Habituation and dishabituation mediated by the peripheral and central neural circuits of the siphon of Aplysia.

The siphon withdrawal response evoked by a weak tactile (water drop) or light stimulus is mediated primarily by neurons in the siphon. Central neurons (abdominal ganglion) contribute very little since the response amplitude and latency are not changed following removal of the abdominal ganglion. Similarly, habituation and dishabituation of this withdrawal response are not different after removal of the abdominal ganglion, indicating that the peripheral neural circuit in the isolated siphon can mediate habituation itself, and thus has many of the properties attributed to central neurons. Response evoked by electrical stimulation of the siphon nerve habituate, depending upon the stimulus intensity and interval. These habituated responses may be dishabituated by tactile or light stimulation of the siphon. These results show that each neural system, peripheral and central, has an excitatory modulatory influence on the other. Normally adaptive siphon responses must be shaped by the integrated activity of both of these neural systems.


Electrophysiological properties of biventer cervicis muscle fibers of normal and roller pigeons.

Cable parameters, excitability characteristics, and contractile response to acetylcholine were measured in biventer cervicis muscles from Helmet pigeons, Racing Homer pigeons and Parlor (nonflying) Roller pigeons. Cable parameters for the three strains, were respectively: calculated diameter, 30.1, 42.5, and 37.3 mum; membrane resistance, 450, 556, and 386 omega-cm2; membrane capacitance, 4.2, 3.9, and 4.5 muF/cm2, and myoplasmic resistivity, 79, 185, and 116 omega-cm. Significant differences between excitability characteristics of Homer pigeon and Roller pigeon fibers were a 17% shorter maximal latency for spike initiation (P less than 0.025) and 24% lower rheobasic current (P less than 0.05) in Roller fibers. Dose-response curves of isolated biventer cervicis to acetylcholine revealed slight, but significant, differences between Helmets and Rollers. These are the first electrophysiological data from pigeon skeletal muscle and the first from any avian biventer cervicis. The biventer muscles of chickens contain mainly "slow" fibers, but our results show that pigeon biventer fibers have properties similar to the "fast" PLD fibers of the chicken. Furthermore, the existence of different myoplasmic resistivities for each strain of pigeons used in this study suggests the need for more careful determination of this parameter in electrophysiological investigations. Although our results show that Roller pigeon fibers differ from those of nonrolling pigeons in the respects described above, these differences are minor in comparison to the severe behavioral abnormalities of Roller pigeons. Some yet untested component of neuromuscular transmission may be directly involved in the rolling phenomenon, but the differences we report may simply be due to strain differences, muscle hypertrophy, or a more severe defect elsewhere in the nervous system.


Isolation and polymerization of brain actin.

The studies presented here confirm earlier reports that an actin-like protein is abundant in brain. However, when the traditional procedures for isolating muscle actin are applied to brain, many different proteins are extracted. Tubulin, a major protein in brain with properties similar to actin, is the major constituent. A method is described for isolating the "brain actin" to a purity of 90-95%. The isolation method begins with an extraction of bovine brain in low ionic strength buffer with ATP and sucrose. The extract is treated with NH4SO4, MgCl, and KCl and incubated  at 37 degrees C. A precipitate is formed which contains primarily tubulin and brain actin. Resolubilization of the brain actin is achieved with a low ionic strength buffer solution with sucrose and ATP. Further purification is accomplished by a cycle of polymerization-depolymerization. This "brain actin" shares with muscle actin the following properties: (1) Similar molecular weight and molecular charge as determined by SDS polyacrylamide gel and ordinary disc electrophoresis; (2) Polymerization to a filamentous form under the same conditions; (3) Contains 3-methylhistidine; (4) Vinblastine sulfate will induce filament formation.


Comparison of lipids in total brain tissue from five mouse genotypes.

Brain tissue from adult male and female mice of the C57BL/6J, C57BL/6J-AW-J, BALB/cJ, SJL/J, and DBA/2J genotypes was examined for brain weight, total protein, total lipid, cholesterol, phospholipid, plasmalogen, sulfatide, nonganglioside-glycolipid sphingosine, and ganglioside N-acetyl neuraminic acid, fatty acid, and sphingosine. No significant differences were found between sexes for any of these constituents. When compared to the overall average obtained for other animals, the DBA/2J, C57BL/6J-AW-J, and BALB/cJ mice contained lower quantities of plasmalogen and sulfatide compared to the overall averages obtained for the other genotypes. In addition, the sterol content in DBA/2J mice was significantly higher than the overall average value obtained for the other animals.


Alterations in the accumulation patterns of polyamines in brains of myelin-deficient mice.

Quaking mutants and jimpy mutants of mice have known deficiencies of myelination of the central nervous system, as well as lesser involvement of the peripheral nervous system. Both mutants also have altered polyamine synthesis and accumulation, particularly in the hindbrain and spinal column. The ratio of spermidine/spermine, which generally is higher in tissues with high rates of biosynthetic activity, was significantly lower in the mutants as compared to their normal siblings. In quaking mutants, 5 months of age, the spermidine concentration of hindbrain and spinal column was 60% that of controls. In contrast, the decreased spermidine/spermine ratio in jimpy mutants resulted from a marked increase in the spermine concentration in both forebrain and hindbrain. Alterations in the spermidine/spermine ratio could lead to reductions in the biosynthetic potential of the brain during development.


Cooperative interaction of glutamate and aspartate with receptors in the neuromuscular excitatory membrane in walking limbs of the lobster.

When applied to lobster muscle fibers, L-glutamate, L-aspartate, and combinations of the two amino acids can induce membrane depolarization. Under normal conditions, a quantitative analysis of the depolarization response or change in membrane conductance was precluded by nonlinearities in the voltage-current relationship of the membrane. By including gamma-aminobutyrate (GABA) in the bathing medium, the voltage-current relationship was made linear in the depolarizing direction over a range of 15-20 mV from the resting potential. However, a meaningful examination of the increase in membrane conductance caused by glutamate and aspartate was still not possible. Therefore, the depolarization responses caused by the excitatory amino acids were taken as a quantitative reflection of receptor activation in the excitatory postsynaptic membrane. In the presence of GABA, aspartate by itself, at concentrations up to 10 mM, had little excitatory activity, whereas glutamate effected an appreciable membrane depolarization at concentrations of 0.1 to 0.2 mM. Aspartate, at concentrations which exhibited no activity alone, markedly enhanced the excitatory action of glutamate. Aspartate shifted the glutamate dose-response curve to the left, but did not appear to affect the maximum depolarization response elicited by glutamate. These observations are consistent with the concept that aspartate increases the affinity between glutamate and the glutamate binding sites. Limiting slopes of log-dose versus log-response curves for the excitatory action of glutamate suggest that the interaction of glutamate with excitatory receptors is a cooperative process. The possibility exists that individual receptors contain multiple and distinct glutamate and aspartate binding sites. These results support the view that neuromuscular excitation in the lobster is mediated by glutamate and aspartate functioning synergistically.


Dissociation of field potential from neuronal activity in the isolated retina: failure of the b-wave with normal ganglion cell response.

The b-wave of the isolated rabbit retina was compared with the ganglion cell response to light before and after modification of the retina's incubating medium. Marked diminution of the b-wave, with no reduction in ganglion cell response, was observed under three experimental conditions: (1) following a short period of anoxia; (2) following a short period in 0.2 mM Ca++; (3) in a small percentage of preparations, simply as a result of prolonged incubation in control medium. In contrast, a short period in 50 mM K+ led to a parallel fall and parallel recovery of both responses. It is apparent that under selected conditions the field potentials which constitute the b-wave are poorly correlated with the retina's neural activity.


Effect of aromatic acids on protein synthesis in subcellular preparations from the rat brain.

The incorporation of [3H]phenylalanine, [3H]tyrosine, and [3H]tryptophan into protein and amino acyl-tRNA was studied in cell-free preparations from rat brain. Tyrosine and tryptophan inhibited the incorporation of phenylalanine into protein, and tyrosine inhibited the incorporation of phenylalanine and tryptophan into amino acyl-tRNAs. In most cases, homogentisate, phenylpyruvate, and phenyllactate inhibited the incorporation of phenylalanine, tyrosine, and tryptophan into protein and amino acyl-tRNAs, and the incorporation of phenylalanine into polyphenylalanine. All other protein amino acids, and phenylacetate, salicylate, and benzoate were wholly ineffectual. The results suggest that the formation of amino acyl-tRNAs may have been the step which was affected most by the inhibitors. The incorporation data at different concentrations of the aromatic amino acids were fitted to the simple Michaelis equation. Homogentisate and phenylpyruvate generally tended to reduce both Km and V in the incorporation of aromatic amino acids into protein and amino acyl-tRNAs, even if V decreased more than Km.


Content of amino acids in axons from the CNS of the lobster.

The contents of alanine, proline, glycine, GABA, glutamate, and aspartate were measured in four bundles of axons (designated areas A through D) from the circumesophageal connective of the lobster (Homarus americanus). The contents of these amino acids were also determined in individual axons within specific bundles and in the external sheath covering the circumesophageal connective. Within the nerve bundles the levels of aspartate were highest of the amino acids measured, ranging from 1.95 +/- 0.12 mumol/mg protein in area C to 7.55 +/- 0.54 mumol/mg protein in area B. On the other hand, GABA had the lowest value in the four bundles; its highest level was found in area C (0.083 +/- 0.006 mu mol/mg protein) and the lowest in area B (none detected). The content of glycine ranged from 1.63 +/- 0.14 (area C) to 2.52 +/- 0.32 mumol/mg protein in area A; that for glutamate ranged from 0.390 +/- 0.019 (area C) to 1.01 +/- 1.03 (area B). The contents of alanine and proline changed relatively little from bundle-to-bundle. The content of aspartate was the highest of any of the amino acids assayed in individual axons (with diameters in the range of 40 to 65 mu) dissected from areas B and C. Glycine had the next highest content followed in order by glutamate, proline, and alanine. GABA was not detected in these axons. With the exception of GABA (which could not be detected), aspartate had the lowest level (0.066 +/- 0.017) and glycine had the highest level (2.00 +/- 0.498 mumol/mg protein) in the external sheath covering the the circumesophageal connective.


Formation of a functional adrenergic input to intraocular cerebellar grafts: ingrowth of inhibitory sympathetic fibers.

