Study of the microbiological environment within long- and medium-range Canadian Forces aircraft. Because of a possible requirement to carry patients with highly virulent communicable diseases, a study was undertaken to observe smoke patterns within Canadian Forces transport aircraft. This was followed by the quantitative evaluation of the spread on non-pathogenic organisms disseminated within a Boeing 707 and a C13OE (Hercules). Thirdly, an attempt to recover respiratory tract viruses during transatlantic flights was made. Smoke patterns showed that an infected patient should be placed at the rear of the aircraft. The spread of the nonpathogenic organisms in a 707 indicated that contamination was largely confined to the rear, except when the aircraft was in an unpressurized mode. In the C13OE, contamination was shown to occur throughout the whole aircraft. No respiratory tract viruses were recovered during the transatlantic flights. It is essential that a 707 should be utilized for aeromedical evacuations. If a C13OE is being considered, then a portable self-contained isolation care unit is mandatory.


Bradycardia induced by negative acceleration. Four volunteers were subjected to negative acceleration in a human centrifuge for the purpose of testing a standard lap belt. Three subjects developed a sinus bradycardia. The fourth developed a sinus arrest with a junctional rhythm at -2 G. With return to +1 G, the sinus mechanism recovered with a prolonged P-R interval. Within 2 h, the P-R interval returned to normal. Negative acceleration maneuvers, well within the capabilities of high-performance aircraft, can effect marked changes in the cardiac rhythm. This phenomenon appears to be vagally induced and is remarkably well tolerated.


Potassium losses in sweat under heat stress. Six healthy, heat-acclimatized subjects were exposed to different hot and humid environments in a climatic chamber and sodium, potassium, and chloride concentrations in their sweat, urine, and blood were determined. The concentration of potassium in sweat was found to be considerably higher than that in the plasma, whereas that of sodium and chloride was very much lower. The concentration of potassium in urine was also 8-12 times higher than that in the plasma as compared to 0.5 to 1.5 times higher for sodium and chloride. The total daily computed losses of potassium in sweat and urine, of a person working in severe heat in the tropics, can be about 116 mEq as against a dietary intake of 97 mEq/d, thereby resulting in negative potassium balance. The potassium depletion in sweat, even in acclimatized Indians, is thus heavy and is likely to play an important role in the causation of heat-illness.


Amelioration of the symptoms of acute mountain sickness by staging and acetazolamide. Treatment by 4 d of residence at 1600 m plus the administration of 500 mg acetazolamide b.i.d. for the last 2 d at 1600 m and the first 2 d at 4300 m was compared with no treatment prior to ascent to 4300 m for prophylaxis of acute mountain sickness. The treatment successfully prevented almost all symptoms of acute mountain sickness. It had no effect on the diminished capacity for maximal or prolonged heavy physical work. The treatment produced a relative acidosis and a comparatively greater arterial oxygen tension at 4300 m.


Mechanism of lung damage in explosive decompression. It is known that pressure equalization via the trachea may diminish or prevent lung damage in explosive decompression. In this report, evidence is presented which demonstrates that closure of the trachea does not affect lethality in mice exposed to maximally rapid decompression. This observation suggests that in maximally rapid decompression the lungs and thorax may be treated as a closed system to which Boyle's Law might be applicable.


Algorithm for analyses of saccadic eye movements using a digital computer. An algorithm for digital computer analyses of electro-oculographically recorded saccardic eye movements is presented. From a brief, 4-min recording session detailed statistical information about saccade velocity, accuracy, and delay time can be obtained. Since this data is not significantly altered by practice of motivational factors, it provides a sensitive functional test of the extra-ocular muscles and their brain control system.


Method for determining pilot stress through analysis of voice communication. Factors inherent in aircraft communication systems hinder customary approaches to voice analysis in the determination of the degree of stress experienced by a pilot during an inflight emergency. By means of a sound spectrogram, the mean vibration space of a voice can be analyzed if the space between the vertical deflections of the vowel sounds is calculated in micrometers. The vibration space shift rate (VSSR) is calculated by comparing the widest vibration space of the voice during the normal phase of the same flight (standard vibration space: SVS) with that encountered during the emergency situation (EVS) by the following formula: VSSR = ((SUS-EVS)/SUS) X 100%. The number of measuring points in each case differs in regard to the length of communication during the emergency. The VSSR can be divided into three phases - normal, urgent, and emergency - each with three grades of 0.5 S.D. apiece.


Comparative muscular strength of men and women: a review of the literature. The results from nine separate studies reporting comparable static and dynamic muscle strength measurements between men and women have been reviewed. The statistical data from these studies are presented in graphical and tabular form illustrating, when appropriate, the mean +/- 1 S.D., and the mean percentage difference between men and women for the given measurement.


Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping. Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.


Cerebral air embolism and cerebral edema: one regimen of treatment. A case of cerebral air embolism responding immediately to compression to 6 atm is described. The patient, however, developed apparent cerebral edema while being decompressed. Subsequent recompression on oxygen was carried out twice daily at 60 ft (18 m, 2.8 ATA) for 60 min until the patient's symptoms had nearly cleared. While a number of other medications known to affect intracranial pressure were used, objective clinical improvement was noted only after hyperbaric oxygen. A question is raised of whether there is an association between the development of cerebral edema and the administration of intravenous 5% glucose in water.


Planning an airport disaster drill.

Planning an airport disaster drill. The authors have prepared this paper to serve as a guide for planning airport disaster drills, particularly at the major air carrier airports. Their recommendations are subject to change according to the needs of the individual airport and the particular circumstances that may be present. Basically, the recommendations are founded on the experience gained by participation in planning and carrying out five separate emergency or disaster drills (Oakland International Airport 1, San Francisco International Airport 2, Los Angeles International Airport 2). The authors also have been involved in a total of three additional disaster drills in California and have been involved in one way or another in an additional 19 airport disaster drills throughout the United States. The presentation is divided into segments according to activity. However, it should be noted that there is a cohesiveness necessary for disaster planning if the drill is to be successful.


Nuclear size and chromatin concentration in transitional cell carcinoma of the human urinary bladder. Feulgen-stained cell nuclei from 25 specimens from transitional cell carcinoma of the human bladder were examined by means of cytophotometric scanning measurements. The mean values of nuclear area, DNA-content and chromatin concentration after scanning of a hundred nuclei per specimen were compared with those from a control group consisting of 10 specimens of normal transitional cell epithelium. Within the same ploidy class the more differentiated carcinoma cells showed nuclear enlargement and decrease of mean chromatin concentration. Undifferentiated tumours could have the same or higher mean chromatin concentration as the control group owing to the many highpolyploid nuclei. Undifferentiated tumours contained numerous giant nuclei, whereas these were rare in well differentiated carcinoma. When allowances were made for variations due to fixation and staining measurement of the nuclear area could serve as means of differentiating between normal and cancer nuclei with a high degree of statistic probability. The question whether nuclear enlargement and decreased chromatin concentration represent physiological changes or are entirely or partly the result of chemical carcinogenesis is discussed.


The significance of random sample size in flow-through photometric prescreening in cervical cytology. The determination of nuclear DNA content by flow-through photometry is employed as a prescreening procedure in cervical cytology. The goal of a prescreening procedure is to obtain the smallest possible number of false negative findings with an economically acceptable number of false positive findings, which must be retested. False negative findings result from the often low relative frequency of atypical cells in a mixed population of normal and atypical cells. Only between 10,000 and 50,000 cells are contained in a random sample from the total suspended smear material. It was the purpose of this study to investigate whether a flow-through photometric study of the entire suspension and thus the larger absolute frequency of atypical cells mught lead to a decrease in false negative results. Flow-through photometric evaluation of the entire smear material is not superior to measurement of a random sample of 10,000-50,000 cells. 1. The relative frequency of atypical cells is unchanged, and thus also the proportion of false negative findings. 2. The number of false positive findings increases by 10% due to the inclusion of aggregates at the bottom of the preparation. 3. The measuring time is increased 10-fold, thus making the prescreening procedure uneconomical.


[Influence of calcitonin on the quantitative cytoarchitecture of juvenile rats, a morphometric study on rat hepatocytes (author's transl)]. 1. Using ultrastructural-morphometric analysis of liver parenchymal cells, following long term calcitonin administration, the suggestion that calcitonin influences intermediate as well as calcium metabolism has been strengthened. 2. The experiments were performed with 10 young male Wiatar rats. 5 animals received salmon calcitonin intraperitoneally every day for 6 weeks, 5 untreated animals served as controls. All animals had free access to water and Altromin-R-standard diet. The morphometric investigations were carried out by a method analogous to that of Weibel (1969). 3. By comparison with controls smaller cells and nuclei were seen. Following calcitonin treatment the mitochondrial content of liver parenchymal cells was markedly reduced. On the other hand the surface of cristae was doubled. A proportional membrane and enzyme production in the sense of an adaption, or a disproportional membrane and enzyme synthesis as a misadaption is discussed as the pathogenetic mechanism. Furthermore the number as well as the volume of peroxisome, and lysosomes was reduced. Total liver calcium decreased, whereas serum calcium concentration increased slightly. This can be explained through raised renal reabsorption as a compensatory effect of parathyroid hormone.


Effect of alcohol on ganglion cells in the superior cervical ganglia of young rats. Light and electron microscopic studies on the superior cervical ganglia of young albino rats after 4 weeks of 32% alcohol ingestion indicate striking degenerative changes in sympathetic nerve cells.


Intracerebral metastatic malignant teratoma in the region of the optic chiasm. An intracerebral metastatic teratoma in a 10-year-old girl is described. This is only the third case that has been reported in literature. Autopsy revealed a cystic tumour measuring 4 cm in diameter in the region of the optic chiasm. Microscopic examination showed that it contained all 3 germinal layers. It was classified in accordance with the criteria of Collins and Pugh as a malignant teratoma intermediate A (M.T.I.A.). Metastases had developed upstream and downstream of the CSF flow in the rostral segment of the pons, the medulla oblongata and the cerebellum as well as in the region of the posterior commissure above the lamina quadrigemina and the pineal body. In addition, there were also leptomeningeal metastases in the region of the left Sylvian furrow. The different opinions of various authors regarding the malignant potency of intracranial teratomas are raised and discussed.


