Body fluid lithium measurements: severity of illness and prediction of outcome.

The authors measured lithium ion in saliva and serum 24 hr after a loading dose of lithium, and recorded the amount of lithium excreted in the urine during the 24-hr test period. Their results support previous work indicating a correlation between serum and mixed saliva lithium levels. On a subsample of manic patients, no correlation could be found between lithium retention and clinical outcome, age of onset, or pretreatment severity of illness. In addition, they were unable to confirm a prior report that the 24-hr postloading dose serum lithium level was a predictor of eventual therapeutic dosage.


Endothelial lesions associated with vascular clamping--surface micropathology by scanning electron microscopy.

The endothelial cell pavement in normal blood vessels is very fragile. In cardiovascular surgery, the need for secure clamping of the aorta results in trauma which may be followed by thrombosis or occlusion. Various types of vascular clamps and other related devices offered commercially were clinically investigated in canine models and their effects on the vascular endothelium were ascertained with the aid of scanning electron microscopy. On the basis of these studies, the Fogarty silicone filled clamp appeared to be the least traumatic. However, further technical developments in this area are needed in order to obtain a completely atraumatic method of temporarily closing major blood vessels.


Comparative studies of hemoperfusion devices. I. In vitro clearance characteristics.

Drug adsorption studies were carried out using three charcoal-based and one resin-based hemoperfusion devices. They were the Sandev Hemocol unit, the Gambro Adsorba 300C unit unit, the Becton-Dickinson Hemodetoxifier, and the Extracorporeal Medical Specialties XR-010 Hemoperfusion column, respectively. Clearance versus time tests of up to six hours duration were performed using solutions of sodium salicylate, sodium barbital, and creatinine in a pH 7.4 buffer which were pumped through the columns at flow rates of either 100 or 200 ml/minute. Short term clearance tests were performed at various other flow rates to determine overall mass transfer resistances for the devices. Further analysis yielded values for the individual fluid-phase and solid-phase resistances. Studies were also done using sodium salicylate in bovine blood. The results provide information on typical adsorption capacities and drug removal rates for the four devices, and indicate the relative extents to which the solid and fluid phases control the drug uptake rates.


Correlation of infrared spectroscopy with platelet morphology in blood compatibility studies of polydimethylsiloxane membranes.

Oxygenator membranes, polydimethylsiloxane elastomer, exposed to flowing heparinized canine blood in a perfusion system have been studied with respect to the platelet activation and the morphology of the membranes. Utilizing Fourier transform infrared spectroscopy couple with attenuated total reflection technique (ATR) and laser Raman spectroscopy, no obvious differences in morphology and composition of the membranes have been detected while electron microscopic study shows difference in platelet aggregation.


Aortic valve mechanics. Part II: a stress analysis of the porcine aortic valve leaflets in diastole.

The stress analysis of the porcine aortic valve leaflets in diastole at 80 mm Hg pressure in-vitro is presented. Incorporation of local geometrical asymmetry, material inhomogeneity, anistropy and non-linearity are applied. The stress theory used is a modified form of the thin membrane stress theory for a homogeneous linearly elastic and orthotropic lamina. Modifications are made so that the Hooke's law constitutive equations of stress may be applied to the inhomogeneous, non-lineary elastic and orthotropic thin (membrane) aortic valve leaflets. Stress calculations are made on the premise that the valve is in pre-transition (i.e. low elastic modulus) in the circumferential direction and post-transition (i.e. high elastic modulus) in the radial direction. It is shown that sigmaCIR less than 1 gm/mm2, and for most of the noncoronary leaflet, 0 less than sigmaRAD less than 30 gm/mm2. The areas of highest stress concentrations are in the areas of mutual leaflet coaptation near the Node of Arantii. A progressive increase of radial stresses from the sinus-annulus edge toward the node is observed.


Forty-one variables following thoracotomy in calves.

Seven calves underwent thoracotomy to study the response of 41 physiologic variables over a 14 day post-operative period for comparison to a recent series of left ventricular bypass pump implants. The experimental protocols were identical to the pump implant protocols except that the sham operated animals did not receive antiplatelet or anticoagulant drugs and the pumps were not implanted. Of the 41 variables studied, 13 changed significantly during the post-operative period. Heart rate, hematocrit, whole blood hemoglobin, and fibrinogen concentration decreased, while fibrinogen survival, stroke volume, cardiac output, arterial blood pH, pCO2 and pO2, plasma sodium concentration, and urinary excretion rates of sodium and potassium increased from the first or second to the fourteenth post-operative day. Heart rate and hematocrit also decreased in the recent series of 18 animals in which left ventricular bypass pumps were implanted. The decrease in heart rate is toward the unoperated control value as the calves recover from the operative stress. The decrease in hematocrit is probably the result of daily removal of blood for the physiologic studies because there was no evidence of hemorrhage or red blood cell destruction.


Effects of yohimbine on squid axons.

Yohimbine, an indolealkylamine alkaloid, reduces the amplitude of the sodium current in the squid giant axon. For doses that reduce sodium current amplitude by up to 50%, there is no significant change in the kinetics or in any of the voltage-dependent parameters associated with sodium channels. The effective equilibrium constant for yohimbine binding to the sodium channel is  3 x 10(-4) M. Repetitive depolarizing pulses increase the inhibition of squid axon sodium current by yohimbine. This use-dependent inhibition is enhanced by increasing the concentration of yohimbine, by increasing the frequency of pulsing, and by increasing the magnitude or the duration of depolarization. It is reduced by hyperpolarizing prepulses. This behavior can be explained by a model wherein yohimbine binds more readily to open sodium channels than to closed sodium channels and wherein the Hodgkin-Huxley kinetic parameters are modified by the binding of the drug. This type of model may also explain the tonic and use-dependent inhibition previously described by others for local anesthetics.


Investigation by focused laser beam scanning of the photoelectric activity of bacteriorhodopsin-containing lipid bilayers.

The photoelectric activity of different parts of lipid bilayer containing bacteriorhodopsin was investigated by moving a small actinic light spot across the Plateau-Gibbs border and the bimolecular part of this reconstituted model membrane. The results give direct evidence that bacteriorhodopsin incorporated into the bimolecular region of the lipid membrane is responsible for the photoelectric activity of this system. A technique for scanning the photoelectric activity of a modified bimolecular lipid membrane is described in detail.


Theoretical and experimental studies on viscoelastic properties of erythrocyte membrane.

The deformation of a portion of erythrocyte during aspirational entry into a micropipette has been analyzed on the basis of a constant area deformation of an infinite plane membrane into a cylindrical tube. Consideration of the equilibrium of the membrane at the tip of the pipette has generated the relation between the aspirated length and the dimensionless time during deformational entry as well as during relaxation after the removal of aspiration pressure. Experimental studies on deformation and relaxation of normal human erythrocytes were performed with the use of micropipettes and a video dimension analyzer which allowed the continuous recording of the time-courses. The deformation consisted of an initial rapid phase with a membrane viscosity (range 0.6 x 10(-4) to 4 x 10(-4) dyn.s/cm) varying inversely with the degree of deformation and a later slow phase with a high membrane viscosity (mean 2.06 x 10(-2) dyn.s/cm) which was not correlated with the degree of deformation. The membrane viscosity of the recovery phase after 20 s of deformation (mean 5.44 x 10(-4) dyn.s/cm) was also independent of the degree of deformation. When determined after a short period of deformation (e.g., 2 s), however, membrane viscosity of the recovery phase became lower and agreed with that of the deformation phase. These results suggest that the rheological properties of the membrane can undergo dynamic changes depending on the extent and duration of deformation, reflecting molecular rearrangement in response to membrane strain.


Shear breakage of DNA.

Determinations were made of the mean length of fragments produced after shearing long (greater than 100 kb) native Hela DNA in a VirTis homogenizer. (VirTis Co., Inc., Gardiner, N.Y.). The mean length (L) is a function of the speed of rotation of the homogenizer blades (omega), time of shearing (t), water concentration ([H2O]), solvent viscosity (eta), temperature (T), and energy of activation (E*), but not a function of the initial length so long as the starting molecules sustain an average of three or more breaks. The relationship of the parameters is expressed by the equation L = (b/omegat1/2eta1/2[H2O])eE*/2kBT, where kB is the Boltzmann constant and b is a constant of proportionality. The breakage rate constant k was determined to have the relationship k = (omega2L2eta[H2O]2/2b2)e-E*/kBT. These equations are valid throughout large ranges of the parameters, and a simple method is described which chooses a final mean length between at least 0.15 and 36 kb by choosing the appropriate shearing conditions and initial fragment length. The heterogeneity of shearing conditions within the shearing vessel permits use of the equations at all breakage rates tested. Based on the work of others using more homogeneous shearing conditions and initial fragment lengths, more complicated forms of the equations are necessary at low breakage rates but not at high ones. A proposed model of the breakage mechanism suggests that molecules with stress-induced localized denaturations break at a rate different from that for native DNA.


Dynamic light scattering from solutions of microtubules.

Calf brain microtubule protein was assembled in vitro to form dilute solutions of microtubules (240 A diameter) having lengths greater than 1 micrometer. The microtubule solutions were examined by dynamic laser light scattering techniques. The angular dependence of the correlation function leads to the conclusion that the correlation function is measuring the translational diffusion constant of the particles. The length dependence of the correlation function, however, shows that the translational diffusion constant is not being measured and that the diffusion constant for the microtubules cannot be straightforwardly determined. These results suggest that a collective property of the rods is being measured by the laser light scattering. Although specific microtubule-microtubule interactions are a possible explanation for the observed results, we present arguments that suggest that the solution can be adequately modeled as a network of entangled polymers.


Estimates of cellular mechanics in an arterial smooth muscle.

