Structural changes associated with parotid "degeneration secretion" after post-ganglionic sympathectomy in rats.

Parotid glands of rat have been examined 12, 24 and 48 hours after avulsion of the cervical sympathetic ganglion and compared with normally innervated left glands. Formaldehyde-induced fluorescence showed a relatively normal complement of adrenergic nerves at 12 hours but most of the nerves had lost their noradrenaline content by 24 hours and no fluorescent nerves were detected at 48 hours. Ultrastructural degenerative changes in axons were rare at 12 hours, common at 24 hours, and the degenerating axons appeared to have disappeared by 48 hours. The glands looked whitish and pale and similar to the controls at 12 and 48 hours but were pinkish and oedematous on the sympathectomised side at 24 hours. Correspondingly the acini were loaded with secretory granules at 12 and 48 hours but were extensively depleted of granules at 24 hours. This loss of granules is considered to be due to sympathetic "degeneration secretion" caused by the release of noradrenaline from the degenerating adrenergic nerves between 12 and 24 hours after ganglionectomy. This is thought to be the first example of morphological change resulting from "degeneration activation" to be recorded microscopically.


Electron microscopic observations on the castration-induced X zone in the adrenal cortex of male mice.

The secondary X zone induced by castration in the adrenal cortex of adult male mice was examined by electron microscopy and radioautography with 3H-thymidine. 10-15 days after castration a thin layer of small eosinophilic cells is formed in the inner-most cortex. Such eosinophilic cells contain irregulary shaped nuclei and spherical or ellipsoidal mitochondria with tubulolamellar cristae, 20-25 days after castration a prominent zone of small eosinophilic cells was clearly identified as the secondary X zone. The typical secondary X zone cells were characterized by the formation of peculiar mitochondrial complexes and whorled sER. The X zone cells with their characteristic organelles incorporated 3H-thymidine. The ultrastructure and formation of the secondary X zone were very similar to those of the primary X zone which appears during normal postnatal development. We demonstrate here the capacity of reticularis cells of adult male mice to transform into typical X zone cells following castration.


The mandibular organ of the lobster, Homarus americanus.

The lobster mandibular organ is well vascularized and its polygonal cells are arranged loosely around blood vessels and blood sinuses. Numerous mitochondria and microbodies (peroxisomes) give the acidophilic cytoplasm a finely granular appearance, but there is no evidence of secretory granules. The abundant endoplasmic reticulum is almost entirely agranular and occurs in two morphologically distinct forms: tubular and cisternal. The tubular reticulum is randomly distributed and may represent the site of synthesis and transport of the mandibular organ product. The cisternal reticulum is frequently associated with microbodies. Both forms of endoplasmic reticulum proliferate during mid to late premolt. Mandibular organ ultrastructure closely resembles that of cells known to synthesize steroids or lipids, which suggests that this organ may have a similar function. There is no functional evidence of involvement in molt control in Homarus, but ultrastructural and other evidence suggests an analogy with insect corpus allatum.


Structural specialization in the dorsal retina of the bee, Apis mellifera.

Electron microscopic investigations on the eye of the worker bee showed that the ommatidia located in the uppermost part of the dorsal half of the eye are characterized by a distinct structural specialization: Nine visual cells contribute microvilli to the rhabdom over its full length. Within these rhabdoms the microvilli are arranged in at least three different directions. This specialization affects an area of at least 60 ommatidia. The most dorsal eye region differs, therefore, structurally from all other regions which have been investigated to date. Because the ommatidia in question are oriented skyward, their peculiar structure is discussed with respect to several concepts of polarized light detection by the bee.


Myelin formation in cultures of previously dissociated mouse spinal cord.

Myelin formation in cultures of previously dissociated spinal cord from foetal mice is described. In addition to the expected pattern of myelination, in which axons are closely wrapped by myelin lamellae, redundant folds of myelin have been found, as have double sheaths surrounding a single axon. Hypotheses concerning the generation of these appearances are discussed. It is suggested that certain intracytoplasmic laminar bodies found in oligodendrocytes in vitro may be of mitochondrial origin.


Mercury inhibition of fatty acid synthesis in chicks.

Male chicks were fed a commercial ration and were given drinking water which contained 0, 50, 100, 150, 200 or 300 mug of mercury/ml as mercuric chloride from hatching to 3 weeks of age. In one experiment, the mercuric chloride was administered by injection into the abdominal cavity rather than in the drinking water. At 3 weeks the chicks were killed, and the livers were removed and weighed. The activity of fatty acid synthetase in the 800 X gav supernatant fractions of the liver homogenates and in vivo incorporation of [14C]acetate into liver and carcass fatty acids and respiratory 14CO2 was determined as indicated. Administration of mercury at a treatment level of 300 mug/ml of drinking water depressed growth, feed and water consumption, liver weight, hepatic fatty acid synthetase activity, and in vivo incorporation of [14C]acetate into liver and carcass fatty acids, and increased the production of respiratory 14CO2 as compared with controls. In experiments in which graded doses of mercury were administered, body weights, liver weights, and feed and water intakes of the chicks receiving 0, 50 and 100 mug of mercury/ml of drinking water were similar to each other, but these parameters were severely depressed by 200 mug of mercury/ml of drinking water. Mercury caused a dose-related decrease of fatty acid synthetase activity. Incorporation of [14C]acetate into carcass fatty acid was depressed by 50 and 200 mug of mercury/ml of drinking water; incorporation into liver fatty acids and production of respiratory 14CO2 was not affected by mercury. Intra-abdominal injection of 6 mg of mercury/100 g body weight (as mercuric chloride) into well alimented chicks depressed hepatic fatty acid synthetase activity at 1 h post-injection. The data are consistent with the hypothesis that a portion of the effects of mercury on fatty acid synthesis are direct rather than a secondary effect of inanition.


Replication of hepatic DNA in rats treated with dimethylnitrosamine.

Replication of DNA containing unrepaired lesions such as depurinated sites, single-strand breaks or methylated bases such as O-6 and N-7 methylguanine was studied in the rat liver. Rat liver DNA was damaged by administering 10 mug dimethylnitrosamine (DMN)/g body wt i.p. 4 h prior to partial hepatectomy. The analysis of DNA on alkaline sucrose gradient revealed considerable damage to the parental strand at the time of and 48 h subsequent to partial hepatectomy. During this time interval, the synthesis of new strands was studied using labeled thymidine. In the control liver, radioactivity in DNA appeared as small fragments at 15 and 30 min following the administration of labeled thymidine which became bigger within 4 h. In the carcinogen-treated livers, the newly made DNA remained as small fragments for longer periods of time. Sometime between 4 and 24 h these became bigger in size than the parental damaged template DNA. Thus, with a delay, the newly made strands became eventually bigger, in spite of the fact that the parental template DNA strand was damaged. Such replication of DNA with unrepaired lesions (miscoding and/or non-coding) offers a mechanism by which the original damage to DNA caused by the carcinogen can be permanently imprinted on the newly made cell, a phenomenon that could account for the initiation of carcinogenesis under certain circumstances.


Effect of plumbous ion on messenger RNA.

The effects of Pb2+, a potent catalyst for the depolymerization of RNA have been studied on brome mosaic virus (BMV) RNA, rabbit globin m-RNA and polyuridylic acid. After exposure of these natural and synthetic messengers to a sufficiently high concentration of Pb2+, they all lost their ability to stimulate amino acid incorporation in cell-free protein-synthesizing systems. There were differences in the susceptibilities of the messengers; gloing the m-RNA for 40 min revealed that there was a threshold Pb2+ concentration below which no loss of m-RNA activity was observed. The threshold concentration was considerably greater than the Pb2+ concentration at which protein synthesis is inhibited in reticulocytes and overt symptoms of plumbism are observed. However, when m-RNA were incubated for an extended period (24 h), even with sub-threshold concentrations of Pb2+, there was destruction of messenger function and globin m-RNA was more susceptible than BMV-RNA. Also the susceptibility of m-RNA to Pb2+ is temperature-dependent, which would indicate that m-RNA, like t-RNA, exists as a population of molecules in different conformational states that are not readily interconvertible.


The binding of [3H]chlorambucil to nuclear proteins of the Yoshida ascites sarcoma.

The binding of [3H]chlorambucil to nuclear proteins, extracted from Yoshida ascites sarcoma cells at 6 h and 24 h after administration of 3H-labelled drug to tumour-bearing animals, has been examined. Both covalent and non-covalent binding was detected. Considerably more drug was found associated with the proteins isolated from the tumour sensitive to the effects of the drug compared with similar proteins isolated from the tumour with an acquired resistance to the effects of alkylating agents. The two-fold difference in binding to total cell protein is attributed to a higher intranuclear protein binding in sensitive cells. In particular the soluble nuclear sap fraction from sensitive cells bound at least five times as much drug as the corresponding fraction from resistant cells. Low levels of binding to histones were demonstrated compared with that to the non-histone chromatin proteins. Binding to the nuclear sap and non-histone chromatin proteins was principally to high molecular weight protein species; these did not appear to represent aggregation products as scans of stained polyacrylamide gels of the extracted protein fractions were unaltered by the treatment of tumour-bearing animals with chlorambucil. Binding to the nuclear proteins from sensitive cells tended to persist over a 24-h period, whereas it was considerably reduced in resistant cells.


Cholesterol autoxidation: identification of the volatile fragments.

The volatile fragments of air-aged cholesterol were analysed by means of gas chromatography-mass spectrometry; The following fourteen compounds were identified: ethanol, acetic acid, acetone, 2-methylpropene, 2-methyl-1-propanol, 2-methyl-2-propanol, 2-butanone, 2-methylpropionic acid, 2-methyl-2-butanol, 2-pentanone, 3-methyl-2-butanone, 2-methyl-1-pentene, 2-methyl-2-pentanol, and 2-methyl-4-penten-2-ol. Their formation via decomposition of initially formed sterol hydroperoxides is discussed.


13C nuclear magnetic resonance spectra of 1,2-dioctadec-cis-enoyl-sn-glycero-3-phosphorylcholines.

The 13C NMR spectra of all sixteen 1,2-dioctade-cis-enoyl-sn-glycero-3-phosphorylcholines have been obtained. Resonance lines of the olefinic, methylene, methyl and carboxyl carbon nuclei are sufficiently characteristic to permit unequivocal designation of double bond position for each isomer. Two resonances of the sn-glycero-3-phosphorylcholine structure have been reassigned.