The intraocular transplantation technique was used to study the ingrowth of peripheral sympathetic adrenergic nerves from the iris into transplants of fetal rat cerebellum, and the possible function of these nerves. The transplants, grown in oculo for one-half to eight months, were analyzed by fluorescence histochemistry and electrophysiological techniques. Peripheral sympathetic adrenergic fibers from the iris were able to grow into the cerebellar transplants and arborize in a pattern similar to that in situ, appearing in all three cortical layers and the noncortical areas of the transplants. The density of visible nerves without pretreatment and after preincubation in 10(-6) or 10(-5) M alpha-methylnorepinephrine was comparable to mature rat cerebellum. The spontaneous discharge of the Purkinje cells in oculo was inhibited by microiontophoresis of norepinephrine (NE) and amphetamine in sympathetically innervated, as well as sympathectomized transplants denervated by ganglionectomy. The NE response was blocked by the adrenergic beta-receptor blocker MJ-1999. GABA also inhibited the Purkinje cell activity while glutamate accelerated the discharge. Parenteral amphetamine inhibited Purkinje cell activity in sympathetically innervated transplants, but was ineffective in denervated transplants. The Purkinje cell spontaneous activity was inhibited by electrical stimulation of the NE fiber input through the cervical sympathetic trunk. This inhibition could be antagonized by parenteral reserpine or the beta-adrenergic antagonist propranolol. The responses of the Purkinje cells within the transplants to drugs and transmitters mimic those of the adult rat in situ. In view of the fluorescence histochemical evidence for an ingrowth of peripheral sympathetic adrenergic fibers into the cerebellar transplants, and the results of stimulating the sympathetic trunk, it is suggested that peripheral adrenergic fibers may be able to establish functional connections with the Purkinje cells similar to the cerebellar adrenergic synapses normally formed in situ by fibers from the locus coeruleus.


Catechol-O-methyl transferase and monoamine oxidase activities in brains of mice susceptible and resistant to audiogenic seizures.

The activities of catechol-O-methyl transferase (COMT), monoamine oxidase (MAO), and a methanol forming enzyme were studied in whole brain homogenates and in livers obtained from DBA/2J, C57B1/6J, and F1 hybrid mice. DBA/2J mice are extremely susceptible to audiogenic seizures, whereas C57B1/6J mice are resistant to sound-induced convulsions. C57B1/6J mice were found to have significantly higher brain levels of COMT, while MAO activities were not different in animals of these genotypes. No methanol forming activity was detected in animals of either strain. No differences were found in hepatic activities of either COMT or MAO. Pyrogallol was shown to protect DBA/2J animals against audiogenic seizures.


Chorea, polycythaemis, and cyanotic heart disease.

Two cases of polycythaemic chorea are described, both of which were complicated by severe heart disease. The first was a child with patent ductus arteriosus and coarctation of the aorta causing severe cyanosis and secondary polycythaemia. Chorea began intermittently at an early age, becoming continuous by his fifth birthday. The second was a middle-aged male with tight mitral stenosis and a story of paralytic chorea in his teens. Polycythaemia rubra vera was eventually diagnosed two years after mitral valvotomy, some seven years after the onset of chorea.


Acute unilateral hydrocephalus resulting from oedematous occlusion of foramen of Monro: complication of intraventricular surgery.

Transcerebral removal of a small choroid plexus papilloma in the region of the foramen of Monro was followed within 48 hours by severe and progressive unilateral hydrocephalus. Acute unilateral hydrocephalus is a hitherto unrecognized complication of intraventricular surgery.


Effects of stimulus site on the pattern of skin conductance responses evoked from spinal man.

The spatial organization of sudomotor responses mediated by the cervically transected human spinal cord was investigated by recording skin conductance responses from the volar surfaces of the hands and feet of 10 patients after pulse trains applied separately to the skin of each extremity. Each stimulus site tended to be associated with a distinctive pattern of skin conductance responses.


Normal ulnar nerve conduction velocity across the thoracic outlet: comparison of two measuring techniques.

Comparison of ulnar nerve conduction across the thoracic outlet in 30 normal individuals using caliper and steel tape measurements is reported. A difference of 11.3 m/s was noted between the two methods (58.9 +/- 4.20 m/s by caliper; 70.2 +/- 5.20 m/s by tape). Comparison of these values with previous studies and the use of the opposite limb as a control are discussed. This procedure is of clinical importance in the diagnosis of nerve compression in the thoracic outlet syndrome.


Myotubular myopathy associated with cataract and electrical myotonia.

A case of myotubular myopathy is described which is unusual because of bilateral cataracts and prominent myotonic-like discharges on the EMG. The significance of these findings is discussed in relation to dystrophia myotonica.


Symptomatic Rathke's cleft cyst with amyloid stroma.

A patient with panhypopituitarism and visual field defects due to a Rathke's cleft cyst is presented. These cysts are commonly found in random pituitaries examined at necropsy, but rarely produce symptoms. Subtle endocrine deficiencies, however, may now be uncovered more frequently with modern diagnostic techniques. An unusual and unreported feature of this cyst was an apudamyloid stroma. This would imply that cells derived from the neural crest participate in the formation of the cyst. Recognition of these cysts at the time of operation is important in avoiding confusion with pituitary adenomas and unnecessarily aggressive treatment.


Note on the scoliosis of Parkinsonism.

A lateral deviation of the spine and a corresponding tendency to lean to one side was found in 19 and 21 consecutive unoperated patients with Parkinsonism encountered in an outpatient clinic. The direction of postural deviation correlated significantly with the laterality of the major signs and symptoms of Parkinsonism. The phenomenon appears to be analogous to the postural asymmetries produced in experimental animals by unilateral lesions of the nigroneostriatal pathways.


Cognitive deficits associated with chronic hepatic encephalopathy and their response to levodopa.

A battery of computer-based psychological tests given to seven patients with chronic hepatic encephalopathy showed them to be intellectually impaired, particularly on speed-based measures, as compared with general hospital patients and with patients with cirrhosis but without clinical or electroencephalographic evidence of encephalopathy. Two of the seven patients  in the latter group also showed evidence of cognitive impairment on some tests. The effects of levodopa were also evaluated by sequential assessment with these tests. Although there was some improvement in speed of performance on certain tasks and a suggestion of deterioration on other measures, there was little overall change. It is concluded that levodopa has an 'arousing' or antidepressant action and that its effect on intellectual functions is secondary to this alerting effect and is consequently dependent on the emotional and attentional status of the patient.


Precentral cerebellar vein in cystic astrocytomas of the vermis.

A peculiar abnormality of the precentral cerebellar vein seen only in cystic astrocytoma of the vermis is reported. Implications of this angiographic finding are discussed. The importance of posterior fossa angiography (especially venography) in the diagnosis of posterior fossa mass lesions is emphasized.


Traumatic disruption of the sacral root sheath.

An unusual case of sacral nerve root injury in a boy aged 6 years is described. Surgical intervention was not undertaken. Recovery of function was complete.


Ventricular size after shunting for idiopathic normal pressure hydrocephalus.

It has been presumed that idiopathic normal pressure hydrocephalus is due to obstruction. We visualized the ventricles in 19 patients subsequent to shunting. We found no consistent relationship between clinical improvement after shunting and reduction in ventricular size. This suggests that the positive effect of shunting in at least some instances is due to some other factor than reduced ventricular size.


Effects of psychotropic drugs on canine cerebral metabolism and circulation related to EEG--diazepam, clomipramine, and chlorpromazine.

The effects of diazepam, clomipramine, and chlorpromazine upon cerebral metabolism and blood flow were examined separately in 18 dogs. After the administration of diazepam or clomipramine, cerebral cortical oxygen consumption (CMRO2) decreased significantly by a maximum of 17% and 13% of control within 10 minutes and 15 minutes, and returned to control at 120 minutes and 90 minutes, respectively. Chlorpromazine, however, decreased by a maximum of 10% of control, a level which continued throughout the period of observation. It was observed that reduction in CMRglucose was followed by the reduction in CMRO2 at an interval during the early stages of CMRO2 depression. Diazepam produced a significant decrease in CBF accompanied by reduction in CMRO2, but neither clomipramine nor chlorpromazine had any effect on CBF in spite of reduction in CMRO2. Reduction in CMRO2 both with diazepam and clomipramine was accompanied by slow wave activities of EEG, but with chlorpromazine reduction in CMRO2 was accompanied with less pronounced slow wave activities. It was concluded that the three drugs examined were cerebral metabolic depressants.


Progressive familial myoclonus epilepsy.

Seven cases of progressive familial myoclonus epilepsy occurring in three families are presented. The patients were in different stages of the illness. The EEG was abnormal in all. It is suggested that these cases belong clinically to the Lafora bodies group. Nystagmus and optic atrophy, seen in one patient, have not been described previously. Myoclonic jerks did not respond to treatment with diazepam and ethosuximide.


Progressive myoclonic epilepsy due to Gaucher's disease in an adult.

A 39 year old Jewish male with a 22 year history of progressive myoclonic epilepsy was found to have Gaucher cells in his sternal bone marrow. The diagnosis of Gaucher's disease was confirmed by the demonstration of beta-glucosidase deficiency in fibroblasts. Although neurological involvement is extremely rare in adults with Gaucher's disease, this disease is another lipidosis which should be considered in patients with progressive myoclonic epilepsy.


Cutaneous afferent activity in median and radial nerve fascicles: a microelectrode study.

Cutaneous afferent activity was recorded in fascicles of the median and radial nerves of normal subjects using percutaneous microelectrodes. Multi-unit fascicular responses were dominated by activity in large myelinated fibres. Easily tolerated electrical stimuli evoked the full spectrum of fast and slow myelinated fibre activity but more intense levels were required to activate unmyelinated fibres. Correlation of the evoked potentials and the sensations reported by the subject suggested that fast myelinated fibres mediate tactile sensations. Pricking pain appeared with the activation of slow myelinated fibres. The only sensations induced by electrical stimuli were tactile or painful.


Fibre function and perception during cutaneous nerve block.

In awake human subjects, neural responses in radial nerves to electrical stimulation were recorded with intrafascicular tungsten microelectrodes. Changes in the activity of individual fibre groups during blocking procedures were recorded and correlated with simultaneous alterations in the perception of standardized stimuli. Light touch sensibility in hairy skin appeared to depend on the integrity of A-beta-gamma fibres, cold and pinprick on A-delta fibres, and warmth and dull pain on C fibres.


Motor unit fibre density in the extensor digitorum communis muscle. Single fibre electromyographic study in normal subjects at different ages.

