition by all contrast media except Diodrast. No conjugates of contrast media with glutathione were formed. It is postulated that intracellular accumulation of contrast media is aided by intracellular binding with ligandin. Inhibition of the GSH transferase activity of ligandin can disrupt the mercapturate formation, an important detoxification process.


[Hemofiltration in the treatment of generalized edema]. 9 fluid overloaded patients, 8 of them with congestive heart failure and 1 patient with acute renal failure, were treated by ultrafiltration without hemodialysis. Using Gambro-major- and Rhone-Poulenc-6-dialysers the patients were deprived of 6,907.14+/-3,586.13 ml or 652.83 ml/h of extracellular fluid, on an average. During the withdrawal of fluid the plasma volume and central venous pressure decreased, whereas the cardiac output slightly increased. After the ultrafiltration, which did not show any undesirable side effects, the patients could be held in a compensative state by conservative therapy (digitalis and diuretics).


[The distribution of HLA antigens in patients with duodenal ulcer]. Over a period of many years, the connection between blood groups and peptic ulcer is discussed. We examined the HLA system and did not find any relation between HLA distribution, and duodenal ulcer.


[67Ga-whole-body-scanning for non-invasive diagnosis and observation of the course of Hodgkin's disease]. Whole body scanning with 67-Ga citrate, could stand the test as a valuable non-invasive agent for the diagnosis and course study of Hodgkin's disease. It shows a differential accuracy in various nodal and extranodal manifestations, as well as in treated and non-treated cases. The method is not capable of replacing the common diagnostic methods which has been thus far used, but it can complete and occasionally correct them. The best diagnostic information can be gained in the thorax and in extranodal manifestations, which are difficult to evaluate by conventional studies. Our own results, which were obtained by means of studies in 18 cases, are discussed in comparison with reported results in the literature.


[The effect of uricosuric and uricostatic drugs on DNA metabolism]. Some of the drugs, which are used in therapy of gout were tested with respect to their influence on semi-conservative DNA-synthesis and DNA-repair in vitro, using different cell systems. The agents (Benzbromarone, Allopurinol, Thiopurinol) were investigated in concentrations similar to blood-levels in normal therapy. The cells were irradiated with ultraviolet or ionizing radiation in order to damage their DNA and DNA-repair (unscheduled DNA-synthesis) was estimated by measuring the incorporation of radioactively labeled thymidine into acid insoluble material under appropriate conditions. The substances showed different effects on DNA-synthesis as well as on DNA-repair, even then, when their supposed influence on enzymes of nucleotide metabolism, was similar.


[I. Psychotherapy and psychopharmacotherapy in dermatology. Psychotherapeutic aspects and indications]. Different dermatoses, known as psychodermatoses, are classified into psychodynamic and psychopathological aspects. The symptoms are differentiated in: psychosomatic-, psychotic-, hiding a psychoneurosis, psychovegetative- and secundary symptom. The only and important instrument for diagnosis is the interview. An example of a patient with chronic urticaria is given. The differentiation is important to indicate the therapy: psychotherapy or psychopharmacological therapy.


[Psychotherapy and psychopharmacotherapy in dermatology. II. Psychopharmacotherapy in dermatology]. The increasing amount of psychopharmacologic drugs and their widespread use in medical disciplines other than psychiatry ask for a basic information of possibilities, risk and limits of these modern therapeutic agents. This paper reviews the most common psychiatric syndroms in dermatologic practice and provides some hints for a reasonable administration of these drugs.


[Epidermolysis bullosa dystrophica inversa: report on 2 sisters]. Two sister cases of epidermolysis bullosa dystrophica inversa are reported. This type, first described by Gedde-Dahl (1971), is characterized by the inverse site of skin involvement, the intermittent course, frequent traumatic corneal erosions, retarded development of skin atrophy and absence of milia formation. Our present cases had all these characteristics except the corneal involvement. The pedigree of this family favors an autosomal recessive mode of inheritance; no consanguinity is demonstrable in the ancestors over four generations. Electron microscopic examination in one of the patients reveals the blistering beneath the basal lamina, which suggests that the pathogenesis may be similar to the Hallopeau-Siemens type rather than to the junctional type of epidermolysis bullosa.


[Melkersson-Rosenthal syndrome in childhood]. A case of cheilitis granulomatosa in an 11-year-old boy is presented. The frequency of Melkersson-Rosenthal-syndrome in childhood is compiled from data in the literature. The Melkersson-Rosenthal-syndrome does not differ in children in its clinical and histological picture known from adults. In childhood, females are more often affected than males. The etiology of the syndrome ist still unknown. Symptomatic and temporal improvement could be achieved following local injections of triamcinolone acetonide suspension.


Behavioral science applied to cardiovascular health: progress and research needs in the modification of risk-taking habits in adult populations. Epidemiological and experimental studies provide evidence that a complex of behavioral, biological and environmental factors interact in the etiology of many cardiovascular diseases. A survey of research and theory concerning training and counseling programs for adult populations is provided. Six basic behavioral recommendations are made for the maintenance of cardiovascular health. Problems in the design of mass media and interpersonal campaigns to alter the health habits of large populations are considered.


