Comparative skeletal mass and radial bone mineral content in black and white women. The age-related changes in both skeletal mass and muscle mass were directly measured in normal black women ages 30-80 yr. The levels of total-body calcium (TBCa) were determined with the use of in vivo neutron activation. The muscle mass was measured by wholebody counting of 40K. In the same population, the bone mineral content of the radius was measured using a photon absorptiometric technique. Although there was no significant difference in stature, black women had a greater skeletal mass and bone mineral content of the radius than age-matched white female subjects. When the TBCa values were normalized for body size (i.e., corrected for height and lean body mass), the TBCa was still higher for the black women but not as high as the absolute TBCa values. Clearly, it is the larger muscle mass (as reflected by the 40K measure) in relation to weight and height that accounts for this difference. The lower prevalence of fracture and osteoporosis observed in black women relative to white women is due in part to this greater quantity of skeleton. American black women with a higher bone density (i.e., skeletal mass) maintain mechanical integrity of the skeleton longer than individuals with a lower bone density. It is suggested that the larger muscle mass in black women is, in part, a determinant of their increased skeletal mass and is partly responsible for their apparent resistance to osteoporosis and fracture of the skeleton.


Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia. The lipoprotein lipase (LPL) and hepatic triglyceride lipase (HL) activities of postheparin plasma were determined by a specific immunochemical method in 17 patients with primary hyperlipoproteinemia before and during treatment with clofibrate. The drug caused a significant reduction of serum cholesterol (11%) and triglyceride (45%) levels. Postheparin plasma LPL activity rose in all subjects, the average change being 46% (p less than 0.001). The increase of LPL was positively correlated to the pretreatment LPL activity. There was no correlation between the serum triglyceride concentration and postheparin LPL activity either before or during clofibrate administration. On the other hand, in the clofibrate responders there was a weak correlation between the relative changes of triglyceride concentration and LPL activity (r = 0.43, p less than 0.05). During clofibrate treatment the LPL activity of the hypertriglyceridemic patients was significantly higher than the corresponding value of untreated healthy normoglyceridemic subjects of similar age. The postheparin plasma HL activity was not influenced by clofibrate.


Effects of acetylsalicylic acid and indomethacin on growth hormone secretion in man. To investigate the possibility that prostaglandins (PG) take part in the control of growth hormone (GH) secretion in humans, we have studied the effects of protracted and acute administration of acetylsalicylic acid (ASA) and indomethacin (ID), two PG synthesis inhibitors, on basal and insulin-stimulated GH secretion in normal volunteers. In eight subjects, oral administration of 3-2 g daily of ASA for 4 days clearly reached GH response to insulin hypoglycemia (p less than 0.01, ANOVA). In six additional subjects, GH response to hypoglycemia was not modified by a 4-day oral treatment with 300 mg daily of ID. The pattern of plasma free fatty acids (FFA) and blood glucose during the insulin tolerance test was not significantly affected by ASA treatment. After ID the O time value of the above parameters was somewhat higher than under basal conditions, while the drop of blood glucose, but not to FFA, was slightly more pronounced. Acute oral administration of 1.5 g ASA in 12 subjects did not appreciably modify baseline plasma GH, FFA, and blood glucose levels. By contrast, a single oral dose of 100 mg ID in 12 subjects caused a moderate but significant rise (p less than 0.05) of plasma GH levels together with a clear elevation (p less than 0.01) of plasma FFA and blood glucose levels with respect to a group of controls treated with a placebo. Collectively these results are compatible with the possibility that PG play a physiologic stimulating role in the control of GH secretion, although an effect of ASA and ID unrelated to PG inhibition cannot be ruled out, In any event, in view of the number of endocrine and metabolic alterations induced by ASA and ID, these drugs seem to merit further study.


Effect of hydrochlorothiazide therapy on the crystallization of calcium oxalate in urine. The effect of hydrochlorothiazide on the formation of renal stones was evaluated by quantitative assessment of the propensity of urine to undergo crystallization of calcium oxalate. In seven patients with calcium urolithiasis (three with absorptive hypercalciuria, one with renal hypercalciuria, and three with normocalciuric nephrolithiasis), the urinary activity product ratio and formation product ratio of calcium oxalate were measured both on and off therapy with hydrochlorothiazide (50 mg orally twice a day). The activity product ratio (state of saturation with respect to calcium oxalate) decreased in the majority of cases, primarily as a result of the fall in urinary calcium. The formation product ratio (limit of metastability) increased in all cases; the cause of the increase was not readily apparent. Both changes reduced the propensity of urine to undergo crystallization of calcium oxalate, and therefore may account for the clinical improvement reported during thiazide therapy in nephrolithiasis.


Partial body calcium measurements on patients with renal failure. The bone calcium status of 39 patients with chronic renal failure on hemodialysis has been measured by in vivo neutron activation analysis (IVNAA) and reported in terms of a calcium bone index (CaBl) which relates the calcium in a patient to that in a normal person of the same height. In 20 of the 39 cases sequential measurements were made over periods of up to 40 mo. The results are compared with data obtained by radiology and by histological examination of bone biopsies. CaBl values varied from below normal to, in one case, above the range of normal. Many of the higher values were associated with demonstrable osteosclerosis. As found in previous work here with IVNAA, significantly low values of CaBl were associated with vertebral deformities; however, some patients with deformity had normal CaBl values, indicating that these had both local mineral loss (resulting in fracture) and osteosclerosis. Taken all together, the data suggest that more than half the patients have osteosclerosis. Sequential data showed no uniform response to treatment.


Permissive role of thyrotropin on thyroid radioiodine uptake during the recovery phase of subacute thyroiditis. Serial measurements of serum triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), and 4-hr thyroidal 131I uptake were carried out in nine patients with subacute thyroiditis. In the acute phase, suppressed TSH and 131I uptake were observed simultaneously with the elevations of T3 and T4. Thyrotropin-releasing hormone (TRH) failed to increase TSH in all patients studied. The mean value of an increment in serum TSH was only 1.8 muU/ml during the recovery phase when 131I uptake was normal or hypernormal. In addition, an elevated 131I uptake was not necessarily associated with an immediate increase in the serum T3 and T4. These observations suggest that the resumption of the iodide pump may be more important than an increment in TSH in producing normal or hypernormal 131I uptake during the recovery phase. There appears to be a dissociation between the reestablishment of 131I uptake and the resumption of the mechanism of hormonal synthesis and secretion in the thyroid.


Nitrogen sparing induced early in starvation by infusion of branched-chain ketoacids. The alpha-ketoanalogues of the branched-chain amino acids were administered to fasting subjects to determine whether or not they promoted nitrogen sparing. Two fasting studies were carried out in each subject. During the first week of one of the two fasts 4.7 g of a mixture of the alpha-ketoanalogues of valine, leucine, and isoleucine were infused daily. No infusions were administered during the other fast, which served as a control. Urinary urea and calculated total urinary nitrogen were significantly lower during both the week of infusions and the ensuing week of fasting after the infusions were discontinued. Immediately after ketoacid infusions, plasma branched-chain amino acids, including allosioleucine, rose, while alanine and several other amino acids (but not glutamine) fell. There were no differences between the two fasts with respect to ketone bodies, free fatty acids, glucose, insulin, or glucagon concentrations. We conclude that branched-chain ketoacids spare nitrogen early in fasting and that this effect persists after they are metabolized.


[Excessive generalized fat embolism in acutely dystrophic fat liver (author's transl)]. We have reported about a 63 year old woman, who, 1 to 2 hours after a meal containing mushrooms, became acutely ill, sank into uncontrollable shock, and died 24 hours later. Autoptically was found an acute yellow liver dystrophy in a previously existing fatty liver. Etiologically an intoxication by Amanita phalloides could be excluded as well as any other exogenic intoxication. The cause of the acute liver dystrophy was most probably a fulminant virus hepatitis. The decay of the fatty liver cells led to an unusally severe generalized fat embolism, which morphologically is regarded as the cause of death.


[Posthepatitic cirrhosis of the liver without symptoms: observance about 22 years (author's transl)]. There are only a few studies about sufficiently documented posthepatitic cirrhosis of the liver for more than two decennaries. Therefore we report about a patient, who showed at laparoscopy in 1954 a posthepatitic cirrhosis of the liver. Since the end of the fifty years the laboratory findings had normalized and the patient worked hard and felt himself well. At a control laparoscopy with liver biopsy in 1975 a complete inactive cirrhosis of the liver was confirmed. Blood samples were normal and HBsAG seronegative. Therefore, it seems to be possible, that in some few cases cirrhosis of the liver remaining without clinical symptoms over many years - for example in late prisoners of the war, who returned home with an inactive full developed cirrhosis of the liver - but now is detected.


Differential chromosomal and mitochondrial DNA synthesis in temperature-sensitive mutants of Ustilago maydis. The amount and type of residual DNA synthesis was determined in eight temperature-sensitive mutants of the smut fungus Ustilago maydis after incubation at the restrictive temperature (32 degrees C) for eight hours. Mutants ts-220, ts-207, ts-432 and ts-346 were found to have an overall reduction in the synthesis of both nuclear and mitochondrial DNA comparison to the wild-type. In mutants ts-20, tsd 1-1, ts-84 and pol 1-1 nuclear DNA synthesis was depressed relative to mitochondrial synthesis. The DNA-polymerase mutant pol 1-1 had persistent nuclear synthesis at about 50% of the rate of synthesis of mitochondrial DNA and similar behavior was observed in a diploid homozygous strain. Mutant ts-84 had an initial burst of DNA synthesis which was reduced for nuclear but not mitochondrial synthesis after three hours preincubation at 32 degrees C. tsd 1-1 and ts-20 had nuclear residual synthesis amounting to about 25% of the relative rate of mitochondrial synthesis which correlates to increasing UV sensitivity of these strains on incubation at 32 degrees C. A pol 1-1 ts-84 double mutant had an additive loss of nuclear DNA synthesis which indicates that the steps of replication involved may be sequential.


