[Molecular mechanisms of receptor. II. Identification of the conformational transition of rhodopsin responsible for the leading edge of the photoresponse of artificial lipid membranes modified by fragments of the outer segment of rods]. Kinetic parameters of photoinduced permeability increase of artificial lipid membranes, modified by ROS fragments (tau20 degrees C = 20 mesec Ea = 33 +/- 2 kcal/mole) coincides with appropriate parameters of photoinduced protein fluorescence intensity decrease and ROS fragments absorption spectra change (metarhodopsin I leads leads to metarhodopsin II transition). Hydroxylamine accelerates this process, its rate is proportional to hydroxylamine at concentrations lower than 0.6 M.


[Electrophoretic study of the heterogeneity of chromatin subunits]. Electrophoretic heterogeneity of chromatin subunits (mononucleosomes) isolated from rat thymus nuclei after mild nuclease digestion has been studied. Just as in the original nuclease hydrolysate of the nuclei and after its fractionation on a Sepharose 4B, mononucleosomes are found to include several fractions (up to four) varying in their protein moieties and sizes of DNA segments Mononucleosomes obtained from the nuclei contain an additional non-histone protein as a minor component. The distribution of rapidly labeled RNA and of newly synthesized DNA among eletrophoretic chromatin fragments has been investigated. Newly synthesized chromatin has a subunit structure typical of the whole chromatin. Rapidly labelled RNA was found in dinucleosomes and mononucleosomes, being predominantly bind to mononucleosome fraction devoid of histone H1.


[Kinetics of poly-enzyme system reactions. II. Nonsteady-state kinetics. Presteady-state and relation modes in a bi-enzyme system and linear sequences]. Kinetic aspects of reactions in homogeneous multienzyme systems under nonsteady state conditions were investigated. An analysis of formal-kinetic relationships, describing the time course of system was conducted with a bienzyme system. Presteady state kinetics of processes in lineal multienzyme systems was investigated. Relax-kinetics methods were applied for the analysis of processes in lineal sequences. Methods of determination of number of stages initial substrate transformations and of number of enzymes were developed as well as methods for the analysis of sequences of intermediates in reaction pathway. Methods of determination of Vmax and Kmax for each individual enzyme are considered.


[Effect of magnesium ions on heat denaturation of DNA]. The dependence of animal DNA denaturation on magnesium ion concentration has been studied in the range (10(-6)--10(-1) M with sodium ion content of 10(-3) and 10(-2) M. Special attention has been given to the effect of multivalent metallic impurities bound to DNA. An increase of DNA thermal stability has been shown to occur in the magnesium concentration rage of 10(-6)--10(-4) M. At concentrations exceeding 10(-3) M the T M begins to decrease. The dependence of the DNA melting range on magnesium ion concentration has a maximum at approximately 10(-5) M Mg2+. At low magnesium and sodium ion concentrations a strong asymmetry of the melting curves has been observed. This effect can be described in terms of the melting theory for DNA complexed with small molecules and is explained by magnesium ion redistribution from the denatured portions of DNA to native ones. The method for calculation of melting curves in the DNA-ligand system has been proposed. Studies of thermal denaturation parameters have been shown to be an effective method for the estimation of binding constants of ligands to native and denatured DNA.


[Isolation of the calcium-binding domain of carp parvalbumin]. Carp parvalbumin has two calcium-binding domains with a similar three-dimensional structure. Using the tryptic hydrolysis at the arginine residue in position 75, it was possible to split off one calcium-binding domain. All lysine residues were protected by maleic groups which were removed at the final stage. The domain (with a peptide thirty-three residues) isolated by ion-exchange chromatography and gel filtration does not have a secondary structure in a solution and is unable to bind calcium.


[Electrostatic interactions of charged groups in an aqueous medium and their effect on the formation of the secondary structures of polypeptide chains]. Analysis of experimental data shows that interaction of charges in an aqueous medium is satisfactorily evaluated by macroscopic dielectric water permeability even at small (approximately 3--4 A) distances. It has been shown that a non-polar molecule located between the charges weakens their interaction. At the same time interaction between charges situated on the non-polar molecules somewhat increases. An estimate is made of the free energy loss of alpha- and beta-structures of polypeptides, resulting from the insertion of charged groups as well as of the free energy of interactions involving charged groups in different secondary structures.


[Splitting of the DNA of new lambdoid bacteriophages by the specific Eco RI endonuclease]. The number of EcoRI restriction sites in DNAs of several lombdoid phages varies from 2 to 7 and the size of fragments ranges from 0.6 . 10(6) to 25 . 10(6) daltons. Effectiveness of restriction determined in vivo weakly correlates with a number of restriction sites, suggesting different sensitivity of different sites to EcoRI action. No correlation between molecular weights of DNA of different phages and the rate of heat inactivation of the phage has been found. The variability of number of the restriction sites and of the molecular weights of the fragments permits to conclude that: 1) closely-related organisms can be possibly used as convenient sources of certain genes (if a construction of new vector lambdoid phages is essential); 2) there is an opportunity to find phages with different distribution of the restriction sites to other restrictases within a group of phages with non-identical EcoRI restriction sites.


[Nuclear magnetic resonance of nucleotidamides. Structure of the intramolecular complex of the methyl ester of deoxyadenylyl-(5'-3')-deoxyadenylyl-(5'--N)-L-phenylalanine]. The secondary structure of methyl ester of deoxyadenylyl-(5'--3')-deoxyadenylyl-(5' leads to N)-L-phenylalanine [l-pheOMe-d (pApA)] has been investigated by proton magnetic resonance. For this compound folded conformation stabilized by hydrophobic interaction in aqueous solution has been shown; and the anti-anti-conformation has been proved to exist. The investigation of chemical shifts of aromatic protons in L-PheOMe-d (pApA) has permitted us to build the conformation model of this compound.


[Small-angle diffuse x-ray scattering on fine muscle filaments]. Theoretical small-angle diffuse scattering curves from muscle thin filament models have been calculated. The curves reveal a maximum at 115' scattering angle. It has been shown that the maximum is due to the pitch of F-actin helix. Theoretical curves are in good agreement with the earlier obtained curves of small-angle diffuse scattering from F-actin dilute solutions.


[Properties of replicating DNA in the regenerating rat liver isolated during phenol fractionation]. Using phenol fractionation in the absence of detergents three DNA fractions differing by the incorporation of radioactive thymidine after pulse label are obtained from regenerating rat liver cells. Two fractions extracted under variety of conditions represent the main bulk of cell DNA (85--90%). DNA non-extractable under conditions used (DNA III) incorporates labelled thymidine 10--15 times faster than the first two DNA fractions. DNA III purified from the interphase layer by pronase, sodium dodecylsulfate and phenol sediments at 26S and has a hyperchromic effect about 40% after alkaline denaturation. Alkaline sucrose density gradient centrifugation of pulse-labelled DNA III revealed that nascent DNA consisted of heterogeneous fragments similar in size to the replication fragments in bacterial cells (9--10S). It was shown by CsCl equilibrium centrifugation that buoyant density of heat denatured DNA III labelled for 5 min with [3H]thymidine is heavier than the bulk of DNA prelabelled for 2 h with [14C]thymidine. After hydrolysis with RNase or alkali, buoyant densities of both DNAs became the same. These results support the idea of initiating role of RNA in the synthesis of discontinuous replicating fragments in regenerating rat liver cells. Specific radioactivity of RNA associated with replication fragments which are labelled for 5 min with [14C] orotic acid is 20 times more than of the same RNA labelled for 30 min. These data demonstrate high metabolic activity of initiating RNA.


[Effect of 6-benzylaminopurine on (14C)leucine incorporation into protein in a cell-free system from isolated squash cotyledons]. Polysomal preparations from isolated pumpkin cotyledons treated with cytokinin [6-benzylaminopurine (BAP), 10 mg/l] were about two-fold more active in the cell-free system of protein synthesis as compared to polysomes from control cotyledons. The time course of 14C-leucine incorporation into protein and its dependence on polysome concentration were studied; sucrose density fractionation have revealed significant differences in polysome distribution between the treated and control cotyledons. All polysomal fractions from BAP-treated cotyledons were more active in protein synthesis than corresponding fractions from control cotyledons. Mixing of BAP-treated and untreated cotyledons before polysome isolation showed that the difference in their activity did not result from isolation procedure. Factors of polysome activation and/or inhibition were tightly bound to polysomes. Treatment of polysomes with 0.175 M KCl reduced markedly their protein-synthesizing activity and abolished the difference between polysomes of BAP-treated and control cotyledons. The initial level of polysome activity could be restored by addition of proteins isolated from the salt wash, but these proteins were not specific in their action. Possible mechanisms of phytohormone action on ribosome activity are discussed. BAP activation of ribosomes in protein synthesis in vitro is fully eliminated by addition of natural inhibitor--abcisic acid--to BAP solution during cotyledons incubation.


[Physico-chemical properties of several phages of Bacillus thuringiensis]. A study was made of biological and physico-chemical properties of phages of Bac. thuringiensis as well as of a number of parameters of nucleic acids isolated from these phages. The phages contain double-stranded DNA. Molecular weights of DNA from three phages--Tg9, Tg10 and Tg13 have been determined by two independent methods: by measuring the contour length of DNA, from the sedimentation constant and for DNA of phage Tg10 also by endonuclease EcRI hydrolysis. These methods gave similar results. On the basis of the temperature of DNA melting the content of GC pairs was found equal to 37.9, 33.4 and 35.1 mole% for DNA's of phage Tg9, Tg10 and Tg13, respectively. On the basis of measuring the intervals of DNA melting a conclusion was made that DNA of the Tg9 and Tg13 phage has a random distribution of base pairs, while DNA of phage Tg10 displays some clustering of base distribution along the molecule. It has been shown that restrictase EcoRI hydrolyses phage Tg10 DNA into 6 fragments of different molecular weights; DNA's of Tg9 and Tg13 phages are not hydrolyzed. A possibility of existance of phage Tg10 DNA in linear and ring forms has been established. The characteristics of phage particles have been determined by electron microscopy.


