Cell cycle in mouse intestinal crypts during halothane or nitrous oxide anaesthesia.

The effects of inspired air, halothane 0.5% and nitrous oxide 64% on the cell cycle were examined by autoradiography in the duodenal and jejunal crypts of mice. The length of cell cycle phases was calculated from the rate of transition of the labelled cells from the DNA-synthetic to the mitotic phase, using a computer program based on a mathematical model of the cell cycle. The computer analysis showed that halothane 0.5% prolonged the post-mitotic gap by 57% in the duodenum and by 60% in the jejunum. The DNA-synthetic time was prolonged by 23% in the duodenum and 30% in the jejunum and the mitotic time by 33% in the duodenum and 46% in the jejunum, when compared with the control animals breathing air. Nitrous oxide 64% had no effect on the cell cycle.


Autonomic hyperreflexia: intraoperative control with pentolinium tartrate.

Autonomic hyperreflexia (AH) is a clinical syndrome associated with the development of severe hypertension. It usually occurs in patients with high-level chronic spinal cord injury, and in response to stimuli associated with the distension of a hollow viscus. Protection against AH by the prophylactic use of pentolinium tartrate (Ansolysen) in doses of 10-15 mg was evaluated in a controlled study of unanaesthetized patients who were either quadriplegic or paraplegic and who were undergoing rectal and bladder surgical procedures. When compared with the control group, the systolic and diastolic arterial pressures during operation were significantly less (P less than 0.05) and remained near normal in the pretreated patients. The use of pentolinium to prevent or control AH during surgical procedures in patients with chronic spinal cord damage is a simple alternative to spinal or general anaesthesia.


Oxygen therapy after thoracotomy.

Arterial blood samples were taken from patients before thoracotomy, and on the 1st day after operation, with the patient breathing first air, and then 24%, 28% and 35% oxygen from a venturi-type mask. PaO2 was reduced markedly by operation, the reduction being related to the value before operation. Oxygen therapy restored PaO2 to a value greater than the value before operation in nine of 11 patients and was not associated with significant increases in PaCO2. The effect of administration of oxygen on PaO2 could be predicted from the PaO2 when breathing air. The pattern of response to oxygen suggested that the hypoxaemia was caused by ventilation/perfusion mismatch in most of the patients.


Disposition kinetics of pancuronium bromide in patients with total biliary obstruction.

Plasma concentrations of pancuronium were measured in nine patients undergoing surgery because of total biliary obstruction. When compared with the averaged model-independent pharmacokinetic parameters obtained for normal patients, the terminal half-life of 270 min was more than twice normal (132 min, P less than 0.001); the plasma clearance of 59 ml min-1 was less than half the normal rate for pancuronium (123 ml min-1, P less than 0.003). These significant alterations to the pharmacokinetics of pancuronium were associated with prolongation of neuromuscular blockade. Following a bolus injection of pancuronium 6 mg, there was a mean time of 114 min (normals 70 min, P less than 0.05) before the evoked twitch response had returned to 5% of the control value. The pattern of urinary excretion of the drug and its metabolites did not differ from that of normal patients. To avoid excessive dosage during prolonged surgery for total biliary obstruction, it is recommended that supramaximal nerve stimulation be used to indicate the need for the administration of further doses of pancuronium.


Bradycardia during antagonism of pancuronium-induced neuromuscular block.

Heart rate was compared in matched patients during antagonism of neuromuscular block induced by tubocurarine, pancuronium or alcuronium with neostigmine 0.03 mg kg-1 preceded by atropine 0.015 mg kg-1. The frequency of bradycardia was greater during antagonism of pancuronium compared with alcuronium. Although there was a difference between the group receiving pancuronium and that receiving tubocurarine, it was not statistically significant. The decrease in heart rate was more rapid and profound in the pancuronium group; seven of the 15 patients who received pancuronium required an additional dose of atropine as compared with only one patient who received tubocurarine. However, the difference in heart rate between those who received pancuronium and those receiving tubocurarine was short-lasting, whereas the heart rate of those who received alcuronium was higher than that in the other groups during the entire 60-min period of observation. The findings with pancuronium may be a result of its inhibitory effect on serum cholinesterase.


Neuromuscular effects of i.a. infusion of lignocaine in man.

Neuromuscular effects of lignocaine during and after i.a. infusion were studied in healthy adult patients, using evoked electromyography. Supramaximal, paired stimuli were applied to the ulnar nerve with variable intervals between the two stimuli. The amplitude of the hypothenar muscle action potential to the second component of the paired stimulus (test response) was compared with that evoked by the first component (conditioning response). During and after i.a. infusion of lignocaine, there were marked decreases of the test response at intervals from 7 to 100 ms after the conditioning stimulus, although the decreases of the conditioning response were slight or negligible. The finding of decreased test responses coincided with the results obtained with tetanic stimulation such as pronounced fade and only slight post-tetanic potentiation. Differences between these findings and those found with muscle relaxants were compared, and it was concluded that the mechanism responsible for these results might be attributed to an effect of lignocaine on the motor nerve terminal.


A study of body temperatures of anaesthetized man in the tropics.

Body core and skin temperatures were measured in 20 African patients undergoing herniorrhaphy in hot and humid conditions; one half of the patients received halothane and the other half received diethyl ether. No difference was found between those two groups. Body core temperatures decreased even with an ambient temperature of 28.7 degrees C and a relative humidity of 72% and all sites reached a new thermal equilibrium at 30 min. It is suggested that the level of the re-established thermal equilibrium is a function of the skin to ambient thermal gradient, which depends on the failure of the countercurrent heat exchange mechanism as a result of redistribution of peripheral blood flow.


Thermal balance during cardiopulmonary bypass with moderate hypothermia in man.

In six patients undergoing coronary vein graft operations under cardiopulmonary bypass and hypothermia, the temperatures of arterial and mixed-venous blood, nosopharynx, oesophagus, liver, rectum, deltoid and vastus lateralis muscles and 10 skin sites were recorded. Whole-body oxygen consumption was measured before cooling and twice during hypothermia. On average, a patient lost 1000 kJ of heat by the end of hypothermia, of which 84% was lost to the heat-exchanger and pump circuit. Evaporative and convective loss amounted to 380 kJ, while the patient's metabolism supplied 220 kJ. During rewarming, the pump returned 670 kJ to the patient. Nasopharyngeal temperature reflected accurately venous, oesophageal and hepatic temperatures in the steady state; however, it was slow to reflect changes. Compared with other sites, muscle remains warmer during hypothermia and cooler after rewarming.


Nitrazepam premedication for minor surgery.

Sixty-one patients received nitrazepam 5 mg by mouth on the night before operation, followed by 2.5 mg given on the morning of operation and were compared with 60 patients who received no premedication. All were undergoing either therapeutic abortion, by dilatation and curettage, or explorative curettage. The plasma concentrations of nitrazepam were determined by gas chromatography and compared with the clinical effects of the drug. The premedicated patients slept better on the night before operation, and were more sedated and less apprehensive. Headache was more frequent following nitrazepam. There was no significant difference between the groups in respect of dizziness and nausea. The unpremedicated patients had a faster average heart rate. There was no obvious relationship between the plasma concentration of nitrazepam and the quality of sleep, degree of sedation, apprehension, excitement or headache.


Haemodynamic responses to isoflurane anaesthesia and hypovolaemia in the dog, and their modification by propranolol.

In six dogs chronically implanted with flow and pressure transducers, equipotent inspired concentrations of halothane and isoflurane were determined as the minimum inspried concentration of each agent which would abolish an individual dog's response to paw clamping. In equipotent concentration, isoflurane (1.2%, SD 0.2%) caused less myocardial depression than halothane (1.0%, SD 0.1%). Dose-response studies were possible up to a mean inspired isoflurane concentration of 3.0%, both before and after propranolol 0.3 mg kg-1, i.v. After propranolol, sensitive indices of myocardial contractility were depressed at all concentrations of isoflurane, indicating a moderate degree of beta-receptor activation by isoflurane. The haemodynamic response to hypovolaemia during isoflurane anaesthesia was not modified by propranolol.


Haemodynamic responses to enflurane anaesthesia and hypovolaemia in the dog, and their modification by propranolol.

The haemodynamic responses to minimum equipotent concentrations of halothane and enflurane were compared in seven dogs. The haemodynamic responses to increasing concentrations of enflurane, and to induced hypovolaemia during enflurane anaesthesia, were studied in the same dogs, both before and after administration of propranolol 0.3 mg kg-1 i.v. In equipotent concentrations, enflurane caused marginally greater impairment of left ventricular function than halothane, and caused a dose-dependent reduction of arterial pressure, cardiac output and myocardial contractility. Following administration of propranolol, these haemodynamic effects of enflurane were marked, and withdrawal of 20% of estimated blood volume was tolerated poorly.


Changes in myocardial performance induced by pancuronium and gallamine in hypercapnic and hypocapnic dogs.

Changes in myocardial performance after administration of gallamine 1.5 mg kg-1 and pancuronium 0.1 mg kg-1 were investigated in hypercapnic (PaCO2 = 7.08 kPa) and hypocapnic (PaCO2 = 2.74 kPa) dogs anaesthetized with thiopentone, nitrous oxide and halothane. Administration of pancuronium during hypocapnia caused a decrease of 25% in dP/dt max (corrected for changes in preload, afterload and heart rate). This change was not seen during hypercapnia, probably because of the associated sympathetic stimulation. By contrast, gallamine was without effect on dP/dt max in both groups. The increase in heart rate and cardiac output caused by the atropine-like action of both groups. The increase in heart rate and cardiac output caused by the atropine-like action of these relaxant drugs differed in the hypercapnic and hypocapnic group of dogs, with the more pronounced response in the latter group. The duration of the chronotropic changes was the same in both groups.


Inhibition of mitochondrial respiration by sodium nitroprusside and the mechanism of cyanide liberation.