Psychosocial correlates of delayed decisions to abort. Two samples of women aborting in New York and Connecticut during 1972 and 1973 were studied. In all, six hundred and fifty eight women about to undergo first and second trimester procedures completed a self-administered questionnaire. Items include: demographic, psychosocial and personality parameters, and a detailed review of the decision process leading to abortion. Analyses of the correlates of delay are organized around four components: acknowledgment of pregnancy; seeing a physician ; deciding to abort; and locating a clinic. Other analyses focus on the role of decisional conflict in delay. Methodological issues, implications for educational practice and for theory of decision-making are discussed.


[Indications for the reconstruction of the unstable thorax due to serial rib fractures and respiratory insufficiency]. Because of the impending danger of bronchopneumonial infection caused by hospital germs we consider it of utmost importance in the care and treatment of patients with instable thorax to shorten the period of intubation and artificial respiration. By stabilizing 3 or 4 chozen ribs within the flailing chest wall, we found it possible to significantly reduce the period of intubation, intensive care and hospitalisation. The splinting of several ribs individually by introducing socalled "Rehbein plates" into the medullary cavity of those in question proved to be a trustworthy method in achieving this goal.


[Perforation of the small intestine in systemic diseases]. Small intestine perforations caused by systemic disorders are, except with M. Crohn, extremely rare. Therefore we report two cases of "spontaneous" small intestine perforations: one with hypersensitivity angiitis and one with Moya-Moya-disease, the latter not yet described in the literature.


[Silicone rubber-- an unsuitable and dangerous material for T-drains]. Four cases of bile peritonitis after removal of silastic T-tubes are described. The removal of the tubes took place 8 to 23 days after operation. This complication has been described only since the introduction of silastic tubing. The therapy consists in early relaparotomy and drainage. In dogs, the behavior of intraperitoneal silastic and rubber tubes was compared. Whereas rubber tubing was completely surrounded by a fibrous sheet not later than 2 weeks after implantation, the silastic tubing was floating freely in the abdominal cavity even after 6 weeks. Therefore, the use of silastic tubes is dangerous in short-time bile duct drainage. On the other hand, this material had advantages for long-term drainage and for endoluminal prostheses.


Semipermeable membranes for improving the histochemical demonstration of enzyme activities in tissue sections. VI. D-glucose 6-phosphate isomerase and phosphoglucomutase. Improved histochemical multi-step techniques for the demonstration of glucose 6-phosphate isomerase and phosphoglucomutase in tissue sections are described. With these techniques a semipermeable membrane is interposed between the incubating solutions and the tissue sections preventing diffusion of enzymes into the medium during incubation. In the histochemical system the glucosephosphate isomerase converts the substrate D-fructo-furanose 6-phosphoric acid to D-gluco-pyranose 6-phosphoric acid, and the phosphoglucomutase converts the substrate alpha-D-glucose 1-phosphate to the same reagent, which in turn is oxidized, by exogenous and endogenous glucose 6-phosphate dehydrogenase to D-glucono-delta-lactone 6-phosphoric acid. Concomittantly the electrons are transferred via NADP+, phenazine methosulphate and menadione to nitro-BT. Sodiumazide and amytal are incorporated to block electron transfer to the cytochromes.


Morphology and histochemistry of the adrenal medulla. I. Various types of primary catecholamine-storing cells in the mouse adrenal medulla. Semithin sections (Araldite) of mouse adreno-medullary tissue were examined in the light microscope after perfusion fixation with glutaraldehyde, glutaraldehyde/formaldehyde or after freeze-drying followed by a treatment with hot formaldehyde gas. The following methods were employed: (i) aldehyde-induced fluorescence of catecholamines, (ii) Schmorl's ferric ferricyanide reaction, (iii) argentaffin reaction, and (iiii) staining with alkaline lead citrate followed by Timm's silver sulphide reaction. The correspondence of results obtained by the various methods was proven in consecutive sections or by successively applying different methods to identical sections. Four types of primary catecholamine-storing cells were identified. NA1 cells contain cytoplasmic granules up to 0.3 mum in diameter which stain black with ammoniacal silver and display a bright white to yellow fluorescence. NA2 cells show smaller cytoplasmic granules which stain brown with the argentaffin method and give white catecholamine fluorescence. NA3 cells appear yellow-earth after applying the argentaffin reaction and show greenish fluorescence. NA4 cells are hardly identified in the light microscope. These cells are significantly smaller than the above mentioned cells and characterized by  a high nucleo-cytoplasmic ratio. They become straw coloured with ammoniacal silver and show greenish fluorescence. The argentaffin reaction was also used to identify these cells in semithin sections of glutaraldehyde/osmium tetroxide fixed material. The fine structure of the various noradrenalin-storing cells was studied in consecutive thin sections. NA1 cells were found to contain two populations of granules, the larger ones measuring between 300 and 350 nm, the smaller ones about 175 nm. The granules in NA2 cells correspond to this latter population (175 nm). NA3 cells contain an uniform granule population with a main diameter of 120 nm. The smallest granules are seen in NA4 cells being in the dimension of 80 nm. Granules in NA1 and NA2 cells show uniformly high density, whereas those in NA3 and NA4 cells display cores of varying density. Granules with moderately dense cores in NA3 and NA4 cells may represent partially emptied sites of noradrenalin storage or dopamin containing particles.