A single fibre EMG study is presented from extensor digitorum communis muscle in sujbects aged 10 to 89 years. The average number of single muscle fibre action potentials generated by muscle fibres in the same motor unit within the uptake area of the electrode is used as a measure of the motor unit fibre density. The fibre density increases slowly during life with a faster progression after the age 70 years. The number of recordings indicating impaired nerve or neuromuscular impulse transmission increases at the same time. The findings indicate degenerative loss of motor neurones with aging, compensated for by reinnervation. The changes are relatively slight in the extensor digitorum communis muscle as compared with other muscles, permitting early pathological changes in this muscle to be recognized independently of age factors.


Spectrum of symptomatic brain-stem metastasis.

Three cases are presented which depict the spectrum of neurological disability attendant on intra-axial brain-stem metastases, ranging from fulminant decline to a more leisurely and less disabling course.  The rarity of primary glioma of brain-stem compared with brain-stem metastases in a general hospital population in the age group from 50 years and over is emphasized. Clinical deficit, certain ancillary findings, and response to therapy do not serve to separate brain-stem glioma from secondary brain-stem metastasis. The primary tumour may not be apparent when central nervous system symptoms appear or even for as long as two years after. It is recommended that the diagnosis of primary brain-stem glioma in the middle-aged adult be provisional and increasingly tentative over the age of 50 years.


"Pure" motor hemiplegia.

Attenuation of cerebral evoked responses after stimulation of the median nerve in the hemiplegic limbs suggested that an apparently pure motor hemiplegia in some patients may not have pure involvement of the corticospinal system. Frontoparietal metastasis, infarction in basis pontis and medullary pyramid, and occlusion of internal carotid artery in the neck resulted in pure motor hemiplegia in some individuals.


Comparative epidemiological studies of multiple sclerosis in South Africa and Japan.

Evidence is presented pointing to an increased incidence of multiple sclerosis having taken place in South Africa during the period 1964 to 1970 and in Tokyo, Japan, during the period 1966 to 1972. There is a possibility that these changes in incidence point to the introduction during the years immediately after the second world war, of an infective element-probably from a high-risk area-to Tokyo and South Africa. If this is so, it lends support to the theory of an infective basis for multiple sclerosis and that the suspected infection in prepubertal susceptibles may produce the symptoms of multiple sclerosis years later. Other factors relevant to multiple sclerosis such as environmental changes, improved diagnostic techniques, and susceptibility are discussed.


Visual failure from pituitary and parasellar tumours occurring with favourable outcome in pregnant women.

Very few cases have been reported of a successful outcome after relief by operation of severe visual failure from a pituitary or other parasellar tumour during the late stages of pregnancy. Two such cases are recorded here together with the obstetric features and follow-up studies of more than three years. Usually the deterioration of vi sion occurs in the latter half of the pregnancy and recovers rapidly after delivery, whether the onset of labour has occurred spontaneously or after induction. In subsequent pregnancies vision deteriorates at an earlier stage and becomes even more marked. Some cases are now occurring even in pregnancies induced by modern fertility drugs. The treatment of choice whenever vision is seriously threatened at any stage of pregnancy is a surgical attack on the pituitary, followed by suitable replacement therapy to ensure that the pregnancy continues.


Absence of papilloedema in cerebral tumors.

Fluorescein fundus angiography in 10 patients with a cerebral tumour of considerable size but without ophthalmoscopic papilloedema does not support the hypothesis that such patients have in fact minimal papilloedema. Absence of papilloedema in these cases usually indicates absence of persistently high CSF pressure.


On the tau-protein in cerebrospinal fluid.

128 cerebrospinal fluid samples were obtained. About 5 mul of each of the samples was subjected unconcentrated to agar gel electrophoresis. The remaining 44 of these samples were concentrated and the concentrates were electrophoresed. The proteins were stained. Analysis of the relative mobilities of the peaks makes two conclusions possible: the albumin in cerebrospinal fluid has the same electrophoretic mobility as purified serum albumin. The tau-protein possibly arises from transferrin by proteolytic breakdown, some products (such as the classical tau-protein) being less unstable than others (the intermediate peaks).


Measles antibodies and immunoglobulins in sera from patients with subacute sclerosing panencephalitis (SSPE) and from an infected ferret.

Cellulose acetate electrophoresis of sera from 2 patients with SSPE revealed a slow-moving and a fast-moving gamma-globulin band. The IgG fractions from sera were isolated by the combination of starch block electrophoresis, Sephadex gel filtration and isoelectric focusing techniques. The purity of each protein was tested by immunoelectrophoresis using a potent goat anti-whole human serum. The isolated IgG preparations were tested in HI, CF and N tests against measles virus envelope, measles virus nucleocapsid and whole measles virus, respectively. The results showed that isolated IgG fractions, having different electrophoretic mobilities, contained high titers of HI, CF and N antibodies, and these titers were proportional to the protein concentration of IgG. Although both IgG fractions appeared to show an increase of K-type chain, neither fraction was devoid of L-type chain. These results indicate that the homogeneous IgG bands observed in the SSPE serum were not monoclonal as they failed to show selective increase of one type of light chain and uneven distribution of measles antibody activity. These findings were compared with the results from a ferret, which developed encephalitis 2 months after intracerebral inoculation with cell-associated measles virus derived from the brain of an SSPE patient. The electrophoretic pattern of the ferret serum was similar to that of the human. High titers of measles HI and N antibodies were seen in the isolated slow- and fast-moving IgG's. The similarities observed in the human and ferret IgG's, with respect to homogeneous bands in electrophoresis and measles HI and H antibody activities, suggest that the ferret may be a useful animal model for studying the immune mechanism of SSPE.


The cortical form of subacute necrotizing encephalopathy of the Leigh type. A light- and electron-microscopic study.

The present paper is a clinico-pathological study of a 14-year-old boy with a chronic, progressive occipital syndrome for which he was operated upon. Postoperatively, metabolic acidosis developed. Pathological anatomy revealed spongy necrosis of the thalamus and corpora quadrigemina with the typical histological features of Leigh's necrotizing encephalopathy. Similar necrotic lesions had developed in the occipital cortex. At this level apart from the typical foci, cavitating necrosis was found as well as involvement of the smaller vessels of the pial circulation. Electron microscopy revealed vascular and glial changes suggestive of primary mesenchymoglial dystrophy. The histiocytes presented intracytoplasmic multiplication of lysosomes and their transformation into lipofuscin pigment. The changes demonstrate a juvenile cortical form of Leigh's subacute necrotizing encephalopathy.


Experimental mitochondrial myopathy produced by in vivo uncoupling of oxidative phosphorylation.

Two uncouplers of mitochondrial oxidative phosphorylation [2,4-dinitrophenol (DNP) and carbonylcyanide-m-chlorophenylhydrazone (CCCH)] were infused intra-arterially into a branch of the lower abdominal aorta of anesthetized rats over a 60-180 min period. An acute, severe, hypermetabolic state with systemic lactic acidosis and stiffness of the lower extremeities developed. In the plantaris muscles, by histochemistry, numerous "ragged red" fibers were present after the infusion. The "ragged red" areas presumably represented an absolute increase in mitochondrial mass in affected muscle fibers. By electron microscopy, linear inclusions were present in the intracristal space of many mitochondria. Simultaneous infusion of DNP and chloramphenicol, an inhibitor of mitochondrial protein synthesis, prevented the formation of ragged red fibers but not the intracristal inclusions. Infusion of relatively large amounts of oleic acid produced histochemical and electron-microscopic changes similar to those caused by the uncouplers. A possible pathogenesis of these reversible mitochondrial changes was discussed and their potential relevance to morphologic abnormalities of skeletal muscle mitochondria in human diseases was reviewed.


Changes of epidural pressures after experimental occlusion of one middle cerebral artery in cats.

Epidural pressures (EDP) were measured in 29 cats. Twenty cats had the left middle cerebral artery (MCA) occluded; pentobarbital was used for anesthesia for 10 of these, and halothane was used for the other 10. Two cats had sham operations: the MCA was manipulated but not occluded. Seven cats were used for testing the reliability of the EDP devices. EDP was measured successfully and was directly related to the swelling of the brain and to the size of the cerebral infarct resulting from MCA occlusion. Side-to-side pressure gradients were demonstrated in 7 cats with marked increases of EDP after occlusion; in these cats, EDP may have reflected the pressure of compressed cerebral tissue rather than the pressure of cerebrospinal fluid. Cats anesthetized with pentobarbital had greater increases of EDP and died before the end of the period of observation more frequently than cats anesthetized with halothane, probably because of respiratory depression and slower recovery with pentobarbital. Measurements of EDP may be useful for studies of the treatment of cerebral edema in experimental models of acute cerebral ischemia.


[Deoxyribonucleases in spontaneous and experimental tumors of the nervous system].

DNA- and RNA-concentrations, as well as in vitro activities of DNase I (EC 3.1.4.5), DNase II (EC 3.1.4.6), and DNase I inhibitor, have been determined in 63 spontaneous (man) and 22 experimentally induced (rat) nervous system blastomas of various types and of different degrees of malignancy. Generally, a distinct elevation of DNA concentrations and of the ratio (Q) of DNase II- to DNase I-activities has been observed when compared with control values. A statistically significant relationship could be demonstrated between increase of DNA concentrations and Q in experimentally induced neurinomas of rats as well as in human astrocytomas and glioblastomas. Whereas the increase of Q may be a biochemical expression of elevated DNA synthesis of tumour cells, no conclusions can be drawn as to the role of DNases in the process of malignant transformation.


Altered states of consciousness in disorders of daytime sleepiness.

Patients with daytime sleepiness present altered states of consciousness. The occurrence of these states impairs their professional, social and familial activities and may threaten life itself. The automatic behavior syndrome is characterized by continuation of mechanical activity and complete amnesia. Episodes lasting from a few seconds to several hours are correlated with repetitive micro-sleep periods. During cataplectic attacks, patients may have a meshing of reality with hallucinatory dream contents. Sleep-induced apnea may lead to abnormal movement and abnormal ambulation during sleep as well as hallucinations in the early morning. These altered states of consciousness must be considered as diagnostic indexes in differentiating epileptic syndromes from syndromes of daytime sleepiness.


Electron-microscopic observations on preterminal fibers in the oculomotor nucleus of the cat. With special reference to the relation between axon diameter and myelin thickness in mammalian gray matter.

