The connections of the trigeminal and facial motor nuclei in the brain of the carp (Cyprinus carpio L.) as revealed by anterograde and retrograde transport of horseradish peroxidase.

The connections of the rostral and caudal parts of the trigeminal and facial motor nuclei in the carp were studied with the horseradish peroxidase technique. Following ionophoretic peroxidase injections in these motor nuclei, retrogradely labeled cells were observed together with anterogradely labeled motor cell processes. Several cellular areas in thalamus, cerebellum and medulla oblongata were shown to project to the V and VII motor nuclei. Labeled cells were found in the inferior lobe and the glomerular complex of the thalamus. In the medulla oblongata, cells in the descending trigeminal nucleus, reticular nuclei and motor nuclei other than those injected were labeled. Besides these conspicuous projections several smaller connections were also found. These findings are discussed on their significance to respiratory function. Anterogradely labeled cellular processes constitute a relatively simple network of fiber connections between the various motor nuclei and the reticular nuclei of the brainstem. This apparently dendritic system of the bulbar motor complex shows a certain degree of similarity to the structure of the motor system in the spinal cord, and might play a role in the coordinated control of the muscular system.


Commissural connections of the dentate area in the rat.

The commissural connections of the area dentata were investigated with the Fink-Heimer silver impregnation method and the commissural terminals in the hilus of the fascia dentata further studied by electron microscopy of anterograde degeneration. The commissural endings in the molecular layer were found to terminate as previously reported by others. In addition it was shown that the hilus also receives a significant commissural input. The commissural afferents to both the molecular layer and the hilus terminate along the full rostro-caudal extent of the area dentata, but with varying densities. The degeneration in the molecular layer is maximal dorso-rostrally and declines in the caudo-ventral direction, whereas the degeneration in the hilus varies inversely. The commissural terminals in the hilus make asymmetrical contacts with dendritic spines and to a lesser extent with dendritic stems. Dark, but otherwise apparently normal terminals with the features of mossy fiber boutons, were encountered in low numbers in both decommissurated and control animals. The commissural projection to the dentate area originates in the opposite hilus and possibly the adjacent part of CA3 (CA3c). Fibers from middle dorso-basal levels of the hilus to the opposite molecular layer are distributed more rostrally than ventrally relative to the level of the source of the fibers.


Development of outer segments and synapses in the rabbit retina.

The peripheral retina of rabbits aged 0 to 60 days was studied by electron microscopy. Ribbon and conventional synaptogenesis was studied with serial sections, and the density of synapses of the inner plexiform layer was measured on large (1,500 micrometer 2) montages. Photoreceptor and bipolar ribbon synapses seem to develop similarly in that processes of the prospective dyad or triad contact the presynaptic ribbon-containing terminal one at a time. No statistically significant difference in the lengths of ribbon lamellae was found at 11 and 30 days. Conventional synapses appear to result from the aggregation of synaptic vesicles on one side of junctions that first existed as symmetrical membrane densities without vesicles. The length of the synaptic membrane specialization constant between 0 and 30 days. The density of inner plexiform layer conventional synapses remains at a low and roughly constant level from 0 to 9 days, after which there is an abrupt increase to a plateau at about 20 days. After nine days the density of ribbon synapses also increases, with an initially steep time course similar to that of conventional synapses. All subcategories of synapse studied (amacrine-to-amacrine, amacrine-to-bipolar, serial, and reciprocal) participate in the general increase between 9 and 20 days. Functional circuits of the inner plexiform layer thus seem to be assembled primarily during the second and third weeks of life.


Maturation of function in the developing rabbit retina.

Retinas isolated from rabbits aged less than eight hours to adult were maintained in a flowing physiological medium. The electroretinogram or activity of single ganglion cells were recorded, and receptive fields were studied using stimulation of the retina with focused light. Retinal activity was stable for at least eight hours of incubation. Retinal ganglion cells are electrophysiologically active on the first day of life. They generate spontaneous bursts of action potentials at rates of 10 to 30 spikes/sec, separated by silent intervals of one to six minutes. Maintained trains of action potentials follow elevation of the concentration of K+ in the incubating medium to 10 mM. Ganglion cells are also stimulated by acetylcholine, with apparent thresholds equal to or lower than those of ganglion cells in adult retinas. The first response of the retina to light is a small cornea-negative transretinal potential at day 6, presumably  PIII of the electroretinogram. Responses of the ganglion cells are seen at eight days, but the responses are weak and adapt quickly to repeated stimulation. Many unresponsive cells are present. By ten days 60% of ganglion cells respond to light, and examples of mature receptive fields are present. Immature receptive fields at ten days fall into two rough classes, one characterized by a large responsive area with no antagonistic surround, and a second in which the surround can suppress the response to illumination of the center but can not itself cause a discharge. Immature fields are progressively replaced by mature ones, and by 20 days the qualitative organization of receptive fields is indistinguishable from adult.


Cytoarchitecture of the tectum mesencephali in two types of siluroid teleosts.

The cytoarchitecture of the tectum mesencephali in the siluroid teleosts Bagrus and Ictalurus was studied by means of the Golgi method. These animals are known to have a restricted visual system and it seemed important to study whether this fact would affect the existence or the shape of the main neuron types which have been described for highly visual teleosts. It had been shown for a variety of teleosts that the retinotectal axons and terminals occupy almost exclusively the stratum opticum and the stratum fibrosum et griseum superficiale. The thickness of these strata in Bagrus and Ictalurus was found to be reduced. However, the main types of especially the vertically oriented neurons, such as the pyramidal, fusiform, large pyriform and periventricular neurons which have been described for highly visual species of teleosts, were also found in Bagrus and Ictalurus. Although their shape was somewhat distorted, these neurons, nevertheless, showed processes distributed to the same tectal layers as in highly visual teleosts and are accessible to horizontally distributed fiber systems such as marginal, telencephalotectal and commissural tectal fibers, as well as the retinotectal fibers. Nonvisual inputs appear to be considerably involved in the maintenance of the main neuron types in the siluroid tectum. For example, the pyramidal neuron's apical dendritic tree, which receives the excitatory input from the marginal fibers, is as well developed in siluroids as in highly visual teleosts.


Anatomical and neurobehavioral investigations concerning the thalamo-cortical organization of the rat's visual system.

The organization of thalamic afferents to the rat's visual cortex was investigated autoradiographically and through the retrograde transport of horseradish peroxidase (HRP) following infections into striate and peristriate cortex. The results revealed that Nucleus lateralis posterior (NLP) projects to a large peristriate cortical field that includes areas 18A, 7, and the anterior portion of area 18, and to a circumscribed temporal area corresponding to Krieg's ('46a,b) area 20. The dorsal lateral geniculate nucleus (LGNd) was shown to project to two spatially discontinuous cortical areas. The largest geniculate receiving area is partially coextensive with Krieg's area 17, but an extension of this projection posterior and medial to the striate cortex was found. In addition, a geniculate projection to a restricted field located in the lateral peristriate cortex was identified. Concurrent investigations were designed to assess the pattern discrimination abilities of rats prepared with striate cortical ablations, lesions in NLP and combined striate-cortical and thalamic ablations. Comparison of these animals with normal control subjects revealed that the striate cortex in the rat (as in the cat [Doty, '71; Sprague et al., '77] and the tree shrew [Killackey and Diamond, '71; Ware et al., '74]) is not necessary for successful pattern discrimination, and that the geniculo-striate and NLP-extra-striate projection systems are both involved in mediating the visual discriminative abilities of the rat. The results add species generality to the concept that the central connections to the visual cortex are characterized by parallel-conducting thalamic channels and contribute to the growing number of demonstrations that the extra-striate cortex and associated thalamic cell groups contribute significantly to the process of visual-pattern recognition.


Orientation of slit pupil and visual streak in the eye of the cat.

The orientation of the visual streak of the cat's retina was compared to that of the long axis of the slit pupil in the same eye. In five paralyzed, anesthetized cats, the retinal projection to the superior colliculus was mapped with electrophysiological techniques. The orientation of the visual streak was estimated from the projection in visual space of the collicular region of high magnification which corresponds to the central projection of the streak. The angle by which the streak was tilted from absolute horizontal was always within one or two degree of the angle by which the pupil axis was tilted from absolute vertical. This relationship was confirmed in three of the animals in which small retinal lesions were placed a known distance from the histologically determined axis of the streak. From the visual coordinates of these lesions, an independent estimate of the streak's orientation was obtained. In each case, the tilt of streak axis from horizontal differed by no more than 0.5 degrees from the tilt of the pupil axis from vertical. The results support the hypothesis that planes containing the long axis of the cat's slit pupil are perpendicular to planes containing the long axis of the visual streak of the same eye.


The nucleus corporis pontobulbaris of the North American opossum.

The nucleus of the pontobulbar body (PBu) in the North American opossum is located, for the most part, adjacent to the motor root of the trigeminal nerve. Material prepared by degeneration and autoradiographic methods shows that the PBu receives projections from the facial motor-sensory cortex, red nucleus, spinal cord and cerebellum. The latter fibers probably take origin within the fastigial nucleus. Each of the afferent connections ends in a restricuted part of the PBu, but there is considerable overlap. Use of the horseradish peroxidase technique reveals that the PBu projects to the spinal cerebellum (anterior lobe, pyramis and paramedian lobules), to visual-auditory areas of the vermis and to the lobus simplex as well as to crus I and II of the hemispheres. Although there is some topography to such projections, it is not sharply defined and many regions of the PBu contain labelled neurons after injections of horseradish peroxidase into widely separate areas of the cerebellar cortex. Because of its embryogenesis and position, the PBu is often considered part of the dorsolateral basilar pons. It appears from our material, however, that the organization of PBu afferent and efferent connections is different from that of the adjacent basilar pons, and arguments for considering the PBu a separate precerebellar nucleus are presented.


Neurons in layer I of the developing occipital cortex of the rat.