Fluorescence histochemistry of peptide hormone-producing cells: observations on the nitroso-naphthol method for the demonstration of tyrosine residues. Nitroso-naphthol reacts with tyrosine residues of peptides (and probably also proteins) to yield intensely fluorescent condensation products. This reaction forms the basis of a fluorescence histochemical procedure designed to demonstrate cells that are rich in tyrosine-containing peptides or proteins. In models the method was found to be specific for p-hydroxylated phenolic compounds. Fluorescence was induced also following formaldehyde vapour fixation. With the nitroso-naphthol technique the zymogen granules of gastric chief cells, intestinal Paneth cells, pancreatic acinar cells and certain peptide hormone-secreting cells such as the GH cells in the adenohypophysis, the insulin cells of the pancreatic islets and the calcitonin cells of the thyroid gave intense fluorescence with spectral characteristics indistinguishable from those ofthe fluorophores of tyrosine-containing peptides. In addition, a population of endocrine-like cells in the antral and intestinal mucosa of certain mammals displayed fluorescence.


Enzymic and morphological studies on catalase positive particles from brown fat of cold adapted rats. Brown adipose tissue of normal and cold-adapted adult rats has been investigated morphologically and cytochemically. In thin-sections catalase-positive particles appear as circular, oval or elongated profiles lying either as single particles or forming groups. Biochemical studies on peroxisomal enzymes show an increase of catalase activity to the tenfold amount after cold adaptation. The tissue is devoid of D-aminoacid oxidase and glycolate oxidase, while low activities of middle-chain-alpha-hydroxyacid oxidases could be detected. The catalase-positive particles were purified by differential and is lower than that of the liver peroxisomes. Enzymic investigations of the fractions render it probably that particles contain carnitine acetyltransferase, whereas they are lacking NAD-dependent glycerophosphate dehydrogenase. The pellets derived from the gradient centrifugation have been checked morphologically for purity. After performing DAB-cytochemistry for identification of the peroxidatic activity of catalase, most of the particles were shown to be structurally intact and homogeneously filled with reaction product.


Electron microscopic localization of adenylate cyclase activity of white and brown adipose tissue of the rat and chicken. Brown adipose tissue of newborn rats and chicken embryos and white adipose tissue of adult rats were studied. Adenylate cyclase (EC 4.6.1.1.) activity stimulated by 0.1 mmol/l noradrenaline was demonstrated using an electron microscopic histochemical method. The reaction product was visualized as a cobalt salt in the plasmalemma of the adipocytes. The adipocytes of the brown adipose tissue of the newborn rats showed most intense reaction in the outer surfaces of their plasmalemma. Alloxan totally inhibited the enzymatic reaction. The histochemical reaction used in the present study probably demonstrated the hormonal receptor sites in the plasmalemmas of the adipocytes which are stimulated by noradrenaline.


Esterase. XXIII. Electron microscopical demonstration of non-specific esterases in the jejunum of the mouse (Mus musc.) with two quinoline derivatives. The intracellular distribution of non specific esterases in various villous cells of mouse jejunum was investigated using two substrates, 8-acetoxiquinoline (Q-O-2) and 8-acetyl mercaptoquinoline (Q-S-2) respectively. With the more selectively staining Q-S-2 a uniform reaction was demonstrated in all enterocytes which was mainly located in the endoplasmic reticulum and the nuclear envelope. Possibly it is a matter of a single enzyme being hardly detachable from the membranes. With the non selectively staining Q-O-2 several esterases were demonstrated Es-2, adn Es-9 among them. The main reaction was found in columnar and Goblet cells, in both at all cellular membranes and in the mitochondrial matrix, additionally in cisterns and vesicles of the endoplasmic reticulum and of the Golgi apparatus and at lipid droplets of the former, finally at mucous droplets of the latter. An extracellular reaction was found in the intercellular cleft and between the microvilli of the brush border.


