The presence  of transfer RNA in the axoplasm of the squid giant axon.

Previous work has revealed that 4S RNA is the primary species of RNA in the axoplasm from the giant axons of the squid and Myxicola. This study shows that axoplasmic 4S RNA from the squid giant axon has the functional properties of tRNA. Axoplasmic RNA was charged with amino acids by aminoacyl-tRNA synthetases prepared from squid brain. Tthe aminoacylation was prevented by incubating the RNA with RNase prior to running the reaction. The amino acid-RNA complex was labile at pH 9, which is characteristic of the acyl linkage between an amino acid and its tRNA. Aminoacyl-tRNA synthetase activity was also present in the axoplasm, primarily in the soluble fraction.


Carnitine deficiency: clinical, morphological, and biochemical observations in a fatal case.

A fatal case of carnitine deficiency is described. The patient had intermittent metabolic acidosis, fluctuating hepatomegaly, and progressive muscle weakness since 22 months of age. One of two liver biopsies revealed lipid accumulation in the hepatocytes, and a muscle biopsy at age 5 years showed a lipid storage myopathy. Type 1 fibres were the most severely affected. Satellite and vascular endothelial cells also contained abnormal lipid deposits. Quantitative electron microscopy demonstrated an approximately 50-fold increase in lipid material, and a twofold increase in mitochondria in myofibres. The muscle carnitine level was less than one-seventh of the lowest value encountered in 74 biopsies from non-weak or neuromuscular disease controls. The basic abnormality in this patient is assumed to be a defect in carnitine biosynthesis.


So-called neuronal ceroid lipofuscinosis. Neurophysiological studies in 60 children.

EEG, ERG, and VEP studies were carried out in 60 children with verified neuronal storage of ceroid/lipofuscin-like material. Comparing and contrasting the EEG/ERG/VER features of each child during the symptomatic phase of the disease, three distinct main groups could be recognised: (1) Progressive diminution in amplitude of the EEG and VEP beginning about the age of 2 years was seen in seven children, and all phasic cerebral activity was unrecordable at 3-4 years of age; the clinical onset with regression in skills began at 1-2 years of age; (2) Large amplitude irregular slow activity and polyphasic spikes appeared in 27 children in whom characteristic discharges were elicited at low rates of photic stimulation (grossly enlarged VEP); the clinical onset was around 3 years of age with an occasional seizure and some clumsiness; (3) Runs of slow wave and spike complexes were seen in the EEG of 10 children with a small or absent VEP; the clinical onset with visual failure began around 5-7 years of age. In the remaining 16 children, the EEG and the clinical features fell into much smaller groups, possibly of rarer type. The ERG became unrecordable at an early symptomatic phase in all 60 children. The present findings suggest that such umbrella terms as neuronal ceroid lipofuscinosis or Batten's disease, which imply a single disease entity, are misleading. Neurophysiological investigations can help in early identification of these separate conditions. When the biochemical basis of these disorders becomes fully understood a more rational nomenclature will be possible.


Diabetes mellitus in normal pressure hydrocephalus.

Seventeen of 33 patients (51.5%) with normal pressure hydrocephalus were discovered to have diabetes mellitus. This was significantly greater than the 12.1% incidence found in age-matched control subjects. The diabetes was not accounted for either by the patients' ages nor by their physical inactivity due to hospitalisation. Diabetes mellitus concurrent with normal pressure hydrocephalus may result from involvement of hypothalamic and brainstem autonomic structures by the expanding ventricles during the evolution of hydrocephalus.


Idiopathic normal pressure hydrocephalus-- a report of 73 patients.

In 1973 we reported results of ventricular shunting in 28 patients with idiopathic normal pressure hydrocephalus. The present report consists of a three year follow-up of the latter (series 1), and an additional 45 patients (series 2) are presented for further insight into the conclusions drawn from the original experiences.


Electrodiagnostic study in delayed facial palsy after closed head injury.

The time course of electrical reactions in this condition varied much from that after section of the facial nerve or after Bell's palsy. It was at least a week before denervation could be suspected in the latter conditions by electrodiagnostic methods. In post-traumatic delayed facial palsy we have demonstrated electrical reactions showing denervation at the time of palsy or even a few days before, and this is probably related to its pathogenesis. Denervation occurred in 82% of cases which is about double the incidence in Bell's palsy.


Anterior horn cell disease associated with pontocerebellar hypoplasia in infants.

Three sibs presented with an identical clinical picture of severe mental retardation, cortical blindness, and extensive peripheral paralysis of lower motor neurone type, and died before one year of age. In the one necropsied case, spinal cord lesions, indistinguishable form those of Werding-Hoffman disease, were associated with extreme hypoplasia and atrophy of the cerebellum, and with atrophy of the ventral part of the pons. No prominent abnormalities were found in the nerves sampled despite gross reduction of motor and sensory conduction velocities in two infants. It is proposed that this familial disorder is distinct from Werdnig-Hoffmann disease, and represents a further subtype in the heterogeneous group of the infantile muscular atrophies.


Ocular bobbing with extra-axial haematoma of posterior fossa.

A patient with a subarachnoid haematoma anterior to the brain stem demonstrated "typical" ocular bobbing. The absence of CNS parenchymal involvement is distinct from previously described posterior fossa lesions associated with this particular eye movement disorder.


Prosopagnosia: a clinical, psychological, and anatomical study of three patients.

Three patients with prosopagnosia are described of whom two had right occipital lesions. An analysis of visual and perceptual functions demonstrated a defect in perceptual classification which appeared to be stimulus-specific. A special mechanism for facial recognition is postulated, and the importance of the right sided posterior lesion is stressed.


Epileptiform syndrome in rats produced by injecting tetanus toxin into the hippocampus.

An epileptiform syndrome in rats produced by injecting small doses (a few (mouse)LD50) of tetanus toxin into the hippocampus is described. The animals had intermittent seizures, with at least a superficial resemblance to human epilepsy, for some weeks but they eventually recovered. They were hyperkinetic for several weeks after the injection of toxin, and showed intermittent aggressive behaviour. Control animals which received similar injections of tetanus toxin first neutralised with antitoxin did not have seizures, and their behaviour appeared normal. EEG recordings showed characteristic seizure activity. Histological examination of the site of injection showed very little morphological damage.


HLA antigens and myasthenia gravis in Japan.

Recent studies have noted an increased association of the histocompatibility antigen HLA-B8 with myasthenia gravis in Caucasian patients. The HLA types of 63 Japanese patients with myasthenia were compared to those of 271 controls. The present study was designed to assess correlations between HLA antigens, sex, age at onset, the presence of autoantibodies and thymic morphology. HLA-B12 was increased Japanese patients, especially females with early age at onset, and in addition it was significantly correlated with thymic hyperplasia. HLA-B5 was frequently found in the patients with thymoma. Statistically the most frequent haplotype found in this disease was HLA-A10-HLA-B12.


Histocompatibility antigens associated with motor neurone disease.

The distribution of histocompatibility antigens was studied in 44 patients with motor neurone disease (MND). An unusually high incidence of HLA antigens A2 and A28 was found, compared to a control population.


Urinary monoamine metabolite excretion in disorders of movement. Effects of amantadine and levodopa.

We have studied the urinary excretion of 1,4-methylhistamine (1,4-MeHm), 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in patients with Parkinson's disease, choreiform movements and essential tremor. The effect of amantadine on urinary excretion has been measured in each group of patients as well as the effect of levodopa in patients with Parkinson's disease. In patients with Parkinson's disease, excretion of 1,4-MeHm and HVA was significantly lower than in controls. Patients with choreiform movements had a reduced excretion of HVA but trends toward low levels of 1,4-MeHm and, in patients with Huntington's chorea, elevated excretion of 5-HIAA, were not significant. In patients with essential tremor, urinary excretion of the amine metabolities studied did nof differ significantly from controls. Administration of amantadine to patients with Parkinson's disease was not followed by increased excretion of monoamine metabolites except in those patients who were already receiving anticholinergic drugs. This increase is not significant and there was no effect in other groups of patients. These findings lend no support to the view that amantadine has a general amine-releasing action although there is limited evidence for such an effect in Parkinson's disease. In addition to the expected increase in HVA excretion, administration of levodopa to Parkinsonian patients was followed by significantly reduced excretion of 1,4-MeHm and 5-HIAA. However, if amantadine and levodopa were given together, excretion of 5-HIAA was still reduced, but that of 1,4-MeHm was normal. Levodopa may thus modify the turnover of histamine, which appears to be reduced in Parkinson's disease, and this effect may be modified by amantadine.


The effect of age on the nucleic acid content of slow- and fast-twitch muscle in normal and dystrophic mice and their litter mates.

RNA, DNA, and NCP content were measured in fast- and slow-twitch skeletal muscle of normal and dystrophic mice (HDM) and their littermates at ages 4 through 29 weeks. In normal and litter mate mice RNA and DNA content were far greater in the soleus than in the gastrocnemius while the RNA/DNA ratio and NCP content were greater in the gastrocnemius. In dystrophic mice, however, the differences between nuleic acid content of the 2 muscles were far less, apparently due to a proportionately higher content in the dystrophic gastrocnemius. Due to a proportionately lower ratio in the gastrocnemius, dystrophic RNA/DNA ratios for the 2 muscles were essentially the same. Age had a marked effect on the nucleic acid content of both muscles in all 3 mice types but to varying degrees. In the soleus, RNA and DNA content rapidly decreased until 9 to 10 weeks of age followed by a gradual decline. Soleus RNA/DNA ratios showed little change with age except in the HDM mice in which there was a significant overall decline. In the gastrocnemius, RNA content followed the same pattern but with a smaller decline in the younger ages. Age had no affect on DNA content in the normal gastrocnemius, but there was significant decline in the HDM gastrocnemius. RNA/DNA gastrocnemius ratios showed marked fluctuations in both normal and dystrophic mice but did not appear to be affected by age.


Asymmetries of the skull and handedness. Phrenology revisited.