The influence of sodium nitroprusside (SNP) on mitochondrial respiration was examined in rat liver mitochondria. The addition of SNP 1 mmol litre-1 during state 3 respiration inhibited the oxygen uptake by 63.4%. A mixture of SNP 1 mmol litre-1 and glutathione (GSH) 1 mmol litre-1 inhibited the oxygen uptake more markedly (by 75.9%). The cyanide concentrations were 0.01 mmol litre-1 with SNP alone and 0.15 mmol litre-1 with the mixture of SNP and GSH. Cyanide production from SNP in the presence of various reducing agents was studied in potassium phosphate 0.1 mol litre-1 buffer solution (pH 7.4) incubated at 37 degrees C. Cyanide was liberated markedly from SNP in the presence of GSH or ascorbate. Less cyanide was produced in the presence of NADH or NADPH. The rate of production of cyanide was dependent entirely upon the concentration of each reducing agent added. No cyanide was liberated when sodium dithionite or the oxidized forms of GSH, NAD or NADP were used. It was concluded that SNP is degradated to cyanide by a hydrogen donor and that the cyanide liberated in this manner inhibits the cytochrome oxidase activity of mitochondria in vivo.


Spontaneous ventilation with the Bain anaesthetic system.

Measurements of ventilation and of inspired gas composition were made while volunteers breathed a non-anaesthetic gas through a Bain anaesthetic system. It was found that rebreathing occurred when the fresh gas flow was between two-and-a-half and three times the minute volume. Fresh gas flows at least three times the minute volume appear to be necessary to prevent rebreathing when using this system.


The inhibition of serum cholinesterase by urea. Mechanism of action and application in the typing of abnormal genes.

The mechanism of action of urea on serum cholinesterase and the application of the inhibition by urea in the typing of the abnormal genes of this enzyme were investigated. Urea caused a competitive, irreversible inhibition of serum cholinesterase, which was most pronounced for the abnormal enzymes. Urea inhibition, used with dibucaine inhibition, allowed differentiation between all the known genotypes of locus E1. In the differentiation of rarer genotypes, the combination of urea numbers (percentage inhibition of serum cholinesterase activity caused by urea 5 mol litre-1) and dibucaine numbers was found, in certain situations, to be superior to the classical combination of fluroide and dibucaine numbers.


Influence of methoxyflurane-nitrous oxide analgesia during childbirth on renal and hepatic function.

Blood urea content and the serum concentrations of sodium, creatinine, uric acid, glutamic oxaloacetic transaminase (g.o.t.), glutamic pyruvate transaminase (g.p.t.) and bilirubin were measured before delivery, on the 2nd and 3rd days and on the 5th day after delivery. In two groups of mothers, one receiving nitrous oxide analgesia and the other a combination of nitrous oxide and methoxyflurane, blood urea and serum sodium and g.o.t. were increased following labour and nitrous oxide analgesia; s.g.p.t. was increased only in the late post-partum period. Serum sodium, creatinine, uric acid, urea, g.o.t. and g.p.t. increased following exposure to methoxyflurance. The increase in serum sodium, uric acid and urea was dose-dependent. Capillary concentrations of uric acid in the neonates showed dose-dependent changes in response to methoxyflurane.


Effects of beclomethasone dipropionate aerosol on nasal mucosa.

Rhinoscopic examination and histological studies of the nasal mucosa in patients with perennial allergic rhinitis and nasal polyposis treated with beclomethasone dipropionate aerosol provided no evidence that this form of treatment, given for one year, produced any harmful effects, such as atrophic rhinitis.


Beclomethasone dipropionate aerosol and nasal mucosa.

1. Biopsies taken from the inferior turbinates of patients undergoing treatment with beclomethasone dipropionate aerosol for allergic rhinitis showed no changes attributable to this treatment. 2. A reduction in oedema and eosinophilia was noted but there was no effect on the thickening of the basement membrane.


Activation of K cells in mice with transplanted tumours differing in immunogenicity and metastasizing capacity.

The effector arm of antibody-dependent cellular cytotoxicity (ADCC) was evaluated using 51Cr-labelled chicken erythrocytes as targets in BALB/c mice transplanted with the Moloney sarcoma virus-induced tumours T-MSV and MS2, and in C57BL/6 mice transplanted with the chemically induced FS6 sarcoma, Lewis lung carcinoma and B16 melanoma. Tumour-bearing animals showed higher levels of ADCC than normal mice, a stimulation confirmed in MS2-bearing mice, using SL2 lymphoma cells as targets in a cytostasis assay. ADCC effector-cell capacity was higher in animals transplanted with the immunogenic, spontaneously regressing T-MSV than in mice bearing the poorly immunogenic metastasizing MS2 sarcoma. The increased ADCC activity detectable in the spleen of tumour-bearing hosts was not abolished by removal of phagocytic-adherent cells.


Monocyte chemotaxis in bronchial carcinoma and cigarette smokers.

Chemotaxis of blood monocytes was measured in 31 patients with bronchial carcinoma and 19 cigarette smokers. Thirteen patients with metastatic bronchial carcinoma had significantly less (P less than 0.005) chemotactic response than matched controls. Those with disease confined to the chest, or with recurrent or operable bronchial carcinoma, had no significant depression of monocyte chemotaxis. There was also no significant difference in monocyte chemotaxis between cigarette smokers and matched controls. These results support the concept that in human cancer there is a defect in monocyte chemotaxis, but in bronchial carcinoma significant depression was only apparent in those with advanced disease.


Effects of repeated applications of two semi-permanent hair dyes to the skin of A and DBAf mice.

Two proprietary semi-permanent hair dyes were tested for carcinogenicity in A and DBAf mice by repeated topical applications in aqueous acetone. Mice of both strains developed lymphoid tumours but experimental differences were marked only in DBAf mice. A number of tumours of the ovary and uterus, and some skin papillomas near the penis, occured in dye-treated but not in control DBAf mice. As many hair-dye constituents are known mutagens, adequate carcinogenicity testing of these substances, and epidemiological study of exposed human populations, are needed for evaluating possible health hazard from hair dyeing.


Effect of di-isopropanolnitrosamine in European hamsters.

The carcinogenic effects of di-isopropanolnitrosamine (DIPN) were tested in hibernating and non-hibernating European hamsters. The results obtained were compared with those produced by the same substance in Syrian golden hamsters and Sprague-Dawley rats. In European hamsters, tumours were produced in the nasal cavity, trachea, lung, liver and pancreas. The main target organs were the anterior part of the nasal cavity and liver. Only cholangiomas and cholangiocarcinomas were found in the liver. Early changes in the intrahepatic bile ducts and duct epithelium of the pancreas were seen 4 weeks after treatment was started. Fourteen out of 144 treated hamsters developed pancreatic-duct tumours, 2 of which were malignant. The tumorigenic response in the target organs was lower in hibernating than in non-hibernating animals.


Interaction of ICRF 159 with radiation, and its effect on sub-lethal and potentially lethal radiation damage in vitro.

ICRF 159 has been shown to increase the X-radiation sensitivity of exponentially growing EMT6 mouse tumour cells in vitro. This was found only with ICRF 159 exposure times longer than 10 h and only when the drug was given before irradiation. The increase in radiation sensitivity was expressed as a reduction of the shoulder of the radiation survival curve. As ICRF 159 was shown to have no effect on the repair of sub-lethal radiation damage, it was concluded that the drug reduced the capacity to accumulate such damage. ICRF 159 was also shown to have no effect on the repair of potentially lethal radiation damage in late plateau cells.


Age variation in the cancer risks from foetal irradiation.

A modified Mantel-Haenszel analysis of data from the Oxford Survey of Childhood Cancers has shown that cases associated with foetal irradiation (X-rayed cases) accounted for a higher proportion of deaths between 5 and 10 years than of earlier or later deaths. This finding is compatible with somewhat later origins for the cancers actually caused by the radiation exposures (radiogenic cases) than for other (idiopathic) cases which proved fatal before 10 years of age. Therefore the usual time for incurring congenital anomalies (or the first trimester of foetal life) could be the commonest time for initiating childhood cancers. The theoretical implications of this and other findings of the Oxford Survey are discussed within the framework of a theory which assumes that all mutant cells have cancer potentialities and that defects in the immune surveillance mechanism favour multiplication of these cells (or endogenous sources of self-replicating foreign proteins) as well as live pathogens (or exogenous sources of self-replicating foreign proteins).


Failure to obtain positive MEM tests in either cell-mediated immune conditions in the guinea-pig or in human cancer.

The macrophage electrophoretic mobility test described by Caspary and Field (1971) and modified by Pritchard et al. (1973) was investigated in various models of cell-mediated immune conditions in the guinea-pig and in cancer in man. No positive results were obtained in 92 guinea-pig experiments. Only 17 of 154 experiments on 74 patients gave definite positives in experiments with human cancer and a few positive results were obtained with normal healthy subjects.


Prognostic value of serum levels of immunoglobulins (IgG, IgA, IgM and IgE) in breast cancer: a preliminary study.

One hundred and sixty women admitted for breast tumour biopsy to the King's College Hospital group have been followed sequentially for 2 years. Sixty-nine women had early operable breast cancer and 91 had benign breast disease. All these women had serum immunoglobulin IgG, IgA, IgM and IgE levels measured preoperatively and postoperatively at 3 months, 1 year and 2 years. No differences were found in any of the serum immunoglobulin levels between the two groups at any time. There was, however, a positive correlation between the extent of metastatic breast cancer and the serum level of various immunoglobulins, particularly IgA. There was no evidence that routine postoperative radiotherapy influenced the levels of serum immunoglobulins. The findings suggest a secondary defence reaction against increasing tumour load, and do not support the theory of an early immune defect in immunoglobulin metabolism which could play a part in the pathogenesis of breast cancer. Although there is no diagnostic value in measuring the levels of serum immunoglobulins in patients with breast tumours, there may be some value in following the levels in cancer patients, as a guide to subclinical spread of the disease.


A method for detecting carcinogenic organic chemicals using mammalian cells in culture.

A method for testing organic chemicals for their carcinogenic potential is described. Baby hamster kidney cells (BHK-21/C1 13) were exposed to different doses of test compound in liquid tissue culture medium containing rat liver post-mitochondrial supernatant and cofactors (S-9 mix) to aid metabolism, but without serum. Survival of cells following exposure to the compound was assessed by cloning in liquid growth medium. Transformation was assessed by colony growth in semi-solid agar. The dose-response curve for survival was used to determine the LC50 of the compound. A dose-response curve for transformation was constructed and a 5-fold increase in transformation frequency at the LC50 was regarded as a positive test result. The method may also be used for testing gaseous compounds. Cells grown in monolayers and overlaid with serum-free medium and S-9 mix were exposed to vinyl chloride gas mixed with air. After exposure, the treated cells were trypsinized, resuspended in growth medium, and survival and transformation assays performed. The methods described are illustrated by examples taken from an evaluation study using 120 compounds and found to be more than 90% accurate in distinguishing between carcinogens and non-carcinogens.


