Sensory functions in chronic neuralgia.

Sensory functions in chronic neuralgia. Eleven patients with sustained neuralgia, in most cases after traumatic nerve lesion, were subjected to quantitative sensory testing with thermal and non-noxious mechanical stimuli. Measurements were made in the pain area and at a homologous site on the contralateral normal side. All patients were hypoaesthetic with raised thresholds for warm and cold or touch, or both. Thermal pain thresholds were also raised in some patients but lowered in others indicating hypersensitivity of the nociceptor system or dysaesthesia for thermal input. In six patients single mechanical stimuli produced a painful response above the touch detection threshold. Reaction time measurements indicated that this painful response to suprathreshold mechanical pulses was measured by magnitude estimation as a function of stimulus amplitude. The results were fitted by power functions, as in normal skin, but with steeper slopes on the abnormal side. Suprathreshold hyperaesthesia (recruitment) may exist in the presence of normal threshold functioning.


Nerve conduction, tactile sensibility, and the electromyogram after suture or compression of peripheral nerve: a longitudinal study in man. In three patients sequential studies were performed of sensory and motor conduction after complete section and suture of the median nerve at the wrist and in one patient after partial section of the nerve. The sensory potential evoked by stimuli to digits III and I and recorded proximal to the suture line at the wrist appeared after a delay of three to four months, corresponding to a growth rate of 1.5-2.0 mm per day. From early in the course of regeneration the sensory potential was dispersed in 40 components. In the adult patient the cumulative amplitude increased for two years slowly and thereafter at a two times faster rate. Amplitude and tactile sensibility were normal after 40 months, but the sensory potential was still five times more dispersed than normal. The overall increase in the amplitude of the sensory potentials in children aged 10 and 12 years was three times faster than in adults. In the adults and in the children the maximum sensory conduction velocity was 10-25% of normal. It then increased at 3% per month during the first two years, and thereafter 10 times slower. Forty months after suture in the adults and 13-19 months after suture in the children the conduction velocity had reached 65-75% of normal. The pattern of discrete electrical activity during voluntary effort and the prolonged duration of motor unit potentials indicate persistent enlargement of the reinnervated motor units by peripheral sprouting. The sensory potential recovered five times faster after a compressive nerve lesion than after section and suture as seen in another patient with an affection of the ulnar nerve at the elbow. Normal tactile sensibility was attained 10 times faster than after section and suture. Maximum sensory and motor condution velocity recovered within one year from 60-70% to 80-90% of normal.


Dopamine receptors and sleep induction in man. Sleep induction has been studied in humans after the administration of apomorphine, a direct stimulant of the central dopaminergic system. The drug induced sleep and vomiting in healthy volunteers while it had no significant effect on 10 Parkinsonism patients treated for a long period with L-dopa. Apomorphine given to a group of Parkinsonism patients not receiving any specific treatment, and with a lower degree of disease severity, induced vomiting and sleep with a pattern similar to that in healthy subjects. A relationship between the dopaminergic system and sleep induction is suggested.


Late components of motor unit potentials in central core disease. Electromyographic studies in five patients suffering from central core disease are presented. A variable amount of late components of motor unit potentials were found in all of them, as others have found in Duchenne muscular dystrophy. This suggests the existence of collateral innervation of the resultant fragments of the muscular fibre splitting present in this disorder.


Blink reflexes in severe traumatic coma. Blink reflexes were studied in 21 patients in coma after severe head injury. Our observations suggest that blink reflexes are a simple, objective, neurophysiological test to evaluate brainstem function. Correlations between these reflexes and the anatomoclinical stanges of coma and the Glasgow coma scale have been established. Presence of the early R1 component shows the integrity of at least a part of the pontine structures. The appearance of the late R2 component is correlated with a better chance of recovery from coma.


Ventriculitis from Acinetobacter calcoaceticus variant anitratus. Ventriculitis from infection with Acinetobacter calcoaceticus variant anitratus occurred in an infant two weeks after surgical repair of a lumbosacral meningomyelocele and ventriculoperitoneal shunting. Recovery took place on replacing the shunt with an extraventricular deviation device and giving gentamicin and ampicillin intravenously.


Reading difficulty as a presenting symptom in Wilson's disease. A case of Wilson's disease is reported in which the major symptom before treatment was a reading disability. This was caused by ocular dysmetria, and the abnormal eye movements were recorded by electronystagmography and optokinetic drum testing.


Clofibrate-induced muscular syndrome. Report of a case with clinical, electromyographic and pathologic observations. In this report the clinical features of a case of clofibrate-induced muscular syndrome, as well as the electromyographic, histochemical, light- and electron-microscopic findings are described. The clinical features are similar to those of previously reported cases. Electromyography was consistent with a myopathy. Histochemical profile was normal. The myopathology included breakdown of contractile material, deranged mitochondria, dilated sarcoplasmic reticulum profiles, accumulation of membrane bound dense bodies, discontinuities in sarcolemma and thickening of capillary basement membrane. Macrophages invaded severely affected fibers.


Myotonia, potassium and taurine. A preliminary report. The effect of taurine administration upon potassium-induced muscular hyperexcitability was studied in patients affected with dystrophic myotonia and in normal volunteers. Intra-arterial infusions of increasing concentrations of potassium chloride were given and venous potassium levels simultaneously monitored. Taurine prevented or remarkably reduced the electric signs of muscular hyperexcitability. Potassium chloride and taurine effects upon muscular excitability are discussed in terms of changes of membrane conductance, particularly for potassium ions.


The limitation of pulsatile flow through the aqueduct of Sylvius as a cause of hydrocephalus. The concept is advanced that hydrocephalus results from limitation in the pulsatile flow of CSF downwards through the aqueduct of Sylvius during systole which is necessary to accommodate for the pulsatile pressure and volume increase that accompanies the propagation of the arterial pulse through the brain. Evidence is given to show that flow through the fixed human aqueduct is disturbed and not laminar. Further, with the pressures availalbe, the aqueduct is only just large enough to pass the quantity of fluid which must be vented extracranially during systole. Should the capacity of this systolic venting mechanism be exceeded, physical strain will cause cellular damage in the periventricular and periaqueductal regions which, if prolonged, will lead to tissue destruction and hydrocephalus. There appear to be two main causes for hydrocephalus resulting from this mechanism. Firstly, structural lesions, restricting the lumina of the CSF-venting pathways, especially the aqueduct, will reduce the volume of CSF that can flow through these pathways during systole. The hydrocephalic process will then be continuous and only limited when tissue destruction reduces the systolic volume expansion of the brain such that it can be accomodated by the restricted CSF venting pathways. Secondly, conditions which may increase the amount of the systolic volume expansion of the brain beyond the capacity of the CSF venting pathways. Raised mean intracranial pressure is the most important of these conditions. In such cases the hydrocephalus will be limited by the duration of the causal process and possibly also by the enlargement of the venting pathways, as a result of tissue destruction. This hypothesis also accounts for hydrocephalus resulting from obliteration of the cortical subarachnoid space, obstruction to the cranial venous drainage, deformities in the region of the foramen magnum and arterial encroachment upon the ventricular system.


A freeze-fracture study of fiber types in normal human muscle. The sarcoplasmic reticulum (SR) and plasma membranes of Type 1 and Type 2 fibers of normal human muscle were examined by the freeze-fracture technique. Total particle counts in the SR appeared much lower than in other mammals and a packing density of about 1200 particles/micrometer 2 was found in both longitudinal and cisternal components of SR. There was no difference in particle density of Type 1 and Type 2 fibers. In freeze-fracture replicas of plasma membranes several fiber type differences were seen. The surface caveolae were uniformly distributed in Type 1 fibers whereas in Type 2 they were clustered preferentially at the I-band levels. Total density of intramembranous particles was greater in Type 1 fibers (347 +/- 68/micrometer 2 in P-face, 58 +/- 11/micrometer 2 in E face) than in Type 2 fibers (207 +/- 30/micrometer 2 in P-face, 80 +/- 9/micrometer 2 in E-face). There was a striking difference in respect to rectilinear arrays which were virtually absent in Type 1 fibers (0--2/micrometer 2) and numberous (up to 50--70/micrometer 2) in Type 2 fibers.


Virus-induced demyelination. Production by a viral temperature-sensitive mutant. Infection of mice with a temperature-sensitive (ts) mutant of Chandipura virus (CV) ts472 CV, induced a slower disease than the respective parental virus and white matter lesions characterized by perivascular mononuclear infiltrates accompanied by primary demyelination. The pattern of these lesions was very similar to that in EAE, a prototypic autoimmune disease and in Theiler's virus infection in which an immunopathologic mechanism of myelin injury is strongly suggested. Results obtained in nude mice supported the possible immunopathological nature of myelin injury in ts472 CV infection. No inflammatory response was elicited in either grey or white matter. However, whereas grey matter presented extensive necrosis, no alterations were present in white matter. Such data suggest that whereas grey matter lesions are produced by direct viral cytolytic activity, white matter pathology is probably dependent on the host immune response for its development. The finding of additional models of virus-induced demyelination with a possible immunopathologic mechanism of myelin injury is significant as it suggests that this type of virus-induced myelin degeneration is not restricted to a single virus like Theiler's, but it may represent a more general mechanism of virus-induced demyelination.


Quantitative electromyography using automatic analysis. A comparative study with a fixed fraction of a subject's maximum effort and two levels of thresholds for analysis. Quantitative electromyographic (QEMG) data recorded with two levels of threshold for the apparatus are compared. Using a fixed fraction of a subject's maximum effort the data are shown to be independent of sex, age and the strength of the muscles. The diagnostic yield of such a method is shown to be better with 50 muV threshold for analysis than with 100 muV, in cases of muscle disorders such as Duchenne muscular dystrophy and polymyositis. However, in cases of neurogenic lesions due to anterior horn cell disease the diagnostic yield remains the same with both thresholds.


Nasal encephalocoele. Treatment by trans-cranial operation. Results are described of 86 intracranial operations for the repair of nasal encephalocoele children at the Lahore Neurosurgical Centre in the last 13 years. These midline lesions at the base of the anterior cranial fossa have been considered in the past to be inoperable and even when operable, unpleasantly difficult. The intracranial approach has made it possible to treat this condition satisfactorily with comparatively few complications. Attempts at extra-cranial repair have met little success as they do not take into account the basic embryology and anatomy of the condition and fail to tackle the sac at the patent foramen caecum, the neck of the sac. This paper describes the embryology, anatomy, basic pathology and clinical features of the condition with characteristic X-rays showing the patent foramen caecum and outlines the operative repair.