Some of the asymmetries noted in cerebral computerized transaxial tomography (CTT) studies are reflected in the shape of the skull resulting most often in backward protrusion of the occipital bone on the left and a less striking forward protrusion of the right frontal bone. Asymmetries are less marked in left-handed individuals but the opposite features, i.e. forward protrusion of the left frontal bone and posterior protrusion of the right occipital bone, are more frequent in left handers than in right handers.


Microscopic analysis of early histopathological spinal cord alterations following trauma in normal and cathecholamine-depleted cats.

The progressive histopathological sequence over the first 3 hr after a 400 g-cm blunt injury to the spinal cord of catecholamine (CA)-intact and CA-depleted cats is described. Norepinephrine levels were measured in all animals. The experiments were designed to determine the role of CA in progressive hemorrhagic necrosis of the spinal cord by removing CA from one group of animals prior to trauma. A second group of CA-intact animals was subjected to identical experimentally-induced trauma. Upon analysis of the histopathological changes, it appears that the sequential nature of the development of hemorrhagic necrosis is both qualitatively and quantitatively similar in both experimental groups. The general conclusion is drawn that catecholamines in greater than normal amounts are present at the lesion site after trauma, but these catecholamines are probably not involved in the process of central hemorrhagic necrosis.


Correlation analysis of stimulus-evoked changes in excitability of spontaneously firing neurons.

1. Theoretical expressions for the cross-correlation function are described which relate the output spike train of a neuron to an input spike train. The cross-correlation function is related to a convolution integral of two functions: 1) a waiting-time density, which describes the probability of observing the next succeeding output spike given an arbitrary input; and 2) a conditional output autocorrelation function, which contains information related to the statistical properties of the output spike train itself, and to the carry-over of the effects of an input to subsequent intervals. 2. The primary synaptic effect appears in the cross-correlation function as a distorted version of the derivative of the PSP. Depending on the duration of the evoked excitability change, as compared to the mean output interspike interval, periodicities due to the spontaneous activity of the cell appear to a greater or lesser extent in the cross-correlation. 3. To estimate underlying excitability changes using correlation techniques, one must estimate both the cross- and the conditional output autocorrelation functions. In cases when the excitability changes are short and do not carry forward to subsequent intervals, the more readily estimated unconditional output autocorrelation can be used in place of the conditional correlation.


A determination of excitability changes in dorsal spinocerebellar tract neurons from spike-train analysis.

1. Responses of DSCT neurons to random electrical stimulation of peripheral nerves of the hindleg at group I intensity were studied using cross-correlation analysis of the output spike train with the stimulus. Three types of response were found: type 1 was due to monosynaptic activation of DSCT cells, type 2 resulted from inhibition of those cells, and type 3 was due to a long-latency excitation that was probably polysynaptic. 2. Most of the units studied responded to stimulation of both proximal and distal flexor and extensor nerves. The extensive convergence of afferent input on DSCT cells is much greater than has been observed previously, with type 2 and type 3 responses totaling 80% of the observed responses. We attribute this to the sensitivity of the analysis in detecting small changes in postsynaptic excitability. 3. The results of the study, particularly the derivation of postsynaptic excitability changes, generally confirm those of earlier work employing intracellular recording. 4. By varying stimulus rate and stimulus intensity in the group 1 range and simulating the resulting correlations, we conclude that excitability changes in DSCT cells are the net result of complex interactions involving excitation and inhibition. A summary of these findings is presented as a model for the minimum circuitry necessary to account for the observed behavior.


Microsurgical treatment of internal carotid artery aneurysms.

Seventy consecutive cases of internal carotid artery aneurysm were operated on utilizing the surgical microscope. There were three deaths (4.3% mortality), one of which occurred in a deeply comatose apneic patient. Fifty-nine patients (84%) had excellent results. Four (6%) had postoperative morbidity directly related to their operation; three of them were operated on within 2 weeks after subarachnoid hemmorrhage and had neurological deficits attributed to cerebrovascular spasm. The low morbidity and mortality rates are partially related to patient selection but also significantly influenced by improved surgical techniques made possible by the microscope and microsurgical instrumentation. It is the authors' opinion that microsurgery should be standard procedure for craniotomy for intracranial aneurysm.  It is suggested that future reported series of aneurysm therapy, regardless of the method of treatment employed, should be compared with the anticipated natural history.


Evaluation of brain function in severe human head trauma with multimodality evoked potentials. Part 1: Evoked brain-injury potentials, methods, and analysis.

Methods for obtaining multimodality evoked potentials, somatosensory, visual, auditory, and auditory brain-stem potentials in patients with severe head trauma are described. A method of analyzing abnormal multimodality evoked potentials (graded evoked brain-injury potentials) is proposed that defines the degree of abnormality of the electrophysiological data and expresses it simply in four grades per modality. Data from 20 normal subjects are given for comparison with the abnormal data obtained from 51 patients with head trauma.


An audible alarm for monitoring air embolism during neurosurgery.

The sensitivity of various monitors during experimental pulmonary air embolization was measured in five dogs. Changes in vital signs, electrocardiogram, Doppler sound, and end tidal CO2 were observed. An audible alarm was incorporated in the end tidal CO2 monitor. The results showed that a 0.01 cc to 0.02cc/kg dose of air triggered the Doppler consistently, but the changes in heart sounds were heard only transiently. The fall in end tical CO2 occurred at 0.5 to 1.0 cc/kg of intravenously injected air and was confirmed by pen write-out. The audible alarm device was constructed to sound after four consecutive breaths with preset percentage fall in end tidal CO2. The changes in vital signs occurred at doses of 4 to 8 cc/kg of air and death occurred at 8 to 10 cc/kg. The sound alarms was used in 30 patients during sitting craniotomies. Eight patients developed air emboli initially detected by transient change in Doppler sound. The alarm called attention to the fall in end tidal CO2 and confirmed the occurence of air emboli.


Management of craniopharyngioma in children.

The authors review 48 cases of craniopharyngioma in children treated during 25 years, 1950 to 1975. Complete excision of the tumor, attempted in 23 patients, was possible in 17. The authors advocate aggressive treatment aimed at complete excision of the tumor, using radiotherapy only when adherence of the tumor to the internal carotid artery precludes total excision, and symptoms recur.


Non-pneumococcal Gram-positive coccal meningitis related to neurosurgery.

Thirty-eight of 154 cases (25%) of bacterial meningitis seen by the authors during a 7-year period were due to non-pneumococcal Gram-positive cocci. Thirty cases (80%) resulted from neurosurgical manipulation; half of these were shunt infections and half were early postoperative complications. Only three cases (8%) occurred de novo in patients with presumably normal host defenses. Signs, symptoms, and laboratory data related more to predisposing factors than to infecting microorganisms. Fever, peripheral leukocytosis, abnormal cerebrospinal fluid (CSF), and positive Gram stain were the most reliable indicators of infection. Prognosis was good with antibiotic therapy and removal of CSF shunt equipment when present.


Experimental head injury in the rat. Part 1: Mechanics, pathophysiology, and morphology in an impact acceleration trauma model.

Impact acceleration was used to elicit cerebral concussion in the albino rat. The pathophysiological response and morphological damage from the concussion were studied in groups of animals. The animals were grouped according to impact velocity (6-11 m/sec), and the threshold and different degrees of the concussive response were established. The concept of concussion as primarily a neuronal, functional disturbance was confirmed. However, this reaction was readily influenced by respiratory and circulatory changes, and morphological damage. Defined reactions could be elicited in groups of animals according to impact velocity. Thus, the model appeared well standardized for further studies of concussion pathophysiology, expressed in terms of cerebral energy metabolism and blood flow.


Exerimental head injury in the rat. Part 2: Regional brain energy metabolism in concussive trauma.

A standardized model of acceleration concussion in the rat was used for the study of cerebral energy metabolism during the acute concussive reaction. Impact velocities of 7 and 9 m/sec were used, and the cerebral metabolic state was determined 1, 4, and 15 minutes after the impact. A concussive response could be sustained with a normal energy state in the tissue, but with the more intense reaction to a 9 m/sec impact, energy depletion usually occurred. At 1 minute these changes were most pronounced in the brain-stem regions. At 4 minutes the reactions were more varied but a progression usually occurred during this time, while at 15 minutes restitution was indicated. Hypoxia due to neurogenic pulmonary edema aggravated the state. The findings are compatible with a high metabolic rate during concussion, but progressive changes indicate the rapid appearance of complicating factors, including hypoxemia and probably also ischemia.


Experimental head injury in the rat. Part 3: Cerebral blood flow and oxygen consumption after concussive impact acceleration.

Cerebral blood flow (CBF) and oxygen consumption (CMRO2) were determined during timmediate posttraumatic period in rats subjected to concussive impact acceleration. According to previous studies an impact of 9 m/sec velocity elicited typical and marked symptoms of experimental concussion and often a prolonged comatose state, accompanied by cerebral metabolic signs of energy failure. During the immediate concussive response there was an increase of the CBF, followed within the next few minutes by a decrease to about one-third of normal flow, and then by a tendency toward normalization of flow 20 to 40 minutes posttrauma. Simultaneous measurements of cerebral oxygen extraction indicated an increase of the CMRO2 during the first minute. During the ischemic phase oxygen extraction increased but the lowest CBF values were only partially compensated for, and normal oxygen availability could not be maintained. The combined data, including cerebrospinal fluid pressure measurements, indicated primary cerebrovascular effects of the concussive trauma. These vasomotor effects may induce critical cerebral ischemia and thus profoundly influence posttraumatic cerebral function, and cause irreversible damage.


Rate of cerebral energy consumption in concussive head injury in the rat.

The metabolic rate was determined in the rat brain during the immediate concussive response to standardized impact accelerations of 7 and 9 m/sec velocity. In one series, the metabolic state was determined in freeze-clamped cortical and brain-stem tissue 20 seconds after the impact. The metabolic rate was calculated from the rate of energy depletion in the adjacent unclamped tissue during 10 seconds of total ischemia. The freeze-clamping procedure per se was shown to enhance the metabolic rate probably by inducing mechanical excitation. In another series, in situ freezing was used for tissue sampling in the same situation. A 10-second period of heart standstill induced a standardized period of ischemia. During the acute concussive response to impact acceleration at 7 m/sec velocity, there was an increase of the metabolic rate in the brain stem. A more intense concussive impact at 9 m/sec velocity further enhanced this reaction and also involved the cortex. It is concluded that the basis of the immediate concussive response is a mechanically elicited neuronal excitation. This may lead to energy depletion unless the increased metabolic demands are met.


