Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization: experiments in sodium-free bathing media.

Voltage clamp hyperpolarization and depolarization result in currents consistent with depletion and accumulation of potassium in the extracellular clefts o cardiac Purkinje fibers exposed to sodium-free solutions. Upon hyperpolarization, an inward current that decreased with time (id) was observed. The time course of tail currents could not be explained by a conductance exhibiting voltage-dependent kinetics. The effect of exposure to cesium, changes in bathing media potassium concentration and osmolarity, and the behavior of membrane potential after hyperpolarizing pulses are all consistent with depletion of potassium upon hyperpolarization. A declining outward current was observed upon depolarization. Increasing the bathing media potassium concentration reduced the magnitude of this current. After voltage clamp depolarizations, membrane potential transiently became more positive. These findings suggest that accumulation of potassium occurs upon depolarization. The results indicate that changes in ionic driving force may be easily and rapidly induced. Consequently, conclusions based on the assumption that driving force remains constant during the course of a voltage step may be in error.


Pig reticulocytes. III. Glucose permeability in naturally occurring reticulocytes and red cells from newborn piglets.

The loss of facilitated glucose transport of red cells occurring in the newborn pig was monitored in 11 density-separated cells from birth to a 4 wk of age. At birth there was a threefold increase in glucose permeability from the lightest cells to the most dense, suggesting that cells having progressively less glucose permeability are released into the circulation as gestation proceeds. Because of extraordinary stimulation of erythropoietic activity, the uppermost top fraction constituting 2-3 percent of the total cells is composed purely of reticulocytes in the growing animal. The glucose permeability of these reticulocytes which at birth has a slow but significant rate of 3.7 mumol/ml cell x min at 25 degrees C is rapidly decreased within 3-4 days to the level of reticulocytes produced in the adult in response to phenylhydrazine assault. Moreover, reticulocytes themselves discard their membrane permeability to glucose in the course of maturation to red cells. Thus, even though reticulocytes at birth are permeable to glucose, they will become red cells practically impervious to glucose within a few days. These findings suggest that the transition from a glucose- permeable fetal state to a glucose-impermeable postnatal state is brought about by two mechanisms: (a) dilution of fetal cells by glucose-impervious cells produced coincidentally with or shortly after birth; and (b) elimination of fetal cells, which have a shorter half-life, from the circulation.


Rates and equilibria at the acetylcholine receptor of Electrophorus electroplaques: a study of neurally evoked postsynaptic currents and of voltage-jump relaxations.

Kinetic measurements are employed to reconstruct the steady-state activation of acetylcholine [Ach] receptor channels in electrophorus electroplaques. Neurally evoked postsynaptic currents (PSCs) decay exponentially; at 15 degrees C the rate constant, alpha, equals 1.2 ms(-1) at 0 mV and decreases e-fold for every 86 mV as the membrane voltage is made more negative. Voltage-jump relaxations have been measured with bath-applied ACh, decamethonium, carbachol, or suberylcholine. We interpret the reciprocal relaxation time 1/tau as the sum of the rate constant alpha for channel closing and a first-order rate constant for channel opening. Where measureable, the opening rate increases linearly with [agonist] and does not vary with voltage. The voltage sensitivity of small steady-state conductances (e- fold for 86 mV) equals that of the closing rate alpha, confirming that the opening rate has little or no additional voltage sensitivity. Exposure to alpha-bungarotoxin irreversibly decreases the agonist-induced conductance but does not affect the relaxation kinetics. Tubocurarine reversibly reduces both the conductance and the opening rate. In the simultaneous presence of two agonist species, voltage-jump relaxations have at least two exponential components. The data are fit by a model in which (a) the channel opens as the receptor binds the second in a sequence of two agonist molecules, with a forward rate constant to 10(7) to 2x10(8) M(-1)s(-1); and (b) the channel then closes as either agonist molecule dissociates, with a voltage-dependent rate constant of 10(2) to 3x10(3)s(-1).


Kinetics of Na+ transport in Necturus proximal tubule.

The dependence of proximal tubular sodium and fluid readsorption on the Na(+) concentration of the luminal and peritubular fluid was studied in the perfused necturus kidney. Fluid droplets, separated by oil from the tubular contents and identical in composition to the vascular perfusate, were introduced into proximal tubules, reaspirated, and analyzed for Na(+) and [(14)C]mannitol. In addition, fluid transport was measured in short-circuited fluid samples by observing the rate of change in length of the split droplets in the tubular lumen. Both reabsorptive fluid and calculated Na fluxes were simple, storable functions of the perfusate Na(+) concentration (K(m) = 35-39 mM/liter, V(max) = 1.37 control value). Intracellular Na(+), determined by tissue analysis, and open-circuit transepithelial electrical potential differences were also saturable functions of extracellular Na(+). In contrast, net reabsorptive fluid and Na(+) fluxes were linearly dependent on intracellular Na(+) and showed no saturation, even at sharply elevated cellular sodium concentrations. These concentrations were achieved by addition of amphotericin B to the luminal perfusate, a maneuver which increased the rate of Na(+) entry into the tubule cells and caused a proportionate rise in net Na(+) flux. It is concluded that active peritubular sodium transport in proximal tubule cells of necturus is normally unsaturated and remains so even after amphotericin-induced enhancement of luminal Na(+) entry. Transepithelial movement of NaCl may be described by a model with a saturable luminal entry step of Na(+) or NaCl into the cell and a second, unsaturated active transport step of Na(+) across the peritubular cell boundary.


The control of ionized calcium in squid axons.

Measurements of the Ca content, [Ca](T), of freshly isolated squid axons show a value of 60 mumol/kg axoplasm. Axons in 3 mM Ca(Na) seawater show little change in Ca content over 4 h, while axons in 3 mM Ca(Na) seawater show little change in Ca content over 4 h, while axons in 10 mM Ca(Na) seawater show gains of 18 mumol/Ca/kgxh. In 10 Ca (Choline) seawater the gain is 2,400 mumol/kgxh. Using aequorin confined to a dialysis capillary in the center of an axon, one finds that [Ca](i) is in a steady state with 3 Ca (Na) seawater, and that both 10 Ca (Na) and 3 Ca (choline) seawater cause increases in [Ca](i). In 3 Ca (Na) seawater-3 Ca (choline) seawater mixtures, 180 mM [Na](0) (40 perecent Na) is as effective as 450 mM [Na](0) (100 percent Na) in maintaining a normal [Ca](1); lower [Na] causes an increase in [Ca](i). If axons are injected with the ATP-splitting enzyme apyrase, the resulting [Ca](1) is not loading with high [Ca](0) or low [Na](0) solutions. Depolarization of an axon with 100 mM K (Na) seawater leads to an increase in the steady-state level of [Ca](1) that is reversed upon returning the axon to normal seawater. Freshly isolated axons treated with either CN or FCCP to inhibit mitochondrial Ca buffering can still maintain a normal [Ca](i) in 1 Ca (Na) seawater.


Intracellular calcium buffering capacity in isolated squid axons.

Changes in ionized calcium were studied in axons isolated from living squid by measuring absorbance of the Ca binding dye Arsenazo III using multiwavelength differential absorption spectroscopy. Absorption changes measured in situ were calibrated in vitro with media of ionic composition similar to axoplasm containing CaEGTA buffers. Calcium loads of 50-2,500 mumol/kg axoplasm were induced by microinjection, by stimulation in 112 mM Ca seawater, or by soaking in choline saline with 1-10 mM Ca. Over this range of calcium loading of intact axoplasm, the ionized calcium in the axoplasm rose about 0.6 nM/muM load. Similar loading in axons preteated with carbonyl cyanide 4- trifluoromethoxyphenylhydrazone (FCCP) to inhibit the mitochondrial proton gradient increased ionized calcium by 5-7 percent of the imposed load, i.e. 93-95 percent of the calcium load was buffered by a process insensitive to FCCP. This FCCP- insensitive buffer system was not saturated by the largest calcium loads imposed, indicating a capacity of at least several millimolar. Treatment of previously loaded axons with FCCP or apyrase plus cyanide produced rises in ionized calcium which could be correlated with the extent of the load. Analysis of results indicated that, whereas only 6 percent of the endogenous calcium in fresh axons is stored in the FCCP-sensitive (presumably mitochondrial) buffer system, about 30 percent of an imposed exogenous load in the range of 50-2,500 muM is taken up by this system.


Distribution of menaquinones in actinomycetes and corynebacteria.

Menaquinones were the only isoprenoid quinones found in 48 corynebacteria and actinomycete strains examined. Dihydromenaquinones having nine isoprene units were the main components isolated from Gordona, Mycobacterium, Corynebacterium bovis, Corynebacterium glutamicum and a strain labelled Nocardia farcinica, but dihydromenaquinones having eight isoprene units were characteristic of other Corynebacterium species and representatives of the 'rhodochrous' complex. Tetrahydromenaquinones having six and eight isoprene units were found in Nocardia strains and in a single strain of Micropolyspora brevicatena, which also contained mycolic acids similar in chain length to those of Nocardia. Menaquinones having nine isoprene units with from one to five double bonds hydrogenated were the main components in Actinomadura madurae, Actinomadura pelletieri, Micropolyspora faeni, Oerskovia turbata and Streptomyces strains. Actinomadura dassonvillei strains had a characteristic pattern of di-, tetra- and hexahydromenaquinones with 10 isoprene units which was slightly different from the pattern in mixtures of similar quinones from Actinomyces israelii and Actinomyces viscosus.


Immunochemistry of extracts from Leptospira interrogans serotype hardjo.

Antigens from Leptospira interrogans serotype hardjo grown in modified Korthof's medium were obtained by ethanol and alkaline extraction procedures and their chemical and serological properties were compared. The protein to polysaccharide ratio in the ethanol extract was 1:1-8 and in the alkali extract was 1-7:1. The lipid content of the latter was twice that of the former (8-5%, w/w). There was an inverse relationship of the protein and carbohydrate contents of the two preparations, the total reducing sugar being higher in the ethanol extract whereas protein was higher in the alkali extract. Both preparations contained arabinose, rhamnose, fucose, xylose, mannose, galactose, glucose and galacturonic acid but in different amounts. No muramic acid or 2-keto-3-deoxyoctonate was detected. Both extracts contained erythrocyte sensitizing substances which, in the passive haemagglutination absorption test, appeared to be closely related antigenically but not identical. In the electron microscope, thin sections of the ethanol extract showed trilaminar outer envelope-like material.