This paper describes the neurons in layer I of the rat occipital cortex, and traces postnatal changes in the numbers and morphology of the different cell types therein. Golgi-Cox and Nissl material from adults and from 0.5,2,4,6,8,10,11,12,13,14,15,16,18,20,24,28 and 35 day-old rats, was utilized. Horizontal, vertical and classical non-pyramidal cells without axons were recognized. Horizontal cells included foetal horizontal cells (Retzius-Cajal cells) and persisting horizontal cells. The former were fully differentiated and numerous at birth and were bipolar, with dendrite and axon extending from opposite poles, and fine ascending (vertical) branches. Some such cells possessed two axons. Almost all degenerated and disappeared over the first two to three postnatal weeks. An analogy with Rohon-Beard cells is drawn and it is suggested that these cells receive an early input which is subsequently withdrawn and/or concentrated on cells in deeper layers. There is no evidence of transformation of foetal to persisting horizontal cells, which are not numerous and most commonly give rise to two dendrites from opposite perikaryal poles. Vertical cells, with spinous dendrites and descending axons, differentiate and reach adult numbers by the end of the first postnatal week. Classical non-pyramidal cells include spinous and spine-free varieties, resemble those in deeper layers, and are mature by the end of the third postnatal week. In the upper stratum of layer I are small numbers of cells without axons.


Adenylate cyclase of human fat cell ghosts. Stimulation of enzyme activity by prostaglandins.

It has been shown that the human fat cell adenylate cyclase is activated by prostaglandins. Of the prostaglandins tested the E-type by causing about a 3-fold increase of enzyme activity, was more effective than the F-prostaglandins. Prostaglandin A2 had no stimulatory effect. Activation by prostaglandin E1 was not influenced by beta-adrenergic blockade in contrast to stimulation by epinephrine. Pretreatment of fat cells with trypsin resulted in an abolishment of PTH-sensitivity, but had no effect on prostaglandin responsiveness. These results suggest that the human fat cell adenylate cyclase is coupled to at least three distinct types of hormone receptors.


Compositional homology of membrane-protein systems and membrane-associated proteins: comparison with milk fat globule membrane and "membrane"-derived xanthine oxidase.

Amino acid compositions of the milk fat globule membrane protein and plasma membrane protein from other sources, as well as the compositions of milk fat globule membrane-derived xanthine oxidase and selected plasma membranes-associated proteins were compared by statistical difference index. Additionally, the average hydrophobicity of xanthine oxidase and selected membrane proteins were compared. These comparisons indicate high orders of apparent compositional homology between the various plasma membranes and membrane-associated proteins. Because the biological functions of membrane proteins are widely diverse, it is speculated that their "relatedness" may reflect on evolutionary convergence to similar amino acid compositions, necessitated by their in situ environment--the lipoidal bilayer. However, compositional relatedness should not imply sequential homology.


Effect of prepartum milk removal on quantitative morphology of bovine lactogenesis.

The effect of prepartum milking on bovine mammary histology and milk composition was studied in five Holstein cows. One udder half was milked twice daily starting 10 days before the estimated calving date. On udder half was not milked until 2 days postpartum when all quarters were milked and two tissue samples per quarter were taken for morphological analyses. Lactose, casein, and fat concentrations differed from prepartum-milked to postpartum-milked quarters (.82, -1.44, and 3.29%). Quarters milked prepartum were more developed: mature epithelium 24.8%, immature epithelium - 8.9%, total epithelium 15.6%, stroma -24.8%, and alveolar lumen 8.5%. Most alveolar cells in prepartum-milked halves had prominent rounded basal nuclei, hypertrophied secretory vesicles, and a mixed array of lipid droplets. Cells within alveoli were morphologically similar. Secretory epithelial cells from postpartum-milked glands had irregular randomly located nuclei, indistinct Golgi, variable lipid content, and less cytoplasm. These differences demonstrate the importance of prepartum-product removal on secretory cell development and subsequent milk production.


A comparative evaluation of techniques for rapid and efficient in vivo labeling of red cells with [99mTc] pertechnetate.

Red blood cells (RBCs) labeled in vivo with 99mTcO4- have recently been recommended for blood-pool imaging, but the optimum conditions for in vivo labeling of RBCs have not been clearly defined. We therefore evaluated several stannous-ion preparations and stannous-ion concentrations to determine which provided the best labeling. The effect of the time interval between the Sn(II) and 99mTcO4- injections and the effect of carrier technetium on labeling efficiency were also studied. Maximal in vivo labeling efficiency was obtained using an intravenous dose of 10 microgram Sn(II)/kg followed 5-30 min later by an injection of 99mTcO4-. Neither the chelated form of stannous ion used in these studies nor the amount of carrier present had a significant effect on labeling efficiency. The biologic half-time of Tc-99m RBCs labeled in vivo was similar to that of Tc-99m RBCs labeled in vitro. In vivo labeling is a rapid and efficient method for the preparation of Tc-99m RBCs.


The measurement of 3-o-methyldopamine in urine and plasma by a rapid and specific radioimmunoassay.

Antiserum against 3-O-methyldopamine (MD) was produced in rabbits immunized with MD hapten conjugated to hemocyanin. The antiserum was used to develop a radioimmunoassay (RIA) for MD. As little as 0.5 ng of MD in 0.1 ml can be detected. The major catecholamines and the phenolic aromatic amines (dopamine, norepinephrine, epinephrine, octopamine, and tyramine) and their metabolites (normetanephrine, metanephrine, homovanillic acid and 4-hydroxy-3-methxymandelic acid) did not bind significantly to the antibody. The RIA of MD was used to assay the endogenous level of MD in urine and plasma of hospitalized children. In children (7 mo to 13 yr), average concentration of MD in plasma was found to be 0.47 +/- 0.11 ng/ml, and in urine 0.15 +/- 0.05 microgram/mg of creatinine (45.0 +/- 16.3 microgram/24 hr). In children with neuroblastoma, there was a 3- to 10-fold increase in urinary excretion and plasma level of 3-O-methyldopamine. In adults, the average urine and plasma levels were found to be 87.4 +/- 3.4 microgram/24 hr and 0.6 +/- 0.2 ng/ml. The diagnostic applicability of the RIA of MD is discussed.


Technetium-99m glucoheptonate in brain-tumor detection: an important advance in radiotracer techniques.

We have compared [Tc-99m] sodium pertechnetate with Tc-99m glucoheptonate in 52 patients studied for various brain lesions. Flow studies as well as delayed scans were performed in all. Especially in primary and metastatic lesions of the posterior fossa, the diagnostic yield was improved by the delayed glucoheptonate (GH) scans. In contrast, no advantage of GH over pertechnetate could be detected in the study of infarcts or other ischemic lesions. Various hypotheses are discussed to explain the observed differences in behavior between the two tracers.


Assessment of regional cerebral blood flow by continuous carotid infusion of krypton-81m.

In order to obtain functional images of brain perfusion, we exploited a new concept, which is to take advantage of the short half-life of a radioactive tracer. Under continuous intracarotid infusion of a solution of Kr-81m (T1/2 = 13 sec; produced from its parent, 4.6-hr Rb-81), this tracer will never reach equilibrium within the brain because of the rapid radioactive decay. Its distribution will therefore reflect regional arrival of the nuclide, indicating regional cerebral blood flow rather than volume. During continuous infusion of Kr-81m, perfusion images can be obtained by simply collecting counts with a gamma camera and recording on Polaroid film. The procedure is readily repeatable in order to get images in multiple veiws or to follow minute-by-minute changes of cerebral perfusion.


Oblique views in lung perfusion scanning: clinical utility and limitations.

Over 300 perfusion lung scans were reviewed to assess the clinical utility of routinely performed anterior and posterior oblique projections. The characteristics of normal anterior and posterior oblique views were analyzed and compared with lateral projections. The four oblique images contributed materially toward characterization of perfusion defects in 63% of all abnormal studies; the contribution of posterior obliques was 48%, anterior obliques, 15%. For scans displaying at least one focal defect, oblique views were of benefit in over 70% of cases, with posterior obliques accounting for 55%. Oblique views contributed little when perfusion abnormalities involved both lung fields diffusely. The posterior oblique projection was of more value than the anterior oblique because of its ability to clarify lower-lobe abnormalities significantly. A scanning artifact in the posterior oblique views, due to attenuation of the near lung activity by scapula and shoulder-girdle musculature, was seen in 90% of normal studies.


Anatomic patterns of Ga-67 distribution in localized and diffuse peritoneal inflammation: case report.

Radiogallium imaging may be useful in identifying localized and diffuse peritoneal disease. The posterior peritoneal reflections can be delineated, providing further anatomical differentiation of disease processes in the peritoneum. This may allow separation of peritoneal from retroperitoneal disorders.


Detection of bronchopleural-subarachnoid fistula by radionuclide myelography: case report.

Radionuclide myeloscintigraphy has previously been used to demonstrate subarachnoid fistulae. In the present case a patient with bronchogenic carcinoma developed spontaneous pneumocephalus postoperatively. Chest radiographs showed an air-fluid level in the postoperative area. Various diagnostic tests were used, but only a radionuclide myeloscintigram showed the presence of a bronchopleural-subarachnoid fistula.


Sensitivity of radionuclide isotope brain scan in cerebral melioidosis: case report.

Melioidosis, an unusual infectious disease formerly confined to the Orient, is being seen with increasing frequency in the United States. We present a report of a patient who had recently traveled in the Far East and subsequently developed pulmonary melioidosis complicated by a fatal encephalitis. Although the radionuclide brain scan was markedly abnormal, computed tomographic studies were minimally abnormal on one occasion and within normal limits on another. The radionuclide brain scan appears to have greater sensitivity in diagnosis of early encephalitis and, therefore, may be the more valuable of the two studies in the diagnosis of this disorder.


Radiopharmaceuticals XXVII. 18F-labeled 2-deoxy-2-fluoro-d-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: tissue distribution and imaging studies in animals.

18F-2-Deoxy-2-fluoro-D-glucose (18FDG) is rapidly extracted by the mouse heart, and the radioactivity in heart (3-4% per organ) remains relatively constant for 2 hr post injection. The brain uptake (2-3% per organ) remained relatively constant throughout the time course of the study. Liver, lungs, kidneys, small intestine, and blood all showed a rapid clearance of radioactivity after injection of 18FDG. At 120 min the heart-to-lung ratio was 12 and heart-to-liver ratio was 32. Urinary excretion of activity was approximately 16% of the injected dose at 60 min. The uptake of radioactivity by dog heart following the intravenous administration of 18FDG was 2.8-4.1% at 60 min and 2.4% at 135 min; it was regionally distributed, the areas of highest activity being the left ventricle and the interventricular septum. The brain activity was 2.1-3.5% at 120 min, with a ratio of gray matter-to-white matter of 2-3:1. Urinary excretion in dogs was 16% and 50% of the injected dose at 60 and 135 min. The chemical form of the activity in the urine, although unidentified, was not 18F-. Cross-sectional images of the myocardium of the dog after intravenous injection of 18FDG were obtained using emission tomography.