Roller mutants of the nematode Caenorhabditis elegans. The wild type nematode, Caenorhabditis elegans, moves in a sinusoidal wave pattern and leaves sinusoidal paths behind it on a bacterial lawn. The nematode crawls on its side on a special cuticular tread that extends straight down the length of its body. Wild type worms also have rows of musculature and a ventral nerve cord that extend straight down the body. Roller mutants rotate around their long axis as they crawl and move in circular paths. Three roller mutants have been studied. Two mutants are left rollers and one is a right roller. The left rollers have left-handed helical treads, body musculatures, and ventral nerve cords whereas these structures are right-handed helices in the right roller. Double mutants constructed from roller mutants and long mutants indicate that long rollers have helices of the same pitch as normal length rollers. Double mutants constructed from rollers and dumpy mutants that are short and fat indicate dumpy phenotype is epistatic to roller. Double mutants constructed from rollers and blister mutants that have cuticular swelling indicate roller phenotype is epistatic to blister. The results suggest that the roller phenotypes are due to cuticular lesions. Rollers can chemotaxe up a gradient of an attractant by turning off their body muscle movement and continuing their head movements.


Formation of merodiploid clones by cojugation in Rhizobium lupini. Off the transconjugants formed in the R. lupini conjugation 0.5 to 5% are merodiploids. When two differently pigmented parents are used in the crossing experiment the diploid transconjugants by their additive pigmentation type. The segregation patterns of these diploid clones were analyzed. The results are in agreement with the theory that the exogenotic donor DNA can be integrated at different sites of the homologous recipient chromosomal region forming a tandem sequence. Consequently the segregants of these merodiploid clones are formed by endochromosomal recombination.


[Follow up of children treated with antibiotics (author's transl)]. Follow up of children treated with antibiotics should include survey of the patient (clinical response, pharmakokinetics, therapy compliance, side effects), the infecting organism (elimination, change of causative organisms, changes in hospital flora), as well as the host-parasite relationship (changing flora in the patients, incompatibilities, defects of the cellular or humoral defense mechanisms).


[Psychological consulting of children awaiting leg amputation (author's transl)]. A 2.3 year old boy and a 3.7 year old girl, brother and sister, burnt their feet and calves during a bath tub accident. Both had to undergo amputation of their feet and lower thirds of their calves. For this, both needed psychological help. The body was less anxious and ready for confrontation with reality. The girl had to be guided through her denial and rejection of reality towards acceptance of the situation. Only then was she able to express fear and accept help. This practical playtherapeutical intervention could only take place on the basis of absolute trust. Time, empathy, adaptation to the children's state, age and personality and repetetive, active playing of the situation and the anxiety provoking future were necessary. Thus panic provoking anxiety could be diminished to realistic fear.


[Comparison of serum fatty acid patterns in mothers and their newborns (author's transl)]. The fatty acid patterns of total serum lipids in the blood of 15 mothers and the mixed cord blood of their newborns were determined by gaschromatography, and the results compared. It is known that the placenta maintains a concentration gradient for lipids between maternal and fetal blood. Quantitative results are given for the total lipid content of the two compartments. The fetal total lipid content was only about one quarter of the mother's. The fatty acid patterns differed characteristically as well, mainly with regard to the concentration of the essential linoleic and arachidonic acid. The linoleic acid level in the maternal blood was high, but low in the mixed blood of the umbilical cord. This was contrasted by low maternal and high fetal levels of arachidonic acid. The placental fatty acid composition was unusual with a 21% content of arachidonic acid. Feeding of a partially-adapted baby food formula resulted in a gradual rise of linoleic acid levels reaching those of adults at the age of 4-9 months.


[Arterial fontanel pulsation].

[Arterial fontanel pulsation]. Infants with bounding arterial pulses frequently show a visible or palpable arterial pulsation of the fontanel. This simple clinical sign is neither described in the textbooks nor mentioned in connection with congenital heart diseases (CHD). To investigate its significance 501 infants were examined 178(35,5%) showed an arterial pulse of the fontanel. Out of 421 with no sign of cardiovascular malformation or disease on physical examination, 111(26,4%) had a fontanal pulse (f.p.). Out of 80 infants with CHD, 67(83,8%) exhibited a fontanel pulse (f.p.), while only 13(16,2%) did not. All infants with CHD had an ECG and biplane chest x-rays taken. In some of them also cardiac catheterization and heart or vessel surgery were performed. 23(79,3%) of 29 infants with PDA and eight of twelve with a VSD had a f.p.. Since other cardiac diagnoses were encountered less frequently, their relation to the presence or absence of f.p. could not be evaluated. From the variety of diagnoses, however, it became obvious that not only lesions with "early aortic runoff" may be accompanied by a f.p. Other clinical features like blood pressure, hemoglobin content and body temperature were discussed as possible causes of f.p.. Only the first mentioned, a high systemic pressure, was frequently accompanied by f.p.. Since the percentage of infants with f.p. and CHD was relatively high (37,6%) this clinical sign is considered to be of some value in the early detection of heart disease in infancy.


[Congenital cerebral arterio-venous fistula with congestive heart failure in the newborn (author's transl)]. Two newborns with cogestive heart failure due to a congenital arterio-venous fistula involving the great vein of Galen are described. The main diagnostic criteria of this anomaly are a hyperactive heart, bounding carotid artery pulses, and a continuous murmur over the skull. The anomaly was visualized by cerebral angiography. In view of the frequent complications such as the development of hydrocephalus, operative treatment seems indicated.


[Acute benign erythroblastopenia with normochromic anemia in childhood (author's transl)]. Two boys with acute benign erythroblastopenia are described. In contrast to patients with Gasser syndrome our two boys showed a severe normochromic anemia. Furthermore, no giant proerythroblasts were detectable in their bone marrow. A blockage of differentiation from hematopoietic stem cells to proerythroblasts is possibly the cause of the disease. A special therapy, besides transfusion of packed red cells if necessary, is not required.


[EEG changes in the course of progressive cerebral disorders in children (author's transl)]. This survey presents EEG-data on the following disorders: Globoid-cell leucodystrophy (Krabbe), Metachromatic Leukodystrophy, GM2 Gangliosidosis I (Tay-Sachs), Neuronal Ceroidlipofuscinosis. During Krabbe's disease the background activity of the EEG slows down, multifocal and generalized hypersynchroneous activity (HSA) appears, in the final stage hypsarrythmia is found occasionally. In contrast HSA during Sulfatide lipidosis appears only in the final stages. The EEG changes in Tay Sachs disease are minimal in the beginning; later only high amplitude slowing and especially focal abnormalities with spikes and sharp-waves will appear and in advanced stages there is generalized depression of amplitudes. The Elektroretinogramm (ERG) remains intact but VEP disappear. In contrast, in Neuronal Ceroidlipofuscinosis irregular spikes and sharp-waves can be found shortly after onset of the disease. Later on there is a generalized depression of amplitudes; photic driving and differences between sleeping and waking diminish from the 3rd year of life on; thereafter, the EEG becomes isoelectric. The ERG is extinguished from the very beginning in infantile, lateinfantile and juvenile type of Ceroid-Lipofuscinosis.


Cytogenetic effects of inhaled ozone in man. Peripheral blood samples were collected from 30 normal male volunteers before and at intervals after inhaling 0.4 ppm ozone for 4 h. Data from 4 of the subjects were excluded from the analysis because of missing data points. The blood samples were cultured for 48 h, slides made and stained with a uniform Giemsa stain, and 100 metaphase spreads per subject per treatment scored for chromosome aberrations. Cells with suspected aberrations were photographed, destained, restained with a banding procedure and rephotographed to identify the specific chromosomes and regions involved. Pre-exposure, immediate post-exposure, 3 days post-exposure, 2 weeks post-exposure and 4 weeks post-exposure means for the percentage of cells with 46 chromosomes were 93.0, 93.6, 91.7, 94.5 and 94.2, respectively; in the same order, the mean number of cells with chromatid and/or chromosome breaks per order, the mean number of cells with chromatid and/or chromosome breaks per 100 cells was 0.96, 0.85, 1.00, 0.88 and 0.81 respectively, and for chromatid and/or chromosome gaps per 100 cells: 1.35, 0.96, 1.35, 0.81 and 0.77, respectively. The means for each of these parameters as well as the mean frequencies of complex aberrations are not statistically significantly different between blood sampling times. The distribution of aberrations by chromosome and light and dark bands is not significantly influenced by ozone exposure. These data indicate no apparent detectable human cytogenetic effect due to exposure to ozone under the conditions of this experiment.


Clinical and angiographic features of carotid transient ischemic attacks. To determine the prevalence of radiologically evident carotid stenosis in patients with transient cerebral ischemic attacks, we analyzed 95 consecutive hospitalized patients who during a two-year period had appropriate symptoms and also underwent angiography. Pure transient hemisphere symptoms affected 52 patients, pure monocular blindness occurred in 33, and 10 experienced each type of attack separately. Tight stenosis (less than or equal to 2 mm) or occlusion was present in 49 patients (52 per cent). Thirteen patients showed intracranial-branch occlusion, nine of whom had no notable stenosis. Only two clinical transient ischemic attack features correlated with angiographic findings: in transient hemisphere attacks lasting for one hour or longer, the carotid arteries revealed no notable stenosis  (0.05 less than P less than 0.1); and separate hemisphere and ocular attacks in the same patient correlated with tight carotid stenosis. On the basis of the angiographic findings, the study indicates there are several distinct groups of patients with carotid transient ischemic attacks.


Mild high-renin essential hypertension. Neurogenic human hypertension? To determine whether the elevated plasma renin activity in some cases of mild essential hypertension expresses sympathetic-nervous-system over-activity, we compared indexes of sympathetic activity in 16 patients with mild high-renin essential hypertension, 15 hypertensive patients with normal plasma renin activity and 20 normal subjects. Patients with elevated activity exhibited a raised plasma norepinephrine concentration (P less than 0.05), a greater fall in cardiac output with cardiac beta-adrenergic blockade by intravenous propranolol (P less than 0.01), reduction in total peripheral vascular resistance with alpha-adrenergic blockade produced by intravenous phentolamine (P less than 0.01), and reduction to normal of blood pressure by "total" autonomic blockade (atropine, propranolol and phentolamine). On psychometric testing, patients with high-renin hypertension, but not those with normal plasma renin activity, exhibited suppressed hostility (P less than 0.01), a behavioral pattern linked to increased sympathetic activity. The hypertension in these patients with high renin activity is neurogenic and possibly psychosomatic in origin.


