A comparison of the cardiac actions of dopamine and noradrenaline in anaesthetized dogs and guinea-pig atria.

1. The positive chronotropic and inotropic actions of dopamine and noradrenaline have been compared in anaesthetized dogs and isolated guinea-pig atria. 2. Inotropic activity was measured with a strain-gauge arch in vagotomized dogs or estimated from max (dp/dt) in dogs with denervated hearts. 3. The effects of propranolol and haloperidol on the concentration-response curves to both amines were studied in isolated atria. 4. In anaesthetized vagotomized dogs noradrenaline was more potent than dopamine but dopamine appeared to have a selective inotropic action, less apparent with noradrenaline. In denervated hearts, doses of noradrenaline and dopamine which caused similar increases in max (dp/dt) also caused similar increases in heart rate. 5. In isolated atrial preparations, concentrations of dopamine and noradrenaline which produced similar increases in force of contraction also had similar chronotropic effects. 6. Propranolol produced a shift to the right of the concentration-response curves to both dopamine and noradrenaline but the antagonism of noradrenaline was quantitatively greater. Haloperidol had not effct in concentrations below those found to cause general tissue depression. 7. It is concluded that neither dopamine nor noradrenaline show any real difference in their relative inotropic and chronotropic activities in the absence of autonomic innervation.


Continuous sampling as a pharmacokinetic tool.

Continuous sampling (CS) of blood through a nonthrombogenic catheter is presented as a tool for determining various pharmacokinetic parameters after a single injection of a drug. In addition to defining many of the usual parameters used in pharmacokinetic analyses, CS provides an accurate and direct determination of the total area under the plasma concentration curve. The theoretic background underlying the CS method is derived, and a practical formulation for its use in a clinical setting is described. The aminoglycoside antibiotic, amikacin, was chosen to exemplify the use of this technique. The drug was administered to 6 children, and CS was used to define plasma and single organ (kidney) clearance, volume of distribution, half-life during the final elimination phase, the shape of the plasma concentration curve, and the exponential factorization of this curve for multicompartmental analysis. The CS method has several theoretical and practical advantages over the usual technique of intermittent blood sampling; such as accuracy in the determination of the plasma concentration-time curve integral, relative model independence, requirement for few samples, and ease in obtaining samples.


The effects of some bronchodilator and anti-inflammatory drugs on prostaglandin F2alpha-induced contraction of guinea-pig isolated trachea.

1. The bronchodilator drugs isoprenaline, salbutamol, theophylline and prostaglandin E1 (PGE1) relaxed the guinea-pig isolated tracheal chain preparation dose-dependently and their potencies were compared by EC50 values. 2. The non-steroid anti-inflammatory drugs flufenamate, mefenamate and phenylbutazone also relaxed the preparation dose-dependently, but were less potent than the sympathomimetic drugs and PGE1. 3. The contractile response to a submaximal concentration of prostaglandin F2alpha (PGF2alpha) was antagonized by flufenamate, mefenamate, phenylbutazone, aspirin, theophylline, isoprenaline, salbutamol and PGE1, at concentrations similar to or less than the clinical peak plasma levels in man. A relatively higher concentration of indomethacin was required. 4. The antagonism was relatively specific for PGF2alpha in the case of the fenamates, which did not cause comparable reductions in responses to equi-effective concentrations of histamine and carbachol. The other anti-inflammatory drugs, theophylline and the sympathomimetic drugs were less or non-specific. 5. The nature of the shifts in the long dose-response curve for PGF2alpha caused by increasing concentration levels of flufenamate indicates a dual competitive/non-competitive type of antagonism.


Diuretic effect and metabolism of bumetanide in man.

Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.


Kinetics of intravenous theophylline.

The pharmacokinetics of theophylline was studied in 6 normal, nonsmoking, adult male volunteers. A constant-rate intravenous infusion of 3.84 to 4.98 mg/kg of theophylline (as the ethylenediamine salt, aminophylline) was administered over 40 min. Serum theophylline concentrations were measured for 24 hr by means of a gas chromatographic method specific for theophylline. Within 30 min of an average intravenous dose of 4.4 mg/kg of theophylline, serum levels reached 10 microgram/ml. The highest serum level at the end of the infusion was 17 microgram/ml. The serum concentration-time data were fitted to a two-compartment open model and yielded a mean serum half-life (t1/2) of 11.02 hr, a value longer than those previously reported. Our results indicated that after the original loading dose of 4.4 mg/kg was infused for 40min, an immediate infusion rate of 1.40 mg/kg/hr (1.65 mg/kg/hr aminophylline) would be necessary to maintain a serum level of 10 microgram/ml.


Kinetics of primidone metabolism and excretion in children.

The metabolism and excretion of orally administered primidone was studied in 12 children, aged 7 to 14 yr during long-term dosing. Plasma concentrations of primidone (Pr) peaked at 4 to 6 hr and declined exponentially from 6 to 24 hr, with half-life (t1/2) values ranging from 4.5 to 11 hr. A mean of 92% (72% to 123%) of the administered dose was recovered within 24 hr from the urine as Pr and its metabolites. Of the total Pr daily dose, 42.3% (15.2% to 65.9%) was recovered as unchanged drug, 45.2% (16.3% to 65.3%) as phenylethylmalonamide (PEMA), and 4.9% (1.1% to 8.0%) as phenobarbital (Pb). The mean rate constant for conversion of Pr to PEMA (K1) was 0.0424 hr-1, for conversion of Pr to Pb (K2) was 0.0045 hr-1, and for excretion of unchanged Pr (K3) was 0.0389 hr-1. Of Pb excreted, 43% (13% to 100%) was unchanged, 15% (0% to 27%) was unconjugated p-OH Pb, 20% (0% to 44%) was conjugated p-OH Pb, and 22% (0% to 33%) was conjugated 3,4-OH Pb. KE appears to be important determinant of the steady-state plasma concentration of Pb, but interindividual differences in K2 have little influence on the overall rate constant for elimination of Pr.


Kinetics of a sulfadiazine-trimethoprim combination.

The pharmacokinetics of a combination of sulfadiazine and trimethoprim has been studied in 16 patients with varying degrees of reduced renal function. In normal renal function, the serum half-life (t1/2) of active sulfadiazine, total sulfadiazine, and trimethoprim were quite close: 7.7, 9.6, and 12.1 hr, respectively. There was a gradual increase in serum t1/2 with reduction in renal function for both active and total sulfadiazine and for trimethoprim. With accurate determinations of endogenous renal clearance, t1/2 estimates may be made from regression curves presented. The relative distribution in the body was unrelated to renal function. It was similar for the two fractions of sulfonamide and higher for trimethoprim. The means were 0.371, 0.176, and 1.104 L/kg, respectively, for active and total sulfadiazine, and trimethoprim.


Adjustment of lithium dose during lithium-chlorothiazide therapy.

There has been a long-held belief that lithium salts cannot be used in the presence of thiazide diuretics. Recently, however, thiazides have been demonstrated to be not only safe, but actually indicated in two situations in which lithium salts are used. The first is in the treatment of lithium-induced nephrogenic diabetes insipidus and the second is in severe manic depressive illness in which high doses of lithium do not produce therapeutic serum  or intraeythrocytic lithium concentrations. This new information now makes it possible for some manic depressive patients with serious medical illnesses (such as hypertension or congestive heart failure), in whom thiazide diuretics are routinely used, to be treated cautiously with lithium carbonate. This paper analyzes data from 13 patients taking lithium carbonate and varying doses of chlorothiazide in order to indicate the approximate magnitude of downward adjustment of daily lithium dose which the clinician must make to safely give 500, 750, and 1,000 mg/day of chlorothiazide.


Pharmacokinetics and pharmacodynamics of ethanol, whiskey, and ethanol with n-propyl, n-butyl, and iso-amyl alcohols.

Plasma ethanol concentration, reaction time, and electroencephalogram (EEG) were recorded in 6 normal men after ingestion of ethanol along (Group 1), whiskey (Group 2), or a mixture of ethanol, n-propanol, n-butanol, and iso-amyl alcohol (Group 3). The peak plasma ethanol concentration and the total area under the plasma concentration:time curve of ethanol did not depend upon the type of drink given, but the half-life of the terminal exponential phase of ethanol elimination was longer in Group 3. In each study period reaction time increased, there was a relative increase in delta activity (2 to 3 Hz) and a fall in mean dominant frequency in EEG activity. The extent of increase in reaction time depended on the rate of increase in plasma ethanol concentration and correlated with the concentration of ethanol while the plasma concentration of ethanol was falling. Differences in the effects of ethanol between study periods were minimal.


Bilary disposition of adriamycin.

A patient with a choledochal T tube and normal liver function received adriamycin as therapy for abdominal histiocytic lymphoma. Plasma, urine, and bile samples were collected after drug administration. Adriamycin and its metabolites were extracted from the samples and separated by thin-layer chromatography. The pharmacokinetics of adriamycin and metabolites in plasma urine resembled those of previous patients, with a plasma elimination half-life for adriamycin of 25.2 hr. Bile contained adriamycin and 11 metabolites, 4 of which were not present in plasma or urine. Forty-one percent of the administered dose of adriamycin appeared in the bile in 7 days; of this amount, 42% was adriamycin, 22% was adriamycinol, the major metabolite, and 36% was other metabolites. Hepatic clearances of adriamycin and adriamycinol showed early, rapid removal of drug by the liver, with subsequent slowing of removal rate as plasma drug concentration declined. Adriamycin was more efficiently cleared than adriamycinol by both liver and kidney. Disease states which impair the capacity of the liver to excrete adriamycin may result in prolonged, high drug levels and increased toxicity.


Bone healing.

Secondary fracture healing with callus fomation involves the immediate reaction of this special kind of connective tissue (as well as others) with rapid increase in the reduplication of periosteal, paraosseal, and, to a lesser extent, endosteal cells. There is increased metabolism of glycosaminoglycan collagen synthesis, and transformation of fibrous and cartilaginous callus, combined with mineralization of the latter and intensified vascular invasion into bone. The glycosaminoglycan content decreases with progressing ossification, while the collagen content increases. In the beginning stages of whole bone fracture healing, vascularization is the first step responsible in part for the several maxima of synthesis and total contents of the specific cell products. Extension of ossification and remodeling in the final phases of bone fracture healing depend on other local and general factors, as well as biophysical and biological factors.