[Relationship between the study of DNA reassociation kinetics of various chromosomal forms of Ellobius and questions concerning the pathways of chromosome rearrangement during evolution]. Fifteen chromosome forms of Ellobius talpinus (from 2n = 31 to 2n = 54) were found in the small area in the Pamirs. Low-chromosome karyotypes evolved from 54-chromosomal ancestral form by Robertsonia centric fusions. The DNA reassociation kinetics of 34- and 54-chromosome forms of E. talpinus have been studied. For comparison DNA of E. lutescens (2n = 17) the karyotype of which seems to have arisen from 54-chromosome ancestor by Robertsonian and other types rearrangements was examined. Reassociation profiles of Ellobius DNA suggest the existence of several repeated sequences families with different frequences of repetitions. The reassociation curves of DNA from 34- and 54-chromosome forms were identical. These data indicate absence of changes in DNA molecular organization during the evolution of E. talpinus karyotypes by Robertsonian fusions. Comparative analysis of DNA reassociation kinetics of E. talpinus and E. lutescens showed identical characteristics of highly repeated sequences and of one from the three intermediate fractions, however Cot 1/2, complexity and repetitive frequencies of two intermediate fractions of E. talpinus and E. lutescens were different. It is possible that non-robertsonian rearrangements of E. lutescens karyotype affected only intermediate repetitions. The alternative explanation of these data is a simple divergence of repeated sequences during the evolution of E. lutescens DNA.


[Molecular mechanisms of receptor-potential generation by the photoreceptor. III. Conformational transition responsible for the tail end of the photoresponse of an artificial lipid membrane modified by fragments of the external segments of rods]. The kinetics of photoinduced changes of protein fluorescence of cattle visual pigment was studied in the presence of hydroxylamine. The rate constant of fluorescence increase is proportional to NH2OH concentration when it is less than 0.4 M. It reaches the maximal magnitude (3.3 +/- 1 sec-1) at higher hydroxylamine concentration. Fluorescence increase rate is controlled by the rate of chemical reaction of rhodopsin with hydroxylamine. It is limited by conformational rearrangement of opsin. This rearrangement does not induce absorbance spectrum change of visual pigment, but confers to it the capability to react with NH2OH and NaBH4. Kinetic parameters of this rearrangement (tau 20 degrees C approximately 300 msec, Eact = 19 +/- 2 kcal/mole) coincide with kinetic parameters of diminishing of the photoresponse of artificial lipid membrane modified by fragments of rod outer segments in the temperature range studied (+2 divided by +25 degrees C).


[Isolation and characteristics of 2 transcribing families of pigeon-genome repetitive sequences]. From pigeon DNA two families of repeats have been isolated: one (frequency of repetitions 30--40 times per haploid genome) actively transcribing and the second (frequency of repetitions 2000--2800 times) weakly transcribing in erythroid cells. The reassociation kinetics, GC-content and size of isolated repeats were investigated. Actively transcribing repeats (average length of 350 nucleotides) contain about 55% GC-nucleotides and alternate in the genome with AT-rich sequences of the unique type. Comparison of isolated families of repeats revealed differences in the structure and posttranscriptional fate of RNA transcribed from them.


[Molecular structure of plant genomes].

[Molecular structure of plant genomes]. The genome structure of several species of Graminea and Drosophila was investigated by DNA renaturation method. Kinetics of DNA reassociation was studied by direct optical scanning and the data obout Cot curve were analized by an improved computer programm "Finger". Differences between structure DNA animals and plants are shown. Plant genomes have no unique fraction which exists in animal genomes. Slowly reassociating fraction in plants comprises about 20% DNA as compared with more than 60% in animal DNA. An analysis of kinetic complexity indicates that the relative content of the slowly reassociating fraction in the genome both of animal and of plants is much higher than that of the highly repeated DNA fraction.


[Effect of the protein product of phage f1, gene 5, on heat denaturation of synthetic polynucleotides]. The influence of phage f1 gene 5 protein on melting of the synthetic polynucleotides has been investigated, using UV-spectroscopy. In our experiments we have varied the proteins concentration. It has been shown, that the protein lowers the melting temperature of the studied polynucleotides (d/A--Tn dAndTn, rAndTn, rAn.r n, dAn.rn). The melting temperatures and the shapes of melting curves of various polynucleotides differ when the same protein concentrations are used. We have shown that the protein binds to the double-stranded polynucleotides, containing ribo-ribo-, deoxyribo-ribo-chains. The difference in melting temperatures and shapes of melting curves was explained using the data about the differences in the secondary structure of these polynucleotides. Only for d/A-Tn renaturation was observed after sample cooling. It may reflect the single-stranded hairpin structure of this polynucleotide.


[Isolation and characteristics of DNA fragments bound to mitochondrial membrane proteins]. Fragments of rat liver mitochondrial DNA were isolated. In vivo these fragments were able to form the complexes with the proteins of inner mitochondrial membrane. The fragments represent unique DNA regions with the secondary structure, their A-T content being equal to 82%. With the aid of phosphomonoesterase, polynucleotidkinase and gamma-(32P)-ATP mtDNA fragments were labeled and analyzed for oligopyrimidine composition. It was shown that they were enriched in di- and tri-oligo-pyrimidine blocks. The fragments are shown to form in vitro a complex with the membrane proteins. A single protein m. wt. 40,000) was reisolated from the complex.


[Comparative analysis of the kinetics of renaturation of newly synthetized and total DNA of eukaryotes as a means of demonstrating selective genome synthesis]. A simple and sensitive method for determining the selective eucaryotic DNA synthesis (amplification, ordered replication) amounting up to 10(-6)% of genome has been proposed. The essence of the method is measuring of the combined renaturation of total and in vivo labelled newly synthesized DNA. By means of a special computer program a theoretical investigation of amplification (from 50 to 2-fold) was accomplished, based on the experimentally found renaturation curve of rat liver DNA. A new method of graphical analysis of experimental results is also proposed based on the changes in the specific activities against Cot values. Some advantages of the new graphical method, i. e. greater sensitivity and reliability, simplicity of calculation of the amplification level and of the proportion of radioactivity in the amplified sequences are shown. The major patterns of the changes in the specific activities in different examples of amplification were revealed. Evidence is presented that the amplification necessarily brings about essential changes in the specific activities of denatured and renatured DNA fraction at high Cot values. On the basis of the method developed, the mode of liver DNA synthesis in normal and hormone-induced rats was established. Both in the normal and hydrocortison-induced rat livers no selectivity of DNA synthesis was found in the sense that hormonal induction of RNA synthesis is not a consequence of additional synthesis of DNA templates.


[Relationship between chlorophyll concentration and the energy reaction between protochlorophyll and chlorophyll in mixed associations]. In the paper results are presented of investigation of protochlorophyll (PChl) and chlorophyll (Chl) mixed associations and of interaction between them within the polymer molecular complex, which forms in mixture of water-dioxane (1 : 4). The initial PChl concentration in all solutions was constant (CPChl = 1 . 10(-5) m/l), and Chl concentration varied from 1.10(-8) m/l up to 2.10(-5) m/l. It is shown that with the rise of Chl proportion in the mixed aggregate the rearrangement of both donor (PChl) and acceptor (Chl) components of complex takes place. The luminescence quenching of PChl and the sensitization of Chl emission in mixed pigment associates were investigated of different Chl levels and the evaluation of efficiency of intracomplex electronic excitation energy transfer, determined from quenching and sensibilization, was performed. Similar dependence of energy transfer effectiveness on Chl concentration, determined by the two above-mentioned methods shows that the excitation migration in an associate takes place without losses. An analysis of results permits to conclude that a small trapping efficiency of PChl excitation by the acceptor part of the complex may be connected with the existence of the prerelaxation reverse energy transfer from Chl to PChl in mixed pigment associates. On the basis of the obtained data a mechanism of energy transfer from protochlorophyllide to chlorophyllide in etiolated leaves and homogenates is discussed.


[Nucleoprotein fusion. III. Causes and conditions for development of the multiphase character of the DNA--protein fusion curve]. The influence of proteins reversibly and irreversibly bound to DNA on the shape of melting curve has been considered. It is shown that the melting curve becomes biphasic in two cases: (i) cooperative binding of proteins with DNA (II) STRONG DIFFERENCE IN THE BINDING CONSTANTS WITH HELICAL AND COILED REGIONS. Simple formulae permitting to determine which of two causes stipulate for biphasic profile of a given experimental melting curve are obtained. Melting curves of DNA-basic oligopeptides complexes have been investigated. It is shown that the oligopeptides, when their chain length does not exceed 10, are able to migrate along DNA and biphasic shape of the melting curve is stipulated by the cooperative manner of their binding with DNA.


[Kinetics of alpha-chymotrypsin catalyzed hydrolysis in equilibrium. II. Comparison of ester and amide substrates]. Kinetic of the alpha-chymotrypsin catalyzed reversible hydrolytic reaction of methyl N-acetyl-L-phenylalaninate and N-acetyl-L-phenylalanylglycinamide at pH 5.5 and equilibrium conditions has been studied. The rates of the labeled reaction products incorporated into the substrate a different methanol concentrations shows that the reaction proceeds by a compulsory mechanism with the formation of N-acetyl-L-phenylalanine-alpha-chymotrypsin complex. For the amide substrate the data obtained are also in agreement with the compulsory mechanism of its hydrolysis. Equilibrium kinetics of ester and amide substrates hydrolysis has been compared.


[Nomogram for the determination of the size of protein molecules and approximation of their molecular weights]. A nomograph is suggested using which one can determine from the molecular weight and one of the dimensions of the molecule the remaining dimension and the axial ratio for the ellipsoid of rotation with the volume equivalent to the volume of the protein molecule. The nomograph permits to determine molecular weight from the molecular size of the dry protein and of the protein dissolved in water. From the molecular size of the dry protein corresponding dimensions for the protein molecule in an aqueous solution can be obtained. At last the nomograph can help to evaluate the correctness of the literature data and experimental data on the molecular sizes of proteins and on their molecular weights.


[Use of the antibiotics actinomycin D and distamycin A to limit the action of restriction endonucleases and to map DNA]. It is shown that distamycin A and actinomycin D protect the recognition sites of certain restriction endonucleases from the attack by these nucleases due to specific interaction of these antibiotics with double-stranded DNA. Distamycin A protects A-T containing sites and actinomycin G-C rich sites. Among Hind II recognition sites which have alternative structure (GTPyPuAC) distamycin A protects only Hpa I similar sites (GTTAAC). It is shown with several restriction endonucleases that antibiotic action depends on the nucleotide sequences in the recognition sites and in their closest environment. Proper concentrations of antibiotic give rise to larger fragments. Use of both distamycin A and actinomycin D allows to obtain a set of overlapping fragments. The data obtained with various DNAs and restriction endonucleases allow to conclude that these antibiotics may be useful for DNA mapping and for preparation of large functional fragments of DNA.


