[Preliminary comparative results of the detection of hepatitis B antigen (HBAg) in the blood of mental patients, using several methods in common use].

Radioimmunoassay (RIA), immunoelectrophoresis (IEP) and latex agglutination (L-HHA) were compared in the detection of hepatitis B antigen in sera from 494 mental patients. Positivity was observed in 39 subjects (7.9%) with RIA, 14 (2.8%) with IEP, and 8 (1.6%) with L-HHA. The dilution titres noted with RIA were many times and significantly higher than those obtained with the other two methods. Antigen was again detected in over 50% of those subjects on whom it was possible to repeat the tests one year later. The advantages of RIA are stressed.


[GH secretion after L-dopa administration in hepatic cirrhosis].

A 500 mg L-Dopa administration in normal and cirrhotic subjects does not determinate a significant varation of plasma glucose and insulin level, while a peak plasma GH level in both cirrhotic and normal subjects occurred at 90' with a significantly greates values in cirrhotics. It is doubtful to affirm that a high plasma GH level is the only one factor which responsable of glucose intolerance in cirrhotic subjects, when there are many others factors contribute to it in synergic way. In order to elucidate the hypothesis on possible pathogenetic mechanism it is discussed some of our own experience and observations.


[Hepatic distomiasis caused by Fasciola hepatica].

A case of bile duct obstruction due to Fasciola hepatica is presented. The evolution, aetiopathogenesis, symptomatology, diagnosis and therapy of this rare syndrome are then discribed.


Plasma cortisol levels in human fetus during parturition.

In several mammalian species, the fetal adrenal cortex plays an important role in the spontaneous onset of labor. No conclusive evidence has yet been presented that a similar mechanism is active in humans. Although in some previous studies the cortisol concentration in human cord blood has been found higher after spontaneous labor than after induced labor, it has not been possible to determine whether this rise in the fetal cortisol level precedes the onset of parturition or is a consequence of labor. In the present study, starting at the earliest possible stage of labor, fetal scalp blood samples were taken sequentially during 16 spontaneous and 13 induced vaginal deliveries. Cortisol levels in these 2 goups of samples were compared with each other and also with cord blood cortisol levels in 11 patients undergoing elective cesarean section. The initial fetal cortisol levels did not differ between groups with different modes of labor onset. A pronounced rise of plasma cortisol levels occurred during labor in simultaneously sampled maternal and fetal blood. These results do not support the concept of a role for the fetal adrenal cortex in the initiation of labor in humans; they invalidate the use of cortisol concentration in cord blood for the estimation of prelabor fetal cortisol level. The origin of the cortisol surge in fetal plasma during labor and also whether the fetal adrenocortical function responds to the stress of labor are discussed. It is concluded that the rise of fetal cortisol levels during labor might mainly be a reflection of the maternal response to stress.


Serum cortisol and 11-desoxycortisol levels in hirsute premenopausal women.

It has been postulated that hirsute patients may have a relative deficiency in 11beta-hydroxylase activity of the adrenal cortex. In order to test this postulate, we have measured the serum levels of cortisol (Cp F) and 11-desoxycortisol (Cp S) and estimated the Cp S/Cp F ratio in 9 nonhirsute and 34 hirsute premenopausal women. As a group, the hirsute patients had significantly elevated (P less than 0.05) mean Cp F and Cp S levels but the mean Cp S/Cp F ratio was not significantly different from normal. Considered individually, only 3 hirsute patients had a Cp S/Cp F ratio greater than 2 SD above the mean normal levels. These ratios were 0.0218, 0.0139, and 0.023. If there is indeed an 11beta-hydroxylase deficiency in these 3 patients, it must be relatively minor, since a patient with documented 11beta-hydroxylase deficiency had Cp S levels of 218 ng/ml and a Cp S/Cp F ratio of 0.7. Our data suggest that 11beta-hydroxylase deficiency is not a common cause of hirsutism.


Incidence of endometriosis among Japanese women.

Clinical experience based on gynecologic practice in Hawaii indicated a high incidence of endometriosis among Oriental women. To investigate this impression, a statistical analysis of gynecologic admissions and of diagnoses of endometriosis was performed on the basis of race at three hospitals, two in Hawaii and one in Japan. The result supports the impression that the Japanese female population has a high incidence of endometriosis. Approximately 10% of their gynecologic admissions were for endometriosis. The order of incidence in other racial groups was non-Japanese Oriental, white, and black.


Venereal transmission of hepatitis B virus. The possible role of vaginal secretions.

The presence of Type B viral (Australia antigen related serum) hepatitis in vaginal specimens was investigated and compared with that in saliva specimens in a group of patients during the acute phase of their illness. Hepatitis B surface antigen was detectable in most vaginal and salivary secretions during the phase of antigenemia and not in hepatitis B surface antigen-negative controls. Despite care in collection, occult blood was detected in the majority of specimens, but the positivity for hepatitis B surface antigen did not depend on the presence of occult blood. Recovery studies were performed in both vaginal fluids and saliva to determine if inhibitors to hepatitis B surface antigen were similar to those observed in stool samples. Significant inhibition was not observed. Although infectivity of the specimens was not established from this study, handling of these specimens as potentially infective material is recommended.


Intrauterine adhesions secondary to elective abortion. Hysteroscopic diagnosis and management.

Ten patients who developed Asherman's syndrome following elective first trimester abortion underwent outpatient hysteroscopy under local anesthesia. Six of the 10 patients had hysterosalpingograms prior to surgery. Correlation between the radiographic findings and those at hysteroscopy was poor. Treatment consisted of hysteroscopic lysis of adhesions, placement of an IUD or Foley catheter, and sequential estrogen-progestin administration. Normal menses were resumed in all women. Hysteroscopy was also used for followup in 4 patients. Outpatient hysteroscopy under local anesthesia is safe and is the method of choice for diagnosing, treating, and following patients with Asherman's syndrome.


Pregnancy following jejunoileal bypass. Effects on fetal outcome.

Four cases of pregnancy following jejunoileal bypass surgery for obesity are presented, and 9 cases from the recent literature are reviewed. Pregnancy after bypass surgery often resulted in low-birthweight infants (46%) at term, and this was especially true when conception occurred within 2 years of the surgery. In light of these findings it may be advisable to postpone pregnancy until after the second postoperative year.


Progesterone levels in amniotic fluid and maternal plasma in prostaglandin F2alpha-induced midtrimester abortion.

Progesterone concentrations in amniotic fluid and maternal plasma were determined in 11 midtrimester pregnant patients following the intraamniotic administration of prostaglandin F2alpha. Samples were obtained at 3-hour intervals until abortion or spontaneous rupture of membranes occurred or fetal heart tones disappeared. In amniotic fluid, the mean progesterone concentrations increased throughout the sampling period. The plasma progesterone levels declined by about one-third of basal values in the first 3 hours after prostaglandin administration. The paradoxic increase in amniotic fluid progesterone is probably secondary to alterations in uterine blood flow and intrauterine pressure.


Gonococcemia in pregnancy.

A case of gonococcemia in pregnancy in which the patient presented with the classic clinical manifestations of gonococcemia--cutaneous lesions, arthritis, and possibly pericarditis--is reported. A review of the literature reveals a dramatic increase in incidence of gonorrhea and the increasing importance of the complications associated with this disease, particularly in pregnancy. Recommendations regarding recognition of gonococcemia, criteria for diagnosis, and treatment are presented.


The effect of drugs on uterine activity.

Uterine activity was measured for a 30-minute preinjection period and a 30-minute postinjection period for six drugs commonly used in labor. Uterine activity was quantitated by measuring the area below the uterine pressure curve with an on-line technic utilizing a voltage control oscillator. Uterine activity readings were obtained every 2.5 minutes and reported in uterine activity units (UAU). Unmedicated labor demonstrated a relatively static increase in UAU per unit of time in labor. On comparing total UAU before and after injection, only magnesium sulfate was noted to cause a decrease in total UAU. Utilizing 10-minute summations of UAU, the pre- and postinjection periods were compared to the calculated expected UAU for the 30 minutes following the preinjection period (assuming no drug had been used). For each of the other drugs, the positive slope of the calculated expected UAU shifted to a negative slope of the actual observed UAU following drug administration.


Oxytocin-induced uterine hypercontractility pressure wave forms.

To identify similarities and differences between uterine contractions in patients with spontaneous labor, oxytocin-corrected hypocontractility, and oxytocin-induced hypercontractility, measurements were made of specific characteristics of the intrauterine wave form, including pressure, rate of change of pressure, and duration. Contractions from oxytocin-treated patients differed from contractions of those with spontaneous labor in their disproportionately high rates of rise of the pressure. The time to reach the maximum rate of the pressure--the start-up time--was reduced in oxytocin-induced hypercontractility. The data demonstrate that the contractions of spontaneous labor and oxytocin-augmented labor are not identical, and the physiologic implications are discussed.


"Prediction" of the one-minute Apgar score from fetal heart rate data.

The value of any fetal monitoring technic is in its ability to predict infant outcome. In the present study, the ability of fetal heart rate (FHR) monitoring data to "predict" a measure of short-term infant outcome, the 1-minute Apgar score, was evaluated using univariate and multivariate statistical analyses. Of 61 monitored high-risk infants, 46 had high (7 to 10) and 15 had low (1 to 6) 1-minute Apgar scores. Computer analysis of FHR/intrauterine pressure (IUP) data for these 61 infants revealed that the infants with low Apgar scores had more than the expected number of late decelerations (LD). Using a threshold of ten LD and univariate analysis, 74% of the infants could be properly classified for high or low Apgar scores, but 60% of the infants with low Apgar scores were not identified. Using discriminant function (multivariate) analysis for the numbers of LD and uterine contractions, 47% of the depressed infants were appropriately identified and simple risk scoring equations were devised. Using additional observation vectors, including the number of accelerations and early decelerations, 67% of the depressed infants could be identified. The results of this study suggest that using multiple observation vectors improves the predictive capacity and, thus, the value of fetal monitoring data. Clinical experience suggests that the value of monitoring data can be further enhanced by simultaneous evaluation of other observation vectors from additional perinatal data sets using the technics of this study.


Fetal heart rate response to amniocentesis in cases of decreased fetal movements.