Studies on the kinetics of unconjugated [14C]bilirubin metabolism in normal subjects and patients with compensated cirrhosis.

1. The kinetics of unconjugated [14C]-bilirubin metabolism have been investigated and analysed in terms of a three-pool model in a group of seven normal subjects and in a group of eight cirrhotic patients who had appreciable impairment of liver cell function. 2. In the patients with cirrhosis, the plasma unconjugated bilirubin was either normal or only slightly increased but the metabolism of unconjugated bilirubin was deranged. 3. The mean volume of distribution, the mean 4 h retention, and the mean mass of the rapidly mixing pool were all significantly greater than in the normal subjects. In contrast, mean fractional clearance rate and mean estimated erythrocyte life-span were significantly less than in the normal subjects. 4. The mean functional transfer rates and fluxes from pool 1 (rapidly mixing pool--'plasma') to pool 3 ('extravascular') and vice versa were significantly greater than the corresponding values in the normal subjects. 5. The results indicate that, in patients with compensated cirrhosis, the efficiency of the liver in extracting unconjugated bilirubin from plasma against a concentration gradient is impaired, even though the liver's capacity to conjugate bilirubin may be normal. As a consequence of the increased volume of distribution, the absolute hepatic clearance of unconjugated bilirubin is relatively well maintained.


The effect of dietary sodium intake on the blood pressure and cardiac output responses to angiotensin II in unanaesthetized rats.

1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium and administered in various sequences. 2. Dose-response curves were shifted to the left in rats on a high-, compared with a low-, sodium intake. This response was maintained for 7 days on changing from high to low sodium. 3. There was no difference in the relation between the fall of cardiac output and the rise of blood pressure in any of the experimental groups. 4. Dose-response curves for peripheral resistance showed the same directional change as seen for the pressor response in rats on high- and low-sodium diets. Since depression of cardiac output was proportional to the pressure rise, the absolute change in peripheral resistance was greater than the blood pressure response. The proportional changes were similar. 5. It is concluded that alterations in the pressor response to angiotensin caused by changes in sodium loading are attributable to changes in peripheral resistance and not to changes in the cardiac output response to the acute rise in blood pressure.


Plasma renin levels and systemic haemodynamics in essential hypertension.

1. Plasma renin concentration, intra-arterial pressure, cardiac output and total peripheral resistance have been studied in 50 patients with essential hypertension and normal renal function. 2. Total peripheral resistance and plasma renin were negatively correlated (r = -0-45), indicating that 'high-renin' essential hypertension is not necessarily associated with arteriolar vasoconstriction. 3. The inverse relation between mean arterial pressure and plasma renin (r = -0-46) suggests a role for the renal baroreceptor mechanism in the suppression of renin in 'low-renin' hypertension. 4. Cardiac output was positively related to plasma renin concentration (r = +0-42). 5. Multiple regression analysis indicates that the described relationships were independent of age.


Mitochondrial functions and content of microsomal and mitochondrial cytochromes in human cirrhosis.

1. Mitochondria and microsomal fractions have been isolated from liver biopsies from patients with alcoholic cirrhosis, cryptogenic cirrhosis or chronic aggressive hepatitis. 2. Cirrhotic livers yieled fewer mitochondria than normal liver. 3. The most significant change was a decrease in mitochondrial respiratory control. Cirrhotic microsomal fractions had a 50% diminution in cytochrome b5 and cytochrome P-450 content. 4. The two patients with chronic aggressive hepatitis showed similar mitochondrial and microsomal changes.


Intestinal absorption of glycine and glycyl-L-proline in the rat.

1. Absorption of [3H]glycine and [14C]-glycyl-L-proline at concentrations between 0-5 and 4 mmol/l was studied by perfusion in vivo of rat jejunal and ileal segments. Absorption was defined as net removal of radioisotope from the perfusate. Radioactivity assays and amino acid analyses were performed on perfusates and on mucosal tissue samples obtained from the perfused segments. 2. At the concentrations studied, absorption rates of glycine and glycylproline were proportional to concentration. Ileal rates were approximately 60% of jejunal rates. Glycylproline absorption was slightly faster than glycine absorption and was associated with the appearance in the perfusate of free glycine and proline in the ratio approximately 3:1. Intraluminal hydrolysis was insufficient to account for the amounts of free amino acids found and glycylproline hydrolase activity at the brush border is known to be minimal. 3. Glycylproline absorption apparently occurred by transport of the intact peptide followed by its intracellular hydrolysis. However, more than one-third of absorbed glycine and one-eighth of absorbed proline returned to the lumen as free amino acid. This reflux of glycine and proline was not proportional to their concentrations in the mucosa.


[Misanthropic effects of civilization].

Increase of cool distance in social relations entails not only higher consciousness of human being but also a shift from primary ingenuous emotional spontaneity of behavior to intellectually controlled thinking and striving. With progress of civilisation, social conformity is dissolving. That causes a clash between contradictory impulses: unruly urge for freedom and independence on the one hand, and insatiable yearning for harmonic community, that means, for imperturbable warm-hearted human relations on the other. In the same measure as modern men are growing unable to endure those restrictions which are unavoidable in every society, hostile motions are obstructing formation and maintenance of durable confidential contacts. In the end, estrangement and, at last, total disintegration of social structures will be conjured up.


[Indirect portraits. An attempt of non-verbal communication in a psychoanalytic group].

A collection of 7 own drawing and 15 related sketches are presented. They have been produced during the time of my participation in an analytic group. Fairly detailed information can be given about how the drawing process developed (first inspiration, initial situation, considerations during drawing). The formative and constituent elements of the drawing conceived consciously during its production are contrasted with those that have only later become conscious. The discussion of this own series of drawings and sketches should facilitate the comprehension of, and approach to, the drawings of the patients, which can also be considered to be 'indirect portraits' of their own personality and of their current environmental situatiion. The drawings were also an attempt at better integration in the group, with regard to group interaction. Advantages and disadvantages of this trial in nonverbal communication are discussed.


Treatment of refractory psoriasis with fluocinonide gel.

Twenty patients with refractory psoriasis that had responded poorly to previous therapy were treated with fluocinonide gel (0.05 percent), unoccluded, for six weeks. Patients were evaluated weekly. By the  sixth week, all patients had improved, and seventeen (85 percent) showed "excellent" improvement. One patient discontinued the trial after four weeks because the lesions had completely cleared. No other patient discontinued using the medication for any reason. Patient complaints were minimal and consisted of stinging (three patients), itching (two patients), and drying (two patients). The study suggests that fluocinonide gel (0.05 percent) is a cosmetically acceptable alternative for the treatment of refractory psoriasis.


Trichophyton tonsurans granuloma in the scalp of an adult.

Tinea capitis with granuloma formation in the scalp of an adult that was caused by Tr. tonsurans infection is presented. The lack of symptomatic findings emphasizes the occasional difficulty in making a clinical diagnosis of this condition. Moreover, the possibility of beauty parlors being the source of scalp infection in adults, as well as children, must be considered.


PUVA: using filtered sunlight as an energy source.

In this preliminary report, twenty-two of twenty-three patients with psoriasis had satisfactory clearing with 8-MOP and natural sunlight given through a Mylar screen. The long-term effects and side effects are not known. Whether this program will provide sufficiently lengthy remissions for summer use in less sunny climates is not, as yet, known.


Granuloma faciale.

The development of our present knowledge of granuloma faciale is summarized, and the clinical picture, absence of systemic illness, and distinct histopathologic features are briefly described. The differential diagnoses are noted, and the fact that the histopathologic features can almost always readily confirm the diagnosis of granuloma faciale is pointed out. A patient with eighteen individual lesions on the face in whom response of several lesions to intralesional triamcinolone occurred is presented.


Skin cancer: comparison of aggressive potentials of sunlight-induced and x-ray-induced tumors.

Differences in clinical behavior between sunlight- and x-ray-induced skin cancer have been shown. The frequency of occurrence of multiple lesions is greater in those induced by x-ray than in the solar or nevoid type. Recurrence and major surgical sequelae appear to be greater with x-ray-induced lesions. The electron microscopic pictures of sunlight-induced and x-ray-induced basal cell carcinoma are different.


Severe reaction to hydroxyurea.

This case illustrates the danger of Hydrea taken for more than three years, even though results of monthly blood studies and platelet counts were within normal limits. In this patient, thrombocytopenia suddenly developed only five weeks after normal laboratory results. Fortunately, the sodium level reverted to normal and the pancytopenia disappeared within a week with no residual effects.


Preleptotene chromosome condensation in mouse oogenesis.

In the embryonic mouse ovary, studies of meiotic onset reveal the existence of a preleptotene stage of chromosome condensation. This stage begins with the appearance of very fine and irregular filaments, which gather around the chromocenters constituted by centromeric heterochromatin. At maximal condensation the nucleus contains 40 compact chromosomal masses. Decondensation engenders the reappearance of filaments more dense and regular than those seen at the onset of the condensation stage. The filaments elongate while progressively taking on the appearance of leptotene-stage chromosomes. The oocytes at different phases of condensation stage represent 41% of the germ cels in the 13-day-old mouse embryo. This proportion reaches 63% at 14 days and then declines to 3% at 17 days. Spectrophotometric studies of the condensation-stage nucleus, following staining by the Feulgen reaction, indicated that the nucleus contains 4C DNA. This observation, together with the morphologic characteristics of this stage, suggests that the oocyte is already engaged in prophase. Time studies indicate that the condensation stage occurs immediately prior to leptotene.


A new approach to quantitative analysis of somatic association.

A formula is proposed for estimating statistically the degree of somatic chromosome association during metaphase. Standard chi-square tests can then be used to determine the presence or absence of somatic association between homologous chromosomes in selected species. The method requires that the chromosomes be morphologically distinguishable and that their circular arrangement on the metaphase plate has not been distorted by the squash used during their preparation.


Assignment of the human gene for enolase 1 to region pter in equilibrium p36 of chromosome 1.

Somatic cell hybrids between mouse cells and human cells carrying a reciprocal translocation between chromosomes 1 and 7 were tested for the expression of human enolase 1 (ENO1) by starch-gel electrophoresis. The results indicated that the gene for human enolase 1 can be assigned to the region p36 in equilibrium pter of human chromosome 1.


