Myocarditis of probable viral origin in chickens.

Severe nonsuppurative myocarditis with Feulgen-positive intranuclear inclusions in six adult White Leghorn chickens is described. Livers of three birds had mild to moderate centrilobular coagulative necrosis, with no inclusions. The myocardial intranuclear inclusions contained a large number of 18-to-20-nm particles; these are compared with members of the family Parvoviridae.


Studies on the pathogeneis of tibial dyschondroplasia in chickens. IV. Some features of the vascular supply to the growth plates of the tibiotarsus.

Several features of the vascular supply to the growth plates of the tibiotarsus were compared in two strains of broiler chickens selected for a high and low incidence of tibial dyschondroplasia. No difference was found between the two strains in the area of the proximal growth plate of the tibiotarsus or in the distance of the nutrient foramen from the same growth plate. Vascular tunnels invading the zone of hypertrophy were significantly fewer in the proximal growth plate than in the distal growth plate, and tunnels invading the zone of hypertrophy of each growth plate were also fewer in the high-incidence chickens than in the low-incidence chickens.


Effects on feed consumption and egg production of coffee bean seed (Cassia obtusifolia) fed to White Leghorn hens.

Coffee bean seed (Cassia obtusifolia) was ground and mixed in the feed at levels of 2,5, and 10% and fed to White Leghorn hens. Feed consumption and egg production were reduced by all three although more so at 5 and 10%. Feed consumption and egg production had not returned to control levels four weeks after the adulterated feed was suspended, though the response was more pronounced in the younger birds. The semitendinosus and pectoralis superficialis muscles were pale and edematous at postmortem examination of the birds, being most pronounced at the 5 and 10% levels.


Production and properties of hemagglutinin of Haemophilus gallinarum.

Production of hemagglutinin (HA) of Haemophilus gallinarum was compared in some media, and its properties were studied. HA was produced in Kato's media, brain heart infusion (BHI) broth containing beta-diphosphopyridine nucleotide, and chicken meat infusion (CMI) broth. The HA in CMI broth different according to the concentration of the chicken serum; no HA titer was found in 0.5% or more chicken serum, but HA was activated by storage in a refrigerator. Cells of H. gallinarum cultured for a long time had markedly decreased HA titer. A weak HA was produced in blood and Kato's agars, but no titer appeared in CMI and BHI agars. HA of H. gallinarum was heat-labile and inactivated by formalin, ethanol, methanol, and ethyl acetate. On the other hand, HA was resistant to chloroform, acetone, and some enzymes. Moreover, the HA titer of cell cultured in CMI broth was enhanced by hyaluronidase. H. gallinarum in Kato's and BHI broths were pleomorphic rods with or without a capsule, but were capsulated ovoid cells in CMI broth, according to electron microscopy.


Spatial and temporal processing in patients with Turner's syndrome.

Thirteen females with Turner's syndrome were examined for spatial abilitles and serial processing, and their performance was compared with that of normal females matched by age, intellignece, and socioeconomic class. Patients with Turners's syndrome performed significantly poorer on tests of spatial ability than controls, but only on spatial tests requiring the integration of isolated elements as synthetic wholes or the remembering of spatial configurations which could not be verbally mediated. Patients also performed less well than controls on tasks of serial processing when the tasks could not be mediated verbally.  2t was concluded that patients with Turner's syndrome may have a selective deficit in cortical functions that are lateralized to the right cerebral hemisphere.


Neonatal androgen injection changes open-field behavior of mice.

Newborn female mice of the C57BL/6J and BALB/cJ inbred strains and their reciprocal F1 hybrids were injected either with testosterone or with oil vehicle alone. Both the repeatablity and mean level of open-field activity scores over a 10-day test period increased in hormone-injected animals compared with controls. Increased activity due to hormonal treatment was greater in hybrid females than in inbred females. There was no consistent effect of hormonal treatment on open-field defecation.


Concerning the origin of handedness in humans.

The origin of right-handedness as the predominant chirality in humans seems to be related to the tendency of human (and presumably prehuman) mothers to hold infants on the left side. The latter practice has previously been ascribed to imprinting and the soothing sound of the mother's heartbeat on the infant. Given the practice of holding the child in this manner, dextral mothers will be more skillful at manipulation of objects and selectively favored.


Aging and frequency-dependent mating in Drosophila.

Frequency-dependent mating behavior has been observed in Drosophila pseudoobcura, but most experiments have used only 4-day-old  virgin flies. One report has indicated that rare-male behavior may be affected by age. Males and females of the Arrowhead strain along with rare orange-eyed males were used in the present study to confirm that frequency-dependent mating behavior is operating with 4-day-old females but is absent by 11 days. The same situation is also observed when Chricahua males and females are used along with rare Arrowhead males.


Direct positive inotropic effect of mannitol on the intact canine heart.

Infusion of 25% mannitol into either the circumflex or left anterior descending coronary artery caused a significant increase in myocardial force development, measured by means of strain gauge in 10 anesthetized dogs. The changes were confined to the area perfused. The increase in developed force was dose-dependent, 20% at an infusion rate of 0.55 ml/min, 28% at 1.4 ml/min, 32% at 2.8 ml/min and 57% at 5.5 ml/min. There was a similar increase in dF/dt. The increase in developed force in the first minute was also dose-dependent, being 9% at 0.55 ml/min and 40% at 5.5 ml/min. No change in developed force occurred in the control (non-perfused) area or during saline infusion of the same artery at similar rates. A decrease in developed force of 10.5% was observed after the initial rise when mannitol was infused at 5.5 ml/min. This effect did not completely abolish the initial increase. No change in blood pressure, heart rate, LV systolic and diastolic pressure of LV dp/dt occurred during the experiment. It is concluded that doses of mannitol which are in clinical use have a direct positive inotropic effect on the intact canine heart.


Effects of acetylcholine on the regional distribution of microspheres in the skeletal muscle of the cat.

The present experiments were performed to study the question whether intraarterially infused acetylcholine changes in local tissue perfusion of the skeletal muscle. In experiments on cats the triceps surae muscles were isolated. While acetylcholine (0.5 mug/kg X min) was infused intraarterially on one side, the opposite side was taken as control. 4 minutes after the start of the infusion non-radioactive microspheres of 15 mum diameter were injected into the ascending aorta. Subsequently the muscles were freeze-sectioned into 1.0 mm thick slices and cleared by sodium hydroxide and glycerine. The concentration of microspheres per mm3 was measured in representative cross sections of the muscle. Higher concentrations of microspheres were observed in the proximal than in the distal slices of the acetylcholine-treated side. The distribution of microspheres was found to be different in the segments as well: higher values were found in the central than in peripheral segments. The untreated side showed a qualitatively similar state. The differences in the distribution pattern, however, were smaller than in the acetylcholine-treated muscles. It is concluded that the increased inhomogeneity of the regional perfusion observed in this study during vasodilation corresponds to the results reporting a changed nutritive tissue perfusion during an acetylcholine treatment.


Heat production and oxygen consumption of the isolated rabbit heart: their relation to mechanical function.

A method is described for simultaneous determination of the heat production and the oxygen consumption of the isolated, isovolumetrically beating rabbit heart. The perfusion of the heart was performed via the aorta at a constant flow rate with carbogen saturated Tyrode's solution at a temperature of 37.0 degrees C. Heart function was varied by stepwise augmentation of the left intraventricular volume (LVV) by means of a balloon catheter. The following mechanical parameter of heart function were determined: enddiastolic pressure (EDP), peak pressure (PP), developed pressure (DP), max. contraction and relaxation velocity (dP/dt-A and dP/dt-B), enddiastolic tension (Tens-EDP), peak tension (Tens-PP), developed tension (Tens-DP), and circumferential tension (Tens-Cir). DP, dP/dt-A and dP/dt-R showed a maximum response to changes of the LVV at 2.0 ml LVV and 19.3 mm Hg EDP. Heat production (H) and oxygen consumption (Q) were correlated closely to mechanical function and to each other (r = 0.89, n = 8). The ratio H/Q was 4.9 cal/ml O2 and remained constant during the experiment. The myocardial energy consumption was significantly correlated toall contraction parameters with the best fit to DP and Tens-Cir (r = 0.934 and 0.933 resp.). On the basis of the calculated mean regression lines, the function-independent and the function-dependent energy consumption were calculated.


Norepinephrine, potassium and overdrive suppression.

The influence of norepinephrine on ventricular overdrive suppression and attendant potassium shifts has been studied in isolated perfused canine hearts with complete atrioventricular block. It was found that: 1) there is a potassium loss during the drive and a potassium uptake after the drive); 2) reducing the driving rate from 240 to 120/min decreases potassium loss; 3) norepinephrine increases potassium uptake and spontaneously beating ventricles and during the recovery from 120/min drive; 4) norepinephrine enhances K loss during and after a 240/min drive; 5) norepinephrine shortens the overdrive pause under all the conditions tested; 6) in ventricles driven at a constant rate, norepinephrine causes a small loss of ptoassium; 7) reserpinized hearts show a small potassium loss during drive and a larger potassium uptake after drive; yet, the suppression is longer; 8) norepinephrine increases K loss with drive and decreases overdrive suppression in reserpinized hearts; 9) norepinephrine enhances the increase in oxygen consumption caused by overdrive; and 10) norepinephrine antagonizes the depressant effect of high [K]0 on automaticity. It is concluded that norepinephrine shortens the pause independently of potassium levels and antagonizes the inhibittory influence of high K. The effect or norepinephrine on K movements depends on the ventricular rate and such rate-dependence is related to oxygen availability with respect to the increased metabolic demand.


[Impedance cardiography, a method to evaluate quantitatively cardiac output? Comparison with the Fick principle (author's transl)].

In 36 children without shunts nearly 280 electrical impedance measurements were carried out in order to estimate the accuracy of the impedance cardiography as a means of calculating output. During evaluation up to 22 combinations of test conditions and possibilities of evaluation per child were tested. As a reference method the Fick Principle was used. The reproducibility of impedance measurements showed itself to be high, but no agreement of the results by impedance cardigraphy and corresponding values by the Fick method could be found. Some reasons give rise to suppose that impedance cardiography only reflects changes in the intrathoracic fluid level occurring during heart action from which because of formal reasons no interference should be drawn about the original cardiac output. Besides physical arguments tell against the possibility of picking up these volume-changes quantitatively by analyzing transthoracic electrical impedance.


