[Effect of the method of feeding on the physical development of infants born with symptoms of intrauterine dystrophy]. In the Clinical Department of Metabolic Studies of the National Research Institute of Mother and Child the attempt was made to stimulate physical development of S-F-D infants through introducing modifications in standard feeding in order to make up for the deficits of foetal age. In the years 1970-1975, 118 infants were under observation: 44 out of this group, in the Clinical Department, 70 in the Outpatient Clinic of Infant Nutrition disorders, 4 were observed both in the Clinical Department and in the Outpatient Clinic. The control group of 40 S-F-D- infants was observed in the Child Outpatient Department of Wola Borough of Warsaw. Foetal age of S-F-D infants underwent anthropometric measurements, psychological and neurological examinations. Investigations of haematological and biochemical indices were also carried out. Physical development of children in 4 (S,G,H,C) dietary groups was observed and compared with the control group. Initial diet differed from the standard diet, used at the National Research Institute of Mothers and Child, by excluding gluten and by replacing saccharose with glucose. In other diets (G, H and C) milk formulas with different quantitative and qualitative protein and fat content were enriched with unsaturated fatty acids. Longitudinal analysis included 61 infants from single pregnancies which were put on regular and sufficiently long (5-12 months) diet. Evaluation of physical development was based on the analysis of mean values, increments and rate of growth of body--length, body weight, arm, scapular and abdominal skin-fold thickness. These data are presented in Tables I-IX, variate curves of individual features in Figures 1-9. Somewhat higher developmental indices were observed in the group of infants fed enriched formulas with unsaturated fatty acids. Growth rate of skin-fold thickness in group S, was extremely intensive all the first year through and decreasing physiological tendencies were not observed in 4th trimester of life.


[Caloric balance in full-term healthy infants in relation to the composition of various milk formulas]. In available literature the results of calorie balance studies carried out systematically during the whole first year of life have not been found. As the knowledge of energy metabolism in infants is still insufficient the longitudinal calorie balance studies of healthy infants as well as of infants with various alimentary tract disorders, and these born with low body weight were undertaken. In this paper the results of calorie balance studies in 15 healthy, full-term and full-size infants are presented. A three-day calorie balance investigations were carried out once a month after 5-10 days of adaptation to the diet. Caloric values of really consumed food, the quantity of calories excreted in faces and urine was determined in the ballistic calorimetric bomb using the method of Miller and Payne. The infants were divided into three groups according to the composition of the test formulas, which were given for the first six months of life. From the third week of life all infants were given juices and vitamins, from the fourth month vegetable soup. In the second semester of life all the infants were fed the same standard diet according to the scheme of artificial feeding in Poland. The test standard diet according to the scheme of artificial feeding in Poland. The test formulas were isocaloric and they differed mainly with protein quantity as well as fat quantity and quality: in two formulas the cow's milk fat was totally replaced with soya oil. The main parameters of calorie balance--calorie intake, calorie excretion in feces and in urine, the metabolizable energy in kcal/kg b.w./24 hrs and as percent of calorie intake were estimated. the relation of gain in weight to calorie intake and caloric efficiency of milk formulas used was counted. The results were presented in tables and figures. In the discussion the relationship between some parameters of calorie balance were evaluated, particularly the relation between calorie intake and gain in weight. According to the data from literature the caloric efficiency of formulas containing vegetable oils is higher than of the formulas containing unmodified cow's milk fat and the daily gain in weight of infants fed fat modified formulas is better. In our investigations there were no differences in the caloric efficiency of formulas used.(ABSTRACT TRUNCATED AT 400 WORDS)


[Effect of the composition of the caloric pool on the indicators of protein metabolism in infants]. The influences of formula composition (more fat or carbohydrates as a source of energy) upon protein utilization and other indices of protein metabolism was studied. 15 healthy, full-size infants were divided into three groups K,L,M, five infants in every group according, to the formula given to them. The composition of formulas is shown in table I. In the second half of the first year of life all the infants were fed according to schema of infants nutrition obligatory in Poland, based on unmodified cow's milk formulas. In these infants, staying at the Clinical Department from 2 weeks until 12 months, once a month nitrogen balance study was carried out and serum urea nitrogen, serum protein and albumin level, urine urea nitrogen, creatine and hydroxyproline in urine were examined. Results of these studies allow for more exact assessment of diet influence on protein metabolism and body composition. The results of the 3 groups presented in the tables were compared using t-Student's test at the level of significance a = 0,05. In the second half of the first year of life investigations aimed at finding eventual influence of formulas given in he first six month of life on metabolism indices. Intake of protein in infants fed formulas K and L amounted to 2,5 g/kg b.w., but the indices of protein utilization were different. In infants fed the formula in which cow's milk fat was totally replaced by soya oil, digestibility index--Di % was higher, as well as NPU and NBI indices, and serum protein and albumin level. In the second half of the first year of life in those infants nitrogen intake as well as nitrogen absorption were higher, than in infants fed unmodified cow's milk fat formula. Too low content of fat formula (1 g of fat/100 g formula) and high content of protein (3 g/100 g formula) is not profitable in protein utilization and physical development indices. Protein intake in infants of group M was 3,3 g/kg b.w./24 hrs, protein utilization was poorer, serum urea nitrogen was higher, more urine urea nitrogen and total nitrogen in urine was excreted. In these infants, as in group L infants, the quantity of hydroxyproline were lower, which was reflected by poorer indices of physical development. It seems to us, that among three studied formulas formula K had the most profitable influence on the totally investigated infant protein metabolism indices.(ABSTRACT TRUNCATED AT 400 WORDS)


Diurnal variations in the analgesic effectiveness of morphine in mice. Response to thermal stimulation and the analgesic effectiveness of morphine during various phases of the diurnal cycle were assessed by the hotplate method. Saline treated controls exhibited shortest reaction times during the last quarter of the light-phase and first quarter of the dark phase. Longest reaction times were recorded during the last quarter of the dark phase. Doses of 4, 8, 16, and 32 mg/kg of morphine was administered IP at the peak and trough of the pain sensitivity rhythm. The ED50 (95% C.L.) during the last quarter of the light phase was found to be 14.60 (10.6-20.0) mg/kg while during the last quarter of the dark phase the ED50 was found to be 5.85 (4.5-7.7) mg/kg. In a second experiment, independent groups of ten mice each were injected SC with 8 mg/kg of morphine at three hr intervals over a 48 hr test session. Peak analgesic activity was obtained in the group injected during the last quarter of the dark phase while minimal analgesic effectiveness was obtained during the third quarter of the light phase. Central administration of morphine via the intraventricular route yielded the same relationship, i.e., maximal analgesic effectiveness during the last quarter of the dark phase.


Temporal analysis of naloxone attenuation of morphine-induced taste aversion. In a dose-response study, 7.5 mg/kg of naloxone produced maximal attenuation of conditioned taste aversion to saccharin induced by 10 mg/kg of morphine. Naloxone was administered immediately after the morphine in this study. In a second experiment, naloxone still caused a significant attenuation of taste aversions when administered with a 1 hr delay after morphine, but not after delays of 4 or 8 hr. These results suggest that behavioral consequences of morphine which peak during the first hr after injection (analgesia, catalepsy, and depression of intracranial self-stimulation) are not correlated with the aversive effect of morphine. Nor can the aversiveness of morphine be attributed to withdrawal effects. Only the facilitative actions of morphine occurring 1 to 4 hr after injection, including the facilitation of intracranial self-stimulation, are temporally correlated with the naloxone-sensitive aversive effect. Thus, a temporal analysis cannot be used to dissociate the paradoxical positive reinforcement and aversive effects of morphine. Rather, the temporal correlation between the two opposite motivational effects of morphine serves to emphasize the nature of this paradox.


Optical studies of the phase behavior of monodomain samples of dipalmitoyl phosphatidylcholine containing calcium chloride. Optical birefringence of the phases exhibited by monodomain samples of dipalmitoyl phosphatidylcholine containing 0.1 M-6 mM calcium chloride is measured over a range of temperature and water content. Little change was observed in the birefringence for this calcium chloride content range, and a phase diagram is constructed from these data and compared with that of monodomain samples of dipalmitoyl phosphatidylcholine and water. Effects of the presence of calcium chloride are most pronounced at low temperature and water content but the interaction with phosphatidylcholine cannot account for the effects observed with calcium on intermembrane interactions.


The behavior of oxonol dyes in phospholipid dispersions. The interaction of a class of oxonol dyes with sonicated phospholipid vesicles was followed optically. The spectra of vesicle-associated dyes resemble those found for the dyes in organic solvents, indicating that the oxonols occupy a hydrophobic region of the membrane. At equilibrium the affinity of the oxonols for the vesicles depends on the structure of the dye, the physical and chemical composition of the vesicles, and the ionic strength of the medium. The oxonols occupy soybean lipid vesicles to a level of 147.9 +/- 17.1 nmol/mg lipid with a dye membrane dissociation constant of 3.33 +/- 0.54 muM. The interaction of the oxonols with soybean lipid vesicles is biphasic. The fast phase has a second order rate constant of 9.04 +/- 0.36 x 10(6)M(-1) s(-1) and the number of "fast" binding sites, 68 +/- 8 nmol/mg lipid, was determined from the ratio of the second order rate constants obtained with lipid and with dye in excess. The dissociation of oxonols from soybean lipid vesicles is also biphasic, and the fast process has a rate constant of 17 +/- 2 s(-1), yielding a dissociation constant for the fast sites (k(-1)/k(2)) of 1.88 +/- 0.15 muM. The slow phases of oxonol association with, and release from, soybean lipid vesicles are not second order and have half times of between 0.2 and 5 min, depending on the physical and chemical composition of the membrane lipids. The amplitudes of the slow phases are sensitive to the composition of the aqueous media on each side of the vesicle membranes, which suggests that the slow processes represent the permeation of the membrane by the oxonols. The importance of the properties of the oxonol dyes in the interpretation of their behavior in natural membranes is discussed.


Direct observation of the hydrocarbon chain tilt angle in phospholipid bilayers. By means of X-ray diffraction we have observed the tilting of hydrocarbon chains within a dipalmitoyl phosphatidylcholine multilayer. The tilting produces a distribution of intensity in the (4.2 A)-1 region that provides a quantitative measure of the angle of tilt. Detailed diffraction investigation of multilayers prepared by a recently developed method and mounted to form a "freestanding" sample has made possible the accurate measurement of intensity in this region. We find the intensity distribution to be different from that previously reported and proceed to develop a new model for tilted chains. The model permits calculation of the intensity distribution as a function of tilt angle which is then fit to the data.


Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. I. Enhancement of cationic conductance and changes of the kinetics of nonactin-mediated transport of potassium. We have found that herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) has the ability to increase the rate of transport of positive ions of several kinds, and to inhibit transport of negatively charged tetraphenylborate ions in lipid bilayer membranes. It has been found that only the neutral form of 2,4-D is transport active, whereas the ionized from of 2,4-D does not modify transport of ions, and does not by itself permeate through lipid membranes. The results suggest that the enhancement of transport of positively charged ions such as tetraphenylarsonium + and nonactin-K+ is dominated by the increase of the ion translocation rate constant. It has been shown that the enhancement of nonactin-mediated transport of K+ by 2,4-D can be accounted for by a simple carrier model. We have observed that a 2,4-D concentration above 3 X 10(-4) M the potassium ion transport in phosphatidylcholine-cholesterol as well as in cholesterol-free glycerolmonooleate membranes is enhanced to such a degree that, depending upon the concentration of potassium ions, it becomes limited by the rate of recombination of K+ with nonactin, and/or by backdiffusion of unloaded nonactin molecules. Furthermore, the effect of 2,4-D is enhanced by ionic strength of aqueous solution. From the changes of kinetic parameters of nonactin-K+ transport, as well as from the changes of membranes conductance due to tetraphenylarsonium + ions, we have estimated the changes of the electrical potential of the membrane interior. We have found that the potential of the interior of the membrane becomes more negative in the presence of 2,4-D, and that its change is proportional to the aqueous concentration of 2,4-D. The effect of 2,4-D on ion transport has been attributed to a layer of 2,4-D molecules absorbed within the interfacial region, and having a dipole moment directed toward the aqueous medium. The results of kinetic studied of nonactin-K+ transport suggest that this layer is located on the hydrocarbon side of the interface.


Carbocyanine dye orientation in red cell membrane studied by microscopic fluorescence polarization. The orientation of an amphipathic, long acyl chain fluorescent carbocyanine dye [diI-C18-(3)] in a biological membrane is examined by steady-state fluorescence polarization microscopy on portions of single erythrocyte ghosts. The thermodynamically plausible orientation model most consistent with the experimental data is one in which the diI-C18-(3) conjugated bridge chromophore is parallel to the surface of the cell and the acyl chains are imbedded in the bilayer parallel to the phospholipid acyl chains. Comparison of the predictions of this model with the experimental data yields information on the intramolecular orientations of the dye's transition dipoles and on the dye's rate of rotation in the membrane around an axis normal to the membrane. To interpret the experimental data, formulae are derived to account for the effect of high aperture observation on fluorescence polarization ratios. These formulae are generally applicable to any high aperture polarization studied on microscopic samples, such as portions of single cells.


Phase behavior of ganglioside-lecithin mixtures. Relation to dispersion of gangliosides in membranes. Ganglioside GM1 and mixed brain gangliosides were mixed with 1-stearoyl-2-oleoyl lecithin (SOPC) and examined by differential scanning calorimetry as a function of ganglioside content and temperature. Low mole fractions of ganglioside GM1 and of mixed brain gangliosides are shown to be miscible with SOPC in the gel phase up to X = 0.3, with the possible exception of a small region of immiscibility for the mixed brain gangliosides system centered around X = 0.05. Above X = 0.3, the low-temperature phases demix into a (gel) phase of composition X = 0.3 and a (micellar) phase of composition X = 1.0. Above the endothermic phase transition temperature, no phase boundaries are discerned. It is pointed out that phase structures need to be determined in each domain delineated in the phase diagrams, and that cylindrical phases may exist at higher temperatures and intermediate compositions. The effects of addition of wheat germ agglutinin, which binds to ganglioside GM1, on a ganglioside GM1-SOPC mixture (X = 0.5), are described and interpreted in terms of partial demixing of ganglioside and lecithin. Behavior of the ganglioside-SOPC system is discussed with respect to the kinetics of cholera toxin action in lymphocytes, as well as to other physiological roles of gangliosides in membranes.


Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine. Deuterium magnetic resonance is applied to the study of the liquid crystalline and gel phases, and of the phase transition, of a multilamellar dispersion of chain perdeuterated (d62)-dipalmitoyl phosphatidylcholine/H2O. Analysis of the deuterium spectra in terms of the moments of the spectra allows one to make quantitative statements concerning the distribution of quadrupolar splittings even in complicated situations, e.g., when using perdeuterated sampled or when there are mixed phases. This analysis indicates that d62-dipalmitoyl phosphatidylcholine in excess H2O undergoes a sharp phase transition (with a width of less than 1 degree C) at approximately 37 degrees C and that there appears to be hysteresis in the phase transition of approximately 1 degree C. In the lamellar liquid crystalline phase above 37 degrees C the spectra show a number of well-resolved features whose quadrupolar splittings can be followed as the temperature is varied. The gel phase near 20 degrees C possesses a very broad, almost featureless spectrum that does not seem to support a model of the gel phase wherein the hydrocarbon chains are fully extended in the all-trans conformation. At temperatures near 0 degrees C the spectra clearly indicate that a large fraction of the lipid molecules cease the rotation about their long axes, giving a spectrum more characteristic of a rigid or solid sample. These results give a picture of the gel phase as a phase characterized by considerable hydrocarbon chain disorder near 20 degrees C and becoming a more solid-like phase near 0 degrees C. The spin-lattice relaxation time, T1, has been measured at 20 degrees C in the gel phase, and at 37 and 45 degrees C in the liquid crystalline phase. The values of T1 obtained for each of the resolvable peaks in the spectrum at 37 degrees C are compared to the values (for each peak) of T2e, the decay time of the quadrupolar echo, obtained at the same temperature. These results are discussed in terms of a simple two-motion model.


Alignment and defect structures in oriented phosphatidylcholine multilayers. The alignment of dilauryl-, dimyristoyl-, and dipalmitoylphosphatidylcholine at various water concentrations into large oriented monodomain multilayers by annealing at elevated temperatures (Powers and Clark, 1975, Proc. Natl. Acad. Sci. U.S.A. 72:840; Powers and Pershan. 1977. Biophys. J. 20:137) is accompanied by the formation and subsequent dissolution of various defect structures. Some of these defects appear similar to those observed in thermotropic and other lyotropic liquid crystals, reflecting the lamellar structure of these materials. The formation and evolution of defects during the alignment of the lipids into the defect-free, monodomain, multilamellar geometry is studied using polarized microscopy. A combination of polarized and dark-field microscopy facilitated characterization of the defects; specific structural models are proposed. A new alignment technique involving compression and dilation of the lipid, which effects sample alignment at temperatures that are lower than those required by the Powers technique, is described. Lower temperature alignment avoids thermal decomposition that will sometimes occur if the lipid is maintained at elevated temperatures for prolonged periods. With this technique, samples (80 micrometer thick) of dilaurylphosphatidylcholine with 20% water by weight were aligned at room temperature.


Effects of C-protein on synthetic myosin filament structure. In the absence of C-protein, synthetic filaments prepared from column-purified myosin exhibit the following features: individual filament diameters are uniform over a long length, but a wide distribution of diameters is apparent over the population; approximately 25% of the filaments have a frayed appearance and take up stain poorly, whereas the remaining 75% are well-stained; optical diffraction of well-stained filaments reveals a 14.3-nm subunit period and a 43-nm axial period (Koretz, 1978; Koretz, 1979). Addition of C-protein to myosin before filament formation affects all of these features in a manner related to C-protein concentration. At the physiological ratio of C-protein to myosin in the banded region of the natural thick filament, synthetic aggregates are uniform in diameter over the population and show less than 10% frays. Whereas the subunit period remains unchanged, the axial period has increased to 114.4 nm, or eight times the subunit repeat. Above and below the physiological ratio, disorder of a specific nature is apparent. Addition of C-protein after filament formation appears to coat the aggregates so that elements of backbone ultrastructure are obscured, and some evidence of axial period change is visible in diffraction patterns. A model is presented for the binding of C-protein to myosin, and its observed effects on filament structure are explained in terms of this model.


Effect of benzyl alcohol on lipid bilayers. A comparisons of bilayer systems. The effect of the small anesthetic molecule, benzyl alcohol, on the structure of various bilayer system has been studied by optical, electrical, and x-ray diffraction techniques. We find that the modifications in bilayer thickness caused by benzyl alcohol differ dramatically for planar (or black lipid) bilayers containing solvent, planar bilayers containing little or no solvent, and vesicular bilayers. Benzyl alcohol increases the thickness of planar bilayers containing n-alkane solvents, yet decreases the thickness of "solvent-free" planar bilayers. The effect of benzyl alcohol on vesicular bilayers below the phase transition temperature also depends on whether solvent is present in the bilayers. Without solvent, gel-state bilayers are reduced in thickness by benzyl alcohol, whereas in the presence of solvent, the thickness is unchanged. Above the phase transition temperature, benzyl alcohol has no measurable effect on vesicular bilayer thickness, whether solvent is present or not. These results indicate that different model membrane systems respond quite differently to a particular anesthetic.


Orientational order and rotational diffusion of the head group in the bilayer membrane. A nuclear magnetic resonance study. An order parameter-based interpretation is applied to the temperature dependence of the deuterium magnetic resonance splittings and the anisotropic contribution to the chemical shift for 31P from the head groups of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). It is shown that the rotational motion of the molecule about its long axis is not a free rotational motion as normally assumed, but instead a biased one. Changes in the degree of biasing appear to be primarily responsible for the variation of the NMR spectra with temperature. The degree of biasing is described by orientational order parameters. With the use of these order parameters, it is shown that the temperature dependence of the anisotropic contribution to the chemical shift for 31P can be predicted from that of the deuterium quadrupole splittings.


X-ray scattering from labeled membranes. We present a new method for the determination of structural parameters in biological membranes. Recording the continuous scattering of heavy-atom labeled membranes and applying elementary Fourier methods we obtain the scattering of the heavy-atom distribution alone. The details of this distribution are explored by developing a simple model and testing for cases relevant to biological membranes. We find that the intensity distribution is highly sensitive to many key parameters. The increased signal from heavy-atom labeling and the use of an improved x-ray system make it possible to record patterns from dilute membrane suspensions. Thus determination of these parameters is possible in the same environment where many membrane biochemical studies are performed. Application of the method is made to a model lipid bilayer membrane, dipalmitoyl phosphatidylcholine by labeling with UO2++ ions. We determine the precise distance between UO2++ layers on either side of the membrane as well as the width of the label on each side. This determination permits estimation of phosphate separation across single labeled bilayers in an aqueous suspension.


