Biologically active macromolecular forms of oxytocin. [8-Lysine]oxytocin as a suitable ligand.

[8-Lysine]oxytocin was synthesized on a solid support and possessed an oxytocic activity of 100 +/- 6 units mumol on the isolated rat uterus. The epsilon-carbamoyl, epsilon-3-carboxypropionyl and epsilon-3-carboxybutryl derivatives were prepared and had uterotonic activities of 400, 55 and 50 units/mumol respectively. [8-Lysine]oxytocin was coupled unambiguously through the epsilon-amino group to the carboxyl groups of carboxymethylated dextrans or epsilon-3-carboxypropionly-gelatin. The macromolecular oxytocins were water-soluble and retained signigicant oxytocic activity. [8-Lysine]oxytocin should prove a useful ligand for affinity chromatography of oxytocin-binding proteins.


Purification and properties of human kidney-cortex hexosaminidases A and B.

Hexosaminidases (EC 3.2.1.30) A and B from human kidney cortex were purified to homogeneity by using concanavalin A affinity chromatography, ion-exchange chromatography and gel filtration. The yield of homogeneous isoenzymes improved approx. 20-fold, giving preparations of hexosaminidases A and B with specific activities of about 200 and 325 units/mg of protein respectively. The kinetic and structural properties of kidney hexosaminidase isoenzymes were studied and compared with the hexosaminidase isoenzymes from human placenta. The amino acid composition of hexosaminidase A was significantly different from that of hexosaminidase B. In the event of success in developing enzyme-replacement therapy for Tay-Sachs and Sandhoff's diseases, this modified procedure can furnish larger amounts of homogeneous isoenzymes.


An automatic method for deriving steady-state rate equations.

A method is described for systematically deriving steady-state rate equations. It is based on the schematic method of King & Altman [J. Phys. Chem. (1956) 60, 1375-1378], but is expressed in purely algebraic terms. It is suitable for implementation as a computer program, and a program has been written in FORTRAN IV and deposited as Supplementary Publication SUP 50078 (12 pages) at the British Library (Lending Division), Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1977) 161, 1-2.


Kinetic evidence for a 'mnemonical' mechanism for rat liver glucokinase.

Inhibition studies of glucokinase were carried out with the products of the reaction, glucose 6-phosphate and MgADP-, as well as with ADP3-, Mg2+ and ATP4-. The results of these, together with those of kinetic studies of the uninhibited reaction described previously [Storer & Cornish-Bowden (1976) Biochem. J. 159, 7-14], indicate that the enzyme obeys a 'mnemonical' mechanism. This implies that the co-operativity observed with glucose as substrate arises because glucose binds differentially to two forms of the free enzyme that are not in equilibrium under steady-state conditions. The mechanism predicts the decrease in glucose co-operativity observed at low concentrations of MgATP2-. The product-inhibition results suggest that glucose 6-phosphate is released first and that it is possibly displaced by MgATP2- in a concerted reaction.


A pulse-radiolysis study of the manganese-containing superoxide dismutase from Bacillus stearothermophilus. A kinetic model for the enzyme action.

The enzymic reaction mechanism of a manganese-containing superoxide dismutase from Bacillus stearothermophilus was studied by using pulse radiolysis. During catalysis (pH 8.9; 25 degrees C), changes occurring in the kinetics of substrate disappearance and in the visible absorption of the enzyme at 480 nm established that the simple two-step mechanism found for copper- and iron-containing superoxide dismutases is not involved. At a low ratio (less than 15) of substrate concentration to enzyme concentration the decay of O2--is close to exponetial, whereas at much higher ratios (greater than 100) the observed decay is predominantly zero-order. The simplest interpretation of the results invokes a rapid one-electron oxidation-reduction cycle ('the fast cycle') and, concurrently, a slower reaction giving a form of the enzyme that is essentially unreactive towards O2-- but which undergoes a first-order decay to yield fully active native enzyme ('the slow cycle'). The fast cycle involves the native enzyme EA and a form of the enzyme EB which can be obtained also by treating the form EA with H2O2. Computer calculations made with such a simple model predict behaviour in excellent agreement with the observed results.


Purification and some properties of the protein component of tissue thromboplastin from human brain.

The protein component of tissue thromboplastib (Factor III) from human brain was purified by extraction of a microsomal fraction with sodium deoxycholate, gel filtration of the extract on Sephadex G-100 and preparative polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. The product, apoprotein III, was homogeneous by anayltical polyacrylamide-gel electrophoresis, and it induced monospecific antibodies in rabbits and goat as shown by immunodiffusion and immunoelectrophoresis. Amino acid- and carbohydrate-analysis data for apoprotein III are presented. The carbohydrate moiety of the protein consists of fucose, mannose, galactose, N-acetylglucosamine and N-acetylneuraminate, amounting to a total content of 6.3g/100g. The apoprotein alone had no procoagulant activity. When Factor III was reconstituted by combining the pure apoprotein with a purified lipid fraction from the deoxycholate extract of crude Factor III, a high and optimal procoagulant activity was obtained at a phospholipid/protein ratio of 1.1g/g. Phosphatidylethanolamine alone had a weak but significant ability to restore activity, whereas phosphatidylcholine and phosphatidylserine separately had almost none. Two-component mixtures were on average more effective, and three-component mixtures far more effective, than the single phospholipids. The inclusion of a small amount of phosphatidylserine was very important for high activity.


An investigation of the interactions of the allosteric modifiers of pyruvate kinase with the enzyme from Carcinus maenas hepatopancreas.

1. Pyruvate kinase purified from the hepatopancrease of Carcinus maenas exhibited sigmoidal saturation kinetics with respect to the substrate phosphoenolpyruvate in the absence of the allosteric activator fructose 1,6-bisphosphate, but normal hyperbolic saturation was seen in the presence of this activator. The activation appears to be the result of a decrease in the s0.5 (phosphoenolpyruvate) and not to a change in Vmax. 2. In the presence of ADP and ATP at a constant nucleotide-pool size the results indicate that phosphoenolpyruvate co-operativity is lost on increasing the [ATP]/[ADP] ratio. 3. Paralleling this change is the observation that the fructose 1,6-bisphosphate activation became less at the [ATP]/[ATP] ratio was increased. This  was due to the enzyme exhibiting a near-maximal activity in the absence of activator. 4. L-Alanine inhibited the enzyme, but homotropic co-operative interactions were only seen with a cruder (1000000g supernatant) enzyme preparation. The inhibition by alanine could be overcome by increasing the concentration of either phosphoenolpyruvate or fructose 1,6-bisphosphate, although increasing the L-alanine concentration did not appear to be able to reverse the activation by fructose 1,6-bisphosphate. 5. In the presence of a low concentration of phosphoenolpyruvate, increasing the concentration of the product, ATP, caused an initial increase in enzyme activity, followed by an inhibitory phase. In the presence of either fructose 1,6-bisphosphate or L-alanine only inhibition was seen. 6. The inhibition by ATP could not be completely reversed by fructose 1,6-bisphosphate.


Immunogenetic control of brain tumor growth in rats.

The susceptibility to intracerebral and s.c. growth of a transplantable gliosarcoma in genetically inbred rats correlated with histocompatibility type. The genetic control of tumor growth was tested in a cross between a tumor-susceptible strain (F344, Ag-B1) and a tumor-resistant strain (YO, Ag-B2). Susceptibility was transmitted as a dominant trait, and at least two genes or gene complexes were involved: one was linked to the major histocompatibility complex and one segregated independently of it. The genetic mechanisms did not appear to be affected significantly by the site (environment) in which the tumor grew. Antibodies to Ag-B1 histocompatibility antigens, which were those of the strain in which the tumor originated (F344), and to tumor-associated antigens were generally present in animals in which the tumor had regressed. Only tumor-specific antibodies appeared in the sera of Ag-B1 animals that had the tumor. A cytotoxic lymphokine was present in the sera of tumor-bearing animals, but its level did not correlate with tumor growth or regression.


Pharmacokinetics and metabolism of vinblastine in humans.

The pharmacokinetics of vinblastine in humans was examined using a radioimmunoassay specific for both the Vinca alkaloids and aromatic ring [3H]vinblastine. The data were consistent with a three-compartment open model system with the following values, alpha phase: t1/2=3.90+/-1.46 min; Vc=16.8+/-7.1 liters. beta phase:t1/2=53.0+/-13.0 min; Vbeta=79.0+/-52.0 liters; gamma phase:t1/2=1173.0+/-65.0 min; Vgamma=1656.0+/-717.0 liters. Most significant was the finding that vinblastine is metabolized to deacetylvinblastine and that this compound is more biologically active on a weight basis than the parent. No other biologically active metabolites appeared to be present in urine or in stool.


Aplysia bursting neurons as endogenous oscillators. I. Phase-response curves for pulsed inhibitory synaptic input.

1. The left upper quadrant bursting neurons in the abdominal ganglion of Aplysia are isochronous, nonlinear oscillators. Transmembrane current and temperature are parameters of the bursting oscillator. 2. The phase-response curve (PRC) for pulsed inhibitory synaptic input from an interneuron describes the phase shift produced by synaptic input at different phases of the burst cycle. 3. The characteristic shape of the PRC consists of two linear functions that intersect at the point in the cycle where the burst of spikes ends. Whether the net effect of the synaptic input at a given phase is phase advance or phase delay depends on 1) the number of spikes inhibited, and 2) the duration of the inhibition relative to the duration of the free-run period. 4. The shape of the PRC remains constant when a stepwise change in a parameter is introduced, when the duration of the synaptic input is increased, when the fast component of the IPSP is blocked, and when a long hyperpolarizing pulse is used to mimic the slow IPSP. 5. The shape of the PRC is changed when short hyperpolarizing pulses or antidromic action potentials are used and when only the pacemaker oscillation is present in the bursting neuron. 6. Therefore, the synaptic modulation of the bursting rhythm is determined by the voltage change produced by the IPSP and its inhibition of spikes in the bursting neuron.


Dominant inheritance of cerebral gigantism.

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.


Subtotal neonatal calvariectomy for severe craniosynostosis.