Eleven women with fetal distress as manifested by a decrease of fetal movements up to cessation underwent amniocentesis for amniotic fluid evaluation under continuous FHR monitoring. All the fetuses showed abnormal heart rate response, manifested by absence of FHR acceleration or early or late deceleration. The pathologic response, or lack of response of fetal heart rate during amniocentesis is suggested as an additional test to evaluate the severity of fetal distress.


The effect of diazoxide on uterine blood flow in pregnant sheep.

Diazoxide, a labor inhibiting agent, was administered intravenously at various rates to seven pregnant, near-term sheep to evaluate its effect on cardiovascular and uterine hemodynamics. Uterine blood flow was measured with electromagnetic flow transducers. Rapid administration of diazoxide resulted in a profound maternal tachycardia with hypotension, an increase in uterine vascular resistance, and a significant decrease in uterine blood flow. With slow infusion of the drug, the changes in heart rate and blood pressure were minimized, uterine vascular resistance was decreased, and uterine blood flow was maintained. Therefore, slow infusion appears to be the preferred method for inhibiting labor with diazoxide.


The synergistic effect of calcium and prostaglandin F2alpha in second trimester abortion. A pilot study.

A clinical use of the basic science phenomenon that prostaglandin is synergistic with calcium in increasing uterine contractility has been demonstrated. Twenty-five women had midtrimester abortions induced with intraamniotic calcium gluconate followed by prostaglandin F2alpha. All patients aborted within 21 hours with minimal toxicity. The mean injection-to-abortion interval was 13.5 hours in the group of women without a preinjection laminaria and 10.1 hours in patients when a laminaria was included in the protocol.


Prostaglandin E2 induction of labor for fetal demise.

Intrauterine fetal demise is a source of anxiety to both patient and physician. Heretofore, the standard treatment was either careful observation until the patient went into labor or attempt at induction of labor with oxytocin. Unfortunately, oxytocin stimulation has not proven to be uniformly successful for this problem. Prostaglandin E2 suppositories have been shown to be effective in inducing uterine evacuation after intrauterine fetal demise. In the opinion of the authors, this approach will in the future replace the sometimes dangerous and emotionally laden convention of watchful delayed therapy.


Gonadal calcification. Indication for gonadectomy in gonadal dysgenesis.

Germ cell tumors, including gonadoblastoma, are usually found in patients with gonadal dysgenesis who have Y chromatin in their genotype. Diffuse calcification is a common finding in gonadoblastomas. Bilateral calcifications in the gonadal sites were seen on the intravenous pyelogram of a patient with 46,XX pure gonadal dysgenesis. Although the calcification was present in the fimbria of the fallopian tube, we suggest that gonadectomy is indicated in the patient with gonadal dysgenesis and probably gonadal calcification.


Scanning electron microscopy of melanoblastomas of the choroid.

With the scanning electron microscopic study of a case of the fascicular and two cases of epithelioid melanoblastomas it has been found that the shape of the cells is more variable than it was believed before on the basis of light microscopy. Certain types of arrangement described in histological observations, e.g. the fascicular type, can also be well demonstrated by scanning electron microscopy.


Peripheral vision in children.

A comparison of peripheral vision in adults and children showed that children had reduced sensitivity in a standard visual field examination. The constriction of the visual field amounted to 0.4 log units at 30 degrees excentricity in a static perimetric test. This loss was maintained in a spatial forced choice experiment without foreknowledge of target location. However, in a temporal forced choice experiment with foreknowledge of target position the difference between children and adults was reduced to 0.1 log units. It is thought, therefore, that the former visual loss in children is due to the nature of the task rather than to deficiencies in the visual mechanisms.


Are the oldest 'fossils', fossils?

A comparative statistical study has been carried out on populations of modern algae, of Precambrian algal microfossils, of the 'organized elements' of the Orgueil carbonaceous meteorite, and of the oldest microfossil-like objects now known (spheroidal bodies from the Fig Tree and Onverwacht Groups of the Swaziland Supergroup, South Africa). The distribution patterns exhibited by the greater than 3000 m.y.-old Swaziland microstructures bear considerable resemblance to those of the abiotic 'organized elements' but rather markedly differ from those exhibited by younger, assuredly biogenic, populations. Based on these comparisons it is concluded that the Swaziland spheroids could be, at least in part, of non-biologic origin; these oldest known fossil-like micro-structures should not be regarded as constituting firm evidence of Archean life.


Abiotic origin of biopolymers.

A variety of methods have been investigated in different laboratories for the polymerization of amino acids and nucleotides under abiotic conditions. They include (1) thermal polymerization, (2) direct polymerization of certain amino acid nitriles, amides or esters, (3) pi, Tokyo 194, Japan.


Evolutionary oscillation in prebiology: igneous activity and the origins of life.

The processes of chemical evolution are responsible for the origin of life. Three such processes have special importance: oscillation, creation, and competition. An oscillation from one kind of environment to another provides a mechanism for instituting processes that can only take place under conditions far removed from equilibrium. Oscillating evolutionary processes are likely to have played an important part in the origin of life. It is a mistake to assume that life originated in any one environment. It did not arrive in a moment of time. It was the result of a long period of chemical evolution during which it passed through a variety of environments. Biopoesis took place in an environment in which a variety of different kinds of protolife were assembled and concentrated. One essential form of protolife involved in these processes is the protocell. The experiments of Fox suggest that the creation of protocells involves violent oscillations of temperature and hydration. Igneous activity is especially characterised by oscillating conditions. Volcanic eruptions consist of violent changes from one extreme condition to another. Temperatures, pressure, phase, concentration and hydration all oscillate violently, and are subject to shock pulses of many kinds. Protolife may well have passed through extremes of environment for wider that those that life itself can sustain. The most probable environment for the assembly of the various forms of protolife would be on mudbanks forming either at the mouth of streams draining regions of active vulcanicity, or round the edge of hot volclanic pools. In this situation one could fins concentrated not only the various stands of protolife necessary for the final act of biopoesis, but also perbiologically formed nutrients necessary as for the first eobionts. As soon as the first protocells start to grow, they start to compete with each other, and so initiate a new additional evolutionary process, that of natural selection. Only after such competition has been initiated is life itself likely to be established"20


[Hypokinetic appearance of huntington's chorea during the childhood (author's transl)].

During the last two years two patients with hypokinetic appearance of Huntington's chorea--beginning in childhood--were investigated in the Neurological Univ.-Clinic of Vienna. Both of the patients descend from families with primary hyperkinetic Huntington's chorea in adult life. The problem of the early manifest hypokinetic form--when the family case history is not attended--are of special interest for the first symptoms can lead into false diagnosis. Therefore oftenly systematic treatment will be done at first just during the adult life, when already the complete picture of Huntington's chorea has appeared. From the point of eugenic deliberations it is very interesting for relatives of families with Huntington's chorea to be informed about the heredity, the most lately appearance of the disease and by the possiblity of anteposition.


[Gastrostomy in paediatric surgery (author's transl)].

Gastrostomy has the same field of application as the feeding tube which is introduced either orally or nasally. With careful nursing and surgical technique, only few and slight disturbances are to be expected. This method, however, ist not suited for routine application by the premature baby because of its possible septic complications.


[Cardiac manifestations in prenatal coxsackie virus myocarditis (author's transl)].

This is a report of 6 single cases of prenatal virus myocarditis originated from an endemic region around Salzburg. The cardiac involvement showed different grades dependent too on time of infection and on transfer of maternal antibodies to the child. Infections immediately before delivery cause severe illness, but infections some weeks before birth less severe damage. Symptoms of meningitis were not noticed. The diagnosis of myocarditis by Coxsackie virus was certain in two deceased newborns (Patient 1 and 2), very probable in one decreased baby (Patient 3) and probable in the surviving children (Patient 4, 5 and 6).


[Cystic changes in the lungs in childhood (author's transl)].

Two boys with presumably congenital cystic changes in the lungs are described. In one child multiple cystic deformations led to acute symptoms of severe respiratory distress necessitating urgent resection of the right middle and upper lobes. The other boy had a large thick-walled cyst in the left upper lobe causing no distress whatsoever. This patient was observed for more than 6 years before operation. Multiple vascular anomalies and anastomoses were revealed during surgery. Both cases are presented in detail and the completely different clinical course is outlined. Only when careful supervision of intrapulmonary cystic changes is guaranteed can operation be postponed for longer than 6 months. Pulmonary cysts may lead to emergency procedures. They are always a potential source of serious complications such as rupture or infection. When no tendency for regression can be discovered surgical removal is indicated. Conservative treatment will not influence the course. Differential diagnosis is discussed briefly.


[Diagnosis and therapy of chronic constipation].

Severe chronic constipation is an extremely rare disorder. Out of 39 370 patients seen in our hospital during the past two years only 309 children (=0,78%) were suffered from severe chronic constipation. Radiologic and electromanometrical examinations revealed as an organic cause anal sphincter achalasia or Hirschsprung's disease in 30,7% of these constipated children. In 54,9% however no pathomorphologic results could be found. Of all cases 14,4% examined were postoperative controls. Careful electromanometric and defecographic examination of every chronically constipated child is crucially important in determining the therapy as in most cases chronic constipation in childhood, is due to a functional asynchronism of the internal and external anal sphincter relaxation reflexes, it can most reliably be diagnosed by electromanometrical examinations. The accuracy and reliability of our electromanometrical method has been proved not only by comparison with radiologic and histologic techniques but also statistically by analysis of discriminance of the recorded parameters. The therapeutic approach depends on the underlying disease. Mechanical obstruction of the intestine, nervous dysregulation of colonic motility causing Hirschsprung's disease and organic anal sphincter achalasia require surgical treatment. In cases of achalasia myotomia of the internal anal sphincter gives excellent functional results. In 73 cases treated by myotomy no symptoms of anal incontinence were seen. Medical therapy includes administration of laxatives combined with high roughage diet, adjustment of living conditions including increased physical activity and bowel training in order to learn a conditioned defecation reflex. The matter can be more easily achieved by administering Dihydroergotamine and Lactulose initially.


[Medullary sponge kidney: a short review and a report of two cases (author's transl)].