Fluorescence discrimination between diploid cells on their RNA content: a possible distinction between clonogenic and non-clonogenic cells.

Flow cytofluorimetric techniques, using acridine orange fluorescence to measure RNA and DNA simultaneously in EMT6 cells, have been employed to discriminate between three diploid DNA populations in vivo on the basis of their RNA content. Cells with the lowest RNA levels seem to be in the process of disintegration. Cells with the highest RNA levels correspond to those with the highest plating efficiency, and those with intermediate RNA levels are those with the lowest plating efficiency. In vitro studies have shown that log-phase cells have higher RNA levels than cells in the late plateau phase of growth.


Development and application of a radioimmunoassay for methotrexate.

An antiserum to methotrexate has been produced in a sheep against a conjugate of ovalbumin and methotrexate (MTX) prepared using a water-soluble carbodiimide. The antibodies produced were specific for substances containing the 2,4-diamino pteridine structure. Naturally occurring folates did not interfere with the assay. A radioimmunoassay has been developed using this antiserum, which can be used to measure MTX concentrations of less than 1 ng/ml in biological samples without prior extraction. The concentrations of MTX in the blood and urine of patients following a single i.v. bolus injection and following oral administration of the drug have been measured. The published radioimmunoassays for MTX have been compared.


Clonogenic assays in the B16 melanoma: response to cyclophosphamide.

The survival of clonogenic cells in the B16 melanoma has been studied simultaneously by 3 methods: an in vitro assay in soft agar, a lung-colony assay, and the end-point dilution technique. Details of the first 2 methods have previously been reported, but those of the third are described here. The 3 methods have agreed well in investigations of the response of the B16 melanoma to cyclophosphamide.


Scanning electron microscopy of a bacterial infection of the human nasal mucosa.

Scanning electron micrographs of a bacterial infection of the human nasal mucosa indicate that the surface attachment of bacteria to epithelial cells is of significance for their pathogeneity in the airways. It is suggested that further scanning electron microscopic studies of natural and experimental infected human nasal mucosa can give valuable information about the initial interaction between micro-organisms and host cell and add to our understanding of airways infections.


Anaerobic bacteriology of chronic bronchial disease. With a refined method of sampling bronchial secretions.

A refined bronchoscopic method of sampling bronchial secretions is presented. The results show that this gives higher yields of aerobic pathogens than examination of expectorated sputum and the method also avoids pharyngeal contamination in suspected cases of anaerobic lung infection. Our results indicate that anaerobic organisms do not play a major role in causing sputum purulence in patients with chronic bronchitis, bronchogenic carcinoma or with less florid degrees of bronchiectasis. Anaerobic infections did not appear to occur as often as suggested by some reports from the United States.


Cigarette abandonment: its significance.

Two hundred and eight interviews with ex-cigarette-smokers in the street and 208 interviews with ex-cigarette-smoker chest patients, all over 45 years of age, gave a composite picture of people commonly smoking until their health is affected. Symptoms were much more important then tobacco tax or propaganda in stopping cigarette-smoking. Of continuing smokers 16% wished that they could stop because of symptoms. Fear of the presence of cigarette-induced disease was thought to explain why some patients gave unconvincing reasons for abandoning cigarettes or had become ex-smokers in the year preceding their examination and many of these had carcinoma of the bronchus. Cigarette abandonment should be accepted as part of the symptomatology of respiratory disease. It sometimes is the first identifiable event in the relevant medical history of chest patients.


Bronchial asthma due to allergy to pancreatic extract: a hazard in the treatment of cystic fibrosis.

The mother of two children suffering from cystic fibrosis developed marked allergic symptoms affecting the eyes, nose and bronchi and severe bronchial asthma ensued. The cause of this allergy proved to be the powder released on opening the capsules of pancreatic extract which she provided for her children at each mealtime. The risk of pancreatic extract to those handling it, and possibly also to patients suffering from cystic fibrosis, is emphasized.


The effect of irradiation on demyelination induced by avirulent Semliki Forest virus.

A dose of 500 rad total body irradiation before Semliki Forest virus infection was the most effective in producing multiple foci of demyelination in Swiss mice. Animals receiving this dose had the highest virus titre of Semliki Forest virus persisting in the brain and a delayed antibody response. In spite of extensive demyelination no obvious clinical signs such as paralysis were observed.


The biological effects of magnesium-leached chrysotile asbestos.

Chrysotile asbestos was leached in N hydrochloric acid for varying times to produce a range of magnesium-depleted samples. The protein adsorptive capacity, the haemolytic activity, and the capacity to cause selective release of acid hydrolases from macrophages were measured for the various samples in vitro. The carcinogenicity of the same materials was determined following intrapleural inoculation in rats. The adsorptive capacity for albumin decreased linearly with magnesium removal. The haemolytic activity also declined until about half the magnesium had been removed, after which there was little further change. The selective release of acid hydrolases from macrophages in culture increased up to the point at which half the magnesium had been removed but by 90% depletion had declined rapidly. The carcinogenicity of 50% -depleted chrysotile was similar to that of intact, but at 90% depletion the incidence of mesothelial tumours had fallen considerably. There was no evidence that the leached samples fragmented more than the unleached in vivo.


The effects of treatment with aspirin and an antithrombotic agent SH1117 upon platelet thrombus formation in living blood vessels.

The work reported here describes an in vivo study, over several days in each animal, of the formation and behaviour of platelet thrombi in injured living blood vessels in response to topically applied adenosine diphosphate in rabbits which have been treated with oral doses of SH1117 alone or together with acetyl-salicylic (ASA) before and after i.v. injection of alloxan. These two substances SH1117 and ASA when given together display a synergism which is similar to that described for dipyridamole and ASA, but the antithrombotic action of SH1117 and ASA seems to be more profound. It may be of significance that oral SH1117 given alone appears to confer a degree of insensitivity of the injured vessel in its response to ADP, as such an effect is not displayed by dipyridamole.


The effect of calcium on the mechanical behaviour of aorta media elastin and collagen.

Mechanical tests were conducted on rings of pig thoracic aorta that had been treated with calcium ions to evaluate their effect on aorta media collagen and elastin. There was an increase in stiffness just before rupture and a decrease in storage energy when calcium was introduced into intact rings, but there was no significant difference in mechanical properties when it was introduced into the elastin framework of the media. The calcium was able to bind to the intact aorta media far more readily than to the elastin alone, suggesting that the collagen and muscle framework were far more susceptible to the introduction of calcium than elastin. The calcium content rose along the length of the aorta, as did the collagen content, whilst the elastin content fell, which was also reflected in the change in mechanical properties along the aorta.


A pharmacological effect of oestrone on human epidermis.

Oestrone has been found to depress the incorporation of tritiated thymidine, proline and histidine in human skin in vitro. The significance of this is briefly discussed.


The role of histidine in human epidermis.

Incorporation of radioactively-labelled histidine into half-thickness skin and into the major protein fraction extracted from epidermis by urea (protein Fraction A) has been measured and compared with the amount of labelled urocanic acid appearing in the same specimen. After a short lag period, incorporation into half-thickness skin and into protein Fraction A was found to be linear up to 23 h of the study. Histidine appeared to be initially preferentially deaminated to urocanic acid. The somewhat erratic presence of urocanic acid at later periods is attributed to its high instability and solubility.


The effects of anti-prostaglandin agents on epidermal proliferation induced by dermal inflammation.

Experimentally induced dermal inflammatory lesions cause epidermal hyperplasia and increased thymidine autoradiographic indices in the overlying epidermis. In the experiments described here anti-prostaglandin agents (indomethacin, aspirin, prednisolone and polyphloretin phosphate) were given to guinea-pigs with experimentally induced dermal granulomata in an effort to learn more about the dermal control of epidermal proliferation. Indomethacin caused a significant reduction in the epidermal hyperplasia and labelling index in the epidermis overlying carageenan granulomata. Similar but less marked reductions in epidermal proliferation were seen with the other agents used. Some reduction, which proved not to be statistically significant, was also seen in the epidermal proliferation due to kaolin granulomata. Slight reduction in epidermal hyperplasia, but no effect on thymidine incorporation, was seen in proliferation induced by tape stripping.


The anatomical distribution of sunlight.

The relative distribution of natural ultraviolet radiation has been measured at ten sites on the surface of an unclothed manikin for 2 h around solar noon on 19 different days during late summer in Canterbury, U.K. The dosimeter used was polysulphone film. The results obtained indicate that vertical surfaces of the body receive about one half of the dose relative to the vertex and that the relative doses at different sites are independent of weather conditions.


Light sensitivity and chromium dermatitis.

In 25 consecutive cases of chromium contact allergy we have made four parallel serial dilution tests and irradiated three of the test rows, two with solar-spectrum-like radiation from a 150 W Xenon lamp (4/5 MED and 4 MED) and one row with long-wave ultraviolet radiation (blacklight) alone. Comparing an unirradiated row (control) and the row irradiated with 4/5 MED, the reactions were significantly more intense in 48% of the cases, i.e. the patients reacted at lower chromium concentrations. In a corresponding comparison with 4 MED a significantly more intense reaction was obtained in 36% of the cases, whereas blackslight showed no significant difference compared with the control row. The most intense reactions were obtained in the cases which were anamnestically photosensitive and had low MED values.


Juvenile elastoma and osteopoikilosis (the Buschke--Ollendorff syndrome).

Sixteen patients from seven different families with the Buschke-Ollendorff syndrome have been studied. Osteopoikilosis was found in two-thirds of the patients radiologically examined and all but two had skin involvement. The predominant clinical pattern consisted of grouped skin coloured papules and discs that were distributed asymmetrically and which usually had presented at an early age. The skin lesions showed the characteristic histological changes of juvenile elastoma which, it is suggested, is the specific dermatological abnormality of the Buschke-Ollendorff syndrome.


Transcapillary escape rate of albumin and plasma volume in patients with varying degrees of psoriasis.

