Muscle weakness caused by an iodine-deficient diet: investigation of a nutritional myopathy. Newborn rats raised on a commercially available iodine-deficient diet developed severe muscle weakness, affecting predominantly their proximal hind limbs, that electrophysiologically and morphologically was determined to be myopathic in type. Follow-up dietary studies, utilizing different combinations of vitamins, minerals, casein and elemental iodine, demonstrated that the myopathy was the result of a deficiency of multiple dietary constituents, particularly casein, and was not due to a deficiency of iodine alone. These findings were compared with those observed in earlier investigations of a variety of nutritional myopathies. In the laboratory study of animals raised on experimental diets, it becomes important to consider the possible contributions of multiple dietary deficiencies in the evaluation of any abnormalities found.


Effects of chronic deafferentation on adrenergic ganglion cells and small intensely fluorescent cells. To determine the reaction of adrenergic ganglion cells and small intensely fluorescent (SIF) cells to chronic deafferentation, catecholamine fluorescence of the major pelvic ganglion (MPG) of the rat has been studied following section of the hypogastric nerve, pelvic nerve and sympathetic trunk. Only minor changes occurred following section of the hypogastric nerve; the fluorescence surrounding a few adrenergic ganglion cells became brighter. In contrast, pelvic neurectomy resulted in the appearance of numerous varicose fibres and an increase in the fluorescent intensity of fibres enclosing many ganglion cells. Varicose fibres seem to originate from adrenergic ganglion cells and SIF cells. In many instances, nests of SIF cells gave rise to radially oriented fibres. Removal of the sympathetic trunk appeared to have no effect on the MPG. It is suggested that the appearance of varicose fibres from SIF cells following deafferentation may be due to collateral sprouting of these cells or to the increased fluorescence of pre-existing processes.


Lack of labelling of microglial cells following microinjection of [3H] beta-alanine: an electron microscopic autoradiographic study. Following axotomy of the facial nerve, the uptake of [3H] beta-alanine into different types of glial cells in the facial nucleus was studied by autoradiography. A marked proliferation of microglial cells, predominantly in a satellite position to neurons, was accompanied by a localization of [3H] beta--alanine over astrocytes and oligodendrocytes but not over microglial cells. Microglial cells therefore appear to be a functionally distinct cell type and should not be classified with the macroglia.


Intracranial pressure changes induced by sodium nitroprusside in patients with intracranial mass lesions. Because of the ability of sodium nitroprusside (SNP) to dilate cerebral blood vessels, intracranial pressure (ICP) should increase with its use. In patients with vascular intracranial tumors following SNP (0.01%) infusion, ICP increased from 14.58 +/- 1.85 to 27.61 +/- 3.33 torr (p greater than 0.0005) and cerebral perfusion pressure decreased from 89.32 +/- 3.5 to 43.23 +/- 4.60 torr (p less than 0.0005) when the mean arterial pressure had reduced by 33%. These results suggest that SNP not be used in patients with raised ICP unless previous measures have been taken to improve intracranial compliance.


A nonlinear analysis of the cerebrospinal fluid system and intracranial pressure dynamics. A mathematical model of the cerebrospinal fluid (CSF) system was developed to help clarify the kinetics of the intracranial pressure (ICP). A general equation predicting the time course of pressure was derived in terms of four parameters: the intracranial compliance, dural sinus pressure, resistance to absorption, and CSF formation. These parameters were measured in the adult cat, and the equation was tested by comparing experimental and calculated values of the time course of pressure in response to volume changes. The theoretical and experimental results were in close agreement, and the role of each parameter in governing the dynamic equilibrium of the ICP was determined. From this analysis, dynamic tests were developed for rapid measurement of CSF formation, absorption resistance, and the bulk intracranial compliance. These techniques are applicable to clinical settings, providing data that are useful in characterizing the physiological mechanisms responsible for raised ICP and assessing changes induced by therapy.


Long-term follow-up review of patients with acute and subacute subdural hematomas. The authors present 149 patients suffering from acute (112) and subacute (37) subdural hematomas admitted during the 10-year period 1965 to 1974, with a follow-up period of 2 to 12 years. During the time of observation, 104 patients died and 45 survived; 73% of the patients with acute and 27% with subacute subdural hematomas died. Of the patients with an acute subdural hematoma, 11% went back to work, as against 32% of those with subacute subdural hematomas. The 5-year survival rate was 28% in patients with acute and 76% in patients with subacute subdural hematomas.


Surgical treatment of bronchogenic carcinoma with a brain metastasis. Twenty-three patients with bronchogenic carcinoma and a brain metastasis had their primary and secondary tumors treated surgically. The 10 men and 13 women had an average age of 52 years. Fifteen patients presented with a lesion of the lung and eight patients presented initially with neurological findings of an intracranial mass lesion. The most common histological type of tumor was adenocarcinoma (48%), followed by squamous cell carcinoma, undifferentiated small cell carcinoma, and bronchoalveolar carcinoma. Twelve patients (52%) had a poor result and died during the first six months. Surgery appeared to improve short-term survival in six patients (26%). Five patients (22%) had a good result and lived longer than 2 years without significant neurological deficit. Three patients (13%) are alive 10 or more years following surgery.