The fine structure of dense lysosomes isolated from rat spleen. A dense fraction from rat spleen was shown to consist of  membrane bound organelles of varying shape and size which were packed with electron dense particles with the appearance of ferritin. Electron microscope microanalysis confirmed that iron was present in the organelles and the amount correlated with the density as noted in transmission electron microscopy. The organelles also stained, positively for acid phosphatase and, therefore, confirmed the biochemical findings that dense lysosomes (L30) had been isolated. The role lysosomes play in the degradation of red blood cells, and as possible sites of iron storage, are briefly discussed.


Dysgerminoma in Turner's syndrome.

Dysgerminoma in Turner's syndrome. The importance of the Y-chromosome for the germ cell tumour development in gonadal dysgenesis has been emphasized many times. In contrast, only two cases of dysgerminoma or gonadoblastoma had been published so far in the XO-Turner's syndrome. With this report, another case of Turner's syndrome developing a dysgerminoma in a gonadal streak is presented. No Y-chromosome containing stemline could be detected in the patient nor in the tumour. A primary genetic etiology or a mechanism related to early secondary regression or dysgenesis of the gonad are discussed as causative factors in germ cell tumour development within gonadal streaks.


[Influence of industrialization on trace element concentration in human lungs]. People who spend their entire lives in highly industrialized regions are in danger of accumulating trace elements by inhalation as a result of the increased amounts of factory-produced smoke. In order to test the environmentally accumulated trace elements in lungs, lung samples of patients who lived their entire lives in the industrial area of Duisburg were compared with those of patients from the less industrialized areas of Cologne and surroundings. Five patients were studied who lived in Duisburg and died at 50-68 years but not primarily as a result of lung diseases. From each patient five samples of the left lung were removed at autopsy. Lungs from 18 patients who died in Cologne were also examined. From each of the latter 2 samples were removed from the left lung. All samples were studied by means of neutron activation analysis and the following elements analysed: Co, Fe, Rb, Se, Cr, Cs, Sb, Sc, Zn and Al. The Al-concentration was analysed only in patients aged 50-68 years. The values of the non-essential Sc, Al and Cs and of the essential trace elements Co were found to be appreciably higher in the samples from Duisburg than in those from Cologne. Sc in the samples from the highly industrialized area was increased up to a factor of 100, Cs, Al and Co to a factor of 10. In the lungs of adults in Duisburg, aged 50-68 years, the concentration of Sc was more than 1,000 times greater than in lungs of children in Cologne, aged 0-10 years. In all samples from Duisburg, the rare element Eu was detectable by means of neutron activation analysis but could  not be detected in a sample from Cologne. It is likely that the different uptakes of trace elements in the lungs depend on correspondingly different concentrations of the elements in the air. The extensive accumulation, especially of the non-essential elements, in the lungs should be an incentive to examine possible detrimental effects on human health in the future. The element Sc which was strikingly accumulated in the lungs and which can be easily measured by neutron activation analysis might be used as a standard for estimating the extent of environmental pollution.


[Malignant melanoma: depth of invasion and histologic typing]. In classifying a malignant melanoma Clark et al. (1969) have suggested histologic typing (lentigo maligna-melanoma, superficial spreading melanoma, nodular melanoma) as well as the determination of the depth of invasion. The experiences made so far need further confirmation through respective research in additional material. This applies to the frequency of histologic types of melanoma and the microstages and primarily to the prognostic significance. There appear to be correlations whether the depth of invasion or the type of melanoma is decisive for prognosis or whether both have to be considered. Between 1967 and 1974 the depth of invasion and the type of melanoma were determined according to Clark et al. (1969) in 139 invasive malignant melanomas. This classification has been carried out routinely following the excision of the tumor since Jan 1st, 1973; in previously operated tumors it was carried out in retrospect without knowledge of the follow-up. Without exception multiple sections of several blocks were used. Uncorrected survival curves and survival rates were drawn up using the acturaial method. Results 1. Of 139 malignant melanomas 3 (2%) were found to be in microstage 2, 50 (36%) in microstage 3, 71 (51%) in microstage 4 and is (11%) in microstage 5. 2. The type of 2 melanomas could  not be defined. Among the remaining invasive malignant melanomas 17 (12%) were lentigo maligna melanomas, 48 (35%) were superficial spreading melanomas and 72 (53%) nodular melanomas. 3. Of the 72 nodular melanomas 53 (74%) were found in microstage 4 or 5; of the 65 other melanomas (lentigo maligna melanomas or superficial spreading melanomas), however, only 34 (52%) p less than 0,001) were in this stage. 4. The uncorrected 5-year survival rate was 100% in microstage 2 and 3 and in tumours diameter of 0.76 mm or more, 55% in microstage 4 and 31% in microstage 5. 5. At equal depth of invasion there are no significant prognostic differences between the various types of melanomas. It was possible to reproduce the type classification of melanomas as introduced by Clark et al. (1969) in our own material from 139 patients. Tumors of microstage 2 were less frequent in our material (2%) than in American and Australian series (17-28%). As far as the frequency of the types of melanoma and the correlation between the type of melanoma and depth of invasion are concerned, the Erlangen material does not show considerable deviation from the reports in the literature on the subject. Among tumors of equal depth of invasion the type of melanoma has little prognostic impact. The depth of invasion is decisive for the prognosis. It can be determined with little effort to a high degree of reliability.


[Reversible hyperplasia and hypertrophy of the mouse liver induced by a functional charge with phenobarbital]. Administration of phenobarbital to rats and mice is well known to cause enlargement of the liver, where the drug is metabolized by hydroxylation and oxydation. The increase of the liver weight is thought to be due to and enlargement of the individual hepatocytes (hypertrophy) caused by an augmentation of the smooth endoplasmic reticulum, as well as to cell multiplication (hyperplasia). The present investigation  deals with the nuclear DNA content of mouse hepatocytes during and after administration of different doses of phenobarbital. The data are related to liver weight with due consideration of mitotic activity and cell loss by necrobiosis. 172 five to six weeks old male albino NMRI mice with a body weight of 23 to 33 gms were randomly divided into four groups, one of which served as the controls. The three test groups received 75 mg and 150 mg phenobarbital per 1 kg body weight intraperitoneally once every day for a total of 10 days. Thereafter the administration of the drug was discontinued. Beginning with the third day of the experiment 3 animals of each group were sacrificed by exsanguination every secound day after their body weight had been carefully determined. Then the liver weights were measured. The nuclear DNA content of the hepatocytes was determined from liver smears by means of acriflavine-Feulgen fluorescence cytophotometry. The number of mitotic figures and of necrobiotic liver cells was counted in histologic sections. With animals receiving 150 mg and 100 mg phenobarbital per 1 kg body weight a rapid increase of the relative liver weight (up to 74% above the controls) was observed, which was reduced back to normal levels within 10 days after discontinuation of the drug. Parallel with the increase of the liver weight a striking DNA-polyploidisation of the liver nuclei occurred which proved to be reversible during the reduction phase. Mitotic figures were found only in the initial phase of the experiment (third to fifth day), while the number of necrobiotic hepatocytes was increased after the drug was discontinued. Similar but markedly less pronounced effects were encountered with animals of the 75 group. It is concluded that the increase of the liver weight of mice after phenobarbital administration is partly due to cell multiplication (hyperplasia) - as is shown by a high number of mitotic figures in the initial phase of the experiment-, partly due to the enlargement of hepatocytes with concommitant polyploidisation of the muclei (hypertrophy). When the drug administration is discontinued the liver weights return to normal levels within 10 days. Since at the same time the number of high-ploidy nuclei is reduced with no evidence of an increased mitotic activity, the reduction of the liver weight should be partly caused by an elimination of high-ploidy hepatocytes, which are no longer required after the hyperfunctional stimulus has ceased...


Properties of the testicular lactate dehydrogenase isoenzyme. 1. Studies were carried out with pure lactate dehydrogenase isoenzymes C4 (LDH isoenzyme X), B4, (LDH isoenzyme 1) and A4 (LDH isoenzyme 5) isolated from mouse testis, heart and muscle tissue respectively; with LDH isoenzyme X purified from pigeon testes and with crude lysates of spermatozoa from man, bull and rabbit. 2. LDH isoenzyme X from all species showed greater ability than the other isoenzymes to catalyse the NAD+-linked interconversions of 2-oxobutanoate into 2-hydroxybutanoate and of 2-oxopentanoate into 2-hydroxypentanoate. 3. Mouse LDH isoenzyme X presented the broadest spectrum of substrate specificity. It exhibited very similar Km values for a variety of 2-oxo acids: 2-oxopropanoate (pyruvate), 2-oxobutanoate, 2-oxo-3-methylbutanoate, 2-oxopentanoate, 2-oxo-3-methylpentanoate, 2-oxo-4-methylpentanoate, 2-oxohexanoate and 2-oxo-3-phenylpropanoate (phenylpyruvate). The corresponding 2-hydroxy acids were also readily utilized in the reverse reaction. A strong inhibition by substrate and product was demonstrated  for the direct reaction. 4. Intracellular distribution of LDH isoenzyme X was investigated in mouse testes. LDH isoenzyme X activity was located in the fraction of "heavy mitochondria" and in the soluble phase. 5. A possible functional role for LDH isoenzyme X is proposed: the redox couple-2-oxo acid-2-hydroxy acid could integrate a shuttle system transferring reducing equivalents from cytoplasm to mitochondria.


Chemical nature and sequence of alamethicin. An n.m.r. spectroscopy study of pure alamethicin shows it to be a linear polypeptide of 19 residues. The N-terminus is blocked by an acetyl group, and the eighteenth residue, glutamic acid, is linked by an amide bond on its side chain to phenylalaninol (Fig. 6). The new formula is confirmed by a comparison between pure chemical compounds and the products of partial hydrolysis.