Patients' knowledge of heart disease in general practice. Interviews with 400 consecutive patients attending a general practice sought their knowledge of the signs and symptoms of an acute heart attack, what action they would take for such an event, and their understanding of the predisposing factors contributing to heart disease. The survey revealed poor recognition of the relevant signs and symptoms of an acute heart attack and lack of knowledge of some of the main predisposing factors associated with heart disease.


[Comparative study of the tRNA-methylases of normal and tumor tissues. II. Positional specificity of renal and carcinoma RA methylases]. A comparative study of the position specificity of tRNA-methylases from normal and tumour tissues was performed on yeast tRNA1Val as the substrates using partially purified enzyme preparations from rat kidney and carcinoma RA. As in the case of rat liver and Novikoff hepatoma, two methylated compounds are formed in yeast tRNA1Val under the action of rat kidney and carcinoma enzyme preparations: m5C is formed in the sequence C49--C52 located in the extra loop and A59 in the Tpsi-loop is is converted into m1A. The activity of m5C-methylase [S-Ado-Met-tRNA-(cytosine-5)methyltransferase] (E. C. 2.1.1.29) is approximately equal in both tissues, whereas the activity of m1A-methylase [S-Ado-Met-tRNA-(adenine-1)methyltransferase] (E. C. 2.1.1.36) in carcinoma is twice as high as in the kidney. The two enzymes do not differ in their position specificity.


[Electron microscopy study of fibrin self-assembly]. The process of fibrin selfassembly has been examined by electron microscopy. Its initial stage is found to consist in fibrin monomer conversion to thin filaments of random shape, probably identical with the well known intermediate polymers of fibrin. When the filaments attain an appropriate size they arrange themselfs into bundles with increasingly ordered structure. At this stage a tendency to form cross bands appears. The cross-band system develops on the basis of substance redistribution within fibrin molecules incorporated into filamentous bundles. It seems hardly warranted to call the complicated process of fibrin fibre formation as "selfassembly". This process represents a "molecular morphopoesis" and includes: selfassembly of filaments; selfassembly of bundles and transformation leading to the establishment of the ultimate fibril structure.


[Translocation mechanism of ribosomes].

[Translocation mechanism of ribosomes]. The paper summarizes studies of the molecular mechanism of the dynamic function of the ribosome, i. e. translocation, performed in the author's laboratory during the past decade. The hypothesis of the locking-unlocking of the ribosomal subparticles and the kinematical model of the working ribosome, the processes of spontaneous (factor-free) and factor-dependent translocation, the sequence of events in the factor-dependent translocation, the energetics of translocation and the contribution of the elongation factors with GTP are considered. The following conclusions are made: (1) the translocation mechanism is intrinsic to the structural organization of the ribosome itself but not introduced by the protein elongation factors; (2) the transpeptidation reaction is one of the sources of energy for the work of the translocation mechanism; (3) the protein elongation factors with GTP impart additional energy to the ribosome, including that for translocation, and thus ensure excess power which is realized, in particular, in the increase of the translocation rate and its resistance against inhibitors and hindrances; (4) the promoting role of the elongation factors with GTP does not proceed by a direct conjugation of GTP hydrolysis with translocation, but through the affinity of the elongation factors to the ribosome, with a subsequent compensation of the affinity at the expense of GTP cleavage.


The oxyhemoglobin dissociation curve in patients with familial hyperchylomicronemia. In order to study the effect of marked chylomicronemia on red cell oxygen release, oxygen hemoglobin dissociation curves (ODC's) from zero to full saturation were determined on whole blood from three siblings with familial Type I hyperlipoproteinemia. In these cases the oxygen affinity of hemoglobin was markedly increased, with P50 act. pH varying between 22.1 and 17.7 mm. Hg (normal value, 27.3 mm. Hg; S.D., 1.3) and the Hill coefficient n reflecting the slope of the ODC was increased. The changes in the ODC's are thought to be secondary to the hyperchylomicronemia for the following reasons: (1) the change was minimized by incubating red cells from the patients in normal donor plasma; (2) normal red cells increased their oxygen affinity when incubated in lactescent plasma; (3) the change was not explainable by a decrease in red cell 2,3-diphosphoglycerate content or in arterial blood hydrogen ion concentration. Based on these findings a decreased erythrocyte oxygen release of one third can be hypothesized. The importance of this observation in relation to the symptomatology of clinical conditions complicating marked chylomicronemia is discussed.


[Temporal characteristics of bacteriorhodopsin as a molecular biological generator of current]. Generation of electric potential difference by bacteriorhodopsin proteoliposomes incorporated into the phospholipid-impregnated collodion film has been studied. It is shown that illumination of this film by continuous light gives rise to the generation of an electric potential difference across the film (plus on the bacteriorhodopsin-free side), which can be as high as 300 mV. Short unsaturating flash inducing single turn-over of bacteriorhodopsin generates the potential difference which is a function of the flash intensity (70 mV at 3 mjoule light). The flash-induced photoelectric response consists of four phases. (1) Very fast (tau less than 1 microsec) generation of a potential difference (minus in the bacteriorhodopsin-free compartment). The amplitude of this phase is rather small (1--5 mV). (2) Fast phase of positive charging of the bacteriorhodopsin-free compartment (tau = 25--50 microsec). (3) Slow phase of positive charging of this compartment (tau = 6--12 msec) Amplitude of the second phase is to that of the third as 1 : 2. (4) A very slow phase of discharge of the flash-induced potential difference (tau = 1 sec at 10(8) ohm X cm2 film resistance). The third phase was specifically inhibited by La3+. Both the second and the third phases are decelerated by substitution of D2O in 4.5--5 and 2 times, respectively, while the amplitude of the first phase increases. Prolonged storage of the system in the dark (tua = 20--25 min) causes the decrease in the amplitudes of the second and the third phases as if the amount of active bacteriorhodopsin molecules were increased by factor 2. Such an inhibition was reversed by 30--60 sec illumination of the system. The dark adaptation is accompanied by some increase in the first phase amplitude. Comparison of these data with results of other studies on bacteriorhodopsin suggests that (1) the first phase is due to the photoinduced change in the retinal dipole; (2) the second phase corresponds to H+ transfer from Schiff base to the water solution in the proteoliposome interior; 3) the third phase represents H+ transfer from the incubation mixture to Schiff base; (4) the dark adaptation is a result of transition of photoelectrochemically active all-trans-retinal to the inactive 13-cis-retinal.


[Comparative study of the tRNA-methylases of normal and tumor tissues. I. Spectrum of renal and carcinoma RA methylases]. A comparative study of rat kidney and carcinoma RA tRNA-methylase activity has been carried out using partially purified enzyme preparations and total E. coli tRNA. Also the nuclease activity of the methylase preparations from kidney and carcinoma was compared. It was established that the methylase activity in carcinoma preparations is higher, whereas the nuclease activity is lower in comparison to the enzyme preparations from liver. No formation of some specific methylated compounds could be established in the case of carcinoma. It was established that the relative contribution of individual methylases to the elevated level of total tRNA-methylase activity in carcinoma is different. Maximal enhancement of activity was established for the methylase forming m5U, whereas the activity of the enzymes, transfering the methyl group to the fifth position of C is practically equal in kidney and carcinoma tissues. Experimental results and theoretical evaluation of the hypotheses suggested to explain the higher methylase activity in tumor tissues allowed to reject some of them.


[Diseases of the central nervous system in diabetes mellitus]. In a series of examinations of more than 1000 psychiatricneurological patients we tried to state the effects of diabetes mellitus on the nervous system. We attempted to diagnose the diabetic metabolic error by means of using the oral glucose tolerance test (100 g glucose), the plasma insulin levels and many other laboratory-technical examinations (altogether about 23 000 individual tests). It was found that 21,6% of the patients had a pathological glucose tolerance, 29.6% of them had a pathological insulin response and 5,5% of them showed a known and manifest diabetes mellitus. The comparison between the number of patients with a metabolic disturbance and the frequency of sick persons to be expected epidemiologically shows that an influence exercised by the diabetic metabolism may be stated in neurological and psychic disturbances of cerebral sclerosis and polyneuropathy. The central syndromes are more frequent than the peripheric ones. Mainly low plasma insulin is present. As a rule, pathological results may be seen more often during pathological glucose tolerance in electroencephalography, pneumencephalography, CSF-examinations, personality and intelligence states. This suggests that a diffuse disturbance upon the nervous system comes from the diabetic metabolism, without any acute metabolic disturbance which we did not find among our patients. This disturbance is evident clinically as so-called diabetic polyneuropathy and also encephalopathy. In opposition to that very often pathological changes can be seen by technical research methods in other neurological and psychiatric diagnoses without influencing essentially the autonomous progress of the psychiatricneurological illness.


[Specific hyposensitization in allergic diseases (author's transl)]. Hyposensitization with semi-depot extracts was effective in 439 of 533 patients (82.4%) with allergic manifestations. The result suggests that treatment will be most effective when (1) the patient is young, (2) the disease is located in the respiratory tract, (3) the disease has been of relatively short duration, (4) the hyposensitization extract contains only one type of allergen, (5) only a few allergens are involved, (6) treatment continues over a long period of time, (7) the final dosage is high, and (8) dosage and time schedules are carefully followed. Success does not depend on the patient's sex or the occurrence of side effects during the treatment.


Reversibility of the "salt-losing" tendency of chronic renal failure. We examined the salt-losing tendency of chronic renal failure in five patients with glomerular filtration rates varying from 5.2 to 16.0 ml per minute. When the studies began, patients were in sodium balance on metabolic diets containing 58 to 342 meq of sodium daily. The sodium content of the diet was then reduced in stages at intervals of at least one week over four to 14 weeks with careful clinical and laboratory monitoring. In four of the patients a salt-losing tendency developed, temporarily requiring intravenous salt replacement in two. At the completion of the studies all the patients remained in sodium balance while ingesting a mean (+/- S.D.) of 5.0 +/- 2.9 meq of sodium per day. There was no change in renal function. Thus, the salt-losing tendency of chronic renal failure is reversible and appears to be a manifestation of the long-term adaptation for sodium excretion.