Replication pattern of the X chromosomes in three X/autosomal translocations.

Three X/autosomal translocations, two familial and one de novo, were analyzed. Late-replicating chromosomes and chromosome regions were studied with R-banding techniques after BrdU incorporation. The first translocation, t(X;4)(q21;q13), was a de novo translocation, found in a woman with amenorrhea. The structurally normal X was late replicating in all cells. The second translocation, t(X;6)(p21;q26), was found in an unbalanced form, 46,XX,der(6), in a phenotypically abnormal girl; her mother carried the balanced translocation. In the mother's blood culture inactivation of the X's followed two modes: In 85% of the cells the normal X was late replicating, and in the remaining 15% the der(X) was inactivated, including the attached fragment of chromosome 6. The third translocation, t(X;17)(p11;q24), was found in three generations. In the phenotypically normal mother, who carried the balanced translocation, the late-replicating X was always the normal X. In her daughters, who had an unbalanced karyotype, 46,X,der(X), and multiple congenital abnormalities, the X part of the translocation chromosome was always late replicating. No spreading of inactivation over the attached autosomal region was observed, resulting for these patients in a partial trisomy of 17q. Their peculiar phenotype is described.


Differences in the order of termination of DNA replication in human chromosomes in peripheral blood lymphocytes and skin fibroblasts from the same individual.

A comparison of the sequence of terminal replication of DNA in human chromosomes has been made between skin fibroblasts and peripheral blood lymphocytes from the same adult male individual. The chromosomes were identified by quinacrine-banding, and the order of termination of replication was determined by autoradiography. Chromosomes 4, 5, 8, and 13 were found to terminate DNA replication later in lymphocytes than in fibroblasts, wheres chromosomes 15, 19, 20, and 22 were found to terminate their replication earlier in lymphocytes than in fibroblasts.


The effect upon coronary blood flow of coronary ostial intubation with an angiographic catheter.

Fifty-two patients undergoing cardiac catheterization were studied to determine whether intubation of the coronary ostium in the course of coronary angiographic studies interferes with coronary blood flow. Pressure at the tip of the catheter and coronary sinus blood flow were measured continuously during insertion of a No. 7.2 French Judkins' catheter into the left coronary ostium and during withdrawal of the catheter from it. In 48 of the 52 patients, there was no change in blood flow related to manipulation of the catheter. In four patients, either a drop in flow following insertion of the catheter or a rise following withdrawal or both were recorded. Two of these four patients had high-grade obstruction of the main left coronary artery, and in the other two the catheter inadvertently advanced and became wedged. In all four cases, reduction in coronary flow was indicated by a drop in or "ventricularization" of the catheter-tip pressure. It is concluded that in the large majority of instances, intubation of the coronary ostium during coronary angiographic studies causes no interference with resting coronary blood flow, but that monitoring of catheter-tip pressure is an important, as well as a valid, procedure for detecting such an interference if it should occur.


Incidence of pneumothorax and pneumomediastinum in patients with aspiration pneumonia requiring ventilatory support.

In a prospective study of patients with ventilatory support, six (38 percent) of 16 patients who had ventilatory support because of aspiration pneumonia developed pneumothorax and pneumomediastinum. In contrast, the incidence of barotrauma in the entire group of patients who had ventilatory support during a year was 4 percent (22/553) (P less than 0.001). This greater incidence in the group with aspiration pneumonia was also observed when patients who were receiving ventilatory support with positive end-expiratory pressure were excluded.


Conscious perception of bronchospasm as a protective phenomenon in asthma.

Ten initially asymptomatic asthmatic subjects underwent methacholine-induced attacks of asthma on a number of occasions, to the point when tightness in the chest was just sensed (threshold point). As baseline lung volumes increased and the caliber of the airways decreased, the relative changes needed to attain a threshold point generally became smaller. Although pulmonary function can deteriorate chronically without increasing dyspnea, it is possible that a mechanism exists at the level of consciousness to protect a subject's breathing at times when pulmonary function is acutely impaired.


Desquamative interstitial pneumonitis. Cellular phase of fibrosing alveolitis.

Since the original description of desquamative interstitial pneumonitis in 1967, several investigators have questioned the specificity of the disease. The concept of desquamative interstitial pneumonitis and usual fibrosing interstitial pneumonitis as two manifestations of a nonspecific disease spectrum has been proposed. Twenty-six patients with desquamative interstitial pneumonitis were evaluated with respect to clinicopathologic correlates. Biopsies were reviewed without knowledge of the patients' clinical course. The absolute histopathologic criteria for the diagnosis were (1) intra-alveolar accumulations of free alveolar cells with PAS-positive diastaseresistant cytoplasmic granules; (2) mononuclear cell interstitial inflammation; and (3) absence of necrosis, hyaline membranes, intra-alveolar fibrosis, asbestos bodies, and birefringent crystalline dust material. Transmission electron microscopic studies revealed the dominant alveolar lining cell to be the granular pneumocyte, with a prominent population of free alveolar macrophages. Patients were segregated into group 1 (cellular phase) and 2 (cicatrized phase). Although favorable short-term responses to corticosteroid therapy were observed in both groups, long-term responses were variable. Apparent complete remissions were noted in both groups.


Desquamative interstitial pneumonia-like reaction accompanying pulmonary lesions.

Six patients with specific pulmonary diseases had pulmonary tissue surgically resected for diagnostic purposes. All six cases were characterized by space-occupying lesions surrounded by a peculiar reaction of the pulmonary parenchyma indistinguishable from desquamative interstitial pneumonia. If small biopsies from these areas had been taken, a diagnosis of desquamative interstitial pneumonia would have been made, and the underlying process would have gone undetected. These cases corroborate even further the concept that desquamative interstitial pneumonia is a pattern of pulmonary reaction, rather than a well-defined disease entity. Furthermore, it seems advisable to make the dianosis of desquamative interstitial pneumonia only when other conditions have been carefully ruled out by thorough clinical and pathologic investigations.


Demonstration of two anomalous bypasses in concealed Wolff-Parkinson-White syndrome.

Two patients with a history of paroxysmal supraventricular tachycardia but no evidence of the Wolff-Parkinson-White syndrome in the conventional electrocardiograms were studied utilizing atrial and ventricular extrastimuli. The evidence obtained in these patients was consistent with a concealed Wolff-Parkinson-White syndrome. In one patient, ventricular extrastimuli revealed three different responses in the curve of ventriculoatrial conduction, depending upon the interval of stimulus. In the other patient, intracardiac recordings, including the left atrial potential, showed that paroxysmal supraventricular tachycardia was induced by an impulse via an anomalous bypass which diverged from the main bypass or stemmed independently from the left ventricle and was maintained by impulses via the main bypass which lay between the left ventricle and the left atrium. The mechanisms for initiation of the paroxysmal supraventricular tachycardia were discussed.


Wolff-Parkinson-White syndrome. Alterations in electrophysiologic characteristics of the bypass tract secondary to ischemia.

Accurate electrocardiographic diagnosis of myocardial ischemia or infarction is difficult in patients with the Wolff-Parkinson-White syndrome; however, myocardial ischemia may also have profound effects on the electrophysiologic characteristics of the bypass tract in these patients. Comparison of studies performed during and two months following an episode of significant myocardial ischemia demonstrated substantial prolongation of the refractoriness of the bypass tract during the period of ischemia. Bypass refractoriness was prolonged by 196 msec, yet atrioventricular nodal refractoriness was not significantly different from normal. These studies, therefore, suggest that, on occasion, the presence of acute myocardial ischemia may, in fact, obscure the electrocardiographic diagnosis of the Wolff-Parkinson-White syndrome.


Quadricuspid semilunar valves.

Forty-seven cases of quadricuspid semilunar valves which were autopsied were reviewed. The ratio of quadricuspid pulmonic valve to quadricuspid aortic valve was 5:1. Among the 35 patients with quadricuspid pulmonic valves, there were ten patients with clinical and pathologic evidence of coexisting congenital cardiac defects, eight of which resulted in severe cyanotic heart disease in infancy. In the remaining 25 patients the quadricuspid pulmonic valve was an incidental finding at autopsy. Three of the seven patients with quadricuspid aortic valves had aortic insufficiency, while the remaining four had no other clinical or pathologic evidence of congenital heart disease.


Long-term physiologic consequences of the adult respiratory distress syndrome.

Six survivors of the adult respiratory distress syndrome were studied. Measurements were made of lung volumes, flow rates, single-breath diffusing capacity for carbon dioxide (Dsb), arterial blood gas levels at rest and during exercise, the ratio of physiologic dead space to tidal volume (VD/VT), alveolar-arterial oxygen pressure difference (P[A-a]O2) and percent shunt (using an assumed arteriovenous oxygen content difference). At the time of study, which varied from 3 to 16 months after recovery, we found minor and inconsistent abnormalities in the lung volumes (reduced vital capacity in one patient, elevated residual volume [RV] in two, and reduced RV in three) and in the flow rates (reduced instantaneous forced expiratory flow after 50 percent of the forced vital capacity had been exhaled in two patients). In those tests having to do with transfer of gas, there were more abnormalities, consisting of a decreased Dsb in three patients, an elevated P(A-a)O2 in four, a low resting arterial oxygen pressure (PaO2) in two, a decrease in exercise PaO2 in three, an elevated shunt fraction (Qsan/Qt) in three, and an elevated VD/VT in one patient. Clinically, at the time of study, the patients all had returned to their status before illness.


A nomogram for planning respiratory therapy.

A nomogram is presented which aids in monitoring and selecting therapy in the treatment of the patient with hypoxemia. It facilitates accurate bedside determination of total shunt fraction and estimation of the arterial oxygen tension (PaO2) attainable at inspired oxygen concentrations of 21 percent to 100 percent. The nomogram permits rapid consideration of changes in hemoglobin concentration, arteriovenous oxygen content difference, and shunt fraction on the PaO2. The uses of the nomogram in several therapeutic contexts are discussed.


Pulmonary parenchymal tissue volume in normal subjects. The effect of age and sex.