This report sets forth an example of a new mode of management of severe craniosynostosis in the neonate: subtotal calvariectomy. An infant with synostosis of sagittal, coronal, and lambdoidal sutures who had signs of increased intracranial pressure with impending neurologic complications was operated on at 13 days of age. Wide excision of the bony calvarium from the underlying dura was accomplished from the supraorbital ridge to near the foramen magnum; the entire area of the coronal sutures was included. Regeneration of the calvarium occurred over two to 12 weeks and was accompanied by the presence of "sutures" in a usual location. These procedures have allowed for normal brain growth without reoperation up to the current age of two years. Neurologic and intellectual performance has been satisfactory, and cosmetic results appear to be preferable to those obtained by more limited surgery. The observations suggest that this approach may permit better craniofacila growth by minimizing secondary deformities in growth of the cranial base.


Cytotoxic agents from Michelia champaca and Talauma ovata: parthenolide and costunolide.

The ethanol extract of Michelia champaca and the petroleum ether extract of Talauma ovata showed activity toward the human epidermoid carcinoma of the nasopharynx test system. The active constituents were sesquiterpene lactones, identified as parthenolide (C15H20O3) and costunolide (C15H20O2). Their identities were proven by elemental analyses, PMR, IR, and mass spectral data, melting-point and mixed melting-point determinations, and comparisons with authentic samples and spectra.


Sustained reduction of cardiac impedance and preload in congestive heart failure with the antihypertensive vasodilator prazosin.

To elucidate the hemodynamic effects of prazosin, an antihypertensive agent, in congestive heart failure, we studied 10 patients with ischemic cardiomyopathy and severe ventricular dysfunction. After an oral dose of 2 to 7 mg, heart rate was unchanged (P greater than 0.05). One hour after prazosin administration, mean arterial pressure declined from 95 to 78 mm Hg (P less than 0.001); left ventricular filling pressure declined from 30 to 18 mm Hg (P less than 0.001), cardiac index increased from 2.1 to 2.9 liters per minutes per square meter (P less than 0.001), and systemic vascular resistance fell from 2074 to 1156 dynes sec cm-5 (P less than 0.001). In both forearms vascular resistance and venous tone were reduced (86 to 48 mm Hg per ml per 100 g per minute, and 59 to 18 mm Hg per ml, respectively [P less than 0.001]). All responses persisted for a least six hours (P less than 0.01). Prazosin benefits severe congestive heart failure by inducing a sustained fall of both cardiac preload and impedance.


Serum gastrin in health and disease.

Recent developments have led to a further appreciation of the various species of circulating gastrin and to provocative tests for the presence of the Zollinger-Ellison syndrome. Studies of serum gastrin levels, together with other studies of physiologic response, have suggested some possible roles of gastrin in the complex gastric acid hypersecretory state that frequently accompanies duodenal ulcer. Finally, investigations of exogenous and endogenous serum gastrin have provided a mechanism to examine the possible physiologic effects of this hormone.


Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble).

The auxotrophic mutant ade -C derived from Chinese hamster ovary cell CHO-K1 lacks the enzyme glycinamide ribonucleotide synthetase and requires exogenous supplement of purines for growth. Cells from this mutant were fused with normal human lymphocytes, and the resulting hybrids were isolated in purine-deficient medium. A total of 32 primary clones and 49 secondary clones were analyzed for various isozyme markers. Cytogenetic analysis with chromosome banding was also performed in some hybrid clones. The results provide evidence indicating that glycinamide ribonucleotide synthetase is syntenic with superoxide dismutase (soluble) and is located on human chromosome 21.


Interaction of transcapillary Starling forces in the isolated dog forelimb.

Three of the four Starling forces were measured in the intact dog forelimb after anesthetization and all four of the Starling forces were measured in the same forelimb which was surgically isolated yet innervated. In the isolated forelimb, isogravimetric capillary pressure (Pci) averaged 15.6 mmHg; colloid osmotic pressure of the plasma proteins (IIp) averaged 19.9 mmHg; mean interstitial fluid pressure (Pif) was +0.4 mmHg, and the average value of interstitial colloid osmotic pressure (IIif) was 4.9 mmHg. Thus the net imbalance in the Starling forces, i.e., (Pci - Pif) - (IIp - IIif), averaged 0.3 mmHg. Furthermore, the value of IIif was consistently decreased after isolation (average decrease of 1.2 mmHg) while Pif was always increased following isolation (average increase of 4.3 mmHg). In addition, it was found that if the forelimb was denervated during isolation, then Pif was increased by an average of 2 mmHg above Pif in the innervated, isolated forelimb. In summary, these studies show that the differences between the intact and isolated forelimb are that Pci averages 10-11 mmHg in the intact forelimb and 15-16 mmHg in the isolated innervated forelimb while interstitial fluid pressure is negative in the intact limb and positive in the isolated limb.


Changing concepts in establishing the diagnosis of breast masses.

Experience with 297 consecutive biopsies of breast masses for 235 benign lesions and 62 carcinomas over a thirty month period has been reviewed. The correct preoperative clinical diagnosis was made in 91% of cases. Of patients with carcinoma, 66% were suspected clinically, and 88% of those clinically suspected were confirmed by needle biopsy alone. The mammographic diagnosis was correct in 89% of cases with 6% false-negatives. The clinical and mammographic diagnosis differed in 27 patients, with the clinical diagnosis being correct in 85%. No patient thought to have cancer on both clinical and mammographic grounds had a benign lesion. These data indicate that the approach to establishing a tissue diagnosis in women with breast masses can be simple and inexpensive. Local anesthesia can almost always be employed, and the diagnosis of breast cancer can usually be confirmed with certainty by needle biopsy alone.


Benign slow paroxysmal atrial tachycardia.

Review of 203 24-h ambulatory electrocardiographic tapes of 140 patients disclosed 32 patients with 66 episodes of paroxysmal atrial tachycardia. In contrast to classic sustained paroxysmal supraventricular tachycardia, these episodes were relatively slow and brief. The median duration was 7 beats and the mean 116 beats/min. All episodes were asymptomatic except for three prolonged paroxysms that produced mild palpitation. Sixty-eight percent (45/66) of these episodes occurred during sleep or sinus bradycardia. This was the most common paroxysmal supraventricular arrhythmia observed, and it occurred in patients with a wide variety of cardiac diagnoses. The majority of these episodes appear to arise from an atrial ectopic origin. We conclude that these brief slow atrial paroxysms represent a benign arrhythmia. This rhythm disturbance is present in as many as one quarter of cardiac patients undergoing ambulatory electrocardiographic monitoring. It should not be confused clinically with classic sustained paroxysmal supraventricular tachycardia.


Gap junction structures. II. Analysis of the x-ray diffraction data.

Models for the spatial distribution of protein, lipid and water in gap junction structures have been constructed from the results of the analysis of X-ray diffraction data described here and the electron microscope and chemical data presented in the preceding paper (Caspar, D. L. D., D. A. Goodenough, L. Makowski, and W.C. Phillips. 1977. 74:605-628). The continuous intensity distribution on the meridian of the X-ray diffraction pattern was measured, and corrected for the effects of the partially ordered stacking and partial orientation of the junctions in the X-ray specimens. The electron density distribution in the direction perpendicular to the plane of the junction was calculated from the meridional intensity data. Determination of the interference function for the stacking of the junctions improved the accuracy of the electron density profile. The pair-correlation function, which provides information about the packing of junctions in the specimen, was calculated from the interference function. The intensities of the hexagonal lattice reflections on the equator of the X-ray pattern were used in coordination with the electron microscope data to calculate to the two-dimensional electron density projection onto the plane of the membrane. Differences in the structure of the connexons as seen in the meridional profile and equatorial projections were shown to be correlated to changes in lattice constant. The parts of the junction structure which are variable have been distinguished from the invariant parts by comparison of the X-ray data from different specimens. The combination of these results with electron microscope and chemical data provides low resolution three- dimensional representations of the structures of gap junctions.


Pathogenesis of temperature-sensitive mutants of Sindbis virus in the embryonated egg. III. Autologous, homologous, and heterologous interference.

Two temperature-sensitive (ts) mutants of Sindbis virus able to synthetize RNA, but not two ts mutants defective in viral RNA synthesis, reduced to lethality of the superinfecting heat-resistant parent strain of Sindbis virus in embryonated chicken eggs as compared with results in controls. Autologous interference (of mutant with parent) was observed under a variety of conditions. Time-course studies in one selected system showed that lower titers of superinfecting parent virus were detected in doubly infected eggs than in controls eggs infected with only parent virus. Homologous interference with lethality (of mutant with an immunologically different yet related group A togavirus) was observed when the interfering virus was a ts mutant of either Sindbis virus or Eastern equine encephalitis virus. Heterologous interference (mutant with unrelated virus) could also be demonstrated with a ts mutant of Sindbis virus against vaccinia virus-induced pock formation or death. In an autologous interference experiment, in which the ts mutant of Sindbis virus was administered by the yolk sac route and the egg was challeged with parent heat-resistant Sindbis virus by the allantoic route, an interferon-like substance was found in the allantoic fluids at the time of challenge. It is concluded that certain ts viruses of togavirus group A can induce autologous, homologous, and heterologous viral interference in vivo.


Conjoined twins and opocephaly in guinea-pigs: 4 cases of congenital malformation.

A case of opocephaly in inbred guinea-pig strain 2/N and another in strain 13/N, a conjoined twin and an opocephaly concurrent with conjoined twins in the Dunkin-Hartley/FD strain are described. The incidence of congenital malformations in the inbred strain 2/N and strain 13/N was 0-0013 and 0-0073% respectively. The incidence in the random-bred Dunkin-Hartley/FD strain was 0-0007%.


Reduction of hypoxic pulmonary vasoconstriction during diethyl ether anaesthesia in the dog.

The activity of the pulmonary vasoconstrictor response to alveolar hypoxia was assessed by measuring the redistribution of pulmonary blood flow in response to the ventilation of one lung with nitrogen. The vasoconstrictor response was depressed during the administration of 5% diethyl ether but returned when the ether was withdrawn. It is suggested that depression of the hypoxic vasoconstrictor mechanism may be one cause of the increased alveolar-arterial Po2 difference noted during ether anaesthesia.


Reduction of hypoxic pulmonary vasoconstriction in the dog during administration of nitrous oxide.

The pulmonary vasoconstrictor response to alveolar hypoxia was assessed by measuring the redistribution of blood flow in response to the unilateral administration of nitrogen or nitrous oxide. The response was diminished when nitrous oxide was administered and returned to previous levels when hypoxia was produced again by nitrogen. It is postulated that depression of the hypoxic vasoconstrictor response by nitrous oxide may contribute to the increased alveolar-arterial Po2 difference during anaesthesia.