Intracranial air on computerized tomography. Intracranial gas may be epidural, subdural, subarachnoid, parenchymal, or intraventricular. Intracranial air can be easily diagnosed and its location correctly assessed by computerized tomography. Potentially serious complications of intracranial air, such as tension pneumocephalus, can be rapidly and accurately identified, facilitating appropriate clinical therapy.


A comparison of radiographic methods of diagnosing constrictive lesions of the spinal canal. Toshiba unit vs. CT scanner. With the advent of computerized tomography (CT), a new method of visualizing the spinal canal in cross-section has been created. Before the introduction of CT scanning, evaluation of the cross-sectional anatomy of the spinal canal was accomplished chiefly by the Toshiba unit. This study compares these two forms of tomography and discusses their relative effectiveness in diagnosing constrictive lesions of the spinal canal.


Experimental neurogenic pulmonary edema in cats. Hemorrhagic pulmonary edema was produced consistently in 19 of 20 anesthetized, paralyzed, ventilated cats when intracranial pressure (ICP) was raised for 30 minutes by intraventricular infusion of mock CSF to 150 mm Hg in 14, or 200 mm Hg in six. However, under identical conditions, except that ICP was raised to only 100 mm Hg, three of seven animals did not develop hemorrhagic edema of the lungs and the remaining four had spotty hemorrhage. Thirteen control animals with normal ICP had normal lungs. Gravimetric lung water analysis by Pearce's method confirmed gross and microscopic appearance of hemorrhagic pulmonary edema. Extravascular lung water (p less than 0.05) and lung blood (p less than 0.05) were significantly greater than control values when ICP was raised to or exceeded 150 mm Hg. Despite hemorrhagic edema, pulmonary gas exchange (O2, CO2) remained unaffected. This animal model allows quantitative measurement of neurogenically-mediated hemorrhagic edema of the lungs before gas exchange is impaired. The model may facilitate clarification of the pathogenesis of neurogenic pulmonary edema and, consequently, refine evaluation of therapy.


Microanatomy of the optic canal.

Microanatomy of the optic canal. The human optic canal, an intricate anatomical structure with several normal variations, was studied in 83 individual cadaver specimens. The landmarks and dimensions of the adjacent structures were noted and correlated with surgical exposure of the area. The transorbital-ethmoidal route for extracranial decompression of the optic canal was also studied.


Fascicular nerve allograft evaluation. Part 1: comparison with autografts by light microscopy. In a comparative experiment, transplantation of orthotopic nerve fascicle was performed on 100 sciatic nerves between inbred, antigenically identified rats. The authors studied cellular response, macrophage reaction, connective-tissue reaction, myelination, and distal/proximal axonal ratios, but no difference could be established between allografted and autografted fascicles after 2 months. Moreover, there was no evidence of any graded rejection phenomenon dependent on differences of tissue typing. Theories for the decreased antigenic reaction of nerve fascicles are proposed.


Fascicular nerve allograft evaluation. Part 2: comparison with whole-nerve allograft by light microscopy. Orthotopic whole-nerve and fascicular nerve grafts were transplanted between inbred rats with known histocompatibility antigen structure. In general, the whole sciatic nerves demonstrated a graded rejection response dependent upon the degree of tissue histocompatibility differences. The fascicular grafts, however, had evidence of greatly decreased rejection and no stigma of a graded response dependent on degree of variability of tissue typing. Limitations of the experiment are outlined, and the possible avenues of further research are briefly discussed.


Ipsilateral cerebral atrophy with thalamic tumor of childhood. Case report. A case of cerebral tumor with ipsilateral cerebral hemiatrophy is presented and five previously reported cases are reviewed. The etiology of this entity is discussed on the basis of the symptomatological and clinicopathological findings noted in these six cases. It is suggested that ipsilateral cerebral hemiatrophy is due to thinning of the cerebral cortex with degeneration and disappearance of ganglion cells, demyelination in the subcortex, and destruction of axons. The mechanism proposed for ipsilateral cerebral hemiatrophy due to thalamic tumor is that thalamic tumor causes degeneration and disappearance of thalamic ganglion cells and nerve fibers, with consequent secondary Wallerian degeneration of afferent and projecting fibers from the thalamus as well as retrograde degeneration of efferent fibers, thus resulting in extensive atrophy of the cerebral cortex and subcortical tissue.


Spontaneous healing of intracranial aneurysms after subarachnoid hemorrhage. Case report. A case of spontaneous intra-aneurysmal thrombosis, verified angiographically, is reported in a patient with subarachnoid hemorrhage and without surgical intervention. The frequency of such an occurence and the factors involved are reviewed and discussed.