Observations on patients with primary ventricular fibrillation complicating acute myocardial infarction.

In order to evaluate the events preceding primary ventricular fibrillation (PVF), continuous tape recording was performed in 262 patients consecutively admitted to the hospital within six hours of infarction in whom antiarrhythmic therapy was withheld. Warning arrhythmias (defined as ventricular ectopic beats occurring with a frequency of more than five beats per minute, in runs, falling in the vulnerable phase of the cardiac cycle or being multiformed) were registered in an equal percentage in patients who did or did not develop PVF. Immediately prior to PVF seven patients showed sinus tachycardia, 10 a sinus rate ranging from 60 to 100 beats per minute and two bradycardia due to complete atrioventricular block. The ventricular ectopic beat initiating PVF had a late coupling interval (QR'/QT larger than or equal to 0.85) in 11 patients and a left bundle branch block configuration as frequent as a right bundle branch block. 1) Warning arrhythmias are not considered good criteria for institution of antiarrhythmic therapy in order to prevent PVF. 2) In patients with sinus rhythm there may be an association between heart rate and onset of PVF. 3) The malignancy of a ventricular ectopic beat is not determined by its coupling interval or its configuration.


Electrophysiologic effects of coronary occlusion and reperfusion. Observations of dispersion of refractoriness and ventricular automaticity.

In order to determine the electrophysiological changes that occur during coronary occlusion and following reperfusion, 19 mongrel dogs were studied. Refractory periods were determined by the extrastimulus method in nonischemic and ischemic zones prior to and after variable periods of left anterior descending artery occlusion and reperfusion. After 15-30 minutes of occlusion, refractory periods in the nonischemic zones remained unchanged while in the ischemic zone they shortened by 17%, resulting in a dispersion of refractoriness. Within three minutes of reperfusion, arrhythmias appeared together with a marked directional change of refractory periods to a prolongation by 34% (P less than 0.001) in the ischemic zone and by 3% (P less than 0.02) in the nonischemic zone. Refractory periods returned to baseline values after 60 minutes of reperfusion. After 60-90 minutes of occlusion, refractory periods in the nonischemic zones were unchanged whereas in the ischemic zone they demonstrated a decrease by 28% (P less than 0.01), again resulting in a dispersion of refractoriness. Within five minutes of reperfusion, refractory periods in the ischemic zone prolonged by 44% (P less than 0.001). Similar but smaller directional changes were also seen in nonischemic zones. Concomitant with the observed prolongation in refractory periods frequent ventricular ectopic activity was again documented. In addition, refractory periods did not return to control values after periods of observation up to 120 minutes in this group. In seven dogs, complete heart block was induced to ascertain the rate of idioventricular pacemaker and the effect of ventricular overdrive on the escape interval. Control ventricular rates (53.3 +/- 5.7 beats/min) remained unchanged (52.3 +/- 5.6) following coronary occlusion, but decreased to 48.0 +/- 4.4 (P less than 0.05) during reperfusion. Mean control escape intervals (1.8 +/- 0.2 sec) did not change after occlusion (1.7 +/- 0.2 sec) but prolonged to 2.1 +/- 0.2 sec (P less than 0.05) following reperfusion. 1) sudden prolongation in refractory periods following reperfusion leads to an overshoot resulting in a dispersion of refractoriness temporally related to the onset of ventricular arrhythmias and 2) re-entry, and not enhanced automaticity, appears to be the mechanism for postperfusion arrhythmias.


A comparative analysis of antegrade and retrograde conduction patterns in man.

Patterns of antegrade and retrograde conduction and refractory periods were studied using His bundle electrogram recordings, incremental atrial and ventricular pacing and the extrastimulus technique. In 36/50 patients antegrade conduction was "better" than retrograde conduction (group I), as evidenced by a) onset of retrograde atrioventricular (A-V) nodal Wenckebach phenomenon at a slower rate compared to the antegrade counterpart (25 patients: group IA) or b) no ventriculo-atrial conduction at all ventricular paced rates (11 pts: group IB). The site of retrograde block in group IB patients was the A-V node. In eight patients (group II), antegrade and retrograde conduction appeared to be equal up to maximum paced rates of 160 beats/min. In six patients (group III) retrograde conduction was "better" than antegrade conduction, as indicated by onset of antegrade A-V nodal Wenckebach periods at slower rates than retrograde Wenckebach periods. During antegrade refractory period studies the area of maximum refractoriness was the A-V node in 19/40 patients, the His-Purkinje system (HPS) 6/40, and the atrial muscle in 15/40. During retrograde refractory period studies the A-V node was the area of maximum refractoriness in 12/36 pts (4/40 patients had A-V dissociation during ventricular pacing), the HPS in 12/36, and the ventricular muscle in 10/36. In 2/36 patients the site of maximum refractoriness retrogradely could not be determined: The area of maximum refractoriness during both antegrade and retrograde refractory period studies was the same in 11 patients (A-V node in seve and HPS in four), was different (i.e., A-V node or HPS) in 18 patients, and was the artrial or ventricular muscle in six patients. In five patients, including four patients in whom V-A conduction failed to occur, the above comparisons were not made. It is concluded that 1) antegrade conduction is better than retrograde conduction in most patients; 2) it is not always possible to predict area of maximum refractoriness during premature stimulation (both atrium and ventricle) from observations made during incremental pacing; 3) it is equally difficult to extrapolate patterns of retrograde conduction and refractory periods from results of antegrade conduction and refractory period studies.


Demonstration of dual atrioventricular nodal pathways utilizing a ventricular extrastimulus in patients with atrioventricular nodal re-entrant paroxysmal supraventricular tachycardia.

In patients with atrioventricular (A-V) nodal re-entrant paroxysmal supraventricular tachycardia (PSVT), atrial extrastimulus technique frequently reveals discontinuous A1-A2, H1-H2 curves suggestive of dual A-V nodal pathways. To further test the hypothesis that these curves in fact reflect dual A-V nodal pathways, a ventricular extrastimulus (VS) was coupled either to A2 at a fixed A1-A2 interval which reliably produced an A-V nodal re-entrant atrial echo (E) with a constant A2-E interval in two patients, or to QRS complex (V) during sustained PSVT with a constant E-E interval in one patient. Three response zones were defined: at longer A2-VS or V-VS coupling interval, VS manifested no effect on the timing of E (Zone 1). At closer A2-VS or V-VS coupling interval, VS conducted to the atrium, shortening the apparent A2-E or E-E interval (Zone 2). At shortest A2-VS or V-VS coupling interval, VS was blocked retrogradely, and no E was induced (Zone 3). The ability of VS to preempt control of the atria (Zone 2 response) strongly suggests the presence of dual A-V nodal pathways in these PSVT patients. If only a single pathway were present, VS would of necessity collide with the antegrade impulse and could not reach the atria. The Zone 3 response occurs because of retrograde refractoriness of the fast pathway. Failure of the echo during Zone 3 probably reflects concealed conduction to the fast pathway, or possibly interference in the slow pathway.


Precordial ST-segment mapping 1. Clinical studies in the coronary care unit.

Precordial ST-segment mapping Was applied serially in the coronary care unit for the study of 46 patients with myocardial infarction (MI), using a 49-lead system. Data from the maps were compared with clinical status of patients, conventional ECGs obtained simultaneously, and serum enzyme levels. Stability of the maps over a one hour period was noted in the early phase of admission. However, a drop of 32% of the sum of ST-segment elevations (+sigma ST) was detected in eight patients with uncomplicated anterior MI over the first 24 hours after admission. Extension of infarction was associated with abrupt rise of + sigma ST, and was diagnosed in two cases from maps in the presence of unchanged standard ECGs. The course of ST elevations was followed more accurately by the map than the standard ECG in eight patients. Pericarditis invalidated the technique completely, due to persistent + sigma ST. The standard ECG was superior to the map in following patients with inferior MI. A case of true posterior MI was more accurately delineated by maps of the posterior thorax than by the standard ECG. Intraventricular conduction defects and pacemaking interfered with maps. Early repolarization produced stable maps; however, mapping showed no advantages over the standard ECG. Preinfarction angina can probably be followed by serial mapping of ST-segment depression.


Echocardiographic features of supravalvular aortic stenosis.

A method for the echocardiographic detection of supravalvular aortic stenosis (SVAS) is described and the findings in a series of patients are presented. When compared to angiography, the echo tended to underestimate the severity of the supravalvular aortic obstruction. However, echocardiography appears to be a valuable, noninvasive method for detecting SVAS.


Cross-sectional echocardiography in assessing the severity of valvular aortic stenosis.

Real-time, cross-sectional echocardiograms were recorded in 28 consecutive adult patients with valvular aortic stenosis using a high resolution, mechanical sector scanner. Using the cross-sectional technique, the aortic valve orifice diameter was recorded in each of the 28 patients. With M-mode echocardiographic examination of these same patients, this value could be estimated in only 21 of these 28 patients (75%). The maximum aortic valve diameter recorded during the cross-sectional study averaged 7.9 +/- 1.8 mm (range 4-11 mm) in 15 patients with severe aortic stenosis; 11.6 +/- 2.3 mm (range 9-15 mm) in five patients with moderate aortic stenosis; 16.9 +/- 2.0 mm (range 14-20 mm) in eight patients with mild aortic stenosis; and 20.5 +/- 2.8 mm (range 15-26 mm) in 25 patients with no evidence of aortic valve disease. Comparing the means of these groups yielded the following: severe vs moderate P less than 0.005; moderate vs mild P less than 0.001; and mild vs normal P less than 0.001. Although there was some overlap between the individual groups, a clear separation existed between patients with severe and mild aortic stenosis. In addition, the group of patients in whom surgical intervention was recommended was also separated from the other subjects. When the aortic valve orifice was recorded using the M-mode technique, there was also a good correlation with the severity of the stenosis; however, the tendency of the M-mode study to overestimate severity in individual patients with calcific aortic stenosis and to underestimate severity in congenital aortic stenosis was again demonstrated. This study suggests that real-time, high resolution, cross-sectional echocardiography should be valuable in the noninvasive assessment of patients with aortic stenosis.