The effects of halothane and ether on the pulmonary circulation in the innervated perfused cat lung.

The effects of halothane and diethyl ether on pulmonary vascular resistance and the pulmonary vasoconstrictor response to alveolar hypoxia were studied in the innervated perfused cat lung. A left and right heart bypass technique was used to allow perfusion of the lungs at constant flow. Neither anaesthetic agent caused a significant change in pulmonary vascular resistance but both agents caused a depression of the pulmonary vasoconstrictor response to hypoxia.


The prophylaxis of malignant hyperthermia by oral dantrolene sodium in swine.

The oral administration of dantrolene for the prophylaxis of malignant hyperthermia (MH) in susceptible swine has been investigated. Complete protection from MH in pigs exposed to the known MH initiating agents, halothane and suxamethonium, was demonstrated.


Determination of MAC for halothane, cyclopropane and ether in the rabbit.

Rabbits have a high rate of ventilation which makes it difficult to obtain a sample of end-tidal gas by the usual procedures. An occlusion technique was developed which provided a gas sample equivalent to an end-tidal gas sample. MAC values were determined using this sampling method. The values obtained +/- SEM were: cyclopropane 15.6 +/- 1.7%, halothane 0.63 +/- 0.06% and ether 2.7 +/- 0.2%.


Interactions between morphine and doxapram in the rabbit and mouse.

Certain actions of doxapram, administered alone and in combination with morphine, have been examined in the rabbit and the mouse. Single doses of doxapram were capable of stimulating respiration in both species. There was an increase in tidal volume in the rabbit and an increase in respiratory rate in the mouse. In both species the duration of action of single doses of doxapram was less than 15 min. In morphine-treated rabbits and mice single doses of doxapram affected neither the time course nor the intensity of the respiratory depression. In the rabbit repeated doses of doxapram did not produce tachyphylaxis with respect to the effect on tidal and minute volumes, and effectively reversed the respiratory depressant actions of morphine. The usefulness of this action must be balanced against the enhanced toxicity of doxapram observed in morphine-treated mice.


Effect of the acute administration of sodium bicarbonate on respiration in the presence of hyperoxia.

The effects, on respiration, of the acute administration of sodium bicarbonate were studied in 10 normal subjects. Carbon dioxide responses curves and tidal volume v. PCO2 relationships were obtained under hyperoxic conditions using a closed-circuit breathing system. During alkalosis, a decrease in the slope, and a displacement of the response curves to the right, were observed. These findings indicate that metabolic alkalosis, induced acutely by the administration of sodium bicarbonate, alters the respiratory response to carbon dioxide and that sodium bicarbonate may have a depressant effect on respiration.


Neutrophil chemotaxis and anaesthesia.

Using a modified Boyden technique, the ability of normal human neutrophils to migrate in response to chemotactic stimulation was evaluated during exposure in vitro to halothane and thiopentone. No abnormality in neutrophil chemotaxis could be demonstrated with either agent at concentrations used clinically. The anaesthetics also did not effect serum complement, which was used as the chemotactic stimulant. It is concluded that halothane and thiopentone have little direct effect on the chemotactic activity of human neutrophils.


Comparison of thiopentone, Althesin and ketamine in anaesthesia for otolaryngological surgery in children.

Thiopentone 4 mg/kg, Althesin 0.055 ml/kg and ketamine 2 mg/kg were compared in 157 children undergoing minor otolaryngological surgery, mostly adenotonsillectomy. Premedication was with pethidine and atropine and anaesthesia was maintained with nitrous oxide in oxygen and halothane. Tracheal intubation was facilitated with suxamethonium. In each group half of the children received pethidine 0.7 mg/kg after intubation and the remainder received saline. Ketamine increased arterial pressure after induction. The cardiovascular responses to intubation were more obvious after thiopentone and Althesin than after ketamine. Operating conditions, cardiovascular changes during operation and the course of extubation were similar in all groups. The recovery after ketamine was longer than after thiopentone and Althesin. Thiopentone was associated with significantly less vomiting immediately after operation than was Althesin and ketamine. In the period immediately after operation Althesin was associated with a higher need for analgesics compared with thiopentone and ketamine. Pethidine prolonged the recovery after thiopentone, decreased the incidence of vomiting immediately after operation associated with Althesin and increased that associated with ketamine.


Anaesthesia for Caesarean section. Analysis of blood concentrations of halothane using 0.2% or 0.65% halothane with 50% nitrous oxide in oxygen.

In 15 patients anaesthesia for elective Caesarean section was maintained with 50% nitrous oxide in oxygen and a 0.65% halothane supplement. In a further 15 mothers a 0.2% halothane supplement was used. In those mothers receiving 0.65% halothane intermittent measurements were made of maternal arterial halothane concentrations during the uptake and the excretion of the agent. At delivery the foetal umbilical venous concentrations were measured also. The mean time between administering halothane and delivery was 10.5 min (SD 3.5). The mean maternal arterial halothane concentration at delivery was 6.03 mg/100 ml (SD 0.75) and the mean umbilical vein concentration was 2.13 mg/100 ml (SD 0.69). The regression of Apgar scores at 1 min after delivery on umbilical vein halothane concentration at delivery was not significant. In the mothers receiving 0.2% halothane measurements of halothane concentration were made in five patients only. The mean maternal arterial halothane concentration at delivery was 1.56 mg/100 ml (SD 0.52) and the mean umbilical vein and artery concentrations were 0.8 and 0.38 mg/100 ml respectively. The use of 0.2% and 0.65% halothane supplements prevented awareness in all the mothers. However, dreaming occurred in two patients given a 0.2% halothane supplement. Studies are required to establish the minimum halothane supplement required to prevent awareness in a larger series of patients.


Management of anaesthesia in an infant with an anomalous lung arising from the oesophagus.

The anaesthetic management of a 19-month-old male infant undergoing pneumonectomy for a rare congenital anomaly is discussed. The trachea communicated solely with the left lung and there was an abnormal communication between the oesophagus and the right main-stem bronchus. Gross infection of the right lung was present. Our experience suggests that the following points are of importance: (1) There is a substantial risk in intubating deeply into the trachea because of the possible existence of a bronchial pouch at the bifurcation. (2) Since the stomach may be full of pus, aspiration of pus before induction of anaesthesia and before extubation is essential. (3) Pneumonectomy with the patient in the supine position is advised.


Effect of polarity on the response of the flame ionization detector to halothane.

Prepared standards of halothane in oxygen were analysed using a Pye Series 104 gas chromatograph equipped with a heated head flame ionization detector and gas sampling valve. The adoption of a positive jet voltage expanded the linear dynamic range of the detector to cover the 0.5-9.0% by volume range, provided that a small (0.5-ml) sample loop was used.


Sodium nitroprusside and regional arterial haemodynamics in the dog.

Blood flow to functionally different vascular beds was examined during a sodium nitroprusside infusion in 10 dogs anaesthetized with halothane (1 MAC) in oxygen. Blood flows were measured in the ascending aorta, and the coeliac, superior mesenteric, renal and iliac arteries. In two dogs, regional vascular impedance and related power were calculated. Regional pressure-flow relationships were measured at systemic pressure reductions of approximately 15, 35 and 55% of control. At pressure reductions of 15-35%, coeliac, mesenteric and aortic blood flow exceeded control values (P less than 0.025); renal and iliac blood flows were reduced, but not significantly. At pressure reductions of 55% a more significant reduction of iliac, renal and aortic blood flow occurred (P less than 0.05). All vascular resistances showed significant monotonic reductions (P less than 0.01) over the entire range of pressure reduction. Total power dissipation was reduced in all beds with a reduction of characteristic impedance in the coeliac, renal and iliac beds; aortic oscillatory pressure power increased.


Inadvertent contamination of anaesthetic circuits with halothane.

All halothane vaporizers tested for leakage when turned off, leaked significant amounts of halothane and this may represent a hazard to patients liable to develop halothane hepatitis or malignant hyperpyrexia. The hazard from leaking vaporizers may be reduced considerably by the use of well-designed bypass units. Circuit contamination by halothane may still result from such sources as neoprene seals around flowmeters, breathing bags and anaesthetic hose which have had previous contact with halothane vapour, whether or not an apparatus is in use. The hazard from contaminated hoses and bags may be reduced considerably by washing and then hanging in a halothane-free atmosphere for a day. The hazard from contamined rubber or plastic components of the anaesthetic machine can be eliminated only by using one apparatus without the vaporizers having been attached at any time during its working life. Similarly, hazards may arise from trichloroethylene vaporizers and from circuit components contaminated with trichloroethylene.


The importance of peripheral vasoconstriction in influencing body temperatures and the part played by certain environmental factors: the effect of inhaled gases.

Core and peripheral temperatures have been studied in 88 dogs of mixed breeds anaesthetized with pentobarbitone. Hyperventilation with cold, dry oxygen was associated with a decrease in peripheral temperature, whilst normoventilation was without effect.


Correlation of alveolar PCO2 estimated by infra-red analysis and arterial PCO2 in the human neonate and the rabbit.

The performance of an infra-red analyser (Beckman LB-2) in sampling alveolar gas at ventilatory frequencies and volumes occuring in the human neonate has been examined. The optimum sampling flow rate was found to be 300 ml/min; at this flow the 90% response time of the analyser-catheter system was 140 ms. Correlation of estimated alveolar PCO2 and arterial PCO2 was performed in the rabbit which has a ventilatory rate and tidal volume similar to those of the human neonate. There was a good correlation between maximum end-expired PCO2 (PE'CO2) and arterial PCO2 over a wide range of ventilatory rates (10-100 b.p.m.); maximum PE'CO2 was a better index than mean PE'CO2 or alveolar plateau PE'CO2.


In vitro study of interactions between i.v. anaesthetics and neuromuscular blocking agents.

The interactions of four anaesthetic drugs (ketamine, propanidid, Althesin and methohexitone) with two neuromuscular blocking agents (suxamethonium and pancuronium) have been investigated. On the isolated rat phrenic nerve-diaphragm preparation, all the anaesthetic drugs examined potentiated suxamethonium more than they potentiated pancuronium. The anticholinesterase agent, ecothiopate, had no significant effect on the potentiation of suxamethonium caused by the anaesthetic drugs. At low concentrations the anaesthetic drugs increased the twitch tension elicited by stimulation of the phrenic nerve, whilst at high concentrations this potentiation was followed by blockade of neuromuscular transmission. With the exception of Althesin, all the anaesthetics decreased the sensitivity of the frog rectus preparation to acetylcholine. The possible sites and mechanisms of these interactions are discussed.


