[The ethmoidal infundibulum and its inflammatory illnesses (author's transl)].

The infundibulum ethmoidale is a cleft-like space situated like a funnel before the maxillary ostium. In this cleft inflammations occur very often. From here they may spread to the paranasal sinuses of the first series (frontal and maxillary sinus, anterior ethmoidal cells), especially to the antrum, and may cause recurrent or chronic inflammations. The walls of the infundibulum may be inspected endoscopically from the middle and inferior meatus, and also from the antrum. Sometimes a direct view in this cleft-like space may be obtained. On this way any inflammations of the infundibulum can be diagnosed exactly and treated endoscopically. This procedure leads not only to healing of the infundibulum, but also of the adjacent paranasal sinuses of the first series.


[Significance of the CEA-Test in malignomas of the head and neck (author's transl)].

Serum carcinoembryonic antigen (CEA) levels were determined in 80 patients, 65 with malignant and 15 with non-malignant affections. Among the malignant tumor bearing patients, in only 30% increased CEA levels were found. On the other hand, in the non-malignant patient group 33% had elevated CEA levels. It is concluded, that the determination of the CEA-Serum levels in malignomas of the head and neck has no diagnostic significance.


Steroid treatment in sudden idiopathic neural deafness? Experimental research.

For the recording of action potential in the auditory nerve two different methods of preparation were used in order to reach at the auditory nerve of experimental animals. The remarkable fact arose that this difference in preparation also produced a difference in signal output during the hypoxygenation experiments. In the one method a solitary P1 peak--the approaching-wave--was recorded from the cochlear nerve during the hypoxygenation, whereas in the other method this solitary P1 was never seen. An explanation for this phenomenon is formulated in this article. At the same time the analogy of the 'sudden deafness' caused by affections of the cochlear nerve is compared with Bell's palsy.


[Audiologic diagnosis of sensorineural deafness by discriminant analysis (author's transl)].

The audiometric test-battery surely is a help to the diagnosis of a lesion of the VIIIth nerve. The discriminant analysis is the most suitable statistic procedure for reduction of the test-battery and for clearer decision in cases of ambigous constellation of findings. The persons are divided into three groups: normals, patients with presumable inner-ear disturbance, and those with lesions of the acoustic nerve. By means of the classification-coefficients (a result of the discriminant analysis) in new cases a diagnosis per conclusionem can be found on-line.


[Septal mucosa grafting for persistent drainage of the sphenoid sinus (author's transl)].

In accordance to fundamental rhinologic rules following surgical intervention in the sphenoid sinus there should be established a persistent access from the nasal cavity by mucosal grafting. Suitable for this seem to be the septum's upper posterior areas. They are pedicled door-leaf-like dorso-laterally, folded into the sphenoid sinus on one or both sides and fixed by tamponade. This procedure is recommended especially to follow transseptal operations of the pituitary gland, biopsies from tumors of the sphenoid sinus and in special cases of isolated empyema of the sphenoid sinus.


Electromyographic study of patients with dysfunction of the Eustachian tube.

In order to determine how often dysfunction of the tube might arise from dysfunction of the tubal muscles, electromyographic examination of the muscles was carried out on 34 patients with occluded or patent tube. Using a monopolar needle electrode inserted through the nose, selective EMG of the tensor and levator veli palatini muscles were picked up during swallowing. It was found that the patients showed neither abnormally reduced nor increased muscle activity. Comparison of muscle activity of the normal tube and of both the occluded and patent tube revealed no significant differences. Therefore, myogenic cause of tubal dysfunction seems improbable from the clinical viewpoint.


[The cumulogram for the sinusoidal rotatory test (author's transl)].

The cumulogram (graphic representation of the cumulative eye position) seems to be a reliable method for studying intensity, symmetry, and regularity of nystagmic responses. Applying sinusoidal rotatory stimulation, the vestibular output can be described in terms of gain and phase difference. The numerical evaluation of cumulograms is demonstrated for sinusoidal tests. The dependence of age is determined for gain and phase difference. While the phase difference appears to be practically independent, the gain of the vestibulo-oculomotor system is strongly correlated with age.


Summating potentials in Menière's disease.

The summating potentials in response to tonebursts of 2, 4, and 8 kHz were studied in a group of 112 patients diagnosed as having Menière's disease, and the results were compared with recordings from 27 normal human ears. Subdivision of the Menière ears into a low-threshold (threshold less than 50 dB HL) and a high-threshold group (greater than 50 dB HL) proved to be functional in relation to the behaviour of the SP. The data of the low-threshold Menière group did not differ significantly from the normal data, whereas the high-threshold Menière group showed significantly smaller summating potentials. Up to hearing thresholds of 50 dB, the detection threshold for the SP was independent of the hearing threshold; at higher hearing losses, the increase in SP threshold equalled the increase in hearing loss. Analysis showed that the correlation found between the changes in SP and hearing threshold in individual patients did not differ significantly from zero for threshold values below 50 dB. The overall conclusion is that in Menière ears hearing losses up to about 50 dB are not related to changes in the hair cells, since the SP does not change, whereas the increase in the amount of hearing loss above 50 dB HL is paralleled by a loss in sensitivity of the summating potential and is therefore related to a functional loss of hair cells.


Transient ischaemic attacks. A neurological challenge.

The problem of cerebral transient ischaemic attacks (TIA) is probably the greatest clinical challenge in the management of cerebrovascular disease. Decisions in this area are as difficult to make as any within the entire field of clinical neurology. The burden of the clinical management of this condition is heavy because the patients tend to be anxious, the risk of angiographic investigation is significant, and the risks associated with either anticoagulant therapy or arterial surgery are not inconsiderable. Above all, many of the issues are controversial where the 'law of diminishing returns' for increasing effort so very much applies.


The neurological examination (spinal).

A correct and accurate diagnosis of paraplegia or tetraplegia due to a spinal cord injury is an important first step in the treatment. A simplified method of performing such an examination is presented to help overcome a diagnostic blind spot of many medical practitioners. Some of the traps and subtleties of diagnosis are discussed.


Evaluation of somatic effects of a health education program for schoolchildren. With special reference to physical activity, nutrition, body composition, and blood lipids.

In a group of 4- to 6-year-old children and a group of 8- to 12-year-old children physical performance capacity, daily physical activity, body composition, blood lipids and daily food intake were determined. Children with a high performance capacity (W170) are more active during the day and do eat more. In the 8- to 12-year-old group it turns out that these extra calories are derived from unfavorable foodstuffs. There are no differences in blood lipids between any of the groups or subgroups. In the 8- to 12-year-old group, children with a low W170 are fatter than those with a high W170. In the younger age group this was not found.


Nutrition, environment and physical performance of preschool children in Italy.

While overt malnutrition is known to interfere with several bodily functions and to cause a deterioration of the level of physical performance, little or no information is available on the effect of marginal nutrition on functional development, particularly at earlier ages. A cross-sectional study of the diet, somatic development and functional response to exercise of 2,241 children, aged 1-6 years, representing contrasting socioeconomic environments, has been carried out. The findings indicate that the upper socioeconomic urban child from Central Italy consumes a better diet and is larger than the underprivileged Southern child. While a greater proportion of the latter group experience a considerable degree of growth retardation, the better efficiency of their heart responses to exercise indicates that the level of nutrition of these children is still good enough to be compatible with a more satisfactory degree of physical fitness. The body fat content and skinfold thickness of the child from the Center have found to be significantly higher than those of the children from the poorer sections of the population, suggesting that at least part of the extra energy available to him for physical activity is being deposited as fat. This raises the question of the desirability of changes in somatic development characteristic of upward social mobility, when accompanied by increased adiposity without a proportional increase in the functional capacity.


The preparation of CMP-sialic acids by using CMP-acylneuraminate synthase from frog liver immobilized on sepharose 4B.

A preparation of frog liver CMP-acylneuraminate synthase (2-10-fold enriched over the homogenate) obtained from DEAE-Sephadex A-50 chromatography of a 105,000g liver supernatant was bound to Sepharose 4B by the CNBr method. The enzyme retained 80-100% activity on binding and showed similar properties to the purified soluble enzyme from the same source with respect to Km, pH optimum and inhibition. The bound enzyme was stable to temperatures above 40 degrees C, in contrast with the soluble enzyme, and could be stored for 4 months at 2 degrees C with loss of 20% activity. The bound enzyme was used preparatively for the synthesis of radioactive and non-radioactive CMP-N-acetylneuraminic acid and CMP-N-glycolloylneuraminic acid. With suitable substrate concentrations and ratios, yields of 80% and over can be achieved.


Affinity chromatography of pig heart fumarase.

2-(5'-Phenylpentyl)fumaric acid was shown to be a competitive inhibitor (Ki 0.5 mM) of pig heart fumarase. After nitration of the aromatic ring, reduction to the amine and diazotization, the acid was attached via azo linkages to a Sepharose 4B-tyramine matrix. The resulting adsorbent was used for the affinity chromatography of crude fumarase, purifications of approx. 20-fold being obtained by specific elution with 0.01 M-citrate.


Generation of aspartate aminotransferase multiple forms by deamidation.

The development of aspartate aminotransferase subforms in vitro was followed by densitometry after thin-film isoelectric focusing. At the same time ammonia production was measured. Each reaction can be expressed in terms of a first-order process in which 2 mol of glutamine or asparagine/mol of dimer are deamidated with a half time of 22 days. The more negatively charged subforms developed in vitro were almost fully active. Another process occurred leading to inactivation by coenzyme modification, and this was independent of deamidation. Although the enzyme formed absorbed maximally at 340nm, it was different from the naturally occurring inactive enzyme that absorbs at this wavelength.


The isolation and properties of pig submandibular kallikrein.