Influence of acute alterations in heart rate and systemic arterial pressure on echocardiographic measures of left ventricular perfornmance in normal human subjects.

To study the effects of acute alterations in heart rate and systemic arterial pressure on the mean velocity of left ventricular circumferential fiber shortening (Vcf) and on mean posterior wall velocity (Vpw), we performed ultrasound studies in 25 normal human subjects between the ages of 21 and 29 years. When heart rate was augmented by the administration of intravenous atropine from 64 +/- 2.2 (SEM) to 98 +/- 2.7 beats/min, mean normalized Vcf increased from 1.22 +/- 0.05 to 1.38 +/- 0.06 circumferences (circ)/sec(P less than 0.001). Mean normalized Vpw increased from 0.76 +/- 0.03 to 0.89 +/- 0.04 sec-1 (P less than 0.001). Mean Vcf and mean Vpw uncorrected for end-diastolic diameter increased in a similar fashion (P less than 0.01). After atropine administration, systemic arterial pressure was augmented by means of a phenylephrine infusion in 23 subjects by an average of 39 mm Hg (range 20-50 mm Hg). During the phenylephrine infusion, average heart rate decreased from 96 +/- 2.6 to 91 +/- 3.1 beats/min (NS), while mean normalized Vcf declined from 1.38 +/- 0.06 to 1.09 +/- 0.05 circ/sec (P less than 0.001) and normalized Vpw from 0.89 +/- 0.04 to 0.65 +/- 0.04 sec-1 (P less than 0.001). Nonnormalized velocities exhibited similar alterations (P less than 0.01). We conclude that in the normal human subject mean Vcf and mean Vpw are sensitive to acute alterations in heart rate and systemic arterial pressure. Thus, when ultrasound measures are used for serial assessment of left ventricular performance, the level of heart rate and systemic arterial pressure at which studies  are obtained must be considered. Further, the sequential use of atropine and phenylephrine, as described in this study, provides an experimental model for the evaluation of the effects of drug treatment and other interventions on left ventricular performance in man.


Temporal heterogeneity of myocardial blood flow in anesthetized dogs.

Temporal variation in perfusion to small segments of the myocardium was studied in 19 opened-chest dogs. In six control dogs, three or four differently labeled 7-10 mu microspheres were injected simultaneously into the left atrium to assess the variability in measured myocardial perfusion due to the microsphere technique. In 13 other dogs, microspheres were injected four times at 5 minute intervals while various hemodynamics parameters (mean aortic pressure, peak systolic pressure, heart rate, left ventricular end-diastolic pressure, and Vmax) were stable (less than 10% variation in any one parameter). The left ventricles were divided into 96 segments, the mean weight+/- SD of each segment was 0.95+/-0.17 grams. The flow to each segment was expressed as a percent of the mean flow of the three or four measured flows to that segment, and the difference between the largest and the smallest percent of each segment was taken as a measure of the variability of flow to that segment. The average variability of segmental flow (mean +/-SD) when the three to four differently labeled microspheres were injected was 14.0+/-4.7; and the variability when differently labeled microspheres injected sequentially was 31.0+/-10.8% (P less than 0.001). Furthermore, in the sequentially injected animals the magnitude of temporal variation was similar in various subdivisions of the ventricle (layers, walls, apex to base). The mean and standard deviation of the variability of flow to the endo, mid, and epicardial layers were 28.7+/-10.2, 30.0+/-11.3 and 34.5+/-12.4%, respectively. These changes may reflect either spontaneous or local autoregulatory changes in precapillary sphincters or arterioles.


Impairment of myocardial O2 supply due to hyperventilation.

Thirteen patients with ischemic coronary heart disease purposely hyperventilated for seven minutes in order to induce hypocapnic alkalosis. One patient experienced chest pain, and one exhibited chemical signs of myocardial hypoxia. Heart rate, blood pressure and myocardial O2 consumption did not change significantly. Coronary blood flow decreased and coronary (a-v)O2 difference widened. Since the alkalosis increased the blood O2 affinity, the fall in PO2 in coronary venous blood was proportionately even greater than the fall in O2 concentration. Thus, hypocapnic alkalosis due to hyperventilation interferes with myocardial O2 supply by 1) coronary vasoconstriction and 2) increased O2 affinity of blood.


Measurement of midwall myocardial dynamics in intact man by radiography of surgically implanted markers.

Tiny radiopaque helices (0.85 times 1.5 mm) of pure tantalum wire were implanted by means of a simple insertor instrument into the left ventricular myocardium in 24 patients at the time of cardiac surgery. The markers were positioned in such a way as to outline the profile of the left ventricle when viewed in a 30 degree right anterior oblique projection. Biplane studies showed that all markers could be placed very nearly in a plane using the surface anatomy of the heart as a guide to implantation. Implantation of markers required approximately two minutes. No intraoperative or postoperative complications ascribable to the markers have occurred. They remain firmly in place and allow acquisition of a noninvasive ventriculogram at any time after surgery. The dynamic geometry of the left ventricle was determined by analysis of cineradiograms of these markers. Utilization of a single-plane (right anterior oblique) cineradiogram to obtain measurements of major transverse ventricular diameters, mean circumferential shortening, and circumferential shortening velocity results in underestimation of lenghts by 1.4%, overestimation of shortening by 1.2% of end-diastolic length, and overestimation of velocity by 0.05 circ/sec, when compared with values obtained simultaneously from biplane cineradiograms.


Left ventricular aneurysm. Preoperative hemodynamics, chamber volume, and results of aneurysmectomy.

Angiocardiographic characteristics of the residual contracting left ventricle (LV) have been examined in 16 patients with anterolateral ventricular aneurysms (VA). In each patient a contractile section (CS) of the LV was clearly demarcated from the remaining aneurysmal section (AS). Using a double hemispheroid model, volumes of CS and AS were separately estimated by a modified area-length method. The volume of CS plus AS agreed closely with the volume of total LV estimated by the conventional area-length method. End-diastolic volume (EDV) of total LV ranged from 79 to 312ml/72. Aneurysmal section volume ranged from 8 to 264 ml/m2. End-diastolic volume of the contractile section ranged from 52 to 159 ml/m2 (mean, 100+/-8 (se); normal, 78+/-6). Contractile section ejection fraction (EF) showed a wide range, from 15% to 79% (mean 40%+/-17% SD). Nine patients underwent resection of VA. Three of six operated patients with CS EF less than 44% died; no survivor in this group has improved by more than one functional class (New York Heart Association classification). Three operated patients had CS EF greater than 45%; all survived and are improved, two having moved from class IV to class I. These data suggest that the EF of the contracting residual LV may be an important predictor of the outcome of resection of VA.


Assessment of aortic insufficiency by transcutaneous Doppler ultrasound.

Using a 2.2 MHZ directional Doppler ultrasound unit, the instantaneous peak aortic velocity pattern was recorded transcutaneously in 15 normal persons and 15 patients with aortic insufficiency. The transducer was positioned in the suprasternal notch and aimed posteriorly to cross the descending aortic arch at an angle approximately parallel to blood flow. The electrocardiogram, phonocardiogram, and carotid pulse tracings were recorded simultaneously. In patients with aortic insufficiency there was significant diastolic flow that was not present in normal persons. The planimetered area under the systolic and diastolic velocity tracings represents the distance forward and backward that the stroke volume moves. The ratio was used to approximate the percent regurgitation, which ranged from 9% to 68%. From left ventricular angiograms in the patients with aortic regurgitation single plane ventricular volume measurements were used to calculate ventricular output and when compared with the Fick cardiac output gave an estimate of true percent regurgitation. A strong correlation was obtained with the Doppler estimate (r=0.91), confirming that this simple ultrasound technique can accurately assess the degree of aortic insufficiency.


Clinical and hemodynamic results of mitral valve replacement with autologous fascia lata grafts. Studies in patients with competent prostheses.

Nine patients with severe mitral disease were studied before and six months after mitral valve replacement with a three-cusp stented prosthesis using fresh autologous fascia lata tissue. Only patients in whom there was no auscultatory and angiographic evidence of incompetence of the replaced valve were selected for restudy. All patients claimed a marked improvement in their exercise capacity after operation and there was a significant reduction in radiographic heart size. The cardiac output at rest and the response to exercise were both reduced before operation and were unchanged after valve replacement. The elevated pulmonary arterial and wedge pressures were significantly reduced after operation in all patients both at rest and during exercise, but in no instance were the postoperative exercise values within normal limits. Left ventricular end-diastolic pressure was within normal limits at rest and during exercise in all patients after  valve replacement but the average pressure gradient across the fascia lata valve was 6+/-1 mm Hg at rest and 18+/-3 mm Hg during exercise. These findings indicate that altough replacement of the diseased mitral valve with a competent fascia lata prosthesis afforded substantial symptomatic relief, reduction of cardiac enlargement and a lowering of the pulmonary vascular pressures, this artificial valve offered a significant obstruction to left ventricular diastolic filling, particularly during exercise.


Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris.

The therapeutic response to propranolol was evaluated in patients with documented coronary artery disease at doses varying from 40 to 320 mg/day. Therapeutic response was quantified by evaluating exercise performance on a treadmill and then related to plasma propranolol concentration. Plasma propranolol was defined in terms of beta-adrenergic blockade by comparison with dose (concentration) response curves in normal subjects. Individual therapeutic benefit occurred at doses which averaged 144 +/- 21 mg/day and at concentrations which averaged 30 +/- 7 ng/ml. There was a wide variation between both dose and concentration among the patients at maximum therapeutic response, but when the plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 to 98% of total blockade. Despite the increased exercise performance in these patients, the double product of heart rate and systolic blood pressure was always less, suggesting either an alteration of the relation between myocardial oxygen consumption and the double product during propranolol or a reduction on oxygen delivery to the myocardium as the result of beta-adrenergic blockade of the coronary vasculature.


Analysis of left ventricular function in response to afterload changes in patients with mitral stenosis.