Tympanometry in the diagnosis of middle-ear effusion. Tympanometry measures the flow of sound energy in the external ear canal under conditions of changing ear-canal pressure. To evaluate this technic as a means of detecting middle-ear effusion, we studied acoustic susceptance and conductance in 91 children. We made the measurements using tones of 220 and 660 Hz over a pressure range of -300 to +300 mm of water. The mean value for susceptance at 660 Hz gave best results: 83 of 84 tympanograms of ears with middle-ear effusion had values less than 0.16 millimhos (mmho). Among 128 studies of normal ears, 113 had values greater than or equal to 0.16 mmho (P less than 0.001). We conclude that a mean acoustic susceptance at 660 Hz less than 0.16 mmho in a child four months of age or older indicates the presence of middle-ear effusion.


Aspirin-induced depression of renal function. We observed elevation of serum creatinine and blood urea nitrogen and decrease in creatine clearance in patients taking anti-inflammatory doses of aspirin. In 13 of 23 patients with systemic lupus erythematosus increases in serum creatinine ranged from 27 to 163 per cent, and those in urea nitrogen from 42 to 270 per cent. Sequential creatinine-clearance studies, available in 11 of the 13 patients, demonstrated decreases up to 58 per cent. Patients with aspirin-induced changes in renal function were more likely to have active renal disease (P =0.035) or hypocomplementemia (P =0.030). Four of 22 patients with rheumatoid arthritis and two of three normal volunteers also demonstrated biochemical changes. The rate of aspirin-induced alterations was significantly higher in systemic lupus erythematosus (P =0.007) than in rheumatoid arthritis. Aspirin, and other nonsteroidal anti-inflammatory agents, can have a major reversible effect on renal function that may influence the interpretation of clinical data.


Television violence--reactions from physicians, advertisers and the networks. In response to our call for letters on television violence we received more than 1500 letters from readers of the Journal. Seventy-two per cent of the leading television advertisers responded to a subsequent letter requesting a description of their policies regarding content of the programs they sponsor. Their responses included exculpating factors such as lack of control over programming, the limited amount of available advertising time and censorship. We presented these responses to network representatives. They commented on the difficulty in defining violence, the current decrease in the amount of violence shown and their activities in response to this issue. We maintain that the burden of proof that television violence does not harm lies with those who introduce it into society. Advertisers and networks will respond, we believe, to the problem of television violence if continuous public pressure is maintained.


Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia. Two patients with nomozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and cholecystostomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. Clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. Bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis.


Pulmonary hypertension in severe acute respiratory failure. We repeatedly assessed pulmonary and systemic hemodynamics in 30 patients undergoing therapy for severe acute respiratory failure of diverse causes. Pulmonary-artery hypertension and elevated pulmonar vascular resistance were observed in all patients after correction of systemic hypoxemia. Increasing pulmonary blood flow by isoproterenol infusion or decreasing pulmonary blood flow by partial bypass of the right side of the heart minimally altered pulmonary-artery pressure. Although neither elevated pulmonary vascular resistance nor low cardiac index reliably predicted death, survivors had preogressive decreases of pulmonary vascular resistance with time, whereas nonsurvivors tended to maintain or increase pulmonary vascular resistance. Right ventricular stroke-work index was markedly elevated in all patients. The work load imposed upon the right ventricle by elevation of pulmonary vascular resistance may be a factor limiting survival in severe acute respiratory failure.


The discovery of drug-induced illness.

The discovery of drug-induced illness. The increased use of drugs (and the concurrent increased risks of drug-induced illness) require definition of relevant research areas and strategy. For established marketed drugs, research needs depend on the magnitudes of risk of an illness from a drug and the base-line risk. With the drug risk high and the base-line risk low, the problem surfaces in premarketing studies or through the epidemic that develops after marketing. If the drug adds slightly to a high base-line risk, the effect is undetectable. When both risks are low, adverse effects can be discovered by chance, but systematic case-referent studies can speed discovery. If both risks are high, clinical trials and nonexperimental studies may be used. With both risks intermediate, systematic evaluations, especially case-referent studies are needed. Newly marketed drugs should be routinely evaluated through compulsory registration and follow-up study of the earliest users.


T4 Bacteriophage-coded RNA polymerase subunit blocks host transcription and unfolds the host chromosome. T4 bacteriophage mutants selected for their ability to grow with cytosine in their DNA are defective in host transcriptional shutoff and host chromosome unfolding. The host RNA polymerase purifed from cells infected by such a mutant lacks a small T4-coded subunit.


DNA base sequence of the po promoter region of phage lamdba. The sequence of a 123 base pair HpaII restriction fragment of bacteriophage lamdba DNA has been determined by the dimethylsulphate-hydrazine technique. Of this fragment 65 nucleotide pairs are transcribed into the 5' proximal part of the oop RNA. The remaining 58 nucleotide pairs preceding the start point of transcription show homologies to the lamdbaL and lamdbapR promoter regions, and are concluded to contain the lamdbapo promoter sequence.


Configuration of tobacco mosaic virus, RNA during virus assembly. When TMV reassembles, the uncoated RNA is folded back along the growing rod, probably down the central hole. This surprising configuration is essential for rapid elongation--presumably supplying RNA to its site of incorporation while keeping the bulk of the free RNA out of the way.


Mathematical models for the evolution of multigene families by unequal crossing over. Mathematical models of homologous but unequal crossing over between sister chromatids are presented. For mispairing by one repeat, the evolution of a multigene family by unequal crossing over can be represented by a linear birth-death process. The fixation rate of one repeat in a multigene family is estimated. For mispairing by more than one repeat, some approximate results are obtained.


Aggregation, migration and population mechanics. A concept is developed for the regulation of populations by density-dependent movement, rather than by overt competition alone. Fitness is seen as maximising the reproductive advantage of a balance between migratory and congregatory behaviours. Population density is shown to be spatially, as well as temporally dynamic and a mechanism is proposed that accounts for observed spatial behaviour.


Tomato bushy stunt virus at 5.5-A resolution. The coat of tomato bushy stunt virus is built from protein subunits having rigid domains connected by a flexible hinge. Two states of the hinge are present in the T=3 icosahedral structure. Each subunit has a binding site for RNA on its inner surface.


Nature of adrenoceptor sites in bovine teat muscles. The motility of smooth muscles excised from the wall of bovine teats was studied "in vitro". These muscle preparations often show spontaneous rhythmic contractions. Administration of isoprenaline results in relaxation and decreased spontaneous motility, these effects being blocked by propranolol. Noradrenaline elicits contraction and stimulates rhythmical activity, these effects being inhibited by dibenamine. The effect of adrenaline is variable as it induces contraction or inhibition or biphasic responses. Dibenamine blocked contractions, whereas propranolol inhibited relaxations. It appears that alpha and beta adrenoceptors are present in teat muscles. Stimulation of the former elicits activation, whereas stimulation of the latter results in inhibition. These "in vitro" results are largely in agreement with "in vivo" responses described previously.


Glucose metabolism in C-1300 neuroblastoma cells after inhibition of hexose monophosphate pathway. 1. Application of 6-AN (0.01 mg/ml) leads to a strong accumulation of 6-PG in C-1300 neuroblastoma cells which, however, only amounts to one third of that found in C-6 glial cells. 2. In C-1300 neuroblastoma cells dephosphorylation of the accumulated 6-PG causes a rise of the intracellular gluconate to eight times the value found for 6-PG. It is four times higher than the gluconate content observed in C-6 glial cells. 3. Although 6-PG is a competitive inhibitor of PGI it causes no reduction of glycolytic flux and ATP content in stationary phase C-1300 neuroblastoma cells in contrast to the strong reduction of glycolytic flux and ATP content observed in C-glial cells. 4. The intracellular Glc-6-P and Fru-6-P content of C-1300 neuroblastoma cells increases by four to five times after treatment with 6-AN. Both this increase and the decrease of Fru-1,6-P2 content point to an inhibition of the phosphofructokinase. 5. In contrast to C-6 glial cells no morphological changes could be observed in C-1300 neuroblastoma cells up to 24 h after administration of 6-AN.


Specific effect of haloperidol on dopamine turnover in the frontal cortex. A single injection of haloperidol (0.08 mg/kg) produced marked increases in HVA in rabbit brain. Of the dopamine-containing areas studied, the elevation of HVA was significantly greater in the frontal cortex than in the striatum, the tuberculum olfactorium or the parietal cortex. After chronic treatment, a tolerance phenomenon to the effects of haloperidol on HVA was observed only in the striatal and limbic areas. The present results suggest that the frontal cortex may be a preferential target for the antipsychotic activity of neuroleptic agents.


4-Acetaminophenoxyacetic acid, a new urinary metabolite of phenacetin. It is shown that 4-acetaminophenoxyacetic acid (APOA) is an urinary metabolite of phenacetin. APOA was isolated by means of silica gel TLC in various solvent systems from the urine of rats, dogs, and humans, collected 24 h after p.o. treatment with phenacetin (rats and dogs: 200 mg/kg; humans: three single doses of 0.5 g). Expressed as a percentage of the dose, APOA was detected at levels of 1% in rats, 0.13% in dogs and 0.04% in humans. 4-Acetaminophenoxyacetic acid was identified as its methylester--synthetized in the reaction of APOA and diazomethene--by thin layer chromatography, UV absorbance, melting point, and mass spectroscopy.