[A pathological classification of pleomorphic adenoma of the salivary glands (author's transl)]. Pleomorphic adenomas of the salivary glands show, despite their pleomorphism, certain histological characteristics. These are based onthe differentiation of the epithelial cell and the amount and nature of the stroma. A systematic histological analysis of 310 pleomorphic adenomas of the parotid gland resulted in the following findings and classification. 1. The most frequent epithelial cell forms were salivary duct and myoepithelial cells (75-90%) seen as epidermoid cell groups (75%). Rarer forms of differentiation were striated duct cells (5%), keratinised squamous epithelium (2,5%), oncocytes (1%), basal cells (1%), and sebaceous gland cells or goblet cells (less than 1%). 2. A myxomatous stroma represented the prototype of stromal differentiation (80%).  A chondroid stroma was found in 10% of cases examined and a mixed mucochondroid stroma in 3%. Further differentiation included hyaline stroma (25%) and fibrous stroma (15%) especially in the older tumour or after irradiation. Rarely was a fascicular (0,5%) or osseous (1%) stromal change found. 3. Four subgroups of pleomorphic adenoma can be classified from consideration of the epithelial and stromal changes. Subgroup 1 (30,5%) is the classical pleomorphic adenoma with a stroma content of 30-50%; subgroup 2 (55%) has a stroma content of 80%; subgroup 3 (9%) has a poor stroma content of 20-30% or less and an epitaelial differentiation similar to subgroup 1; and subgroup 4 has also a poor stroma content (6%) with a relatively monomorphic epithelial structure. 4. Recurrences (13,5%) were seen more in stroma-rich pleomorphic adenomas than in stroma-poor tumours. 5. On the basis of cytological differentiation, pleomorphic adenomas develop from indifferent tissue adjacent to salivary intercalated or striated ducts.


[Causal therapy for diseases of the inner ear? (author's transl)]. The examples of sudden deafness and Meniere's Disease are used to discuss the possibilities of causal therapy for inner ear dysfunctions. In sudden deafness, etiological and therapeutic considerations are focused on the problem of disorders of the arterial and venous microcirculation, contributing to oxygen deprivation of the organ of Corti. Disruption of the arterial microcirculation leads to irreversible damage of the sensory organ within minutes and non-responsiveness to therapy, whereas even serious venous circulation disturbances can be treated successfully within days after onset of the acute disease. While knowledge of pathological changes in sudden deafness is still limited, temporal bone studies in Meniere's disease provides important information on its pathogenesis. Many authors have described enlargement of the cochlear duct as evidence for endolymphatic hydrops. Maximum enlargement of the endolymphatic system disrupts the membrane system which separates endo- from perolymph, and can be confirmed by histologic examination. This indicates that a change of the ionic concentration in the inner ear fluids is responsible for inner ear dysfunction. Thus, the acute Meniere attack can be explained as a consequence of the "burst hydrops." Because of the still unknown etiology of hydrops, only its consequences can be treated at the present time: i.c., immediate removal of the toxic potassium concentration from the perilymph by increasing the microcirculation of the inner ear before irreversible damage occurs.


[Applies phoniatry. III. Stuttering and Cluttering (author's transl)]. Stuttering is caused by many factors, and consequential verbal communication may be abolished partially or even totally. Medical management should not concern itself solely with the speech problem, and the individual problem and behaviour of each patient should be considered. Unlike stuttering, cluttering does not mean poor communication, but again in its treatment, individuality must be considered. Treatment is based on frequent tuition of a slower speech and of control of the impulsive personality traits.


[Possibilities of error in tympanometry (author's transl)]. The possibilities for error in tympanometry are described. Mechanical difficulties in adaptation of the measurement tubes to the external auditory canal may be encountered. Tympanograms are discussed in patients with adhesive processes and otosclerosis which lead to incorrect results because of deviation from standard results. In the presence of adhesive processes, soft scars may produce a normal tympanogram so that the use of the Siegle speculum in connection with the Brüning magnifier is recommended. A normal tympanogram may also be absent in patients with otosclerosis. The height of the compliance curves generally does not allow conclusions as to the extent of the middle ear process so that in cases of doubt, the final determination of pathology can only be obtained by exploratory tympanotomy.


[The aetiology and management of the frontal sinus mucopyocoele (author's transl)]. The pathogenesis of frontal sinus mucopyocoele is assessed in 33 patients seen between 1958 to 1972. In 45% there has been previous frontal sinus surgery. The importance of the frontonasal duct and healthy mucosa is stressed. The unexpectedly high number of mucopyocoeles following surgery permitted critical assessment of the procedures employed. The most successful and least complicated of which involved preservation or reconstruction of a drainage canal, removal of the obstructing middle turbinate and use of an indwelling drainage tube for at least 6 months. Regular follow-up and adequate early treatment of intercurrent infection are essential.


Enhancement of the auditory evoked response by conditioning. Averaged electroencephalic audiometry has previously demonstrated that cortical responses to auditory stimuli increase and decrease in a direct relationship with stimulus sensation levels. This study utilized a conditioning paradigm with bimodal stimulus presentations in order to effect an enhancement of the auditory evoked response at low sensation levels with normal hearing subjects. The conditioning procedure that was used was found to enhance significantly the percentage of responses as well as the response amplitude. The individual specificity of the response remained unaffected by the conditioning. Response latencies were increased as a result of conditioning. Response latencies were increased as a result of conditioning.


Milk transfer of pyrrolizidine alkoloids in cattle. A study was conducted to determine if pyrrolizidine alkaloids from Senecio jacobaea (tansy ragwort) are passed into milk of lactating cows. Four cows were given dried tansy ragwort via rumen cannula at a dosage of 10 g/kg/day for 2 weeks. Chemical assay of pyrrolizidine alkaloid content in the dried plants averaged 0.16% by weight. By use of thin-layer chromatography, 5 alkaloids were isolated from the plant materials. The only alkaloid isolated from the milk was jacoline. Condition of the cows and nursing calves was monitored via measurement of blood leukocyte count, and serum protein, albumin, and globulin content. Sorbitol dehydrogenase values and liver biopsy specimens were used to assess liver function. In the cows, marked changes were observed in blood leukocyte count, sorbitol dehydrogenase values, and liver biopsy findings. No changes of any type were observed in the calves. Pyrrolizidine alkaloid content of the milk ranged from 9.4 to 16.7 mug/100 ml of milk.