[Mitral valve and mitral ring movement in mitral stenosis. An ultrasonic study with different valve models (author's transl)].

We constructed three different mitral valve models in order to investigate the different mechanisms which account for the concordant opening and closing movement of the posterior compared to the anterior mitral valve in mitral stenosis. Three different types of movements are possible: a dorso-anterior movement of the mitral ring, opening and closure of the valve itself and a rotation of the entire valve apparatus. Our in-vitro studies showed that the best explanation for the concordant diastolic movement of the posterior valve is given by the assumption that during the early diastolic opening phase of the valves the whole stenotic valve apparatus is rotated upward, i.e. towards the transducer. This rotation, has a higher amplitude compared to the residual downward-oriented opening movement of the posterior valve.


[Influence of electrical stimulation of the heart on coronary circulation (author's transl)].

Coronary perfusion was measured in anaesthetized dogs under sinus rhythm, after creation of an acute AV-block, and during pacing of the heart at frequencies of 60 to 150 min-1. With increased heart rate coronary perfusion was enhanced. The close relation between heart rate and coronary perfusion is not influenced by artificial stimulation. The improvement in coronary circulation under pacing after creating of the A-Vblock is due exclusively to the rise in heart rate.


The release of calcium from cardiac mitochondria: the importance of the calcium-protein ratio.

Using a DW 2 dual wavelength spectrophotometer (AMINCO) and murexide as a Ca2+ sensitive indicator it is shown that guinea-pig heart mitochondria can release accumulated Ca2+ without the influence of non-physiological material. The main factor which decides if accumulated Ca2+ is spontaneously released is the Ca2+/mitochondrial-protein ratio. Under appropriate assay conditions a critical intramitochondrial Ca2+ concentration is reached. Increasing this concentration leads to Ca2+-release.


[Glomerular filtration rate in newborn infants with idiopathic respiratory insufficieny syndrome (IRDS)].

The speed of glomerular filtration (GFR) was studied in 16 healthy newborns and in 19 with idiopathic respiratory insufficiency syndrome (IRDS). It turned to be 30.22 +/- 10.23 ml/min/1.73 m2 for healthy cases and of 17.49 +/- 9.71 for those with IRDS; significant dirrerence (p less than 0.001). The same situation was true when preterm or healthy full term cases were compared with those with IRDS. No correlation was shown among GFR with the degree of hypoxemia, hypercapnea or acidosis and even if GFR was 13.89 +/- 10.40 ml./min/1.73 m2 in infants with IRDS who died, if compared with 19.32 +/- 9.17 in those who survived, the difference was not significant. At the end, it is concluded that infants with IRDS have decreased GFR, but the constitutents participating in the phenomenon have not been yet identified.


[What is wrong with the measles vaccine in Mexico? Study of an epidemic outbrake of measles].

The study included 205 children with measles seen after an epidemic outbreak in Distrito Federal during the first six months of 1976. 65.8% of the cases had not been given specific immunization and out of the 70 vaccinated cases (34.2%), one half of them were under one year old and were not given re-enforcement afterwards. The clinical picture suffered no changes in vaccinated children, 40% of infants showed initial exanthema on chest and abdomen with centrifugal distribution and in 41.5% of them, diarrhea appeared during the prodromal period. The most outstanding elements of this epidemic outbreak were the high number of sensible cases and the high percentage of children vaccinated before the age of one year and who were not later given re-vaccination. Indequate handling of the vaccine or combination of vaccine withe gammaglobulin used in 1969 and 1970, are also mentioned as a possibility to explain failures of the vaccine in ths group of well vaccinated children.


[Use of mannitol and dexamethasone in the management of acute cerebral edema of infectious origin].

The study included 22 patients with meningoencephalitis and hypertensive cranial syndrome from cerebral edema. Mannitol was given to 13 cases and dexamethasone to 9. There were three therapeutic failures in the group given mannitol and none in that of dexamethasone (p greater than 0.05). Both drugs showed similar effect in the duration of the hypertensive cranial syndrome (39-44 hrs). Patients treated with mannitol showed hyponatremia after 48 hours. No untoward effects appeared in patients given dexamethasone.


[The Wilson-Mikity syndrome. Report of a case].

The case of an infant with Wilson-Mikity syndrome is reported; both the clinical evolution and the radiological findings were characteristic and the diagnosis was confirmed at autopsy. Etiology, differential diagnosis, supportive treatment and care of complications are discussed.


[Cholestyramine in a case of a prolonged diarrhea after a partial ileocolectomy].

The author reports the case of a 10 years old female child with history of retrocecal appendicular abscess complicated with terminal ileum and right colon necroses which called for partial ileocoletomy. Following this operation, the patient presented diarrhea which caused a loss in weight of 6 kgs. in two months. Antiacids and diphenoxylate were given with negative results. A low fat diet was then given and the patient recovered 1 kg. in weight, but the diarrhea persisted with high excretion of fats. Thereupon, cholestyramine and a normal diet were given followed, within the next 48 hours, by a remission of the diarrhea; the weight loss was recovered within the next 3 months. At present, the patient is still taking very small doses of cholestyramine with a normal diet.


[Acrodermatitis enteropathic treated with zinc sulfate. Report of a case].

A case is reported of a girl with acrodermatitis enteropathica who was treated succesfully with zinc sulfate at 75 mg/day PO. A remarkable increase in weight was evident through the course of 12 months of treatment, reaching the percentile 50 by the age of 3 years; however the height remained close to percentile 3. Possibly, the zinc deficiency is secondary to a selective defect in the metal absorption. Treatment with zinc sulfate in these patients substitutes with greate advantages the use of diiodohydroxyquin. Possibly, zinc supplements must be given for a life time to these patients.


[New aspects in the classification of the nutritional status].

Considerin recent advances in nutrition somatometry the authors set forth the necessity to bring up to date Gomex's classification with the idea to incorporate other parameters, besides weight, in its application. To this respect, they propose the use of standard deviation as unity to measure the differences between actual values and those taken as reference patterns. Such system offers the advantage to make applicable to all ages the classification mentioned and to obtain an easier and more realistic somatometric comparison among different groups. Other considerations are made on the use of Gomez's classification and examples are set to base their propositions with data from a somatometric inquest.


[Hemorrhagic disease of the newborn. Analysis of 50 cases].

The study included 50 cases with this disease which were divided into 2 groups: above and under 2,500 g. A relationship was established among weight and bleeding site, type of delivery, prothrombin activity and lethality. It was found that those under 2,500 g. bled earlier than those above 2,500 g. With higher percentage, the bleeding site was the digestive tract in both groups. Most of both groups bled between the 2nd and 6th day and a group of special interest was made up of 8 patients who bled between the 10th and 28th day of life and that we included as hemorrhagic disease of the newborn because bleeding appeared within the neonatal stage; these patients fell within the group showing the lowest prothombin activity. Bleeding within the central nervous system was frequent and showed the highest lethality.


[Focal sclerosing and segmentary nephropathy in children].

The cases of 23 nephrotic children in whom percutaneous renal biopsies or postmortem studies showed focal and segmentary sclerosis were reviewed. It was more common in males and the average age at the onset was 6 years. The main symptoms were edema, hematuria and unspecific general manifestations. On admission, nephrotic syndrome was present in 91% of the cases and in a lesser proportion, edema hematuria and high blood pressure were found. The lesion was diagnosed at the first biopsy in 19 cases and in 4, subsequent biopsies or postmortem studies supported the diagnosis. Only 9 out 21 patients treated showed response to steroids and 5 of the resistant cases were given cyclophosphamide, but only one responded. They were checked at different periods of time ranging from 7 months to 10 years and by the end of the study, 11 patients were still under control showing normal renal function in six of them; 4 other cases showed mild renal insufficiency and in the remaining one, there was moderate renal insufficiency. Two died. A good correlation was evident between response to steroids and conservation of renal function. The findings are compared to those from other authors and emphasis is placed on the need to suspect the entity when a nephrotic syndrome with minimal changes is resistant to steroids, or when persistent hematuria is present; also, in cases showing initial lesions of tubular atrophy or interstitial fibrosis.


[Somatometry in the full-term newborn infant (preliminary report)].

As a preliminary comunication, the authors report a somatometric study carried out in 315 full term newborns from different socioeconomic situation; 152 were born at the Hospital General, S.S.A. and 163, in a private hospital where middle and high class families are attended. The information is grouped on whether measurements are related to physical growth, th state of nutrition or to physical development. Several conditions which necessarily must be taken as independent variables in a study of this sort, such as the age of the parents, but specially of the mother, the period of gestation and of course, the socioeconomic level, were analyzed. The finding of up to 17% of case with height under 47 cm. and/or weight under 2,500 g., outstands the necessity to study the homeorrhesis phenomenon as a very important detail in this type of material.


[Asymptomatic nephritis in relatives living with children with acute poststreptococcal glomerulonephritis].

We studied a group of 114 persons living together with children admitted in the hospital because of poststreptococcal glomerulonephritis; minute count of the urinary sediment, antistreptolysin 0 and throat culture were done. An increased was found in the urinary excretion of erythrocytes in 31% of the population studied; 71% showed a rise of serum antistreptolysin 0 and 9% showed beta hemolytic streptococci in their throat culture. It is important to search for these asymptomatic patients among relatives and follow their course; there is a possibility that some will developed chronic nephritis. It is also important to erradicate the streptococcal infection.


[Surgical management of intestinal atresia].

The study included 33 newborns with the diagnosis of intestinal atresia after discarding those of the duodenum. According to the clinical conditions of the patient and of the malformation, surgery was carried out by derivative ileostomy or primary anastomosis. Survivorship reaches 67% for ileostomy and 65% for anastomosis which are much higher figures than those obtained before.


[Economy of coupons: its application to a program of weight reduction in adolescents].