Mobility of sodium dodecyl sulphate - protein complexes. Reduced and unreduced lysozyme aggregates formed by formaldehyde cross-linking comprise a set of model compounds for studying the effects of protein conformation on the electrophoretic mobilities of sodium dodecyl sulphate-protein complexes. The reduced aggregates were indistinguisable from normal proteins, but the unreduced aggregates migrated anomalously fast by about 14%. Contrary to expectations, plots of logarithm Rf versus Kr (retardation coefficient) failed to reveal an unusual conformation for the unreduced aggregates. Thus the anomalous mobility caused by several intramolecular disulphide bonds escaped detection by the above two diagnostic plots. Also included in this paper is a discussion of the implications of these results with regard to current models for sodium dodecyl sulphate-protein complexes.


Preparation and activity of guanidinated or acetylated erabutoxins. 1. Erabutoxins, a, b and c, neurotoxic proteins of a sea snake Lacticauda semifasciata, were guanidinated with O-methylisourea. The amino groups of all the lysine residues and those at the N-termini of the toxins were modified. The lethal activity of the toxins decreased to 50% (erabutoxins a and b) or 17% (erabutoxin c) of the original value on the modification. The c.d. (circular dichroism) maximum at 227 nm of the modified toxins became lower, whereas the whole profile of the c.d. curve remained unchanged. 2. The amino groups of erabutoxin b were acetylated with acetic anhydride. All the five monoacetyl derivatives were isolated from the reaction products by CM-cellulose and Bio-Rex 70 column chromatography. [1-Nalpha-acetylarginine]-, [15-N6-acetyl-lysine]- and [51-N6-acetyl-lysine]-erabutoxin b retained the toxicity of the native toxin, whereas [27-N6-acetyl-lysine] and [47-N6-acetyl-lysine]-erabutoxin b were 17 and 8% active respectively. The overall profile of c.d. spectrum of erabutoxin b remained unchanged on the monoacetylation.


Triterpenoid carotenoids and related lipids. Triterpenoid carotenoid aldehydes from Streptococcus faecium UNH 564P. 1. The identification of two novel triterpenoid xanthophylls from Streptococcus faecium UNH 564P is described. 2. Both are aldehydes and were identified as 4,4'-diaponeurosporen-4-al and 4,4'-diapolycopen-4-al. 3. A pathway is presented for the biosynthesis of these and other triterpenoid carotenoids in S. faecium.


The theory of the deoxyribonucleic acid - ribonucleic acid hybridization reaction. A general equation is derived describing data of DNA-RNA hybridization in the presence of a competing self-annealing reaction of RNA. The well known double-reciprocal relation and the Scatchard equation are shown to be limiting cases of this general equation. Some new hybridization data at various temperatures are presented and analysed by using the new equation. The results can only be explained if we assume that the behavior of DNA towards single RNA molecules is the same as that towards the annealed form, (RNA12. The variation of the equilibrium constant of the hybridization reaction with temperature is small, indicating a small heat of reaction. The maximum amount of hybridized RNA at equilibrium appears to be independent of temperature.


A new subunit of horse liver alcohol dehydrogenase and subunit composition of the polymorphic form. The most cathodal (on starch-gel electrophoresis), steroid-active band of horse liver alcohol dehydrogenase, whose catalytic properties were shown to be dependent on the livers used as a starting material [Pietruszko (1974) Biochem. Biophys. Res. Commun. 60, 687-694], has been prepared from A-type and S-type horse livers by identical methods. Results presented here show that different isoenzymes are present in these preparations.


A method for the direct demonstration of the lectin-binding components of the human erythrocyte membrane. 1. A method which allows the characterization of lectin-binding components is described. This method should be useful in defining the nature and heterogeneity of these components in cell membranes. 2. The method, which we have used on erythrocyte "ghosts", involves the fixation of "ghost" components after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and incubation with purified 125I-labelled lectins. 3. Each of the four lectins used shows an individual pattern of reactivity towards "ghosts" components. Band 3, the major membrane-penetrating glycoprotein, is bound by the lectins from Ricinus communis and Phaseolus vulgaris (phytohaemagglutinin) and by concanavalin A. The major erythrocyte sialoglycoprotein is bound by the lectins from R. communis, P. vulgaris and Maclura aurantiaca. 4. Three of the lectins displays binding for other membrane components, some of which are not demonstratable by conventional protein- and carbohydrate-staining techniques.


The membrane change in En(a-) human erythrocytes. Absence of the major erythrocyte sialoglycoprotein. We investigated the membrane of En(a-) human erythrocytes as part of a study of the structure and biochemical function of the surface glycoproteins of the mammalian cell. 2. En(a-) erythrocytes were selected because they have more extensive changes at the cell surface than any other known erythrocyte variant. 3. Our results show that in En(a-) erythrocytes: (a) the major membrane sialoglycoprotein is lacking; (b) the other major membrane-penetrating glycoprotein (band 3) has an altered electrophoretic mobility. 4. The apparent clinical normality of En(a-) cells suggests that the change in band 3 may compensate for the loss of the membrane sialoglycoproteins. It is clear that a viable erythrocyte can exist despite the absence of one of its major surface components.


Further evidence for an allosteric model for ribonuclease. Evidence is presented from three experimental systems to support the allosteric model of Walker et al. (1975) (Biochem. J. 147, 425-433) which explains the substrate-concentration-dependent transition observed in the RNAase (ribonuclease)-catalysed hydrolysis of 2':3'-cyclic CMP (cytidine 2':3'-cyclic monophosphate). 1. Kinetic studies of the initial rate of hydrolysis of 2':3'-cyclic CMP show that the midpoint of the transition shifts to lower concentrations of 2':3'-cyclic CMP in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, 3'-UMP and Pi; 2'-CMP and 2'-UMP do not cause such a shift. 2. Trypsin-digestion studies show that a conformational change in RNAase to a form less susceptible to tryptic inactivation is induced in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, and 3'-UMP. 2'-CMP, 2'-AMP and 2'-UMP do not induce this conformational change. 3. Equilibrium-dialysis experiments demonstrate the multiple binding of molecules of 3'-CMP, 3'-AMP and 5'-AMP to a molecule of RNAase. 2'-CMP binds the ratio 1:1 over the analogue concentration range studied.


Beta-amylase-resistant amylose. Effect of urea on the limited hydrolysis of amylose by beta-amylase. Amylose prepared from starch dispersed in 10M-urea, pH6.2, was found to be resistant to the action of beta-amylase and phosphorylase, though it was degraded by alpha-amylase. Amylose isolated by conventional methods was similarly refractory after urea treatment, and was hydrolysed by beta-amylase to the extent of 32-35%; it had no inhibitory effect towards beta-amylase. The physical and chemical properties of the modified amylose were in general comparable with those of normal amylose with a beta-amylolysis limit of 94-98%. Starch and amylopectin were unaffected by urea treatment, i.e. the presence of amylopectin protected amylose against changes induced in it by urea. It is speculated that urea treatment "freezes" amylose molecules in a conformation that renders non-reducing termini inaccessible to the active site of the exo-enzymes. Such changes may limit the degradative action of beta-amylase and phosphorylase.


Studies on the use of sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucopyranose for the large-scale purification of hepatic glucokinase. The synthesis of N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucose is described and it was shown to be a competitive inhibitor (Ki, 0.75 mM) with respect to glucose of rat hepatic glucokinase (EC 2.7.1.2). After attachment to CNBr-activated Sepharose 4B, this derivative was able to remove glucokinase quantitatively from crude liver extracts and release it when the columns were developed with glucose, glucosamine, N-acetyl-glucosamine or KC1. Repeated exposure of the columns to liver extracts led to rapid loss in their effectiveness as affinity matrices because proteins other than glucokinase are bound to the columns. The nature of such protein binding and methods for the rejuvenation of "used" columns are discussed along with the effect of the mode of preparation of the Sepharose-ligand conjugate and the concentration of bound ligand on the purification of glucokinase. Glucose 6-phosphate dehydrogenase is cited as an example of both non-specific protein binding to the affinity column and of the importance of the control of ligand concentration in removing such non-specifically bound proteins. Some guidelines emerged that should be generally applicable to other systems, particularly those which involve affinity chromatography of enzymes that are present in tissue extracts in very low amounts and possess only a relatively low association constant for the immobilized ligand.


The purification in high yield and characterization of rat hepatic glucokinase. A new improved procedure for the purification of rat hepatic glucokinase (ATP-d-glucose 6-phosphotransferase, EC 2.7.1.2) is given. A key step is affinity chromatography on Sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-d-glucopyranose. A homogeneous enzyme, specific activity 150 units/mg of protein, is obtained in about 40% yield. The molecular weight of the pure enzyme was determined by several procedures. In particular, sedimentation-equilibrium studies under a variety of conditions indicate a molecular weight of 48000 and no evidence for dimerization; reports in the literature of other values are discussed in the light of this evidence on the pure enzyme. The amino acid composition suggests that hepatic glucokinase is closely related to rat brain hexokinase and also the wheat "light" hexokinases.


A study of the supposed hydroxylation of tyrosine catalysed by peroxidase. The claim that peroxidase (rather than tyrosinase) is the enzyme responsible for the conversion of tyrosine into dopa (3,4-dihydroxyphenylalanine) in melanogenesis was investigated. The spectral changes that occurred during the action of horseradish peroxidase in the presence of H2O2 on dopa, tyrosine and mixtures of dopa with tyrosine or other phenolic compounds were studied. The effect of ascorbic acid or dihydroxyfumaric acid on some of these changes was also investigated. No evidence was found that tyrosine was hydroxylated by peroxidase in the presence of H2O2 and dopa as cofactor, although tyrosine or other phenolic compounds increased the rate of oxidation of dopa to dopachrome (indoline-5,6-quinone-2-carboxylic acid). Peroxidase was, however, effective in oxidizing tyrosine to dopa in the presence of dihydroxyfumaric acid and oxygen.