Postsynaptic effect of i.v. anaesthetic agents at the neuromuscular junction.

The effects of sodium thiopentone 19-757 mumol/litre, sodium pentobarbitone 25-806 mumol/litre, propanidid 74-1186 mumol/litre, Althesin 55-220 mumol/litre, diazepam 17.6-140 mumol/litre and ketamine 1.8-116.8 mumol/litre on the time-course of miniature end-plate currents of the excised mouse diaphragm were investigated. The currents were detected by means of extracellular electrodes and recorded with a transient recorder. The drugs had no significant effect on the growth phase of the current, but all six shortened the time-constant of the decay phase. This reduction in the duration of end-plate currents reduced the amplitude of postsynaptic potentials. A similar effect at central synapses may account for a failure of synaptic transmission caused by anaesthetic drugs and it is suggested that a reduction in the lifetime of open postsynaptic ionic channels is a common action of anaesthetic drugs.


No mutagenic effect of enflurane on cultured cells.

Enflurane was tested by the 8-azaguanine system for any evidence of mutagenic effects. No significant increase in the number of mutant colonies compared with controls was found after 24 h of exposure of Chinese hamster cells to 1.5-6.5% enflurane and no damaged chromosomes were seen in metaphase cells on slides. Studies of inhibition of growth rate by enflurane show that in this respect its effects were similar in magnitude to other commonly used inhalation anaesthetic agents, but with regard to cell survival (as measured by colony-forming ability) there was surprisingly little increase in toxicity with increasing concentrations of enflurane.


Oxygen therapy after abdominal surgery.

Arterial blood was sampled from 10 patients, on the day after upper abdominal surgery, breathing air, and during oxygen therapy from 24, 28 and 35% venturi masks. PaO2 during breathing each concentration of oxygen correlated with PaO2 during air breathing. The difference between pulmonary end-capillary and arterial oxygen content was used as an index of the impairment of oxygen transfer in the lung. This difference was reduced by oxygen therapy. The response to oxygen therapy did not correspond to predictions based on an iso-shunt lung model. These findings suggest that hypoxaemia in these patients is predominantly caused by ventilation/perfusion mismatching.


Does sodium nitroprusside improve tissue oxygenation during cardiopulmonary bypass?

Eight patients undergoing cardiopulmonary bypass with hypothermia received, during part of the hypothermic phase, an infusion of sodium nitroprusside (SNP). Oxygen consumption was measured during the infusion and during control periods. Despite causing a marked reduction of arterial pressure, SNP was not shown to have any significant effect upon whole-body oxygen consumption or lactate concentration in the blood.


A study of eye movement for assessing recovery from anaesthesia.

A test for assessing recovery from general anaesthesia is proposed, using electro-oculographic (e.o.g.) measurements. The eyes, when exploring a flat area, progress by "jerking" movements. After general anaesthesia, incomplete recovery is associated with smooth sinusoidal movements. In a series of 16 patients, different e.o.g. patterns were compared with clinical signs of awakening and related to the anaesthetic drugs used. In a further group of 19 patients, assessment of recovery using e.o.g. techniques was made 2 h following the end of operation. In both groups, this simple test appeared to be very reliable. In addition, the test provides a record which can be filed. This may be of value in day-case anaesthesia, where the safety of the patient and medicolegal considerations would be aided by an objective measurement of recovery.


The rational use of i.v. hydrochloric acid in the treatment of metabolic alkalosis.

A method for the assessment and management of factors both causing and maintaining a primary metabolic alkalosis is presented. During a 2-year period 65 patients with metabolic alkalosis were treated with saline and potassium chloride infusions. In four patients the alkalosis was refractory and required additional therapy. An infusion of hydrochloric acid 0.12-0.24 mol/litre through a central venous line corrected the alkalosis without causing haemolysis or tissue necrosis. The maximum rate of infusion suggested is 0.2 mmol H+-kg body wt-1-h-1.


Evaluation of peripheral arterial pressure on the thumb following radial artery cannulation.

The effects of cannulation of the radial artery were studied in 23 patients. Distal arterial pressure on the thumb, measured during radial or ulnar artery compression, was compared with the result of a modified Allen test performed before operation. Distal arterial pressure on the thumb was monitored for approximately 10 days after removal of the cannula. It was found that radial artery thrombosis, as defined by a thumb arterial pressure of less than 10 mm Hg during ulnar artery compression, occurred with a frequency of about 40% depending on the duration of cannulation. Furthermore, thrombosis of the radial artery resulted in a decrease in perfusion pressure in the thumb of from 17 to 33% of the values before cannulation. However, a satisfactory result from a carefully performed Allen test seems to ensure that post-thrombotic perfusion pressure in the thumb is not decreased to values associated with compromised nutrition of the tissues.


Awareness during anaesthesia. A prospective study.

One hundred and thirty-eight patients were anaesthetized using a nitrous-oxide-oxygen technique with neuromuscular blockage under standard conditions. None showed any evidence of awareness during the course of anaesthesia, irrespective of the type of premedication used.


Monocytes and macrophages in malignant melanoma. I. Peripheral blood macrophage precursors.

A micro-assay designed to assess the capacity of peripheral blood mononuclear cells to differentiate in vitro into mature macrophages is described. In patients with "final common pathway" malignant melanoma, there was a highly significant deficiency in macrophage precursors (MPs). By conventional morphological criteria such patients did not show a significant monocytopenia. Serum factors do not seem to contribute to the MP defect in the patients. We conclude that these patients have an intrinsic functional defect in their peripheral blood monocytes, but the mechanisms responsible for this defect are as yet unknown.


Influence of tumour size on hypoxic fraction and therapeutic sensitivity of Lewis lung tumour.

Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours.


Fate of methyl methacrylate in rats.

Up to 88% of a single dose of methyl[14C]methacrylate in rats is expired as 14CO2 in 10 days (65% in 2 h), irrespective of the route of administration and of the specific labelling of the propylene residue of the molecule. The implications of this observation, and of the excretion of small amounts of [14C]methylmalonate, [14C]-succinate and probably of [14C]beta-hydroxyisobutyrate and 2-formylpropionate, and of the formation of [14C] normal, physiological metabolites that may be accounted for by anabolism both from 14CO2 and from [14C]acetate emergent from the citric acid cycle, are that the metabolic pathway concerned involves intermediary metabolism and relates to mitochondrial function. Present findings are discussed in relation to the imputations of a report of carcinogenic risk.


Hodgkin's disease in children.

Fifty-nine children with Hodgkin's disease were seen over a 34-year period. Compared with Hodgkin's disease in adults, there was an increased male incidence, especially in the younger children. This was associated with an increased male incidence of lymphocyte-predominant histology. Forty-six patients underwent lymphography as part of their staging, and 13 had staging laparotomies. The 5-year survival for the entire group was 85%, with a median survival of 10 years. Response to radiotherapy in children with Stages I-IIIA disease was: 12 children treated with involved-field radiotherapy after inadequate clinical staging had a 3-year remission rate of 13%, and a median length of remission of 18 months; 24 children treated with extended-field radiotherapy after adequate clinical staging, including lymphography, had a 3-year remission rate of 72%, and a median duration of remission not yet reached; 3 children treated with elective local radiotherapy for Stage IA disease after intensive clinical staging remain in complete remission for periods of up to 34 months. Eight out of 10 children with Stages IIIB-IV disease, treated with combination chemotherapy, achieved complete remission with a 3-year remission rate of 70%; 7 children treated with combination chemotherapy following relapse after radiotherapy all achieved complete remission with a 3-year complete remission rate of 66%. Thirteen children underwent laparotomy and splenectomy as a staging procedure. Five were found to have intra-abdominal disease, including 4 with splenic involvement. These results show that there is no place for involved-field radiotherapy after inadequate clinical staging, in the management of childhood Hodgkin's disease. Extended-field radiotherapy after adequate staging, and combination chemotherapy, produce results which are as good as those for adults, but the benefits of these treatments and of staging laparotomy must be balanced against the possible complications when they are used in children. These problems are discussed and a scheme of management is proposed.


Cancer in Yogyakarta, Indonesia: relative frequencies.

Some 1220 male and 2102 female cases of malignant neoplasms diagnosed histologically at the Department of Pathology of the Gadjah Mada University in Yogyakarta during the period 1970-73 were analysed. The most frequent tumour sites were among men: nasopharyngeal cancer, 21-8% and skin cancer, 17-6%. Among women the genital cancers were the most frequent with: cervix uteri, 25-7% chorionepithelioma, 3-7%, other uterus, 4-4% and ovary, 7-4%. Breast cancer comprised 17-0%, skin 9-6% and nasopharyngeal cancer 7-9%. Low frequencies were observed in both sexes for cancers of the gastro-intestinal tract and of the respiratory organs; previous reports of the rarity of gastric cancer were confirmed. The observed distribution is discussed in the light of possible biases, and compared with other material on the frequency of cancer from South East Asia.


Intravascular coagulation resulting from intravenous injection of C. parvum in mice.

In mice, i.v. C. parvum induces intravascular coagulation. This is a prolonged reaction lasting up to 7 days. It results in thrombosis in hepatic vessels with consequent hepatic necrosis, and thrombosis in pulmonary and splenic vessels. This may be important in the assessment of the tumour-inhibitory activity of C. parvum.


Non-specific cytotoxicity of spleen cells in mice bearing transplanted chemically induced fibrosarcomas.

Spleen cells collected from mice bearing transplanted chemically induced syngeneic fibrosarcomas non-specifically inhibited DNA synthesis of sarcoma and lymphoma target cells in vitro. Splenocytes from mice hyper-immunized against a syngeneic sarcoma specifically inhibited DNA synthesis of the tumour used for immunization. The impairment of tumour-cell DNA synthesis was associated in vitro with cytostasis, and lysis of the target cells was not seen. Since treatment with anti-theta serum and complement did not impair cytostatic action of the spleen cells, and since thymus-deprived animals showed similar activity to normal mice, T lymphocytes were not involved in non-specific cytostasis. Removal of phagocytic adherent cells by carbonyl iron markedly inhibited the cytostatic activity of the spleen cells, suggesting a role in this reaction for cells of the monocyte-macrophage series. The presence of an actively growing sarcoma was a prerequisite for the expression of non-specific cytostasis, since surgical excision resulted in complete disappearance of this activity of spleen cells.