Resection of a vertebral hemangioma after preoperative embolization. Case report.

Preoperative arterial embolization of a vertebral hemangioma allowed surgical excision of the vertebral body, restoration of normal anatomic continuity of the spinal canal, and improvement in myelopathy.


Pneumocephalus secondary to cerebrobronchial fistula formed by a ventriculoatrial shunt. Case report.

A case is presented in which the atrial tip of a ventriculoatrial shunt formed a fistulous connection with the bronchial tree in a child. This resulted in acute bronchopneumonia, pneumocephalus, and ventriculitis. Pneumocephalus was created by an artificial respirator forcing air along the shunt tract during treatment of bronchopneumonia. Sudden death was related to transtentorial herniation. The diagnosis of a cerebrobronchial fistula should be entertained in shunt patients with respiratory distress and radiographic pulmonary densities unresponsive to antibiotics.


The syndrome of acute central cervical spinal cord injury after gunshot lesion. Case report.

The authors describe a unique case in which a bullet was lodged in the spinal canal at the C2-3 level. The patient exhibited clinically the syndrome of acute central cervical spinal cord injury. The pathogenesis is discussed with reference to three similar cases in the literature.


Elephantiasis of eyelids following repeated craniotomy. Case report.

A case is reported in which craniectomy for removal of right frontal meningioma was complicated by porencephaly. A peculiar granulomatous area was found over the brain at reoperation for cranioplasty. Iodine solution was used to paint the reactive material under the scalp flap. Giant swelling of the isilateral eyelids gradually developed, ascribed to interference with lymphatic drainage from the eyelids. There was no communication between eyelids and cerebrospinal fluid spaces. The enlarged eyelids were removed by ophthalmic plastic surgery.


An intracranial complication of nasogastric intubation. Case report.

A case is presented in which a patient who had suffered severe facial fractures erroneously had a nasogastric tube placed in the intracranial cavity. It is believed that no such complication of nasogastric intubation has been reported previously.


Supplementation of a semipurified casein diet for catfish with free amino acids and gelatin.

Semipurified diets with casein as the sole protein source were supplemented with gelatin, arginine, cystine, methionine or tryptophan, and fed to channel catfish (Ictalurus punctatus) fingerlings. Increasing the arginine level from 1.1% to 1.7% of diet by the isonitrogenous substitution of gelatin for casein resulted in a significant enhancement of growth. However, the addition of free arginine, cystine, tryptophan or methionine to casein had little effect on growth or food conversion. These data substantiate a previous report that suggested catfish were similar to carp in their inability to utilize free amino acids.


Effects of a prolonged vitamin E deficiency in the rat.

Rats fed a vitamin E-deficient diet containing 10% "stripped" corn oil had reduced growth rate and elevated platelet count by 12 weeks of age, and a normocytic anemia with elevated reticulocytes by 16 weeks of age. After 5 months, rats became emaciated and developed kyphoscoliosis. Some rats developed skin ulcers and tremors, and mortality was high. Neuromuscular lesions included a chronic necrotizing myopathy and localized axonal dystrophy. There was also a selective activation of lysosomes in the central nervous system microcirculation. Liver ascorbic acid of deficient rats was the same as in those receiving vitamin E. Urinary excretion of p-hydroxyphenylpyruvate after a tyrosine load was also the same in deficient and control rats. It was concluded that neither vitamin C synthesis or utilization was affected the E-deficient rats.


Exclusion of pancreatic exocrine secretion from intestine in the pig: existence of a digestive compensation.

The apparent digestibility of a diet was studied over a period of 87 days after ligature of the pancreatic duct, in the growing pig. Sham operated pigs were used as controls. Feces and urine collections were made during three periods of 10 days each. Mean daily gain of sham operated pigs was higher (560 g/day) than that of pancreatic duct ligated pigs (421 g/day), throughout the experiment. Within the first period (15-24 days after ligature), the apparent digestibility of nitrogen was most affected (-35.6%) while that of energy decreased by 12.1% as compared to values obtained in sham operated pigs. Nitrogen retention was similar in all pigs. Between the 1st (15-25 days) and the 3rd period (78-87 days) after exclusion of the pancreatic secretion from intestine, the apparent digestibility of nitrogen increased by 20% and that of energy by 6%, which might suggest digestive compensation. At the end of the experiment, weights of empty small intestine and liver were significantly higher in the pancreatic duct ligated pigs. The origin of the digestive compensation is discussed.


Analogous effects of zinc deficiency and aspirin toxicity in the pregnant rat.

At or near term, zinc deficient pregnant rats are depressed and exhibit difficult and extended parturition with excessive bleeding. This investigation was designed to develop objective measures of this pathology and to apply these parameters to the assessment of possible interrelationships of zinc with aldosterone and the prostaglandins. Female rats were fed during gestation a low zinc diet based on soybean protein (less than 1 ppm Zn) or the same diet supplemented with zinc (100ppm). Some of the rats were treated with aldosterone or aspirin, a prostaglandin inhibitor. Following parturition, both body temperature and blood pressure were depressed in the zinc deficient dams. Bleeding time and blood loss were also increased. Plasma potassium value were slightly elevated, adrenal weights increased and thymus weights decreased. Aldosterone had no effect on the incidence of the postpartum illness: temperature and blood pressure were unchanged. Toxic doses of aspirin produced pathologic signs analogous to those of zinc deficiency, including extended gestation period, difficult and prolonged parturition, excess bleeding, and low blood pressure and rectal temperature. The results suggest a role for zinc in prostaglandin metabolism.


Influence of estrogen treatment on hepatic cystathionine synthase and cystathionase of female rats fed varying levels of vitamin B-6.

Diets containing 8, 4, 2, or 0 mg vitamin B-6/kg were fed to intact, female rats designated high-, medium-, low-, and deficient-diet groups, respectively. After receiving the diets for 2 weeks, each group was subdivided so as to receive scheduled subcutaneous injections of corn oil with or without estradiol benzoate (Es and NoEs rats, respectively). In experiment 1, rats were fed ad libitum and injections given daily for 2 weeks. In experiment 2, rats were pair-fed and injections given every other day for 3 weeks. Es injections contained 10 microgram and 20 microgram of estradiol benzoate in experiments 1 and 2, respectively. Hepatic cysthionine synthase (CStase) and cystathionase (CNase) activities were determined both with and without exogenous pyridoxal-5-phosphate (stimulated and basal activities, respectively). Regardless of estradiol treatment, the deficient-diet decreased food intake, weight gain, and the basal and stimulated activities of both enzymes with the exception of stimulated CNase activity in Es rats. Estradiol reduced stimulated CNase activity in the medium- and high-diet groups in experiment 1. In experiment 2, estradiol reduced basal CNase activity of all diet groups and reduced stimulated CNase of low- and high-diet groups. It had little effect on CStase activity.


Influence of dietary fat on fatty livers of choline-deficient rats.

Our purpose was to evaluate the influence of type of dietary fat on nature and severity of liver lipid changes induced in male weanling rats by low choline diets. Beef tallow, a blend of tallow and safflower oil (SO) each provided 48% of total energy value of a control diet and a low choline diet. Livers from choline-deficient rats fed tallow, blend, or SO diets contained approximately 4.5, 5, and 2.5 times as much lipid, respectively, as livers from corresponding control groups. Liver lipids from rats fed SO diets as compared with those from rats fed tallow diets contained lower percentages of saturated and monounsaturated fatty acids, and higher percentages of polyunsaturated fatty acids. Values for groups fed blend diets were intermediate, except for 18:0 and 20:4 in the control group. Choline deficiency resulted in significant increases in proportions of the predominant fatty acid(s) of the dietary fat in liver lipids (but not in fat pad lipids) at the expense of 18:0 and 20:4. Ratios of 16:0 to 18:0 in both liver and fat pad lipids were greater in choline-deficient than in corresponding control groups, probably reflecting greater fatty acid synthesis.


Effects of selenium and vitamin E deficiencies on reproduction, growth, blood components, and tissue lesions in sheep fed purified diets.

Three 2 X 2 factorial experiments were conducted with sheep fed purified diets to determine the effects of selenium and vitamin E on the incidence of white muscle disease (WMD) and blood components. All lambs reaching 6 weeks of age in the group receiving no vitamin E or selenium developed WMD lesions, whereas only a few lambs in either the +E - Se or -E + Se treatment groups developed these lesions. Plasma activities of creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase were significantly elevated in lambs receiving no vitamin E or selenium, whereas these enzyme activities in those receiving only selenium were non-significantly elevated. The enzyme activities in plasma of those on the +E - Se or +E + Se treatments were maintained at low levels, suggesting vitamin E alone is more effective in preventing WMD than selenium alone. The metabolic interactions of these essentials are discussed.


Effects of selenium and vitamin E on blood selenium levels, tissue glutathione peroxidase activities and white muscle disease in sheep fed purified or hay diets.

The effects of selenium and vitamin E on blood selenium levels and tissue glutathione peroxidase activities were determined in sheep fed purified and hay diets. A significant increase of blood levels of this element and tissue glutathione peroxidase activities was found in sheep given selenium as compared to those not receiving this element. Of the tissues examined, the highest glutathione peroxidase activity was found in the heart. Vitamin E had no influence on either the blood selenium levels or upon the tissue glutathione peroxidase activity. With hydrogen peroxide as the substrate, tissue glutathione peroxidase activity was not correlated with the incidence of white muscle disease. Evidence is presented to suggest that 0.1 ppm dietary selenium is not sufficient under some conditions to meet the physiological requirements for this element.


Valine requirement of the growing kitten.