Electron microscopy of myelinated fibers in main lateral cell groups of the cat oculomotor nucleus reveals the majority to have diameters of less than 3 mum, with more  than one-half less than 1 mum in diameter. The values of the ratio g (axon diameter/total fiber diameter) range between 0.58 and 0.88, with a mean of 0.74. There is no definite relation between g and fiber diameter. The morphological data are consistent with physiological data on preterminal conduction velocities in the oculomotor nucleus, and extend the dimensional analysis of myelinated fibers in gray matter, which has previously been confined to lower vertebrates, to the mammalian central nervous system.


Parabiotic reinnervation in normal and dystrophic mice. Part 1. Muscle weight and physiological studies.

A technique called parabiotic reinnervation has been developed. This technique consisted of suturing the sectioned peripheral end of the common peroneal nerve of a normal mouse, strain 129 ReJ +/+ to that of the distal stump remaining after sectioning that same nerve in a dystrophic mouse, strain 129 ReJ dy/dy. The animals were then parabiosed and allowed to recover and thus it was possible to innervate a dystrophic muscle with a normal nerve and vice-versa. This made it possible to test the hypothesis that a derangement of the trophic function normally exerted by a nerve on a muscle might be an element in the pathogenesis of muscular dystrophy in the adult mouse. Studies on the weights and isometric twitch characteristics of such parabiotically reinnervated muscles led to the conclusion that a derangement of the trophic function exerted by a nerve on a muscle is not an element in the pathogenesis of muscular dystrophy in the adult 129 ReJ dy/dy strain of mouse.


The occurrence and characteristics of non-myelinated neuromas within central nervous tissue.

Three cases are described in which neuromas composed of non-myelinated axons were present within central nervous tissues in areas of tissue destruction, together with neuromas of peripheral myelinated axons. The non-myelinated neuromas were larger than the myelinated, but contained very much fewer Schwann cells and less connective tissue fibers. It is suggested that they took origin from heterotopic non-myelinated peripheral nerves, just as the myelinated neuromas are thought to take origin from heterotopic myelinated peripheral nerves. The non-myelinated neuromas are very much less common than the myelinated neuromas, and the inference may be drawn that their nerves of origin may be very much less common, a malformational rarity. Because of their rarity, and the very limited proliferation of Schwann cells which follow their injury, these non-myelinated perivascular nerves are not likely to provide the Schwann cells which produce the regenerated peripheral myelin about some denuded but perserved central axons in myltiple sclerosis. These may take origin from multipotential primitive reticular cells within the central nervous tissues, as is consistent with the thesis perviously offered that Schwann cells are mesenchymal in character. It may also be inferred that any neurogenic control of cerebral circulation would be limited to an effect on the larger, extracerebral vessels in the subarachnoid space.


Do neurological signs occur in experimental allergic encephalomyelitis in the absence of inflammatory lesions of the central nervous system?.

Guinea pigs with paralysis or other severe neurological signs of experimental allergic encephalomyelitis (EAE) always exhibited typical histological inflammatory lesions. A few animals inoculated with either the encephalitogenic emulsion or only the control adjuvant emulsion had mild weakness or slowness but no histologic lesion. In some instances, these signs were explained by coincidental non-neural disease or trauma. Therefore, such mild clinical signs cannot be considered pathognominic of EAE. Reports from the literature suggesting that animals have developed clinical signs without histological lesions in EAE are considered invalid because of the nonspecificity of clinical signs, the occurrence of intercurrent diseases, the inadequacy or incorrect timing of histologic evaluations, and the lack of controls for specificity of the signs. There is no basis for the supposition that autoimmunity can cause major neurological signs in the absence of inflammatory lesions in the nervous system.


Fluorescence histochemical and ultrastructural studies of locus coeruleus of human fetal brain.

Catecholamine (CA) containing neurons and processes of the putative locus coeruleus (LC) of human fetal brain have been identified by the use of a modified Falck-Hillarp fluorescence histochemical technique and have been examined by light and electron microscopy. Fetuses were received as surgical specimens following abortion by hysterotomy. Estimated gestational ages varied between 11 and 18 weeks. Small granular vesicles (SGV) ranging from 450 to 650 A and large granular vesicles (LGV) ranging from 700 to 1050 A were identified in variable numbers along with agranular vesicles in the cell bodies and processes of neurons in the LC of all fetal specimens examined by electron microscopy. The occurrence of SGV in association with green fluorescence within the LC of a 12-week-old human fetus suggests a relatively early ontogenetic development of a storage mechanism for CA within this nucleus.


Quantitative ultrastructural studies of the axon Schwann cell abnormality in spinal nerve roots from dystrophic mice.

Lumbo-sacral spinal roots and the nerve to the medial gastrocnemius muscle (NMG) from normal and dystrophic mice were examined by quantitative ultrastructural techniques. It was demonstrated that, although many axons at this level were totally devoid of Schwann cells, totatl axonal numbers were approximately normal. Some axons in these roots were surrounded by Schwann cells but their myelin sheaths were abnormally thin. In addition, cells resembling oligodendrocytes were observed in the dorsal roots of the dystrophic mice. In contrast, Schwann cells and myelin sheaths were normal in the more peripherally situated NMG and the regenerative response of these nerves to crush injury was not significantly different from that of control nerves. Thus, the main abnormality of neural morphology in dystrophic mice is a localized absence of Schwann cells. Such a deficiency does not appear to have influenced axonal growth or the capacity of these axons to regenerate when crushed distally.


Chemotherapeutic implications of growth fraction and cell cycle time in glioblastomas.

Four patients received 3H-thymidine 4 to 7 days and vinblastine 4 to 6 hours prior to operation for recurrent malignant gliomas (three glioblastomas and one anaplastic astrocytoma). Tumor biopsies obtained at operation were fixed for routine histological studies and radioautography. The tumors' growth fractions averaged 0.28 with a range of 0.14 to 0.39. The tumor cell cycle time calculated in three patients had a mean duration of 57 hours with a standard deviation of 6 hours. The authors concluded that: 1) single short-term courses of cell-cycle specific chemotherapeutic agents alone will probably fail to achieve either significant reduction in tumor mass or dramatic clinical improvement; 2) cell-cycle phase-specific drugs should be administered to maintain effective blood levels over 2 to 3 days for maximal tumor cell kill. Tumor growth rate appears to correlate with the fraction of proliferating cells rather than the length of the tumor cell cycle. The scientific basis for combination drug and multimodality therapy is discussed.


Computer-assisted analysis of intraventricular pressure after mannitol administration.

The effect of prolonged mannitol infusion upon intraventricular pressure was investigated with the aid of a specially-designed automatic digital recording system; the data recorded were processed off-line by a minicomputer. The character of the pressure curves is thought to result from interaction between the mannitol effect and the observed system's shifting equilibrium position, which is caused by other factors. The character of the pressure curves prior to mannitol infusion must be taken into consideration in estimating the actual effect of the drug; the authors suggest that in certain cases it might be possible to decrease further the rate of mannitol administration. The advantages of statistical approach to the evaluation of intracranial pressure variations are discussed.


Oxygen tension in spinal cord gray matter during exposure to hyperbaric oxygen.

Adult female rats were exposed to 60 psig of 100% oxygen for 60 minutes. Oxygen tensions in the gray matter of the lumbosacral enlargement of the spinal cord, electroenecephalograms, electrocardiograms, and respirations were monitored before, during, and after the compression periods. Oxygen tensions were found to rise sharply to as high as 1050 mm Hg during compression and remained at significantly high levels throughout the entire hour of exposure. These data support the hypothesis that spinal cord lesions induced by exposure to hyperbaric oxygen are the result of excessive tissue oxygenation.


Miniature intravascular pCO2 sensors in neurosurgery.

In this study the authors compared PaCO2 measurements from a newly developed miniature intravascular pCO2 sensor for continuous on-line monitoring with those from a Radiometer bench instrument. In 10 patients undergoing craniotomy procedures, 84 paired comparisons were made. At the same time it was possible to follow continuously the trend of PaCO2 during deliberate hyperventilation, during the apneic period following hyperventilation, and during spontaneous respiration in the postoperative period. The comparisons showed an average difference in pCO2 of 1.62 +/- SE 0.15 torr. The apneic threshold for PaCO2 after passive hyperventilation was lower than in the awake patient. After the period of apnea no hypoxemia occurred. In the recovery room the PaCO2 increased and the PaO2 decreased. The latter decreased to subnormal levels in two patients more than an hour postoperatively.


Empty sella syndrome as complication of benign intracranial hypertension.

An empty sella was demonstrated on air study in five patients with the benign intracranial hypertension (BIH) syndrome. All patients had a protracted course and very high cerebrospinal fluid pressure; two required a shunt procedure. No patient had any endocrine symptoms or visual field defects but an air study was done to exclude a mass lesion in the sella region. Among the last 50 patients seen with the BIH syndrome, there were five cases of an associated empty sella (10%). In these cases, the empty sella is a probable consequence of the long-standing intracranial hypertension associated with a congenital deficiency of the diaphragma sellae.


Long-term survival of patients treated with BCNU for brain tumors.

The authors present three patients who, after excision and irradiation of their brain tumors, were treated with BCNU for recurrence. All three patients responded well and now are without evidence of tumor, 37, 30, and 36 months after BCNU was stopped. Although these patients represent only a small fraction of those treated with BCNU, they indicate the potential role of chemotherapy in the management of glial tumors.


Convexity leptomeningeal cysts diagnosed by scinticisternography.

The scintigraphic diagnosis of eight convexity leptomeningeal cysts is described; the cysts appear as a local collection of abnormal radioactivity, best seen at 48 hours. The correlation of the scintigraphic findings with clinical, radiological, and operative findings is discussed.


Neurological manifestations of primary rhabdomyosarcoma of the head and neck in children.

The authors describe four of their own cases of primary rhabdomyosarcoma (RMS) of the head and neck and summarize an additional 25 cases collected from the world literature, each manifesting neurological involvement. The need for early diagnosis and radical surgery is stressed.


Choroid plexus carcinoma.

The authors report a case of carcinoma of the choroid plexus and review the 22 cases reported since 1844 that adhere to the criteria for primary choroid plexus carcinoma. Two-thirds of the tumors are found in children and all of these are located in the lateral ventricles. In adults most of the tumors are present in the fourth ventricle. Differentiation of this neoplasm from papillary ependymomas, choroid plexus papillomas, secondary carcinomas, and "collision tumors" is discussed.