The kallikrein from pig submandibular glands was highly purified, with an overall yield of 31%. Affinity chromatography on bovine basic pancreatic trypsin inhibitor linked to Sepharose 4B was an especially effective step in the purification procedure, giving a purification factor of 80. The enzyme is a single-chain molecule, occurring, as does pig urinary kallikrein, as a major B-form of apparent mol.wt. 39600 and minor amounts of an A-form of apparent mol.wt. 35900; the two forms can be separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The amino acid composition of pig submandibular kallikrein is very similar to, but not quite identical with, that of the two-chain beta-kallikrein isolated from pig pancreatic autolysates. Submandibular kallikrein contains notably more glucosamine and hexoses than does pancreatic beta-kallikrein. Submandibular kallikrein, and also urinary kallikrein, exhibit an unusual biphasic hydrolysis of substrate esters that is not shared by pancreatic beta-kallikrein. For the submandibular enzyme, the K(m) for the initial reaction phase of the hydrolysis of alpha-N-benzoyl-l-arginine ethyl ester is 0.15+/-0.01mm (mean+/-s.e.m.), but rises to 0.69+/-0.04mm (mean+/-s.e.m.) in the stationary reaction phase; the V(max.) does not differ significantly between the two phases. The esterolytic activities of submandibular and urinary kallikreins on a number of esters of different amino acids resemble each other much more closely than those of pancreatic beta-kallikrein.


The biosynthesis of methylcitrate.

Citrate synthase catalyses the formation in vitro of two diastereoisomers of methylcitrate from propionyl-CoA and oxaloacetate. The proportion of diastereoisomers produced is temperature-sensitive. In the presence of oxaloacetate and a thiol trap, the enzyme catalyses the exchange of both alpha-protons of propionyl-CoA with 2H2O. The pro-S-proton at the alpha-carbon atom is exchanged 15 times faster with 2H2O than is the pro-R-proton. The exchanges are over 1000 and 100 times faster respectively than Vmax. These results are interpreted in the light of recent reports that 2R,3S- and 2S,3S-methylcitrates are produced by the enzyme-catalysed condensation and also excreted by patients with propionic acidaemia.


Binding of human liver hydrolases by immobilized lectins.

The binding of 22 human liver hydrolase activities by immobilized lectins of six different carbohydrate specificities, namely alpha-D-mannose (glucose), D-N-acetylglucosamine, D-N-acetylgalactosamine, L-fucose, alpha-D-galactose and beta-D-galactose, were examined. Differences in binding among these enzymes and within specific enzymes were observed. For example, the neutral forms of alpha-mannosidase and beta-xylosidase were bound by the Ulex europaeus lectin I (specific for L-fucose), whereas the acidic forms were not. Bandierea simplicifolia lectin (specific for alpha-galactose) bound 65% of beta-glucuronidase activity; recycling experiments demonstrated complete binding of the enzyme that had been eluted with the competitor D-galactose and no binding of the fraction that was not initially bound. These results suggested the presence of two forms of this enzyme. Similar data were obtained for acidic beta-galactosidase activity. These experiments may provide the basis for the expanded use of immobilized lectins for purification and characterization of hydrolases and other glycoproteins.


Purification and partial characterization of the exotoxin of Corynebacterium ovis.

1. The toxin from Corynebacterium ovis, a phospholipase D (sphingomyelin phosphodiesterase D) that acts on 2-lysophosphatidylcholine and sphingomyelins, was purified by about 400-fold to homogeneity as judged by several criteria. [The EC number of the toxin (EC 3.1.4.41) has been allotted by the Nomenclature Committee of IUB, but has not yet been published.] 2. A new assay method performed in vitro, based on inhibition by the toxin of erythrocyte lysis by staphylococcal beta-haemolysin, was developed to facilitate the purification. 3. The toxin was found to be a basic (pI9.1) glycoprotein of mol.wt. 14,500 +/- 1,000. 4. The amino acid composition of the toxin was highly reminiscent of that of collagen, since it contained hydroxyproline, hydroxylysine and a high proportion of glycine, but preliminary tests showed no other similarities to collagen or proteins with similar compositions.


Intraspecies heterogeneity of epidermal keratins isolated from bovine hoof and snout.

The alpha-keratins, the principal components of the tonafilaments, were extracted, characterized and compared in bovine hoof and snout epidermis. The alpha-fibrous proteins of these tissues are similar with respect to their molecular weights, amino acid composition and percentage of helical structure. However, distinct differences in the polypeptides comprising these proteins were observed. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis of these proteins consistently showed that the polypeptide chain in snout, designated as band B (mol.wt. 67,000), was completely absent from hoof preparations. This was confirmed with several alternative preparative procedures. The peptides produced by digestion of the intact keratins from hoof and snout with CNBr were distinctly different. Finally, digestion of keratins from hoof and snout with trypsin yielded products that differed in size and resistance to further digestion. Thus, in addition to the interspecies polypeptide heterogeneity documented in the literature, this report establishes the intraspecies heterogeneity of keratins and suggests that these differences are due to either the expression of different gene products or differences in post-translational modifications in these two tissues.


Alkaline phosphates from human milk. Comparison with isoenzymes from placenta and liver.

Alkaline phosphatase was partially purified from human milk and its antigenic, functional and structural properties were characterized. By immunochemical and enzymic criteria, the enzyme resembled the alkaline phosphatase isoenzyme found in human liver. Two-dimensional electrophoretic analysis showed that the milk enzyme differed from the liver both in subunit molecular weight and in isoelectric point. These differences were shown to result from variation in sialic acid content.


Accumulation of UDP-glucose pyrophosphorylase by axenically grown amoebae of Dictyostelium discoideum.

Amoebae of the slime mould Dictyostelium discoideum AX2 possess only low UDP-glucose pyrophosphorylase activity when grown on autoclaved Klebsiella aerogenes (approx. 30 units/mg of protein), but accumulate the enzyme to approx. 150-200 units/mg of protein during vegetative growth in axenic medium. The vegetative accumulation of UDP-glucose pyrophosphorylase by axenically grown cells is prevented if autoclaved K. aerogenes are included in the axenic medium, suggesting the absence of a specific inducer. Affinity chromatography using anti-(UDP-glucose pyrophosphorylase) antibody and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis indicate that the enzyme accumulated during axenic growth and that normally accumulated during development are immunologically cross-reactive and that both are composed of two subunits with mol.wts. 55,600 and 57,500 present in approximately equal amounts in the active enzyme.


Partial non-cleavage by cyanogen bromide of a methionine--cystine bond from human serum albumin and bovine alpha-lactalbumin.

When human albumin was treated with CNBr, a fragment designated D was obtained and attributed to the absence from some of the albumin molecules of methionine at position 123 [Lapresle & Doyen (1975) Biochem. J. 151, 637-643]. The present study shows that methionine-123 is converted into homoserine without cleavage of the subsequent methionine-cystine bond. With bovine alpha-lactalbumin, a further example of non-cleavage of a methionine-cystine bond with conversion of methionine into homoserine is reported.


Utilization of endogenous and exogenous sources of substrate for cholesterol biosynthesis by isolated hepatocytes.

The rates of cholesterol biosynthesis in isolated rat hepatocytes were determined by using a method based on measurement of the rate of formation of desmosterol (cholesta-5,24-dien-3beta-ol), which accumulates during inhibition of cholesterogenesis by the drug triparanol. Incubation of cells from normal or 24h-starved animals in a medium containing albumin, glucose, amino acids and acetate as the only organic constituents led to an accelerating rate of sterol formation during the earlier stages of a 6h incubation period. The contribution of exogenously added acetate (initial concentration 3.34mm) to sterol synthesis in both types of cells reached an early maximum and then continually declined. Exogenously added pyruvate and lactate were more efficient sources of sterol carbon than was acetate. Exogenous glucose even at relatively high concentrations (11.1mm) was incapable of providing more than 6% of the total sterol carbon. Although the proportion of total sterol carbon supplied from exogenous acetate increased with increasing concentrations of the extracellular substrate, the rates of total sterol synthesis in both types of cell remained unchanged. Similar observations were made when lactate or pyruvate was the cholesterogenic precursor in normal cells. These studies suggest that, although exogenous substrates were capable of expanding an intracellular pool of cholesterol precursor, the normal supply of intermediary metabolites was not rate-limiting for cholesterogenesis.


Evidence for the existence of isoenzymes of glycerol phosphate acyltransferase.

Subcellular-fractionation studies confirmed previous findings that rat liver glycerol phosphate acyltransferase was located in both mitochondria and the microsomal fraction. Studies of the two activities revealed several differences between them. The mitochondrial enzyme had a lower Km for sn-glycerol 3-phosphate and was more resistant to heat inactivation than was the microsomal enzyme. Some preparations of the mitochondrial enzyme were inhibited by high concentrations of glycerol phosphate. The mitochondrial enzyme was not inactivated by thiol-group reagents, whereas the microsomal enzyme was very rapidly inactivated by these compounds. However, the microsomal enzyme could be specifically protected against this inactivation by low concentrations of palmitoyl-CoA. The results indicate the existence of distinct isoenzymes of glycerol phosphate acyltransferase with different intracellular locations.


Glycolipids and fatty acids of two dog kidney cell lines.

Glycolipid and fatty acid compositions were studied in whole cells and plasma membranes from two dog kidney cell lines (Madin-Darby and SV40-transformed cells) grown in monolayer and suspension cultures. Glycolipids, which account for 5% or less of the total lipids in dog kidney cells, were substantially increased in plasma membranes relative to whole cells. Sialoglycolipids more complex than a Tay-Sachs-like ganglioside were not found in any whole-cell or plasma-membrane preparation of this study. Dog kidney cells transformed by SV40 virus contained primarily a less complex sialoglycolipid, haematoside. Neutral glycolipids comprised 26-43% of the total glycolipid content in Madin-Darby preparations, whereas in transformed cells and membranes neutral glycolipids constituted only 1-22% of the total glycolipid content. Ceramide trihexoside was found in Madin-Darby cultures, but not in transformed cultures. The values for short-chain fatty acids from neutral glycolipids and for saturated fatty acids were generally higher than the values for these fatty acids in calf serum.


The characterization of the non-histone chromosomal proteins of the main classes of nuclei from rat brain fractionated by zonal centrifugation.