Technetium-99m-labeled n-(2,6-dimethylphenylcarbamoylmethyl) iminodiacetic acid (tc-99m HIDA): a new radiopharmaceutical for hepatobiliary imaging studies.

An easily formulated, stable kit preparation of technetium-99m HIDA, suitable for use in humans, was developed and tested in mice and dogs. The tracer was cleared rapidly from the blood and excreted predominantly by the liver in both species. In dogs, the hepatobiliary clearance of Tc-99m HIDA was significantly greater than that of C-14 HIDA and Sn-113 HIDA. The LD50 for HIDA in mice, 168 mg/kg, exceeded the average human dose by a factor of 1000 on a per-weight basis. Blood clearance curves for Tc-99m HIDA in 12 normal subjects were biexponential with half-times of 4.6 +/- 1.0 min and 31.5 +/- 7.0 min, and cumulative 90-min urine samples contained 14.2 +/- 1.8% of the injected dose. Images in normal subjects and nonjaundiced patients showed rapid concentration of tracer by the liver and activity was present within the biliary system in 10-20 min. In jaundiced patients, the tracer blood clearance was delayed and urinary excretion increased, but intestinal activity, indicating biliary patency, was imaged in those patients without complete focal obstruction of the common duct. Technetium-99m HIDA is a nontoxic radiopharmaceutical useful for clinical evaluation of hepatobiliary disorders in humans.


Left fascicular hemiblocks in the elderly.

A three-year follow-up study was made of 45 elderly subjects with left anterior hemiblock, either alone or associated with right bundle-branch block. In the LAH + RBBB group, there was a higher mortality rate and frequent evolution toward complete A-V block. The prognostic significance of left fascicular hemiblocks is discussed.


Temporal arteritis.

Temporal arteritis (granulomatous inflammation) usually involves the temporal and ophthalmic arteries, but may be part of a more widespread inflammation of the medium and large vessels. The patient usually presents with an associated group of constitutional symptoms (fever, malaise, anorexia, weight loss, anemia) and rheumatic complaints (polymyalgia rheumatic complaints (polymyalgia rheumatica). The diagnosis should be considered in any patient over 55 years old in whom these symptoms develop or in whom there is evidence of recent onset of headache, visual loss of localized arterial involvement. The diagnosis is also to be considered when the erythrocyte sedimentation rate is over 50 mm/hr, and the presence of arteritis is confirmed by temporalartery biopsy findings. Visual loss may occur in 50 percent of affected patients; other serious complications are less common. A strong clinical suspicion of temporal arteritis will permit diagnosis of the more uncommon and atypical presentations of the syndrome. Although cases of temporal arteritis may be self-limited, treatment is imperative because of the threat of blindness. Patients respond well to steroid (prednisone) therapy, which should be maintained for a prolonged period.


Regression of metastatic hypernephroma.

A 71-year-old woman had massive pulmonary metastases from a right hypernephroma, as shown by a chest roentgenogram. Nine days after nephrectomy, there was no roentgenographic evidence of such metastases. This represents the most rapid regression of clear-cell pulmonary metastases ever reported. Metastases reappeared six months postoperatively and the patient died of widespread metastatic disease 18 months after nephrectomy. The unpredictable behavior of metastatic hypernephroma is discussed.


Precordialgia as a manifestation of vertebrobasilar insufficiency.

In 6 patients with vertebrobasilar insufficiency (VBI), precordialgia and autonomic-nervous-system manifestation such as diaphoresis and tachycardia were associated with the symptoms of VBI. Investigation ruled out cardiac and gastrointestinal causes. Possible mechanisms are discussed on the basis of intermitent ischemia of the central autonomic centers supplied by the posterior circulation.


Treatment of the aged mentally ill: further unmasking of the effects of a diagnosis of chronic brain syndrome.

Six elderly persons with a diagnosis of "chronic brain syndrome," who resided in a home for the aged, received bi-weekly sensory stimulation and group therapy for three months. This pilot project demonstrated that the symptoms used to classify "chronic brain syndrome" are flexible and can improve with such treatment. Not only does this cast doubt on the accuracy of this diagnosis are used, but it provides further evidence of the utility of such treatment for this type of patient. Since group therapy and sensory stimulation over a relatively short period can result in clinical and testable improvement, the diagnosis of "chronic brain syndrome" in the elderly should not be allowed to preclude the provision of appropriate psychiatric therapy.


The changing attitudes of physicians toward prolonging life.

This follow-up survey of physicians' attitudes and practices reveals a changing approach toward the care of terminal patients. It shows that: 1) communication with dying patients is becoming more open, 2) support for the omission of life-prolonging treatments is increasing, and 3) opposition to the use of death-hastening measures remains strong. It indicates that the physician's experience with terminal patients and the setting of his practice influence his attitude towards these patients and the approach to treatment.


Fractures of the radial head in the geriatric patient: case report.

Fractures of the radial head and neck occur frequently. Although reports in the literature advocate both operative and nonoperative modes of treatment, the trend is toward the nonoperative approach. In many instances this yields results that are comparable, if not superior, to those obtained by surgical intervention-as in the 62-year-old man who is the subject of the case report.


Research in orthokeratology. Part VI: statistical and clinical analyses.

In this paper, the rationale, statistical methods and results of this study are given. Specifically, it is shown that contact lenses produce clinical effects on the eye which are statistically significant. Moreover, the orthokeratology procedure was found to produce more corneal and refractive change than conventional contact lens wear. Variability and predictability of data are discussed along with pertinent clinical considerations. Certain factors and their influence on corneal change are examined and quantified.


The EOG ratio and its evaluation of retinal function.

The evaluation of 116 normal ratios with a 10 ft. lambert ganzfield illumination confirmed that ratios over 200% can be considered as normal. Individual variation led to the proposed classification of 175% to 200% as being low or suspicious. Ratios below 175% are abnormal and are useful in establishing the diagnosis of pathology.


Visual consideration and correction for respiratory protective masks.

The visual consideration in the selection of respiratory protective masks and the visual correction required by the wearer are discussed. Included is a list of manufacturers and suppliers of protective masks that have been designed for the mounting of corrective lenses inside the mask.


Aberrant ocular parasympathetic innervation: an explanation to an unusual pupillary response.

A case has been reported where drinking fluid elicited pupil constriction on one side and dilation on the other. An attempt to give a neurological explanation to this abnormal pupil response is presented. It is postulated that aberrant parasympathetic fibers from the glossopharyngeal (IX) nerve will reach the eyeball via the pterygopalatine ganglion.


The effect of a visual training program on juvenile delinquency.

In order to demonstrate a relationship between visually related learning disabilities and juvenile deliquency, a study was conducted on institutionalized youth at Lookout Mountain School, an educational facility for committed delinquents. Complete visual testing was done, and visual therapy provided if deemed necessary. Data from the evaluations showed the most marked visual deficiencies to be in order of severity, accommodative flexibility, saccadic fixations, visual memory, No. 17B recovery, pursuits, No16B recovery No10 recovery. Recidivism was reduced in the group receiving visual therapy from 18% to 4%. A case study of educational and visual remediation on one student is discussed.


[Intimate mechanism of premature separation of the normally inserted placenta].

Retro-placental haemorrhage comes from rupture of patent utero-placental arteries which are neither sclerosed nor thrombosed. This applies whether the form of haemorrhage is minor (simple depression found when the placenta is examined) or grave with utero-placental apoplexy (with complete detachment of the placenta and syndrome of shock). The method by which the arteries rupture depend on the intensity and excessive duration of uterine contractions: --moderate; normal uterine contractions give rise to a prolonged blockage of the return circulation, whereas the arterial flow has not stopped. Rupture occurs because the distended utero-placental arterial wall bursts under the insult of raised pressure during the uterine contraction; --intense; these anomalies come from total blockage, both veinous and arterial, and the arterial rupture is due to anoxaemic necrosis of the utero-placental arterial wall. The rupture of the utero-placental arterial wall, which is normally very fragile because it has no elasticity in its musculature, gives the explanation for the histogenesis of retro-placental haemorrhages.


[X chromosome with deletion of the long arm].

The authors review cases published in the literature having had a case of chromosome abnormality due to deletion of the long arm of an X. There are very few such cases. After they had indexed the somatic and chromosomal results that have been revealed, they conclude that, with the exception of dysmorphias, it is not possible to correlate the lesions that have been found with the localisation on the chromosome X. These lesions are very minor when the long arm is missing, which is contrary to the lesions that are found when the short arm has been lost. The authors draw attention to the value of modern methods of chromosome localisation. By them, marking of the break in the band 21 of the long arm as well as the diagnosis of late replication of chromosome X is made possible. A bibliography is given.


[Detection of cancer of the fallopian tube by intra-uterine cytology. Apropos of a case].

The authors present a case of cancer of the Fallopian tube and the finding of malignant cells obtained from the cavity of the uterus. There was little in the clinical findings and the only positive sign was free post-menopausal bleeding on account of which a full assessment was undertaken. By using the Gravlee sound passed through the cervical canal the uterine cavity was washed out and this gave the opportunity of finding malignant cells when curettage had only shown benign polyps. At operation a cancer of the left ampulla which was encircling the ovary on the same side was removed.


[Necrotizing colitis after total hysterectomy].

After an uneventful hysterectomy for fibroids carried out in a woman of 48 years of age peritonitis developed on the 5th post-operative day. It was due to necrosing sigmoiditis which occurred in spite of normal bowel action having been resumed on the 3rd post-operative day. This is a rare but usually very severe post-operative complication. Immediate operation saved the patient but she had to have two further operative procedures.


[Cholestasis in pregnancy].