Estimates of force generation or shortening obtained from smooth muscle tissues are valid for individual cells only if each cell is contracting homogeneously and if cells anatomically arranged in series are mechanically coupled. These two assumptions were tested and shown to be valid for the pig carotid media under certain conditions. Homogeneity of cellular responses in carotid strips was estimated from the motion of markers on the tissue during K+ -induced isometric contractions. When tissues were stretched to L0 (the optimum length for force generation), there was little marker movement on stimulation. However, considerable marker movement was observed on stimulation at shorter muscle lengths, reflecting localized shortening or stretching. The mechanical coupling of the very small cells in the media was determined by measuring the dependence of cell length on tissue length. Tissues were fixed with glutaraldehyde during isometric contractions at various tissue lengths (0.4--1.1 x L0). The fixed tissues were macerated with acid and the lengths of the dispersed cells were measured. Cell lengths were broadly distributed at all muscle lengths. However, the direct proportionality between mean cell length and muscle length (as a fraction of L0) indicated that cells which are anatomically in series are coupled force-transmitting structures. We conclude that valid estimates of cellular mechanical function in this preparation can be obtained from tissue measurements at lengths greater than about 0.9L0.


Structure-strength relations in mammalian tendon.

The stress-strain relations in mammalian tendon are analyzed in terms of the structure and mechanics of its constituents. The model considers the tensile and bending strength of the collagen fibers, the tensile strength of the elastin fibers, and the interaction between the matrix and the collagen fibers. The stress-strain relations are solved through variational considerations by assuming that the fibermaxtrix interactions can be modeled as beam on elastic foundation. The tissue thus modeled is a hyperelastic material. It is further shown that on the basis of the model, the dominant parameters to the tendon's behavior can be evaluated from simple tensile tests.


The compensation of potential changes produced by trivalent erbium ion in squid giant axon with applied potentials.

The transmembrane potential of voltage-clamped squid giant axon is increased to compensate for a reduction in the rate of potassium channel kinetics when artificial seawater with trivalent erbium ion is substituted for artificial seawater. The additional potential required to produce an equivalent rise time is a measure of the potential shift produced by the erbium ions. When the kinetics of K+ channels are matched in this manner, the maximal K+ currents are larger for the larger transmembrane potential. This observation requires a functional separation of the open K+ channel and the voltage sensor for the gating mechanism of this channel.


A virial expansion for discrete charges buried in a membrane.

Recent experiments (1,2) have shown that hydrophobic ions adsorbed to lipid membranes repel each other significantly at densities as low as one charge every few tens of square nanometers. This paper shows how to calculate the mutual repulsion of a population of such ions, assumed to be discrete but free to diffuse laterally in the plane of the membrane. The results fall between those for uniformly smeared charges (the "three-capacitor" model) and those for discrete charges immobilized on a periodic lattice.


Sodium inactivation mechanism modulates QX-314 block of sodium channels in squid axons.

Blocking action of Na channels by QX-314, a quaternary derivative of lidocaine, was studied in internally perfused and voltage-clamped axons of squid. In axons with intact Na inactivation, QX-314 exhibited both a frequency- and a voltage-dependent block of Na channels. Repetitive pulsing to more positive potentials enhanced the degree of block. Both frequency- and voltage-dependent blocks disappeared in axons in which Na inactivation had been destroyed by either pronase or N-bromoacetamide treatment. These results support the notion that Na inactivation not only modulates the frequency-dependent block but also involves the voltage-dependent binding reaction between QX-314 and Na channels.


Association kinetics with coupled diffusion III. Ionic-strength dependence of the lac repressor-operator association.

The repressor-operator association is treated in a model where the repressor molecule can find its specific binding site, the operator, on a large DNA chain by performing a one-dimensional diffusion along the chain. The ionic-strength dependence is calculated by introducing a screened electrostatic potential around the DNA chain and coupling the free diffusion of the repressor in this potential to the proposed one-dimensional diffusion along the chain. The main influence on the association rate comes from the competitive binding of ions to the unspecific DNA sites. It is also demonstrated that during the time that the repressor is bound in a global sense, the diffusion along the chain will be made up of a strictly one-dimensional motion over fairly short distances, interspersed with many local dissociations during which the repressor in essence is free in solution.


Analysis of ion concentration effects of the kinetics of protein-nucleic acid interactions. Application to lac repressor-operator interactions.

The effects of monovalent and divalent cations on the bimolecular rate constant of the reaction of a positively charged ligand with a nucleic acid polyanion are analyzed for two possible reaction mechanisms. One mechanism postulates that the association reaction occurs without intermediates, and that ion effects on the rate constant result entirely from the screening of the charged reactants by ionic atmospheres of low molecular weight ions (a screening-controlled mechanism). This mechanism is analyzed by analogy with the Bronsted-Bjerrum theory for the kinetics of interaction of low molecular weight ions. The second mechanism to be considered here postulates the existence of a ligand-DNA intermediate which is in rapid equilibrium with the reactants (pre-equilibrium mechanism). Ion concentration effects on the association rate constants for the pre-equilibrium mechanism result mainly from the release of counterions from the DNA upon formation of the intermediate. Both of the above mechanisms predict that the logarithm of the association rate constant, ka, will be a linear function of the logarithm of the monovalent cation concentration, [M+] (in the absence of competition by divalent cations or anions). Knowledge of the salt dependences of ka and of the observed equilibrium constance Kobs of the ligand-nucleic acid interaction should usually be sufficient to determine whether a screening controlled mechanism or a pre-equilibrium mechanism is suitable to describe the process. If the association reaction can be described by a pre-equilibrium mechanism, the number of ionic interactions involved in the ligand-nucleic acid intermediate can be estimated. This analysis, extended to include the effects of divalent cations on screening or on the pre-equilibrium step, is applied to literature data on the salt dependence of the kinetics of the interaction of lac repressor with lac operator DNA. When the operator is present on bacteriophage lambda DNA, the observed reaction kinetics are consistent with the formation of an intermediate repressor-DNA complex in a pre-equilibrium step. On the other hand, the kinetics of association of lac repressor with synthetic lac operator fragments may be an example of a screening-controlled reaction.


Cooperative and non-cooperative binding of large ligands to a finite one-dimensional lattice. A model for ligand-oligonucleotide interactions.

A combinatorial approach is employed to calculate exact expressions for the extent of binding to a finite one dimensional lattice of ligands which cover more than one lattice site. The binding may be either cooperative or non-cooperative. It is found that the assumption of an effectively infinite lattice is generally a good one, except with relatively low concentrations of strongly cooperative ligands. An approach to analyzing experimental data is suggested which makes explicit use of the lattice length dependence of binding to extract more information about the binding parameters than can be obtained using the infinite lattice approximation. It is shown that irreversible binding cannot be viewed as a limiting case of reversible binding. The reasons for this difference are discussed, and expressions for the extent of irreversible binding are derived.


The interactions between nucleic acids and polyamines. I. High resolution carbon-13 and hydrogen-1 nuclear magnetic resonance studies of spermidine and 5'-AMP.

In 0.5 M solution at pH 7.6, interaction of spermidine and 5'-AMP is demonstrated by downfield proton NMR shifts. Shifts of ribose and adenine protons support a model in which triprotonated spermidine engages the phosphate anion with the C-3 diamine segment in a conformation to maximize interaction and the C-4 amino segment extended to interact with adenine N-7 (base anti, 2' endo, g'g' and gg nucleoside conformation). Changes in carbon-13 chemical shifts fro ribose C-5' (downfield), C-2' C-3', and C-4' (upfield) and for adenine C-6 and C-8 (upfield) support this model. In 0.006 M solution no significant changes in proton shifts and therefore no evidence for interaction was found. Spermidine and 5' -UMP (0.006 M) showed interaction at pH 10.5 (small upfield shifts in the proton nmr) interpreted as changing conformation by solvent interaction. In 0.00l M 3'-UMP at pH 10.5 small downfield proton shifts induced by spermidine are attributed to interactions with phosphate anion.


Effect of tetramethylammonium ions on conformational changes of DNA in the premelting temperature range.

The reversible conformational change of DNAs and polydeoxyribonucleotides occurring before melting was followed by circular dichroism. deltatheta/deltaT, the rate of change of ellipticity theta with temperature, was used mainly as a measure of this premelting phenomenon. If sodium ions were replaced by tetramethylammonium ions deltatheta/deltaT decreased for poly (dA) poly (dT) and poly (dA.dT) poly (dT.dA), but increased for poly (dG.dC) poly (dC.dG). DNAs of different base composition showed no more premelting (deltatheta/deltaT approximately 0) even at low molarities of TMACl provided the Na/TMA ratio was very small. For all cases studied the theta values at 0 degrees C and at a given ionic strength were smaller in NaCl than in TMACl. When studying the series of ammonium ions from NH4+ to (C2H5)4N+, the deltatheta/deltaT values first decreased, going through zero with TMA+ ions, and then increased again. A tentative and qualitative explanation of our results can be given: (a) Hydration of the polymers increases in presence of TMA ions and their average stability decreases; locally, however, (AT) pairs are preferentially stabilized by TMA ions owing to a specific interaction at the level of O2 of thymine. (b) In order to explain the different behaviour of (AT) polymers and DNA, it is assumed that only the B structure is able to accommodate TMA ions in the small groove of the double stranded helix.


Structural evidence on DNA carcinogen interactions. N-acetoxy-N-2acetylaminofluorene binding to DNA.

Linear dichroism (LD) gives useful information on the interaction between DNA and the directly acting carcinogen N-acetoxy-N-2acetylaminofluorene (AAAF). In 50% methanol solvent with low ionic strength only a weak complex (van der Waals) appears. However, above 40 degrees C strand separation takes place and a covalent aminofluorene complex forms. After renaturation a characteristic positive LD band is observed at 306 nm. The average angular orientation of the long-axis of the fluorene moiety (47 degrees to the local helix axis) is inconsistent with intercalation. It can be explained for instance by a free rotation around a C(DNA)-N(aminofluorene) bond or by a major groove site. The occupation density was 1--2 aminofluorene residues per 100 bases. With native DNA, AAAF slowly forms a covalent complex which has a negative LD at 307 nm. The orientation (70--90 degrees) is consistent with steric direction by the strand.


Two components of extracellularly-recorded photoreceptor potentials in the cephalopod retina: differential effects of Na+, K+ and Ca2+.