Subcellular fractionation by differential and zonal centrifugation of the trypanosomatid Crithidia fasciculata.

Homogenates of Crithidia fasciculata were fractionated by differential centrifugation. Mitochondria were sedimented quantitatively at 10(4) g-min and accounted for approximately 10% of the total recovered protein. Catalase was found exclusively in the supernatant fraction whilst NADH:cytochrome c oxidoreductase and p-nitrophenylphosphatase were found in all the fractions. Zonal centrifugation confirmed that catalase was non-sedimentable. Clean separation of mitochondria was obtained in both high-speed and rate zonal experiments, but no NADH:cytochrome c oxidoreductase activity could be detected in these organelles. Separation of large lysosomal vacuoles which contained p-nitrophenylphosphatase activity was obtained and these were clearly resolved from mitochondria by both high-speed and rate zonal centrifugation.


A factor involved in chloramphenicol resistance in Streptomyces coelicolor A3(2): its transfer in the absence of the fertility factor.

An element controlling chloramphenicol resistance (chl) was detected in Streptomyces coelicolor A3(2). Strains sensitive to 1 microgram chloramphenicol ml-1 were obtained among dark scarlet variants. Transfer of the resistance factor was attempted in matings between chloramphenicol-resistant (Chl+) and chloramphenicol-sensitive (Chl-) strains, both of which lacked the SCP1 fertility factor. Transfer of chl was obtained at a much higher rate than that expected for chromosomal markers in SCP1- X SCP1- matings. However, in these particular crosses the latter was also several times higher than usual. All recombinants for chromosomal markers were Chl+. Attempts to locate the chl element failed to distinguish between a chromosomal and an extrachromosomal site. The observed increase in the recombination frequency for chromosomal markers suggests that the chl element may promote recombination.


Differences in efficiency of protective effect caused by high ambient temperature in mice infected with diverse substrains of rabies virus.

We have shown previously that a non-fatal outcome of infection with street rabies virus occurs more often when mice are exposed to a high ambient temperature (HAT = 35 degrees C) early in the course of the infection. To determine what influence the virus strain had on this protective effect of HAT, we have extended these observations to studies of a fixed rabies strain, CVS and several substrains of CVS virus derived from temperature-sensitive (ts) mutants. In all cases, mortality was reduced to some extent by exposure of the animals to HAT; however, dramatic strain-specific differences in the extent of the effect were noted. Although each of the virus substrains tested was revertant in the ts character (as tested in vitro using a non-permissive temperature of 40-5 degrees C), several substrains (ts 1, ts 4, RT51) caused disease that was sensitive (greater than 90% reduction in mortality) to HAT. Mortality induced by the parental CVS virus was reduced approx. 50% at HAT. A single CVS virus substrain, VSW89, caused disease that wal less affected by HAT than was disease induced by the parental strain. As in previous studies with street virus, the incubation periods for infection with CVS virus substrains were consistently prolonged at HAT.


The mechanism of the inactivation of human fibroblast interferon by mechanical stress.

Interferon derived from human fibroblasts is readily inactivated during agitation and filtration. This inactivation has been shown to be largely a product of mechanical stress, and has been studied in detail by subjecting interferon to controlled shear stress using a rotational viscometer. The possible mechanism of this phenomenon is discussed.


Reagents which inhibit disulphide bond formation stabilize human fibroblast interferon.

Fibroblast interferon may be stabilized against many inactivating influences by the addition of certain simple sulphydryl reagents. The use of such easily removable and relatively non-toxic stabilizers should help in the preparation and purification of fibroblast interferon for clinical use.


Telepathy in mental illness: deluge or delusion?

The belief that one can read others' minds has long been considered a symptom of psychosis, despite reports in the parapsychological literature of veridical telepathy. All patients admitted to an inpatient psychiatric unit were screened for paranormal beliefs, and those claiming telepathic abilities were tested in a free-response ESP task. Eighteen per cent of the inpatient population claimed telepathic abilities; of the nine patients who completed the task, none performed above chance expectations. Higher frequencies of paranormal experiences than those reported previously in the psychiatric literature were attributed to the context of the study. Schneider's first rank symptoms and a belief in telepathy discriminated schizophrenics more reliably than other paranormal experiences. Possible psychodynamics of delusions of telepathy were discussed in view of the predominance of women and younger men reporting them, as were the possible effects of such research on patients' delusions.


Depressive disorders and religious conversions.

The sparse psychiatric literature concerning religious conversions is reviewed. Four case histories of diagnosed depressive illness followed by religious conversion are presented. In two obsessive-compulsive patients, the religious experience failed to resolve the depression, and both ended in suicide. Two hysterical personalities had a resolution of depressive symptoms following the religious experience. The authors suggest that religious conversion dynamically strengthens repression in hysterical persons, but in some cases fails to resolve obsessive isolation of affect and ambivalence.


Excitatory effects of cholinergic, adrenergic and glutaminergic agonists on a buccal muscle of Aplysia.

The anterior extrinsic protractors in the buccal mass of Aplysia are symmetrical sheets of branching bundles of muscle fibers which form an electrical syncytium. The addition of potassium or cholinergic, adrenergic, and glutaminergic agonists to the sea water bathing medium produces contracture of the muscle. Strychnine and cholinergic or adrenergic antagonists all block contractures produced by cholinergic and adrenergic agonists but not those produced by potassium or glutamate. Iontophoretic application through microelectrodes of acetylcholine or dopamine anywhere on the muscle surface produced a graded depolarization of the membrane. By contrast, glutamate produces depolarization only at discrete membrane sites. Endogeneous contractions often appeared spontaneously or could be induced by drug exposure. ATP inhibits endogeneous contractions.


Effects of methylazoxymethanol given at different stages of postnatal life on development of the rat brain. Comparison with those of thyroid deficiency.

Newborn rats were treated at different stages of their development with low doses of methylazoxymethanol acetate. The postnatal increase of the DNA content of the cerebrum did not differ from that of controls. In the cerebellum, the DNA content was transitorily reduced, but later, the external granular layer became thicker and DNA deposition increased in comparison with controls; finally, the cerebellar DNA returned to a normal value. Morphological abnormalities of the cerebellum, abnormal orientation of migrating cells, scattering of Purkinje cell bodies within the internal granule cells and specially striking abnormalities of the morphology and orientation of Purkinje cell dendrites were noted in rats treated with MAM from birth to day 3. The effects of the Purkinje cell morphogenesis persisted but were much less marked when MAM was given from 4 to 7 or from 8 to 11 days. Neonatal thyroid deficiency, as MAM-treatment between days 0 and 3, leads to an abnormal position of Purkinje cell bodies within the cerebellar cortex; it also leads to morphological abnormalities of their dendritic arborization which closely resemble those observed after MAM-treatment during the second postnatal week. It also alters the cell formation in the cerebellum. Thyroid deficiency probably exerts its effect on cell formation earlier than previous biochemical studied have shown. On another hand, the morphological abnormalities of Purkinje cell arborizations in the thyroid-deficient animals may be partly due to the perturbations of cell formation which persist later in the cerebellum.


Spreading depression elicited by thermal effects of ultrasonic irradiation of cerebral cortex in rats.

Cortical spreading depression (CSD) was elicited by focused ultrasonic irradiation (800 kHz) of exposed cerebral cortex in anesthetized rats. With the acoustic output of 0.64 W at the probe-tissue contact (3 mm in diameter), CSD was elicited after 28-sec irradiation in normothermic rats. Reduction of cortical temperature to 31 degrees C increased the threshold irradiation time to 82 sec on the average. Ten- to thirty-sec heating of cerebral cortex with a thermode elicited CSD when surface temperature exceeded 47 degrees C. Histological examination of the cortical areas exposed to threshold irradiation revealed a central coagulation lesion surrounded by edema. It is concluded that the ultrasonic irradiation elicits CSD by dissipated heat. Differences in threshold duration of irradiation in hypothermic and normothermic rats were used to compute the threshold temperature which had to be exceeded in the critical volume of cortex in order to start CSD.


Monosynaptic reflexes in falling man.

We have examined peripheral proprioceptive input during fall in man. The first 80 ms of unexpected free fall, both in a parachute harness and while seated, has been studied using the monosynaptic Hoffman (H) and Achilles tendon (T) reflexes. Facilitation of the H reflex begins about 30 to 40 ms after release, representing the onset of motor neurone facilitation before the electromyographic activity which begins about 80 ms after release. Earlier facilitation of the T reflex may represent spindle excitation due to change in muscle shape as suggested by Matthews and Whiteside (1960), but the T reflex inhibition described by these authors after 50 ms of seated fall is probably a purely mechanical phenomenon.


Preservation of a certain motoneurone group of the sacral cord in amyotrophic lateral sclerosis: its clinical significance.

Histopathological description of a special nerve cell group of the sacral spinal cord in five cases of amyotrophic lateral sclerosis is presented. Remarkable preservation of this group of neurones (the X group of Onuf) was noted in each case, and this is discussed with particular reference to vesicorectal function, since it is well known that the function of bladder and rectal sphincters is often intact until the latest stage of the illness.


Hemispheric disconnection syndrome with a "crossed avoiding" reaction in a case of Marchiafava-Bignami disease.

A clinicopathological study is presented of a case of Marchiafava-Bignami disease with a hemispheric disconnection syndrome, an association that does not appear to have been reported previously. Gross and microscopic examination of the brain revealed necrosis of the corpus callosum (sparing a small area in front of the splenium) and of the anterior commissure, cortical and subcortical infarction of the right lingual gyrus, diffuse cortical lesions of the laminar sclerosis type, and lacunae in the basal ganglia and the pons. The patient was unable to grasp objects presented to the right visual half-field with the left hand, or to respond to contralateral somaesthetic stimuli with either of the upper limbs. This motor inhibition, with the associated extended posture, is described as a "crossed avoiding reaction", and attributed to the inability of one hemisphere to respond to visual or somaesthetic stimuli projected to the other hemisphere. Clinicopathological correlations and visuomotor coordination mechanisms are discussed in the light of previous clinical and experimental studies. Anomia to pictures projected tachistoscopically to the left visual field, disturbances in the transfer of somaesthetic information, left sided ideomotor apraxia with agraphia, right sided dyscopia, and ideational apraxia especially marked in the right visual field were observed.


Topographical amnesia.