In order to assess left ventricular function in patients with rheumatic mitral stenosis, left ventricular function curves (plotting stroke work index vs left ventricular end-diastolic pressure) were constructed using angiotensin to augment, and nitroprusside to reduce, afterload. Hemodynamic responses to these alterations in afterload were measured. Resting ejection fractions and qualitative assessment of left ventricular angiographic contraction abnormalities were also determined. Changes in left ventricular end-diastolic pressure following afterload interventions could be linearly related to changes in mean aortic pressure, but mitral valve gradients were unaffected. Afterload reduction with nitroprusside did not augment cardiac output. Afterload elevation with angiotensin significantly depressed both cardiac output and calculated mitral valve areas. Patients with normal resting ejection fractions evidenced normal ventricular function curves and those with depressed ejection fractions showed flat or declining function curves. Contraction abnormalities, generally in the posterobasal area, correlated well with abnormal left ventricular function curves.


Attributable risk, population attributable risk, and population attributable fraction of death associated with hypertension in a biracial population.

In 1961, blood pressure was measured in the 40-69-year-old segment of the population of Evans County, Georgia. Mortality was monitored for up to ten years. The relationship found between hypertension and mortality is characterized in this report by four parameters: attributable risk, prevalence, population attributable risk, and population attributable fraction. Attributable risk of death, a measure of the over-all impact of hypertension on those in each race-sex group with hypertension, is high in white males, black males, and black females, and is lowest in white females. Population attributable risk, a measure of the impact of hypertension on each entire race-sex group, is highest in black males and females due to the high prevalence of hypertension in blacks. It is somewhat lower in white males and lowest in white females. The fraction of all deaths attributable to hypertension (population attributable fraction) is highest in black females and lower in the other three groups. The population attributable fraction (ranging from 0.26 to 0.54 for systolic hypertension) is of such magnitude that if the 50% reduction in mortality achieved in the Veteran Administration Cooperative Study could be repeated in the general population, life expectancy after 40 years of age could be substantially increased.


Comparison of ejection phase indices of left ventricular performance in infants and children.

Ejection phase indices of left ventricular myocardial performance, mean velocity of circumferential fiber shortening (mVcf), mean systolic ejection rate (mSER), and ejection fraction (EF) were determined in 248 pediatric patients, utilizing left ventricular projections of cineangiograms. Heart rate significantly affected mVcf and mSER values in the normal group (r=0.74, 0.79, respectively). A method for heart rate compensation was presented, utilizing a ratio of actual value to expected normal value (A/E) for that heart rate. All indices were significantly lower in the myocardial disease group (12 patients) than in the normal (NI) group (55 patients), but only mVcf (A/E) gave complete separation. There was complete or nearly complete overlap of right ventricular volume and pressure load and left ventricular (LV) pressure load groups (20, 38, and 28 patients each) with NI. For LV volume load (95 patients) mVcf, and mVcf (A/E) mean values were low (P less than 0.025, less than 0.001, resp.). Patients with patent ductus arteriosus had high mVcf and mSER values (P less than 0.05, less than 0.025). MVcf (A/E) was superior to the other indices in identifying patients with depressed myocardial performance.


Double-outlet right ventricle associated with persistent common atriventricular canal.

A variant of double-outlet right ventricle (DORV) associated with common atrioventricular (A-V) canal was identified. As yet, this syndrome has not been successfully repaired. Of 16 patients with this diagnosis, 14 had the diagnosis confirmed at postmortem examination and two had the diagnosis confirmed by exploratory cardiotomy. The 16 patients were divided into two groups according to the position of the cardiac apex: group 1, ten patients with levocardia, and group 2, six patients with dextrocardia and ventricular inverson. When pulmonary stenosis was present, the clinical presentation was similar to that in tetralogy of Fallot, and when such stenosis was not, the presentation was similar to that in ventricular septal defect with bidirectional shunting. The electrocardiogram had the typical feature of common A-V canal. The right ventricular angiocardiogram had features typical of DORV. The left ventricular angiocardiogram revealed left ventricular outflow deformity typical of A-V canal in patients with levocardia but not in those with dextrocardia. Splenic anomalies were commonly seen (nine of the 16 patients). Asplenia was present in seven, and polysplenia in two. Ten patients had persistent left superior vena cava, seven had common atricum, six had anomalous pulmonary venous connection, and three had subaortic stenosis. Twelve of the 16 patients had pulmonary stenosis. Of the 16, 14 had common A-V canal (Rastelli type C) and two had a ventricular septal defect of the persistent common A-V type.


Coarctation of the aorta associated with aortic valvular atresia.

The aortas in 41 specimeans of aortic atresia (ten with associated mitral atresia) were studied for the presence of coarctation of the aorta. The basic lesion, causing varying degrees of obstruction, was observed in 31 instances (75%), 24 minor, seven with major degrees of obstruction. In half, the aortic lesion lay proximal to the ductus, and in the majority of the remainder, opposite the ductus arteriosus. The location of lesion and degree of obstruction was essentially the same whether aortic atresia occurred alone or in association with mitral atresia. Angiography is a fairly reliable method of identifying coarctation associated with aortic atresia. An additional point of interest was that in aortic atresia alone there was strong dominance of the male sex, while this tendency was not observed when mitral atresia was associated with aortic atresia.


Aberrant course of the left anterior descending coronary artery assoicated with anomalous left circumflex origin from the pulmonary artery.

We have presented a two year nonoperative follow-up of an asymptomatic 14-year-old girl with an unusual anomaly of the coronary arteries. Systolic and diastolic murmurs heard preoperatively did not change following severance of a patent ductus arteriosus. Postoperative selective coronary arteriography revealed (1) anomalous orgin of the left anterior descending artery from the right aortic sinus of Valsalva crossing between the aorta and pulmonary artery, (2) aberrant circumflex artery orgin from the pulmonary artery and (3) collaterals from the left anterior descending and right coronary arteries to the circumflex artery. This combination of coronary anomalies has never been described previously.


Gas-liquid chromatographic and mass fragmentographic determination of catecholamines in human plasma.

Quantitative analytical methods for plasma catecholamines and their conjugates by the use of gas-liquid chromatography have been developed. Epinephrine and dopamine have also been determined by mass fragmentography. The contents of catecholamines in the plasma of normal adults and patients with hypertension, neuroblastoma and pheochromocytoma have been demonstrated.


Gas-liquid chromatographic and mass fragmentographic determination of 3-O-methylated catecholamines in human plasma.

Plasma 3-O-methylated catecholamines, i.e. 3-methoxytyramine, normetanephrine and metanephrine, were separated from catecholamines by passing through alumina and further purified by adsorbing on weakly acidic resin and Amberlite XAD-4. The amines were trifluoroacetylated and determined by gas chromatography or mass fragmentography. Tracer quantities of tritiated 3-MT, NMN or MN were used as internal standards for total recovery estimations. The contents of 3-O-methylated catecholamines in the plasma of normal persons and patients with hyperthyroidism, hypertension, neuroblastoma and pheochromocytoma were measured.


A simple chromatographic procedure for the concurrent estimation of urinary 4-hydroxy-3-methoxymandelic acid (HMMA) and homovanillic acid (HVA) using a scanning technique.

A rapid and simple procedure is described for the concurrent determination of 4-hydroxy-3-methoxymandelic acid (HMMA) and homovanillic acid (HVA). The acids are separated by chromatography and estimated by a scanning technique. The urinary output of HMMA and HVA over 24 h from 123 normals (80 males, 43 females) gave mean values of 3.3 +/- 0.94 and 4.9 +/- 1.3 mg, respectively. There was no significant difference in the 24 hour urinary output of HMMA and HVA between the male and femal groups.


[Study of the zinc levels in serum and erythrocytes in burn patients (author's transl)].

Following a statistical study of four groups of burned people, determined in function of the UBS coefficient, a curve of blood zinc variations has been drawn:Immediately after burning, blood zinc is low. It rises to normal and then increases above normal. A group of patients (very serious or lethal burns) definitely differs from the others in respect of an important and persistent fall of blood zinc. These blood zinc values suggest a possible need for a zinc supply to this group of patients.


The sialic acid and carbohydrate content and the synthesis of glycoprotein from radioactive precursors by tissues of the normal and diseases upper intestinal tract.

The sialic acid and total hexose content of perorally obtained mucosal biopsies have been determined. Gastric mucosa has a higher content of sialic acid/mg protein and a lower content of total hexoses/mg protein than does jejunal mucosa. There were no differences chemically between gastric biopsies from subjects with or without peptic ulcers. Neither were there any differences between normal jejunal mucosa and jejunal mucosa from patients with untreated or treated coeliac disease. The studies of the incorporation of radioactive glucose into glycoprotein using all these tissues indicate that bacteria make a major in vitro contribution. This method is not suitable for study of de novo synthesis in either gastric or jejunal mucosa. Results are presented which suggest that bacteria may normally be present within the mucous layer of the stomach.


Lipidex chromatography in the radioimmunoassay of serum and urinary cortisol.

A highly specific method for the determination of cortisol in human serum and urine is described. The sample is first extracted with diethyl ether/ethyl acetate (1 : 1, by vol.), then chromatographed on a highly lipophilic derivative of Sephadex (hydroxyalkoxypropyl Sephadex, Lipidex) in light petroleum/chloroform (1 : 1, by vol.), and finally cortisol is measured by radioimmunoassay using a cortisol-21-BSA antiserum. Bound and unbound radioactivities are separated using dextran-coated charcoal technique. The 8 a.m. values (mean +/- S.D.) of cortisol among 11 young females and 16 young males were 152 +/- 32 ng/ml (range 111-235) and 185 +/- 21 ng/ml (103-232), respectively. The respective values at 4 p.m. were 84 +/- 29 ng/ml (26-117) and 84 +/- 36 ng/ml (32-172). The importance of Lipidex chromatography was demonstrated with assays of serum samples from children with congenital adrenal hyperplasia; without chromatography cortisol values were 6 times those with chromatography. Specific cortisol assays from pregnancy serum also necessitated Lipidex chromatography. Among 11 young men and 9 young women the mean daily urinary cortisol excretion was 56 +/- 26 mug (32-109) and 60 +/- 24 mug (39-109), respectively. Specific urinary cortisol determination could not be achieved without Lipidex chromatography.


Effect of estrogen-containing oral contraceptives on urinary corticosteroid sulfate excretion.