Metabolism and excretion of 3H-1,25-(OH)2-vitamin D3 in healthy adults. The synthesis of very high specific activity 25-OH-vitamin D3 (78 Ci/mmol) has made possible the study of the metabolism and plasma disappearance of 3H after a single dose of 3H-1,25-(OH)2-D3 in quantities that are only 10-20% of the endogenous plasma pool. We studied seven healthy adults who were given doses of 1,25-(OH)2-D3 ranging from 30-2300 pmol. Plasma disappearance was rapid with only 14 +/- 2% of administered 3H remaining in the plasma pool 4 h after labeling. Plasma metabolite profiles during the first 4 h showed only 1,25-(OH)2-D3. Thereafter, significant amounts of other metabolites were detected. The 6-day cumulative excretion of 3H in urine and feces (virtually all associated with metabolites of 1,25-(OH)2-D3) averaged 16 +/- 3% and 49 +/- 11% of the dose, respectively. Compartmental analysis of the isotope data for two subjects who received the smallest doses of 1,25-(OH)2-D3 indicated that endogenous renal 1,25-(OH)2-D3 synthesis rates approximate 0.8-2.4 nmol/day (0.3-1.0 microgram/day).


[Central and peripheral mechanisms of hypotension induced by dl-propranolol in the dog]. The IV injection of 1-2 mg/kg dl-propranolol in dogs elicited a reduction of arterial blood pressure accompanied by a blockade of hypertensive responses to carotid occlusion or stimulation of the central trunk of the vagus. The same fall of blood pressure and identical blockades were seen following propranolol injected in the cisterna magna at a total dose of 2-5 mg. This late treatment also abolished the hypertensive response to KCl injected into the cisterna magna. On the other hand, propranolol failed to modify significantly responses to the electrical stimulation of hepatic and splenic sympathetic fibers and did not influence the hypertensive effects of adrenaline and noradrenaline. These findings are compatible with the notion that propranolol lowers systemic blood pressure via an action on central nervous system vasomotive centers.


Thyroid-stimulating antibodies in patients with autoimmune disorders. A radioreceptor assay was used to measure thyroid-stimulating antibody (TSAb) in 1) patients with Graves' disease with untreated hyperthyroidism, selected for absence of clinically significant eye disease; 2) patients with Graves' ophthalmopathy, with and without previously treated hyperthyroidism; 3) patients with other thyroid disorders; 4) patients with other autoimmune disorders; and 5) normal subjects. TSAb was detected in 14 of 15 (93%) patients with Graves' hyperthyroidism and in 10 of 16 (63%) patients with Graves' ophthalmopathy. Of the patients with Graves' ophthalmopathy, TSAb was detected in 9 of 10 patients who had once been hyperthyroid and in only 1 of 6 patients who had never been hyperthyroid (euthyroid Graves' disease). TSAb was detected in 1 patient with idiopathic Addison's disease (autoimmune adrenalitis) and in 1 patient with juvenile diabetes mellitus (both of whom were euthyroid), and borderline levels were found in 1 patient with Sjögren's syndrome and 1 patient with methyldopa-induced antired blood cell antibodies. TSAb was not detected in normal subjects or patients with other thyroid disorders. The conclusions are: 1) the test is very useful in the diagnosis of Graves' disease; 2) Graves' eye disease may be a frequently associated but separate disorder; and 3) because TSAb may be present in some euthyroid patients with other autoimmune disorders, TSAb production may occur primarily because of a disorder in the immune system.


Difference in pituitary-thyroid feedback regulation in hypothyroid patients, depending on the severity of hypothyroidism. In an attempt to study pituitary-thyroid interplay during replacement therapy for hypothyroidism, T4 (75-150 micrograms/day) was administered for at least 3 months. A small dose of T4 (75 micrograms/day) significantly depressed basal and TRH-stimulated TSH levels in normal subjects without significantly elevating serum T4 and T3 concentrations. In patients with severe hypothyroidism and marked enlargement of the sella turcica, T4 (2.53 micrograms/kg BW) normalized the serum T4 and slightly elevated the serum T3 but failed to normalize basal and TRH-stimulated TSH levels. In patients with moderate hypothyroidism and moderate enlargement of the sella turcica, T4 (2.0 micrograms/kg BW) normalized serum T4, T3, and basal TSH concentrations but failed to normalize TRH-stimulated TSH levels. In patients with slight hypothyroidism and slight enlargement of the sella turcica, T4 (1.84 micrograms/kg BW) normalized serum T4, T3, and TSH (both basal and TRH stimulated) concentrations. In five patients, an apparent paradoxical increase of basal serum TSH level was found shortly after starting thyroid hormone treatment. It is suggested that pituitary-thyroid interplay during the first 3-6 months of replacement therapy for hypothyroidism varies greatly depending on the severity of hypothyroidism.


Elevated levels of polyamines and histamine in adenocarcinomas of the thyroid. The concentrations of polyamines (putrescine, spermidine, and spermine) and of histamine in normal and diseased thyroids were determined with an automated amino acid analyzer. A total of 39 specimens was investigated: 7 specimens of normal tissue, 6 adenocarcinomas, 2 specimens of tissues adjacent to adenocarcinoma, 13 specimens from treated Graves' disease, 7 follicular adenomas, 2 adenomatous goiters, and 2 specimens of Hashimoto's thyroiditis. Mean putrescine levels in tissues from normal thyroid, adenocarcinomas, Graves' disease, and follicular adenoma were 26, 143, 20, and 12 nmol/g wet tissue, respectively. The mean levels of both spermidine and spermine were slightly but significantly higher in adenocarcinomas than in other thyroid tissues. The molar ratio of spermidine to spermine was about 0.5 both in the normal and diseased thyroid tissues, except for specimens of thyroiditis. Histamine was detected in 3 of the 6 cases of thyroid carcinomas, and in  case of adenomatous goiter. The data suggest that measurement of polyamines, especially putrescine, may be useful for diagnosis of thyroid adenocarcinomas.


3'-5'-Diiodothyronine in health and disease: studies by a radioimmunoassay. A simple, reproducible, and highly specific RIA has been developed for measurement of 3',5'-diiodothyronine ((3',5'-T2) in unextracted serum. Interference in binding of radioactive 3',5'-T2 to anti-3',5'-T2 by serum proteins was minimized by using 0.4 M phosphate buffer (pH 6.2) and merthiolate. The detection  threshold of the RIA was 2.5 ng/100 ml. Recovery of nonradioactive 3',5'-T2 added to serum averaged 99%. T4, T3, and rT3 cross-reacted with 3',5'-T2-binding sites on anti-3',5'-T2 antibody only to the extent of 0.0025, less than 0.0004, and 0.22%, respectively. 3'-Monoiodothyronine cross-reacted 1.7%. Serum 3',5'-T2 concentrations were (mean +/- SD) 6.4 +/- 2.4 ng/100 ml in 53 normal subjects, 4.2 +/- 3.5 ng/100 ml in 7 hypothyroid patients, 14.9 +/- 7.7 ng/ml in 25 patients with hepatic cirrhosis, and 14.3 +/- 5.3 ng/100 ml in 31 newborns' cord blood sera. The values in each of the latter four groups were significantly different from normal. The mean serum 3',5'-T2 concentration of 7.7 +/- 2.5 ng/ml in eight subjects in the third trimester of pregnancy did not differ significantly from normal at a time when serum T4 and T3 were clearly elevated. Oral administration of 300 microgram rT3 to 9 normal subjects led to a mean maximal increase in serum 3',5'-T2 concentration of 45% at 1 h. Total fasting in 3 obese subjects was associated with a significant increase in serum 3',5'-T2 from 8.6 to 16.3 ng/100 ml at 6-8 days; serum rT3 increased similarly, while serum T3 decreased and T4 did not change. Administration of dexamethasone (2 mg also associated with nearly parallel increases in serum 3',5'-T2 and rT3 and a decrease in serum T3. 3',5'-T2 concentrations were also measured in amniotic fluids at different stages of gestation; the mean value of 15.2 ng/100 ml at 15-20 weeks gestation was significantly higher than that of 5.8 ng/ml at 33-40 weeks gestation. Pronase hydrolysates of 9 autopsy specimens of normal thyroid glands contained (mean +/- SD) 350 +/- 144 microgram T4 and 0.24 +/- 0.15 microgram 3',5'-T2/g wet wt. On the basis of these data and those available for MCRs of 3',5'-T2 and T4, it was estimated that thyroidal secretion contributes less than 1% of 3',5'-T2 measured in serum of normal man. The various data suggest that: 1) 3',5'-T2 is a normal component of human serum; 2) almost all 3',5'-T2 in human serum derives from extrathyroidal sources; and 3) changes in serum 3',5'-2 generally parallel those in rT3.


The effect of repeated administration of ipodate (Oragrafin) in hyperthyroidism. This report describes the effect of administration of repeated doses of ipodate (Oragrafin; 3 g orally every third day for five doses) in six hyperthyroid patients. Baseline serum concentrations of immunoassayable T3, rT3, and T4, were 926 +/- 206 ng/100 ml, 165 +/- 31 ng/100 ml and 21 +/- 2.7 micrograms/100 ml (mean +/- SEM), respectively. Within 24 h after the first dose of ipodate, serum T3 fell by 54% and it remained between 66-77% below baseline until the third day after the fifth dose; subsequently, there was a gradual recovery from the effect of ipodate. Serum T4 also decreased after ipodate administration; it was 23-31% lower than baseline from the second day after the third dose to the sixth day after the fifth dose. Serum rT3 increased after each dose of ipodate; peak values of 97%-203% above baseline value were observed at 24-48 h after each dose. There was a subjective improvement in clinical symptoms of hyperthyroidism in all cases. Resting pulse rate and pulse pressure dropped significantly (P less than 0.02) by the ninth day of study and remained so thereafter. Body weight increased significantly by the ninth day of the study. The various data suggest that ipodate may serve as a useful adjunct in the early treatment of hyperthyroidism.