Mechanism of the anti-tumour effect of glucans and fructosans: a comparison with C. parvum.

The anti-tumour activity induced by glucans (lentinan, yeast cell walls, pseudonigeran, dextran, DEAE-dextran and dextran sulphate) and fructosans (levan and carboxymethyl-levan) was compared with the activity of C. parvum. The following effects on tumour systems in CBA mice were assayed: (a) adjuvant activity on the immune response against tumour-specific transplantation antigens (TSTA) with a methylcholanthrene-induced fibrosarcoma; (b) cytostatic activity of peritoneal macrophages against radiation-induced leukaemia cells; and (c) inhibition of tumour nodule formation in the lungs following i.v. injection of fibrosarcoma cells. All the polysaccharides induced cytostatic macrophages, but the dextrans and levans did so only after i.p. and not i.v. injection. Only lentinan, yeast cell walls and pseudonigeran were active in the lung-nodule inhibition test; and only lentinan and dextran sulphate showed slight adjuvant activity for TSTA. It is concluded that the anti-tumour activity induced by these polysaccharides is predominantly non-specific macrophage-mediated and much weaker than that found with C. parvum.


Cell survival in B16 melanoma after treatment with combinations of cytotoxic agents: lack of potentiation.

The extent of tumour, cell kill, produced by treating B16 melanomas with vincristine, cyclophosphamide, 5-fluorouracil and gamma-rays, alone and in combination, was determined using an in vitro colony assay. Cell kill by vincristine was revealed as a reduction in the yield of cells obtained by trypsinization, and as a decrease in the colony-forming ability of the extracted cells. The reduction in cell yield was interpreted as evidence of rapid cell lysis. Cyclophosphamide and gamma-rays also reduced both cell yield and surviving fraction, but in this case the small decrease in cell yield was due to an increase in cell volume. FU had no effect on cell yield, but surviving fraction was reduced. Tumour weight was also measured, and used in conjunction with cell yield and surviving fraction data to calculate the fraction of surviving cells per tumour following treatment with the agents. In combination studies, single doses of two different cytotoxic agents were given either simultaneously, or up to 24 h apart in either sequence, and assays were performed 24 h after the second drug was given. Combinations of vincristine + cyclophosphamide and 5-fluorouracil + gamma-rays were chosen because they had been shown by other workers to exhibit marked schedule dependency, including considerabl potentiation, against leukaemic cell lines. However, in the B16 melanoma there was no evidence of schedule-dependent cell killing with either of these combinations. For all sequences studied, the fraction of surviving cells per tumour was slightly greater than the predicted additive response calculated from single-drug controls.


Reactions of the tumour bed to lethally irradiated tumour cells, and the Révész effect.

Subdermal inoculation of the foot of the rat with lethally irradiated (LI) Walker tumour (W256) cells, mixed with viable (V) W256 cells, decreased the latent period for initiation of allogeneic tumour growth without significantly affecting its rate. This Révész effect decreased with increase in the number of inoculated V cells, and with decrease in age of recipient. LI cells of a different (Y-P388) rat tumour exerted a Révész effect, even in recipients which had been immunized with LI (Y-P388) tumour cells. Local pre-irradiation of the site of inoculation of V cells decreased both the latent period and rate of tumour growth. It acted independently of a Révész effect, and the decrease in tumour growth rate was partly due to emigration of V cells from the inoculum, producing metastases. LI, but not heat-killed cells, induced prolonged swelling of the tumour bed in unimmunized and tumour-immunized rats, which, unlike inflammatory swelling, was inhibited by pre-irradiation of the foot. It is postulated that the Révész effect is due to enhancement of survival of V cells by trophic substances which are principally elaborated by LI (AND V) cells, but also by the tumour bed, due to innate growth and trophic reactions of its tissues to the presence of tumour cells.


Agenesis of the lung.

Agenesis of the lung is rare. The cases of ten patients with this malformation are recorded and illustrated. Most had congenital malformation of other organs, especially the heart, as well. All had hypoplasia of the pulmonary artery or its branches. A pantaloon-like appearance of the trachea and the main bronchi on the bronchograms is described. Exercise tolerance was impaired in all patients.


Mortality from respiratory disease at follow-up of patients with asthma.

Over a 20-year period 765 men and 1127 women with asthma were followed up; 272 men and 282 women died compared with expected deaths of 165 men and 185 women. As anticipated there was an appreciable number of deaths attributed to asthma but an even higher absolute excess of deaths attributed to bronchitis when compared with the expected numbers. The relative excess from asthma and bronchitis was highest in the younger subjects. Mortality from all other causes was lower than expected.


The kidney and aldosterone in acclimatization at altitude.

Five climbers were studied during an ascent of a 7500 m mountain in the Hindu Kush. Representiative samples from 24-hour urines were preserved from five subjects at 5400 m and 6600 m and from two at 7000 m. Sodium and cortisol excretion was normal, but that of potassium and especially aldosterone was low, especially in two climbers who had episodes of peripheral oedema. Hypoaldosteronism is a feature of high altitude acclimatization but its cause and significance have still to be elucidated.


Mediastinal cavernous haemangioma.

The case of a patient with a mediastinal cavernous haemangioma and other malformations is described and discussed.


Cellulitis in complicated pneumococcal pneumonia.

Serious complications of pneumococcal pneumonia have become uncommon. This has been attributed to decline in pneumococcal infection (van Roy et al. 1971; Foy et al. 1975), but in this country it is more likely to be due to effective antibiotic therapy. We report a case of pneumococcal pneumonia with severe complications (including a very unusual one) which probably arose through antibiotic failure.


Nutritional influences of pellagra on sebum composition.

Sebum composition has been measured in 51 patients with varying degrees of pellagra and compared with a control group of subjects in the same geographic area. In the pellagra group the wax ester percentage was 14-9 versus the normal of 21-9%. The squalene percentage was increased in the pellagra group (11-6%) versus a control value of 8-4%. A small increase in the percentage of cholesterol was also noted. These changes, which previously have been observed in starved but otherwise normal subjects, were reversible with adequate refeeding.


Essential fatty acid deficient hairless mouse: the effects of topical agents on the epidermis.

Essential fatty acid deficient (EFA deficient) hairless mice were used to test the ability of topical agents to reduce the high epidermal DNA synthesis and acanthosis present in EFA deficiency. An established therapeutic agent known to be effective in psoriasis (betamethasone 17-valerate) significantly reduced the epidermal DNA synthesis, mitotic count and epidermal cell thickness. Linoleic acid reduced DNA synthesis and returned epidermal histology towards that of normal skin. Prostaglandin E2 analogue (15 (S)-15-methyl PGE2 methyl ester) reduced epidermal DNA synthesis both in treated and distant skin sites. Prostaglandin E2 was less effective than the analogue but slightly reduced epidermal DNA synthesis and thickness. Prostaglandin F2alpha had no obvious effect on the epidermis. Chlorambucil reduced epidermal DNA synthesis and thickness. Vitamin A acid increased DNA synthesis and epidermal cell thickness but reduced the hyperkeratosis of EFA deficiency. A rapid epidermal cell transit was found in EFA deficient mice, approximately three times faster than in normal mouse epidermis.


A modified technique (using polyester tape) of skin surface biopsy. Its interest for the investigation of athlete's foot.

A technical modification of skin surface biopsy has been introduced by using plastic tape instead of glass as holder, mainly to investigate mycological infections of skin folds. Among various brands of plastic sheets, a polyester film (Melinex O UCB-SIDAC) has been demonstrated as the most suitable. A direct microscopic comparison has been made between our modified technique and conventional scraping as procedures for collecting material from interdigital spaces in 30 patients with bilateral athlete's foot. It has been shown that the skin surface biopsy gives a slightly greater number of positive results (presence of dermatophytes or Candida species) than the conventional scraping technique, although the difference between both techniques is not statistically significant at the 0-05 level (0-05 less than P less than 0-10). Some advantages of the modified skin surface biopsy are emphasized.


X-linked ichthyosis.

In the period 1962-1974, 36 patients with X-linked ichthyosis, belonging to 22 families, were selected for study. The frequency of this genodermatosis is higher in the province of Salamanca than in other countries. In most of the cases, the lesions were apparent at birth or shortly after. In 41% of the patients studied by slit-lamp microscopy, posterior embriotoxom was seen. Hyperkeratosis was seen in follicular and sweat duct orifices. Statistical analysis of the pedigrees showed a higher proportion of affected males among the offspring of carriers and also among the offspring of the ichthyotics' sisters. In addition, among the patients' descendants, the higher ratio of females is statistically significant, showing that there is likely to be selection in  favour of the X chromosome.


Elevated serum IgE and IgG4 in patients with atopic dermatitis.

The quantitative measurement of the IgE and IgG subclass levels in the sera of 29 patients with atopic dermatitis has revealed significantly elevated levels of IgE and IgG4 in a relatively high proportion of patients with this condition compared to non-atopic patients with warts and to a group of normal volunteers studied previously. The possible significance of these observations is discussed in relation to current evidence suggesting the involvement of IgG4 in certain immediate-type hypersensitivity disorders.


Percutaneous absorption of 1,3-bis (2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in mycosis fungoides.

The total percutaneous absorption of 1,3-bis(2-chloroethyl)-I-nitrosourea (BCNU, carmustine) in 5 patients with mycosis fungoides, based on the 5 day urinary excretion of 14C-labelled BCNU, ranged from 5 to 28%. Absorption through diseased skin was greater than through uninvolved skin.


Effects of topically potent glucocorticoids on human diploid fibroblasts in vitro.

A wide range of concentrations of both cortisol and a topically more potent synthetic derivative, fluocinolone acetonide, was found not to inhibit the growth of cultured human skin fibroblasts; fluocinolone acetonide produced a slight increase in the growth rate. Both steroids had a transient stimulatory effect on fibroblasts, promoting an earlier entry into the period DNA synthesis (S) which was also accompanied by a substantial increase in the length of S.


Treatment of porphyria cutanea tarda with chloroquine and phlebotomy.