The clinical relationship between acoustic reflexes and loudness perception. Speech-elicited acoustic reflexes and three measures of subjective loudness perceptions were administered to 10 normal ears and to 20 ears with confirmed sensorineural hearing loss. Most notable was the comparison between loudness discomfort level and the acoustic reflex, revealing a limited relationship. The use of the acoustic reflex as a clinical predictor of loudness discomfort is questioned.


Prescription of hearing aids: a rationale. A rationale is presented for a hearing aid prescription. Once the choice of ear(s) to be fitted is determined and whether air or bone conduction fitting is appropriate, output and gain-frequency response characteristics are prescribed on the basis of audiometric test data. The specific prescription data for ouptut are based on uncomfortable loudness levels, and gain-frequency response data are based on a formula that was determined by imposing typical speech parameters over a given hearing loss. A hearing aid prescription is not only intended to predict amplification needs but, just as important, it also provides a method for testing the results of those predictions.


Epidemiologic analysis of oral and pharyngeal cancer in dogs, cats, horses, and cattle. Four hundred sixty-nine oral-pharyngeal malignancies diagnosed in dogs, cats, horses, and cattle and submitted to the Viterinary Medical Data Program between March 1, 1964, and Dec 31, 1974, were analyzed. Of these cases, 84% were in dogs. The most frequent oral-pharyngeal cancer in dogs was melanoma; in cats and horses, it was squamous cell carcinoma. In dogs, the risk of developing melanoma increased more with age than did the risk of developing squamous cell carcinoma and fibrosarcoma. Male dogs had significantly greater risk of developing fibrosarcomas and melanomas than did female dogs. The German Shorthaired Pointer, Weimaraner, Golden Retriever, Boxer, and Cocker Spaniel breeds had significantly higher risk and Dachshunds and Beagles had significantly lower risk, as compared with all breeds combined. There was no significant difference between observed and expected numbers of tonsillar carcinomas diagnosed at veterinary colleges located in small urban areas (less than 50,000 persons) as compared with large urban populations (greater than 500,000).


Consideration of an association between geographic distribution of caves and occurrence of rabies in foxes. Establishing a causative relationship for the association between geographic distribution of caves and the occurrence of rabies in foxes in the United States will require the demonstration of a plausible biological mechanism and proof from carefully designed epidemiologic studies. Considerable data implying biological plausibility exists in the form of rabies as an enzootic disease in bats, bat predation by ground animals, bat migratory patterns, and several possible virus transmission routes to the fox. Further data showing development of rabies in the fox following appropriate bat contact are needed. Evidence leading to the acceptability of a causal relationship should distinguish between spurious, causal, and indirect hypotheses. An alternative hypothesis is whether cave areas are superior fox habitats and harbor far greater populations of foxes than do noncave areas.


Unoccluded bone conduction screening as an alternative to impedance screening. The present study was undertaken to determine which intensity level of an unoccluded bone-conducted (BC) signal might be best suited for use as a supplemental procedure to an individual pure-tone air-conduction school screening program. Four intensity levels (0, 5, 10, 15 dB hearing level) of a 500 Hz BC tone were presented in ascending order to a public school population in addition to screening by impedance audiometry and pure-tone air conducted signals. Tetrachoric analysis using impedance screening results as a standard comparison revealed that a 10-dB unoccluded BC signal at 500 Hz provided an effective supplemental procedure for identifying conductive pathology in the population studied.


Blood lead concentrations of children and dogs from 83 Illinois families. In comparison of blood lead concentrations (BLC) of 119 children and 94 dogs from 83 low-income suburban Illinois families, the mean BLC in the children was 8.9 mug/100 ml greater than that in the dogs. Demonstration of a BLC of diagnostic significance in a family dog increased the probability sixfold of finding a child in the same family with a BLC similarly increased. A history of pica in a family dog also increased the likelihood of finding pica in the family's children. It was concluded that family dogs may be useful sentinels of lead poisoning in children, and that veterinarians seeing dogs in clinical situations may have public health responsibilities with regard to lead poisoning.


Effects of practice on SISI scores and the relationship of SISI score to the intensity difference limen. The standard short increment sensitivity index (SISI) was given to 24 normal hearing subjects 10 times in two test sessions. For each subject the intensity difference limen was determined with a quantal method using the SISI apparatus. Although the group data indicated a statistically significant improvement in scores across presentations, the change was not clinically significant, in that the highest mean score continued to be "negative" in clinical interpretation. Four individual subjects, however, moved from initial sntations. Highest scores achieved by the subjects were found to be significantly related to intensity difference limen. The results suggest that the clinician must be aware of a potential for a clinically significant improvement in SISI score with practice on the part of some subjects.