The results obtained in a group of 12 obese adolescents are reported. They were managed following a motivational system called economy of coupons with the purpose of obtaining a drop in the overweight they showed. The study was divided into three stages: A, B and C. Only stage B included the experimental variable (economy of coupons). The patients kept a notebook with daily records of weight, diet and physical exercise to be evaluated by the research workers. If they reached the goals set for them, they were given strengthening stimuli to support such activity. From the analysis of the group for the body weight and its statistic comparison, it was found that in the A - B interaction, the "p" level was significant in the weight loss. In the B - C interaction, the value for "p" was less than 0.05 in relation to the ponderal increment and in A - C interaction, there was no significance. From this study, the evidence showed that results of A - C interaction were poor and therefore, rehabilitation was not obtained. From the above results, the inclusion of a fourth stage is suggested for further studies where the application of economy of coupons would gradually disappear until a desired behavior is maintained.


Comparison of the effects of labetalol and propranolol in healthy men at rest and during exercise.

1. Oral labeltalol and propranolol have been compared in healthy men with regard to the effects on heart rate, blood pressure and peak expiratory flow rate (PEFR) at rest and the changes induced by exercise. 2. Labetalol caused a dose-related reduction in standing diastolic pressure at rest whereas propranolol did not but neither drug altered standing systolic pressure at rest. 3. In the doses compared, propranolol was consistently more potent than labetalol in influencing blood pressure changes induced by exercise, in lowering heart rate at rest and reducing PEFR at rest. 4. Labetalol and propranolol are both beta-adrenoreceptor antagonists and the observed differences in the profiles of the two drugs are probably directly related to the additional alpha-adrenoreceptor blocking property of labetalol not possessed by propranolol. Because of these differences labetalol may be expected to have advantages in the treatment of hypertension.


[Toxoplasmosis. Anatomo clinical characteristics and morphological indentification of the parasite using the silver-impregnation technic].

The clinical and anatomicopathological characteristics of acute and chronic toxoplasmosis are described as they affect different structures and systems. The lesion to adrenal glands is compared to that seen in disseminated herpes simplex; however, the question remains as to why in both congenital infections, necrosis of adrenal glands appears without inflammatory reaction. The investigation of special techniques for localization and identification of Toxoplasma gondii "groups" or cysts, leads to the conclusion that Grocott's silver impregnation technique used for the identification of Entamoeba histolytica is also useful to discover Toxoplasma in tissues.


Acute haemodynamic effects of metoprolol in hypertensive patients.

1. The acute haemodynamic effects of metoprolol (0.15 mg/kg body weight) intravenously were studied at rest and during exercise, in a recumbent position in five patients with arterial hypertension of WHO Stage 1 or 2. 2. Significant decreases in heart rate, cardiac output and arterial blood pressures, both at rest and during exercise, were seen. There were no changes in the calculated stroke volume or systemic vascular resistance. 3. The apparent absence of any relative preponderance of the alpha-adrenoreceptors after acute beta-adrenoreceptor blockade with metoprolol warrants further studies on metoprolol in arterial hypertension.


[Intestinal immunoglobulins in children without infection].

Immunoglobulins in duodenal content were measured by immunodiffusion in children without infection. Two groups were studied: group I with 11 infants 1 to 35 months old without infectious problems and group II with 14 children 3 to 13 years old who one month previously had suffered typhiod fever. Two groups of commercial plates were used both designed to detect low levels. The plate for values of 1 to 10 mg. % was selected for the study. Secretory IgA (IgAS) was determined using a standard of human colostrum. Total proteins were measured by Biuret's method. The values obtained in Group I were: 2.3 +/- 0.44 for IgAS, 4.9 +/- 1.29 for IgM, 2.3 +/- 1.0 for IgG and 461.09 +/- 160.89 mg. % for total proteins. In Group II, in the same order, the values were: 2.28 +/- 0.59, 3.70 +/- 0.98, 1.57 +/- 0.37 and 333.91 +/- 64.63 mg.%. No sataistically significant difference was found for any of the values mentioned when comparison between the two groups was made; therefore, when values for the two groups were added, the final results were: 2.29 +/- 0.35 for IgAS, 4.23 +/- 0.74 for IgM, 1.89 +/- 0.45 for IgG and 389.86 +/- 70.53 for total proteins. Between serum and intestinal IgA (r = 0.11), there was no correlation. No statistical difference was either found when grouped by sexes or ages (less than 3 and greater than 3 years). It is concluded that the method applied allows the use of very small amounts of the sample, avoids the inconveniences of concentration, is available to any laboratory and permits detection of values as low as 0.5 mg. %.


Effects of (+) and (-)-propranolol on the responses of the human isolated basilar artery to cerebrospinal fluid obtained from patients with subarachnoid haemorrhage and cerebral arterial spasm.

1. The human isolated basilar artery has been used as a model to investigate the aetiology of cerebral arterial spasm associated with rupture of intracranial aneurysms. 2. The isolated artery is contracted by 5-hydroxytryptamine, noradrenaline, six prostaglandins and cerebrospinal fluid from patients with ruptured aneurysms and cerebral arterial spasm. 3. These contractions are reversed by (+/-)--, (+)-- and (--)-propranolol in concentrations known to produce local anaesthetic effects on isolated frog sciatic nerve; the (+) isomer was 2.5 to 10 times more potent (-)-propranolol in antagonising all contractions. 4. As the two isomers are known to have similar local anaesthetic potency but (-)-propranolol has greater beta-adrenoreceptor blocking effects we conclude that the antagonistic effects described do not involve beta-adrenoreceptor blockade. 5. The data indicate that propranolol may be of clinical use in reversing cerebral arterial spasm.


[Continuous infusion of heparin in newborn infants with disseminated intravascular coagulation].

This study was carried out in ten infants with DIC who were given heparin at the rate of 100 U. per kilogram of body weight and per day in continuous perfusion. Successful therapeutic results were achieved in nine cases made evident by recovery and quick clinical control of their DIC condition, shown by normalization of hemostatic and fibrinogen tests and negative paracoagulation tests.


Enzyme induction and renal function in man.

1. In a previous study in rats, an increased PAH clearance was found following chronic phenobarbitone administration. These results formed the basis for the present study in which fifteen healthy male volunteers were investigated and the parameters of liver microsomal enzyme activity and renal function were measured. 2. As parameters of liver microsomal enzyme activity, the antipyrine elimination in the plasma, the gamma-glutamyl-transpeptidase and the D-glucaric excretion in the urine were measured. Endogenous creatinine clearance, 51Cr-EDTA and 125I-Hippuran clearance were determined as measurements of renal function. 3. No correlation was found between any of the parameters of microsomal enzyme activity and renal function. 4. Of the fifteen volunteers, seven having a mean antipyrine half-life of 13.3 h were given antipyrine (500 mg) daily for 3 weeks. Afterwards all measurements of liver microsomal enzyme activity and renal function were repeated. The antipyrine half-life decreased to 8.5 h, while the antipyrine clearance was increased by about 56%. gamma-glutamyl-transpeptidase and D-glucaric acid were also significantly increased, while renal function remained unchanged. 5. Therefore, an increased PAH-clearance, as found in the rat, is not obtained in man following induction of liver microsomal enzyme activity.


[Characteristics of the spinal fluid in the neonatal stage].

The characteristics of the cytochemistry of the spinal fluid (LCR) were evaluated in 123 newborns that were divided into four groups according to their postnatal age. Following this, proteins were 103.25 +/- 49.05; 85.09 +/- 41.89; 66.31 +/- 43.44 and 55.38 +/- 20.91 mg/100 ml. respectively for the 10, 20, 30 and 50 days of life groups, with significant differenece (p less than 0.01) of the first group with the third and fourth. Values for glucose fluctuated form 53.56 +/- 20.32 mg/100 ml. to 63.16 +/- 22.80 for the different groups, but without statistical difference among them. A similar situation was found with the number of cells that fluctuated as an average form 4.28 to 7.38 mm3. Finally, the results from other work groups are reported showing similar outcome as ours.


[Humoral immune response in hepatic and intestinal amebiasis in children].

The various classes of immunoglobulins with antibody function against E. histolytica were studied in 8 children with amebic liver abscess and in 7 with acute intestinal amebiasis. The predominant fraction was IgG in 7 patients from the first group and in 1 from the second; this suggests a secondary type humoral immune response which implies a previous experience with E. histolytica antigens. A definitive predominance of IgM was shown in a patient with amebic liver abscess, the same as in primary humoral immune response. Humoral antibodies did not develop in the remaining 6 patients with acute intestinal amebiasis. The disparateness of the humoral immune response found in these cases make it difficult to speculate on the role of immunoglobulins in the pathogenesis or in immunologic protection in amebiasis. Possibly, the most important is the participation of cellular immunity.


Fate of [14C]-bumetanide in man.

1. The fate of bumetanide was studied in four healthy volunteers both after intravenous oral administration of [14C]-bumetanide (0.5 mg). 2. The absorption of oral [14C]-bumetanide was rapid (absorption half-life 0.61 h) and complete with a urinary recovery of about 80% of the intravenous or oral dose during 48 h. 3. The elimination of [14C]-bumetanide was rapid with a half-life of elimination (T 1/2 beta) of 1.5 h. 4. Protein bound fraction of [14C]-bumetanide in plasma was 95%. No bumetanide was found in red blood cells. 5. Four metabolites of [14C]-bumetanide were found in urine. Together they accounted for about one third of the radio-activity excreted into urine during the first 6 h after the administration of the drug. 6. Bumetanide is rapidly and completely absorbed from the gastrointestinal tract, bound extensively to plasma proteins, metabolized to some extent and excreted rapidly, principally into urine.


[Analysis of 50 cases of Lomotil poisoning in children].

The authors reviewed the clinical histories of 50 children admitted to the Emergency Department of Hospital de Pediatría, C.M.N., I.M.S.S. from 1971 through 1975, with the diagnosis of lomotil intoxication. No differences were found as to sex. Frequency was greater at ages from 2 to 3 years from accidental mechanism, which increased between 1973 to 1975. Lethality was similar to that reported by other authors. In the clinical picture, the depressive action of diphenoxylate and the anticholinergic action of atropine were outstanding, without being possible to establish the limits between the two, with somnolence and flushness as main symptoms. The treatment given followed the purpose to eliminate the toxic: emesis, gastric washing and in cases of respiratory depression, naloxone was given. Therefore, it is concluded that since the value of lomotil in the treatment of diarrhea has not been proved and that the risk of its administration is greater than the benefit, this product should be proscribed, specially for pediatric use.


Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid-containing regimens.

1. The acetylator phenotype of over 600 pulmonary tuberculosis patients treated with intermittent isoniazid-containing regimens in two controlled clinical trials was determined using either sulphadimidine or a slow-release isoniazid formulation. 2. Both methods unequivocally classified over 99% of the patients as being either slow or rapid acetylators. 3. Rapid and slow acetylation did not differ in their ability of hydrolyse acetylisoniazid to isonicotonic acid plus monoacetylhydrazine, or to conjugate isonicotinic acid with glycine. 4. Rapid acetylators acetylated the monoacetylhydrazine liberated in vivo more rapidly than slow acetylators, demonstrating that this compound is also polymorphologically acetylated in man. 5. The acetylator phenotype of the patients was without prognostic significance when they were treated on a twice-weekly basis with isoniazid plus streptomycin plus pyraziniamide, or with isoniazid plus rifampicin. However, when patients were treated once every week for 12 months with isoniazid plus rifampicin, 5% of the rapid acetylators had an unsatisfactory response as contrasted to the complete success of the treatment in the slow acetylators.


The pharmacokinetics of ciclazindol (Wy 23409) in human volunteers.

1. The pharmacokinetics and metabolism of ciclazindol, a potential anti-depressant drug, have been studied after oral administration of the compound to male and female volunteers. 2. The mean +/- S.E. mean maximum plasma concentration of the unchanged drug was 422 +/- 31 ng/ml. This level was seen between 2 and 4 h after dosing. 3. Elimination of the ciclazindol from plasma was apparently monexponential with a half-life of approximately 32 h. A large proportion of the drug-related substances in the plasma was unchanged drug. 4. Excretion of radioactivity took place predominantly via the renal route, less than 15% of the dose being recovered in the faeces. The urinary elimination process was apparently monoexponential with a half-life of 28 h. 5. Daily dosing with ciclazindol for 3 weeks did not appear to induce the enzymes of its own metabolism.


Ethical review in the pharmaceutical industry.

1. There seems no reason why clinical pharmacology studies conducted within the pharmaceutical industry should be exempt from the requirement of ethical review, and independent review in this situation reduces the vulnerability of the company and its employees, in addition to serving its primary function of protecting the volunteer subjects. 2. Experience within one company has shown that independent ethical review need not seriously influence the pace of research. 3. It is important that such committees should be seen to be independent and competent.


The periodontal membrane in systemic sclerosis.

The periodontal membrane is markedly involved in about 30% of patients with systemic sclerosis and some widening occurs in about 20% of the teeth at risk. Thickening of the periodontal membrane is not specific to systemic sclerosis and can occur with clinically obvious chronic periodontal disease and, to a mild extent, in normal individuals in whom it mainly involves the coronal third of the teeth. In systemic sclerosis the whole root is more likely to be involved. There is no direct relationship in systemic sclerosis between widening of the periodontal membrane and other systemic changes, and prognosis.


A method to facilitate the isolation and handling of stratum corneum.

A specially designed frame is being used in this laboratory to facilitate the isolation and handling of human cadaveric stratum corneum of the upper back. Although it is in the early stages of use, the ease of isolation and subsequent handling of the stratum corneum has prompted the writing of this short report.


Actinic keratoses and the epidermis on which they arise.

The appearance of the epidermis and epidermal autoradiographic labelling indices were compared in actinic keratoses and paralesional skin in seventeen patients after injection of tritiated thymidine. The skin on the buttock area was also studied as a "non-sun exposed" control. Labelling indices obtained from skin removed after 1 hwere as follows: actinic keratoses 17-4%; paralesional skin 11-2%; buttock skin 5-4%. Many of the epidermal cells in the keratoses that incorporated tritiated thymidine were bizarre and not restricted to the basal or suprabasal regions but were scattered through the thickness of the epidermis. Paralesional skin also showed epidermal thickening and cytological abnormalities including the formation of multinucleate epidermal cells. These findings suggest that the development of actinic keratoses takes place in epidermis that is itself abnormal. The changes suggest that there is a gradual stepwise progression of sun damage epidermis via the clinically obvious keratosis to squamous cell epithelioma.


Epidermolysis bullosa hereditaria letalis: pathology, natural history and therapy.

A patient with epidermolysis bullosa hereditaria letalis had the characteristic electron microscopic lesions not only in the skin, but also in the gastro-intestinal, genito-urinary and respiratory tracts. Administration of dexamethasone to this patients resulted in a significant decrease in the blistering. Although the patient died, long term survival in this disease is not rare. We report that staining tissue specimens from patients with epidermolysis bullosa with fluorescein-labelled bullous pemphigoid antibody is a reliable method for differentiating between junctional and dystrophic disease.


Lupus erythematosus hypertrophicus et profundus.

A patient with a sudden onset of severe lupus erythematosus hypertrophicus et profundus was noted to have extensive serological abnormalities; in addition to antinuclear antibody, leukopenia, anaemia, decreased serum complement, abnormal renal function, and positive immunofluorescence, she also had antibodies against clotting factors.


Lupus erythematosus profundus (Kaposi-Irgang) with monoclonal gammopathy.

The appearance of subcutaneous nodules of lupus erythematosus profundus on the face and neck of a woman with a long history of lupus erythematosus (LE) is reported. Of note were the three distinct stages in the course of the disease: (1) discoid LE, first appearing at the age of 42; (2) systemic LE, appearing 10 years later; (3) LE profundus, appearing 21 years after the diagnosis of discoid LE was made. The finding of monoclonal gammopathy is of particular interest, although its relationship to the basic disease has not been clarified.


Transepithelial elimination in necrobiosis lipoidica.

Elimination of necrotic material through the hair follicle as a means of excretion has been observed in three cases of necrobiosis lipoidica. Clinically this process presents as comedo-like plugs localized mainly in the periphery of the lesions.


Buschke--Ollendorff syndrome (disseminated dermatofibrosis with osteopoikilosis).

The case is reported of a woman aged 47 years with disseminated dermatofibrosis associated with osteopoikilosis. Her two children also showed skin lesions typical of the Buschke--Ollendorff syndrome and these lesions were said to have been present at birth.


Hypopigmented sarcoidosis in the negro. Report of eight cases with ultrastructural observations.

The dermatological aspects of eight negro patients with hypopigmented sarcoid lesions are described. Light microscope histochemical studies in patients did not reveal the mechanism of the hypopigmentation. However, electronmicroscopy of lesions in two patients showed melanocytes undergoing changes resembling those observed in other acquired hypopigmentary conditions. It is suggested that in these disorders, melanocytes react morphologically in a similar non-specific manner, whatever the prime pathological process.


The value of typing basal cell carcinomas in predicting recurrence after surgical excision.

A classification, based on growth pattern was devised and applied to 156 basal cell carcinomas from 134 patients. The tumours were divided into four main groups; (I) nodular; (2) nodular with infiltrative margin; (3) infiltrative; (4) multifocal. The infiltrative and multifocal types exhibited a high rate of recurrence following surgical excision whereas recurrence of nodular tumours was much rarer. It is therefore suggested that growth pattern should always be stated in the routine histopathological reporting of these neoplasms. Other features were studied and found to have no prognostic value. These included the various types of epithelial differentiation and such stromal factors as the degree of lymphocyte and plasma cell infiltration and the presence of amyloid or elastic fibres.


Striation of bones in focal dermal hypoplasia: manifestation of functional mosaicism?

Striation of the metaphyseal regions of the long bones, a characteristic feature of the focal dermal hypoplasia syndrome, may be explained by functional X chromosome mosaicism. The following arguments are in favour of this hypothesis: (I) The striation of bones coincides with the zones of osteogenesis. (2) The skin lesions are distributed in a linear pattern as well. (3) The syndrome is probably inherited as an X-linked dominant trait. Thus, the linear pattern of both skin and bone lesions could be due to random X inactivation.


Histocompatibility antigens in discoid and systemic lupus erythematosus.

A study of histocompatibility (HLA) antigens in 69 patients with discoid lupus erythematosus (DLE) showed an increased incidence of HLA-B7 and HLA-B8 related to the age at onset and sex of the patient. Young females and males aged 15-39 years at onset were associated with HLA-B7 and females aged over 40 years with HLA-B8. This supports previous studies concerning sex and age specific onset rates in DLE which suggests that there is more than one genotype in this disorder. Female patients with systemic lupus erythematosus (SLE) at all ages of onset showed a significant association with HLA-B8. Female patients, with onset 15-39 years, with either SLE or DLE which has transformed to SLE, show a significant increase in HLA-B8 compared with the females in the same age onset group who have the discoid disease. The presence of HLA-B8 in a young female with DLE may represent a risk factor for the development of the systemic disease.


Is there a relationship between lupus erythematosus and lichen planus?

Three patients showing features of both lupus erythematosus and lichen planus are described together with their histological, immunofluorescence and other investigative findings. The similarities between lupus erythematosus and lichen planus are discussed and it is suggested that these may be the result of common pathophysiological pathways.


Essential fatty acid deficient hairless mouse: a model of chronic epidermal hyperproliferation.

Epidermal DNA synthesis has been shown to be increased approximately three-fold in hairless mice that were fed a diet deficient in essential fatty acids (EFA deficient) for 65 days, compared with animals fed a standard diet. Autoradiographic labelling indices showed a 330% increase in the EFA deficient mice over controls. The animals developed evidence of a diffuse thickening, scalping and loss of elasticity of the skin after 40 days on the EFA deficient diet. Histologically, the epiderma of the EFA deficient animals showed acanthosis, hypergranulosis, hyperkeratosis and increased intracellular epidermal spaces. Increased mitotic indices were found with Feulgen staining. This is further evidence that deficiencies of essential fatty acids are associated with disturbance of normal epidermal cell proliferation and control of keratinization. A single application of topical 0.1% betamethasone valerate to EFA deficient mice reduced the epidermal DNA synthesis to that of normal diet mice. Ten percent linoleic acid topically over 2 weeks also returned epidermal DNA synthesis to normal levels.


The binding of topically applied glucocorticoids to rat skin.