The failure of microglia in normal brain to exhibit mononuclear phagocyte markers. The origin of brain macrophages or "reactive microglia" has been the subject of considerable controversy. The fundamental question is whether or not there is a morphologically and functionally distinct population of cells, called microglia, which are resident in normal brain and differentiate into macrophages in response to inflammatory stimuli. The present study was performed to determine if any cells in the normal brain have the common markers of mononuclear phagocytes; phagocytosis, IgGFc receptors or macrophage specific antigens. In studies of the newborn and the adult murine brain and adult human brain no cells were detected which had any of those markers, although the highly sensitive marker methods were capable of detecting mononuclear phagocytes in all other tissues where they are known to occur. The results suggest that microglia, if they exist as a distinct cell type, are unrelated to mononuclear phagocytes. Furthermore, they suggest, but do not prove, that all inflammatory macrophages are derived from hematogenous precursors.


Pathology of Shy-Drager syndrome.

Pathology of Shy-Drager syndrome. In four patients with the Shy-Drager syndrome, detailed pathological findings in the central nervous system are described. All four patients had striatonigral degeneration, olivopontocerebellar atrophy, pyramidal tract degeneration and ventral horn cell loss. Along with the multisystem degeneration, there was widespread loss of thoracolumbar autonomic neurons, which was demonstrated by comparative cell counts of the intermediolateral horns in two of the four patients. In all four patients, autonomic nuclei of the sacral cord, particularly the Onuf's and intermediolateral nuclei, were severely affected and diffuse cell loss in the nuclei seems to account for disordered bladder, rectal and sexual functions in Shy-Drager syndrome.


Olivopontocerebellar atrophy with velopharyngolaryngeal paralysis: a contribution to the somatotopy of the nucleus ambiguus. The authors report a case of olivopontocerebellar atrophy (OPCA) with velopharyngolaryngeal paralysis. The cerebellar syndrome appeared in a 66 year-old woman and ran its course until her death at 75. The velopharyngolaryngeal paralysis occured two years after the beginning of the cerebellar symtomatology and was limited for 6 months to a Gerhardt syndrome. Postmortem examination showed typical lesions of OPCA, and on serial sections of the medulla a massive loss of neurons in the lower two thirds of the nucleus ambiguus, bilaterally. The association of OPCA with velopharyngolaryngeal paralysis is exceptional. The anatomical findings in this case contribute to the somatotopy of the nucleus ambiguus in man by demonstrating the location of the velopharyngolaryngeal centers in this formation. The upper third plays only an accessory role in the velopharyngolaryngeal functions, and in the two lower thirds one finds, from the oral to the caudal extremity, first the velopharyngeal, then the laryngeal centers.


A freeze-fracture study of the plasma membrane of muscle fibres of a patient with chronic creatine kinase elevation suspected for malignant hyperthermia. The muscle biopsy from a 12-year-old boy with chronic creatine kinase elevation was studied by electron microscopy. At the age of 7 years the patient had a possible abortive attack of malignant hyperthermia. The biopsy specimen contained many fibres with segmental contracture and necrosis; thin sections showed defects of the plasma membrane with loss of glycogen granules into the interstitium. Freeze-fracturing of the plasma membrane showed clustering of intramembranous particles and some membrane areas were devoid of particles and of pinocytotic caveolae. The E-face showed irregular elevations and the P-face corresponding defects. These deviations of the fracture-plane were due to manifest membrane openings, to abnormalities of the structure of the lipid bilayer, to clustering of membrane particles or to the fact that intracellular membranes often were abnormally close to the plasma membrane. The findings suggest that a disintegration of the lipid-protein system of the membrane precedes the formation of manifest defects. The manifest defects resembled those in Duchenne muscular dystrophy. It is unknown whether the changes seen by freeze-fracturing were specific for a myogenic disorder and whether they were due to a basic membrane abnormality or to defects in other systems of the muscle cell.


Subependymal giant cell tumor of tuberose sclerosis. A light and ultrastructural study. In a small number of cases of tuberose sclerosis, tumors develop in the cerebral subependymal region. Their exact nature has been the subject of debate. The cytology, histology and electron microscopy of a tumor which developed in a 16 year old male suffering from tuberose sclerosis are presented and the findings are discussed.


Fine structure of arachnoid cysts.

Fine structure of arachnoid cysts. Recent studies of the fine structure of the cranial meninges of laboratory animals and man have shown that there is no subdural space. The latter is formed artificially by the tendency of meningeal tissues to cleave along a collagen-free zone, the dura-arachnoid interface layer. This layer is composed of an outer zone of dural border cells and an inner arachnoid barrier layer. The fine structure of nine arachnoid cysts was studied to determine the derivation of the cyst's wall from the various components of normal human meninges. A cleaved dura-arachnoid interface layer covered only the dome of the cyst where the latter had abutted the dura mater. The interface layer did not partake in forming the cyst's wall. The dominant phenomenon of the cyst's wall was an absence of the normal trabeculation of the subarachnoid space, the trabecules being replaced by tightly packed collagen fibrils and a few scattered cells in between. Some cells were layered discontinuously at the inner face of the cyst wall, but there was no organized inner lining. No evidence was found for either a tight sealing of the extracellular spaces in the cyst's wall, nor for the existence of an active transcellular fluid movement.


Recurrent transient ischemic attacks secondary to an embolizing saccular middle cerebral artery aneurysm. Case report. Over a 1-year period, a 60-year-old woman had nine episodes of transient weakness, clumsiness, and hypesthesia of the right upper extremity. Angiography revealed normal extracranial vessels and a left middle cerebral artery aneurysm. The aneurysmal sac, removed at operation, had an organized thrombus, which was believed to be the cause of the transient ischemic attacks. Postoperatively, the patient has remained free of neurological symptoms.


Cerebellar infarction resulting from traumatic occlusion of a vertebral artery. Case report. A case is reported of a patient who suffered a gunshot wound of the neck which resulted in occlusion of a vertebral artery. Within a few hours he deteriorated neurologically to a comatose state with a gaze paresis and a facial paresis ipsilateral to the occluded vertebral artery. The diagnosis of cerebellar infarction with brain-stem compression was made clinically, and a posterior fossa decompression was carried out promptly. The patient has made an excellent recovery. Cerebellar infarction, like cerebellar hemorrhage, may act as a posterior fossa mass requiring neurosurgical decompression. This report emphasizes that such a pathological process may occur after certain injuries that are likely to result in occlusion of a vertebral artery.


Empty sella secondary to suprasellar colloid cyst of foregut (respiratory) origin. Case report. An enlarged sella turcica was discovered in a 40-year-old man who had bitemporal headaches. A pneumoencephalograph revealed a third ventricular cyst, dilated lateral ventricles, and an empty sella. The colloid cyst was lined by foregut epithelium, probably originating in the respiratory tract, and dense connective tissue. This case is the first instance of an empty sella associated with a colloid cyst of the third ventricle. It is proposed that enlargement of the mass in the third ventricle caused increased pulsation pressure of the cerebrospinal fluid, and that in the presence of an incompetent diaphragma sellae the subarachnoid space expanded into the sella. The origin of third ventricle cysts is reconsidered. It is concluded that suprasellar colloid cysts may arise from endoderm, ectoderm, neuroepithelium, or a combination of these epithelia.


Primary epidural Ewing's sarcoma presenting as a lumbar disc protrusion. Case report. Primary neoplasms of the spinal epidural space are uncommon. One of the rarest of these is a soft tissue sarcoma indistinguishable from Ewing's sarcoma of the bone. Only 39 such cases have been reported previously, of which only three arose within the epidural space. The authors report an additional case, which presented in an atypical manner, and review the pertinent literature.


Relative cerebral glucose metabolism evoked by dental-pulp stimulation in the rat. Electrical stimulation of dental pulp is widely acknowledged to produce a sensation that is predominantly or exclusively noxious in character. The authors report the pattern of local cerebral glucose utilization evoked by dental-pulp stimulation in the barbiturate-anesthetized rat, using the [14C]2-deoxyglucose method of Sokoloff. Autoradiographs were prepared from cryostat-cut brain sections of animals given an intravenous pulse of [14C]2-deoxyglucose and sacrificed after 45 minutes of continuous bipolar stimulation of the incisor tooth pulp. Areas of high optical density on the autoradiographs identified brain regions where glucose consumption, and hence functional activity, was maximal. Stimulus-related increases in glucose utilization were seen ipsilaterally in an uninterrupted column from the lower levels of trigeminal nucleus caudalis to the rostral extent of the main sensory nucleus. Mandibular incisor pulp stimulation yielded increased deoxyglucose uptake in relatively restricted dorsal portions of the nuclei, while maxillary pulp stimulation produced a more extensive area of uptake ventrally. Elevated deoxyglucose uptake was also seen in the contralateral ventrobasal thalamus and sensory cortex with maxillary, but not mandibular, pulp stimulation. No changes in metabolic activity were detected in extralemniscal or limbic structures. These initial results suggest that the [14C]2-deoxyglucose method may be a useful means of mapping central structures involved in nociception.


Intracranial aneurysms. Age, sex, blood pressure, and multiplicity in an unselected series of patients. All cases of intracranial aneurysm, arteriovenous malformation, and subarachnoid hemorrhage of undetermined etiology seen at one hospital over a 13-year period were reviewed to assess relationships between age, sex, systolic and diastolic blood pressure, and number of aneurysms. There were 350 patients, of whom 212 had aneurysms. The major findings were as follows: 1) Hypertension was not significantly more prevalent in the aneurysm population than in the age-matched general population, except for females aged 18 to 54 years (systolic pressure elevation of 10 to 15 mm Hg). 2) Under 55 years of age, both male and female hypertensive patients were twice as likely to have multiple aneurysms as normotensive patients. 3) Females were more likely than males to have multiple aneurysms. 4) For females but not males, increasing age, higher systolic pressure, and higher diastolic pressure all correlated with an increasing number of aneurysms. Hypertension appears to be more prevalent in certain subgroups of the total aneurysm population, although the individual relationships between hypertension, atherosclerosis, and aneurysms cannot be determined from either the present or previous studies. The possible role of familial factors, as well as implications for both diagnosis and further research, are briefly noted.


