An analysis of the impact of the loss of a primary care physician on a patient population.

A case study was undertaken to analyze the effect of the loss of a primary care physician upon the population he served. While the physician in this study retired, the effects of his retirement can be extrapolated to the situations of sickness, death, etc, in which the services of a primary care physician are lost. A sample population of the patients who had lost their "family doctor" was interviewed in depth regarding the problems incurred by this loss. The mechanisms of informing the patients, transfer of patient records, exchange of responsibility and continuity of care, patterns of primary vs specialty care, and use of the Emergency Room before and after the retirement were investigated. It was found that only one out of every six families established a reliable and permanent relationship with a new physician within six months without experiencing "great difficulty". While recognizing the limitations of one case study, recommendations are made to mitigate the "difficult" aspects of such transfers in the future.


The analysis of family practice workloads by seriousness.

There is a need for a measure of the overall seriousness of a given family practice workload. In the past, such measurements have been attempted in various ways. In this work, the rubrics of the Canuck Book Classification (a classification of health problems in family practice) were rated for seriousness. There was sufficient agreement on 96 rubrics for them to be used as indicators of the seriousness of workloads in general. Some examples of the uses of the system are shown. Several difficulties were encountered; these are not insuperable, and the method deserves to be developed further.


The impact on patient satisfaction of the introduction of family medicine residents into a model practice facility.

This study examines the effects on patient satisfaction of the introduction of family medicine residents into the staff of an ongoing private practice that joined a Department of Family Medicine. Questionnaires were administered to clinic patients during a four-week period four months prior to when residents began seeing patients at the clinic and again five months after residents joined the clinic staff. Satisfaction at both times was high; however, significant declines from Time 1 to Time 2 were noted on most items. Analysis showed that this decline was not related to dissatisfaction within the residents. A questionnaire was also mailed to a sample of patients who had not visited the clinic more than once during the first year of the resident program there. Three fourths of these individuals still viewed themselves as patients of the clinic. Implications of these findings for family medicine residency training programs are discussed.


Recent advances in the treatment of pathological fractures.

Pathological fractures present challenging and difficult management problems. Conservative treatment frequently results in non-union, while open reduction and internal fixation usually involves prolonged immobilization and bed rest with attendant medical complications. The use of methylmethacrylate as an adjunct to conventional forms of internal fixation represents a recent advance in the management of unstable, pathological fractures. The hospital stay can be markedly shortened and the patient's functional capacity increased relatively early in the postoperative period. This paper reports the results of this approach to therapy in a series of over 75 patients, and outlines indications and timing of this procedure before pathological fractures occur in instances where early diagnosis of bone malignancy has been made.


Patients with psychogenic pain.

This article describes characteristics of groups of patients with a high probability of having pain complaints on an emotional basis. An approach to patients with psychogenic pain, including management suggestions, is emphasized, with particular reference to the use of extensive history for their identification and the importance of minimizing unnecessary medical and surgical procedures.


Compendium of drug abuse jargon.

Drug abuse slang is an originative and a protean language,which poses the problem of identification and definition of terms. This compilation of nomenclature provides an extensive list to serve as a resource for the busy family physician, who frequently deals with drug abuse problems.


The immediate management of suicide attempts in children and adolescents: psychologic aspects.

Adolescent suicide is steadily on the increase. Many attempters have previously consulted a physician, but have concealed their suicidal intent. When the attempt is made the family doctor is often the first physician contacted. In children under 12 years of age, the population at risk for suicide includes those who feel abandoned because of neglect, child abuse, or bereavement. The early adolescent may suicide by mis-adventure. Adolescents at risk include those who experience rage associated with feelings of utter helplessness and hopelessness and those who use self-destructive behavior to manipulate other people in the expectation that these other people will gratify their wishes. To ensure adequate medical and psychologic care, the physician should hospitalize the suicide attempter. Future suicide attempts are less likely if the physician can elicit the adolescent's awareness of his anger, diminish the child's self-contempt, help him to explore nondestructive solutions to his problems, and increase his awareness that his death by suicide would cause irreparable emotional damage to his family. The initial management provides the data required for formulation of an aftercare plan that the physician may coordinate and monitor.


Classification and coding of psychosocial problems in family medicine.

Disease and problem classification systems for primary care have recognized that psychosocial problems are integrally related to more traditional medical problems which patients present to physicians. These classification systems remain inadequate for the description of primary care problems, especially as several disciplines interrelate in primary care, such as medicine, nursing, and social work. This paper presents a classification and coding system of psychosocial problems gleaned from a number of existing coding systems. The purpose of presenting it here is to contribute to a dialogue which will result in the establishment of a common psychosocial language for all health professionals. By so doing, progress in research, education, patient care, and administration in the psychosocial area will be facilitated.


The proximal negative response and visual adaptation in the skate retina.

The proximal negative response (PNR), a complex extracellular potential derived mainly from amacrine cell activity, was studied in the all-rod retina of the skate. Tetrodotoxin (10(-6) mg/ml) did not affect either the waveform or the latency of the response, indicating that the PNR reflects the graded, nonregenerative components of the amacrine cell potential. As regards its adaptive properties, the PNR exhibited both the extreme sensitivity to weak background light and the slow time course of light and dark adaptation that are characteristic of other responses from the proximal retina. Thus, the PNR, like the b-wave and ganglion cell discharge, appears to reflect adaptive processes located within the neural network of the inner retina.


Transport of uridine in human red blood cells. Demonstration of a simple carrier-mediated process.

The kinetic properties of the mediated transport of uridine in human erythrocytes are investigated. Different methodological procedures are use to acquire a complete kinetic description of the system...


Rhodopsin photoproducts and rod sensitivity in the skate retina.

The late photoproducts that result from the isomerization of rhodopsin have been identified in the isolated all-rod retina of the skate by means of rapid spectrophotometry. The sequence in which these intermediates form and decay could be described by a scheme that incorporates two pathways for the degradation of metarhodopsin II (MII) to retinol: one via metarhodopsin III (MIII) and the other (which bypasses MIII) through retinal. Computer simulation of the model yielded rate constants and spectral absorbance coefficients for the late photoproducts which fit experimental data obtained at temperatures ranging from 7 degrees C to 27 degrees C. Comparing the kinetics of the thermal reactions with the changes in rod threshold that occur during dark adaptation indicated that the decay of MII and the fall in receptor thresholds exhibit similarities with regard to their temperature dependence. However, the addition of 2 mM hydroxylamine to a perfusate bathing the retina greatly accelerated the photochemical reactions, but had no significant effect on the rate of recovery of rod sensitivity. It appears, therefore, that the late bleaching intermediates do not control the sensitivities of skate rods during dark adaptation.


Variation in the prevalence of antibiotic resistance of Staphylococcus aureus from human skin and nares.

Patients whose skins are colonized with Staphylococcus aureus resistant to penicillin and/or tetracycline may carry variants that are sensitive to these antibiotics. The skin of most individuals yields the fully resistant type as the predominant flora and the nose harbours the sensitive version. This probably represents plasmid loss in vivo. The plasmid-positive cells were not more resistant to desiccation or more deeply pigmented than plasmid-negative cells. The explanation for such distributions is unknown.


The effect of nalidixic acid on the cell cycle of synchronous Rhodopseudomonas palustris cultures.

The influence of the DNA synthesis inhibitor, nalidixic acid, on the properties of synchronous cultures of selected Rhodopseudomonas palustris swarmer cells was examined. There was little alteration in the changes in morphology, extinction, volume distribution and leucine incorporation up to bud development, and photosynthetic membrane lamellae were still synthesized de novo in the bud. However, there was no subsequent division, or flagellum or holdfast synthesis. Instead cells elongated by continued outgrowth of the abortive bud. Since DNA synthesis was also inhibited, this suggested a dependence of cell division, and flagellum and holdfast synthesis, on the completion of chromosome replication. By addition or removal of nalidixic acid at various times in the cell cycle, periods were demonstrated when the organism was insensitive to the antibiotic indicating that there was a pre-synthetic and post-synthetic gap in the pattern of DNA synthesis in R. palustris swarmers.


Genetic determination of methylenomycin synthesis by the SCP1 plasmid of Streptomyces coelicolor A3(2).

Evidence is presented that genes determining the pathway of methylenomycin A synthesis are carried on the SCP1 plasmid. All 16 mutations (mmy) leading to lack of antibiotic synthesis were SCP1-linked. Phenotypic classification, by co-synthesis and other criteria, suggested that they fell into at least five classes. When the wild-type SCP1 plasmid was transferred to Streptomyces lividans or Streptomyces parvulus, material that was chromatographically and biologically indistinguishable from methylenomycin A was produced. Recombination between some pairs of mmy mutations was detected. In crosses of mmy mutants of NF (integrated SCP1 donor) strains with SCP1-, a very high frequency of chromosomal recombination occurred; thus methylenomycin production appears not to be an important cause of the ultra-fertility normally associated with NF X SCP1- crosses.


The effect of anaerobiosis and bile salts on the growth and toxin production by Vibrio cholerae.

Environemntal conditions which might be present in the human intestinal lumen, such as anaerobiosis, a temperature of 37 degrees C and the presence of bile salts, were examined for their effects on the growth and toxin production by Vibrio cholerae strains 569B and B1307 in Syncase and in peptone water media. Using aerobic conditions at 30 degrees C, which are commonly used for enterotoxin production, toxin (5 mug ml(-1)) and pleomorphic cells were detected during the exponential phase of the growth cycle. When the incubation temperature was raised to 37 degrees C, no toxin ( less than 0-1 mug ml(-1)) and no pleomorphic forms were found. In cultures incubated anaerobically at 30 or 37 degrees C, the organisms grew poorly, forming pleomorphic cells which lysed after the cultures reached a maximum turbidity at 640 nm of 1-45 at 12 h. Toxin (2-5 mug ml(-1)) was present at 12, 24 and 48 h. When 0-1% sodium deoxycholate was incorporated into the culture medium, growth was inhibited under aerobic conditions at 30 and 37 degrees C. At 30 degrees C under aerobic conditions and at 37 degrees C under anaerobic conditions, the toxin yield was not significantly affected by the presence of sodium deoxycholate; but at 37 degrees C under aerobic conditions, sodium deoxycholate caused an increase in the toxin yield (5 mug ml(-1)) due to the release of cell-bound toxin.