The excretion of corticosteroid sulfates and free cortisol in urine, and the total plasma cortisol, have been determined in 41 women receiving an estrogen-containing oral contraceptive and 53 age-matched female controls. The contraceptive steroids caused increases in the urinary corticosteroid sulfates and plasma cortisol similar to those observed in pregnancy; urinary free cortiscol was unchanged.


The determination of kynurenine in plasma.

A method is described for the estimation of kynurenine in plasma via alkaline cleavage, extraction and diazotisation and coupling. Tryptophan interference, which is demonstrated in an earlier method, has been eliminated. Data on the specificity of the present method and the normal adult male range of fasting plasma kynurenine are presented. The time course of plasma tryptophan and kynurenine after a tryptophan load are studied in 3 subjects as an additional validation of the method, and as an example of its application. The method described is convenient and requires no complex apparatus.


Serum guanase activities after myocardial infarction.

Serum guanase, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and hydroxybutyrate dehydrogenase activities were measured in 290 blood samples from 96 consecutive patients admitted to a Coronary Care Unit. Elevated serum guanase activities (greater than 2 U/l) were found in 19 patients (20%). The magnitude and frequency of these elevations did not negate the value of guanase as a "liver function test", since all cases with raised guanase also had abnormal serum alanine aminotransferase activities. This fact, together with other information in the literature, indicated that elevated serum guanase activity following myocardial infarction was consequent upon some degree of sub-clinical hepatic necrosis. Caution must be exercised when serum asparate aminotransferase is used as an index of heart muscle necrosis unless guanase or some other "liver specific" enzyme is known to be normal, or unless creatine phosphokinase or hydroxybutyrate dehydrogenase activities are elevated.


An estimate of the turnover rate of bone-derived plasma alkaline phosphatase in Paget's disease.

A through-knee amputation for suspected osteogenic sarcoma was performed on a patient with Paget's disease of the tibia. Plasma alkaline phosphatase (AP) activity fell to normal values, apparently as a single exponential function of time, with a half-life of 1.7 days. The daily turnover of bone-derived plasma AP was estimated to be approximately 200 I.U. from the Pagetic tibia and 20 I.U. from the rest of the skeleton.


The content of unbound polyamines in blood plasma and leukocytes of patients with polycythemia vera.

In the blood plasma and isolated leukocytes of 11 patients with polycythemia vera and 3 healthy subjects, the polyamines putrescine, spermidine and spermine were determined. The average values in the leukocytes of the healthy volunteers were found to be 1.8 +/- 1.4 nmol putrescine/10(8) cells, 3.0 +/- 0.9 nmol spermidine/10(8) cells and 12.9 +/- 3.8 nmol spermine/10(8) cells. In the plasma of healthy persons the amounts of the polyamines were below the sensitivity level of the method employed. In 4 patients with polycythemia vera no polyamines were detected. In contrast, in 7 cases 0.1 to 3 nmol polyamines/ml were found. The level of polyamines in the leukocytes of 6 of these patients was decreased and in one patient corresponded to the values found in the normal range (17.7 +/- 6.0 nmol polyamines/10(8) cells). Continued blood-letting therapy on 3 patients led to values approaching the concentrations found in normal subjects in both blood plasma and leukocytes. A decreased amount of these diamines in the leukocytes of the patients was seen to correlate with an elevated concentration in the plasma.


The measurement of sulphated and non-sulphated bile acids in serum using gas-liquid chromatography.

A method is described to assay sulphated and non-sulphated bile acids in serum using gas-liquid chromatography. Previously described techniques have been substantially modified to allow analysis of free and conjugated salts of the four major bile acids with particular care to ensure quantitative recoveries of lithocholic acid, its conjugates and sulphate esters. Losses of lithocholic acid inherent in some methods have been reduced by avoidance of column chromatography with alumina and extraction of lipid contaminants into heptane. Assay of the proportion of serum bile acids present as sulphate esters is achieved by the routine use of column chromatography to separate sulphated bile acids from non-sulphated bile acids followed by solvolysis of the sulphated bile acids before deconjugation. Careful selection of the conditions of strong alkaline hydrolysis ensures deconjugation of all bile salt conjugates including lithocholic conjugates which are not completely hydrolysed in weaker alkaline solutions. The trifluoroacetate derivatives of the methyl esters of the bile acids are chromatographed using 5-beta-cholanic acid as an internal standard with clear separation of the four major bile acids from the internal standard. In 10 fasting control subjects the mean serum total bile acid concentration was 5.3 muM (RANGE 1.1-16.4) including 0.7 mum sulphated bile acid (range 0-1.8). In 10 patients with acute viral hepatitis the total bile acid concentration was elevated in some but normal in others (mean 44.9 muM, range 2.7-80.3). The percentage of the total bile acid sulphated was not significantly different in the hepatitis patients compared to controls (controls 13%, range 0-35; hepatitis 23%, range 0-52). Lithocholic acid made up 13% of the total bile acid in controls (0-32%) and 18% in hepatitis patients (0-53%). Most of this lithocholic acid was sulphated (controls 81%, range 30-100; hepatitis 67%, range 37-100). Unconjugated bile acids were demonstrated in the serum of a few patients with acute viral hepatitis but in no control subjects.


Clinical application of a new method for the determination of aminoacylase in human serum.

Serum aminoacylase was assayed in 242 patients with various internal disases. The enzyme activity was normal in 89 cases without hepatic involvement and above normal in all forms of liver disease, the highest values being seen in acute viral hepatitis. Obstructive liver disease and hepatic carcinoma likewise caused a distinct enzyme increase, but this elevation was referred to secondary liver damage as in cases of congestive heart failure. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and aminoacylase activities were closely correlated, and aminoacylase is regarded as a sensitive and specific indicator of hepatic affections.


A rapid quantitative determination of triglycerides by means of thin-layer chromatography.

A quantitative chromatographic method for determining triglycerides in serum is described. The serum is applied directly to a thin-layer plate and after partition with one developing solvent the fractions are charred with 10% sulphuric acid. Charring takes 20 minutes. The concentration of triglycerides is measured against a triolein standard, which in itself is corrected for having too many double bonds by scanning the charring of the triglyceride fraction with a "flying spot"-scanner or a slitscanner. The results are compared with other methods of determination.


Elastolytic activity of human duodenal contents.

Elastolytic activity of human duodenal contents was determined using the new chromogenic substrate succinyl-trialanine-p-nitroanilide (Suc-Ala3-NAp). The mean output values after pancreatic stimulation with pancreozymin and secretin were significantly higher in controls than in subjects with impairment of other secretory values (volume, bicarbonate, amylase, lipase). Agar gel electrophoresis and chromatography on DEAE-Sephadex revealed one to two fractions which differed in mobility (cathodic and anodic fraction), elution with different NaCl concentrations (0.15 M, cathodic fraction; 0.3 M, anodic fraction), and in behaviour towards synthetic and natural substrate (Suc-Ala3-NAp) and elastin-Congo Red). The cathodic fraction cleaved both substrates, whereas the anodic fraction cleaved only Suc-Ala3-NAp. After trypsin and enterokinase treatment the anodic fraction behaved as the cathodic fraction on DEAE-Sephadex chromatography. The molecular weights (Sephadex G-100) and the Michaelis constants (Suc-Ala3-NAp) of both fractions were identical (24 500; 0.45 X 10(-3) M). These fractions represent probably diffenent activation forms of pancreatic elastase.


[Comparative studies of the initial rate method (modified Centrifi Chem method) and the Frankonit method to assay creatinine in serum and urine (author's transl)].

In the method described, by modification of the measurement according to changing reagent blanks (7 g albumin/100 ml + reagent for serum, and water + reagent for urine), excellent agreement with the results obtained by the Frankonit method was found. 262 parallel determinations with serum and 103 with urine were carried out. With a correlation of 0.99, the regression line y = x was almost maintained.


Characterization of protoporphyrin in red blood cells of patients with erythropoietic protoporphyria.

It was investigated whether the protoporphyrin that can be extracted from red blood cells of erythropoietic protoporphyria (E.P.P.) patients is present in the cells as free molecules or protein-bound. With isoelectric focusing and with starch gel electrophoresis it could be shown that virtually all protoporphyrin in the erythrocytes is protein-bound. It is very likely that the protoporphyrin is bound to hemoglobin at heme-binding sites. This was indicated by several observations: 1. With isoelectric focusing the protoporphyrin-protein complex is focused at a pH only slightly higher than the isoelectric point of hemoglobin. 2. With chromatography on Sephadex columns it appeared that hemoglobin and the protopotphyrin-protein complex have the same molecular weight. 3. A Heme-protoporphyrin exchange occurred when the heme-globin bond was labialized by conversion to hemiglobin. The resulting protoporphyrin-hemoglobin complex had the same electrophoretic mobility with starch gel electrophoresis as the protoporphyrin-protein complex, extracted from red blood cells of E.P.P. patients.


[Comparative studies of the acid hydrolases of human leucocytes and human and guinea pig alveolar macrophages. I. Study of the activities of glycosidases, arylsulfatase and acid phosphatase (author's transl)].

Acid hydrolase activities were compared in human leucocytes, guinea pig and human alveolar macrophages. Several enzymes were characterized: N-acetyl-beta-D-glucosaminidase, N-acetyl-alpha- and beta-D-galactosaminidase, alpha and beta-D-galactosidase, alpha-D-mannosidase, alpha-L-fucosidase, beta-D-glucuronidase, neuraminidase, acid phosphatase and arylsulfatase. The enzymatic activities were lower in leucocytes than in alveolar macrophages, higher in human macrophages than in guinea pig macrophages, except for beta-D-glucuronidase, acid phosphatase and arylsulfatase activities.


The influence of preoperative drug treatment on the histological appearances and in vitro 131I uptake of human hyperplastic thyroid gland.

The specimen of thyroid resected at partial thyroidectomy from 103 patients with primary thyrotoxicosis was studied with histometric and organ culture techniques. Twenty-seven patients had been prepared for operation with propranolol and seventy-six with carbimazole: all received Lugol's iodine for 10 days before operation. The resected specimen and deduced total thyroid weight was greater in the patients prepared with carbimazole. There was no absolute qualitative histopathological difference in the appearance of the glands of the two groups of patients, but histometry showed that the volume percentage of colloid and total gland colloid weight was significantly greater in the patients prepared with carbimazole: the volume percentage of epithelial cells and the total gland epithelial cell weight was similar in the two groups. The iodide concentrating capacity per g wet weight thyroid tissue or per unit volume of colloid did not differ significantly between the two groups. However, the iodide concentration capacity per unit volume of epithelial cells was significantly higher in the carbimazole prepared patients than in those prepared with propranolol.