Control of the release of newly synthetized 3H-5-hydroxytryptamine by nicotinic and muscarinic receptors in rat hypothalamic slices. The effects of various cholinergic agonists and antagonists on the spontaneous release of newly synthetized 3H-5-HT were examined in rat hypothalamic slices. 3H-5-HT was measured in incubating medium at the end of a 30 min incubation carried out with L-3H-tryptophan in the presence of the various drugs tested. ACh (10(-5) M) in the presence of eserine (2 X 10(-4) M), and carbachol (10(-5) M) stimulated the release of 3H-5-HT. In contrast, oxotremorine (10(-5) M) reduced the 3H-amine release. The effect of carbachol was blocked by two nicotinic blockers, mecamylamine (10(-6) M) and d-tubocurarine (10(-6) M). It was not reduced by the muscarinic antagonists, atropine (10(-6) M) and scopolamine (10(-6) M). In fact, each of two antagonists added alone to the incubating medium enhanced 3H-5-HT release. The scopolamine (10(-6) M) stimulating effect on 3H-5-HT release was suppressed by d-tubocurarine (10(-6) M). Finally, the inhibiting effect of oxotremorine on 3H-5-HT release was not prevented by d-tubocurarine (10(-6) M) but was in the presence of atropine (10(-6) M) or scopolamine (10(-6) M). In the concentrations used in the release study, the cholinergic agonists and antagonists had no effect on the total formation of 3H-5-HT and 3H-5-HIAA from L-3H-tryptophan and on the accumulation of L-3H-tryptophan in tissues. In these concentrations, except for eserine, they did not affect the uptake of exogenous 3H-5-HT in hypothalamic synaptosomes (P2 fraction). These results suggest that cholinergic receptors of the muscarinic and nicotinic type are involved in the control of 3H-5-HT release; since the stimulation of the muscarinic and nicotonic cholinergic receptors resulted in an inhibition and an activation of 3H-5-HT release, respectively. As in the case of peripheral noradrenergic and central dopaminergic neurons the cholinergic receptors could be localized on serotoninergic terminals.


Relationship between the uptake of 3H-(+/-)metaraminol and the density of adrenergic innervation in isolated rat tissues. 1. The uptake of 3H-(+/-)metaraminol (MA) by tissue slices or pieces was studied in vitro in several peripheral rat organs of varying density of sympathetic innervation (the tissue level of endogenous noradrenaline ranging from 1.7-99.1 nmoles/g). In each individual tissue preparation amine uptake was corrected for entry into the 14C-D-sorbitol space. 2. When the tissues were incubated with 1.4 muM MA, the rate of total amine uptake (i.e., neuronal plus extraneuronal uptake of MA) remained virtually constant for up to 7 min. Therefore, rates of uptake were determined after 2 min of incubation with substrate concentrations ranging from 0.25-12.2 muM. In all tissues the total uptake of MA was saturable. 3. Under the condition of inhibition of neuronal uptake by the presence of 100 muM cocaine, the uptake of MA (considered as extraneuronal amine uptake) was no longer saturable. When tissues were exposed to 1.4 muM MA, the relative contribution by extraneuronal (measured in the presence of cocaine) to total amine uptake (measured in the absence of cocaine) was inversely correlated with the log endogenous noradrenaline content. 4. After correction of the rates of total MA uptake for the cocaine-resistant distribution of the amine, a saturable component of uptake was obtained for each tissue. This uptake was considered to be neuronal; it was subjected to kinetic analysis. 5. Apparent Km values for the neuronal uptake of MA were very similar in all tissues and did not show any dependence on the tissue level of endogenous noradrenaline (average Km = 1.2 muM). 6. V max values for the neuronal uptake of MA were linearly correlated with the endogenous noradrenaline content of the tissues (r = 0.976; P less than 0.001), the V max for the vas deferens being excluded. When related to the content of endogenous noradrenaline, the V max obtained in the vas deferens was lower than that for all other tissues. 7. The results presented here strongly suggest that the membrane site involved in neuronal amine uptake (operationally characterized by the Km of MA) is likely to be identical in all rat tissues and that the number of uptake sites available per nerve terminal does not vary greatly between tissues.


[Hepatitis A and hepatitis B. Clinical, epidemiological and differential immunological elements]. The Authors have already related in various papers the results of their research on humoral and cellular immunity in the course of viral hepatitis in relation to the behaviour of HBsAg determined with various methods and recently with the radio-immune assay. Since the high sensitivity of this latter technique consents a sufficiently precise differentiation of hepatitis into HBAg-positive (hepatitis B) and HBAg-negative (hepatitis A), the Authors have intended studying in this work the eventual clinical epidemiological and immunological differences between the two types of hepatitis, analyzing the results of their previous studies, extending the case data and gathering numerous other personal observations, clinical and laboratory, not yet published. The study was limited to 136 patients with viral hepatitis in wwhich the test for HBsAg was effected with RIA: of these 58 were HBAg+ and 78 HBAg-. Initially is discussed the incidence of two types of hepatitis in relation to age and sex and then the comparative incidence between them of the various routes of contagion. Particularly emphasized is the possibility of direct transmission of HBAg+ hepatitis, often responsible for infection within the family. The comparative determination of transaminases, bilirubin, immunoglobulins and complement has revealed some interesting variations in the behaviour of the two types of hepatitis. Instead, cellular immunity, studied by the rosette E technique, appeared depressed in the initial phase of sickness in both types of hepatitis. Space is dedicated to the behaviour of HBsAg in acute HBAg+ hepatitis in relation to the immunoglobulins and complement and in relation to the normalization of the transaminases and bilirubinemia. After a few brief observations on the frequent appearance of a joint symptomatology in the course of viral hepatitis, particularly in the HBAg+ form, the Authors report the data relative the evolution of the hepatitis cases examined. The percentage of a complete cure are about equal between hepatitis A and hepatitis B even recovery is significantly faster in the first type of hepatitis (HBAg-).


[Asthma as a psychosomatic disease and its treatment with tranquilizing agents]. On the basis of personal research and experience, it is concluded that the majority of asthmatics also suffer from psychoneurosis and that psychological alterations are primary and not secondary to dyspnoea. Some hypotheses are put forward relating the onset of asthma and psychoneurosis.


[Capillaroscopic pictures of the hyponychium of surgical interest]. Capillaroscopic pictures regarding situations of surgical interest are presented. Apart from the purely symptomatological parameter, an attempt is made to interpret the pictures, with reservations.


[The Martorell ischemic hypertensive leg ulcer]. The aetiopathogenesis and diagnosis of Martorell's supra-malleolar hypertensive ulcer are discussed in the light of 3 clinical cases. Stress is laid on the overriding need for proper general management designed to normalise the serious arterial hypertension. It is felt that raubasine vasokinetics (such as Circolene), and taurine tissue oxygenators (0-due) are useful supplementary aids, particularly when administered by slow infusion. Lumbar gangliectomy will be necessary in the case of persistently painful ulcers. Its success, however, is dependent on prior normalisation of pressure. Dermo-epidermal grafts would appear to be superfluous, while frequent topical application of trophodermic creams are apparently useless.


[Use of thermo-mammographic and cholesteric methods in the early diagnosis of breast carcinoma]. In 1973, 600 women aged between 19 and 70 and belonging to various social strata were examined. Some came spontaneously without symptomatology, for the sole purpose of preventive screening, others presented various symptoms. Thermography was used on all patients. Complementary mammography was carried out on some of them while others were subjected to cutaneous application of a personally prepared cholesteric strip with various thermic range. An Eastman Kodak cholesteric mixture at 10% solution and with thermic range varying from 35 degrees to 39 degrees was used. Solutions with thermic excursion of 1 degree C were adopted. (This examination was carried out for scientific purposes as it is absolutely not yet part of diagnostic routine). A comparison was then made between the thermo mammographic and cholesteric methods in the early diagnosis of mammary carcinoma.


[Modifications induced by diaphragmatic kinesitherapy on various spirographic parameters]. The effect of diaphragmatic kinesiterapy on some spyrographic parameters was investigated. The best results were obtained with an association of kinesiterapy and drugs.


[Gilbert's jaundice. Current clinico-nosographic, physiopathological and therapeutic aspects. III. Therapeutic action of enzyme inductors with reference to unconjugated bilirubin icterus]. The value of phenobarbital in the treatment of free bilirubin icterus is demonstrated by a series of clinical experiments in which the drug was administered to patients with bilirubinaemia, even at high levels, the situation being brought back to normal within about two weeks. The percentage excreted with the urine in a conjugated form of various drugs proved higher in subjects treated with phenobarbital than in controls, thus proving that the drug acts as an enzymic inductor. Moreover it is ineffective in patients genetically lacking in the capacity to synthesize glycuronyltransferase. The induction of this latter enzyme, however, does not exhaust the effects of the barbiturate for it has been shown that phenobarbital is capable of speeding up the disappearance of exogenous bilirubin from the plasma in animals, of stimulating bile flow and increasing uptake of the pigment by the liver. The increase in bile flow is of the order of 30% and takes place by way of a modification in the flow fraction independent of bile salts. It would also appear that the drug is capable of increasing the activity of 7-alpha-hydroxylase, an enzyme that represents the rate limiting step in the synthesis of biliary salts. Other drugs commonly used in the treatment of free bilirubin icterus such as ethanol, rifampicin and uridindiphosphoglucose are considered. Finally the case of a female patient who from birth had presented persistent free bilirubin icterus of about 8 mg% is reported. After 14 days treatment with phenobarbital (100 mg X 2) blood levels of the pigment had returned to normal.


[Etiopathogenetic and clinical notes on the syndrome of the micropolycystic hyperandrogenic ovary and matrimonial sterility]. The nosological, clinical, aetiopathogenetic and therapeutic aspects of hyperandrogenic micropolycystic ovary are examined with particular reference to matrimonial sterility. There is not doubt about the existence of a syndrome substantially characterized, clinically, by menstrual trouble, inability to procreate, more or less evident signs of hyperandrogenism and a tendency to obesity and, morphologically, by ovarian micropolycystic alterations of typical pathognomonic aspect: the marked production of androgens on the part of the female gonad possibly accompanied by peripheral alterations interfering with their metabolism. The syndrome is not too frequent and, in personal experience, occurs in less than 1% of the series. The main therapeutic approach remains cuneiform resection of the ovary. Still in personal experience, 21.2% of cases treated led to pregnancy but not more than eight-ten months after operation. The effect would therefore appear to be transitory and the operation is decisively rejected where unmarried women are involved.