Effect of feeding pine needles on ovine reproduction. Estrous cycles were not altered in 30 mature ewes fed pine needles 11 to 13 days prior to breeding. Pregnancy and lambing rates were not affected by the feeding of pine needles. An antiestrogenic effect of pine needles on the reproductive process in ewes was not clinically detectable. There was no indication of any toxic effects on ewes consuming a 37% pine needle diet.


Differential diagnosis of viral leukoencephalomyelitis of goats. In clinical evaluation of 13 kid goats with viral leukoencephalomyelitis, diseases goats were found to be usually 2 to 4 months old, afebrile, and with unaltered mental status. The most frequent neurologic signs were posterior paresis and ataxia. Pleocytosis and lymphopenia were consistent antemortem laboratory findings. Absence of other abnormal laboratory and radiographic changes were also typical of the disease. Confirmation of the diagnosis can be obtained only be thorough histologic examination of the brain and spinal cord.


Problems with earphone calibration using a manikin. The response of a single TDH-39 receiver mounted in a MX-41/AR and an Auraldome cushion was measured psychoacoustically and electroacoustically using standard couplers and the Zwislocki coupler mounted in KEMAR (Knowles Electronic Manikin for Acoustic Research). Although the psychoacoustic data were similar for both cushions, electroacoustic responses differed across cushions and across couplers. It was concluded that an accurate method for evaluating circumaural earphones has not yet been developed and the manikin, in its present form, is unsuitable for supra-aural or circumaural earphone calibration.


Situational cues in visual speech perception by geriatric subjects. Situational cues have been known to enhance visual speech perception. In the present study  the influence of relevant and nonrelevant visual and auditory background information on visual perception of everyday sentences was measured in geriatric subjects using videotaped material. Results indicated that visual speech perception with relevant situational cues was significantly different from performance when nonrelevant cues were provided and when situational cues were absent. Individual subject deviations in performance were noted and their therapeutic implications were presented.


Ichthyosis in two dogs.

Ichthyosis in two dogs. Ichthyosis in 2 dogs was characterized by extreme hyperkeratosis on all or part of the skin and by extreme thickening of the digital and metapodial pads. The skin disorder closely resembled human lamellar ichthyosis, in which the histologic features include a thickened granular layer, mitotic figures, and dense collections of coarse keratohyaline granules. The disease was believed to be inherited, probably autosomal recessive, inasmuch as none of the parents was affected. Treatment of 1 dog with 5% lactic acid in hydrophilic ointment reduced the hyperkeratosis and decreased the shedding of scales.


Radiologic and gross anatomic evaluation of bone healing in the dog. Bone healing associated with 3 techniques of midshaft femoral fracture fixation in 36 young adult Beagle-type dogs was evaluated in radiographic and gross pathoanatomic studies. A serrated transverse fracture was surgically and aseptically created on the midshaft of either the left or the right femur of each dog. The fixation devices used were intramedullary (IM) pin, IM pin and 1/2 Kirschner device, and tension bone plates. The radiographic evaluation was done in series. The first radiographs were taken during surgery. Radiographs were then taken immediately after surgery, to record the status of reduction, alignment, and fixation. Radiographs were taken at the 4th and 10th postoperative weeks, to monitor healing. All dogs were euthanatized at the 10th week. Both the normal femur and the healing femur were removed from all dogs, all soft tissue was removed from the bone, and each femur was examined grossly. Each type of fixation was associated with a distinct mode of osteogenesis. Bony union and clinical union (that stage in the healing process when fixation can be removed) were defined as a successful conclusion to each case. Malunion and nonunion were defined as unsuccessful conclusions. Delayed union was defined as neither successful nor unsuccessful. The IM pin cases had a 64.2% success rate and a 14.2% failure rate. The IM pin and 1/2 Kirschner cases had a 100% success rate. The bone plate cases were 91% successful, with 0% failure. A problem identified with IM pinning was axial rotation (6 of 14 or 42% of the cases). It was concluded that IM pins should not be used alone for the fixation of femoral fractures in adult dogs.


Morphology of the epididymal region and ductus deferens of the turkey (Meleagris gallopavo). The ductal system of the reproductive tract of the male domestic turkey was studied by gross dissection and light microscopy of paraffin and Epon embedded tissues. The succession of ductules as one passes caudally from the testis was as follows: seminiferous tubules; rete testis; ductuli efferentes; connecting ductules; ductus epididymidis; ductus deferens; receptaculum ductus deferentis; papilla ductus deferentis. Non-ciliated cells of the male tract consisted of squamous and low cuboidal cells of the rete testis, granulated columnar cells lining the ductuli efferentes and connective ductules; agranulated columnar cells which formed the epithelium of the ductus epididymidis, ductus deferens, receptaculum and papilla ductus deferentis; and basal cells which were found in increasing number from the ductuli efferentes to the papilla. The basal cells had a reduced amount of cytoplasm and stained more intensely than the other cell types. Ciliated cells were apparent in the ductuli efferentes and connecting ductules, and these consistently stained lighter than the non-ciliated cells. Non-ciliated columnar cells of the ductuli efferentes and connecting ductules contained chromatophilic granules. Cytoplasmic blebbing into the ductal lumina was found associated with these non-ciliated cells as well as the agranular cells of the ductus epididymidis and deferens. Evidence obtained from this study suggests that the non-ciliated cells of the ductuli efferentes, ductus epididymidis and ductus deferens have a contribution to make to the seminal plasma by apocrine secretion.