Focal porta hepatis scintiscan defects:  What is their significance?

A total of 537 consecutive liver scintiscans were retrospectively reviewed and 80 of them revealed suspicious focal decreased activity in the region of the prota hepatis. Postmortem, surgical, or biopsy correlation was obtained in 40 of these cases: 14 were pathologically negative; 9, cirrhosis or fibrosis; 10, metastases; 3, dilated bile ducts; 1, viral hepatitis; 1, hepatic laceration; 1, falciform ligament cyst; and 1, ruptured gallbladder with abscessed head of the pancreas. Thus, only 42% represented significant disease. Sixty-eight percent of the defects were seen only on the anterior scintiscan. Appearance of the majority of defects was nonspecific. Subjective grading of defects according to size and comparative decrease in density was not beneficial. Elevations of serum alkaline phosphatase, total serum bilirubin, and serum glutamic-oxalacetic transaminase were nonspecific.


"Cold" lesions on bone imaging.

Photon-deficient foci or "cold" lesions were demonstrated on 99mTc-polyphosphate bone imaging in eight individuals with various malignancies and one in sickle cell crisis. The bone radiographs of five of these persons failed to show corresponding bony changes at the time of the imaging. Most of the "cold" lesions observed on bone imaging were located in the denser and tubular bones. A postulate has been advanced regarding the factors that might influence the different gamma-imaging manifestations of radiographically demonstrable lytic lesions. The cases presented herein further emphasize the importance of recognizing the existence of "cold" areas in the images of bones and the need to place these in proper perspective when interpreting scans.


Acute pulmonary embolus associated with transient ventilatory defect: Case report.

In a patient with a clinical history highly suggestive of pulmonary embolism and angiographic evidence also indicative of embolism, the ventilation/perfusion pattern was that usually observed with parenchymal disease of the lung. The possible basis of this contradiction is discussed.


Accumulation of 99mTc-polyphosphate in two squamous cell carcinomas of the lung: Case report.

Technetium-99m-polyphosphate was found to accumulate in two squamous cell carcinomas of the lung. In one case, microscopy and electron microscopy failed to demonstrate calcification in the tumor. Possible mechanism(s) of accumulation of polyphosphate in nonosseous tissues was reviewed.


Pre- and postoperative myocardial and blood pool scans in a case of left ventricular aneurysm: Case report.

Myocardial perfusion scans (using 131Cs) and blood pool scans (113mIn) were performed on a patient before and after resection of a left venticular aneurysm. Although the huge aneurysm was revealed by preoperative scans, preservation of a significant mass of myocardium was evident. Postoperative scans show the reconstructed heart and the amount of residual damage. The operative findings confirmed the reliability of the scan information.


Hepatic artery traumatic aneurysm.

The diagnosis of intrahepatic aneurysm was suspected following radioisotope scintigraphic studies. A patient developed abdominal pain following blunt abdominal trauma. The scintigrams of the liver revealed a large intrahepatic defect and separation between lung and liver. Angiogram revealed a large false aneurysm of the right hepatic artery.


Liver scanning and the intrahepatic gallbladder: Case report.

Hepatic focal defects identified with 99mTc-sulfur colloid imaging procedures are nonspecific. This report describes a case of an ectopic gallbladder localized by cholecystography and 131I-rose bengal studies in a patient with cirrhosis and suspected intrahepatic neoplasm.


Plague and the gallium scan: Case report.

Inflammation in the right axillary lymph nodes and the meninges was detected by 67Gacitrate scans in an 11-year-old boy with Yersinia pestis infection. This case provides another example of 67Ga localizing to areas of infection, indicating potential utility in future cases of bubonic plague.


A new and superior adrenal scanning agent, NP-59.

The first synthesis of 131I-19-iodocholesterol had a 10-25% radiochemical impurity that was not iodide ion. This impurity has been identified as 6beta-131I-iodomethyl-19-nor cholest 5(10)-en-3beta-ol (NP-59) and has been synthesized. Tissue distribution studies with 131I-NP-59 in rats and dogs revealed a higher adrenal uptake and adrenal-to-tissue ratios compared to 131I-19-iodocholesterol, probably less in vivo deiodination, and superior adrenal images. A high uptake was seen in the adrenal medulla in addition to that in the cortex. Iodine-131-NP-59 is being evaluated for the early detection of adrenal-cortical disorders and as a potential scanning agent for detecting structural abnormalities of the adrenal medulla.


Sodium trimetaphosphate as a bone-imaging agent. I. Animal studies.

When used is conjunction with stannous ion and 99Tc, the nonsequestering, cyclic, trimeric phosphate anion, (P309)3-, introduced in the form of its sodium salt, exhibits admirable properties as a bone-visualizing agent as demonstrated by animal studies. These studies show that this combinatation is easily prepared reproducibly and, compared to the agents described in the recent literature (all based on sequestering phosphates), is at least equivalent for bone visualization while being considerably less toxic.


Relationship of chemical structure and solvent to in vivo scintigraphic distribution patterns of 11C compounds. II. 11C aminonitriles.

The preparation and scintigraphic evaluation of the distribution patterns in dogs of a series of structurally related aminonitriles labeled with 11C is described. Carbon-11-HCN was collected in water containing carrier NaCN following 22 MeV proton bombardment of 99% N2 and 1% H2 gas mixture for 1 hr. Ten 11C alphaN-alkylaminophenylacetonitrile hydrochlorides and 12 11C alpha-N-arylaminoarylacetonitriles were prepared from 11C-NaCN and the corresponding Schiff base, Ar-CH=N-R(Ar). Those 11C aminonitriles that were administered intravenously in aqueous solution showed some initial accumulation of activity in the liver followed by diffuse whole-body distribution and some small accumulation in urine. Aqueous insoluble 11C aminonitriles, which were administered intravenously in ethanol, ether, or DMSO, showed variable initial partial retention of activity in the lungs with prominent accumulation of activity in liver and excretion in bile. Several of these compounds showed pronounced and rapid accumulation of activity in the brain. Such activity in the brain was largely cleared within 15 min. Concentration of activity in the cerebrospinal fluid following clearance from the brain was 30 times greater than blood and equivalent in concentration to that noted in bile 18 min after intravenous administration of 11C alpha-anilinophenylacetonitrile in ethanol. These results suggest the possible correlation of regional brain uptake of activity of certain 11C aminonitriles with regional brain perfusion. Use of these or similar materials could permit assessment of brain tissue morphology followed by scintigraphic imaging of the bulk flow characteristics of cerebrospinal fluid.


Dosimetry of four heart-imaging radionuclides: 43K, 81Rb, 129Cs, and 201Ti.

In conjunction with research into the relative clinical suitability of radionuclides for heart imaging, estimates of the radiation dosimetry for 43K, 81Rb, 129Cs, and 201Tl were calculated. Estimates of absorbed radiation dose for the heart, kidneys, liver, lungs, testes, and whole body of the standard man were computed from published distribution data in rats via the MIRD method by assuming that the concentration in each organ per initial mean whole-body concentration is the same in rats and humans. The whole-body absorbed radiation doses from 81Rb, 129Cs, 201Tl, and 43K are 0.08, 0.17, 0.24, and 0.60 rads/mCi administered intravenously. In general, the organ doses from the four radionuclides follow the same order.


Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents.

Indium-113m complexed with polyfunctional phosphonates EDTMP (an analog of EDTA with carboxylic groups replaced by phosphate groups) and DTPMP (an analog of DTPA) showed preferential skeletal localization in experimental animals. Excellent images of the rabbit skeleton were obtained with both 113mIn and 111In complexes using the scintillation camera. In tissue radioassay using 85Sr as a simultaneous biologic standard, 113mIn-EDTMP compound showed higher concentration in the skeleton than the DTPMP complex and its bone uptake was comparable to that of 85Sr. Renal excretion was greater for the DTPMP complex (70% vs. 50% for EDTMP at 4 hr) and its blood clearance was faster than EDTMP. EDTMP was found to be the superior agent also to two other polyfunctional phosphonates, NTMP and HMDTMP. Because of the excellent skeletal localization with minimal soft-tissue levels, 113mIn-EDTMP may find use in bone scanning in humans wherever 99mTc bone-imaging agents are not available. These compounds may prove useful also in demonstrating acute myocardial infarcts, particularly for repeat studies after 99mTc bone agents have already been administered.


Radiometric identification of Streptococcus Group A in throat cultures.

Streptococcus Group A may be identified in simulated and patients' throat cultures by the selective inhibition of Group A streptococcus carbohydrate metabolism in the presence of specific antisera.


Selective uptake of 99mTc complexes and 67Ga in acutely infarcted myocardium.

The suitability of various radiopharmaceuticals (99mTc-tetracycline analogs, 99mTc-glucoheptonate, 99mTc-diphosphonate, and 67Ga-citrate) for use in imaging acute myocardial infarction was assessed by determining their biologic distributions in experimentally infarcted dogs. The highest infarct-to-normal myocardial concentration ratio was found with 99mTc-diphosphonate (27.9:1); the highest infarct-to-liver ratio was also found with 99mTc-diphosphonate (15.9:1). The infarct-to-bone ratio, however, was 0.4:1 with 99mTc-diphosphonate. There was an excellent positive linear correlation between blood-flow reduction and uptake of the radiopharmaceutical after a threshold reduction in blood flow with 99mTc-glucoheptonate and 99mTc-tetracycline. Technetium-99m-tetracycline accumulated only in infarcted tissue while 99mTc-diphosphonate was increased in both ischemic and infarcted tissue. Thus, 99mTc-diphosphonate has characteristics best suited for scintigraphic imaging. Since 99mTc-tetracycline accumulates only in infarcted tissue, however, this tracer more accurately defines the size of an acute infarction.


Detection and size estimation of acute myocardial infarction using 99Tc-glucoheptonate.

Twenty-seven patients with suspected acute myocardial infarction were studied by precordial scanning after intravenous administration of 99mTc-gluchoheptonate 2-48 hr after the onset of chest pain. Fifteen of the patients had clinically documented acute myocardial infarctions. Twelve of these 15 (80%) had areas of distinctly increased tracer uptake in the region of the heart. The three infarctions not identified by scan had peak serum CPK values of less than 300. In seven patients without infarction, no distinct areas of increased tracer uptake were found in the region of the heart. Five patients could not be classified as to whether infarction had or had not occurred. Three had abnormal scans, the significance of which is uncertain. Infarct size was estimated from the area of increased 99mTc-glucoheptonate concentration on scan and compared to peak serum CPK values. A linear correlation with a correlation coefficient of 0.77 was found. Technetium-99-m-glucoheptonate scanning was useful for the identification and size estimation of moderate- to large-size transmural and nontransmural acute myocardial infaractions.