Plasma albumin, plasma volume and the transcapillary escape rate of albumin (TERalb), i.e. the fraction of the intravascular mass of albumin that passes to the extravascular space per unit time, were determined using 125I-labelled albumin in 26 patients with varying degrees of psoriasis. For the patients as a group the plasma albumin concentration and the TERalb values were not significantly different from the control group. This contrasts with earlier findings in erythrodermic patients. The plasma volume was significantly reduced whether it was expressed in relation to body weight, height or surface area (P less than 0.001). Thus the intravascular mass of albumin (IVM), determined as the product of the plasma volume and the plasma albumin concentration, was also significantly reduced (P less than 0.001). We found no correlation between the involved skin area and any of the above mentioned parameters. The possible mechanisms in the reduction of the plasma volume and the IVM are discussed. It is suggested that reduced IVM may reflect reduced total albumin mass due to lowered rates of albumin synthesis or increased rates of turnover.


High-resolution autoradiographic localization of 3-methylcholanthrene-3H in the skin of Balb/c mice after topical application.

Tritiated 3-methylcholanthrene (MC) was traced by electron microscope autoradiography in Balb/c mouse epidermis 24 h after topical application in vivo. Quantification of the autoradiographs indicated that the distribution of radioactivity was non-random. The frequency of silver grains was similar in both nuclei and cytoplasm of epidermal cells. A concentration of labelling was detected in association with nuclear and cell membranes but to a greater degree with the dermo-epidermal junction. Results are consistent with previous work on the binding of hydrocarbons to soluble proteins and nucleic acids. The significance of the association of radioactivity with the dermo-epidermal junction is discussed.


Wrinkles due to idiopathic loss of mid-dermal elastic tissue.

Widespread areas of fine wrinkling of the skin had been noted for 2 years by a 42-year-old healthy white woman. Histological study disclosed a selective absence of elastic tissue strictly limited to the mid-dermis of the involved areas. It was postulated that an antecedent urticarial process may have led to such a specific zonal destruction of elastic tissue. The elastolytic process did not change or extend, and no urticarial lesions were seen during a year of observation.


Orf: a family with unusual complications.

Three members of a farming family and their local postman contracted orf. One of those affected had had no direct contact with infected sheep. Two of the family developed a widespread papulo-vesicular eruption of the skin and mucosae with pyrexia, malaise and lymphadenopathy lasting 4-5 weeks. The eruption did not resemble erythema multiforme or the toxic erythemas usually associated with this infection.


Herpetiform pemphigus induced by penicillamine.

A patient with arthritis is described who developed a dermatitis herpetiformis-like rash after 8 months of D-penicillamine therapy and which cleared soon after the drug was discontinued. The histopathological findings were compatible with a diagnosis of pemphigus, showing intra-epidermal vesicles and spongiosis but no acantholysis. Intercellular antibody was detected by indirect immunofluorescence at the onset of the eruption (titre 1 in 160) and also found in serum taken prior to penicillamine treatment (titre 1 in 20). It is now well known that D-penicillamine can induce pemphigus. The findings reported here suggest the possibility that the patient was predisposed to develop the eruption before the drug was given.


Haemophilia, hepatitis and porphyria.

A patient with haemophilia A developed hepatitis B, seemingly as a consequence of treatment with blood products. Six years later, bullae, photosensitivity, and the biochemical findings of porphyria cutanea tarda developed.


Gluten-free diet in dermatitis herpetiformis. I. Clinical response of skin lesions in 81 patients.

Eighty-one patients with dermatitis herpetiformis were treated with a gluten-free diet (GFD) for periods varying from 6 to 36 months. At the end of the treatment the daily requirement of dapsone was significantly lower in patients treated with a GFD than in 49 patients on a normal diet. 93% of the patients on a GFD were able to reduce the dose of dapsone whereas only 16% of the patients on a normal diet were able to do this. Complete remissions occurred only in patients on a GFD. 28% of the patients on a GFD were able to stop dapsone completely and were continuously asymptomatic when they observed a strict diet. A response to a GFD was noted on the mean daily requirement of dapsone as soon as the treatment was initiated although the length of time for an individual response varied. After one year on a GFD the patients needed on average about 40% and after 3 years about 20% of the dose required to control skin symptoms at the beginning of the diet. The patients responded to a GFD irrespective of changes found in the jejunal mucosa and irrespective of the presence of absence of HLA-B8.


Granuloma annulare and sarcoidosis.

Granuloma annulare (GA) and sarcoidosis are two diseases of unknown cause which involve the skin and whose basic pathology is a mononuclear histiocytic cellular reaction. Biopsy plays the major role in the diagnosis of both diseases, and no other routine laboratory test for either disease is currently available. Sarcoidosis is generally considered to be an allergic or immune granuloma with inconstant defects in cell-mediated immunity (Broom & MacLaurin, 1973). There have been no immunological studies of GA. We recently studied 14 cases and found circulating lymphokines (macrophage migration inhibition factor) in 11 which correlated with circulating macrophage migration inhibition factor in sarcoidosis (9 of 10 cases) (Umbert, Belcher & Winkelmann, 1976). The co-existence of GA and sarcoidosis in 5 patients suggests to us that there are very similar immunological reactions as well as pathology in both diseases and that the elucidation of the pathogenesis of one disease should aid in understanding the other. To our knowledge, there are no prior reports of systemic sarcoidosis coexisting with or manifesting the histological picture of GA. In this report we have demonstrated by clinical and histological criteria that GA and sarcoidosis can co-exist.


Black grain mycetoma. Atomic absorption and spark source mass spectrophotometry of the tissue grain in Madurella mycetomi infection.

The tissue grain of Madurella mycetomi infection shows a spread of mineral constituents which is somewhat higher than the known values for the dermis, but differs little in relative concentrations. The unique physical resistance of the grain cannot be related to departures in concentration of calcium or of trace elements. Our earlier hypothesis of a tanned protein structure for the grain therefore still holds (Findlay & Vismer, 1974).


Characterization of a leukotactic factor derived from psoriatic scale.

A study was made on the in vitro characteristics and in vivo biological activities of a leukotactic factor derived from psoriatic scale (PLF). Sephadex G-75 chromatography showed that PLF eluted in the region of the 12,500 dalton protein marker. It resisted heating, lyophilization, acidity (pH 3) and alkalinity (pH 11), but was destroyed by trypsin digestion. The substance attracted polymorphonuclear leukocytes (PMNs) in vitro; this ability was inhibited by antiserum to C3a and was partially reduced by antiserum to C5. Although PLF showed strong chemotactic activity for PMNs, its activity for mononuclear cells was only mild. Intradermal injection of PLF into man or guinea-pig produced an erythematous response with dense tissue neutrophilia, the time course of which was similar to that of the Arthus response. PLF also provoked increased vascular permeability in guinea-pig skin. Moreover, repeated intradermal injection of PLF to the same site in guinea-pigs led to moderate acanthosis of the overlying epidermis. These observations strongly suggest that transepidermal migration of leukocytes in psoriatic lesions is provoked by PLF, whose activity appears to reflect that of complement cleavage products, particularly C3a, presumably produced by complement activation in the subcorneal region of the epidermis. Furthermore, it is postulated that PLF may be a factor which plays a crucial role in the production of typical psoriasiform tissue changes.


UVA-induced inhibition of proliferation of PHA-stimulated lymphocytes from humans treated with 8-methoxypsoralen.

Lymphocytes from healthy human donors were used as a model system for studying the combined effect of 8-methoxypsoralen (8-MOP) plus UVA. Two hours after oral administration of therapeutic doses of the drug enough 8-MOP was taken up in vivo by the circulating peripheral lymphocytes to cause significant inhibition of phytohaemagglutinin induced lymphocyte proliferation when the cells were exposed in vitro to UVA irradiation. The inhibition of proliferation as monitored by a reduced 3H-thymidine incorporation into cellular DNA was shown to be UVA-dose dependent. Control cultures of 8-MOP containing lymphocytes which were not UVA irradiated showed normal blast transformation. In lymphocytes obtained from the same donors prior to 8-MOP intake, PHA-induced lymphocyte transformation was not impaired by UVA irradiation. In 8-MOP containing lymphocytes exposed repeatedly to UVA during the 72 h culture period a cumulative effect of irradiation could be observed. A varying sensitivity towards 8-MOP plus UVA was noted when the cells were irradiated at different times after PHA stimulation. The cells were most vulnerable to UVA irradiation during the DNA-synthesis phase of the proliferating lymphocytes. The results suggest that dermal inflammatory infiltrates containing locally proliferating lymphocytes are influenced by systemic photochemotherapy since UVA penetrates well into the dermis.


Topical mechlorethamine therapy for mycosis fungoides.

Patients with limited skin involvement by mycosis fungoides were treated with daily topical mechlorethamine. Seven of thirteen patients had a complete remission of diseases. Six of these seven experienced a contact dermatitis and four underwent a successful topical desensitization programme. The possible beneficial therapeutic effects of developing a contact allergy are discussed.


Onchocerciasis treated with diethylcarbamazine.

One hundred patients with onchocerciasis were treated with diethylcarbamazine: a single course of treatment led to clinical cure in 48% of the patients; no means of anticipating which patients might require only a single course of treatment was found.


Vasoconstrictor activities and bio-availabilities of seven proprietary corticosteroid creams assessed using a non-occluded multiple dosage regimen; clinical implications.

The bio-availabilities and activities of commercial creams (Metosyn, Synalar, Betnovate, Locoid, Alphaderm, Dioderm and Efcortelan 1%) were assessed using a multiple dosage regimen vasoconstrictor assay in ten volunteers. The blanching response first increased but then diminished with continued application over a 5-day period: following a 2-day 'resting period', when no steroid was applied, the application sites recovered considerably but tachyphylaxis again resulted from subsequent repeated applications. Acute tolerance occurred with the hydrocortisone formulations (Alphaderm, Dioderm and Efcortelan 1%) in a manner similar to that observed with the potent preparations. Metosyn was significantly more active (P less than 0.05), and Efcortelan 1% was significantly less active (P less than 0.05), than the other formulations. Apart from the reversal of Dioderm and Alphaderm the rank order of preparations was similar to that previously noted in the 6 h occluded single-application vasoconstrictor test. The results may have significance in dosage from design and application for topical corticosteroid formulations.


Monosomy 7 in two patients with a myeloproliferative disorder.