The ability to learn to criterion a visually-guided stylus maze was found impaired in patients with right posterior cerebral damage, not only in comparison with controls but also with other hemisphere-damaged groups. The contribution of the corresponding left sided area to this task is dubious, and certainly not substantial. This finding points to the independent organisation of long-term spatial memory in the right posterior cerebral cortex, an inference that was further supported by the study of two cases. The first was a female patient with right temporo-parietal softening (as suggested by clinical, EEG, and brain scan data) who showed topographical amnesia and inability to learn the visual maze over 275 trials. On an extensive battery of tests she was found free from disorders of space perception, and from verbal and visual memory impairment. The second was a patient presenting with severe global amnesia who, nevertheless, had no difficulty in route finding, and reached the criterion on the maze in 31 trials.


Occult lumbar spinal stenosis.

Twenty-eight patients presenting with low back pain, associated with sciatic or femoral neuropathy, were found to have lateral recess stenosis occurring as a result of hypertrophy of the facet joints, with preservation within normal limits of the sagittal AP diameter of the lumbar canal. Pathology was believed to be traumatic in origin, and the variable nature of the adhesions suggested recurrent inflammation; the hypertrophy of the facet joints may have been the result of traumatic inflammatory hyperaemia. Radiological investigations were unhelpful. The diagnosis of the condition was made at the time of surgical exploration by the findings of alteration of the facet joints, adhesions and fixity of the nerve roots, normal sagittal AP diameter of the canal, and absence of other significant lesions. Gratifying results were obtained with decompression by wide laminectomy with excision of overhanging facet joints and release of adhesions.


Carpal tunnel syndrome related to antebrachial Cimino-Brescia fistula.

Two patients are described in whom symptoms of the carpal tunnel syndrome were provoked by haemodialysis for which an antebrachial arteriovenous fistula had been established. The symptoms in one case were partially relieved by ligation of the radial artery distal to the fistula, and in both they were abolished by decompression of the median nerve by section of the flexor retinaculum at the wrist. There is evidence that the median nerve is abnormally susceptible to ischaemia in the carpal tunnel syndrome, and it is suggested that in these patients the symptoms were provoked by a vascular steal mechanism related to the fistula.


Suprasellar neoplasm with a granular cell component.

A classification of granular cell lesions of neuropathologic interest is presented along with an unique case in which a suprasellar neoplasm having light and electron microscopic features of a meningioma contained multifocal nests of granular cells which apparently persisted in this tumor over a period of nearly five years. A spectrum of cell differentiation suggested the development of granular cells from small, electron-dense mesenchymal elements having numerous mitochondria. No evidence for a Schwann cell origin was found. It is proposed that the pituitary-hypothalamic axis, where intracranial granular cell nests and granular cell tumors are most common may also give origin to rare mixed neoplasms with a granular cell component.


The nodes of Ranvier in the nerves of mice with muscular dystrophy.

Light microscopic, and scanning and transmission electron microscopic studies of the nodes of Ranvier of the distal peripheral nerves of mice with muscular dystrophy (dy/dy) are reported. Extensive widening of the nodes, retraction of Schwann cell cytoplasm and myelin, paranodal thinning of the myelin sheaths, and loss of nodal gap substance were observed. There was no loss of myelinated fibers. The changes at the nodes of Ranvier probably explain the slowed maximum conduction velocity observed in dystrophic peripheral nerves.


Fine structure of the afferent synapse of the hair cells in the saccular macula of the goldfish, with special reference to the anastomosing tubules.

The fine structure of the afferent synapse has been studied in the hair cells of the goldfish saccular macula. A spherical dense body which is surrounded by synaptic vesicles is observed in association with the presynaptic membrane. An alternating, parallel arrangement of dense bars and of rows of synaptic vesicles is observed on the presynaptic membrane beneath the dense body. Each row consists of five to six immediately available synaptic vesicles, and five to six such rows of vesicles are observed per synapse. Sometimes anastomosing tubules are found around the dense body. The tubules are formed by direct infolding of the plasma membrane. Many coated vesicles are found at the periphery of the anastomosing tubules. A possible role of the anastomosing tubules in the turnover of the synaptic vesicle membrane is discussed.


Replication of measles virus in a cell culture from a glioblastoma of human origin.

A cell culture from a glioblastoma of human origin infected with the Edmonston strain of measles virus produced and released infectious measles virus. All cellular types seemed to be involved in the process of virus replication. Staining with hematin-eosin revealed the presence of eosinophilic intracytoplasmic and intranuclear inclusions. Examination with the electron microscope revealed viral nucleocapsids in the cytoplasm and, rarely, in the nuclei of infected cells.


Changes in sizes of the adrenaline-containing vesicles and their cores in frog cardiac sympathetic nerves after pharmacological treatments.

The sizes of adrenergic vesicles and their cores, as made visible by an acrylic aldehyde in sodium dichromate fixative, have been measured in electron micrographs of the sympathetic nerves amongst the frog's ventricular muscle. The animals were either normal or previously treated with drugs expected to affect the catecholamine content of the heart. The sympathetic nerves contain two overlapping populations of vesicles. A graphical method was used to separate these and determine the mean diameter of each population. The distribution of vesicles between the 'large' and 'small' populations is variable in normal animals. No changes could be detected in the experimental animals. The mean size of the 'large' vesicles is variable in normal animals. No changes could be detected in the experimental animals. Four injections of 5-hydroxydopamine caused a 5.8% increase in the diameter of the 'small' vesicles. No other treatment produced significant changes in vesicle size. Four injections of 5-hydroxydopamine caused a 50% increase in the diameter of the cores of the 'small' vesicles. Two injections of reserpine caused a 20% reduction in the diameter of the visible cores in the 'small' vesicles, and 34% of the vesicles lost their cores entirely. One injection of 6-hydroxydopamine or ten injections of alpha-methyl-tyrosine caused small reductions in 'small' core diameter. It is postulated that core formation in adrenergic nerves under these conditions is not solely dependent on their catecholamine content, but on this and another factor which may be part of the storage complex.


Lumbar motoneurons of man: I) number and diameter histogram of alpha and gamma axons of ventral root.

The numbers of large and intermediate diameter myelinated fibers of 17 ventral lumbar (L3, L4 and L5) spinal roots (vsr) of man (ages 17-81 years) have been evaluated using the improved methods of histologic processing and morphometry now available, semi-automatic methods of measurement and programmed calculation and plotting. A population of small diameter myelinated fibers as found in thoracic (T11) vsr, which are presumed to be preganglionic sympathetic fibers, were essentially absent from L3, L4 and L5 roots. On the average, there were 5716 (70%) large diameter fibers and 2625 (30%) intermediate diameter fibers in the L3 ventral spinal root. Comparable figures for L4 vsr were 4900 (70%) and 2152 30%) and for L5 vsr were 5043 (75%) and 1559 (25%). On the assumption that these lumbar roots contain few if any small diameter myelinated pre-ganglionic sympathetic axons, the large diameter fibers correspond to alpha motoneuron axons and the small diameter fibers to gamma motoneuron axons. With age, a decrease in the number of myelinated fibers was estimated to be 350 fibers per decade (approximately 5% per decade).


Selectivity of neuronal degeneration produced by chronic guanethidine treatment.

Chronic guanethidine treatment of rats produced extensive damage to sympathetic neurons of the superior cervical ganglion and pelvic plexus. No ultrastuctural changes were observed in parasympathetic cholinergic neurons in the ciliary ganglion and pelvic plexus, nor in sensory neurons in nodose and dorsal root ganglia. A total of only six nerve cell bodies free of degenerative changes were observed in sections of superior cervical ganglia from 20 rats. This suggests either that the earlier estimates of 5% cholinergic neurons in the superior cervical ganglion based on acetylcholinesterase staining are too high, or implies that sympathetic cholinergic neurons, unlike parasympathetic neurons, are damaged by chronic guanethidine treatment.


Synaptic replacement in the dentate gyrus after unilateral entorhinal lesion: electron microscopic analysis of the extent of replacement of synapses by the remaining entorhinal cortex.

In response to a unilateral entorhinal lesion the input from the contralateral entorhinal cortex to the dentate gyrus appears to increase. We have studied this crossed projection by electron microscopy in normal animals and in animals one year or more after a unilateral entorhinal lesion. In normal animals few degenerating boutons are found after a contralateral entorhinal lesion. However, when the contralateral lesion was made one year after an ipsilateral entorhinal lesion, degenerating boutons were readily identified. The boutons were relatively few in number, but formed an abnormally large number of synaptic contacts. These results support the previous conclusion that fibres from the contralateral entorhinal cortex form additional synapses when their ipsilateral homologues are removed. However, these new cortical synapses probably account for only a small portion of those formed in response to the lesion. Thus an anatomically homologous input does not, in this case, selectively capture most of the newly available synaptic sites.


The morphometric myelinated fiber composition of D11 as compared to L3, L4, and L5 ventral spinal roots of man.

As compared to the diameter frequency distribution of myelinated fibers of L3, L4 and L5 ventral spinal roots (VSRs) which have two well developed peaks [large-diameter axons (AL) and intermediate-diameter axons (AI)] and a poorly developed or non-existent peak of small-diameter axons (AS), D11 VSRs contain small AL and AI peaks and a prominent AS peak. Because the ratio of AL to AI myelinated fibers of D11 VSRs is similar to that in L3, L4 and L5 VSRs and it is known that D11 VSRs contain many pre-ganglionic autonomic fibers it seems likely that AS is composed predominantly of preganglionic autonomic fibers. The mean diameter of the AS peak in D11 VSRs is approximately 2.4 micrometer. Average numbers of AS, AI and AL myelinated fibers for D11 VSRs are 3835, 738, and 1545 per root. These values should be useful as controls for morphometric studies of various neuropathies. The average diameter positions of the peak of AL, AI and AS of D11 VSRs as compared to those of L3, L4 and L5 are displaced to smaller diameter categoried which may reflect the smaller axon diameters of neurons which are shorter.


Quantitative and electron microscopic studies of sensory ganglion cells of the Sprawling mouse.

The L4-6 sensory root ganglia of young and adult Sprawling (Swl) and normal mice were studied. Cell counts showed a great reduction in the total number of ganglion cells in Swl. Cell degeneration was observed in young Swl animals but not in normal littermates. Most of the remaining ganglion cells showed morphological abnormalities very similar to those seen in chromatolytic neurons-enlarged nucleolus, eccentric nucleus with an infolded nuclear membrane, loss of juxtanuclear Nissl bodies and an increase in neurofilaments, Golgi membranes, autophagic vacuoles, and dense bodies. In contrast to the classical changes of chromatolysis the abnormalities in Swl neurons persisted throughout the lifespan of the animals. Reconstructions from serial sections showed that ganglion cells in Swl were highly irregular in shape.