The ERG of the isolated, superfused half-eye of the cephalopod Sepiola atlantica, evoked by a brief (10 micro second) light flash, has been studied by recording intraretinal potentials with glass microelectrodes. The intensity-response characteristics of the potentials recorded at an electrode fixed at the surface (Vs) can be fitted by a simple equation derived from an equivalent circuit model based on a sodium conductance increase mechanism. Raising the external potassium level reduces the maximal response (deltaVm), but does not alter the half-saturation intensity value (I0). Reducing external sodium does not affect deltaVm, but increase I0. Reducing external calcium also does not affect  delta Vm, but decrease I0. These effects are adequately described by the model if it is also assumed (a) that changing the external sodium does not significantly alter the transmembrane sodium gradient, and (b) that sodium and calcium ions compete for the sensitivity control mechanism. Differential-depth recording between the fixed electrode at the surface and another electrode that could be moved into the retina revealed that the two component appearance of the transretinal ERG arose from the superposition of two vitreal-negative waveforms. An initial "fast" component was mainly recorded in the photoreceptive distal segments while a "slow" component was prominent in the more proximal regions of the retina. Perfusion with high K+ salines resulted in a decrease in the amplitudes of both fast and slow components of the response whereas reducing external Na+ reduced the amplitude of the fast component at all light intensities but reduced the amplitude of the slow component only at low intensities. The amplitudes of both the fast and slow components increased on reducing external calcium, but the rate of rise and fall of the fast component was independent of external calcium. The rate of rise of the slow component was also independent of the external Ca2+ level but a minimum in the recovery time (tF) was shifted to a lower intensity value at lower calcium concentrations. The shift of the minimum was to a higher intensity value with lowered sodium perfusing solutions. On the basis of the differential sensitivity of the two components to ion changes, as well as stimulus intensity and intraretinal distribution of the components, it is suggested that they reflect two distinct processes in the light-evoked potential of the photoreceptor cells.


Proteolysis and flash photolysis of bacteriorhodopsin in purple membrane fragments.

Pronase treatment of aqueous suspensions of purple membrane fragments from H.halobium leads to the cleavage of bacteriorhodopsin. The protein fragments remaining in the membrane after treatment with relatively small concentrations of enzyme (2% w/w) in normal daylight range in molecular weight from 20,000--21,000 daltons, indicating that cleavage occurs mainly near the extremities of the protein chain. At higher enzyme concentrations the relative amounts of protein fragments having smaller molecular weight increase. Generally, the relative loss of retinal chromophore is larger than that of protein and thus the retinal binding site seems to be located near one of the chain ends that is cleaved off by enzyme. Irradiation with white light during the time of proteolysis (at both low and high enzyme concentrations) results in extensive cleavage, so that under certain conditions no high molecular weight components can be detected in SDS-polyacrylamide gels. It, therefore, appears that parts of the bacteriorhodopsin chain become more exposed to enzyme digestion when the purple membrane is illuminated. Enzyme treated aqueous purple membrane fragment suspensions still show photocycle activity. The main consequence of proteolysis is a pronounced appearance of biphasicity in the decay of M412 and the regeneration of bR570. Simultaneously the yield of O660 is reduced. As with untreated purple membrane, the correlation between the rates of decay of M412 and regeneration of bR570 is greatest when the yield of O660 is lowest.


Transport of lipids through water as exchange mechanism between two liposome populations.

A theoretical description of lipid exchange between two liposome populations as a linear transport phenomenon is presented. As a special case of the general theory in which two different lipids are simultaneously exchanged we also obtain formulae for "one-way" lipid transfer. The case in which the lipids differ only by a radioactive label is also included in a natural way. The predictions of the model are shown to be in excellent agreement with two recent experiments. This provides additional strong support for the hypothesis that lipid transfer takes place mainly through the aqueous phase.


Stacking interaction of nucleobases: NMR investigations. III. Molecular aspects of the solvent dependence.

The stacking interaction between nucleic acid bases has been investigated by the determination of the self-association of 6-methylpurine in various mixtures of water and nonaqueous solvents in order to elucidate the solvent effect. The parameters of stacking association as well as of local solvent-solute interactions have been measured by means of NMR technique. The influences of local hydration and of solvent-solvent interactions on the stacking ability are discussed.


Laboratory-scale production of acetoin plus diacetyl by Enterobacter cloacae ATCC 27613.

Conditions for the laboratory-scale production of acetoin plus diacetyl by Enterobacter cloacae ATCC 27613 were studied. Thirty-five g acetoin plus diacetyl/50 g sucrose were obtained when fermentation was carried out in 2.5 liter medium containing 12.5 g peptone and 12.5 g yeast extract, at pH 7.0, in a 5 liter conical flask on a shaker (240 rpm) at 28-30 degrees C for 48 hr. Recovery of pure diacetyl was 85% of the total acetoin plus diacetyl.


Recognition in adult patients of malformations induced by folic-acid antagonists.

Three patients are reported, two of whom had mothers who revealed ingestion of abortifacient drugs during pregnancy. All patients resemble one another and those described earlier with malformations that were probably either aminopterin- or methotrexate-induced. It is likely that Patients I and II have abnormalities associated with the teratogenic action of these folic-acid antagonists. The etiology of Patient III's defects remains uncertain.


The facio-genito-popliteal syndrome.

In summary, we have presented data supporting the variable expression of an autosomal dominant gene that produces a spectrum of facial, genital, and musculo-skeletal abnormalities. We are not in the position to completely rule out genetic heterogeneity but on the basis of the data presented we feel confident in stating that the popliteal pterygium syndrome, in most cases, is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance.


Aplasia of the Müllerian system: evidence for probable sex-limited autosomal dominant inheritance.

Thirteen unrelated females ranging in age from 15 to 28 years old have recently been recognized to have aplasia of the müllerian duct derivatives. They presented one or both of two major complaints: amenorrhea and difficulty or pain on attempted sexual intercourse. Clinically all cases were characterized by absence of vagina and failure to palpate the uterus rectally; normal mature external genitalia; normal stature, intellect, hearing and vision; normal secondary sex characteristics including breast development, pubic and axillary hair. Libido was normally preserved and sexual self-identification was unambiguously feminine. Apart from the pelvic findings, the affected individuals were phenotypically unremarkable women. Laparoscopic examination revealed absent uteri, absent or rudimentary tubes, but normally developed ovaries. Cytogenetic evaluation disclosed normal female karyotypes with normal banding patterns on all patients. Endocrine investigations revealed female cyclic pattern consistent with normal ovarian endocrine function. Biopsy specimens on the ovaries of 5 patients were histologically unremarkable with evidence of normal follicular activity. Investigation of the families of these patients revealed similarly affected individuals in 10 families. In 8 of these the pattern of transmission was consistent with autosomal dominant inheritance with sex limitation to XX individuals; in 2 the distribution of affected individuals was compatible with either sex-limited autosomal dominant or autosomal recessive inheritance. Though unlikely, polygenic inheritance remains a formal possibility. In 3 families, apart from the propositae, no other affected females were ascertained. In these, the etiology is either teratogenic or genetic with autosomal dominant or recessive inheritance, and sex limitation to females. Three further cases with partial aplasia or the Rokitansky-Kuster-Hauser syndrome (RKHS) were ascertained. No other similarly affected individuals were encountered in their families.


[Electrical potentials of the cat parotid gland monitored from the body surface].

Correlation of the changes of the electrical potential on the parotid gland surface and on the corresponding body surface in the stimulation of the secretory nerves and under other effects was shown in cat. The absence of the potential gradient with the electrode on the body surface confirmed the macrostructure of the total field of the salivary gland. The experimental results point to the glandular origin of the electrical responses on the body surface.


[Representation of the phrenic nerve in the cerebral cortex].

Electrical stimulation of the phrenic nerve gives rise to early (with latency of 8--12 msec) and late (with latency of 30--40 msec) surface-positive potentials in the contralateral sensory-motor cortex of cats. The early potentials occur only in two discrete areas of the rostral part of the posterior sigmoid gyrus: just rostromedial to the post-cruciate dimple and at the lateral tip of the cruciate sulcus. In contrast to the early potentials, the late ones can be recorded not only from the whole surface of the posterior sigmoid gyrus but also from the anterior sigmoid gyrus. The early potentials presumably appear on stimulation of group I muscle afferents. It is possible that impulses reaching the cerebral cortex from the phrenic nerve participate in provocation of the sensation of breathlessness.


[Age and the relationship between temperature and the cell membrane repolarization process in the adrenal cortex].

In experiments on the isolated adrenal glands of rats aged 5 and 28--29 months no age-related differences in the membrane potential were found in the cells of zona fasciculata of the adrenal cortex. The temperature dependence of the membrane repolarization of the adrenal cortex zona fasciculata was was investigated within the range of 7--17 degrees C following preliminary cooling of the adrenal glands. The calculated value of the temperature coefficient of the repolarization process was much higher in old than in young rats. With ageing the reactions with high energy activation made a greater contribution to the total balance of processes determining membrane repolarization in the adrenal cortex cells.


[Reflex reactions of the spinal cord in hypoparathyroidism].

Experiments were carried out on parathyroprival cats with varying degree of motor disorders. Disturbed reflex activity of the spinal cord was characterized by activation of motoneurons and the system of intercalary neurons, abatement of the phenomenon of posttetanic potentiation as well as by conductivity facilitation in the reflex arch. Marked tetany was accompanied by diminution and, in some cases, by complete absence of monosynaptic responses with enhancement of polysynaptic reflex discharges. After intravenous injection of calcium chloride the test animals showed a tendency to recovery of the reflexes recorded. It is concluded that the disordered functional state of the spinal cord segmental apparatus is mainly due to hypocalciemia and may be one of the causes of parathyroprival tetany.


[Changes in the content of eosinophils, corticosterone and catecholamines during liver regeneration following resection].

Experiments on albino rats demonstrated changes in the-blood eosinophil level, as well as in the content of catecholamines and corticosterone in the plasma, the adrenal glands, and the heart following partial hepatectomy. Phasic character of the hypophysis-adrenal system responses to resection and the processes of the liver regeneration was revealed, and this is reflected in the eosinophil level.


[Thyroid gland reaction to experimental resection and complete removal of the pancreas].