Early 67Ga scintigraphy for the localization of abnominal abscesses.

Sixty patients suspected of having abdominal abscesses were evaluated by early and delayed 67Ga scintigraphy. The 67Ga scintigraphs obtained 6 hr after injection correctly localized 18 of 20 abdominal or retroperitoneal abscesses. An additional 13 patients with abnormal scintigraphs had clinically established infections. In no instance was an abscess or inflammatory focus present on delayed scintigraphs that was no evident on the 6-hr study. Two false-positive and two false-negative studies were recorded. Early 67Ga scintigraphy is warranted in patients with suspected abdominal abscesses.


A useful, objective criterion for determining the healing potential of an ischemic ulcer.

Peripheral vascular perfusion studies utilizing intra-arterial injections of radioactive microspheres were performed on 60 patients who had ischemic ulcers of the lower extremity. Point counting over the lesion and adjacent areas was utilized to qualitate and quantitate the relative hyperemia of the lesion. When this this relative hyperemia ulcers healed. In those without this degree of hyperemia only approximately 10% eventually had their ulcers healed without surgical intervention. Assessment of relative hyperemia of the ulcer bed is a useful, objective, prognostic indicator of the healing potential of an "ischemic" ulcer.


Usefulness of gallium scintigraphy in primary and metastatic breast carcinoma.

Gallium-67-citrate whole-body scintigraphy was incorporated into the evaluation of 125 patients with primary and metastatic breast carcinoma. A prospective analysis of these patients demonstrated gallium scanning to be limited in its corroborative value and of practical use only in detecting metastatic breast carcinoma in the mediastinum. Since the extent of tumor involvement is a significant prognostic factor, the gallium scan merits consideration for the detection of mediastinal metastases.


Avoidance behavior in vitamin B-6 deficient rats.

Pyridoxine deficiency was induced during the postweaning period in infant and young adult male rats and the effects on active avoidance and escape learning were studied. Five weeks of pyridoxine deficiency was sufficient to produce a deficit in active avoidance learning in the postweanling animals, whereas up to 10 weeks of deficient diet ingestion produced no effect on young adult animals. Mild motor impairment was produced in the young pyridoxine-deficient rats but the avoidance learning deficit could not be explained away on this basis, because a deficit in passive avoidance was also produced by the deficiency. Reversal of the deficiency by pyridoxine injection restored the active avoidance learning to normal within 1 week.


Effects of a high fructose diet on lipogenic enzyme activities in some organs of rats fed ad libitum.

The effect of a high fructose diet on lipogenesis was studied in rats. Male and female rats were divided into three groups and were fed a high carbohydrate diet ad libitum for 4 days: group 1 was fed a high cornstarch diet, group 2 was fed a high fructose diet without starvation, and group 3 was fed a high fructose diet after 2 days of starvation. The activities of lipogenic enzymes, i.e., glucose-6-phosphate dehydrogenase and malic enzyme were assayed in liver, adipose tissue, and small intestine. The lipid content of liver was also determined. On day 4, the lipid content of group 1 was about 45 mg, that of group 2 was about 70 mg, and that of group 3 was about 115 mg (female) and 145 mg (male) per gram of wet weight. Groups 2 and 3 showed significantly higher activity of hepatic malic enzyme than group 1. The activity of intestinal malic enzyme was highest in group 1 and not significantly different between groups 2 and 3. The malic enzyme activity in adipose tissue of females of group 3 was higher than that in either sex of the other groups.


Effect of maternal protein deprivation on in vitro neonatal intestinal function in rats.

Pregnant rats were fed a 27% (normal) protein diet or an 8% (low) protein diet. The in vitro absorptive capacity of the small intestine of the 2-day-old offspring of these animals was studied. The intracellular accumulations of a prototype amino acid (L-leucine) and sugar (D-galactose) were measured at initial velocity. The offspring of females fed the 8% (low) protein diet demonstrated a 32% decrease in the intracellular accumulation of leucine and a 19% decrease in the intracellular accumulation of galactose. The results are suggestive of a decrease in available transport sites in the offspring of protein-deprived females.


Lead poisoning in vitamin E-deficient rats.

Weanling male rats were fed either a vitamin E-deficient Torula yeast diet or the same diet supplemented with 100 ppm vitamin E for a period of 3 months. One group of animals fed each diet received 250 ppm lead in the drinking water, whereas another group of animals fed each diet received no lead in the water. Vitamin E deficiency per se had little or no effect on hematocrit value, reticulocyte count, spleen weight, or erythrocyte mechanical fragility in rats not poisoned with lead. On the other hand, the decreased hematocrit, increased reticulocyte count, and splenic enlargement due to lead poisoning were much more pronounced in vitamin E-deficient rats than in rats supplemented with vitamin E. The resistance to mechanical trauma of red blood cells from vitamin E-deficient lead-poisoned rats was much less than that of red cells from vitamin E-adequate lead-poisoned rats. Dietary vitamin E status had no significant influence on the increased mechanical fragility of erythrocytes from nonpoisoned rats caused by exposure to lead in vitro. These results suggest that vitamin E deficiency enhances the susceptibility of animals to the in vivo hemolytic effect of lead poisoning.


The Bronx study -- a trial of health care management.

We have reviewed our experiences in the Bronx study, which was a one-year pilot study by the New York Telephone Medical Department, aimed at expanding our involvement in the health care of company employees without duplicating what already existed in the community. We learned much from the study, chiefly in its evolution of a concept which we call Health Care Management (HCM). The three basic elements of HCM are (1) to deliver just enough care in-house to gain from the employee his authority to let us manage his health, (2) to document all of his health data confidentially, and (3) to work closely with community care resources in treating those clinical episodes needing their services. We learned that the two key ingredients of such a program are an adequate, comprehensive record system and thorough training of every member of our in-house HCM team. We are intensively developing both of these in preparation for incorporating HCM into our medical program throughout the New York company.


Filter model for lightness and brightness on different backgrounds.

A filter model is proposed to account for the effects of background luminance on perceived brightness or lightness of a target area. Special attention is focused on a crispening effect describable as a local increase of the rate of change of brightness with target luminance, as target luminance passes through the level of background luminance. The model is based on the assumption of competition, in the form of mutual-shunting-feedback inhibition, between target and surround.


Instrument myopia.

The basis for instrument myopia, the tendency to accommodate inappropriately while viewing through an optical instrument, was investigated in three experiments. The first demonstrated that the distance of a peripheral surround, analogous to a field stop, influences accommodation but that the magnitude of the effect cannot account for instrument myopia. The second experiment re-examined the hypothesis that perceived distance can affect accommodation. The data indicate that perceived distance is unlikely to influence accommodation and does not provide an explanation of instrument myopia. The last experiment tested the hypothesis that instrument myopia is a manifestation of the return of accommodation to an intermediate state of rest or equilibrium in the absence of an adequate stimulus for accommodation. Implications of the intermediate-resting-state hypothesis are discussed.


Night myopia and the intermediate dark focus of accommodation.

The phenomenon of night myopia, the tendency to overaccommodate for distant objects as luminance is decreased, results from the passive return of accommodation to an individually determined intermediate resting or dark focus. More generally, accommodation is viewed as a compromise between the subject's individual resting focus and the accommodative stimulus. Under optimum viewing conditions, accommodation tends to correspond to the distance of the stimulus, but is biased progressively toward the dark focus as the adequacy of the accommodative stimulus is degraded by decreased luminance. Control experiments suggest that optical aberrations are not major factors that contribute to this effect.


Articular and cutaneous prodromal manifestations of viral hepatitis.

The association of arthritis, arthralgia, and various types of skin rashes, as a prodrome to viral hepatitis, although well recognized in adults, has not been well described in children. In an 18-month period, three children presented with this serum sickness-like illness before the onset of evident liver involvement. In one case, the prodromal symptoms occurred four weeks before biochemical or clinical evidence of hepatitis. The SSLI tended to subside with the onset of clinically evident liver disease. Hepatitis B surface antigen (HBsAg, Australia antigen) was detected in the sera of two patients, but free antibody to the antigen was not demonstrable in either one. Serum complement levels were low during the prodromal phase and tended to return to normal value at the onset of extensive liver involvement. The diagnosis of viral hepatitis should be considered in children presenting with polyarthritis, polyarthralgia, and a rash (serum sickness-like illness) of uncertain etiology.


Myelofibrosis in children with chronic renal insufficiency.

During investigation of splenomegaly in a boy with chronic renal failure and osteodystrophy, bone marrow aspirates resulted in "dry taps," whereas biopsied material provided evidence that the marrow had been replaced by fibrous tissue. In a study of six other children with chronic renal failure, similar changes were observed. These findings suggest that the anemia of chronic renal failure may in part be a result of myelofibrosis, and the resulting reduction of functional bone marrow may limit the tolerance to immunosuppressive agents in patients who undergo renal transplantation.


Exercise-induced electrocardiographic changes in children with congenital aortic stenosis.

The relationship of exercise-induced electrocardiographic changes to severity of obstruction in congenital aortic stenosis was studied in 44 children. Twelve subjects, with ST segment depression of 1 mm or more lasting 0.08 seconds after the J Point, had left ventricular-aortic peak systolic pressure differences (gradients) ranging from 54 to 112 mm Hg. The remaining 32 children had less than 1 mm or no ST segment depression. Thirty-one of these had gradients ranging from 10 to 48 mm Hg and one had a gradient of 52 mm Hg. Vectorcardiograms, electrocardiograms, and chest roentgenograms were not useful in the identification of the severity of the lesion. The study suggests that children with severe gradients develop electrocardiographic ST segment changes with exercise, thereby helping to select those patients who should have catheterization studies to delineate the severity of the lesion. In those with a normal exercise test, cardiac catheterization may be safely delayed, but the exercise test should be repeated to identify those who develop progressive obstruction.


Hyperdibasicaminoaciduria, hyperammonemia, and growth retardation: Treatment with arginine, lysine, and citrulline.