Evaluation of the age of subdural hematomas by computerized tomography.

The computerized tomography (CT) scans of 50 patients with surgically proven subdural hematomas were subdivided into three groups on the basis of the attenuation coefficients of the subdural fluid collections: 28% were more dense, 24% isodense, and 48% less dense than the surrounding brain. The 42 patients with the available data were then subdivided into three groups; acute, subacute, and chronic, according to the time interval between trauma or duration of symptoms and date of CT scanning. Subdural hematomas were found to be hyperdense in 100% of acute patients, isodense in 70% of the subacute group, and hypodense in 76% of the chronic group.


Glossopharyngeal neuralgia.

Various factors have been considered in the etiology and pathogenesis of glossopharyngeal neuralgia. Vascular compression of the involved cranial nerves has been demonstrated in sporadic cases. In this series of six patients, it was noted with the aid of the operating microscope that the ninth and tenth cranial nerves were compressed by a tortuous vertebral artery or posterior inferior cerebellar artery at the nerve root entry zone in five cases. In selected patients, microvascular decompression without section of the nerves may result in a cure.


Etiology and definitive microsurgical treatment of hemifacial spasm. Operative techniques and results in 47 patients.

The clinical and operative findings are reviewed in 47 patients with intractable hemifacial spasm. The syndrome was classical in its features in 45 patients and atypical in two. Mechanical compression distortion of the root exit zone of the facial nerve was noted in all 47 patients. In 46 the abnormality was vascular cross-compression, usually by an arterial loop. In one patient, a small cholesteatoma was discovered and removed. Morbidity and postoperative results are discussed.


Delayed radiation necrosis of the brain.

The cases of six patients are presented to delineate the clinical profile of delayed radiation necrosis of the brain. In five the diagnosis was verified histologically. Symptoms most often begin 9 months to 2 years after radiotherapy. Progressive visual impairment and dementia are common following perisellar irradiation, while hemispheric signs predominate following irradiation of the cerebrum. Cerebrospinal fluid protein may be elevated. Focal delta slowing is usually present on electroencephalography. The necrotic brain may appear on radionuclide brain scan as an area of abnormal uptake and also act as an avascular space-occupying lesion. With computerized tomography, radiation necrosis appears as an intracerebral area with diminished absorption coefficient that is often enhanced with intravenous contrast medium. The syndrome may be sufficiently characteristic to eliminate the need for surgical exploration and biopsy in some cases. Cumulative experience suggests that the risk-to-benefit ratio of radiotherapy becomes increasingly unfavorable for most patients with benign intracranial neoplasms when the standard brain tumor dose of 5000 to 7000 rads is fractionated at greater than 200 rads per day.


Treatment of experimental spinal cord compression caused by extradural neoplasms.

Epidural spinal cord compression was produced in rats by injection of Walker 256 carcinoma cell suspension anterior to the T-12 or T-13 vertebral body. The tumor grows through the intervertebral foramina to compress the spinal cord and produce paraplegia in 3 to 4 weeks. The effect of several treatments upon clinical signs was assessed. Dexamethasone caused a significant but transient improvement in neurological function. Radiation therapy likewise improved neurological function, and was more effective when given by a high-dose protracted course than when given either in a single dose or a low-dose protracted course. Laminectomy was not helpful in relieving neurological symptoms. Dimethyl sulfoxide did not relieve neurological symptoms. Cyclophosphamide was most effective in relieving neurological symptoms, and most of the animals that were treated with that drug when they were severely weak but still able to move their hind limbs recovered fully. Some animals that were totally paraplegic when treatment began recovered function after radiation therapy or cyclophosphamide treatment, but recovery was better if treatment was started when animals could still move their hind limbs. This animal model appears to be a useful way of studying the treatment of human spinal cord compression produced by epidural neoplasms.


Elasticity of the spinal cord dura in the dog.

The elasticity of the spinal cord dura in the dog has been investigated histologically, in situ, and by measurement. The dura was composed of collagenous and elastic connective tissue fibers. The collagenous fibers were arranged in longitudinal bundles, straight when stretched and wavy when unstretched, with a delicate network of fine elastic fibers coursing in all directions. Transecting the cord and dura at T-5 caused a separation of 25 to 30 mm of the dura and a 15- to 20-mm gap in the cord. By means of an appropriate sequence of transections of nerve roots and denticulate ligaments within the dura, and transections of the dural sheaths and nerves outside the dura, the strain on the dura was found to be imposed by the attachments of the dural nerve sheaths from T-6 to S-7. The filum terminale was not appreciably strained. By adding weights to a suspended dura, two components of elasticity were found. For loads of 0 to 50 gm, the incremental displacements in the length were large. The elastic modulus was about 4 X 10(6) dynes/sq cm, which was comparable to that of elastic fibers. For loads of 50 to 150 gm the displacements in length were small. The elastic modulus was about 5 X 10(8) dynes/sq cm, which was comparable to that of collagenous fibers.


The spinal cord central canal in kaolin-induced hydrocephalus.

In order to study the cause of the great individual variations in kaolin-induced hydrocephalus, the lower brain stem and upper spinal cord were examined histologically in a series of young rabbits that had received injections of kaolin into the cisterna magna. Animals with complete occlusion of the outlets from the fourth ventricle into the subarachnoid space showed only a moderate ventricular dilatation, while cases with marked hydrocephalus also plugs of kaolin in the caudal part of the fourth ventricle. The intraventricular kaolin was adherent to the roof of the fourth ventricle by strands of connective tissue and it is suggested that the plugs served as valves that initially occluded the opening of the central canal and were then lifted away as the ventricle dilated and the roof moved posteriorly. The animals with marked hydrocephalus also had extensive dilatation of the central canal with cleft formation in the posterior columns. The observations support the concept that in hydrocephalus the central canal may serve as an alternative resorption route for the cerebrospinal fluid through communication with the spinal subarachnoid space.


Prolonged vasospasm produced by the breakdown products of erythrocytes.

The cause of cerebral vasospasm has been generally attributed to the vasoconstrictive substances released from platelets. The role of extravasated erythrocytes in vasospasm has never been well analyzed. To elucidate this point, the basilar arteries of cats were exposed and subjected to topical application of various blood fractions in their fresh state and after prolonged incubation for 1 to 7 days. Incubation was done to test stability of the vasoconstrictors. Severe vasospasm was induced by application of fresh and incubated fractions of lysed erythrocytes. Fresh, intact erythrocytes had no vasoactivity, but by incubation they lysed and gained vasoconstrictors. Vasospasm induced by lysed erythrocytes both in their fresh state and after prolonged incubation never relaxed, and tended to increase in severity during observation up to 24 hours. Fresh serum and platelet-rich plasma had vasoconstrictors, but they were lost after incubation. Apparently platelet-induced vasoconstriction is of short duration and contributes only to the early phase of vasospasm. Later, 12 to 24 hours after hemorrhage, iron pigments released by lysis of extravasated erythrocytes (oxyhemoglobin or methemoglobin) irritate the arterial wall and induce prolonged vasospasm. It is emphasized that the study of cerebral vasospasm should be focused on the role of the breakdown products of extravasated erythrocytes.


Significance of vasospasm in the treatment of ruptured intracranial aneurysms.

The authors have analyzed a total of 96 consecutive cases in which vasospasm followed subarachnoid hemorrhage (SAH). The SAH was caused by ruptured intracranial aneurysm or developed after aneurysm surgery. Usually at least 4 days elapsed between SAH and the onset of vasospasm. Vasospasm subsided an average of 2 weeks after onset. Of 68 patients with preoperative vasospasm, eight died due to cerebral edema resulting from ischemia, and 49% of survivors had neurological deficits. Preoperative vasospasm was not aggravated by surgical intervention when operations were carried out more than 7 days after the onset of vasospasm. Postoperative vasospasm was found in 25 of 52 patients who underwent operation within 1 week after SAH (excluding cases in Grade V). Five of these patients died, all of whom underwent surgery between the fourth and seventh day after SAH (the day of SAH was counted as the first day). There were no deaths among 20 patients operated on within the first 3 days after SAH. Postoperative vasospasm was always mild in these cases, when it occurred, probably because blood clot or blood-stained cerebrospinal fluid was removed by operative procedures. In all cases, 4 to 11 days elapsed between the last SAH and the onset of postoperative vasospasm regardless of the timing of surgery.


Primary pigmented carcinoma of the choroid plexus. A light and electron microscopic study.

Pigmented carcinoma of the choroid plexus was found in a 33-year-old man. Autopsy revealed no primary tumor in the skin or eyes. A slightly cystic pigmented tumor was present in the right lateral ventricle infiltrating the thalamus and striatum. Metastatic implants were found in both temporal lobes and the cerebellum. The spinal cord was covered by black meningeal nodules, and the cauda equina was completely encased by the tumor. Metastases were found in the liver, pancreas, and kidney. Microscopically the mass contained normal choroid plexus with psammoma bodies adjacent to carcinomatous epithelium forming prominent papillae and tubules. Melanin granules were found within the neoplastic cells and in the stroma. Electron microscopy demonstrated melanin granules in various stages of development in the cells, which were joined one to another by desmosome-like structures. This is the second reported case of pigmented carcinoma of the choroid plexus and the first with metastases outside the central nervous system.


Symptomatic Rathke's cleft cyst. Morphological study with light and electron microscopy and tissue culture.

A rare case is reported in which a symptomatic Rathke's cleft cyst was studied by light and electron microscopy and tissue culture. The findings are compared with those of a craniopharyngioma studied in the same way. The patient was a 26-year-old woman presenting with headache, chiasmatic syndrome, and hypopituitarism. A cyst containing a mural nodule was partially removed and an Ommaya reservoir placed in the operative site for further treatment. The cyst wall was composed of connective tissue and three kinds of epithelial cells: non-ciliated squamous, ciliated columnar, and mucous-secreting cells. The morphology of these cells in vitro was similar to prickle cells seen in craniopharyngioma and the epidermis. It is concluded that both Rathke's left cyst and craniopharyngioma originate in remnants of Rathke's pouch, but at times may show some histological differences.


Effects on the products of conception of protein supplementation of the diets of rats.