It has been possible by seeing twenty cases of cholestasis in pregnancy to define certain characteristics of the condition. This pathology of pregnancy is frequently associated with twin pregnancy. The prognosis for the fetus is especially affected by prematurity. There is no evidence of small-for-dates babies, but the neonate gains weight slowly. Anaemia and jaundice in the neonates are common. The treatment of threatened premature labour using beta-mimetic drug is useful and of no danger to the mother.


[Neonatal listeriosis. Apropos of 53 cases].

53 cases of neonatal listeriosis were seen during the last five years at the Intensive Care Unit for newborn infants (Pr Minkowski) and the Neonatal Center (P. Varangot) of the Port-Royal Maternity Hospital. The significant decline in mortality to 22 p. 100, when compared with previous years, was attributed to improvements in the diagnosis during the first hours of life and the contribution of artificial ventilation. The most frequent initial clinical sign was respiratory distress (58 p. 100) whereas meningitis was relatively rare (11 p. 100). Discoloration of the amniotic fluid and a fever in the mother at the time of delivery, were also important diagnostic clues. The macroscopic examination of the placenta and particularly placental smears containing listeria monocytogenes (15 of the specimens) as well as the hematological alterations, particularly an increase of the fibrinogen level above 3-4 g/1 during the first 48 hous of life (72 p. 100 of the cases) contributed to an early diagnosis.


[Surgical treatment of trophoblastic diseases].

Early diagnosis of a developing hydatidiform mole gives an opportunity to evacuate this by intrauterine suction. This atraumatic procedure which is sure in its outcome has considerably lowered the indications for curettage, for hysterectomy and for hysterotomies. On the other hand, when trophoblastic disease persists chemotherapy is indicated so long as the indications are strictly grounded on biological criteria. The real indication for surgery is found when an isolated focus is resistant to medical treatment.


Total wrist arthroplasty: a preliminary report.

Evaluation of 26 Meuli total wrist arthroplasties in 22 patients 7 to 17 months after operation revealed that 92 percent (24 wrists) were relieved of pain. Postoperative motion averaged 32 degrees of dorsiflexion. 27 degrees of palmar flexion, 2 degrees of radial deviation, and 23 degrees of ulnar deviation. Failure of the prosthetic design to place the center of rotation properly in the capitate resulted in a tendency toward flexion and ulnar deviation deformities. Reoperation was required in nine (35 percent) of the 26 wrists. After reoperation of these nine wrists, 77 percent (20 wrists) of the total group had good or excellent results, 11.5 percent (three wrists) fair, and 11.5 percent (three wrists) poor.


Silicone-rubber interposition arthroplasty of the carpometacarpal joint of the thumb.

Since 1969, a slightly modified silicone-rubber neurosurgical burr-hole cover has been used for a type of interposition arthroplasty of the carpometacarpal joint of the thumb. The short stem of the device fits into a hole burred into the distal surface of the trapezium. The flat surface of the device covers the distal surface of the trapezium. Forty-nine operations were done on 42 patients, 35 women and seven men. The age range of the patients was 34 years to 72 years, with an average of 55 years. The average follow-up time was 31 months. Forty results were rated as excellent. There were two failures due to breakage of the device, and in both cases the breakage was due to a technical error.


An appropriate treatment for postoperative Z-formed deformity of the duplicated thumb.

The Z-shaped deformity of the remaining thumb, often one of the sequelae to treatment of congenital duplicated thumb, may be due to a scar contracture, poorly functioning thenar muscles, and an abnormal insertion of the long flexor and extensor tendons. The deformity occurred in 14 of 49 patients treated for duplication of the thumb. A rotation flap instead of a Z-plasty was used to release the scar contracture, the flexor tendon was detached and reinserted on the ulnar side, and the radial half of the extensor tendon was removed.


Experience with distraction lengthening of digital rays in congenital anomalies.

To improve function and appearance of the hands in 11 children with congenital hypoplasia or aplasia of the digits, the method of distraction lengthening of remaining metacarpal structures was used. Four illustrative cases are discussed in detail.


Irreducible dorsal dislocation of the distal interphalangeal joint of the finger.

Two patients with irreducible dislocation of the distal interphalangeal joint underwent surgical exploration. In each patient the volar plate, having been disrupted proximally, was trapped between the joint surfaces, preventing closed reduction.


The quantitative histologic distribution of pyridoxal phosphate in the rat stomach, effects of drugs influencing secretion.

The quantitative histologic distribution of pyridoxal phosphate (PLP), the coenzyme of histidine decarboxylase in the biosynthesis of histamine as well as the coenzyme of other enzyme systems, was established in the rat glandular stomach in different secretory states. This was accomplished by analyzing PLP with an improved fluorometric microprocedure in histologically identified fresh-frozen microtome tissue sections cut serially through the stomach wall of fed and 24-hr fasted rats, and of the latter injected with drugs that stimulate (histamine, theophylline and urecholine) or inhibit (atropine) secretion. In fasted compared with fed rats, and in fasted rats injected with histamine (low dose) or theophylline, compared with saline injected controls, the PLP level was reduced not only in the chief cell region where PLP is utilized in histamine production, but also in the parietal and mucous neck cell region, indicating PLP function in other enzyme systems in these sites. No change in PLP level occurred when histamine was injected at a high dose known to suppress histidine decarboxylase activity. Administration of urecholine or atropine had negligible effect on the PLP levels, indicating a lack of vagal stimulatory or inhibitory influence.


Psychological differentiation, event uncertainty, and heart rate.

Psychological differentiation and uncertainty about receiving a painful noise were examined for their effects on heart rate during the anticipatory, impact and recovery phases of the tone presentation. Psychologically differentiated and nondifferentiated subjects were randomly assigned to three event uncertainty conditions (5 percent, 50 percent, 95 percent probability of noise). Subjects were informed of the probability of receiving the noise, as well as the time of occurrence as indicated by a sequentially numbered visual display. Subjects received the noise on the second of the experiment's two trials. Cognitive style and event uncertainty interacted during the anticipatory phase--i.e., differentiated subjects showed a monotonic increase in heart rate with increasing probability of receiving the noise that represents preparation for instrumental activity. Results are consistent with the theory that meaningful personality-stress relationships may be obtained when examining stimulus-oriented dispositions.


Physiologic reactions to social challenge in persons evidencing the type A coronary-prone behavior pattern.

Physiologic measures were recorded in Type A1 (n = 10) and Type B (n = 14) subjects while they engaged in a reaction-time task after receiving instructions emphasizing the need for rapid and accurate performance. Although resting levels were not significantly different, Type A's responded with significantly greater increases than B's in both heart rate and systolic blood pressure, suggesting greater sympathetic arousal. A significant baseline difference between the Types in heart rate variability was also observed suggesting greater lability in sympathetic-parasympathetic function in Type A's. No differences between the Types were obtained for either galvanic skin potential (GSP) or speed of reaction. It is suggested that the paradigm used in the present study offers an inexpensive and efficient means by which cardiovascular reactivity in Type A's and B's may be explored in other and larger groups of subjects.


Occupational incidence rates of mental health disorders.

This study attempted to provide occupational health professionals with an empirical basis for identifying and selecting specific occupations for further research into the relationship between job stress and worker health. Specifically, this involved an examination of the admission records of community mental health centers throughout one state (Tennessee) to determine the incidence rate of diagnosed mental health disorders for 130 major occupations (i.e., occupations employing 1,000 or more workers in the state). These occupations were then rank-ordered by incidence rate to provide a general scheme for evaluating the relative frequency of mental health disorders among the select occupations. The results indicated a disproportionate incidence of mental health anomalies among the hospital/health care professions. Some tentative explanations of this finding are presented, and suggestions are made for future research efforts.


Microassay using radioiodinated protein A from Staphylococcus aureus for antibodies bound to cell surface antigens of adherent tumor cells.

A new microassay which utilizes radioiodinated staphylococcal protein A (SpA) to detect antibodies bound to cell surface antigens (CSA) was developed for monolayers of viable cultured tumor cells. Optimal detection of bound antibodies occurred at 37 degrees C with incubation periods of one hour each for antiserum and 131I-SpA. Labelling target cells with 125I-iododeoxyuridine facilitated expression of results relative to tumor cell number or protein concentration. Quantitation of antibody depended on CSA (tumor cells) and 131I-SpA being in excess of antibody; under these conditions, 0.25 ng of cell surface bound antibody could be detected readily. Initial studies utilized cultured human neurobodies in human serum which bound to CSA were removed by absorption with glutaraldehyde-insolubilized fetal calf serum (FCS) suggesting that FCS or FCS-like determinants can be CSA. Rabbit antisera, after extensive absorption, bound to cultured neuroblastoma and lung adenocarcinoma cells in a cell type specific pattern. These experiments demonstrated the value of this assay in quantitating anti-CSA antibodies and in serological analysis of tumor CSA.


Development of a radioimmunoassay for aprindine.

We have developed a radioimmunoassay for aprindine, a new antiarrhythmic drug used in the treatment of ventricular disorders. The antibodies were produced by immunization of New-zealand rabbits with aprindine coupled to human serum albumin. Their biochemical characteristics have been determined. Tritiated aprindine was used as radioactive competitor. The cross-reactivity with several metabolites of aprindine was studied too. Finally, the results obtained by RIA in plasma and tissues of dogs were compared to those obtained by gas-chromatography.


Production of large amounts of antibodies, complement, and leukocytes in ascitic fluids of guinea pigs.

A method is described for the production in guinea pigs of large amounts of ascitic fluid containing non-specific IgG, antiprotein antibodies, complement, other serum proteins and leukocytes. The method is an adaptation of a procedure previously applied to mice. A major difference is the extended schedule of inoculations required for the induction of ascites in guinea pigs; a requirement for boosting with antigen intradermally while repeatedly inoculating adjuvant intraperitoneally; and the much larger quantities obtained. The average yield of ascitic fluid, when antigen was not used, was 113 ml per animal, and the average yield of IgG was 0.87 g. With antigen (keyhole limpet hemocyanin) the average yields were 143 ml and 1.6 g of antibody per guinea pig. Complement titers were 41 to 74% of those in serum. The number of leukocytes per ml of ascites ranged from 7 X 10(6) to 20 X 10(6). The method should be useful for the production of large amounts of leukocytes, antibodies and other serum proteins from a small colony of laboratory animals. In addition, cells can be obtained without the need to sacrifice the animal.