1. Non-histone chromosomal proteins were isolated from the cell nuclei of whole rat brain and nuclei from different types of brain cells. 2. Brain nuclei were fractionated by zonal centrifugation into five zones deriving from five main categories of brain cells. These are the neuronals, astrocytes I, astrocytes II, oligodendrocytes I and oligodendrocytes II. 3. The non-histone chromosomal proteins were analysed by (a) sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, (b) electrofocusing electrophoresis and (c) two-dimensional electrophoresis. The results of this analysis showed a limited specific pattern of non-histone chromosomal proteins from the different classes of nuclei. Differences were found to exist between the proteins from neuronal and glial nuclei. In particular one polypeptide band with mol.wt. 10000 and pI8.5 was found to be present in the non-histone protein fractions of neuronal nuclei, and absent from the corresponding fractions of nearly all the other classes of nuclei. 4. Two other classes of nuclear proteins, buffered-saline-soluble and 0.35m-NaCl-soluble, were analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis along with the non-histone chromosomal. The similarities and differences among these groups of proteins are discussed. 5. The patterns of non-histone chromosomal proteins during development were investigated by studying them in two age groups of animals: in infant rats (10 days old) and adult rats. The polypeptide that was found to be specific for the proteins of neuronal nuclei of adult rats is present in all the classes of nuclei of infant rats.


Activation of cathepsin D by glycine ethyl ester.

Cathepsin D purified from bovine spleen is activated by glycine ethyl ester. A maximum of 70% activation was observed at a glycine ethyl ester concentration of 0.1 M and at pH 4.5. The activation effect appears to be reversible.


The breakdown of 2,3-bis(phospho)-D-glycerate by Fe(III)-haemoglobin.

Fe(III)-haemoglobin is shown to catalyse the hydrolysis of 2,3-bis(phospho)-D-glycerate to Pi and 3-phosphoglycerate, although the rate is slow, even when the protein is present at concentrations in the millimolar range. The rate of hydrolysis is proportional to the subtrate concentration up to at least 10 mM, so if the process is enzymic, the Km must be high.


The synthesis of phenyl(2-3H)glyoxal.

A simple inexpensive method has been developed for the synthesis of [2-3H]acetophenone, which has been converted into phenyl[2-3H]glyoxal. The latter compound has been used to modify arginine residues in alkaline phosphatase from two sources, and also a sialidase.


The postnatal methylation of transfer ribonucleic acid in brain. Evidence for the methylation of precursor transfer ribonucleic acid.

Incubation of 3-day-old rat brain with L-[methyl-3H]methionine resulted in the rapid labeling of low-molecular-weight cytoplasmic RNA. Electrophoresis in 15% polyacrylamide gels provided evidence for the methylation of precursor tRNA molecules, and high-performance liquid chromatography demonstrated N2-methylguanine to be the predominant methylated base formed during the first 2 min of labelling.


Characterization of a proteolytic-enzyme inhibitor with allergenic activity. Multiple functions of a parasite-derived protein.

1. A trypsin inhibitor from the tick Boophilus microplus was purified by ion-exchange chromatography and gel filtration. 2. It is pure by the criteria of constant specific activity on gel filtration and by electrophoresis on polyacrylamide gels containing sodium dodecyl sulphate. 3. The protein undergoes reversible polymerization, dissociating at low pH. 4. The apparent molecular weight measured by electrophoresis on polyacrylamide gels containing sodium dodecyl sulphate is 18,500. 5. Inhibition of trypsin occurs by formation of a 1 :1 molar complex. 6. Chymotrypsin is also inhibited, though the dissociation constant of the complex formed is larger than with trypsin. The protein possesses independent sites for the inhibition of chymotrypsin and trypsin. 7. The inhibitor preparation gives an immediate hypersensitivity reaction on intradermal injection into cattle that have been exposed to the tick. The allergenic activity is due to the inhibitor protein itself and not to contaminating material, since the two activities were not separated during purification or in two subsequent affinity-chromatography procedures. 8. The hypersensitivity reaction is a true immunological response, since it is found in almost all cattle that have been exposed to the tick, but not in unexposed animals. In addition, passive cutaneous anaphylaxis can be demonstrated with serum from exposed, but not from unexposed, animals.


Purification, properties and specificity of the restriction endonuclease from Bacillus stearothermophilus.

The restriction endonuclease BstI was purified from 70kg of Bacillus stearothermophilus. The final product is at least 97% pure as judged by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis; this major protein species co-migrates with the enzyme activity on native polyacrylamide-gel electrophoresis and isoelectric focusing. Pure restriction endonuclease BstI has a subunit mol.wt. of 26,000 and is probably a loosely associated dimer. The enzyme shows maximum activity at pH values between 7 and 9.5, and in the presence of 0.5-2mM-Mg2+. NaCl inhibits the restriction enzyme activity. Restriction endonuclease BstI cleaves DNA in a position identical with that cleaved by endonuclease BamHI (for Bacillus amyloliquefaciens), i.e.: (formula: see text). In the presence of high concentrations of enzyme, DNA cleavage occurs at secondary sites. This side-specificity is enhanced by the addition of glycerol. Preliminary studies indicate that these sites are of the type: (formula: see text).


Diamine-induced inhibition of liver ornithine decarboxylase.

Repeated injections of 1,3-diaminopropane, a potent inhibitor of mammalian ornithine decarboxylase, induced protein-synthesis-dependent formation of macromolecular inhibitors or ;antienzymes' [Heller, Fong & Canellakis (1976) Proc. Natl. Acad. Sci. U.S.A.73, 1858-1862] to ornithine decarboxylase in normal rat liver. Addition of the macromolecular inhibitors, produced in response to repeated injections of diaminopropane, to active ornithine decarboxylase in vitro resulted in a profound loss of the enzyme activity, which, however, could be partly recovered after passage of the enzyme-inhibitor mixture through a Sephadex G-75 columin in the presence of 0.4m-NaCl. This treatment also resulted in the appearance of free inhibitor. In contrast with the separation of the enzyme and inhibitory activity after combination in vitro, it was not possible to re-activate, by using identical conditions of molecular sieving, any inhibited ornithine decarboxylase from cytosol fractions obtained from animals injected with diaminopropane. However, the idea that injection of various diamines, also in vivo, induces acute formation of macromolecular inhibitors, which reversibly combine with the enzyme, was supported by the finding that the ornithine decarboxylase activity remaining after diaminopropane injection appeared to be more stable to increased ionic strength than the enzyme activity obtained from somatotropin-treated rats. Incubation of the inhibitory cytosol fractions with antiserum to ornithine decarboxylase did not completely abolish the inhibitory action of either the cytosolic inhibitor or the antibody. A single injection of diaminopropane produced an extremely rapid decay of liver ornithine decarboxylase activity (half-life about 12min), which was comparable with, or swifter than, that induced by cycloheximide. However, although after cycloheximide treatment the amount of immunotitrable ornithine decarboxylase decreased only slightly more slowly than the enzyme activity, diaminopropane injection did not decrease the amount of the immunoreactive protein, but, on the contrary, invariably caused a marked increase in the apparent amount of antigen, after some lag period. The diamine-induced increase in the amount of the immunoreactive enzyme protein could be totally prevented by a simultaneous injection of cycloheximide. These results are in accord with the hypothesis that various diamines may result in rapid formation of macromolecular inhibitors to ornithine decarboxylase in vivo, which, after combination with the enzyme, abolish the catalytic activity but at the same time prevent the intracellular degradation of the enzyme protein.


Proteinase and proteinase-inhibitor activities of rat uterine myometrium during pregnancy and involution.

A supernatant fraction was prepared from rat uterine myometrium by homogenization, sonication and centrifugation. In this supernatant the protein concentration and the activities of an acid proteinase, an acid phosphatase and a proteinase inhibitor were measured. From the fibrous sediment, after washing with 0.5% Triton X-100 and with water, an actomyosin-containing solution was obtained by extraction with 0.6M-NaCl, and in this extract the protein concentration and a neutral proteinase activity were measured. The myometrial wet weight and the activities of the acid proteinase, acid phosphatase and proteinase inhibitor increased by factors of 3-15 during pregnancy and decreased to the same or a greater extent during involution. The amount of protein extracted with 0.6M-NaCl increased by a factor of only 2.3 and the neutral proteinase activity remained essentially constant during pregnancy and involution. The pH optimum of the neutral proteinase, and its pattern of activity compared with those of the lysosomal enzymes, show that the neutral proteinase is not of lysosomal origin. Actomyosin is degraded by the neutral proteinase activity in vitro. Since actomyosin is rapidly broken down only after parturition, the action of the neutral proteinase activity on actomyosin, if this occurs in vivo, must be regulated in some way. The proteinase-inhibitor activity measured in the first supernatant varied in a manner which suggested that it could be involved in this control.


Frequency of systemic lupus erythematosus in different ethnic groups in Hawaii.

A survey of systemic lupus erythematosus (SLE) patients was conducted in civilian general hospitals on Oahu, Hawaii for the years 1970-75. One hundred sixty-eight cases were ascertained, of which 107  were considered "definite." Age-adjusted prevalence rates per 100,000 were estimated for definite cases at the end of 1975 as follows: white 5.8, Chinese 24.1, Filipino 19.9, part-Hawaiian 20.4, and Japanese 18.2. There was a heavy preponderance of females in each ethnic group, averaging 90% of the definite cases overall. Review of vital statistics for the United States and Hawaii during this period showed age-adjusted SLE mortality rates per million as follows: U.S. white 3.04, U.S. non-white 8.82, Hawaii white 1.89, Hawaii non-white 14.46. The cause of the very high SLE prevalence and mortality in the Oriental and Polynesian people of Hawaii is not clear.


Therapeutic effect of prolonged hyperbaric oxygen in adjuvant arthritis of the rat.

Development of adjuvant disease in the rat is suppressed if hyperbaric oxygen is administered within one day after the inoculation of an oil suspension of Mycobacterium tuberculosis and continued for 16 to 17 days. Although 10 to 40% of the rodents developed mild arthritis after discontinuance of therapy, most remained symptom-free for at least 50 days. Oxygen administered after arthritis is advanced still exerted a significant curative effect. Possible mechanisms underlying the therapeutic action of oxygen are discussed.


Collagen-induced arthritis in rats. Comparison of vitreous and cartilage-derived collagens.

An oil emulsion of purified type II collagen from bovine articular cartilage when injected intradermally into rats induced an inflammatory polyarthritis in 4 of 12 animals. When similarly injected, collagen purified from bonve vitreous induced arthritis in 6 of 12 animals. Studies of humoral and cell-mediated immunity to both collagen preparations demonstrated complete cross-reactivity. It is concluded that vitreous collagen shares the arthritogenic property of cartilage-derived type II collagen and that collagen from the two sources is indistinguishable in arthritogenic and immunologic properties.


Epidemiology of Ankylosing spondylitis in Rochester, Minnesota, 1935-1973.