Pregnant rats were ad libitum fed diets of varying casein content from conception. The food intake was measured. The control rats the first 17 days of gestation and 25% casein plus 2.5% DL methionine during the remainder; the second experimental group was given the 25% casein plus 2.5% DL methionine throughout pregnancy. Maternal food intakes were little changed by the supplement, but the rats in the second experimental group ate considerably more. The dietary regimens of the experimental groups had no effect on lean body mass, but did significantly increase carcass fat content. A protein supplement given in late pregnancy, at the time of the fetal exponential growth phase, was found to increase the weight, protein content and cellularity of fetal brains and carcasses. It also increased the weight and protein content of placentas, but had no effect on their cellularity.


Pyridoxine deficiency and postnatal development of brain aspartate and alanine aminotransferase activities, and cholesterol levels in chicks.

Feeding a pyridoxine deficient diet, for 2 weeks after hatching, had no effect on post-hatching development of chick brain aspartate aminotransferase (L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) activity or on cholesterol deposition in the brain, but significantly depressed the development of brain alanine aminotransferase (L-alanine:2-oxoglutarate aminotransferase, EC 2.5.1.2) activity. Feeding a pyridoxine deficient diet from 3 to 8 weeks of age had no effect on any of the three parameters studied.


Zinc excretion in young women on low zinc intakes and oral contraceptive agents.

Zinc excretion under conditions of negligible zinc intake (0.17 mg/day) was measured in women taking a combination oral contraceptive agent (+OCA) and in women with normal menstrual cycles (-OCA). A semipurified, constant formula diet, providing negligible amounts of zinc, copper and iron, but adequate levels of other essential nutrients, was fed. During the 35--day study, serum and urinary zinc declined more markedly in the +OCA than -OCA groups. Serum zinc dropped 47% in the +OCA and 21% in the -OCA; urinary zinc declined 83% and 62% in the two groups. After pre-study, zinc was cleared from the gut, fecal zinc decreased about 40% in both groups. Whole body integumental zinc losses were similar for both groups, about 0.7 mg/day. For -OCA, zinc losses via this route were higher during the luteal phase than during menstruation. Menstrual fluid zinc contents were negligible and similar for both groups, about 5 microgram/day. The data suggest that accessible zinc stores are not extensive and that depletion of these stores, as a result of the low-zinc diet, caused the fall in serum zinc. The use of OCA influenced the response to the low-zinc diet, but endogenous zinc losses calculated for day 1 were nearly the same for both groups, about 1.6 mg/day.


Effect of dietary fats on oxidative phosphorylation and fatty acid profile of rat liver mitochondria.

Hydrogenated coconut oil or safflower seed oil were fed at 20% levels to weanling male albino rats for 2 months. The fatty acid patterns of the liver homogenates, mitochondria and the microsomes were determined by gas chromatography as were also the fatty acid patterns of the liver cholesterol esters and the phospholipids. The mitochondrial phospholipids were fractionated by thin layer chromatography and the fatty acid moieties of the individual phospholipids were screened on a gas chromatograph. The oxidative phosphorylation in the liver mitochondria was determined using glutamate, malate and succinate as substrates. The liver fatty acid pattern, especially that of the subcellular particles, seemed to be dependent upon the dietary fat. The fatty acid composition of the mitochondrial phospholipids varied with the dietary fat. Oxidative phosphorylation for glutamate and malate was higher in the group fed safflower oil compared to that in the group fed saturated fat; in the case of succinate, no such difference was noticed. These results suggest that the changes in the phosphorylation capacity are due to the changes in the mitochondrial phospholipids which reflect the composition of the dietary fat.


Nutritional implications of the Maillard reaction: the availability of fructose-phenylalanine to the chick.

Fructose-phenylalanine, the Amadori compound resulting when glucose reacts with phenylalanine, was administered to chicks receiving a phenylalanine-deficient crystalline amino acid diet. The chicks did not respond to oral administration of this molecule which indicated it was nutritionally unavailable as a source of phenylalanine. In vitro protein synthesis studies on liver tissue showed that the rate of incorporation of 14C-phenylalanine into liver solids/mg tissue was significantly lower in chicks fed 0.404%-fructose-phenylalanine than in those not fed this compound. However, when fructose-phenylalanine was added directly to the incubation medium, no reduction of amino acid incorporation occurred. The discrepancy between in vitro and vivo results suggests, therefore, that fructose-phenylalanine is metabolized to another molecule which is causative in reducing liver protein synthesis.


Influence of diet on in vitro and in vivo rates of fatty acid synthesis in coho salmon [Oncorhynchus kisutch (Walbaum)].

The site and the influence of diet on fatty acid synthesis in juvenile coho salmon were investigated. Tritiated water was used to obtain estimates of the rates of fatty acid synthesis. Liver slices and mesenteric glucose and tritiated water. The rate of fatty acid synthesis averaged 1172 +/- 126 and 40 +/- 8 nmoles tritium incorporated into fatty acids per 2 hours per 100 mg of liver and adipose tissue, respectively. The pattern of [1-14C]acetate incorporation into fatty acids in the liver slices indicated that de novo fatty acid synthesis, rather than chain elongation, was occurring. In vivo rates of fatty acid synthesis in liver were approximately linear for 30 minutes. In vivo rates of fatty acid synthesis averaged 244 +/- 14 and 44 +/- 11 dpm of tritium incorporated into fatty acids per 20 minutes per 100 mg of liver and adipose tissue, respectively. Consumption of a high-fat diet or fasting for 2 days decreased the in vitro and in vivo rates of fatty acid synthesis in fish liver. Refeeding fasted (48 hours) fish with a high-carbohydrate diet for 4 hours increased the rate of hepatic fatty acid synthesis. The major site of fatty acid synthesis in coho salmon appears to be the liver, and dietary alterations influence the rate of fatty acid synthesis in the liver.


Genetic influence on zinc metabolism in mice.

A previous study resulted in the discovery of a unique, undesignated strain of mice, referred to as SM (Super Mouse), whose progeny exhibited a resistance to dietary zinc deficiency when pups from the strain suckled dams fed a zinc-deficient diet. Examination of the zinc metabolism in these mice demonstrated in the study reported here that SM mice accumulated significantly more zinc during in utero development than do mice of other strains. Adult mice of the SM strain contained significantly more bone zinc than did mice of other strains. Adult SM mice excreted significantly less 65Zn than did mice of other strains when the mice were fed a zinc-deficient diet. These observations suggest that SM mice are able to resist periods of zinc-deficiency as a result of the development of highly efficient systems for storing and reabsorbing zinc.


Analysis of chromium induced carbohydrate intolerance in the rat.

Carbohydrate tolerance was studied by intravenous glucose tolerance tests in normal and chromium deficient rats. A significant difference in glucose metabolism between chromium deficient and chromium supplemented rats was demonstrated only when the glucose decay constant was calculated from the line fitting the plotted logarithms of the excess plasma glucose concentrations. Calculation of the glucose decay constant from the line fitting the logarithms of the total plasma glucose concentrations showed no significant difference between the two groups. This finding suggests that either the first method is more sensitive to mild changes in intravenous glucose tolerance in the rat, or the observed difference is a methodological artifact.


Effects of malnutrition on some aspects of RNA metabolism in the maternal liver and fetal tissues at different stages of pregnancy in the rat.

A comparison was made between rats fed diets containing either 5% casein or 25% casein, both being supplemented with DL-methionine, from the first day of pregnancy. Livers of dams killed on days 7, 14, and 21 and whole fetuses on days 12, 14, and 21 were weighed, analyzed for protein, RNA and DNA content and assayed for ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase (SAMD). Free and total alkaline ribonuclease activity were also measured in the maternal livers. Malnutrition reduced the characteristic increase in content of DNA, RNA and protein in the maternal liver and fetus. In control rats total hepatic RNase activity increased and free RNase activity decreased during late pregnancy. In the deprived group, total activity decreased and free activity increased during late pregnancy. Liver and fetal ODC and SAMD activities were reduced by undernutrition. These studies show that malnutrition reduced both growth and the accretion of RNA in livers and fetuses of rat dams. These changes coincide with a reduced activity of polyamine synthesizing enzymes suggesting that there is a functional relationship between polyamines and RNA. High hepatic free RNase activity in malnourished dams may help to limit any build up in RNA content.


Vitamin B-6 deficiency in germfree rats.

Germfree and conventional rats were used to investigate the influence of gut microflora upon vitamin B-6 deficiency. The body weights of conventional rats fed a vitamin B-6-deficient diet for more than 5 weeks plateaued, but the rats remained alive until the end of week 9 of deficiency. The body weights of germfree rats fed the same deficient diet decreased, andmost of rats were moribund around the end of week 9 of deficiency; three died. Urinary xanthurenic acid excretion following tryptophan load continued to rise at each experimental week in deficient germfree rats, while such a progressive increase in the level of the excretion was not observed in deficient conventional rats. Autopsy revealed that some of deficient germfree rats suffered from partial or toal lunficient conventional rats. The lung atelectasis was presumed to be the result of the respiratory muscle insufficiency which was closely related to the changes of the peripheral nerves innervating these muscles. The results may suggest that the presence of gut microflora made some contribution to improvement of the vitamin B-6 deficiency.


Metabolism of protein and RNA in liver of rats deprived of tryptophan.

Rat lost body weight after the second day of feeding a tryptophan free diet. After 15 days of tryptophan deprivation, they had lost 17% of body weight, whereas pair-fed controls had gained weight. Liver weights of deprived rats were significantly lower than those of controls. Water, protein, RNA, and DNA in the livers were not significantly changed after 15 days of tryptophan deprivation. Amounts of free typtophan and alanine in livers of derpived rats decreased to 40% of the controls after 15 days, whereas amounts of most other amino acids were nearly constant. Protein synthesis in livers of deprived rats for 15 days was impaired to about 55% of controls. Incorporation of orotic acid into different types of cytoplasmatic and nuclear RNA remained unaffected up to the tenth day. After 15 days of deprivation, more orotic acid had been incorporated into RNA fractions that correspond to the precursor ribosomal fractions.


Vinyl chloride cytogenetics.

This report presents cytogenetic findings from a group of 209 workers employed for up to 28 years in the manufacture of vinyl chloride monomer at the Texas Division of Dow Chemical U.S.A. Cytogenetic evaluation results from this group were compared to results found in examination of individuals being considered for employment. Statistical analyses were performed on a group basis for chromatid aberrations, chromosome aberrations and proportion of abnormal cells; no statistical difference of significance was found between the two groups. Comparison of these results with reported studies suggests that the level of cytogenetic aberrations in vinyl chloride workers is probably related to the length and level of exposure, and that risk of adverse genetic effect can be avoided in controlled, minimal-exposure environments.