The effects of graded experimental trauma on cerebral blood flow and responsiveness to CO2. The effects of graded mechanical cerebral trauma on cerebrovascular reactivity to CO2 was studied in 26 cats. A fluid-wave percussion model was employed which delivered an epidural trauma of fixed duration and variable amplitude. The animals were maintained at arterial normoxia, with constant monitoring of intracranial and systemic arterial pressures, electroencephalograms, and end-tidal CO2. Following trauma, cerebral blood flow was measured using the H2 ion clearance technique at PaCO2 levels ranging sequentially from 20 to 60 mm Hg. Cerebrovascular reactivity for control animals (uninjured) was 2.7%. In the group with mild trauma (0.76 to 1.90 atm) reactivity was impaired (1.7%), and it was abolished in the severely injured group (2.90 to 4.60 atm). Mild injuries did not alter resting blood flows, while severe trauma resulted in a significant decrease in cerebrovascular resistance. Intracranial and systemic arterial pressures were altered proportionately to the level of cerebral injury. The authors propose that trauma to the brain-stem vasoregulatory centers accounts for these findings.


Surgical treatment of giant intracranial aneurysms. The authors report the cases of 32 patients with aneurysms measuring 2.5 cm or greater in diameter found among 1080 patients with saccular cerebral aneurysms. Of the 32 patients, 24 patients were treated by direct operation, four by common carotid ligation, and the other four by conservative therapy. The appropriateness of surgery and surgical method are discussed.


The two-stage excision of huge acoustic neurinomas. Total removal of huge acoustic neurinomas was carried out in 23 patients by means of a two-stage suboccipital transmeatal approach with microsurgical technique. There was no operative mortality. Good results were obtained in 18 (78%) of the patients who have returned to normal activities or full-time employment. Five patients (22%) have residual preoperative neurological deficits causing a reduced level of activity. All of these, except one, are able to care for themselves. None of the patients has had any further significant neurological deficit caused by the operative procedures. Anatomical integrity of the facial nerve was maintained in 17 patients (74%). Surgical technique, operative morbidity, and results are thoroughly discussed. The potential advantages of this technique are stressed.


The specificity of serum prolactin as a diagnostic indicator of pituitary adenoma. Serum prolactin levels were determined in 205 patients with a variety of intracranial diseases, including 70 cases with pituitary tumors. It is concluded that although the absence of elevated prolactin levels does not help to rule out pituitary pathology, the presence of hyperprolactinemia is highly specific for diseases of the pituitary and hypothalamus, and prolactin determination should be part of the regular work-up of pituitary tumor suspects. Excluding known causes of hyperprolactinemia, such as tranquilizing drug ingestion, the presence of neurological disease outside the hypothalamic-pituitary area was not associated with increased serum prolactin concentrations.


Capillary ultrastructure in human metastatic brain tumors. The ultrastructural characteristics of blood vessels within 18 metastatic neoplasms of the brain have been studied. The abnormal permeability to protein-bound tracers was found to be related to defective capillary endothelium. Abnormalities include gap functions, fenestrations of membranes, and open normal junctions. The abnormal capillaries had the character of capillaries from current tissue. Endothelium cell abnormalities were not found in surrounding edematous brain.


Cytotoxic antibody responses in astrocytoma patients. An improved allogeneic assay. Early diagnosis of brain tumors may be facilitated by a microcytotoxicity assay which the authors have used to detect a humoral immune response against an allogeneic glioblastoma cell line. Sixty-seven of 82 serum samples (82%) from astrocytoma patients elicited significant cytotoxicity, while only six of 65 samples (9%) from normal blood-bank donors demonstrated a similar response. Positive results were more frequently obtained in lower-grade astrocytomas. Meningiomas, acoustic schwannomas, pituitary adenomas, and metastatic tumors were positive in variable numbers of cases. A small series of serum samples were platelet-absorbed to insure that cytotoxicity was not merely due to histocompatibility antigens, and seven of eight samples, when retested on the target cell line, remained significantly positive. The assays were performed under strictly monitored conditions that afforded optimum reliability and minimal experimental variability. As the specificity of this test increases, it may lead to early detection of astrocytomas.


Influence of hypoxia on the composition of isolated edema fluid in cold-induced brain edema. The isolation of edema fluid from cats with cold-induced cerebral edema allowed the study of changes of Na+ and K+ content, lactate dehydrogenase and creatine phosphokinase activity, colloid osmotic pressure and the level of intravenously administered 99mTc-albumin in the edema fluid during a period of hypoxia. The changes consisted of an increase of all mentioned parameters, except Na+; and could be interpreted as a concentration of solutes (but for Na+) in the extracellular edema fluid, concomitant to a reduction of the extracellular space, as the oxygen deficiency caused improper functioning of the cellular Na+-K+ pump, with a resulting shift of fluid (including Na+) into the cellular elements.


Relation of age and cerebral ventricle size to central canal in man. Morphological analysis. The central canal of the spinal cord in man with and without hydrocephalus was studied histologically. The lumen was patent in most patients in the first two decades of life. Cells lining the canal in the prenatal and newborn state and in the first decade of life were predominantly pseudostratified ciliated epithelium. In the second decade, the epithelium became simple columnar or cuboidal. The central canal closed in most cases after the age of 20 years, secondary to proliferation of ependymal cells and astrocytes. Mechanisms whereby the number of glial cells increase are considered. The canal was closed in all adults with normal ventricular size, and in 94% of persons with various degrees of hydrocephalus. In the remaining 6% of cases with hydrocephalus, the lining of the canal resembled that seen in the first two decades, and could have acted as a pathway of cerebrospinal fluid (CSF) absorption. Three cases of severe hydrocephalus in the first two decades of life were encountered; the central canal was patent in one, and occluded in two. Based on these data, the canal was not a significant pathway of CSF absorption in most instances of hydrocephalus and in persons with dilated ventricles who were older than 20 years of age.


Recurrent subarachnoid hemorrhage associated with aminocaproic acid therapy and acute renal artery thrombosis. Case report. Epsilon aminocaproic acid (EACA) has been used to prevent rebleeding in patients with subarachnoid hemorrhage (SAH). Although this agent does decrease the frequency of rebleeding, several reports have described thrombotic complications of EACA therapy. These complications have included clinical deterioration and intracranial vascular thrombosis in patients with SAH, arteriolar and  capillary fibrin thrombi in patients with fibrinolytic syndromes treated with EACA, or other thromboembolic phenomena. Since intravascular fibrin thrombi are often observed in patients with fibrinolytic disorders, EACA should not be implicated in the pathogenesis of fibrin thrombi in patients with disseminated intravascular coagulation or other "consumption coagulopathies." This report describes subtotal infarction of the kidney due to thrombosis of a normal renal artery. This occlusion occurred after EACA therapy in a patient with SAH and histopathological documentation of recurrent SAH. The corresponding clinical event was characterized by marked hypertension and abrupt neurological deterioration.


Direct surgical treatment of bilateral intracavernous internal carotid artery aneurysms. Case report. Bilateral intracavernous internal carotid artery aneurysms are described in a 3-year-old child. The etiology was uncertain, although the aneurysms may have been mycotic. As there was clinical and radiological evidence of progressive enlargement of both aneurysms, the more conventional forms of treatment were not applicable. A direct surgical approach was made to both aneurysms with exploration of the intracavernous portion of the internal carotid artery under deep hypothermia and cardiac arrest.


Management of extracranial carotid stenosis and intracranial aneurysms. Twenty patients with extracranial carotid stenosis and intracranial aneurysms are reviewed. Fifteen of these patients had transient ischemic attacks (TIA's) and incidental aneurysms. The other five presented with symptoms referrable to an aneurysm, and angiography revealed significant carotid stenosis. None of the patients who presented with TIA's and underwent endarterectomy suffered subarachnoid hemorrhage. However, those patients who presented with symptoms referrable to an aneurysm and underwent endarterectomy seem to be at greater risk for subarachnoid hemorrhage.


Some observations on aneurysms of the proximal internal carotid artery. The author reports on 41 aneurysms of the proximal internal carotid artery (PICA) demonstrated in 36 patients with subarachnoid hemorrhage. The patients included a striking preponderance of women, and there was a high incidence of multiple aneurysms. In cases with multiple aneurysms the PICA aneurysm was usually found incidentally, a more distal aneurysm on the internal carotid artery being the source of hemorrhage. An infundibulum at the origin of a posterior communicating artery was unusually common in these patients. The origin of the ophthalmic artery is proposed as the angiographic landmark of the level at which the internal carotid artery penetrates the dura mater.


In vitro assay of contractile activities of spastic canine basilar artery and its surrounding blood clot. A prolonged vasospasm was produced in the canine basilar artery by injection of fresh autogenous arterial blood into the chiasmatic cistern. Homogenates of lyophilized blood clot around the spastic artery, were made, and their contractile activities were studied in vitro. The homgenates of the lyophilized spastic arteries usually induced a dose dependent sustained contraction, whereas those of the lyophilized normal arteries often produced a dose-dependent transient contraction, and those of the lyophilized blood clot induced a dose-dependent transient or sustained contraction. The initial maximum contractions produced by the homogenates of the lyophilized normal and spastic arteries were significantly different in their values, suggesting the presence of a vasoactive agent in the spastic artery itself. Preliminary pharmacological analysis of the vasoactive agent was attempted using methysergide and phentolamine.


Percussive injury to peripheral nerve in rats. Weights were dropped on rat sciatic nerves. Teased fibers and light and electron micrographs of nerves removed between 10 minutes and 2 weeks later were examined. Axonal alterations were seen 10 minutes after injury, and subsequently interruption of axonal continuity with preservation of the basal lamina was apparent. Dissolution of myelin began within 30 minutes and progressed. At 14 days, a segment of some large fibers was devoid of myelin and, by 2 weeks, remyelination had commenced. Demyelination of significant number of fibers was always accompanied by Wallerian degeneration of other fibers of the same nerve. Percussive injury of nerves caused a mixed lesion in which the early and late pathological features were clearly distinguishable from those following crush or compression by a cuff. Any explanation of the transient interruption of function that has been described following such an injury is at present speculative.


Cavernous hemangioma of the orbit.