Plasma glucagon response to arginine infusion in children and adolescents with diabetes mellitus.

Plasma glucagon response to an arginine infusion was studied in children and adolescents belonging to the following groups: (I) twenty-two controls; (II) six subjects with delayed insulin peak during oral GTT; (III) ten diabetics on diet and/or oral therapy; (IV) six newly diagnosed uncompensated diabetics; and (V) eight diabetics on insulin therapy. The fasting glucagon concentrations and rise of glucagon in response to arginine in the patients of Groups II, III and V were similar to those of the controls (Group I). The basal levels and rise of glucagon in the newly diagnosed, uncompensated dibetic children (Group IV) was elevated compared to the other groups but the difference was statistically not significant. The results of this investigation favour the hypothesis that the hyperglucagonaemia in diabetes is a secondary effect to the metabolic derangement, bearing a direct relationship to the degree of homeostastic decompensation.


Response of plasma aldosterone to fludrocortisone in primary hyperaldosteronism and other forms of hypertension.

The response of plasma aldosterone to fludrocortisone administration (400 mug 12-hourly for 3 days) was studied in twenty-two patients with primary hyperaldosteronism. No difference was observed in the response between those patients with an adrenal adenoma and those with bilateral adrenocortical hyperplasia, there being no significant change in plasma aldosterone levels across the test period. No separation between the groups was seen when basal plasma renin concentration was related to the aldosterone level following fludrocortisone. It is concluded that the test is of little value in the pre-operative differentiation of these conditions. Twenty-three patients with no demonstrable cause for their hypertension and four with elevated levels of plasma deoxycorticosterone were similarly studied for comparison. These groups demonstrated a normal fall in plasma aldosterone levels following fludrocortisone.


Radioimmunoassay of plasma dihydrotestosterone in normal and hypogonodal men.

A radioimmunoassay for determination of dihydrotestosterone (DHT) in man is described. After extraction from plasma, DHT is separated by paper chromatography. The radioimmunoassay is performed using an antiserum to dihydrotestosterone-3-oxime-BSA and a charcoal-dextran mixture is used to separate the free from the bound fraction. The reliability criteria of the method in terms of precision, accuracy, sensitivity and specificity have been evaluated. The mean level of DHT in plasma samples from young (age 21-37) and old (age 65-90) normal men is respectively (mean+/-SD) 54-7+/-19 ng/dl (n = 17) and 39-1+/-19 ng/dl (n = 14). The difference is statistically significant (P less than 0-01). The values found in seven patients with Klinefelter's syndrome (21-0+/-6 ng/dl) are significantly lower than normal young subjects (P less than 0-01). Lastly, the DHT levels found in a mixed group of male hypogonadism (azoospermia, due to tubular failure, germinal cell aplasia and anorchia) are reported.


Plasma testosterone and prolactin in the menstrual cycle.

Daily hormonal studies during nine ovulatory menstrual cycles showed that plasma prolactin and testosterone concentrations fluctuated randomly and independently. Mean plasma testosterone levels were found to be higher during the 7 days before and after the mid-cycle LH peak when compared to the premenstrual phase (P less than 0-01). No correlation was found between daily levels of prolactin and those of LH, FSH, oestrogen or progesterone and no correlation was seen between peaks of prolactin and testosterone or mean prolactin and testosterone levels. The lack of correlation between blood levels of prolactin and testosterone during the menstrual cycle suggests that prolactin is unlikely to have any direct controlling influence on the cyclical nature of testosterone production observed during ovulatory menstrual cycles.


The effects of large doses of the anabolic steroid, methandrostenolone, on an athlete.

Doses of the anabolic steroid, methandrostenolone, nearly ten times greater than those used therapeutically, have resulted in a marked depression of levels of testosterone in urine and blood, and in some depression of gonadotrophin excretion by a male athlete. The administration of the drug has been checked and its metabolism studied from the pattern of urinary metabolites.


Familial translocation, t(2;5) (p23; g31).

A reciprocal translocation, t(2;5) (p23; q31) was found in healthy individuals through two generations of a family. The balanced aberration resulted in a derivate chromosome 2 in two malformed offspring in the third generation. The family was ascertained through the two unbalanced carriers whose phenotype abnormalities resembled those of two other offspring who died prior to the cytogenetic examination.


A study of certain traits accompanying some inherted neurological disorders.

Feeblemindedness, dementia, mental disorders, and epilepsy, as well as optic atrophy, tapeto-retinal degenerations, cataract, ophthalmoplegias, and neural hearing loss were found more frequently in patients suffering from hereditary ataxias (HA) and allied disorders than in the general population. Mental disorders and squints, and in certain instances also ocular myopathy, feeblemindedness, and cataract were found also in non-HA family members. These traits were particularly frequent in subjects with minor neurological signs previously defined as having an "unspecific neuropathy" (Un), and belonging to kindreds in which autosomal dominant HA segregated. Un clustering in such families is probably caused by other genetic (or other) mechanisms different from that governing the classical HA in the family. These presumably polygenic conditions are thought to be introduced into the HA kindreds by a negative selection. Optic atrophy, tapeto-retinal degenerations, surdity, epilepsy, and possibly also dementia, were found together with monomeric disease, as well as in the Un subjects, particularly in families with recessive HA. Such traits were equally rare in unaffected family members and controls. Un in such families as well as the traits mentioned may reflect manifestation of HA genes in heterozygotes. They could also reflect the presence of genes linked to the HA genes.


Otodental dysplasia: a "new" ectodermal dysplasia.

Otodental dysplasia is an ectodermal dysplasia characterized by abnormal crown morphology of the teeth and sensorineural hearing loss. It was documented in six generations of a kindred of Italian extraction. Thirty-three of the 119 examined family members were affected. Twenty-six persons had characteristic dental anomalies combined with a hearing loss. Two had the dental anomalies alone, four had a hearing loss only and one of those with dental anomalies could not be tested for hearing. The teeth of the 29 with dental anomalies had large, bulbous crowns. The normal relationship between cusps and grooves was obliterated. Molars, both deciduous and permanent, were involved. Deciduous canines were large and bulbous. Absence of premolars was documented in 14 of the 29 individuals with abnormal teeth. Those premolars which were present were frequently small. Radiographs of the teeth showed denticles and taurodontia. Twenty-six of the 30 individuals with a hearing loss had concomitant dental anomalies. Of the four with isolated hearing loss, one was proven to have the syndrome. The remaining three were conjectured to be affected. The age of onset of the hearing deficit ranged from early childhood to middle age. The results of a chi-square test supported autosomal dominant inheritance. The pleiotropy in this syndrome is postualed to be due to a genetic defect in the neuroectoderm.


Aminocentesis: its impact on mothers and infants. A 1-year follow-up study.

In a 1-year follow-up study, the effects of amniocentesis for genetic diagnosis upon 22 infants and their mothers were assessed. The infants were tested at 1 year of age on the Bayley Infant Scale of Mental and Motor Development. No deviations from normal mental or motor development were found. The mothers were interviewed at the same time, in order to better understand the emotional aspects of the experience. Women between ages 35-39 with no previously affected child tended to accept amniocentesis easily, as an appropriate part of parnatal care. Mothers with a previous defective child tended to have more painful emotional reactions, including higher anxiety over the test and more conflict about a possible abortion. They needed more intensive and extended counseling. We suggest that the issue of abortion is important, even if manageable by most women, and that a chance to discuss it may be significant.


The effect of structural aberrations of the chromosomes on reproductive fitness in man. I. Methodology.

Methods are presented to estimate relative fitness of carriers as a function of fertility, survival, are generation time in pedigrees under incomplete ascertainment. A large sample of diverse chromosomal aberrations reveals significant effects on all three parameters, giving a relative fitness of .769 +/- .039. There is no significant shift in segregation frequency. Implications of these results for population dynamics of structural rearrangements are discussed. The following paper applies these methods to specific classes of aberrations.


The effect of structural aberrations of the chromosomes on reproductive fitness in man. II. Results.

Reproductive fitness was measured in the following seven classes of pedigrees: (1) D/D Robertsonian translocations ascertained through a euploid proband; (2) D/G Robertsonian translocations ascertained through a euploid proband: (3) reciprocal translocations ascertained through a euploid proband; (4) inversions ascertained through a euploid proband; (5) all translocations and inversions ascertained through an aneuploid proband; (6) those ascertained through a proband with a ring, marker, or supernumerary chromosome; (7) those ascertained through a proband with an extreme variant chromosome. For each group reproductive fitness was calculated in two ways. One method was based on live births, fetal and infant deaths and generation time of those individuals carrying a chromosome abnormality or variant by comparison with their first degree relatives who were known to have a normal chromosome constitution. The second method was based on the proportion of sporadic cases obtained from segregation analysis. The results obtained using both methods are presented and discussed.


Adducted thumb syndromes.

The adducted thumbs syndrome is characterized by cleft palate, microcephaly, and dysmyelination. A fifth case of this syndrome is presented. Several other syndromes which may present with adducted thumbs are reviewed and re-assessed. The original contributions consist of discussions of (1) the possible pathogenesis of adducted thumbs in the congenital clasped thumb syndrome, and (3) the significance of adducted thumbs as a possible marker in sex-linked hydrocephalus.


The oro-facial-digital syndrome.

Two patients, a mother and her daughter, are presented who manifest the clinical features of the oro-facial-digital syndrome (OFD I). Many of these features are shared with Mohr's syndrome (OFD II). Confusion arises when a patient presents with features common to both syndromes. The features which are always or sometimes associated with these syndromes are tabulated. The Tables also show which abnormalities are common to both syndromes and to our cases. Additional clinical and radiological features which have not been considered part of these syndromes are described. We present these cases to suggest that these syndromes should be "lumped" together as one syndrome. We propose expanding this syndrome to include ear and renal abnormalities. Our cases follow an X-linked dominant inheritance pattern and, therefore, do not help determine the genetic controversy of these two syndromes.