Agarose medium turbidimetric assay for cross reacting antigens.

Appropriate concentrations of carrageenan and antibody to carrageenan were mixed in a medium consisting of 0.1% agarose in 0.01 M phosphate-buffered saline pH 7.4 at 37 degrees C. The kinetics of precipitation were followed by turbidimetric analysis with a double beam Unicam spectrophotometer set at 420 nm. Addition of agarose enhanced the antigen--antibody reaction as judged by turbidity and served as a stabilizing medium permitting extended periods of continuous monitoring. The initial rate of precipitation was found to vary linearly with the concentration of antigen in the antibody excess zone. Both the critical rate of precipitation and final optical density were characteristic of the specific antigen-antibody reaction. These two parameters are used to quantitate the extent of a cross-reaction and to calculate an index of homology for the cross-reacting antigen to the homologous antigen.


Apatite crystals in pseudoxanthoma elasticum: a combined study using electron microscopy and selected area diffraction analysis.

Calcium deposits in elastic fibers of involved skin of patients suffering from pseudoxanthoma elasticum have previously been reported. In the present work, the crystalline structure and composition were studied. Involved skin was obtained from 5 patients. Bright-field and dark-field electron microscopy and selected area electron diffraction of the calcium deposits were applied. The study demonstrates calcium apatite crystals.


[3H]Thymidine labeling of dermal endothelial cells in scleroderma.

The purpose of this study was to estimate [3H] thymidine labeling of endothelial cells of skin capillaries in localized scleroderma (LS) and systemic scleroderma (SS). Skin specimens from 14 patients with SS, 5 with LS, and 9 matched controls were studied by in vitro autoradiography. Capillaries from patients with SS showed a statistically significant increase in endothelial cell labeling when compared to vessels from controls (p less than 0.0005).


Biologic changes due to long-wave ultraviolet irradiation on human skin: ultrastructural study.

Alteration of the skin induced by single and repeated long-wave ultraviolet (UVA) exposures was studied. Following a single exposure to relatively large doses of UVA, pronounced dermal damage was observed. In the papillary dermis, superficial dermal vessels showed widely open endothelial gaps and extravasation of blood cells. Marked changes of fibroblasts were also seen in the superficial dermis. In the reticular dermis, extravascular fibrin deposition was seen. After repeated exposures to UVA the formation of cross-banded filamentous aggregations ("Zebra bodies") was observed in the superficial and reticular dermis. These were often found in amorphous masses surrounding the blood vessels. These striking dermal alterations were absent in skin irradiated by solar stimulating radiation and in control skin. Dyskeratotic "sunburn cells" were occasionally seen in the epidermis after single as well as repeated exposures to UVA. The number of these cells was less than that seen after a single exposure to solar simulating radiation.


Flux of fatty acids during epidermal differentiation.

Fetal rat skin prior to cornification (18 days of gestation) was prelabeled with [14C] linoleic acid in vitro and subsequently allowed to differentiate and cornify in organ culture. During 48 hr in culture total epidermal 14C fatty acids and 14C dienes decreased in phospholipids and increased in triglycerides and sterol esters as granular layers and stratum corneum formed. During the second 24-hr period, there was no net loss in 14C fatty acids from the epidermis, suggesting that the changes in phospholipid and neutral esters represented translocations of fatty acids within the cornifying cells. The findings are consistent with the hypothesis that fatty acids liberated by hydrolysis of phospholipids are salvaged by reesterfication as neutral lipid esters during epidermal cornification.


Experimental endocarditis due to Pseudomonas aeruginosa. II. Therapy with carbenicillin and gentamicin.

Rabbits with left-sided endocarditis due to Pseudomonas aeruginosa were treated with a high dose (7.5 mg/kg) of gentamicin for six days, a low dose (5 mg/kg) of gentamicin for six days or two weeks, carbenicillin (400 mg/kg) for six days or two weeks, or a combination of the lower dose of gentamicin and carbenicillin (400 mg/kg) for six days or two weeks. Sterilization of cardiac vegetations was accomplished more effectively in rabbits given the higher dose of gentamicin for six days (44% with sterilized vegetations) or combination therapy for 14 days (64%) than in rabbits given the lower dose of gentamicin or carbenicillin alone for two weeks (23.5% and none, respectively). Combination therapy for two weeks prevented relapse in all of six treated rabbits that were followed after treatment; in contrast, all four animals treated with carbenicillin and four of six animals treated with the lower dose of gentamicin relapsed after two weeks of treatment. Levels of creatinine in serum became elevated in four of nine rabbits that received gentamicin along for two weeks. Therapeutic success was associated with a synergistic antibiotic combination, a peak bactericidal titer in serum of greater than or equal to 1:16, and a high level of gentamicin in serum.


Characteristics of 11 rabies virus isolates in mice: titers and relative invasiveness of virus, incubation period of infection, and survival of mice with sequelae.

Mice were inoculated intracerebrally or in the footpad with 11 salivary gland suspensions from rabid foxes, skunks, and bobcats. The 11 isolates differed in their ratios of intracerebral titer to footpad titer, a result indicating that the "invasiveness" of different isolates varies markedly. The degree of invasiveness could not be correlated with the species of animal. The inoculation of the less invasive isolates resulted in an appreciable number of permanently paralyzed animals (survivors with sequelae). These animals had high titers of neutralizing antibody in serum but no neutralizing antibody in the brain, a finding suggesting that virus had invaded only the peripheral nervous system or the spinal ganglia. Pathological examination of the paralyzed mice and normal mice confirmed this finding.


Persistence in humans of antibody to subtypes of Venezuelan equine encephalomyelitis (VEE) virus after immunization with attenuated (TC-83) VEE virus vaccine.

We studied the persistence of antibody to Venezuelan equine encephalomyelitis (VEE) virus subtypes in sera of 20 volunteers inoculated seven or nine years previously with attenuated TC-83 VEE virus vaccine. Serological patterns were compared with those of 10 other persons from whom samples of serum were obtained 28 days after vaccination with TC-83 virus. Vaccines had no other known exposure to a group A arbovirus. Titers of neutralizing antibody of greater than or equal to 1:10 were measured against the homologous TC-83 strain of virus in all long- and short-term vaccinees. In both groups of vaccinees the percentage of antibody-positive persons and their geometric mean titers of antibody to the epizootic subtypes I-A, I-B, and I-C were higher than titers to the enzootic subtypes I-D, I-E, II, III, and IV. However, proportionally fewer long-term vaccinees  than short-term vaccinees had detectable neutralizing antibody reactive with enzootic strains. These results reveal long-lasting circulation of neutralizing antibody to TC-83 virus and closely related epizootic variants in 95%-100% of vaccinees. The relatively lower rate of antibody conversion and the loss of antibody to more antigenically remote enzootic subtypes of VEE virus suggest that vaccinees may be less well protected against infection by these strains.


Emergence of variant forms of Staphylococcus aureus after exposure to gentamicin and infectivity of the variants in experimental animals.

Exposure of a large inoculum of Staphylococcus aureus in vitro to concentrations of gentamicin that exceeded the minimal bactericidal concentration regularly resulted in the emergence of aminoglycoside-resistant bacterial variants. Variants lacked typical properties that are associated with S. aureus: they produced small, nonhemolytic colonies that were mostly coagulase-, deoxyribonuclease-, and mannitol-negative. In some instances phage type also differed from that of the parent forms. Animal models of subcutaneous and intravenous infection were studied with use of parent and variant forms of S. aureus. Subcutaneous injection of variants into rats readily produced abscesses, and intravenous inoculation into mice caused pyelonephritis, although in each experimental model in which equivalent bacterial inocula were used, parents produced more extensive disease. These data show that variants of S. aureus cause infection in experimental animals, although these variants appear to be somewhat less virulent than the parents from which they are derived. Preliminary studies in our laboratory have also shown that gentamicin-resistant variants of gram-negative bacilli can be induced by a single in vitro exposure to gentamicin. The virulence of these organisms and their role in antibiotic-susceptibility patterns of hospital flora warrant further investigation.


Pharmacokinetics of ampicillin during pregnancy.

Levels of ampicillin in plasma and urine were studied in 26 pregnant women during the 8 hr following an oral as well as an intravenous dose. Identical doses were given to the same women after pregnancy, and the resulting plasma and urine levels were compared. Assays were performed by means of a disk agar diffusion method. Renal plasma clearance was calculated. Plasma levels were significantly lower during pregnancy than after. The difference was unrelated to body weight and length of gestation but was associated with a significant increase in distribution volume and renal plasma clearance in pregnant women. Recovery of ampicillin in urine during 8 hr was identical during pregnancy and after. It is suggested that pregnant women require higher doses of ampicillin per kg of body weight than nonpregnant women in order to achieve similar concentrations in plasma. The experimental design used in the present study is suitable for evaluation of pharmacokinetics in pregnancy.


Maternal-fetal transfer of cefazolin in the first twenty weeks of pregnancy.

Maternal-fetal transfer of cefazolin was investigated with use of a single 14-mg/kg intramuscular dose administered to 40 gravidas before elective hysterectomy. The half-life of cefazolin in maternal serum was 1.5 hr with mean concentrations at 2 and 4 hr of 39 and 16 microgram/ml, respectively. By microbiological assay, cefazolin was not detected in brain, cerebrospinal fluid, lung, liver, or kidney of the fetus but was present in concentrations of 1-11 microgram/ml in 12 of 27 individual samples of fetal serum from 0.75 to 10.66 hr. Cefazolin appeared in fetal urine from 2.17 to 19.5 hr at levels of less than 5 microgram/ml with a half-life of 5.4 hr. Cefazolin was present in the amniotic fluid of fetuses older than 14 weeks in concentrations of less than 1 microgram/ml from 9 to 21.75 hr. After administration of a single dose to the mother early in pregnancy, the fetal distribution of cefazolin is limited to the body fluids.


Prevention of virus-induced cerebellar diseases by defective-interfering lymphocytic choriomeningitis virus.