The valine requirement of the kitten was studied using a crossover design with two groups of three weanling kittens. The kittens were fed a semipurified diet containing only free amino acids as a source of nitrogen containing 0.0%, 0.6%, or 1.8% valine. The mean +/- SE of the linear components of growth (g/day) of the six kittens were respectively:-13.8 +/- 1.7, 17.3 +/- 4.8, and 15.3 +/- 2.6. Corresponding food intakes were 26.0 +/- 3.9, 50.4 +/- 2.5, and 44.0 +/- 1.5. Nitrogen balance was positive with the same amount retained for the two valine-containing diets while nitrogen balance was negative for the kittens fed the valine-free diet. Plasms valine dropped markedly when the dietary valine was decreased from 1.8% to 0.6% (363 +/- 59 versus 66 +/- 13 nmole/ml), and was further decreased (33 +/- 13) when the valine-free diet was fed. It does not appear that the valine requirement of the kitten exceeds 0.6% of a diet containing 25% fat. These results support the hypothesis that the high protein requirement of the kitten is not a result of a high requirement for all the essential amino acids, but a result of a high "nitrogen" requirement.


Effect of supplementation of limiting amino acids on tyrosine toxicity in rats fed wheat gluten diets.

The effect of supplementation of limiting amino acids on rats fed a 10 or 20% wheat gluten diet containing 5% tyrosine has been investigated. Growth-limiting amino acids in a 20% wheat gluten diet were lysine and threonine. When rats were fed a 20% wheat gluten diet containing excess tyrosine, the addition of 1.0% lysine-HCl or 1.0% lysine-HCl and 0.4% threonine completely prevented the development of tyrosine toxicity, and was accompanied by a lowering of free tyrosine concentrations in plasma, liver and muscle. In rats receiving a 10% wheat gluten diet, lysine, threonine and methionine were limiting for growth. The addition of 1.0% lysine-HCl to the 10% wheat gluten plus 5% tyrosine diet failed to alleviate the tyrosine toxicity, but the supplement of 1.0% lysine-HCl and 0.4% threonine could partially alleviate the toxicity. The combined addition of 1.0% lysine-HCl, 0.4% threonine and 0.5% methionine was most effective. The free tyrosine concentrations in plasma, liver and muscle were lowered greatly by the supplementation of three limiting amino acids, but amounts of free tyrosine and phenolic metabolites excreted in the urine did not decrease with addition of these limiting amino acids.


Nutritional quality of rice protein compared with whole egg protein.

The nutritional quality of rice protein was compared with that of whole egg protein by slope ratio assay. Diets for each food at four levels of protein, 4, 6, 10 and 15% and a protein-free diet were given to male weanling rats of the Sprague-Dawley strain for 21 days. The slopes of the regression lines of the whole egg and rice groups calculated from the changes of body weight (Y in g/21 days) with nitrogen intake (X in g/21 days), including and (excluding) zero protein group were, respectively, Y=27.39 X-12.26 (Y=24.41 X-1.86) and Y = 13.86 X-8.06 (Y = 12.54 X +0.50). Assuming a potency of 100 for the egg protein, the relative potency of rice estimated from body weight gain with nitrogen intake was 51 (51). The values for rice calculated from body water gain and nitrogen retention with nitrogen intake were, respectively, 51 (47) and 46 (44). These values were compared with RNV of several varieties of conventional rice and high-protein rice.


An improved method for the purification of eggplant trypsin inhibitor.

The trypsin inhibitor in eggplant, Solanum melongena L., was isolated and purified by the improved method with the techniques of dialysis using acetylated cellulose tube and ion-exchange chromatography on DEAE-Sephadex. The final preparation was found to be homogeneous by disc and SDS-polyacrylamide gel electrophoresis. This inhibitor had the molecular weight of about 6,200, the pI value of 4.7, and furthermore characteristic amino acid composition lacking in tryptophan, histidine, valine and methionine. The trypsin inhibition data indicated that the purified inhibitor combined with bovine trypsin [EC 3.4.21.4] in the molar ratio of 1:1. These properties of this inhibitor were in agreement with those of the dialyzable eggplant trypsin inhibitor previously purified, indicating that the dialyzable and non-dialyzable inhibitors in eggplant are identical.


Identification and properties of reactive sites in protein capable of binding carbon dioxide in a gas-solid phase system.

In order to identify the functional groups which really contribute to the carbon dioxide gas adsorption by proteins, epsilon-amino groups of lysine residues of egg albumin were chemically modified with trinitrobenzene sulfonic acid to various degrees. About 60% of the total amount of carbon dioxide gas absorbed by solid egg albumin diminished by complete modification. The amount of carbon dioxide gas adsorbed by lysozyme, its hydrolyzates and gelatin hydrolyzates depended upon the lysine content, arginine content and average molecular weight. The good correlation was obtained between the amount of carbon dioxide gas absorbed and the total of lysine and arginine content of them. The ability of carbon dioxide gas adsorption by alpha-amino group of amino acids and oligopeptides was found to be developed by the elongation of the peptide chain of glycine and other amino acid, by the removal of alpha-carboxyl group of histidine and tyrosine to corresponding amines and by the esterification of alpha-carboxyl group of leucine with p-nitrophenol. These results clearly indicate that CO2 binding sites in protein in the gas-solid phase system are epsilon-amino, alpha-amino and guanidinium groups.


Tocopherol level in human fetal and infant liver.

This investigation was undertaken to decide if tocopherol is actually depleted in the fetus and newborn infant by measuring liver tocopherol level. First, a reliable assay method was established as follows. The colorimetric values obtained by Emmerie-Engel's principle from liver extracts which were eluted through a floridine column were corrected by using the ratios of the tocopherol band area to the ratios of the tocopherol band area to the total scanning values of TLC analysis by densitometry carried out simultaneously. The recovery of tocopherol added to the liver homogenate was always greater than 90%, as measured in this procedure. Thus, tocopherol levels were determined in the human fetal, infant and adult liver with this method. The levels were very low in the fetal liver even though they gradually increased throughout fetal life. After birth, a slight elevation in tocopherol levels was observed during infancy when compared with those in fetal life, but they were still one-third or less of the adult level.


Apparent effect of an azodicarbonamide on the lungs. A preliminary report.

This preliminary study calls attention to the possible pulmonary reactivity of inhaled finely ground azodicarbonamide to which small numbers of workers may be exposed. The conditions in this particular plant involving significant exposure to respirable dust in the mg/m3 range may occur in other plants handling these fine powders. Engineering controls are indicated to protect the workers. We hope that this report will stimulate more detailed studies to validate or refute these observations.


Aberration tolerances for visual optical systems.

The effects of aberrations on images formed by a total system, including the eye, are assessed in terms of modulation threshold, grating detectability, and modulation transfer functions. The effects of approximately one and two waves of third-order spherical aberration, coma, and astigmatism on the total system modulation transfer function are investigated using three-bar resolution targets and Ronchi rulings in two separate psychophysical experiments. The results of both experiments indicate that the experimentally determined system modulation transfer function is closely approximated by the theoretically calculated modulation transfer function of the total system optics (dioptrics included) in the presence of instrument aberrations. The data indicate that the eye accomodates of a "best focus" when spherical aberration and astigmatism (but not coma) are present in the instrument. The quantitative data are used to determine aberration tolerances for instruments that are designed for specific visual tasks and that employ simple targets similar to those investigated.


Saturation of colored samples at various levels of reflectance.

The dependence of saturation on the level of reflectance of colored surfaces was measured by numerical estimation and by matching judgments. Four sets of chromatic samples, one for each hue--blue, 460 nm, green, 510 nm, yellow, 580 nm, and red, 620 nm--within a range between 4% and 65% reflectance, were presented to the observers. The largest changes of saturation were observed at the high and low values of reflectance. The effect is more pronounced for the yellows than for the reds and greens, and relatively less apparent for the blues. For each hue, saturation grows faster at intermediate values of reflectance. The four families of saturation functions permitted us to draw a map of equal-purity contours. There are values of colorimetric purity for which saturation remains constant for all levels of reflectance.


Analysis of chromatic-adaptation effect by a linkage model.

Hunt suggested that an adaptation-dependent linkage in the visual pathway from the retina to the brain can explain the variation of saturation produced by change of adapting luminance. If variation of saturation is caused by change of linkage, this change must also be involved in chromatic adaptation to light sources that have different chromaticities. By considering the effective adaptation levels of receptors, the model is extended and formulated for application to prediction of chromatic adaptation. It is tested by use of experimental results for chromatic adaptation obtained by Burnham et al. Suitable selection of parameters that specify the state of linkage produces good predictions of the effects of chromatic adaptation.


Perceived saturation in complex stimuli viewed in light and dark surrounds.

Two similar complex targets, consisting of neutral patches ranging from white to black, were viewed, one in a dark surround and the other in an extended illuminated surround of 20% reflectance. Each target was viewed from a distance of three times its width, which is typical of picture viewing. The luminances of corresponding areas of the two targets were adjusted to produce equal apparent brightnesses and contrasts. Pairs of test colors of equal hues and apparent lightnesses and 2 degrees subtense were positioned successively within the pair of complex targets and were judged for relative color saturation. Under these conditions of equalized brightnesses, approximately the same purities were required for equal saturation in light-surround and dark-surround viewing conditions. These results, which differ from those reported for simple stimuli, are important in establishing aims for color reproduction.


Photoreceptor diameter and spacing for highest resolving power.

The maximum center-to-center angular spacing delta phi of photoreceptors tolerated for reconstructing the highest spatial frequency passed by a diffraction-limited pupil of diameter D is delta phi - lambda/D square root 3 when the photoreceptors are packed in a hexagonal array, where lambda is the wavelength in vacuum. This spacing gives the maximum signal-to-photon noise ratio when the inner segments touch. The mean luminance required for an eye to achieve its highest resolving power is independent of eye size, provided the retina is designed to sample the highest spatial frequency passed by the diffraction-limited optics.


Maturing neuroblastoma and ganglioneuroblastoma: a study of four cases with long survival.