Comparison of the biophysical and biochemical properties of Penicillium cyaneo-fulvum virus and Penicillium chrysogenum virus.

The biophysical and biochemical properties of Penicillium cyaneo-fulvum virus (Pc-fV) and Penicillium chrysogenum virus (PcV) have been compared. In sucrose density gradient sedimentation, purified virus preparations gave one major component, L, and three minor components E1, E2 and H with sedimentation coefficients of 145S, 80S, 102S and 172S respectively in each case. E1, E2 were shown to be empty particles. Pc-fV L particles contained only double-stranded RNA, which separated in polyacrylamide gel electrophoresis into four components with mol. wt. 2-21 X 10(6), 2-08 X 10(6), 1-98 X 10(6) and 1-93 X 10(6). PcV L particles gave three double-stranded RNA components, which were indistinguishable in polyacrylamide gel electrophoresis from the larger three RNA components of Pc-fV. In both viruses each RNA component was separately encapsidated. In both viruses H particles gave rise to the same double-stranded RNA components as their L particles, but contained, in addition, small amounts of single-stranded RNA. Pc-fV and PcV have been shown to consist of isometric particles of the same size and to be serologically related, and the amino acid compositions of their capsid polypeptides were found to be very similar. The capsid polypeptides of the two viruses were examined by SDS-polyacrylamide gel electrophoresis. In each case E2, L and H particles gave one major polypeptide gamma1, with mol. wt. 130000, whereas E1 particles contained one major polypeptide gamma2 with mol. wt. 115000. The mol. wt. of L particles, determined from sedimentation and diffusion coefficients, was 9-8 X 10(6) for both Pc-fV and PcV. The capsid of the L particles of each virus was estimated to contain 60 molecules of polypeptide gamma1.


A solid-phase radioimmunoassay for IgG and IgM antibodies against measles virus.

A solid-phase radioimmunoassay (RIA) was used to determine the presence of IgG and IgM antibodies to measles virus in human serum and cerebrospinal fluid (CSF). Purified measles virus was adsorbed on to polystyrene balls, which were then exposed to serial dilutions of test serum or CSF. The presence of antibody was measured by its capacity to bind 125I-labelled specific anti-human IgG or IgM. Serum from a variety of patients as well as measles-immune clinically healthy persons were tested; binding ratios (using negative human serum controls) were usually between 10 and 30, but with subacute sclerosing panencephalitis (SSPE) ratios were as high as 50. Of ten CSF specimens tested, all but one, which was taken early in the convalescent phase of measles infection, had detectable IgG antibody. In six patients with acute measles, IgM antibodies were found in all serum specimens taken one or more days after the onset of rash. Maximal titers of 1:10000 to 1:40000 were found about 7 days later. Thereafter, IgM titres decreased rapidly but were still detectable at 40 days. A purified ribonucleoprotein of measles virus was also used successfully as an antigen in this RIA method.


Polypeptide phosphorylation in adenovirus-infected cells.

Cells infected with human adenovirus type 5 have been labelled with 32P-orthophosphate under various conditions and extracts examined, after denaturation in sodium dodecyl sulphate (SDS), by polyacrylamide gel electrophoresis (PAGE) followed by autoradiography. A number of polypeptides appear to be phosphorylated specifically as a result of infection. Early in infection, phosphorylation of a polypeptide of apparent mol. wt. 26 K associated with ribosomes can be detected. Two other phosphorylated polypeptides of apparent mol. wt. 72 K and 18 K can also be seen, the former being mainly confined to the nucleus and capable of being precipitated by the previously described virus-specific P antiserum. The 18 K phosphorylated polypeptide is found mainly in association with membrane fractions. Later in infection phosphorylated polypeptides of apparent mol. wt. 100 K and 39 K can be recognized, the former being associated with ribosomes but removed, however, with a high salt wash; the latter component is mainly detected in the nucleus. Analysis of the purified 32P-labelled virus by the SDS PAGE technique indicated that a structural polypeptide of apparent mol. wt. 66 K (IIIa) was also phosphorylated.


Temperature-sensitive and other mutants of the Essex 70 strain of Newcastle disease virus as vaccines.

The most reliable method of distinguishing strains of low virulence amongst a collection of stock strains of Newcastle disease virus (NDV) was by their failure to produce a good c.p.e. in monolayers of baby hamster kidney cells and of chick embryo cells. This method was of no help in identifying avirulent mutants that emerged in the Essex 70 strain of NDV following ultraviolet light, nitrous acid, hydroxylamine or N-methyl-N'-nitro-N-nitrosoguanidine (NTG) treatment. A marked reduction in the ability to kill developing chick embryos at 41 degrees C was a much more reliable indicator. Several of these temperature-sensitive mutants, most of which had been isolated from NTG-treated virus, were non-lethal for young chicks but they did have a depressive effect on their growth rate. The immunity produced by three of these mutants in chicks free of NDV antibody, but not in chicks possessing appreciable amounts of antibody, was probably even better than that produced by Hitchner B1 strain. All three mutants reverted to virulence during passage in chicks, although in no case were the revertants as virulent as the original Essex 70 strain. The virulent revertants obtained from one of the mutants had lost their temperature-sensitivity and proliferated in large numbers in the tissues of infected chicks. Those obtained from the other two had either not lost, or only partly lost, their temperature-sensitivity; they were found only in low concentrations in the tissues of infected chicks, their concentrations being little different from that found in the tissues of chicks infected with the mutants from which they were derived.


Bacteriophage 7-7-1 adsorbs to the complex flagella of Rhizobium lupini H13-3.

Bacteriophage 7-7-1 is shown to adsorb specifically to the complex flagella of its host Rhizobium lupini H13-3. Deflagellation of motile cells before the addition of phage leads to a complete inhibition of phage propagation for at least 60 min. Among phage-resistant mutants, many non-motile (mot) and non-flagellated (fla) derivatives of R. lupini H13-3 have been selected. Electron microscopic observations indicate that bacteriophage 7-7-1 attaches with its short tail fibres to the conspicuous helical filament of R. lupini flagells. This attachment is reversible; irreversible phage adsorption takes place at the flagellar base. It is postulated that phage 7-7-1 moves along the rotating flagellum towards a final receptor next to the insertion site of the flagellum, where tail contraction and injection of phage nucleic acid occurs.


Desynchronization of electrical activity in rats induced by deprenyl--an inhibitor of monoamine oxidase B--and relationship with selective increase of dopamine and beta-phenylethylamine.

Electrophysiological and biochemical effects of deprenyl and beta-phenylethylamine were studied in rats. d,1-Deprenyl, 1-deprenyl (4-6 mg/kg) and beta-phenylethylamine (75 mg/kg) induced a desynchronization of ECOG after i.p. administration of drugs. The effects lasted several hours. The biochemical analysis indicate that d,1-deprenyl (4 mg/kg) nearly doubled the concentration of brain dopamine (DA) while the concentration of noradrenaline was not altered. The maximal increase was reached at 60 min and the enhanced concentration of DA stayed at this level up till 180 min after administration of drug. Treatment of rats with alpha-methyl-p-tyrosine (200 mg/kg) did not antagonize a deprenyl induced desynchronization of ECOG. However, even low dose of haloperidol (0.1 mg/kg) abolished the arousal effect of d,1-deprenyl and beta-phenylethylamine. It is suggested that desynchronization of EEG induced by deprenyl is more likely due to increased endogenous beta-phenylethylamine than to increased concentration of endogenous DA in the brain.


Serum dopamine-beta-hydroxylase in parkinsonism.

Serum dopamine-beta-hydroxylase activities of a group of 16 parkinsonian patients under L-Dopa plus decarboxylase inhibitor showed a distribution with a drift towards higher activities compared to a group of normals of the same age range. Acute doses of L-Dopa failed to cause any change in the serum enzyme activities as well as in the serum concentration of 3-methoxy-4-hydroxyphenylethylene glycol, in parkinsonian patients and in normals. The data support the idea of a limited influence of L-Dopa on the noradrenaline synthesis and release in parkinsonism.


Effects of precocious pinealectomy and hemicastration on pituitary and plasma LH levels in immature male rats.

In the immature male rat (7 to 28 days of age) precocious hemicastration provokes a marked compensatory testicular hypertrophy accompanied by a significant increase in pituitary LH content, and a non-significant increase in plasma LH level. In pinealectomized and sham-pinealectomized animals, hemicastration had the same effect with some exceptions at certain ages. Pinealectomy alone causes less evident changes in pituitary LH content than hemicastration. Only a transient effect was found, which was more evident in the hemicastrated rats. Plasma LH was only increased in the pinealectomized hemicastrated rats at days 16 and 18. It is concluded that pinealectomy in immature male rats seems to have only a transient stimulatory effect on pituitary and plasma LH levels, which is more striking in hemicastrated rats. So, hemicastration seems to sensitize the animals to the effect of pinealectomy.


The pineal gland of nocturnal mammals. I. The pinealocytes of the bat (Nyctalus noctula, Schreber).

The ultrastructure of the pinealocytes of noctule bats, mammals which live most of the time in darkness or very low light intensities, was examined and compared with the pinealocytes of other mammals. Two different populations of pinealocytes (I and II) were observed. They differ in general aspect, in location and especially in their content of cell organelles involved in synthetic processes. Mitochondria, ribosomes, lysosomes and lipid inclusions were present in the perikaryon of pinealocytes of both populations. In the pinealocytes of population I some granular vesicles, of presumed Golgi origin, and some other structures were observed. Pinealocytes of population II are characterized by many glycogen granules, more or less associated with a large vacuolar system. Moreover, some small vacuoles originating from cisterns of the granular endoplasmic reticulum and containing flocculent material of a moderate electron density are described. The possibility is discussed that these small vacuoles are involved in one of the secretory processes of the pineal gland while the granular vesicles of the pinealocyte of the population I are the products of another.


Electron microscopic evidence of glycogen storage in the dark pinealocytes of the rabbit pineal gland.

Electron microscopic evidence is given that the small dark granules in the rabbit dark pinealocytes represent glycogen. The conception is put forward that this glycogen, synthesized at the membranes of the rough endoplasmic reticulum, is taken up by lysosomes to participate then in the conversion of the lysosomes into pigment bodies.