Defective-interfering (DI) lymphocytic choriomeningitis virus (LCMV) prevented disease in the central nervous system produced by standard LCMV. Standard LCMV injected into Lewis rats two days after birth produced a disorder distinguishable clinically by weight loss and ataxia and histologically by infiltration of mononuclear cells and necrosis of the cerebellum. Concurrent injection of DI LCMV with standard LCMV prevented the disease and markedly reduced the synthesis of standard LCMV and of viral antigens in the brain. Because inhibition of viral synthesis occurred early (day 3) after infection and because no interferon activity could be demonstrated, it was concluded that the interference effect was likely due to DI virus-mediated homologous interference. Other experiments showed that DI LCMV blocked viral antigen synthesis in culture. The curtailed production of viral antigens and cytolytic standard virus by DI virus may play a role in control of acute and persistent viral infections.


Characterization of Toxoplasma gondii from the feces of naturally infected cats.

Feces of 1,000 cats from a humane shelter in Columbus, Ohio, were examined microscopically for oocysts of Toxoplasma gondii and by inoculation into mice. From the first 541 cats examined, oocysts of Toxoplasma were found in the feces of seven cats but in none of the remaining 459 cats. Results of the dye test in these seven cats showed titers of antibody of less than 1:2 in four cats, and of 1:8, 1:6, and 1:32 in the remaining three cats. The pathogenicity and infectivity of oocysts and cysts of all seven strains were compared in mice after oral and intraperitoneal inoculations. Oocysts and cysts were more pathogenic when administered by the oral route than by the intraperitoneal route. The cysts were less pathogenic than the oocysts. Excellent cross-immunity between six of these seven feline strains and the M-7741 strain was deomonstrated in cats by the fact that oocysts were not shed in feces of cats challenged with cysts of homologous or heterologous strains.


High-performance liquid chromatographic radioenzymatic assay for plasma catecholamines.

A new assay method for plasma CA's requiring only 50 microliter has been developed, which uses HPLC. The NE, D, and E compounds found in plasma are radioactively o-methylated with 3H-SAM by the reaction of COMT. The reaction is terminated and a standard mixture of nonradioactive o-methylated analogues of NE, D, and E is addded to act as a carrier. Following separation by HPLC, the NMN, 3-MOT, and MN radioactive peaks are collected which represent NE, D, and E, respectively. Then MNM and MN are oxidized to vanillin, and 3-MOT is acetylated. The products are subsequently separated by solvent extraction. This is necessary in order to avoid high radioactive blanks and to allow quantitation of the radioactivity by liquid scintillation spectrometry. The mean supine levels of NE, D, and E in normal subjects were respectively 182, 33, and 87 pg/ml of plasma. Similar assays on patients with pheochromocytoma revealed 797, 80, and 470 pg/ml.


A new method for the hydrolysis of conjugated catecholamines.

A new method of hydrolysis of conjugated CA's in plasma and urine has been developed. It is based on the lyophilization of dilute perchloric acid solutions of plasma and urine. The hydrolysis of the CA conjugates was more complete by this method than by the standard method by enzymatic hydrolysis. The identity of the products was verified by TLC. DA, undetectable in 95% of normal subjects, was found to exist almost exclusively in the conjugated form, averaging 0.74 +/- 0.17 (S.E.) ng/ml. Free and conjugated NE and E in human plasma were 0.23 +/- 0.03 and 0.32 +/- 0.27 ng/ml, respectively. The new and simple method of hydrolysis of conjugated CA's may help in the search for the physiological meaning of the conjugation.


A radioreceptor assay for serum insulin.

A method is described for the measurement of insulin in serum by RRA with normal human sRRA. The sensitivity of the assay is similar to that of a commonly used immunoassay. There is no detectable interference from somatomedin or NSILA, whereas proinsulin has only about 5% of the activity of insulin in the assay. There is a high degree of correlation between the results of immunoassay and the RRA over the physiological range of serum insulin. However, the greater ability to differentiate between insulin and proinsulin, together with greater ability of receptor binding to exclude altered (biologically inactive) insulin, present advantages of this assay over the RIA, which may be significant in abnormal situations.


Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats.

In order to evaluate the effects of iron deficiency on the absorption of pollutant metals, an iron-deficient diet was fed to young rats until their tissue-iron stores were depleted. Prior to the development of anemia, the iron-deficient rats and littermate controls were administered an intragastric gavage of lead-210 or cadmium-109 and were killed 48 hr later. The body burden of lead was approximately 6 times greater, and that of cadmium approximately 7 times greater, in iron-deficient rats than in the controls. No consistent effects were observed on concentrations of serum total lipids or serum proteins nor on protein electrophoretic patterns in rats with a deficit in iron stores.


Postsurgical granulocyte dysfunction: studies in healthy kidney donors.

In order to determine whether surgical trauma affects granulocyte function, we performed sequential studies of granulocyte phagocytic and bactericidal function, chemotaxis, and adherence on 25 otherwise healthy subjects undergoing donor nephrectomy for kidney transplantation. All values were normal prior to surgery, and bacterial killing and phagocytosis were unaffected by surgery. Granulocyte chemotaxis and adherence were significantly impaired immediately following surgery, returning to normal in 24 hr. Anesthesia alone did not affect chemotaxis. Generation of chemoattractants from postoperative plasma was normal, and inhibitors of chemotaxis could not be demonstrated, suggesting an intrinsic cellular defect. We suggest that these postoperative abnormalities of granulocyte chemotaxis and adherence may contribute to the high incidence of infectious complications following surgery.


Mechanical trauma in leukocytes.

Mechanical and surface traumas in cardiopulmonary bypass circuits alter the function and morphology of human leukocytes. The effect of controlled in vitro shear stess (0 to 2,000 dynes/cm2, 2 to 10 min, 37 degrees C) on electronic cell count, morphology, adhesiveness, and phosphatase cytochemical staining was studied on whole blood from normal donors. Electronic cell counts droppped significantly after shear stress exposure (25% at 600 dynes/cm2 for 10 min). The frequency of disrupted leukocytes in blood smears increased with shear stress above 150 dynes/cm2, and aggregates of the disrupted cells appeared after exposure to higher shear stresses (450 dynes/cm2, 10 min). Cytochemical staining of the alkaline phosphatase in the granules of intact neutrophils was significantly reduced by the application of shear stress (150 dynes/cm2 for 10 min, or greater), but staining of acid phosphatase-containing granules was almost unaffected. Increased cell retention in columns of nylon fibers suggests that increased leukocyte adhesiveness results from exposure to shear stress. Thus exposure to shear stress may alter or disrupt leukocyte morphology and function at values somewhat lower than the 1,500 dynes/cm2 for 2 min which is required to hemolyze erythrocytes.


Age-dependent separation of erythrocytes by preparative electrophoresis.

Human and rat erythrocytes have been fractionated according to charge by density-gradient electrophoresis. Some 1 to 2 ml, or about 10(10) of packed cells, can be electrophoresed up a stabilizing sucrose gradient, and require 3 to 4 hr for effective fractionation. The fastest migrating erythrocytes were the least fragile, were larger, incorporated the most 59Fe, and contained more glucose 6-phosphate dehydrogenase activity. These findings are consistent with the most negatively charged erythrocytes being the youngest cells, agreeing with other separative procedures based on density, phase partitioning, or serial osmotic hemolysis.


A glucose 6-phosphate dehydrogenase Gd (-) Castilla variant characterized by mild deficiency associated with drug-induced hemolytic anemia.

Erythrocyte G-6-PD deficiency is an X-chromosome-linked hereditary trait which is common in many ethnic groups. A deficiency of G-6-PD in red cells is often associated with hemolytic anemia. This report defines a new variant designated as Gd (-) Castilla, which is associated with drug-induced hemolysis. The red cell G-6-PD activity of the variant subject is about 20% of normal. The variant enzyme is thermolabile in vitro and it has faster than normal anodal electrophoretic mobility and normal substrate affinity. The hemolytic problem of the subject might be correlated to sensitivity to NADPH inhibition and molecular instability of the variant enzyme.


Catabolism of chylomicron triacylglycerol and cholesteryl ester in genetically obese rats.

The catabolism of chylomicrons was investigated in genetically obese rats and their nonobese littermates, and was compared with catabolism in older Sprague-Dawley rats with body weights similar to the obese rats and their younger controls. Labeled thoracic-duct lymph was collected from donor rats and the catabolism of the labeled chylomicrons was studied after a single intravenous injection or during steady intravenous infusion in unanesthetized, nonfasting, recipient rats. In the genetically obese rats clearances from the plasma of chylomicron triacylglycerol and cholesteryl ester were less than in their nonobese littermates. Fractional clearance rates were reduced for both triacylglycerol and cholesteryl ester but triacylglycerol turnover rate (mg min(-1)) was greater than controls. Chylomicron triacylglycerol clearance was more efficient than cholesteryl ester clearance so that radioactivity remaining in the plasma was relatively depleted in triacylglycerol. The large-bodied old Sprague-Dawley rats showed no reduction in clearance of chylomicron radioactivity in comparison with younger controls. These results suggest that hyperlipidemia in genetically obese rats may be due in part to an accumulation of chylomicron remnants in the plasma. Flotation characteristics of plasma lipoproteins in the obese rats were consistent with this interpretation. However, separate experiments showed that genetically obese, fasting rats also accumulated more triacylglycerol in the plasma after injection of Triton WR 1339. The enlarged plasma triacylglycerol pool appears to derive from a mixture of hepatic and intestinal triacylglycerol-rich lipoproteins which, together, overload their common removal mechanism. Addition of cholesterol to the diets of the obese rats exacerbated their hyperlipemia and hepatic steatosis whereas their nonobese littermates and the large-bodied Sprague-Dawley rats were unaffected.


Effect of ethynylestradiol on biliary excretion of bile acids, phosphatidylcolines, and cholesterol in the bile fistula rat.