A retrospective study of four tumours of the peripheral nervous system originally diagnosed as neuroblastomas or ganglioneuroblastomas has been made. The patients have all survived since the original diagnosis. Evidence of residual tumour was seen only in one patient, and was associated with evidence of increasing histological differentiation over a period of time. Maturation of primitive cell types is known to alter the prognosis of neuroblastic tumours. It is suggested first, that even minimal evidence of maturation indicates a better prognosis. Second, that evidence of maturation may be uneven, small areas occurring in otherwise totally undifferentiated tumours, or, immature areas remaining even in apparently benign fully mature tumours; if these areas show maturation the prognosis remains good and the tumour should not be confused with a composite ganglioneuroblastoma. Third, that maturing tumours may behave in a malignant fashion, invade and metastasise, but but with maturation of the primary tumour and its metastases the ultimate prognosis may be better than the initial behaviour suggests.


The Schistosoma mansoni egg granuloma: quantitation of cell populations.

Granulomas were induced by the intravenous injection of eggs of Schistosoma mansoni into the lungs of mice which were either unsensitised, sensitised by prior intraperitoneal injection of eggs, or naturally infected with S. mansoni. At various time intervals after egg injection (8, 16 and 32 days in unsensitised mice; 4, 8 and 16 days in sensitised mice; and 8 days in mice infected for 4, 8 16 and 24 wk) the lungs were removed from groups of mice and were placed in a Waring blender at low speed. Complete intact granulomas were isolated, the lesions were dispersed with collagenase and pronase and the cell populations quantified and classified as eosinophils, neutrophils and mononuclear cells less than or equal to 12 or greater than 12 micron in diameter. Small mononuclear cells consisting almost exclusively of lymphocytes were the predominant cells initially, but eosinophils became the most common cell type, reaching a peak of 71% of cells in sensitised animals 16 days after injection. Large mononuclear cells remained relatively constant at about 30% of the total cells. Neutrophils neverreached more than 10% of cells. Sensitisation by a prior intraperitoneal injection of eggs led to an acceleration of granuloma formation. In infected mice, the granulomas with the largest cell counts were seen 8 wk after infection while the smaller granulomas in the mice infected for 16 or 24 wk confirm the previously reported modulation of this immunopathological reaction.


The mechanism of escape of plasma protein from small blood vessels in the mucosa of the small intestine of the rat.

A study has been made in rats of the relative rates of escape of plasma protein, measured by accumulation of Evans Blue, and of the large marker particle, HgS, into uninjured small bowel and into an area of intradermal injection of histamine. The rate of escape of Evans Blue, per unit mass of tissue, into small bowel and into an area of histamine-stimulated skin were found to be almost the same, but leakage of HgS into the bowel was only about 1/10 of leakage of the same tracer into a site of intradermal histamine injection. If it be assumed, as is generally accepted, that all the protein that leaks from histamine-stimulated vessels does so via gaps in vascular endothelium that are large enough to allow escape of large marker particles like  HgS, these findings show that only a small fraction of the protein that leaks into normal intestinal mucosa can escape via gaps, and that most of the leakage must occur by a route not permeable to particles of HgS. The findings give no indication of the nature of the alternative route for escape of protein.


Mannosidosis--pathogenesis of lesions in exocrine cells.

The finding of zymogen granules within lysosomal storage vesicles in pancreatic exocrine tissue in bovine mannosidosis may explain the widespread vacuolation of exocrine cells in this disease. It is uncertain if they enter the lysosomal system by the process of crinophagy but if so it would indicate that this regulatory mechanism could operate in normal exocrine tissue as well.


Vascular changes in the lungs of rats after the intravenous injection of pyrrole carbamates.

The effects on the lung of some synthetic compounds related to monocrotaline pyrrole have been studied and compared with those previously found with that compound. When injected into a systemic vein doses of pyrrole mono- and dicarbamate produced acute pulmonary oedema. Pyrrole alcohol and ethyl carbamate had no such effect and although furyl carbamate did not cause pleural effusion in rats it did so in mice. Like monocrotaline pyrrole, when injected into other vessels the pyrrole carbamates produced oedema in the region of the first capillary bed encountered. When colloidal carbon was injected intravenously after the pyrrole carbamates, carbon "labelling" was seen in both the post-capillary venules and the capillaries of the lungs. On the whole, venular "labelling" occurred before capillary "labelling" which was best seen when the carbon was injected more than 4 hr after the pyrrole. The distribution of the carbon as seen by electron microscopy is described. No "labelling" was seen after furyl carbamate. The effects of the synthetic pyrrole esters were similar to those of monocrotaline pyrrole. Although both the pyrrole carbamates were less active on a molecular basis they had a broader action on the pulmonary vasculature causing venular as well as capillary "labelling". To affect the lungs acutely the compound had to have the pyrrole ring structure and at least one ester side-chain.


Primary "flat" melanoma of the trachea.

A 47-yr-old woman, complaining of shortness of breath, had a chest X-ray showing a right parahilar mass and bronchoscopic examination disclosed a bluish flat lesion on the posterior wall of the trachea at the level of the fifth and sixth rings. Histological examination of the resected segment of trachea and an adjacent lymph-node revealed a primary tracheal melanoma with lymph-node metastasis. Review of five reported cases and of the literature on mucosal melanomas disclosed that the flat configuration of the tumour and the abundance of melanophages observed in the present case were unique. Possible relationships to mucosal melanosis and squamous metaplasia were briefly discussed.


Subcellular reactions to injury. I. Ultrastructural and biochemical investigations on the hepatic cellular damage produced by haemorrhagic shock in dogs.

The ultrastructural changes produced by haemorrhagic shock in hepatocytes have been studied in dogs. The associated biochemical and biophysical system alterations allow us to propose a unitary pathogenetic mechanism of the cellular injury based on oxygen deprivation and its effect on the function and structure of the cellular compartments.


Ultrastructural changes in rat lung arterioles in conditions of altered permeability.

By means of the colloidal carbon technique and injection of a barium-gelatin mixture into the pulmonary artery, the ultrastructure of lung arterioles in a state of increased permeability has been studied. In certain conditions pulmonary arteriolar permeability changes are frequent and the carbon particles adhere to the endothelium. Leakage of carbon into the interstitial space is observed only rarely. It is concluded that the pulmonary and systemic vessels have different patterns of response to altered permeability.


Vascular and glomerular changes in the ageing kidney.

Glomerular size, shape and number were examined in 44 human kidneys obtained at necropsy. Intrarenal vascular appearances were assessed histologically and by post-mortem angiography. The mean cross-sectional area of glomeruli varied nearly three-fold and glomerular number varied more than three-fold when kidneys from different adult subjects were compared but kidneys from the same subject resembled one another in glomerular size and number. A significant negative correlation existed in the adult between glomerular number and dimensions. Glomerular numbers in the few immature kidneys studied were similar to those in adult kidneys but glomeruli were smaller. Glomerular numbers tended to decline as age and severity of age-related vascular changes increased but correlation was poor. The possibility remains that glomerular involution in the senescent kidney occurs independently of events in the vessels. In men, but not in women, totally hyalinised glomeruli were observed more frequently with increasing age but their presence did not appear to be related to the degree of vascular change. In the senescent kidney, glomerular lobulations tended to disappear. This, together with glomerular loss, must result in a reduction in the area available for filtration. Assessments of total glomerular surface area should take account of glomerular shape and dimensions as well as numbers.


Ultrastructural alterations of APUD cells during nitrosamine-induced lung carcinogenesis.

Groups of Syrian golden hamsters were treated twice weekly for life with 1/10 LD50 DEN, or once weekly for life with 1/5 LD50 DBN. The sequential alterations in the ultrastructure of Apud cells in their bronchial lining were examined. Both carcinogens caused pronounced proliferation of this cell type during the initial treatment period. Thereafter, the formation of increasing numbers of filamentous bundles was observed in the cytoplasm of the Apud cells, whereas their neurosecretory granules decreased in number. The present findings suggest that after an initial phase of proliferation, the Apud cells undergo squamous metaplasia when treated with the two nitrosamines investigated.


Ultrastructure of hypoxic hypertensive pulmonary vascular disease.

Ten adult female Wistar albino rats were subjected to a sub-atmospheric pressure of 380 mm Hg for periods up to 35 days. Five control rats were also studied. The rats exposed to chronic hypoxia developed right-ventricular hypertrophy secondary to hypoxic hypertensive pulmonary vascular disease. Electron microscopy of control rats revealed individual smooth muscle cells immediately beneath the endothelium of pulmonary arterioles. On exposure to chronic hypoxia there was a hyperplasia of immature smooth muscle cells to form a distinct media between external and internal elastic laminae. The external lamina is thick and represents the original single lamina of the normal pulmonary arteriole. The inner lamina is thin and is newly formed internal to the smooth muscle cells. In hypoxic hypertensive pulmonary vascular disease there is no form of intimal proliferation so that the associated pulmonary hypertension is reversible.


Comparative study of the ultrastructural alterations in the pulmonary vessels of rats treated with alpha-naphthylthiourea (ANTU) and ammonium sulphate.

A comparative study of the ultrastructural changes in rat pulmonary vessels was made in two different situtations of increased vascular permeability: one caused by alpha-naphthylthiourea (ANTU) and the other induced by ammonium sulphate (AS). AS had a more destructive effect on the capillaries but showed little alteration in vessels larger than capillaries. ANTU provoked milder ultrastructural lesions but acted on capillaries, arterial and venous structures. In both conditions intravenously injected carbon particles adhered to the vessel wall and leakage into the interstitial space was rarely seen despite the presence of endothelial gaps. It was concluded that ANTU and AS provoke different ultrastructural alterations and that pulmonary and systemic vessels react differently when undergoing changes in permeability.


Long-term results of superficial defects in articular cartilage: a scanning electron-microscope study.

Superficial defects produced in rabbit articular cartilage were studied with the scanning electron microscope over a period of 2 yr. It would appear that at first a new layer of matrix forms on the injured surface but that this is abraded away by joint movement so that even after 2 yr the defect does not heal. In some instances the general articular surface developed superficial fissures, deep ravines, and foci of fibrillation.


The morphology of the endocrine system in congenitally athymic (nude) mice.