Anaerobic spinal epidural abscess. Case report. An acute spinal epidural abscess is reported from which a pure growth of the anaerobe Fusobacterium necrophorum was isolated. The mode of infection and pathogen makes it unique. The literature concerning the bacteriology of epidural abscess and the implications of anaerobic epidural infection are discussed.


Intracranial extracerebral brain heterotopia. Case report. The authors describe a case of intracranial heterotopic brain located on the medial one-third of the left sphenoid ridge, and enveloped in a huge cystic cavity. The heterotopic brain was resected successfully with satisfactory clinical results. The resected brain was 8 X 4 X 3 cm in diameter, of 7 or 8 months gestational age, and consisted of cerebrum, brain stem, and cerebellum. Anatomical and cytoarchitectural findings of the heterotopic brain are presented.


Intradiploic epidermoid cyst of the occipital bone with torcular obstruction. Case report. The authors describe a patient with a giant occipital intradiploic epidermoid cyst with compression of the torcular and other posterior fossa structures.


Sequential angiographic studies demonstrating delayed development of an acute epidural hematoma. Case report. A case is presented in which the delayed development of an acute epidural hematoma within 12 hours of a head injury was documented by serial cerebral angiography. A possible mechanism for the delayed evolution of the epidural hematoma is discussed.


Cerebral artery spasm. A histological study at necropsy of the blood vessels in cases of subarachnoid hemorrhage. From a larger series of autopsies with subarachnoid hemorrhage (SAH), 20 cases were selected for the known complication of cerebral vasospasm. Evidence for vasospasm was radiological and pathological in 17 cases and pathological alone in three. A systematic histological examination of the large arteries in places known formerly to have been in spasm showed that, in the 12 early cases (death before 3 weeks), there were relevant changes in all the layers of the arterial wall, the most significant being evidence of necrosis in the tunica media. In the eight late cases (death after 3 weeks), in addition to the sequelae of the earlier acute changes, there was marked concentric intimal thickening by subendothelial fibrosis, again located in the segments of arteries formerly in spasm. Changes were also found in the small arteries, capillaries, and veins, both in the early and late cases but these changes, although striking, were thought to be caused by the ischemia due to the vasospasm; similar changes were also seen in the control cases with ischemia from arterial occlusion.


Carotid paraclinoid aneurysms with intradural origin and intracavernous location. Five cases of a congenital berry aneurysm of the internal carotid artery with origin partially intradural and fundus mainly intracavernous are presented. Angiography does not allow a precise definition of the amount of aneurysm that is intradural, a fact of importance when planning treatment of these cases. However, the angiographic features are characteristics of the type and suggest that these aneurysms be grouped together as a separate entity.


Vertebrobasilar spasm: a significant cause of neurological deficit in head injury. Cerebral vasospasm in the anterior circulation has been recognized as a significant factor in the sequelae of head injury; however, vertebrobasilar spasm resulting from trauma has received much less attention. In the past year we have observed six patients where spasm in the major vessels of the posterior circulation was primarily or in part responsible for the neurological deficit. In such cases, the neurological examination may suggest a supratentorial mass with herniation and, in three of our cases, burr holes or carotid angiography were performed first. However, in every instance neurological signs present on admission indicated primary brain-stem dysfunction. In each of the six cases vertebral angiography demonstrated significant spasm in either the vertebral or basilar arteries. Intracranial pressure was monitored in each of the six patients and did not exceed 25 mm Hg in any. In cases of head injury where the neurological examination indicates brain-stem dysfunction inconsistent with or after a supratentorial mass has been excluded, vertebral angiography may aid in the diagnosis and subsequent management of such patients.


Moyamoya disease associated with aneurysm. Five cases of moyamoya disease associated with aneurysm are reported. In three cases, the aneurysms were located at the peripheral portion of the posterior choroidal artery, and in two at the basilar artery. Based on these cases, the symptoms and mechanisms of formation of aneurysms in moyamoya disease are discussed.


Aphasia and left thalamic hemorrhage.

Aphasia and left thalamic hemorrhage. Left thalamic hemorrhage as a cause of aphasia has not been widely recognized. Large thalamic hemorrhages cause coma, making speech examination impossible; smaller thalamic hemorrhages were difficult to document until recent diagnostic advances. Nine cases of thalamic hemorrhage with aphasia have been described in the literature. This report presents four additional cases. These patients had acute onset of aphasia, supranuclear paralysis of upward gaze, right hemisensory deficits, and mild right hemiparesis. Three of the four patients responded to ventriculostomy drainage with rapid clearing of the supranuclear paralysis of upward gaze, and two later required placement of permanent ventricular shunts. After 1 year, two patients exhibited no clinically detectable speech malfunction and the other two were severely aphasic. The hemiparesis, hemisensory deficits, and ocular pareses all cleared. These cases are discussed with respect to present models of the role of the thalamus in speech.