Pulmonary parenchymal tissue volume (Vt) and pulmonary capillary blood flow were determined by the acetylene-inhalation technique of Cander and Forster in 66 normal subjects (31 male and 35 female subjects) ages 8 to 66 years. In subjects under the age of 20 years, values for Vt, when factored by alveolar volume (VA) to correct for differences in body size, were essentially identical in both male and female subjects (0.248 +/- 0.039 in male subjects and 0.242 +/- 0.079 in female subjects). In subjects between the ages of 21 and 40 years, Vt/Va was significantly lower in men than women, 0.125 +/- 0.057 vs 0.193 +/- 0.046 (P less than 0.001), respectively. In subjects over the age of 41 years, although Vt/VA increased, there was no significant difference between the sexes; ie, Vt/VA decreased with advancing age up to the age of 35 years (more so in male than female subjects) and then increased back to pubertal values. The reason for the intersex changes is a greater increase of VA in male than female subjects for the same Vt. The reasons for the increase in Vt/VA in subjects over the age of 35 years are obscure.


Technique for accurate determination of the blood nitrogen tension by mass spectrometer.

Heretofore, the technical difficulties encountered in the measurement of blood nitrogen tension (PN2) by gas chromatographic techniques effectively prevented the utilization of PN2 as a clinical tool to characterize mismatching of pulmonary ventilation and perfusion. The development of mass spectrometric techniques allows for the accurate measurement of blood gas tensions; however, due to the dependency of the measurement upon flow, this technique has proven to be inaccurate for determinations of blood PN2. This technical impediment has been effectively circumvented by the development of commercially available attachment (Searle in vitro module) to a mass spectrometer. Tonometrically analyzed water was used to evaluate the validity of the measurement and the error inherent in the technique. A significant difference between the values for tonometrically analyzed water and tonometrically analyzed blood was not detected. Since the blood PN2 is a measure of the nitrogen dissolved in the water of the plasma, these studies show that tonometrically analyzed water is a valid standard of calibration for this mass-spectrometric method of determining the blood PN2.


Codeine-induced pulmonary edema.

We recently treated a patient with pulmonary edema and an oral overdose of codeine. Although overdoses of other opiate drugs are known to cause pulmonary edema, the association of an overdose of codeine with pulmonary edema has not been reported previously.


Pneumothorax complicating aseptic cavitating pulmonary infarction.

This report documents a pulmonary infarction secondary to an angiographically proven pulmonary embolus with complicating aseptic cavitation and pneumothorax. These two rare complications of pulmonary infarction have not previously been clinically or radiographically documented to occur simultaneously. The patient recovered uneventfully.


Primary ventricular fibrillation. Some unusual features.

A 47-year-old man experienced ventricular fibrillation three times during a 3 1/2-year period. Each episode was  preceded by an auditory aura, and no ventricular irritability was identified between episodes. The results of coronary arteriographic, hemodynamic, and intracardiac electrophysiologic studies were all normal. Hypokalemia and abnormal oxyhemoglobin dissociation were present. The possible relationships of these unusual features to the patient's disturbances in rhythm are discussed.


Disseminated histoplasmosis followed by disseminated coccidioidomycosis.

A case of disseminated histoplasmosis followed later by disseminated coccidioidomycosis is described. The clinical illness and immunologic studies suggest subtle defects that may have existed antecedent to infection and, thus, provided an opportunity for widespread dissemination by these normally nonopportunistic organisms. Poor correlation was noted between the clinical course and in vitro tests of cell-mediated immunity.


Removal of foreign bodies (two teeth) by fiberoptic bronchoscopy.

In special situations the flexible fiberoptic bronchoscope, with its increased visual range and extended capabilities for extraction, may be utilized to augment rigid bronchoscopy. Recently developed tools for extraction (claw, basket, forceps, and balloon catheter) may be inserted through the channel of the fiberoptic bronchoscope to capture small, peripheral foreign objects. We present the case of a 76-year-old man in whom two aspirated teeth were removed from the right lower lobe (RB9a and RB9b) using the fiberoptic bronchoscope, a wire basket, and a Fogarty balloon catheter. Rigid tube bronchoscopy was contraindicated because the patient had just sustained a fractured skull and jaw in an automobile accident.


Staphylococcal aortic pseudoaneurysm. Treatment employing ascending aorta-abdominal aorta bypass graft.

An adult patient developed infection of the anastomosis after resection of an isthmic coarctation, with subsequent formation of a pseudoaneurysm. He was treated successfully by an ascending aorta-abdominal aorta bypass graft. The graft was placed retrosternally and passed through the diaphragm into the retroperitoneal space. After surgery the patient developed systolic hypertension. A faint murmur was heard over the chest and abdomen, caused by the turbulent flow through the graft.


Pulmonary injury following exposure to chlorine gas. Possible beneficial effects of steroid treatment.

Two sisters were exposed to chlorine gas in toxic quantities in the same room of their home during an industrial accident. One was hospitalized and treated with corticosteroids and oxygen therapy, while the other received evaluation in the emergency room, and brief oxygen therapy and was released without corticosteroid therapy. Pulmonary physiologic studies have been performed on both patients at intervals following the exposure. The treated patient was stable, with normal results on studies of pulmonary function at the end of two years, while the sibling not treated with corticosteroids had demonstrable abnormalities of gas exchange which persisted during 55 months of observation. This "natural experiment" gives evidence of prolonged detrimental effects of sublethal exposure to chlorine gas on human pulmonary function in some patients. The effect of the differences in treatment between the two siblings cannot be definitely assessed in this single situation.


Ebstein's anomaly of the left atrioventricular valve with congenital corrected transposition of the great arteries. Diagnosis by intracavitary electrocardiography.

We present the findings in a 13-month-old infant with angiographically confirmed congenital corrected transposition of the great arteries and insufficiency of the left atrioventricular valve. Simultaneous intracavitary electrocardiographic and pressure recordings across the left atrioventricular valve were similar to those obtained in Ebsteins' anomaly and suggested Ebstein's disease of the left atrioventricular valve. To our knowledge, this is the first reported case with intracavitary electrocardiograms in a patient with congenital corrected transposition of the great arteries with Ebstein's malformation of the left atrioventricular valve. The usefulness of the simultaneous recording of the intracavitary ECG and pressure in the diagnosis by catheterization of Ebstein's anomaly of the left atrioventricular valve in patients with congenital corrected transposition of the great arteries is emphasized.


Bilateral sequestrations of different type with mirror-image vascularization.

The case of a 15-year-old boy with coexistent bilateral intralobar and extralobar sequestrations is reported. The interesting variant lies in the vascularization of each sequestration as a mirror-image of the other, the arterial supply originating from a common trunk of the thoracic aorta and the venous drainage converging to a unique channel into the azygos system.


Measuring the cost of caring for a foster child.

The problem of determining this cost is complex. Total costs include the direct or out-of-pocket costs and indirect costs, or the value of time devoted to rearing foster children. The use of secondary data for estimating coses in local areas is recommended.


Day care: have we forgotten the school-age child?

There is a serious lack of research on and programs for day care for the school-age child. This article examines the opinions of working mothers of school-age youngsters, and the arrangements they make.


Individualizing behavior therapy for children in group settings.

Individualizing behavior-modification programs in group settings requires a carefully devised plan applying general principles and specific procedures. This description of techniques may serve as a model for such programs.


"There's always adoption": the infertility problem.

The adoption worker can play a significant role in helping couples understand and surmount, prior to adoption, the trauma normal to infertility.


Adoption trends: 1976.

The number of children accepted for adoption by voluntary agencies decreased last year, but the number accepted by public agencies showed an increase. Nonwhite homes approved for adoption continued in short supply.


[Clinical and arthrographic aspects of the popliteal cysts].

Arthrography revealed extended meniscus lesions in 68 of 78 patients with popliteal cysts. In the remaining cases mechanical damage or inflammatory diseases of the knee were responsible for cyst genesis. Popliteal cysts should be removed only after causal diagnosis of the underlying chronic relapsing effusion leading to increased joint pressure and cystic dilatation of the often communication submembranous bursa.


[Report on 938 bimalleolar luxation fractures. 2. Late results in operated cases and consequences for the surgical technic].

In the first part of this paper the authors reported on the treatment of 938 bimalleolar luxation fractures. 256 of these patients underwent operative treatment. 109 of these were examined clinically and by X-ray 3-13 years after the operation. The analysis of late results allowed conclusions about complaints and function in connection with the new development of arthrosis deformans posttraumatica. Owing to these conclusions the operative method was partly changed. There are no new aspects regarding postoperative treatment.


[Hemangiopericytoma of the stomach].

The case is reported of a 46-year-old man who was succesfully operated for a tumor that had its origin in the greater curvature of the stomach and grew into the gastrocolic ligament. After two false diagnoses (pancreatitis and retroperitoneal tumor) this tumor was histologically identified as a hemangiopericytoma. The possibility of recurrence and its prevention are discussed.


[Crohn's disease with several intestinal foci ("skip lesions")].

A 35-year-old man underwent a resection of part of the ileum due to six "skip lesions" in Crohn's disease. At reoperation four years later, in addition to a typical terminal ileitis, two stenosing lesions were found at the ileal-jejunal junction. In connection with this rare observation, a report is made on multiple lesions and the diffuse type of Crohn's disease, both of which must be included in the therapeutic concept. "Adequate" resections including all segmental lesions are demanded, different resections in additional distant lesions, and conservative medical treatment in the widespread diffuse type of the disease.


Orientation of interphase chromosomes as detected by Giemsa C-bands.

The orientation of Giemsa C-bands has been studied in mitotic and interphase cells of Allium cepa. A sativum and of Aloe vera. The C-bands in these three species are located at the telomeres, secondary constriction region of the nucleolar chromosomes and the centromeric regions, respectively. Observations in A. cepa and Aloe indicate clearly that the interphase chromosomes are non-random in their orientation and possibly maintain their telophase configuration through the attachment of telomeres and perhaps of kinetochores with the nuclear membrane. Electron micrographs of onion cells also reveal that certain heterochromatic segments are associated with the nuclear membrane.--The nucleolar interstitial C-bands in A. sativum remain free in the nucleoplasm and may come close to each other due to heterochromatic attraction. Such a heterochromatic attraction is also evident between telomeric regions and between centromeres. However, a two by two attachment could not be noticed. A diagrammatic representation of the orientation of interphase chromosomes has been presented.