The end or the central part of the pancreas was resected or pancreatomy was performed in dogs. The morphological and functional state of the thyroid gland was investigated by the histological, histochemical, and morphometrical methods at different postoperative periods. The changes revealed showed structural and functional alterations of the thyroid gland to be dependent primarily on the type of surgical interventions on the pancreas. Resection of the terminal sections caused temporary and insignificant changes in the thyroid gland, but complete removal of the pancreas was followed by acute dystrophy and atrophic changes in the thyroid gland, this leading to the functional exhaustion.


[Effect of protracted infusions of polyglucin during the resuscitation period on metabolic and morphologic characteristics of the brain].

Polyglucine infusions (10 ml/kg) during the first 10 days of postresuscitation period after 4-hour hypovolemic hypotension promotes normalization of general RNA content, quick mobile protein fractions, corresponding prealbumins, albumins, postalbumins, ceruloplasmin, transferrin, and alpha-globulins. Macromolecular protein fractions beta- and gamma-globulins--remained considerably changed: beta-globulins doubled, and gamma-globulins decreased 1.7-fold. Acid phosphatase specific activity increased in the postmitochondrial supernatant by 53%; an increase in the acid phosphatase activity was revealed in the neurons, glia, and vascular endothelium. The amount of Purkinje's cells in the cerebral cortex in the experimental group did not differ essentially from the control values. Thus, the results obtained emphasize the importance of prolonged polyglucine infusions together with other resuscitation measures in the treatment of hypovolemic states.


[Adrenaline lipolysis in the adipose tissue of rats with spontaneous and renal hypertension].

The lipolysis in the adipose tissue obtained from adrenalectomized and intact rats with spontaneous and renal hypertension and from rats of corresponding control groups was studied. Lypolysis under the effect of epinephrine and without it was evaluated by the concentration of nonesterified fatty acids in the tissue and by glycerine release into the incubation medium (in vitro). Reaction of the adipose tissue in response to epinephrine was the same in hypertensive and control rats when the adrenal glands were intact. Preliminary adrenalectomy which eliminated the corticosteroid action reduced the epinephrine lypolysis in the adipose tissue in control normotensive rats, but not in hypertensive rats ("facilitation" of catecholamine action on the lypolysis mechanism). This phenomenon is regarded by the authors as the alteration of plasmatic membranes adipocytes function in hypertensive animals. The adrenal cortex hypertrophy and the enhanced corticosteroid secretion in the types of hypertension studied are therefore considered as the measure for compensation of disturbances of the cell plasmatic membranes function in the internal environment tissues.


[Mechanism of methylation of DNA bases by symmetrical dimethylhydrazine].

The effect of disulfiram on the alkylation of purine bases of the liver and colon DNA in rats exposed to 1,2-dimethyl-hydrazine-3H has been studied. The pretreatment of rats with disulfiram which inhibits the DMH N-oxydation was found to prevent the methylation of guanine with DMH. However, the radioactivity was readily incorporated into normal (non-methylated) purine bases during synthesis. The lack of DNA methylation in animals pretreated with disulfiram indicated carbonium ion rather than methyl radical to alkylate DNA.


[Changes in the composition of heart proteins during early ontogenesis in normal subjects and in the presence of reduced uteroplacental blood flow].

The heart was studied on the 11th, 12th, 14th, 16th and 18th days of the rabbit embryo development under normal conditions and in decreased uteroplacental circulation. Under normal conditions the heart weight/embryo weight ratio was particularly high during the intensive development of hemodynamic functional "embryo -- placenta -- uterus" system (on the 12th and the 14th day), and then this ratio decreased. An increase of the total heart nitrogen and alterations in fractional composition on account of increase of contractile proteins and stroma proteins was particularly high by the 18th day. In pathology a decrease of the embryo and heart weights was noted in the course of all the days of the experiment. By the 18th day the heart/embryo weight ratio suggested the beginning of spontaneous rehabilitation due to gradual increase of the uteroplacental circulation. However, the total nitrogen in the heart in all the test groups remained the same as in control or increased, this pointing to the heart dehydration. Changes in the fractional composition of the heart proteins indicated deep biochemical disorders in it, and this could serve as one of the causes of the heart functional derangement.


[Porphobilinogen biosynthesis from delta-aminolevulinic acid by the internal organs of white rats].

The capacity for porphobilinogen (PBG) biosynthesis from aminolevulinic acid (ALA) in the homogenates of the lung, heart, liver, kidney, pancreatic and small intestinal tissues of 77 albino rats was determined, and all the mentioned organs were found to be capable of PBG biosynthesis. The greatest ALA dehydratase activity was found in the tissue of the liver, then -- in the order of decreasing activity -- in the tissues of the kidneys, lungs, pancreas, small intestine, heart and spleen. On addition of lead solution to the synthesizing system a significant reduction in the activity of the enzyme was revealed in the tissue of the liver; the activity was unchanged in the kidney tissue. No changes in the toxic effect of lead were found on simultaneous addition of lead and D-penicillamine.


[Cholesterol biosynthesis in the blood of rabbits with experimental atherosclerosis].

Blood of normal rabbits and those on atherogenic cholesterol diet was incubated with 2--14C-acetate of sodium. After incubation cholesterol and its precursors -- squalene and lanosterin -- were found and identified in the non-saponified fractions of leukocytes and platelets. The maximum specific activity was revealed in cholesterol, next in turn were lanosterin and squalene of leukocytes both in the normal rabbits and in those with atherosclerosis. In platelets the label was mainly accumulated in lanosterin.


[Effect of nonachlazine and oxyphedrin on a focus of myocardial ischemia].

In experimental angina pectoris of dogs developed by Sze-keres et al, 1976, and modified by the authors it was shown that nonachlazine in doses of 3 and 5 mg/kg decreased or even completely prevented the ST segment elevation on the epicardial electrogram from the focus of myocardial ischemia. Oxyphedrine in doses of 0.05, 0.1, and 0,3 mg/kg had no such effect. In doses of 0.1 and 0.3 mg/kg the drug aggravated the epicardial electrogram.


[Effect of insulin and prednisolone on the transport of organic substances in the kidneys of dogs].

Single injection of insulin (1 AU/kg) enhanced maximal glucose absorption, cardiotrast secretion and decreased sodium excretion without any changes of glomerular filtration in dogs. These effects depended on the direct action of insulin so far as the effect is expressed in the kidney only at the side of infusion when the preparation is administered into one of the renal arteries. Prednisolone had no significant effect on the glucose and cardiotrast transport in single injection (3--4 mg/kg) and 10-day (1.5--2 mg/kg daily) injections.


[Effect of intravenous administration of calcium chloride on the effectiveness of infusion therapy of acute massive blood loss].

In acute experiments on 70 dogs at the late stage of the organism response to acute massive blood loss hemotransfusions, infusion of decalcinated gelatinol, or of a 0.9% solution of sodium chloride were incapable of preventing death of the animals. Intravenous infusions of a 10% calcium chloride solution following such therapy promoted survival of most of the animals.


[Bone marrow microenvironment transfer by clones of stromal mechanocytes].

Clones of bone marrow stromal fibroblasts harvesed from monolayer cultures of mice and guinea pig bone marrow cells are transferring the hemopoietic microenvironment when transplanted in vivo. Individual fibroblast clones form bone tissue and create the microenvironment for erytroid, myeloid and megakariocyte differentiation of hematopoietic cells simultaneously.


[Role of the liver in the development of dyshormonal diseases of the mammary glands in rats].

Intermittent administration of CCl4 combined with permanent illumination resulted in a decrease of the frequency of mastopathy and of the mammary gland tumours in immature female rats and prolonged the period of their appearance. It is suggested that during regression of cirrhotic lesions the liver can lose its capacity to activate estrogens.


[Role of the spleen in regulating thrombocytopoiesis].

It was shown in experiments on dogs that splenectomy resulted in thrombocytosis, as well as in a decrease of the adhesive-aggregation capacity of platelets and their average life span. Daily thrombocytopoiesis was increased, and a sharp shift in megakariocytogram toward mature forms was noted. Megakaryocytes count in the bone marrow decreased. It is suggested that a factor controlling megakaryocytes cells precursors differentiation was produced in the spleen.


[Development of the response of rabbit fetal tissues to thyroxine].

Development of rabbit fetal tissues sensitivity to thyroxin was studied on the basis of changes in alpha-glycerophosphate oxidase activity in the liver mitochondria of pregnant rabbits and their fetuses to which thyroxin was administered at different stages of pregnancy. T4 administration up to the 23rd day of gestation caused an increase in the enzyme activity in the maternal liver mitochondria only, whereas in the fetus it was at the control level. From the 24th day of pregnancy an increase of the alpha-glycerophosphate oxidase activity was seen in the fetal liver mitochondria. This can be explained by the appearance of rabbit fetal tissues sensitivity to maternal thyroxin at this period of gestation, increasing by the end of pregnancy.


[Kinetics of cell proliferation in regenerating rat liver following subtotal resection].

Partial (78--80%) hepatectomy was conducted in male rats. The maximal mitotic activity of hepatocytes was seen 38--48 hours after the operation. It was found with thymidine-3H (pulse label) that the G2 period lasted 6 hours and the minimal duration of the S-period was 6 hours. During the liver regeneration after its subtotal resection there was asynchronization of the hepatocyte entrance into the S-period and mitosis, and cell retardation in the G1-and G2-periods. The mentioned changes in the hepatocyte proliferation are the results of intracellular metabolism disturbance under conditions of an excessive functional requirement.


[Rhythm of ornithine decarboxylase activity in slices of rat parotid gland].

Ornithine decarboxylase activity and the rate of protein synthesis were measured in the rat parotid gland slices incubated in vitro. A circahoralian rhythm of the enzyme activity preceding by phase that of the protein synthesis was found. These data are consistent with the assumption that ornithine decarboxylase may participate in the maintenance of the protein synthesis circahoralian rhythm in the parotid gland cells.


[Topography of the auxiliary structures of chemo- and mechanoreceptor formations in the tongues of adult rats according to scanning microscope findings].

The surface of an adult rat tongue was investigated by scanning microscopy. Structural organization of the chemo- and mechanoreceptor formations of the tongue was described and their topographic chart was drawn on the basis of the experimental material. An attempt was made to explain the functional significance of these formations.


[Role of carbohydrate-protein complexes in the organization of the microstructure of fibrous connective tissue].