The Mayo Clinic records linkage facility for residents of Rochester, Minnesota, Yielded 102 cases of ankylosing spondylitis (AS) diagnosed from 1935 through 1973. The incidence did not change significantly over the 39 years. Three times as many males as females were affected. In contrast to another recent report, survivorship of males with AS was not different from that of the general population, whereas survivorship of females with AS was reduced. The overall prevalence was 129/100,000.


Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis. Comparison of two dosage schedules of choline magnesium trisalicylate.

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a ddecrease of 1 mg/dl in mean minimum concentration.


Studies on vaccine-induced rubella arthritis. Serologic findings before and after immunization.

Rubella hemagglutination inhibition (HI) antibody responses were measured before and after immunization with HPV-77 DE/5 vaccine in 7 adult females with recurrent arthritis following rubella immunization and 24 hospital personnel studied prospectively while undergoing routine rubella immunization. The only distinctive serologic characteristic observed in all subjects developing rubella arthritis was a preimmunization HI titer of less than 1 : 8. No association was observed between the development of arthritis after immunization and prolongation of rubella HI IgM responses or elevation of rubella HI IgG responses.


Factor XII deficiency with systemic lupus erythematosus. Biological implications.

A patient with Factor XII (Hageman) deficiency and fulminant systemic lupus erythematosus is presented. The Factor XII deficiency was noted prior to the onset of clinical systemic lupus erythematosus and persisted throughout the patient's course without associated hemorrhagic manifestations. There was no evidence for a circulating anticoagulant. The patient had a rapidly progressive fatal course unresponsive to corticosteroid therapy. Factor XII levels did not increase during therapy with steroids. Despite absence of Hageman factor, evidence for activation of complement by the classic pathway and thromboembolic phenomenon was observed. The role of Factor XII in coagulation and inflammatory pathways and the influence of the factor deficiency on the course of the patient's illness are discussed.


Motility, acrosome morphology and fertilizing capacity of cold-shocked hamster spermatozoa.

When fresh epididymal spermatozoa were cold shocked for 10 or 30 min, then warmed to 24 degrees C, sperm motility was normal, but cold shocking ejaculated or capacitated spermatozoa caused a significant decrease in the percentage of motile spermatozoa and, for capacitated spermatozoa, in the rate of motility. The acrosomes of motile fresh epididymal and ejaculated spermatozoa became crenulated after cold shock, and the percentage of spermatozoa with crenulated acrosomes increased with longer periods of cold shock and was higher when spermatozoa were cold shocked in serum than in saline. When epididymal spermatozoa were cold shocked after incubation for 4 h at 37 degrees C, the acrosomes on spermatozoa which had not undergone an acrosome reaction became swollen and elevated instead crenulated. Epididymal spermatozoa which were cold shocked and then incubated for 4 h at 37 degrees C exhibited acrosome reactions and activation of motility, but had reduced fertilizing capacity when tested in vitro. Spermatozoa incubated in serum and cold shocked were able to penetrate zone-free ova even though their tails had been bent through 180 degrees. It is suggested that cold shock decreases the fertilizing capacity of hamster spermatozoa by interfering with the ability of spermatozoa to bind to and/or penetrate the zone pellucida.


Pyogenic granuloma of the cornea simulating squamous cell carcinoma.

A case of pyogenic granuloma involving the cornea simulated recurrent squamous cell carcinoma clinically and was misdiagnosed as invasive squamous cell carcinoma on biopsy. Ophthalmologists and pathologists should be aware of the capability of the corneal or conjunctival tissues to mount a granulation tissue response to injury.


Immune thrombocytopenia in lymphoproliferative diseases.

We have studied the thrombocytopenia of lymphoproliferative disorders using a measurement of membrane-bound IgG by an antiglobulin consumption assay. Nine patients with chronic lymphocytic leukemia (CLL) and thrombocytopenia had increased membrane-bound IgG. Two patients with non-Hodgkins lymphoma and 1 patient with Hodgkins disease also had thrombocytopenia and increased membrane-bound IgG. Five of the patients with CLL had positive direct antiglobulin (Coombs) tests on red cells; of these, 3 patients had hemolytic anemia. In eight of the 9 patients with CLL, thrombocytopenia, and increased platelet-bound-IgG, the platelet count increased with the administration of prednisone or an alkylating agent, with splenectomy, or with a combination of these.


Chromosome analysis in two unusual malignant blood disorders presumably induced by benzene.

Two patients with presumably benzene-induced malignant blood disorders with preleukemic phases were cytogenetically monitored through the courses of their diseases. Patient 1, in addition to a familial chromosome translocation [t(3;16)], developed karyotypic abnormalities in 100% of the marrow cells, including two translocation: t(9;16)] and t(4;15). Monosomy of chromosome 7 characterized the cells of patient 2. Cytogenetic monitoring of the patients at various phases of their diseases served as an important indicator of the transformation or progression of the preleukemia into frank leukemia and of the unusual behavior of such leukemic cells.


Effect of anti-P1A1 antibody on human platelets. II. Mechanism of the complement-dependent release reaction.

We studied the mechanism by which complement activated by anti-P1A1 antibody elicits the platelet release reaction. Anti-P1A1 antibody mediates its action through the classic complement pathway, and its effect depends on the concentration of IgG antibody on the platelet surface. At relatively high concentrations of anti-P1A1 antibody the release reaction was mediated by a mechanism in part independent of extracellular ADP and metabolic energy and inhibited by only high concentrations of PGE1. However, at lower concentrations of anti-P1A1 antibody the release reaction was dependent on metabolic energy and ADP, and the concentration of PGE1 required to inhibit platelet release was similar to that required to inhibit ADP-induced release. The cyclooxygenase inhibitor acetylsalicylic acid inhibited the release reaction at all nonlytic antibody levels studied. None of the agents studied inhibited the induction of platelet lysis by very high concentrations of anti-P1A1 antibody, and no effect of antibody on platelet 14C-serotonin uptake was observed at antibody concentrations that did not mediate direct in vitro alteration. These studies suggest the possible use of pharmacologic agents in modifying some complement-mediated platelet alterations.


Evidence for production of oxidizing radicals by the particulate O-2-forming system from human neutrophils.

The particulate O-2-forming system from human neutrophils was found to oxidize methional and 2-keto-4-methylthiobutyric acid (KMB) to ethylene, indicating the formation by this system of strongly oxidizing radicals. Conforming this interpretation was the observation that ethylene production was inhibited by the radical scavengers benzoate, ethanol, and mannitol. Ethylene production was also sharply reduced by superoxide dismutase, implicatin O-2 as a precursor of oxidizing radicals. In our system catalase only partially inhibited ethylene generation from either methional or KMB, suggesting that oxidizing radicals are generated at least in part by the reacton of O-2 with compounds other than H2O2. We propose that in neutrophils oxidizing radicals are formed in a reaction between O-2 and a peroxide according to the following equation: O-2 + ROOH leads to RO . + OH- + O2, in which ROOH may be hydrogen peroxide, an alkyl peroxide, or an acyl peroxide (i.e., a peroxy acid).


Congenital deficiency of blood clotting factors II, VII, IX, and X.

A patient congenitally deficient in factors II, VII, IX, and X has been further investigated after a follow-up of 15 yr. At birth, these factors, when determined by clotting assays, were undetectable. Following therapy with vitamin K1, the clotting activity of these factors rose but never exceeded 18% of normal. Immunologic assays revealed much higher levels of these factors than did clotting assays, thus suggesting that the vitamin-K-dependent factors were present in abnormal forms. Two-dimensional crossed immunoelectrophoresis showed that at least two forms of prothrombin were present in the patient's plasma. One form was similar to normal prothrombin; the other had the same mobility as acarboxyprothrombin. In addition, the majority of this fast-migrating peak was not adsorbable onto insoluble barium salts. These observations suggested that some molecules of the patient's prothrombin lacked the normal complement of gamma-carboxyglutamic acid residues. This observation was confirmed by a specific assay for gamma-carboxyglutamate. Since malabsorption of vitamin K, warfarin intoxication, and hepatic dysfunction were excluded as causes of this patient's syndrome, this rare congenital abnormality could represent either a defective gamma-carboxylation mechanism within the hepatocyte or faulty vitamin K transport.


An assay for intrinsic factor based on blocking of the R binder of gastric juice by cobinamide.

An in vitro assay for measurement of gastric juice intrinsic factor (IF) was developed based on the ability of the cobinamide (Cbi) [(CN, OH) Cbi] to bind to the gastric juice R-type binders of cobalamin (Cbl) and not to the IF binder. Subsequently added radioactive Cbl, CN-[57Co] Cbl, binds only to the IF binders and allows for direct measurement of this Cbl binding protein. This Cbi blocking assay was found to function as well as the more conventional methods of IF measurement, G-100 column chromatography, and IF blocking antibody assay. The present assay has the advantage of eliminating the need for elaborate forms of protein separation and does not rely on a source of antibody.


Human myeloid progenitor cells expressing HLA antigens.

Marrow cells of known HLA type were incubated with HLA antiserum plus complement and then plated in soft agar. Colony formation was consistently inhibited by appropriate HLA antisera. Mixing experiments excluded an indirect effect on CFU-C by lysis of mature leukocytes. We conclude that human CFU-C express HLA antigens.


[Early mechanical respiration with prolonged inspiration in the treatment of acute respiratory insufficiency in the newborn].

The experience at the Servicio de Medicina Perinatal Pediátrica of the Centro Hospitalario "20 de Noviembre" of the ISSSTE is reported on the application of a ventilatory assistance criterion to treat the severe respiratory distress syndrome in the newborn. Early application of intermittent mechanical ventilation (IMV) is established to avoid clinical impairment. The mechanical ventilator is used in such a way that without withdrawing therapeutic effectiveness, it may cut down to a minimum complications derived from the use of IMV. The results show increase in survivorship, specially among the lower weight population and less complications than with the previous management method, in spite of a 70% increase in the use of IMV.


[Management of patients with phenylketonuria in Mexico].