Radiologically the collecting tubules in the medulla are dilated up to cystic proportions. There may be no clinical symptoms, but frequently the dilated tubules predispose to infection and lithiasis. Such cysts do not interfere with renal function. X-ray diagnosis, frequency, therapy and etiology are discussed. Two further cases of MSK in childhood are described.


[Manifestation of diabetes in the first to third year of life. Later fates of 43 patients (author's transl)].

Life expectancy of diabetics since early childhood is differently judged. Out of 43 own patients with diabetes started between the first and third year of life, no less than 33 have passed their twentieth year of life; 16 patients are aged between 25 and 46 years; one woman patient lived to the age of 64! In all cases the duration of diabetes is more than 10 years, in 26 cases 20 years or more. In 24 cases angiopathy developed chiefly in the form of retinopathy, nephroapthy and arterial hypertension (none in 19 cases). 7 patients died of uraemia. While there is hardly any difference between the two groups (with or without angiopathy) as far as duration and quality of diabetes-control are concerned, in the angiopathy-group hereditary taint clearly prevails. The early beginning of diabetes does not at all represent an absolutely unfavourable symptom, rather the reverse (O. Imerslund).


[Secondary cystathioninuria due to vitamin B 6 deficiency in familial neuroblastoma].

In this study numerous amino acid analyses were performed in a family with increased incidence of tumors of the sympathetic nervous system. Since in 9 respectively 10 of a total of 13 surveyed persons an elevated urinary excretion of cystathionine was demonstrated with thin layer and column chromatographic methods, this constitutes the first report on cystathioninuria in familial neuroblastoma. Two family members also presented a homocystinuria in the spontaneously voided 24-hours urine. The only person whose plasma amino acids were analysed showed nearly normal levels. After oral loading with L-methionine the urinary excretion of cystathionine raised considerably. The different reaction of the two vitamin B6-dependent enzymes, cystathionine-synthetase and cystathionase, points at a different methionine induced sensitivity. The determination of pyridoxal phosphate and pyridoxal kinase detected a vitamin B6-deficiency, which corresponded well with an increased excretion of oxalic acid and a low normal urinary taurin excretion. Therefore these alterations of the amino acids are explained and thus urinary excretion of cystathionine can be interpreted as secondary cystathioninuria. Furthermore it was possible to provoke corresponding biochemical changes by oral administration of vitamin B6 such as reduction of the cystathioninuria and disappearance of the homocystinuria. In an infant the cystathioninuria could be observed over a period for 5 months, by which a transitory deficiency of the apoenzyme appears to be unlikely. The analysis of 24 hours urine samples of a gravida showed the persistance of cystathioninuria also during pregnancy. After radiation of a 5 year old girl with ganglioneuroblastoma an increase of the urinary cystathionine excretion and a first occurrence of homocystinuria was noted. These observations give rise to various considerations. The vitamin-B6-deficiency in familial neuroblastoma supports the assumption, that also the cystathioninuria in nonhereditary cases may be caused by vitamin-B6-deficiency. Since in this family the excretion of catecholamines was examined in a prior investigation a comparison of these two studies does not support the suggestion of a direct connection between the excretion of catecholamines and cystathioninuria, as it has been assumed to occur in sporadic neuroblastoma. The vitamin-B6-deficiency as seen in this family can also be considered in relation to tumor development. In the discussion about this possibility also the appearance of cystathioninuria in other tumors of early childhood is mentioned. Furthermore the relation of vitamin B6 to teratogenesis is commented on.


[Prophylactic replacement therapy in hemophilia. A case report (author's transl)].

In a six year old boy with severe hemophilia prophylactic substitution of factor VIII was started in 1973 in order to prevent early invalidity due to series of bleeding in the right anklejoint. A substitution of factor VIII over 8 months with 21 resp. 30 U/kg body-weight did not lead to a significant improvement. But since the factor VIII in a dosage of 18 U/kg body-weight is given three times a week no bleeding occurred during the treatment time of 14 months and also the ability to walk improved to an excellent degree.--So far no signs of hepatitis or an factor-VIII-antibody could be detected.--Some results from the prophylactic treatment of severe hemophilia and Christmas disease are cited from the literature.


Effect of chronic anemia on left ventricular ejection time and myocardial performance in man.

The duration of systolic time interval in ten anemic, (mean Hb 3.46) and otherwise healthy individuals (mean age 15) was measured from simultaneous recording of electrocardiogram, phonocardiogram and carotid pulsation. The preejection period (PEP); left ventricular ejection time (LVET) and ratio of PEP/LVET from 20 consecutive beats were calculated and averaged. Anemia was corrected slowly and study was repeated (mean 3 1/2 weeks) later and a similar data for comparison was obtained; heart rate decreased, LVET lengthened and the ratio of PEP/LVET remained unchanged. The lengthening of the LVET was due to slower heart rate. LVET before and after correction of anemia could be predicted from regression formula reported for normals. The unchanged PEP/LVET before and after the anemia indicates no significant alteration in myocardial performance at rest.


The range of antistreptolysin-O titer among 3129 healthy individuals in winter and summer in Tehran, Iran.

A rise in ASO titre can be demonstrated in 75-80% of patients following untreated streptococcal upper respiratory infection. The difficulty, however, is that there is no such thing as normal ASO titre. The levels encountered in a given population depend upon age, geographical location, season, etc. It was, therefore, on this basis that sera were taken from 3129 healthy individuals during winter and summer in Tehran for the determination of ASO titres. Sixty-three individuals were treated both during summer and winter. During summer only 4 (6%) had titres above 250 T.U. and 59 (94%) below 250 T.U. The same individuals, when tested during the winter, showed that 7 (11%) had ASO titres above 250 T.U. and 56 (89%) below 250 T.U. This seasonal difference is statistically significant. In another study 320 individuals were tested during summer and another 394 individuals during winter. Among the summer group 31 (10%) were above 250 T.U. and 289 (90%) were below 250 T.U. In the winter group 55 (14%) were above 250 T.U. and 339 (86%) were below 250 T.U. This difference is again statistically significant. Further, 35 samples of pooled sera representing 2289 individuals were treated during the winter. Here 563 (24%) were above and 1723 (76%) were below 250 T.U. The possible sources of error in this group, in comparison with the other, are discussed.


Atmospheric pollen counts in Tehran, Iran, 1974.

Daily pollen counts were made in Tehran by placing a Durham sampler on the roof of the College of Pharmacy building at the University of Tehran. Three pollen seasons were identified in Tehran. Tree season extended from the first week of February through the middle of October. Important pollens of tree season were Willow, Cedar, Sycamore, Pine, Alder, Walnuts, Elm, Cottonwood, Oak and/or Maple, Birch, and Beech. The grass season started from the first week of May and extended into the second week of November. The weed season began at the middle of May and lasted until the last week of December. Important weed pollens belonged to various members of the Order Chenopodials, particularly Burning Bush, and Russian Thistle. Sagebrush and English Plantain were also abundant during the weed season.


The stimulation of daughter redia production during the larval development of Fasciola hepatica.

In snails maintained at 20 degrees C rediae of Fasciola hepatica merge from sporocysts from 11 days after infection onwards. The number of mother rediae rises steadily thereafter until at least 40 days after infection. Daughter rediae are seldom observed in mother rediae dissected from snails maintained at 20 degrees C. Their production can, however, be stimulated by subjecting the snail host to starvation, to low, and to high temperature shocks. The parasite is susceptible to stress from immediately after infection for about 16 days, when maintained at 20 degrees C. In general, the more extreme the shock, the greater is daughter redial production. Increasing the length of the period of stress from 12 h up to 9 days does not increase the production of daughter rediae, nor does repeated on/off cold shocks or continuous maintenance at 10 degrees C. Daughter rediae develop more rapidly than cercariae and leave the mother rediae several days earlier. There is no evidence that presence of daughter rediae coincides with the suppression of cercarial production. The findings are discussed with reference to possible mechanisms by which parasite development might be controlled.


The cell coat of Crithidia fasciculata.

A prominent filamentous and granular cell coat is associated with the plasma membrane of haptomonads of Crithidia fasciculata attached to the cuticular lining of the hindgut of Anopheles gambiae. This surface material is completely absent from morphologically identical haptomonads from the mosquito foregut and from rosettes in culture. On the basis of these observations, it is suggested that cell coat formation is dependent on suitable environmental conditions. A cytochemical staining technique indicates the presence of carbohydrates in (a) the cell coat, (b) the outer leaflet of the plasma membrane of haptomonads from all locations and (c) small cytoplasmic vesicles and multivesicular bodies in all haptomonads. It is suggested that these cytoplasmic organelles represent stages in the intracellular pathway for material ingested by pinocytosis rather than elements involved in surface coat formation.


Partial purification of antigens collected during in vitro cultivation of the larval stages of Taenia pisiformis.

Larvae of Taenia pisiformis were cultured in vitro in medium containing 2-5, 5 or 20% (v/v) of normal rabbit serum (NRS). Greatest development occurred in 20% NRS, and the potency of antigens collected in medium from each culture tested by intradermal (2/d) skin tests in infected rabbits paralleled the in vitro growth rate of larvae. 'Culture' antigens from 5% NRS stimulated good immunity in rabbits to a challenge infection with T. pisiformis eggs, although they were poorly reactive in skin tests. T. pisiformis larvae were also cultured in 10% (v/v) of filtrates of serum reduced to one-half of its volume by passage through 300 000 MW cut off (XM300F) or 100 000 MW cut off (XM100F) ultrafiltration membranes. Larvae cultured using XM300F had growth rates comparable with those cultured in 20% NRS, and the antigens release into the culture medium had equal potency in i/d tests and in stimulating protective immunity in rabbits. Larvae did not develop in XM100F or produce skin-reactive or protective antigens. Crude 'culture' antigen from cultures in 20% NRS was separated into 4 fractions by filtration on Sephadex G200. All of these fractions gave i/d skin reactions in infected rabbits. Fraction 3 (F3) was the most active, but was shown by acrylamide gel electrophoresis and immunoelectrophoresis to be highly contaminated with rabbit serum proteins. F3 was separated into fractions on DEAE-Sephadex A50, and the third fraction from this was as active as the original culture medium in i/d skin tests, but had only 5% of the original protein concentration. Electrophoresis demonstrated few serum contaminants, and 2 indistinct protein bands that were not present in a similar fraction of NRS. Neither Sephadex G200 F3 nor DEAE-Sephadex F3 stimulated protective immunity in rabbits, suggesting that antigens stimulating immunity against the establishment of T. pisiformis in rabbits and those provoking cell-mediated immune reactions may be different.