An ultrastructural study of implantation in the golden hamster. II. Trophoblastic invasion and removal of the uterine epithelium. Sixty six implantation sites from 18 golden hamsters were examined with light and electron microscopy between 4 and 5 1/2 days of pregnancy (post-ovulation). At 4 days some blastocysts began to invade the uterine epithelium, with trophoblastic processes penetrating and engulfing portions of the uterine epithelium. The majority of epithelial cells appeared normal before invasion, although at two implantation sites three or four adjoining epithelial cells were necrotic before penetration by the trophoblast. In general the epithelial cells were degenerating at the time the trophoblast invaded the epithelium. Inclusions, representing portions of the engulfed epithelium, and varying in size and electron density, were present throughout the invading trophoblast cells at 4 1/2 and 5 days of pregnancy. At 5 1/2 days the uterine epithelium had disappeared and the embryo was now almost completely surrounded by blood lacunae.


Freeze-fracture replication of organized tissue without cryoprotection. Fresh pieces of rat liver and pancreas were rapidly frozen without prior chemical fixation or cryoprotection, and replicated folloing freeze-fracture. Replicas revealed small peripheral areas free of ice crystals or damage and, within such areas, general ultrastructural morphology was essentially similar to that seen in conventionally processed material. On fracture faces of plasma and nuclear membranes a population of less prominent particles in addition to conventional membrane-associated particles was seen, and smooth areas devoid of particles of any type were seen on some nuclear membranes. These smooth areas did not appear to be similar to smooth areas allegedly arising as artifacts of conventional processing. Tight junctions and gap junctions appeared as they do in cryoprotected specimens. The results provide a base-line for assessing the possible effects of processing steps or agents on the ultrastructure of organized tissues as revealed in freeze-fracture replicas.


Casts of hepatic blood vessels: a comparison of the microcirculation of the penguin, Pygoscelis adeliae, with some common laboratory animals. Latex casts of the hepatic blood vessels of the penguin, Pygoscelis adeliae, and of some common laboratory animals were compared. There was general similarity between the different species, but the portal venous and hepatic arterial systems of the penguin were simpler than those of other species. Measurements were made of the volume and length of portal veins and it appears that the portal venous system is capable of being a more efficient blood reservoir in the penguin than in other species studied. The peribiliary plexus was especially well formed in the penguin and was drained by long veins which usually joined portal venous branches. Some of the long veins drained directly into the hepatic venous tree: these translobular veins were more prominent than in mammals. Anastomoses between hepatic artery and portal vein were not present in penguins, and the supply to the sinusoids appeared to be separate. The morphology of small hepatic veins of all the species appeared to be similar.


The postnatal development of the alimentary canal in the opossum. I. Oesophagus. The oesophageal epithelium of the newborn opossum generally is two to three cells in depth and in some regions appears pseudostratified. By the 9th postnatal day the epithelium shows two distinct strata. Ciliated cells and occasional goblet cells also are observed within the epithelium during this stage and in subsequent stages. Cilia persist in the oesophagus of the adult opossum, but are restricted to the depths of the transverse folds found in the distal part of the organ. The epithelium covering the transverse folds of the adult likewise has an immature appearance. By 4-5 cm (ca. 20 days), the epithelium has assumed a more mature appearance and is of greater depth. This and later stages show three basic strata: a germinal layer, a spinous layer and, adjacent to the lumen, a flattened layer of cells that retain their nuclei. The epithelium throughout the postnatal period and in the adult does not undergo complete keratinization. The oesophageal glands begin as outgrowths from the epithelium just prior to 4-5 cm (ca. 20 days). The glands continue their development throughout the remainder of the postnatal period. The secretory units of the oesophageal glands of the the major portion of the secretory elements, and a light, rounded cell type which is less numerous and which occupies the terminal portions of the secretory units. Secretory material of the former appears complex, consisting of both neutral and acid glycoproteins. The secretory product of the light cell type is unknown at present. Both cell types are encompassed by myoepithelial cells. The relationship of the mitotic sequences to the observations made by microscopic examination of the developing oesophagus is discussed.


Destruction of hyaline cartilage in the sigmoid notch of the human ulna. In an ulna from an adolescent a fossa nudata divided the articular surface of the sigmoid notch into olecranon and coronoid areas. In the floor of the fossa a layer of loose avascular pannus covered a thin layer of articular cartilage. The pannus appeared to have been formed by removal of chondroitin from the cartilage, freeing the cells and unmasking the fibres. Probably the change followed loss of contact between the articular cartilages of the sigmoid notch and trochlea during postnatal growth.