[Supraregional operation control system for rescue and repatriation flights]. The air rescue service, organized by regions in the Federal Republic of Germany, is conducted by helicopters and comprises 24 operation stations. 9 independently operating airline companies take part in supraregional repatriation flights. The coordination of the availability of regionally controlled rescue helicopters with repatriation flights to be conducted on supraregional level seems to be urgently necessary in order to avoid duplication of operations and futile flights and to control the influx of patients to the specialized hospitals. The ground rescue service has to be included in the overall coordination system. Information and data required for coordinating purposes in a supraregional operation control center will be presented in detail.


Short term variation of human immunoglobulin levels with an estimation of the day to day physiological variability. In this work serum Ig levels were determined daily for 14 days in 12 subjects, every two days for 14 days in 19 subjects, every week for 1 month in 11 subjects and fortnightly in 11 subjects for 6 months. The serum IgG, IgM and IgA levels were quantitated by the linear plate method. The day-to-day reproducibility of the technique was checked for a period of one months on seven different samples. The mean coefficient of variation in the reproducibility experiments was found to be 4.8% for IgG, 8.2% for IgM and 5.2% for IgA. Since the observed variation in all groups of subjects was found to be higher than the methodological variation, it appears that physiological variability occurs in the serum Ig levels of an individual. No difference was found between the physiological variances of IgG, IgM and IgA observed in the group with daily analysis and those with determinations every two days. The physiological variations increase when longer periods are considered between consecutive determinations, but the variability of IgG and IgA in the group with fortnightly determinations is less important than that observed in the group with weekly analyses. Some evidence is presented indicating a periodic fluctuation of serum IgG and IgA levels with an amplitude of nearly 20% and with a recurrence rate of two weeks.


[Study of the reference values and nyctohemeral cycle of serum iron]. Marked variations in the same individual of serum iron levels may be due to a circadian rhythm. We determined the reference values of serum iron in a population of blood donors who had no blood disease. The very wide reference interval found (0.47 to 1.75 mg/l in man and 0.36 to 1.66 mg/l in women) was due to physiological variations rather than analytical variations. We also demonstrated in individuals with a normal life rhythm, a circadian rhythm for iron with maximal levels in the morning (8 to 12) and minimal levels in the evening (8 p.m. to midnight) the ratio of these levels is usually between 1.5 and 2, but may reach much higher figures. On the other hand, the total fixation capacity varies little over 24 hours. In night workers, one may note a displacement of the cycle with a maximum towards 8 p.m. a minimum at 8 a.m. In diabetics, the circadian rhythm exists but with a lower amplitued than in healthy subjects. In a few cases a hemochromatosis, one may note disappearance of the cycle.


Failure of plasma from human schistosomiasis mansoni patients to protect mice from Schistosoma mansoni cercarial challenge. Plasma samples obtained from patients with well defined Schistosoma mansoni infections, or control subjects, were passively transferred to CF1 mice. Three, 12, or 24 hours after passive transfer, the recipient and control mice were challenged with either 200 or 600 live cercariae, and the adult worm burdens or schistosomula lung recoveries, respectively, were determined 7 weeks or 6 days after challenge. None of the human plasmas afforded the recipient mice protection against the development of schistosomes. Worm and larval yields were equivalent in all cases, even though many of the patient plasmas were shown, as assessed by an in vitro eosinophil-dependent cytotoxic antibody assay, to contain high levels of antischistosomular antibody.


Atrial pacing from the coronary vein. Ten-year experience in 50 patients with implanted pervenous pacemakers. During the past ten years, pervenous atrial pacemakers have been implanted in 50 patients (mean age 68 years, 60% males) using an electrode positioned in the coronary vein. The indications for atrial pacing were symptomatic sinus bradycardia (72%), atrial brady-tachy syndrome (20%), and recurrent tachyarrhythmias (8%). Atrial pacemakers have been implanted for a total of 1531 pacing months, average 31 months per patient, median 26 months and range 3-97 months. Effective atrial pacing has been achieved with Medtronic model 5818 and 6904 electrodes. Unipolar or bipolar atrial pacing has been equally effective, and commercially available Medtronic 5950, Cordis 162 and CPI 602 pulse generators have been utilized without difficulty. A total of 11 electrode related malpacing events occurred in the ten-year period with a malpacing event rate of 10% in the first pacing month, 1.1% per paced month during the next six months, and 0.25% per paced month thereafter. Life table analysis reveals that effective atrial pacing was achieved in 76% of the patients during a follow-up of more than five years. This experience substantiates the long-term safety and effectiveness of atrial pacing from the coronary vein using standard pacemaker electrodes and generators.


Paroxysmal supraventricular tachycardia in patients with mitral valve prolapse. The mechanism of supraventricular tachycardia was evaluated in twelve patients with mitral valve prolapse utilizing standard intracardiac recording and stimulation techniques. Eight patients had normal electrocardiograms, three had a short PR interval and normal QRS (Lown-Ganong-Levine syndrome) and one had Wolff-Parkinson-White type A. Six of the eight patients with normal electrocardiograms were demonstrated to have atrioventricular bypass tracts. Five patients had A-V nodal re-entrant supraventricular tachycardia. In two patients the bypass tract could be demonstrated to conduct antegradely when the left atrium was paced via the coronary sinus, while in four the bypass tract only conducted retrogradely. In all seven patients with atrioventricular bypass tracts, the accessory pathway was left-sided. We conclude that a) supraventricular tachycardia in the mitral valve prolapse syndrome appears related to a high frequency of bypass tracts; b) electrophysiological studies are required to diagnose these bypass tracts; and c) the atrioventricular bypass tracts may be related to the mitral valve abnormality since they are always left-sided.


Efficacy of propranolol in the control of exercise-induced or augmented ventricular ectopic activity. The effect of propranolol on exercise-induced or augmented ventricular ectopy was studied in sixteen male patients, six of whom had documented coronary artery disease. Fifteen patients were exercised after two weeks of oral therapy, fourteen after single oral therapy and eight patients after intravenous therapy. Propranolol dosage was titrated to produce maximal beta-adrenergic blockade. Effective reduction of exercise-induced ventricular ectopy occurred in ten of fifteen patients (P less than 0.001), and in five of six patients with coronary disease (P less than 0.02). Propranolol therapy abolished ventricular couplets in eight of twelve patients and ventricular tachycardia in four of the patients. Single oral and intravenous therapy had similar or greater effects. Plasma propranolol levels following different routes of administration did not correlate with exercise-induced maximal heart rates or percent reduction in ventricular ectopy. When compared to exercise in eleven patients, ambulatory monitoring underestimated the severity, particularly the highest grades, of ventricular ectopy.


Effect of phasic respiration on left ventricular dimension and performance in a normal population. An echocardiographic study. Echocardiographic examination of the left ventricle (LV) in 30 normal subjects, 5 to 47 years of age, was performed in order to analyze the effects of phasic respiration on LV dimensions and derived LV function. Peak expiratory and peak inspiratory LV diastolic and systolic dimensions were measured and extrapolated to volume estimates using a standard formula. Although there was wide variation in the individual measurements, and particularly in systolic dimension, the mean peak inspiratory diastolic dimension, derived diastolic volume, and stroke volume all decreased significantly (P less than 0.001); a smaller decrease in ejection fraction was seen (P less than 0.02), while the changes in mean end-systolic dimension and end-systolic volume were not significant. While these observed changes may reflect a true physiologic variation, an artifactual component cannot be excluded. Regardless of their physiologic significance, however, these data show that the effect of phasic respiration is a factor to be considered in correlative echocardiographic studies of LV function in both normal and, possibly, pathologic cardiovascular conditions.


Detection of tricuspid regurgitation with two-dimensional echocardiography and peripheral vein injections. "Contrast echocardiography", utilizing a two-dimensional ultrasound system and peripheral venous injections, was used for the detection of tricuspid regurgitation in 30 patients. The appearance of contrast in the inferior vena cava and the back and forth movement of contrast across the tricuspid valve were considered evidence for tricuspid regurgitation. Echocardiographic findings were correlated with clinical and angiographic data. Patients were assigned on the basis of clinical data to one of three groups. Group I included five patients whose clinical findings were diagnostic for tricuspid regurgitation. Group II included patients (15) whose clinical findings were equivocal for tricuspid regurgitation and patients whose recognized primary problem is frequently associated with tricuspid regurgitation. Group III contained ten patients serving as controls. All group I patients had positive echocardiographic studies for tricuspid regurgitation, while all group III patients had negative studies, suggesting that this technique may be specific for tricuspid regurgitation. Among the group II patients were three who had positive echocardiographic studies despite the absence of specific clinical findings of tricuspid regurgitation, suggesting that this technique may be more sensitive than the methods in common use.


Diffuse coronary artery disease in diabetic patients: fact or fiction? To compare angiographically-determined coronary artery disease in diabetic patients with controls, 1,653 patients coming to cardiac catheterization were reviewed retrospectively to find 37 diabetic and 79 control patients matched for sex, age (+/- 3 years), and risk factors (hypertension, hyperlipidemia, and smoking). The severity of coronary artery disease was assessed using an angiographic grading system. The following results were obtained: 16 of 37 diabetic patients (43%) had three-vessel disease compared to 20 of 79 controls (25%). Seventy-six of 111 (68%) diabetic vessels were diseased compared to 110 of 237 control vessels (46%) (P less than 0.005). The total coronary score reflecting total extent of disease for diabetic patients was 371 (mean 10.0 +/- (SEM) compared to 594 for controls (mean 7.5 +/- 0.7, (P less than 0.01). Diabetic patients had a statistically similar number of diffusely diseased vessels as controls (28% vs 22%). There were only three of 76 diabetic vessels (4%) considered inoperable compared to seven of 110 (6%) control vessels. We conclude that diabetic patients with chest pain have more coronary artery disease than nondiabetics, but no more diffuse or inoperable disease.