Seasonal variation in the population dynamics of Caryophyllaeus laticeps.

The biological parameters which generate seasonal fluctuations in the size of populations of Caryophyllaeus laticeps are examined in detail. A mathematical model is formulated to describe the dynamics of the adult parasite within the fish host Abramis brama, and the predictions of the model are compared with observed population data. The seasonality of parasite population size is shown to be caused by the combined effects of a temperature dependent mortality rate and flucate of larval parasites. The observed overdispersed distribution of adult parasite numbers within the host population is shown to be generated by variability in feeding habits between individual members of the fish population. The theoretical population model is used as a framework for the investigation of, among other factors, the comparative influences of the immigration and death rates on the dynamics of the adult parasite, the future behaviour of the system under altered environmental conditions and the importance of chance effects in the dynamics of individual parasite populations within a single host. The stability of the dynamics of the complete life-cycle of C. laticeps is discussed in relation to the inherent biological complexity of host/helminth parasite interactions.


Accelerated expulsion of adult Trichinella spiralis in mice given lymphoid cells and serum from infected donors.

Immunity to the adult stage of Trichinella spiralis, assessed by an acceleration of worm expulsion, was transferred to recipient mice with mesenteric lymph node cells (MLNC) or serum taken from infected donors. Immunity was transferred most effectively by MLNC taken from donors infected for 8 days, i.e. donors actively responding to infection. Transfer of both MLNC and serum brought about a marked acceleration of worm expulsion in all cases, even where MLNC or serum given separately failed to transfer a significant degree of immunity.


The growth of secondary infections of Hymenolepis microstoma in mice: the effect of various primary infection regimes.

Groups of mice were infected with 1, 5 or 10 cysticercoids of Hymenolepis microstoma. Infections were terminated with the anthelmintic 'Zanil' after 5, 15 or 30 days and the mice challenged with 6 cysticercoids. The growth of the worms in the secondary infections decreased as either the intensity (number of cysticercoids administered) or duration of the primary infections increased. It is postulated that the results have an immunological basis.


Eimeria maxima: a comparison of two laboratory strains with a fresh isolate.

Oocysts of the Weybridge and Houghton strains of Eimeria maxima and a fresh field isolate were similar and measured on average 30-9 X 22-4 mum. The Weybridge strain and the field isolate produced similar pathogenic effects in 6-week-old chickens, high doses causing 50-80% mortality and severe weight loss. The Houghton strain was slightly less pathogenic and few birds died but more oocysts were produced. With each strain, a single dose gave complete immunity to a light challenge with the homologous strain. Two or 3 immunizing doses gave complete immunity to a heavy homologous challenge but were not sufficient to protect against heterologous challenge.


Milk-borne infection of rats with Strongyloides ratti and Nippostrongylus brasiliensis.

The numbers of mature worms which developed in young rats after their mothers were injected with 4000 L3 late in lactation were 1% (Nippostrongylus brasiliensis) and 24% (Strongyloides ratti) of the dose administered. The low value for N. brasiliensis validates the conclusion that milk is a real and important vehicle for infection in S. ratti since possible errors from skin invasion of the young would have been common to both species. The level of mature S. ratti infection in lactating mothers in this experiment was negligible, 97-99% of the adult worms appearing in the offspring. These results may indicate that the milk route is possible with N. brasiliensis even though it is quantitatively insignificant.


The isolation and characterization of a Babesia from red deer (Cervus elaphus).

On three occasions, antibody positive blood from wild red deer produced overt infections with Babesia when inoculated into splenectomized red deer. One of the deer also became infected with Eperythrozoon sp. Babesia divergens, B. capreoli and the Babesia of red deer are morphologically similar and the marginal position of the parasites in the host cell is characteristic. Babesia were not seen and no antibody was formed in five out of six splenectomized bovine calves which were injected with parasitaemic red deer blood. Two of these calves when challenged with B. divergens were fully susceptible. A transient infection with the deer Babesia may have occurred in the sixth calf since antibody was detected and the animal resisted challenge with B. divergens. In indirect fluorescent antibody tests there was little or no difference in the titre of sera from naturally or experimentally infected cattle and deer when reacted with B. divergens or the red deer Babesia antigens. Despite their similarities, specific status for B. divergens and the red deer Babesia is probably justified; at present there is insufficient evidence to justify separation of the red deer Babesia from B. capreoli.


Fine structural observations on oocyte development in monogeneans.

The ultrastructural changes accompanying oocyte differentiation in the ovaries of the monogeneans, Diclidophora merlangi, Diplozoon paradoxum and Calicotyle kröyeri have been described. In each case, oogenesis in the ovary proceeds as far as meiotic prophase in the primary oocyte. A three-stage sequence of development based on oocyte morphology is proposed: (1) Oogonia and early, immature primary oocytes are typically undifferentiated, with chromatin-laden nuclei occupying most of the cell volume. The cytoplasm contains small clumps of mitochondria and unattached ribosomal aggregates. There is evidence of mitosis and, in later stages, meiotic prophase is indicated by the appearance of nuclear synaptonemal complexes. (2) Maturing primary oocytes are characterized by increased nucleolar volume associated with the production of RNA for export to the cytoplasm. An organized GER and Golgi apparatus are established and involved in the synthesis and packaging of membrane-limited cortical granules. Annulate lamellae and nucleolus-like bodies appear in the cytoplasm and, with development, the cells increase in size and, peripherally, become interdigitated. (3) Mature primary oocytes represent a resting phase when cellular activity is minimal. Golgi disappear and the ER fragments or becomes reduced in dimensions. Mitochondria and free ribosomes are numerous and cortical granules move to the cell periphery. The cells separate and, when mature, are released from the ovary. There are minor species differences in oocyte ultrastructure and development.


Immunity to coccidiosis: stages of the life-cycle of Eimeria maxima which induce, and are affected by, the response of the host.

An attempt was made to determine the relative importance of the different life-cycle stages of Eimeria maxima in the induction of immunity and also those stages most affected by the immune response of the host. In one experiment the life-cycle was controlled by chemotherapy but in all other experiments partial life-cycles were induced by transfers of infected mucosa between hosts. The results indicated that the second generation schizont stage is probably that most concerned in the induction of protective immunity and that sexual stages are most susceptible to immune inhibition. After initial inhibition in the immune host the earlier asexual stages were able to resume development when transferred to a susceptible host. The longer the period of exposure to the immune environment, the less able was the parasite to recover.


Different levels of acquired immunity to Schistosoma mansoni in two strains of hamster.

A primary infection with schistosoma mansoni, of 5 or more weeks duration, stimulated a high level of resistance to a challenge infection in the WO outbred strain of golden hamster. In sharp contrast, the LGN strain showed no statistically significant immunity to reinfection in most experiments and where detected the level of resistance was only about half that observed in the WO strain. Immunity to reinfection was assayed with the lung recovery method which assesses resistance a few days after challenge and with the conventional perfusion assay which measures immunity 6 weeks after challenge. Wide differences in the immune response to S. mansoni in different strains of the same host species have not been reported previously.


Cross-immunity to Schistosoma mansoni and S. haematobium in the hamster.

Hamsters (WO strain) with a primary infection of Schistosoma mansoni or S. haematobium rapidly developed immunity to homologous challenge judged by the lung recovery assay. Immunity was detected at 4-5 weeks and reached a plateau 6 weeks after infection. Using this information, hamsters with an 8-week primary infection with S. mansoni or S. haematobium were tested for resistance to homologous reinfection and resistance to a challenge with the other species of schistosome. Primary infection with S. mansoni or S. haematobium conferred a high level of immunity to reinfection with either species of schistosome judged by the perfusion assay, involving recovery of adult worms 6-10 weeks following challenge. Estimation of the level of immunity with the lung recovery assay, 5 days after challenge, indicated that immunity due to a primary infection with S. mansoni acted at or before migration of the challenge through the lungs but immunity stimulated by a primary S. haematobium infection was only partially effective at the lung stage and substantial destruction of challenging organisms occurred at a later stage of development. Antibodies in immune sera of hamsters with a primary S. mansoni or  or S. haematobium infection were shown to bind to common antigens on the surface of young  schistosomula of either species by u.v. microscopy using as detecting agent a fluorescein-labelled rabbit antiserum directed against hamster globulins.


The number and size of ovarian balls of Moniliformis (Acanthocephala) from laboratory rats.

By means of conventional light microscopical and counting procedures, estimations have been made of the average number and size of ovarian balls from unfertilized and fertilized female Moniliformis dubius. The observations were made on worms recovered from experimental primary infections lasting 1, 2, 3, 4, 5, 8, 11, 14, 17 and 20 weeks in male rats. The number of ovarian balls rises to about 6300 per worm, with the maximum being attained more rapidly in unfertilized than in fertilized females. On average more ovarian balls were present in unfertilized than in fertilized females, but a marked decline in number occurred in both groups of worms towards the end of the experimental period. Similarly, on the basis of the area within the elliptical profiles of fixed ovarian balls, it appeared that those from unfertilized females were generally larger on average than those from fertilized worms.


Molecular structure and morphology of glycogen isolated from the cestode, Moniezia expansa.

A particulate polysaccharide was isolated by differential centrifugation and alkali extraction from homogenates of the cestode Moniezia expansa. The polysaccharide had the structure of a glycogen. Its chemical properties, infra-red spectrum and optical rotation showed that it consisted of alpha-1,4- and alpha-1,6-linked glucopyranose units. Examination of the complex with iodine and the precipitate with concanavalin-A showed that the structure was highly branched. Oxidation with periodate and hydrolysis with alpha- and beta-amylase were used to measure mean chain lengths. For the particulate preparation the average chain length was 12-9 glucose units and the exterior and interior chain lengths were 9-0 and 2-9 units respectively. The particulate preparation had a very high sedimentation constant (s20, w = 910) with a smaller component at about s20, w = 600, but the alkali extracted material had an s20, w = 61 similar to that shown by alkali degradation of the particulate preparation. The morphology of the particulate material was similar to that of rat liver glycogen, alpha, beta- and possible gamma-particles being identified by electron microscopy. The alpha-particles were relatively stable under acidic conditions remaining intact down to pH 2-5. At pH 1-7 the alpha-particles dissociated into their constituent beta-particles with a consequent decrease in the opalescence of the solution. The nitrogen content of 0-9% was high for a glycogen.