Cavernous hemangioma of the orbit. The clinical and pathological data of 66 patients with orbital cavernous hemangioma are presented. This tumor occurs in females more frequently than in males, and has its peak incidence in early middle age. Visual disability results from a high degree of relative hyperopia or from optic-nerve compression. Postural or temporal variation is proptosis is not characteristic. Multiple cavernous hemangiomas are rare, but may occur simultaneously or separated by long intervals. In this series, incompletely excised lesions did not cause recurrent proptosis. Relative hyperopia may persist, in spite of complete removal of the tumor. Improved preoperative localization with modern techniques appears to be reducing the morbidity associated with surgical excision of the lesion. A local hemodynamic disturbance may initiate proliferation of vascular channels that undergo progressive ectasia. Growth of the lesion may occur intrinsically by the budding-off of capillary channels from cavernous spaces into the interstitium. Clinical and pathological findings fail to demonstrate any relationship between this lesion and capillary hemangioma of childhood.


A new method for testing the force of clips for aneurysms or experimental spinal cord compression. A new method is described for the determination of force-distance curves for aneurysm clips. A dissecting microscope with a goniometer eyepiece was used to determine the angle between the clip blades as various forces were applied to open the clip. The cosine law was then used to calculate the force-distance curves. The method allows accurate characterization of different clips and is especially useful for the early detection of clip weakening.


Familial lumbar spinal stenosis with acute disc herniations. Case reports of four brothers. The case histories are reported of four brothers with lumbosciatic syndrome due to acute disc herniations, and associated spinal stenosis. Hereditary factors, although not hitherto reported, may be implicated for these spinal lesions, as the parents had also undergone spinal operations previously.


Congenital astrocytoma presenting with intracerebral hematoma. Case report. A massive left intracerebral hematoma was surgically evacuated from a 2-week-old infant. Pathological examination showed that the hemorrhage had developed within a fibrillary astrocytoma. Neonatal intracerebral hemorrhage should raise the question of congenital tumor because such a hemorrhage in this age group is rarely the result of trauma, bleeding diathesis, or vascular malformation.


Enlarging histoplasmomas following treatment of meningitis due to Histoplasma capsulatum Case report. This report describes a case in which an intracranial histoplasmoma was successfully treated with surgical removal and amphotericin B. This is the third reported case of its kind. The authors discuss problems of preoperative diagnosis in a patient with depressed cell-mediated immunity, and no evidence of extracerebral dissemination.


Vancomycin treatment of cerebrospinal fluid shunt infections. Report of two cases. The successful use of vancomycin is reported in two children with shunt infections due to Staphylococcus epidermidis which failed to respond to shunt removal. The previously reported experience with this drug is reviewed. The use of vancomycin should be considered in cases of shunt infections due to susceptible microorganisms and refractory to other therapeutic measures.


Excision of a brain-stem epidermoid cyst. Case report. An intra-axial epidermoid cyst of the brain stem is presented. X-ray studies revealed a mass within the brain stem; computerized tomography showed the mass to be cystic. The epidermoid cyst was successfully removed surgically. Six months after operation the patient is stable with sixth and seventh nerve palsies but resolution of right spastic hemiparesis.


Acute spontaneous otorrhagia resulting from a ruptured petrous carotid aneurysm. Case report. A 35-year-old man experienced sudden spontaneous arterial bleeding from his left ear. Arteriography demonstrated a left petrous carotid aneurysm. The bleeding was initially controlled with packing and ultimately by left common carotid ligation and transection.


Influence of vitamin B-6 upon reproduction and upon plasma and egg cholesterol in chickens. Vitamin B-6 deficiency in the laying hen causes an immediate anorexia, loss of body weight, greatly reduced body fat stores and severe effects upon primary and secondary sex characteristics resulting in severely reduced hatchability culminating in complete cessation of egg production. While inanition may have been largely responsible for involution of the ovaries and oviducts in the vitamin B-6 deficient hens, regression of combs and wattles appears to be a more specific sign of vitamin B-6 deficiency. Serum cholesterol levels of vitamin B-6-deficient hens were lower than those of hens receiving an adequate diet. Egg cholesterol values remained relatively constant regardless of dietary B-6 levels or of alterations in serum cholesterol. No ataxia or mortality was observed in vitamin B-6-deficient hens or roosters. The effects of vitamin B-6 deficiency were almost completely reversed upon repletion of the hens with adequate dietary vitamin B-6.


Effects of guar gum and wheat bran on lipid metabolism of rats. The effects of guar gum and wheat bran on blood and liver lipid levels of rats were measured. In experiment 1, rats were fed ad libitum a 55% sucrose diet containing 0, 15 or 25% wheat bran for 3 weeks. Postprandial plasma triglyceride, liver triglyceride and liver cholesterol values in rats fed the sucrose diet with wheat bran were significantly lower than values for rats fed the diet without wheat bran. Neither fasting plasma triglyceride nor cholesterol values were altered by wheat bran. In experiment 2, rats were meal-fed one of four experimental diets for 3 weeks: sucrose, sucrose-cholesterol, sucrose-cholesterol-bran or sucrose-cholesterol-guar gum. Rats fed sucrose-cholesterol-guar gum diet had significantly lower fasting plasma total cholesterol, liver triglyceride and liver cholesterol values, but higher plasma high density lipoprotein (HDL) cholesterol values than those fed sucrose-cholesterol diet. These values were similar for the sucrose-cholesterol and sucrose-cholesterol-bran groups. Fasting plasma triglyceride levels were not altered by wheat bran or guar gum. These studies indicate that while guar gum lowers fasting plasma total cholesterol and raises HDL cholesterol, wheat bran does not.


The effects of dietary self-selection upon the overshoot phenomenon in starved-refed rats. The food intake, liver composition and hepatic activity of pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G6P-DH), malic enzyme (ME) and acetyl CoA carboxylase (AcCoA Cx) were studied in starved-refed rats. When rats were refed a mixed diet for 3 days, food intake significantly increased (by 33%) from day 1 to 3 and the glycogen accumulation was maximal after 24 hours, but decreased significantly by day 3 (by 34%). In contrast, liver triglycerides sharply increased (10-fold) from day 1 to 3. Furthermore, during refeeding a large increase of G6P-DH, ME and AcCoA Cx was reached on day 3 when the average activity was 5.5- to 6.5-fold higher than before fasting. When rats were refed under conditions of self-selection (carbohydrates, lipids and proteins) total food intake was the same each day, but lipid and carbohydrate intakes varied reciprocally: lipid intake decreased whereas carbohydrate consumption increased during the 3 day refeeding period. Liver glycogen level was unchanged and both the triglyceride accumulation and the overshoot of lipogenic enzymes were highly attenuated: on day 3, they reached 50% of values observed in mixed diet refed rats. Administration of 8-azaguanine during refeeding under self-selecting conditions lowered food intake but had no effect on the pattern of food intake on the first day. In the following days, lipid intake fell dramatically. Azaguanine does not alter liver glycogenesis, but prevents both liver triglyceride accumulation and the overshoot of lipogenic enzymes.


Tissue-specific incorporation of positional isomers of dietary cis- and trans-octadecenoic acids in the rat. The total lipids of liver, heart, blood serum, adipose tissue, testes and adrenals of rats fed a partially hydrogenated fat were found to contain each of the dietary delta 5- to delta 15- cis- and delta 3- to delta 16- trans-octadecenoic acids. The pattern of incorporation of individual isomeric octadecenoic acids was found to be specific for the different tissues. trans-Isomers were preferentially incorporated into liver and heart, whereas cis-isomers were enriched in the testes. The composition of positional isomers of both cis- and trans-octadecenoic acids in adipose tissue, testes and adrenals was similar to that of the dietary lipids, whereas the corresponding compositions in liver, heart and serum were distinctly different. Thus, within the series of cis-octadecenoic acids, less oleic acid (delta 9-isomer) and correspondingly higher proportions of vaccenic acid (delta 11-isomer) were found in liver and heart than in the dietary lipids. Within the series of trans-octadecenoic acids, the isomers ranging from delta 12 to delta 16, especially the delta 14-isomer, were preferentially incorporated into liver, heart and serum, whereas the delta 10- and delta 11-isomers, were distinctly excluded from these tissues.


Effect of dietary methionine and arginine on uric acid excretion of cocks fed a protein-free diet. Cocks were fed a protein-free diet supplemented with methionine plus arginine or glutamic acid for 25 days to investigate the effect of these amino acids on fecal and urinary nitrogen excretion. Addition of either methionine plus arginine or glutamic acid did not change the fecal nitrogen excretion. Methionine plus arginine supplementation reduced the urniary nitrogen excretion compared to the protein-free diet, whereas glutamic acid supplementation increased it. The reduced urinary nitrogen excretion resulting from supplementation with methionine plus arginine was mostly accounted for by a reduction in uric acid excretion. In the methionine plus arginine group, free amino acid analysis showed that free glutamine and glutamic acid content significantly decreased in liver while no differences were found in plasma. Since glutamine may play an important role in the formation of uric acid for chickens, the reduced amount of free glutamine and glutamic acid in the liver of cocks fed the diet suplemented with methionine plus arginine might account for the reduced excretion of uric acid, and therefore for the nitrogen sparing action of methionine plus arginine in chickens fed a protein-free diet.


Association between plasma and liver vitamin A levels in the calf; weanling pig, rabbit and rat; and adult goat fed fixed intakes of vitamin A. To reexamine the relationship between plasma and liver vitamin A levels, data from various species of animals fed fixed intakes of vitamin A ester (expressed as retinol equivalents/kg liver weight/day) were vitamin A ester (expressed as retinol equivalents/kg live weight/day) were studied. The intakes ranging from deficient to toxic were for 48 calves, 4 to 17,600 micrograms; 39 pigs, 17.6 to 19,842 micrograms; 86 rabbits, 4.5 to 287 micrograms; 138 rats, 4 to 16,384 micrograms; and 40 goats, 1 to 17,640 micrograms. Following the feeding of these intakes for periods of between 5 and 133 weeks, blood and liver samples were taken for vitamin A determinations. Plasma vitamin A concentrations reached minimum values at low liver vitamin A levels whereas liver vitamin A levels reached maximum values at high plasma vitamin A concentrations. Upon elimination of data pairs at the extremes, linear regressions of log10 (total liver vitamin A) on plasma vitamin A concentrations and of plasma vitamin A concentrations on log10 (total liver vitamin A) were statistically significant. Therefore it was possible to estimate within limits the log10 (total liver vitamin A) from plasma vitamin A. Applicable limits were for the calf 8 to 46 micrograms/100 ml of plasma, for the pig 14 to 32, for the rabbit 14 to 74, for the rat 5 to 51 and for the goat 22 to 55. Simple correlation coefficients were 0.92, 0.60, 0.93, 0.92 and 0.75.