Hemodynamic, reflexive, and metabolic alterations induced by acute and chronic timolol therapy in hypertensive man. The hemodynamic, cardiovascular, and metabolic effects of acute (intravenous) and prolonged (four weeks oral) timolol treatment were assessed in 16 patients with mild or moderate essential hypertension. Fifteen patients completed the outpatient study and ten showed a fall in mean arterial pressure of at least 10 mm Hg. They also demonstrated a significant fall in supine systolic (7%), diastolic (9%), and mean arterial pressure. Hemodynamic evaluation was performed in 13 patients and cardiac index was found to be reduced with both intravenous (20%) and oral timolol (13%). There was no correlation between the decrease in cardiac index and arterial pressure. Calculated total peripheral resistance rose with intravenous timolol and returned toward, but not below, pretreatment values with the oral therapy. Left ventricular ejection rate also fell significantly with intravenous timolol but returned toward pretreatment levels with oral therapy. Plasma renin activity was reduced similarly with both modes of administration and its reduction also did not correlate with the fall in arterial pressure. Plasma volume fell in eight of 13 patients. Reflexive responses to the Valsalva maneuver were considerably modified by both intravenous and oral timolol but responses to 50 degrees upright tilt and handgrip were not. Timolol is an effective oral antihypertensive agent with similar hemodynamic and metabolic effects to propranolol.


Hemodynamic effects of intravenous sodium nitroprusside in the conscious dog. The hemodynamic effects of 7 min i.v. sodium nitroprusside (NP) were studied in conscious dogs previously instrumented for measurement of arterial pressure, cardiac output, regional blood flow distribution, left ventricular (LV) pressure, and internal dimensions. Nitroprusside, 25 microgram/kg/min, reduced mean arterial pressure by 23 +/- 3%. Cardiac output increased initially by 39 +/- 7% and returned toward control by the end of the infusion. Regional blood flows increased initially; the relative rise was greatest in the coronary (+ 225 +/- 39%), intermediate in the mesenteric (+ 98 +/- 23%) and iliac (+ 38 +/- 6%), and least in the renal (+ 10 +/- 3%) bed. By the end of the infusion period the vasodilation was unchanged in the iliac bed, less intense in the coronary and mesenteric, while in the iliac bed, blood flow was reduced and resistance was actually increased by 33 +/- 11% above control. A generalized vasonconstriction ensued after cessation of infusion. In contrast, when the drug was administered intra-arterially to the iliac bed, arterial pressure did not fall and only iliac vasodilation was observed. Peak cardiac effects were characterized by increases in heart rate and LV dP/dt, along with marked reduction in LV end-systolic diameter (- 13 +/- 2%), and in end-diastolic diameter (-17 +/- 2%) and pressure. LV end-diastolic diameter fell even heart rate was maintained at a constant rate by pacing. Thus, in the conscious dog, NP reduced LV dimensions substantially, while inducing changes in peripheral beds. The differences in these effects depend on interactions between the direct effects of NP and the opposing effects of reflex adjustments which appear sufficiently powerful to result in net constriction of the iliac bed late during the infusion.


Comparison of effects of nitroprusside and prazosin on left ventricular function and the peripheral circulation in chronic refractory congestive heart failure. We compared cardiocirculatory actions of nitroprusside (NP) to prazosin (PZ) in eleven chronic coronary patients with refractory congestive heart failure. Each drug equally lowered systemic arterial pressures mildly while heart rate was unaltered. NP decline (P less than .001) in left ventricular filling pressure (28 to 17 mm Hg) and rise (P less than .005) in cardiac index (2.20 to 2.96 L/min/m2) were similar to PZ (30 to 17) and (2.08 to 3.00). PZ and NP equally enhanced cardiac efficiency of stroke work and myocardial oxygen consumption index. Total systemic vascular resistance declined (P less than .001) the same with NP and PZ. Forearm vascular resistance (FVR) and venous tone (FVT) diminished equally with NP and PZ. Similar FVR/FVT percent changes of 0.88 and 0.64 with NP and PZ indicated relatively balanced systemic arteriovenous relaxation. Sinze PZ effects persisted six hours with symptomatic improvement, oral PZ is the best vasodilator for long-term use, extending in-hospital NP-like actions to ambulatory heart failure therapy.


The absent pulmonary valve syndrome. Considerations of management. The absent pulmonary valve syndrome consists of a severely hypoplastic pulmonary valve with anular stenosis, aneurysmal dilatation of the main pulmonary artery with one or both pulmonary branches also dilated, and a ventricular septal defect. From 1955 to 1975, 15 patients were seen at Texas Children's Hospital with this syndrome. Although anatomically similar to tetralogy of Fallot, the most significant symptoms during early infancy were secondary to bronchial compression resulting from the dilated pulmonary arteries and enlarged left atrium. Intracardiac repair performed on two infants at four months of age failed to ameliorate the respiratory symptoms and both died. Seven patients from 2.3 to 16 years of age were operated upon, with one late postoperative death. Five other patients have not yet received surgical intervention. We recommend vigorous continual respiratory therapy for for infants and small children and intracardiac repair in older children since repair in infancy does not relieve respiratory symptoms. We do not recommend a prosthetic pulmonary valve unless there is persistently elevated main pulmonary artery pressure.


The course of the conduction system in dextrocardia. This is a serial section examination of the conduction system of five hearts of various types of dextrocardia. In one case of dextroversion the conduction system was found to be normal. In one case of mirror-image dextrocardia the conduction system was normal but in the opposite spatial position. In one heart of mixed (discordant) dextrocardia, the sinoatrial node was in correct morphologic position. There were two atrioventricular nodes - a posterior node close to the coronary sinus and an anterior node in the roof of the morphologic right atrium. They formed two separate bundles which joined in the left ventricle to form a "sling". In two cases of presumptive mirror-image dextrocardia, with a common atrium in situs inversus according to the morphology of the atrial appendages, with common atrioventricular orifice (CAVO), the sinoatrial node was situated in wrong positions. Two atrioventricular nodes and bundles again formed a sling. There are various types of slings in discordant dextrocardia.


Effectiveness of unsupervised and supervised high intensity physical training in normalizing serum lipids in men with type iv hyperlipoproteinemia. The effect of high intensity physical training (HIPT), conducted in an unsupervised (group A) or supervised (group B) setting, was studied in 23 middle-aged men with Type IV hyperlipoproteinemia (HLP). Following 10 weeks of HIPT intervention, significant metabolic changes were observed such as reductions in both fasting triglyceride and insulin levels, but no changes in fasting serum cholesterol or glucagon levels were found. Other favorable results noted included a significant improvement in physical fitness, as measured by increases in aerobic power, and a decrease in body fatness with only minimal weight losses. There were no significant differences in the results when groups A and B were compared. It was concluded that HIPT is an effective means of lowering fasting triglyceride and insulin levels in Type IV HLP individuals. In addition, such physical training programs can be conducted in either an unsupervised or supervised setting, provided the subjects are highly motivated.


Active valvulitis associated with chronic rheumatic valvular disease and active myocarditis. From ten patients aged 15 to 40 years with chronic rheumatic valvular disease and histologically proved Aschoff bodies of active rheumatic myocarditis, the valves were evaluated for incidence, distribution and degree of severity of active inflammation. Prior to death, there had been clinical evidence of active rheumatic fever. In each case, active rheumatic valvulitis was present in at least one valve. Of the individual valves studied, 83% were involved by active inflammation of the leaflets or the anulus or both. The aortic valves was involved in 100% of cases, the mitral valve in 86%, the tricuspid valve in 78% and the pulmonary valve in 70%. The mitral and aortic valves were most frequently involved, but the mitral and tricuspid valves were most severely involved when affected. In every case, active rheumatic lesions of the left atrial appendage were present, but these tended to be less widely distributed than the myocardial Aschoff bodies. The high incidence of active valvulitis supports the concept that chronic fibrosing rheumatic valvular disease results from recurrent active inflammation. Such inflammation may occur without clinical suspicion of active rheumatic fever.


Myocardial perfusion scintigraphy in patients with mitral valve prolapse: Its advantage over stress electrocardiography in diagnosing associated coronary artery disease and its implications for the etiology of chest pain. Patients with mitral valve prolapse (MVP) frequently experience chest pain which may, expecially in older subjects and males, be difficult to differentiate from angina pectoris. Electrocardiographic (ECG) changes, ventricular arrhythmias, metabolic abnormalities and rare reports of myocardial infarction and sudden death further suggest the presence of an ischemic process in these patients. The recognition of accompanying coronary artery disease (CAD) and exclusion of other causes of ischemia, therefore, may be important in determining the prognosis and appropriate therapy for such patients.


Cryoablation of drug-resistant ventricular tachycardia in a patient with a variant of scleroderma. A 37-year-old man with a benign variant of scleroderma (CRST syndrome: calcinosis circumscripta, Raynaud's phenomenon, sclerodactyly, and telangiectasia) presented with recurrent ventricular tachycardia. Preoperative electrophysiologic study suggested that the mechanism of tachycardia was an ectopic pacemaker focus in the right ventricle. Right ventricular dilatation, tricuspid insufficiency, normal pulmonary pressures, and normal coronary arteries were also demonstrated. At surgery, epicardial mapping localized the site of origin of ventricular tachycardia to the anterior right ventricle near the crista supraventricular. Intramural recordings of the site of tachycardia demonstrated autonomous activity unreflected on the peripheral ECG during brief periods of sinus rhythm. Local epicardial cooling of this area with a cryoprobe promptly terminated ventricular tachycardia with resumption of tachycardia on warming. The focus was ablated by freezing the area at -60 degrees C. The patient remained free of dysrhythmia on no anti-arrhythmic agents for eight months at which time he had a single recurrence of ventricular tachycardia from a different site in the right ventricle. This technique offers a method for ablating sites of dysrhythmia arising in diffusely diseased myocardium.


Spontaneous near closure of coronary artery fistula. An asymptomatic 14-year-old male was found at cardiac catheterization to have a coronary artery fistula involving a vessel originating from the left main coronary artery and terminating in the right heart. Chest X-ray and electrocardiogram were within normal limits and shunt flow was too small to be detected by oximetry although a large vessel was seen angiographically. One year later, the previously loud continuous murmur had disappeared and repeat catheterization demonstrated near closure of the fistula. This is the first report documenting the spontaneous closure of a coronary artery fistula.