Lung cancer among black migrants. Interaction of host and occupational environment factors.

A study of Ohio residents by place of birth identified an increased cancer risk (100% excess) among black migrants born in the South compared with blacks born in Ohio. The migration of blacks from South to North for the purpose of industrial employment was extensive between the years 1940-1970. The hypothesis is that biological and social imprints (poverty, malnutrition, genetics), endemic of the early years of life, provide a physiological imbalance which provides the basis for increased susceptibility to adverse environmental stresses subsequent to migration. Findings consistent with this hypothesis were obtained in a prospective study of steel workers in which 2,543 men in coke plant operations were included, in which a prior high rate for lung cancer had already been established. A strong association was found between place of birth and place of death from lung cancer in the nonwhite coke plant workers. Examination of these death certiricates revealed that 33 of 35 deaths of lung cancer occurred among men born in the South.


Two-band model of heterochromatic flicker.

We have attempted to reconcile the results of several recent chromatic flicker studies. By adjusting the relative amplitudes of red and green sine-wave stimuli that were flickering in opposite phase, we obtained conditions varying from purely chromatic (red-green) stimulation, through each "silent-cone" condition, to purely luminous (homochromatic) stimulation. We also tested the effects of adapting backgrounds in each condition. Our results can be explained in terms of a low-frequency band that represents the opponent-color response, and a high-frequency band that represents the achromatic response. These two bands respond in various proportions, depending on the red-green stimulus ratio. Chromatic adaptation generally affects the low- and high-frequency bands differently and hence changes the shape of the flicker sensitivity curve. However, if the temporally varying waveform and the adapting background are both chosen to stimulate the same cone type, then the opponent-color and achromatic bands are both attenuated by the same amount. In this case, the shapes of the silent-red and silent-green flicker curves are preserved under chromatic adaptation. We conclude that none of these flicker curves are controlled by the temporal characteristics of independent cone types.


Reading retardation:a 12-year prospective study. Implications for the pediatrician.

A 12-year study has (1) assessed the predictive efficiency of a preschool test battery in relation to short- and long-term school achievement; (2) evaluated socioeconomic locale and operational school structure as indicators of subsequent progress; (3) observed the effects of some correctional experiences on later school performance. Almost 1,000 children have been involved; 606 remain in the project. Mental ages have ranged from 54 to 104 months though the mean chronologic age at school entry was 74 months. Twenty-three percent failed to complete first-grade requirements in the first year. Failure rates within separate schools ranged from three to 71% and had an inverse relationship to socioeconomic level. Within the middle-class area, children in an open-space school had double the failure rate of their peers in traditional classrooms.


Cerebrospinal fluid lactic acid levels in meningitis.

Measurement of cerebrospinal fluid lactic acid by gas liquid chromatography and by an enzymatic Monotest lactate test was evaluated for the early detection of bacterial meningitis in 396 patients. Spinal fluid specimens from 62/62 patients with a bacterial or mycoplasma etiology yielded lactate levels greater than the upper limits of normal, whereas specimens from 334 patients with no bacterial involvement gave values within the normal range. The duration of elevated CSF lactate values coincided with the clinical response to therapy. When considered along with the history and physical examination of the patient, determination of lactic acid proved to be a rapid and reliable diagnostic test for the early detection of untreated as well as partially treated pyogenic meningitis.


Postpubertal evaluation of gonadal function following cyclophosphamide therapy before and during puberty.

Evaluation of pituitary gonadotropins, gonadal steroids, spermatogenesis, and menstrual function was undertaken in 32 patients (19 males and 13 females) treated with cyclophosphamide because of nephrotic syndrome. Patients were treated before, during, or after puberty. Evaluations took place after or in very late puberty. Spermatogenic dysfunction occurred in six of 15 boys who received the entire course before and during puberty and was probably dose related. Menstrual dysfunction did not occur following treatment of six prepubertal or pubertal girls, though only low total doses were used. Therapy after puberty was associated with spermatogenic dysfunction in all four boys, but did not cause menstrual dysfunction in any of seven women. Tentative guidelines are suggested that many minimize gonadal toxicity when cyclophosphamide is used in children with nephrotic syndrome. Factors of particular importance in the interpretation of gonadotropin determinations and of sperm counts in young cyclophosphamide-treated patients are discussed.


Transient diabetes mellitus in a neonate. Evaluation of insulin, glucagon, and growth hormone secretion and management with a continuous low-dose insulin infusion.

This neonate developed marked hyperglycemia four days after birth and required insulin therapy for eight weeks. During the acute phase of the disease, immunoreactive insulin was undetectable in portal venous serum. Neither tolbutamide nor theophylline administration significantly triggered insulin secretion. Somatostatin infusion inhibited growth hormone release but had no effect on plasma glucagon or blood glucose concentrations. At 2 1/2 months, two weeks after insulin withdrawal, the infant was still intolerant to an oral glucose load, insulin response was markedly delayed, and growth hormone secretion was paradoxical. At five months, the insulin, glucagon, and growth hormone responses to glucose and to somatostatin were normalized. Thus, in this patient, insulin secretion was transiently deficient. Peculiarities of glucagon and growth hormone secretion were also present but are more characteristic of this age group than of diabetes. The hyperglycemic state was managed by intraportal infusion of 0.1 to 0.2 IU regular insulin/kg/hour. This mode of insulin administration proved efficient, secure, and easy to manage.


Thyrotoxicosis detected in a mass-screening program for neonatal hypothyroidism: demonstration of placental transfer of an immunoglobulin with marked lipolytic activity.

A female infant born to a mother with active Graves disease and a strongly positive LATS developed neonatal thyrotoxicosis. The diagnosis was confirmed rapidly by the markedly elevated filter paper spot T4 (5.45 ng/40 microliter) taken on the fifth day of life as part of the Quebec Screening Program for Neonatal Hypothyroidism. Although the infant's serum was negative for LATS, it reacted strongly (as did the maternal serum) in the lipolytic assay for LATS. This case illustrates the ability of screening programs for neonatal hypothyroidism to detect cases of neonatal thyrotoxicosis and supports the hypothesis that this condition is secondary to the placental transfer of a thyroid-stimulating immunoglobulin.


Severe coagulation abnormalities in Reye syndrome.

Coagulation studies were performed on 13 children with clinical diagnoses of Reye syndrome. Four had abnormalities so severe that transfusion of coagulation factors and platelets were required prior to percutaneous liver biopsy. In one of these, abnormalities frequently found in association with acute hepatic failure were present. Disseminated intravascular coagulation was noted in two, while in the fourth child laboratory data were most consistent with that process. Although the coagulation defect associated with Reye syndrome is most often due to decreased production of all coagulation factors except VIII, these patients demonstrate that consumption can also occur. The severity of the coagulopathies found indicates that bleeding can become a major complication in the diagnosis and management of Reye syndrome.


The Lenz-Majewski hyperostotic dwarfism. A syndrome of multiple congenital anomalies, mental retardation, and progressive skeletal sclerosis.

A distinct syndrome is delineated on the basis of two previously reported and one newly described case. The syndrome combines multiple congenital anomalies with a progressive skeletal dysplasia-dysostosis, The gradual evolution of the skeletal disorder is demonstrated in the present patient. It will now be possible to diagnose this syndrome at birth.


Dicarboxylic aminoaciduria: an inborn error of amino acid conservation.

A 38-month-old apparently healthy male has been followed for three years because of a massive glutamic and aspartic aminoaciduria detected shortly after birth in a neonatal screening program. Amino acid clearance studies revealed the presence of renal wastage of dicarboxylic amino acids. Intestinal transport and in vitro oxidation of dicarboxylic amino acids were found to be intact. Clinical and metabolic data obtained on a previously described patient and the present case suggest that some patients with dicarboxylic aminoaciduria might have a selective renal conservation defect without clinical abnormalities, whereas others might demonstrate an additional defect in intestinal transport associated with fasting hypoglycemia.


Assessment of gestational age by examination of the anterior vascular capsule of the lens.

The disappearance of the anterior vascular capsule of the lens (pupillary membrane was found to be useful in the preterm infant to estimate accurately gestational age between the twenty-seventh and the thirty-fourth weeks. Before the twenty-seventh week, the cornea was to opaque to allow good visualization of this vascular system. After the thirty-fourth week, these vessels had generally atrophied completely. One hundred infants between 27 and 34 weeks' gestational age as assessed by the Dubowitz scoring system were studied with the direct ophthalmoscope following dilatation of the pupil. Disappearance of the anterior vascular capsule was arbitrarily divided into four grades. The correlation between gestational age and the grade of anterior vascular capsule was found to be highly significant (p less than 0.001).


Syndrome of inappropriate antidiuretic hormone secretion in neonates with pneumothorax or atelectasis.

Nine episodes of the syndrome of inappropriate antidiuretic hormone secretion occurred in five newborn infants following atelectasis or pneumothorax. All infants had pre-existing lung disease and were being treated with positive pressure ventilation. The mean interval between acute atelectasis or pneumothorax and the development of diagnostic hyponatremia, hypo-osmolal serum, hyperosmolal urine, and oliguria was 13.4 hours. Fluid restriction and removal of the triggering event resulted in resolution of the abnormalities within 1.5 to 4 days. Infants who develop atelectasis or pneumothorax should be evaluated for the subsequent occurrence of SIADH; the administration of a water load to them may result in dilutional hyponatremia, for which fluid restriction, not sodium infusion, is the proper therapy.


Prenatal diagnosis of achondrogenesis.

Severe rhizomelic and mesomelic dwarfism was demonstrated in a 20-week gestation fetus by amniography. A systematic progressive approach to prenatal diagnosis  in the absence of a definitive diagnosis and the use of contrast radiography is discussed.


Prenatal diagnosis of recurrence of Saldino-Noonan dwarfism.

The occurrence in a family of three spontaneous abortions and two siblings with Saldino-Noonan dwarfism supports an autosomal recessive etiology and raises the possibility of lethality early in utero. No long bones were visualized in radiographs at 19 weeks' gestation in the second affected pregnancy. highlighting the difficulties of distinguishing technical limitations from fetal anatomic abnormalities. Ultrasound studies demonstrated oligohydramnios. Radiologic prenatal diagnosis can rule out this condition prior to 20 to 24 weeks' gestation and affected fetuses can be suspected if not proved by radiographs and ultrasound examination.