The endocrine system (adenohypophysis, thyroid, adrenals, ovaries, testes) and the submandibulary salivary gland of both female and male congenitally athymic (nu/nu) B10LP mice at various ages post partum (2, 4, 6, 8 and 12 wks) were studied morphologically and compared with their heterozygous thymus-bearing (+/nu) littermates. The animals were held under conventional conditions. The adenohypophysis of male nu/nu mice showed a decrease in size of the acidophilic cells. In the thyroid glands a slight hyperactivity of the follicles was seen in both female and male nu/nu mice in comparison with the +/nu mice. No changes were observed in the adrenals. The ovaries of the nu/nu females showed degeneration in the follicles while the corpora lutea were absent or, if present, degenerated. In the testes of nu/nu mice only a slight retardation in spermatogenesis was seen at wk 4. In the submandibular salivary glands of the nu/nu males the normal sex-dependent presence of well-developed tubular structures was absent from wk 4 onwards. The results were compared with those described in the literature for athymic mice with another genetic background and for thymectomised mice. It was concluded that alterations in immunological reactivity in athymic mice are not necessarily due to changes in the immune system, but may also be dependent on changes in endocrine function.


Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats.

Paraquat was administered to rats by gavage or intravenously at doses which were approximately equitoxic (680 mu. moles/kh and 65 mu. moles/kg respectively) and the lungs examined by light and electron microscopy at intervals up to 48 hours. No significant changes were observed in alveolar endothelial cells at any of the time intervals studied. After intravenous administration the first ultrastructural changes were observed at 4 hr in the type I cells which were less electron dense and contained few organelles. At 8 hr these lesions were more marked and in some places the basement memebrane was denuded. Type II cells were also showing damage to mitochondria and loss of microvilli. After oral dosing, the type and sequence of changes was similar but the first changes were not seen until 22 hr. Intravenous injection of 0-03 micron carbon particles 1 hr before killing showed no significant leakage from the alveolar endothelium. This study provides no morphological evidence that the oedema of the lung caused by paraquat in rats is due to damage to endothelial cells. It appears that, following dosing by the two routes, the difference in interval between dosing and the development of lesions is due to the accumulation of paraquat. Lesions in type I cells therefore occurred when a certain concentration of paraquat is known to be present in the lung. It is suggested that a prime compartment into which paraquat is accumulated is the alveolar epithelial cell.


Osteoarthrotic articular cartilage lesions of the femoral head observed in the scanning electron microscope.

A topographical study of the articular surface of 21 femoral heads removed for surgery of osteoarthrosis was made using the scanning electron microscope. Sections of degenerate cartilage were pretreated with H2O2 and trypsin to reveal the collagenous framework. Torn and frayed collagen bundles were evident on all the specimens studied, the length of these bundles varying from 20 to 150 micron. The frequency of the bundles over the degenerate fibrous areas varied considerably, and bundle sizes ranged from 20 to 70 micron. The topography of a single femoral head removed from a rheumatoid arthritic was very much smoother, with torn fibre ends ruptured at the same level. Although the exposed bone was considerably "smoother" than the residual fibrocartilage, ruptured osteons and trabeculae revealed large voids in the surface which would presumably alter the lubrication and fluid flow characteristics of the functioning joint. The effects of these changes on joint tension and lubrication are discussed.


Fusion of macrophages following simultaneous attempted phagocytosis of glutaraldehyde-fixed red cells.

A model for the fusion of macrophages in areas of chronic inflammation in vivo has been presented which is derived from the associations of macrophage fusion in vivo and in vitro. It is suggested that in granulomata, where macrophages are closely packed in the presence of endocytogenic material, this material may on occasion attach simultaneously to more than one macrophage. Ensuing endosome margin formation may then lead to the endosome margins of one macrophage fusing with those of the other. By causing macrophages to phagocytose glutaraldehyde-fixed red blood cells in vitro under circumstances which more closely reflect in-vivo phagocytosis than the phagocytosis of the red cells by macrophages in a glass adherent monolayer, it has been shown that simultaneous attachment leads to macrophage fusion. It is suggested that giant cell formation in vivo in granulomata results from the process of simultaneous attempted endocytosis.


The identification and significance of early stromal invasion in papillary carcinomas of the urinary bladder.

The incidence of early stromal invasion in apparently non-invasive papillary carcinomas of the bladder has been investigated, using methenamine silver/periodic acid-Schiff stains (MS/PAS). It is shown that where there is some difficulty in making this assessment in haematoxylin and eosin stained sections, MS/PAS stains are helpful. It has also been shown that three of 44 non-invasive tumours show evidence of invasion at deeper levels in the paraffin block. Finally, contrary to expectations, the presence or absence of invasion could not be used as an indication of subsequent behaviour.


Organic fragmentation in pulmonary thrombo-emboli.

Organic fragmentation is a cell-mediated process whereby the periphery of thrombo-emboli is broken up into multiple tiny fragments lined by flat cells and separated by endothelialised clefts and spaces. The process was looked for in 238 lung emboli from 107 subjects and was observed in 45 emboli (41 subjects). The true incidence is much higher since fragmentation is preceded by the surfacing of emboli by flat endothelial cells. Among such emboli its frequency was 41%. Fragmentation can involve emboli of all sizes though it is most frequent and extensive in small ones. The process is important for the resolution of emboli and helps the canalisation of the embolised arteries. It reduces the size of emboli and may also undermine mural attachments and thereby lessen the extent of anchoring to the vessel wall. The mechanism of fragmentation and the origin of the cells responsible are discussed.


Neonatal lactic acidosis and renal failure: the role of peritoneal dialysis.

Lactic acidosis accompanied by acute renal failure in the newborn period was studied in two infants with circulatory insufficiency and hypoxia. Peritoneal dialysis was necessitated by  anuria and serum potassium concentrations of 12.0 and 8.9 mEq/1. Plasma lactate concentration was 35 and 50 mM/1 and blood pH 7.23 and 7.18, respectively, at the time dialysis was instituted. Because of the uncontrollable anaerobic metabolism in these two patients, and the attendant inability to metabolize lactate, the use of commercial lactate-containing dialysates as a source of base was shown to be ineffective in correcting the acidosis and hypothesized to cause a worsening of metabolic acidosis due to a loss of bicarbonate from extracellular fluid into dialysate. Stabilization or improvement in the metabolic acidosis occurred with the utilization of a dilaysate containing bicarbonate with a gradient favoring movement of bicarbonate into, and lactate out of, extracellular fluid.


A study of factors affecting blood pressure and angiotensin II in newborn infants.

Blood pressure has been measured using the Doppler ultrasonic technique in 144 infants in the first 11 days of life. Venous angiotensin II levels measured by radioimmunoassay were determined in 75 of these babies. Highly significant correlations were found between systolic blood pressure and gestational age and body weight. AII was inversely related to blood pressure and significantly related to birth weight. Babies with respiratory distress were found to be significantly hypotensive and to have markedly raised AII levels.


The lack of nurse-infant transmission of type B hepatitis in a special care nursery.

Twenty-four infants cared for by a nurse who developed acute B hepatitis with HBsAg present in her serum and saliva were examined for serologic evidence of hepatitis B virus transmission. None of the infants had HBsAg by radioimmunoassay or anti-HBc by complement fixation. One infant had anti-HBs whose transient presence was consistent with passive acquisition. Using sensitive serologic tests, no identifiable risk to newborn infants in a special care nursery could be documented as a result of exposure to a nurse who developed acute type B hepatitis during their period of care.


The effects of methylphenidate on the handwriting of children with minimal brain dysfunction.

Fifty children with minimal brain dysfunction who had handwriting deficits received methylphenidate or placebo under double-blind conditions. Twenty-six children (52%) showed improvement in hand-writing following treatment with methylphenidate for four weeks. One child receiving placebo had improvement in handwriting, but his handwriting improved further after he was switched to methylphenidate. In general, handwriting tended to deteriorate promptly when drug treatment was discontinued. Thirty-six patients (72%) receiving methylphenidate for four weeks were rated behaviorally improved by teachers; in contrast, seven children (14%) showed behavioral improvement following treatment with placebo. Improvement in attention and behavior, which was ascertained by the use of Conners' Abbreviated Teacher Rating Scale, did not always correspond with improvement in handwriting. Advances in handwriting skills following treatment with methylphenidate may have been directly related to improvement in fine motor coordination. Gains in handwriting were maintained for up to 26 months of follow-up in 21 children who received methylphenidate on a long-term basis.


Globin biosynthesis in sickle cell, Hb SC, and Hb C diseases.

The wide range of globin synthesis ratios reported in patients with sickle cell disease casts doubt on whether the presence of genes for alpha- or beta-thalassemia in combination with Hb S can be detected by globin synthesis studies. We have studied globin synthesis in 20 patients with Hb SS who had a mean betaA/alpha ratio of 1.05+/-0.04, similar to that of 28 control children. In nine of these patients the percentage of newly synthesized radioactive alpha-chains in dimer or monomer forms was 16.3%+/-1.3, also similar to the control subjects. The remainder of alpha-chain was in hemoglobin tetramer. In nine patients with Hb SC, the (non-alpha)/alpha ratio was 0.97+/-0.04, and the free alpha-chain pool radioactivity in four patients was 14.1%+/-4.2. In three patients with Hb CC, betac/alpha ratios were 0.99, 1.07, and 1.10. These results indicate that globin synthesis ratios and alpha-chain radioactivity in the free alpha-chain pool of peripheral blood of patients with Hb SS, Hb SC, and Hb CC have narrow ranges, close to those of nonthalassemic controls. The data provide a basis for detecting syndromes with Hb S or Hb C associated with alpha- or beta-thalassemia. This precise differentiation is important for clinical studies of severity in sickle cell disease and for genetic counseling.


Management of severe childhood hypertension with minoxidil: a controlled clinical study.

The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.


The mental health of children in an HMO program.

Collaboration between pediatricians and mental health clinicians in an HMO has provided a useful method of identifying and caring for the usual spectrum of developmental and situational disturbances in children and the associated parent-child conflicts. A social worker is included in the primary-care team in pediatrics; other mental health resources are available when indicated. In 1974, 5.7% of total visits and 8.9% of all children under 19 years of age were noted to have emotional problems. A follow-up study carried out early in 1976 disclosed that most of the observed emotional problems were resolved or quiescent.