Purification and properties of a kininogenin from the venom of Vipera ammodytes ammodytes. A kininogenin (EC 3.4.21.8) was purified from the venom of Vipera ammodytes ammodytes (European sand viper) by a combination of gel filtration and ion-exchange chromatography. The enzyme is approximately six times more active than bovine trypsin in its ability to release vasoactive peptides from a plasma precursor. The kininogenin is a glycoprotein containing 18-20% by weight of carbohydrate. It showed a mol. wt. of 40500 on gel filtration. Gel electrophoresis of the reduced sample in the presence of sodium dodecyl sulphate and 2-mercaptoethanol revealed the presence of two major components of mol.wt. 34300 and 31300. The heterogeneity, which was also observed on disc electrophoresis, was removed by incubation with neuraminidase. After incubation with neuraminidase the kininogenin retained full enzymic activity and possessed an isoelectric point of pH7.2. The carbohydrate content has been decreased to 10% by weight, and the single component seen on electrophoresis in the presence of sodium dodecyl sulphate and 2-mercaptoethanol corresponded to a mol.wt. of 29500.


The heterogeneity of arginases in rat tissues. Arginase reactions in rat tissues were shown to be catalysed by three isoenzymes which can be separated by bidirectional electrophoresis on polyacrylamide gels. Anodic electrophoresis reveals a migrating band (isoenzyme I) present in all-non-hepatic tissues except submaxillary gland and a non-migrating band found in all tissues. The latter is resolved by cathodic electrophoresis into isoenzymes III (characteristic of liver and submaxillary gland) and a non-moving band (isoenzyme II), present in kidney, intestine and pancreas. Sequential electrophoresis, in the two directions, of mixture of liver and kidney extracts in the same gel columns separated all three isoenzymes. Differences in the solubilization properties, heat-sensitivity and substrate specificity of arginases from different tissues could be correlated with their electrophoretic behaviour. L-Canavanine could replace arginine as substrate in extracts of kidney but not of liver. Both kidney isoenzymes hydrolysed L-canavanine equally well, whereas isoenzyme III from submaxillary gland showed only very low activity. Antiserum against liver arginase interacted with the enzyme with submaxillary gland, but did not inactivate or adsorb arginase from kidney, intestine or pancreas. The distribution of arginase among 16 normal adult rat tissues is presented; the improved, sensitive, assay method was applicable to tissues containing as little as 0.1% of the hepatic activity.


The structure of haem in pyridine/water mixtures and its implication in studies of haem catabolism. 1. A study of haem spectra in pyridine/water mixtures at low pyridine concentrations revealed changes in haemochrome structure consistent with an aggregation process. No corresponding change in the structure of the haemichrome species was observed. 2. This aggregation has been correlated with a previously observed sharp decrease in the rate of coupled oxidation (degradation) of haem as pyridine concentration is decreased. The decrease appears to be due primarily to haem aggregation and not to changes in the hydrophobic nature of the solvent. The effect of ethanol and butanone addition was examined and supports this conclusion. 3. Evidence is presented that coupled oxidation occurs via the iron (II) species (haemochrome).


Chiral recognition of prochiral centres and general acid-base catalysis. Necessarily interrelated manifestations of active-site structure. On the basis of Ogston's [(1948) Nature (London) 162, 963] argument, the following conclusions are indicated by the stereochemistry of the reversible oxidation of glycollate by lactate dehydrogenase: (1) general acid-base catalysis is involved in the reaction; (2) the transformation of enzyme-bound (tetrahedral) substrate into enzyme-bound (trigonal) product involves a conformational transition of the enzyme-coenzyme complex.


Activities of citrate synthase and other enzymes of Acetobacter xylinum in situ and in vitro. The activities of a number of enzymes, extracted from Acetobacter xylinum, that are involved in carbohydrate metabolism may be accounted for in situ in permeabilized cells. The kinetic properties of citrate synthase and glycerokinase observed in vitro are also retained in situ. So is the regulatory sensitivity of these enzymes. Both in vitro and in situ, (a) citrate synthase, in contrast with the enzyme for other Gram-negative bacteria, is inhibited by ATP and is insensitive to NADH, and (b) glycerokinase is inhibited by fructose diphosphate and the ratio of its activities towards glycerol and dihydroxyacetone is the same.


Artifacts in the centrifugation of ribosomal and heterogenous ribonucleic acid in "99%-dimethyl sulphoxide" gradients. Increasing the total quantity of RNA located on 99%-dimethyl sulphoxide gradients profoundly altered the sedimentation pattern of heterogenous RNA and (to a smaller extent) that of rRNA. Aggregation of small quantities of rRNA with fast-sedimenting heterogenous RNA was also found to occur in these gradients.


The metabolism of the phosphonium analogue of choline in cultured cells. A useful nuclear-magnetic-resonance probe for membrane phosphatidylcholine. 1. Replacement of choline by the phosphonium analogue does not affect the growth rate of P815Y, NIL, 3T3, and SV40/3T3 cells in culture. 2. The fatty acid composition of the resulting phosphonium phosphatidylcholine is similar to that of phosphatidylcholine. 3. The rate of synthesis and degradation of phosphatidylcholine and of the phosphonium analogue are similar. 4. Phospholipid-exchange protein does not distinguish between phosphatidylcholine and the phosphonium analogue. 5. By contrast, incorporation of phosphonium choline into sphingomyelin occurs to only a minor extent. 6. It is concluded that, since the enzymes involved in the turnover of phosphatidylcholine do not discriminate between quaternary N and quaternary P in the polar head-group region, phosphonium choline should prove to be a useful probe for 31P nuclear-magnetic-resonance (n.m.r.) studies of natural membranes.


Variants of hamster fibroblasts resistant to Ricinus communis toxin (ricin). 1. Variant baby-hamster kidney (BHK) cell lines were isolated that grow in the presence of high concentrations of ricin, the toxic lectin of castor beans (Ricinus communis). The variant lines were independently derived from several cultures of normal BHK cells which had been exposed to the mutagen, methyl-N-nitro-N-nitrosoguanidine, before selection by ricin. 2. The cell lines maintain a high degree of resistance to ricin after growth in lectin-free medium for prolonged periods and therefore exhibit stable phenotypes that are different from normal BHK cells. 3. A preliminary classification of the phenotypes was made. Several cell lines bind normal amounts of 125I-labelled ricin, whereas other bind the lectin poorly. 4. A loss of surface receptors for two other lectins, R. communis RCA and Axinella polyploides, which have specificities similar to ricin, was also found in some but not all of the cell lines showing decreased surface concentrations of ricin receptors. 5. The binding to the ricin-resistant cells of lectins of different sugar specificity, namely Lens culinaris lectin and concanavalin A, was similar to, or higher than, to normal BHK cells. 6. Several of the ricin-resistant cell lines were shown to be cross-resistant to the weak cytotoxicity of Phaseolus vulgaris lectin. By contrast, some cell lines were more sensitive to concanavalin A than were normal BHK cells.


Arterio-venous differences of choline and choline lipids across the brain of rat and rabbit. The concentration of unesterified choline in the plasma in the jugular vein of the rat (0.85 nmol/ml) was found to be three times that of the arterial supply to the brain (0.25 nmol/ml), indicating a higher efflux than uptake of unesterified choline by the brain. No such difference was found for the rabbit and no arterio-venous difference for phosphatidylcholine or lysophosphatidylcholine was observed in either species. No arterio-venous difference was found for choline in blood cells. The infusion of [Me-3H]choline into the circulation of the rat or rabbit indicated an uptake of radioactive choline by the brain and an efflux of non-radioactive choline. In the rabbit such an infusion produced a steady rise in the labelling of phosphatidylcholine and lysophosphatidylcholine in the plasma. When [14C2]ethanolamine was injected intraperitoneally into the rat there was a labelling of phosphatidylcholine, lysophosphatidylcholine and sphingomyelin in the plasma and cells of blood from the jugular vein and the arterial supply, as well as in the brain tissue. However, no labelling of unesterified choline in these tissues could be detected. Unesterified choline was shown to be liberated into the plasma when whole blood from the rat or man, but not the rabbit, was incubated for short periods at 30 degrees C.


Lipid synthesis in vivo by tissues of the maternal and foetal guinea pig. The rate of lipid biosynthesis in vivo was determined in pregnant guinea pigs after maternal and foetal injections of 3H2O. Synthesis in the maternal tissues was low and in the foetal liver and adipose tissues relatively high. In the foetal liver it reached a peak at about two-thirds of gestation, whereas that in the foetal adipose tissue occurred later. These results were used to support the view that lipid synthesis in the foetal guinea-pig liver at two-thirds of gestation is largely from short-chain fatty acids, whereas in foetal adipose tissue glucose is probably the major substrate.


Inhibition of protein synthesis in reticulocyte lysates by trichodermin. 1. The effect of trichodermin as an inhibitor of eukaryotic protein synthesis was studied in a reticulocyte cell-free system. 2. Trichodermin at a concentration of 25 mug/ml inhibits total protein synthesis instantaneously and stabilizes polyribosome profiles. Conversely, at a concentration of 0.25 mug/ml the drug inhibits total protein synthesis by only 70-75% and allows 30-35% breakdown of the polyribosomes in the system. These effects were compared with those produced by two other drugs (pactamycin and anisomycin) examined under conditions identical with those used for trichodermin.


Studies on the catabolism of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine in the rabbit. 1. The routes of elimination of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine were investigated in the rabbit. 2. Analyses showed low plasma concentrations of these amino acids (around 1 nmol/ml) and ratios similar to those found in tissue proteins. The concentrations of these amino acids in extracts of brain, kidney, liver and spleen were similar except that liver had a lower concentration of Ng-methylarginine and Ng, Ng-dimethylarginine. Cerebrospinal fluid contained traces of each amino acid.