Evaluation of methods for the quantification of experimental myocardial infarction. Several invasive and noninvasive techniques used in determining the size of experimental myocardial infarction were evaluated after acute ligation of the left anterior descending (LAD) coronary artery in ten dogs. Systemic blood pressure, left ventricular end-diastolic pressure (LVEDP), and heart rate did not change significantly for up to 24 hours after coronary occlusion. Left ventricular wall motion abnormalities were detected by left ventriculography in the distribution of the LAD but these changes did not correlate well with the infarct weight determined at autopsy. On the other hand, the number of epicardial sites with ST-segment elevation of greater than or equal to 2 mm (mean 15.1 sites +/- 0.6 SEM) and the infarct area as measured by 99mTc-glucoheptonate (TcGH) myocardial imaging (15.7 sq cm +/- 0.6) did correlate strongly with the infarct weight (16.8 g +/- 0.7) determined by the nitroblue tetrazolium (NBT) technique (r = 0.91). TcGH myocardial scintigraphy and epicardial ST-segment mapping allowed early and accurate quantification of experimental myocardial infarcts ranging from less than 1 g to 28 g.


Effects of pharmacologically-induced hypertension on myocardial ischemia and coronary hemodynamics in patients with fixed coronary obstruction. Twenty patients with fixed coronary artery obstruction were studied during rapid atrial pacing and methoxamine infusion. During pacing to heart rates of 142 +/- 4 (mean +/- SEM) beats per minute coronary sinus flow increased from 108 +/- 8 to 187 +/- 15 cc/min and myocardial oxygen consumption increased by + 80 +/- 11%. During methoxamine infusion that raised arterial systolic pressure to 196 +/- 5 mm Hg, similar increases in coronary sinus flow (to 179 +/- 13 cc/min) and myocardial oxygen consumption (+ 77 +/- 12%) occurred. Chest pain and ischemic ST segment changes developed in 17 and 14 patients respectively during atrial pacing, an incidence significantly greater (P less than 0.05) than during infusion of methoxamine (6 and 3 patients). Myocardial lactate extraction which averaged 26 +/- 4% during control was decreased to 10 +/- 8% during pacing and to 24 +/- 7% during methoxamine; the difference between decreases was not significant. The data show that at similar increases in myocardial oxygen consumption stress of increased heart rate results in more myocardial ischemia than stress of increased afterload.


Effects of reperfusion on the regional contraction of ischemic and nonischemic myocardium following partial coronary obstruction. In 14 dogs the effects on regional tension (Walton-Brodie gauges) and length (mercury-in-silastic) following 50% reduction (52.9 +/- 2.1) in coronary flow for two hours and reperfusion afterwards for one hour were addressed. Within five minutes of partial coronary occlusion, ejection tension in the ischemic zone decreased to 36.3 +/- 7.2% (P less than 0.001) and total tension to 64.4 +/- 5.7% of control (P less than 0.001) while phasic segment length increased to 165.2 +/- 16.3% control. No further significant changes in regional tension or length were observed throughout the two hour period of partial occlusion. Ejection tension remained positive and segment length maintained systolic shortening during the ejection phase throughout the period of occlusion. Following reperfusion, ejection tension in the ischemic zone increased from 35.1 +/- 5.9 to 87.0 +/- 22.0% (P less than 0.05) and total tension increased from 56.6 +/- 5.4 to 70.2 +/- 7.2% (P less than 0.02) while segment length decreased from 149.3 +/- 6.5 to 105.7 +/- 5.7% (P less than 0.001) within five to 15 min of reperfusion. The improvement in both regional tension development and segment length shortening was maintained throughout the one hour period of reperfusion. No significant changes were seen in the nonischemic zone. The present experimental study suggests that partial coronary occlusion producing a 50% reduction in coronary blood flow results in regional contractile changes. These changes are reversible at least twice as long as those following complete occlusion.


Mummification of the infarcted myocardium by high dose corticosteroids. There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.


The role of the exercise test in the evaluation of patients for ischemic heart disease. A cohort of 1472 patients who underwent both exercise stress testing and coronary angiography within six weeks was examined. The data indicated that a combination of exercise parameters is both diagnostically and prognostically important. Almost all patients (greater than 97%) who had positive exercise tests at Stage I or Stage II had significant coronary artery disease. More than half of these (greater than 60%) had three vessel disease and over 25% had significant narrowing (greater than 50%) of the left main coronary artery. Patients who achieved Stage IV or greater exercise durations with either negative or indeterminate ST-segment response had less than a 15% prevalence of three vessel disease and less than a 1% prevalence of left main coronary artery disease. A low risk subgroup (75% of all non-operated patients) was identified with a twelve month survival greater than 99%. A high risk subgroup (11% of all nonoperated patients) was identified with a twelve month survival of less than 85%. The exercise test is a noninvasive, reproducible method to assess the presence and extent of anatomic disease and the prognosis when significant disease has been defined. It should be used in conjunction with other noninvasive tests to determine optimal management in patients evaluated for ischemic heart disease.


Improved efficiency of treadmill exercise testing using a multiple lead ECG system and basic hemodynamic exercise response. One hundred consecutive men with a normal ECG at rest had a maximal treadmill test using 14 leads during and post-exercise. Coronary arteriography performed the following day revealed coronary stenoses greater than or equal to 70% in 66 patients. Test results obtained from a V5 lead were compared to different lead combinations and were correlated with arteriographic findings. A positive exercise test occurred in 37 men using an isolated V5 lead compared to 50 men (P less than 0.05) using 11 leads, 52 men (P less than 0.05) using a combined CM5, CC5, Cl (inferior) lead system and 58 (P less than 0.001) men using all 14 leads. The predictive value of a positive test varied between 89-95% and was not changed significantly by the addition of multiple leads. The 14 lead ECG was positive in 43/45 (96%) patients with multivessel disease. Parameters which helped to predict multivessel disease using 14 leads were 1) the time that ischemia first appeared 2) the pressure-rate product at the time ischemia first appeared, and 3) the maximum workload that could be attained. In general, the magnitude of ST-segment depression and the time required for a positive ECG to return to normal postexercise were not useful predictors of multivessel disease. We conclude that the use of multiple leads improves the sensitivity and efficiency of the maximal treadmill exercise test. The usefulness of exercise test results can be further improved if multiple leads are combined with physiologic data collected during exercise.


Maximal heart rate and treadmill performance of healthy women in relation to age. Maximal treadmill exercise heart rate, work capacity and electrocardiographic response were studied in 95 asymptomatic, predominantly sedentary women between the ages of 19 and 69 years. Average maximal heart rate (MHR) was found inversely related to age, such that MHR = 216 -0.88 (years of age) +/- 10 beats/min (X +/- 1 SD). Treadmill exercise endurance was 7.64 min +/- 1.99. The reduction of treadmill endurance with advancing age was not statistically significant. Asymptomatic ST-segment depression occurred in 6% of subjects. In 5% the ST segment sloped upward, and in 1% it was flat. Mean age of women with ST depression was 52 years, compared with 39 years mean age of all subjects. Premature beats during exercise were found in 20 of 95 subjects, and were not related to age. Graded exercise testing of women employing target heart rates should use heart rate tablets developed especially for women. These tables do not require correction for athletically trained for sedentary life-style.


Alpha and beta adrenergic effects on human atrial specialized conducting fibers. We determined the effects of epinephrine on automaticity and action potential characteristics of right atrial specialized fibers (RAF) from human atria obtained during cardiac surgery. RAF were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. A biphasic response to epinephrine was seen, rate slowing at low agonist concentrations and increasing at high concentrations. The epinephrine-induced slowing of spontaneous rate was due to a decrease in the slope of phase 4 depolarization. At the high epinephrine concentrations RAF hyperpolarized. The alpha-adrenergic blocker, phentolamine, shifted the dose-response curve upward and to the left and enhanced the hyperpolarization of RAF. The beta blocker, propranolol, shifted the curve to the right and decreased the degree of hyperpolarization. Our study suggests the presence of alpha and beta receptors in RAF. The alpha response consists of a slowing of rate, the beta response of an acceleration of rate and hyperpolarization of RAF.


Cardiac trauma from angiographic injections. A quantitative study. To relate angiographic injections to potential cardiac trauma, we verified a mathematic theory that allows quantitative definition of the kinetic energy content of contrast jets emanating from the exit holes of angiographic catheters. Cineangiographic recordings of a range of jets of known energy content were obtained in 18 cardiac canine experiments and energy content and dissipation were quantified precisely from center line to jet edge. All contrast jets produced in clinical angiographic practice were turbulent, even those from hand injections into the coronary arteries. Energy content was related to an estimated cardiac wall damage threshold. At energy levels and damage thresholds predicted by the theory and computations, a traumatic spectrum was found by cineradiology and microscopic examination. A unique curve independent of jet Reynolds number was discovered relating the penetration of the contrast jet into the intravascular blood to the potential for cardiac trauma. This curve allowed ready calculation of hydraulic energy dissipation for any clinically used angiographic catheter and the definition of safe operational injection flow rates. Thus potential cardiac trauma can be anticipated and prevented.


Coronary sinus pacing clinical follow-up. Coronary sinus pacing is a safe and effective means of pacing from the atrium. In 66 patients with an average follow-up of 14 months, there was a 14% failure rate. There were transient problems in 14% which were subsequently corrected. There was a 6% death rate which was not pacemaker related. Successful atrial pacing with thresholds up to 6.0 mA is feasible. Atrial pacing was successful in 18 of 19 patients with varying degrees of atrioventricular block. Our experience with a new electrode has been very satisfactory.


Changes in gastric glandular cell kinetics after small bowel resection in the rat. The proliferation of gastric mucosal cells was studied in male Sprague-Dawley rats after a 50% resection involving the proximal small intestine. Two months after the operation, resected and control animals were given either a single or four successive intraperitoneal injections of 1 muCi of [3H]thymidine per g of body weight. Animals from each group were killed 1 hr after the single injection and 3, 7, 30, and 60 days after the first multiple dose injection [3H]thymidine. The number of labeled parietal, chief, and mucous cells of the gastric glands were measured. At the 3-, 30-, and 60-day periods, the percentages of labeled parietal and chief cells were significantly increased in animals with small bowel resection when compared with corresponding controls. The percentages of labeled mucous cells of the gastric glands were also increased in animals with small bowel resection at the 3- and 7-day periods. One hour after a single injection of [3H]thymidine, the percentage of labeled gastric mucosal progenitor cells in animals with small bowel resection, although increased, was not significantly different from that in controls. It is, therefore, believed that the increases in percentage labeling of gastric glandular epithelial cells at 3, 7, 30, and 60 days could not solely be explained on the basis of an increased turnover rate of gastric progenitor cells. Rather, it might be concluded that the increase in glandular epithelial cells is accomplished, in part, by increased differentiation of gastric progenitor cells.