Clinical and laboratory data are presented for two patients with a dyshaematopoietic disorder, and monosomy 7 in their bone marrow cells. The first patient, a 55-year-old woman, had been treated with chlorambucil for an ovarian carcinoma. After 4 years an oligoblastic myeloid leukaemia was diagnosed and she later died with an acute transformation of the disease. The second patient, a 21-year-old male, has had a dyserythropoietic anaemia with transient pancytopenia for over 5 years without any signs of malignancy. The possible relationship between therapy, the monosomy 7 and the other bone marrow abnormalities is briefly discussed.  From an analysis of the data of these and comparable cases in the literature it appears that loss of chromosome No. 7 material is often associated with erythropoietic disorders such as erythroid hyperplasia and erythraemia. The reduction or absence of the Colton blood group antigens found in our patients and in a few other monosomy 7 cases also points to an abnormality of the red cell line.


Normal human bone marrow cultures in vitro: cellular composition and maturation of the granulocytic colonies.

The analysis of single haemopoietic colonies grown in methylcellulose and in agar was performed at intervals by a cytocentrifugation method. Correlation was established between morphology of the whole colonies and their cellular content. Three main cell lines predominated: neutrophils, macrophages, eosinophils; a few colonies contained a pure population of basophil-like granulocytes. Development was followed from myeloblasts to polymorphs, both being present in most of the colonies. Cumulated results showed that (1) the proliferating compartment remained quite large till day 14, with 58% of cells in S phase, and rapidly decreased after day 16, and that (2) the polymorphs rapidly disappeared from the culture medium. Differentiation proceeded at different rates from one colony to the other, thus suggesting heterogeneity between colony forming cells (CFC). Neutrophil colonies appeared and lysed more rapidly than did eosinophil colonies. Macrophages arose from large immature cells with many promyelocyte features; such cells were present in mixed colonies, containing both neutrophils and macrophages. It is very likely that granulopoiesis results from the development of distinct committed CFC. This work was carried out using normal human bone marrow and may be a useful tool for studying pathological material in the future.


Iron stores in pregnancy.

Serum ferritin concentration has been measured during the course of pregnancy in 154 women. There was a rapid decrease in iron stores during early pregnancy irrespective of any iron therapy. Oral iron did, however, prevent the stores reaching iron deficient levels during the second half of pregnancy. The results suggest that maternal erythroid activity starts early in pregnancy and may exhaust the iron stores before the fetal demands for iron can be met.


Transferrin uptake by rabbit alveolar macrophages in vitro.

Rabbit alveolar macrophages were shown to bind 125I-human transferrin in vitro. The binding reaction was characterized by three stages: (1) adsorption of transferrin to the cells, followed by (2) rapid uptake of the protein to reach (3) a constant level of cell-bound transferrin. The latter two stages were dependent upon temperature and metabolic energy. Macrophages released 125I-transferrin rapidly when incubated with unlabelled transferrin. Small quantities of 125I-rabbit and 125I-bovine serum albumin, by comparison, were bound to and released by the cells; the attachment of these proteins may be solely the result of adsorption. Transferrin, 80% saturated with iron, was bound to a greater extent than 10 or 50% saturated transferrin; 10% saturated transferrin was bound more readily than the 50% saturated preparation. The findings are consistent with the presence of a transferrin receptor on the cell membrane of the alveolar macrophage and imply that transferrin may interact directly with this cell type in order to remove or donate iron.


Stimulation of monocyte procoagulant activity by adherence to different surfaces.

During in vitro incubation for several hours human circulating blood leucocytes developed procoagulant activity (PCA) which was identified as tissue thromboplastin-like activity and which remained specifically associated with monocytes. Adherence of monocytes to glass stimulated these cells to generate PCA. When cuprophane was used, both the degree of adherence of monocytes and PCA generation by these cells was significantly less. In addition, when the monocytes were incubated upon a monolayer of cultured endothelial cells only minor PCA generation was detectable. After incubation on glass the non-adherent monocytes had negligible PCA in comparison to the adherent monocytes. Protein synthesis inhibitors (cycloheximide and actinomycin D) inhibited PCA generation but did not affect monocyte adherence. These results demonstrate that adherence of monocytes is a stimulus for the generation of PCA.


Binding of thrombin to functionally defective platelets: a hypothesis on the nature of the thrombin receptor.

The initial step in the interaction of thrombin with human platelets is binding of thrombin to specific structures on the platelet surface. Data are presented which show that platelets from thrombasthenic patients bind thrombin similar to controls. In contrast, platelets from a patient with Bernard-Soulier syndrome had lower thrombin binding capacity. It is suggested that glycoprotein one (GP-I) on the platelet surface might be the receptor for thrombin.


Ferritin synthesis in inflammation. I. Pathogenesis of impaired iron release.

Plasma iron turnover (PIT) and ferritin synthesis in the liver and spleen were studied in rats within the first 24 h of inflammation produced by turpentine injection. Comparison of the sequential changes in PIT and ferritin synthesis showed that alterations in ferritin synthesis preceded the changes in plasma iron exchange throughout the study. Thus, after 4 h inflammation ferritin synthesis was twice normal whereas plasma iron and PIT were still unchanged. Conversely, maximal reduction in plasma iron occurred after 12 h inflammation, at a time when ferritin synthesis had already declined to normal rates. These correlations seem to indicate that, in analogy with other acute phase reacting proteins, increased ferritin synthesis is a primary nonspecific response which is part of a general pattern of the systemic effects of inflammation. This increase in ferritin synthesis is assumed to be responsible for the diversion of labile iron into ferritin stores, and its reduced availability for release from tissues.


Effect of erythropoietin therapy on the red cell volume of uraemic and non-uraemic rats.

Studies were performed to determine the effect of injecting repeated doses of erythropoietin (Ep) on the red cell volume of chronically uraemic rats and on that of non-uraemic sham operated ones. After 13 doses of Ep (5 u/dose), started either 5 or 21 d after removal of five-sixths of the renal mass, the increase in the red cell volume of uraemic rats was as great as that of non-uraemic ones. The significance of these results is discussed.


Compared effects of irradiation and cyclophosphamide induced erythroid aplasia on the catabolism of exogenous erythropoietin.

The effect of erythroid aplasia on the clearance rate of exogenous erythropoietin from the circulation has been studied in irradiated (200, 400 and 800 r) and cyclophosphamide (50 mg/kg) treated rats. After irradiation, the T1/2 was increased from 1.5 h in controls to 2.3 h. In spite of similar aplasia, the T1/2 observed after cyclophosphamide administration was identical to the T1/2 in controls. These results suggest that the action of X-rays on the catabolism of erythropoietin is independent of erythroid aplasia and could be related to an extramedullary effect of irradiation.


200 kV xeroradiography in occupational exposure to silica and asbestos.

Some details of the physics of xeroradiography, and the bearing these have on films of the lung obtained by this technique, are discussed. In experiments designed to obtain useful films with a minimum of radiation exposure it was found that an exposure range of 10-30 mas at 200 kV at 1.35 m (4 1/2 ft) without a grid or air gap gave very satisfactory results. The positive model of development was considered to give more information than the negative mode. One hundred and fourteen miners who had been exposed to silica dust, asbestos dusts or both, were examined by this technique. The xeroradiographs were compared with silver halide films taken at 200 kV. The xeroradiographs were considered to be superior in several respects, especially in the delineation of vascular shadows, normal and abnormal linear opacities. Linear opacities in asbestos-exposed subjects were better shown on the xeroradiographs and were occasionally seen on these films when the 200 kV conventional film was entirely normal. Small rounded opacities of silicosis were very poorly shown on the xeroradiographs. Pleural thickening and pleural plaques may be very well demonstrated.


A mortality study of coke oven workers in two South Wales integrated steelworks.

Six hundred and ten coke oven personnel were studied retrospectively over a period of 11 years (1954-65). During this time 82 died, 88 retired and 80 left, but all were treated. The Standardised Mortality Ratios (SMRs) have been calculated for four principal causes which have then been further analysed into 30 subgroups. The work was limited because the population was small and the records not detailed enough to analyse the mortality rates according to environmental exposures. Differences between SMRs obtained at the two works were quite marked (73 and 98) and the overall SMR of 85% was better than expected. The observed number of deaths from respiratory disease, malignant neoplasms and all other causes excluding cardiovascular, was very near that expected, but the numbers of deaths from cardiovascular disease and in particular arteriosclerotic disease, showed a significant deficit.


Measurement by gas chromatography of urinary hippuric acid and methylhippuric acid as indices of toluene and xylene exposure.

A gas chromatographic method was applied to the determination of the urinary glycine conjugates, hippuric, o-, m- and p-methylhippuric acids. These were extracted with ethyl acetate from urine after acidification with hydrochloric acid. The internal standard solution (heptadecanoic acid methanol solution) was added before extraction and a diazomethane-ether-ethanol solution was subsequently added to the dried extracts. The methylated residues were dissolved in methanol and injected into a gas chromatograph as described by Buchet and Lauwerys (1973). By the combined use of gas chromatography and mass spectrometry the methyl esters of hippuric acid and m-methylhippuric acid were identified in the urine of a volunteer who had been exposed to toluene and m-xylene vapours. When the urine specimen contained salicyluric acid (a urinary metabolite of salicylic acid) two sharp peaks were observed. The faster peak coincided with m- or p-methylhippuric acid. The upper limit of urinary hippuric acid concentration in healthy subjects with no occupational exposure was calculated by this method to be 1.026 microgram/ml (fiducial limit 5%) after correction to 1.024 for variation in urinary density.


Quantitative determination of hippuric and m-methylhippuric acids in urine by high-speed liquid chromatography.

High-speed liquid chromatography employing an ultraviolet photometric detector has been applied to the simultaneous determination of hippuric and m-methylhippuric acids in urine. Reversed-phase partition chromatography is carried out on a muBondapak C18 column with methanol-water as the eluent system. This method obviates the necessity for isolation or reaction of these acids before assay. The only pretreatment necessary is extraction of sample with ethyl acetate. A linear relationship is obtained between the peak heights and the hippuric or m-methylhippuric acid concentrations. Mean recovery of hippuric and m-methylhippuric acids in urine is 99.8% and 99.3% respectively. The determination of hippuric acid by this method gives lower concentrations in normal urine than does the colorimetric method of Umberger and Fiorese (1963).


The neurotoxicity of toluene: EEG changes in rats exposed to various concentrations.