Variation in the centromeric banding of chromosome 19.

The centromeric banding pattern of chromosomes 19 exhibited considerable variation. The variants were present in the majority of cells from an individual and consisted of additional dark-staining areas. There was no abnormal phenotypic effect associated with any variant and it is concluded that these additional dark-staining areas do not contain any functional genes.


Location of aldosterone-producing adenomas by the determination of plasma aldosterone in adrenal vein or renal vein blood.

1. Aldosterone-producing adenomas were located before operation in eighteen patients by comparison of aldosterone concentrations in blood obtained by percutaneous catheterization of the adrenal vein or renal vein. The concentration of aldosterone in the venous effluent from the adrenal glands containing adenomas was significantly greater than in the venous effluent from contralateral glands. 2. Cathetherization of the adrenal vein is, however, technically difficult. The location of adrenal adenomas was also possible by analysis of blood from the renal vein. 3. If the concentrations of aldosterone in blood from the left renal vein were higher than those from the right, the existence of a left adrenal adenoma was suggested. A high value in plasma, obtained from the inferior vena cava above the entry of the right adrenal vein, showed a right adrenal adenoma. This procedure identified very small functional adenomas which could not be demonstrated radiographically, or seen or palpated at surgery. 4. It was concluded that differential aldosterone measurement after percutaneous bilateral adrenal vein or renal vein catheterization can be used as a definitive test for the location of an aldosterone-producing adenoma, where this is uncertain.


Effect of proportional reduction of sodium intake on the adaptive increase in glomerular filtration rate/nephron and potassium and phosphate excretion in chronic renal failure in the rat.

1. The influence of dietary sodium intake on the glomerular filtration rate (GFR/nephron) and potassium and phosphate excretion was examined at three stages of progressive chronic renal failure produced in rats by sequential partial nephrectomies. 2. The adaptive increased sodium excretion per nephron in the control group receiving a constant sodium intake did not occur in the experimental group that had a gradual reduction of dietary sodium in direct proportion to the fall in GFR. 3. Despite the difference in sodium excretion, the increase in GFR/nephron, the daily variation in the amount of potassium and phosphate excreted, the increase in potassium and phosphate excretion per unit nephron, and the plasma potassium and phosphate concentrations were the same in the two groups. 4. The concept of 'autonomous adaptation' in chronic renal failure is presented.


Exaggerated phosphaturic response to volume expansion in patients with essential hypertension.

1. Tubular handling of sodium in hypertensive patients has been evaluated with urinary phosphate excretion used as a marker for proximal tubular reabsorptive capacity. 2. Nine hypertensive patients and nine normal control subjects were studied during sustained water diuresis and the intravenous infusion of isotonic sodium chloride solution to produce volume expansion. 3. In the hypertensive patients there was exaggerated phosphaturia, natriuresis and enhanced distal delivery of sodium. Sodium reabsorption in the diluting segment was normal. 4. The enhanced distal delivery and augmented phosphaturia suggest that a decreased reabsorption of sodium in the proximal tubule is the most likely explanation for the exaggerated natriuretic response to volume expansion in hypertensive patients.


Leucocyte sodium transport in uraemia.

1. In sixteen patients with severe chronic renal failure the rate constant for total sodium efflux from leucocytes was significantly reduced compared with that in thirty control subjects. This difference lay chiefly in the glycoside-sensitive ('active') moiety of sodium efflux. 2. In sixteen patients receiving regular haemodialysis, the rate constant for total sodium efflux from the leucocyte was significantly greater than in the undialysed uraemic patients though still subnormal. 3. In individual patients, an increase in sodium efflux could be detected as early as 1 week after regular haemodialysis was started. 4. These results are compatible with the existence of a dialysable molecule in uraemic plasma affecting leucocyte sodium transport.


Airway function in healthy subjects and patients with left heart disease.

1. In forty non-smoking healthy subjects and seventy-two patients with left heart diseases measurements were made of the volume expired in the first second of a forced expiration (FEV1) and the total volume expired in a forced expiration (FVC) before and after inhalation of salbutamol. Before and after salbutamol the healthy subjects and patients also inhaled maximally an inspirate, the first part of which contained 133Xe and, during controlled expiration, the radioactivity of the expirate was measured and plotted against its volume. the resulting curves were divided into phases of different slope by eye, the point at which phase 3 changed to phase 4 being nominated the closing volume. 2. In forty non-smoking healthy subjects inhalation of salbutamol was followed by significant increase in FEV1 but FVC and closing volume did not change. 3. Change in posture from seated erect to supine in thirty of these healthy subjects was accompanied by significant reduction in FEV1 and FVC and as closing volume was not significantly different in the two positions the ratio closing volume/vital capacity was increased with recumbency. 4. In seventy-two patients with left heart diseases without a history of cough or wheeze, FEV1, FVC, closing volume and the ratio closing volume/vital capacity were significantly different from values in the healthy subjects. There was no significant difference between non-smokers and ex-smokers amongst the patients. 5. Significant increase in FEV1, FVC and reduction in closing volume and the ratio closing volume/vital capacity followed inhalation of salbutamol in patients with heart diseases but the values remained significantly different from those recorded in the healthy subjects. 6. In twenty patients with heart diseases, FEV1 and FVC were reduced by change in posture from seated erect to supine but the ratio closing volume/vital capacity and the regression with age of this ratio were not significantly changed by change in position. 7. In patients with heart diseases the ratio closing volume/vital capacity was significantly correlated with severity of breathlessness and length of symptom-history but not with left ventricular end-diastolic or pulmonary vein wedge pressures.


The influence of diet on unconjugated hyperbilirubinaemia in the Gunn rat.

1. The influence of dietary carbohydrate, protein and lipid on the unconjugated hyperbilirubinaemia of Gunn rats has been studied. 2. In the first set of experiments, after a control period without restraint, the animals were restrained for 72 h and were either starved or received isocaloric amounts of glucose, protein hydrolysate or soya bean oil through a gastrotomy cannula. 3. A second study was performed with groups of unrestrained animals which were fed with diets supplemented with carbohydrate, protein and lipid for 7 days after a control period. 4. Both these studies showed that diets composed predominantly of carbohydrate or protein doubled the plasma bilirubin concentration. Starch, glucose and fructose produced similar effects. 5. A high-lipid diet in the absence of carbohydrate caused a slight reduction plasma bilirubin concentration. This effect was observed with both soya bean oil and pork fat. 6. It has not been established whether the increase in hyperbilirubinaemia resulted from the high-carbohydrate content of the diet or the absence of lipid.


Effect of lysine acetylsalicylate on biliary lipid secretion in dogs.

1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.


Heterogeneity of hepatic vitamin B12 in the rat after parenteral cyanocobalamin.

1. The rate of radioactive vitamin B12 excretion into plasma and bile from the isolated perfused rat liver and into bile in vivo has been measured after the intramuscular injection of radioactive cyanocobalamin at various time-intervals before study. 2. With an interval of labelling of 10 or more days, the release of radioactive vitamin B12 over 4 h by the isolated perfused liver was linear and constituted approximately 3-5% and 1% of the hepatic radioactivity into plasma and bile respectively. 3. In contrast, after a shorter period of prelabelling (less than 7 days), there was a biphasic release of radioactive vitamin B12: an initial rapid rate followed by a slower rate after about 1 h of perfusion. The total radioactive vitamin B12 was considerably increased (e.g. 25% and 5% of hepatic radioactivity into plasma and bile respectively during a 4 h perfusion of a liver labelled 18 h previously). Confirmation of coexisting stable and labile pools of intrahepatic vitamin B12 was provided by: (a) the patterns of hepatic release after double labelling with 57Co-labelled and 58Co-labelled cyanocobalamin at different times before liver perfusion; (b) the rates of biliary excretion of 57Co-labelled and 58Co-labelled vitamin B12 in vivo after different periods of prelabelling. 5. The rate and pattern of release were not altered by changes in the quantity of precursor cyanocobalamin, by phenobarbitone treatment or by the addition of cycloheximide to the perfusion. 6. The injection into rats of subcellular preparations of rat liver labelled in vivo with radioactive vitamin B12 demonstrated that hepatic heterogeneity did not depend on physical compartmentation. 7. Despite the rapid release rate from the liver of recently administered radioactive cyanocobalamin, the hepatic radioactivity increased progressively with time after labelling in vivo, in contrast to the other tissues, where it decreased. In the presence of rapid bidirectional fluxes the ability of the liver to store vitamin B12 can be largely explained by the reduction in the rate of hepatic release that continues for about 10 days after parenteral administration of cyanocobalamin.


Leg blood flow and muscle metabolism in occlusive arterial disease of the leg before and after reconstructive surgery.

1. Leg blood flow, uptake of oxygen and glucose and release of lactate by the leg and changes in intramuscular concentrations of metabolites were studied at rest and during exercise of increasing work loads in thirteen patients with occlusive disease of the iliac or superficial femoral arteries. 2. Leg blood flow (dye-dilution technique) and oxygen uptake during exercise were low and levelled with increasing work load. Considerable increases were noted in muscle lactate concentration and in the net release of lactate from the exercising leg. Muscle content (needle-biopsy technique) of ATP and creatine phosphate decreased during exercise, with an almost complete depletion of creatine phosphate in three patients. The decrease in muscle glycogen during work did not differ significantly from that of control subjects. 3. Repeated exercise after reconstructive surgery showed a considerable improvement in physical working capacity. Leg blood flow and oxygen uptake during exercise were significantly higher than before surgery and increased linearly in relation to work intensity. The decrease in creatine phosphate and lactate concentration of the thigh muscle during exercise was less pronounced and the release of lactate was lower than before vascular reconstruction. 4. It is suggested that the onset of the severe muscle symptoms during exercise in patients with occlusive arterial disease of the leg may be related to a low concentration of ATP and creatine phosphate in the affected muscles.


Effect of diazoxide on renal handling of sodium in the rat.

1. To assess whether diazoxide-induced sodium retention is due to a direct renal action of the durg, independent of its systemic haemodynamic effects, diazoxide was infused directly into one renal artery of hydropenic rats. During the infusion period there was a small fall in mean systemic arterial blood pressure. There were no significant changes in the clearances of inulin or p-aminohippurate by either kidney. 2. Absolute and fractional excretion of sodium were unchanged on the non-infused side. On the side of infusion, there was a significant increase in absolute and in fractional sodium excretion. 3. Thus natriuresis rather than sodium retention seems to be the direct renal effect of diazoxide and may be related to its vasodilator properties.