Samples of the tendons and fascia subjected to the action of amylolytic and proteolytic enzymes (protorysin, trypsin) were examined by scanning electron microscopy. Degradation of the carbohydrate-protein complexes proved to bring about disappearance of the characteristic morphological signs of the collagen fibers. It was shown that a network of thin anastomosing filaments forming a framework connected with the carbohydrate-protein matrix underlay construction of the collagen fibers. As assumed, the net-like structure was a common principle in the structural organization of fibrous connective tissue.


[Effect of hydration and dehydration of the bodies of animals on bioenergetic and mediator processes in the neurosecretory cells of the anterior hypothalamus].

Activity of redox enzymes, and of mediator-inactivated enzymes in the neurosecretory cells of the anterior hypothalamus under hydration and dehydration conditions of the rabbit organism was investigated by the histochemical methods. The activity of the Krebs' cycle enzymes and of the electron transport system responded by an increased activity to dehydration and by decreased one to hydration. The activity of alpha-glycerophosphate dehydrogenase and glucose-6-phosphate dehydrogenase increased as compared to the control in both cases. Changes in the monoamine oxidase activity diminished in dehydration and rose in hydration. As to acetylcholinesterase -- the changes in its activity had a reciprocal character.


[Specific secretory inclusions in the pyloric portion of the mouse stomach].

Aldehyde-fuchsin stainable secretory granules were found in the epithelium of the pyloric part of the mouse stomach. The granules are PAS-negative and nonstainable with lead hematoxylin. In intact mice only a small zone of the pylorus is engaged in production of such granules. Alpha-adrenergic stimulation causes expansion of the zone containing the granules. In mice exposed to general chilling after the propanolol injections there is a sharp extension of the zone in which the specific granules are distributed.


Evaluation of non-stimulated nitroblue-tetrazolium test in patients with malignant lymphomas.

The NBT-test was performed in 54 patients with Hodgkin and non-Hodgkin lymphoma showing no bacterial infection exept for one case. 18 patients presented, at onset of the disease, a number of neutrophilic NBT-reducing granulocytes at pathological levels (greater than 12%). In order to evaluate the influence of cytostatic drugs on NBT-test serial blood samples were taken during polychemotherapy in 17 patients with lymphoma. In our experience, cytostatics (COPP) do not necessarily lessen NBT-reducing activity of granulocytes. The results suggest that the NBT in malignant lymphomas could not be used as an indication of bacterial infection.


[Primary shape change of platelets in vitro (author's transl)].

Studies with interference contrast microscopy reveal that platelets undergo a typical shape change within 30--60' after venepuncture, i.e. swelling, formation of large tentacles, tiny protrusions and vesicles at the platelet surface. This "shape change" can be observed in citrated blood and PRP, heparinized blood and EDTA-blood as well. It is enhanced by low incubation temperatures (4 degrees C, 10 degrees C) and delayed at 37 degrees C as compared with room temperature. An increased number of primarily shape changed platelets is found if platelets are strongly mechanically irritated at blood sampling. The shape change is partly reversible in vitro, it is completely or almost completely reversible in vivo. Some antiaggregating agents inhibit the in vitro shape change at varying degrees (Bencyclan, SH 869  greater than ASA greater than D-Propranolol). The shape change is partly inhibited after oral or i.v. administration of ASA. A typical transformation of platelets into "spheric" forms can be observed following the addition of Bencyclan, SH 869 and D-Propranolol to PRP in vitro. The spontaneous "primary shape change" which occurs in PRP or blood after blood sampling is probably different from the secondary ADP-induced shape change. The primary shape change may influence the results of different platelet function and aggregating tests. The shape change kinetics of "healthy" subjects and patients with Hodgkin's disease differ significantly. The described method may gain more clinical interest in the future.


[Secretory aspects and differentiation of B cells of the synovial membrane in mice].

The intimal layer of the synovial membrane (SM) includes essentially 2 cell types: A-cells with macrophagic functions and B-cells generally assimilated to fibroblasts. A comparative study of the B-cells in some mammals revealed that these cells possess specific polypeptidergic secretory features which are particularly clear in the mouse. The B-cells, which are more numerous than A-cells and often entirely line the synovial cavity, probably play an essential role in the metabolism of the SM. A study of the development of the SM in the mouse shows that the primitive cleft is formed before any differenciation of the synovial mesenchyme through degradation of the fine mesenchymal layer in direct contact with the chondrogenic layers. The differenciation of the SM coincides with the clarification and dilatation of the synovial cavity. As soon as the SM organizes into intimal and sub-intimal layers (6 days of life), the 2 intimal cell types can be identified by their macrophagic (A-cells) and secretory (B-cells) features. The B-cells, however, only show an appreciable content of typical secretory vesciles at 13 days. Our ultrastructural observations suggest that the B-cells are the source of some specific proteins of the synovial fluid and that they participate in the maintenance of the peculiar structure of the intimal interstitial tissue.


[Comparative study of afferent connections in the habenula in rats and cats after injection of horseradish peroxidase].

The habenular complex of 11 cats and 13 rats was injected with horse Radish peroxydase (HRP) (30% solution, 0,05--0,4 microliter). Retrograde labelling of cells was visualized after a survival period of 24 to 48 hours by means of the method of Lavail et al. (1973). The resultats obtained with this method suggest significant species differences regarding the habenular afferents in cats and rats. One of the most striking differences is that the entopeduncular nucleus of the cat contains very few HRP labelled cells after lateral habenular nucleus injection in comparison to the entopeduncular nucleus of the rat which can be shown to be the major source of afferents to the lateral habenular nucleus by the same method.


[Study of polysaccharides present in palatal shelves of rats shortly before their fusion].

When slices of rat palatal shelves removed by dissection from 16 days 8 hours old fetuses, just before fusion, are treated by the periodic acid Schiff reaction (PAS), colored substances may be detected especially in the epithelium of the potential fusion zone; these substances are normally observed at the free surface of the epithelium. Our histochemical research, realized with the aid of the photonic microscope and of the transmission electron microscope, shows that most of the PAS positive material consists in glycogen; at the surface, this polysaccharide remains in the cytoplasm of flat degenerating cells and cannot be confused with the "cell coat" which presents no particularity, at this level, after demonstration by ruthenium red and by lanthanum nitrate.


[Tridimensional vestibular study of important aspects of the human frontal region during growth].

The frontal bone, during its growth, has been analysed in the three dimensions of space, oriented by the vestibular axes of reference by the means of the coordinates of its noteworthy points, its notable linear measures and the distance of its elements relatively to the center of the axes. Its variability has also been explained by the construction of equiprobable ellipses of tolerance. These ellipses show the part due to growth and the part due to variation, the latter being more pronounced on the level of the dome of the skull than on the level of the basis.


[Ontogenic development of the surface of craniofacial sagittal angular sectors in man and chimpanzee].

By means of a technique for measuring surfaces by direct reading, six angular sectors have been studied (3 for the face and 3 for the skull) at various ontogenic periods of Man, common chimpanzee and dwarf chimpanzee. The growth curves have been drawn for absolute values and for relative values. They show a certain evolutive parallelism between the frontal bone and the parietal bone, and between the face and the mandible, with a special fate for the occipital bone.


[Presence of cell fusions in human malignant glioma].

The observation in malignant glioma of multinucleated cells possessing nuclei at different stages of the cell cycle, micrographs never encountered in benign glioma, led us to propose the hypothesis that, at least in this series of tumors, cell fusion was a criterion of malignancy. We tried to confirm this hypothesis by grafting malignant human gliomas into the brains of new-born mice for the purpose of making hybrid cells possessing human and murine characteristics conspicuous, we found these same multinucleated cells in these grafts. We demonstrated the hybrid nature of these cells by means of a fluorochrome, 33,258 Hoechst, which has the property of fixing itself selectively in the chromocentres of mice. We found quenched human cells, very fluorescent mice cells, and hybrid cells with syncaryons presenting a mixture of fluorescent and quenched chromocentres. These malignant cells are therefore capable of fusing with normal cells at a frequency which remains to be determined.


Cerebral malakoplakia.

A newborn male developed diffuse myoclonus. Right frontal craniotomy revealed a thin hemispheric mantle and a cyst communicating with the right lateral ventricle. In the biopsy of the cyst wall there were the characteristic findings of malakoplakia, granulomatous inflammation with von Hansemann histiocytes and Michaelis-Gutmann bodies. The child died at 1 1/2 years of age.


Changes in auditory perception in the menstrual cycle.

In a attempt to specify the critical functional components involved in the menstrual fluctuation of the upper frequency limit of the binaural beat we have obtained evidence of better performance in a variety of tasks at period and mid-cycle than at other times. These tasks include detection of physical beating, low-frequency octave matching, and lateralisation of clicks having interaural time delays in the 100 musec region. Continuous pure-tone frequency discrimination did not show a significant cyclical pattern overall but there was a tendency for low-frequency discrimination to show the described pattern. An attempt is made to reconcile some of these results with those of Wynn (1973) on absolute pitch, in terms of possible physiological and biochemical correlates. Three conclusions can be drawn: (1) The representations both of low-frequency tones and of the interaural time differences involved in some localisation tasks are particularly susceptible to alteration by the biochemical changes of the menstrual cycle: (2) The changes underlying perceptual variations are multiple, and inevitably confounded in any single task. (3) The distinction between the sensitivity and bias parameters of performance appears to be valuable in specifying menstrual effects. Several further lines of enquiry are suggested, but methodological difficulties in cycle research make it likely that more progress will come from better understanding of the physiological bases of psychoacoustic tasks using other methods, rather than from investigating natural menstrual effects.


A new theory of cochlear function based on quasi quantum considerations.

A new theory of cochlear function is proposed. It locates the 2nd filter in the IHC which are regarded as biological resonators. The OHC play no part in frequency discrimination. Confirmation of the theory is derived from the fact that it offers plausible explanations for many otherwise unexplained paradoxes in the distribution of cochlear microphonics. It also explains why combination tones only occur in very restricted frequency regions, and it predicts their relative audibility. Finally a test is proposed whereby the theory must stand or fall.


A theoretical approach to the loop induction system.