Cerebellar hemorrhage in adults. Diagnosis by computerized tomography. A series of 10 adult patients with cerebellar hemorrhage diagnosed by computerized tomography (CT) is described. Hypertension was the most common etiological factor, accounting for 70% of the cases. The clinical presentation appeared to fall into two basic groups. The first group (60% of the cases) ran a progressive course with early brain-stem compression. The second group had a benign course with findings of focal cerebellar dysfunction. The CT findings reflected the two clinical categories. The scans of Group 1 patients revealed a lorge hematoma (greater to or equal to 3cm) and substantial ventricular dilatation. In contrast, scans of Group 2 patients demonstrated a small hematoma (less than 3 cm) without ventricular dilatation. Use of CT scanning allowed the accurate diffferentiation of cerebellar hemorrhage from primary brain-stem and intraventricular hemorrhage. The findings of the CT investigations proved very helpful in defining appropriate therapy.


Variations in response of human brain tumors to BCNU in vitro. A microtiter assay was used to study the sensitivity of 24 cultured human astrocytomas to the chemotherapeutic agent 1,3-bis(2-chloroethyl)-1 nitrosourea (BCNU). The tumor cell lines testes originated from patients who were being treated with post-operative chemotherapy within the past 24 months. At a dose level comparable to the maximum in vivo therapeutic dose level, 18 of the 24 cell lines tested showed a significant response to the drug. If in vitro response can eventually be correlated with clinical response, this microtiter assay could help to form a basis for planning more specific chemotherapeutic treatment.


The effect of dexamethasone on electroencephalograms in patients with brain tumors with specific reference to topographic computer display of delta activity. Nine patients with primary or metastatic brain tumors were examined with topographic computer display of delta activity before and after administration of dexamethasone. In six cases with primary malignant or metastatic brain tumors a diminution of delta distribution was observed following intravenous administration of dexamethasone, and no significant changes of the topographic map of the delta wave were obtained in two cases of benign brain tumor without clinical signs of increased intracranial pressure. Some of the changes of delta activities are believed to be correlated with the amount of peritumor edema. It is noteworthy that the change of focal delta activities by steroid was detected 20 minutes after administration.


Surface ultrastructure of tissues occluding ventricular catheters. Specimens of material occluding ventricular catheters removed at shunt revision operations were studied by scanning electron microscopy. Immediate fixation allowed examination of human choroid plexus and ependyma which resembled living tissue.


Malignant astrocytoma following radiotherapy of a craniopharyngoima. Case report. A 9-year-old schoolgirl received 6007 rads to the suprasellar region for craniopharyngioma. Five years later, a malignant astrocytoma developed in the right temporal lobe. We cite clinical and experimental evidence to support our suspicion that the glioma may have been induced by radiation.


Infantile retrocerebellar cyst with immature neural tissue. Case report. A retrocerebellar cyst was excised from a 17-day-old infant with hydrocephalus. The cyst wall contained not only ependyma-like epithelium, choroid plexus tufts, and glial rests, but also prominent areas of immature neural tissue.


Spinal intramedullary metastatic medulloblastoma. Case report. Metastatic spread of medulloblastoma along the neuraxis by leptomeningeal seeding through the cerebrospinal fluid pathways is well known. The occurrence of extracranial metastases outside the neuraxis has been well established, but the occurrence of intramedullary spinal cord metastases not related to surface seeding is rare. A histologically documented case of the latter type is described.


Atlantooccipital instability. Case report. A patient is presented who had neck pain and transient episodes of visual-field defect followed by unconsciousness when he hyperextended his neck. Radiographic examination revealed atlantooccipital instability on flexion and extension views. Treatment by fusion of the occiput to C-2 resulted in relief of symptoms.


Foramen magnum syndrome caused by a giant aneurysm of the posterior inferior cerebral artery. Case report. The authors present a case of giant aneurysm of the posterior inferior cerebellar artery. It was successfully excised with reversal of neurological deficits.


Basal rupture of saccular aneurysm. A pathological case report. In a case of subarachnoid hemorrhage, the arteries of the circle of Willis were left undisturbed and undissected at postmortem examination. A block of frontal lobe tissue with the attached vessels was serially sectioned disclosing in its entirety a saccular aneurysm that had ruptured at the base rather than the dome. The histology of the hemostatic process was clearly depicted.


Spinal subarachnoid hemorrhage during myelography. Case report. Neoplasms of the conus medullaris and cauda equina have been shown to cause subarachnoid hemorrhage (SAH). In such instances, the hemorrhage has been the presenting symptom. A patient with a neurofibrom at T12-L1 experienced spinal SAH during myelography for suspected lumbar disc disease. The roentgenograms showing the lesion itself first and the subarachnoid clot subsequently may be unique. The cause of hemorrhage in this patient may have been the shearing of bridging capsular veins because of diminished cerebrospinal fluid pressure below the almost obstructing lesion.


Xanthogranulomas of the choroid plexus in a neuro-epileptic child. Case report. Bilateral xanthogranulomas arising from both choroid plexues were found in a 6-year-old child with epileptic seizures and psychomotor retardation. Both masses were surgically removed without adding any neurological deficits. The xanthogranulomas were fairly large, and the posterior part of both lateral ventricles were slightly dilated, but clinical symptoms and the location of the xanthogranulomas could not be clearly correlated in this case.