Biochemical analysis of meiosis in the male mouse. I. Separation of DNA labelling of specific spermatogenic stages.

Spermatogenic cells of the mouse have been separated by gravity sedimentation using a modification of a previously published method. Details are given for the collection of purified samples of specific meiotic stages and for the collection of labelled cell fractions following injection of 3H-thymidine. Suppression of semi-conservative meiotic DNA synthesis, essential to the biochemical analysis of pachytene DNA metabolism, has been achieved by in vivo administration of 1 M hydroxyurea.


Biochemical analysis of meiosis in the male mouse. II. DNA metabolism at pachytene.

The DNA metabolism of mouse spermatogenic cells was investigated by intravenous administration of isotope and Staput fractionation of the cells. The pattern of metabolism is virtually identical with that observed in Lilium microsporocytes. A programmed single strand nicking of DNA occure at pachytene such that at least 50% of the DNA is in the form of 62S fragments. Repair replication of endogenously nicked sites is fully achieved during pachytene. The sites of nicking and repair are preferentially located in sequences that are repeated about 400 times. These results are considered as strong evidence for a universal pattern of meiotic prophase DNA metabolism which is associated with crossing-over.


Schizophrenia--phenomenological and biological aspects.

This manuscript attempts to integrate certain biological aspects of schizophrenia with the clinical symptoms of this condition and the schizophrenic experience. Neurophysiological, biochemical, and dynamic aspects of schizophrenia involving reticular activating system, split brain studies, and the role of serotonin are discussed. The author feels that inability to selectively attend to a stimulus is the core defect in schizophrenia. Other related possibilities are alluded to.


The measurement of emotional concepts in patients with temporal lobe epilepsy.

Eleven temporal lobe epileptics, implanted with depth electrodes, 21 post-lobectomy epileptics, and 24 orthopedic controls were given a semantic differential test, which measured responses along 4 scales (evaluative, potency, activity, and danger) of 18 emotional and 1 non-emotional concepts. Results showed that post-lobectomy females thought of themselves as more dangerous than did orthopedic control females. Both post-lobectomy and implantation patients found the anger-hostility and fear-anxiety concepts less bad, potent, active, and dangerous than did the orthopedic controls. The post-lobectomy and implantation patients found the concept "sexual intercourse" and other non-sexual love-related concepts to be worse and more dangerous, but less potent and active than did the orthopedic controls.


Post-traumatic psychoneurosis: evaluation of drug therapy.

This study evaluates the results of drug therapy and psychotherapy in post-traumatic psychoneurosis. The study was undertaken because of the frequent need to estimate the costs of treatment since the illness may at times be the result of a compensable injury. Patients with this illness are frequently parties in litigation. Over the past twelve years, fifty patients that had been diagnosed as having Post-Traumatic Psychoneurosis were treated. In order to attempt to evaluate the effects of treatment the patients were selected alternately for therapy with psychotherapy or with drug therapy. The results of therapies are compared and evaluated.


Post head trauma syndrome in an adolescent treated with lithium carbonate--case report.

A twelve year old black male sustained closed head trauma, following which he developed agitated hypomanic behavior. After failure to respond to several treatment modalities, he was begun on lithium carbonate for six months, at which time the medication was discontinued without recurrence of pathological behavior.


Normal pressure hydrocephalus: a case presentation.

There are presently no successful medical treatments available for most of the chronic dementias. For this reason it is most important to diagnose potentially reversible syndromes such as Normal Pressure Hydrocephalus and to determine if that patient is a candidate for neurosurgical treatment. A typical clinical case exemplifying the most common features of this syndrome is presented. This is followed by a discussion of the physiology, etiology, signs and symptoms, methods of diagnosis, and treatment of this illness. Material for this discussion was obtained from personal clinical experience and a review of the medical literature.


Cerebellar role in smooth pursuit movement.

It is generally believed that pursuit eye movements are unaffected by cerebellar cortical atrophy or cerebellectomy. The present study was performed on patients who underwent partial vermis and hemisphere ablations as a result of severe cranial injury or cerebellar tumors. Eye movements were measured by DC electro-oculography. A clear disparity of the slow phase of the optokinetic nystagmus was observed. When eye movements were contralateral to the ablated side the slow phase of optokinetic nystagmus was statistically slower than drum or visual field velocity. It is suggested that the cerebellum network is involved in the mechanisms of the smooth pursuit movement.


The cerebellum involvement in the generation of saccades.

It was assumed that the cerebellum is not essential for eye movements, playing only a modifying and influencing role. Recently it has been shown that the directions of the saccades can be related to a stimulated cerebellar site. This study was done on patients who underwent partial vermis and hemisphere ablations as a result of severe cranial or cerebellar tumors. The results further indicate that lack that lack of some cerebellar neural structure affects the nature of the saccade: it does not move the eyes in one saccade to acquire the new target and its amplitude duration relationship changes. It is suggested that cerebellar cortex generates a neural pulse based on teleceptive information about stimulus location with respect to an observer's head, corrects this information for initial eye position and sends out a signal to the saccadic pulse generators which move the eyes to acquire the new target.


New developments in fluorescein angiography.

New developments in fluorescein angiography concern the apparatus employed, technique and the photographic laboratory. A wide-angle retinograph has been developed which enables us to photograph the periphery of the fundus. Television, with a very sensitive camera, permits us to obtain very well defined dynamic views with pictures at the rate of 25 per second. This technique enables us to resolve some new problems. The use of television produces stronger fluorescence than that achieved by ordinary photography and allows us to choose the best pictures relating to a clinical problem.


A new ultrasonic apparatus for ophthalmology using manuel compound scanning.

A new ultrasonic equipment for ophthalmological diagnosis has been developed. Manual compound scanning using water immersion made acurate representation of cross-section of the orbital structure possible. A large, focused transducer brought resolution and sensitivity. Gray scale display of the ultrasonogram increased information concerning intensity of echoes. Ultrasonograms of retinoblastoma, vitreous hemorrhage, melanocytoma, optic disc coloboma and unilateral exophthalmos are presented.


Ultrasonographic refraction of aphakic infants and children.

A simple method of aphakic refraction using ultrasonographic axial length measurement and corneal curvature determination is presented. This method was compared with skiascopy in refraction eleven eyes of aphakic infants. No significant differences were found between the relative errors measured by these two methods.


Applications of nuclear medicine in ophthalmology.

Diagnostic techniques using radioactive isotopes can be used for the investigation of cerebral, orbital and intraocular tumours and for the dynamic study of tear flow. The value of such techniques in the study of obstruction of the nasolacrymal system (particularly partial and functional obstructions) has been established and the possibility of using Tc99m clearance for the investigation of dry eyes is being investigated.


Correction of aphakia with contact lenses.

The correction of unilateral and bilateral aphakia with contact lenses has given good results. The contact lens of choice today is either the hard corneal lens or the soft hydrophilic lens. High-water-content lenses have excellent oxygen permeability which permits continuous wear. Experience with the 'Sauflon 85' lens is described.


A trichromatic test for spheric and astigmatic refraction.

An improved chromatic rotatable refraction test for simultaneous spheric and astigmatic refraction is described. Its new features are interposition of a bright yellow stripe between the conventional red and green fields and a pair of parallel test lines, which traverse vertically all colored fields. Thereby astigmatic errors become easily visible.


Optical and long wave holography: potential applications in ophthalmology.

The first part of this paper describes the process of optical holography, and discusses the possibilities and some of the merits of the application of optical holographic techniques in the field of ophthalmology, such as: 1. Holographic observation of the eye and the light-path through the cornea and the lens, leading to the evaluation of the optical constants of the eye. 2. Holographic  interferometric measurements of the configuration changes which accompany accommodation or changes in the intra-ocular pressure. 3. Three-dimensional observations of the fundus. The second part of the paper is devoted to long wave holography, which has attained special attention in electromagnetic (non-optic) and ultrasonic wave propagation. Although these two forms of wave propagation differ in their physical properties, there are many similarities in their signal processing techniques, the collection of wave fronts emerging from the object, and in the visualization of images.


The computer in clinical research. Prevalence of glaucoma.

The prevalence of glaucoma in a rural population of 6232 people over the age of 40 years, including patients with previously diagnosed glaucoma, was found to be 1.21%. There were 41 cases of open-angle glaucoma compared to 32 cases of angle-closure glaucoma. The prevalence of glaucoma among subjects over the age of 60 years was 3.07%.


A data retrieval system for the eye clinic. I. Clinical aspects.

The use of a data retrieval system for patients' ophthalmic records is described. Input is by using simple forms and output is in batch. The system is adaptable for on-line use as soon as a terminal is established in the clinic. To date there are over 6000 patients on file, of whom about one half have no other form of ophthalmic medical record.


A data retrieval system for the eye clinic. II. The programmed system.

The programmed system of a data retrieval system for the eye clinic is described. The system uses an IBM 370/168 computer, involves programmes to minimize the possibility of entering errors and a magnetic tape back-up system to reduce the cost of storing rarely required material and as a safeguard against the accidental erasion of material on disc.


Blur: a sufficient accommodative stimulus.

Experiments under a variety of open and closed loop feedback configurations demonstrate that accommodative responses to target blur are equivalent to those to defocus blur; this supports blur as the 'sufficient' neurological stimulus to accommodations. The hunting action of accommodation compensates for the even error aspect of blur and also adaptively minimizes any close loop error components while finally accepting open loop components.


Pseudoepidemics of heroin addiction.

Smooth unimodal skewed distributions, sometimes referred to as "epidemic-like" curves, are often used as evidence of time to time changes in incidence. Data on year of onset from groups of treated heroin addicts are generally alleged to reflect incidence, and this distribution is used to evaluate effectiveness and predict future needs. This paper describes the development of simple demographic models which demonstrate the production of epidemic-like curves without changes in incidence, ascertainment or duration of disorder. These graphic models are relevant to other non-infectious disorders where there is continuing exposure to the etiologic agents and where intervals between onset and ascertainment are not uniformly distributed.


The drunken driver: a psychosocial study.