The epidermis of rat skin was shown to be the major site of accumulation of label after the topical application of [3H]-cortisol, [3H]-corticosterone and [3H]-triamcinolone acetonide. However, incubation of the skin in vitro in a way which ensured contact only between the dermal side of the skin and the steroid showed preferential accumulation of label from [3H]-cortisol and [3H]-corticosterone in the epidermis whereas label from [3H]-triamcinolone acetonide appeared evenly spread in the dermis and epidermis. The affinity of corticosterone to soluble proteins in skin homogenates was greater than that of cortisol as measured by displacement binding and correspondingly glucose uptake into the skin in vitro was inhibited for 18 hr after a single application of corticosterone but was not inhibited by cortisol.


Tap water iontophoresis in palmo-plantar hyperhidrosis.

Plain tap water iontophoresis as a method of treatment of idiopathic palmo-plantar hyperhidrosis was evaluated. In the present study, different strengths of current were used for varying periods of time and the treatment was given 6 days a week, until the patients became euhidrotic. Whereas previous workers have used the two electrodes in separate pans, we, in one study, placed them in the same pan of tap water, so that electrolysis occurred at the electrodes on which palms or soles were resting, the current passing through the medium. It was observed that, irrespective of the method used, euhidrosis of palms or soles were achieved. The time and the amount of current required to produce euhidrosis were significantly greater with the single pan technique (average 14-1 sittings in Group I) as compared to the separate pan method (average 7-09 sittings in group II) (t = 3-41, P less than 0.01). The euhidrosis persisted for between 6 and 8 months (average 6-26 months). In our study 90% of the patients treated developed anhidrosis on both the anode and cathode treated palms or soles. In 10% of the subjects, the effect was, however, greater on the anodal side.


Ichthyosis with unusual hair shaft abnormalities in siblings.

An autosomal recessive disorder characterized by lamellar ichthyosis, an usual structural defect of the scalp hairs and amino aciduria occurred in two siblings in a South Indian family in Madras. In addition the female sibling was physically and mentally retarded. The disorder differs from typical Netherton's syndrome in several ways. The hair abnormality specific for this disorder appears to be splitting of the shaft. The possible mechanism of production of the split hairs is discussed.


An unusual presentation of Trichophyton violaceum infection.

A case with encapsulated Tricophyton violaceum abscesses in the skin is recorded. Defective cell mediated immunity was shown in the patient and his two cousins. This defect combined with malnutrition, hypoadrenalism and griseofulvin resistance gave unusual lesions and chronicity. A probable genetic factor for the defective cell mediated immunity is postulated.


Systemic lupus erythematosus presenting as a recurrent sore throat and oral ulceration: a case report.

A patient is described who presented with a 2-year history of repeated sore throats and associated oral ulceration. There were shown to be due to systemic lupus erythematosus (SLE). There was no clinical evidence of involvement of any other system. We are not aware of a previous report of SLE presenting in this manner.


Physical characteristics and ventilatory function of 404 commercial divers working in the North Sea.

The physical characteristics and simple lung ventilatory indices (FVC, FEV 1, FEV 1/FVC) of 404 commercial divers employed by companies operating in the North Sea were analysed. These findings were correlated with the diving experience and maximum operating depth of each diver. All the divers were men of average height 176-9 cm, and weight 77-1 kg which is greater than average for active Western males, but only 6% were more than 120% of their predicted weight. The average duration of commercial diving was 7-1 years, 11% of divers having less than one year's experience. Sixty-seven per cent had worked at a maximum depth of 200 ft (61 m) and only 6% had worked deeper than 500 ft (153 m). The mean forced vital capacity (FVC) was 120-4% of the predicted value which indicated that they could voluntarily move large amounts of gas in and out of their lungs. This was greatest in the divers who when deepest. The mean forced expired volume in one second (FEV 1) was 117% of the predicted value showing that expiratory airflow capacity was also increased, but to a lesser extent than the FVC. Thper and activated by zinc. Plasma protein protected the enzyme from both inhibition and activation. ALAD activity was found to be an indicator of the total metal ion concentration in the blood and was therfore considered to be of doubtful value in screening large population for increased lead absorption.


Urinary mercury excretion and proteinuria in pathology laboratory staff.

The use of mercuric chloride as an histological fixative was associated with high environmental atmospheric concentrations of mercury vapour (up to 0-5 nmol/l) as well as mercury compounds (total Hg to 1-0 nmol/l). Technicians exposed to this environment showed increased urinary mercury (median value 265 nmol/24h) and protein outputs (median value 117 mg protein/24h). Routine control measures, ventilation and careful handling of mercuric chloride solutions, reduced the level of atmospheric mercury vapour levels to within acceptable limits (threshold limit values 0-01 mg/m3 (0-05 nmol/l) alkul compounds and 0-05 mg/m3 (0-25 nmol/l) for all forms except alkyl). This reduction was associated with the disappearance of trace proteinuria from the technicians' urine. Contamination of histology laboratories by mercuric chloride should be minimised.


The effect of metal ions on the activity of delta-aminolevulinic acid dehydratase.

The effects of lead, iron, copper, and zinc ions on delta-aminolevulinic acid dehydratase from red blood cell haemolysates in humans, both in the absence and presence of plasma proteins, have been investigated. delta-aminolevulinic acid dehydratase (ALAD) was not found to be a specific indicator of blood lead concentrations since it was also inhibited by copper and activated by zinc. Plasma protein protected the enzyme from both inhibition and activation. ALAD activity was found to be an indicator of the total metal ion concentration in the blood and was therefore considered to be of doubtful value in screening large populations for increased lead absorption.


Retention, distribution, and excretion of lead by the rat after intravenous injection.

The distribution and excretion of lead was studied during a period of about a week after a single intravenous injection of 203Pb as chloride accompanied by less than 1 microng of lead carrier. The peak concentration in venous blood was reached after about an hour when it contained 35 to 40% of the administered activity. The subsequent decline in concentration was much more rapid than is observed in man. The main storage organs were the kidneys and bone. Initially, 20% of the dose could be accounted for in the kidney and the biological half-life was about 100 hours. The level in bone built up rapidly at first and then more slowly. After a week, between 25 and 30% of the dose was present in bone.


Trichloroethylene exposure. Simulation of uptake, excretion, and metabolism using a mathematical model.

The absorption, distribution, and excretion of trichloroethylene, as well as the kinetics of formation and elimination of trichloroethanol (TCE) and trichloroacetic acid (TCA) were simulated by a mathematical model. The results of this model have been satisfactorily compared with those obtained experimentally from pulmonary elimination of the solvent and from urinary excretion of the metabolites. The model permitted a study of the distribution of the solvent in the different tissues of the organism as well as an evaluation of the body burden of TCE and TCA. The influence of the duration and repetition of the exposure on the urinary eliminations of TCE and TCA was studied, and showed that the excretion of the first metabolite represents the most recent exposure while that of the second is related to the average exposure of the preceding days. The study of the pulmonary elimination of trichloroethylene during single or repeated exposures showed a linear relationship between the alveolar concentration of the solvent approximately 15 hours after the end of the exposure and the quantity of trichloroethylene accumulated in the fatty tissues.


A pharmacokinetic model to study the excretion of trichloroethylene and its metabolites after an inhalation exposure.

For a better understanding of absorption, distribution, excretion, and metabolism of trichloroethylene the time-course of blood concentration of the vapour and urinary excretion of its metabolites was examined using a pharmacokinetic model. After a single experimental exposure in which four men inhaled 100 parts per million (ppm) of trichloroethylene for four hours an elimination curve showed three exponential components, that is, X=1-0005e(-16.71t)+0-449e(-1.710t)+0-255e(-0.2027t), where X is that blood concentration in mg/l and t the time in hours from 0 to 10. The overall rate constant for the disappearance of trichloroethylene was found to a agree with the theoretical one, estimated by means of a mathematical model for the blood concentration data. A D8- XD plot, developed from a mathematical model for urinary excretion, could also give a good estimate of rate constant for the transfer of trichloroethylene in the body. The rate constant thus estimated from urinary excretion was consistent with data on the blood concentration.


The prediction of delivery date by ultrasonic measurement of fetal crown-rump length.

The ultrasonic measurement of the fetal crown-rump lenght (CRL) in early pregnancy was utilized to predict the date of delivery in 220 patients with reliable menstrucal histories and in 186 patients with unreliable menstrual dates who began labour spontaneously; Ninety-five per cent and 96.2 per cent respectively were delivered within 12 days of the predicted date. The CRL was found to be better than biparietal diameter measurements (p greater than 0.001) and as good as a reliable menstrual history (p greater than 0.5) in predicting the time fo spontaneous onset of labour.


The effect of normal pregnancy upon the renal handling of uric acid.

Twenty-four women were investigated serially during and after normal pregnancy. Plasma uric acid concentration appeared to be inversely related to uric acid clearance under infusion conditions, and comparison with simultaneous inulin clearance suggested an alteration in renal function resulting in increased 'net tubular reabsorption' of uric acid as pregnancy progressed. No difference was detected between primigravidae and multigravidae. The implications of these changes are discussed with reference to the renal handling of uric in pre-eclampsia.


Sonar evidence of early pregnancy failure in patients with twin conceptions.

During a four-year period 30 patients were diagnosed by sonar in the first trimester of pregnancy as having twin conceptions. Of these 30 patients, 14 eventually gave birth to twins. Eleven of the remaining 16 patients were found to have a normal pregnancy and a coexistent blighted ovum (empty sac), and ultimately all but one gave birth to a single baby; the eleventh patient aborted a fresh fetus at 25 weeks of gestation. Of the last five patients, four were diagnosed as having twin blighted ova, and one a blighted ovum and missed abortion; these five patients either aborted spontaneously or had an elective termination of pregnancy. The results suggest that the incidence of twin conceptions is higher than commonly accepted figure of 1 in 80.


Smoking in pregnancy--effects on birth weight and on cyanide and thiocyanate levels in mother and baby.

A total of 45 expectant mothers (20 smokers and 25 non-smokers) and their babies was studied and, after 14 smokers and 14 non-smokers had been closely matched for age, height, parity and social class, significant differences were observed between smokers and non-smokers in the birth weights of the babies and in cyanide and thiocyanate levels in maternal blood and urine.


Evidence for a local control of prostaglandins within the pregnant human uterus.