Plasma lipid and lipoprotein responses of rats to starch and sucrose diets with and without brewer's yeast. The effect of starch and sucrose diets, with and without brewer's yeast, on plasma total cholesterol and triglyceride concentration and on the lipoprotein distribution in plasma was studied in male rats. The rats were fed a cereal based stock diet, a starch or a sucrose diet, plus or minus brewer's yeast, for 4 weeks. The plasma cholesterol concentration increased to similar levels in rats fed the starch or the sucrose diets but remained unchanged in rats fed the stock diet. The plasma triglyceride level increased in rats fed stock diet, but was unchanged in those fed starch or sucrose diets. Brewer's yeast did not modify the cholesterol value in any of the three groups but reduced the triglyceride level in rats fed the stock and the starch diets. In rats fed the starch diet there was a reduction in the relative amount of prebeta lipoproteins, but no significant alterations in the beta, prealpha and alpha fractions, as compared with rats fed stock diet. Rats fed the sucrose diet had lower prebeta, beta and alpha lipoprotein percentages and a much higher prealpha percentage than rats fed the stock diet. Brewer's yeast had no consistent effects on the lipoprotein distribution. The results support the contention that there might be a dissociation between dietary effects on the plasma lipid level and on the lipoprotein distribution.


Alterations of short-term tastant-containing fluid intake in zinc deficient adult rats. Previous studies have demonstrated that zinc deficient rats have elevated taste preferences for tastant-containing solutions normally preferred or rejected by zinc sufficient rats when tested in a two-bottle, 24-hour procedure. Since that test does not control for postingestional determinants upon fluid consumption, we employed a two-bottle, 1-hour test combined with a restricted 3-hour eating period to evaluate taste preferences in seven rats fed a zinc deficient (1.3 ppm zinc) diet and nine rats pair-fed a zinc sufficient diet (100 ppm zinc). After 31 days of feeding, all rats were tested for 2 days (1 hour/day) with a choice between water and each of the following solutions: 0.15 M sodium chloride (NaCl), 2.5 X 10(-3) M Hydrochloric acid (HCl), 0.15 M NaCl, 2.5 X 10(-3) M HCl, 1.28 X 10(-6) M quinine sulfate (QS), 0.30 M NaCl and 1.28 X 10(p6) M QS. The zinc deficient rats demonstrated significantly greater preferences for all of the tastant-containing solutions but showed both significant increases and decreases in total volume intakes. Analysis of the individual water and tastant-containing fluid intakes demonstrated that the zinc sufficient rats consumed significantly more water but significantly less tastant-containing fluid than the zinc deficient rats. These results demonstrate that the increased preferences of zinc deficient rats may be related to preingestional, i.e., taste, rather than postingestion cues.


Regulation of glucose-6-phosphate dehydrogenase and malic enzyme in liver and adipose tissue: effect of dietary trilinolein level in starved-refed and ad libitum-fed rats. The responses of glucose-6-phosphate dehydrogenase (G6PD) (EC 1.1.1.49) and malic enzyme (ME) (EC 1.1.1.40) were studied in liver and adipose tissue of rats fed for 2 days a high glucose diet containing levels of synthetic trilinolein ranging from 0 to 25% (w/w) of the diet (trilinolein was substituted for glucose). One group of rats was starved for 2 days before the trilinolein-containing diets were fed (starved-refed); a second group of rats was fed a fat-free diet for 7 days before the trilinolein-containing diets were fed (ad libitum). Liver G6PD activity decreased exponentially and liver ME activity decreased linearly with increasing dietary trilinolein in starved-refed rats, but did not decrease significantly in ad libitum fed rats. Total liver lipid decreased exponentially with increasing trilinolein in starved-refed rats, but increased exponentially in ad libitum fed rats. Adipose tissue G6PD and ME activities decreased slightly with increasing trilinolein in starved-refed rats, but did not decrease in ad libitum fed rats. When the data were adjusted by analysis of covariance for differences in glucose intake, the liver responses in starved-refed rats were still significant but the adipose tissue responses were not, indicating that the responses of adipose tissue (but not of liver) may have resulted from decreased glucose intake rather than from increased trilinolein intake. The results suggest that dietary trilinolein inhibits the characteristic increase in liver G6PD, ME and total lipids upon starvation-refeeding. However, after the levels of these parameters have been increased by feeding a fat-free diet they cannot be decreased by dietary trilinolein in 2 days.


Selenium, vitamin E and the response to swimming stress in the rat. Experiments were conducted to determine the effects of exercise on rat glutathione peroxidase system enzymes and lipid peroxidation among animals supplemented and unsupplemented with selenium (Se) and vitamin E (E). Liver, muscle and blood were taken before, immediately after and 24 hours after exercising to exhaustion by swimming. No effect of exercise was found on muscle or liver enzymes, although exercise resulted in depressed glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) activities in erythrocytes immediately after exercise. Dietary Se supplementation did result in increased hepatic muscle and erythrocyte glutathione peroxidase activity, and decreased hepatic GR, G6PD and "malic enzyme" activities. Thiobarbituric acid reactive substances, and indicator of lipid peroxidation, increased in liver and muscle subsequent to exercise. This increase was reduced in liver, but not eliminated, by dietary E supplementation. The increase was not affected by dietary E in muscle, nor by dietary Se in either tissue.


Sites of organic acid production and patterns of digesta movement in the gastro-intestinal tract of the raccoon. Twelve raccoons were used to assess the movement of fluid and particulate digesta through their gastrointestinal tract and to determine the diurnal variations in organic acid levels for the various segments of the tract. Fluid and particulate markers were administered at the time of meal feeding. Animals were killed at given intervals after the administration of markers. The gastrointestinal tract was removed and divided into seven segments for measurement of markers, pH, volatile fatty acids (VFA) and lactic acid content. The results indicate a rapid transit of the digesta through the entire gastrointestinal tract, with a mean retention time of less than 24 hours for all fluid and particulate markers. Particulate markers up to 2 cm in length were passed rapidly, with limited retention within the tract, much unlike animals with greater gut complexity. The apparent requirements for gut complexity and digesta retention presumably necessary for digestion by gut microflora were not evident in the raccoon. However, even in the absence of these characteristics, microbial fermentation of the ingesta occurred, as evidenced by the levels of organic acids produced. Colonic VFA concentrations achieved levels comparable to levels observed in the ruminants' foregut and the large intestine of the pony. Lactic acid was found throughout the entire gastrointestinal tract.


Dietary cellulose, zinc and copper: effects on tissue levels of trace minerals in the rat. This study was designed to examine the effect of graded levels of cellulose, zinc and copper on tissue mineral levels. Tissue mineral levels were assayed by atomic absorption spectrophotometry in samples collected from a study which involved 12 treatments in a 3 X 2 X 2 factorial arrangement. This study involved three levels of cellulose (0, 8, and 16% of the diet), two levels of Cu (deficient and adequate; 2 and 18 mg/kg of diet, respectively), and two levels of Zn (marginal and abundant; 10 and 120 mg/kg of diet, respectively). Six weanling, male Sprague-Dawley rats were assigned to each treatment and after 9 weeks they were killed. Reductions of tissue Cu content were observed in the serum, liver, tibia and testis of the rats fed the Cu-deficient diets. The Fe content of the tibia and testis was reduced, but that of liver was elevated in the rats fed Cu-deficient diets. Reductions in tibial Zn levels were observed in the rats fed marginal-Zn as compared to those fed the abundant-Zn diets; and in the rats fed Cu-adequate as compared to those fed Cu-deficient diets. Increases in cellulose resulted in increased liver and testicular Cu content only in rats fed the Cu-deficient diets. Additions of cellulose appeared to have no adverse effect on the distribution of Zn, Cu and Fe in tissues which are sensitive to dietary deficiencies. With the exception of rats fed the copper-deficient, marginal zinc diets, the rats fed the other diets demonstrated a small reduction in serum zinc values as cellulose was increased.


Effects of the unsaturation of dietary fat and of arachidonate supplementation on cholesterol pool expansion in the guinea pigs. We have studied the effects of methyl arachidonate supplementation on the lipid metabolism of guinea pigs fed cholesterol. Four groups of guinea pigs were fed a purified diet containing 9.5% hydrogenated coconut oil (HCNO), a highly saturated fat with or without the addition of 1% cholesterol, for 15 weeks. One half of the animals fed the control and the cholesterol-containing diets were supplemented with 15 mg methyl arachidonate three times per week. Supplementation with methyl arachidonate did not alter the concentration of plasma total (TC) or unesterified (FC) cholesterol, erythrocyte cholesterol and plasma phospholipid or the ratio of plasma FC/TC. Accumulation of cholesterol in the major organs of the cholesterol-fed groups was also unchanged. In both control and cholesterol-fed groups, methyl arachidonate decreased the proportion of oleic (18:1) and linoleic acids (18:2) and increased arachidonic acid (20:4) content of plasma and liver phospholipid. A comparison between the results of this study and studies using cottonseed oil showed that the type of dietary fat modifies the effects of cholesterol: plasma cholesterol levels were higher and liver cholesterol storage was lower in animals fed the saturated fat than in those fed the fat rich in polyunsaturated fatty acids (PUFA). Furthermore, in spite of similar changes in erythrocyte cholesterol content and shape abnormalities, no overt hemolytic anemia was observed in the groups fed cholesterol and saturated fat, in contrast to those fed cholesterol + PUFA-containing fat. We conclude that in guinea pigs supplementary methyl arachidonate had no hypocholesterolemic effect at the levels we fed, that circulating cholesterol levels are not a measure of cholesterol accumulation by organs and that the decrease of serum cholesterol in response of PUFA is due in part to an increase of cholesterol storage in the liver.


Efficacy of the D- and L-isomers of N-acetylmethionine for chicks fed diets containing either crystalline amino acids or intact protein. Chick growth assays were used to evaluate the efficacy and toxicity of the L- and D-isomers of N-acetylmethionine when fed as a source of methionine in crystalline amino acid diets. In agreement with earlier rat studies employing intact protein diets, N-acetyl-L-methionine had a methionine-sparing value of 100% and N-acetyl-D-methionine a value of zero. The former was also observed to be fully effective as a methionine supplement when added to a methionine-deficient diet containing equal protein contributions from soybean, casein and gelatin. Isosulfurous levels of excess L-methionine or N-acetyl-L-methionine were equally growth depressing, but L-methionine elevated spleen iron deposition to a greater extent than N-acetyl-L-methionine. N-acetyl-D-methionine in excess depressed growth only slightly, due entirely to a depression in voluntary food intake, and no evidence of splenic hemosiderosis was observed from this addition.