A self-administered questionnaire was used to compare selected psychosocial variables of 306 convicted male drunk drivers with those of 294 alcoholics and 253 controls. The drunk driver group fell between the other groups on many parameters but resembled the alcoholic group on many others. While over 68% of the drunk drivers appeared to be alcoholics, in general they showed significantly less psychosocial incapacity than the alcoholic comparison group. The differences between the alcoholic and presumed non-alcoholic drunk drivers were not sufficient to clearly dichotomize the drunk driver group.


Alcohol use among black youths in a rural community.

The results of this study lead to the conclusion that the circumstances which surround the act of youth drinking in the black population of an abstinence setting are somewhat different from those recorded elsewhere. Although fewer students drink, the drinking styles reveal several dimensions frequently associated with alcohol abuse. As a rule, users do not have parental permission to drink and for the most part they identify with churches that condemn alcohol on moral grounds. Because many of the youth procure their beverages from illegal sources or in an illegal way, they tend to drink in a surreptitious manner in a setting absent of restraint. Consequently, a significant number of youths were drinking without normal propriety and were exhibiting several social complications as a result. This suggests that less drinking can be expected in abstinence settings but, among those young people who drink, problems may be more frequent. This is logical since the user is at variance with the normative prescriptions of the community, church and home. Obviously, drinking under these conditions may actually be an expression of a general test of the limits of the adult world or a symbol of rejection of adult standards. Subsequently, the abuse of alcohol may decrease with maturity. Regardless of their meaning, however, the findings do point to a need for education about alcohol at the school level.


Narcotic addiction in two Asian cultures: a comparison and analysis.

Our current knowledge regarding the effects of open access to narcotic drugs is limited. This study was undertaken to clarify issues regarding availability of these drugs. Two ethnic groups in Laos were compared: the Hmong (or Meo), a tribal group with access to opium in their homes; and the Lao, a peasant people with more limited access, usually in opium dens. Of 15 demographic and clinical variables studied, 10 showed significant differences between the two cultures. Eight of these 10 could be readily accounted for by differences in drug availability. Only two differences could be ascribed to socio-ecologic factors not related to drug availability. Similarities between the two groups appeared due to (1) pharmacologic effects of narcotic addiction and (2) low social opprobrium toward addiction in both cultures. In this study, open availability of narcotic drugs appeared to favor the following: a greater proportion of female addicts; younger age of opiate usage and addiction; use of the more intoxicating route of administration; earlier onset of problems related to addiction; and shorter duration of addiction before seeking treatment.


[Rubella immunization--immunity after 4 years (author's transl)].

The rubella antibody titres were evaluated in 158 girls who had been seronegative prior to immunization and had been immunised 4 years previously (1971) with the rubella vaccine HPV77DE5. In 138 girls (87%) the 1975 titres were unchanged in comparison with 1971. Only in 5 girls (3.2%) the titres had decreased by up to 2 log2 steps. In two patients the titre reached the critical value of 1:8 which must be considered negative due to the high sensitivity of the haemagglutination inhibition test. A titre increase by two or more steps was observed in 15 girls (9.5%). A third of the titre increases might be due to reinfection with rubella wild virus which would correspond to a reinfection rate of less than 1% per year. Present knowledge indicates that reinfection during pregnancy does not endanger the unborn child.


[The value of pneumocystography in diagnosis of breast tumours (author's transl)].

Pneumocystography was performed regularly in mammographically benign tumours. During 1974 and 1975 16892 breast were investigated radiographically of which 1031 had palpable tumours. In 614 cases the results of palpation correlated with radiography and indicated a cyst. These tumours were punctured with the aim of demonstrating the cyst wall by air filling and subsequent pneumocystography. This procedure enabled 4 out of 10 women (430 out of 1031) to avoid operation despite clinically palpable tumours. In 184 cases biopsy was necessary. In 12 cases the pneumocystogram showed tumours needing excision in addition to unremarkable cysts, in 11 cases the cyst walls showed radiological changes, 161 tumours were apparently solid. Since December 1975 we have started to aspirate breasts with radiographically suspected cysts in the absence of palpable tumour and to perform a pneumocystogram. This attempt was successful in all 19 cases. Removal of unremarkable cysts should not be accepted any longer. Prior to removal of a palpable tumour of the breast radiological investigated is indicated.


[Evaluation of treatment with hemineurine in delirium tremens].

The authors make a sum-up of all cases of delirium tremens admitted to the Lausanne University Psychiatric Clinic during the period 1970-1974. All were treated by intravenous and oral chlormethiazole (hemineurine), its technique being described. The need to restablish the fluid and electrolitic balance is stressed. Side effects are not important and there is a shortening of the acute phase, as compared to other techniques. Mortality is nil. The authors suggest that chlormethiazole is an indication of choice in the treatment of delirium tremens and are surprised that this substance has not yet taken its place in the U.S.A.


[Aphasia and artistic creation].

An artist active drawing and waterpainting, most prominent in sculpture, suffered an apopleptic insult at 66 years of age. Right hemiparesis and severe motor aphasia remained but this with rare unexpected and sometimes rather complicated productions in spoken, and also in written language in spite of modest progress in writing exercise. His behaviour witnessed of the memory of remote and complicated stored material. Some months after the insult he resumed his artistic activity using his left hand and continued it principally in the same manner as before his illness. His drawing and water-painting displayed some uncertainty of lines and sometimes coarseness of the stain spots. His pieces of sculpture regained the quality of his earlier works, as proven already by the first statue he made after the insult. While it is generally accepted that the motor aphasia does not essentially affect the artistic production, even of high quality, in painting, this is the first instance which proves that the same holds true for sculpture. In this case the mechanisms inciting the finest innervation on the side of the cortical center of the left hand, can work with promptness. In motor aphasia the mechanisms indispensable for the correct realisation of the function are affected without a final extinction of the function itself. Motor asphasia is an instrumental disorder not necessarily accompanied by disturbances of the intelligence.


[Repeated sessions of sleep deprivation in the treatment of depression].

30 depressed patients were submitted to repeated sessions of sleep deprivation. The results obtained in a previous study were confirmed: after 36 hours of wakefulness there is an important overall improvement, albeit followed by a partial or total relapse the second day after. There are no counter-indications, even for elderly subjects with psycho-organic symptoms.


Conversion of radiolabeled human growth hormone into higher molecular weight moieties in human plasma in vivo and in vitro.

Purified human growth hormone (hGH) was iodinated with 131I ([131I]iodo-hGH) and purified on Sephadex G-100. The monomeric [131I]iodo-hGH (mol wt about 20,000 daltons) was injected as a bolus iv in healthy volunteers and plasma obtained at 10, 20, and 40 min. Then continuous infusion with [131I]-iodo-hGH was started and further plasma samples obtained after 120 min when a plateau of immunoreactive hGH (IR-hGH) had been attained. In one individual the bolus injection was followed further to 60 and 120 min. Fresh plasma was immediately chromatographed on Sephadex G-100 and the IR-hGH profiles evaluated. In all instances following iv injection, larger and occasionally smaller immunoreactive moieties than the injected [131I]iodo-hGH appeared. When [131I]iodo-hGH was incubated at 37 C with fresh human plasma from 4 different individuals from 10 to 120 min, the larger molecular weight forms, noted in the in vivo studies, were again demonstrable. Only the monomeric [131I]iodo-hGH was found when [131I]iodo-hGH was incubated at 37 C for 120 min with human serum albumin or gamma globulin.


Insulin-like activities and insulin-potentiating actions of a modified insulin B21-26 fragment: beta-Ala-Arg-Gly-Phe-Phe-Tyr-NH2.

A modified sequence of insulin B21-26, beta-Ala-Arg-Gly-Phe-Phe-Tyr-NH2 (DP-432), was synthesized and tested for its biological activities. The hexapeptide, ip injected to mice, stimulated [U-14C]-glucose incorporation into diaphragm glycogen and adipose tissue total lipid. Neither plasma glucose nor FFA (free fatty acid) was reduced by the injection. However, when injected with epinephrine, the peptide prevented a rise of plasma FFA but not that of plasma glucose due to epinephrine. In vitro, the peptide stimulated glucose oxidation and inhibited epinephrine- or isoproterenol-stimulated lipolysis of mouse adipose tissue. Furthermore, when added along with insulin to incubation media, the peptide exaggerated the effects of insulin on both glucose oxidation and isoproterenol-stimulated lipolysis. The hexapeptide thus seems to have an insulin-potentiating action as well as insulin like activities on peripheral tissue.


Heterotransplantation of human fetal pituitaries in nude mice.

The heterotransplantation of minced human fetal pituitaries into adult thymus-aplastic nude mice is described. Development and growth of such grafts were observed in 16 of 21 recipient mice. Histological examinations of the transplants showed typical adenohypophyseal cells. Neurohypophyseal cells could never be detected. The levels of human growth hormone (hGH) varied between 0.8 and 42.0 ng/ml in the plasma of the hosts (mean value 7.2 ng/ml, by radioimmunoassay).


Renin and aldosterone in the cardiomyopathic hamster in congestive heart failure.

The renin-aldosterone system was studied in cardiomyopathic hamsters (CMH) before and after the onset of untreated clinical congestive heart failure. Age-matched random-bred hamsters (RB) served as controls. Before heart failure, there were no differences in body weight accretion, sodium balance, plasma renin activity or in vitro aldosterone production. After the onset of heart failure in CMH, body weight increased at a greater rate than in RB and positive sodium balance was nearly twice control levels. Although plasma renin activity was greater (P less than 0.005) in CMH than in RB (23.4+/-4.2 (mean+/-SEM) vs. 3.8+/-1.8 ng/ml/h), aldosterone production (101+/-15 vs. 95+/-16 ng/h) did not differ. Plasma aldosterone was low or undetectable in RB and in CMH in heart failure. In response to angiotensin stimulation, aldosterone production increased in both strains and did not differ. No difference in muscle potassium content, potassium balance or excretion was detected. Thus, in CMH, congestive heart failure is attended by increased plasma renin activity without a significant increase in aldosterone production, a dissociation which does not appear to be due to adrenal unresponsiveness to angiotensin II or to potassium depletion.


The metabolic clearance rate, the brain extraction and distribution and the uterine extraction and retention of progesterone and R 5020 in estrogen-treated ovariectomized rabbits.