A bioassay capable of measuring 1 picogram of 1,25-dihydroxyvitamin D3. Fetal rat bones in organ culture constitute a sensitive system for assay of the vitamin D metabolite, 1 alpha,25-dihydroxyvitamin D3. Significant bone resorption is obtained with as little as 2 pg 1,25-dihydroxyvitamin D3 after 48 h of culture and with 1 pg after 64 h of culture. In the current study, organ cultures of fetal rat bone are used as a bioassay for 1,25-dihydroxyvitamin D i normal human plasma, which was prepared for assay by extraction with dichloromethane, chromatography on Sephadex LH-20, and purification on silicic acid by high pressure liquid chromatography. The concentration of 1 alpha,25-dihydroxyvitamin D3 in normal adult human plasma was 24.8 +/- 2.0 pg/ml (n = 19) by this assay.


[Calcium requirement in infants with intrauterine dystrophy (ID). Report II. Effect of differentiated diets with regard to quantity and quality of protein and fat on the calcium balance in infants with intrauterine dystrophy]. In the former report on he calcium requirement in Small-for Date (S-f-D) infants it was observed that the ability of calcium absorption of S-f-D infants is lowered in 1-st semester of life. From this point of view it seemed purposeful to study the influence of 3 modified cow's milk formulas (see table) on the calcium absorption in S-f-D infants. Modification of these diets in regard to cow's milk depended on: 1) partial replacement of cow's milk fat with soya oil. 2) change of the proportion between fat and protein. 3) partial replacement of milk casein with lactoalbumin . The infants were divided into 3 groups G, H and C according to the kind of diet. Observation in the first 2 groups lasted for the whole first year of life, C group of infants was observed only in 1-st half year of life. In the first month of life G and H infants were fed the same unmodified cow's milk formulas (diet S) 3-day balance-studies. Were carried out once a month. The data of these 3 groups of infants were compared with each other and the data of S-f-D infants fed unmodified cow's milk formulas (group S) described in he former report. In group S, calcium intake was the highest in 1-st and in 2-nd semester of life among all compared infant groups, but the difference was not statistically significant. The lowest (%) absorption was noted in group G infants (fig. 2, table III and IV). The difference was statistically significant in 1-st semester of life between group G and S and in 2-nd semester between G and S as well as G and H groups. Calcium retention mg/kg was also the lowest in group G infants, and the difference was statistically significant in 1-st and in 2-nd semester between G and S groups. The infants fed H formula in spite of the lowest indices of calcium absorption % and retention mg/kg in the first (see table) and the second month of life and in spite of the lowest intake of calcium among all compared infants groups cough up absorption (%) and retention (mg/kg b.w.) with groups S in 2 semester of life.(ABSTRACT TRUNCATED AT 400 WORDS)


[Risk of damage to the organ of vision in low birth weight infants]. The authors presented their own material of years 1974-1977. During this period 8788 children were born, in it 737 (8,3%) with low birth weight (below 2500 g). Retrolental fibroplasia was diagnosed in 4 children, it was 0,5% of newborns with low birth weight, and 0,04% of the all live-borns. The retrolental fibroplasia was diagnosed in: 1) the child born in 27 week of pregnancy with 1000 g of body weight, 2) in two children born in 32-33 week of pregnancy with 1450 g and 1350 g of body weight, 3) in a child born in 31 week of pregnancy with 1600 g of body weight. The infants were nursed in incubators with about 30% of oxygen during 36 to 46 days. Contemporary hypoglycemia, hypoproteinemia, atelectasia of lungs with respiratory insufficiency were diagnosed. In the discussion the authors underlined the role of immaturity and hypoxia of the premature baby, which play the role in the secondary injury of vessel's walls of retina. The disturbancy of carbohydrate and protein metabolism were certainly secondary pathogenic agent sin retrolental fibroplasia. There exists the necessity of oxygen therapy of premature baby, but to take cre of the infant in the incubator does not mean the necessity of oxygen therapy . Even with controlled oxygen dosage in incubator the retrolental fibroplasia may occur as a result of relative hyperoxydation induced by the constriction of retina vessels. The authors underlined the necessity of repeated ophthalmologic examination of premature babies in about every 2 weeks, what makes very early diagnosis possible.


[Factor XII deficiency - Hageman trait. Additional diagnostic procedures]. In the previous paper published in the Bulletin for Hematology and Blood Transfusion we described the congenital deficit of Hageman factor (HF) with the basic findings. Now we provide addilioval laboratory -diagnostical tests in order to confirm definitively that our patients have the deficit of Factor XII, and not of some other factors of the contact coagulation phase as: Fletcher, Fitzgerald, Williams and Flaujeac. On the other hand, in order to enlight the laboratory-diagnostical problems which one can face in solving of these cases, we have reviewed the basic biochemical characteristics of the contact factors and the mechanism of the beginning of the internal pathway of blood coagulation.


Determination of brain death via pulsatile echoencephalography. For cerebral death to occur there must be many levels of cerebral function destroyed. Cortical and subcortical irreversible damage is evident by unresponsiveness to any stimuli. Brain stem and basal ganglia damage is indicated by absence of spontaneous respirations, cephalic reflexes, and thus cerebral circulation. All elements of the criteria for cerebral death must be met. The decision should be made by the attending physician in consultation with his peers. The life support mechanisms should be discontinued after the diagnosis of cerebral death has been made. Absence of pulsatile echoes means absence of cerebral circulation and cerebral function, or a definitive diagnosis of cerebral death. It is a final parameter in the criteria and allows definite measures to be taken. But it behooves one to remember that this phenomenon of cerebral death makes organ donation and transplantation possible. It has not been created in order to supply the needs for organ transplant!


Effects of dietary potassium and race on urinary excretion of kallikrein and aldosterone in man. Urinary excretion of kallikrein by 16 normal and 8 hypertensive subjects was studied at three levels of dietary potassium: 85 meq/day for 5 days, 185 meq/day for 7 days, and 25 meq/day for 10 days. Excretion of kallikrein varied directly with potassium intake and paralleled excretion of aldosterone in both normotensive and hypertensive subjects. Mean levels of excretion of kallikrein at 85, 185, and 25 meq intake of potassium were 10.8, 19.1, and 5.8 esterase U/day (EU/day), respectively, for the normotensive subjects and 8.8, 13.9, and 6.1 EU/day for the hypertensive subjects. Mean levels of excretion of kallikrein were significantly higher in white that in black subjects among normals and hypertensives [13.0 vs. 5.9 EU/day for normals (P less than 0.05) and 13.7 vs. 4.0 EU/day for hypertensives (P less than 0.05) on the 85 meq/day diet]. The parallel changes in excretion of kallikrein and aldosterone support the hypothesis that changes in effective levels of aldosterone induce changes in the excretion of kallikrein. Because of racial differences in excretion of kallikrein, matched groups should be used for comparisons of the kallikrein system in disease states.


The prostaglandin and kallikrein-kinin systems in mineralocorticoid escape. To evaluate the interactions of the renal prostaglandin and kallikrein-kinin systems during mineralocorticoid escape, we administered desoxycorticosterone acetate (DOCA; 20 mg im daily for 10 days) to five normal men and then repeated the study 2-16 weeks later with simultaneous indomethacin (200 mg/day) or ibuprofen (1600 mg/day) for prostaglandin inhibition (PI). Plasma aldosterone, PRA, and urinary prostaglandin E (PGE) were measured by immunoassay; urinary kallikrein activity was measured by esterase activity. With DOCA, subjects gained 2.0 +/- 0.1 (SE) kg and retained 485 +/- 125 milliequivalents (meg) sodium; serum potassium fell from 4.6 +/- 0.2 to 3.2 +/- 0.1 meq/liter, aldosterone fell from 3.8 to 2.2 ng/dl, and PRA fell from 0.9 to 0.1 ng/ml . h (all P less than 0.05). Kallikrein increased from 6.4 +/- 1.6 to 65.3 +/- 18.8 esterase U (P less than 0.01), but PGE (820 +/- 110 vs. 780 +/- 80 ng/day) did not change. With DOCA and PI, PGE fell by 80%. Subjects again gained 2.0 kg and retained 530 +/- 106 meq sodium; aldosterone fell to 1.1, PRA fell to 0.2, and potassium fell to 3.3 (all P less than 0.05 from basal, but P less than 0.4 from DOCA alone). Kallikrein again rose to 56.0 +/- 19.2 (P less than 0.01). However, the rate of sodium retention was enhanced slightly but significantly. These studies demonstrate that with DOCA, urinary kallikrein activity increases but PGE is unaltered. The minimal effects of prostaglandin inhibition and the lack of change in PGE excretion suggest that prostaglandins do not play an important role in mineralocorticoid escape. There is no apparent interaction of prostaglandins with the kallikrein system in this model; however, the kallikrein-kinin system may still play a direct role in the escape phenomena.


Decision making in nursing: an analytical approach. Decision making is a basic function of all nurse leaders. Because of the complex nature of many decision situations faced by nurses, problem solving and decision making in nursing are as much an art as a science. The Vroom and Yetton model of decision making is an appropriate tool through which nurses involved in patient care management can examine their decision making and improve their decision behavior. Use of this model is suggested as an approach to teaching decision making at the undergraduate and graduate level of nursing education. Case material has been presented to help readers identify their favored methods of decision making and to point out possible deficiencies in these methods.


Prevention by specific perceptual remediation for vulnerable first-graders. Controlled study and follow-up of lasting effects. In a pretest-posttest design with two matched control groups, 86 first-graders screened as vulnerable to academic failure and behavioral decompensation were each assigned to one of three groups: (1) channel-specific perceptual stimulation, (2) regular academic tutoring (contact controls), or (3) no contact. On most measures, including perceptual and achievement tests and behavior ratings by teachers, group 1 showed more improvement than either of the control groups. Several of these differences were significant (P less than .05, two-tailed). In general, the two control groups came closer to each other than to group 1. With no further intervention, follow-up one year later showed more dramatic significance. On every measure, group 1's improvement surpassed that of the control groups, and diverged from them even more than at posttest; this divergence was significant on most measures. Group 1 improved significantly (P less than .05 to P less than .01) in reading, IQ, and three behavior scales, while both control groups showed only deterioration on these measures. Group 1 gained five IQ points on the Wechsler Intelligence Scale for Children, while the controls lost five. On the Davids Scale, group 1 improved significantly (P less than .01) to "probably not hyperkinetic," while both control groups deteriorated to "probably hyperkinetic." The hypothesized mechanism of group 1's behavioral superiority at follow-up was its significant (P less than 0.1) reading improvement, with secondary emotional benefits.