Evasion of the haemocytic defence reaction of certain insects by larvae of Hymenolepis diminuta (Cestoda).

Larvae of Hymenolepis diminuta develop in the haemocoele of the beetles Tribolium and Tenebrio, and of the locust Schistocerca gregaria, without being encapsulated by haemocytes. The mechanism of this evasion of the haemocytic defence reaction has been examined using various techniques. Larvae grown in culture and injected into S. gregaria have a few or no haemocytes adherent even after 8h, although latex beads injected at the same time have been thickly encapsulated. This, and results of transplanting cysticercoids and host tissue between different insect species, suggests that the surface of the larvae may bear an inherent similarity to the surface of host tissues and thus escape recognition as 'not-self' by the host's haemocytes.


Symphalangism with metacarpophalangeal fusions and elbow abnormalities.

Three generations of a family manifest similar skeletal abnormalities: proximal symphalangism with several unusual features, metacarpophalangeal synostoses, massive tarsal and carpal fusions and abnormalities of the elbows (radial head dislocation, radiohumeral synostosis). Two members of this family were previously reported by Pearlman et al. as examples of the Nievergelt syndrome, but the affected individuals lack the mesomelic dysplasia that is an integral part of that entity. Moreover, the Nievergelt syndrome does not include symphalangism. The term "Nievergelt-Pearlman syndrome" should be dropped.


Giant idiopathic thymomegaly.

Apart from the anterior mediastinal position and the usual size of the normal thymus, aberrant locations and extreme size variations may occur. This is illustrated by an eight month old boy whose histologically normal thymus presented as a large mass in the right hemithorax. It is the largest normal thymus on record in an infant. Thus, idiopathic thymomegaly should also be considered in the differential diagnosis of peripheral intrathoracic mass lesions.


Traumatic para-mediastinal air cyst. A case report.

The roentgenographic features of a paramediastinal air cyst following chest trauma are reported. After an initial period of enlargement the lesion completely resolved in one month. Experience with this patient and a review of similar cases reported in the literature suggests that lesions of this type may be observed for spontaneous resolution.


Epiphyseo-metaphyseal cupping following infantile scurvy.

A five year old girl presented with short femora, cupped distal metaphyses and flexion deformity of the knees suggesting previous epiphyseo-metaphyseal damage. The aetiology was suggested by finding a history of previous infantile scurvy with separated distal femoral epiphyses. The rarity of this complication and possible contributing factors are discussed.


The neuro-radiological examination of endocrine disorders of central origin in the child (precocious puberty, hypopituitarism).

The neuro-radiological findings in 38 cases of precocious puberty of central origin and 9 cases of hypopituitarism (craniopharyngiomas excepted), are reported. The radiological examination consisted of plain films of the skull and pneumo-encephalography. In the 9 cases with hypopituitarism radiological examination was normal in 4 and localised but quite diverse anomalies were discovered in 5. Out of 38 patients presenting with isosexual precocious puberty, 29 were female and 9 male. Out of the 29 girls, neuro-radiological examination was normal in 20 and showed a hypothalamic anomaly in 9. Out of the 9 boys, 8 had a hypothalamic anomaly, and only one examination was normal. In precocious puberty we found 1 ectopic pinealoma and 2 gliomas of the chiasma. In these three cases the clinical context and radiological examination made the diagnosis obvious. Masses were discovered in 7 (3 spongioblastomas and 4 heterotopias). In 2 cases (spongioblastomas) neurological symptoms were present and made an operation mandatory. In 5 cases (1 spongioblastoma, 4 heterotopias) precocious puberty was an isolated finding. It was not possible to make, on a clinical or radiological bases, a distinction between spongioblastoma and heterotopia. As time has passed the role of surgery has changed. Formerly, surgery aimed at excision of the lesion, but with advances in medical treatment surgical intervention is now directed towards biopsy and the histological study of lesions which may be treated by radiotherapy.


Arteriographic diagnosis of brain death in children.

Transfemoral cerebral angiography was performed in four children with brain death secondary to increased intracranial pressure. Findings not previously described are filling of the cavernous, petrous and cervical portions of the contralateral internal carotid artery via the anterior communicating artery, filling of the basilar and vertebral arteries via the posterior communicating artery and anterior displacement of the basilar artery.


Radiographic findings in children with psychosocial dwarfism.

The diagnosis of psychosocial dwarfism is established through history, the determination of delay in growth and skeletal maturation, the lack of evidence of organic disease and accelerated growth and psychomotor development in a nuturing environment. Radiographically temporary widening of the cranial sutures may be detected in a follow up examination or less often already at the time of initial examination. Determination of wide cranial sutures may be contributary in establishing the diagnosis of psychosocial dwarfism. In a patient with this syndrome and lack of neurological signs or symptoms widening of the cranial sutures is an expected finding and no further neuroradiologic studies are necessary.


Radiologic features of "adult type" polycystic kidney disease in the neonate.

Two cases are reported of adult type polycystic renal disease (autosomal dominant) presenting in the newborn as a unilateral abdominal mass. The radiographic findings in the involved kidney simulated the ectatic tubules of infantile polycystic disease, yet histologic examination was consistent with the adult variety and both infants had other family members with adult type polycystic kidneys. These cases emphasize some of the ambiguities that exist in the definition and classification of polycystic renal disease.


Multiple bladder filling defects in children with cystitis.

Two children with cystitis presented with multiple filling defects in the urinary bladder. They were proven to be cases of cystitis glandularis with proliferative changes of the bladder epithelium. The radiographic findings are described and the differential diagnosis from neoplasms is outlined.


Postmortem angiocardiography in newborn infants with congenital malformation of the heart and great vessels.

In congenital malformations of the heart and great vessels with a fatal outcome a postmortem angiocardiography may contribute to diagnosis. In this technique the heart is not dissected and the topographical relationships remain unchanged. A postmorten angiocardiography is of particular interest if no autopsy is to be performed. Some patho-anatomical details are demonstrated in three selected cases: newborn infants with 1. hypoplastic left heart syndrome, 2. truncus arteriosus communis with interruption of the aortic arch, and 3. aortic-left ventricular tunnel.


Experiences with triggered pulmonary exposures in children.

With conventional manual triggering technique pulmonary exposures expected to time and end-inspiration were made on 51 small children. These exposures showed a random distribution. Transthoracic impedance reflects the variations in the pulmonary air-fluid ratio during respiration. In 94 infants and small children the transthoracic impedance was monitored while pulmonary exposures were triggered by a pulse given at the level of end-inspiration or end-expiration. It was found that transthoracic impedance as a triggering device permitted precise matching of the exposures to end-inspiration or end-expiration.


Hodgkin's disease in children: clinico-roentgenologic features of the lesion in the chest.

The roentgenologic features of Hodgkin's disease were studied in 105 patients under 14 years of age. The mediastinal and hilar nodes were involved in 64.7% of patients. Some consistency of extent and pattern of disease was observed in that mediastinal lymphatic lesions could be associated with cervico-supra-clavicular and retroperitoneal lesions. There was lung infiltration in 14.3% of patients and the frequency of this lesion dependent on the histological type. It was commoner in nodular sclerosis, mixed cellularity and lymphocytic depletion. Lung infiltration usually developed in continuity with the lymphatic gland lesion and only rarely in a metastasis-like form.


Preoperative diagnosis of benign hepatic hamartoma by correlation radioisotopic and angiographic studies.

The case of a 12 year old girl with a hamartoma of the liver is reported. A preoperative liver scan showed accumulation of technetium-99m sulfur colloid in the tumor with isotopic and contrast arteriography demonstration of a hypervascular intrahepatic mass. Although these diagnostic findings are not pathognomonic of hamartoma, they are indicative of a benign lesion within the liver.


The radiolucent liver.

Changes in the liver density on the plain film of the abdomen may be seen when there is a change in the nature of the liver structure. Increased amount of fat is associated with increased radioluceny which can be detected when looked for specifically. Since 1972, we have had the chance to make a diagnosis of fatty liver on the plain film of the abdomen in five patients. In all these cases, histological sections showed severe fatty change. This finding becomes easier to appreciate on the early films of an I.V.P. examination, especially when large doses are used.


Magnification renal scintigraphy in the differential diagnosis of septa of Bertin.

Eight consecutive patients, referred because intravenous urography (IVP) raised the question of hypertrophied septum of Bertin versus a pathologic mass, were examined using 99mTc labeled radiopharmaceuticals with magnification renal scintigraphy. The areas of concern showed a spectrum of activity, from normal to markedly increased, as compared to surrounding tissue. The activity correlated with the size of the mass effect on IVP. Increased resolution provided by pinhole magnification was important in evaluating these patients. We feel that magnification renal scintigraphy is valuable in the evaluation of intrarenal masses.


Calcified thrombus in the inferior vena cava in infants and children.

Calcified thrombi in the prerenal (suprarenal) segment of the inferior vena have a characteristic radiographic appearance that permits accurate "plain film" diagnosis. Most have been fortuitously discovered in infants and young children. None of the affected individuals has had clinical evidence of venous obstruction. Vena caval obstruction is usually incomplete. Uncalcified clot caudal to the calcified thrombus caused complete obstruction of the inferior vena cava and renal veins in one of our patients, a healthy infant; since collateral flow was adequate surgery was not advised. We believe that aggressive diagnostic and therapeutic measures are unnecessary in the management of infants and children with calcified thrombi in the inferior vena cava.


A form of metatropic dwarfism in two brothers.

Two brothers are described with identical features of short-limbed dwarfism, normal face, hands and feet, respiratory difficulties and mild scoliosis. It proved impossible to offer a definitive diagnosis, though radiological features as a whole bore similarities to those of metatropic dwarfism, with the most notable feature the narrowing of the ossified components of the vertebral bodies.


Anomalous left pulmonary artery with an unusual barium swallow.