The action of phosphatidylinositol-specific phospholipases C on membranes. A phospholipase C prepared from lymphocytes readily hydrolysed pure phosphatidyl-inositol but was relatively ineffective against phosphatidylinositol in erythrocyte "ghosts" and rat liver microsomal fraction and also against sonicated lipid extracts from these membranes. In contrast, a phospholipase C prepared from Staphylcoccus aureus readily hydrolysed phosphatidylinositol in sonicated lipid extracts but had only low activity against purified phosphatidylinositol. Unlike the enzyme from lymphocytes, the S. aureus phospholipase C did not require Ca2+ for its activity and was inhibited by cations. The previously reported specificity of this enzyme was confirmed by our observation of hydrolysis of approx. 75% of the phosphatidylinositol in ox, sheep and cat erythrocyte "ghosts" together with no detectable effect on the major erythrocyte membrane phospholipids. The phosphatidylinositol of rat liver microsomal fraction was hydrolysed only to a maximum of 15%. Some preliminary experiments showed that approx. 60% of the phosphatidylinositol of ox or sheep erythrocytes could be hydrolysed without causing substantial haemolysis.


Effect of vitamin A nutritional status on the growth of oestrogen-primed chick oviduct. Growth and development of the oestrogen-primed oviduct of immature chicks in terms of weight, length, total protein, total RNA, total DNA and total phospholipids are markedly arrested on deprivation of vitamin A; supplementation with retinyl acetate reversed the effect of the deficiency almost fully, whereas retinoic acid was only partly effective.


Role of oxygen on growth rate and gene activity in cultured chick-embryo heart cells. Environmental oxygen is shown to have a regulatory role in growth rate and the mechanism of gene de-repression in chick-embryo heart cells; it modulates the intracellular concentration of polyamines, and this appears to be closely related to histone acetylation.


The conversion of 3-Hydroxy-2,4,5-trihydroxymethylpyridine into pyridoxine by Kloeckera apiculata. Kloeckera apiculata, a vitamin B-6-dependent yeast, grows in the presence of 3-hydroxy-2,4,5-trihydroxymethylpyridine in vitamin B-6-free media. On a molar basis the growth-promoting activity of this compound is approximately one-tenth that of other forms of vitamin B-6. [G-3H]3-Hydroxy-2,4,5-trihydroxymethylpyridine is converted into radioactive vitamin B-6 compounds of the same specific radioactivity by growing cultures of K. apiculata.


Amino acid transport in normal and glutathione-deficient sheep erythrocytes. 1. Uptake rates for 23 amino acids were measured for both normal (high-GSH) and GSH-deficient (low-GSH) erythrocytes from Finnish Landrace sheep. 2. Compared with high-GSH cells, low-GSH cells had a markedly diminished permeability to D-alanine, L-alanine, alpha-amino-n-butyrate, valine, cysteine, serine, threonine, asparagine, lysine and ornithine. Smaller differences were observed for glycine and proline, whereas uptake of the other amino acids was not significantly different in the two cell types.


Synthesis and turnover of plasma-membrane proteins and glycoproteins in a neuroblastoma cell line. A kinetic analysis of the appearance of 14C-labelled proteins in the surface membranes isolated from exponentially growing neuroblastoma cells (N2a) showed that the total membrane proteins reached a steady-state specific radioactivity in 18-20 h. However, examination of individual protein bands resolved by sodium dodecyl sulphate-urea-polyacrylamide-gel electrophoresis illustrated that differences in the kinetics of specific surface-membrane proteins could be detected. Although most of the protein bands reached a steady-state specific radioactivity at a time similar to that for total membrane proteins, at least two bands (mol. wt. 180000 and 130000) attained the steady-state within 8-10 h. It was shown by the use of dual-labelling techniques that these two protein bands turned over in the surface membranes of neuroblastoma N2a cells at least 180 and 150% faster than the total membrane protein. These two proteins were glycosylated and located on the outer surface of the cells, since they were labelled with radioactive carbohydrates and readily removed by treatment of the intact neuroblastoma cell with proteinases.


Subcellular distribution and activity in different rat tissues of a deoxyinosine-activated nucleotidase. A nucleotidase (EC 3.1.3.31) isolated previously from rat liver cytosol was specifically measured in 14 different rat tissues and in subcellular fractions of liver and spleen, taking advantage of the stimulation exerted on it by deoxyinosine. The intracellular distribution studies showed that the enzyme is located almost entirely in the soluble cytoplasm except for the possible presence of 1-2% of the enzyme in the nucleus. The enzyme was present in various amounts in all the tissues studied. Spleen, thymus, and intestinal mucosa showed higher specific activities than any other tissue. On a per cell basis spleen, liver and intestinal mucosa had the highest enzyme activity, whereas bone marrow, brain, thymus, heart and skeletal muscle had activities in the lower range. The results may suggest that the enzyme plays a role in the recovery of endogenous nuclear material for nucleic acid synthesis.


The regulation of haemoglobin synthesis in cultured chick blastoderms by steroids related to 5beta-androstane. 1. After 24h of incubation, the blastoderm may be dissected from the early developing chick embryo and successfully maintained under conditions of organ culture in vitro. 2. Low concentrations of steroids related to 5beta-androstane stimulate the synthesis of foetal haemoglobins, types E and P, in a highly steroid- and tissue-specific manner.


Synthesis of hepatic polyamines, ribonucleic acid and S-adenosylmethionine in normal and oestrogen-treated chicks. 1. The hepatic synthesis and accumulation of polyamines, RNA and S-adenosylmethionine were studied in normal and oestrogen-treated immature male chicks. 2. Ornithine decarboxylase activity in chick liver and in whole chick embryo homogenate was preferentially located in the soluble supernatant fraction. 3. In general the activities of the enzymes involved in the synthesis of polyamines and S-adenosylmethionine decreased with increasing age.


[Evaluation of the use of sodium bicarbonate in a group of children with diarrhea, 10 per cent dehydration and metabolic acidosis]. Considering the disparity of criteria regarding the use of sodium bicarbonate in the management of infants with diarrhea, dehydration and metabolic acidosis, a prospective study was done in 25 infants (13 managed without and 12 with bicarbonate) where it was demonstrated; a) The use of bicarbonate does not lead to a more rapid correction of the metabolic acidosis. b) Bicarbonate should not be used in patients with serum bicarbonate levels of 5 mEq/1. or over. c) Patients with dehydration and metabolic acidosis show hyperglycemia that returns to normal when the dehydration is corrected. This fact is of great interest because these children should not be considered nor managed as diabetics.


Gonadal changes in nephrological patients treated with cyclophosphamide. Therapeutic use of immunosupressive drugs in progressive renal diseases has increased during the last decade. Information concerned severe gonadal damage after such therapy, stresses the need for careful evaluation in each particular case before deciding to use these drugs. Gonadal lesions were investigated in 18 patients who were treated with cyclophosphamide and in one who received chlorambucil at variable doses and length of time; there were frequent relapses in patients with idiopathic nephrotic syndrome and with progressive forms of glomerulonephritis. Nine patients were females and received cyclophosphamide therapy at the ages of 11 a 16 years, being evaluated from 11 to 22 years of age with vaginal smears, gonadotropins and 17-ketosteroids. No alterations were found in these parameters and two of the girls became pregnant and had successful deliveries of healthy babies. Ten patients were males; one of them received chlorambucil and all the others received cyclophosphamide at the ages of 8 to 15 years; they were evaluated from 9 to 19 years of age. Because of their ages, gonadal function was not studied in 3 children, but the other 7 showed azoospermia, testicular atrophy was present in four out of these patients in whom testicular biopsy was performed. The patient who received chlorambucil was among this group. From these results and from the literature, we conclude: 1) immunosuppressive therapy is less risky in girls than in boys; 2) it is imperative to evaluate the risk/benefit ratio before deciding this therapy in any case and 3) doses not above 2 mg/kg/day and for periods no longer than 6 weeks may be considered safe.


[Megaloblastic anemia in the recovery of the malnourished child]. With the purpose of analyzing the evolution in weight before and after treatment of megaloblastic anemia with folic acid, we studied the clinical changes and the evolution in weight in 8 malnourished children who developed this type of anemia during their recovery. Seven out of the 8 cases were less than 20 months of age; 5 of them came from mothers who had had five or more pregnancies; in 7 a history of diarrhea of prolonged course was presented and 2 cases had been given sodium diphenylhydantoin. Increase in weight before treatment of anemia with folic acid was lesser than the one for the days following treatment in seven of the patients. Simultaneously, an important change in behavior was appreciated, without being possible to atribute this change or the increase in weight to a quantitative change favorable to the ingestion of proteins and calories.


[Iron and transferrin metabolism].

[Iron and transferrin metabolism]. The study comprised 36 patients who were divided into two groups. In the first one, there were acute or chronic infectious diseases and the second was a control group. In all of them, the following laboratory counts were done: hemoglobin, hematocrit, leukocyte; also, measurement of protein electrophoresis, of serum iron and of total fixation capacity of iron (transferrin). The procedure was that of a blind study, so that the laboratories responsible for the measurements were not given any clinical information on the different patients. Hypochromic anemia of different degrees of severeness was reported in all infected patients and was attributted to nutritional and infectious factors. In spite of decreased levels of hemoglobin and iron, it was shown that transferrin did not rise, but otherwise, dropped in these patients; therefore, the capacity to convey and fix iron is decreased. This would be a fact resulting in a greater susceptibility, to suffer infections, as has been confirmed in previous studies. A close relationship was found at pediatric level among hypochromic anemia, drop in transferrin levels, poor nutrition and increase of infectious diseases.


[Liver hydatidosis in an eight-year-old child]. The first pediatric case of hepatic hydatidosis diagnosed in Mexico is reported. Previous to surgery, the diagnosis was established, based on a cystic tumor of the liver, the X ray findings, defects in the liver uptake, eosinophilia and Casoni's positive intradermal reaction. Besides, the immunoelectrophoresis test showed specific antibodies. Clinical and epidemiological considerations, related with the pathology and treatment of hydatidic disease are made, stressing the importance to know the symtoms of the illness, in order to establish the diagnosis and treatment. Likewise, the prognosis is evaluated considering the remaining cysts of the liver and the possible seeding of the parasite into the peritoneal cavity. Pertinent literature on the subject is reviewed.