Effect of estradiol and testosterone on catechol-O-methyl transferase activity of rat superior cervical ganglion, pineal gland, anterior hypophysis and hypothalamus.

The effect of estradiol and testosterone on the activity of catechol-O- methyl transferase (COMT) of the superior cervical ganglion, pineal gland, anterior hypophysis and hypothalamus were examined in castrated rats. In female rats a single injection of 2 mug of estradiol caused a significant 25% increase of hypothalamic COMT, whereas after 3 daily injections no differences in enzyme activity were observed between hormone- and vehicle-injected controls. In male rats testosterone propionate (0.5 mg) increased hypothalamic COMT by 53%; this effect was not detectable in animals treated with the androgen for 3 days. COMT activity of the superior cervical ganglion, pineal gland and anterior hypophysis did not exhibit significant changes after any of the hormone schedules used.


Central deopaminergic receptor supersensitivity and its relevance to Parkinson's disease.

The degeneration of the substantia nigra that characterises Parkinson's disease may cause an alteration in sensitivity of striatal dopamine receptors. The development of denervation supersensitivity has been held to be responsible for some of the effects of chronic levodopa therapy. The rotating rodent is an animal model commonly used to study the phenomenon of striatal dopamine receptor supersensitivity, and to investigate drugs which may prove to be beneficial in the treatment of Parkinson's disease. We have investigated as to whether long-term oral administration of levodopa to mice with unilateral destruction of striatal dopaminergic nerve terminals influences dopaminergic receptor denervation supersensitivity as judged by the circling response following systemically administered levodopa. It does not do so and the relevance of these findings to the treatment of Parkinson's disease is discussed.


Distribution of growth hormone and thyroid-stimulating hormone in cerebrospinal fluid and pathological compartments of the central nervous system.

Human growth hormone (HGH) radio-immunoassay (RIA) was adapted for an accurate measurement of immunoreactive HGH concentrations in the CSF in different cases of hypothalamic-somatotropin dysfunctions. In control subjects (n = 43) mean HGH levels were 0.35 +/- 0.03 ng/ml in CSF and 1.95 +/- 0.2 ng/ml in plasma with a CSF/plasma ratio of 17%. The thyroid-stimulating hormone (TSH) RIA gave in controls mean basal levels of 2.65 +/- 0.2 muU/ml in CSF and 5.95 +/- 0.3 muU/ml in plasma with a CSF/plasma ratio of 44%. HGH and TSH concentrations in CSF and plasma show a very good correlation; but the regression curves for both hormones are distinctly different and appear specific for each polypeptide hormone. Hypothalamic-somatotropin hyperreactivity was reported in diabetic retinopathy (DR). CSF and plasma HGH concentrations in a group of diabetic patients with progressing retinopathy (n = 27) were not different from those in normal subjects (respectively 0.35 +/- 0.05 in CSF and 2.10 +/- 0.25 ng/ml in plasma with a CSF/plasma ratio of 16%). The HGH regression curve obtained in diabetics is similar to that of controls. These data do not substantiate the hypothesis of an HGH hyperreactivity in diabetic retinopathy. In somatotropin hypersecretion (acromegaly) without adenoma suprasellar extension, higher HGH concentrations recorded in CSF than in plasma cannot be attributed to an anatomical break-down of the CSF blood-brain barrier and suggest an active transport process of pituitary hormones to the CNS. HGH and TSH concentrations were measured in the cystic fluid of CNS tumors. In 1 case of a cystic dysembryoma, the HGH and TSH of CF were considerably increased. In gliomas (n = 8) the HGH and TSH cystic fluid concentrations were more elevated (respectively 0.72 +/- 0.2 ng/ml and 3.6 +/- 0.7 muU/ml) than in the CSF of controls.


Parkinsonism following encephalitis of unknown etiology.

The patient, a clinical case of parkinsonism, was a 32-year-old man, born in 1942, long after the prevalence of von Economo's lethargic encephalitis in Japan. Anatomically, the neurons in the substantia nigra of the mid-brain were extensively degenerated, and presented Alzheimer's neurofibrillary tangles. At the same time, melanin pigment was scattered in the tissue and was phagocytized by glia cells. Perivascular cuffing was observed in the frontal lobe, parietal lobe, temporal lobe, hippocampus, and thalamus as well as in the substantia nigra. Neuronophagia was noted in the thalamic nuclei. The present case was believed to have parkinsonism not clinically or pathologically related to von Economo's encephalitis or to Japanese encephalitis, but following a mild encephalitis of unknown etiology.


Stimulation of lymphocytes by cholinergic receptor in myasthenia gravis.

Lymphocytes from 13 myasthenic patients were incubated in vitro with membranes enriched in nicotinic cholinergic receptor obtained from Torpedo marmorata electric organ. When autologous serum was present in the incubation medium, the lymphocytes were highly stimulated. In contrast, no stimulation occurred when lymphocytes were cultured in presence of AB serum. These results suggest that an immune response against the Ach cholinergic receptor is present in myasthenic patients and give further support to the hypothesis that an autoimmune response against muscular receptors may be involved in Myasthenia Gravis pathogenesis.


Lead encephalopathy in neonatal Long-Evans rats: morphologic studies.

Lead encephalopathy was produced in neonatal Long-Evans rats by administering daily doses of lead acetate (600 milligrams of lead acetate/kilogram of body weight) through an esophageal catheter. Experimental rat pups showed behavioral changes, failed to gain weight at the same rate as controls, developed a paraplegia and died by 15 days of age. Lead analysis showed very high blood and tissue lead levels. Sequential histopathologic changes were studied in the cerebellum with observations also made in the choroid plexus, cerebral cortex and corpus striatum. Emphasis was placed on the cerebellum because this region of the brain was most severely altered. Petechial hemorrhages were evident in the cerebellum at three days and two days later the hemorrhagic lesions were almost confluent. The molecular and Purkinje cell layers were most extensively damaged by the hemorrhage. At eight, nine and ten days hemorrhages were fewer and massive amounts of edema fluid accumulated in the internal granular layer. Vascular anomalies of developing lead poisoned rats were examined with electron microscopy and with Golgi preparations. The evidence indicates that growing capillaries are the primary structure of the central nervous system (CNS) damaged by lead intoxication. The endothelial bud (or angioblast) appears to be a structure sensitive to lead poisoning and the encephalopathy probably results from the death of many of these buds.


A comparison of total body and local spinal cord irradiation in experimental allergic encephalomyelitis.

Spinal cord distribution spaces of 3H-mannitol (M.W. 182) were measured to compare the effects of both total-body gamma irradiation and local (spinal cord) x-irradiation on the development of experimental allergic encephalomyelitis (EAE). Single doses of 700R, 500R, 300R, 200R and 100R total body gamma irradiation, administered 6-8 days after EAE induction, appeared to delay the onset, reduce the severity, and hasten recovery of the disease. The magnitude of this effect was approximately prportional to the administered radiation dose. A single 1000R x-irradiation dose, delivered to a 1 x 2cm area in the thoracolumbar region of the spinal cord 7 or 10 days after induction appeared to increase the severity of EAE. Mannitol distribution spaces were mildly elevated in the thoracic regions and significantly elevated in the lumbar spinal cords of cord-irradiated animals. A marked exacerbation of the disease was observed in cord-irradiated rats treated with 5000R, administered over a period of 5 days. Rats progressively lost weight during the normal course of EAE, and a simultaneous increase in wet weights of the spinal cords was seen. Slight changes in these two parameters were observed in cord-irradiated, but not in total-body irradiated animals.


Effect of bilateral nerve injury on the migration of labelled mononuclear cells to hypoglossal nuclei.

Whether cells responding to injury in the central nervous system are of local or hematogenous origin is still a question that has not been answered unequivocally, although ample evidence in favor of a dual origin exists. In the present investigation, mononuclear blood cells were labelled with 3HT one day before left hypoglossal nerve injury. In addition to the initial injury, some of the animals received an injury of the right nerve at a later time. The fate of labelled cells responding to the initial injury when a second injury was made was studied. With two lesions the total number of labelled cells responding was twice the number present with a single lesion at the period of peak response. This was more than could be accounted for by simple migration from left to right. The data presented suggest that mitosis and migration of cells present at the initial lesion accounted for part of the increased number of cells. The possibility that some of the cells responding to the second injury were of recent hematogenous origin was not ruled out.


Motor consequences of motor area ablations in man.

Motor disorders reported in the present paper do not result from cortical ablations stricto sensu since some white matter was excised in every patient. However they appear to suggest that, as suggested by Walshe (1935), the central region and premotor area are a functional entity, i.e. they work as a whole. The extensive lesions of the premotor area, leaving untouched the motor region, have the same motor and tonic consequences as lesions limited to the central region. This point which appears specific for man does not imply that the premotor region subserves activities similar to those subserved by the central region. Rather it may suggest a deafferentiation of the central region, the consequences of which would be more important than is generally assumed. Extensive central or premotor lesions determine various tonic disorders: a well known spasticity, with exaggeration of the stretch reflex, associated with an increase in passive swinging of segments of limbs and in extensibility of joints. These two latter phenomena are usually defined as hypotonia. With premotor and precentral lesions the  hypotonia disappears and a hemiplegic posture is observed. This hemiplegic posture is a dystonia which apparently does not result directly from the exaggeration of the stretch reflex. Anatomically it appears to result from lesions of both central and premotor regions. This is in agreement with Denny-Brown's (1966) contention that an extrapyramidal region lies rostral to the prerolandic sulcus. As suggested by Evarts (1973) motor regions appear to control automatic as well as voluntary movements. They probably play a role in the trophic function of muscle, since, despite rehabilitation, amyotrophy was present in every case reported in the present paper.


Electrophysiological observations on the spinal cord of the normal and dystrophic mouse.

A method of carrying out electrophysiological experiments on the mouse spinal cord is described. The conduction velocity in the spinal dorsal roots (DR) of the normal mouse was in the range 10-100 m sec-1 and in the ventral roots (VR) 50-70 m sec-1. In the dystrophic mutant (129 ReJ dy/dy) the conduction velocity for both roots was usually in the range 0.1-2.0 m sec-1. Reflexes from DR to VR were recorded in both mutant and wild type animals and it was concluded that the delays in the mutant reflex were probably due to the slower conduction velocity in the roots. Postsynaptic inhibition and presynaptic inhibition were demonstrated and records were made from Renshaw cells and intracellularly from motoneurones. Delayed activity in spinal reflex paths, probably of supraspinal origin, was more pronounced in the dystrophic mutant. It is concluded that if the dystrophic mouse mutant were to be regarded as a model for human disease then similar reflex delays should be demonstrated in human subjects with muscular dystrophy.