Prostaglandin F (PGF) and 13, 14-dihydro-15-keto-PGF (PGFM) have been measured in amniotic fluid in late human pregnancy. The method used to obtain amniotic fluid greatly influenced the levels of prostaglandins: fluid obtained by vaginal amniotomy contained significantly higher levels of both PGF and PGFM than samples taken at amniocentesis, reflecting an increase in synthesis and/or release of prostaglandin rather than a decrease in the rate of metabolism. After 36 weeks gestation there was no increase in levels of either PGF or PGFM if samples obtained by amniotomy and amniocentesis were considered separately, although if such samples were considered together a significant increase could be obtained. The apparently rapid change in prostaglandin concentrations in amniotic fluid in response to amniotomy strongly supports a local control of these compounds within the pregnant uterus.


The oxytocin challenge test and antepartum fetal assessment.

The oxytocin challenge test (OCT) was performed 537 times on 364 high-risk patients over a three-year period. It was shown that a positive test had a highly significant correlation with a worsened perinatal outcome as measured by stillbirth rate, fetal distress in labour, intrauterine growth retardation, Apgar scores and the need for neonatal resuscitation and intensive care. However, one-third of positive tests were falsely positive when tested by labour. A negative test proved reassuring for a further week of intrauterine life in 98.2 per cent of cases. The role of the OCT in antepartum fetal monitoring is discussed.


Effects of spontaneous and artificial membrane rupture in labour upon fetal heart rate.

This study reports the effects of spontaneous rupture of membranes and artificial rupture of membranes on fetal heart rate patterns during labour in 87 normal and 25 complicated pregnancies. The incidence of early deceleration patterns following membrane rupture was 6.25 per cent during the first 15 minutes and 1.78 per cent after 45 minutes, regardless of whether the pregnancy was normal or complicated. It is concluded that rupture of membranes does not significantly increase the incidence of early deceleration patterns. However, the occurrence of other heart rate alterations such as late decelerations, loss of beat-to-beat variability, changes in base line and tachycardia, need to be investigated further in larger collaborative studies.


The effect of doxapram on fetal breathing in the sheep.

In five ewes of 105 to 120 days gestation intravenous doxapram (1.8 to 3.85 mg/kg) administered to the mother produced a dose-related increase in fetal breathing. This effect of doxapram might prove useful as a test of human fetal health. Fetal breathing movements could be a sensitive indication of the effects of drugs on the human fetal respiratory system.


Water intoxication and oxytocin infusion.

The case reports are presented of two patients who developed water intoxication after high-dose oxytocin infusions. Plasma sodium and urine flow were studied in two further patients given high-dose oxytocin infusions. The findings are related to previously published observations.


Microinvasive squamous carcinoma of cervix in the Tayside region of Scotland.

A total of 117 patients with microinvasive squamous carcinoma of the cervix encountered between 1960 and 1972 is reviewed. No lymph node metastases were found in the 42 patients who had pelvic lymphadenectomy and only one died from her disease. The proposal is made that when the depth of invasion is 3 mm or less, microinvasive carcinoma can be treated in the same way as carcinoma in situ.


Severe intravascular coagulation preceding severe pre-eclampsia.

A patient is described in whom clinical and laboratory evidence of intravascular coagulation preceded the development of fulminating pre-eclampsia necessitating the delivery of a fresh stillbirth by Caesarean section at 31 weeks.


Grey-scale ultrasonography in the diagnosis of hydatidiform mole with a coexistent fetus.

A patient is presented who had a hydatidiform mole with a coexisten fetus and bilateral theca lutein cysts. The complete diagnosis was made by grey-scale ultrasonography.


Effects of noise on human placental lactogen (HPL) levels in maternal plasma.

The levels of human placental lactogen (HPL) in the serum of expectant mothers both subjected to and not subjected to aircraft noise were measured. The HPL levels in the quiet reference area and in the noise area were similar before the 29th week of pregnancy. However, the HPL levels of subjects in the noise area tended to be lower than those in the reference area after the 30th week of pregnancy and the difference became significant after the 36th week of pregnancy. The lower HPL levels were associated with lower birth weight for infants of mothers who lived in the noise area.


The treatment of hirsutism with cyproterone acetate (an anti-androgen).

The rationale of anti-androgen treatment for hirsutism is explained. The results are presented of treatment with cyproterone acetate of idiopathic hirsutism or hirsutism associated with polycystic ovarian disease. Ten out of 14 patients showed a good response after six months treatment. The response was dramatic in two patients.


Immunoglobulin concentrations in cervical mucus in patients with normal and abnormal cervical cytology.

The cervical mucus of 31 patients with normal and 16 patients with abnormal cervical cytology was investigated at each stage of the menstrual cycle for immunoglobulin IgG, IgA and IgM. IgG and IgA were present in every mucus sample, while IgM was only occasionally found in trace amounts. IgG and IgA increased towards the last week of the menstrual cycle, the increase being in general more marked for IgA. Patients with abnormal cervical cytology showed increased IgG and, more strikingly, IgA concentrations in their cervical mucus, but there was no correlation between the IgG and IgA concentrations at any stage of the menstrual cycle. Whereas in patients with normal cervical cytology the IgG and IgA concentrations correlated throughout the menstrual cycle.


Termination of pregnancy with vaginal administration of 16, 16 dimethyl prostaglandin E2 p-benzaldehyde semicarbazone ester.

A 16,16 dimethyl prostaglandin E2 p-benzaldehyde semicarbazone ester was used for termination of pregnancy in 54 late first trimester and second trimester patients. The drug (750 microng in gelatine glycerine pessaries) was administered every four hours. Fifty patients (92-5%) aborted during the 36 hours treatment. Side effects were mild and consisted of vomiting in five patients, diarrhoea in three patients and transient pyrexia in two.


Use of the nitrazine yellow swab test in the diagnosis of ruptured membranes.

Throat swabs impregnated with nitrazine yellow have been used to detect pH change in the vagina before and after amniotomy. The effect of infection on the test has been examined. A negative result is of use in excluding the diagnosis of ruptured membranes. A positive result is highly suggestive of the presence of amniotic fluid.


Genital herpesvirus infection in a prepubertal girl.

An episode of acute vulvovaginitis which was found to be due to herpesvirus is described in an eight-year-old girl. The significance of such infections is discussed.


Endometrial stromal sarcoma of the broad ligament arising in an area of endometriosis in a paramesonephric cyst. Case report.

A 63-year-old Jamaican negress had an endometrial stromal sarcoma arising in a paramesonephric cyst of the broad ligament. Morphological evidence is presented to show that the tumour arose from an area of endometriosis within the cyst wall. Subsequent metastases responded for a few months to cyclophosphamide therapy and the patient died 14 months after the onset of symptoms.


Postmenopausal tuberculosis of the cervix. Case report and review.

A patient with tuberculosis of the cervix who presented with postmenopausal bleeding is reported and the related literature is reviewed.


Uterus didelphys with a pregnancy in each horn. Case report.

A patient with uterus didelphys presented with a pregnancy in each horn which ended in the vaginal delivery of two infants who survived.


Haemostatic mechanisms in maternal, umbilical vein and umbilical artery blood at the time of delivery.

Studies of the haemostatic mechanism were made on paired samples from the umbilical vein and artery and from a maternal peripheral vein immediately following delivery in 80 healthy patients with uncomplicated pregnancies. Neonatal blood showed a significant decrease in clotting 'activity' and platelet function, and a significant increase in fibrinolytic activity. The umbilical vein, in in comparison to the umbilical artery, showed increased clotting 'activity' increased platelet function and decreased fibrinolytic activity. The possible adverse influence of the placenta on haemostasis in the fetus and newborn is discussed.


Oestrogen excretion and ovarian pathology in postmenopausal women with atypical hyperplasia, adenocarcinoma and mixed adenosquamous carcinoma of the endometrium.

Urinary oestrogen and pregnanediol excretion were measured before and after hysterectomy and bilateral salpingo-oophorectomy in 26 postmenopausal women with adenocarcinoma of the endometrium, 10 postmenopausal women with mixed adenosquamous carcinoma and 11 postmenopausal women with atypical hyperplasia (the patient groups). The results were compared with the values obtained in 22 active postmenopausal women, 20 hospitalized postmenopausal women and 18 women who had been subjected to hysterectomy and bilateral salpingo-oophorectomy for cancer of the cervix (the control groups). The ovaries and Fallopian tubes obtained at operation were examined for evidence of current or past excessive oestrogen production. Preoperative oestrogen values were higher in the patient groups than in the controls and the elevated values persisted after oophorectomy. The implications of these findings are discussed.


A critical evaluation of tests used to assess gestational age.

The reliability of eight methods for estimating gestational age in the third trimester of pregnancy has been assessed in patients with fetuses of known maturity. Late ultrasound cephalometry, amniotic fluid creatinine estimations and lecithin/sphingomyelin ratio were found to be significantly more reliable than the other five methods. The mean of estimated gestational ages provided by the three techniques used in combination gave a significantly more accurate prediction of fetal age than any single test and allowed formation of a 'maturity profile'.


The relative efficacy of bed rest, cervical suture, and no treatment in the management of twin pregnancy.

We compared 60 twin pregnancies treated by bed rest, 37 treated by cervical suture and 36 receiving no active treatment. The incidence of the spontaneous onset of labour before 36 weeks of gestation, the mean gestational age at delivery, mean birth weights of the first and second twins and the incidence of 'small-for-dates babies' were similar in all three groups.


Ultrasound measurement of the fetal head to abdomen circumference ratio in the assessment of growth retardation.

Fetal head and abdomen circumference measurements have been made using pulsed ultrasound techniques. The mean head to abdomen (H/A) circumference ratio with 95% confidence limits was determined in 568 normal pregnancies from 17 to 41 weeks menstrual age. The mean ratio was 1-18 at 17 weeks, but decreased slowly until 29 weeks when the ratio was 1-11; thereafter there was a sharp fall in the mean ratio to 1-01 at 36 weeks and 0-96 at 40 weeks. The H/A circumference ratio was also determined in 31 small-for-dates fetuses within one week of delivery. In all cases the fetal weight as predicted from the fetal abdomen circumference measurement was below the 5th centile weight for gestation. The ratio was above the 95th centile limit in 22 (71%) of these fetuses and evidence is presented to suggest that the H/A circumference ratio can be used to distinguish between symmetrical and asymmetrical growth retardation.