Breast milk distribution of theobromine from chocolate.

Six nursing mothers ingested 113 gm of Hershey's milk chocolate containing 240 mg of theobromine. Samples of plasma, saliva, and breast milk were assayed for theobromine by high pressure liquid chromatography. Peak theobromine concentrations of 3.7 to 8.2 mg/l were found in all fluids at 2 to 3 hour after ingestion of chocolate. The disposition half-life of theobromine averaged 7.1 +/- 2.1 hours, body clearance was 65 +/- 20 ml/hour/kilogram, and the apparent volume of distribution was 0.62 +/- 0.13 l/lk. Theobromine is only slightly bound to plasma and milk proteins and concentrations in milk and saliva matched plasma data closely. The mean concentration ratios were 0.82 +/- 0.17 for milk/plasma and 0.92 +/- 0.17 for saliva/plasma. If a mother ate a 4-ounce chocolate bar every 6 hours and the infant nursed when the theobromine concentration in milk was at its peak, the infant could ingest about 10 mg of theobromine per day.


Clinical pharmacology of hexachlorophene in newborn infants.

Bathing with soap containing hexachlorophene was instituted during two major staphylococcal epidemics in a Neonatal Intensive Care Unit. Infants who weighed less than 1,200 gm, those with a postconceptional age of less than 35 weeks, and those with large areas of abraded skin were at highest risk to achieve elevated blood HCP concentrations. T 1/2 of HCP ranged from 6.1 to 44.2 hours and appeared to follow first order kinetics. Time of peak blood concentrations of HCP following a bath ranged from 6 to 10 hours. One infant with liver disease achieved a concentration of HCP of 4,350 ng/ml after seven baths and developed clinical symptoms consistent with HCP toxicity.


Paradoxical behavior of serum digoxin concentrations in an anuric neonate.

Serum digoxin values were determined in a newborn infant with severe heart failure and renal failure. The half-life of digoxin in the serum appeared to change, possibly the result of prolonged distribution and/or absorption owing to circulatory insufficiency, or to the accumulation of cross-reacting metabolites of digoxin in the serum. No clinical toxicity was apparent, and no cardiac arrhythmia was observed. The need for monitoring serum digoxin concentration and clinical effect in newborn infants is emphasized.


Vitreous loss following infantile cataract surgery.

Vitreous loss occurred in 50 of 475 consecutive eyes undergoing infantile cataract aspirations over a 10-year period. Vitreous loss occurred in eyes predisposed to such loss and in other eyes following the use of faulty instrumentation, poor surgical judgment, or from errors in operative technique. Vitreous loss was managed by the techniques outlined by Castroviejo and Maumanee. An analysis of this series revealed that the operative loss of vitreous in children does not predispose to undesirable sequelae. Postoperative complications are not correlated with the loss of vitreous itself, but rather with the presence of other coincident ocular pathology and/or the persistence of vitreous in or attached to anterior chamber structures. The final attained visual acuity in patients suffering vitreous loss is not different from the average of the same population. Although vitreous loss consequences may be minimized, the authors do not advocate the disturbance of the intact vitreous face either accidentally or intentionally.


Visual acuity and binocularity in children with unilateral acquired aphakia.

Seventeen cases of unilateral aphakia secondary to acquired cataracts and dislocated lenses were presented. Final visual acuity was 20/70 or better in 12 of our 17 patients. Binocular single vision has been maintained in four cases. Ten patients had a posttherapy tropia. Early surgery and treatment particularly in the young child is stressed in order to maintain normal binocular single vision. Where once traumatized eyes were felt to be "sick" eyes and better left alone, current surgical and therapeutic methods make restoration of vision and binocularity a reasonable goal.


Opacities of the lens indicating carrier status in the oculo-cerebro-renal (Lowe) syndrome.

Three families with a total of five patients with Lowe's syndrome are described. We tried to trace female heterozygotes by ophthalmological abnormalities in order to realize prevention of this serious X-chromosomal recessive disease. Of the fourteen female relatives examined, eight showed pathological opacities of the lens, two of these being proven heterozygotes. In our opinion, in Lowe's syndrome, examination of the eyes can play an important role in the detection of heterozygotes.


Congenital teratoma of the orbit.

A congenital teratoma of the orbit is described. Histologically, the tissues forming the tumor appeared derived from the three germinal layers and showed an advanced degree of differentiation. An exenteration was performed because of suspicion of malignant tumor in the orbit and because of the severe keratitis with impending perforation which ensued the lagophthalmos.


Occult rupture of a main stem bronchus.

This report described a patient with multiple injuries in whom a major bronchial tear was not diagnosed early because the lung reexpanded initially. When pulmonary sepsis intervened and the bronchial injury was discovered, repair could not be accomplished because of continuing sepsis. The case emphasizes the need for early bronchoscopic evaluation in suspected bronchial injury even in the face of multiple other injuries which may draw the focus of attention away from a correctible bronchial disruption.


Bronchogenic squamous cell carcinoma in childhood; a case report.

Primary carcinoma of the lung is unusual in children and the squamous cell variant is extremely rare. This, to the best of our knowledge, is the sixth reported case of bronchogenic squamous cell carcinoma in childhood.


Chylothorax in neuroblastoma.

This is a brief case report of a patient who developed chylothorax subsequent to abdominal radiation for neuroblastoma, treated by aspirations and local chemotherapy, and mediastinal irradiation.


Pneumoperitoneum without ruptured viscus in the neonate: a case report and review of the literature.

A premature infant with severe respiratory distress developed the clinical and radiologic signs of pneumoperitoneum. At operation, free intraperitoneal air without visceral perforation was found. This case is unique in that pneumothorax was never observed and that interstitial emphysema or ischemic gastrointestinal lesions were not present at autopsy. The patient, however, was on a positive pressure ventilator for some time because of hyaline membrane disease and early pulmonary oxygen toxicity. Reduced parenchymal compliance could predispose to alveolar rupture. Although there was no clinical or anatomic evidence to point to a source of the intraperitoneal air, an undetectable pulmonary rupture with prompt dissection into the peritoneal cavity is the most likely explanation for the pneumoperitoneum.


Detection of learning disabilities using the visually evoked cortical potential.

It was proposed that the Visually Evoked Cortical Potential (VECP) could be used to detect learning disabilities. It was found that a comparison of the responses from the two parietal lobes to a checkerboard pattern could provide such a detector. The latency differences had a correlation of .79 with scores on a test of learning disabilities for high school aged children.


Ocular pathology in infantile type of neuronal ceroid-lipofuscinosis.

Ocular pathology of the infantile type of ceroid-lipofuscinosis is reported. The material comprised 10 eyes of five autopsies in which the diagnosis had been confirmed by neuropathological autopsy. The condition is clinically characterized by its age of onset from eight to 18 months, rapid psychomotor retardation, ataxia, and muscular hypotony. The patients become blind by the age of two years with optic atrophy and retinal hypopigmentation as the main ophthalmoscopic features. In the retina a complete disappearance of the visual cells, the bipolar cells and the ganglion cells was observed with marked reactive gliosis. Loss of pigment from the retinal pigment epithelium had taken place. The optic nerve showed atrophy and gliosis with complete loss of myelin sheaths. Granular deposits stainable with PAS, and Sudan black B stains were observed in the nonpigmented ciliary epithelium of the pars plana, the pigment epithelium as well as the glial cells of the optic nerve. Granular deposits were also noted in the cytoplasm of large pigmentladen macrophages in the retina. Electronmicroscopy revealed osmiophilic granular deposits in the cytoplasm of many retinal glial cells.


A malformation of the pancreatico-biliary system as a cause of perforation of the biliary tract in childhood.

Three cases of biliary tract perforation are presented. They had in common an anomalous arrangement of the pancreatico-biliary system, a cylindrical dilatation of the biliary tree, and an inflammatory thickening of the wall of the bile duct. The etiological importance of the anomalies is discussed. Bypass procedures are necessary at the final operation.


Pediatric dosing considerations in ophthalmology--dosage adjustments based on aqueous humor volume ratio.

By simplifying a pharmacokinetic treatment, an equation can be derived which predicts that equal areas under aqueous humor concentration-time profiles can be obtained by administering a dose to infants which is some fraction of the normal adult dose. This fraction is obtained by dividing the aqueous humor volume of the child by that of the adult. This theory has been tested using rabbits as an experimental model. Using literature values for aqueous humor volumes, it was possible to calculate what fraction of a dose of pilocarpine administered to 20-day-old rabbits would result in the same ocular concentrations of drug as in 60-day-old rabbits. When the experiment was performed, agreement between predicted and experimental values was excellent. Although admittedly an oversimplified treatment, these results are the first step in a comprehensive pharmacokinetic model which should result in a more rational approach to ophthalmic drug delivery in infants and children.


Congenital cysts of the head of the pancreas.

A very rare case of an infant with a huge multilocular congenital cyst of the head of the pancreas is presented. The symptomatology, diagnosis and surgical approach are discussed, while reviewing the few scattered reports in the English literature. Selective celiac arteriography is considered to be of definite aid in the differential diagnosis of cystic lesions of the head of the pancreas and has important implications on the choice of surgical procedure. We believe this to be the first case of a congenital cyst of the head of pancreas to be diagnosed accurately preoperatively by means of selective celiac and gastroduodenal angiography. Cystoduodenostomy proved to be a simple and effective procedure.


Nonpulsatile exophthalmos in carotid-cavernous sinus fistula.

An unusual case of carotid artery-cavernous sinus fistula with pulseless exophthalmos is presented in a two and one-half year old child. Though exophthalmos and increased episcleral venous distention were present, the ophthalmic artery pressure was not significantly altered as determined by ocular pneumoplethysmography. Consequently there was no evidence of hypoxic sequelae which frequently occur with this arteriovenous shunt. The combined use of arteriography and ocular pneumoplethysmography is advocated for determining and characterizing the presence of significant intracranial arteriovenous disease.


Arteriovenous fistula of the eyelid: secondary to a chalazion.

An arteriovenous fistula developed on the surface of a chronic chalazion of the upper eyelid of a 21-year-old patient during pregnancy. Surgical removal of the vascular mass with ligation of the feeder arteries resulted in a complete cure.


Nonischemic intussusception.