In a study of the properties of hearing aids with loop induction coils, it was observed that a group of high-powered aids used primarily for their extended low frequency responses had poor low frequency responses when used on loop input. The consequences of these characteristics are discussed. To asisst in the problem of loop design, equations are presented expressing the magnetic field strength at any point in terms of the electric current and loop location. These were found to predict the field strength with good accuracy, and may be used to calculate the field strength and its variation, produced by almost any loop configuration.


[Genetics and society].

With the use of mathematical models it was attempted to calculate the probability of eugenic or dysgenic effects as a consequence of medical treatment and of procedures used in human genetics. 1. Modern medicine will cause mainly an increase in multifactorial malformations and diseases. But the resulting burden for the general public most probably will be considerably smaller compared to to-day expenses for the care of those affected with chronic inherited diseases. 2. For many families concerned prenatal diagnosis is the only reasonable approach to obtain healthy children of their own. In order to reduce substantially the number of affected individuals prenatal diagnosis would have to be applied as a prospective mass screening which in many cases would be too demanding.


[Structure of interphase chromosomes].

The chromosomes are based on a structural unit, the nucleosome. It consists of a protein care and about 200 base pairs of DNA arranged on its outside in a regular way, probably as a spiral. The protein care is a histone octamer containing two copies each of the four main types of histones, H2A, H2B, H3, and H4. The shape of the nucleosome ressembles a short wedge shaped cylinder of 110 A x 110 A x 60 A. The nucleosomes are closely spaced and linked by the continuous DNA. Since the fifth histone, H1, stabilizes the interaction of adjacent nucleosomes, it is considered to be involved in the formation of higher structural orders in the chromosomes.


[Ultrastructure of human chromosomes].

The structural elements of chromosomes are chromatin fibrils of about 100 A diameter (see the preceeding paper by NOLL). The chromosomes of most eukaryontic species are single stranded. Each chromatid consists of only one chromatin fibril and thus only of one DNA-double helix. In interphase the chromatin fibril is loosely and irregularly folded. With the onset of mitosis it becomes more densely but still irregularly packed to form the long and thin prophase chromosome. Metaphase chromosomes are formed by a coiling of the thin prophase chromatids (major coils). Chromosome banding can be produced with the aid of specific fluorescent dyes or by special pretreatments before staining. The banding is due to many factors but an important one is the different AT- ad GC-content of bandlike regions. In very thin chromosomes such as premature condensed chromosomes the bands are very fine and can be correlated in size to the chromomeres of polytene giant chromosomes.


Congenital chromosome anomalies.

The introduction of chromosome banding techniques has led to the detection of a greatly increased number of congenital chromosome anomalies, especially those involving duplication and/or deficiency of short segments of chromosomes. Of most widespread use are the general banding techniques: Q-, G- and R-banding. Special staining methods provide help in certain cases. These include C-banding, G11 staining of some C-bands, Ag-staining of active ribosomal RNA gene clusters, differential staining of sister chromatids and differential staining of early or late replicating bands. Every banding method that can be produced by a fluorescent or nonfluorescent dye can be duplicated by the use of antinucleoside antibodies, providing strong support for the idea that the organization of DNA of particular nucleotide base composition and sequence is responsible for chromosome banding. As a result of the application of banding methods, a wealth of structural chromosmoe changes have been detected. In the balanced form, as translocations or inversions, these may have no effect on their carrier. However, such carriers have a markedly increased risk of having children with congenital chromosome anomalies. Most of these can be diagnosed prenatally using the generally available banding techniques.


Genetic analysis of cell malignancy--evidence from somatic cell genetics.

When normal nontumorigenic cells are fused with tumorigenic cells some of the resulting hybrids are nontumorigenic in respect to their ability to grow in immune-deficient nude mice. Comparison of the chromosome content of nontumorigenic with tumorigenic hybrids, as well as with the cells of tumors which develop from the latter, reveals that in normal human x tumorigenic Chinese hamster hybrid crosses, two specific human chromosomes of the nontumorigenic parental line are very likely responsible for the suppressive effect. In some other hybrid crosses these and additional human chromosomes also seem to cause suppression. These findings suggest that a tumorigenic cell has lost at least two and possibly more gene functions which determine normal growth responses. The chromosomes from a normal cell can apparently correct these defects, although it is not yet clear if this is true genetic complementation or due to introduction of other genes which control cell growth or a cell's response to environmental growth regulatory stimuli. These findings led support to the view that genetic alterations are important in the process of malignant transformation and allow the development of a working hypothesis for the possible mechanisms involved. Some findings of other workers in this area also suggest that malignant cells may be producing some cell membrane proteins which are different from those of nontumorigenic cells. If this turns out to be true then it may ultimately be possible to develop immunotherapeutic procedures, i.e., to produce tumor cell specific antisera.


[Early diagnosis of neoplasms].

Cancer is a generic term for a variant manifestation of life caused by genetic mutations of somatic cells. It is not only carcinogenesis which is basically a genetic phenomenon, but also tumor progression which can be influenced by various genetic factors. A group of tumors is known to be inherited in a Mendelian fashion. In addition a great number of single gene disorders is associated with the development of maligne tumors. The further study of these diseases will allow new insights into the fundamental mechanisms leading to clinical cancer. In this respect a series of immunodeficiency diseases is of particular interest. Several organ tumors which seem to occur more frequently in relatives of tumor patients are of practical importance. A more sophisticated classification of these tumors may illuminate their genetic behavior. The geneticist cannot only define groups of individuals with a high cancer risk, but he can identify genetic, e.g. chromosomal, aberrations of cancerous cells which enables him the early detection of neoplasia.


[Future problems of medical genetics].

The following future problems of medical genetics can be identified: 1. Description and analysis of new genetic diseases, especially in developing countries 2. Biochemical analysis, especially of dominant diseases 3. Elucidation of genetic causes for common diseases and their interaction with specific environmental factors (drugs and other chemicals). In the near future it will be possible to provide every newborn with a list of specific advises for prevention of health hazards; this list will be based on the genetic polymorphisms and their impact on health and disease.


The effects of acetylcholine on the membrane and contractile properties of smooth muscle cells of the rabbit superior mesenteric artery.

1 Effects of acetylcholine (ACh) on the membrane potential and mechanical properties of rabbit superior mesenteric artery were investigated by the use of microelectrode and isometric tension recording methods. The membrane potential was -62.5 +/- 3.0 mV (s.d.). The maximum slope of the membrane depolarization produced by tenfold increase in [K](0) plotted on a log scale was 48 mV. Excess [K](0) and low [K](0) depolarized the membrane and produced contraction (contracture). The minimum depolarization to produce contraction was 10 mV.2 Low concentrations (10 and 100 ng/ml) of ACh hyperpolarized the membrane. Increased concentrations of ACh (1 and 10 mug/ml) hyperpolarized the membrane further in adult rabbit, while increased concentrations of ACh produced a smaller hyperpolarization in young rabbit. These potential changes produced by ACh in immature and adult rabbits were suppressed by treatment with atropine (0.1 mug/ml).3 ACh (10 ng to 1 mug/ml) consistently generated contraction in Krebs solution. However, ACh relaxed the contraction induced by either K(+) or noradrenaline in the adult rabbit, and it enhanced contraction produced by this treatment in the immature rabbit. In Ca-free EGTA solution, the action of ACh on the mechanical response was markedly suppressed, although high concentrations of ACh still evoked contraction. However, treatment with atropine (1 mug/ml) completely prevented these actions of ACh.4 ACh-induced relaxation during either K(+)-induced or noradrenaline-induced contraction was not caused by the hyperpolarization of the membrane.5 It is concluded that ACh possesses dual actions on smooth muscle cells of the rabbit superior mesenteric artery in Krebs solution, i.e. ACh hyperpolarizes the membrane, while it consistently generates contraction. These ACh actions on the muscle cells were modified by aging.


The effects of diltiazem (CRD-401) on the membrane and mechanical properties of vascular smooth muscles of the rabbit.

1 The effects of diltiazem on electrical and mechanical properties of vascular smooth muscles of the rabbit were examined by various experimental procedures. 2 In the pulmonary artery, diltiazem (0.1 to 10 microgram/ml) did not modify the membrane potential (-56 mV), length constant of the tissue (1.47 mm) or rectifying properties of the membrane. Diltiazem (0.1 to 10 microgram/ml) did not modify the membrane potential of the mesenteric artery (-62.5 mV). 3 Diltiazem (1 to 10 microgram/ml) suppressed mechanical responses of pulmonary and mesenteric arteries induced either by direct stimulation of the muscle (1.0 s pulse) or by neural activation (0.5 ms pulse, 30 Hz and 10 s total duration). Diltiazem suppressed the contraction induced by nerve stimulation to a greater extent than that induced by direct muscle stimulation. 4 When the depolarization-contraction relationship of the smooth muscle of the pulmonary artery was observed by voltage clamp technique, diltiazem (1 to 10 microgram/ml) raised the critical membrane potential to evoke contraction from 5 mV to 12 mV, and reduced the amplitude of contraction obtained at any given depolarization level. 5 In the pulmonary artery, diltiazem (10 microgram/ml) suppressed K-induced contraction and raised the mechanical threshold, while K-induced depolarization was not suppressed. Diltiazem (1 to 10 microgram/ml) also suppressed noradrenaline-induced contraction, raised the mechanical threshold and suppressed noradrenaline-induced depolarization. 6 The vasodilator actions of diltiazem on the vascular smooth muscle were compared to vasodilator actions observed with other Ca-antagonists.


Antagonistic effect of compound 48/80 on the inhibitory actions of morphine and methionine-enkephalin on electrically-induced contractions of the guinea-pig ileum.