Prediction of birth weight by ultrasound measurements of the fetus.

Fetal biparietal diameter, transverse thoracic diameter abdominal circumference and area were measured by ultrasound in 50 pregnant women at term not more than 48 hours before delivery. Multiple regressions correlating birth weight with all these parameters were obtained and estimated birth weight (calculated from the regressions) was compared with the actual birth weight. The error in prediction was under 200 g in 56%, under 300 g in 66% and under 400 g in 84% of patients when all fetal measurements were used. It was under 200 g in 48%, under 300 g in 66% and under 400 g in 74% when only the abdominal area was used; and it was under 200 g in 46%, under 300 g in 56% and under 400 g in 82% when the abdominal circumference alone was used. Biparietal diameter and transverse thoracic diameter alone were not useful in predicting birth weight.


Serum oestrogens and progesterone in mother and infant at delivery.

Whereas maternal venous levels of progesterone and oestrogens have been studied intensively in relation to parturition, little attention has been directed to fetal levels. In this study progesterone, oestrone (E1), oestriol (E2) and oestriol (E3) were measured in umbilical artery (UA) and umbilical vein (UV) serum at vaginal delivery (after induced or spontaneous onset of labour) and at elective Caesarean section. At least 14 samples were included in each group. All UV serum steroid levels were consistently higher than UA serum steroid levels. Cord serum levels of progesterone and arterio-venous differences were higher at vaginal delivery than at Caesarean section although maternal levels changed little. E1 and E2 levels were similar after spontaneous labour and at Caesarean section but were higher (P less than 0-05) after induced labour although E3 levels did not alter. E1 and E2 were higher and progesterone lower in primiparae than in multiparae. Fetal sex made no differences. These results suggest that induction of labour with oxytocin results in altered fetal hormone levels, that maternal hormone levels provide a poor reflection of fetal changes,and that current views about the mechanism of the onset of labour in animals may not be appropriate for man.


Relation between corticosteroid and albumin concentrations in umbilical vein plasma and the duration of labour.

The concentration of corticosteroids in the umbilical vein plasma of babies delivered after a spontaneous onset of labour showed a significant positive correlation with the duration of labour (r=0-593; P less than 0-001) and the length of the second stage (r=0-48; P less than 0-02). Similar results were also obtained for induced labours. For labours of both induced and spontaneous onset, the albumin concentration in cord plasma also correlated significantly (r=0-46; P less than 0-01) with the corticosteroid concentration. It is concluded that the stress of labour and vaginal delivery, and possibly changes in the concentration of proteins which bind corticosteroids, are impoertant in determining the corticosteroid concentration in cord plasma obtained after delivery of the baby. The significance of these findings in relation to mechanisms responsible for the onset of human labour is discussed.


Plasma renin and aldosterone in pregnancy complicated by adrenal insufficiency.

Serial measurements of plasma renin and plasma aldosterone were made throughout pregnancy in two women with adrenal insufficiency. The values were compared with levels obtained in eight normal primigravidae. Aldosterone levels were low or undetectable in adrenal insufficiency and plasma renin levels were grossly elevated in one patient with adrenal insufficiency but within the normal range in the other.


Plasma human placental lactogen profiles over 24 hours in normal and diabetic pregnancy.

Plasma human placental lactogen (HPL) concentrations have been measured at frequent intervals over 24 hours in 24 normal women, 13 chemical and 13 insulin dependent diabetic patients during the third trimester of pregnancy. Most of the women studied displayed variation in HPL levels during the day, but there was no evidence of a diurnal rhythm, nor significant changes following meals or during the nocturnal fast. The mean plasma HPL concentrations over 24 hours in the chemical and insulin dependent diabetic patients (5-9+/-SD 1-3 and 5-9+/-1-7 microng/ml respectively) were greater than those in normal women (5-1+/-1-2 microng/ml) but this difference was not significant. No significant change in plasma HPL concentrations was observed during a five-hour oral glucose tolerance test in either the normal or chemical diabetic group. It is suggested that in normal pregnant women HPL does not itself contribute to glucose homeostasis but acts as a 'regulator' which alters the actions of certain maternal hormones to achieve a favourable environment for fetal growth.


Relationship between fetal urine production and amniotic fluid volume in normal pregnancy and pregnancy complicated by diabetes.

The hourly fetal urine production rate (HFUPR) was calculated from ultrasonic measurements of fetal bladder volume. A normal HFUPR reference curve, constructed from measurements in 189 normal pregnancies between 24 and 42 weeks gestation, showed a rapid increase of HFUPR from 3-3 to 24-4 ml up to 40 weeks followed by a slight decline. The amniotic fluid volume was estimated by the p-aminohippuric acid method within 12 hours of HFUPR measurements. In 67 normal pregnancies, there was no relationship between HFUPR and amniotic fluid volume measured between 36 and 41 weeks gestation. In 12 patients with fetal growth retardation, a relationship was found between reduced fetal urinary output and low amniotic fluid volume between 36 and 38 weeks gestation. In the 16 diabetic patients studied between 28 and 40 weeks gestation, there was no relationship between HFUPR (within or below normal range) and the high amniotic fluid volume (above 1500 ml in 13 patients). The implication of these findings are discussed.


Comparison of histological changes seen in placental tissue cultures and in placentae obtained after fetal death.

The histological changes in placental tissue cultures were observed and compared with those seen in placentae obtained after intrauterine fetal death. Early damage of the syncytiotrophoblast and improvement in the appearance of cytotrophoblast were seen in both cases. It is suggested that it is the cessation of the fetal circulation which causes these changes.


Ciliary activity in the human oviduct.

Ciliary activity of the human oviduct was investigated using a cinematographic technique. Oviducts from preovulatory, postovulatory and puerperal subjects were analyzed and the fimbrial, ampullary and isthmic regions were compared. It was found that cilia beat more rapidly after ovulation, this difference being significant in both ampullary and isthmic regions, but not in the fimbriae. The implications of these findings are discussed.


The cellular composition of the human oviduct epithelium.

Epithelium from human Fallopian tubes was examined to determine the ratio of ciliated to secretory cells. A comparison was made between results from oviducts from women at different stages of the menstrual cycle, and also between the fimbrial, ampullary and isthmic regions of the oviduct. A high percentage of ciliated cells was found in each case, including the isthmic region, with little difference seen throughout the cycle. The role of cilia in ovum transport is discussed.


A clinico-pathological study of gonadoblastoma.

The clinico-pathological features of 12 patients with a gonadoblastoma are analyzed.


Absence of upper limbs (amelia) in surviving intrauterine twin after salpingectomy for ectopic pregnancy.

A patient is described who had simultaneous tubal and intrauterine pregnancies. The tubal pregnancy was treated by salpingectomy at 51 days after the onset of the last menstrual period. The surviving twin was born after 42 weeks gestation and had no upper limbs (amelia).


Adverse reaction to extra-amniotic prostaglandin E2.

An immediate and severe reaction to prostaglandin E2 (PGE2), given by the extra-amniotic route to induce the abortion of a hydatidiform mole, is reported.


Peripheral iridectomy in closed angle glaucoma-- late complications.

Of 70 eyes with therapeutic peripheral iridectomy (PI), 51% suffered a loss of two or more lines on the Snellen chart; 57% developed posterior synechiae (PS) and 57% showed lens opacities. Thirty-three per cent of eyes that underwent PI prophylactically had a vision drop of two lines or more, 39% developed PS and 42% showed varying degrees of lens opacities. Although vision drop, lens opacities and PS were less marked in the prophylactic group, it appears that PI is a surgical procedure not without its hazards. We therefore suggest that peripheral iridectomy should not be performed routinely on the second eye not suffering an acute attack. This procedure should be undertaken only in cases with positive provocative tests and/or clinical signs of closed angle glaucoma.


Mixed glaucoma.

Two hundred and sixty-seven eyes which underwent peripheral iridectomy for presumed angle-closure glaucoma were investigated. The diagnosis of angle-closure glaucoma was confirmed postoperatively in 258 eyes, in 201 of which the intraocular pressure became normal without further treatment and in 57 of which the postiridectomy IOP was elevated because of visible damage to the anterior chamber angle. Three eyes had open-angle glaucoma with a narrow angle. Six eyes had possible mixed (combined mechanism) glaucoma (2-2%). Mixed glaucoma is a rare, fortuitous combination of open-angle and angle-closure glaucoma rather than a distinct entity, and it might be advisable to avoid the term, which tends to be used for primary glaucomas of uncertain classification.


The optic disc in glaucoma II: correlation of the appearance of the optic disc with the visual field.

Examination of stereoscopic optic disc photographs allowed accurate prediction of glaucomatous and normal fields to be made in 82 and 95% of eyes respectively and for visual field loss to be correctly located in upper and lower half in 83 and 91% of cases respectively. Despite this high correlation the existence of false positive and fale negative predictions means that the total reliance on optic nerve examination without visual field estimation in the evaluation of the glaucoma patient should not be made. Optic disc examination is too insensitive for long-term follow-up of visual function in a glaucoma patient. The high correlation between the state of the visual field and the optic disc means that, in the evaluation of the visual functions of a glaucoma patient, the appearance of the optic disc and the visual field should be in agreement.


Microhaemangiomas of the iris with spontaneous hyphaema and acute glaucoma.

A case of bilateral microhaemangiomas of the pupillary borders in a 69-year-old woman is described. When first seen she presented with acute angle closure glaucoma and spontaneous hyphaema. Photographs and iris fluorescein angiography are presented and microhaemangiomas are discussed.


Comparative study of Watson's and Cairns's trabeculectomies in a Black population with open angle glaucoma.

A comparative study of the effectiveness of Watson's and Cairns's trabeculectomy in a Black South African population with open-angle glaucoma is presented. The eventual success rate of 91-6% is comparable with that found in Whites, and the results were similar with both methods.


Implants for draining neovascular glaucoma.

The implant design, surgical technique, and pharmacological methods of controlling bleb fibrosis, used to treat neovascular glaucoma, are described, together with the results of 14 operations performed on 12 eyes.


Fluorescein angiography in chronic simple and low-tension glaucoma.