Benign course of extreme hyperbilirubinemia in sickle cell anemia: analysis of six cases.

Since the approach to the management and outcome of extreme hyperbilirubinemia in patients with sickle cell anemia is not clearly defined, we reviewed our experience with marked hyperbilirubinemia in six children with sickle cell disease. Intrahepatic sickling (sickle hepatopathy) rather than hepatitis or biliary stones appeared primarily responsible for the extreme jaundice in at least four children and possibly in all six. Signs and symptoms were few, and laboratory abnormalities were not striking other than marked hyperbilirubinemia (total serum bilirubin concentrations ranging from 20.4 to 57.6 mg/dl with approximately one half conjugated). All of the children improved within days to weeks and currently are well, without recurrence of hyperbilirubinemia or evidence of chronic liver disease. The patients described here suggest that sickling within the liver, previously reported to be a serious and even fatal syndrome, usually is a benign and self-limited process.


Computerized tomography in the management of intracranial bleeding in hemophilia.

Computerized tomography was used to evaluate the severity of six episodes of suspected intracranial bleeding in four patients with hemophilia. In all instances the CT scan rapidly provided information on the extent and location of the intracranial hemorrhage. Results of the initial scan provided a rational basis for therapy, and subsequent scans were a noninvasive means of evaluating the effects of treatment. If available, computerized tomography is a valuable aid in the management of the hemophiliac patient with intracranial bleeding.


Nutrition and growth.

Longitudinal growth data on children who developed obesity during childhood reveal a distinct tendency for height gain to accelerate coincident with or after the onset of excessive weight gain. The magnitude of the relative height increment is related to the degree of overweight. Overnutrition accelerates growth, just as undernutrition retards it.


Osteopetrosis in children: a report of 26 cases.

We have observed 26 cases of osteopetrosis among 165,594 children hospitalized over a period of 10 years in the National Children's Hospital. The hospital serves Costa Rica, a country of nearly 2,000,000 inhabitants with 60,000 live births per year. All patients had characteristic roentgenographic bony changes. Among the early manifestations of the disease, nasal obstruction and an adenoidal expression were common. The facial appearance of the patient is characteristic. Serious complications of the disease are hematologic and neurologic disorders.


Potassium-renin-aldosterone relationships during the first year of life.

In order to gain insight into factors controlling aldosterone secretion during the first year of life, we studied the relationships between PRA, serum potassium, sodium, and serum aldosterone levels. While we found a dissociation during the early neonatal period, there was a high degree of correlation between serum aldosteron, PRA, and serum potassium by 3 to 12 months of age. This suggests that aldosterone secretion in the 3- to 12-month-old child, as in adults, is regulated by the circulating levels of potassium and angiotensin II.


Familial nephrosis, nerve deafness, and hypoparathyroidism.

Two male siblings with nephrotic syndrome, nerve deafness, and hypoparathyroidism are described. Each child, one at five years of age and the other at eight years, died in renal failure. At autopsy the parathyroid glands were absent in one child and hypoplastic in the other one. Two twin male siblings presented with similar findings and died at the age of three years. At autopsy their parathyroid glands were fibrotic, and glomerular basement membranes were thickened. This may be the first recorded association of familial nephrosis, nerve deafness, and hypoparathyroidism. The mode of transmission is compatible with autosomal recessive inheritance.


Effect of phototherapy on growth of low-birth-weight infants--two-year follow-up.

The effect of phototherapy on subsequent growth of low-birth-weight infants has been evaluated at two-year follow-up of infants from two separate controlled neonatal studies. Growth of weight, length, and head circumference in the treated infants of Group I was slower than that of control subjects. Growth was comparable in treated infants and control subjects in Group II, and the two control groups, although not concurrent were also similar. Infants whose heads were growing at a normal rate, even though below 2 SD from the norms, were developing normally. Only infants who had deceleration in rate of head growth were abnormal. It is unlikely that phototherapy was responsible for the slow growth patterns seen in Group I, since these patterns were not reproducible in Group II.


Possible urate nephropathy of the newborn infant as a cause of transient renal insufficiency.

Oliguric renal failure, bilateral renal enlargement, and hyperuricemia were noted in three term infants. The findings on intravenous pyelography and radionuclide renography were consistent with intratubular obstruction to urinary outflow in two of the infants. The onset of diuresis appeared to follow intravenous pyelography in these infants. Urinary urate crystalluria was prominent in each infant in the first few days after the onset of diuresis, during which normal serum urate concentrations and normal renal function were established.


Current controversies in childhood obesity.

The conclusions that one can state with assurance are remarkably few. Adiposity in children is best monitored clinically by the measurement of skin-fold thickness. The likelihood that obesity will progress from infancy to childhood to adult life is still questionable and may be more important in the individual child than as a significant cause of adult obesity. Behavioral and social factors pedominate in etiology, yet biologic factors, including genetic, are also involved. Behavioral and social factors are critical in the significance of obesity to the individual. Although there are definite disease hazards, they appear to be predominantly confined to the very obese. The best treatment appears to be prophylaxis, again heavily involving behavioral and social factors as well as the wide-spread distribution of sound nutritional information. When prophylaxis fails, the behavioral modification approach to therapy currently holds the greatest promise.


Correlation between gestational age, weight, or ponderosity and serum thyroxine concentration at birth.

Thyroxine levels were measured in cord blood sera from 2,1800 healthy infants born of "low-risk" mothers in Los Angeles. Variations of T4 with gestational age, birth weight, ponderosity (size related to weight), sex, and race were studied, as well as the variation of W and P with GA. Over the range of GA 30 to 47 weeks, serum T4 concentrations, W, and P each increase with GA, leveling off to approximately constant values from 42 to 47 weeks; the increases are 12, 66, and 20%, respectively. For a fixed GA, T4 increases with increasing W but is not correlated with P; W, GA, and their product are useful measurements for predicting T4, but P is not. Formulas for predicting cord T4 are given for possible use in improving computer-assisted screening programs for congenital hypothyroidism; mean T4 values (+/- I SD) are tabulated against W and GA.


Pancreatitis in children and adolescents.

Normal serum amylase values were established for the pediatric age group (47.7 +/- 28.6 mg/dl); these are higher than previously stated. Average serum amylase values increased with increasing age (r = 0.55). The three commonest causes of pancreatitis in 54 patients studied were drug induced (16), idiopathic (10), and traumatic (7). Prednisone was the most frequently implicated drug. Midepigastric pain and vomiting were the presenting symptoms in 75% of the patients. Serum amylase values were more than three times normal in 63.8% of patients; 17% of patients presented with normal serum amylase values. The typical patient received intravenous therapy for 5.4 days and was hospitalized for 9.4 days. Treatment with antibiotic and anticholinergic drugs did not alter mortality or morbidity rates. Mortality rate for acute interstitial pancreatitis was 17.5%, and for acute hemorrhagic pancreatitis was 86%.


Hyper-M-immunoglobulinemia in children with bronchial asthma.

Radial immunodiffusion was used to measure the concentrations of IgG, IgA, and IgM in the sera of 224 asthmatic children, ages 6 months to 14 years. IgM was greater than two standard deviations above age-matched normal values in 51% of these asthmatic subjects. Immunoglobulin profiles were repeated up to four years later in 29 individuals with elevated IgM and increased IgM synthesis was sustained in 14 of these asthmatic subjects. Serum IgE concentrations were elevated in 23 of 35 asthmatic patients. There was no statistical difference in mean IgE between asthmatic children with normal or increased IgM. The distribution of IgE in each group was similar. Only 10 of 224 subjects had an IgA concentration less than 2 SD below age-matched control subjects. The significance and possible mechanisms of hyper-M-immunoglobulinemia are discussed.


In vitro effects of fatty acids on serum-ionized calcium.

Ionized calcium was determined in vitro in human serum in relation to increased concentrations (0.32 to 10 mM) of free fatty acids. Serum iCa levels varied inversely and linearly with increasing FFA concentrations. It is suggested that the formation of Ca-FFA complexes at clinically attainable levels of FFA decreases iCa and that elevated serum FFA levels may be a factor in the development of hypocalcemia.


5-oxoprolinuria: biochemical observations and case report.

We have studied a patient with 5-oxoprolinuria who presented with hemolysis and metabolic acidosis as a neonate; he has had normal growth and development to one year of age. Compensated hemolytic anemia persists, and he requires alkalinizing agents for correction of acidosis. Biochemical studies have confirmed that a deficiency of glutathione synthetase is responsible for the 5-oxoprolinuria. Genetic heterogeneity was apparent on comparative study of glutathione synthetase kinetics in cells from two patients with this disorder. The consequences of the deficiency of glutathione synthetase, decreased intracellular glutathione, and overproduction of 5-oxoproline are discussed with reference to the possible cellular roles of these compounds.


Prolidase deficiency: report of a second case with quantitation of the excessively excreted amino acids.

The second documented case of prolidase deficiency is presented. Clinical manifestations include chronic otitis media and sinusitis, dermatitis, and splenomegaly. Prolidase is undetectable in the white blood cells of the patient and near or less than the lower range of normal in each parent. The peptide chromatographic pattern of the urine is similar to that of the previously reported patient with prolidase deficiency. The quantity of amino acids excreted in urine per 24 hours is at least three times that of the upper range of normal (of these same amino acids) for the patients age group. More than 80% of the total amino acids excreted are in peptide form. The proline-to-hydroxyproline ratio suggests that the dipeptides are the catabolic products of other proteins in addition to collagen.


Recurrent myoglobinuria and muscle carnitine palmityltransferase deficiency.