Workers exposed to toluene develop many central and autonomic nervous symptoms. It has been suggested that the effects of toluene on the central nervous system may be detectable by EEG. In the present experiments, changes in EEG and behaviour of rats exposed to toluene were monitored in an attempt to clarify the relationship between exposure to toluene and central nervous system reaction. Chronically implanted electrodes were used in Wistar albino male rats to record EEG in cortex and hippocampus, cervical EEG and pulse rate. The rats were exposed to 4000 ppm, 2000 ppm and 1000 ppm toluene vapour for four hours. The sleep cycle was divided into five phases (wakeful, spindle, slow-wave, preparadoxical and paradoxical) judged by the cortical and hippocampal EEGs, the cervical EMG, and behaviour. This classification should be useful in assessment of the effects of toluene on the central nervous system. In our experiments, the changes in the sleep cycle suggest that 4000 ppm and 2000 ppm of toluene vapour disturb the sleep, and 1000 ppm of toluene vapour prevents sleep entering the slow-wave phase but facilitates its entry into the paradoxical phase. The changes of EEG components were peculiar to each concentration. The results suggest, in effect, that analysis of the changes in the EEG components would be helpful as an index to the reaction of the central nervous system to toluene vapour.


Amenorrhoea and loss of weight.

Amenorrhoea due to loss of weight was diagnosed in 39 of 170 consecutively investigated patients with amenorrhoea: 24 patients had anorexia nervosa but in the remainder this diagnosis could not be made with certainty. The only difference detected between the two groups was in their lowest weights. Endocrine tests revealed subnormal oestrogen production, low serum LH levels and a failure to ovulate in response to clomiphene. All patients were encouraged to put on weight and 14 resumed ovulatory menstrual cycles. In these patients the mean weight at resumption of ovulation exceeded the mean weight at presentation by 3.6 kg; in contrast, in the patients who remained amenorrhoeic, there was no significant increase of weight by the time of the last visit. Of 8 patients who complained of infertility, 5 ovulated and conceived. Thus dietary treatment of patients with amenorrhoea and loss of weight may replace gonadotrophin therapy for induction of ovulation in a significant proportion of patients with anovulatory infertility.


A survey of amniocentesis in 925 patients at high risk of fetal genetic disorder.

Over a nine-year period, 925 pregnancies at an Israeli medical centre were selected for investigation by amniocentesis for genetic reasons. In only 30 pregnancies did failure of laboratory methods or difficulty with amniocentesis lead to a lack of results with which to assess the normality of the fetus. The information obtained by examination of the amniotic fluid in the other 895 pregnancies is presented and discussed.


Haematological indices of the mother and baby during labour.

Haematological indices were obtained by Coulter Counter analysis from 325 women in the first stage of labour, and from the cord blood of their newborn babies. The mean maternal haemoglobin concentration was 12.49 g/dl and the mean cord haemoglobin 16.18 g/dl. The mean corpuscular volume measured directly was 89.00 fl from maternal blood and 106.73 fl from the cord blood; the two ranges barely overlapped and it should be possible by automated analysis to differentiate between fetal and maternal blood obtained at amniocentesis or artificial rupture of the membranes at term.


Falling amniotic fluid palmitates in diabetic pregnancies.

Palmitic acid levels were measured in samples of amniotic fluid obtained from 15 patients with diabetes. Seven patients had palmitate values which decreased at some time in pregnancy but only one of the infants developed respiratory distress. Eight of the 15 patients had final amniotic fluid palmitate values which were greater than 0.07 mmol/l and one infant developed respiratory distress. The other seven patients had final amniotic fluid palmitate values of 0.07 mmol/l or less and one of the infants developed respiratory distress. The significance of falling amniotic fluid palmitate values is discussed.


Correlations of sialomucins and IgA in the maternal serum of primiparous and multiparous subjects at delivery.

Attention is drawn to correlations between placental coefficients and maternal serum levels of IgA at delivery in primiparae and multiparae. These correlations associate maternal serum IgA with gestational performance and appear to discriminate between groups which differ in that respect. Similar correlations exist between the placental coefficient and maternal serum seromucoid, with group discrimination preserved in primiparae, but not multiparae. Direct correlations between serum seromucoid and IgA in maternal serum can be attributed to their mutual dependence on the size and state of the feto-maternal interface, and may provide a means of detecting placental insufficiency in multigravidae.


The relationship between serum oestradiol levels and serum triglyceride, cholesterol and phospholipid levels in normal human pregnancy.

Blood samples were obtained for serum lipid and oestradiol measurement from 365 women between 7 to 41 weeks of normal pregnancy. In an additional 21 women serum lipid and oestradiol were measured at 20 to 23 weeks gestation and again at 30 to 33 weeks. Significant correlations were noted between changes in the serum triglyceride and oestradiol levels (P less than 0.001) and between changes in serum cholesterol and oestradiol levels (P less than 0.05). The changes in phospholipid and oestradiol levels were not significantly correlated (P less than 0.1). The serum triglyceride level (mean +/- SEM) was highest at 37 weeks gestation (3.8 +/- 0.3 mmol/l), an increase of 400 per cent over the level at 7 weeks. The serum phospholipid level increased by 108 per cent to its highest levels (5.0 +/- 0.2 mmol/l) at 38 weeks and the cholesterol level increased by 93 per cent to its peak (8.7 +/- 0.3 mmol/l) at 38 weeks.


Biochemical changes in prolonged labour in the tropics.

Serum electrolytes, creatinine, urea and urine osmolality were estimated in 25 healthy pregnant women at term, 25 women in early normal labour, and 25 healthy parturients in prolonged labour. A statistically significant fall in serum potassium was found in early labour with a further significant fall in prolonged labour. Bicarbonate changes followed the same pattern of a progressive fall. Sodium fell slowly, reaching significant levels only in prolonged labour and chloride fell even more slowly. There was a conspicuous or significant rise in serum urea with a smaller, not significant rise in creatinine. The rapid insensible loss of water in tropical areas was reflected in the rise in serum urea while homeostatic mechanisms maintained a slower fall in sodium and chloride by renal conservation.


Epidemiological aspects of hydatidiform mole in the Republic of Paraguay (South America).

A total of 227 hydatidiform moles was recorded in Paraguay over a 10-year period (1960 to 1969). Using demographic studies, the annual incidence of hydatidiform moles was calculated as 0.229 per 1000 pregnancies or 1 per 4369 pregnancies, with the highest incidence occurring at the extremes of reproductive life.


Male intersexuality presenting at puberty.

A 15-year-old girl was referred to the Endocrine Unit because of a deep voice and the absence of menstruation. Secondary sex hair showed a male pattern of distribution and there was a phallic clitoris 4 cm long, with the urethral orifice posterior. Plasma testosterone was within the normal male range. The karyotype was 46XY. Gonadectomy and clitoridectomy were performed. Histology suggested a diagnosis of anatomical testicular failure, which, in view of the imperfect attempt at masculinization, was thought to be only partial. Possible causes are discussed.


Twenty-five years experience of the drug treatment of tuberculosis of the female genital tract.

A study has been made of women with proved, tuberculosis of the genital tract who were treated with drugs between 1st January, 1951, and 1st July, 1976. Seven different drug programmes were employed and 566 women were treated. Apart from the last two schedules employing the newer antituberculosis drugs, which were too recent for a follow-up to be available, the best results were obtained with a combination of streptomycin, PAS and isoniazid for 18 months or two years. In this group, 87.7 per cent were regarded as cured after an average follow-up of six years and six months. Drug cover was employed in 79 patients in whom surgery was found to be necessary and the results were uniformly satisfactory. Toxic drug reactions occurred in 18.2 per cent of the patients treated.


Pelvic tissue and serum concentrations of various antibiotics given as pre-operative medication.

Talampicillin, cephalexin and clindamycin were administered orally, and ampicillin, cephazolin, clindamycin and spectinomycin intramuscularly as preoperative medication to 49 women who were having an abdominal hysterectomy. Antibiotic levels in serum, myometrium or cervix, and Fallopian tube were estimated. Antibiotic absorption from the gastrointestinal tract was delayed, but intramuscular therapy produced serum levels compatible with those reported in ambulant volunteers. None of the antibiotics produced a concentration which inhibited all the potential pathogens causing pelvic inflammatory disease. Inhibitory concentrations were produced by cephazolin except against Bacteroides; by clindamycin except against enterobacteria; by ampicillin except against Bacteroides and enterobacteria; and by spectinomycin except against resistant strains of streptococci. The need for a reassessment of dose regimens and route of administration as well as the possible need for using two antibiotics together for the treatment of pelvic inflammatory disease is suggested.


Corpus luteum function in early pregnancy following ovulation induction with bromocriptine.

Serum and prolactin levels and urinary oestrogen and pregnanediol excretion were measured during early pregnancy in 12 hyperprolactinaemic subjects who became pregnant during treatment with bromocriptine. Prolactin levels were suppressed below normal whilst taking the bromocriptine, but rose significantly when this drug was stopped and by eight weeks of gestation reached values significantly higher than those observed in normal pregnancy. Further increases in prolactin levels were, however, not observed. Urinary oestrogen and pregnanediol excretion was initially normal but, following cessation of bromocriptine, urinary pregnanediol excretion decreased and was significantly less than normal at 11 to 14 weeks gestation. These results suggest that elevated prolactin levels affect corpus luteum function of early pregnancy. Because the effect is maintained until at least 14 weeks gestation, prolactin may also affect progesterone production by the placenta.


Plasma urate and serum deoxycytidylate deaminase measurements for the early diagnosis of pre-eclampsia.

The value of measuring plasma urate and serum deoxycytidylate deaminase (dCMP deaminase) for the early diagnosis of pre-eclampsia has been investigated in 45 patients. A combination of increased blood pressure and increased plasma urate identified 19 patients with a high incidence of fetal and maternal morbidity ascribable to pre-eclampsia. Seventeen of the 19 patients also had an increased serum dCMP deaminase. Serial antenatal observations for a mean period of 104 days (36-179 days) on 33 of the patients demonstrated that plasma urate and serum dCMP deaminase increased together as early changes in the development of pre-eclampsia. In six patients, blood pressure, plasma urate and serum dCMP deaminase all increased but in only one was the rise in blood pressure the first change. Elevations of plasma urate and serum dCMP deaminase are therefore both early features of pre-eclampsia. Serial measurements can give warning of the disorder before the appearance of other clinical features. The change in dCMP deaminase is probably another reflection of early renal involvement in the pre-eclamptic process.