This paper shows the results of the dietary management of 9 children with phenylketonuria diagnosed at the Clinic for Inborn Errores of Metabolism of the Hospital del Niño-Instituto de Investigaciones Biomédicas UNAM. The age at which the diet was instituted was variable: in one case before the age of 8 weeks; in another one at 5 months and in the remainder after 10 months. The management is multidisciplinary and involves a geneticist, a pediatrician, a neurologist a psychologist, a nutritionist, and a social worker. In spite of the difficult control of the diet in some patients, in most cases satisfactory phenylalanine levels were maintained most of the time. The body growth and development have been normal. With regard to the mental development, the results support the importance of an early diagnosis since the case treated from the age of one month has shown normal development; the patient diagnosed at 5 months has had a low normal IQ and the rest, all diagnosed after 10 months of age, show some improvement, but do not reach normal levels. The need of neonatal screening for early diagnosis is emphazised.


[Arterial pressure during the neonatal transitional period].

A total of 288 determinations of blood pressure were practiced in newborns using an ultrasonic unit with the purpose of establishing the blood pressure in the newborn during the neonatal transitional period in a sampling cycle divided into four stages (0:30, 4:00, 6:00 and 10:00 hours). The results were analyzed in a descriptive fashion by means of variation indexes that show the changes occurred in B.P. between one and the other stages of the sampling cycle.


[Congenital syphilis with nephrotic syndrome].

A patient with congenital syphilis and nephrotic syndrome is reported. The renal biopsy with light microscope showed glomerulopathy with epithelial proliferation. Irregular, nodular, electrodense material was identified with the electron microscope in subepithelial spaces and immunofluorescence showed irregular granular positivity for IgG, IgM and fibrin, which confirmed a disease due to immune complexes. Pencillin and physical rehabilitation were sufficient therapy for the recovery of this patient.


[Chondroectodermal displasia (Ellis-van Creveld syndrome)].

The present paper describes a case with clinical and radiological characteristics of Ellis-van Creveld syndrome. He was the first offspring from non-consanguineous parents. We comment the differential diagnosis between chondroectodermal dysplasia with types of dwarfism for genetic conseling purposes.


[Carcinoid tumor of the appendix in children].

Carcinoid tumor of the appendix has been known since 1808, and currently we know that it may appear all along the intestinal tract, biliary tree, ovaries, bronchi, lungs and pancreas. It is usually uncommon during infancy, representing 1.8% of all the tumors of the intestinal tract, approximately 70% of the appendiceal tumors and 0.16 to 0.7% of all operated appendixes. It is more frequent in females. With no typical clinical picture, it is usually an incidental finding, as well as a cause of inflammatory processes of the appendix. When the diameter is less than 1.0 cm, the treatment of choice is appendectomy; and in tumors of larger size, surgery is more extensive. Two cases are reported.


[Congenital lobar emphysema].

A case of congenital lobar emphysema is reported in a male child four years old. The clinical and radiological studies are described. Besides, this case was the basis to review the topic of Congenital Lobar Emphysema and the corresponding literature, considering that this is an uncommon disease in our milieu.


[Congenital megacolon and Duhamel Grob's surgical technic].

The authors present their own experience and results when treating patients with congenital megacolon by performing the Duhamel-Grob's surgery. The clinical aspects and the surgical treatment performed are analized in detail as well as the post-operative complications which were also compared to reports in the literature.


[Acrodysostosis].

Two unrelated males of 16 and 8 years of age with acrodysostosis were studied. They showed short stature, broad and hypoplastic nose and severe acromelic shortness. X-ray studies revealed bilateral brachymetacarpaly, brachymetatarsalia and brachyphalangia with hyperplasia of the first ray in hands and feet. Psychometric studies revealed an IQ of 85, the highest observed in the 22 cases so far reported. The variable expressivity of the syndrome is discussed on this basis. The hypothesis of an autosomal dominant "de novo" mutation as the cause of the entity is supported by the finding of increased paternal age.


[Capillary and central serum bilirubin: reliability of values].

At the Servicio de Medicina Perinatal Pediátrica of the Centro Hospitalario "20 de Noviembre" of the ISSSTE, 141 samples of bilirubin were obtained from 47 icteric newborns within the first 72 hours of hospitalization. Determinations were made for total serum bilirubin, indirect and total capillary bilirubins. The results obtained were submitted to analysis of plain linear regression followed by determination of correlation coefficient to establish statistical reliability. The capillary samples showed a greater statistical reliability by a lesser dispersion index. The determination of capillary bilirubin makes necessary the investigation by microtechnics of the potentially toxic fraction of bilirubin. However in the indistinct utilization of capillary and central venous samples, capillary values may be more useful because their reading is more reliable.


[Genetic counseling of acrocephalosyndactylia].

The present paper describes a case with clinical and radiological characteristics of Apert's syndrome. He was the first offspring from second cousins marriage. We considered that in this case, consanguinity is an associated feature. Perhaps this case may be the third one reported in the literature with consanguineous parents. We comment the different classifications of the acrocephalosyndactylias for genetic counseling purposes.


[Adaptation of the Pudenz system of variation for the lumboperitoneal derivation in communicant hydrocephalia in children].

This paper is a technical report of the procedure we follow at the Neurosurgical Pediatric Service at the Centro Médica La Raza, IMSS for the lumboperitoneal derivations to which we have adapted the Püdenz system for this purpose having excellent results and avoiding the "valve dependency" of the patients.


[Inhibition of nociceptive responses of spinal dorsal horn neurons by periaqueductal gray stimulation (author's transl)].

In order to analyze analgesic effects of periaqueductal gray stimulation, experiments were carried out in nitrous oxide anesthetized cats. Spinal dorsal horn neurons receiving C-fiber inputs from the posterior tibial and/or superficial peroneal nerves were excited by noxious heat stimulation of the ipsilateral hindpaw. The evoked spike discharges were inhibited by repetitive stimulation of the periaqueductal gray at currents 300--900 microamperemeter. Effective sites for inhibition were distributed throughout the ventral half of the periaqueductal gray bilaterally. A monotonous relationship was found between stimulus intensity (skin temperature) and number of spike discharges; As predicted by Stevens' law, the number of spike discharges psi grew as a power function: psi = K(psi--psi0)beta where psi is the stimulus intensity, psi0 is the effective threshold, and K is a slope constant of the spike discharges versus stimulus intensity curve depending upon neurons. The exponent beta was approximately 1.0. The periaqueductal gray stimulation resulted in a decrease in the slope constant kappa, without alteration either in the threshold constant psi0 or in the exponent beta.


[Hematologic characteristics of anemia associated with infectious processes].

The study included 30 children with anemia and significant infectious process. The hematologic characteristics of this anemia were identified in their evolution and these findings were correlated with levels of serum iron to disclose whether variations are present to support the diagnosis of mixed etiology of the anemic syndrome. Transferrin saturation index was found to be the best parameter to diagnose iron deficiency in cases of anemia associated to infectious processes and due to the fact that 50% of these cases showed mixed etiology anemia, it seems reasonable that further integral studies should be carried out in this anemic syndrome.


[Prevalence of anemia in a sample of school children in Durango City].

The circulatory levels of hemoglobin and the frequency of anemia were determined in a representative sample of children with a mean age of 6.7 years. A random sample of 500 children of the city of Durango was studied. Durango has an altitude of 1893 m above sea level. The mean value of hemoglobin was 12.57 g/100 ml, with a range of 9.4 to 15.0 and a SE of 0.05. There was no difference statistically significant between the sexes. Considering 12.0 as the lower normal limit for hemoglobin values, it was found that 16% of the children were anemic, 49% of the anemic children were iron deficient, with iron serum levels of less than 60 ug/100 ml. The relationship between anemia and number of living children, birth order and weight was established. The frequency of anemia was higher among children coming from families with 4 or more living children.


[Deep Sylvian psammomeningioma, report of a case (author's transl)].

The authors reported a case of 31-year-old female who had episodes of fainting attack. She had no significant neurological deficit but had EEG abnormality. Carotid angiography showed a tumor stain, ca. 1.7 cm in diameter, near the right insula. CT scan also revealed a high density area at the same site. At the time of operation, a small tumor located deeply in the right sylvian fissure was found out and successfully removed. Histologically, this tumor was diagnosed as a meningioma having some typical psammomatous features. This type of meningioma, named as deep sylvian psammomeningioma dy Cushing and Eisenhardt, is extremely rare; we could found only 19 cases in the literature.


Baroreflex sensitivity in hypertension during beta-adrenergic blockade.

Baroreceptor function was measured in 18 patients with essential hypertension by plotting the change in pulse interval against a phenylephrine-induced transient rise in systolic blood pressure. The influence of propranolol (160 mg daily for at least 4 weeks) on this function and on heart rate after maximal exercise was studied and correlated with the plasma propranolol level. In 13 out of the 18 patients only baroreflex resetting occurred with no change in sensitivity during propranolol administration. A definite correlation was found between the degree of beta-adrenergic blockade, expressed as the reduction in maximal exercise heart rate and the change in mean arterial pressure. No relation could be shown between plasma propranolol steady state levels and these changes. The fall in blood pressure during beta-adrenergic blockade with a low dosage of propranolol apparently does not depend on changed baroreflex sensitivity, but on the intrinsic action of this drug on beta-receptors.


Echocardiographic findings in prolapsed aortic cusp with vegetation.

A patient with severe aortic regurgitation showed abnormal echoes in the left ventricular outflow tract compatible with aortic vegetation or flail aortic cusp. At operation, a pedunculated vegetation on a prolapsed aortic cusp was found. The case illustrates some of the pitfalls in the echocardiographic distinction of the two conditions.


An operation for anomalous origin of left coronary artery.

Successful surgical correction for anomalous origin of the left coronary artery from the pulmonary artery in a 4-year-old child is reported. An aortopulmonary fistula was created and a pericardial baffle was inserted within the pulmonary artery to connect the fistula to the ostium of the left coronary artery. The clinical, haemodynamic, and angiographic features of the anomaly are presented. The child's progress is satisfactory 17 months after the operation.


Haemostatic defects in cyanotic congenital heart disease.

An investigation of defects of the haemostatic mechanism in 41 children with cyanotic congenital heart disease concluded that such abnormalities were common and normally involved factors synthesised in the liver, that is the vitamin K dependent factors (rothrombin, factors VII and IX) and factor V. No evidence was found of activation of the coagulation or fibrinolytic systems. The defects can be explained by deficient synthesis resulting from systemic hypoxia as well as from sluggishness of the local microcirculation caused by high blood viscosity. Vitamin K parenterally had no demonstrable effect. Replacement of these factors, possibly combined with measures to improve the microcirculation, therefore, appears to be the appropriate treatment.