An atypical finding on barium swallow in a child with an anomalous left pulmonary artery causing obstructive emphysema in the right lung is described. The value of bronchography and need for early surgical intervention is stressed.


Cervical herniation of the lung. Report of a case and review of the literature.

Cervical herniation of the apex of the lung into the soft tissues of the neck is a rare finding in the pediatric age group. Whereas in adults the etiology is either post-traumatic or secondary to chronic respiratory disease, in children the condition appears to arise spontaneously as the result of a congenital defect in the costovertebral fascia. Surgical treatment is rarely indicated unless there is evidence of incarceration, or progressive increase in size with resultant cosmetic deformity.


Calcified subvalvular left ventricular aneurysm: an unusual case in a 4-year-old-child.

An unusual form of left ventricular aneurysm affecting young Negroes has recently been described at the aortic or mitral valve ring; constitutional factors have been postulated. A 4-year-old Negro boy was observed with a left ventricular submitral aneurysm, probably one of the largest and one of the most calcified to be reported. Tuberculous lymphadenitis involving some of the mediastinal lymph nodes was found on postmortem examination; tuberculosis was believed to be a secondary contributing factor. A review of the literature disclosed only 5 other children with calcified left ventricular aneurysms, of which 2 were of the subvalvular type.


[Serum IgE in patients suffering from IgA deficiency with or without atopy].

Numerous studies, based upon the frequency of allergic and auto-immune disorders in association with selective deficiency in IgA, as well as the abnormally high proportion of IgA deficiency in atopic patients, have led to the hypothesis that allergy results from a deficiency in IgA during the first months of life. Thus subjects with an initial transient deficiency in IgA (followed by normal or greater than average production) produce an excess of IgE. The aim of this study, carried out by multifactorial data analysis, was to determine whether serum IgE levels were related to those of IgA. Comparison of the serum Ig levels of 4 groups of individuals, with or without IgA deficiency, showed that the production of IgE was more closely related to the respiratory condition responsible than to IgA levels. According to IgA and E levels, the 4 groups differ distinctly, atopic patients without asthma constituting a "bridge" between the control group and those with asthma. In the presence of an apparently identical situation, i.e. an IgA deficiency, individuals may react in two different ways: some produce an abundance of IgE whilst others fail to do so and are more susceptible to recurrent infective episodes. The role of the genetic control of IgE as well as environmental factors in the pathogenesis of allergic manifestations is discussed.


[Echotomography of the liver with three-dimensional representation of the organ].

Three-dimensional representation facilitates the reading of ultrasonic seriographs of the liver. It uses a conducing wire to provide a correspondence between the xipho-umbilical line and the information collected on the seriographic polaroids. Proceeding from image to image, a more thorough interpretation is possible. This analytical study provides a synthetic representation of the organ. When present lesions are seen on these diagrams and their location and dimensions clearly defined. A precise indication of the height, breadth and thickness of the organ is given, which makes it possible to obtain an accurate approximation of the hepatic volume, taking the morphotype into consideration.


CD spectra of 5-methyl-2-thiouridine in tRNA-Met-f from an extreme thermophile.

5-Methyl-2-thiouridine (S) in tRNA-Met-f from an extreme thermophile is located in the TpsiC region, replacing T, and has a positive CD band centered at 310 nm. Upon heating, the profiles of the change in this band were similar to the UV melting profiles of the change monitored at 260 nm. This strongly suggests a close relation between heat denaturation of the tRNA and the conformation of the S base. Oligonucleotides containing S showed negative CD bands at 320-330 nm, like the monomer S itself, but when the 3'-2/5 fragment containing S formed a complex with the complementary 5'-3/5 fragment, a positive CD band appeared at 310 nm. These results suggest that combination of the TpsiC loop containing S with the hU loop is necessary for the positive band of S at 310 nm. S may serve to strengthen the association of the TpsiC loop with the hU loop in tRNA of the thermophile.


Reactivity and selectivity in light-induced free radical reactions of 2-propanol with purine and pyrimidine mononucleotides and dinucleoside monophosphates.

Photoalkylation reactions with 2-propanol, initiated with di-tert-butyl peroxide, of a variety of purine and pyrimidine mononucleotides and dinucleoside monophosphates lead to the substitution of an alpha-hydroxyisopropyl group for the H-8 atom of adenosine and the addition of the alcohol across the 5,6-double bond of the pyrimidines. Adenosine moieties blocked at their 3'-hydroxyl group are alkylated faster than those blocked at their 5'-hydroxyl. The reactivity of the uridine moieties of 3'-UMP, 5'-UMP, and uridylyl-(3',5')-uridine is not affected by the location of the phosphate group. However, the uridine moiety of uridylyl-(3',5')-adenosine is modified faster than that of adenylyl-(3',5')-uridine. It is suggested that steric hindrance imposed by the phosphate group determines the reactivity of adenosine moieties, while base stacking involving adenosine determines the reactivity of uridine moieties. These two effects play a major role in controlling the nature and degree of the selectivity of these photoalkylation reactions for either adenosine or uridine. Cytidine has been found to be inert in these reactions.


Detection of DNA and RNA polymerase activities in situ following electrophoresis in polyacrylamide gels.

A procedure is described for the detection of DNA dependent DNA and RNA polymerase activities in intact polyacrylamide gels that contain DNA. After electrophoresis under non-denaturing conditions, the intact gels are incubated with DNA or RNA polymerase reaction mixture in which one of the four deoxyribonucleoside or ribonucleoside triphosphates is radioactively labeled. The acid insoluble radioactivity associated with the intact gel is then analyzed by autoradiography of the intact gel or by liquid scintillation spectrometry of the sliced gel. Inhibition of the enzymatic activities by low molecular weight compounds such as N-ethylmaleimide or rifampin can be demonstrated by this procedure.


Organisation of subunits in chromatin.

There is considerable current interest in the organisation of nucleosomes in chromatin. A strong X-ray and neutron semi-meridional diffraction peak at approximately 10 nm had previously been attributed to the interparticle specing of a linear array of nucleosomes. This diffraction peak could also result from a close packed helical array of nucleosomes. A direct test of these proposals is whether the 10 nm peak is truly meridional as would be expected for a linear array of nucleosomes or is slightly off the meridian as expected for a helical array. Neutron diffraction studies of H1-depleted chromatin support the latter alternative. The 10 nm peak has maxima which form a cross-pattern with semi-meridional angle of 8 to 9 degrees. This is consistent with a coil of nucleosomes of pitch 10 nm and outer diameter of approximately 30 nm. These dimensions correspond to about six nucleosomes per turn of the coli.


Two restriction endonucleases from Bacillus globiggi.

The sites of action of the restriction enzyme Bgl II on lambda DNA are mapped. This enzyme recognises the sequence 5' ...AGATCT...3' and makes staggered cuts producing sticky ends. In lambda DNA, the second A in this sequence is methylated about 50% of the time by a bacterial methylase absent in E. coli dam. In contrast to Bgl II, Bgl I makes many cuts in lambda DNA and produces 5' terminals which are not substrates for polynucleotide kinase.


Persistence of the ten-nucleotide repeat in chromatin unfolded in urea, as revealed by digestion with deoxyribonuclease i.

It is shown by enzymatic digestion of chromatin from rat liver or Guerin ascites tumour (GAT) that treatments, which abolish the 180 base pair repeat, as revealed by digestion with micrococcal nuclease (shearing in salt solutions of medium ionic strength, sonication, fixation with formaldehyde in the presence of 5 M urea), have little effect on the 10 nucleotide repeat, observed in deoxyribonuclease I digests.


An improved synthetic route to the beta-hydroxyethyl esters of 5'-nucleotides.

A simple method is described for the preparation of the beta-hydroxyethyl esters of nucleoside 5'-phosphates by treatment of the appropriate 2',3'-isopropylidene nucleoside with 2-chloro-2-oxo-1,3-dioxaphospholane. Unambigous structural assignments were based on 13C nmr spectroscopy. Chemical shifts and 13C-31P spin-spin coupling constants are discussed.


Diversity of sequences in total and polyadenylated nuclear RNA from Drosophila cells.

Complementary DNA was synthesized using polyadenylated nuclear RNA of cultured Drosophila cells as template. The kinetics of hybridization of this cDNA with nuclear RNA indicated that the complexity of this RNA population is five to ten times greater than that of cytoplasmic mRNA. The same difference in the fraction of DNA represented was obtained when nuclear and cytoplasmic RNA were hybridized with labeled unique sequence DNA. The fraction of the DNA sequences represented in total number of polyadenylated nuclear RNA is much higher than that represented in cytoplasmic RNA.


The base catalysed anomerisation of beta-5-formyluridine; crystal and molecular structure of alpha-5-formyluridine.

On treatment with strong base beta-5-formyluridine undergoes an anomerisation to give a mixture of the alpha- and beta-anomers. The anomers have been separated by fractional recrystallisation and the absolute configuration of the alpha-anomer has been determined by X-ray analysis.


Regenerating rat liver DNA polymerases: disimilitude or relationship between nuclear and cytoplasmic enzymes?

The possible relationship between the nuclear and cytoplasmic DNA polymerases of regenerating rat liver was studied by sucrose gradient analysis, salt dissociation, and with specific inhibitors. After aqueous subcellular fractionation and removal of the nuclear membranes, three species of DNA-dependent DNA polymerases were characterized: 1) a DNA polymerase-beta in the nuclei. 2) a DNA polymerase-alpha in the cytosol which was not dissociated at high salt concentrations; and 3) an intermediate form in the cytosol and in the Triton wash containing the nuclear membranes. The latter form behaved like DNA polymerase-alpha et low salt concentration but was dissociated at high salt concentrations to a low molecular weight species with properties like DNA polymerase-beta (resistance to inhibition by N-ethylmaleimide, heparin and KCL). In vitro reassociation experiments suggest that this intermediate form corresponds to the association of DNA polymerase-beta with a membrane component or cytoplasmic protein(s) which appear(s) in regenerating rat liver.


Chromatin and nucleosome structure.