[Medullary carcinoma of the thyroid gland. Report of a case]. The case of a twelve years old boy with unilateral medullary carcinoma of the thyroid gland, whose main symptoms were cough, hemoptisis, fever and weight loss is reported. The diagnosis was made by lymph node biopsy, high levels of serum calcitonin and a positive skin test for histaminase. The main clinical, anatomical and genetic features of this tumor are discussed. The familial study did not show any other affected member. Therefore, it was considered as a sporadic case. Emphasis is made on the diagnostic methodolgy.


[Electrocardiography and central venous pressure during exchange transfusion]. Electrocardiographic and central venous pressure (CVP) records were taken during 30 exchange transfusions practiced to 26 newborns. The technique of two vessels was employed in 26 cases. Operations lasted 84.8 minutes as an average. There was only one death and the transfusion was discontinued in another case because of clinical aggravation and many disorders in the ECG. These disorders reached 40% of the cases with marked predominance of hypocalcemia which appeared as "initial" in three babies with previous history of transfusion. CVP was usually higher than reported for normal newborns and was equal to values found in a similar group of isoimmuned infants. It was high in seven cases, out of which, four complained of severe hemolytic disease and obviously, of anemia. Initial removal of 10 to 20 ml. of blood in these cases, allowed a drop of 3 to 4 cm. of H2O in CVP and its further maintenance at stable levels.


[Development and prognosis of diffuse endocapillary and focal extracapillary proliferative glomerulonephritis]. Early renal biopsies performed in children with primary nephritic syndrome of acute onset have identified various glomerular pathological patterns with distinct evolution. Complete recovery has been observed in those cases with diffuse endocapillary proliferation. However, progressive disease has resulted from most of the other forms. A histological type characterized by diffuse glomerular endocapillary proliferation with a variable number of glomeruli affected by extracapillary proliferation with crescents, has been observed. A diffuse form of this entity, that is, crescents in 80 to 100 per cent of the glomeruli, has been described in the so-called "rapidly progressive glomerulonephritis". This lesion usually progresses to renal insufficiency in less than six months. Information concerning the focal form, that is, the presence of crescents in less than 80 per cent of the glomeruli, is limited and the long-term prognosis of this morphological finding has not been conclusively established. This communication deals with: 1) history and initial clinical features in 48 patients with focal endo and extracapillary glomerulonephritis, and 2) the correlations between streptococcal etiology, initial features, percentage of glomeruli with crescents and the final outcome, in 27 cases followed for more than two years. Age of patients at the onset of the disease was between 11 months and 14 years; 63 percent of the patients were male. Streptococcal infection was documented in 20 out of the 48 cases. Nephritic syndrome at onset was found in all the 48 cases. Twenty-nine patients had significant proteinuria and in 16 of these, the characteristics of the nephrotic syndrome were also present; 10 patients presented severe arterial hypertension and in other 6, acute renal failure was an initial feature.


[Recurrent hematuria of glomerular origin]. Nine hundred and forty children with hematuria were admitted to the nephrology service from 1958 to 1973. Percutaneous renal biopsies were performed in all of them. Thirty cases out of this group had recurrent hematuria and constitute the clinical material of this study. The clinical picture was: acute nephrotic syndrome in 19; monosymptomatic hematuria in 8, anaphylactoid purpura nephritis in 2, and hematuria associated with nephrotic syndrome in one patient. All patients with nephritic syndrome showed in their biopsies various types of glomerular lesions; most of the patients with monosymptomatic hematuria had normal glomeruli; at the light microscopy, the immunofluorescence was positive in some of them. Both patients with anaphylactoid nephritis showed diffuse endocapillary and focal extracapillary proliferation and in the only one with nephrotic syndrome, the hematuria was familial and the biopsy showed features of Alport's syndrome. Twenty-four patients who were followed for over two years showed no relationship between the age of onset, sex, initial significant proteinuria, hypertension, frequency of bouts of hematuria and the clinical evolution. At the end of the study, 7 patients had prolonged remission: the light microscopy showed normal glomeruli, endocapillary proliferation and endo and extracapillary proliferation with less than 30% of the glomeruli affected by "crescents". The remaining cases were still active and one of them with endo and extracapillary glomerulonephritis with more than 30% of the glomeruli affected by "crescents", developed chronic renal insufficiency. In conclusion, the prognosis of recurrent hematuria of glomerular origen is related with the type of glomerular lesions and constitutes an indication for renal biopsy. Renal specimens must be studied under light microscopy and immunofluorescence techniques; electromicroscopy is required when hematuria is present in more than one member of the family.


[D-xylose absorption and weight increase during treatment of celiac disease]. Four patients were studied during the early phase of celiac disease treatment, observing a close correlation between weight increase and the ability to absorb d-xylose.


[Evaluation of the urinary and plasma urea ratio and osmolarity in newborn infants  and malnourished children with pathological and normal renal function]. Previous evaluation of diagnostic tests for acute renal failure in children demonstrated that osmolality urine/plasms (U/P) ratio below 1.3, urea ratio below 4.8 and a negative mannitol test (absence of a diurteic response within one hour after intravenous administration of 60 ml/m2 of 12.5% mannitol solution) may be considered as valuable factors in this diagnosis. However, the validity of those ratios were in doubt in selected populations such as newborns and in severe malnourished children in whom an impairment in concentrating urine capacity can be anticipated. With the purpose to test the validity of these parameters, a group of 53 newborns and 68 children with severe malnutrition were studied. They were admitted to the hospital with dehydration secondary to acute diarrhea presenting oliguria and hyperpnea and before any treatment was given, urine and blood samples were taken to determine urea and osmolality U/P ratios besides routine chemistries. Mannitol test was performed when urine could not be obtained and in some cases in whom U/P results deserved confirmation with the biological test. Seven of the 53 newborn patients developed acute renal failure with negative mannitol test and further clinical course of persistent oliguria. Urea and osmolality U/P ratios were 3.0 +/- 1.5 and 1.07 +/- 0.01 respectively, whereas the remaining 46 newborns had afterwards an uneventful recovery presenting U/P ratios of 12.4 +/- 8.5 for urea and 1.32 +/- 0.57 for osmolality. The difference between the average values of urea U/P ratio of the patients with acute renal failure and those with functional oliguria, were statistically significant at the level of p less than 0.01, but there was no significant difference between osmolality ratio values.


[S-beta thalassemia hemoglobinopathy. Report of 2 cases in a Mexican family]. Two new cases of hemoglobin S-beta thalassemia are being reported. Twenty-six relatives are studied. The two cases were classified as Mediterranean variety. The diagnostic problem and the therapeutical possibilities are considered.


[The pediatrician and the intersexuality problems. I. Classification]. The author discusses the classification of human intersexuality and considers chromosomic sex, genetic sex, type of sex apparent in the newborn, legal sex, social sex and psychological sex.


[Effect of furosemide on water and sodium excretion in apparently normal infants]. Nine infants without evidence of nephropathy were studied. After a control period, furosemide, 1.0 mg/kg. of body weight, was administered intravenously and urine was collected. In all patients, urinary volume increased from a mean of 0.15 ml/min. during the control period, to 0.69 ml/min. after furosemide and urinary sodium excretion rose from 1.77 micro Eq/min. in the first period, to 50.13 micro Eq/min. in the second. There was no significant change in urinary osmolarity and in serum electrolytes. Three hours after furosemide, all children showed dehydration from light to moderate and saline infusion was necessary. No correlation was found between age and weight of the infants with the response to furosemide. Because this diuretic has an energetic action in infants as in children and adults, it must be used carefully and it is proposed that the initial dose of furosemide in infants be 0.5 mg/kg.


[The pediatrician and social sciences].

[The pediatrician and social sciences]. The social aspects of child health have been emphasized recently. A better understanding requires of Humanities, Behavioral and Social Sciences, Public Health and Health Sciences. The application of these is requested in the pediatric activities.


[SI units in medicine].

[SI units in medicine]. The current concepts of a standarized reporting system in medicine and in clinical pathology (Systeme International d'Unites. SI); is reviewed. SI units in medicine permit a better physiological approach to the understanding of biochemical alterations of disease. The usefulness of the SI system in different areas of clinical pathology, and a report form of the laboratory are outlined.


Clinical, haemodynamic, and angiographic findings in Löffler's eosinophilic endocarditis. Detailed haemodynamic and angiographic findings in Löffler's endocarditis are presented for the first time in a report of 3 cases of this rare disease. In 2 of the cases the right ventricular cavity was obliterated; in one of them this was shown by biopsy to be caused by organized thrombus. In the third case, there was progressive mitral regurgitation.


Vectorcardiographic study of aberrant conduction anterior displacement of QRS: another form of intraventricular block. Aberrant ventricular conduction was induced in 44 subjects by introduction of atrial premature beats through a transvenous catheter-electrode. Multiple patterns of aberrant ventricular conduction were obtained in 32 patients and, in the whole group, 116 different configurations were recorded. Of these, 104 showed a classical pattern of mono- or biventricular conduction disturbance. The pattern frequencies were as follows: right bundle-branch block, 28; left anterior hemiblock combined with right bundle-branch block, 21; left anterior hemiblock, 17; left posterior hemiblock combined with right bundle-branch block, 12; left posterior hemiblock, 10; complete left bundle-branch block, 10; and incomplete left bundle-branch block, 6. The remaining 12 configurations could not be classified into the usual categories of intraventricular blocks. In 7 of them, the alterations only consisted of trivial modifications of the QRS contour. In the other 5 instances, aberrant conduction manifested itself by a conspicuous anterior displacement of the QRS loop, with increased duration of anterior forces. The latter observation is worthy of notice, as it indicates that, in the differential diagnosis of the vectorcardiographic pattern characterized by prominent anterior forces, conduction disturbances should be considered a possible aetiological factor in addition to right ventricular hypertrophy, and true posterior wall myocardial infarction.


Morphogenesis of univentricular hearts.