[The neurovegetative system in the pathogenesis of bronchial spasm]. The therapeutic efficacy of atropine and salbutamol sprays alone or in association was experimented in patients with atopic bronchial asthma as part of an investigation of the bronchodilatatory drugs and the pathogenesis of bronchospasm. As personally observed in other situations, combination of these drugs does not allow their maximum effect to be obtained.


Modern management of the diabetic pregnancy. The effect of modern antepartum and intrapartum fetal monitoring technics on the outcome of the pregnancy complicated with diabetes was studied by comparing the perinatal mortality of 2 groups of patients whose management differed primarily by the use of these tests. The perinatal death rate was halved to 9.2%, and when corrected for major congenital defects and referred fetal deaths it was 5.3%. Modern fetal diagnostic tests clearly add a degree of objectivity in the management of the diabetic pregnancy not previously available.


Significance of amniotic fluid corticosteroid levels in human pregnancies. Retrospective analysis of 103 samples of amniotic fluid was performed. Twenty-four samples were obtained prior to midtrimester abortion, 31 were from patients who delivered spontaneously, 14 were from patients in whom labor was induced, and the remaining samples were obtained from patients who were delivered by cesarean section. In all normal pregnancies, there was a rising trend in corticosteroid levels in amniotic fluid as the gestation advanced. This was less marked in abnormal pregnancies. There is a suggestive fetal role in initiation of normal spontaneous labor, as reflected by a significant increase in amniotic fluid corticosteroid levels, in patients immediately prior to vaginal delivery as opposed to abdominal delivery. There was a significant correlation between the birthweight of babies born vaginally with the amniotic fluid corticosteroid levels, as compared to the weight of babies born by cesarean section.


Effect of betamethasone administration on estrone, estradiol-17 beta, and progesterone in maternal plasma and amniotic fluid. As part of a series of studies on the endocrine consequences of corticosteroid treatment during late pregnancy, the levels of unconjugated estrone (E1), estradiol-14 beta (E2), and progesterone were followed in maternal plasma and amniotic fluid before and after treatment. Ten gravidas in the 30th-35th gestational week received 12 mg betamethasone daily for 3 days for prevention of idiopathic respiratory distress syndrome (IRDS) and were compared to 5 controls. The steroid concentrations were determined by radioimmunoassay. The plasma levels of E1 and E2 were depressed to 38% and 29%, respectively, while that of progesterone was not affected. No significant change of the steroid concentrations in amniotic fluid was observed. The decreased E2: progesterone ratio in maternal blood after betamethasone treatment in the human is in contrast to the increased ratio observed in ruminants after corticosteroid administration and preceding the spontaneous onset of labor. The fall in the E2: progesterone ratio accords with the earlier observed inability of intramuscular corticosteroid treatment of elicit labor in women at this stage of gestation. The earlier demonstrated marked depression of cortisol in fetal plasma after betamethasone seems paradoxical in view of the seemingly high availability of progesterone, considered as a precursor for the cortisol biosynthesis in the human fetal adrenal cortex.


The effect of amniography on amniotic fluid L/S ratio. This report provides data indicating that the water-soluble dye combination commonly used in amniography raises the amniotic fluid lecithin/sphingomyelin ratio.


A reevaluation of the value of hCS determination in the management of prolonged pregnancy. In an initial study at the Yale-New Haven Hospital human chorionic somatomammotropin levels were reported to have predictive significance for the antepartum diagnosis of the postmaturity syndrome. Expanded data from the same institution do not support the original findings.


Fetal heart rate acceleration in relation to the oxytocin challenge test. Fetal heart rate (FHR) acceleration was evaluated in 1570 oxytocin challenge test (OCT) results, which were performed on 565 high-risk patients. In positive OCTs a significant decrease or lack of FHR acceleration was noted. Fetuses with positive OCTs and lack of FHR acceleration were more compromised than those with better FHR acceleration.. Negative OCTs were associated with a good FHR acceleration approximately 95% of the time. Study of FHR acceleration in suspicious OCTs proved to be helpful in determining the significance and prognosis of a suspicious OCT.


Association of premature rupture of membranes with idiopathic respiratory distress syndrome. A retrospective study involving all admissions to two neonatal intensive care centers over a 4-year period was carried out to assess the protective effect, or lack of it, of prolonged rupture of membranes (ROM) on the prevalence of idiopathic respiratory distress syndrome (IRDS) in premature infants. Significantly fewer cases of IRDS were found in patients in all gestational age groups when ROM was greater than 24 hours as compared with those with ROM of less than 12 hours' duration. However, prolonged ROM was not consistently associated with a difference in prevalence of respiratory failure accompanying IRDS, or in the prevalence of sepsis or neonatal mortality in this patient population. It is concluded that benefit to a premature infant in the form of reduced risk of developing IRDS is possible if the mother is allowed 24 hours after ROM before the delivery is initiated.


The obstetric complications of the infertility patient. This study was undertaken to compare the outcome of pregnancy in patients treated for some type of infertility problem to that of a control group of patients from the same obstetric unit and also to the reported literature. Reported are the primary outcomes of 122 pregnancies in 104 patients treated for infertility and 106 pregnancies in patients of a control group delivered over the same period of time. Thirty-six percent of the treated patients had no pregnancy complications, whereas 54% of the control group had no pregnancy complications.


Small bowel obstruction in pregnancy. A review and report of four cases. Four gravid patients with small bowel obstruction secondary to adhesions were seen during a 17-year span (1955 through 1971) at the Mayo Clinic. Three of these patients had been referred to us for definitive diagnosis and treatment. During the time span under investigation, there were 25,189 deliveries at our institution. As the incidence of surgical procedures increases, small bowel obstruction is likely to be seen more frequently. One must consider this diagnosis in any pregnant patient with an abdominal scar and the characteristic signs and symptoms of obstruction. When mechanical intestinal obstruction has been diagnosed, the recommended treatment is surgery regardless of the gestational age or status of the fetus.


Plasma levels of estrogen, luteinizing hormone, and follicle stimulating hormone following castration and estradiol implant. Plasma levels of luteinizing hormone, follicle stimulating hormone, and estrogen were studied serially in 20 patients before and after hysterectomy and bilateral salpingo-oophorectomy. Ten patients received an implant of estradiol-17 beta (100 mg) at the time of operation. Ten patients who did not receive an implant acted as controls. Patients recorded the severity of vasomotor symptoms before and after hysterectomy. In those patients who did not receive an implant, plasma estrogen levels fell from a mean preoperative level of 18.1 +/- 10.4 ng/100 ml to 8.7 +/- 1.4 ng/100 ml by 24 hours after oophorectomy and they remained in this range for the 6 months of the study. No significant change in the plasma estrogen level was noted after oophorectomy in those patients who received an implant. The implant prevented the rise in gonadotropin levels and the appearance of vasomotor symptoms seen in those patients who underwent oophorectomy without an implant. Insertion of an implant into oophorectomized patients caused the plasma estrogen level to return to premenopausal levels within 2 weeks and the gonadotropin levels to premenopausal values within 6 weeks. Hot flashes were alleviated within 2 to 6 days. The usefulness of this type of therapy in preventing the appearance of vasomotor symptoms at the time of oophorectomy in premenopausal patients is confirmed.


Studies on the muscular structure of the human uterus. II. Fasciculi cervicoangulares: vestigial or functional remnant of the mesonephric duct? Two muscle bundles, the fasciculi cervicoangulares (FCAs), are present at the lateral aspect of the human uterus bridging cervix and fundus uteri. Epithelial remnants within this muscle bundle are morphologically identical with mesonephric duct remnants. It is postulated that the longitudinal muscle coat of the mesonephric duct may develop into the two FCAs and that these bundles may serve as a system for conduction or coordination of muscle contractions in the adult uterus.


A morphologic study of mesotubarium ovarica in the human. In order to clarify the mechanisms by which the egg is transported from the ruptured follicle into the fimbrial end of the fallopian tube in the human, the mesotubarium ovarica (MTO), the unique anatomic structure which connects the tubal fimbriae and the ovary, was studied in seven human adnexal specimens histochemically and electronmicroscopically. The results demonstrated clearly the presence of smooth muscle cells in the MTO, and failed to demonstrate the presence of cilia in the lining epithelial cells of the MTO. A possible role of the MTO in the mechanisms of ovum pick-up at the time of ovulation is discussed.


Primary trabecular carcinoid of the ovary. Eighteen cases of primary trabecular carcinoid of the ovary were analyzed from a clinicopathologic viewpoint. The patients ranged in age from 24 to 74 years and presented with symptoms of an ovarian mass; none had the carcinoid syndrome. Although the carcinoid always proved to be unilateral, the contralateral ovary was sometimes enlarged by a dermoid cyst. The carcinoid usually formed a small mass in an otherwise obvious dermoid cyst, but in six instances it formed a large, solid mass, and in 2 of these cases no other teratomatous elements could be demonstrated. The prognosis was nearly always favorable after removal of the neoplasm, although 1 patient had a recurrence after 2 years and died after 51/2 years. Primary trabecular carcinoids are characterized by a distinctive pattern of ribbons of argentaffin cells and should not be confused with a Sertoli-Leydig cell tumor, a strumal carcinoid, or a metastatic trabecular carcinoid.


Embryonic testicular regression. A clinical spectrum of XY agonadal individuals. Aberrations of fetal sexual development were studied in three XY agonadal individuals. Two were phenotypic females with primary amenorrhea, sexual infantilism, and no internal genital structures. Plasma androstenedione and testosterone concentrations were similar to those of prepubertal children and increased after ACTH infusion. The daily production rates of estrone were low. The third agonadal XY individual, a phenotypic male, developed gynecomastia in response to approximately 40 mug of estrone produced daily by the extraglandular aromatization of plasma androstenedione. All plasma testosterone was accounted for by the conversion of plasma androstenedione. The absence of internal genitalia, the prepubertal external genitalia in the phenotypic females, and the incomplete growth of both the internal and external genital structures in the phenotypic male subject suggest that testicular elaboration of müllerian regression substance occurred, but that regression of the testes occurred subsequently during varying stages of embryogenesis. In the females, testicular regression occurred prior to the initiation of fetal testicular production of androgen. On the other hand, in the male subject, testicular activity persisted longer; thus, both müllerian duct regression and embryonic virilization of wolffian ducts and genital tubercles occurred.