The metabolic clearance rate (MCR), uterine extraction, uterine retention and brain distribution of the synthetic progestin R 5020 and progesterone were studied in estrogen-treated ovariectomized rabbits. The MCR of R 5020 was 163+/-15 (SE) 1/day and was lower than that of progesterone. The uterine extraction of R 5020 (51.4+/-3.9 (SE)%) was greater than that of progesterone (33.7+/-7.7%) as was the uterine tissue:arterial blood ratio (28.1+/-4 vs. 7.3). The brain and pituitary retention and distribution of R 5020 and progesterone were the same and provided no evidence for a selective accumulation of a progestin in the pituitary or hypothalamus.


Evidence for androgen participation in induced ovulation in immature rats.

Rabbit antiserum to testosterone injected intravenously (iv) together with 10 IU human chorionic gonadotropin (hCG) markedly reduced the number of tubal ova in intact or hypophysectomized immature rats primed with 5 IU pregnant mare's serum gonadotropin. Normal rabbit serum (NRS) injected instead of the antiserum resulted in a normal complement of ovulated ova. Ten microgram of testosterone or 5alpha-dihydrotestosterone dissolved in NRS administered iv 1 h after simultaneous injection of hCG and antiserum to progesterone (anti-P) restored ovulation that would otherwise have been blocked by anti-P, with a comparable number of ova to control animals not given anti-P. The results indicate active participation of androgen in induced ovulation in immature rats.


Estrogen hormones and lipid metabolism. Effect of ethynyl-estradiol on liver lipases.

Lipase activities assayed in liver subcellular fractions from rats given ethynyl-estradiol are lowered, while triglycerides increase and cholesterol decreases in blood. Triester lipase in microsomes is the most altered activity. Such enzymatic changes might play a role in the development of lipid abnormalities in blood of women taking estrogens as oral contraceptives.


Carbon-14 tracer studies in rat-liver perfusion experiments under conditions of gluconeogenesis from lactate and pyruvate.

The intracellular events in the metabolic pathway of gluconeogenesis from lactate and pyruvate in liver tissue were assumed to be understood. Nevertheless the results of several 14C-tracer experiments gave rise to the postulation of still unknown intracellular interactions under this condition. We have tried to contribute to the solution of this problem by using different 14C labeled tracers such as [1-14C]lactate or pyruvate and [2-14C]lactate or pyruvate, [14C]bicarbonate and [1-14C]octanoate in perfusion experiments with livers from rats under conditions of gluconeogenesis from lactate and pyruvate. The 14C labeling patterns of intracellular metabolites as malate, citrate, phosphoenolpyruvate, phosphoglycerate and newly synthesized glucose were analysed under different conditions. A comparison with values calculated by using metabolic models, based on the generally accepted concepts of intracellular interactions, showed some fundamental discrepancies, which justify the postulation of still unknown intracellular interactions in the pathway of gluconeogenesis from lactate and pyruvate.


Carbon-14 tracer studies in the metabolism of isolated rat-liver parenchymal cells under conditions of gluconeogenesis from lactate and pyruvate.

In rat liver perfusion experiments under conditions of gluconeogenesis from lactate and pyruvate 14C-labeling patterns of metabolites with (1-14C)-labeled and (2-14C)-labeled lactate or pyruvate, [14C]bicarbonate and [1-14C]octanoate as tracers, have been obtained, which do not agree with generally assumed reaction schemes. The experiments have been repeated with incubations of isolated rat-liver parenchymal cells. The results demonstrate that the discrepancies between expected and analysed 14C-labeling patterns of metabolites were still existent. From this observation it may be concluded, that 14C-labeling patterns of metabolites are indicative for the existence of still unknown metabolic relationships in liver parenchymal cells. Furthermore the results of our experiments prove that conclusions based on the exclusive analysis of metabolite levels are of limited value for studying intracellular events, because of uncharacterized compartmentations, which become evident in 14C-tracer studies. It cannot be answered by our studies, whether the apparent existence of differently labeled species of citrate, oxoglutarate or acetyl-CoA, represent intracellular compartmentation or whether it is the result of metabolic heterogeneity of liver parenchymal cells.


The nature of DNA synthesized in nuclei from mouse L1210 cells.

A DNA-synthesizing system in vitro from mouse L1210 cell nuclei is described. A high proportion of the DNA synthesized by the L1210 nuclei in vitro appeared to be covalently linked complementary DNA. DNA synthesis by L1210 nuclei was not inhibited by the anti-leukaemia compound 4'-9-acridinylamino)-methansulphon-m-anisidine, although this drug binds to isolated DNA and is active against L1210 leukaemia.


A deoxyribonuclease from Chlamydomonas reinhardii. 2. Substrate specificity, mode of action and products.

A deoxyribonuclease purified Chlamydomonas reinhardii has been shown to be specific for single-stranded DNA. The enzyme is most active on thermally denatured DNA, but also degrades single-stranded termini from double-stranded DNA. The enzyme has no effect on single-stranded or double-stranded intact circular phiX174DNA, suggesting that it requires DNA termini for activity. DNA is digested progressively to oligonucleotides and then mononucleotides. The product of the reaction is nucleoside 5'-monophosphates. The enzyme has no effect on RNA, nor does it possess phosphatase or phosphodiesterase activity. No specificity was demonstrated for phosphate or hydroxyl groups at either the 5' or 3' termini of DNA. The enzyme may be able to initiate hydrolysis at either the 3' or the 5' termini, since radioactivity was released more rapidly from 5' and 3' termini than from bulk DNA. The enzyme has been tentatively named Chlamydomonas reinhardii exonuclease 1.


Urea as a selective inhibitor of argininosuccinate lyase.

The effect of urea on various ornithine cycle enzymes has been investigated. It was demonstrated that argininosuccinate lyase was the only ornithine cycle enzyme inhibited by urea in a competitive manner. Based on the data presented the possible role of urea in maintaining a physiological range of intracellular and extracellular urea concentration by controlling hepatic ureogenesis was discussed.


Initiation of protein synthesis in eukaryotes. Binding to Sepharose-heparin and partial purification of initiation factors from Krebs II ascites cells.

By means of affinity chromatography of lysates from Krebs II ascites cells and rabbit reticulocytes on Sepharose-heparin an active fraction of initiation factors has been obtained. The fraction is eluted from the column at 350 mM KCl using a linear gradient and displays a number of activities, i.e. binding of Met-tRNAfMet to form a ternary complex with GTP; transferring this complex to 40-S subunits in an A-U-G-independent step and finally coupling of the 40-S initiation complex to the 60-S subunit, a reaction which is completely A-U-G-dependent. Moreover, MettRNA is bound into the P-site as is indicated by its puromycin sensitivity. The method is very suitable for large-scale preparation. Further purification and characterization of the factors have been carried out on DEAE-cellulose and phosphocellulose columns. Evidence is presented that the polysomes present in a lysate that has been passed through the Sepharose-heparin column can only complete their nascent chains, initiation of new polypeptides is completely dependent on addition of initiation factors.


Tissue limited mosaicism for unbalanced autosomal translocation in a child with congenital anomalies and mental retardation.

We studied a patient with a sporadic mental retardation/multiple congenital anomalies syndrome. Chromosome analysis showed a 46,XX, inv(9)(p 11;q13) karyotype in all lymphocytes. Fibroblasts from two separate skin biopsies revealed a mosaic karyotype. Some 22.5% of fibroblasts had a karyotype like that of the lymphocytes, while 77.5% of fibroblasts had a karyotype 46,XX,inv(9)(p11;q13),der(12),t(12;?)(P13;?). The data in this case emphasize the drawbacks of confining cytogenetic analysis to lymphocytes.


The characteristics of amylase activity and the isoamylase pattern in serum and urine of infants and children.

Determination of amylase activity and isoamylase patterns were performed in serum and urine of normal newborns, infants and children of different ages. In the serum of newborn infants measurable amounts of amylase were present. The activity increased with the age and reached the normal adult level by approximately 8 months of age. Isoamylase analysis revealed that the low level of serum amylase in infants was mainly due to deficiency of the pancreatic-type isoamylase. The absence of the pancreatic isoamylase in newborns and young infants is a physiological and developmental phenomenon. Great caution is therefore necessary when amylase isoenzymes are used in the diagnosis of abnormal pancreatic function and such results have always to be interpreted in relation to the age of the child.


Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies, newborns and young infants.

Administration of low and high molecular weight dextrans in the initial phase of shock is no longer controversial. The special conditions in newborns, however, have been insufficiently considered in planning therapy. This investigation aimed at determining the biological half-lives of dextran 40 (Rheomacrodex) and dextran 60 (Macrodex) in this age group. The half-life of dextran 40 was found to be 60 min and that of dextran 60 3 h. Preterm babies and newborns excrete up to 25% less dextran 40 and 60 in 24 h than infants and adults. Normal adult values for excretion are only reached towards the end of the first year of life.


The effects of oral alanine administration on blood glucose, pyruvate, lactate, serum glucagon and insulin in human newborns.

Alanine (500 mg/kg body weight) was given orally to 27 healthy full term newborn infants, and the changes in blood glucose, pyruvate, lactate, alanine, glucagon and insulin were determined. Significant increments in blood glucose were found in 15 infants with blood glucose levels below 60 mg/100 ml, 4 of whom showed significant elevation of serum glucagon levels on day 1. This observation suggests that hepatic gluconeogenesis is possible immediately after birth.


Mechanism of diet-induced uraemia and acidosis in infants.

Five patients aged between 40 and 70 days were admitted to our Clinic with an initial diagnosis of "renal failure", but the high levels of urea nitrogen, metabolic acidosis and oliguria were found to be related to a high renal solute load and to the very high protein and electrolyte content of the diet. By calculating urinary output (V/m'), clearance of osmotically-active substances (COsm), clearance of free water (CH2O), maximum tubular reabsorption of water (TcH2O) and the change in metabolic H+ production, it has been possible to demonstrate that dietary protein and electrolytes were both responsible for the high blood urea nitrogen levels and metabolic acidosis.


3,3',5'-Triiodothyronine (Reverse T3) in amniotic fluid and cord serum.