Morphogenesis of univentricular hearts. Two main theories exist for the explanation of univentricular hearts. One states that the bulboventricular septum becomes realigned to form the interventricular septum, and that univentricular hearts are a consequence of failure of this realignment. The other states that bulboventricular and interventricular septa are different structures, and that the univentricular heart results from failure of formation of the posterior interventricular septum. Four hearts are described in which both the posterior septum and an anterior bulboventricular septum are present. In each heart, therefore, the right ventricular sinus is separated both from the left ventricular sinus and from a discrete outlet chamber which supports the pulmonary artery. It is argued that these findings militate strongly against theories proposing reorientation of the bulboventricular septum to form the definitive interventricular septum. They support strongly the concept that the definitive right ventricle is formed in part from the bulbus and in part from the primitive ventricle. On the basis of these findings, it is suggested that the distinctive feature of the univentricular heart is absence of the posterior septum. Such hearts can properly be termed 'primitive ventricle'. It is also suggested that hearts with atretic or straddling valves should be included within this category.


Regional pulmonary blood flow in mitral disease studied by xenon radiospirometry. Regional lung perfusion was measured in the sitting position by 4 external detectors after intravenous injection of 133Xe in 24 patients with mitral valve disease and in 8 people with no cardiopulmonary disease acting as normal controls. Right- and left-sided heart catheterization was carried out on the patients on the following day. Mitral valve stenosis was found in 9, mitral valve regurgitation in 8, and both stenosis and regurgitation in the remaining 7. Regional lung perfusion in the normal people fell linearly from the basal to the apical sections of the lungs. The perfusion distribution in patients with mitral valve disease and a pulmonary capillary vein (PCV) pressure lower than 15 mmHg (2-0 kPa) did not differ significantly from that of the controls. A redistribution of the regional perfusion, with an increase in the apical perfusion and a fall in the basal perfusion of the lungs, was seen in patients with a raised PCV pressure. The hyperperfusion of the apical lung sections correlated with the mean pressure in the pulmonary artery (r=+0-795, P less than 0-001), while the basal hypoperfusion correlated with the PCV pressure (r=0-842, P less than 0-001). The PCV pressure can be predicted with an exactitude of +/- 7 mmHg (0-9 kPa) (95% confidence limits). Neither the cardiac index nor the pulmonary vascular resistance correlated with the changes in perfusion. Xenon radiospirometry is a rapid and reliable method for evaluating PCV pressure before or after operation in patients with mitral valve disease.


Immunological studies in congestive cardiomyopathy in Cameroon. Significantly higher levels of immunoconglutinin were found in the sera of 40 Cameroonian patients aged between 15 and 80 years with congestive cardiomyopathy than in a matched group of normal Cameroonian controls. C3 values were also abnormal in the group with congestive cardiomyopathy, and a negative correlation was found between the C3 and immunoconglutinin values, indicating complement incorporation into immune complexes. Further, the levels of immunoglobulins G, M, and A were all raised, the most striking increase being of IgM, which was greater than in the normal controls and in a group with 'other cardiac disease' studied for comparison. Complement-fixing autoantibodies to cardiac muscle of the class IgG and IgM were found by immunofluorescence techniques in a significant proportion of the patients with congestive cardiomyopathy. Finally, evidence of trypanosomiasis was found by immunofluorescence tests in 27-5 per cent of patients with congestive cardiomyopathy, compared with 8-5 per cent of patients with other cardiac disease, and 1-9 per cent of normal Cameroonian controls selected randomly. We think that some cases of congestive cardiomyopathy in Cameroon may be caused by untreated subclinical attacks of African trypanosomiasis which produce immune complexes that damage the cardiac tissue where the parasite is lodged. Secondary autoimmune carditis modifies the course of the disease, with the resulting end-stage picture.


A comparison of cardiovascular effects of dobutamine and isoprenaline after open heart surgery. In a cross-over study, the cardiovascular effects of dobutamine were assessed in 11 patients who had undergone operation for replacement of the mitral or aortic valve approximately four hours earlier. In 9 of these the effects of isoprenaline were assessed for comparison. Dose-response curves were obtained using four dose levels of dobutamine in the range 1.25-10 mug/kg per min and of isoprenaline in the range of 0.005-0.04 mug/kg per min. Both drugs produced similar dose-dependent increases in heart rate and cardiac output and a dose-dependent decrease in peripheral resistance. Mean arterial pressure was only slightly increased by either drug. The positive inotropic effect of dobutamine was confirmed, but the chronotropic effect was not significantly different from that of isoprenaline. This contrasts with the findings of previous studies, and possible reasons for this are discussed.


Echocardiographic diagnosis of left atrial myxoma. Usefulness of suprasternal approach. Three cases of left atrial myxoma were studied by echocardiography. In one case the atrial tumour was prolapsing through the mitral orifice into the left ventricular cavity; in the other two cases it was not. The angiocardiographic and operative findings correlated well with those from echocardiography. A systematic echocardiographic study is important; the suprasternal approach is useful in the echocardiographic exploration of the left atriu, especially for nonprolapsing tumours.


Left anterior descending coronary artery obstruction. Clinical, electrocardiographic, and angiographic correlates. Seventy-six patients with severe (greater than 80%) occlusive left anterior descending coronary artery disease by coronary angiography were examined for the electrocardiographic characteristics of this disease in the presence (group A 59 patients) or the absence (group B 17 patients) of anterior wall asynergy (akinesis or dyskinesis). The incidence of clinically documented anterior myocardial infarction in these two groups of patients was examined. The collateral circulation to the left anterior descending coronary artery was also examined in the groups of patients with and without anterior wall asynergy. Thirty-eight of 59 (64%) patients with anterior wall asynergy (group A) showed electrocardiographic signs of anterior myocardial infarction, 17 per cent showed probable electrocardiographic signs of anterior myocardial infarction and 19 per cent showed no electrocardiographic signs. None of the 17 patients without anterior wall asynergy (group B) showed electrocardiographic signs of anterior myocardial infarction. In group A 74.6 per cent had documented clinical evidence of previous anterior myocardial infarction. Collateral filling of the distal left anterior descending coronary artery was seen in 71 per cent of group A and 100 per cent of group B patients. There was a significantly higher incidence (P = 0.02) of collateral filling in the patients without electrocardiographic evidence of definite anterior myocardial infarction (93% of 28 patients), than in those who showed definite electrocardiographic evidence of anterior myocardial infarction (66% of 38 patients).it is concluded that severe occlusive left anterior descending coronary artery disease with anterior wall myocardial asynergy is usually associated with electrocardiographic signs of anterior myocardial infarction, whereas equally severe left anterior descending coronary artery disease without anterior wall asynergy is rarely associated with electrocardiographic abnormalities of anterior myocardial infarction. Severe left anterior descending coronary artery obstruction without electrocardiographic and angiographic evidence of anterior myocardial infarction is usually associated with collateral circulation to the left anterior descending coronary artery and collateral circulation to the left anterior descending coronary artery is present less frequently when obstruction is associated with anterior myocardial infarction.


Idiopathic aortitis with calcification of ascending aorta, and aortic and mitral valves. A young woman with unexplained radiographic calcification of the ascending aorta was found at necropsy to have healed idiopathic aorititis. Calcification also involved the aortic valve which was stenosed and the mitral valve. Death was the result of infective endocarditis of these valves with aortic ring abscess, rupture of aortic root, and cardiac tamponade.


Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals. After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.


Porcine malignant hyperthermia. I: Metabolic and physiological changes. Porcine malignant hyperthermia was studied in seven Pietrain pigs under standardized experimental conditions. In five animals malignant hyperthermia was triggered with suxamethonium and halothane, but in two pigs suxamethonium alone was used. Characteristic metabolic and physiological changes were found and these are discussed with regard to a possible mechanism to explain the malignant nature of the syndrome.


Porcine malignant hyperthermia. II: Heat production. The contributions of aerobic and anaerobic muscle metabolism to the heat produced in porcine malignant hyperthermia were studied in seven Pietrain pigs. Oxygen consumption measurements were used to calculate the increase in muscle temperature as a result of aerobic metabolism and this was compared with the observed muscle temperature. The results show that in the initial stage of porcine malignant hyperthermia heat production is largely aerobic in origin. Terminally, aerobic metabolism can account for about half the observed temperature increase.


Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. I: Halothane dose-response studies. The effect of pretreatment for 3 weeks with propranolol 20 mg/kg/day on cardiovascular function during increasing depths of halothane anaesthesia (range 1.0-2.5% inspired halothane with IPPV and normocapnia) were studied in a group of seven closed-chest dogs which had been implanted previously with cardiovascular flow- and pressure-measuring instruments. The results were compared with those observed in a similar group of five untreated dogs. Propranolol pretreatment resulted in a small degree of additional cardiac depression at any inspired halothane concentration. The cardiac depressant effects of propranolol and halothane were found to be simply additive and therefore predictable. The presence of propranolol did not result in morbidity or mortality at any depth of halothane anaesthesia.


Effects on ionized calcium of a correction of acidosis with alkalinizing agents. A rational basis for the administration of calcium in cardiac resuscitation. The effects on the ionized calcium concentration of a correction of various forms of acidosis with sodium bicarbonate or (tris-hydroxymethyl)aminomethane (THAM) were investigated in vitro in human plasma. Calculation of least square regression equations of ionized calcium (m mol) on pH yielded the following regression coefficients: hydrochloric acidosis: -0.65 +/- 0.06; lactic acidosis: -0.27 +/- 0.05; hydrochloric acidosis corrected with sodium bicarbonate: -0.65 +/- 0.02; lactic acidosis corrected with sodium bicarbonate: -0.51 +/- 0.03. The results indicate that after correction of lactic acidosis the ionized calcium concentration will be below the control values while pH is restored to the normal range. This effect is even more pronounced when THAM is used. The findings point to the need for calcium administration in cardiac resuscitation.


Pharmacokinetics of pancuronium in patients with normal and impaired renal function. Plasma concentrations of pancuronium were measured using a fluorimetric method in six patients with normal renal function and seven patients in chronic renal failure.  A tow-compartment open model was used in the pharmacokinetic analysis of the data. With this model, the clearance of pancuronium was found to be reduced significantly in the patients with renal failure, and in these individuals the volume of the central (distribution) compartment was increased significantly. The clinical implications of these findings are discussed.