A newly designed multipurpose microneurosurgical head frame. Technical note. A new multipurpose head frame has been designed for microneurosurgery. It consists of a head holder with a frame to hold self-retaining brain retractors, hand rests, instrument holders, a plate for cotton patties, and skin-flap retractors. It has been satisfactorily used in 100 operations for 1 year.


Scintigraphic detection of congenital intracranial vascular malformations. Nine children with arteriovenous malformations (AVMs), and a tenth with a cerebral aneurysm, had computer-processed dynamic scintigraphy with static scintigrams, transmission computed tomography (CT) both with and without contrast injection, and radiopaque cerebral angiography. All ten lesions were detected by dynamic scintigraphy and angiography, whereas two AVMs were missed on CT scans and the aneurysm and two AVMs (one missed by CT) were not identified on static scintigrams. Time-activity curves generated from regions of interest placed over the cerebral hemispheres, AVMs and/or various venous structures permitted, respectively, estimation of interhemispheric partition of perfusion, estimation of the fraction of total cerebral hemispheric perfusion preferentially directed into a malformation, and indication of the route of venous drainage from the lesions. While dynamic scintigraphy and CT scanning both identified the aneurysm, scintigraphy was the most effective screening test for detecting AVMs owing to its accuracy, lower cost, and lack of required anesthesia, heavy sedation or iodinated contrast agents.


The role of bone scanning in osteomalacia. The presence of eight "metabolic features" was assessed on the bone scintigrams of ten patients with osteomalacia. In all of these bone images, sufficient features were present to strongly suggest a metabolic disorder. There scintiphotos were included in a controlled blind study using 30 normal bone scans and 20 scans of metastatic disease. Nine of the ten metabolic bone images were correctly identified by two independent observers. Skeletal uptake of radiotracer, expressed as bone-to-soft tissue ratio, was significantly higher in the osteomalacic patients than in a group of 80 controls.


The predictive value of myocardial perfusion scintigraphy after stress in patients without previous myocardial infarction. Seventy-five patients who had chest pain but no history or ECG evidence of myocardial infarction (MI) underwent myocardial-stress perfusion scintigraphy (MSPS) with thallium-201, treadmill-stress testing (TST), and coronary cineangiography (CA). The sensitivities of MSPS and TST for coronary stenosis greater than or equal to 75% were 68% and 71%, respectively; their specificities were 97% and 79%, respectively (0.1 greater than p greater than 0.05). When the character of a patient's chest pain is considered, Bayesian analysis leads to the following conclusions: (a) MSPS can be useful in pre-CA screening of patients with chest pain but no MI if their pain is thought to be of uncertain or nonischemic origin: (b) the sensitivity of Tl-201 MSPS is not sufficient for pre-CA screening of patients without MI who have typical or atypical angina pectoris; (c) the sensitivity of MSPS would have to be approximately 95% in order for the test to be useful in pre-CA screening of patients who have atypical angina pectoris; (d) MSPS may be superior to TST in these applications; and (e) it is not clear that there is any advantage in combining MSPS and TST into a single screening test rather than using MSPS alone.


Techniques and errors in scintigraphic measurements of gastric emptying. For the monitoring of gastric emptying, a gamma camera or scanner operating from one side of the patient is subject to variations of counting efficiency due to the changing depth of radioactivity. A double-headed scanner was used to investigate the effects of such changes. Tc-99m and In-113m were used as labels for the solid and liquid components of a meal. It was found that the depth of Tc-99m within the stomach decreased by a mean of 13 mm during the first half hour of emptying. Anterior detection alone underestimated emptying rates by an average of 26%. Death changes also introduced errors into "early emptying" measurements made unilaterally. Such artifacts of measurement may compromise mathematical analyses of emptying patterns.


The complementary role of gallium citrate imaging and computed tomography in the evaluation of suspected abdominal infection. Fifteen patients with a suspected abdominal abscess were examined by both gallium-67 and computed tomographic scanning. The Ga-67 scan was a useful screening examination, correctly identifying all eight cases of infection, whereas the CT scan missed one case of a pericecal phlegmon. Misdiagnosis of infection by Ga-67 scan occurred in 2/8 cases without infection but the CT scan correctly identified all noninfected patients. While this series is too small to decide whether there is significant difference in the ability of the two procedures to suggest the correct diagnosis, it is felt that Ga-67 and subsequent CT scans may be complementary in that a Ga-67 scan can initially locate the abnormality and thus direct the CT scan, which can confirm the diagnosis or avoid a misinterpretation of the Ga-67 scan. Computed tomography also provides more anatomical detail, better location of the lesion, and demonsrates lesions noninfectious in nature.