Percutaneous biopsy of the liver as a procedure for outpatients. Hepatic biopsy was performed in 107 outpatients and 68 inpatients in the last 18 months at this hospital. Only 1 patient had a complication; he bled from the biopsy site, The minimal cost saved per patient was $153.00. Biopsy of the liver in outpatients is both safe and economical.


Liver biopsy: complications in 1000 inpatients and outpatients. We prospectively evaluated risk factors in 1000 consecutive patients who underwent liver biopsy: 829 outpatients and 171 inpatients. The two groups were similar except that the outpatient group had a higher percentage of patients with hepatitis-cirrhosis and a lower percentage with neoplasia when compared with the inpatient group (P less than 0.01). The inpatient group had more relative contraindications (P less than 0.01). Among the 1000 patients, none died and none required laparotomy. If moderate to severe pain or hypotension or both developed (5.9%), they first became manifest during a 3-hr period of observation after biopsy. Forty-four outpatients (5.3%) were hospitalized; 39 were dismissed within 36 hr and 5 within 4 days. Complications were more often experienced by those with relative contraindications (P less than 0.05) and increased number of passes (P less than 0.01). Inpatients with hepatitis-cirrhosis experienced more complications (P less than 0.05) than did patients with other diagnoses (12.8 versus 3.8%). Complications were not related to type of needle, site of entry, or experience of operator. Liver biopsy as an outpatient procedure is safe if facilities are available for 3 hr of observation and hospital support; 5% of patients will require immediate hospitalization.


Idiopathic intestinal pseudoobstruction. Report of a case, with intraluminal studies of mechanical and electrical activity, and response to drugs. Intraulminal recordings of motility were made from a patient with chronic idiopathic intestinal pseudoodstruction. Contractile activity was recorded from esophagus and duodenum with and without cholinergic stimulation. Electrical activity was recorded from duodenum with and without cholinergic stimulation. Contractile and electrical activities were recorded from the sigmoid colon at rest and after morphine. Gastric fundic relaxation was measured during balloon distention. This patient showed abnormalities of esophageal function similar to achalasia, while gastric fundic relation was impared, with a more rapid rise in pressure on distention than is seen in normal persons. Duodenal and colonic electric control and response activities were present on occasion. Duodenal contractions occurred in response to both bethanechol and edrophonium. Therefore, the efferent cholinergic system of the small bowel appears to be functional in this case of idiopathic intestinal pseudoobstruction. The nonardrenergic inhibitory control of esophagus and gastric fundus appears to be functioning abnormally.


Intrahepatic hematoma resulting in obstructive jaundice. An unusual complication of liver biopsy. A patient who developed obstructive jaundice as a complication of a liver biopsy is presented. The jaundice was found to be attributable to obstruction of the biliary tree at the level of the bifurcation by an intrahepatic hematoma. The patient had a complete and spontaneous recovery.


Intraabdominal bleeding from variceal vessels in cirrhosis. A cirrhotic patient with hemoperitoneum was found, at laparotomy, to be bleeding from variceal vessels in the peritoneum lateral to the ascending colon. Radiological in vestigations before surgery did not identify the source of blood loss. Despite hemostasis being obtained, the patient died postoperatively. The 5 previously reported cases of intraabdominal bleeding from variceal vessels are reviewed.


Proximal enterectomy stimulates distal hyperplasia more than bypass or pancreaticobiliary diversion. To determine the contribution of intraluminal factors to postresectional intestinal hyperplasia, cell proliferation in the distal intestine of male rats was studied after 50% proximal enterectomy or 50% proximal bypass and also after transposition of the duodenal papilla to the mid small bowel. Within 48 hr all three operations increased RNA and DNA content s in the ileal mucosa 16 to 50% over control values. At 48 hr and 1 week the response distal to resection exceeded that of bypass or pancreaticobiliary diversion; nucleic acid contents, DNA specific activity, villous height, crypt depth, and luminal circumference were greatest 1 week after resection. By 1 month, however, chemical and histological values after resection were equalled or surpassed by those in the other two groups. In excluded jejunum itself, mucosal atrophy lowered RNA and DNA contents to 60% of control levels 1 month postoperatively. Neither pancreaticobiliary diversion nor proximal enteric bypass produces the same rate of distal hyperplasia as proximal resection. Modest colonic hyperplasia may contribute to intestinal adaptation after proximal enterectomy. Adaptive postrescetional cell proliferation appears not to be mediated simply by intraluminal nutrition or enteric secretions; hormonal factors may also be important.


Pathogenesis of diverticulitis complicating granulomatous colitis. The involement of diverticula by granulomatous colitis may cause an increased incidence of diverticulitis. Of 21 patients with Crohn's disease and associated diverticulosis who underwent resection, sigmoid diverticulitis was pathologically confirmed in 10 (48%). The clinical recognition of the coexistence of the two diseases is often difficult. The radiological signs of peridiverticulitis complicating granulomatous colitis usually show clear evidence of the underlying pathological changes. They include localized diverticular performation, perhaps with multiple communications via a paracolonic sinus tract, mass pressure from the paracolicabscess, and occasionally some degree of communication with deep fissuring ulcers of Crohn's disease. Because diverticula breach the colonic wall, histological analysis confirm that their involvement by the transmural process of granulomatous colitis predisposes to peridiverticulitis and/or abscess formation.


Removal of gastrin by various organs in dogs. In 6 anesthetized dogs receiving 400 pmoles kg-1 hr-1 of natural human little gastrin intravenously, blood samples for radioimmunoassay of gastrin were taken repeatedly from a carotid artery, jugular vein, femoral vein, renal vein, and mesenteric vein. The calculated removal of gastrin in a single passage through these four vascular beds ranged from 21 to 30% and did not differ significantly among them. In 6 additional dogs, the carotid arterial to hepatic venous removal was 40%. We conclude that the percentage removal of gastrin is about the same in all of the major vascular beds of the body.


Role of caloric intake in the weight loss after jejunoileal bypass for obesity. Sixty-five patients were studied prospectively after jejunoileal bypass for obesity. Dietary intake pre- and postoperatively was measured either directly by weighing food or by a research dietary history. Of 65 measurements, 59 were made at least 6 months after operation, when over 75% of weight loss had been achieved. Fat absorption was measured in 42 of the patients. The entire group ate fewer calories (mean +/- SE = 2595 +/- 135) postoperatively than preoperatively (mean +/- SE = 3261 +/- 138). This difference was highly significant (P less than 0.001). Forty-eight patients ate less after their operation. The caloric deficit calculated from the observed weight loss could be accounted for entirely by the estimated decrease in intake in 22 of the 48 patients who ate less postoperatively. Moreover, measured fat malabsorption accounted for only 31% of the observed weight loss in those who ate more postoperatively and 21% in those who ate less. We conclude that a decrease in caloric intake, along with malabsorption, is an important factor in the long term postoperative weight loss (1-9 months) after jejunoileal bypass for obesity.


Cirrhotic portal hypertension: morbidity of continued alcoholism. The morbidity of continued alcoholism was examined among 172 cirrhotic patients participating in controlled trials of portacaval shunts. Of 159 surviving more than 30 days, 76 continued drinking (group A), 68 became abstinent (group B), and 15 (group C) were chronically institutionalized (without potential access to alcohol). The mean  number of days in hospital postrandomization and prevalence of bleeding varices, ascites, and encephalopathy were similar for A and B (P greater than 0.05 for each comparison). Jaundice at hospital readmission, however, occurred in 50% of group A but in only 28% of B (P less than 0.01). Mortality and complication rates were substantially greater in C than in A or B, emphasizing the significance of progressive liver disease in institutionalized patients. Although continued alcoholism was associated with recurrent jaundice, a major impact on other criteria of morbidity was not demonstrated.


Intrahepatic pigment and crystal forms in patients with cerebrotendinous xanthomatosis (CTX). Liver specimens from two patients with cerebrotendinous xanthomatosis revealed intracellular inclusions that appeared either as amorphous pigment or in a crystalloid form. The pigment was usually found in assoication with the smooth endoplasmic reticulum and occasionally free floating in the cytosol. The chemical nature of these inclusions has not yet been determined. However, the accumulation of such material may indicate the presence of nonmetabolizable bile alcohols resulting  from a defect in bile acid synthesis.


Inhibition of hepatic metabolism of azathioprine in vivo. Glutathione-mediated thiolysis of azathioprine in the liver is believed to be the main mechanism for the conversion of this drug to 6-mercaptopurine. This metabolic step was inhibited in vivo by pretreating rats with probenecid as indicated both by less hepatic glutathione depletion and by a greater proportion of unmetabolized azathioprine in the liver. Less hepatic gluthathione depletion was also found in the hyperbilirubinemic Gunn rat. These findings indicate that the conversion of azathioprine to 6-mercaptopurine in vovo is mediated enzymatically by the glutathione S-transferases.


An X-ray diffraction comparison of myelins from the human nervous system. Earlier small-angle X-ray diffraction studies have indicated that central and peripheral nerve myelins may be significantly different structurally, although relatively few examples for each system and for individual species have been examined. In order to understand better the intra- and inter-system relationships, this study has developed more extensive information for a single species: six cases centrally and ten peripherally, featuring cranial nerves and a few others of the human nervous system. Peripheral myelin spacings (membrane pair thicknesses) are relatively similar, 184.4 +/- 1.40 A, and the ratios of diffraction peak height intensities of the second to fourth orders are also closely bunched: 1.85 +/- 0.216. Central myelin spacings and intensity ratios are distinctly different and more variable: spacings 160.3-165.8 A and intensity ratios 2.81-4.46. It appears that within a given species or between closely related (e.g., mammalian) species peripheral myelins possess relatively invariant structures, though significant spacing declines are encountered for both systems as phylogenetic relationships become more distant. The observed greater variability of CNS structures within a single species may correspond to known compositional differences between CNS regions or result from observational difficulties. In any case there is a marked discontinuity between the myelin structures of CNS and PNS nerves.