Clients and patients of mental health services. To determine how a cohort of patients admitted to a mental health center in a single month used the center's clinical services over a year's time, an index of service utilization for each patient was developed. The weighted score took account of days of inpatient and day hospital care and minutes of outpatient time consumed. It was found that 15% of the cohort (48 patients of 330 admitted) used 70% of the total clinical services delivered to the cohort. Analyses of the data on patient characteristics as related to the index or score included the chi 2 test and multiple regression analysis. Not a single sociodemographic variable predicted high utilization of services. Only such clinical characteristics as severity of psychopathology as reflected in patients' diagnoses, suicidal behavior, and a history of prior inpatient treatment contributed to the prediction. The largest group of entrants had relatively brief encounters with the center, and the bulk of the services were actually delivered to a small, severely disturbed minority.


El hospital invisible. A study of Curanderismo. This report presents the results of interviews with 16 Mexican-American folk healers (curanderos and curanderas) in San Antonio, Tex. Curanderismo was found to be alive and well in San Antonio, though its practitioners tend to be older and its future unclear. Several salient characteristics of the practitioners were clarified such as the process of becoming a healer, referral practices, types of disorders treated, and treatment of the traditional folk illnesses. We take a basically conservative position on whether curanderos can ever be incorporated into the health care delivery system. However, this study confirms that the practitioners and their clients simultaneously utilize the folk medical system and the scientific medical system.


Lost subjects. Source of bias in clinical research? This report describes a study of subject refusal as a source of bias limiting the generality of psychiatric research results. Fifty psychiatric patients who refused to participate in a battery of research interviews and psychological tests were compared with 50 participant patients. Between-group comparisons were made on an extensive and detailed set of clinical, treatment, and demographic data. Results revealed a remarkable lack of difference between the participant and refusal groups in demographic features, type or duration of hospitalization, and type or degree of pathology as defined by symptoms, prognostic measures, and diagnoses. These results and a review of related studies suggest that sample bias in psychiatric research resulting from loss of eligible subjects by refusal depends on the amount of institutional contact and the severity of disorder in the sample studied.


Human rights and interviews.

Human rights and interviews. Regulations from the US Department of Health, Education, and Welfare define consent in the conduct of research involving human beings. As requirements expand, these regulations have assumed considerable importance for psychiatric research, including research interviews. The author's experience with one committee on research involving human beings provided the impetus for the present report. Subjects were drawn from a prospective study of couples in a home dialysis program. Thirty couples were systematically interviewed concerning social, personal, medical, and psychiatric history. After completion of the interview, subjects were asked a series of questions concerning their feelings about being interviewed. Although most subjects found the experience to be pleasant, nearly half believed it might upset other patients. However, none believed any long-term harm could come from the conduct of the interview itself. It is therefore concluded that the potential harm of structured interviews in severely medically ill patients and their spouses is essentially nil.


Mortality and community mental health. The Alachua County, Florida, mortality study. This study reports the results of a household survey and search of death certificates that show a relationship between depression, anxiety, and subsequent mortality. It is part of an effort to develop practical epidemiologic techniques for continuous assessment of community mental health. Use is made of the population attributable mortality rate, estimated from a comparison of the prevalence of a given factor in life and at death. The study estimated attributable mortality prospectively by following up participants in a mental health survey of Alachua County, Florida, for up to four years. Of eight mental scales examined, five (mood, depression, somatic symptoms of anxiety, the Health Opinion Survey, and selected psychopathologic symptoms) showed significant association of scores with community mortality. The data suggest linkages of mental factors to mortality of an order of magnitude sufficient to warrant consideration of these factors as leading causes of death.


Time experience during depression.

Time experience during depression. Before antidepressant medication was therapeutically effective, 30 severely depressed hospitalized patients (primarily unipolar) were compared with 30 controls on several aspects of time experience. In comparison to controls, depressed patients were most preoccupied with past events, focused less on present and future events, attended to more distant past events and memories, focused on more imminent future events, reported longer time spans for present story productions, and overestimated 160-second, 240-second, 15-minute, and 30-minute time intervals. Confirming the objective time estimations, depressed patients indicated on a verbal report measure that they experienced time passing slowly during the experiment, that they generally overestimate time, and that previously time did not seem to pass so slowly.


Preventive intervention with the recently bereaved. To study the effectiveness of preventive intervention in lowering postbereavement morbidity, 200 widows were assessed in the early weeks following their husbands' deaths. Subjects at risk for postbereavement morbidity were selected and randomly allocated to experimental (N = 31) and control (N = 33) groups. Specific support for grief and encouragement of mourning was carried out with the experimental group during the first three months; no intervention was given to the control group. All were followed up 13 months later with a validated health questionnaire. There was a significant lowering of morbidity in the intervention group as compared to the control group (P less than .02). The most significant impact of intervention occurred with the subgroup of intervention and control subjects who perceived their social networks as very nonsupportive during the bereavement crisis (P less than .001).


Effects of chlordiazepoxide and oxazepam administration on verbal hostility. We compare the effects of chlordiazepoxide, oxazepam, and placebo on hostility, as both an inner motivational or potential state and verbal interpersonal behavior. This article reports the findings relevant to the latter dimension of hostility and integrates them with those findings, presented in an initial report, relevant to hostility as an inner motivational state. The verbal data again support the hypothesis that chlordiazepoxide-induced increases in verbal interpersonal hostility, following frustration, are greater than those associated with placebo. With regard to oxazepam, the verbal hostility data were consonant with the motivational data that suggested that oxazepam does not substantially disinhibit hostility but did not as consistently differentiate oxazepam and chlordiazepoxide at the level of overt hostile behavior.


Propoxyphene on demand. Analgesic-seeking behavior in psychiatric inpatients. Although anxiety is known to enhance a patient's response to pain, the exact relationship is unclear. This problem is particularly acute among psychiatric patients where analgesics are frequently both used and abused. This study attempts to evaluate factors associated with analgesic use among these patients with the hypothesis that anxiety, other measures of psychopathology, and ward tension would be associated with frequent analgesic use. An unselected series of psychiatric admissions during a three month period were administered the State-Trait Anxiety Inventory, MMPI, and a questionnaire dealing with prior drug use. Propoxyphene napsylate (Darvon-N) was made freely available on request from nurses who recorded details of the interaction on a prepared card. The nursing staff also recorded unusual incidents on the unit and evaluated daily the level of ward tension. The results indicate that, when made freely available to psychiatric inpatients, propoxyphene was used very conservatively and for appropriate complaints. Factors associated with drug seeking behavior are discussed in relation to other research regarding the use and abuse of analgesics.


Incidence of polypharmacy in a long-term care facility. The incidence of polypharmacy was investigated in a 200-bed long-term care facility. One hundred residents were drawn at random for the study. The average number of drugs prescribed per patient was 3.33, and the average number of pills was 6.34 daily. The most frequently prescribed drugs were the analgesics, followed in order by antihypertensive agents, cardiotonic preparations and antimicrobials. The literature is reviewed with respect to the incidence, causes and end-results of polypharmacy. It is recommended that long-term care facilities develop enlightened and aggressive pharmacy committees to monitor and evaluate drug use routinely in an institutional setting.


Neurobiologic antecedents of schizophrenia in children. Evidence for an inherited, congenital neurointegrative defect. In chronic schizophrenics, disordered motor development in childhood is followed by more early cognitive and social impairment and poorer outcome; childhood schizophrenics represent the most extreme variants of this. Preschizophrenic infants show a fluctuating dysregulation of maturation--or "pandevelopmental retardation" (PDR)--that involves physical growth; gross motor, visual-motor, and cognitive development; proprioceptive and vestibular responses; muscle tone; and possibly arousal. Pandevelopmental retardation was significantly related to a genetic history for schizophrenia (less than .05), but not to obstetric complications. The severity of PDR was significantly related to the severity of later psychiatric and cognitive disorder (less than .01). Pandevelopmental retardation provides a "marker" in infancy for the inherited neurointegrative defect in schizophrenia. These disordered functions should be studied by anyone interested in the biology of the schizophrenic genotype or in specific early interventions for children at risk.


Cell-bound cations of the moderately halophilic bacterium Vibrio costicola. Over most of the range of salt concentrations in which the moderately halophilic bacterium Vibrio costicola could grow, the sum of the cell-associated Na+ + K+ ions was at least as high as in the external medium. This is in contrast to other moderate halophiles, which have substantially lower internal than external salt concentrations for most of their growth range. The relative amounts of Na+ and K+ in V. costicola varied with environmental conditions. The K+/Na+ ratio fell during anaerobic incubation or when cells were poisoned. As Na+ ions left the cells, K+ ions entered. However, movement of these ions was not tightly coupled, since K+ content of cells could increase without a corresponding decrease in Na+ content. The Mg2+ contents of cells varied little with environmental conditions.


Different binding sites for entry and exit of amino acids in whole cells of Mycobacterium phlei. On the basis of mutual inhibition of uptake with different amino acids in whole cells of Mycobacterium phlei, it was demonstrated that the binding site of proline was different from those of all other amino acids studied. Other groups of amino acids share a common binding site: lysine, histidine, and arginine; valine, leucine, and isoleucine; tryptophan, tyrosine, and phenylalanine; glutamic acid and aspartic acid. The exit and entry processes were studied for proline, glutamine, and glutamic acid. It was observed that in each case the entry and exit processes were mediated by different membrane sites.


Gliding motility of Mycoplasma pulmonis. The gliding movements of freshly isolated Mycoplasma pulmonis cells were observed and measured. The motile cells had a characteristic appearance, an average speed of 0.4 to 0.7 micron/s, and a maximum speed of 1 micron/s.


Hemin-dependent growth stimulation and cytochrome synthesis in Corynebacterium pyogenes. Growth of Corynebacterium pyogenes, an important pathogen in animals, was greatly increased on addition of hemin to a medium of tryptose plus mineral. The synthesis of a type b cytochrome in this organism appeared to depend on the presence of hemin in the growth medium.