Quantitative evaluation of spinal cord lesions in canine globoid leukodystrophy.

Lesion distribution in the spinal cord was investigated by sampling an average of 26 spinal cord segments in each of ten dogs severely affected by canine globoid leukodystrophy (GLD). GLD lesions were quantified by subdividing spinal white matter into small unit areas and judging the quartile extent of lesion involvement for each unit area. Along the length of the spinal cord, lesions declined from cranial to caudal, decreasing precipitously in the midlumbar region. The lumbosacral region had the least amount of lesion, and, based on lesion per unit area, the thoracic region was most severely involved. The dorsal funiculus had the greatest concentration and the least dispersion of lesion generally amoung the three funiculi. White matter at the periphery of the spinal cord was involved earlier and more severely than white matter adjacent to gray matter. Amount of lesion per spinal cord could be estimated adequately by sampling one segment from each of five regions. Dogs could be divided into two groups based on rate of lesion development. Clinical signs did not correlate closely with total amount of lesion per spinal cord. Of the total amount of variability among dogs in amount of spinal pathologic involvement, 78% could be accounted for by a mathematical model expressing spinal cord pathologic involvement as a quadratic function of age at onset and duration of the clinical syndrome.


Delayed myeloradiculopathy produced by spinal X-irradiation in the rat.

Rats were subjected to 3,500 r of X-irradiation in a single dose while breathing oxygen at 1 ATM pressure. Comparison was made between the delayed effects of irradiating thoracic, lumbar, and the cauda equina fields. The lumbar field involved the alpha-motoneurons and spinal roots supplying the sciatic nerve, while the cauda equina field involved these spinal roots but spared the alpha-motoneurons in the spinal cord. Thoracic irradiation produced paraplegia after an interval of 127-150 days. In the irradiated zone, the spinal cord was severely damaged, but the thoracic spinal roots were spared. Lumbar irradiation produced paraplegia after an interval of 83-211 days. In the irradiated zone, the alpha-motoneurons were largely spared, the spinal cord showed mild to moderate white matter damage, but the most severe damage was of the lumbosacral spinal roots. The posterior roots were more affected than the anterior. In longer interval cases the degeneration of the roots appeared to be due to focal devitalization. Evidence is advanced that root degeneration had been progressing for at least 4 weeks before the onset of paraplegia. In the cauda equina series the lumbosacral spinal root changes were similar to those in the lumbar series. This study indicates that different levels of the neuraxis have different degrees of susceptibility to X-irradiation. The thoracic cord appears more susceptible than the lumbosacral; the lumbosacral roots appear more susceptible than the thoracic; the posterior roots are more susceptible than the anterior. These findings may have relevance to the study of radiation damage in man, even though the dose schedule used in this experimental study differs greatly from that used for radiotherapy.


Increased T3 deiodination in dystrophic and neonatally denervated mouse muscle.

T3, free iodide levels and morphological features were compared in normal, 129 ReJ dy/dy dystrophic and neonatally denervated skeletal muscles of mice, killed 6 hr after a single intraperitoneal injection of iodine-labelled hormone. Both the dystrophic andthe denervated muscles were found to contain equal amounts of T3 but more iodide than the normal specimens. Increased iodide levels are considered to reflect augmented T3-catabolism by muscle dehalogenase and may indicate low free hormone levels in the soluble enzyme fraction of the cell, despite its normal overall T3 content. The close light-microscopic resemblance of 129 ReJ dy/dy dystrophy and neonatal denervation is confirmed. The possibility is discussed that one or several of the muscular dystrophies are forms of target organ hypothyroidism.


Anticonvulsant prolongation of survival in adult murine lymphocytic choriomeningitis. I. Drug treatment and virologic studies.

Lymphocytic choriomeningitis virus-induced central nervous system disease is characterized by death during a seizure approximately seven days after intracerebral inoculation. This process is mediated by thymus dependent lymphocytes, sensitized against viral antigens. Various forms of immunosuppressive treatment prevent the seizure death and produce persistently infected survivors. In this study, anticonvulsant treatment (particularly diazepam treatment) of LCM virus infected mice prolonged survival without affecting viral replication, or suppressing immune responsiveness. This prolongation of life did not lead to a reversal of pathologic processes and there were no survivors. However, anticonvulsant treatment permitted study of more advanced stages of the choriomeningitis than has previously been possible.


Retrograde invasion of lobster stretch receptor somata in control of firing rate and extra spike patterning.

1. Extra spikes may be interleaved in the otherwise rhythmic discharge pattern of the lobster stretch receptor neuron, about 2 ms after an expected spike. A constant input to the neuron is maintained by injecting current intrasomatically. The axon recovers its excitability while the retrograde invasion of the soma and dendrites is still in progress, which provide electrotonic currents to reexcite the axon. 2. While extra spikes in the axon often arise from a prolonged somatic (dendritic?) depolarization, they may also arise from a delayed retrograde invasion of the soma. 3. Failure of retrograde invasion may cause a sudden jump in the rate of rhythmic discharge, demonstrating the role of the soma-dendritic afterhyperpolarization in the regulation of rhythmic firing rate. 4. The history of repetitive firing is often important. Because extra spikes often first appear during a decline in firing rate, turning on and then off, an additional current may sometimes activate the extra spike mode, thus doubling the resting firing rate in a metastable manner. Another mestastable state is associated with failure of retrograde invasion. 5. Extra spikes augment the high end of the frequency-current curve in some receptor neurons; in other cases, the extra spikes are seen only at low rhythmic firing rates, dropping out as current reaches intermediate values to create a paradoxical negative-sensitivity region (decline in total spikes per second with increasing current). 6. The results suggest that both the extent and the speed of active retrograde invasion of the soma and dendrites are likely candidates for pathophysiological mechanisms, since they may control whether extra spikes are generated.


Simple striate neurons in the cat. I. Comparison of responses to moving and stationary stimuli.

1. Peristimulus time (PST) histograms of simple striate responses to static presentations of narrow bright and dark bars in an array of receptive-field (RF) positions have demonstrated one to four response regions with distinct response properties. 2. There is a high degree of correlation of these responses with PST histograms of responses to the same stimuli moving smoothly ("dynamic" stimuli) in a direction perpendicular to the long axis of the RF. 3. Trailing responses to smoothly moving bar stimuli usually occur as the stimulus leaves an apparently inhibitory (for that stimulus) RF region. 4. Spatially leading responses to smoothly moving stimuli occur just as a bar stimulus enters an excitatory RF region, and may be based on certain gradient-detecting properties of neurons. 5. Close agreement in peak firing rates and in positions of responses for statically and dynamically elicited responses in units that are not strongly directionally selective suggests the possibility that in most respects smooth movement responses may be the sequential linear superposition of static responses. A quantitative superposition of static responses from two units supports this conclusion. 6. The dependence on a steady background for sustained responses to static presentation of dark bars illustrates the significance of steady illumination in the RF and raises questions about the efficacy of using edge stimuli as elemental visual probes.


Simple striate neurons in the cat. II. Mechanisms underlying directional asymmetry and directional selectivity.

1. Directionally asymmetric (DA) units respond preferentially to one direction of image movement. If that preferred direction is independent of stimulus contrast then the DA unit is considered directionally selective (DS). We have analyzed receptive-field (RF) properties of striate units with these properties by presenting bar-shaped stimuli that are moved in a stepwise sequence. Short interstimulus durations for certain ranges of step size elicit DA responses similar to those from smooth movement, while still allowing identification of on- and off-components of the response. 2. We have been able to isolate three mechanisms underlying DA and DS. The simplest, superposition, explains the dependence of preferred direction on stimulus contrast found in some DA units. It relies completely on asymmetries in static RF regions to provide an advantage for one direction of image motion by means of the simultaneity of image elements leaving an apparently inhibitory region and entering an excitatory one. 3. For all DA and DS units we have encountered forward inhibition of otherwise excitatory influences that reduces the responsiveness in the antipreferred direction. The spatial specificity of inhibitory target RF regions and the nonlinearity of the effect suggest that lateral inhibition may be transmitted via sequence-detecting subunits. 4. Units that do not show superposition in the preferred direction exhibit forward facilitation of responses in a nonlinear and target-specific way which suggests that facilitation may also be transmitted via sequence-detecting subunits. 5. Each of these mechanisms depends on short-lived influences that are laterally transmitted between 0.125 and 0.5 degrees in visual space. These spatial and temporal values are appropriate for the analysis of smooth movement by the visual system. 6. Stepwise movement sequences using dark bars on a bright background demonstrate for some DA units exactly the same mechanisms as demonstrated using bright-bar sequences in other units or, in the case of DS units, in the same units. In such DS units, which do not normally exhibit strong stationary RF asymmetries, differential sensitivity of the nonlinear DS mechanisms to stimulus elements of either contrast will yield an effective preferred movement direction for complex stimuli.


Visual and presaccadic neuronal activity in thalamic internal medullary lamina of cat: a study of targeting.

1. Visual responses and eye movement-related activities were studied in single neurons of the thalamic internal medullary lamina (IML) of alert cats. The animals faced a tangent screen on which stationary or moving spots of light were presented. Of 95 units, 26% discharged in relation to photic stimuli but not eye movement, 6% in relation to eye movement but not photic stimuli, and 68% in relation to both. These units were intermixed in the same region. 2. Visual responses varied from transient to sustained. IML units were not found particularly sensitive to stimulus movement when the eyes were fixed. Strong and consistent responses could be elicited by extremely dim and weakly contrasted stationary stimuli (e.g.) 3.4 mcd/m2, 2.6% of illumination background) binocularly viewed. Receptive fields (from 250 to 800 deg2) were determined, in absence of eye movements, by computing the position of effective stimuli relative to the point of fixation of the gaze. An area of greatest responsiveness in the receptive field of most units could be detected on the basis of either higher probability of response, minimum latency, greater number of spikes in initial transient burst, or stronger sustained activity. Whole fields or their areas of greatest responsiveness were located on the side toward which saccades were accompanied by increased firing of the unit. 3. On trials in which a delay occurred between stimulus presentation and the cat's targeting saccade, the majority of the units studied changed their activity twice: after the stimulus and before the eye movement. In 16 units, the presaccadic activation occurred only with targeting, not with spontaneous saccades. 4. These results suggest that cells in the IML region of the cat play a significant role in the control of visually elicited eye movements. The resemblance of these cells to the monkey's tectual cells is discussed and hypotheses are proposed a) to relate the receptive field characteristics to the targeting operation, and b) to account for the double activation--sensory and motor--of many IML cells.