1 The effect of compound 48/80 was studied on the twitch-like contractions of the longitudinal muscle of guinea-pig ileum induced by electrical stimulation of intramural cholinergic nerves. 2 Compound 48/80 alone, at concentrations up to 30 microgram/ml, had no effect on the twitch contractions. The contraction to exogenously applied acetylcholine was slightly depressed by the compound. 3 At 100 microgram/ml, compound 48/80 caused a weak but long-lasting increase in tone and irregular contractile activity in the ileum, part of which was reduced but not completely abolished by pretreatment with chlorpheniramine (1 muM) or by repeated applications of compound 48/80. 4 The inhibitory effects of morphine and methionine-enkephalin on the twitches were antagonized by the presence of compound 48/80 (3 to 30 microgram/ml), possibly in a competitive manner. The antagonism was not affected by pretreatment with the antihistaminics, chlorpheniramine and/or metiamide. 5 The inhibitory effects of noradrenaline and adrenaline on the twitches were slightly but significantly increased by the presence of compound 48/80 (10 or 30 microgram/ml), whereas that of ATP was not modified. 6 Thesese results indicate that compound 48/80 acts as a selective and competitive antagonist at opiate receptors located in the intramural cholinergic nerves of guinea-pig ileum.


The effects of pentobarbitone and urethane on pulmonary airway resistance in guinea-pigs and their interactions with drugs.

1 Propranolol increased pulmonary airway resistance (PAR) in the conscious guinea-pig, whereas atropine had no effect, suggesting the existence of a continual sympathetic bronchodilator tone. 2 The direct bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were modified by autonomic reflexes: a bronchodilator one, abolished by propranolol, and a cholinergic bronchoconstrictor one, seen with histamine. 3 Pentobarbitone increased PAR, an effect which was reduced by propranolol but which was unaffected by atropine. The bronchoconstrictor effects of histamine, acetylcholine and 5-hydroxytryptamine were potentiated by pentobarbitone. 4 Pentobarbitone therefore appears to inhibit the adrenergic bronchodilator tone and to depress adrenergic reflexes, these being the preponderant autonomic influences in these experiments. 5 Like pentobarbitone, urethane increased PAR in the conscious guinea-pig and potentiated the bronchoconstrictor effects of the three amines. These actions are similarly attributed to a reduction in adrenergic influences.


A pharmacological investigation of the electrically evoked convulsive activity induced by administration of catechol in the anaesthetized rat.

1 The response evoked by electrical stimulation at the wrist has been recorded from muscles of the forelimb of anaesthetized rats induced to convulse by administration of catechol.2 This response can be divided into three temporally distinct components, the characteristics of which have been described.3 The probability of occurrence of the two early components of the response has been measured before and after administration of various drugs. The results show that the first component is not affected by cholinoceptor or adrenoceptor blocking drugs or anticholinesterase agents. The probability of occurrence of the second component is significantly reduced by cholinoceptor blocking drugs and increased by physostigmine.4 The implications of these results in explaining the convulsant actions of catechol are discussed.


Pharmacological analysis of histamine receptors in musculature and vasculature of the dog trachea in situ.

1 The role of histamine H1- and H2-receptors in the musculature and vasculature of the dog trachea was investigated in the blood-perfused trachea in situ. 2 Histamine and acetylcholine caused increases in blood flow (tracheal, vasodilatation) and in intraluminal pressure (tracheal constriction) in a dose-dependent manner. Histamine was almost equipotent to acetylcholine in causing tracheal vasodilatation but was about 30 times less potent in causing tracheal constriction. 3 The histamine H2-receptor agonist, dimaprit, caused a dose-dependent increase in tracheal blood flow but failed to cause tracheal constriction. 4 The tracheal constriction produced by histamine was inhibited strongly by diphenhydramine but not modifed by metiamide. The tracheal vasodilatation produced by histamine was antagonized by both diphenhydramine and metiamide; diphenhydramine was more effective than metiamide. 5 It is concluded that in the tracheal musculature, histamine receptors are exclusively of the H1-type and mediate constriction, whereas in the tracheal vasculature, both histamine H1- and H2-receptors mediate vasodilatation but histamine H1-receptors are predominant.


Effects of nicotine on cardiac prostaglandin and platelet thromboxane synthesis.

1 Rabbit hearts were perfused with a solution containing [14C]-arachidonic acid (AA) and various concentrations of nicotine (3 x 10(-8) to 3 x 10(-5) M). The venous effluent was collected and extracted for lipid acid material, which was subsequently subjected to thin layer radiochromatography. 2 Human platelets were incubated with nicotine (10(-8) to 10(-4) M), in the absence or presence of unlabelled AA. The amount of smooth muscle stimulating activity resulting from 30s of incubation was tested on a rabbit aortic strip. 3 In hearts perfused with [14C]-AA; nicotine induced a dose-related depression of the release of [14C]-6-keto-prostaglandin F1alpha, and a parallel increase of [14C]-prostaglandin E2. 4 Nicotine neither induced synthesis of thromboxane in human platelets, nor affected the platelet synthesis of thromboxane induced by AA. 5 It is suggested that nicotine affects the metabolism of prostaglandin endoperoxides in the heart by inhibiting their conversion to prostacyclin and facilitating, directly or indirectly, the formation of prostaglandin E2.


Responses of the simultaneously-perfused hepatic arterial and portal venous vascular beds of the dog to histamine and 5-hydroxytryptamine.

1 The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. 2 Histamine and 5-hydroxytryptamine (5-HT) were injected intra-arterially and intraportally in graded, increasing doses. 3 Intra-arterial histamine evoked decreases in hepatic arterial vascular resistance (HAVR) and increases in hepatic portal vascular resistance (HPVR). 4 Intraportal injections of histamine caused increases in HPVR and decreases in HAVR. 5 The time courses of the arterial responses to intraportal histamine and of the portal responses to intra-arterial histamine, compared with any systemic effects, showed that these effects on the liver vasculature could not be the result of recirculation of histamine. 6 Intra-arterial 5-HT evoked biphasic changes in HAVR and small falls in HPVR. Intraportal 5-HT caused falls in HPVR at low doses and rises at high doses, together, typically, with biphasic effects on HAVR. 7 It is unlikely that the arterial effects of intraportal 5-HT and the portal effects of intra-arterial 5-HT were due to recirculation of the vasoactive material. 8 Pathophysiologically, both histamine and 5-HT are released from the gastrointestinal tract into the portal vein. These experiments show that such release may affect the hepatic arterial vascular resistance (and therefore blood flow) even though vasoactive levels of the autacoids are not attained in the systemic circulation.


Sympathomimetic effects of pancuronium bromide on the cardiovascular system of the pithed rat: a comparison with the effects of drugs blocking the neuronal uptake of noradrenaline.

1. The effects of pancuronium bromide on the cardiovascular system of the pithed rat were examined. Pancuronium had two effects, a short-lasting cardiovascular stimulation following injection and a longer-lasting potentiation of responses to sympathetic nerve stimulation. 2 The initial effect of pancuronium was compared with that of tyramine. The cardioaccelerator but not the pressor responses to both pancuronium and tyramine were significantly reduced following sympathectomy with 6-hydroxydopamine (6-OHDA). 3 The action of pancuronium in potentiating sympathetic nerve responses was compared with that of known blockers of the neuronal uptake of noradrenaline (NA). Pancuronium (1 mg/kg) and cocaine (0.5 mg/kg) potentiated cardioaccelerator and pressor responses to sympathetic stimulation. These effects of pancuronium could be obtained following adrenalectomy and during neuromuscular blockade with gallamine. Pancuronium and uptake blockers potentiated the cardioaccelerator response to NA, reduced the response to tyramine, but did not affect the response to isoprenaline. Pancuronium and uptake blockers potentiated the pressor response to NA, but did not affect the response to tyramine or clonidine. 4 Following sympathectomy with 6-OHDA, pancuronium failed to potentiate cardioaccelerator and pressor responses to NA. 5 These results are discussed in relation to two main cardiovascular effects of pancuronium; an indirect sympathomimetic action and blockade of the neuronal uptake of NA.


The effects of dorsal bundle injections of 6-hydroxydopamine on avoidance responding in rats.

1 The effect of injection of 6-hydroxydopamine (6-OHDA) into the fibres of the dorsal noradrenergic bundle on acquisition, retention and extinction of active avoidance in rats were examined. 2 6-OHDA injections severely depleted noradrenaline in all forebrain areas assayed, with the interesting exception of the septum. No significant effect on dopamine concentrations in various forebrain regions was found. 3 Acquisition and retention of active avoidance was not altered by the lesion. Marked resistance to extinction was seen when the unconditioned stimulus (shock) was removed. 4 A comparison with work by other authors in which both forebrain noradrenaline and dopamine were depleted suggest that the alteration in extinction seen in both studies is a noradrenergic effect, whereas the deficits in acquisition and retention found previously are dopaminergic in origin.


Release of [3H-noradrenaline from the motor adrenergic nerves of the anococcygeus muscle by lysergic acid diethylamide, tyramine or nerve stimulation.

1 A method is described for labelling the neuronal noradrenaline (NA) stores of rat anococcygeus with [3H]-NA and detecting subsequent release of 3H from the superfused tissue by nerve stimulation or drugs. 2 Lysergic acid diethylamide (LSD) or tyramine but not barium chloride or carbachol increased the efflux of 3H although each drug produced an equivalent contractile response. This confirms that LDS has an indirect sympathomimetic action. 3 LSD was found to produce a proportionately smaller reduction of the nerve-induced efflux of 3H than of the accompanying contractile response. 4 The inhibition of nerve-induced contractile responses by LSD was shown to be independent of the neuronal uptake of noradrenaline and any post-junctional inhibition demonstrated to be non-specific.


Written treatment contracts: their use in planning treatment programmes for in-patients.

The formation of a therapeutic relationship involves the negotiation of a treatment contract which conforms to the general principles of any contractual agreement. Attempts have been made to formalize the therapeutic alliance, and this paper reports the development of a written contract for psychiatric in-patients.


A new distinction between the euphoric and the anti-depressant effects of methylamphetamine.

The psychological effects of an injection of methylamphetamine have been measured in 22 drug-free patients with endogenous depressive illness and in 9 patients with other psychiatric illness. A new distinction between the time course of the euphoric and anti-depressant effects is described. The euphoric effects were seen in the first hour after the injection, but the anti-depressant effects were delayed for 1--3 hours and then lasted for as long as 36 hours. These findings are at variance with the noradrenaline depletion hypothesis of depressive illness which (in its simplest form) predicts an immediate alleviation of depression as a result of an immediate rise in the concentration of noradrenaline at central receptor sites.


Cognitive functions in manic-depressives: effects of lithium and physostigmine.