Copper requirement of baby pigs fed purified diets. Three experiments involving 52 baby pigs were conducted to determine the minimum copper requirement of baby pigs fed purified diets. Diets were supplemented with anhydrous cupric sulfate to yield the following copper concentrations (ppm, by analysis) when the three experiments were combined: 0.6, 0.9, 1.3, 1.9, 2.0, 2.8, 3.2, 4.0, 4.9, 5.6 and 9.3. Parameters examined include weight gain, hematocrit, hemoglobin concentration, mean corpuscular hemoglobin concentration, plasma ceruloplasmin activity, plasma copper concentration, copper balance, brain and erythrocyte superoxide dismutase activity, copper concentration of liver, kidney, spleen, heart, brain, femur and hair, liver ferritin-iron and total iron concentration, strength characteristics of the femur, and gross and histological appearance at necropsy. Weight gains were subnormal at dietary copper concentrations below 1.9 ppm; plasma ceruloplasmin activities, and plasma and tissue copper concentrations were depressed at dietary copper levels below 2.8 ppm. Bone histopathology was evident at dietary copper levels below 3.2 ppm, and copper balance was low at dietary copper levels below 4.9 ppm. Some evidence of anemia was present at dietary copper levels below 5.6 ppm. Under the conditions of this study, the copper requirement of the baby pig fed a purified diet was judged to be approximately 5.6 ppm (6 ppm copper, dry basis).


Intestinal absorption of pyridoxal-5'-phosphate: disappearance from perfused segments of rat jejunum in vivo. The luminal disappearance of unlabeled pyridoxal-5'-phosphate (PLP) was studied in vivo in rat jejunum utilizing a perfused segment model. The PLP was measured by a tyrosine decarboxylase assay. [14C]Dextran was used as a nonabsorbable marker to calculate net water absorption. Initial studies validated the use of [14C]dextran as a nonabsorbable marker and established proper conditions of segment perfusion and sample collection for the measurement of PLP luminal disappearance. Subsequent studies demonstrated significant (67.2%) but incomplete inhibition of PLP disappearance by 80 mM phosphate. When nonperfused PLP in 1.1 mM phosphate buffer or perfused PLP in 80 mM phosphate buffer were incubated in vitro for 15 minutes at 37 degrees in a water bath, only negligible changes in PLP concentration were noted. However, when perfused PLP in 1.1 mM phosphate buffer was similarly incubated in vitro, there was a rapid decay in PLP concentration. L-Phenylalanine (5 mM) significantly inhibited this in vitro decay. Conclusions derived from these studies are: 1) The model used is a valid means of studying in vivo luminal disappearance of PLP in the rat jejunum; 2) a major portion of the disappearance seems to involve hydrolysis by alkaline phosphatase; 3) a significant portion of this hydrolysis occurs intraluminally; and 4) a second mechanism of PLP disappearance, which is nonphosphatase-mediated, also appears operative and may represent absorption of the intact, phosphorylated vitamin.


The effects of maternal ethanol consumption in the rat on the development of their offspring. The effects of ethanol on the physical development and maturation of the CNS in the offspring of lactating rats were investigated. Dams were fed: 1) regular stock diet (control), 2) liquid diet containing 35% of the calories as ethanol (ETOH) or 3) liquid diet with maltose-dextrin substituted for the calories supplied by ethanol (isoenergetic = IE). Diets were administered from the 14th day of gestation until 3 weeks post-partum (pre- and post-natal exposure) or from birth until 3 weeks post-partum (post-natal exposure). Body weight, crown-rump length and tail length, as well as brain weight were followed longitudinally in the pups. The growth in the pups of dams fed ETOH diet and those fed IE diet were significantly less than that observed in the pups of control dams. Furthermore, pups of dams fed the ETOH diet showed retardation in growth indices and brain weight at various ages when compared to pups of equivalent age from dams fed the IE diet. Therefore, administration of ethanol to pregnant or lactating dams impaired the physical growth, including central nervous systems (CNS), of their offspring more than those changes caused by nitritional deprivation.


Studies on the effects of rapeseed meal on thyroid status of cattle, glucosinolate and iodine content of milk and other parameters. The effects of feeding rapeseed meals (RSM) containing low (Tower) or high (Target/Turret) levels of glucosinolates on thyroid status, iodine and glucosinolate content of milk and other parameters were studied in dairy cows and young calves. RSM (Tower and Turret) fed to dairy cows at 25% of the grain mixture reduced iodine content of milk. Diets containing Tower and Turret RSM tended to reduce plasma thyroxine (T4) in cows and increase the size of thyroids in rats. Calf diets containing Target and Tower RSM resulted in increased liver and thyroid weights, but only those containing Target tended to reduce plasma T4 levels. Feed intake, weight gain, hemoglobin, blood cell volume and erythrocyte count in calves were not affected by diets containing Tower RSM, but Target RSM reduced all these parameters. In addition, diets containing Target caused more pronounced histological changes of the calves' thyroid than those containing Tower RSM. No measurable amounts of intact glucosinolates were detected in milk of cows fed RSM. Similarly the glucosinolate aglucones, isothiocyanates or vinyl oxazolidinethione, were not transferred to milk although small amounts of unsaturated nitrile (1-cyano-2-hydroxy-3-butene) and inorganic thiocyanate were detected in milk. Rats receiving milk from cows fed Turret RSM developed larger thyroid than those receiving milk from control-fed cows. Supplemental iodine (61.0 microgram/d) in the rat prevented the thyroid enlargement.


Pantothenic acid requirements of channel catfish fingerlings. In 8- and 12-week feeding trials, channel catfish fingerlings were fed purified diets containing four levels (0, 10, 30 and 60 mg/kg) and six levels (0, 5, 10, 20, 40 and 80 mg/kg) of supplemental calcium pantothenate, respectively. The dietary pantothenate level required for maximal growth, feed conversion and prevention of gross deficiency signs was approximately 10 mg/kg of diet. Fish fed the unsupplemented diet showed severe anorexia, loss of weight, clubbed gills, anemia, high mortality rates and eroded skins, lower jaws, fins and barbels. Fused gill filaments were not obtained as reported in pantothenate deficient salmonids.


Maintenance energy requirements, energy retention and heat production of young obese (ob/ob) and lean mice fed a high-fat or a high-carbohydrate diet. Female obese (ob/ob) and lean mice were weaned at 21 days of age, placed in wire-mesh cages maintained at 25 to 30 degrees, and fed a high-fat or a high-carbohydrate diet for 21 days. The body energy balance procedure was utilized to determine the maintenance energy requirements, and the efficiency of dietary energy utilization, above maintenance, in these mice. Heat production of each mouse was measured weekly in a gradient-layer calorimeter. Regressions of changes in body energy per kg3/4 on metabolizable energy intake per kg3/4 indicated that the maintenance energy requirement averaged 72 kcal/kg3/4/day for obese mice and 124 kcal/kg3/4/day for lean mice. Diet composition did not influence the maintenance energy requirements, but utilization of energy, above maintenance, in obese mice fed the high-fat diet was 41% more efficient than observed in obese mice fed the high-carbohydrate diet and 38 to 71% more efficient than observed in lean mice. Heat production, per unit body weight was lower in obese mice than in lean mice. The lowest heat production was observed in obese mice fed the high-fat diet. The 40% lower maintenance energy requirement of the obese mice is a major factor contributing to the high efficiency of energy retention in these mice. Consumption of a high-fat diet further improved the ability of the obese mice to retain dietary energy.


Assessment of indispensable and dispensable amino acids for the immature dog. A completely purified L-amino acid diet was used to determine the indispensability of leucine, lysine, valine, phenylalanine and arginine in the immature dog. An additional study showed that asparagine, alanine, aspartic acid, cystine, glutamic acid, proline, tyrosine, serine and glycine can be classified as dispensable amino acids for the immature dog. Deletion of these indispensable amino acids resulted in a marked negative nitrogen balance. Increased plasma and urinary urea were also observed when a dietary indispensable amino acid imbalance occurred. Estimates are made for the dietary requirements for leucine, lysine, valine and phenylalanine in the immature dog.


Absorption of monoferric phytate by dogs. Recent studies have shown that the iron in wheat is predominantly in the form of monoferric phytate (MFP). Unlike phytate complexed with two or more iron atoms, MFP is soluble at pH 7.0 and above and may therefore be a relatively available form of dietary iron. To examine this point, we tested iron absorption in adult dogs using a double radioisotope method and total body counting. When given without food, MFP was about one-half as available as ferrous sulphate at an iron-equivalent dose of 1.5 mg and only about one-seventh as available at a dose of 15 mg iron. When administered with food, MFP underwent complete isotopic exchange with the nonheme pool of dietary iron. When added to meals of either high or low iron availability in amounts that might be used for iron fortification, the absorption was the same for MFP iron as for the major pool of dietary inorganic iron.


Effect of glucocorticoids and calcium intake on bone density and bone, liver and plasma minerals in guinea pigs. The purpose of this study was to see what effect glucocorticoids would have on bone density and mineral distribution in guinea pigs. Adult female guinea pigs were given prednisolone, a synthetic analogue of cortisol, for up to 24 weeks. Bone density and bone, liver and plasma levels of zinc, copper, iron, manganese, chromium, magnesium and calcium were studied in these animals. In one study, the effect of menopause was simulated by using ovariectomy. In another study, dietary calcium was varied to investigate its effect with glucocorticoids. Animals treated with 1 mg prednisolone/kg body weight showed increased femur density compared with controls, but no changes in tissue mineral concentrations. Animals fed 100 mg prednisolone/kg body weight experienced decreased femur density. Differences in effects were not observed between ovariectomized and intact animals. Bone loss was greatest in animals fed the cereal-based closed-formula diet and least in animals fed the low-calcium diet. Changes in mineral content of femurs observed in animals which lost bone mass were increased iron concentration and decreased magnesium concentration. Total liver stores of zinc and magnesium increased. Liver copper increased in concentration per gram as well as in total content. Liver concentration of manganese decreased. Plasma changes in animals fed the high level of drug were decreased iron and calcium, and increased copper. Hemoglobin and hematocrit increased with increasing drug levels. It is suggested that glucocorticoids have marked effects on mineral metabolism which may be related to the bone loss and that these effects may be modified by dietary changes.