A 9-year-old girl with hereditary dibasicaminoaciduria has been studied for three years. Initially, clinical features were: growth failure; anorexia and aversion to protein, spontaneous daily protein intake averaging only 10 gm; fasting and postprandial venous hyperammonemia; subnormal plasma concentrations of lysine, arginine, ornithine, and citrulline, with generalized hypermonobasicaminoacidemia; abnormally high renal clearances of lysine, arginine, and ornithine; and intestinal malabsorption of lysine and arginine. Intestinal absorption of citrulline, a precursor of arginine and ornithine, was normal. The patient was observed during four sequential 6-month periods as follows: no treatment (Period I); dietary supplement of arginine and lysine (Period II); dietary supplement of citrulline and lysine (Period III); no treatment (Period IV). During Periods II and III growth rate increased 3- to 4-fold, spontaneous protein intake increased 2- to 3-fold, and abnormalities in blood NH3 and the plasma aminogram were partially corrected. In most respects the citrulline plus lysine supplement was more beneficial than that of arginine plus lysine.


Combined portal and vena caval hypertension in Gaucher disease: The value of preoperative venography.

Portal hypertension in Gaucher disease is unusual; the seventh known patient with this complication is reported. Prior to portacaval shunting in this child, a localized obstruction of the inferior vena cava at the subdiaphragmatic level was demonstrated by caval manometry and inferior vena cavography. At autopsy, centrilobular hepatic fibrosis seemed to be responsible for the portal hypertension. Nodular enlargement of the right and caudate lobes of the liver was the cause of the caval obstruction; elevated caval resistance may have contributed to the portal hypertension and possibly was responsible for failure of a portacaval anastomosis. The value of preoperative inferior vena cavography in addition to arterial portography in children with portal hypertension is stressed.


A prospective search for congenital dermal abnormalities of the craniospinal axis.

Nineteen-hundred and ninety-seven consecutive term newborn infants were examined for cutaneous abnormalities of the craniospinal axis. Fifty-eight of the neonates (3%) had one or more abnormalities. The major findings included 28 (1.4%) deep dimples; 23 (1.2%) presumed sinuses; six (0.3%) skin tags,and one nodular mass. Fifty children were seen in follow-up at 4 to 12 months; in 40 infants the initial major finding persisted unchanged. Surgery has been performed on five children. One dermal sinus was found to terminate at the dura, three sinuses terminated at the coccyx, and a skin tag was associated with a fibrous band that extended to the coccyx. The management of congenital dermal sinuses is discussed.


Pneumonitis following inclusion blennorrhea.

A pregnant woman and her husband had proved chlamydial genital tract infections. She gave birth to a male infant who developed inclusion blennorrhea (inclusion conjunctivitis of the newborn infant). While on topical chemotherapy for his eye disease, the infant developed pneumonitis. Chlamydiae were recovered from his sputum at a time when conjunctival specimens were sterile. This finding raises the possibility that the agent of inclusion conjunctivitis may cause systemic infections in neonates exposed during passage through an infected birth canal.


Transplacental passage of maternal erythrocytes with sickling.

Sickled erythrocytes served as a marker for maternal blood in a cell transfer study of placentas from uncomplicated term pregnancies of women with sicklemia. The incidence of concurrent sickling in maternal and fetal blood was 100% in the 44 cases examined. Maternofetal passage of the erythrocytes was found four times more frequently in umbilical or chorionic veins (8.4%) than in arteries (1.9%). Deported chorionic villi were found in the veins in three of 44 cases but not in the arteries. These findings indicate fresh maternofetal leakage of blood during the third stage of labor.


Renal response of the lamb fetus to partial occlusion of the umbilical cord.

The role of the fetal kidney during impairment of placental exchange was studied in eight fetal lambs, intact in utero; a standard asphyxial insult for a period of 1 hour was produced by occluding the umbilical cord sufficiently to lower the fetal heart rate by 35 +/- 5 beats/min and the pH by 0.15 units. This asphyxial stress caused a fall in urine output from a control of 0.17 to 0.03 ml/kg/min and of glomerular filtration rate from 1.2 to 0.3 ml/min; release of the occlusion was followed by mild diuresis. The fall in urine output was accompanied by a rise in total primary solutes including  concentrations of electrolytes; this rise continued for 1 to 2 hours following the release of the occlusion. Because of the low urinary output during the period of occlusion, there was a fall in excretion of electrolyte; an increase in net acid excretion occurred only after the release of the cord. These experiments show that, although the fetal kidney is capable of contributing to elimination of acid following compression of the cord, there may be an associated net loss of water and electrolytes.


Intravenous diazoxide in acute poststreptococcal glomerulonephritis.

Twenty-six patients with hypertension secondary to acute poststreptococcal glomerulonephritis were treated by the rapid intravenous infusion of diazoxide. The average pretreatment systolic pressure was 159 mm Hg. Five minutes after administration, the average systolic pressure was 122 mm Hg (a 23% reduction). The average initial diastolic pressure was 104 mm Hg, which fell 5 minutes after diazoxide injection to 71 mm Hg (a 32% reduction). No hypotensive episodes were noted. Occasional episodes of nausea occurred. Concentrations of blood glucose increased after administration of diazoxide; however, no values were above 155 mg/dl. Diazoxide appears to be a safe antihypertensive drug that is effective in the treatment of hypertension secondary to acute poststreptococcal glomerulonephritis.


Sodium nitroprusside treatment of severe arterial hypertension in children.

Severe arterial hypertension in children constitutes a high-risk situation requiring rapid and effective therapy. We have assessed the clinical value of sodium nitroprusside as a rapidly acting antihypertensive agent. Twenty children admitted with hypertensive crises of renal origin were treated with intravenous infusion of sodium nitroprusside at an average rate of 1.4 mug/kg/min. Desired levels of blood pressure were reached in all patients within one to 20 minutes. Rapid improvement of cardiac failure was observed in all patients, and neurologic signs of distress disappeared in 16 of the 20 children within 24 to 48 hours of treatment, permitting substitution of oral medication. One patient died of cerebral hemorrhage without improvement of encephalopathy. There were no undesirable effects of therapy or deterioration of renal function in any patient.


Age-dependent dose response to gentamicin.

Serum gentamicin concentrations were measured 30 minutes after 140 intravenous doses in 60 children and nine adults with normal renal function. Distinct interpatient variation was observed but individual patients tended to have similar pharmacokinetics with repeated doses. Age had a significant effect in that mean peak serum concentrations were  1.58 mug/ml per 1 mg/kg dose in children between 6 months and 5 years, 2.03 mug/ml per 1 mg/kg in those between 5 and 10, and 2.86 mug/ml per 1 mg/kg in children 10 to 15 years of age. The mean calculated single dose of gentamicin necessary to achieve a peak serum concentration between 4 and 5 mug/ml is 2.5 mg/kg for  ages 0.5 to 5 years, 2.0 mg/kg for ages 5 to 10 years, and 1.5 mg/kg for individuals over 10 years of age.


Effects of parents' and pediatricians' worry concerning severe gastroenteritis in early childhood on later disturbances in the child's behavior.

Probands who had been hospitalized for gastroenteritis between the ages of 2 and 5 years were studied at the ages of 8 to 12 years. More conduct problems and a tendency to excessive dependence were found (1) in probands who were severely ill by objective criteria than were others and (2) in probands whose parents were specifically worried that their child might die as a result of the illness. General worry in the parents had different consequences. Other data suggest that pediatricians, because they are no longer worried about the illness after the child is discharged, may be failing to take appropriate preventative measures at opportune moments in the years following the hospitalization.


Acute liver disease and encephalopathy mimicking Reye syndrome. A report of three cases.

Three patients are described whose clinical presentation suggested Reye syndrome, and in whom the initial laboratory investigations supported the diagnosis. The subsequent clinical and biochemical evolution of the illness differed from that of Reye syndrome. The liver biopsy of each patient revealed changes in centrilobular hepatocytes rather than the diffuse small droplet fatty change characteristic of Reye syndrome. In each of them normal liver functions were regained. The findings in these patients suggest that a firm diagnosis of Reye syndrome cannot be made without histologic examination of the liver.


Reye syndrome: results of intensive supportive care.

Thirty-six patients with Reye syndrome were admitted to St. Louis Children's Hospital during a ten-year period from January, 1966, through June, 1975; ten patients (28%) died. Seven (64%) of the ten deaths occurred in the 11 patients admitted between 1966 and 1971, whereas only three (12%) of 25 patients died thereafter. We attribute this reduction in case fatality rate to early diagnosis, recognition of milder cases, and intensive medical support including continuous intravenous infusion of hypertonic glucose, intermittent infusion of hypertonic mannitol, and early elective endotracheal intubation. Analyses of metabolic, hormonal, and blood gas data obtained serially during the acute illness in 16 of these patients provide a basis for a discussion of the pathophysiology of this disorder.


Reye syndrome: treatment by exchange transfusion with special reference to the 1974 epidemic in Cincinnati, Ohio.

The treatment of 66 children with Reye syndrome proved by hepatic biopsy or autopsy is described. Prior to the utilization of exchange transfusion early in the course of the disease, our case fatality rate was 100% of nine patients. With early diagnosis and early exchange transfusion, the case fatality rate was reduced to 27% of 44 patients. During the 1974 epidemic of Reye syndrome, 26 children were treated. In 18 children the diagnosis was established by hepatic biopsy; 16 received one or more exchange transfusions. There were no deaths among these 26 patients. In the 1974 epidemic, the national case fatality rate was estimated to be 40%. Exchange transfusion appears to have been an important factor in the reduction of the case fatality rate among our patients.


Liver dysfunction and histologic abnormalities in neonatal hypopituitarism.

Pituitary aplasia or hypoplasia occurs in anencephalic and normocephalic infants. Two infants with hypopituitarism are described; in each the diagnosis was made clinically. The infants had frank clinical and histologic evidence of the neonatal hepatitis syndrome. There may be more than a chance relationship between the clinicopathologic findings of neonatal hypopituitarism and hepatitis.


Spectrum of function of neutrophils from carriers of sex-linked chronic granulomatous disease.