Treatment of porphyria cutanea tarda (PCT) with chloroquine risks serious side-effects so we have combined it with phlebotomy. One to four venesections were performed before the administration of chloroquine in 10 PCT patients. Equally high excretion of urinary porphyrins was achieved but the side-effects were reduced. Chloroquine may be used as a provocative diagnostic test for patients with a questionably latent PCT but this is safe if phlebotomy is performed beforehand.


Acquired chronic candidiasis treated with transfer factor.

A patient with acquired chronic oral and vaginal candidiasis resistant to topical and parenteral therapy was found to have impaired cell mediated immunity to Candida antigen and loss of skin test response to tuberculin (Mantoux). Treatment with Candida-active transfer factor produced clinical remission lasting 1 year and restitution of in vitro and in vivo immune parameters. Relapse occurred while receiving a second lot of transfer factor from the same donor. Subsequent treatment with levamisole was associated with onset of agranulocytosis.


Livedo reticularis and nodules due to cholesterol embolism in the lower extremities.

A case is described of livedo reticularis and nodules, resembling polyarteritis nodosa but shown to be due to emboli of cholesterol crystals.


Erythema elevatum diutinum, cryoglobulinaemia, and fixed urticaria on cooling.

A mixed cryoglobulin (IgG/IgM) was detected in a patient with erythema elevatum diutinum. Cold exposure activated the complement system and provoked a fixed urticarial reaction with the histology of a leukocytoclastic vasculitis.


An unusual form of chronic neutropenia in a father and daughter with hypogammaglobulinaemia.

Chronic neutropenia, with an abundance of mature neutrophils in the bone marrow, was discovered in a father and daughter who also had common variable hypogammaglobulinaemia. Under the stress of infection or following the administration of typhoid vaccine, release of neutrophils from the marrow was enhanced sufficiently to abolish neutropenia temporarily. Although their morphology was abnormal, the function of neutrophils in vitro was normal. Thus, the increased susceptibility to infection that characterized these patients appeared to be due primarily to their defect in humoral immunity rather than their neutropenia.


Intravascular phagocytosis in the rabbit bone marrow: a possible fate of normal senescent red cells.

Perisinal macrophages in the rabbit bone marrow can penetrate the sinus wall and phagocytose circulating red cells intraluminally. Serial sectioning reveals that the penetration occurs through the cytoplasm of a single endothelial cell. This phenomenon may provide an effective mechanism for monitoring the circulation and removing normal senescent red cells.


The role of iron in the regulation of hepatic transferrin synthesis.

The role of iron supply in the regulation of hepatic transferrin synthesis by the isolated perfused rat liver was studied using nutritional iron deficiency as the experimental model. The increased transferrin release encountered in iron deficiency could be equated with enhanced de novo synthesis as evidenced by the inhibitory effects of cycloheximide and measurements of intrahepatic protein pools before and after perfusion. Refeeding with iron, sufficient to restore plasma iron and hepatic ferritin iron but before correction of anaemia, promoted a reduction towards normal in the transferrin synthetic rate. This effect was not produced by transfusional correction of the anaemia, suggesting a specific response to iron supply. Phenobarbitone treatment, which produced a marked fall in hepatic ferritin iron concentration but no change in haemoglobin or plasma iron concentrations, promoted a specific enhancement of transferrin synthesis in both control and iron deficient livers. The concentration of liver iron stores appears to be a major regulatory factor in the control of hepatic transferrin synthesis.


Aspects of folate metabolism in renal failure.

Plasma and urine folate fractions were evaluated after ingestion of radioactive N5-methyl-tetrahydrofolic acid by a normal control (subject I), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radiofolate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject I to be compatible with N5-methyl-tetrahydrofolic acid (peak I). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10-formyl-tetrahydrofolate. Peak I was minimally present in subject 3. This limited study suggest a defect of methyl-tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se. In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks I and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis-resistant (bound plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate 'binder' detected with haemoglobin-coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.


Incorporation of 32PO4 into phospholipids of blood platelets.

Human or rabbit platelets in an artificial medium without phosphate were incubated with carrier-free [32P] orthophosphate for I h, washed and resuspended in Tyrode-albumin solution containing unlabelled phosphate. Aliquots of platelet suspension were subjected to lipid extraction at various times and the extracted phospholipids were separated by thin layer chromatography. The specific radioactivities of triphosphoinositide (TPI) and diphosphoinositide (DPI) were highest during the labelling period and then declined rapidly after the platelets were resuspended in the medium containing unlabelled phosphate. The percentage of total phospholipid 32P in TPI and DPI decreased from over 95% at 1 h to less than 50% at 12 h with either rabbit or human platelets. The specific radioactivity of monophosphoinositide (MPI) reached its greatest value 6-8 h after labelling. In the in vitro incubation studies, phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE) were negligibly labelled in the initial hours but at 12 h (rabbit or human platelets) PC contained more than 30% of the radioactivity. PE and PS contained less than 10% of the total phospholipid-bound radioactivity at the end of the incubation period. The pattern of incorporation of [32P]orthophosphate into the inositol phospholipids, PC, PS and PE that had been found in the in vitro studies was confirmed by an in vivo study in which rabbit platelets labelled with 32P in vitro were infused into rabbits and harvested after 35 h. These findings indicate that the phosphates of all the phospholipids studied in these experiments turn over in vitro and in vivo but the phosphates of the inositol phospholipids turn over most rapidly.


Impairment by heparin of primary haemostasis and platelet [14C]5-hydroxytryptamine release.

Heparin was administered to 34 normal subjects by intravenous injection (100 mu/kg) and the template bleeding time was significantly increased both 10 min and 120 min following injection. Before heparin the bleeding time was 5-3 +/- 1.0 min (mean +/- 1 SD); 10 min after injection it was 9.8 +/- 5.6 min (P less than 0.001); and 120 min after injection it was 7.2 +/- 3.9 min (P less than 0.001). Increases in the bleeding time were unrelated to changes in platelet count, and independent of heparin's effect on plasma coagulation. In blood drawn 10 min and 120 min following heparin injection, there was significantly less [14C]5-HT released from platelet-rich plasma (PRP) in response to collagen, 0.41 mM epinephrine and 8 micron ADP, although in vitro addition of heparin (0.1 mu/ml, 0.5 mu/ml and 2.5 mu/ml) to baseline PRP of three subjects did not depress [14C]5-HT release. Our experiments suggest that intravenous administration of a therapeutic dose of heparin can cause a significant reversible inpairment of platelet haemostatic properties, possibly by an indirect mechanism.


Proliferation of erythroid colonies in semi-solid agar.

Growth of human erythroid cells in soft-agar culture with no added erythropoietin was demonstrated. This growth was particularly marked in patients with diseases such as myelofibrosis (MF) in which patients had a previous history of polycythaemia vera (PV) characterized by excessive red cell production. A rapid assessment of the proportion of erythroid colonies was obtained by directly staining the culture with benzidine. Fixed and stained preparations of these agar-grown cells revealed elements in all stages of erythroid maturation. The morphology of these erythroid colonies was characteristic of 'erythroblastic islands' containing central, iron-containing macrophages, surrounded by erythrocytic precursors, with the more mature erythrocytes found at the periphery of the colony. These observations document that erythropoiesis may be maintained in agar cultures, and suggest that this technique may be of diagnostic value in disease states characterized by abnormalities of red cell production.


Transferrin receptors in developing murine erythroid cells.

Techniques of cell separation were used to isolate murine erythroid cells at different stages of maturation. The number of transferrin receptors in these cell populations was assayed by measuring binding of 125I-labelled transferrin. Nearly 23 times as many receptors were found in the least mature cells, chiefly pronormoblasts, as in reticulocytes. Iron transport, determined by measurement of the rate of 59Fe uptake from 59Fe-labelled transferrin, was proportional to the number of receptors at all stages of differentiation. Electron microscope radioautographic studies of the interaction of 125I-labelled transferrin with erythroid precursor cells demonstrated that 15-33% of cell associated transferrin was intracellular in erythroid precursors.


Iron deficiency in pregnant women in Ibarapa District of Western Nigeria.

Ninety-nine pregnant women with anaemia (haematocrit less than 0.30) were detected by antenatal screening in Ibarapa District. Studies on 23 anaemic women and 17 non-anaemic women from the same clinic on the same day showed that eight out of 23 anaemic women had a transferrin saturation of less than 15%. The mean level (19.5%) for the anaemic patients was significantly less than that found in the nonanaemic controls; mean 33.0% (P less than 0.01). Bone marrow studies on 32 anaemic women revealed megaloblastic change and absent iron in 27 of the 32 patients. In a trial of parenteral iron treatment in 66 patients the mean haematocrit of Imferon treated patients rose from 0.27 to 0.32 in 6 weeks but remained at 0.28 or less in the controls. There was a significant difference between the iron-treated group and the comparable group receiving no imferon (P less than 0.001 at 6 weeks). The method of using parenteral iron treatment to make a diagnosis of iron deficiency anaemia is discussed together with the possible advantages and disadvantages of giving iron.


Adenosine diphosphate induced platelet aggregation and release reaction in heparinized platelet rich plasma and the influence of added citrate.

Platelets in heparinized platelet-rich plasma (PRP) from 54 volunteers were examined for their ability to aggregate and to release tritiated 5-hydroxy tryptamine (3H-5HT) in response to adenosine diphosphate (ADP). Release of 3H-5HT was considerable in 26 of the preparations. When release was high, lower concentrations of ADP were required to induce irreversible aggregation. Second phase aggregation reflected extensive release reaction. Citrate always augmented the release induced by ADP.


Thrombin activation of factor VIII: the effect of inhibitors.

Factor VIII is a large glycoprotein which can be separated into a high molecular weight component which retains factor VIII-related antigens and supports ristocetin-induced platelet agglutination, and a low molecular weight component which has procoagulant activity. It has been suggested that this separation, observed in high ionic strength buffers, might be the consequence of proteolysis by plasma proteins. To consider this possibility, we have examined the interaction of the proteolytic enzyme thrombin with factor VIII. This study, carried out with highly purified materials, has used thrombin-mediated factor VIII proagulant activation as an indicator of this interaction. Several proteolytic inhibitors have been studied to determine their ability to inhibit factor VIII activation by thrombin. Under the current experimental conditions, diisopropylfluorophosphate (DFP) and hirudin inhibited the reaction, while heparin was an effective inhibitor only when plasma proteins were added. Benzamidine inhibited factor VIII activation when used at high concentrations, and phenylmethyl sulphonylfluoride and soybean trypsin inhibitor were found to be ineffective. These results show that DFP and hirudin prevent thrombin alteration of factor VIII and will be useful in purification and characterization studies of the factor VIII molecule.