Human reaction to bovine TSH: concise communication. The incidence of allergic reactions to bovine TSH and its relation to dose have been studied in 42 patients with thyroid cancer who had total ablation of functioning thyroidal tissue and have been followed prospectively for up to 25 yr. Of these patients, 43% showed an allergic reaction to bovine TSH. The remaining 57% have shown no reaction, even though they have received cumulative TSH doses larger than those who did show a reaction. The reaction rate is linear up to a cumulative dose of 150 units and is not dose-related therafter.


Radionuclide study in pulmonary sequestration. A radionuclide hemodynamic study was helpful in demonstrating blood supply from the aberrant artery in pulmonary sequestration. Two regions of interest were set up in corresponding lower lung fields of a patient suspected of sequestration in the left lower lobe. Following i.v. injection of Tc-99m albumin, radioactively appeared in the the left target area 8-10 sec behind that on the right. This delay is due to the systemic arterial supply to the sequestration, rather than through the pulmonary artery.


Focally accentuated uptake in an area of increased activity in tc-99m HEDP brain scans. Brain scans performed with Tc-99m HEDP in two patients with suspected intracranial lesions showed abnormal uptake characterized by a focal area of accentuated concentration in a region of increased radioactivity. Surgery revelaed that the focal uptake represented the attachment of meningioma and the general region of increased activity corresponded to the meningioma itself.


Localization of Ga-67 in inflammations in the absence of circulating polymorphonuclear leukocytes. Two cases are reported in whom there were no circulating polymorphonuclear leukocytes, on peripheral blood smears, at the time when Ga-67 citrate studies were carried out. In both of these women, Ga-67 accumulated at sites of inflammation. This shows that nonpolymorphonuclear pathways are sufficient to deliver Ga-67 and to allow its accumulation. The possible roles of lymphocytes or of noncellular pathways (such as transferrin to tissue lactoferrin) are mentioned.


Comparative evaluation of fatty acids labeled with C-11, Cl-34m, Br-77, and I-123 for metabolic studies of the myocardium: concise communication. Various long-chain fatty acids have been labeled with C-11, Cl-34m, Br-77, and I-123 and evaluated for their potential application in measuring myocardial metabolism in vivo. Comparative studies of the kinetics of accumulation and clearance from the heart muscle of mice indicate that the extraction of omega-halofatty acids is more efficient than that of alpha-halofatty acids. Among the omega-halofatty acids, the highest uptake is observed for the 17-iodoheptadecanoic acid, which shows an extraction behavior almost identical to that of [1-11C] palmitic acid, although with a higher radioactivity level in blood due to the release of free iodide.


Quantitative potentials of dynamic emission computed tomography. Statistical uncertainties in emission computed tomography were simulated in 60 computer studies involving various numbers of events and distributions of activity. Previous studies have shown that for a uniform disc of activity of rms percentage of uncertainty per resolution cell is: 120 X (number of resolution cells)1/4 X (number of events per resolution cell)- 1/2. In this work we examined the more general situation where one or two regions of uniform activity are surrounded by a uniform background, and found that for an equal number of recorded events the uncertainties were reduced when the activity was concentrated in a portion of the field. The empirical relation rms % uncertainty in nt = 120(N)1/4(nt)-3/4, where nt is the number of events in an average target (organ) resolution cell and N is the total number of events recorded, satisfactorily described the relationships between uncertainties, contrast, total number of detected events, and number of resolution cells for all 60 computer studies. By means of this relation, we show the theoretical possibility of gated cardiac imaging with 20% uncertainty in 1 cm X 1 cm regions, and of 1-sec cerebral blood-flow images with 20% uncertainty in 2 cm X 2 cm regions.


Implementation of a digital image superposition algorithm for radionuclide images: an assessment of its accuracy and reproducibility. An operator-interactive algorithm to achieve superposition of organ images has been used with a dedicated nuclear medicine computer system. Its purpose is to achieve organ registration in 128 X 128 digitized images before a direct numerical comparison of the regional distribution of a deposited radiotracer is performed. The accuracy and reproducibility of the algorithm for myocardial images has been tested by four operators, using a set of 28 image pairs in which the relative position of the heart differed by more than 10 mm for each pair. Comparing their results with the known displacements on two occasions provided an assessment of these two important parameters. The accuracy and reproducibility for superposing myocardial images by this digital technique are found to be well within the spatial resolution (FWHM) of the imaging system of the Tl-201 tracer studied.


Inexpensive EKG gate for computer-processed cardiac motion study. A simple EKG gating device was constructed from two commerically available integrated circuits. It can be directly interfaced to a computer for motion studies of the heart.


An optimized collimator for single-photon computed tomography with a scintillation camera. The problem of nonuniform response, which is inherent in scintillationcamera emission computed tomography, can be minimized by proper collimator design. A specially fabricated collimator, optimized for emission computed tomography, was designed. This collimator has a calculated full width at half maximum of 1 cm at 15 cm in front of the collimator. When this collimator is used in conjunction with averaged opposed views, excellent uniformity across the reconstruction plane is achievable.