Pathology of the heart in Kawasaki disease. Pathologic studies were done on 20 hearts of patients who had typical clinical signs and symptoms of Kawasaki disease. The cardiac lesions were classified according to the duration of illness at the time of death. Stage I (zero to nine days) was characterized by acute perivasculitis and vasculitis of the microvessels (arterioles, capillaries, and venules) and small arteries, and acute perivasculitis and endarteritis of the three major coronary arteries (MCAs). Pericarditis, myocarditis, inflammation of the atrioventricular conduction system, and endocarditis with valvulitis were also present. Stage II (12 to 25 days) was characterized by panvasculitis of the MCAs and aneurysm with thrombus in the stems. Myocarditis, coagulation necrosis, lesion of the conduction system, pericarditis, and endocarditis with valvulitis were also present. In stage III (28 to 31 days), granulation of the MCAs and disappearance of inflammation in the microvessels were noted. Patients in stage IV (40 days to 4 years) had scarring with severe stenosis in the MCAs. Fibrosis of the myocardium, coagulation necrosis, lesions of the conduction system, and endocardial fibroelastosis were also present. The features observed revealed Kawasaki disease to be acute and inflammatory. The angiitis begins in the microvessels and fibrinoid necrosis of the media is rare. The disease is one with a pathologic pattern previously unknown.


Craniosynostosis associated with limb reduction malformations and cleft lip/palate: a distinct syndrome. Craniosynostosis associated with short stature, radial and fibular aplasia, and cleft lip and/or palate represents a distinct syndrome. One original case and one previously undiagnosed case from the literature were found to have many distinct features in common, permitting them to be separated from craniosynostosis with radial or fibular aplasia, Robert's syndrome, pseudothalidomide or SC syndrome, and the hypomelia-hypotrichosis-facial hemangioma syndrome. Each had multiple craniofacial abnormalities: dysplastic ears, hypertelorism, strabismus, and malocclusion. Ulnae and humeri were hypoplastic; tibiae were bowed and hypoplastic. Testes were small. Associated mild to moderate mental retardation may be related to early institutionalization.


Receptive language development in preterm children as related to caregiver-child interaction. Fifty preterm children who had experienced a range of biological hazards were divided into two competence groups on the basis of their receptive language development at 24 months. The groups were then compared in terms of the kinds of caregiver-child interactions the children and their primary caregivers engaged in three months earlier in a laboratory assessment. The two language skill groups did not differ on perinatal factors such as birth weight and gestational age, or on length of hospitalization, but did differ in social transactions. The more competent group as compared to the less competent group had caregivers who were more stimulating, the children themselves emitted more vocalization, and the caregivers and children engaged in more reciprocal social transactions.


Factors leading to delay in the diagnosis and affecting survival of children with head and neck rhabdomyosarcoma. Rhabdomyosarcoma of the head and neck often presents with vague symptoms which mimic other disease conditions. These factors lead to undue delay in the establishment of the correct diagnosis and the delivery of acceptable therapy, including surgery, radiation therapy, and chemotherapy. There is, however, evidence of improved results of treatment of these tumors since the addition of multiple drug chemotherapy to surgery and radiotherapy.


Longitudinal evaluation of neonatal nosocomial infections: association of infection with a blood pressure cuff. Nosocomial infections acquired in a special care nursery were surveyed longitudinally. The rates of acquired infection were determined, allowing the evaluation of specific infection control measures. A blood pressure cuff, utilized for all infants in the nursery, was associated with an increased rate of infection.


Persistence of antibody after administration of monovalent and combined live attenuated measles, mumps, and rubella virus vaccines. Hemagglutination-inhibiting antibodies were retained in comparable levels eight years after vaccination with Enders' original Edmonston and more attenuated Moraten (Attenuvax) and Schwarz line measles vaccines. Neutralizing antibody persisted without substantial decline in titer for at least 9.5 years after administration of Jeryl Lynn mumps virus vaccine (Mumpsvax). Antibodies were retained without important decline in children and adults for at least 7.5 and 7 years, respectively, after administration of HPV-77 duck-modified rubella vaccine (Meruvax). The patterns of antibody persistence 7.5 years after administration of combined measles-mumps-rubella (M-M-R) and mumps-rubella (Biavax) vaccines, 6 years after administration of measles-rubella vaccine (M-R-VAX), and 4 years after administration of measles-mumps vaccine (M-M-VAX) were the same as for the monovalent vaccines, indicating no alteration in the retention of immunity. Subclinical reinfection evidenced by increase in homologous antibody titer was observed to follow vaccination the same as occurs after natural infection.


Idiopathic atrial flutter in infancy: a review of eight cases. The experience of three institutions in the management of atrial flutter in infants under 2 years of age without associated heart disease is reviewed. Five babies with neonatal onset were treated with digoxin and had uncomplicated resolution of their arrhythmia, although one continued to have episodes of paroxysmal supraventricular tachycardia for six years. Two of the three older infants required DC cardioversion for complications after quinidine was substituted for digoxin therapy. Digoxin continues to be the preferred initial therapy for non-acutely ill patients; those showing signs of cardiac decompensation should be converted with DC countershock.


Candida albicans meningitis in a premature neonate successfully treated with 5-fluorocytosine and amphotericin B: a case report and review of the literature. Candida albicans meningitis was diagnosed in a 45-day-old premature infant whose birth weight was 1,616 gm. Symptoms consisted of poor weight gain and poor suckling. The combined use of amphotericin B and 5-fluorocytosine (5-FC) resulted in negative CSF cultures after 12 days of therapy. Amphotericin B was given for 45 days (total 83 mg) and 5-FC for 60 days (total 19 mg). Only one other premature infant has been reported in the literature who had similar treatment. A review of Candida meningitis diagnosed before death in 11 other infants less than 1 year of age is presented.


Acetaminophen: report of an unusual poisoning. This is a report of an unusual acetaminophen poisoning in a 3-year-old girl who, three days after the ingestion of an estimated thirty-five 325-mg tablets of acetaminophen, had the highest levels of hepatic enzymes ever recorded at Duke Hospital. Although she was only moderately ill with an enlarged liver, she was discharged from the hospital on the seventh day in good condition. The liver enzyme levels returned to normal when last assessed, 50 days after ingestion. The importance of determining acetaminophen plasma concentration at different times to evaluate more precisely the plasma half-life is discussed, along with the current suggested therapy now being recommended for acetaminophen poisoning.


Myocardial necrosis following general anesthesia in hemoglobin SC disease. A 4-year-old girl with hemoglobin SC disease died following general anesthesia. Autopsy showed widespread intravascular sickling; staining with hematoxylin-basic fuchsin-picric acid demonstrated newly developed massive myocardial necrosis, a rarely documented finding. Anesthesia may produce conditions that provoke "crises" in patients with sickle hemoglobinopathies. Preoperative identification of sickle states and careful attention to hydration and oxygenation may minimize anesthetic risks in these patients.


Blood glucose and plasma amino acid concentrations in infants of diabetic mothers. Postnatal blood glucose and individual plasma free amino acid levels were measured in 14 newborn infants of diabetic mothers. All infants had a significantly lower blood glucose concentration than normal controls but no significant correlation was observed between the blood glucose values and any of the amino acids determined. As regards the quantitative and qualitative changes of the plasma aminogram, the total concentration of amino acids and the level of a few individual amino acids (glycine, alanine, taurine, and valine) were significantly elevated in full-term babies. However, no significant difference was found in the total plasma concentration of amino acids between premature infants of diabetic mothers and premature control infants, but the plasma alanine level was higher in the former. It is of interest that total plasma amino acid, alanine, and glycine levels were elevated in the asphyxiated babies. This suggests that the postnatal hyperaminoacidemia observed in infants of diabetic mothers was due to birth asphyxia rather than to impaired gluconeogenesis. The possible role of a defective gluconeogenesis in the etiology of postnatal hypoglycemia in infants of diabetic mothers is not supported by these data.


Wegener's granulomatosis in the pediatric age group. Six cases of Wegener's granulomatosis (WG) occurring in patients younger than 21 years are described. Only 11 other cases in the pediatric age group have been reported, and all 17 of these patients had the onset of the disease during the second decade of life. Wegener's granulomatosis is a systemic disease characterized by a clinical triad of paranasal sinus and nasal mucosa involvement, pulmonary infiltration and cavitation, and renal disease with hematuria. The most common presenting symptoms are malaise and fever, sinusitis, epistaxis, and hematuria. Most patients have roentgenographic evidence of pulmonary and sinus disease and laboratory evidence of renal involvement on initial evaluation. The prognosis of WG was formerly dismal; more than 90% of patients died in less than two years, but with recent therapeutic regimens, more than 50% of these patients are surviving. The treatment we recommend consists of nitrogen mustard with adrenocorticotropic hormone or prednisone for the induction of remission, followed by cyclophosphamide and prednisone as maintenance drugs. This regimen has proved effective in inducing a remission in four of four patients.


Nafcillin-induced neutropenia in children. Neutropenia developed in three pediatric patients treated intravenously with nafcillin. This association has not been, to our knowledge, previously reported in children. One of the patients is the youngest reported who had neutropenia associated with any penicillin; another patient had a prolonged recovery. The literature pertaining to marrow suppression by all penicillins is reviewed. This usually occurs 10 to 25 days after the inception of high-dose intravenous therapy and resolves when the penicillin therapy is discontinued. An absolute neutrophil count of less than 1,000/ml is an indication to change to an antibiotic other than a penicillin. Children receiving intravenous penicillins should have WBC counts with differential analysis two to three times a week.


Tetracycline photo-onycholysis.

Tetracycline photo-onycholysis. Photo-onycholysis is a rare complication of tetracycline therapy. Its occurrence is probably greater than the few reported cases indicate. It is hoped that this case report will alert physicians to its occurrence.


Comparative distribution of gentamicin, tobramycin, sisomicin, netilmicin, and amikacin in interstitial fluid in rabbits. We compared the penetration of five aminoglycosides into interstitial fluid (IF). IF was obtained in rabbits from Silastic tissue cages. Intramuscular injections were made: 1.5 mg/kg per dose for gentamicin (G), tobramycin (T), sisomicin (S), and netilmicin (N) and 7.5 mg/kg per dose for amikacin (A). Serum levels and IF concentrations were studied for 12 h after a single injection. IF levels were also compared in a six-injection study (one injection every 8 h). Peak serum levels were significantly higher with A than with G, T, S, and N, which gave similar concentrations. In IF, G gave the highest levels 1 h after the first injection. At 4 and 8 h, the concentrations achieved with G and A were similar but significantly greater than those achieved with T, S, and N. Twelve hours after a single injection, N gave higher IF levels than the other drugs except A. In the six-injection study, the IF levels of G and A reached 4.6 +/- 1.5 and 5.27 +/- 1.1 microgram/ml, respectively, at 48 h. S and N gave identical concentrations (2.07 +/- 0.25 and 2.42 +/- 0.42 microgram/ml, respectively). T induced the lowest levels (1.17 +/- 0.30 microgram/ml). Thus, in this rabbit model, the IF concentrations achieved with G and A were above the minimal inhibitory concentrations for most susceptible strains. Possible relations between IF aminoglycoside concentrations and therapeutic efficiency or toxicity are pointed out but deserve further studies.