Identification of two species of alpha motoneurons in cat's plantaris pool.

1. Single units of the plantaris pool were isolated in ventral root filaments of decerebrate cats and their critical firing levels (CFLs) were determined. Motoneurons of similar size, as judged by their CFLs and other criteria, were compared in firing rate (FR) during repetitive stimulation of the plantaris nerve. 2. Such units either differed very little or quite widely, suggesting that they were sampled randomly from two populations, one firing rapidly, the other slowly. The relationship between the two rates remained approximately constant, regardless of the intensity or rate of input the units received, as long as both of them discharged rhythmically. 3. In single experiments 10-15 of the smallest units in the pool (all with CFLs in the 0-8% range) were isolated and compared. Statistical analyses and visual inspection of these small samples again suggested the existence of two species of motoneurons. 4. Statistical analyses also indicated that the FRs of units in single experiments were not sampled from any one of a variety of parametric, single-modal distributions. This suggests that the data were sampled from a distribution having more than one mode, indicating the existence of separate populations or species of motoneurons among the small units of the pool (0-8% range of CFL). 5. Pooling of the normalized data from different experiments revealed a bimodal histogram, reinforcing the conclusion that there are two species of small alpha motoneurons in the plantaris pool.


Sinusoidal analysis of electroretinogram of squid and octopus.

1. An isolated eye or eye plus optic lobe preparation (in oxygenated chilled seawater) from Loligo opalescens, Octopus bimaculata, and O. bimaculoides was used to study the electroretinogram (ERG) for small signal intensity-modulated stationary spots of light. 2. If light intensity was modulated sinusoidally (modulation depth 0-50%) the ERG response is sinusoidal with less than 2% of the power present in the next five harmonics compared to the fundamental. Bode plots, amplitude and phase shift plotted against frequency, were constructed from these sinusoidal input-output experiments. 3. Linearity and time invariance were tested: a) an increase in amplitude of sinusoidal modulation by a constant factor caused an increase in response amplitude by the same factor but caused no change in shape of the Bode plot gain or phase curves; b) the transfer function represented by the Bode plot could be used to predict waveshape of the response to a brief flash (Green's or impulse-response function); c) the Fourier transformed square-wave response could be used to obtain a Bode plot which coincided with that obtained by sinusoidal input-output experiments. 4. The Bode plot can be fit by the transfer function of 5-12 (depending on conditions and on the preparations) series cascaded low-pass filters whose corner frequences are distributed between 0.2 and 40 Hz. Alternatively, 3-7 filters plus a delay of 25-130 ms fits the Bode plots equally well. The series filter model is compatible with a simply physical model consisting of cascaded chemical reactions whose forward rate constants are reciprocals of the filter time constants, whose reverse rate constants are negligible, and in which the concentration of an intermediate product controls membrane current. 5. As mean intensity is increased, the gain decreases. This effect is more pronounced at low frequencies than at high frequencies. Thus, the system is nonlinear for large intensity changes. The process of adaptation involves not only a change in gain, but a change in shape of the Bode plot, i.e., change in filter corner frequencies. In terms of the reaction chain model, this means that some rate constants change as the state of adaptation is changed.


Effects of unilateral ablation of auditory cortex on monaural cat's ability to localize sound.

1. Cats with one cochlea destroyed were trained to localize sound. After behavioral measures of the animal's accuracy of localization were made, cortical auditory areas were ablated unilaterally. 2. The results showed: a) like binaural localization, monaural localization of sound in space, as measured by the ability of an animal to move toward a sound source, depends on integrity of auditory cortex; b) it is only ablation of cortex contralateral to the functional ear that seriously affects localizing behavior; ablation of cortex ipsilateral to the intact cochlea has little or no effect on localizing behavior. 3. To explain the results, we suggest that auditory cortex is essential for an organized perception of space including the relation of the animal's position to other objects in space. We also suggest that auditory cortex contralateral to a given ear is necessary in order for the animal to recognize that a stimulus is presented to that ear of, when both ears are intact, to recognize that the stimulus to the given ear differs in some way (intensity, time of arrival, sequential arrangement of sounds) from the stimulus to the opposite ear.


Responses and receptive-field organization of cones in perch retinas.

1. Cones in the retinas of two closely related species of perch, the walleye and sauger (S, vitreum vitreum and S. canadense), are remarkably large. This paper reports a first series of intracellular recordings obtained from 77 of these cones. 2. A small spot of light evokes a sustained hyperpolarizing response from perch cones which may exceed 10 mV in amplitude, is graded with stimulus intensity, and is markedly reduced when the spot is decentered. Most cones seem to be orange sensitive with peak sensitivity at about 600 nm. 3. Enlarging the stimulus diameter from 0.04 to 0.25 mm produces a modest increase in the hyperpolarizing response. However, larger stimuli which illuminate surrounding regions of the retina often evoke a delayed depolarizing potential which antagonizes the sustained phase of the cone's hyperpolarizing response to central illumination. 4. The outer diameter of the region of the antagonistic surround is at least 2.2 mm in extent. An annulus evokes a depolarizing response only if the central region of the receptive field is simultaneously activated. 5. The present results provide the first direct evidence that the receptive fields of cones in fish retinas have an antagonistic center-surround organization. Luminosity-type horizontal cells probably serve as the interneurons which mediate the depolarizing influence of the surround.


Saccular and utricular input to cat neck motoneurons.

1. In two series of cats all vestibular afferents except those innervating the saccular or utricular macula were transected and allowed to degenerate. Subsequent anatomical and physiological verification showed that the saccular nerve had been selectively spared in six cats. The utricular nerve was wholly or partly spared in five cats, but there was some possibility of contamination from other vestibular afferents. 2. The connections of the remaining nerve with dorsal neck motoneurons were studied 27-179 days after the initial surgery in preparations anesthetized with chloralose. 3. Stimulation of the saccular nerve usually evoked IPSPs in contralateral, EPSPs in ipsilateral neck motoneurons. Some of the potentials were disynaptic, many were later and probably trisynaptic. 4. The effects of utricular nerve stimulation were more complex, perhaps because of contamination by other vestibular, particularly canal, afferents. The predominant pattern consisted of ipsilateral inhibition and contralateral excitation, opposite to the effects of saccular nerve stimulation. Many potentials were disynaptic. 5. Various factors that may complicate interpretation of the results, including plastic changes following denervation, are considered. It is concluded that they are not a significant factor. 6. Our main result is a demonstration that the sacculus can contribute to vestibulospinal reflexes acting on the head.


Antidromic activity in visual radiation during evoked cortical responses.

1. Antidromic stimulation of the visual radiation of cats has been used to investigate the possibility that some of the activity in principal geniculate cells following an optic tract stimulus is antidromic. Single spikes were selected from two classes of poststimulus activity to condition the antidromic test spike--the undoubted orthodromic postsynaptic spike and the later spikes, occurring up to 100 ms after the optic tract stimulus. 2. In 15 of 39 cells the minimum antidromic activation times and the minimum spike-spike intervals were found to be shorter and latencies for antidromic stimulation were longer when the conditioning spikes belonged the class of late poststimulus activity. The differences are in accord with the assumption that some of the conditioning spikes were antidromic. 3. Test spikes were frequently found to have long and variable latency when the conditioning spike occurred more than 45 ms after the optic tract stimulus. Possible reasons are briefly discussed. 4. It is suggested that antidromic activity may occur in conditions of the cortex that are more physiological than those associated with a penicillin-induced seizure focus. Some possible mechanisms and functional significance are briefly discussed.


The SOSSUS report and its impact on neurosurgery.

The recently completed report of the Study on Surgical Services for the United States (SOSSUS) reveals several features of interest to neurosurgeons. There are approximately 2000 individuals practicing neurosurgery in the United States at the present time. Three-fourths of them are board-certified, and about 100 residents complete their training each year. Neurosurgical training rates have been increasing at six to 10 times the growth rate for the nation's population. Despite moderate variation in regional geographic distribution of practicing neurosurgeons, there is no real evidence of underserved areas. Distribution is even in communities with a population of 75,000 and greater. A critical feature of practice is that of work loads. Diagnostic studies make up a large protion of neurosurgical work, and the SOSSUS Area Studies reveal that complex operations are relatively relatively infrequent. This has serious implications regarding the maintenance of clinical competence, and in concentration sufficient clinical experience to train future generations of neurosurgeons. It is important to realize that the number of neurosurgeons now in practice is sufficient to meet the nation's needs. Selective cutbacks in training programs by approximately 20% seem to be in order, in coordination with similar cuts in other surgical specialties as well. This should be accompanied by a readjustment to a modest growth rate, approximately 1% per 5 years, in the ratio of neurosurgeons per 100,000 population. An accurate system of data collection is needed to provide the basis for future change in response to alterations in national needs.


Brain-tumor therapy. Quantitative analysis using a model system.

A recently developed colony-formation assay has been used to evaluate in vivo 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) therapy of a transplantable rat brain-tumor model. A comparison of the in vitro colony-forming capacity of treated and untreated tumor cells permits calculation of the fraction of clonogenic tumor cells surviving in vivo therapy; The plateau that we previously observed o the BCNU dose-response curve is not the result of repair of potentially lethal damage, since no change in the 0.1% of surviving clonogenic tumor cells occurs during the first 2 to 4 days after treatment. Although reanalysis of the dose-response curve indicates that sublethal damage exists, its repair is probably minimal. The most likely explanation for the observed limitation of the BCNU effect is the drug's failure to reach all clonogenic cells. A dose of BCNU that kills more than 99.9% of clonogenic tumor cells within 30 minutes of treatment results in only a 60% decrease in tumor weight by Day 14. This disparity is explained by retarded removal of dead cells, and, along with a previously determined 90% cell-kill threshold necessary to appreciate increased animal survival, demonstrates the inherent limitations of measurements of tumor size (including brain scans and clinical patient evaluations) in evaluating the efficacy of brain-tumor therapy. Following at LD10 dose of BCNU the surviving clonogenic tumor cells increase in number after latency period of 2 to 4 days; during regrowth the cell doubling time is 40 hours. Marked variability in tumor response and regrowth was noted. The determination of information regarding disturbed tumor cell kinetics and tumor heterogeneityis essential for the proper planning of combination chemotherapy and multimodality regimens.