[131I] Hippuran renography in the detection of orthostatic hypertension. Scintigrams in prone and standing positions were done in 11 hypertensive women. All had nephroptosis with ventral rotation. On the basis of the renograms, seven patients were identified as suffering from orthostatic hypertension. Nephropexy resulted in normalization of blood pressure in six of the seven patients and normalization of the renograms of all seven. We believe that sequence scintigrams in prone and standing positions offer a simple method of identifying patients with orthostatic hypertension.


Retained gastric antrum syndrome diagnosed by [99mTc] pertechnetate scintiphotography in man: hormonal and radioisotopic study of two cases. Retained-antrum syndrome is a rare condition, occurring in Billroth II gastrectomised patients, in which an ulcer recurs associated with high levels of circulating gastrin. Some gastrin tests are useful to differentiate a retained antrum from a gastrinoma, but a firm diagnosis is sometimes very difficult. We have studied two cases of retained-antrum syndrome both by gastrin tests and by [99mTc] pertechnetate scintiphotography. By this method a prominent area of activity was observed on the anatomic site of the duodenal stump bottom. It appeared after 20 or 30 min and lasted for the 2 hr of observation. After surgical resection, no area of activity was observed at the scintiphotographic followup. No false positive was observed out of the more than 30 subjects studied. Scintiphotography by pertechnetate seems able to demonstrate the presence and the size of retained gastric antrum in B II gastrectomised patients with recurrent ulcer.


Altered body distribution of [99mTc] pertechnetate in iatrogenic hyperaluminemia. Failure of intravenously administered [99mTc] pertechnetate to leave the vascular space was observed in a patient with hyperaluminemia due to treatment with an antacid drug containing aluminum hydroxide. A repeat study 3 mo after discontinuing medication, when the plasma aluminum level had fallen, revealed normal in vivo distribution of pertechnetate. It was found that instant thin-layer chromatography, using pertechnetate and an 85% methanol system, can detect plasma aluminum levels as low as 50 microgram/l.


Early diagnosis of disc-space infection using Gallium-67. A 4-year-old boy had had progressive central lumbar pain and hamstring spasm. He had a normal lumbar-spine x-ray except for minimal L-5, S1 spondylolysis, but gave an abnormal gallium-67 scan in the region of the low lumbar spine. Eight weeks following intensive antibiotic therapy, confirmation of the diagnosis of disc-space infection was established by roentgenographic studies that demonstrated narrowing of the L 4-5 intervertebral disc space. A technetium-99m diphosphonate bone scan, performed concurrently with the gallium-67 study, was normal.


Characterization of tin-technetium colloid in technetium-labeled albumin preparations. The Tc-99m human serum albumin (HSA) system has been reinvestigated with gel filtration as the assay method. Other than Tc-99m HSA, two radioactive components have been isolated by this technique. Both components are tin-technetium colloids of differing particle sizes, and the relative quantity of each one is pH-dependent. The colloid has been further characterized by protein-induced x-ray emission analysis (PIXE) and by tissue distribution in rats. By this gel-filtration method, commercial Tc-99m HSA kits have been evaluated and have revealed varying amounts of colloids present.


Image artifacts at high photon fluence rates in single-crystal NaI(T1) scintillation cameras. A method that simulates a clinically relevant situation is used to measure the amount of pulse pileup in the gamma image by distinguishing between correctly and incorrectly positioned events. Comparison was then made between responses from different cameras. These investigations show the influence of pileup rejection on counting rate. Pileup effects can be determined for some cameras at such low count rates as about 10,000/sec with a 30% energy window. Parameters affecting the total count rate of the scintillation camera--such as scattering media, source geometry, collimator, and energy window--have been investigated. It is shown that the energy distribution of the photon fluence striking the crystal determines the counting losses and image distortion, rather than the counting rate in the energy window. The approach described here might fulfill the requirements for a new method to compare scintillation cameras. It is important to note that measurements without scattering medium yield results irrelevant for clinical situations.


A simple device for efficient transfer and unit dose packaging of Xe-127: concise communication. An inexpensive system has been devised for the efficient transfer of Xe-127 gas from the manufacturer's ampule into individual dose vials for patient use. By displacing the gas with an aqueous solution, the initial transfer is made from an ampule of known activity into an evacuated serum vial of predetermined volume with transfer efficiency greater than 99%. A similar principle is used to transfer Xe-127 from the stock serum vial into individual dose vials, with total xenon recovery exceeding 98%. Ability to deliver the desired activity to each vial is within 90-110% of that predicted by calculation. Reproducibility in delivering a given activity was excellent, with all vials falling between 95 and 105% of the mean activity. Stability studies showed that 94% of the Xe-127 activity can be removed from the vials with only 6% absorbed in the rubber stopper after 5 wk of storage. The device costs less than $25.00 and can be constructed easily from common laboratory materials.


A technique for the handling and dispensing of Xe-127: concise communication. Xenon-127, which provides photon energies better suited to the Anger camera and reduces radiation dosage to the patient compared with Xe-133, has become commercially available from Brookhaven Laboratories. Its higher cost and longer shelf-life require improved handling and dispensing of shipment ampoules containing gas of high specific activity. The technique described permits individual doses to be prepared for gaseous administration, or dissolved in saline for i.v. injection.