The management of midtrimester abortion failures by vaginal evacuation. The management of 58 failed midtrimester primary abortion procedures by vaginal uterine evacuation is described. The indications, technic, and complications of this procedure are presented. This method was the only means of managing failed primary abortion over a 3-year period in which 2045 elective midtrimester abortions were performed. With the development of experience this technic offers significant advantages over other procedures, such as hysterotomy, in the management of such patients.


The effect of oral contraceptive steroids on branches of the uterine artery. Uteri from 38 patients exposed to oral contraceptive steroids and from 7 unexposed controls were examined for lesions in small branches of the uterine artery. Moderate or severe cellular proliferation of the intimal layer was found in 82% of patients exposed to exogenous steroids, but minimal or no involvement was found in the remaining 18% and in unexposed patients. The severity of involvement correlated with duration of exposure to contraceptive steroids but decreased in those patients who had stopped medication prior to surgery. This lesion has been reported previously in autopsy studies of women receiving contraceptive steroids and dying from vascular disease, but is now shown to be common in asymptomatic women receiving oral contraceptive pills.


A spring-loaded needle for amniocentesis. The spring-loaded needle for amniocentesis that is described has theoretic advantages over a spinal needle. These include increased safety for the fetus and better recognition of when the needle enters the uterine cavity.


Management of the lost intrauterine contraceptive device. In order to establish that a lost IUD is within the uterine cavity, a special hook-type instrument was designed to enable removal of the device when it was located within the uterine cavity. This instrument was 100% successful in removing 17 IUDs with no visivle tails and which were within the uterine cavity. Failure to remove a lost IUD by this method in 4 other patients indicated the device's absence from the uterine cavity. The technic is simple and has not been associated with any patient discomfort or complications. X-ray procedures or operative manipulations may thereby be avoided. Therefore, when the tail of an IUD is no longer visible, immediate removal can be attempted in order to establish the intrauterine location of the device. If the patient wishes to continue using this form of contraception, a new device should be inserted.


A false negative oxytocin challenge test. A negative oxytocin challenge test has been considered a very reassuring finding in managing pregnancies in which the fetus is at risk from uteroplacental insufficency. In the case described here a fetal death in utero occurred 4 days after a negative oxytocin challenge test in a Class D diabetic patient, but in that period of time the patient's metabolic status deteriorated. A negative oxytocin challenge test does not protect the fetus from a subsequent acute event such as abruptio placentae, a cord accident, or diabetic ketoacidosis.


Placental loctogen levels associated with gross fetal abnormality. Four cases of severe congenital abnormality associated with persistently low maternal serum human placental lactogen levels are described. It is thought that this pattern might act as a warning of severe fetal abnormality.


Fetal heart rate response to acute hemorrhage. Intrapartum fetal bleeding from an anomalous umbilical cord vessel has been associated with a perinatal mortality rate of over 50%. Fetal blood volume is relatively small. Thus, an insignificant hemorrhage by adult standards may quickly lead to fetal shock and death. This paper documents the fetal heart rate (FHR) response to acute intrapartum hemorrhage. The onset of fetal bleeding is marked by a tachycardia followed by a bradycardia with intermittent accelerations or decelerations. Small amounts of vaginal bleeding associated with FHR abnormalities should raise the suspicion of fetal hemorrhage. This condition demands prompt delivery and immediate reexpansion of the neonatal blood volume.


Chromosome 6/15 translocation with multiple congenital anomalies. A female infant with multiple congenital anomalies was found to have an abnormal karyotype: 45,XX,--6,--15, +t (6;15). Precise identification of the translocation was made by trypsin-Giemsa banding technic. The congenital malformations include hypertelorism, microphthalmia, beak nose, low-set ears, cleft palate, micrognathia, simian crease, hypertrichosis, and low hairline. The unbalanced translocation is apparently responsible for the abnormal phenotype.


[Mycoplasma pneumonias in childhood (author's transl)]. During the winter months 1974/75 we were able to observe a number of unusual respiratory tract infections particularly in children over 6 years of age which appeared as pneumonias. Characteristic clinical findings included a dry, hacky cough, refractive to the usual antitussives, starting 1--2 weeks prior to admission, fever up to 104, malaise, headache, anorexia, shortness of breath and cyanosis. Several Pts were treated prior to admission with a number of antibiotics and failed to respond. Laboratory findings showed a peripheral polymorphonuclear leucocytosis with toxic granulations of neutrophiles. A sedimentation rate above 40 in the first hour occurred in most Pts. X Ray of the lung revealed a characteristic mottled appearance with patchy infiltrations, atelectasis and nodular densities. Frequently a shift of the mediastinum towards the infiltrate was seen. One of the hallmarks on physical examination was the discrepancy between the severity of the clinical illness and the paucity of physical findings. Decreased breath sounds over affected lung areas were often the only findings on auscultation; find rales, rhonchi or dullness on percussion were less often heard. The combination of a typical history, physical examination, laboratory tests and X Ray findings enabled us to make a presumptive clinical diagnosis of Mycoplasma pneumonia before serologic test results were available and to start with the appropriate antibiotic (Erythromycin, Tetracycline) early in the course of the disease. Complement fixation tests with a titer of 1 : 20 and a fourfold rise over the next two weeks or an initial titer of 1 : 80 and above were considered significant for acute disease.


[The work of the school physician as a basis of preventive medicine. What we need are fulltime school medical officers (author's transl)]. Like antenatal and postnatal care, medical attendance at school is the most important basic element of all kind of preventive medicine. This applies in particular to the present situation, as both parents are employed very often, thus not having enough time for watching the beginning of illnesses, disturbances in the development, or behavioural anomalies of their children, and letting them have appropriate medical care. While elementary and intermediate school children are medically looked after in regular intervals by public welfare officers in the cities, the job of a school physician will be performed by the district medical officer in the market-towns and villages. Medical service at general secondary schools and technical colleges is usually rendered by a local general practitioner who again is only in a position to take that job as a sideline to his occupying general practice. Necessity is therefore pointed out of a thorough and regular medical care at school, particularly during the years of puberty and development of the youths during their period of growing up. Furthermore, it is shown that the school physician not only has to investigate and diagnose conscientiously, but also the numerous problems are being discussed he has to deal with in the attendance of youths from a physical and a psychical aspect. In this context it is tried to make clear why it is so important to establish personal contact with the young people, with their parents, and with the teaching staff. A series of serious illnesses is enumerated that were detected by the school physician and handed over to the general practitioner or the specialist for further exploration and treatment. The most frequent illnesses are high blood-pressure, heart- and eye troubles. With regard to his great and manyfold tasks the school physician will have to stick to his hours of duty in order to be ready for help and advice at any time. It is, therefore, not possible to perform this job on a side-line, as it would be a fulltime job to be a conscientious school physician. Finally, suggestions are made how to make the school medical officer a fulltime job and what has to be done in order to secure his financial existence.


[The congenital lobar emphysema (author's transl)]. The congenital lobar emphysema has no uniform etiology. We can however suppose that malformations especially of the cartilage are of importance. The whole lobe is mostly involved, with predilection of the left upper-lobe. The symptomatology of the congenital lobar emphysema is a manifold one. Striking are respiratory embarrassement with dyspnea and cyanosis. For the diagnosis an X-ray is necessary. Remarkable is a transparent lung in which you can still see an unimportant pattern. For the differential diagnosis et first congenital cysts come in question. By intercurrent infections a sudden severe deterioration can result, also if the cases show a favourable course. The method of choice is a timely operation, necessary is the resection of the affected lobe. This is a report of 17 own observations. In 11 cases we found a congenital lobar emphysema, in 6 cases congenital lung-cysts. We could examine 10 patients till to eleven years from the beginning of the disease. All the children had a normal development, except of insignificant residues.


[The oedema of the scrotum, as first sign of an intraabdominal inflammation (author's transl)]. The oedema of the Scrotum, or the swelling of the Labia majora, could be the first sign of an intraabdominal inflammation. Two case reports should demonstrate these symptoms.


Akrodermatitis papulosa infantilis. An Australia antigen disease. Several items characterize the papular acrodermatitis: 1. the clinical picture and the localisation 2. inguinal and axillary lymphadenitis 3. acute usually anicteric hepatitis 4. presence of hepatitis B antigen in all patients. Other members of the family are carriers of HB-Ag, too. One of them usually had icteric hepatitis weeks before or after PAC. At present we consider PAC as the clinical disease due to the primary infection of HB-Ag in childhood. The cycle of HB Ag is shown in a scheme. It suggests why the disease is rare, asymptomatic infections occurring in the majority of the cases. It appears in children without HB-antibodies and a particular reactive condition. After parenteral inoculation PAC and lymphadenitis do not develop. Some chronic HB Ag carriers may have become so after PAC in the childhood.


[Indication for cardiac catheterization and angiocardiography in congenital heart disease (author's transl)]. This brief report shows that the age for absolutely necessary investigation depends on the kind of symptoms of congenital heart disease. This indication for heart catheterization and angiocardiography is given with respect to the operative possibilities.


[Wide-spread haemangioma racemosum of the mediastinum associated with paresis of the diaphragm; a finding to be considered in the differential diagnosis of the arteriovenous aneurysm of the thorax (author's transl)]. The paper reports on a 5 year old boy showing a sprawling haemangioma racemosum of the right side of the mediastinum. The vascular tumor is fed by a tortuous A. thoracica interna dextra and numerous arterial vessels arising from the right subclavian artery and from the aorta including the right coronary artery and branches from the abdominal aorta. The child presents also paresis of the right diaphragm probably secondary to the pressure of the pulsatile tumore along the course of the phrenic nerve. After ligation of three major feeding arteries the continuous murmur disappeared and fatigability and anorexia became less. Apart from this report a review of the literature on vascular malformations of the arterio-venous fistula type within the thorax sums up the most important features of these vascular anomalies: haemodynamics, localisation, clinical signs, therapy, natural history, therapy and etiology.