A 16-year-old boy with a two-year history of recurrent attacks of myalgia, muscle cramps without weakness, and myoglobinuria was shown to have a deficiency in muscle carnitine palmityltransferase. Serum concentrations of creatinine phosphokinase, serum glutamic oxalacetic transaminase, and aldolase were elevated. An electromyogram was consistent with a nonspecific myopathy as were microscopic and ultrastructural examinations of biopsied muscle. Venous lactic acid response to ischemic exercise was compatible with paroxysmal idiopathic myoglobinuria. Activities of muscle phosphorylase A and B, phosphofructokinase, muscle palmityl CoA synthetase, carnitine, and serum carnitine were normal as was the glycogen content. Activity of muscle carnitine palmityltransferase (2.7 microM/minute/mg protein), as measured by a spectrophotometric method and by radioactive assay, was significantly reduced when compared to normal control subjects (14.5 microM/minute/mg protein) and ischemic control subjects (13.8 microM/minute/mg protein). Muscle carnitine acetyltransferase (13.4 microM/minute/mg protein) was approximately 50% of normal control values (25.5 microM/minute/mg protein). This is the third reported case of myoglobinuria in a patient associated with a deficiency of muscle carnitine palmityltransferase activity.


Toxicity to bilirubin in neonates: infant development during first year in relation to maximum neonatal serum bilirubin concentration.

Neurologic and developmental performance during the first year of life was correlated with maximum neonatal serum bilirubin levels for 27,000 infants in the Collaborative Perinatal Project. The infants were grouped by race and by five birth weight/gestational age categories to control for the effect of these factors on hyperbilirubinemia and developmental outcome. Low mean eight-month motor scores and delayed one-year motor development were associated with serum bilirubin levels in the range of 10 to 14 mg/dl and above. This relationship was strongest for low-birth-weight/short-gestational-period infants. A persistent association of developmental outcome with hyperbilirubinemia was found over and above the variation of maturity within the birth weight/gestational age categories.


Development of anaerobic fecal flora in healthy newborn infants.

Stool samples from 196 healthy infants less than ten days of age were cultured to delineate bacterial colonization patterns of the intestine. By one week of age, isolation rates of Bacteroides fragilis and other anaerobic bacteria in term infants following vaginal delivery and formula feeding approach that of adults. Differences in gestational age, type of delivery, and type of feeding are associated with significantly different colonization patterns of anaerobic and aerobic bacteria in the first week after birth.


Quantitative nitrobluetetrazolium reduction by normal newborn monocytes.

The phagocytosis-induced metabolic burst of human newborn monocytes, as evaluated by their capacity to reduce NBT, was comparable to that of adult monocytes. The NBT reduction assay constitutes a simple method of ascertaining the functional capacity of human monocytes.


Intrapatient variability in theophylline kinetics.

Seven asthmatic children had repeat determinations of theophylline pharmacokinetic measurements over three- to nine-month intervals. Significant intrapatient variability was found in the theophylline clearance and t1/2, which determine the dosage regimen necessary to provide given average, peak, and trough theophylline plasma levels. Repeat clearance values were, on average, 52% different from the original clearances, with a range of -57% to +142%. A single determination of theophylline kinetic measurements in any individual patient cannot be used routinely to predict future theophylline dosage regimens for that patient.


A colobomatous optic disc anomaly and associated retinal detachement.

A case is presented of a two-year-old white female with an optic nerve anomaly and an associated retinal detachment. A unilateral colobomatous disc was noted to be surrounded by a chorioretinal pigmentary alteration in the form of an annulus. A clear zone with absence pigmentation ringed the more central gray-black area. The retinal vessels were noted to come directly out of the deeply colobomatous disc area and to run between the cystic convolutions of the adiacent retinal tissue. A surrounding area of retinal detachment extended for a distance of three disc diameters from the disc. This case is one of a few yet reported in the literature.


One hundred consecutive coarctation resections followed from one to thirteen years.

The technique of operative repair for coarctation of the aorta is now well standardized and the immediate surgical mortality has been lowered to less than 5% in most large series. Long term follow up, however, is only recently being reported. This paper describes the current status of 100 consecutive patients who underwent elective resection from 1--13 yr ago. There was only one operative death. In contrast with other reports, residual systemic hypertension is rare in the 97 survivors. These observations confirm that coarctation of the aorta can be repaired surgically with an acceptable operative mortality; the outlook of the survivors appears excellent.


Sector shaped membranous cataract.

A sector shaped membranous defect of the lens is described. Possible causes for the defect are discussed. An injury to a small area of the anterior layer of epithelial cells plus a localized rupture of the capsule occurring between the third and eighth months of development might account for this defect.


Modified Blalock shunts utilizing pericardial tube grafts.

In the last decade, 14 patients underwent an aorticpulmonary shunt for cyanotic heart disease, at which time the subclavian artery was either deemed too small or too short to function satisfactorily as a Blalock shunt. In each case a rectangular piece of pericardium was excised, rolled into a tube, and sutured down one edge to create a tube graft. One end of the graft was sutured to the stump of the subclavian artery near its takeoff and the other end was sutured end-to-side to the corresponding pulmonary artery. During the same period, 5 children had azygos vein grafts and 2 had Teflon grafts inserted to create a modified Blalock shunt. This article will discuss the indications, techniques, and long term results of aorticpulmonary shunts of all types, and more specifically the complications and long term results in patients where these grafts were used.


Surgical correction of pectus excavatum.

It has been observed that some patients who had correction of funnel chest deformity by methods which failed to provide fixed elevation of the involved sternal segment developed progressive sagging in later years in spite of looking good at the operating table. This has led to the adoption of a new technique of double sternal support. This procedure has resulted in 35 of 37 children (94%) being classified as excellent or satisfactory. This double support was initially established in 1959 by overlapping the upper transsected sternum while maintaining elevation of the lower end with a soft tissue sling of perichondrium and intercostal muscle. Beginning in 1961, a rigid bridge of rib or stainless steel bar was substituted at the lower end of the sternum. This has provided better support and the current preference of using the steel bar has been validated in this group of patients. The few disappointments were related to removal of the bar earlier than desired, failure to excise all the protruding sternal cartilage stumps or rib graft tips and inability to cover the lateral sternal edges with pectoral muscles. If possible, the steel bar should not be removed before 12 mo. When these pitfalls were avoided, the results were almost uniformly excellent. The wisdom of excising all depressed cartilaginous segments, as advocated by Ravitch in 1949, has been substantiated. A submammary transverse incision has provided an excellent cosmetic appearance. The morbidity has been low and the mortality zero. In spite of the absence of objective evidence of cardiopulmonary dysfunction, there seems to be an almost uniform improvement in appearance and in patient activity following successful correction of the funnel chest. The latter may be as much a psychological response as a physiologic one. The low morbidity, satisfactory long term results, and general improvement in the patient's body image and outlook on life indicate the need to offer correction of the severe pectus excavatum deformity to low risk children.


Spiral looping of retinal artery.

An isolated retinal vascular anomaly in the form of an arterial loop is presented in a 32-year-old male. This loop originated on the retina beyond the optic disc border and returned to the lower branch of the central artery on the retinal tissue after making six spirals. The retinal circulatory dynamics of this eye, defined by fluorescein angiography, was observed over a period of 12 years with no loss of function to the involved eye.


Peripheral uveitis in children.

The treatment of peripheral uveitis in the young patient requires close supervision. Early diagnosis of the inflammation will permit the ophthalmologist versed in the use of local, periocular, and systemic corticosteroid therapy to control the inflammation in these young patients and to preserve their vision. Treatment should be instituted when vision decreases to less than 20/40, and when optic nerve or retinal changes appear to be progressing. The use of general anesthesia in patients less than 14 years of age is necessary when they are treated with periocular injections.


Transtracheal drainage of lung abscesses in children.

Experience with three patients with primary lung abscesses indicates that transtracheal catheter drainage of lung abscesses is a safe and beneficial procedure in childhood. The ability to drain abscesses not easily reached percutaneously will promote emptying and collapse of the abscess and provide bacteriological information which will enable the physician to select the correct antibiotics.


Early recognition and aggressive treatment of gastroesophageal reflux following repair of esophageal atresia.

Twelve patients with gastroesophageal reflux following repair of esophageal atresia are presented. Reflux produced recurrent stricture, failure to thrive, repeated pneumonitis, and in one patient, respiratory arrest and nearly death. Treatment consists of positional therapy or fundoplication operation both of which seem less successful in this combination of lesions than with GER and a  normal esophagus. There was one death as a late postoperative complication of fundoplication.


The Vogt--Koyanagi--Harada syndrome in children.

Two cases of the Vogt--Koyanagi--Harada syndrome in children, a very rare disorder in this age group, are reported; one patient had the chronic diffuse type, and the other had neurologic symptoms and exudative retinal detachments. Various theories of causation of the syndrome have been proposed, including viral infection, sympathetic ophthalmia, and altered immunologic status, but the etiology remains obscure.


Subcutaneous reduction clitoroplasty.

Congenital clitoral hypertrophy should be corrected in infancy. Most surgeons perform a total clitroectomy or one of several kinds of clitoral recession procedures. There are some reasons for dissatisfaction with both of these alternatives. An operation in which the corpora cavernosum are resected subcutaneously and the glans sutured to the pubis preserves blood supply and sensation and results in a perineal appearance close to normal. The author has performed this operation infive cases of clitoral hypertrophy associated with adrenogenital syndrome and suggests a wider trial of procedure.


Intussusception in the 1970s: indications for operation.

Eighty-one patients with proven intussusception were treated at the Cincinnati Children's Hospital from 1970-1974. One died. Seven of these had ileo-ileal intussusception, all treated surgically. Seventy-four had colonic components of their intussusceptions. In 58 of these patients (78%), reduction was attempted at barium enema, successfully in 32. Hydrostatic reduction was abandoned and the patient operated upon when the intussusception was not pushed out of the colon, when barium failed to reflux into several loops of ileum, or when there was a large persistent filling defect in the cecum or terminal ileum. Primary operation without barium enema was done in 16 patients. The appearance of intestinal obstruction by abdominal x-ray seemed to give the best warning about the complicated, incarcerated, or gangrenous intussusception. Primary operation is, therefore, advised for the patient with intussusception if there is x-ray evidence of intestinal obstruction. The age of the patient and the duration of his symptoms do not seem important in this regard, except as they correlate with peritonitis or obstruction. For the patient without peritonitis or intestinal obstruction, attempted reduction of the intussusception at barium enema seems safe and effective, regardless of the patient's age or duration of his symptoms.