Intraneoplastic injection of methotrexate for experimental brain-tumor chemotherapy.

The retention and distribution of tritiated methotrexate (MTX-3H) after direct intracerebral or intraneoplastic injection were studied in mice bearing subcutaneous or intracerebral ependymoblastomas. After intracerebral injection of MTX-3H in nontumor-bearing animals, a large amount of the drug was retained in the head, much more than could have been retained after systemic administration, and there was rpaid spreading of the drug through the ipsilateral hemisphere. Intraneoplastic injection of subcutaneous and intracerebral tumors produced rapid spreading of the drug through the tumors. Intially, the drug was mainly in the intersititial fluid of the tumors followed by earlier cellular uptake than was seen after intravenous injection. Even though the distribution of the drug in the intracerebral tumors was not uniform, and some intracranial tumor deposits contained less radioactivity than areas closer to the site of injection, intraneoplastic injection may have advantages for brain-tumor chemotherapy. However, further experimental study is necessary before clinical application can be recommended, especially evaluation of neurotoxicity after intracerebral, intraneopasltic injection of MTX or other chemotherapeutic agents.


Therapy of an experimental glioma with systemic or intraneoplastic methotrexate or radiation.

An intracranial mouse glioma model was used to study the effectiveness of chemotherapy with methotrexate )MTX) or radiotherapy. Maximum tolerable doses of MTX were established by toxicity studies in nontumor-bearing mice for the intraperitoneal and intracerebral routes of drug administration with and without leucovorin as an antidote. These maximum tolerable doses were then given either by the intraperitoneal route or directly into the tumor to mice bearing intracerebral tumors. The glioma model proved to be extremely useful for assessing the modalities studied, including repeated intraneoplastic injection of MTX. Dosage schedules were successfully developed for administering large amount of MTX and for preventing systemic toxicity by the administration of the antidote. Radiotherapy in single doses and 800 rads delayed the median day of death and produced several long-term survivors. Higher doses were toxic. Intraperitoneal or intraneoplastic MTX was completely ineffective as a chemotherapeutic agent for this tumor, even though very large amounts could be delivered due to the protection from systemic toxicity afforded by leucovorin. It is concluded that MTX is a poor chemotherapeutic agent for this experimental brain tumor, but that the technique of intraneoplastic administration of chemotherapeutic agents is feasible with this model system and should be studied further.


Measurement of CBF and carotid artery pressure compared with cerebral angiography in assessing collateral blood supply after carotid ligation.

Angiographic assessment of collateral circulation to the brain at the circle of Willis was compared with measurements of cerebral blood flow (CBF) and internal carotid artery pressure during temporary carotid clamping in the prediction of tolerance of unilateral carotid ligation as treatment for intracranial carotid aneurysms in 92 patients. From CBF studies it was predicted that a substantial number of patients (27%) would suffer severe cerebral ischemia if carotid ligation were carried out. No single angiographic feature provided this predictive information. Bilateral fetal type of posterior communication arteries were associated with significantly lower carotid artery back pressure on temporary carotid occlusion, and unilateral absence of posterior communicating arteries was related to llower CBF, but neither feature was associated with a signifiant reduction in the rate of successful carotid ligation. We believe that preliminary percutaneous digital corotid compression with electroencephalographic monitoring, followed by intraoperative measurement of the change in regional CBF and internal carotid artery pressure during temporary carotid clamping provides a safe method of selecting patients for carotid ligation. Carotid angiography with or without contralateral carotid compression is of little value in this respect.


The mechanism of spinal cord cavitation following spinal cord transection.

Transection of a spinal cord is followed by massive accumulation of lysosomes and release of lysosomal hydrolases within both the rostral and the caudal spinal cord stumps. The lysosomal activity begins at 3 hours after cord transection, maintains its peak for 3 to 7 days, and declines at 14 days after transection. The process if associated with autolysis of the cord stumps and subsequent cavitation. Lysosomal accumulation is greatly diminished, and, paradoxically, superior wound healting is the result at the stumps of a 5-mm segment of isolated spinal cord produced by double cord transection.


A new surgical approach to the treatment of coronal synostosis.

The authors described a surgical technique for the treatment of unilateral coronal synstosis, which they have carried out successfully in 16 children. Frontal craniotomy, removal of the lesser wing of the sphenoid, orbital unroofing, and removal of the entire orbital rim are recommended as essential elements of carnio-orbital reconstruction in the treatment of plagiocephaly.


A physiological sealant for cerebrospinal fluid leaks.

A combination of concentrated platelets, thrombin, and fibronogen was used to adhere a pericranial graft to surgically produced cerebrospinal fuild (CSF) fistulas in dogs. This sealant successfully stopped leakage of CSF in all fistulas produced in both acute and chronic preparations. All control animals leaked CSF acutely. In chronic control animals the CSF leaks sealed spontaneously but the grafts were not well incorporated. Histoligical examination of the grafts and underlying brain showed not injury to the brain of meningeal vessel from exposure to the platelet glue. Good fibrous union of the grafts to the dura was confirmed.


Definitive treatment of chronic subdural hematoma by twist-drill craniostomy and closed-system drainage.

A simple method of bedside twist-drill craniostomy and closed-system drainage for evacuation of chronic and subactue subdural hematoma is introduced. The principles and theoretical considerations that form the basis for this technique are discussed. The technique was used in 21 patients with chronic or subacute subdural hematoma; it has produced results superior to those of the conventional methods used in our patient population. Possible mechanism responsible for the better results with the simple twist-drill closed-system drainage are described.


Calcified cervical intervertebral discs in children. Report of three cases.

Calcified cervical intervertebral discs in children are manifestations of an uncommon, distinct disease of unknown cause. Acute symptoms are usually followed by a benign course of spontaneous recovery, frequently culminating in resorption of the calcium. Rarely herniation of the disc may cause neurological complications. Two cases are presented as examples of the typical syndrome. A third case was operated on because of herniation with radiculopathy; the clinical, radiographic, and pathological findings are reported in detail.


Occipital mesenchymal tumors of infancy. Report of three cases.

Mesenchymal tumors arising from the dura in three newborn babies are described, with discussion of their clinical and pathological significance.


"Congenital" plexiform neurofibroma of the occipital scalp. Case report.

An occipital scalp tumor first noted in a Nigerian girl during the first month of her life gradually increased in size and 13 years later measured 10 X 16 X 17 cm. A skull film revealed a 2 X 4-cm skull defect underneath the tumor over the lambdoid suture. Complete excision of the tumor was achieve although it was adherent to the dura of the transverse sinus. It was histologically confirmed to be plexiform neurofibroma. There were no other signs of van Recklinghausen's neurofibromatosis.


Cortical vein thrombosis in Wegener's granulomatosis. Case report.

A patient with Wegener's granulomatosis is reported in whom a life-threatening cortical vein thrombosis was identified as the process causing acute neurological deterioration. The literature dealing with the neurological and neuropathological manifestations in Wegener's granulomatosis is reviewed.


Entrapment of median nerve by supracondylar process of the humerus. Case report.

The supracondylar process of the humerus has been described by anatomists and anthropologists in man and lower animals. Infrequently this process may cause compression of the median nerve. We are presenting such a case along with a brief review of the literature. Excision of the bone process led to immediate disappearance of symptoms.


Demonstration of massive traumatic brain swelling within 20 minutes after injury. Case report.

The authors documented by computerized axial tomography a case of massive brain swelling occurring within 20 minutes of a closed head injury. It is suggested that the cause of the brain swelling is acute vascular dilatation.


Visualization of a bullet track on brain imaging. Case report.

A case is reported in which an intracerebral bullet track was demonstrated by brain imaging, The possible advantages of technetium-99-m localization and the role of brain imaging in gunshot injuries of the head are discussed.


99mTc-DTPA scintillation-camera renography: a new method for estimation of single-kidney function.

A new method of combined serial scintigraphy and renography, using a scintillation camera and 99mTc-DTPA is evaluated. Renographic curves, corresponding to light-pen "areas of interest" over the renal parenchyma, were processed. "Blood-background" curves were recorded from an external detector over the temporal region of the head and also from an "area of interest" corresponding to the aorta and inferior vena cava. The uptake phase of the renogram was always linear. The sum of the slopes of the uptake phase of both kidneys correlated well with the measured glomerular filtration rate in 25 patients with renal insufficiency of various degrees. Single-kidney function estimated from the slopes correlated reasonably well with single-kidney function estimated from 131I-Hippuran renography with external detectors. The method described minimizes errors in the estimation of single-kidney function, and both anatomic and functional information is obtained.


Clinical comparison of 99mTc-labeled preformed phytate colloid and sulfur colloid: concise communication.

An in vitro preformed colloid preparation of 99mTc-Sn-phytate was compared both qualitatively and quantitatively with a commercial 99mTc-sulfur colloid kit in 30 patients. The degree of liver and spleen deposition of radiocolloid was, for practical purposes, the same. A slightly higher background was visually noted in 33% of the patients receiving preformed colloidal 99mTc-Sn-phytate, but it did not interfere with the diagnostic quality of the liver and spleen images. The only advantage of the phytate compound was a preparation time of less than 5 min.


Can 99mTc-pertechnetate be used to assess the secretion of gastric acid in pernicious anemia?

The gastric secretion of 99mTc-pertechnetate as a means of assessing parietal cell function was investigated in 12 pernicious anemia (PA) patients with histamine-fast achlorhydria. Twelve control subjects were either normal volunteers or patients proven not to have either PA or any other gastrointestinal disease. The results indicated that, while the stomachs of PA patients secreted no hydrochloric acid, they continued to secrete 99mTc-pertechnetate, indicating that 99mTcO4 - is secreted not by parietal cells alone or else not by parietal cells at all. The gastric pertechnetate activity, therefore, cannot be used as an index of gastric acid secretory activity in PA.