Factor VIII-related antigen and factor VIII coagulant activity in normal and pre-eclamptic pregnancy.

The changes in the ratio between factor VIII-related antigen and factor VIII activity were compared in ten patients with normal pregnancies and in ten patients with severe pre-eclampsia. In the patients with pre-eclampsia, a highly significant increase in the ratio was observed during the third trimester. No difference in the ratio between the two groups was found on day 7 of the puerperium. In the pre-eclamptic patients, the highest ratios for factor VIII-related antigen to factor VIII activity were associated with either a perinatal death or with the delivery of a severely growth retarded infant. These findings are in keeping with an increased rate of thrombin production in women with pre-eclampsia, and suggest that the ratio of factor VIII-related antigen to factor VIII activity may reflect the severity of the effect of the disease process on the fetus.


Sequential studies in pre-eclampsia using plasma fibrinogen chromatography.

The technique of plasma fibrinogen chromatography was used to study sequential changes in coagulant and fibrinolytic activity in six patients with severe pre-eclampsia. Plasma soluble fibrinogen-fibrin complex and plasma fibrinogen-fibrin degradation product levels were measured as indices of coagulant and fibrinolytic activity respectively. Clinical deterioration antenatally was accompanied by increasing coagulant and decreasing fibrinolytic activity, while a more stable clinical picture was associated with steady coagulant and increasing fibrinolytic activity. Following delivery, a surge in fibrinolytic activity accompanied or preceded clinical recovery. The pattern of increased coagulant and diminished fibrinolytic activity would seem to favour the development of disseminated intravascular coagulation in these patients and it is possible that the balance between coagulant and fibrinolytic activity may influence the clinical course and outcome of the pregnancy.


Comparison between linear array real time ultrasonic scanning and conventional compound scanning in the measurement of the fetal biparietal diameter.

Ultrasonic measurements of fetal biparietal diameter (BPD) obtained by the Real Time scanning (Dynamic Section Scan) and conventional compound scanning (Static Section Scan) in twenty patients were compared. A comparison between two operators, one of whom was relatively inexperienced, was also made, both measuring the same BPDs. The mean variance of 20 groups-of-four 'blind' measurements was reduced using dynamic scanning, particularly for the less experienced operator. A significant difference was observed between operators using conventional scanning but not when using dynamic scanning. Both operators were able to obtain results in a shorter time with dynamic scanning, the faster operator averaging less than one minute for each observation. Apparent advantages of dynamic scanning are discussed. The terms 'Dynamic Section Scan' and 'Static Section Scan' are suggested to emphasize the difference between  the two imaging systems.


Strain uterography in labour.

Multi-strain measurements of uterine contractions were made on 36 women at 36 to 42 weeks of pregnancy. The tracings obtained supported the existence of one dominant pacemaker area in the fundal region of the uterus and indicated that the contractile wave travelled in a downward direction with an average speed of 6 cm/second. The analysis of all normal labours showed that strains of the longitudinal muscle fibres changed from extension in the fundal region of the uterus to compression in its lower part, through a local zero strain in a narrow zone below the umbilicus. Intensity of the uterine contractions reached 6 per cent in extension and -2 per cent in compression. Information about the number of peak contractions, the frequenty of contractions and the tonus of the myometrium during relaxation are of importance in the evaluation of uterine dysfunction.


Increase of the prostaglandin precursor, arachidonic acid, in amniotic fluid during spontaneous labour.

Concentrations of free arachidonic acid have been measured by gas liquid chromatography in amniotic fluid obtained during spontaneous labour at term. Levels of arachidonic acid ranged from 0.14 to 2.9 microgram/ml and increased significantly (P less than 0.01) with advancing cervical dilatation. Concentrations of arachidonic acid showed no significant relation to concentrations of either prostaglandin F or 13,14-dihydro-15-keto-prostaglandin F. These findings are discussed with respect to the role of arachidonic acid in the control of prostaglandin biosynthesis during human parturition.


The clinical significance of marginal and velamentous insertion of the cord.

The claims that marginal and velamentous insertion of the cord are associated with a high incidence of abortion, low birth weight, premature delivery, fetal malformation, fetal hypoxia and intrauterine fetal death have been investigated. A study of 1000 cases has failed to demonstrate any such association.


Pregnancy-induced leucocytosis in Africans, Asians and Europeans.

In the light of widespread neutropenia in healthy Africans, an assessment was made of the magnitude of pregnancy-induced leucocytosis in 264 African women by comparing their haematological values at term with those of 47 European and Asian counterparts in Lusaka, Zambia. No statistically significant differences were found the absolute counts of neutrophils, lymphocytes, or eosinophils between the three races. The fact that pregnancy did not exaggerate the neutropenia, or hamper the leucocytosis response, would suggest that the African woman has a normal marrow which suffers from insufficient stimulation possibly as a result of some dietary factor.


Spontaneous extrusion of Hulka-Clemens spring-loaded clips after vaginal hysterectomy: two case reports.

Two patients had previously been sterilized by the application of Hulka-Clemens spring-loaded clips to the Fallopian tubes, had a vaginal hysterectomy. In each patient a clip that was left attached to its tubal remnant was spontaneously extruded through the vaginal vault during the postoperative period.


Bilateral cataract extraction in one session: report on five years' experience.

Six hundred and seventy-six patients had both their cataracts removed in one operating session because of the rural and economic conditions of Malawi. These operations were performed over a period of 5 years. The final visual results were satisfactory and the number of complications acceptable in relation to the environmental conditions and medical facilities available. However, the incidence of infection is higher than would be acceptable in a sophisticated medical environment. Three eyes were lost owing to infection, but fortunately in all 3 cases the fellow eye was not affected. Furthermore, broken capsule and vitreous loss occurred more frequently than expected in a sophisticated facility in the eye first operated on. This allowed measures to be taken by the surgeon in many cases to prevent these complications from recurring in the second eye.


Differences and similarities in a series of cases with bilateral intraocular lenses and evaluation of the results.

A review is given of the results of intraocular lens implantation in 38 patients, that is, 76 eyes. The observation time was up to 7 1/2 years. Only 5 cases were done as a secondary procedure. The Binkhorst 4-loop lens was preferred. Most of the lenses were fixated with an iris-lens suture. Out of 8 lens luxations 2 were fixed with an iris suture. The final visual acuity and the difference in refraction in spherical as well as cylindrical power are surveyed. The astigmatism and the astigmatic axis are compared in the 2 eyes of each patient. Most of the patients regained stereoscopic vision. It is concluded that neither the lens position, the lens type, the number of iris sutures, nor the number of iridectomies had any influence on the eventual results.


Aphakic macular oedema: a two-year follow-up study.

A 2-year follow-up study was carried out on patients known to have developed aphakic macular oedema 6 weeks postoperatively, and the results were compared with those in a control group who had not developed oedema. Four eyes (12%) still had macular oedema, the visual acuities ranging between 6/5 and 6/9. There was no significant difference in visual acuities at 2 years between the 2 groups of patients. Visual acuity had significantly improved between 6 weeks and 2 years in the eyes that had macular oedema at 6 weeks after extraction. Factors causing persistence of aphakic macular oedema are discussed.


Outflow changes in positive provocative tests.

The outflow changes in 26 eyes were measured during the course of a positive provocative test with pilocarpine and phenylephrine. Three separate patterns of response occurred: (1) One dose of pilocarpine and phenylephrine produced an acute attack with a large reduction in outflow. (2) The first dose of pilocarpine and phenylephrine produced a fall in pressure and increase in outflow. The second dose reversed this effect and closed the angle. (3) The first dose of pilocarpine and phenylephrine increased pressure by an insignificant amount and decreased outflow. The second dose accentuated this response and produced an acute attack.


Outflow changes in normal eyes after closed-angle glaucoma.

Twenty-four patients with spontaneous acute closed-angle glaucoma in one eye were selected for study. All 24 eyes had a peripheral iridectomy, were normotensive, and had no gonioscopically visible peripheral anterior synechiae. Of the 24 contralateral eyes 14 gave a positive response to provocative tests and had peripheral iridectomy. The remaining 10 eyes did not give positive responses to the tests and were on no treatment. The 24 pairs of eyes were provoked with pilocarpine and phenylephrine. Tonography was performed at the start of the test, 1 1/2 hours later, and at its termination. At the start of the test the 24 eyes that had had spontaneous closed-angle glaucoma showed a higher pressure and lower outflow facility than the 24 contralateral eyes. This difference disappeared as the test progressed. It is concluded that apparently normal eyes--after an acute attack--do none the less show a significant degree of damage to the outflow system. Ten pairs of eyes from 10 normal persons were provoked in a similar fashion and at no point did a significant difference appear between right and left eyes.


Circulating lipoprotein and blood glucose levels in association with low-tension and chronic simple glaucoma.

Circulating lipoprotein and blood glucose levels were determined for 53 patients with low-tension glaucoma and 39 patients with chronic simple glaucoma. The incidence of hypercholesterolaemia was significantly higher in the low-tension group than in the chronic simple glaucoma group and control data obtained elsewhere. Preliminary follow-up results of the effects of treatment are also reported. The incidence of raised fasting blood glucose levels was not significantly increased in either group.


The influence of pregnancy on the sensitivity of the cornea.

Corneal touch thresholds (CTT) were measured in 30 non-pregnant women serving as a control group and 29 pregnant women at different times during and after pregnancy. The results show that CTT becomes significantly higher after 31 weeks of pregnancy. However, only 86% of the subjects showed a difference in CTT during and after pregnancy, while 52% reported having some swelling. The loss of sensitivity (CTT-1) is assumed to be related to the water retention occurring during pregnancy, a view which is supported by some measurements of corneal thickness. It is suggested that this study may have exposed a new, hitherto unknown, way of monitoring pregnant women.


Corneal sensation in scleritis and episcleritis.

A series of 59 patients were examined for loss of corneal sensitivity. Thirty-five of them suffered from scleritis and 24 suffered from episcleritis. There was a difference between the 2 conditions in that significantly more patients with scleritis were affected than patients with episcleritis. It was also found that among the scleritis patients there was a close relationship between the number of quadrants affected and decrease in sensitivity. Five patients had necrotising scleritis, and they all showed marked loss of sensitivity. Sensitivity returned to normal when the scleritis resolved except when a large area of scleral ectasia resulted. The test is of importance because it is one of the easiest methods of detecting the onset of necrotising scleritis in its earliest stages.