Chromatin nucleosomes (mononucleosomes through pentanucleosomes) have been isolated by staphylococcal nuclease digestion of calf thymus nuclei. The peak value ellipticity is the same for all oligomers, 1900 deg cm2, mol-1 at 280-nm, 23 degrees C. The dh280/dT vs T show a progressive increase in Tm of the main thermal band (73.5 degrees C, monomer; 79 degrees C, pentamer). Very small amounts of free DNA can be observed in the melting profiles, and shoulders at 60 degrees C and 93 degrees C appear and increase in magnitude as the particle size increases. The magnitude of the change, delta[theta]280, increases with oligomer size. This pattern could result from an initial unfolding of an asymmetric assembly of nucleosomes (polynucleosome superhelix) in addition to the denaturation of the internal nucleosome structure, and a subsequent or simultaneous denaturation of the double strand DNA. The extent of this unfolding appears to depend upon the size of the oligomer and therefore implies interactions between asymmetrically assembled neighboring nucleosomes.


Circular dichroism studies of ethidium bromide binding to the isolated nucleolus.

Circular dichroism in the 300-360 nm region and fluorescence induced by intercaltating binding of ethidum bromide to both DNA and RNA components were studied in isolated HeLa nucleoli. Both DNA and RNA compoents contribute to the induced dichroic elliticity. Digestion of nucleoli by RNase or DNase shows that most of the induced ellipticity comes from the DNA component. In nucleoli with an RNA/DNA = 0.8/1.0 the RNA component gives only 20% of the total ellipticity when measured at an ethidium bromide/DNA = 0.25. Spectro-fluorometric titration shows that ethidium bromide intercalates mostly into DNA in nucleoli. Both circular dichroism and fluorescence studies indicate that both DNA and RNA components in isolated nucleoli are less accessible to intercalating binding by ethidium bromide when compared to purified nucleolar DNA, DNA in chromatin or purified ribosomal RNA. Circular dichroic measurements of intercalating binding of ethidium bromide to to nucleoli may be used to study changes in nucleoli under different physiological or pathological conditions.


Thermal denaturation of sheared and unsheared chromatin by absorption and circular dichroism measurements.

Thermal denaturation of chromatin is observed by simultaneously monitoring absorption and circular dichroism at 276 nm as functions of temperature. Either observation indicates that sheared chromatins shows less thermal stability than native chromatin. The temperature-dependent ellipticities at 276 nm of these chromatins show features not seen in the absorption curves: the ellipticity of unsheared chromatin increases with temperature, while this increase is abolished or greatly reduced in the same chromatin after shearing. After its first thermal transition (prior to the helix-coli transition) the unsheared chromatin achieves the same ellipticity as sheared chromatin.


Preparation and properties of a poly A resin and its use in the isolation of naturally occurring poly U sequences.

A method for the covalent attachment of poly A, as well as other nucleic acids and nucleosides, to a methylene dianiline derivative of starch is described. The properties of this poly A resin and its use for the recovery of poly U sequences from both nuclear and cytoplasmic extracts of HeLa cells is described.


Structural studies on the two forms of 8-bromo-2',3'-O-isopropylideneadenosine.

The crystal and molecular structures of two forms of 8-bromo-2',3'-O-isopropylideneadenosine have been determined by X-ray methods. In one form, the molecular structure has planar conformation in the sugar moiety and no intramolecular hydrogen bond. On the other hand, the molecular structure of the second form has C(2')-endo conformation and an intramolecular hydrogen bond. No stacking interaction between adjacent bases is found in either form, but two modes of the base-pairing hydrogen bond exist in the second form.


The conservation of poly-A-containing RNA during the dormant state of the moss Polytrichum commune.

The moss Polytrichum commune can be dried to less than 2% of free water and kept for some weeks without losing its viability. Upon rehydration of the moss, protein synthesis starts about 60 minutes before incorporation of radioactive precursors into RNA can be observed. Pulse labeled total RNA and poly-A-containing RNA do not show quantitative or qualitative alterations during desiccation up to 20 days.


Chicken globin gene number.

Using complementary DNA prepared from adult chicken globin messenger RNA, we show the existence of 2-3 non-cross-hybridising globin sequences in the chicken genome, each of which is present in only one copy per haploid genome. This was done by solution hybridization to total DNA under conditions of cDNA excess. The data agreses with results of RNA-driven hybridisation of globin complementary DNA, and with protein data.


Sequence specific fragments in the field desorption mass spectra of dinucleoside phosphates.

In field desorption mass spectrometry of ribodinucleoside phosphates the formation of nucleoside cyclophosphates can be used to determine the base sequence.


Effects of phytohormones on thermal denaturation profiles of Cymbidium DNA: indication of differential DNA replication.

Protocorm pieces of the orchid Cymbidium were aseptically cultured either without phytohormones, or with one of the growth promoting substances, auxin cytokinin, and gibberellin. The derivative melting profiles of the extracted DNA's differ from each other with respect to the size of various AT- and GC- rich fractions. Evidence has been obtained for the increase of the more AT--rich fractions in auxin-treated cultures, while gibberellin stimulated the expansion of the GC-rich fractions. These results are consistent with earlier cytological and cytochemical findings and indicate the involvement of hormone-controlled differential DNA replication in the development of Cymbidium protocorms in vitro.


The absence of histone H1 from the chromatin fraction obtained by sonication of calf thymus nuclei under "quasiphysiological" ionic conditions.

The minor chromatin fraction was isolated from the sonicated calf thymus nuclei on the basis of its differential solubility in the "quasiphysiological" salt medium (0.1 M KCl-0.05 M NaCl-l mM MgCl2-1 mM CaCl2). Histone Hl is almost completely absent from this fraction. DNA isolated from this fraction occurs in three discrete low mol. wt. fragments. The fraction of chromatin which lacks histone Hl can also be obtained by two other methods. On of them consists in salt precipitation of the chromatin gel and its subsequent sonication. The second method includes precipitation of the sonicated chromatin gel by salts. In the first case the properties of the chromatin fraction which remains in the supernatant after centrifugation closely resemble those of the original salt-soluble nuclear fraction. The second method yields supernatant fraction also lacking histone Hl but containing heterogeneous DNA. Comparisons were also made of the sonically-solubilized nuclear fractions obtained in the complete salt medium and its mono and divalent cationic constituents.


Partial purification of a double-stranded RNA specific ribonuclease (RNAse D) from Krebs II ascites cells.

In a search for eucaryotic enzymes which might process the heterogenous nuclear RNA (HnRNA) from animal cells into messenger RNA, a ribonuclease called RNAse D analogous to E. coli RNAse III in its ability to cleave specifically synthetic or viral double-stranded polyribonucleotides has been detected and extensively purified from the cytosol of Krebs II mouse ascites cells. The purification procedure involved cellular fractionation followed by DEAE-and CM-cellulose chromatography and resulted in an RNAas D preparation contaminated with trace amounts of single-strand specific RNAse (equivalent to less than 0.3 ng per ml) as assayed against poly (rC). Significant levels of RNAse H activity against poly (rA)-poly (dT) were still present in these preparations.


On the mechanism of tRNA methylase-tRNA recognition.

In order to further elucidate the mechanism of tRNA methylase-tRNA intreaction the methylation of some individual tRNAs separately and by pairs was performed. In conditions of tRNA excess the methylation rates of positionally analogous nucleotides in tRNA molecules are not summed up when two substrates are simultaneously present in the reaction mixture. The inhibitory action of yeast tRNASer, possessing m5c in position 29, on the methylation of C29 in other individual tRNAs was shown. Yeast tRNAVal which possesses an A residue in position 27 was shown to inhibit the methylation of G27 in E. coli tRNAMet. The data obtained confirm the suggestion that tRNA methylases recognizes the tertiary structure of tRNAs. They show also that the recognition and the proper catalytic action are two  autonomous processes and that the former at least in its first stage is rather unspecific.


Metabolism of pyrimidine L-nucleosides.

The intraperitoneal application of L-nucleosides (L-Cyd, L-Urd, L-dThd) to mice results in distribution of these compounds into tissues of the organism and their gradual excretion in the unchanged form. The residual level has been observed with L-ribonucleosides only and contains in addition to the L-nucleoside its 5'-phosphate. The phosphorylation in vivo is catalyzed by nucleoside-kinase and utilizes ATP as the phosphate donor while glycerol 1-phosphate and creatine phosphate are inactive. The L-cytidine derivatives are in vivo deaminated to the derivatives of L-uridine. On the other hand, when L-uridine is applied in vivo, derivatives of L-cytidine are obtained on the level of both the nucleoside and 5'-ribonucleotide.


Effects of DL-ethionine on mouse liver tRNA base composition.

Treatment of mice with DL-ethionine and adenine causes a reduction of all methylated bases of liver tRNA. This effect is dose-dependent and specific for the methylated bases. Individual methylated components are affected to different extents, m22G being most sensitive to inhibition.


Preparation and physical characterization of a homogeneous population of monomeric nucleosomes from HeLa cells.

We describe a method of isolating a homogeneous population of "trimmed" monomeric nucleosomes from Hela cells. These nucleoprotein particles contain a 140 +/- 5 base pair length of DNA and have a histone/DNA ratio of 1.2. They lack H1 and contain equal amounts of the four smaller histones. The DNA contains no single strand nicks. The particles sediment with an S20,w of 11S in D2O density gradients. After formaldehyde fixation, they band at a density of 1.4370 in neutral CsCl. Digestion of nucleosomes with either micrococcal nuclease or DNase I generates the same pattern of DNA fragments observed when intact nuclei are digested. Circular dichroism spectra indicate that the 280 nm positive ellipticity maximum of nucleosomes is about one-half that of chromatin. In the presence of 6 M urea, nucleosomes sediment with an S20,w of 6S, have a multiphasic thermal denaturation profile, and exhibit a circular dichroic spectrum nearly identical to that of B-form DNA. Our yield of purified nucleosomes (10-15% of the input DNA) is similar to the yields of other methods; our nucleosome population is substantially more homogeneous than those previously reported.


Protection of particular cleavage sites of restriction endonucleases by distamycin A and actinomycin D.