Diagnostic value of the unstressed antepartum cardiotocogram.

The unstressed antepartum cardiotocogram (CTG) is principally judged by two aspects: baseline irregularity, and reaction to Braxton Hicks contractions and fetal movements. A classification into normal, sub-optimal, decelerative, and terminal CTG was devised. The ominous significance of the terminal CTG was confirmed in 26 patients; nine of the fetuses died in utero and the other 17 were delivered by elective Caesarean section; only one newborn was neither small-for-dates nor acidaemic. The significance of the other three categories was evaluated in 428 patients in whom labour was induced. All patients with repeated decelerative antepartum CTG showed signs of fetal distress during labour and most of them required Caesarean section; patients with a normal or sub-optimal CTG rarely showed signs of fetal distress during labour. The incidence of growth retardation was 41 per cent in the combined decelerative and sub-optimal groups against 9 per cent in the normal group. In comparing these results with studies of the oxytocin challenge test, it was concluded that, except in the case of a sub-optimal CTG, the oxytocin challenge test has no place in obstetrics.


Epidural analgesia during labour in twin pregnancy.

We report on the use of epidural analgesia during labour in 58 out of a total of 234 twin deliveries performed over a five-year period. A comparable control group consisted of 44 twin pregnancies delivered consecutively during the year preceding the introduction of epidural analgesia into our department. Epidural analgesia shortened the mean time of labour and made possible the performance of all necessary instrumental and obstetrical manoeuvres, without additional anaesthesia or adverse effects on the second twin. The epidural group required oxytocin more often due to an increased incidence of hypotonic uterine dysfunction. There was also a considerable increase of instrumental deliveries in the epidural group. The condition of the newborn infants of both groups, evaluated by Apgar score at one minute, was similar, but there was a higher perinatal mortality among pre-term infants delivered under epidural analgesia. Epidural analgesia was found to be an acceptable method of relieving pain in twin labour, but because of the increased necessity to use oxytocin and the relatively high perinatal mortality observed among pre-term infants, further experience is necessary before it can be claimed that this is the method of choice for relief of pain in twin labour.


Bacterial motility and intrauterine catheter-borne infection.

It has been suggested that monitoring of uterine activity by placement of intrauterine catheters can cause an increase in maternal and fetal infection. The ways in which intrauterine catheters could transmit infection have been investigated. The risk of infection occurs primarily during placement of the catheter, although a risk also exists if bacterial nutrients are present in the fluid filling the catheter. Recommendations are made to minimize these risks.


The effect of indomethacin on plasma levels of prostaglandin F2alpha in women in labour.

Prostaglandin F2alpha was measured by means of radiommunoassay in the serum of women in the active phase of term labour before and after rectal indomethacin administration. Samples of blood were collected every 20 or 30 seconds, between and during contractions. There was a significant decrease of the level of PGF2alpha in plasma 30 to 30 minutes after indomethacin administration, but the pattern of rapid short-term fluctuations in prostaglandin levels was unaltered.


The effect of intravenous salbutamol upon plasma and urinary potassium during premature labour.

Plasma potassium and urinary potassium excretion were measured in eight patients in premature labour treated with salbutamol, and in ten patients at full term in spontaneous labour. There was a significant fall in plasma potassium concentration following salbutamol infusion, but no change during labour in the control groups. Urinary potassium excretion was similar in both groups.


The effect of intravenous and oral salbutamol on fetus and mother in premature labour.

Salbutamol was administered intravenously to 14 patients in premature labour. Inhibition of uterine contractions occurred on 22 out of 23 occasions. The mean increase in maternal and fetal heart rate and blood pressure were within clinically acceptable limits but there were wide individual variations. The mean delay achieved when the intravenous regime was supplemented with oral salbutamol was greater than that achieved by intravenous salbutamol alone, but the difference was not statistically significant.


Correlation between thromboplastic activity and lecithin/sphingomyelin ratio in amniotic fluid preliminary report.

THe thromboplastic activity of amniotic fluid was correlated with the lecithin sphingomyelin (L/S) ratio in 59 pregnancies. It was shown that the thromboplastic activity and the L/S ratio in amniotic fluid had a coefficient of correlation of r = --0-73 (P less than 0-004). The thromboplastic activity was estimated by a modified method for prothrombin time, and a time of 113 seconds appeared to correspond to an L/S ratio of 2, in that it was the border line between maturity and immaturity of the fetal lungs. Thirty women were delivered within 24 hours of a sample of amniotic fluid being obtained. In the three patients whose babies developed the respiratory distress syndrome, the thromboplastic activity was estimated as being slower than 113 seconds.


A comparative study of plasma 17beta-oestradiol, progesterone, placental lactogen and chorionic gonadotrophin in abortion induced with intra-amniotic prostaglandin F2alpha.

Serial estimations were made in plasma of 17beta-oestradiol (E2), progesterone and human placental lactogen (HPL) in 43 patients and of human chorionic gonadotrophin (HCG) in 34 patients during mid-trimester abortions induced with intra-amniotic prostaglandin F2alpha (PGF2alpha. Mean plasma concentrations of all the hormones showed a progressive fall after PGF2alpha. There was no relationship between the fall in levels of progesterone, HPL and HCG and the induction-abortion interval, signs of fetal distress or of intrauterine fetal death. Both the control level and the rate of fall of E2 were related to the induction-abortion interval and a rapid decline preceded intrauterine fetal death. The relationships of the progesterone/E2 ratio and the amniotic fluid volume/progesterone ratio to the induction-abortion interval were examined. The variation in the time at which significant falls in the concentration of individual hormones occurred was probably related to their respective half-lives in plasma.


Beta-human chorionic gonadotrophin and carcino-embryonic antigen in the management of ovarian carcinoma.

Measurements of HCG and carcino-embryonic antigen (CEA) were made in 26 patients with ovarian cancer to evaluate these substances as tumour markers; 13-4 per cent of 194 CEA estimations and 14-6 per cent of 144 HCG estimations were abnormal. CEA values were abnormal in 9 out of 26 patients and HCG values in 13 out of 26 patients. The implications of these findings particularly the presence of HCG are discussed.


Polycystic ovarian disease: diagnosis, frequency and symptoms in a general gynaecological practice.

A study was undertaken to assess the relative frequency of polycystic ovarian disease (POD) among patients with menstrual irregularities and/or hirsutism, and was based on 24-hour urinary steroid profiles under basal conditions, after dexamethasone suppression and after human chorionic gonadotrophin (HCG) stimulation. The final diagnosis was confirmed by laparoscopy or laparotomy and ovarian histology. Fifty-six patients were studied, 38 (38 per cent) of whom had POD. Laboratory results were subjected to multivariate discriminant analysis and a discriminant function was calculated to classify patients into POD, and non-POD subgroups. Steroid profiling under basal conditions was sufficient to classify most of the patient into one of three groups: normal, POD and other endocrinopathies. Of the patients with POD, 70 per cent had an abnormal reaction to dexamethasone or HCG. Significant differences were found in the steroid profiles of ovulating and non ovulating patients with POD.


Pregnancy following metergoline treatment in a patient with hyperprolactinaemia.

A 33-year-old woman who had had amenorrhoea and galactorrhoea for ten years and had hyperprolactinaemia was treated with metergoline, a serotonin antagonist. There was a marked decrease in plasma prolactin levels. After two months, ovulation and pregnancy occurred. This is the first such report.


Intrauterine growth retardation associated with hypoxia due to bronchiectasis.

Two pregnancies in a young patient who had undergone lobectomy for bronchiectasis are described. Both were complicated by intrauterine growth retardation. The only abnormality detected was maternal hypoxaemia, and this was assumed to be causal.


Ruptured renal artery aneurysm in pregnancy. Case report.

A patient who survived rupture of a renal artery aneurysm in pregnancy is described. The aneurysm was caused by fibromuscular dysplasia of the renal artery.


Home and hospital confinement in Newcastle upon Tyne, 1960 to 1969.

During the decade 1960 to 1969, perinatal mortality rates in Newcastle upon Tyne fell in parallel with national trends, in association with a marked reduction of domiciliary midwifery. Analysis of the records of women booked for confinement at home or in specialist hospitals showed that the reduction of mortality occurred with unexpected uniformity in both categories, in low risk as well as high risk patients, and in all causes of mortality except congenital malformations. It could not be attributed to improvements in maternal characteristics nor to increased size of babies at birth. The most probably explanation seems to be a combination of many improvements in the quality of care, with increased awareness of risks, better selection of high-risk groups, and improved supervision and management throughout. There is no indication that single factor in obstetric management, such as more intervention during labour, had a dominant effect.


North-east Essex perinatal mortality survey--1971 to 1975.

A method of carrying out a Perinatal Mortality Survey in a non-academic district obstetric service is described. The results show a trend of improving perinatal mortality and the various factors that may be influencing this trend are discussed.


Erythrocyte 2,3-diphosphoglycerate and associated haematological parameters during the menstrual cycle and pregnancy.

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and associated haematological parameters were measured throughout the normal menstrual cycle, in each trimester of pregnancy and on the third day post partum. There was no significant change during the menstrual cycle but the 2,3-DPG concentration was increased early in pregnancy, and thereafter gradually decreased. Although other metabolic changes are likely to contribute to the increase in 2,3-DPG concentration, it is concluded that 'functional anaemia', secondary to increased oxygen demand, is a more important stimulus than the decrease in haemoglobin concentration. The implications of a decreased oxygen affinity of haemoglobin, secondary to the rise in 2,3-DPG concentration, are discussed in relation to anaemia and blood transfusion in pregnancy.


Ferritin as an assessment of iron stores in normal pregnancy.

In Glasgow, the iron stores in healthy women and in normal pregnant women on prophylactic iron supplementation have been assessed by measurement of plasma ferritin. Ferritin concentration fell progressively to a low level in late pregnancy suggesting that the average iron store was inadequate to meet the demands of pregnancy and that dietary iron supplements were therefore required. There was no evidence that iron supplementation led to excessive iron stores.