Treatment of osteomyelitis and septic arthritis with cefazolin. Sixteen cases of severe osteomyelitis and septic arthritis caused by staphylococci, streptococci, gonococci, and a variety of gram-negative bacilli were treated with 4 to 8 g of parenteral cefazolin per day; nine received subsequent therapy with oral cephalexin or ampicillin. Of 16 infections, 15 were apparently cured. Cefazolin concentrations in those patients were: serum (peak), 25 to 216 micrograms/ml; synovial fluid, 24 to 46 micrograms/ml; and bone, 3.2 to 10.6 micrograms/g. Bacterial pathogens had minimal inhibitory concentrations of cefazolin of 2 micrograms or less per ml and seemed to be eradicated from foci of infection during therapy. One infection in a diabetic patient did not respond; despite high concentrations of cefazolin in serum, no detectable antibiotic was present in her infected metatarsal, and the infecting Escherichia coli (minimal inhibitory concentration, 16 micrograms/ml) was not eradicated during therapy. Concentrations of cefazolin in bone in 10 uninfected patients who received 1-g intramuscular doses prophylactically before surgery were also measured. Concentrations in bones from those who had normal renal function ranged from less than 0.6 to 2.8 micrograms/g.


Susceptibility of Campylobacter fetus to twenty-two antimicrobial agents. In vitro susceptibility of 11 recent clinical isolates of Campylobacter fetus to 22 antimicrobial agents was determined by an agar dilution technique. Unlike most obligate anaerobic gram-negative bacilli, C. fetus isolates tested were relatively resistant to penicillin and cephalosporins, but exquisitely susceptible to tetracyclines and aminoglycosides. All strains were also inhibited at concentrations achievable in serum by clindamycin, chloramphenicol, metronidazole, carbenicillin, ticarcillin, and with rare exceptions, ampicillin. They were variably susceptible to lincomycin and erythromycin and highly resistant to vancomycin.


In vivo susceptibility of the Legionnaires disease bacterium to ten antimicrobial agents. The susceptibility of the Legionnaires disease bacterium to various antimicrobial agents was determined by inoculation of embryonated eggs via the yolk sac. When administered prophylactically, the minimal dose of drug preventing all deaths due to the infection was as follows: rifampin, 0.02 mg; gentamicin, 0.25 mg; streptomycin, 0.39 mg; erythromycin, 0.62 mg; sulfadiazine, 1.56 mg; chloramphenicol, 2.50 mg; and cephalothin, 20.0 mg. Smaller amounts delayed deaths, and larger or equal amounts rendered the embryos free of infection. Oxytetracycline in the largest tested amount, 5.0 mg, protected 80% of the embryos from death, and as little as 0.31 mg delayed death. Chlortetracycline (0.50 mg) and ampicillin (10.0 mg) were ineffective. The six most effective drugs were studied in an experiment in which they were administered at various times after infection in doses that were twice the minimal prophylactic dose preventing all deaths. In this therapeutic experiment, rifampin, and erythromycin allowed 100% survival when given even 72 h after infection; gentamicin, streptomycin, sulfadiazine, and chloramphenicol did so when given 48 h after infection. All six drugs increased mean survival time when administered 72 h after infection.


Infections due to gentamicin-resistant Staphylococcus aureus strain in a nursery for neonatal infants. An apparently homogeneous strain of Staphylococcus aureus resistant to gentamicin (Gmr), kanamycin, tobramycin, and sisomicin, but susceptible to amikacin and netilmicin, caused multiple infections in neonatal infants in a special care nursery. Nasal cultures revealed a high rate of carriage of the Gmr staphylococcus in infants without clinical infection. Segregating patients according to a modified cohort system and use of careful aseptic techniques led to apparent elimination of the Gmr strain. The resistance to aminoglycosides in this strain was mediated by an aminoglycoside 6'-N-acetyltransferase and a gentamicin phosphotransferase. Genetic determinants for these enzymes were borne on a circular covalently closed plasmid of approximately 11 megadaltons. These resistance determinants closely resemble those found in isolates of S. aureus that have caused nosocomial infections in patients in Europe.


Interactions between Neisseria sicca and viridin B, a bacteriocin produced by Streptococcus mitis. Viridin B, a bacteriocin produced by Streptococcus mitis (mitior), is bactericidal to Neisseria sicca. Oxygen consumption by actively growing N. sicca cultures ceased immediately upon exposure to viridin B. Adenosine triphosphate production was slightly enhanced within 1 h of exposure to the bacteriocin but was subsequently repressed. The uptake and incorporation of glucose was prevented in the presence of viridin B. The bacteriocin also blocked uptake of an amino acid mixture in chloramphenicol-pretreated cells. Pretreatment or concomitant treatment with a variety of antibiotics known to inhibit specific synthetic pathways did not alter the inhibition of macromolecular synthesis produced by the bacteriocin. Although viridin B blocks protein and nucleic acid syntheses, no degradation of such macromolecules was observed. The inhibitory effects of viridin B on macromolecular synthesis and on viability required the presence of sufficient nutrients to allow active metabolism of N. sicca. The bacteriocin did not inhibit viability or macromolecular synthesis in anaerobically incubated N. sicca. Thus, active, oxidative metabolism by N. sicca cells is essential for viridin B action. A model for viridin B action is proposed.


Nephrotoxicity of netilmicin in combination with non-aminoglycoside antibiotics. To assess the possibility that non-aminoglycoside antibiotics may adversely affect the nephrotoxicity of the new semisynthetic aminoglycoside netilmicin, we gave ampicillin, carbenicillin, methicillin, cefamandole, and clindamycin, either singly or in combination with netilmicin, at two dose concentrations in rats. Results were compared as to the effect of netilmicin given singly and to saline-injected and noninjected controls. Antibiotic combinations resulted in no greater nephrotoxicity than did netilmicin alone. Netilmicin concentrations in renal tissue were high, and these levels were not consistently affected by the other drugs. The data suggest that in rats the nephrotoxicity of netilmicin is not affected adversely by the presence of non-aminoglycoside antibiotics.


Rapid determination of serum 5-fluorocytosine levels by high-performance liquid chromatography. A method for the rapid, quantitative determination of 5-fluorocytosine (5-FC) in serum by high-performance liquid chromatography (HPLC) has been developed. After initially ultrafiltrating the serum, a portion was injected onto a cation exchange column. 5-FC was separated by using an ammonium-phosphate buffer as the mobile phase and detected by ultraviolet absorption at 254 nm. Quantitation of 5-FC was based on the linear relationship between peak area in the chromatograms and known concentrations of 5-FC in a set of serum standards (prepared by adding from 10 to 200 micrograms of 5-FC to 1-ml aliquots of pooled human serum). This method was compared with the standard microbiological method for 5-FC. Advantages of the HPLC method include: Determination of 5-FC levels within 30 min; lack of interference from other antimicrobial drugs, particularly amphotericin B; more accurate determination of true 5-FC level, particularly at concentrations of less than 25 micrograms/ml or greater than 100 micrograms/ml; and ease with which the assay may be automated for routine use.


Comparative in vitro studies of nalidixic acid, oxolinic acid, and a new analog with thieno (2,3-b) pyridine structure. Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattern of the new compound was found to be very similar to that of nalidixic acid.


In vitro activity of chlorhydroxyquinoline against mycoplasma species. The in vitro activities of 5-chloro-8-hydroxyquinoline (CHQ) against single strains of 12 different species of mycoplasma and the impacts of repeated exposure of these strains to CHQ on their susceptibility to this agent have been studied. On initial exposure, the minimal inhibitory concentrations for these strains ranged from 0.24 to 1.92 micrograms of CHQ per ml of test medium; activities remained unchanged during 10 serial transfers in CHQ-containing medium.


Interference of granulocyte function by the vehicle of miconazole. The vehicle of miconazole inhibited adherence and leukotaxis, but did not affect nitroblue tetrazolium reduction and trypan blue exclusion by granulocytes at 0.33% concentration and above.


Aminoglycoside antibiotics moderately impair granulocyte function. By in vitro methods, five aminoglycoside antibiotics (amikacin, kanamycin, gentamicin, tobramycin, and netilmicin) were shown to produce modest changes in granulocyte adherence (increase) and migration (decrease) and no change in phagocytosis or nitroblue tetrazolium reduction.


The ocular manifestations of juvenile rheumatoid arthritis. We followed 210 cases of JRA closely for 14 years. Thirty-six patients (17.2%) developed iridocyclitis; it most frequently occurred in young females (0-4 years) with monarticular or pauciarticular form of the disease. In 30% of the patients iridocyclitis was first detected after 16 years of age. Forty-two percent had active iridocyclitis on entry. By combining quantitative antinuclear antibody titers with age, sex, and time on onset of arthritis, it has been possible to define the risk of developing iridocyclitis in individual patients. Our approach was effective in detecting iridocyclitis in new cases and exacerbations of the disease in established cases. Forty-four percent of patients with iridocyclitis had one or more identifiable early signs or symptoms. Iridocyclitis in 36% of patients did not respond to more than 6 months of intensive topical treatment with corticosteroids and mydriatics. Despite this statistic, patients had a better outcome than those experiencing the 50% incidence of blinding complications cited in earlier studies. Cataract and band keratopathy occurred in only 19% and 11% of our group, respectively. Only one case of chorioretinopathy was found in 173 patients who had received antimalarials; a significant number of posterior subcapsular cataracts were found in 75 patients who had received systemic corticosteroids. Keratoconjunctivitis sicca developed in 3 patients with iridocyclitis. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.


Pathologic aspects of juvenile chronic polyarthritis. The pathological changes in juvenile chronic polyarthritis are similar to those of adult chronic polyarthritis, although perhaps rather more variable, according to the severity and the phase of the disease. The differences that are seen depend on age, developmental stage, growth, and perhaps a greater regenerative capacity. The nodules of seronegative diseases resemble those of rheumatic fever and are not seen in adult onset seropositive rheumatoid arthritis. In addition, ankylosis of the cervical spine is a characteristic feature seen also in adult onset Still's disease.