A foreign body in the larynx. A case report. A young patient with a head injury inhaled a dental plate 60 hr after injury.


Tracheal intubation with a Robertshaw tube via a tracheostomy. A patient who had a permanent tracheostomy needed to be anaesthetized for thoracotomy. Anticipated difficulty with airway and lung control did not occur following successful intubation via the tracheostomy with a Robertshaw double-lumen tube.


Urban mobile resuscitation: training and service. The establishment of a Mobile Resuscitation Unit based on a District General Hospital is described. The Unit is manned by hospital-trained ambulance men and by an anaesthetist when necessary. The training of the ambulance men, organization of the service and the results are discussed. The authors recommend the establishment of such a unit in association with an urban district general hospital for the immediate care of all patients who suddenly become seriously ill, regardless of the cause of their illness or accident.


The influence of carrier gas on the output of automatic plenum vaporizers. The effect of the physical characteristics of the carrier gas on the output of automatic plenum vaporizers was studied. The Vapor and Fluomatic halothane output at all dial settings was highest with oxygen as the carrier gas, as compared with helium and nitrous oxide and was a function of carrier gas viscosity at all dial settings. The output of the Fluotec Mark 2 at the 0.5 and 1% settings was highest with nitrous oxide as the carrier gas, but at 2, 3 and 4% settings it was highest with oxygen; at the 0.5% and 1% dial settings it was a function of carrier gas density, but at 2%, 3% and 4% it was a function of carrier gas viscosity.


Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. II: The effects of acute arterial hypoxaemia at increasing depths of halothane anaesthesia. Beta-adrenergic blockade may impair the normal cardiovascular response to hypoxia occurring during general anaesthesia. The haemodynamic effects of acute hypoxia, induced by a 90-s period of ventilation with nitrogen, were studied during increasing depths of halothane anaesthesia up to a maximum of 2.5% inspired halothane in dogs chronically implanted with intracardiac catheters, a left-ventricular pressure transducer and an aortic blood flow transducer. An untreated group of dogs and a group which had been treated for 3 weeks with propranolol 20 mg/kg/day were compared. The beta-blocked group had lesser cardiac output values, left-ventricular contractility indices, external left-ventricular work and peak left-ventricular power at all depths of anaesthesia except 2.5% halothane, but both groups responded to hypoxia similarly at each depth of anaesthesia. Cardiac performance was enhanced in both groups during acute hypoxia. No adverse haemodynamic effect of the combination of propranolol, halothane and hypoxia was demonstrated.


Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. III: The effects of haemorrhage during halothane and trichloroethylene anaesthesia. We have examined the haemodynamic effects of 0.8% trichloroethylene and 1% halothane anaesthesia in a control group of five dogs, chronically implanted with cardiovascular flow- and pressure-measuring apparatus and compared them with a similar group of six dogs pretreated for 3 weeks with oral propranolol (20 mg/kg/day). The effects of graded haemorrhage of 25% of the estimated blood volume and re-transfusion were studied. Cardiovascular function was satisfactory at all stages of the study except during trichloroethylene anaesthesia in the beta-blocked dogs when the response to blood loss was impaired severely. Therefore the use of trichloroethylene in the presence of propranolol may not be advisable in clinical practice.


Hepatic pathology and skin test reactions to trifluoro-acetylated autologous protein after repeated halothane anaesthesia in the guineapig. The aetiology of the rare hepatic failure following halothane anaesthesia is not known. In an attempt to develop an experimental model, three groups of guineapigs were exposed to air or oxygen, a single 1% halothane administration, or five exposures of 1% halothane at weekly intervals. In an attempt to identify a hypersensitivity reaction, all animals were skin-tested with the common final metabolite of halothane, fluroxene and isoflurane: trifluoroacetic acid, prepared as a complex with autologous serum protein. Hepatic necrosis was found in all groups and did not correlate with positive skin reactions. There was an increase in fatty changes in the liver in animals anaesthetized with halothane.


Pain during continuous nitrous oxide administration. The continuous administration of nitrous oxide, in subjects who remain conscious, caused only a relatively small increase in the threshold of appreciation of pain, induced experimentally by tibial pressure and a hot wire applied to the thenar eminence. The threshold reached a maximum at 10 min. A concentration of 50% nitrous oxide caused only a marginally greater effect than 33%. In some subjects pain thresholds returned to control values during administration of the gas. In contrast, when a concentration of 50% nitrous oxide was approached in step changes of 7-10% over a period of 45 min, the effect on the pain threshold was more than doubled. It was concluded that, with respect to analgesia, adaptation of the nervous system to a constant concentration of nitrous oxide can occur in some subjects.


A theoretical study of gaseous homeostasis in the Magill circuit. Equations have been derived to determine the alveolar gas concentrations which occur when the Magill (Mapleson A) circuit is used with a low fresh gas flow. Alveolar oxygen and carbon dioxide concentrations are determined by the fresh gas flow and composition, carbon dioxide output and oxygen uptake. Gas mixing within the circuit and alterations in the inspired gas concentrations do not affect the final equilibrium. If oxygen uptake and carbon dioxide output are constant, the alveolar gas concentrations are unaffected by alterations in ventilation.


An experimental study of gaseous homeostasis and the Magill circuit using low fresh gas flows. Gas concentrations and ventilation levels have been measured within a conventional Magill circuit when conscious volunteers breathed a non-narcotic gas mixture at varying fresh gas flows. When evidence of rebreathing of alveolar gas was detected, the fresh gas flow was kept constant until a steady state developed. All subjects showed evidence of rebreathing when the fresh gas flow approached the predicted alveolar ventilation levels. A variety of subject-circuit interactions was seen and shown to be precipitated by naturally occurring breath-to-breath variations in ventilation. A single large breath could perturb the system. This could have a temporary effect, when the fresh gas flow was sufficient to wash the increased aliquot of expired carbon dioxide from the circuit. At other times a progressive response occurred as ventilatory stimulation as a result of the increased inspired carbon dioxide concentrations caused alveolar gas to reach the reservoir bag and converted the system behaviour from that of a simple added deadspace to that of a total mixing device. Whilst marked changes occurred commonly in both ventilation and inspired gas concentrations, only slight changes in end-tidal gas concentrations occurred.


Identification and quantitation of hypersensitivity reactions to intravenous anaesthetic agents. It is not possible to distinguish between direct pharmacological effects and immune-mediated hypersensitivity reactions by clinical observation alone and errors may occur in the absence of laboratory tests. A convenient and simple test is the measurement of plasma complement C3 consumption and conversion in sequential blood samples taken at intervals over the 24 h following an adverse response.


Alterations in response to somatic pain associated with anaesthesia. XXIII: Further study of naloxone. Tibial pressure analgesimetry has been employed to study the antagonistic effects of small doses of naloxone in pethidine-induced analgesia. The dose of pethidine was 100 mg and the doses of naloxone 0.2, 0.1, 0.05 and 0.025 mg/60 kg body weight, and all drugs were given i.v. These doses of naloxone reduced the analgesia produced by pethidine and the degree of antagonism was probably dose-related. It was also found that naloxone antagonized the side-effects of pethidine, especially nausea.


A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia. A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia, peritoneal dialysis using a cold dialysate, is described. Experimental observations in a young man on a regular peritoneal dialysis regime showed that significant heat extraction can be obtained when either a cool (20 degrees C) or cold (9 degrees C) dialysis fluid is used. The maximum heat exchange observed was 17.5 kJ/min when 2 litre of cold dialysis was instilled for a mean time of 10 min. This rate of heat exchange is within the 10--40 kJ/min range of excess heat production that occurs in malignant hyperpyrexia. Since peritoneal dialysis is, technically, a very quick and simple procedure, it is suggested that it might play a very useful role in the emergency treatment of malignant hyperpyrexia. The dialysis treatment would also correct some of the biochemical disturbances that occur in this condition.


A comparison of oesophageal and central venous pressures in the measurement of transpulmonary pressure change. Oesophageal (oes) and central venous pressure (CVP) were compared as indices of transpulmonary pressure change (deltap). The mean increase of deltaPoes over deltapCVP was 2.8 cm H2O. The size and variability of the increase were similar to the expected difference between oesophageal and pleural pressure fluctuations occurring in the supine patient. Central venous pressure may be more accurate and reliable than oesophageal pressure for estimations of transpulmonary pressure change in the supine position.


Foetal bradycardia during caudal analgesia: A discussion of possible causative factors. A 31-year-old female had caudal analgesia during labour, using 0.5% bupivacaine. Nine minutes after the block, the foetus developed severe bradycardia which lasted for 9 min but recovered spontaneously. Thereafter the foetal heart rate was within the normal range until the end of labour when variable decreases in rate occurred, suggesting cord compression. At the time of delivery there was a knot of the umbilical cord which was also forming a loop around the neck of the baby. There was no abnormality of the Apgar scores or blood-gases in the baby; the plasma bupivacaine concentrations in both mother and child were within the expected range. The possible causative factors for this bradycardia are explained.


Intravenous regional anaesthesia in children. Fifty children, aged 3-12 yr, received intravenous regional anaesthesia for the treatment of either simple forearm fractures or elbow injuries. The technique obviated delays in treatment and allowed the child to be discharged from hospital immediately after treatment. There were no complications resulting from anaesthesia, but there was one anaesthetic failure.


Towards blood-gas autoanalysis an evaluation of the radiometer ABL. The performance of the Radiometer ABL 1 blood-gas analyser has been evaluated using tonometered blood samples of known PO2 and PCO2. The pH electrode was compared with two other pH electrode systems and the haemoglobin estimations were compared with measurements made by the standard cyanmethaemoglobin method. The accuracy of the machine compared well with standard blood-gas equipment, but the haemoglobin values had a small error because of a zero offset in the machine. The analyzer is simple to operate and has low running costs.


Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells. The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man.