The effects of ethynylestradiol on endogenous bile acids, their capacity to conjugate and excrete intravenously infused cholic acid, the concentrations of biliary cholesterol and lecithin, and the individual molecular species of phosphatidylcholine have been determined in male and female Sprague-Dawley rats. Endogenous biliary bile acids were analyzed by gas-liquid chromatography-mass spectrometry. Eleven bile acids were identified and several minor bile acids, primarily muricholates, could not be completely characterized. After 5 days of treatment with ethynylestradiol (1 mg/kg per day), the percentage of cholic acid decreased and the percentage of 6beta-hydroxylated bile acids, including several monounsaturated species, increased. Ethynylestradiol caused a decrease in bile acid-independent bile flow. Intravenous infusion of cholic acid at a high concentration caused cholestasis in control animals but, after ethynylestradiol treatment, cholestasis developed during the infusion of a much lower concentration of cholate, indicating a lowered threshhold for bile acid-induced cholestasis. In the treated rats, there was a slight increase in excretion of unconjugated endogenous bile acids, and a striking impairment of conjugation of intravenously administered cholic acid. One of the few sex-related differences observed was an increased concentration of biliary phospholipids in untreated male rats. Both phospholipid and cholesterol concentrations in the bile were higher in the treated animals. The molar percentage of cholesterol was always 1-2%, but it was slightly higher in treated animals, especially males. Ethynylestradiol treatment also affected biliary phospholipid by causing a marked increase of phosphatidylcholine species containing palmitic and oleic acid residues and a decrease of species containing stearic and linoleic acid residues. There was no increase in biliary excretion of long chain polyunsaturated species, which might have indicated damage to membranes, in response to ethynylestradiol either alone or with cholic acid infusion. Some of these ethynylestradiol-induced changes in biliary bile acid and lipid excretion are probably peculiar to the rat, but others, such as the increase in molar percentage of cholesterol and cholestasis, may be relevant to disorders in man, especially cholesterol gallstones and idiopathic cholestasis of pregnancy.


Metabolism of 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid in normal subjects with an intact enterohepatic circulation.

The formation of cholic acid from 3alpha, 7alpha, 12alpha-trihydroxy-5beta-cholestan-26-oic acid (THCA) was studied in two normal subjects. [3H]THCA and [14C]cholic acid were administered intravenously by simultaneous injection and the specific activities (percent injected amount/mumol) of [3H]- and [14C]cholic acid were measured in bile samples collected over a 5-day period. If the administered [3H]-THCA is rapidly and completely metabolized into cholic acid, the areas under the specific activity curves of [3H]- and [14C]cholic acid should be identical. In these two subjects, the area under the [3H]cholic acid specific activity decay curves was only 18.4% and 9.0% less than the area under the [14C]cholic acid specific activity decay curves. Thus, there is rapid and nearly complete metabolism of intravenously administered [3H]THCA into cholic acid.


An improved assay of gangliosides separated by thin-layer chromatography.

There were no differences in the recoveries of ganglioside sialic acid from silica gel G thin-layer chromatograms when they were sprayed with resorcinol reagent varying in normality between 3 and 10. However, both the temperature at and the time for which the plates were heated after spraying did affect the recoveries, which can reach 100% when the plates are heated for 6 min at 135degreesC.


A more sensitive and stable colorimetric determination of free fatty acids in blood.

A sensitive method is proposed for the colorimetric determination of free fatty acids (FFA). Diphenylcarbazide containing diphenylcarbazone is used as the color developing reagent instead of diethyldithiocarbamate which was employed in the previous method (1965). J. Lipid Res. 6: 16-20). The present method was successfully applied to the determination of FFA present in as little as 40 microliter of whole blood.


Short-term memory in the pigeon: delayed-pair-comparison procedures and some results.

A discrete-trials, delayed-pair-comparison procedure was developed to study visual short-term memory for tilted lines. In four experiments, pigeons' responses on left or right keys were reinforced with food depending on whether a comparison stimulus was or was not the same as a standard stimulus presented earlier in the same trial. In Experimental I, recall was an increasing function of the exposure time of the to-be-remembered stimulus and was a decreasing function of the retention interval. In Experiment II, retroactive interference was investigated: recall was poorer after a retention interval during which was presented either a tilted line or contextual stimuli in the form of the illuminated experimental chamber. In Experiment III, a subject was required to engage, throughout the retention interval, in one or the other of two different behaviors, depending on which of two stimuli a subject was to remember. This mnemonic strategy vastly improved recall after 15- and 20-second retention intervals. In Experiment IV, the opposite end of the performance continuum was studied: by combining the effects of a larger stimulus set and the effects of what presumably was an increased memory load, performance was reduced to approximately chance levels after retention intervals shorter than 1 second.


Interlocking schedules: the relationship between response and time requirements.

Rats were exposed to an interlocking fixed-ratio 150 fixed-interval 5-minute schedule of food reinforcement and then to yoked variable-ratio schedules in which individual ratios corresponded exactly to the ratios of responses to reinforcement obtained on the interlocking schedule. After additional training with the interlocking schedule, the rats were exposed to yoked variable-interval schedules in which intervals corresponded to the intervals between successive reinforcements obtained on the second interlocking schedule. Response rates were highest in the yoked VR condition and lowest in the yoked VI, while intermediate rates characterized the interlocking schedule. Break-run patterns of responding were generated by the interlocking schedule for all subjects, while both the yoked VR and VI schedules produced comparatively stable local rates of responding. These results indicate that responding is sensitive to the interlocking schedule's inverse relationship between reinforcement frequency and responses per reinforcement.


Keys to the diagnosis of occult urologic disease in children.

All physicians who care for children should be aware of the many indications for further urologic examination. A straightforward algorithmic approach to urologic diagnosis is not possible. The physician must individualize and carefully weight the indications for the often-times expensive and uncomfortable tests that are required for urologic diagnosis. The reward is ample when a significant correctable lesion is recognized early enough for salvage on the basis of seemingly unrelated signs or symptoms.


Starting the person with diabetes on insulin in the outpatient setting: a teaching guide for physicians and nurses.

When a physician decides that a diabetic patient requires insulin treatment, more teaching is necessary than when initiating most other medications. It has been found advantageous, in treating persons with diabetes mellitus who are not severely compromised metabolically, to introduce them in an outpatient setting to the administration of insulin. The objective of this article as a teaching guide is to enable the health-care provider to cover all essential points clearly and effectively in a minimal period of time and thereby allow the patient to confidently inject himself/herself properly, and to become a member of the team that is managing and controlling his/her disease. This paper deals only with the use of insulin in the diabetic patient. It is recognized that other aspects of patient care and patient education must be addressed concurrently in the total care of the patient with diabetes.


The problem patient as perceived by family physicians.

Views of family physicians, in training and in practice, were obtained on problem patients. Both groups identified problem patients by the presence of vague complaints of a functional nature and the presence of psychiatric symptoms. Views of problem patients did not change with age of physician or length of time since training. Neither group identified problem patients by the type of physician-patient relationship, a finding that probably contributes to increased difficulties with this group of patients.


The elderly in family practice: an evaluation of the geriatric visiting nurse.

The Geriatric Visiting Nurse (GVN) is a health-care professional who, assisted by a checklist, screens patients in their homes, carries out basic tests, and facilitates effective follow-up of patients. Utilization of the GVN in a rural Well-Elderly Clinic associated with the University of Iowa Department of Family Practice is described, and the GVN's participation in the clinic is compared with the screening services provided for physicians by geriatric nurses in advanced communities in various countries. Subject to careful planning, the GVN can play an important role in case-finding, and can, when incorporated into the family practice team, promote efficient utilization of the physician's time.


The Residency Assistance Program in family practice.

The Residency Assistance Program in family practice was inaugurated in September 1975 as a plan to mobilize and finance the matching of consultant expertise in family practice residency education with program directors desiring to improve the quality of their residency programs through consultative assistance. The Residency Assistance Program is administered by a Project Board composed of representatives of four national family practice organizations. A panel of 30 consultants, carefully selected by the Project Board, are prepared for rendering effective consultative services through intensive training in consultative skills. They operate under the guidance of concensually developed standards for quality graduate education in family practice. Consultations are only scheduled at the written request of a residency program director. The confidential, nonpunitive, and voluntary nature of a Residency Assistancy Program consultation is carefully guarded, because it is felt that these qualities enhance the information-sharing, collaborative problem-solving nature of the consultative process. This paper describes the development, features, and operational process of this Program.


The content of family practice: a family medicine resident's 2 1/2-year experience with the E-book.

The purpose of this paper is to present the content of office family practice problems seen over a 2 1/2-year residency period and to afford comparison with the well-known Virginia Study. It illustrates the usefulness of the diagnostic E-Book, with which all the data were collected and preserved. Over a 2 1/2-year period, the author cared for 592 patients in the family practice office. The ratio of one physician to 592 patients compares to the Virginia Study's one physician to approximately 745 patients. A total of 1,640 problems were coded in the E-Book. In this study 55 problems/physician/month were seen, whereas in the Virginia Study approximately 177 problems/physician/month were noted. Respiratory illnesses were the most common diagnostic category in both studies. Among specific problems, obesity ranked first at Hershey, with afebrile colds second, hypertension and Beta streptococcal pharyngitis third, and smoking fourth. Obesity and smoking were ranked considerably lower in the Virginia Study, whereas "health maintenance examinations" were ranked number one. Finally, for age-sex practice profiles, the present data revealed two peak age groups for both sexes, whereas the Virginia work noted only one peak age range.


Interpreting educational concepts for the teaching family physician: some parallels between patient care and undergraduate clinical education.

Three of the most widely used concepts in education, objectives, curriculum, and evaluation, have direct parallels in primary care. This parallelism suggests an approach which may help family physicians both in understanding these educational concepts and in applying them with judgment. By drawing specific attention to the parallels and by the use of examples drawn both from clinical practice and from teaching, the author hopes to encourage physicians to view their teaching as an analog of clinical skills that are already familiar to them. This approach is applied to the problem of accommodating to individual differences in students, the most difficult obstacle to the proper application of educational concepts.


Referral patterns in an individual family practice.

This retrospective study of referral patterns in an individual private practice demonstrates that the family physician provides a definitive care for the large majority of patient problems in everyday practice and does not function primarily as a triage officer. Ninety-seven percent of all patient contacts, both ambulatory and in-hospital, were managed by the individual physician and his staff. Two-and-one-half percent of patient contacts required consultation with local specialists, and only .5 percent required referral to a tertiary care center. These results are compared with other large-scale population studies of the "ecology" of medical care and with other recent studies of referral patterns in family practice.


Effective patient scheduling.