Effect of pre- and postnatal essential fatty acid deficiency on brain development and myelination. Pregnant mice were fed an essential fatty acid (EFA) deficient diet from day 1 of gestation. Several biochemical parameters of postnatal brain growth and myelination were measured on their progeny and compared with controls fed a normal diet containing 4% corn oil or a commercial breeder diet. Measurements of brain DNA, RNA and protein content of the EFA deficient mice suggested a retardation of brain growth and development of about 1 week compared to controls, with the most striking differences noted at ages below 15 days. DNA content of both control and experimental mice became comparable at 20 to 22 days but brain protein and RNA content remained lower in deficient mice at all ages studied. The levels of several myelin specific constituents were also measured in experimental and control brains. The brain galactolipid content was severely depressed at levels 21% of controls at 40 days of age. Proteolipid protein was also significantly reduced (23% of controls at 40 days of age). In contrast, the activity of the myelin marker enzyme, 2',3'-cyclic nucleotide-3'-phosphodiesterase, appeared to be totally unaffected by EFA deficiency. The results indicate that pre-and postnatal EFA deficiency results in a retardation of brain development and a profound reduction of some but not all myelin specific components.


The kinetics of 75Se-selenium in relation to dose and mode of administration to mice. To investigate the effect of selenium in relation to different environmental conditions a study on the kinetics of the element in mice has been carried out on 54 female mice. 75Se (selenite) was administered as a single dose or continuously through drinking water. Different dosage levels were used ranging from "tracer dose" to subtoxic doses. Wholebody counts revealed a biphasic elimination. The first rapid phase was strongly dose-dependent, while the slower second phase of elimination appeared independent of dose as well as mode of administration with a biological half-life of 14.4 +/- 3.2 days. Liver, blood, kidney and lungs were found to contain most of the selenium, here also a two-phased elimination was observed. The biological half-lives for elimination calculated during the second phase gave a mean of 10.7 days with a range of 8.7 to 12.5 days. With continuous administration through drinking water a steady state was obtained after 300 to 400 hours of administration according to concentration. A linearity between amount retained at steady state and log concentration in drinking water is indicated. The results on biological half-lives are discussed in relation to previous publications.


Effects of life span feeding of ruminant-derived human diets to rats. A freeze-dried human diet, based on linoleic acid-enriched food stuffs derived from ruminants, was evaluated and compared with a similarly-prepared diet based on conventional ruminant-derived foodstuffs, using Porton rats in a whole-of-life study. A cereal-based stock diet was used for comparison. Serum biochemical and histopathological examinations were carried out at 0.25, 1.1 and 2.1 years of age and other rats were left until they died of natural causes. Although some diet-specific biochemical differences were noted, triglyceride and cholesterol levels showed changes which were more age-specific than diet-specific. Longevity did not seem to be influenced by quantity or quality of dietary fat. The most common cause of death was a bronchopneumonia at about 2 years of age. Dietary fat also did not affect incidence of tumors. The most common tumor was a pituitary adenoma which occurred most often in females. Only minor causes of death were specific to diet with waxy intra-cardial plaques occurring in less than 5% of rats fed both of the high-fat diets and severe systemic hypertension occurring in rats fed the low-fat stock diet at the same frequency. No deleterious changes were noted that were unique to the linoleic acid-enriched diet.


The influence of early nutrition on the serum cholesterol of the adult rat. In two experiments, young rats were preconditioned with dietary cholesterol by: 1) nursing from dams with a high cholesterol milk or, 2) receiving 10 mg cholesterol dissolved in 0.5 ml of corn oil daily from 6 to 30 days of age. When rats preconditioned with dietary cholesterol in early life were fed stock diet supplemented with 10% lard and 0.5% cholesterol ("cholesterol challenge diet") there was no protection against dietary induced hypercholesterolemia in adult life. In a third experiment, two groups of newborn rats were intubated with: 1) a cholesterol free formula, 2) the cholesterol free formula plus 50 mg% cholesterol. A third group of pups suckled normally. After weaning all pups were fed a stock diet supplemented with 10% lard and 0.5% cholesterol for 1 month. There was no difference in the serum cholesterol in either group of artificially reared rats after the "cholesterol challenge" (106 +/- 6 mg/100 ml). Suckled rats, however, had a lower serum cholesterol after the "cholesterol challenge" (75 +/- 2 mg/100 ml). All experiments conducted refute the hypothesis that early exposure to dietary cholesterol protects against dietary induced hypercholesterolemia in adult life. It appears, however, that cholesterol metabolic systems are affected in early life because of the decreased ability of artificially reared rats to handle a "cholesterol challenge." Possible factors include a component of the dam's milk, growth and development, and the psychological and emotional stress of the artificial rearing process.


Zinc absorption in the rat determined by radioisotope dilution. Zinc absorption in rats was examined by use of an isotope dilution technique. Young rats and mature rats fed varying levels of dietary zinc were injected intramuscularly with 65Zn. Nine days later, a zinc balance study was begun and continued for 5 days. The rats were then decapitated and the intestines and kidneys were removed and analyzed for zinc and 65Zn content. The feces were analyzed for zinc and 65Zn content and the specific activities of the intestines and kidneys were used to compute the contribution of endogenous zinc to total daily zinc excretion and thus calculate the true daily absorption of zinc. The zinc concentration of the intestines and kidneys did not differ significantly among groups but the specific radioactivity in these organs decreased as dietary zinc intake increased. Endogenous zinc excretion was greatest in mature rats and young rats fed the highest level of dietary zinc. Mature rats actually absorbed as much or more zinc than young rats fed the same dietary level of zinc. The results demonstrate that zinc homeostasis in rats is maintained by zinc secretion from the intestine rather than by regulation of zinc absorption.


Effects of pectin and cellulose on growth, feed efficiency, and protein utilization, and their contribution to energy requirement and cecal VFA in rats. Graded levels of cellulose (0 to 20%) or of pectin (0 to 10%) were incorporated in purified diets with either 22 or 8.5% casein as the protein source. Weanling male rats were fed these diets for 4 weeks. Body weight gain, food consumption, feed efficiency, protein biological value, apparent digestion of food, fiber and protein, cecal weight and cecal volatile fatty acids (VFA) were recorded. Cellulose was largely and inert diet diluent causing increased weight gains when protein was limiting but not when protein was sufficient. The 25% disappearance in the gut was due, at least in part, to compaction in the ceca and in increased cecal VFA. Pectin caused progressively greater depressions in body weight gain, food intake and efficiency and protein digestion at both levels of dietary protein. At least part of the 75% disappearance of pectin during passage through the gut could be attributed to increased cecal VFA. However, a rat growth bioassay for energy showed that pectin as well as cellulose, agar and gum arabic contributed no measurable energy to young rats.


Fascioliasis: nitrogen balance studies and the disposition of excessive proline in rats. Nitrogen balance studies were conducted and the results compared between rats infected with Fasciola hepatica and uninfected rats as follows: Rats with 90 to 100 day infections were randomly selected and then matched by weight to uninfected controls. All rats were then fed a 6% protein diet for 3 days. Nitrogen balance data indicated that infected rats excreted significantly higher urinary nitrogen than the healthy ones. As large quantities of proline were known to be released into the host in fascioliasis it was suggested that the excessive proline might cause depressed nitrogen balance. In view of this possibility and because any pathological effects of the excessive proline would likely be most apparent in the organs involved in its handling, a proline disposition study was carried out. For this part of the study, the levels of the proline in various regions of the gut, the urine, the feces and the portal blood of both infected and control rats were measured and compared. Proline levels were found to be elevated in portal blood, duodenal contents, colonic contents, urine and feces.


Effect of gamma irradiation on nutritional value of dry field beans (Phaseolus vulgaris) for chicks. The effect of gamma irradiation (60Co) of different varieties and breeding lines of dry field beans (Phaseolus vulgaris) on chick growth was determined using a chick growth assay in which the diet contained approximately 50% beans. Total protein (N X 6.25) in beans was not changed appreciably by irradiation (21 Mrad) but protein solubility in water was decreased. Irradiation increased in vitro enzymatic digestibility of bean protein by pepsin and by a mixture of trypsin, chymotrypsin and peptidase. In the bioassay the diet was formulated to derive half of the total protein (22.6%) from beans. Autoclaved Pinto and Pink beans gave significantly better growth than Red Mexican and White Pea beans. The differences between Red Mexican and White Pea beans were not significant except for Red Mexican breeding line number RS-59. The nutritional value of all varieties of beans, based on chick growth, was significantly improved by gamma irradiation. The irradiation treatment of beans tended to increase nitrogen retention by chicks and decrease uric acid nitrogen excretion in relation to nitrogen intake.


Lysine deficiency and voluntary exercise in the albino rat. The relationship between low dietary protein and voluntary wheel running was investigated by feeding weanling male white rats a natural diet deficient in lysine, by bioassay criterion. Lysine deficient rats ran more than those pair-fed or ad libitum fed the same diet with lysine added. Body composition of active and inactive rats on the three dietary regimens was compared. Of the carcass components, total and percent protein reduction correlated most strongly with running. Control animals matched in growth to the lysine deficient rats showed hyperactivity earlier, but to the same extent as the lysine deficient rats.


Running fits and gamma-aminobutyric acid of the superior colliculus of the mouse. The present experiment was performed to examine the relationship between the content of gamma-aminobutyric acid of the superior colliculus and running fits induced by injection of semicarbazide (SC), an antivitamin B6, into the superior colliculus of the mouse. (1) The distribution of 4-aminobutyrate: 2-oxoglutarate aminotransferase [EC 2.6.1.19] of the superior colliculus was studied histochemically. A high activity was observed in the superficial and medial gray layers of the superior colliculus. Pretreatment with aminooxyacetic acid at a dose which inhibits running fits induced by intracollicular injection of SC depressed the activity. (2) The contents of gamma-aminobutyric acid in superior colliculi of mice which received an intracollicular injection of SC were 60 per cent of the control, when measured immediately after the first running fit. Administration of pyridoxine together with SC inhibited the fall. (3) Intracollicular injection of thiosemicarbazide and 4-deoxypyridoxine, other antivitamins B6, also induced running fits. These results suggest that the running fits by SC injected intracollicularly are induced by the decrease of gamma-aminobutyrate due to insufficient vitamin B6 in the superior colliculus.