Discontinuous transition of myelin structure at the junction between central and peripheral components of the eighth cranial nerve, as disclosed by X-ray diffraction. Scanning along human acoustovestibular nerves from cross-sections closely proximal to the brain to locations distinctly peripheral thereto, by means of small-angle X-ray diffraction, has disclosed transitional junctions at which the myelin structure typical of central nervous system (CNS) axons gives way to one characteristic of peripheral (PNS) fibers. The junctions correspond to regions along the nerves, previously recognized histologically, at which the satellite cells responsible for axon myelination change character, from the oligodendrocytes of the CNS to the Schwann cells of the PNS. Thus the structural discontinuity between the CNS and PNS myelins can be ascribed to differences in the biosynthetic processes of the respective satellite cells. Junctions of this kind are to be expected in all cranial and spinal roots near the locations where they leave the CNS.


Physiological and morphological changes in cells of the lateral geniculate nucleus in monocularly-deprived and reverse-sutured cats. In the present study the size of large samples of cells and the relative frequency of Y-cells were measured in the lateral geniculate nucleus of monocularly-deprived and reverse-sutured cats. Due to deprivation large cells shrink more than smaller cells. This shrinkage is irreversible even over two years of reverse suture although over the same time the animals showed a remarkable pattern discrimination ability, which, in these animals, depends on the integrity of the geniculo-cortical system. Physiologically, a significant increase in the probability of recording Y-cells in the early-deprived laminae of the LGNd was found after a reverse suture. The relative frequency of Y-cells in the early-deprived layers and in the late-deprived layers was almost equal and not different from normal, although after the early deprivation by itself only 20% Y-cells were found in the deprived layers. The latter results confirm our previous observation (Sherman et al., '72). The increase in the number of recorded Y-cells following a reverse suture after monocular deprivation is accompanied by only small changes in the distribution of cell sizes in the LGNd. The number of very large cells in the early-deprived layers was increased but the mean cell size remained unaltered after long forced usage of the deprived eye.


Receptive field characteristics of superior colliculus neurons and visually guided behavior in dark-reared hamsters. Visual response properties of single neurons in the superior colliculus of golden hamsters reared from birth to adulthood in total darkness were compared to those of normal hamsters. Directional selectivity, speed preferences, and receptive field organization in dark-reared hamsters were essentially the same as those found in normally reared animals. Subtle neurophysiological effects of visual deprivation were indicated by the longer latencies of "on" responses to flashed spots of light in the dark-reared animals. Also, in the visually deprived animals three cells were encountered which changed their responses from phasic to tonic as the size of the visual stimulus was increased. In normally reared animals all cells responding to stationary stimuli showed only phasic responses regardless of spot size. Behaviorally, dark-reared animals could not be distinguished from normal animals on the basis of visual orienting and following tests. It was concluded that in the golden hamster visual experience during development has a minimal role in the induction or maintenance of the normal functional development of the superior colliculus.


Anaerobic osteomyelitis.

Anaerobic osteomyelitis. We have presented eight case histories of patients with anaerobic osteomyelitis and have reviewed an additional 193 cases from the world literature. The incidence, predisposing factors, clinical localization, bacteriology, modes of presentation and natural history of anaerobic osteomyelitis are discussed. This disease entity appears to be more common than has been previously recognized. Seven distinct clinical syndromes of anaerobic osteomyelitis are described and related to the anatomical locations in which they tend to occur. The signs and symptoms of these entities have been outlined to aid in their recognition by practitioners. An approach to the therapy of anaerobic osteomyelitis is outlined. Emphasis is placed on adequate surgical intervention combined with antimicrobial agents chosen for each particular clinical situation. The lack of definitive data upon which to base a decision regarding dosages and duration of antimicrobial therapy is discussed and the authors' own preferences enumerated.


Collateral ventilation in man.

Collateral ventilation in man. To determine whether collateral ventilation (defined as the ventilation of alveolar structures through passages or channels that bypass the normal airways) changes with age or emphysema, we compared the mechanics of collateral ventilation in seven young normal subjects, three old normal subjects and five patients with emphysema. In supine normal subjects at the end of a quiet expiration, resistance to airflow was greater through collateral channels than through bronchi and bronchioles. In emphysema, airways resistance could exceed collateral resistance, causing air to flow preferentially through collateral pathways. We conclude that high collateral resistance minimizes collateral airflow in supine normal subjects. When peripheral airways become obstructed or obliterated in emphysema, collateral channels may provide for more even distribution of ventilation.


A follow-up study of residents in internal-medicine, pediatrics and obstetrics-gynecology training programs in Massachusetts. Implications for the supply of primary-care physicians. A questionnaire survey of physicians who had been residents in internal medicine, pediatrics or obstetrics-gynecology in Massachusetts during the years 1967-1972 was undertaken to determine that specialties they now practice and the extent to which they deliver primary care. Over 600 physicians (74 per cent) responded. Devoting more than half their practice to a primary-care specialty were only 28 per cent of the former residents in internal medicine as compared with 56 per cent of those in pediatrics and 74 per cent of those in obstetrics-gynecology. For each group the fraction of full-time equivalent primary-care physicians produced was 0.27, 0.42 and 0.39 for the internal-medicine, pediatrics and obstetrics-gynecology programs respectively. These findings indicate that, although Massachusetts is meeting the requirements of PL 94-484 concerning the percentage of residency positions in the primary-care specialties, such compliance does not guarantee an adequate future supply of primary-care practioners.


Smokers' polycythemia.

Smokers' polycythemia. Twenty-two smokers with elevated hematocrits (mean, 54 per cent) had elevated blood carboxyhemoglobin (mean, 11.6 per cent; normal, less than 1 per cent) and a "left-shifted" oxygen-hemoglobin dissociation curve (mean P50, 21.6 +/- 2.3 [+/- S.D.] torr; normal, 26.7 +/- 1.1). Red-cell volume was increased in 14 of 18, and plasma volume reduced in 14 of 18. Fatigue and headache were common, and syncopal attacks occurred in four patients. Symptoms disappeared and the elevated red-cell volume decreased markedly in all five patients who were able to reduce severely their smoking habit; low plasma volume increased in three of four patients studied. We conclude that carbon monoxide exposure from cigar and cigarette smoke is a frequent cause of an elevated red-cell volume or a reduced plasma volume (or both). Measurement of carboxyhemoglobin should be a routine part of the evaluation of all polycythemic subjects.


Uterine sacculation.

Uterine sacculation. A case of uterine sacculation is reported in which a classic cesarean section was required for safe delivery. The definition and diagnosis of the condition and some difficulties in management are discussed.


Pulmonary embolization of trophoblastic tissue in molar pregnancy. A case of pulmonary embolization of trophoblastic tissue is described. The signs and symptoms of this syndrome are discussed, and its optimal management is outlined.


Hypertrophic tuberculosis of the vulva.

Hypertrophic tuberculosis of the vulva. Hypertrophic tuberculosis vulvae is a rare genital infection. Treatment is essentially with antitubercular drugs. However, when the hypertrophy is so excessive that it interferes with normal life, surgical treatment is necessary. A case is presented in which combined treatment by surgery and antitubercular drugs restored the patient's health.


Psychosomatic vulvovaginitis.

Psychosomatic vulvovaginitis. Psychosomatic vulvovaginitis is a real clinical entity that should be suspected in any patient whose vaginal complaints do not correlate with the physical findings. Such patients have usually seen multiple physicians, are "allergic" to most vaginal medications, and exhibit signs of emotional lability. In many cases, psychiatric evaluation and therapy can be of great benefit.


The effect of magnesium sulfate on fetal heart rate baseline variability. Variability of the baseline fetal heart rate is correlated with good fetal outcome, and loss of baseline variability has been observed as a sign of fetal distress. Central nervous system depressing drugs may also decrease fetal heart rate variability, and thus recognition of the effect of medication on the baseline fetal heart rate is important for accurate interpretation of fetal monitor tracings. In the cases reported, marked decrease in fetal heart rate variability was observed within 4 minutes of intravenous administration of magnesium sulfate, and fetal outcome was good in all cases.


Primary adenocarcinoma of the vulva originating in misplaced cloacal tissue. Primary adenocarcinomas of the vulva are rare tumors and usually arise from the Bartholin's gland. However, other potential sources of adenocarcinoma exist. A case is reported where it is believed that the source of the primary adenocarcinoma was a misplaced cloacal remnant. The method of treatment was by radical surgery and the prognosis is uncertain.


Endometrial stromal sarcoma arising from vaginal endometriosis. The present case reports the concurrence of endometriosis of the vaginal cuff with endometrial stromal sarcoma in association with high-dose estrogen. This case raises the question of whether chronic high-dose estrogen might be associated with malignant transformation of endometrial stroma. Although there is no definitive evidence of a causal relation between estrogen and endometrial stromal sarcoma, the possibility should be explored further. Therapy of this neoplasm is discussed and salient clinical and pathologic features are reviewed.


Clear cell adenocarcinoma arising in endometriosis of the rectovaginal septum. Malignant transformation in a focus of endometriosis is uncommon (less than 1%). The ovary is by far the most common site, followed in frequency by the rectovaginal septum. A case of clear cell adenocarcinoma arising in endometriosis of the rectovaginal septum is presented and its pathogenesis discussed.


Fetus papyraceus in twin pregnancy.

Fetus papyraceus in twin pregnancy. Three cases of fetus papyraceus in twin pregnancy were seen over a 4-month period. They were associated with an antepartum stillbirth and intrauterine growth retardation of the larger twin. Two of the 3 mothers exhibited hypertension. It is concluded, therefore, that the appearance of a fetus papyraceus frequently indicates the presence of a hostile intrauterine environment. We suggest that serial ultrasonic examinations be performed to confirm the diagnosis of fetus papyraceus. In this way, appropriate therapy may be directed toward a better outcome for the second twin.


A testosterone-secreting adrenal adenoma. A third case of a testosterone-secreting adrenal adenoma is presented. It differs from the other 2 cases in additionally having glucocorticoid abnormalities. Clinically, the patient had been considered as having polycystic ovaries and did show some improvement with estrogen therapy. In fact, were it not for enlarging uterine leiomyomata on this therapy which prompted a more in depth investigation to look for alternative therapy, this potentially malignant adrenal lesion may never have been discovered.