Location and vascular supply of sinus node in human heart.

The exact location of the sinus node was determined in 25 infant hearts using reconstructive techniques. The sinus node was found to lie on the lateral aspect of the superior cavo-atrial junction in the great majority (22 hearts). In only 3 hearts was it found to straddle the summit of the crest of the right atrial appendage where it is popularly believed to be located. In the majority of instances a single artery supplied the node (in 11 hearts the artery approached posteriorly, and in 10 the artery approached anteriorly), though there was considerable variation in the exact anatomy of the arterial supply. Connections between the sinus node and atrial myocardium were diffuse and abundant but in no instances were tracts of specialised cells observed leaving the node and traversing any distance through the atrial wall. These findings are relevant to the sinus node dysfunction that may follow cardiac surgical procedures.


Postoperative haemodynamics in tetralogy of Fallot. A study of 132 children.

Our study was undertaken to determine the type, incidence, and functional significance of residual anomalies in patients who have undergone corrective repair for tetralogy of Fallot. We reviewed data from cardiac catheterisations performed on 132 survivors. A significant residual ventricular septal defect was present in only 12 patients. Resting right ventricular systolic pressure was less than 80 mmHg in 100 patients and ranged from 80 to 150 mmHg in the other 32 patients. Thirty-five patients were studied both at rest and during supine exercise. In most patients, the relation between oxygen consumption and cardiac output was normal during exercise. The stroke index and right ventricular end-diastolic pressure at rest and on exercise were compared in 34 patients. Seventeen showed a normal response to exercise. In the other 17 patients, right ventricular end-diastolic pressure rose on exercise; in 5 of these the stroke index fell during exercise, indicating abnormal myocardial response. Our studies indicate the frequent occurrence of residual abnormalities, even in patients who appear asymptomatic, after total correction of tetralogy of Fallot.


Echocardiographic study of right and left ventricular dimension and left ventricular function in patients with tetralogy of Fallot before and after surgery.

Right and left ventricular dimensions and function were determined by one-dimensional echocardiography in patients with tetralogy of Fallot before and after corrective surgery. Thirty-five children (mean age: 5.9 years) were examined; 5 of them died immediately after operation; 5 had palliative operations only. The remaining 25 had repeat echocardiography 2 to 4 and/or 8 weeks after total correction. Compared with normal values, preoperative left ventricular dimensions were smaller than expected for body surface area (mean = 85.4% +/- 1.9 SEM, range 65 to 105% of normal); 21 values were below the 5th centile. Postoperatively, left ventricular dimensions increased significantly and reached normal values in most cases (mean = 103.2 +/- 2.0% SEM, range 81 to 121%). The main increase took place in the first 4 weeks (P less than 0.001; mean difference 0.7 +/- 0.14 cm). The 5 children who died after operation had smaller left ventricular dimensions than the survivors (P less than 0.01). Left ventricular function was evaluated by measuring mean circumferential fibre shortening, per cent shortening, and ejection fraction; they were normal in most patients and diminished only insignificantly after corrective surgery. Right ventricular dimensions were increased preoperatively but decreased significantly (P less than 0.001) postoperatively. Septal movement was normal in direction and excessive in displacement in most patients before operation; immediately after operation it became flat or showed paradoxical motion. Two months after operation 50 per cent of the children showed a return to normal septal movement. Early appearance of normal septal movement could be related to the presence of significant pulmonary stenosis. It is concluded that a high percentage of patients with tetralogy of Fallot have underdeveloped but normally functioning left ventricles which adapt well to the new postoperative state.


Analysis of left ventricular behaviour in diastole by means of finite element method.

The human left ventricle in diastole can be modelled as a passive structure with incremental internal pressure change being considered as the load. Recent developments in engineering stress analysis provide techniques for predicting the behaviour of structures with complex geometry and material properties, as is the case with the left ventricle. That which is most appropriate is the finite element method which requires the use of a large digital computer. The ventricles of 2 patients have been studied during diastole, the geometries having been derived from cineangiographic data (biplane), and the pressure by means of catheter-tip manometers. Various descriptions of myocardial stress/strain relations have been assumed and applied to the left ventricular wall in order to obtain the best match between the calculated and observed deformation patterns. The manner in which the value and distribution of stiffness in the left ventricle influences the shape change can therefore be determined, and possible clinical implications deduced.


Detection of postinfarction left ventricular aneurysms by first pass radionuclide ventriculography using a multicrystal gamma camera.

Eighteen patients with a history of previous anterior myocardial infarction and suspected left ventricular aneurysms were studied both by contrast left ventriculography and by first pass radionuclide ventriculography using Technetium99m and a computerised multicrystal gamma camera. The radionuclide study successfully identified all 14 patients with aneurysms and all 4 with diffusely hypo-kinetic ventricles. Ejection fraction calculated from the change in radioactive counts in the left ventricle correlated well with that calculated from the area-length method from the contrast angiogram (r = 0.83). Ventricular volumes calculated from the area-length formula for both contrast and radionuclide angiograms correlated closely (r = 0.85 and r = 0.89 for end-systolic and end-diastolic volumes, respectively). In the patients with aneurysms, there was a close correlation between the extent of akinesis, as assessed by the two methods (r = 0.94). The ability of the radionuclide ventriculogram to provide accurate information on global and segmental ventricular function, and to differentiate between segmental and diffuse ventricular dysfunction, enables the method to act as a screening procedure in the investigation of patients with suspected left ventricular aneurysms.


Failure of aneurysmectomy to improve left ventricular function.

Biplane left ventricular angiography was performed in 22 patients with isolated obstructive disease of the anterior descending branch of the left coronary artery and with an anterior aneurysm following transmural myocardial infarction. Six patients were restudied between 6 and 10 months after aneurysmectomy. Left ventricular reserve was estimated by analysis of a spontaneous postextrasystolic beat. Using angiographic techniques a contractile section, a transitional section, and a noncontractile section were identified. From the surgical patients the excised aneurysm and a transmural needle biopsy of the transitional section were investigated by light microscopy. With increasing volumes of noncontractile and transitional sections, total end-diastolic volume (r = 0.81, P less than 0.001) and end-systolic volume (r = 0.94, P less than 0.001) increased linearly, while the ejection fraction decreased (r = 0.70, P less than 0.001). No relation was found between the combined volumes of the noncontractile and transitional sections on the one hand, and the end-diastolic volume, the end-systolic volume, or the ejection fraction of the contractile section on the other hand. After aneurysmectomy a significant decrease was found in end-diastolic volume (194 to 133 ml/m2, P less than 0.001) and end-systolic volume (124 to 83 ml/m2, P less than 0.001) but no change occurred in ejection fraction (35 to 37%) and left ventricular end-diastolic pressure (23 to 25 mmHg). Surgical resection included part of the transitional section, which before surgery had an average ejection fraction of 27 per cent during a normal beat, rising to 41 per cent in a postextrasystolic beat. The transitional section after surgery now formed a large akinetic area of the anterior wall. We conclude that aneurysmectomy in isolated left anterior descending artery disease with anterior aneurysm fails to improve left ventricular function because the effect of reduction of left ventricular volumes is offset by the destruction of contractile behaviour in the transitional section.


Electrophysiological effects of L 9394 (benzoyl-indolizine) in man.

The electrophysiological effects of L 9394 (benzoyl-indolizine), a substance chemically related to amiodarone, but devoid of iodine atoms, were investigated by programmed electrical stimulation of the heart in 12 patients with various forms of tachycardia. Four subjects had electrocardiographic evidence of the WPW syndrome and episodes of circus movement tachycardia. Paroxysmal supraventricular tachycardia, confined to the atrioventricular (AV) node, was found in 3 patients. In 2 cases, where a short PR interval was present, the main complaint was the occurrence of paroxysmal atrial fibrillation. In the remaining 3 instances, the arrhythmia consisted of slow ventricular tachycardia (1 case), supraventricular tachycardia of the focal type (1 case), and episodes of primary ventricular fibrillation, not related to acute myocardial ischaemia (1 case). L 9394 injected intravenously was seen to lengthen the transnodal conduction time as well as the effective and functional refractory periods of the node. Similar effects were found on the retrograde VA pathway. The drug had no action on the infra-Hisian conduction system, on the refractory periods of ventricular muscle, or on the refractory periods of accessory bypasses. The drug was injected during an episode of tachycardia in 6 cases with reproducible supraventricular re-entrant tachycardia. Three had a tachycardia circuit confined to the node. In those instances, the drug had beneficial effects (slowing and interruption of tachycardia, decrease or abolition of echo zone; loss of ability to induce tachycardia). In the other 3 cases, an accessory pathway was incorporated in the circuit. L 9394 interrupted the tachycardia in 2 instances (by anterograde AV block), but failed to protect all 3 patients against reinitiation of tachycardia by premature stimuli. It is concluded that L9394 does not share all the pharmacological properties of amiodarone and will not replace it in all its indications.


Disposition of the sinus node in left-sided juxtaposition of the atrial appendages.

In view of the complex cardiac anomalies frequently associated with left-sided juxtaposition of the atrial appendages the disposition of the sinus node has been studied in 6 of these hearts. While the sulcus terminalis still provides a landmark to the position of the node, the nodes were in an anterior position in all 5 hearts with complete juxtaposition, 2 being inferior to the crista terminalis. The node was in a more normal, lateral position in the sixth case with partial juxtaposition.


Surgical treatment of ventricular septal defect in infancy. Primary repair versus banding of pulmonary artery and later repair.

Results of primary closure of ventricular septal defects are compared with those of two-stage repair, with banding of the pulmonary artery followed by debanding and closure. Apart from the high incidence of unsatisfactory results after banding and a significant morbidity with the two-stage approach, the mortality for primary repair (2.4%) is considerably lower than that achieved with the staged repair (19.3%). Primary repair of ventricular septal defect is advocated for infants resistant to maximal medical treatment. A more flexible policy is adopted for patients with multiple ventricular septal defects and those with associated anomalies.


Echocardiographic and exercise evaluation of results of mitral valvotomy operations.