Fluorescein angiograms were performed on a group of low-tension glaucoma and chronic simple glaucoma patients with similar extent of visual field loss, under standardised conditions, to see whether differences attributable to chronic intraocular pressure elevation could be detected. There was no evidence for difference in circulation times between these two groups. There was no evidence that hypoperfusion of the peripapillary choroid contributed to optic nerve hypoperfusion. Low-tension glaucoma patients demonstrated focal sector hypoperfusion of the optic nerve in every case, while the chronic simple glaucoma patients demonstrated a wide range of optic nerve fluorescence, suggesting both focal and diffuse optic nerve head hypoperfusion. It was concluded that, while focal hypoperfusion of the optic nerve may reflect susceptible vasculature at the nerve head with or without intraocular pressure elevation, diffuse hypoperfusion suggested that prolonged intraocular pressure elevation may simultaneously affect the whole of the optic nerve head. This could be a direct effect on blood vessels or a mechanical effect with secondary vascular changes.


A note on stray light in the Tübingen perimeter.

Measurements were made of the relative intensity of light scattered in the neighbourhood of the large and small targets on the Tübingen perimeter. Two target intensities were studied. The scattered light fraction ranged from 0-1 to 25% and its effect was detected more readily by young than by older observers.


Cataract in childhood: photograph methods in assessment.

The slit-lamp examination of the child's lens with cataract can yield useful prognostic signs, especially when this is supplemented by slit-image photography and measurement. A normal lens size for the subject's age is a good prognostic sign and is usually associated with a static cataract or with very slow deterioration in a developmental cataract. A small lens and absence of the anterior subcapsular clear zone are each associated with progressive cataract. Nuclear lamellar cataracts are shown to become smaller in diameter with time, which favours medical treatment with mydriasis.


Senile disciform macular degeneration in the second eye.

Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk of developing disciform degeneration in the second eye.


Response of the human eye to laser irradiation of the iris.

Irradiation of the iris of glaucoma patients with either a ruby or an argon laser caused no obvious disruption of the blood-aqueous barrier (as visualised by fluorescein angiography), in contrast to a sudden and pronounced effect in the rabbit eye. Only a low and variable increase in intraocular pressure occurred in the human subjects after the laser irradiation in comparison with a consistently high rise of ocular tension in the rabbit. This investigation indicates that the human eye is much less responsive to injury.


Incidence and causes of blindness among the under 5 age group in Malawi.

The expected incidence of blindness among children under 5 years of age in Malawi is 34 cases per 100 000 children. Direct ocular infections were responsible for the blindness in 32% of the cases (bacterial infections 20% and measles 12%). The instillation of traditional medicine in these cases worsened the ocular condition and induced in all of the cases a "hopeless" situation of total melting of the cornea and protrusion of the uvea. Congenital factors (excluding retinoblastomas) were responsible for 30-8% of the blind cases. Among these, 11 cases of congenital cataracts were successfully treated and will not appear as blind in future. A high incidence (9-3%) of cortical blindness was recorded. Trauma was implicated in 5-3%, while retinoblastoma was found in 8%. It is believed that adequate preventive measures should be able to lower the incidence of blindness among this age group to 5 cases instead of 34 per 100 000 children.


A case report of fowl plague keratoconjunctivitis.

A case of human fowl plague keratoconjunctivitis occurred after accidental laboratory exposure. The conjunctivitis was characterised by follicle formation and a mucopurulent discharge, and ran a self-limiting course over two weeks. The keratitis was of an unusual type and consisted of small intraepithelial opacities, which appeared after one week and resolved completely over the next three weeks. The infection, confirmed by viral culture, was produced by Dutch strain (Hav 1 Neq 1) of fowl plague virus.


Ticarcillin in the treatment of experimental pseudomonas keratitis.

In rabbits with experimental Pseudomonas aeruginosa keratitis the subconjunctival administration of either ticarcillin or gentamicin significantly ameliorated the keratitis and reduced the number of organisms to be found in the cornea. The use of these drugs in combination had an additive effect in vitro studies and a significantly more beneficial effect on the clinical disease than the use of either drug alone.


Conjugated polyene fatty acids on fluorescent probes: spectroscopic characterization.

This paper is the first in a series which extends introductory studies of parinaric acid and its phospholipid derivatives as membrane probes (Sklar, L.A., Hudson, B., and Simoni, R.D. (1975), Proc. Natl. Acad. Sci. after U.S.A. 72, 1649; (1976), J. Supramol. Struct. 4, 449). Parinaric acid has a conjugated tetraene chromophore and exhibits many spectroscopic properties common to linear polyenes. Its absorption spectrum is characterized by a strong near-ultraviolet transition with vibronic structure, which is strongly affected by solvent polarizability. The fluorescence emission occurs at considerably lower energy than the absorption and the wavelength of the emission is nearly independent of the solvent. The fluorescence quantum yield and lifetime are strongly affected by temperature and solvent. These spectral features are interpreted in terms of an excited electronic-state order such that a weak transition occurs at longer wavelengths than the strongly allowed transition which dominates the absorption. The sensitivity of the fluorescence quantum yield an lifetime to environment is shown to be due primarily to variations in the nonradiative rate, although changes in the radiative rate constant are also observed and interpreted. The absorption spectrum (epsilon max greater than 65 000) is in the 300-320-nm range, a region relatively free of absorption due to intrinsic biological chromophores. Shifts of several nanometers are characteristic of different environments. These shifts are compared to similar effects observed for a series of diphenylpolyenes for which new data are given and are correlated using a simple but adequate theory of solvent shifts. The intrinsic (or radiative) fluorescence lifetime is near 100 ns in a wide variety of environments. This is much longer than the intrinsic lifetime calculated from the absorption spectrum and strongly supports the proposed excited-state order.


Conjugated polyene fatty acids as fluorescent probes: synthetic phospholipid membrane studies.

The preparation of polyene fatty acid membrane probes cis- and trans-parinaric acid and parinaroylphosphatidylcholines and their use in studies of several one- and two- component lipid systems are described. The fluorescence quantum yield of trans-parinaric acid in dipalmitoylphosphatidylcholine at 20 degrees C is approximately 0.3; the quantum yield in aqueous solution is negligibly small. Thermal-phase transitions in single-component phospholipid dispersions are monitored with absorption and fluorescence excitation peak position, fluorescence intensity, lifetime, and polarization. The transition temperatures observed are consistent with previous determinations. Shifts in the absorption peak position are related to the bilayer expansion as it undergoes the gel to liquid-crystalline transition, while fluorescence depolarization provides semiquantitative information concerning molecular motion of the probe in the bilayer. A long fluorescence lifetime component is observed for parinaric acid in the solid phase (up to 50 ns), and a short lifetime component is observed (ca. 5 ns) in the fluid phase of dipalmitoylphosphatidylcholine; both lifetime components are observed in the transition region. In most phospholipids, cis-parinaric acid detects the melting transition at about 1 degree C lower than trans-parinaric acid. Partitioning experiments involving mixed populations of phospholipid vesicles show that trans-parinaric acid preferentially associates with solid-phase lipids, while cis-parinaric acid shows a more equal distribution between solid and fluid lipids. The binding of cis-parinaric acid to dipalmitoylphosphatidylcholine at 25 degrees C is described as partitioning of parinaric acid between lipid vesicles and the aqueous phase with a partition coefficient of 5 X 10(5). Several rates are observed in the binding process which are interpreted as rapid outer monolayer uptake and a much slower process of interlamellar exchange. The phase diagram of the binary lipid mixture dipalmitoylphosphatidylcholine-dipalmitoylphosphatidylethanolamine has also been examined and found to be essentially identical to the one constructed using a nitroxide probe.


The progeny of rabbit articular chondrocytes synthesize collagen types I and III and type I trimer, but not type II. Verifications by cyanogen bromide peptide analysis.

The radioactive collagens synthesized by the fourth subculture progeny of rabbit articular chondrocytes were extracted and purified after limited pepsin digestion by neutral and acid salt precipitation. In order to identify the different types of collagen present, denatured collagen chains were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis on 5% gels, electrophoretically eluted, and cleaved with cyanogen bromide, and the resultant peptides were fractionated by a new sodium dodecyl sulfate electrophoresis system (tris(hydroxymethyl)aminomethane-borate buffer, 15% gels). Comparison of these separate peptide profiles with those from alpha1(I) and alpha1(III) collagen chains permitted the unambiguous identification of these chains in the radioactive collagen synthesized by chondrocytes. Although cartilage slices predominantly synthesized alpha1(II) chains, only alpha1(I) chains were made by cells in fourth subculture. A large fraction of these alpha1(I) chains could not be accounted for by the presence of type I collagen. While in a native, triple-helical conformation, some of these extra alpha1(I) chains were completely separated from type I collagen by their solubility at pH 8.0 in 2.6 M NaCl and therefore identified as [alpha1(I)]3, type I trimer. In addition to type I collagen and type I trimer, these chondrocyte progeny also synthesized type III collagen and two new collagen chains, X and Y. Each collagen type was further characterized by carboxymethylcellulose chromatography and its distribution between the medium and the cell layer. These findings support the idea that cultured chondrocytes assume a collagen phenotype similar to that of their undifferentiated mesenchymal cell precursors.


The complete amino acid sequence of the major component myoglobin of dwarf sperm whale (Kogia simus).

The complete amino acid sequence of the major component myoglobin from the dwarf sperm whale, Kogia simus, was determined by specific cleavage of the protein to obtain large peptides which are readily degraded by the automatic sequenator. Three easily separable peptides were obtained by cleaving the protein at its two methionine residues, and five peptides were obtained from the methyl acetimidated protein by cleavage with trypsin at the four arginine residues. Sequenator analysis of these fragments and the apomyoglobin provided over 80% of the covalent structure of the protein. The remainder of the primary structure was determined by further digestion of the two larger cyanogen bromide fragments with trypsin and staphylococcal protease. To reconfirm many of the substitutions found in this protein, the apomyoglobin was treated with 1,2-cyclohexanedione, and the resulting arginine protected protein was cleaved at its lysine residues with trypsin. This myoglobin differs from that of the sperm whale at 6 positions, and from the other cetacean myoglobins at about 16 positions. The appearance of a histidine residue at position 35 has no precedent in any myoglobin. The substitutions seen at positions 21, 51, and 132 are unique to date for cetacean myoglobins.