Transport of solutes through cartilage: permeability to large molecules. A review of the transport of solutes through articular cartilage is given, with special reference to the effect of variations in matrix composition. Some physiological implications of our findings are discussed. Also, results of an experimental study of the permeability of articular cartilage to large globular proteins are presented. Because of the very low partition coefficients of large solutes between cartilage and an external solution new experimental techniques had to be devised, particularly for the study of diffusion. The partition coefficients of solutes were found to decrease very steeply with increase in size, up to serum albumin. There was, however, no further decrease for IGG. The diffusion coefficient of serum albumin in cartilage was relatively high (one quarter of the value in aqueous solution). These two facts taken together suggest that there may be a very small fraction of relatively large pores in cartilage through which the transport of large molecules is taking place. The permeability of cartilage to large molecules is extremely sensitive to variations in the glycosaminoglycan content: for a threefold increase in the latter there is a hundredfold decrease in the partition coefficient. For cartilage of fixed charge density around 0-19 m-equiv/g, there is no penetration at all of globular proteins of size equal to or larger than serum albumin.


Observations on some additional abnormalities in situs inversus viscerum. The abnormal findings in a case of Situs inversus totalis are described. The duodenum was placed abnormally and retained its primitive mesentery. The proximal 22 in of jejunum were retroperitoneal. The attachment of the root of the mesentery to the posterior abdominal wall had a 7-shaped appearance, and there was a partial failure of the primitive mesocolon to adhere to the posterior abdominal wall. The common hepatic artery arose from the superior meseneric artery, which also provided a branch to the proximal jejunal loop. The right vagus nerve was found anterior to the oesophagus at the oesophageal hiatus in the diaphragm, and the left vagus was posterior. A double ureter was present on the right side. The findings are discussed in relation to mid-gut development.


The root surface in human teeth: a microradiographic study. In an attempt to clarify the nature of the human cemento-dentinal junction, ground sections of incompletely formed and fully formed extracted teeth were prepared and their histology compared with their microradiographic appearances. The results showed that incompletely formed teeth possess distinctive surface layers outside the granular layer of Tomes. The evidence indicates that these layers are of dentinal origin; their presence during development supports previous explanations by the author of the hyaline layer of Hopewell-Smith and of so-called intermediate cementum. The results also indicate that the granular layer of Tomes does not represent the outer limit of root dentine. The relationship of these surface layers to the definitive cementum which is present in fully formed teeth was studied in both young and older patients. From the results it was concluded that cementum formation begins in the more apical region of the teeth at a time when root formation is well advanced, and that it spreads towards the crown rather than in the generally accepted reverse direction.


Development and cytodifferentiation of the rabbit pars intermedia. II. Neonatal to adult. Material from pars intermedia obtained from rabbits ranging from the second week post-partum to the adult stage, and including specimens from pregnant animals, was studied. The rate of cell division became greatly reduced early in postnatal) development. The commonest type of cell (the pars intermedia-glandular cell) becomes increasingly PAS-positive during the early stages of development. Although by 35 days differentiation of all the ACT-type cells is complete, the pars intermedia-glandular cells take as long as 53 days to mature. The epithelioid border of the hypophysial cleft persists throughout life, commonly containing dark cells. A ciliary fringe frequently appears in neonates and persists in pregnancy. Possible functions of such cilia are discussed. Throughout development the fine structure of the vasculature was studied. Secretory granules resembling those within the cells were seen in and around the blood vessels, and the mode of endocrine secretion in the pars intermedia tissue is discussed. The pars intermedia-glandular cells of the pregnant rabbits appeared hyperactive. The functional significance of the mammalian pars intermedia is discussed.


Langerhans cells in the human oesophagus. The dendrite cells of Langerhans, first identified in the epidermis, have now been observed in the middle and superficial layers of the normal human oesophageal mucosa. They exhibit typical Langerhans granules, but no desmosomes and tonofilaments. They often have irregular indented nuclei, with a relatively pale cytoplasm contrasting with that of the adjacent squamous cells. These cells are sometimes difficult to distinguish from intra-epithelial lymphocytes, which are also encountered in the oesophageal mucosa and which share certain ultrastructural characteristics with Langerhans cells.


Changes in the total number of neuroglia, mitotic cells and necrotic cells in the anterior limb of the mouse anterior commissure following hypoxic stress. The effects of hypoxic stress (390 mmHg) on the total number of glia, cell division, and cell death in the anterior limb of the anterior commissure were studied. There was a significant (P less than 0-01) fall in the total number of glia following exposure to hypoxia at 390 mmHg for two days. No significant change was observed in the total number of glia between the hypoxic and recovery group one week after return to sea level (ca. 760 mmHg). No change was observed in the number of mitotic figures in the control, hypoxic or recovery groups, but significant falls were observed in the mean number of necrotic cells between both the control and hypoxic groups (P less than 0-05) and the hypoxic and recovery groups (P less than 0-012). The decrease in necrotic cells may be due to a large number of elderly and effete cells, which would normally have undergone degeneration over a period of weeks, dying rapidly after the onset of hypoxia, thus temporarily reducing the daily cell death rate.