Distribution of orally administered bromine-82 in tubercular meningitis: concise communication.

Bromine-82 as ammonium bromide (0.6 muCi/kg) was administered orally to 86 children with neurologic manifestations of tubercular meningitis (TBM). The cerebrospinal-fluid-to-plasma activity ratios were obtained at 48 hr. A serum-to-CSF ratio below 1.9 was highly specific for TBM (40 of 42 patients), and only 4 of 44 patients with neurologic disorders other than TBM had ratios below 1.9. An attempt to simplify the diagnosis of TBM was carried out in 44 of the 86 patients by obtaining external counts over the head, heart, and thigh at 4, 24, and 48 hr after Br-82 administration, but these external counts did not distinguish TBM patients from the other patients in our series.


Radionuclide imaging of aortic involvement in Buerger's disease: case report.

Complete obstruction of the descending aorta, at a level just below the diaphragm, was diagnosed during a renal dynamic flow study. This is the second reported case of Buerger's disease causing aortic obstruction and the first such case initially diagnosed using nuclear medicine techniques.


Diagnosis of chylothorax with 131I-triolein: case report.

Communication between the thoracic duct and the pleural space can be demonstrated after oral administration of radiolabeled triglycerides or fatty acids of suitable chain length. A case of chylothorax was confirmed in this manner using 131I-triolein. The technique may be most useful in cases where the chylous nature of a pleural effusion is not apparent on inspection of the pleural fluid.


Pancreatic scanning in diagnosis of macroamylasemia: case report.

Macroamylasemia and acute pancreatitis are both associated with a high serum amylase. The former is an incidental laboratory finding and seems to have no apparent clinical significance or specificity. On the other hand, acute pancreatitis is a serious illness demanding recognition and treatment. Persistently normal pancreatic scans convincingly exclude acute pancreatitis and should alert one to the possible presence of macroamylasemia.


Thallium-201 for medical use. Part 3: Human distribution and physical imaging properties.

Studies were undertaken to determine the biologic distribution of thallium-201 in man. The disappearance from the blood is extremely rapid and intracellular deposition is nearly immediate. The biologic half-time of thallium was measured by both the Brookhaven whole-body counter and the Donner whole-body scanner, with excellent agreement. The effective whole-body half-time of thallium-201 is about 57 hr. Concentration of activity was seen in the heart, kidneys, large bowel, and thyroid. The whole-body radiation dose is 0.21 rads/mCi.


Organ distribution of 99mTc- and 51Cr-labeled autologous peripheral blood lymphocytes in rabbits.

The present series of experiments was designed to compare 99mTc with 51Cr as a lymphocyte label in rabbits and to correlate organ distribution patterns as determined by postmortem counting with those observed by 99mTc gamma imaging. The distribution of 51Cr and 99mTc-labeled, viable and nonviable, unreduced or SnCl2-reduced autologous lymphocytes was determined 2 hr following intravenous injection. Viable 99mTc-labeled lymphocytes localized primarily in the liver, lungs, and kidneys or remained circulating in the blood. These compartments accounted for 34-54% of the injected radioactivity. One to three percent of the injected dose was recovered from the spleen, thyroid, bladder, and stomach, and all remaining organs accounted for less than 1%. Reduced, nonviable cells showed increased localization in the lungs and liver (48%) compared to viable unreduced cells (15%). Chromium-51-labeled lymphocytes were distributed primarily to the liver, lungs, and spleen or remained circulating in the blood. Hepatic localization differed from that observed with viable, unreduced 99mTc-labeled lymphocytes (32 vs. 12%), but vascular compartmentalization was similar (18 vs. 15%). The distribution of pertechnetate and reduced 99mTc was different from that of 99mTc-labeled cells. The urine and blood accounted for 84% of the recovered radioactivity, and for 43-45% of the injected dose, indicating that the patterns we observed with 99mTc-labeled lymphocytes truly represented cell-associated radioactivity. Similarly, the distribution of Na251CrO4 differed from that of 51Cr-labeled cells. The kidneys and urine accounted for 26% of the injected dose, compared with 5% for 51Cr-labeled lymphocytes, and only trace amounts of radioactivity were found in the lungs and spleen. The distribution of 99mTc-labeled cells, as determined by scintigraphy 90 min after injection, correlated well with data obtained by postmortem counting, suggesting that 99mTc may be applicable as a lymphocyte label for diagnostic gamma-imaging procedures.


Fluorine-18-labeled diethylaminosulfur trifluoride (DAST): an F-for-OH fluorinating agent.

A new fluorinating agent was developed by incorporation of 18F into diethylaminosulfur trifluoride (DAST), a reagent capable of replacing hydroxyl and carbonyl oxygen with fluorine. The DAST was synthesized using sulfur tetrafluoride and trimethylsilyldiethylamine in a freon-11 solvent at -78 degrees C and purified by reduced-pressure distillation. Labeling was then accomplished by exchange with anhydrous 18F-hydrofluoric acid, which caused more than 80% of the available activity to be incorporated into the DAST. Fluorine-18-labeled methyl fluoride, ethyl fluoride, and 2-fluoroethanol were prepared from methanol, ethanol, and ethylene glycol, with yields of 20%, 25%, and 12%, respectively.


Cardiac blood pool imaging over the complete cardiac cycle with a multiformat imager.

A new method of obtaining scintigraphic images of the cardiac blood pool for the study of ventricular wall motion is described. The method, which is based upon an inexpensive modification of a commercial multiformat imaging device, yields a set of serial gated images covering the entire cardiac cycle. These images may be converted into a film loop to yield a continuous motion picture of the mechanical cycle of the heart.


Evaluation of a thyroid fluorescent scanning system of concentric source-detector design.

A concentric source-detector system for thyroid fluorescent scanning is described, including fundamental parameters of system response and adaptation of a conventional rectilinear scanner for use with it. The basic system consists of twenty 1-Ci sources of 241Am, a 500-mm2 Si(Li) detector, and associated pulse-height electronics. The image-forming equipment of the rectilinear scanner is retained. We have developed a clinical imaging technique that provides a photon density of 600-800 counts/cm2 over the thyroid gland in subjects with normal iodine pools. Comparisons are made between the outrigger design for fluorescent scanning and conventional emission scanning.


Clinical significance of scintillation camera electronics capable of high processing rates.

The use of larger scintillation detectors with high-efficiency converging collimators has greatly increased the photon input rate to the crystals of scintillation cameras in many clinical studies. To process these high-count-rate data accurately, modifications have been made by some manufacturers in the electronics of scintillation cameras. Cameras with new electronic design were compared with earlier models with respect to count rate processing capability and the effect of high input rate on spatial resolution, pulse-pair pileup, image size, and instability of the amplification of energy pulses. The improvements with the new electronic design result in shorter imaging times, better preservation of resolution, increased statistical reliability, and reduced distortion of dynamic tracer curves used for quantitative analysis.


Effects of noise on the determination of ejection fraction from left ventricular time-activity curves.

The effects of Poisson noise on three estimates of ejection fraction made from left-ventricular time-activity curves have been investigated. All three methods are based on a sinusoidal model of left-ventricular volume changes. The first, developed by Schelbert et al., overestimates the ejection fraction for low-activity levels and low ejection fractions. The second estimate, which is merely a first-order correction for the contribution of Poisson noise to the first estimate, appears to be more accurate when both estimators are applied to simulated time-activity curves, and the resulting ejection fractions are compared. A third, "maximum likelihood" estimator, when applied to the same data, is apparently more accurate than the first two.


Studies of radiopharmaceutical-enclosing lipid-protein vesicles formed from native plasma components.

Vesicles 500-600 A in diameter were formed by sonicating diluted samples of rat and mouse plasma. An average preparation of these vesicles formed from 1 ml of plasma contained 7.5 mg of plasma lipid and 7.3 mg of plasma protein. Plasma vesicles could be made to enclose such radiopharmaceuticals as 99mTcO4-, and the vesicles were found to be impermeable to this anion. We have studied the in vivo distribution patterns of 99mTc after intravenous injection into the rat or mouse of pertechnetate-plasma vesicles formed from rat or mouse plasma, and we find that the radioactivity remains primarily within the circulation even at 60 min after injection. In contrast, vesicles formed from artificial lipids are rapidly removed by the liver and spleen. Formation of vesicles from native plasma constituents offers a means of carrying drugs and radiopharmaceuticals in vivo in packages that have a low risk of being either toxic or antigenic.


Dietary influences on gastric emptying of carbohydrate versus fat in the rat.

The degree to which the rat stomach empties carbohydrate in preference to fat was studied in rats fed a diet or various test means providing carbohydrate and fat in a 3:1 (w/w) ratio. When rats were adlibitum fed a glucose-containing diet, the glucose:fat ratio in gastric contents was consistently lower than in the diet and was 10% as great at noon as at midnight. When starved rats were fed a single meal of the same diet the average fractional emptying rate for carbohydrate exceeded that for fat; and the ratio of these rates ("the gastric emptying ratio") was essentially the same when calculated from gastric contents observed 1, 2, 4, or 6 hours after the test meal. The gastric emptying ratio was also not changed when test means were made with hard, soft, or liquid fat or with no or extra protein (lactalbumin). Use of finely divided glucose monohydrate, dried crystalline glucose or of cornstarch resulted, respectively, in high, intermediate and low gastric emptying ratios. The kind and form of carbohydrate in the meals and the ease of its extraction with water appear to be important factors governing the degree to which carbohydrates is preferentially emptied from the stomach.


Influence of (-)-hydroxycitrate on lipigenesis in chickens and rats.