Bactericidal and metabolic activities were compared for polymorphonuclear leukocytes from normal controls, patients with sex-linked chronic granulomatous disease, five obligate carriers, and six potential carriers of CGD. Bacteria surviving at one hour were quantitated in a standardized assay which employed 1.25 Staphylococcus aureus per neutrophil. Heat-killed bacteria or a chemical agent, phorbol myristate acetate, were used to stimulate increases in utilization of oxygen, oxidation of [1--14C] glucose, and reduction of neotetrazolium chloride by PMN. The results demonstrate that PMN from the individual obligate carriers of CGD have a broad spectrum of functional capabilities. Neutrophils from one obligate carrier performed in the above in vitro tests and others on a par with normal control cells, whereas the PMN of others displayed deficiencies nearly as profound as those of the affected CGD patients. The observations parallel the broad range of phenotypic expression observed in heterozygotic carriers of other sex-linked recessive disorders as a result of random inactivation of the X chromosome. Although predictable from the current concept of random X inactivation, the spectrum has not been previously demonstrated for carriers of sex-linked recessive CGD and thus has important implications for the detection and counseling of carriers of CGD.


Defective neutrophil chemotaxis with variant ichthyosis, hyperimmunoglobulinemia E, and recurrent infections.

Host defense mechanisms were evaluated in a 4-1/2-year-old boy with recurrent pyogenic infections and a unique hyperkeratotic skin disorder. The patient's neutrophils were consistently defective in chemotactic responsiveness but had normal NBT reduction, glucose oxidation, and iodination. Serum concentrations of IgE were markedly elevated and the secondary antibody response was abnormal. No T-cell dysfunction was detected. These findings suggest a relationship between this patient and patients with other syndromes associated with recurrent infections, cutaneous disease, defective chemotaxis, immunodeficiency, and hyperimmunoglobulinemia E.


Serum complement profiles in infants and children.

The purpose of this study was to examine normal serum values for the complement components, C3, C4, and C5, and total hemolytic complement (CH50) activity in 163 healthy infants and children, in the age range from birth through 14 years. There were statistically significant relationships of C3, C4, and C5, but not CH50 with age. None of the complement components or CH50 could be differentiated by sex or race. Tolerance limits for high and low values were projected for each complement measurement for 75%, 90%, and 95% of the general population. Our data confirm the differences in complement levels between children and adults and demonstrate a wide range of values within each group, reflecting the biologic variability of complement measurements. These results emphasize the importance of establishing normal pediatric values in any laboratory that measures complement profiles in various diseases of childhood.


Growth hormone excess and sexual precocity in polyostotic fibrous dysplasia (McCune-Albright syndrome): evidence for abnormal hypothalamic function.

A 5-5/12-year-old boy with gigantism and precocious puberty associated with the McCune-Albright syndrome is presented. Serum concentrations of growth hormone were extremely elevated (128-163 ng/ml) and were not suppressed by hyperglycemia or chlorpromazine. Serum LH (7.4 +/- 1.0 SD mIU/ml) and FSH (5.3 +/- 0.3 SD mIU/ml) concentrations were in the range observed in midpuberty. The secretion pattern of LH was episodic. The administration of estradiol suppressed the secretion of FSH and had an apparent positive feedback effect on release of LH. These findings are compatible with abnormal hypothalamic function as the mechanism for the endocrinopathies associated with the McCune-Albright syndrome.


Recent trends in the mortality rate from renal disease in children and young adults in New York City.

Analysis has shown that the over-all death rate from renal disease for residents of New York City under 25 years of age has declined from 4.6 per 100,000 in 1950 to 2.3 per 100,000 in 1970. Nephritis and nephrosis was the major disease category accounting for this decrease in deaths. A similar trend was found for the United States as a whole. Other causes of renal disease did not manifest consistent changes in death rates. The decline in deaths from nephritis and nephrosis could not be ascribed solely to changing diagnostic habits or terminology. A possible alternative explanation is a change in the natural history of these diseases. Data of this type might be useful as an index to future trends in the mortality rate from renal diseases and as one basis for projections of potential future needs for dialysis and renal transplantation. Using 1965 data, we estimate the number of such potential candidates in New York City would have been 9 per 1,000,000 for the 5 to 14 year age group and 23 per 1,000,000 for the 15 to 24 year age group. There are significant limitations of projections based on such data. These estimates of potential candidates for chronic dialysis or renal transplantation are the first available for children in the United States.


Non-Hodgkin lymphoma of the head and neck in childhood.

A retrospective analysis of pediatric patients with non-Hodgkin lymphoma localized to the head and neck revealed a survival rate of 51.7%. This contrasts with a survival rate of 9% computed from the literature for children with local and regional non-Hodgkin lymphoma in various parts of the body. Major factors influencing survival appeared to be: (1) stage of lymphoma (12 of 17 Stage I survived); (2) histology (7 of 7 patients whose lesions were classified as nodular survived as compared to 5 of 17 with lesions classified as diffuse); and (3) anatomic location. Leukemia developed in seven patients with lesions of the diffuse histologic type. Recent experience suggests that aggressive, integrated treatment with surgery, radiation therapy, ano chemotherapy may favorably alter the course of the disease in patients with unfavorable histologic lesions.


Insulin antagonism of cortisol action on lechithin synthesis by cultured fetal lung cells.

In monolayer cel cultures from late gestation (28-day) rabbit fetal lungs, cortisol (5.5 X 10(-6)M) enhances lecithin synthesis and reduced cellular growth. The addition of insulin (25-100 muU/ml) abolishes the stimulatory effect of cortisol on lecithin synthesis but does not affect its growth-inhibiting activity.


Fetal alcohol syndrome in dizygotic twins.

A pair of fraternal twins with stigmata of the fetal alcohol syndrome are described. Apparently differences in susceptibility to the dysmorphogenic influence of ethanol caused one twin to be more severely affected than the other one. Both infants are growing poorly postnatally, and both are at risk for retarded development. Any evidence of the fetal alcohol syndrome, however, subtle, should be considered a warning of possible future developmental delay.


Radiographic technic, safety, and interpretation in the newborn nursery.

The technic and safety aspects of the radiographic evaluation of neonates with RDS are discussed. A study of radiographs taken in an intensive care nursery revealed that densitometric measurements are helpful in distinguishing changes in lung aeration from changes in radiographic quality. The radiation exposure to neonates was 5.1 (SD 2.3) mR per film and 44.9 (SD 39.7) MR per neonate. Limited chromosomal studies revealed no detectable abnormalities. The radiation exposure to the staff was minimal. The low-radiation exposure to the staff and neonates is the result of careful attention to radiation hygiene.


Leg growth following umbilical artery catheter-associated thrombus formation: a 4-year follow-up.

Fourteen children were re-examined 4 years following the radiographic demonstration of umbilical artery catheter associated thrombus formation. Positive correlations could not be established between radiographically determined femoral and/or tibial lengths, length differences, pulse pressure differences, and the location of thrombi noted on the 1971 aortograms.


The lack of effect of phototherapy on serum bilirubin-binding capacity in newborn infants.

Using a Sephadex G-25 separation technique, the total bilirubin-binding capacity was measured in 18 jaundiced infants before and after phototherapy. The initial total bilirubin-binding capacity obtained at 20 to 113 hours of age averaged 17.5 +/- 4.4 mg/dl (mean +/- SD) and was unchanged during phototherapy at 34 to 135 hours of age. In ten infants, the total bilirubin-binding capacity was measured before, during, and 24 hours after the cessation of phototherapy. Here too, phototherapy did not significantly influence the TBBC. These data indicate that in vivo, phototherapy does not alter the serum bilirubin binding capacity of newborn infants.


Evaluation of rifampicin in the treatment of tuberculous meningitis in children.

Of the 20 patients given rifampicin and isoniazid, 19 survived and one died. Twelve patients recovered from the disease without any significant neurologic defect. Seven patients had moderate to severe handicaps which included hemiparesis in four, hydrocephalus in two,mental retardation in three, and blindness in one. There was no hearing deficit. The average hospital stay in this group was 3-1/2 weeks. Among the 13 patients given streptomycin, PAS, and isoniazid, four are dead. Only three patients recovered with a completely good condition. The remainder had either single or multiple neurologic defects. The moderate degree of nerve deafness was also observed in two patients.


Problems after adoption: some guidelines for pediatrician involvement.

Adoptive families face several important parent-child confrontations relevant to the adopted status of the child, for which early intervention is indicated. These postplacement difficulties are often not rooted in psychologic disturbance but rather reflect the problem of information deprivation in adoptive parents. Specifically, confrontations arise out of telling the child of the adoption, the adoptee's need for information about the biologic parents, and the tendency of adoptees to place adoptive parents in competition with the biologic parents. The nature of these problems and guidelines for intervention by the pediatrician are detailed in this paper.


Blood volume and blood pressure in infants with respiratory distress.

Mean aortic blood pressure volume were measured in true premature infants with respiratory distress syndrome. Seven infants had Type I RDS (hyaline membrane disease) and ten had transient tachypnea of the newborn (Type II RDS). Blood volume in the infants with Type I RDS was significantly lower than in the infants with Type II RDS. The difference was due to a low red cell volume. Mean aortic blood pressure was within the range of normal in all infants and therefore did not reflect the low blood volume of infants with Type I RDS. Normal mean aortic blood pressure does not indicate normal blood volume or normal circulation in infants with RDS.


Development of the sheep as an animal model to study placental lactogen physiology.

Ovine placental lactogen, purified from term sheep cotyledons, has been found to have chemical and biologic properties similar to those of human placental lactogen, ovine growth hormone, and ovine prolactin. OPL stimulates lactation in vivo and in vitro and binds to prolactin and growth hormone membrane receptors. Its binding to growth hormone receptors is approximately 20 times greater than that of hPL, suggesting that its somatotrophic potency is greater than that of hPL. Preliminary in vivo studies in the sheep indicate that oPL affects maternal carbohydrate, lipid, and protein metabolism and that its effects are, in part, similar to those of hPL and growth hormone.


Juvenile Wilson disease: histologic and functional studies during penicillamine therapy.

Because the long-term effects of penicillamine on hepatic morphology in Wilson disease are virtually unknown, seven patients with this disorder were studied two to seven years after the onset of drug treatment. All were without symptoms at follow-up. By comparison to initial biopsies (four patients), posttreatment specimens showed either considerable reduction in portal fibrosis (two patients) or no significant change (two patients); portal inflammation and necrosis were greatly diminished or absent in three. In none was there complete restitution of normal architecture. Three patients lacked initial biopsies. In these, portal cirrhosis, inflammation and necrosis, and fatty vacuolization of the hepatocytes were present three, five, and seven years after onset of therapy. Lipofuscin pigment was abundant in follow-up biopsies. The data demonstrate that morphologic improvement is achieved in some patients with Wilson disease receiving penicilliamine, but that this is not predicted by biochemical factors. Sequential biopsies are necessary to evaluate completely the extent of healing.