Patient appointments and scheduling of patients and physicians are the first step in any health-care delivery system. This paper deals with the conventional method usually found in preprinted appointment books, and the "wave" method. A method of testing this system is any practice environment is described, together with the comparative benefits of the wave method over the conventional method of scheduling. This paper also exemplifies one kind of research that can be accomplished in the private, ambulatory sector of medicine.


An integrated medical record and data system for primary care. Part 5: Implications of filing family folders by area of residence.

A discussion of the advantages of filing family folders by geographic location is presented in addition to several methods for determination of socioeconomic status. Advantages of current filing techniques at the University of Rochester-Highland Hospital Family Medicine Program are detailed. Examples are given of the use of such information to estimate health-care utilization as determined by factors of distance from practice, socioeconomic status, natural barriers, and family size.


Joint pain of recent onset.

A joint pain of recent onset is a common and often challenging problem to the family physician. The many etiologies of acute arthritis require a systematic approach to a careful definition of the problem which is essential to safe and effective therapy. The proper evaluation of joint pain of recent onset requires a detailed history and physical examination as well as a rationally selected battery of laboratory studies. This paper provides the busy physician with a specific approach to the diagnosis of acute joint pain as the basis for precise management.


A prolonged, voltage-dependent calcium permeability revealed by tetraethylammonium in the soma and axon of Aplysia giant neuron.

The soma but not the axon of the giant neuron, R2, of Aplysia can generate an all-or none Ca spike in Na-free or TTX-containing medium (Junge and Miller, 1974). Extracellular axonal recordings made at several distances from the soma provide evidence that the transition in ability to fire a spike in Na-free medium occurs within the first 250 micrometer of the axon. Application of 25 mM TEA-Br to the bathing medium causes a more than tenfold increase in the duration of the somatic action potential. The duration of the axonal action potential in TEA decreases with distance from the soma. At distances greater than 3 mm from the soma this concentration of TEA causes little or no increase in the duration of the axon spike. The effect of 25 mM TEA on both the soma and proximal axon is blocked reversibly by 30 mM CoCl2 or 1 mM CdCl2. The duration of the somatic action potential in TEA increases with an increase in Ca concentration of the bath. At a constant concentration of Na, the voltage level of the somatic plateau increases with Ca concentration in the manner predicted for a Ca electrode. In the presence of 11 mM Ca2+ the potential of the plateau is relatively insensitive to Na concentration. The TEA plateau in R2 reveals a prolonged voltage-dependent permeability to Ca. The duration of the plateau may indicate the degree of Ca activation during a spike.


The role of the electrosensory system in postural control of the weakly electric fish Eigenmannia virescens.

The role of the electrosensory inputs in postural control was examined in the weakly electric fish Eigenmannia virescens. These fish exhibit tonic postural tilt in response to a tilted plexiglas substrate in both transverse and longitudinal planes (rolling and head-up pitching responses, respectively), but not to electrically "transparent" agar substrate. The fish's pitching and rolling responses were abolished when the electrosensory inputs from the trunk were bilaterally eliminated even though the fish's visual and mechanosensory lateral-line systems remained intact. Unilateral lesion abolished the rolling response but not the pitching response. These results demonstrate the functional role of the electrosensory system in postural control, in addition to its known role in social communication and in object location, and the underlying neuronal mechanism is discussed.


Excitation of the common inhibitory motor neuron: a possible role in the startle reflex of the cockroach, Periplaneta americana.

The responses of the widespread common inhibitory motor neuron (CI) to tactile stimulation of the cercus and the abdomen and electrical stimulation of the cercal nerve and the abdominal connectives are investigated. Tactile stimulation produces high frequency (greater than 500 impulses/s) spike discharge in CI with the onset of CI activity preceding the discharge of the excitatory motor neurons. Electrical stimulation of the connectives demonstrates a monosynaptic connection between at least one intermediate sized fiber (conduction velocity =3.7 m/s) in the abdominal connective and the ipsilateral CIs in the meso-and metathoracic ganglia. Electrical stimulation of the cercal nerve suggests a disynaptic path from cercal nerve to CI. Arguments are presented for a cercal afferent-to-CI reflex and the possible functional role of early excitation of CI is discussed.


Effect of denervation on the permeability of acetylcholine-activated channels to organic cations.

Experiments were perfomed on chronically denervated frog sartorius muscles to determine the permeability of the acetylcholine-activated channels to organic cations. The membrane voltage response to bath-applied acetylcholine was measured with the moving electrode when the muscles were bathed in normal Ringer and in Ringer in which all of the Na+ had been replaced with an organic cation. The magnitude of the maximum voltage response was used to estimate the permeability of the channel to the organic cation. These results were compared with those which have been reported for innervated frog sartorius muscles (Maeno, Edwards, and Anraku, 1977). It is concluded that the permeability to a wide range of organic cations is virtually identical for the extrajunctional channels which develop following denervation and the channels with are localized at the junctional region of innervated muscles.


Carbohydrate metabolism in motor neurone disease.

Eight patients with classical motor neurone disease, and eight control patients with neurological disease and matched for degree of wasting, were studied. Both groups had abnormal glucose tolerance, but the patients with motor neurone disease had a significantly lower insulin response both to oral glucose loading and to intravenous tolbutamide. These results suggest that in patients with motor neurone disease there is an impaired synthesis or release of insulin due to islet cell damage. Blood pyruvate and lactate, and cerebrospinal fluid pyruvate, lactate, and citrate, did not differ significantly from the control group. Blood citrate levels were significantly higher in patients with motor neurone disease compared with the controls. Triglyceride levels were raised in patients with motor neurone disease compared to the control patients. This may be secondary to the increased citrate levels.


Diagnostic yield of the analysis of the pattern of electrical activity of muscle and of individual motor unit potentials in neurogenic involvement.

The pattern of electrical activity and the properties of individual motor unit potentials were analysed in the flexor muscles of the forearm of 15 patients with motor neurone disease and 15 patients with a lesion of the brachial plexus. The best diagnostic yield from the pattern of electrical activity was obtained when the force was 30% of maximum: The number of spikes (turns/15 s) was diminished in 70% of the patients; none showed the increase in turns characteristic of myopathy. The decrease in the number of turns was often associated with an increased incidence of long time intervals between turns and with an increased amplitude between turns. The mean duration of individual motor unit potentials was prolonged in 78% of the patients; none showed the decrease in mean duration characteristic of myopathy. Prolongation of the mean duration of motor unit potentials produced by cooling of normal muscle, led to a decrease in the number of turns. This suggested that the diminished number of turns in neurogenic involvement was due mainly to the prolonged duration of motor unit potentials.


Axonal dysfunction in the neuropathy of diabetes mellitus: a quantitative electrophysiological study.

The extent of axonal dysfunction in a group of patients with diabetes mellitus has been investigated using recently introduced quantitative techniques of electromyography. In 40 diabetic patients, estimates of motor unit numbers in the extensor digitorum brevis muscles and measurements of the parameters of electrically evoked motor unit potentials therein are presented, along with significant correlations between these parameters and motor nerve conduction velocities and distal motor latencies in the lateral popliteal nerves. The results indicate that axonal dysfunction and concomitant collateral reinnervation are prominent and integral features of the neuropathy of diabetes mellitus. Axonal dysfunction is present in proportion to and parallels the severity of the demyelinative lesion. It is also extensive in patients without clinical evidence of neuropathy in whom the accompanying collateral reinnervation is of sufficient magnitude to mask the clinical signs of motor involvement.


Effect of diphenylhydantoin on gamma aminobutyric acid (GABA) and succinate activity in rat Purkinje cells.

A study has been made of the effect of diphenylhydantoin (DPH) upon the levels of gamma aminobutyric acid (GABA) and succinic dehydrogenase in rat Purkinje cells. DPH was administered over 26 days in chronic experiments using controls receiving the same injection vehicle without DPH. Animals in this group received daily 1.25 mg/kg body weight, 12.5 mg/kg body weight, and 50 mg/kg body weight DPH. Acute experiments were carried out over the course of not more than four days, three groups of animals receiving 75 mg/kg body weight, 87.5 mg/kg body weight, and 100 mg/kg body weight DPH. No effect upon succinic dehydrogenase could be demonstrated at any dose level. There was a significant progressive loss of GABA with increasing dosage of DPH.


Conditioning of H reflex by a preceding subthreshold tendon reflex stimulus.

The soleus H reflex excitability cycle has been studied using, as conditioning stimulus, a mechanical tap, subthreshold for the tendon reflex, which was applied either on the Achilles tendon, the short biceps tendon, or the quadriceps tendon. In all cases there was an early facilitation followed by a longlasting inhibition of the test H reflex. The same results were obtained in patients with a complete spinal cord section. Wherever the site of the conditioning stimulation, these modifications disappeared after ischaemia of the leg. It is concluded that the effects observed are due to the activation by the tendon tap of the Ia nerve fibres from the soleus muscle, and that the longlasting inhibition is probably due to a transmitter depletion.


Critical cerebral blood flow for production of hemiparesis after unilateral carotid occlusion in the gerbil.

Transient cerebral ischaemia, produced by temporary unilateral common carotid artery (CCA) occlusion, was studied in the gerbil by means of chronically implanted hydrogen electrodes. Unilateral CCA occlusion produced behavioural signs of neurological deficit only when regional cerebral blood flow values in the ipsilateral cerebral hemisphere fell below a critical range of 0.20-0.22 ml/gm brain/min. Postischaemic poor perfusion (no-reflow) was an infrequent observation after removal of CCA occlusion.


Oculopharyngeal myopathy with distal and cardiomyopathy.

Two patients are described with distinctive clinical features including an insidious onset, slow progression, bilateral ptosis, weakness of facial muscles, dysphagia, muscle atrophy, and weakness with a distal distribution in the extremities, and cardiomopathy with conduction system disorders. Electromyographic studies and muscle biopsy showed features highly suggestive of a myopathic disorder. One case is considered to be sporadic. The other seems to be a familial disorder, because of the presence of a mild atrioventricular block and right incomplete bundle branch block in the patient's son and the presence of eyelid ptosis in his sister. This may be a variant of oculopharyngeal myopathy with distal and cardiomyopathy. It will be necessary to perform long-term follow-up studies in these families.