Prognosis of juvenile rheumatoid arthritis. The true prognosis of JRA is unknown. The best interpretation of reports to this date may be that at any given time of examination between 5 and 15 years after onset, 30-50% of children will have grossly active disease and that 70-90% of patients will be in class I-II functional status. Published studies, however, are not comparable because of differing criteria and selection of support data to be reported. Close analysis of four cases of JRA illustrate some of the difficulties in utilizing loosely defined criteria. A preliminary plan for improving the precision of reporting course and prognosis of JRA has been outlined.


The clinical spectrum of systemic lupus erythematosus in childhood. The onset and course of 108 children with systemic lupus erythematosus have been analysed. There were more black patients than one would expect from hospital population statistics. There was a greater preponderance of boys with onset of the disease at less than 12 years of age and there is a large number of familial cases. Major signs and symptoms differed from those observed in adults only in the greater degree of reticuloendothelial involvement and in a possibly greater propensity for children to change renal biopsy category. Diffuse proliferative renal lesions remain a major contributor to death both in children and in adults, but the importance of the extrarenal mortality factors plus the greater proportion of male deaths is emphasized.


Dermatomyositis in the pediatric patient. Forty-one children with dermatomyositis who were treated with corticosteroids and who have been followed over a period of 15 years have been presented. Progressive proximal muscle weakness was seen in all and 60% had muscle pain. The skin rash considered classic for dermatomyositis was seen in 33 children at the time of diagnosis. Elevation of serum muscle enzymes, electromyographic abnormalities, and muscle biopsy evidence of acute myositis were of confirmatory diagnostic value. The course of the disease in this study group has reconfirmed the efficacy of adrenal corticosteroid treatment in conjunction with an individualized physical therapy program and consistent followup. Prognosis for life and minimal functional disability has been good. There have been 3 deaths recorded in this series, only one of which was certain in its relationship to dermatomyositis.


Scleroderma in children.

Scleroderma in children. Fifteen children with scleroderma have been presented. All had characteristic cutaneous abnormalities at onset and during the course of disease. All were girls. All had visceral involvement, primarily of the gastrointestinal tract, heart, and lungs. The presence of visceral disease might have been missed without specific and extensive diagnostic procedures, including gastrointestinal barium studies, esophageal motility, pulmonary function and carbon monoxide diffusing capacity, and plethysmography. Raynaud's phenomenon was frequent and accompanied by evidence of occlusive vascular disease. Contractures around joints were readily evident and arthralgias were common, but evidence of objective arthritis was absent. Sixty percent of the patients in this series had ANA. Overlap syndromes with myositis and SLE were present in 7 patients. Three of 15 children died 6-10 years after onset of disease.


Mixed connective tissue disease in children. Seven girls and 3 boys with MCTD have been described. As a group their clinical characteristics and serological findings are similar to those reported in adults, with several important differences. Children with MCTD may have marked thrombocytopenia and more frequently they have RF. Significant cardiac and renal involvement are more common in children, may lead to longer and higher dose corticosteroid therapy, and may contribute to a less optimistic prognosis than that described in adults.


The changing picture of rheumatic fever. Rheumatic fever has decreased in frequency and severity, but the disease has not been eradicated in this country, especially in low socioeconomic populations. Carditis is less common, and changes in the frequency of other rheumatic manifestations such as chorea has made the clinical diagnosis more difficult. Streptococcal antibody tests are still the most useful laboratory aid, but care must be taken against overinterpretation. The search for the answer to the pathogenesis puzzle continues. Until the nature of the disease is better understood, it is unlikely that rheumatic fever will be eradicated. In the meantime, however, the incidence of the disease can be reduced further by improved medical care for deprived populations.


Ankylosing spondylitis of childhood onset. Ankylosing spondylitis begins in childhood in a significant number of patients. The disease may begin in one of two ways: with early hip girdle and low back complaints, or with peripheral arthritis affecting a few large joints. Ankylosing spondylitis should be suspected in seronegative boys over the age of 8 years who have pauciarticular arthritis, particularly if there is associated hip girdle involvement. Early recognition of ankylosing spondylitis may be helpful in appropriate therapy and followup of patients.


Reiter's syndrome in childhood.

Reiter's syndrome in childhood. Seven boys with Reiter's syndrome are described. Three had diarrhea and 2 had venereal contact as antecedent events. All developed the complete triad of symptoms in a 5- to 24-day period. Joint involvement of the lower extremities was seen in each boy. HLA-B27 typing was positive in 6 of 7 (86%). Serum and synovial fluid levels of CH50 and C3 were elevated in 5 boys and confirm similar findings in adults. Two boys recovered spontaneously without therapy and 3 boys received aspirin with a rapid and complete resolution of symptoms. The two oldest boys had the most severe joint involvement and were receiving phenylbutazone with continuing active arthritis when they were lost to followup. Reiter's syndrome in children may be infrequently reported because its antecedents and the triad symptoms are common occurrences in pediatric practice.


Nonsteroidal antiinflammatory agents.

Nonsteroidal antiinflammatory agents. The nonsteroidal antiinflammatory agents do offer encouraging alternatives to presently used medications. The ultimate role of the agents will have to be established by usage and systematic study by such groups as the Pediatric Rheumatology Collaborative Study Group.


Corticosteroids in juvenile rheumatoid arthritis. Corticosteroids, although potent suppressors of symptoms and signs of disease, are not effective in curing rheumatoid arthritis in adults or children. Prolonged use of corticosteroids is attended with multiple serious side effects. In JRA, the outlook for most children is good; potentially dangerous drugs should be avoided if at all possible. The indications for corticosteroid usage in JRA might be summarized as: Severe systemic disease unresponsive to salicylates Chronic iridocyclitis unresponsive to topical steroids. Only very rarely for severe arthritis per se; and then with the realization that, although symptoms are being suppressed, the natural history of the disease may not be greatly affected.


Postmortem pink teeth.

Postmortem pink teeth. A series of cases is reported in which pink teeth were observed during the postmortem period. Most cases were associated with decomposition in a moist environment. Experimental procedures led to the extraction of pink material from dentin and demonstration that hemoglobin and serum proteins were present. The pink-tooth phenomenon was duplicated in human teeth by instilling into the pulp chambers whole blood and blood with the red cells hemolyzed. The change was manifested in teeth of dogs after freezing, heating, and decomposition in a moist environment. The authors postulate that pink teeth occur as a result of breakdown of red blood cells in the pulp chamber of the tooth and diffusion of hemoglobin and other serum proteins into the dentin via the dential tubules. Histochemical studies show that the brown or gray material in some teeth subjected to postmortem aging is probably hemoglobin and serum proteins. Factors of age, vascularity of the pulp chamber, and postmortem conditions are discussed in relation to the postmortem development of pink teeth.


Rifle wounds from high velocity, center-fire hunting ammunition. Wounds inflicted by high velocity, center-fire rifles firing hunting ammunition are radically different from wounds caused by handguns or .22 rim-fire rifles. Injuries from pistol or .22 rim-fire bullets are confined to tissue and organs directly in the wound track. In contrast, high velocity rifle bullets can injure structures without actually contacting them. This is due to the temporary cavity produced by such missiles with the resultant shock waves having pressures of up to 200 atmospheres (20 MPa). Organs struck by such high velocity rifle bullets may undergo partial or complete disintegration. Hunting ammunition, as it passes through the body, tends to shed fragments of lead from its core, producing a characteristic snowstorm picture on X-ray. The maximum range at which powder tattooing of the skin occurs from center-fire rifles depends on the physical form of smokeless powder used as propellant. In a test with a 30-30 rifle, cartridges loaded with ball powder produced powder tattooing out to a range of 30 in. (76 cm), while similar cartridges, loaded with the traditional cylindrical powder, produced tattooing out to only 12 in. (30 cm) of range.


Sudden and unexpected deaths after the acute onset of diabetes mellitus. Four cases of sudden and unexpected death caused by the acute onset of diabetes mellitus are reported. Three are examples of acute juvenile diabetes while the fourth demonstrated the aketotic form of diabetic coma. Such instances can present a diagnostic problem to the forensic pathologist. The usefulness of vitreous humor glucose analysis to diagnose such a condition is stressed.


Determination of the age of bloodstains using immunoelectrophoresis. The technique of immunoelectrophoresis was used to determine the age of bloodstains. The immunoelectrophoretic patterns (IEP) of bloodstains ranging from 15 days to one year old were obtained by the use of high titer anti-whole human serum. The IEPs revealed gradual disappearance of beta-globulins and gamma-globulin with increase in the age of bloodstains. A comparative study of the IEP of normal human serum with those of the experimental bloodstains showed the absence of some of the corresponding proteins. The absence of a particular serum protein in the IEP of a given bloodstain will indicate the age of that bloodstain.


Occurrence of myocarditis in sudden death in children. This study suggests that the prevalence of "silent" myocarditis may be higher in the pediatric population than is generally suspected and may contribute to a significant number of sudden and unexpected deaths in children, particularly those older than one year of age. The incidence of histologic myocarditis in children dying a violent death is similar to that reported as an incidental finding in adults.


Subjective responses and excretion patterns of dextroamphetamine after the administration of therapeutic doses. Twelve male medical and graduate students received dextroamphetamine sulfate in doses of 0, 5, 10, and 15 mg/70 kg body weight. The study was conducted in a double-blind manner, and treatments were assigned according to randomized, complete block design. The drug was given orally and subjects were instructed not to eat 3 1/2 h prior to administration. After administration, total urine output was collected for 12 h; no attempt was made to control urinary pH to more realistically approach the general clinical usage of amphetamines. The urine was pooled into two 6-h segments and analyzed for amphetamine concentration. Subjective impressions of the treatments were also evaluated by means of the Cornell Medical Index Questionnaire. Results showed that approximately 30% of the total dose was excreted unchanged within 12 h after administration. The amount excreted agreed very closely with the doses given and paralleled the scores for subjective impressions by the subjects. None of the subjects felt that their driving would be impaired for any of the doses administered. This study indicates that under ordinary conditions (in which pH is not artificially controlled), therapeutic doses of dextroamphetamine can be detected in urine for up to 12 h after oral administration.


Metabolite sensitivity in the methaqualone radioimmunoassay. Recent literature reflects the increased use of RIA as a qualitative and quantitative tool. This study exemplifies the problems that may arise when this technique is used for quantitation. Caution must be exercised, and a physiological and toxicological understanding of each particular drug is essential to provide credible results. It is evident that the sensitivity and ease of the RIA method for methaqualone makes it invaluable as a screening test, but confirmation and quantitation of this drug must remain with those methods that can quantitate each metabolite.