It is shown here that distamycin A and actinomycin D can protect the recognition sites of endo R.EcoRI, EcoRII, HindII, HindIII, HpaI and HpaII from the attack of these restriction endonucleases. At proper distamycin concentrations only two endo R.EcoRI sites of phage lambda DNA are available for the restriction enzyme--sRI1 and sRI4. This phenomenon results in the appearance of larger DNA fragments comprising several consecutive fragments of endo R.EcoRI complete cleavage. The distamycin fragments isolated from the agarose gels can be subsequently cleaved by endo R.EcoRI with the yield of the fragments of complete digestion. We have compared the effect of distamycin A and actinomycin D on a number of restriction endonucleases having different nucleotide sequences in the recognition sites and established that antibiotic action depends on the nucleotide sequences of the recognition sites and their closest environment


Effect of ribosylzeatin isomers on the enzymatic degradation of N6-(delta2-isopentenyl) adenosine.

Cytokinin oxidase has been partially purified from cultured tobacco tissue. This enzyme converts N6-(delta2-isopentenyl)-adenosine to adenosine. The reaction is inhibited by the two isomers of ribosylzeatin [n6-4-hydroxy-3-methylbut-2-enyl)adenosine]. Trans-ribosylzeatin inhibits the reaction more than the cis-isomer.


Some properties of tobacco protoplast chromatin.

Chromatin was prepared from tobacco-leaf protoplasts. Its solubility in increasing molarities of NaCl was studied and the structure of the soluble fraction observed by electron microscopy. We demonstrate that in plants, the DNA and histones are associated in beaded structures similar to those called omicron-bodies or nucleosomes in animal chromatin. The nucleosomes were associated with DNA in either compact or extended forms. The compact arrangement was predominant in the fraction solubilized between 0.1 and 0.4 M NaCl. The extended form, present at 0.5 and 0.6 M NaCl. showed DNA filaments of various lengths interspacing the nucleosomes. At these ionic strengths ring structures were present, associated with the DNA. At 0.7 M NaCl and above, only DNA filaments were present, occasionally associated with big rings, and nucleosomes were compoetely dissociated. Free DNA molecules were present at all ionic strengths used. The possible origin and significance of the rings are discussed.


Electrocardiographic surface mapping of the heart following myocardial infarction and the influence of beta-blockade.

It is generally accepted that ST segment elevation is one of the characteristic electrocardiographic features of acute myocardial infarction. In experimental myocardial infarction the degree of ST segment elevation has been related to the degree of change in coronary flow. Surface mapping in patients of the electrocardiographic potentials gives an indirect representation of the epicardial ST segment change and in indication of the area of underlying myocardial damage. A number of patients who had sustained myocardial infar-tion within 72 hours were studied. All the patients had a history of prolonged ischaemic cardiac pain, electrocardiographic changes and a rise in serum enzymes. Electrocardiagrams were recorded from 72 points on the chest surface. Control maps were constructed from the ST segment changes measured at each of these points and plotted on a standard diagram. Electrocardiograms were recorded during a control period immediately before 20 mg of practolol was given intravenously over a period of five minutes. In all patients practolol produced a significant reduction in the area of ST segment elevation as represented by a reduction in the number of points with ST elevation of more than 2 mm. The significance of these findings is discussed.


Propranolol in acute myocardial infarction in man: effects of haemodynamics and myocardial oxygenation.

Improvement of myocardial oxygenation is a major goal in the treatment of ischaemic heart disease. Propranolol, 0-1 mg/kg intravenously, was administered to 20 patients with acute myocardial infarction without clinical evidence of left ventricular failure. The most important haemodynamic response was a substantial decrease in myocardial contractility. This was reflected by a fall in cardiac index (average of 0-4 l/min/M2, P less than 0-001) and of arterial mean pressure (average of 16 mmHg, P less than 0-001) with little change in systemic vascular resistance. Heart rate, not strikingly increased at the control state in the majority of patients, decreased an average of 7 beats/minute (P less than 0-001). Pulmonary wedge pressure varied; it decreased in 6 patients with high values (greater than 15 mmHg) prior to propranolol. These changes in wedge pressure in the presence of decreased contractility are probably related to improved left ventricular compliance, produced by propranolol. Propranolol markedly improved myocardial metabolism. Arterial-coronary sinus oxygen difference decreased an average of 0-72 ml/100 ml (P less than 0-001). Myocardial lactate production shifted to extraction (average of -8% to 14%) or the rate of lactate extraction increased (average of 20% to 29%). Coronary blood flow decreased an average of 13 ml/100 g/min (P less than 0-001). The finding, that myocardial metabolism improved, suggests that decrease in coronary blood flow was mediated by reduced myocardial oxygen requirements. None of the 20 patients developed left ventricular failure or other complications related to beta-adrenergic blockade. Severe chest pain, unresponsive to conventional therapy in four patients, was relieved by propranolol. These findings demonstrate that acutely administered propranolol improves myocardila oxygenation in patients with uncomplicated acute infarction without endangering perfusion of other vital organs.


Propranolol in patients with acute myocardial infarction at the Royal Melbourne Hospital from 1965: a review.

This review presents our experience in the use of propranolol in the management of cardiac infarction. The drug has now been shown to have a definite place, not only in  the prevention of cardiac infarction, but also in the treatment of some of the complications. The drug has also been advocated because it may minimize the extent of myocardial damage.


The use of drug concentration measurements in studies of the therapeutic response to propranolol.

The dose of propranolol which produces the optimal therapeutic effect in patients with angina pectoris has been found to vary widely among patients. Because the plasma concentration of propranolol also differs markedly due to interpatient variability in absorption it seemed possible that this might be the reason for the wide range of effective doses in angina and that plasma propranolol might provide a useful guide to therapeutic response. To examine this possibility we selected ten patients with coronary artery disease complicated by angina and studied them at varying propranolol doses to a maximum of 320 mg/day. Exercise capacity was tested on a treadmill and plasma propranolol concentration was measured by gas liquid chromatography. In seven normal subjects beta-blockade was quantified precisely as inhibition of exercise tachycardia and was related to plasma propranolol levels at various doses. Maximal beta-blockade occurred at 100 ng/ml of plasma propranolol, but the dose response curve of blockade was relatively flat and the ED50 of plasma propranolol was 8+/-1 ng/ml. In the patients maximal therapeutic benefit from propranolol occurred at 30+/-7 ng/ml and at a dose of 144 mg/day. This resulted in an increase in exercise capacity from an estimated 12-7+/-0-8 ml/kg/min of oxygen consumption during control to 17-2+/-1-1 ml/kg/min on the drug. Thus, there was a wide variation of both dose and concentration among these patients at the maximum therapeutic response. However, when plasma propranolol was related to pharmacologic activity, the maximum therapeutic response was observed between 64 and 98% of total blockade. These studies indicated the extent of beta-blockade necessary to produce an effective therapeutic response in angina, but demonstrate that plasma drug levels provide no practical guide to therapy in patients with angina pectoris. A further study was conducted measuring plasma propranolol in twenty hypertensive patients to investigate the fall in blood pressure in relations to the change in plasma renin activity and the inhibition of cardiac adrenergic receptors. The inhibition of plasma renin closely resemble the response seen in heart rate inhibition in that the maximum response is seen at 100 ng/ml and the ED50 was 11 ng/ml. In contrast propranolol is shown only to begin to have a significant effect on blood pressure at a plasma level of 30 ng/ml and the effect becomes progressively greater as the plasma level increases. This suggests that the hypotensive effect of propranolol may be dissociated from the beta-blocking effects of cardiac and renin releasing receptors.


Haemodynamic effects of beta-blockade in patients with angina pectoris.

The pressure-volume relationship of the intact human ventricle during ischaemia and following the administration of a drug commonly used to treat ischaemic heart disease has been studied. Precise quantitation of the effects of the non-selective beta-adrenergic blocking drug propranolol (0-15 mg/kg body weight) on left ventricular function, segmental wall motion and diastolic pressure-volume relationship in man has been performed. High fidelity left ventricular pressure measurements and simultaneous single-plane angiograms were recorded and volumes calculated by a light-pen computer system. Patients were transvenously atrially paced for constancy of heart rate during drug infusion or paced to angina. In patients with coronary heart disease paced to angina, logarithmic pressure-volume relationship showed change in slope (P greater than 0-05) of the regression line and upward shift in intercept b (+0-25; P greater than 0-001). The diastolic effects of propranolol may include substantial increases in ventricular volumes in those patients with impaired cardiac function. With respect to the intact human ventricle, propranolol may increase diastolic volume for a given level of ventricular pressure. Thus, in a static sense, the ventricle in these patients could be viewed as being more compliant following propranolol administration. However, the fact that the length-tension relationship as measured by the slope of the logarithmic pressure versus volume plot is unaltered by propranolol, suggests that the muscle comprising the ventricle itself exhibits no alteration in its passive elastic properties.


Patient acceptability of propranolol and the occurence of side effects.

The incidence of adverse effects is reported in a group of more than 400 patients treated with propranolol between 1964 and 1974. Severe side effects necessitating withdrawal of the drug were found in less than 10%; dose-limiting side effects were found in less than 15%. Tolerable side effects are studied in detail. Pharmacologically based side effects are recorded and ways of minimizing their frequency are discussed. The acceptability of propranolol in general terms and its advantages are assessed.


Safeguards in the treatment of schizophrenia with propranolol.

Early results for an uncontrolled study of 555 patients with florid schizophrenia suggest that propranolol can be used safely in high dosage, and in a proportion of cases it appears to control schizophrenic symptoms. This method of treatment is now being submitted to controlled trial. Evdence from this uncontrolled study suggests that there was a therapeutic dose range in which symptoms steadily improved as a low dose was ineffective and a high dose, particularly if reached too rapidly, caused toxic effects. Rapid increases (400-800 mg) in the daily total intake when given in divided doses (4 to 10/day) produced gross toxic effects that included ataxia with unprotected falls, drop attacks, visual hallucinations, and confusional states. Severe toxic effects were uncommon when the dose was raised by regular, gradual increments (e.g. by 40-80 mg/day), when propranolol was given twice daily, when the dose was held steady as the patient started to improve, and when the daily total dose was reduced if the fall in pulse rate or blood pressure was excessive, or if there was evidence of toxicity. The observation of gradual, progressive improvement was the most valuable positive guide to the dose of propranolol. All schizophrenic symptoms remitted, at least temporarily, in 26 of 55 patients (in 15 of 17 patients who had been ill for less than one year and in 11 of 38 patients who had been ill for longer than a year). Patients who then stopped propranolol usually relapsed within hours or days.