Cognitive functions were investigated in seven manic depressive patients while on lithium, after two weeks off lithium, and after a subcutaneous injection of physostigmine while on lithium. Test performance was unaffected by lithium, but after physostigmine the I.Q. score of a shortened version of the WAIS was significantly increased.


A rating scale for mania: reliability, validity and sensitivity.

An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.


A psychiatric clinic in a probation office.

A weekly clinic was held for one year in a London probation office with 41 probation officers. Only 23 cases were referred but the clinic was found to be a valuable forum for discussion of problems with the officers, 10 per cent of whose clients were estimated to be receiving psychiatric treatment elsewhere. Suggestions are made to improve collaboration between psychiatrists and probation officers.


Eysenck's theory of criminality applied to women awaiting trial.

American women awaiting trial were administered the Eysenck Personality Questionnaire. Compared to a heterogeneous control group, these women scored significantly higher on the neuroticism and psychoticism scales and on Burgess's 'hedonism' variable, though they did not differ with respect to extraversion or lie scale scores. Women awaiting trial were more likely to fall in the neurotic-extravert quadrant (a trend more marked for non-white women). In general, the results support Eysenck's theory of criminality and the usefulness of Burgess's 'hedonism' variable.


The two-year predictive validity of the Clifton Assessment Schedule and the Shortened Stockton Geriatric Rating Scale.

Assessment of cognitive and behavioural disability on 100 elderly psychiatric admissions was carried out by means of the Clifton Assessment Schedule and the Shortened Stockton Geriatric Rating Scale. The results provided useful predictive indices, confirming the relationship between cognitive impairment and unfavourable outcome at two-year follow up.


Chlorpropamide-alcohol flushing: a dominantly inherited trait associated with diabetes.

A simple test was devised to identify people susceptible to chlorpropamide-alcohol flushing (CPAF). Subjects were given a placebo tablet, followed by sherry 12 and 36 hours later. They then received a chlorpropamide tablet and sherry again after 12 and 36 hours. This single-dose challenge test was given to non-insulin-dependent diabetics, insulin-dependent diabetics, and normal subjects. CPAF was common in the non-insulin-dependent diabetics but rare in the other groups. When the test was used in identical twins and families of affected subjects CPAF appeared to be a dominantly inherited trait. We conclude that facial flushing after alcohol in people taking chlorpropamide is related to non-insulin-dependent diabetes, especially when there is a strong family history of diabetes, but not to insulin-dependent diabetes. It is a dominantly inherited trait.


Chlorpropamide-alcohol flushing: a definition of its relation to non-insulin-dependent diabetes.

The single-challenge test for chlorpropamide-alcohol flushing (CPAF) was used to study two groups of patients with non-insulin-dependent diabetes and a family history of the disease who were distinguished only by their age at diagnosis (under and over 30). Their relatives were also studied. The proportions of patients showing CPAF in both groups were similar, and the family histories suggested dominant inheritance. When offspring of diabetics in whom the disease was diagnosed early were studied CPAF seemed to precede the appearance of diabetes. We conclude that the patients in both groups had the same, distinct syndrome, which is characterised by diabetes diagnosed at any age that is inherited as an autosomal dominant trait and associated with CPAF. This syndrome, which constitutes about one-fifth of all cases of non-insulin-dependent diabetes, may be detected with a single-challenge CPAF test before the onset of glucose intolerance. CPAF therefore acts as a genetic marker for the syndrome.


Myocardial ischaemia in patients with frequent angina pectoris.

One hundred patients with angina pectoris underwent 16-point electrocardiographic (ECG) mapping of the left hemithorax during a standardised exercise test. Forty-five patients had maximum ST-segment depression at position V5, while 35 had no ECG signs of ischaemia at this position. In 20 V5 was on the edge of the precordial area, which showed less severe ST-depression than the central positions. An Oxford ECG recorder and highspeed analyser were modified and used in 50 of the patients with daily angina for recording ST-segment changes over 24 hours. Serial 24-hour ambulatory recordings from the edge of the precordial area of ischaemia identified during exercise detected a mean of only 14 +/- SD 3% of the episodes of ST-segment changes recorded from the centre of the same area. Only 16 +/- 2% of the episodes detected by ECG were accompanied by chest pain. More episodes occurred between 4 am and 6 am than at any other time during the night. This study shows the importance of recording ECG evidence of ischaemia from the precordial position showing maximum changes during exercise. ECG evidence of ischaemia occurs more frequently than anginal pain. These objective measurements add important information to the frequency of chest pain reported by patients with ischaemic heart disease.


Precordial exercise mapping: improved diagnosis of coronary artery disease.

Surface mapping of the exercise electrocardiogram (ECG) provides a measure of the precordial area, severity, and time course of ST-segment changes occurring after exercise. Sixteen-lead isopotential surface maps were recorded before and after exercise in 109 patients with probable angina who subsequently underwent coronary arteriography. In addition, exercise ECGs with three orthogonal leads were obtained in 53 of these patients, and with a single unipolar chest lead in all 109. Of the 109 patients, 85 had significant (greater than or equal to 70%) narrowing of at least one major coronary artery. The sensitivities of the precordial surface mapping, orthogonal leads, and single chest lead (V5) when compared with the findings at coronary arteriography were 95%, 68%, and 64% respectively, while the specificities of the three lead systems did not differ significantly. The technique of precordial surface mapping after exercise may easily be applied in clinical practice and requires only conventional equipment available in most hospitals. It effectively aids diagnosis of coronary artery disease.


Effects of propranolol and metoprolol on the peripheral circulation.

The effects of single doses of propranolol and metoprolol on skin temperature and skin and muscle blood flow were compared in 10 normal subjects and four patients with essential hypertension. In normal subjects the mean skin temperature fell by 1.30 +/- 0.62 degrees C 90 minutes after 80 mg propranolol and 0.15 +/- 0.05 degrees C after 100 mg metoprolol. Skin blood flow and resting muscle blood flow were not affected by metoprolol but fell significantly after propranolol. Both drugs reduced post-exercise muscle hyperaemia, propranolol by more than metoprolol. Similar changes were seen in the hypertensive patients. Propranolol should be used with care in patients with known vascular disease.


Liver enzyme concentrations as measure of possible infectivity in chronic asymptomatic carriers of hepatitis B.

Fifty-two British-born blood donors who were chronic carriers of hepatitis B surface antigen (HBsAg) were tested for the presence of hepatitis B e antigen (HBeAg) and antibody to HBeAg by an immunoradiometric assay. The presence of HBeAg was closely associated with a slight rise in serum liver enzyme concentrations, a high HBsAg titre, and male sex. We suggest that the finding of persistently raised serum liver enzyme concentrations in an asymptomatic HBsAg carrier might be useful as a likely indicator of HBeAg and high infectivity.


Haemodynamic effects of buprenorphine after heart surgery.

The effect of buprenorphine on the cardiovascular system was examined in 11 patients during the period of reduced cardiac reserve after open-heart surgery. Within 10 minutes of giving the full analgesic dose (5 microgram/kg) intravenously the mean heart rate had fallen significantly by six beats/min. Although in two patients the mean arterial pressure fell by 24 mm Hg, there was no overall change in mean arterial pressure, cardiac output, or peripheral resistance. In a further six patients buprenorphine was used successfully as the sole analgesic after open-heart surgery. Buprenorphine appears to be safer than morphine for use in patients with reduced cardiac reserve and is of similar analgesic efficacy.


A miniature Wright peak-flow meter.

A new miniature Wright peak-flow meter has been designed and produced. The meter is tubular with a spring-loaded piston and a longitudinal slot through which air escapes. Its dynamic characteristics have been carefully designed to make it respond only to peak flow and not to rate of rise. Performance tests on early instruments showed fairly close correlation with the Wright peak-flow meter but with a constant error of + 38 1/min. On later models the correlation was increased to 0.990 and the error reduced to + 3%. The mini-meter correlates as well with the standard instrument as two standard instruments correlate with each other and should prove useful clinically.


Neurogenesis in spinal cord of mouse: an autoradiographic analysis.

An autoradiographic analysis of the time and sites of origin, and the migration and settling patterns of neurons was made in the spinal cord of the mouse. The neurons originated on days 10--14 of gestation with temporal gradients along the ventrodorsal and rostrocaudal axes. The motor neurons originated on days 10 and 11 of gestation; the neurons in the intermediate gray region originated on days 11--14 of gestation; the neurons of the head of the dorsal horn originated on days 12--14 of gestation. The neurons that originated on days 10 and 11 originated and migrated primarily from the basal plate, and they settled in the adjacent regions of the intermediate zone; those neurons formed on days 12--14 originated and migrated primarily from the alar plate, and it was concluded that these neuroblasts similarly settled in the adjacent regions of the intermediate zone. Extraventricular proliferation, which presumably signaled the initial stages of gliogenesis, was first observed on day 12 of gestation. This study supports the classical idea of the mosaic pattern of neurogenesis in the embryonic spinal cord.


Messages conveyed by descending tracts during scratching in the cat. II. Activity of rubrospinal neurons.

(1) The activity of rubrospinal (RS) neurons giving axons to the lumbosacral spinal cord was recorded during actual and fictitious8 scratching in thalamic cats. (2) During both actual and fictitious scratching, the discharge frequency of many RS neurons was rhythmically modulated. Different neurons were active in different parts of the scratch cycle, but most neurons were active in the flexor phase. (3) The discharge frequency within the bursts during fictitious scratching was, on the average, equal to that during actual scratching. Immobilization usually resulted only in a small displacement of the burst position in the scratch cycle. Therefore, rhythmical modulation of RS neurons is determined mainly by central mechanisms and not by a rhythmical sensory input. (4) In decerebellate cats, the overwhelming majority of RS neurons had no rhythmical modulation. Very weak modulation was found only in a few neurons. (5) Transection of the ventral spinocerebellar tract (VSCT) resulted in considerable reduction or complete cessation of rhythmical modulation in RS neurons during fictitious scratching. On the contrary, transection of the spino-reticulocerebellar pathway (SRCP) resulted in just a small decrease of modulation. Therefore, of the two pathways (the VSCT and SRCP) transmitting messages about intraspinal processes to the cerebellum during scratching2,3, the VSCT is of major importance for modulating RS neurons.