An introductory report on the use of Bioplast in ophthalmic surgery.

Bioplast is an excellent material for implants. It lends itself readily to cutting and suturing and is easily applied. It is highly suited to ophthalmic surgery. It has the great advantage of having no antigenic properties and is quickly absorbed. Our cases recovered without complications, and the results were satisfactory both functionally and cosmetically. For these reasons we recommend Bioplast in ophthalmology.


Bee and wasp stings of the eye. Retained intralenticular wasp sting: A case report.

Two different stages should be considered in the management of bee and wasp stings to the eye. The first is the acute stage of activity of the specific insect venom on the structures the eye. The reaction of the eye to the particular insult is considered here in regard to the anterior and posterior segments of the eye. The second stage is that of the retained intraocular foreign body, the inert sting. Little is known about the reaction of the eye to the presence of chitinous sting and its effect on the structures of the eye. We report a follow-up study of a sting retained for 28 years, and emphasise the benign and quiescent course of the case. Guidelines for treatment and management in such cases are described.


Diathermo-trabeculotomy ab externo: indications and long-term results.

The authors present the results of 2 years' observation of 47 eyes operated with diathermo-trabeculotomy ab externo. This technique, based on a diathermic effect in association with trabeculotomy ab externo, allows an ample opening of Schlemm's canal and of the trabecular meshwork, with normalisation of intraocular pressure and outflow facility, for a period of up to 2 years, in open-angle and congenital glaucoma.


Structural alterations of extraocular muscle associated with Apert's syndrome.

An inferior oblique muscle from a patient with Apert's syndrome was examined by light and electron microscopy. Alterations in the muscle fibres, the myoneural junctions, and intramuscular nerves were observed. These data are not compatible with the widespread notion that motility disturbances in this syndrome are solely due to mechanical limitations.


Diagnosis and measurement of cyclodeviation.

A simple, convenient, and accurate method of detecting and measuring even the smallest degree of cyclodeviation with the help of two special major amblyoscope slides is described. Routine use of these slides in the investigation of all paralytic squints to detect and measure cyclodeviation is suggested. This will prove useful in the correct diagnosis and in the adequate management of a case of cyclovertical muscle palsy.


Unusual ocular presentation of acute toxoplasmosis.

Four patients with toxoplasmosis are reported with unusual presenting ocular lesions. One patient had an active lesion that appeared to involve the optic nerve as well as focal toxoplasmosis chorioretinitis at the macula. A second patient had a pale optic nerve in association with the classical chorioretinal scars of toxoplasmosis. The third patient had toxoplasmosis chorioretinitis of the macula with subretinal neovascularisation. The fourth patient had a branch artery occlusion complicating acute retinitis.


Bull's eye maculopathy with early cone degeneration.

Seven patients with acquired cone degeneration were investigated. The initial visual acuities in 6 of the series were normal or near normal but later deteriorated, although they did not fall below 6/60 in any patient. All the patients tested had colour vision defects and abnormalities on electrodiagnostic testing referable to the cone system. The typical picture was of a bull's eye maculopathy accompanied by an annular scotoma around the fovea, but the clinical and electrophysiological investigations showed that there were considerable variations especially in the early stages.


An unusual presentation of Best's disease.

We diagnosed an unusual case of Best's disease in a patient with multiple geographic macular and extramacular lesions. Initial confusion in the diagnosis arose because of a past history of intravenous drug abuse by the patient. The electro-oculogram was helpful in establishing the correct diagnosis.


An improved objective slit-lamp fluorophotometer using tungsten-halogen lamp excitation and synchronous detection.

A new design of fluorophotometer is described. The instrument can measure lower concentrations of fluorescent dye with greater accuracy than previous models.


A cannulated probe for torn inferior canaliculus repair.

A cannulated probe and silicone tube for the repair of the torn inferior canaliculus are described and illustrated.


Rapid deterioration of visual fields during bromocriptine-induced pregnancy in a patient with a pituitary adenoma.

A 28-year-old woman with an amenorrhoea-galactorrhoea syndrome was suspected of a microadenoma of the pituitary. She was treated with bromocriptine. In the subsequent pregnancy she developed rapid deterioration of the visual fields (ODS). A large temporal defect in the right eye and a moderate temporal defect in the left eye appeared in the 28th week of pregnancy, threatening the visual acuity of both eyes. Other examinations showed no evident lesion of the sellar region. An adenoma of the pituitary was removed, and the visual fields returned to normal after operation.


Variation in the weight, specific gravity and composition of the antlers of red deer (Cervus elaphus L.).

1. Antlers were removed in September from 2-4 year old red deer (Cervus elaphus L.). Both well-fed penned stags and less well-nourished grazing stags were studied. 2. For deer of the same age, both log antler weight and log antler specific gravity were related to body-weight in September and to body-weight gain between March and September. The antlers of 3- and 4-year-old stags were heavier and tended to be denser relative to body-weight and body-weight gain than those of 2-year-old stags. 3. For grazing stags of a given age, antler weight and specific gravity, and body-weight and body-weight gain, were progressively less in the three successive years of the study. This appeared to reflect increasing stocking rate over this period. 4. The composition of the antlers did not vary significantly between penned and grazing stags or with age. However the concentrations of ash, phosphorus and magnesium in dry matter showed significant positive correlations with specific gravity, that of zinc a significant negative correlation, while calcium, copper and manganese showed no significant correlation. 5. The antlers evidently provide a useful index of the changes in body-weight of the stags.


Amino acid uptake in chickens subjected to increasing levels of quantitative food restriction.

1. Three groups of cockerels were reared from 3 to 11 weeks of age on increasingly severe quantitative food restriction treatments, resulting in body-weight values of 12, 19 and 27% below that of a control group which was fed ab lib. 2. The rate of uptake of L-arginine, glycine, L-lysine and L-phenylalanine was measured in vitro using intestinal rings, over a 5 min incubation period. 3. Uptake of L-arginine was significantly increased with increasing degrees of body-weight restriction. This amino acid and L-lysine were the only two to show a significantly enhanced uptake rate as a result of the restriction treatments. 4. No significant differences were noted in the case of glycine or L-phenylalanine uptake following food restriction, indicating a certain selectivity in the alteration of absorption rates following food restriction, when such tests are conducted in vitro.


Studies of fatty liver and kidney syndrome in chickens: dynamics of glucose metabolism.

1. Fatty liver and kidney syndrome (FLKS) was induced in a proportion of a group of 4-week-old chickens by giving a diet of meat meal and wheat; inclusion in the diet of animal tallow for 54 h substantially reduced the occurrence of FLKS. 2. Measurements of dynamic aspects of glucose metabolism were made with single injections of [2-3H]glucose which indicated that birds given the 'FLKS-inducing' diet and showing physical symptoms of FLKS had significantly lower rates of synthesis of glucose than birds given either the same diet supplemented with tallow or a commercial diet. 3. In a second series of experiments glucose metabolism was studied in birds (1) with or without physical symptoms that were given the 'FLKS-inducing' diet and (2) birds given the same diet supplemented with tallow or biotin. Affected birds fed the 'FLKS-inducing' diet had significantly lower plasma glucose concentrations, pool sizes and synthesis rates than birds fed the same diet and not showing symptoms, or birds fed the supplemented diets. 4. It is suggested that the cause of death in birds with FLKS is a low rate of gluconeogenesis during periods without feed which results in a lack of glucose to meet essential functions.


The relationship between rumen bacterial growth, intake of dry matter, digestible organic matter and volatile fatty acid production in buffalo (Bos bubalis) calves.

1. The production rates of bacteria in the rumen of buffalo (Bos bubalis) calves were estimated using an isotope-dilution technique. A series of fifteen experiments was done with animals given green maize and nine experiments with animals given cowpea (Vigna unguiculata). 2. The turnover time ranged from 205 to 567 min in the group given green maize and from 330 to 648 min in animals offered cowpea. The production rates of bacteria were (mean +/- SE; g/d) 145.77 +/- 7.240 and 237.09 +/- 11.847 in animals given green maize and cowpea respectively. 3. There was a significant correlation between bacterial production rates and dry matter intake, digestible organic matter and total volatile fatty acids formed in the rumen. 4. Regression equations obtained for the two foodstuffs were different suggesting that the bacterial growth rate may vary depending upon the quantity and quality of foodstuff digested and possibly the ratio nitrogen:energy of the foodstuff.


Anthropometric studies on African athletes who participated in the 1st African University Games.

1. Height, weight, skinfold thicknesses and mid-arm circumference were measured in 540 males and 117 females aged 20-24 years who took part in the 1st African University Games, held at the University of Ghana, Legon. Body fat content, Quetelet's index (weight divided by height X 100; Khosla & Lowe (1967)) and mid-arm muscle circumference were derived from the measurements taken. 2. The physique or body-build of the subjects as assessed by Quetelet's index showed that both male and female subjects from the various countries were of medium body-build. The body fat content for males was between 10 and 12% with the exception of the Egyptians (12.8%) while that of females was between 23-24%. 3. Body measurements of the subjects compared favourably with that of international standards (WHO, 1966) with the exception of the triceps skinfold thickness which was only approximately 60% of the standard value. 4. The low values for triceps skinfold thickness are probably due to differences in the distribution of subcutaneous fat at different sites in the body as found between caucasian and non-caucasian population groups. The results are discussed in relation to the findings of other workers on ethnic differences in skinfold thickness.


Design and development of a long-term rumen simulation technique (Rusitec).

1. The paper describes the development and construction of an apparatus for maintaining a normal microbial population of the rumen under strictly controlled conditions over long periods of time. 2. The apparatus is simple to construct and operate. It is possible to do four replicate experiments at the same time. 3. The results of three experiments are given. The experiments showed that when the steady-state was reached it could be maintained indefinitely, with the type and quantities of products of fermentation very similar to those in the rumen of donor animals, including the maintenance of normal protozoal populations for up to 49 d. 4. It was found that within wide ranges, the digestibility of rations and the output of products were independent of dilution rate. 5. Except for the lowest 'level of feeding', the digestibility was independent of the level of feeding. The output of products was proportional to the amount of food digested and was the same as would be expected in sheep on similar rations. 6. An experiment in which a ration of hay was changed to a mainly concentrate ration showed that the fermentation characteristics were determined mainly by the food given.