3,3',5'-triiodothyronine (reverse T3, rT3) was measured in 122 samples of amniotic fluid obtained between the 29th--40th weeks of gestation, and in the blood of 37 newborn and their mothers. The mean rT3 concentration in amniotic fluid was 0.769 +/- 0.47 ng/ml, with a slight decrease from the 29th--40th weeks of gestation which was not statistically significant. Because of the great scatter of rT3 concentrations in amniotic fluid, its estimation does not seem to be useful in prenatal diagnosis of hypothyroidism. The mean rT3 concentration in cord blood (2.62 ng/ml; range 1.4--4.9 ng/ml) was greatly elevated in comparison to the mean maternal level at delivery (0.34 ng/ml; range 0.08--0.69 ng/ml). The possible use of rT3 measurements in cord blood as a screening test for congenital hypothyroidism is discussed.


Congenital sinus bradycardia combined with congenital total atrioventricular block.

Sinus bradycardia and total atrioventricular block were found at the age of seven months in a boy who is now 16 1/2 years old. According to Yaters (1929) criteria, these are likely to be congenital disorders. While the frequency of the ventricular impulse generator in the upper bundle of His only slowed in accordance with age during the period of observation, the sinus node activity deteriorated considerably. Finally potentials could only be sporadically demonstrated. Under heavy stress and with a simultaneous slight increase in ventricular frequency, a re-occurence of regular but slow sinus node activity came about. The cause of this binodal disorder of rhythm is unknown. There is no indication of family affliction or of myocarditis in early childhood. Congenital heart disease could also be excluded.


The effect of aging on synaptosomal Ca2+ transport in the brain.

The effect of aging on Ca2+ -transport in synaptosomal preparations from rat brains was assessed by measuring the accumulation of radioactive 45Ca within these particles. Four groups of rats at 6, 12 24 and 30 months of age were used for this study. Synaptosomal particles were isolated from the cerebral cortex of each animal and the radioactive 45Ca inside the particles were measured after incubating the particles with media containing an energy source and 45Ca Cl2. Results indicated that the transport of 45Ca was lower in the younger rats than the older groups. A 20% increase was consistent with the old rats (30 mo) as compared with the young ones (6 mo). The increase in Ca2+ -transport across synaptic plasma membranes may be related to the transmitter release and behavioral activity after senescence.


Age-related decline in receptivity in normal, neonatally androgenized female and male hamsters.

The pattern of female sexual behavior shown by aging male and female hamsters was related to exposure to perinatal androgen. Twenty-five female and 37 male hamsters in Experiment 1 was gonadectomized on the day of birth or at 43 days of age. The received 11 tests for receptivity between the ages of 28 and 66 wk. In Experiment 2, 83 females were implanted with a Silastic pellet containing 3, 1, 3 or 9% testosterone (T) or testosterone propionate (TP) by weight from the second to the tenth day of life, and tested approximately every 2 wk from 22 to 58 wk of age. Receptivity was induced by estradiol benzoate and progesterone injected before each 600 sec mating test. Normal females exhibited the highest lordosis scores, followed by minimally androgenized females and males castrated at birth. High doses of exogenous or endogenous perinatal T suppressed receptivity throughout the animal's lifespan, but did not accelerate the rate of decline in female behavior over time. Non-androgenized animals showed the greatest decrease in receptivity with advanced age.


Behavior of immature and middle-aged mice as a function of dietary protein.

The differential effects of continued maintenance on a 12% vs. 24% protein diet were examined in immature and middle-aged male and female C57BL/6J mice. Exploratory behavior, body weight and fluid consumption of water, saccharin and quinine were monitored over 9 weeks of presentation of the special diets. No rehabilitation datawere obtained. The dietary manipulations differentially effected the various groups, but the pattern of change in behavior was a function of the age and sex of the subject and the specific measure employed.


Determinants of anagram problem solution in adulthood.

An evaluation of the indices proposed in the literature regarding measures of anagram difficulty was made by asking three groups (ages 17-26, 39-51, 59-76) of adults (n = 54) to solve a list of 30 anagrams. Results indicated that only two of these indices (Thorndike-Lorge and Bigram Rank measures) significantly predicted frequency of solution in samples beyong college age. It was also found that the cognitive variable mediating the effects of these indices in middle aged and elderly subjects was crystallized ability, suggesting an experiential basis for the effects of both task and organismic variables as determinants of anagram problem solving in adulthood. The role of fluid ability as a mediator of problem solution in the young received limited support.


Sex differences in serial learning for aged persons with high verbal ability.

Serial rote learning was examined in men and women with high verbal ability aged 60-74 years. No sex differences were found in total errors, commission errors, or omissions errors. The results are in accord with the findings reported in a study by Wilkie and Eisdorfer (1977) and suggest that high verval ability may, in part, mediate sex differences in serial learning.


Aging, and crosslinking in mammlian collagen.

The amount and type of borohydride-reducible crosslinks in collagen have been examined as a function of animal age. In a variety of bovine, canine and human tissues the level of redicible crosslinks decreases with time and the ratios of individual compounds change. There is both tissue and species specificity in the extent of these changes. A decrease in the level of reducible crosslinks correlates with the cessation of growth. Loss of reducible crosslinks does not imply a small total number of crosslinks since physical changes with age imply the opposite. We conclude that reducible crosslinks are converted to a stable nonreducible state and the persistence of low levels of reducible crosslinks may be indicative of a low level of turnover in the tissue. Changes in ratios of reducible crosslinks are of doubtful functioal significance and may simply reflect variation in post-translational modification of lysine residues.


The effect of metiamide in in vitro and in vivo canine models of type I hypersensitivity reactions.

The histamine H2-receptor antagonist metiamide was evaluated in in vitro and in vivo canine models of immediate-type hypersensitivity reactions. At concentrations of 2 and 4 X 10(-4) M, the antagonist significantly increased the amount of histamine present in the medium surrounding passively sensitized canine lung fragments which had been challenged with ascaris antigen. In contrast, the compound was without effect on the release of a slow reacting substance of anaphylaxis. On the basis of these observations metiamide was investigated in an in vivo canine model of allergic asthma. At doses of 10, 30 and 50 mu moles/kg, the antagonist did not enhance the ascaris antigen-induced pulmonary pathophysiology. Similarly, at 10 and 50 mu moles/kg metiamide did not alter histamine-induced increases in pulmonary resistance or decreases in dynamic lung compliance. Insofar as the canine model of allergic asthma may be predictive of the human disease, it could be anticipated that the use of histamine H2-receptor antagonists may not be deleterious to allergic asthmatics.


Interactions of substance P with putative mediators of inflammation and ATP.

Substance P has recently been localized in sensory nerves and has been suggested to be the mediator of antidromic vasodilatation. Interactions of substance P with putative mediators of inflammation and adenosine 5'-triphosphate were studied in rats using a quantitative Evans blue dye-leakage technique. Rats anaesthetized with either were given Evans blue. i.v. and intracutaneous injections of inflammatory agents were given into the shaved abdominal skin. Doses of substance P, 1-5 X 10(-10) mol, produced graded dye leakage. A low dose of substance P (5 X 10(-11) mol) potentiated responses to 5-hydroxytryptamine (2.5 X 10(-10) mol), bradykinin (5 X 10(-10) mol), prostaglandin E1 (5 X 10(-10) mol) and adenosine 5'-triphosphate (2.5 X 10(-7) mol) but no histamine (2 X 10(-8) mol). A higher dose of substance P (5 X 10(-10) mol) was potentiated by prostaglandin E1 (5 X 10(-11) mol) and adenosine 5'triphosphate (5 X 10(-9) mol) but but not by histamine (5 X 10(-10) mol) or bradykinin (5 X 10(-11 mol) and was inhibited by 5-hydroxytryptamine (5 X 10(-12) mol). If substance P is released from sensory nerves in some inflammatory states these interactions might be of importance in determining the response observed.


Amphetamine discrimination as a test for anti-parkinsonism drugs.

Rats were trained and tested on a two-lever discrimination task based upon the presence or absence of 0.8 mg/kg d-amphetamine. After 80% criterion performance was attained, dopaminergic drugs reported to be effective in the treatment of Parkinson's disease were tested to investigate their ability to produce d-amphetamine-like responding. Amantidine (50 mg/kg), apomorphine (2.5 mg/kg), n-propylnoraporphine (0.1, 0.2 and 1.0 mg/kg), and piribedil (25 mg/kg) were all observed to produce d-amphetamine-appropriate responding. These results indicate that discriminative behavior controlled by d-amphetamine is mediated by central dopaminergic systems and the use of this technique in the evaluation of potential anti-Parkinsonism drugs is discussed.


Central serotonin-like activity of 6-chloro-2-[1-piperazinyl]-pyrazine (CPP; MK-212).

CPP, administered systemically, elicited four distinct responses characteristic of serotonin-receptor activation in the central nervous system. The crossed extensor reflex in the acutely spinalized rat was enhanced by treatment with CPP, 1-16 mg/kg. CPP, 1.11-10 mg/kg, elicited a dose-related increase in head twitches in mice. A complex motor syndrome in rats similar to that produced by pargyline plus tryptophan (or other treatments effecting increased activation of central serotonin receptors) was produced by 1.25-5 mg/kg of CPP. An increase in twitch frequency of the mylohyoideus muscle in the urethane anesthetized rat occured after CPP at 0.1 mg/kg or less. Complete abolition of all four effects of CPP was achieved by pretreatment with the centrally acting indoleamine antagonist methergoline. The peripherally acting serotonin antagonist xylamidine was ineffective or only weakly active, depending upon the test procedure, in preventing the serotonin-like actions of CPP. These findings indicate that CPP has a serotoninmimetic action in the central nervous system.


Delayed appearance of propranolol sensitivity in cultured heart cells.

Examination of the appearance of adrenaline responsiveness and propranolol sensitivity with culture age in myoblasts cultured from neonatal rat hearts shows that propranolol sensitivity lags behind adrenergic responsiveness. Such a finding may illustrate subtle differences in sites for agonist and antagonist at the beta-receptor of these cells.


Radioimmunological determination of thromboxane release in cardiac anaphylaxis.

A sensitive and specific radioimmunoassay for thromboxane B2 were detected in perfusates of anaphylactic guinea pig hearts. Indomethacin decreased thromboxane B2 levels in the perfusates to below the detection limit of the radioimmunoassay and concomitantly delayed the onset of coronary vasoconstriction after antigenic challenge.