The influence of (-)-hydroxycitrate on in vitro rates of fatty acid synthesis in chicken and rat liver and in rat adipose tissue was investigated. Following acute and chronic administration of (-)-hydroxycitrate to chickens and rats, changes in rates of fatty acid synthesis in vivo and in lipogenic enzyme activities were also determined. Addition of 1 mM (-)-hydroxycitrate to a buffer containing 10 mM glucose and liver slices from chickens or rats depressed the rate of 3H2O incorporation into fatty acids. Acute administration of (-)-hydroxycitrate to chickens and rats also depressed in vivo rates of fatty acid synthesis in the livers of these species. Chickens appeared to be more sensitive to the inhibitory effects of (-)-hydroxycitrate than did rats. (-)-Hydroxycitrate was incorporated into the diets fed to the chickens and rats. Hepatic citrate cleavage enzyme activities were increased several fold in livers of chickens and rats fed (-)-hydroxycitrate. However, the rates of fatty acid synthesis in chicken and rat livers were depressed when expressed per g liver. Livers of chickens fed (-)-hydroxycitrate for 14 days were enlarged. Dietary (-)-hydroxycitrate did not depress rates of fatty acid synthesis per liver in these birds. Consumption of (-)-hydroxycitrate did not alter liver weight in rats. In vivo rates of fatty acid synthesis in rat adipose tissue were not influenced by consumption of a diet containing 52.6 nmoles (-)-hydroxycitrate/kg diet. Plasma triglyceride levels were increased two-fold in chickens, but unchanged in rats, fed (-)-hydroxycitrate for 2 to 3 weeks. There are species-specific as well as organ-specific responses to (-)-hydroxycitrate.


Nitrogen metabolism, tissue carnosine concentration and blood chemistry of gravid swine fed graded levels of histidine.

Three nitrogen metabolism experiments were conducted to determine the qualitative and quantitative histidine need of first-litter gilts during the last third of pregnancy. A completely purified, crystalline 8amino acid diet was formulated to meet all nutrient needs of the gravid gilt when 2 kg/day was fed. Experiments 1 and 2 were 9-day nitrogen balance studies, each consisting of three littermate gilts subjected to three levels of dietary L-histidine in a Latin square arrangement of treatments. Nitrogen retention was depresed, but not significantly, when less than 0.12% histidine was fed. Complete deletion of histidine, however, did not depress retention below that observed when 0.06% was fed. This suggested that either histidine biosynthesis or its release from endogenous reserves was confounding retention data. Therefore in a third experiment, two gilts were fed a histidine-free diet for 24 days in an attempt to deplete endogenous reserves. For comparison, two siblings were fed 0.12% histidine during this same period. Nitrogen retention tended to be lower for gilts fed the histidine-free diet during each of three consecutive collection periods. Blood hemoglobin, muscle and olfactory bulb carnosine concentration, plasma protein and glutamic-oxaloacetic transaminase activity, and blood urea nitrogen were all unaffected by treatment. Offspring from gilts fed the histidine-free diet had lower blood hemoglobin concentrations than their counterparts from gilts receiving histidine. A tentative recommendation of 0.12% dietary L-histidine would seem justified for gravid swine.


Uptake of pyridoxine hydrochloride by the rat jejunal mucosa in vitro.

The kinetics of mucosal membrane transport of pyridoxine hydrochloride were evaluated in vitro in the rat jejunum. Utilizing everted sacs and a double-label isotope technique, short-term incubation within the period of initial linear tissue uptake indicated: 1) no evidence of saturation of uptake over a wide pyridoxine-HCl concentration range (0.01 muM-10 mM); 2) failure of 4-deoxypyridoxine (10 muM), anoxia, iodoacetamide (5 mM), Na+ replacement and ouabain (1 mM) to inhibit uptake of 2 muM pyridoxine-HCl significantly; and 3) a low Q10 value of 1.31. Using single-label techniques, sacs were also incubated for 1 hour in 2 muM pyridoxine HCl with determination of the apparent tissue water-mucosal fluid concentration ratio and chromatographic separation of the various forms of vitamin B6 in tissue. Results demonstrated a failure of pyridoxine in tissue water to achieve a concentration in excess of that in the incubation medium. Data, therefore, were most consistent with passive diffusion as the mechanism for in vitro jejunal mucosal uptake of pyridoxine-HCl in the rat.


Dietary carnitine and adipose tissue turnover rate in exercise trained rats.

Rats trained by 12 weeks of treadmill running were divided into two groups and fed a control diet or an identical diet supplemented with 0.5% L-carnitine. Adipose tissue fatty acid turnover was subsequently estimated by an odd-carbon fatty acid enrichment method utilizing undecanoate as a marker representative of adipose tissue fatty acids. Compared to sedentary untrained control rats, exercise training increased perirenal adipose tissue turnover rate approximately 70%. Trained rats fed the carnitine supplemented diet did not exhibit any further increase in turnover rate. Neither [1-14C]palmitate oxidation by skeletal muscle homogenates nor palmitycarnitine acyl-transferase activity in skeletal muscle mitochondria was affected by carnitine feeding. The results of this study indicate that exercise training increases the turnover rate of adipose tissue fatty acids, but supplemental dietary carnitine does not. Under the conditions of this study, endogenous skeletal muscle carnitine levels in trained rats appear to be adequate to support the rate of fatty acids oxidation incurred by daily treadmill running.


Influence of dietary copper on lead toxicity in the young male rat.

An investigation of the influence of dietary copper (1, 5, 20 ppm) on toxicity of dietary lead (0 and 200 ppm) in the young male rat in a 4-week period indicated that as dietary copper increase so did the severity of lead toxicity. Evidence included increased lead concentration in kidney and a two- to threefold increase in the excretion of urinary delta-aminolevulinic acid. Liver copper concentration was also found to increase in rats receiving lead at the two lower copper levels. The data suggest that supplementary dietary copper doesnot lessen the severity of lead toxicity but rather exaggerates it.


Insulin sensitivity and adipose tissue weight of rats fed starch or sucrose diets ad libitum or in meals.

The deposition of edidymal and perirenal fat, serum insulin levels, and insulin sensitivity of epididymal fat, expressed as the insulin-stimulated production of CO2 from glucose, were determined in Wistar rats fed diets containing either 54% starch or sucrose ad libitum or pair-fed in meals. Regardless of the pattern of feeding, sucrose-fed rats deposited more adipose tissue per 100 g body weight and exhibited less insulin sensitivity than did starch-fed rats. Significant differences in adipose tissue weights were not always accompanied by significant differences in body weights. Meal-fed rats deposited less adipose tissue and showed a greater insulin sensitivity than did ad libitum rats fed the same carbohydrate. However, when changes in feeding pattern negated the difference in adipose weights there was no difference in the insulin sensitivity of the meal-fed and ad libitum-fed rats. Rats consuming the sucrose diet generally exhibited significantly higher fasting serum insulin levels than did rats consuming the starch diet. The serum insulin values tended to be higher in the ad libitum-fpididymal tissue from the meal-fed and starch-fed rats tended to be greater than that of the sucrose-fed or ad libitum-fed rats, respectively, suggesting differences in adipocyte composition. Since obesity, insulin insensitivity, and hyperinsulinism are associated with an impairment of glucose tolerance, the observed metabolic effects of dietary sucrose are considered to be undesirable.


Effects of dietary protein, glycine, and tryptophan on iron metabolism in the growing chick.

Experiments were conducted to determine the effects of feeding diets low in protein, glycine, or tryptophan on iron metabolism in the growing chick. Three-day-old chicks, which were fed the experimental diets to 2 weeks of age, were given orally a solution of 59FeSO4 in order to determine the percentage of iron absorbed and excreted (determined by the fecal recovery method) and iron utilized and stored (determined by the radioactivity retained per unit liver, gastrocnemius muscle, and whole blood) 7 days post dose administration. The feeding of diets low in protein (5.4%, 8.5%, or 10.8%) or tryptophan (0.12%) but adequate in iron to growing chicks caused: a marked reduction in growth, rate of erthropoiesis, and percentage iron absorption; an excessive increase in iron deposited in the liver and muscle, and percentage iron collected in the excreta; and anemia which was attributed to the deficiency of protein or tryptophan respectively, in the diets fed. The feeding of diets low in glycine (0.33%) but adequate in iron caused: a marked reduction in growth and percentage iron, absorption, and a transitory increase in percentage of iron excreted without causing anemia or affecting the distribution of absorbed iron in liver, muscle and blood. The total plasma protein concentration was reduced in protein deficient chicks, but was not affected by a tryptophan or glycine deficiency.


Preventive effect of selenium, methionine and antioxidants against encephalomalacia of chicks induced by dilauryl succinate.

The protective effect of supplemental selenium, methionine, ascorbic acid, menaquinone and five antioxidants against encephalomalacia of chicks fed a diet containing dilauryl succinate was examined. Diauryl succinate induces vitamin E deficiency signs such as fragility of the erythrocytes and encephalomalacia. Supplementation of selenium and methionine with or without simultaneous supplementation of a low level of dl-alpha-tocopheryl acetate had little effect on preventing encephalomalacia. The preventive effect of ascorbic acid, methylene blue, ethoyquine, 2,6-ditertiary-butyl-p-cresol and butylated hydroxyanisole was roughly in proportion to their dietary level, and a high level of any of them could almost completely protect the chicks from encephalomalacia, while diphenyl-p-phenylenediamine was not as effective and the effect was not proportional to the dose. Menaquinone had little effect. No difference was observed in the plasma tocopherol levels and peroxide levels in the adipose tissueof the chick fed eith er dilauryl succinate or cornstarch. The effect of dilauryl succinate appears to be independent of peroxides generated in the chick.


Effect of crude fat and crude protein on reproduction and weaning growth in four strains of inbred mice.

Diets made from natural ingredients were fed to four inbred strains of mice (BALB/cAnN, C3H/HeN, C57BL/6N and DBA/2N) to study the effects of different concentrations of dietary crude protein, 18% and 24% with crude fat concentrations of 4%, 8%, and 12% on reproduction and weanling growth. The parameters measured included the number of litters and pups born, the number of litters and pups weaned, weanling mortality and weanling weight. Neither crude protein nor crude fat concentrations had significant effects on any of the reproductive parameters tested. However, a significant fat x protein interaction was observed for reproduction. These results indicate that the absolute concentrations of crude protein and crude fat in diets for inbred mouse production are not as important as the ratio of these two nutrients. There was also a differential response in reproduction among the strains due to the level of fat which indicates different dietary requirements for fat among these four inbred strains for maximum reproduction. In contrast to the results for reproduction, crude protein and crude fat independently had significant effects on weanling weight, but there was no effect due to the ratio of the nutrients. There was a significant increase in the weanling growth rate for all four strains as the dietary fat level increased, but a decrease in growth rate as the protein level increased. The reduced growth rate due to the increased protein was not of the same magnitude for all four strains which indicates specific protein requirements among the strains for weanling growth.