M-mode echocardiography was performed in 54 patients 1 month to 3 years after mitral valvotomy for dominant mitral stenosis. The mitral valve closure index (MVCI), an index previously shown to correlate well with the calculated mitral valve area, was used to diagnose residual mitral stenosis. Using the equation MVCI = 33 MVC--12, 12 patients (22%) were deemed to have mild, 4 (7%) moderate, and 2 (4%) severe residual stenosis. Repeat cardiac catheterisation confirmed the diagnosis in 7 patients. The postoperative mitral valve closure index correlated significantly with patients' subjective symptoms and objective exercise indices. It was higher in patients in whom the posterior mitral leaflet movement became normal after valvotomy, and was lower in patients in whom the anterior mitral leaflet excursions below 14 mm before operation. The mitral valve closure index is a sensitive index for diagnosing residual mitral stenosis after valvotomy.


Haemodynamic effects of sodium nitroprusside in 21 subjects with congestive heart failure.

Twenty-one patients in severe congestive heart failure refractory to conventional medical management were treated with sodium nitroprusside on 22 occasions. On 14 occasions (responders) there was significant improvement in clinical and haemodynamic indices. On 8 occasions (non-responders) hypotension developed without haemodynamic improvement and nitroprusside treatment had to be abandoned. The initial mean arterial pressure and the capillary wedge pressure tended to be higher in the responders while the cardiac index tended to be higher in the non-responders. The systemic vascular resistance was higher in the responders than in the non-responders (2560 +/- 160 vs 1800 +/- 180 dynes s cm-5, P less than 0.001). All of the responders had systemic vascular resistance greater than 1900 dynes s cm-5, while only one of the non-responders had a systemic vascular resistance in this range. Thus, a variable response to vasodilator therapy for congestive cardiac failure is documented. The favourable response appears to be limited to patients with a high systemic vascular resistance.


Non-invasive assessment of left ventricular response to Valsalva manoeuvre in normal and diabetic subjects using praecordial accelerocardiography.

The left ventricular response to the Valsalva manoeuvre was studied in 5 normal subjects (group 1), 6 diabetics without autonomic neuropathy (group 2), and 5 diabetics with autonomic neuropathy (group 3), using the maximum amplitude of the praecordial accelerocardiogram (DE) as a noninvasive index of left ventricular performance. During the Valsalva manoeuvre DE decreased in all 3 groups. In groups 1 and 2, DE increased significantly above the control value after release of the manoveuvre (DE overshoot) but this did not occur in group 3. It is suggested that the overshoot of DE in groups 1 and 2 reflects an increase in left ventricular contractility after release of the Valsalva manoeuvre and the absence of an overshoot in DE in the patients with autonomic neuropathy is the result of loss of cardiac adrenergic innervation. The ability to detect an abnormal cardiovascular response to the Valsalva manoeuvre using the non-invasive technique of praecordial accelerocardiography may be of practical value in the assessment of left ventricular function.


Electrocardiographic changes resembling myocardial ischaemia in asymptomatic men with normal coronary arteriograms.

T wave and ST segment abnormalities in 20 asymptomatic men aged 18 to 55 were investigated because they were identical with myocardial ischaemic changes, and the professional livelihood of the subjects was jeopardised. Coronary arteriograms showed unobstructed arteries in all except one in whom a 50 per cent lesion of the left anterior descending artery was present. Left ventricular angiograms showed a normal contraction pattern, Ejection fractions were normal in 12 and increased in 8. Three characteristic electrocardiographic patterns were observed: flat or inverted T waves in leads II, III, aVF, and V4 to 6 designated type 1; deep T inversion particularly evident in leads V2 to 5 designated type 2, and minor ST segment depression in the inferior and lateral leads without T changes designated type 3. Characteristically, type 1 changes were temporarily suppressed by either beta-blockade or an overnight rest and were more abnormal in the standing position. Type 2 and 3 changes were relatively uninfluenced by these manoeuvres. Maximal treadmill exercise tests were positive in 6 and borderline or negative in 14. When repeated after oxprenolol all tests were negative. Echocardiograms showed asymmetric septal hypertrophy in 3 subjects (ratio of greater than 1.5 between ventricular septum and posterior left ventricular wall). After normalisation by an overnight rest, type 1 T wave abnormalities were reproduced by intravenous adrenaline infusion (0.024 to 0.18 microgram/kg/min) but not by noradrenaline or by adrenaline after prior administration of oxprenolol. When the T waves had remained deeply inverted before infusion despite rest (type 2) adrenaline infusion normalised them and again noradrenaline was without effect. This effect was also prevented by oxprenolol. Type 3 changes were uninfluenced by catecholamine infusion. Plasma catecholamine estimations suggest that catecholamine hypersecretion and hypersensitivity may both be relevant, particularly the latter. The apparent bimodal response of the ventricular myocardium to adrenaline infusion is not surprising since in vitro experiments suggest that reversal of T wave polarity in either direction may result from summation of changes in action potential duration in different parts of the heart. Such changes may be unimodal, that is both areas involved show lengthening or shortening of action potential duration, but by occurring at different rates may lead to a bimodal change in the differences in duration which generate the T wave.


Left ventricular ejection power in coronary artery disease during atrial pacing.

Peak and mean left ventricular ejection power were measured during atrial pacing in 6 normal subjects (group I), 6 patients with coronary artery disease without myocardial infarction (group IIa), and 10 patients with coronary artery disease after myocardial infarction (group IIb). Pacing rates were 80 and 120/min. Power was determined by computer analysis of pressure, volume, and time. Data were normalised by end-diastolic volume and left ventricular muscle mass. Peak left ventricular ejection power normalised by end-diastolic volume values at a pacing rate of 120 min were significantly lower in group IIa and IIb than in normal subjects. Mean muscle mass in normal subjects was 179 g and in group IIa 216 g (P smaller than 0.05). Peak power normalised by muscle mass in normal subjects tended to increase at 120/min whereas in group IIa it declined by 26 per cent (P less than 0.001). These data indicate that the energy output of the left ventricle at rest may be the same in patients with significant coronary artery disease as in normal subjects. Increasing the heart rate from 80 to 120/min in a normal myocardium augments power but in coronary artery disease it remains static or falls.


Effects of propranolol in a case of orthostatic hypotension.

In a hypertensive patient with orthostatic hypotension, the changes in several haemodynamic indices with respect to posture were evaluated. In the upright position, systemic blood pressure was reduced as compared with the supine position, and peripheral vasodilation was present, as shown by an increase in Jantsch's index of the impedance plethysmographic tracings. Systolic time intervals remained unchanged with changes in posture. Propranolol 10 mg intravenously brought the response to normal. In fact, after beta-blockade in the standing position the blood pressure remained unchanged and normal peripheral vasoconstriction was observed. Similar results were seen during atrial pacing at a constant heart rate of 130 beats/minute. In this patient, propranolol appears to normalise the response to the posture change, by restoring normal vasoconstriction in the upright position.


Corrected transposition of great vessels and Ebstein's anomaly of tricuspid valve. Echocardiographic findings.

A case is reported concerning echocardiographic findings in a patient with congenital corrected transposition of the great vessels and Ebstein's anomaly of the tricuspid valve. This presented an unusual opportunity to study atrioventricular valve closure in a patient in whom the Ebstein's malformation involved the systemic atrioventricular valve. The mitral to tricuspid valve closure interval was 68 milliseconds and represented significant delay in tricuspid valve closure. This closure interval is similar to closure intervals previously reported for patients with Ebstein's anomaly without ventricular inversion.


Coarctation, tubular hypoplasia, and the ductus arteriosus. Histological study of 35 specimens.

A histological study has been made in an attempt to study further the relation between the ductus arteriosus, coarctation, and tubular hypoplasia of the aortic arch. Thirty-five aortic arch systems were studied using serial sectioning techniques. Twelve were from patients with coarctation and/or tubular hypoplasia. The other 23 hearts were from patients without aortic obstructive lesions, 7 from anatomically normal hearts, and the others from malformed hearts with anomalies elsewhere from the aortic arch. The anatomical study of the hearts with obstructive aortic lesions emphasised the necessity of distinguishing 'coarctation' from 'tubular hypoplasia', since the curtain lesion of coarctation was found to coexist with tubular hypoplasia in some cases. The histological study showed that the ductus was easily distinguished from the walls of the aorta or pulmonary artery. In all these cases with coarctation or tubular hypoplasia a sling of ductal tissue was located around the aortic isthmal orifice. In 6 hearts a diaphragm of ductal tissue was seen to form the coarctation lesion.


Developmental anatomy of the membranous part of the ventricular septum in the human heart.

The anatomy of the membranous part of the ventricular septum is described in 25 hearts from patients ranging in age from 15 weeks of gestation to the ninth decade of adult life. Both atrioventricular and interventricular components were recognised in all the adult subjects, and the atrioventricular component was evident in all 25. The interventricular membranous septum was present in only 1 of the fetal hearts and 4 of the infant subjects. We consider that these findings indicate that the transformation of the membranous septum into atrioventricular and interventricular components occurs in the late fetal and early postnatal period rather than during closure of the embryonic interventricular foramen. It is associated with the liberation of the medial leaflet of the tricuspid valve from the muscular ventricular septum.


Morphological variations in pulmonary atresia with intact ventricular septum.

The morphological features of a series of 37 specimens of pulmonary atresia with intact ventricular septum were reviewed with particular emphasis on features which might influence the results of pulmonary valvotomy. The degree of right heart hypoplasia was quantified by measuring right and left heart dimensions and comparing them with 20 normal infant hearts. Right ventricular cavity size was usually smaller than normal but constituted a spectrum ranging from tiny to a dilated ventricle larger than normal. There was a positive correlation between triscuspid annular size and right ventricular size but no correlation between the size of the pulmonary artery and the right ventricle. Successful pulmonary valvotomy with subsequent adequate right ventricular function would have been precluded by a tiny right ventricular cavity or infundibular atresia in 14 specimens and by severe tricuspid stenosis or regurgitation in an additional 4. Severe right or left ventricular endocardial fibroelastosis may have adversely affected ventricular function in several others. Ten specimens displayed convex bulging of the left ventricular septal surface. If these these anatomical findings are representative for the condition as a whole, they provide a good explanation for its disastrous prognosis.


Conduction disturbances after surgical correction of ventricular septal defect by the atrial approach.