[Anthelmintic therapy with mebendazole in children with broncho-pulmonary infections (author's transl)]. The fact that the incidence of infection significantly increases in patients being a poor physical condition is commonly known. Especially in children a high rate of helminthic infection is to be expected as could be assessed by the present investigation. The easy diagnostic technique can now be combined with a highly effective new treatment, extremely well tolerated and devoid of side effects. Results obtained with the new polyvalent anthelmintic Mebendazole are described in the present study.


[Respiratory therapy in childhood asthma. Part 2. Eutonic training]. Children with obstruction mainly due to spasms of bronchial smooth muscle will benefit most from breathing exercises. Attainment of the individual physiological balance of muscular, nervous and psychogenic tensions--the eutonic tension--is of great importance for control of regular unhurried breathing. This will be supported by stimulation of nasal breathing which increases diaphragmatic excursion. The eutonic state is the fundamental basis for success of chest rotations and rhythmic movements to stimulate further relaxation. Awareness of the fact that breaths come by themselves -- "automatically" -- reduces anxiety of shortness of breath. Observations of a group of asthmatic children in a summer camp support this form of treatment of asthma.


[Spasmopuls -intoxication in infancy (successful treatment by blood exchanged transfusion) (author's transl)]. An intoxication by Spasmoplus in a four weeks old infant is reported. The suppository was given believing it was a laxative. A few hours later symptoms of a Codein-intoxication were present. 24 hours after that time the situation was extremely dangerous by means of the intoxication by aminophenazon. Lifesaving was blood exchange transfusion.


Atrio-ventricular conduction defects and arrhythmias by selective perfusion of the A-V conduction system in the canine heart. Ligation and cannulation of the anterior septal artery in 43 canine hearts caused changes in ST-T segment of the electrocardiogram in all animals. Perfusions of 0.9% NaCl, one to ten micrograms of acetylcholine, isoproterenol, epinephrine and norepinephrine, into the anterior septal artery caused variations in the ECG ranging from exaggerated ST-T changes to PR prolongation, ectopic atrial, nodal and ventricular beats, A-V blocks and dissociations, atrial fibrillation and ventricular fibrillation. The response seemed to be somewhat specific for cholinergic versus adrenergic agents showing more conduction defects by the former against greater changes in automaticity by the latter agents.


Antagonism of cadmium and alloxan-induced hyperglycemia in rats by Trigonella foenum graecum. This study was stimulated by popular belief that Trigonella foenum graecum has antidiabetic activity in which the hypoglycemic effect has been confirmed by several investigators. However, the mode of action appears to be unclear. To gain some insight, the stems and leaves of the plant as well as the known active seeds were extracted at room temperature (ca 20 C) for three days with water or acetone and by soxhlet 70 C, and tested by oral administration to rats. Acetone and CC14 extracts before use, were evaporated below 30 C under vacuo, and the residue dissolved in distilled water containing Tween 80. Hypoglycemic activity of these extracts were tested on 20 hour fasted normal, alloxan and cadmium treated rats. The latter has been shown to cause hyperglycemia by releasing epinephrine in intact rats and inhibiting insulin release in the isolated perfused rat pancreas. Results showed that with seeds the CC14, soxhlet acetone extracts were inactive in normal animals as were the water and acetone extracts of stems and leaves. These observations may be compared with room temperature acetone extraction of seeds which exhibited what appeared to be dose related hypoglycemic effects. The hyperglycemia induced by cadmium or alloxan was antagonized by room temperature acetone seed or stem and leaves extracts. Tentative interpretation of the above results, are that Trigonella acetone extract appears to act, at least in part, at the cellular level to produce its hypoglycemic effects on normal rats or those as treated with cadmium or alloxan.


Pharmacology and clinical use of silver sulfadiazine and related topical antimicrobial agents. Silver sulfadiazine (Silvadene(R), US; Flamazine UK; Flamazine, Netherlands; Sulplata South America) is proving to be a highly successful topical antimicrobial agent for control of burn wound infections. The advantages of wide spectrum of activity, painless application, negligible toxicity and ease of application contribute to the usefulness of this compound. These advantages have led to its use for wound infections other than burns, for skin ulceration and for certain dermatologic lesions; also for the prevention and treatment of various vaginal infections. Described also are zinc sulfadiazine which can provide zinc for wound healing and cerous sulfadiazine which contains the rare earth metal cerium. Their unique effects on cell biology may determine their specific roles in topical therapy.


A model teacher education program in health occupations at the University of Illinois, Urbana-Champaign, Illinois, USA. The Health Occupations Teacher Education Program at the University of Illinois, Urbana-Champaign, U.S.A. has been shown to be a viable and productive model for the preparation of health occupations teacher for both traditional and non-traditional educational settings. Since 1971 the undergraduate program has grown from twelve students to 30 students on-campus, with more than two hundred students in the extramural and part-time programs. Recruitment has been accomplished through professional association meetings, journals and personal contacts. More recently, persons have heard of the program through extramural classes and from students, graduates or University personnel who have become familiar with the program. Program development has been effected through the "capstone" concept, which allows for transfer of technical credit in one's specialty, capped by teacher education courses and concentrated courses to enhance one's expertise in the teaching role. Courses developed by the HOTEP faculty are based on perceived student needs, and were designed as both integrative and collaborative courses to be taken with other health care practitioners and teachers. Evaluation procedures have shown the health occupations teacher education program to be effective in preparing graduates for their predicted roles. The numbers of new students, kinds of health practitioners, and numbers of graduates have increased steadily. Implementation of courses into the Health Occupations Teacher Education Program curriculum has been gradual, so that the undergraduate core of courses is now considered to be nearly complete. Much curriculum planning has already been completed on the master's program, from which some students have already graduated. A doctoral program is also open to those ready for this level of preparation. More time and effort needs to be and will be expended on courses for the master's and doctoral level programs being developed. This health occupations teacher education has been a transportable model for similar programs begun at several other U.S. universities. Many requests have been received from health occupations teacher educators from other states wishing information on this program. Experience gained in this program shows that there is a need for more health occupations teachers in the State of Illinois (2). More requests are being received both at the program and individual levels. Graduates of the program have attested to the benefits of a multidisciplinary program in its effectiveness for preparation in the health care team concept. Student teaching, according to present students and graduates, is the single most effective experience in preparation for the future teaching setting. Since students are placed in a facility resembling as closely as possible the one in which they expect to be employed, there is a real identification with the school and students. The uniqueness of this program lies in its mix of students from the various health fields...


Typhoid fever with myocarditis in children. Two children with typhoid myocarditis have been presented. Although the mortality rate with this complication particularly in presence of heart block is high both patients survived. Heart block was successfully treated with isoproterenol and xylocaine. The possibility of myocarditis must be considered in any child with typhoid.


Strabismus in childhood.

Strabismus in childhood. We have discussed what constitutes a normal visual and ocular system in children and the inherent mechanisms that help each person develop and maintain normal visual function. This ideal status should include good visual acuity in each eye, straight eyes, and the development of fusion. Strabismus represents an obstacle to obtaining these goals and may be caused by poor vision, refractive errors, or anatomic, structural, or innervational abnormalities. Each of these conditions is treatable and correctable when discovered early. With early identification, proper treatment can be instituted and the patient can have the opportunity to develop optimal vision with fusion and depth perception -- a lifetime benefit. Several other types of strabismus respond poorly to the use of glasses, prisms, exercises, or medications and can be effectively treated only by surgical methods. Most divergent and vertical deviations fall into this group, as do ocular deviations associated with paretic or structurally abnormal muscles.


Amblyopia and the pediatrician.

Amblyopia and the pediatrician. Amblyopia is one of the most common eye ailments in children. Early treatment can frequently eliminate this problem. The responsibility for early recognition falls primarily on the pediatrician. The following summarizes what ought to be done for each age group to rule out amblyopia and its associated condition. Newborn to age four months. Make sure the eyes appear normal externally and have a clear red reflex (no cataracts). Infants after age four months. Check fixation with each eye with a penlight. Check for symmetrical corneal light reflexes. Also check red reflex and fundus. Age two to four years. Be particularly aware of any family history of strabismus or amblyopia. The examination should include an observation of the fixation pattern with each eye, the symmetry of the corneal light reflex, and an evaluation of the fundus and the red reflex. Age four. Visual acuity in each eye should be measured. Ideally, all children should be referred for a complete eye examination and refraction if this is economically feasible. School age. Check vision yearly. If a person is going to have one complete routine eye examination by an ophthalmologist in the first half of his lifetime, checking him at age four would be ideal. It should include a cycloplegic refraction to tule out excessive farsightedness, nearsightedness, astigmatism, or unequal refraction in the two eyes. This should be done by a person thoroughly schooled in recognizing eye diseases rather than by a nonmedical practitioner. Annual eye examinations by an ophthalmologist are probably unnecessary if visual acuity is good and the child is asymptomatic.


Neuro-ophthalmology, for the pediatrician. The pediatrician needs to develop some skills in evaluating afferent visual functions and ocular motor abnormalities. He must know some fundamental neuro-ophthalmologic facts to prevent his patients from undergoing unnecessary diagnostic and surgical procedures. In addition, he needs to understand the fundamentals of strabismus and amblyopia, which are briefly considered in this article but are explored thoroughly elsewhere in this issue of PEDIATRIC ANNALS. First, the most common type of nystagmus in children is congenital nystagmus. These children often have a head turn or tilt. Also, it should be remembered that numerous drugs may cause nystagmus. Second, any child with a head turn or tilt must be considered to have some ocular motor abnormality until a complete ophthalmologic evaluation has eliminated this possibility. In addition, before a child is considered to have an isolated sixth-nerve palsy, Duane's retraction syndrome should be looked for. Also, before an inferior oblique palsy is diagnosed, a Brown's tendon sheath syndrome should be considered. Thus, any ocular muscle abnormality deserves an ophthalmologic evaluation. Third, when bilateral swollen optic nerves are noted as an incidental finding, drusen of the optic nerve head should be suspected. A unilateral swollen disk with decreased visual acuity and a Marcus Gunn pupil should bring to mind a papillitis, which is a local inflammatory condition of the optic nerve head. Remember, papilledema is a bilateral condition secondary to increased intracranial pressure with normal vision. Children with papilledema usually have other signs of increased intracranial pressure. If the article has convinced you of only two facts -- that head tilts and turns are usually ocular in origin, and that bilaterally swollen optic nerves in an otherwise asymptomatic child may be optic nerve drusen -- it has accomplished its purpose.