A fatal case involving propranolol and codeine.

Tissue concentrations are given in a fatal case involving both propranolol and codeine. Methods for the detection and quantitation of the compounds are briefly described.


Thiopental suicide -- case report.

Thiopental was indicated in the suicide death of a hospital employee. The blood thiopental level was determined to be 27.9 mg% by ultraviolet spectrophotometry, and positive identification was accomplished using gas chromatography, thin-layer chromatography, and infrared spectrophotometry.


Computer retrieval of articles on the therapy of poisonings.

This paper describes the joint efforts of the Cleveland Poison Information Center and the Cleveland Health Sciences Library to develop a workable system for scanning the current journal literature for relevant articles on the therapy of poisonings and to develop a suitable system for reorganizing the present reprint files for the city's two units of the Poison Information Center. The use of the MEDLINE computer retrieval system for retrieving relevant current articles is discussed in detail as is the proposed reorganization of the Center's reprint file.


Single extraction GLC analysis of six commonly prescribed antiepileptic drugs.

A simple gas-liquid chromatographic technique for the quantitation of ethosuximide (Zarontin), methsuximide (Celontin), mephobarbituate (Mebaral), phenobarbituate, primidone (Mysoline), and diphenylhydantoin (Dilantin) is described. The drugs and internal standards are extracted from whole uncoagulated blood using an organic solvent, re-extracted to eliminate interferences, and chromatographed using temperature programming on 3% OV-225. The results compare very favorably and eliminate some difficulties associated with derivation methods.


Iterative computation of metabolic flux and stoichiometric parameters for alternate pathways in rumen fermentation.

A model is presented which has been derived to compute the end-products of rumen fermentation from knowledge of the input of feedstuff. The model comprises a set of algebraic equations for the fermentation of each of the following feedstuff components: soluble sugars, starch, cellulose, hemicellulose and protein. The equations were derived from known biochemical stoichiometric relationships. A iterative, non-linear least sqares method (steepest descent) was used to estimate parameter values. In a sample run the inputs used were from an experiment where eight sheep were fed white clover. The model predicted values were in good agreement with the experimental values.


A model of heat flow in the sheep exposed to high levels of solar radiation.

The fleece is an important component in thermoregulation of sheep exposed to high levels of solar radiation. A model written in CSMP has been developed which represents the flow of energy between the sheep and its environment. This model is based on a set of differential equations which describe the flux of heat between the components of the system--fleece, tip, skin, body and environment. It requires as input parameters location, date, time of day, temperature, relative humidity, cloud cover, wind movement, animal weight and linear measurements and fleece length. At each integration interval incoming solar radiation and its components, the heat arising from the animal's metabolism and the heat exchange by long-wave radiation, convection, conduction and evaporative cooling are computed. Temperatures at the fleece tip, skin and body core are monitored.


A prototype segmental model for blood flow and heat transfer in the limb.

A general modeling technique for characterizing the blood flow and heat tranfer properties in the human limb is reported in this paper. The basic idea is to take the segmental approach so that a lumped model for each segment can be constructed. Consequently, a prototype segmental computer model is proposed which describes, in general terms, the interrelationships between the circulatory system and the thermal system of the limb. Simulation study of digital response to hand cooling is made and the results agree very well with the experimental data.


A computer algorithm for spatio-temporal patterns in interactive neuron populations.

A computer algorithm has been developed which enables numerical computations to be performed for interactive neuron populations whose spatio-temporal behaviors are represented by a set of certain integro-differential equations. The computation is based on the fact that the eigenfunctions of a symmetric Hilbert-Schmidt operator form a set of complete orthonormal functions in L2 space. This algorithm differs from the ones which computes the value of the solution at each (x,t) point in that it computes the coefficients corresponding to the eigenfunctions. Therefore it is shown that the error in the coefficient of one eigenfunction does not propagate to that of another eigenfunction from one sampling time to the next one. This enables us to analyze the temporal behavior of one spatial frequency which is not affected by that of the other spatial frequencies.


Computer simulation of overshoot in saccadic eye movements.

The human horizontal eye movement system produces quick, precise, conjugate eye movements called saccades. These are important in normal vision. For example, reading tasks exclusively utilize saccadic eye movements. The majority of saccades have dynamic overshoot. The amplitude of this overshoot is independent of saccadic amplitude, and is such that it places the image of the stimulus within the retinal region of maximum acuity within a minimum of time. A computer based model of the saccadic mechanisms was used to study the origin of this overshoot. It was discussed that dynamic overshoot cannot be attributed to biomechanism properites of the eye movement mechanism, but must instead be explained by variations in the controlling nervous activity. The form of this neural controller signal is very similar to that required for a time optimal response of an inertial system.


Integral control in accommodation.

Models of the accommodation system available inthe literature may be classified as proportional controller, optimal bang-bang controller and pure integral controller types. Each of these models explains only some aspects of the experimental behavior of the system and conflicts with other experimental observations. Based on two different experiments in which the built-in phyiological feedback loop has been opened, a leaky-integrator element is proposed for the accommodation controller. This element appears to resolve the conflict between the proportional and integral controller models and also explains the experimental observations better than any of the existing models.


Modeling static and dynamic human cardiovascular responses to exercise.

A human performance model has been developed and described [9] which portrays the human circulatory, thermo regulatory and energy-exchange systems as an intercoupled set. In this model, steady state or static relationships are used to describe oxygen consumption and blood flow. For example, heart rate (HTRT) is calculated  as a function of the oxygen and the thermo-regulatory requirements of each body compartment, using the steady state work values of cardiac output (CO, sum of all compartment blood flows) and stroke volume (SV, assumed maximal after 40% maximal oxygen consumption): HTRT=CO/SV. The steady state model has proven to be an acceptable first approximation, but the inclusion of transient characteristics are essential in describing the overall systems' adjustment to exercise stress. In the present study, the dynamic transient characteristics of heart rate, stroke volume and cardiac output were obtained from experiments utilizing step and sinusoidal forcing of work. The gain and phase relationships reveal a probable first order system with a six minute time constant, and are utilized to model the transient characteristics of these parameters. This approach leads to a more complex model but a more accurate representation of the physiology involved. The instrumentation and programming essential to these experiments are described.


An inverse correlation (dose-response between 5-methyl-cytidine and the fate of spontaneous tumours in mice.

Tumour-bearing mice, 248 in number, have been injected with 5-methyl-cytidine dissolved in physiological salt solution. The mice were divided into 5 series depending upon the amount of 5-methyl-cytidine they received. Mice of a successive series received 43.2, 28.8, 14.4 and 7.2 mg/kg body weight. There was a progressive increase in the percentage of mice showing regression of tumours in the successive series, as follows: 45%, 50%, 65%, 60%, and 67.8% respectively, giving an average percentage of regressions of 59.7%. The incidence of mice developing multiple primary tumours increased in the same successive series respectively as follows: 25%, 43.8%, 58.3%, 73.3%, and 70%, thus giving an average of 58.3%. The evidence obtained indicates an inverse correlation (dose-response) between the amount of the 5-methyl-cytidine injected and the percentage of regressions of spontaneous tumours.


Studies on the cytogenetic activity of some common fungicides in higher plants.

Seeds of barley and secondary roots of Vicia faba were exposed to treatments with 23 of the most commonly used fungicides with a view to discovering the effect of these fungicides on the germination, seedling injury and chromosome abnormalities in the former, and the spectrum and frequency of chromosomal aberrations in the latter. Sixteen fungicides reduced the percentage of seed germination, induced seedling injury and produced cytological anomalies of varying degrees in barley. More potent fungicides were further tested in the secondary roots of Vicia faba which were found to produce a significant amount of chromosomal aberrations in the form of chromatid and isolocus breaks and exchanges of chromatid type. Based on theseo bservations, fungicides Dexon, Benlaté, Cerasan, Copperson, Lonocol, Morestan, Hexasan and Karathane could be classified as strong radioimimetic agents. Their role as environmental mutagens in enhancing the spontaneous mutation rate has been discussed and it has been concluded that these constitute genetic and environmental hazards of great magnitude to the eco-system where they are released.


Ultrastructural aspects of infertility.

Organ culture studies have demonstrated that 17beta oestradiol can cause the rapid deterioration and dissolution of pre-existing nuclear channel systems in the human endometrial glandular cell. The importance of the nuclear channel system in implantation is emphasized and the implications of secretory activity in the endometrium of an infertile woman are discussed.


Long-term results of continuous oxygen therapy at sea level.

Twelve patients with hypoxemia associated with severe chronic obstructive pulmonary disease were treated with continuous portable oxygen therapy and have been followed up for a mean period of 25.2 months at sea level. Pulmonary function testing has revealed no further significant deterioration at long-term follow-up (17 months). After oxygen therapy was initiated, arterial carbon dioxide tension increased slightly, but decreased to pretreatment levels when patients were allowed to breathe room air. The electrocardiogram, which was unchanged at one month, has shown some reversal of cor pulmonale in five patients. Six patients have died, yielding a 56 percent survival rate at two-and-one-half years by the life table analysis. Five patients were autopsied, with possible oxygen toxicity being present in only one. The quality of life in our patients was improved and was especially represented by a reduction in hospital admissions for respiratory illness. We believe that continuous oxygen therapy is beneficial and worthwhile economically in certain patients.


Depression of hypoxic and hypercapnic ventilatory drives in severe asthma.

Because of the previous finding of an attenuated hypoxic ventilatory drive in a teenager with severe asthma, the ventilatory responses to hypoxia and hypercapnia were examined during remission in 16 patients with the history of severe asthma. Spirometric and body plethysmographic pulmonary functions were normal or nearly normal just prior to ventilatory drive testing. The ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia were studied. Both hypoxic and hypercapnic drives were significantly depressed in the asthmatic patients. Factors known to blunt the ventilatory drives were not present in this group of patients. Hence, the etiology of these changes is unclear. In some patients, these depressed respiratory drives might contribute to hypoventilation, to severe hypoxemia, and to respiratory failure during severe asthma.