Nonischemic intussusception is defined as a variant of acute intussusception exhibiting less acute symptoms of abdominal pain, vomiting, and diarrhea in the older child, longer duration of symptoms (usually 4-14 days), signs of imcomplete bowel obstruction, and absence of intestinal ischemia. Over a 10 yr period (1964-1973) 20 children with this disease were treated without mortality or recurrence at three children's hospitals in Chicago, Illinois. The higher incidence of diarrhea, the lower incidence of a palpable abdominal mass, and the lower incidence of blood per rectum in nonischemic intussusception predispose to diagnostic errors and delays in treatment. Despite the longer duration of symptoms, this variant of intussusception can be treated initially with a careful attempt at barium hydrostatic reduction. If this fails, easy operative manual reduction is the rule.


Benign intraparotid neurilemoma of the facial nerve.

Parotid gland tumors are uncommon in children and intraparotid tumors of the facial nerve are even less so. It thus seems worthwhile to record this case of a neurilemoma of the right facial nerve within the parotid gland of a 14 yr old boy.


Congenital neurogenous sarcoma with rhabdomyosarcomatous differentiation.

A congenital malignant peripheral nerve sheath tumor contained small rhabdomyosarcomatous portions in both the retroperitoneal pelvic primary and in the subpleural lung metastasis. There was no family history of Von Recklinghausen's disease. Of the 10 patients with this tumor previously reported, the youngest is 14 yr old, and eight had familial neurofibromatosis.


Agenesis of the right diaphragm: repaired with marlex.

A case of a female newborn with agenesis of the right hemidiaphragm is presented. The defect was corrected with a double sheet of Marlex, attached to a rim of endothoracic fascia and muscle. At the age of 5 yr, the child is in perfect health.


Bleeding gastric ulcer in a newborn infant diagnosed by transumbilical aortography.

Transumbilical aortography has been utilized for the first time to diagnose the cause of massive upper gastrointestinal hemorrhage in a newborn infant. We consider it a safe and accurate method in cases that meet the following criteria: massive hemorrhage uncontrollable by blood transfusions and supportive medical therapy, and hemorrhage active at the time of study as indicated by fresh blood draining from nasogastric tube.


Ectopic pancreas presenting as an umbilical mass.

This report describes the first known case of isolated ectopic pancreatic tissue presenting as an umbilical mass.


Necrotizing enterocolitis occurring in an infant three months of age.

Necrotizing enterocolitis (NEC) is usually described as occurring in newborn premature of low-birth-weight infants who have been stressed by hypoxia, exchange transfusion, or severe sepsis. It occasionally occurs in full term neonates. The age of onset is between day 1 and day 35. This communication describes the occurrence and course of NEC in a 3 mo old infant with a short intestine.


Pediatric Spigelian hernia: a case report.

Report of a Spigelian hernia in a 13 yr old girl. The condition may well be more common than generally believed, and the diagnosis should be considered in all children with intermittent abdominal pain, even in the absence of a palpable mass.


Hydrocolpos, vaginal atresia, and urethrovaginal fistula in a neonate: abdomino-perineal-vaginal pull-through.

The combination of high maternal estrogenic stimulation of the secretory glands of the reproductive tract of the newborn female and vaginal obstruction results in an abdominal mass due to vaginal distention (hydrocolpos). Prior experience with two infants with hydrocolpos (LG) led us to perform abdomino-perineal-vaginal pull-through, as advocated by Ramenofsky and Raffensperger, in the newborn period. So far as we can ascertain this is only the second infant so reported in the literature.


A long term evaluation of infants who received a beta-mimetic drug while in utero.

The administration of beta-mimetic drugs to pregnant women poses the problem of possible long-term repercussions in the children born to these mothers. 42 children from women who had been treated with 60-80 mg a day of ritodrine hydrochloride (Pre-par), during a period varying from 3 to 93 days, were closely matched with infants from untreated mothers. Each child, (aged from one to 3 years), was fully investigated on the basis of: a detailed questionnaire to the mother; careful clinical examination; assessment of psychomotor development; the Denver test; electrocardiography and urine analysis. There was no statistically significant difference between the two groups for any of the variables of development that were studied. One child had left ventricular hypertrophy, which was probably incidental. It is concluded that administration of ritodrine hydrochloride to pregnant women induces no harmful long-term effects in their offspring.


A behavioral study of obedience in children.

Using Milgram's original test of obedience, 192 Jordanian subjects were tested in a 2 X 2 X 3 design in which sex, two kinds of punishment instructions, and three levels of age groups (6-8, 10-12, and 14-16 years) were combined factorially. The instructions issued to the experimental group were identical to those used in Milgram's paradigm in that teacher subjects were asked to administer shock to confederate learners each time the latter made a mistake in a paired-associate task and to increase the shock level with each additional mistake. The subjects in the control group were given a free choice of delivering or not delivering shock each time the learner made a mistake. The results showed that 73% of all experimental subjects, as opposed to 16% of the control subjects, continued to deliver shock to the end of the shock scale. Neither age nor sex differences in obedience rate were found. However, significantly more obedient females than males reported that they punished the learners because they were obeying orders.


Kinetics of drug-drug interactions in sheep: tolbutamide and sulfadimethoxine.

The interaction between sulfadimethoxine and tolbutamide in sheep involving displacement from protein binding sites was investigated quantitatively. A 52% increase in the unbound plasma concentration of tolbutamide was observed in vitro at 37 degrees after the addition of sulfadimethoxine (100 microgram/ml) to sheep plasma containing tolbutamide (50 microgram/ml). Transient changes in tolbutamide's unbound and total plasma concentrations were noted after acute intravenous administration of sulfadimethoxine to sheep receiving a constant intravenous infusion of tolbutamide. These observations were consistent with displacement of tolbutamide from plasma and tissue binding sites and redistribution of the displaced tolbutamide into body water spaces. The steady state of both agents featured little change in the total plasma tolbutamide concentration, a 150% increase in the unbound plasma tolbutamide concentration, and an inhibition of tolbutamide oxidation by sulfadimethoxine. A model is presented and mathematical relationships are derived that permit a quantitation of the interaction and that indicate the sulfadimethoxine's constant of metabolic inhibition (K1) for tolbutamide metabolism is 65 microgram/ml.


Mathematical model for enteric film coating of tablets.

The enteric film coating of placebo tablets, using a methacrylic acid-methyl methacrylate copolymer as the film former in the coating solution, was studied by statistical techniques. The effects of four independent formulation and process variables on the disintegration time of the coated film in simulated intestinal fluid and on the resistance to disintegration of the coated film in simulated gastric fluid were studied. The results of a statistically designed set of experiments were used as the input data. Regression analysis of these data resulted in two first-order polynomial equations. The linear model obtained for the disintegration time of the coating in the simulated intestinal fluid was analyzed by the steepest descent method to determine the most suitable combination of the independent variables.


Degradation of carmustine in mixed solvent and nonaqueous media.

The degradation rate of carmustine in several solvent mixtures and in mannitol solution was investigated at 5, 22, and 37 degrees. The solvents chosen were those utilized as parenteral diluents. The apparent first-order degradation rate constants were computed using a linear regression procedure. The most nonaqueous solvent mixtures demonstrated minimum apparent degradation rates. The apparent degradation rate constant decreased with a decrease in the macroscopic dielectric constant. From the data at several temperatures, the apparent activation energies for carmustine degradation in the several solvent mixtures were calculated. There was no evidence for a relationship between the apparent activation energy and the dielectric constant.


Parameter for assessing parenteral cleanliness based on particle-size distributions.

A new parameter for assessing the particulate matter content of large-volume parenteral solutions was developed and tested. Some problems and shortcomings associated with previously proposed standards are discussed, together with the potential advantages of employing the proposed parameter. Cleanliness factors were compared with another parameter and were less susceptible to changes resulting from the method of measurement utilized and the premeasurement conditions encountered by the solution. The use of these cleanliness factors in conjunction with an automatic particle counter is proposed as a worthwhile supplement to the USP-NF standard for monitoring the quality of large-volume parenteral solutions.


Dissolution kinetics of cholesterol in simulated bile I: Influence of bile acid type and concentration, bile acid-lecithin ration, and added electrolyte.

A physical model approach was utilized to investigate cholesterol monohydrate dissolution kinetics in simulated bile. The static pellet method and the Berthoud theory were employed to assess the contributions of the diffusion-convection mass transfer resistance and those of the interfacial resistance to the overall kinetics. For almost all situations studied, the interfacial resistance was the dominant rate-determining factor. The effects of four bile acids and their concentrations, the bile acid-lecithin ratio, and the added electrolytes and their concentrations on the interfacial resistance were examined. The results were correlated with those obtained with human bile samples, and the indications were that the kinetics of cholesterol dissolution in bile may be explainable on the basis of the principal bile acids, lecithin, and the electrolytes in the bile.


Cholesterol gallstone dissolution rate accelerators I: Exploratory investigations.

Various compounds that might function as cholesterol gallstone dissolution accelerators were studied. The dissolution rates of cholesterol monohydrate pellets in synthetic bile (116 mM sodium cholate-32 mM lecithin) containing the agent at various concentration levels were determined. In the absence of any dissolution rate accelerator, the dissolution kinetics for cholesterol previously were found to be interfacial resistance controlled, and the rates were around 20 times less than the diffusion-controlled rates in the present experiments. Primary, secondary, and tertiary amines and quaternary ammonium compounds were effective accelerators. When the alkyl chain lengths were long enough and/or when the agent concentrations were high enough, the dissolution rates generally approached diffusion-controlled rates. Steroidal amines generally had good activity. Anionic and nonionic surfactants had little or negative activity.


Chromatographic assays for folic acid.

TLC and high-pressure liquid chromatographic (HPLC) assays for folic acid were developed. In the TLC procedure, the folic acid band was extracted from the silica gel after development and determined spectrophotometrically by an oxidation and Bratton-Marshall sequence. A column packed with octadecylsilane chemically bonded to microparticulate silica gel was used for the HPLC assay. Potentiometric determination of water in folic acid samples was necessary to obtain accurate purity values. In a comparison of four assay methods, a direct colorimetric method gave precise, but unspecific, results, while the USP XIX colorimetric method lacked both precision and specificity. The two chromatographic methods were both precise and specific and gave the same assay results. Both methods separated p-aminobenzoic acid, N-(p-amino-benzoyl)-L-glutamic acid, 2-amino-1,4-dihydro-4-oxo-6-pteridinecarboxylic acid, 2-amino-4(1H)-pteridinone, and several unidentified impurities from folic acid.