Pregnancy heartburn in Nigerians and Caucasians with theories about aetiology based on manometric recordings from the oesophagus and stomach.

A study by questionnaire of the incidence of pregnancy heartburn in two groups of Nigerians and one group of Caucasians showed an incidence of 9-8 per cent in all Nigerians as against 78-8 per cent in Caucasians. The difference was highly significant (chi 2 = 102-75; P less than 0-0001). An oesophageal manometric study of the lower esophageal sphincter in 12 non-pregnant women and in 12 pregnant Nigerians (10 without heartburn and 2 with heartburn) showed that the mean lower oesophageal sphincter pressure (+/- SD) in the pregnant patients without heartburn was 20-1 +/- 7-0 mm Hg as against 17-9 +/- 7-0 in the non-pregnant women. While one pregnant subject without heartburn had a lower oesophageal sphincter which was partially displaced into the thorax, none of the non-pregnant women had such sphincter displacement. The two pregnant women with heartburn had low resting sphincter pressures and in both of them the sphincters were partially in the thorax. It is argued that pregnancy heartburn is due to the displacement of the lower oesophageal sphincter into the negative pressure environment of the thorax where the sphincter is less capable of resisting reflux. It is also argued that pregnancy heartburn is commoner in Caucasians that in Nigerians because the spincter in non-pregnant Caucasians is often partly intrathoracic and is thus more easily displaced completely into the thorax by the pregnant uterus.


Large airways function during normal pregnancy.

Specific airways conductance and forced expiratory volume in one second were measured monthly from the first trimester until term in 30 subjects in the course of a normal pregnancy. Measurements were also made in the postpartum period. There was no significant change in these measurements either throughout pregnancy or compared with postpartum values. Our results suggested that the function of the larger pulmonary airways was not altered in pregnancy.


A multifactorial survey of neonatal juandice.

Concern about a neonatal jaundice rate of 8-6 per cent prompted a retrospective survey of 981 full term infants. There was a highly significant association between increased oxytocin dosage and neonatal jaundice in induced labours. A significant association was also demonstrated between neonatal jaundice and both breast-feeding and minor infections. No association was demonstrated between neonatal jaundice and the method of delivery of birth weight. The results of the survey suggest that while oxytocin in high doses should be used with caution, the benefits obtained from the drug outweigh the risk of hyperbilirubinaemia which it may cause.


Intercellular spaces and cell junctions in endometrial glands: their possible role in menstruation.

Intercellular spaces and cell junctions in human endometrial glands were studied by elctron microscopy following different methods of fixation. The size of the spaces, known to alter during the cycle, was found to depend also on the method of fixation. Various intrusive cells and different types of cell debris were seen in these spaces. The three most widely recognized cell junctions (desmosomes, tight junctions and gap junctions), were all most abundant near the cell apices. The possible significance of these findings in elucidating the cellular mechanism of menstruation is discussed.


A simple and sensitive radioimmunoassay for pregnancy-specific beta1-glycoprotein.

A simple, sensitive and relatively rapid radioimmunoassay for pregnancy-specific beta1-glycoprotein (PSbetaG) is described. The concentrations of PSbetaG in plasma from cord blood and in amniotic fluid were approximately 0-1% and 1-0% respectively of the maternal plasma levels. The amniotic fluid PSbetaG levels in pregnancies associated with an anencephalic fetus were not significantly different from normal levels.


A review of 50 pregnant patients with kyphoscoliosis.

An analysis of the obstetric and medical complications in 50 pregnant kyphoscoliotic patients is presented.


A study of plasma diazepam levels in mother and infant.

A 10 mg dose of diazepam was given intravenously to mothers at 15 to 205 minutes before delivery, and plasma diazepam concentrations were measured by gas-liquid chromatography in mothers and infants at delivery and again 24 hours later. The plasma levels in the infants were always significantly higher than in the mothers but there was no evidence to suggest that the newborn were unable to metabolize the drug. All infants had a good Apgar score at birth.


Blood coagulations studies in pregnant patients with infective hepatitis.

Coagulation studies were made on 22 pregnant women with acute infective hepatitis and on 15 normal control pregnant women in third trimester. Fourteen hapatitis patients had clinical evidence of liver failure and all of them had a haemorrhagic diathesis; none of the patients without liver failure showed clinical evidence of haemostatic defects. Coagulopathy was present in most patients, its severity being greater in those with hepatic failure. Significant alterations were observed in bleeding time, whole blood clotting time, prothrombin time, thrombin time, plasma fibrinogen and serum levels of fibrinogen degradation products. The last three disturbances were most frequent in patients with liver failure. Increased fibrinolysis and disseminated intravascular coagulation also appeared to play a contributory role, particularly in patients with hepatic failure.


Characteristics of normal labour among different racial groups in Malaysia.

The characteristics of normal labour in 977 Malay, Chinese and Indian parturients were established from a retrospective study. Indian babies were found to be significantly smaller than Malay babies which were significantly smaller than Chinese babies (P less than 0-05, P less than 0-05). The mean duration of the first stage of labour taken from the time of admission to the labour ward was 3-4 hours in primiparae and 2-7 hours in multiparae. The mean durations of the second stage of labour were 23-7 minutes and 13-1 minutes respectively. Curves of mean dilatation of cervix and probit analysis at 80% revealed significant differences in the progress of normal labour in primiparae among the three racial groups. The Indian primiparae not only had a slower rate of cervical dilatation but seemed to reach the accelerated phase of dilatation later. No significant differences were noticed in the labours of multiparae.


The relation between umbilical cord tissue prostaglandin E2 levels, mode of onset of labour, fetal distress and method of delivery.

The tissue concentrations of prostaglandin E2 (PGE2) were measured by radioimmunoassay in components of the umbilical cord. The levels were significantly higher in the walls of arteries than in non-vascular tissue from the umbilical cord. The highest values were found after emergency Caesarean sections and the lowest after induced ending in normal delivery. The use of forceps and the presence of fetal distress were both associated with significantly raised tissue concentrations of PGE2.


Changes in the concentration of cortisol in amniotic fluid after intra-amniotic prostaglandin for midtrimester abortion.

The effects of intra-amniotic prostaglandin E2 (PGE2) and PGF2alpha on the concentration of cortisol in amniotic fluid and in maternal peripheral plasma of patients undergoing abortion between 16 and 23 weeks gestation have been examined. There was a significant (P less than 0-01) increase in the concentration of cortisol in amniotic fluid for hours after PGE2, but not after PGF2alpha. The concentration of cortisol in the maternal peripheral plasma increased in both groups with the progression of abortion, but the levels were not significantly correlated with those in amniotic fluid. These results suggest that by mid-pregnancy fetal cortisol production can be stimulated by PGE2 but the mechanism of this action remains to be elucidated.


Plasma oestrogens in a pregnancy associated with chronic haemodialysis.

Pregnancy in a patient undergoing regular haemodialysis at home is described. The pregnancy was complicated by antepartum haemorrhage due to a Type I placenta praevia, and premature labour occurred at 32 weeks, resulting in spontaneous vaginal delivery of a live infant which survived. Plasma progesterone oestrone, unconjugated oestradiol and oestriol levels were normal during the last two weeks of pregnancy, but failed to show a characteristic fall in the puerperium. The conjugated oestriol fraction was 20 to 30 times the normal mean level and did not fall after delivery. These findings are discussed.


The effects of intramuscular norethisterone oenanthate used as a contraceptive on intravenous glucose tolerance and on blood coagulation factors VII and X.

Intravenous glucose tolerance tests, and estimations of prothrombin time, and plasma coagulation factors VII and X, were made on 12 women receiving 200 mg norethisterone oenanthate intramuscularly as a contraceptive. These estimations were made before, and at 2 and 12 weeks after, a single injection of norehisterone oenanthate. There was no significant effect on the intravenous glucose tolerance, prothrombin time, or on plasma coagulation factors VII and X, further confirming the safety of norehisterone oenanthate when used as a short-term injectable contraceptive.


Primary echinococcal infection of the ovary.

An Iranian Moslem patient with primary echinococcal infection of the ovary is described. Echinococcal infection is extremely rare in practising Moslems.


Primary splenic pregnancy. Case report.

A patient with a primary splenic pregnancy is described.


Rapid B-scanning of the vitreous.

Ultrasonic examination is an essential investigation in most patients awaiting vitrectomy. Rapid B-scanning of the vitreous is described utilising a new system capable of high resolution and good tonal quality. Several patterns of haemorrhagic invasion of the vitreous cavity are illustrated, together with detachment, collapse, and retraction of the vitreous gel.


Retinal mobility and retinal detachment surgery.

A series of 200 consecutive retinal detachments was examined prospectively to consider the physical sign of mobility of the detached retina. Retinal mobility was found to be absent in 28 cases, and this immobility is caused by periretinal membrane formation. The importance of retinal mobility when considering the case for non-drainage retinal surgery has been examined with particular emphasis on the tear/buckle relationship at the end of the operation. It was found that there was an excellent prognosis (92% success rate) for cases in which the retina was found to be mobile in the vicinity of the retinal tear, and a high proportion of these cases (71%) can be successfully treated with a non-drainage operation.


Fluorescein pupillary flow in aphakics with intact and spontaneous openings of the vitreous face.

The passage of fluorescein dye, injected into the general circulation, from the posterior to the anterior chamber was studied in 60 selected aphakic eyes between 2 days and 4 weeks after an uneventful cataract extraction. In a group of 22 eyes with intact anterior hyaloid, fluorescein was seen to pass only through the pupillary margin, mostly within 20 seconds of the beginning of the eye injection. In 24 eyes with rents in the anterior hyaloid the dye was seen percolating only through the vitreous face openings. No fluorescein passed through the pupillary margin or the peripheral iridectomy in this group of eyes. The appearance time of the dye was delayed to about twice the normal appearance time. In 8 eyes with rents in the anterior hyaloid the dye passed only through the pupillary margin. In 4 eyes with anterior vitreous rents the fluorescein appeared through the anterior vitreous face opening. From the analysis of the data it appears that the spontaneous breaks in the anterior vitreous face may represent a 'self-c,re' of pupillary and iridectomy block by the vitreous in aphakics in a high proportion of cases. It is our impression that 3 peripheral iridectomies and a very tight closure of the wound can prevent the complication of spontaneous breaks of the vitreous face.