Conduction disturbances have been documented after correction of ventricular septal defects by the ventricular route. Recently, repair of the ventricular septal defect has been through the right atrium to overcome damage to the conduction system and a right ventriculotomy. Thirty-nine children with ventricular septal defects under the age of 5 years were operated upon by the atrial route (group 1). The incidence of conduction disturbances in this group was compared with that occurring in 19 children of comparable age with a ventricular septal defect repaired via a right ventriculotomy (group 2). Complete right bundle-branch block developed in 13 of 39 children (33.3%) in group 1, compared with 15 of 19 children (78.9%) in group 2. This was a statistically significant reduction in complete right bundle-branch block in group 1. The incidence of left axis deviation occurring with complete right bundle-branch block was similarly statistically reduced. Transient complete heart block and arrhythmias were not statistically different in the two groups. The atrial approach to the repair of the ventricular septal defect significantly reduced the incidence of complete right bundle-branch block alone and occurring with left axis deviation.


Open heart surgery in first year of life using profound hypothermia (core cooling) and circulatory arrest. Experience with 134 consecutive cases.

Between April 1970 and December 1977, 134 infants aged 2 days to 12 months underwent open heart surgery using profound hypothermia and total circulatory arrest. The technique of bypass (core) cooling is described. Results are reviewed for 4 principal diagnoses: 'simple' transposition of the great vessels, total anomalous pulmonary venous connection, ventricular septal defect, and Fallot's tetralogy. A mortality of 44 per cent in 32 cases during the first 3-year period has been reduced to 22 per cent in 102 cases during the subsequent 5 years. The overall mortality for the entire period was 28 per cent. The policy for the management of each diagnostic group is outlined.


Poor response to oral indomethacin therapy for persistent ductus arteriosus in very low birthweight infants.

Administration of oral indomethacin to treat cardiorespiratory failure in 7 low birthweight infants, after failure of conventional therapy, produced an improvement in only 2 infants. These infants had a higher birthweight than the group as a whole. Surgical ligation, rather than oral indomethacin, may be the treatment of choice for persistent ductus arteriosus in very low birthweight infants.


Study of left ventricular pressure-volume relations during nitroprusside infusion in human subjects without coronary artery disease.

Studies were made on 21 patients, 8 without any symptoms of left ventricular failure, group 1, and 13 with clinical symptoms of heart failure, group 2. Cardiac output, mean aortic and left ventricular pressures (using catheter tip micromanometer), and ventricular volume (obtained from left ventricular cineangiograms) were measured before and during nitroprusside infusion. The heart rate did not change in either of the groups. Only in group 2 did cardiac index and stroke volume increase significantly. Mean aortic pressure and total systemic vascular resistance decreased significantly in both the groups. Left ventricular end-diastolic pressure decreased significantly in both the groups, but this decrease was greater in group 2 (9 mmHg compared with 3 mmHg for group 1). The decrease in the left ventricular end-diastolic volume was similar in both the groups. The decrease in left ventricular end-systolic pressure was greater in group 1, but the decrease in the left ventricular end-systolic volume was greater in group 2. These facts are explained by the differences in the active and passive left ventricular pressure-volume relations in the two groups.


Concentration of catecholamines in human cardiac muscle.

A trihydroxyindole fluorescent technique was used to measure the concentration of catecholamines in heart muscle taken from 42 patients undergoing open heart surgery. Noradrenaline was the dominant catecholamine and its depletion in the failing heart was confirmed. The distribution of catecholamines within the heart was such that the highest value, 2.64 +/- 0.68 microgram/g, was found in the nonfailing right atrium and the lowest, 0.53 +/- 0.40 microgram/g, in the failing left ventricle.


Atrial infarction leading to rupture.

In the case described, necrosis of the atrial musculature led to rupture of the chamber. This was overlooked for 4 days until the patient died of ventricular rupture. This unusual complication of atrial infarction may be amenable to surgical repair if recognised in time. The high gain recording of P waves in the presence of AV block made it possible to evaluate the P wave changes during atrial infarction: (1) changes in the configuration and width of the P wave, probably resulting from intra-atrial conduction defect; (2) depression of the PR segment (0.04 to 0.07 mV); and (3) a previously unrecorded convexity in the first portion of the PR segment, in the leads in which the depression of the PR segment was observed.


Attenuation of the diuretic effect of dopamine by droperidol in man and dogs.

The effects of dopamine 0.5--6.0 microgram kg-1 min-1 on urine flow and the excretion of sodium and inorganic phosphate were studied in patients and dogs. In both the patients and the animals the diuretic effect of dopamine was augmented by the i.v. administration of droperidol 0.25 mg kg-1. Similarly, the excretion of sodium and inorganic phosphate was increased by droperidol.


The relative potencies of thiopentone, ketamine, propanidid, alphaxalone and diazepam. A statistical study in man.

The potency of five i.v. anaesthetics (thiopentone, ketamine, alphaxalone (Althesin), propanidid and diazepam) was studied by determining the dose required to produce unconsciousness in 50% (UD50) and 95% (UD95) of patients. UD50 and UD95 were determined using the probit method. The effect of age on the anaesthetic requirement has been studied also. Relative to thiopentone, the potency was alphaxalone 9.22, diazepam 5.24, ketamine 4.37 and propanidid 1.006.


Influence of airway resistance and ventilatory pattern on PaCO2 during enflurane anaesthesia.

Tidal volume, respiratory frequency and PaCO2 were measured in 21 healthy, premedicated adults during anaesthesia with enflurane and 60 or 66% nitrous oxide in oxygen. The increase in PaCO2 correlated with the value of FEV1/VC determined before anaesthesia. PaCO2 during anaesthesia correlated with an index of airway resistance (FEV1/height) and was influenced by the pattern of breathing. These correlations are similar to those reported for halothane.


Effect of preanaesthetic medication on etomidate.

The effects of diazepam and pethidine, when given as preanaesthetic medication, on the induction of anaesthesia and the postanaesthetic sequelae following etomidate were studied in women undergoing minor gynaecological procedures. Pain on injection was present in all the groups. However, the frequency was significantly less with the polyethylene glycol and propylene glycol formulations of the drug compared with the aqueous solution. A fast injection and pethidine premedication decreased the frequency also. The high frequency of excitatory phenomena in unpremedicated patients was decreased significantly by premedication with diazepam and pethidine, especially the latter. Respiratory and cardiovascular effects of the drug were not major problems. The frequency of emetic sequelae was high. Recovery was rapid even in the groups receiving sedative premedication.


Etomidate for induction of anaesthesia at caesarean section: comparison with thiopentone.

Thirty mothers undergoing elective Caesarean section received thiopentone 3.5 mg kg-1 and 30 received etomidate 0.3 mg kg-1 for induction of anaesthesia. Subsequent management of anaesthesia was identical in both groups. Maternal to fetal base excess differences and the degree of biochemical correlation between mother and infant were more favourable following etomidate than following thiopentone. The clinical status of the newborn was considered superior with etomidate.


Effects of enflurane anaesthesia and surgery on endocrine function in man.

Forty-five patients underwent enflurane anaesthesia and surgery. Anaesthesia alone evoked little change in the plasma concentrations of ACTH, cortisol or antidiuretic hormone (ADH), but there were significant increases during surgery. The plasma concentrations of aldosterone increased during anaesthesia alone, and a further increase was noted during surgery. Neither enflurane anaesthesia nor surgery significantly influenced plasma concentrations of renin activity and thyroxine. A significant decrease in the plasma triiodothyronine concentrations was detected during anaesthesia alone, and a further decrease was found during and following surgery. Enflurane anaesthesia did not affect the plasma concentration of luteinizing hormone (LH) in male subjects throughout surgery, but a significant decrease in female patients was detected to the first day after operation. The plasma concentrations of testosterone decreased during anaesthesia alone and surgery, and a further decrease was noted on the first day after operation.


Arrhythmia during oral surgery: fascicular blocks in the cardiac conducting system.

Two hundred and four patients were monitored during oral surgery using three surface e.c.g. leads simultaneously. In nine patients, sustained supraventricular tachycardia was observed during surgical stimulation. The role of sympathetic stimulation and halothane anaesthesia in producing arrhythmia is discussed.


Dose-related tachycardia induced by pancuronium during balanced anaesthesia with and without droperidol.

Pancuronium 0.02--0.08 mg kg-1 induced a dose-related increase of heart rate in patients anaesthetized with nitrous oxide supplemented with either fentanyl 0.003 mg kg-1 or fentanyl 0.003 mg kg-1 plus droperidol 0.15 mg kg-1. The tachycardia was more marked following the administration of droperidol.


Preoperative starvation and plasma glucose concentrations in children undergoing outpatient anaesthesia.

Thirty-one children aged less than 5 years were studied while attending hospital for anaesthesia as outpatients. Plasma glucose concentrations were measured after the induction of anaesthesia. The mean plasma glucose concentration was 4.70 mmol litre-1. No patients had a plasma glucose concentration less than 2.8 mmol litre-1, despite at least 8 h of starvation. This is unexplained. It is suggested that the conclusions drawn from studies made in young inpatients may not be applicable to young outpatients.


Effect of haemothorax on pulmonary artery wedge pressure. A case report.

The pulmonary artery wedge pressure was increased because of the development of a haemothorax. After drainage of the haemothorax, the pulmonary artery wedge pressure was found to be less than that required to maintain an effective cardiac output and a rapid infusion of blood was required.


Some physiological and metabolic effects of sodium nitroprusside and cyanide in the dog.

The cardiovascular and acid-base changes following equivalent i.v. bolus doses of sodium nitroprusside (SNP) and potassium cyanide (KCN) have been studied in two groups of anaesthetized dogs. In a third group, the metabolic changes produced by i.v. infusion of SNP 1.5 mg kg-1 at a constant rate over 1 h have been studied. In contrast to a decrease in arterial pressure following SNP, hypertension and tachycardia occurred after the administration of KCN, with hyperventilation and an increase in packed cell volume. During infusion of SNP, increases in plasma cyanide concentrations were associated with an increase in arterial base deficit, plasma lactate and excess lactate and a decrease in oxygen consumption. The occurrence of lactic acidosis with SNP 1.5 mg kg-1 suggests that this may be the maximum safe dose for short term infusion. However, all these changes reversed spontaneously following discontinuation of SNP, indicating that base deficit is an adequate metabolic monitor during administration of SNP.