Effect of voluntary exercise on physiological function and feeding behavior of mice on a 20% casein diet or a 10% casein diet. The effects of voluntary exercise on growth and food intake, body composition, organ weight, and fatty acid composition of adipose tissue of mice fed on a 20% casein diet or a 10% casein diet were examined. The weight gain was greater for the 20% casein nonexercise group (20% NE) than that for the 20% casein exercise group (20% E), 10% casein exercise group (10% E) and 10% casein nonexercise group (10% NE). There were no significant differences between the groups except the 20% NE. In 20% E and 10% E, body fats decreased markedly. On the other hand, a very high ratio of protein was present in the body composition of both groups. In the 20% and 10% casein diet groups, food intake was increased by voluntary exercise, but there was no significant difference between 10%E and 10% NE except occasional periods during these experiments. After 6 weeks of age, 10% E had a tendency to undertake more voluntary exercise than 20% E, though the difference was not statistically significant. Development of the heart and gastrocnemius muscles was accelerated by voluntary exercise and epididymal fat tissue was markedly decreased.


Subcellular ascorbic acid in scorbutic guinea pig brain. In scorbutic guinea pigs fed an ascorbic acid-deficient diet for 18 days, the ascorbic acid contents of the liver and plasma were less than 4% those of the control animals, while the content in the brain was about one-third that of the controls. In normal animals, the concentration of ascrobic acid was highest (7.55 +/- 1.46 micrograms of ascorbic acid/mg protein) in the S3 fraction and was also fairly high (5.37 +/- 0.91) in the P2p fraction (cytoplasm of nerve terminals). During ascorbic acid deficiency, the contents in the P2p and microsome fractions decreased slightly faster than those in other fractions. Even after 18 days' deficiency, no significant change was found in the acetylcholine content of the brain.


Isolation and characterization of trypsin inhibitors from wheat germ. Trypsin inhibitors were isolated from wheat germ and two major inhibitors (trypsin inhibitors I and II) were purified by various chromatographies including ion-exchange chromatographies on DEAE-Sephadex and CM-Sephadex as well as gel filtration on Bio-gel and Sephadex. Both inhibitors were polypeptides composed solely of amino acids. In the presence of 1% SDS, inhibitor I showed a single symmetrical sedimentation boundary of 1.6 S and a single band in SDS-gel electrophoresis, but in the absence of SDS, it tended to aggregate. Inhibitor II was found to be homogeneous in gel electrophoresis and velocity sediemntation with or without SDS in the solutions. The molecular weights of inhibitors I and I were approxiamtely 16,000 and 10,000, respectively, by SDS-gel electrophoresis. Some other properties of the two inhibitors, including specific inhibitory activities, amino acid compositions and UV spectral properties are presented.


Further heterogeneity within lethal neonatal short-limbed dwarfism: the platyspondylic types. Twelve infants, initially considered to have thanatophoric dysplasia, were studied by a combined radiographic-histochemical-biochemical approach. Three distinct forms of platyspondylic lethal neonatal short-limbed dwarfism could be distinguished: (1) Thanatophoric type, (2) Torrance type, and (3) San Diego type. The latter two disorders had similar radiographic abnormalities that were clearly different from those of typical thanatophoric dysplasia. All three disorders had clearly different condroosseous histopathologic abnormalities. Preliminary biochemical studies have revealed different electrophorectic abnormalities in solubilized type II collagen chains of cartilage in each of these three disorders.


Oxandrolone therapy in patients with Turner syndrome. Long-term, low-dosage androgen treatment of patients with Turner syndrome results in more rapid growth and significantly greater adult height than in control patients who receive only estrogen for pubertal development. Seventeen patients treated with oxandrolone for one year and ten treated for two years had significantly greater growth velocities during than before treatment. Mean adult height of 25 patients treated with oxandrolone, fluoxymesterone, or both was significantly taller than the height of adult patients with Turner syndrome treated with estrogen only. Excessive skeletal maturation was not generally observed.


Additional evidence against measles vaccine administration to infants less than 12 months of age: altered immune response following active/passive immunization. Quantitative serologic responses following the inoculation of infants less than one year of age with live, further-attenuated measles virus vaccine were compared to those of infants and children inoculated after one year of age. Active/passive immunization resulted in reduced antibody formation in some infants especially those less than 9 months of age. Thirty-seven infants identified as "vaccine failures" following their initial inoculation at less than one year of age were revaccinated after one year of age. Fifty-one percent had no detectable HI antibody by eight months postrevaccination, contrasted to 6.8% of the vaccinees with no detectable HI antibody following one inoculation after one year of age; 49% responded optimally to revaccination. In face of an observed altered response in many infants less than one year of age, it would appear prudent to withhold vaccine in this age group until the consequences of such an approach are better defined.


Pathogenesis of rickets in chronic hepatobiliary disease in children. To investigate whether hepatobiliary rickets is caused by defective intestinal absorption of vitamin D or by impaired hepatic hydroxylation of the vitamin, we studied three children who developed severe rickets, hypocalcemia, and hypophosphatemia, two despite having received 400 to 800 IU vitamin D per day by mouth, and one despite prolonged treatment with 10,000 IU daily. On oral vitamin D therapy, plasma vitamin D and 25-hydroxyvitamin D levels were low. When two children were treated with weekly intravenous doses of 3,000 IU vitamin D to approximate the recommended prophylactic allowance, their plasma calcium and phosphate values improved promptly, the radiographic lesions healed, and the plasma concentrations of vitamin D and 25-hydroxyvitamin D became normal. Our studies indicate that the primary cause of hepatobiliary rickets is intestinal malabsorption of vitamin D, not impairment of the hepatic metabolism of the vitamin.


The high risk of chronic liver disease in multitransfused juvenile hemophiliac patients. Eighty-seven asymptomatic children with either hemophilia A or B were treated before they were 21 years of age. Seventy-two received factor concentrates and 15 cryoprecipitate or fresh-frozen plasma only. Thirty-two of the 72 in the former group have persistently elevated alanine aminotransferase values compared to one of 15 in the latter group. In a subset of children treated with factor concentrates before five years of age, four of seven are chronically HBsAg positive. Liver biopsies were performed in 13 of the 32 asymptomatic patients with abnormal ALT values in the fraction group. It is recommended that until further data become available, children with mild hemophilia and all less than 5 years of age should receive only cryo or FFP.


Caroli disease: the diagnostic approach. Two new pediatric examples of Caroli disease are reported; one was diagnosed by operative cholangiography and one by percutaneous transhepatic cholangiography. Although a variety of approaches may lead one to suspect the diagnosis, percutaneous transhepatic cholangiography is now the method of choice to establish the diagnosis.


The spectrum of the DiGeorge syndrome.

The spectrum of the DiGeorge syndrome. Clinical and autopsy data on 25 patients with DiGeorge syndrome and its variants are presented. Congenital heart disease was the most common presenting complaint; 15 patients came to medical attention in the first 48 hours of life because of cyanosis, cardiac murmurs, or tachycardia and tachypnea. Two unusual anomalies, interrupted aortic arch or truncus arteriosus, were seen in 17 patients. Clinically documented hypocalcemia associated with seizures was seen in ten patients, with a median age at onset of eight days. Fifteen of our 25 patients died at less than one month of age. Most of the patients surviving the first month of life developed purulent rhinitis, maculopapular rashes, failure to thrive, and developmental delay. Sixteen patients had major congenital anomalies not localized to the anterior neck and thorax; these anomalies included arhinencephaly, cleft lip, palate, or uvula, diaphragmatic abnormalities, hydronephrosis, malrotation of the gut and imperforate anus. The 24 autopsied cases constitute 0.7% of the 3,469 sequential postmortem studies done in the period 1950--1975 at The Children's Orthopedic Hospital and Medical Center.


Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature. Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.


Thrombocytosis and increased circulating platelet aggregates in newborn infants of polydrug users. Thirty-three prospectively studied neonates born to mothers using methadone plus other drugs developed significant thrombocytosis by the second week of life compared to platelet counts performed during the first week. This increase persisted for over 16 weeks, with a further short-lived significant peak at 10 weeks of age. Platelet counts exceeding 1,000,000/mm3 were found in seven infants. Thrombocytosis was not related to withdrawal symptoms or treatment (phenobarbital or paregoric). No thrombocytosis was found in 36 normal control infants up to eight weeks of life. Twenty-eight of the study group infants were evaluated for circulating platelet aggregates. Thirteen patients had a normal aggregate index and a mean platelet count of 468,000/mm3; 15 patients had increased aggregates and mean platelet count of 754,000/mm3. The risk for increased circulating platelet aggregates correlated directly with an increase in platelet count. Thrombocytosis and increased circulating platelet aggregates may be factors in the pathogenesis of the focal infarcts, and subarachnoid and germinal plate hemorrhages, described at autopsy in infants of addicted mothers.


Late-onset nonketotic hyperglycinemia and spinocerebellar degeneration. Investigation of a 15-year old boy with progressive optic atrophy and spinocerebellar degeneration revealed elevated plasma, cerebrospinal fluid, and urine glycine concentrations. During an oral glycine loading test, the patient's plasma glycine concentration rose to a higher level than control values, although the initial rate of rise was slower; there was no concomitant rise in the plasma serine concentration. An oral serine loading test resulted in a prompt rise of both glycine and serine serum concentrations. The renal glycine clearance was elevated, and the renal tubular glycine reabsorption was diminished. These findings of decreased intestinal uptake and increased renal tubular glycine clearance suggest that a generalized derangement of glycine entry into cells may account for the phenotypic manifestations of the disorder.


Acute suppurative thyroiditis in children. Ten cases of acute suppurative thyroiditis were studied. All patients remained euthyroid clinically during the course of this disease and during the follow-up. Of seven cases in which bacterial cultures were performed, an aerobic bacterium alone was isolated in one patient and anaerobic bacteria alone in four patients. Mixed aerobic and anaerobic microorganisms were recovered from one patient and cultures were negative in one case. Plasma TSH, T4, T3, and PBI levels were normal except in one case. The 131I uptake values were normal in six of seven cases. Plasma TSH response to TRH stimulation was normal in four of five cases. Antibodies against thyroglobulin and thyroid microsome were negative in four of six cases. These findings suggest that anaerobic bacteria may play an important role in the pathogenic process of acute suppurative thyroiditis and that the pituitary-thyroid functions are not impaired.