Computerized axial tomography in clinical pediatrics. Computerized axial tomography (CAT), a noninvasive radiologie method, provides a new dimension in screening and diagnosis of intracranial pathology. Evaluation of 725 scans in infants and children demonstrates that CAT may be performed with negligible risk, although sedation and restraint are essential to the successful performance of studies in children under 6 years of age. CAT is the preferred initial diagnostic method in suspected hydrocephalls and is accurate in the detection and precise localization of brain tumors. The management of hydrocephalus and brain tumors has been significantly altered by the availability of CAT. Few invasive neuroradiologic procedures are required and pneumography is especially curtailed. Serial scanning is the best available method of monitoring ventricular alterations in hydrocephalus, tumor size during radiotherapy or chemotherapy, and postoperative recurrence of benign neoplasms. Complex intracranial anomalies are detectable with computerized tomography, but complete definition of pathology often requires angiography and air studies. Limited clinical experience in detecting neonatal intraventricular hemorrhage suggests that CAT will be a valuable tool for futlre investigations of that problem.


Sympathetic pupillary activity in infants. In an attempt to learn the contribution of the sympathetic system to smaller pupillary size in infants, pupillary responses were tested to agents acting on this system in 12 ihfants and 23 young adults. Phenylephrine dilated the pupils of both groups by the same ratio, with infants' pupils reaching a lesser diameter. The responses to cocaine and hydroxyamphetamine were lower in children. It is concluded that in the first months of life the postganglionic sympathetic nerve releases less norepinephrine. This may be due to a lower number of sympathetic neurons. The post-synaptic apparatus may not be fully developed in infants.


Simultaneous iothalamate, creatinine, and urea clearances in children with renal disease. Glomerular filtration rate (GFR) is often used to evaluate and manage patients with renal disease. Few studies in children have compared accurate estimations of GFR (clearance of inulin and/or iothalamate) with the clearance of creatinine which, because of simplicity, has been used as an approximation of GFR. At reduced levels of GFR, studies in adults suggest that the mean of the creatinine and urea clearances closely approximate the GFR. The present investigation shows that the clearance of creatinine approximates the GFR at normal levels; however, at reduced levels the creatinine clearance and the mean of the creatinine and urea clearances both overestimate the GFR as measured by iothalamate. The clearance of creatinine remains a useful clinical tool if its limitations at low levels of GFR are realized.


Male pseudohermaphroditism with partial androgen insensitivity. Androgen insensitivity was demonstrated in two male siblings with partial masculinization of the external genitalia. They had a previously undescribed defect characterized postpubertally by high plasma testosterone and luteinizing hormone concentrations with low serum follicle-stimulating hormone levels. Studies in skin fibroblasts showed normal androgen receptor affinity and capacity for 5alpha-dihydrotestosterone (DHT), normal nuclear retention of the receptor-DHT complex, and normal conversion of testosterone to DHT.


Reye's syndrome: relapses and neurological sequelae. Twenty-two children aged 2 months to 11 years were seen at our institution from January 1970 to March 1975 with clinical, laboratory, and/or histological features consistent with the diagnosis of Reye's syndrome. There were three pairs of siblings. Severity of the illness ranged from relatively benign to rapidly fatal forms. Five received live attenuated vaccines within the three weeks prior to admission. Four relapsed 1 to 21 months after the initial episode, and in one there were multiple recurrences. Six developed major neurological sequelae. All patients graded levels IV and V by EEGs on admission subsequently died in contrast to none from grades 1 and 2. Peritoneal dialysis was carried out in the more severely affected patients. The procedure did not influence final outcome as predicted by the first EEG and is thought to be of limited value.


Atrial fibrillation in children.

Atrial fibrillation in children. Atrial fibrillation is rare in children. Previous reports associated it with severe rheumatic heart disease and a poor prognosis. This review is of the unique experience of 35 cases of atrial fibrillation in children in the past 22 years; 23 patients were boys. The age of onset ranged from 1 day to 19 years (average, 8 years). Associated cardiac conditions were severe rheumatic mitral regurgitation (3 cases), cardiomyopathy (5), atrial tumors (2), infective endocarditis (1), paroxysmal atrial tachycardia of infants (4), idiopathic paroxysmal atrial fibrillation (1), Marfan's syndrome with mitral regurgitation (1), endocardial fibroelastosis (1), and structural congenital heart malformations (17). Surgical correction of congenital heart lesions was directly related to the development of atrial fibrillation in 14. Varying arrhythmias of the sick-sinus syndrome were observed in five children. The atrial fibrillation was paroxysmal or transient in 21 patients and persistent in 14. Treatment depended on the underlying condition. Digoxin was used in all cases and cardioversion attempted in ten; no patient was given anticoagulants. Three children had cerebral emboli, with residual defects. Eighteen patients are known to be alive, 13 are dead, and 4 are lost to follow-up. Atrial fibrillation in childhood is an indication for complete investigation of the patient and for the institution of treatment appropriate to the underlying disease.


Microcephaly in a normal school population. Heights, weights, and head circumferences were obtained on 1,006 students, ages 5 to 18 years, attending regular classes in four schools in a suburban Seattle school district. From the 1,006 students initially examined, 19 (1.9%) had a head circumference two or more standard deviations below the mean for age and sex. Intelligence quotients and academic achievement scores were obtained on these children and compared with normal controls. No significant difference was found between mean IQs of the study subjects and the controls (99.5 vs. 105), but mean academic achievement scores were significantly lower in the study  subjects (49 vs. 70; P less than .001). In addition, although mean IQs were not significantly different between those subjects whose head circumference was proportional and those whose head circumference was relatively small, mean academic achievement scores were significantly higher (60 vs 39; P less than .02) in those subjects whose head size was proportional.


Helping parents cope with the diagnosis of congenital heart defect: an experimental study. An experimental study was designed to help parents cope with the implications of the diagnosis of congenital heart disease. Intervention strategies involving clarification of medical information, discussion of psychological issues, and a combination of the two, were more effective than no intervention in helping parents to gain an accurate understanding of the diagnosis and other medical information. Regardless of the intervention strategy used, satisfaction was generally high, and parent anxiety did not appear to fluctuate during the course of the visit. The team approach was recommended for use in pediatric specialty clinics where time is often short, and more personal interaction may be needed.


A follow-up study of traumatized children. This study compared 17 abused children with 17 children who had been in accidents, matched for age, race, sex, and socioeconomic status, eight years after all had been studied as infants. Each traumatized group was also compared with a matched untraumatized group with no known history of abuse or infantile accident. The majority of all children were lower-class. Hypotheses were that the abused children would fall below the nonabused in health history and physical development, intellectual functioning, language, and self-concept; and that the abused children would score higher in impulsivity and aggression. Clinical assessments revealed few group differences. The surprising finding was the extent of various problems across the entire sample. Seventy percent of the children had speech problems; over 50% showed some degree of disturbance; and 39% were achieving poorly in school. However, these disabilities were distributed randomly among abuse, accident, and comparison children. Most of the children appeared sad and fearful of personal attack by adults or other children. Many mothers' reports indicated that the families, whether abuse, accident, or comparison, experienced constant violence, both environmental and personal. It was concluded that the effects on child development of lower-class membership may be as powerful as abuse.


Sudden death in an infant from methemoglobinemia after administration of "sweet spirits of nitre". The administration of "sweet spirits of nitre" (4% ethyl nitrite CH3CH2ONO in 70% ethyl alcohol) was followed by acute methemoglobinemia and severe anoxic metabolic acidosis in infant twins, Methylene blue administration reversed methemoglobinemia in both, but one twin died from the consequences of hypoxemia. Hemoglobin electrophoresis and methemoglobin reductase determinations were normal for age. This medicine is available without prescription and contains the potent oxidant ethyl nitrite. In infants with sudded death or onset of cyanosis, appropriate toxicological and historical information should be obtained.


Tricyclic antidepressant overdoses in adolescent patients. Tricyclic antidepressant plasma levels were measured in nine hospitalized adolescent oversdose patients to define the medical seriousness of the drug ingestion. Seven out of nine of these patients ingested medication prescribed for treatment of their psychiatric symptoms. Indications for tricyclic therapy in adolescents are vague. The more frequent use of these drugs makes the potential for life-threatening ingestions relatively common. The amount of drug ingested is usually poorly documented. Plasma measurements are of value in assessing the efficacy of the various medical treatments of overdose patients. Two of these nine overdoses were medically serious as defined by plasma measurements. Supportive care with cardiac monitoring was adequate in one case; however, a fatality occurred in the other under what could be described as optimal patient management conditions.


Cricoarytenoid arthritis and airway obstruction in juvenile rheumatoid arthritis. Laryngeal arthritis is a rare manifestation of JRA. The difficulty of indirect laryngoscopy in small children has precluded the type of study which has demonstrated this manifestation in up to one quarter of arthritic adults. Recognition of cricoarytenoid arthritis in the patient reported might have prevented the need for tracheostomy, and eventually led to satisfactory reduction of corticosteroid medication and healing of the tracheostomy stoma.


[Tentative organisation of disease recording in the poultry production. Collection and processing of condemnation results from 6 poultry slaughterhouses in Northern Jutland (author's transl)]. According to condemnation lists collected from 6 poultry slaughterhouses in northern Jutland there has been an increase in condemnation rate for broilers from 0.8 to 1.0% (Table I). The most important causes of condemnation have been emaciation, CRD, hock disorder and enteritis (Table II). Only a few slaughterhouses were involved in processing of hens, turkeys and web-footed birds showing inconstant distributions (Tables III and IV). Variation among slaughterhouses appears from Tables II-IV. The cause of variation and the value of central disease recording are discussed.