Technetium-99m stannous phytate as an imaging agent for lymph nodes. This report describes preliminary results using technetium-99m stannous phytate as a lymph-node imaging agent in animals. After the subcutaneous administration there is good visualization of the draining nodes, best obtained 2-4 hr from the time of injection. There is also visualization of the liver, spleen, kidneys, and bladder. This agent appears suitable for lymph-node imaging in areas where the extranodal concentration does not interfere.


Radionuclide imaging of primary renal-cell carcinoma by I-131-labeled antitumor antibody. A goat antibody against human renal-cell carcinoma reacted on immunofluorescence with renal-cell carcinomas from 20 patients, but not with normal adult human tissues, including kidney. After i.v. administration the I-131-linked antibody showed preferential tumor localization in six of seven patients with primary renal carcinoma. Labeled antitumor antibodies may have the specificity for tumor imaging that current radiopharmaceuticals lack.


Monitoring of I-125 contamination using a portable scintillation camera. A technique has been developed using a portable scintillation camera to monitor I-125 contamination of personnel. The procedure takes less than a minute to complete and can detect 3 nanocuries; its use minimizes dissemination of I-125 throughout the hospital, emphasizes safe iodination practices and proper handling of radioactive materials, and reduces radiation exposure by undetected contamination.


Microsphere angiography of the liver.

Microsphere angiography of the liver. Radionuclide microsphere angiography of the liver, utilizing capillary blockade of the hepatic arterial system, is presented as a means of evaluating hepatic mass lesions. Masses with an arterial circulation of greater density than normal liver will be identified as focal areas of increased activity. The technique can also document perfused volume and catheter location during organ perfusion chemotherapy.


Validation of the diagnostic value of plasma pyridoxal 5'-phosphate measurements in vitamin B6 nutrition of the rat. The relationship of plasma pyridoxal 5'-phosphate (PLP) to PLP content of tissues and activities of PLP-dependent enzymes was examined to establish its value in assessing vitamin B6 nutrition. Weanling rats were fed ad libitum for 9 weeks purified diets which supplied 0, 4, 12, 24, and 100 micrograms of pyridoxine daily. Growth increased with increasing pyridoxine intake, reaching a maximum at 24 micrograms/day. Liver and brain PLP also increased, attaining maximal values at 12 micrograms. By contrast, muscle and plasma PLP did not saturate when vitamin B6 intake was increased to 100 micrograms. Erythrocytic holoenzyme activity of aspartate (Asp) aminotransferase became maximal with 24 micrograms but that of alanine (Ala) aminotransferase did not. Hepatic holoenzyme activities of Ala, Asp and tyrosine aminotransferases reached maximal values with only 4 micrograms vitamin B6 but that of serine dehydratase became maximal with 12 micrograms. Measurement of coenzyme saturability suggested that apoenzyme degradation, coenzyme affinity and PLP transfer determine the activities of these enzymes. It is concluded that plasma and muscle PLP behave as mobilizable storage pools and that plasma PLP is a sensitive and reliable indicator of vitamin B6 nutrition.


Protein utilization and lysine metabolism in obese and non-obese growing rats. Efficiency of protein utilization and lysine metabolism were studied in growing rats of the Zucker 13M strain, both obese and lean, and in the Charles River CD strain. When graded levels of wheat gluten or wheat gluten supplemented with lysine were fed to these three types of rats, no significant differences in the efficiency of protein utilization were found. However, under these dietary conditions, the Zucker obese rats appeared to be about 167% more efficient in energy utilization than the Zucker lean rats or the Charles River strain. The response of liver lysine-ketoglutarate reductase to the dietary treatment was similar in these three types of growing rats. The enzyme activity was induced by dietary lysine. Rats fed a lysine-deficient purified diet had a significantly lower enzyme activity than those fed a protein-free diet indicating that the same adaptive mechanism for lysine conservation as previously observed in adult rats also occurred in the growing animal. Interaction between dietary and genetic factors on fatty liver was found in this study. The most severe fatty liver was observed in the Zucker obese rats fed the most lysine-deficient diet containing 8% wheat gluten protein.


Amino acid induced orotic aciduria.

Amino acid induced orotic aciduria. Twenty amino acids were examined for their effects on urinary orotic acid excretion. Except for arginine and ornithine, all of the remaining amino acids tested induced a mild orotic aciduria in rats 2 hours post feeding. Two ammonium salts, and urease also acted, as inducers of orotic aciduria. The ammoneogenic properties of the amino acids tested could not solely explain the induced excretion of orotic acid. Only serine, glutamine, NH4Cl, (NH4)2CO3, and urease increased orotic acid excretion in the 24 hour fasted rat. Administration of 0.5 mmoles of arginine or ornithine ameliorated the mild orotic aciduria induced by either glycine or lysine. Arginine was shown to be more efficacious in preventing glycine induced orotic aciduria than was ornithine. Amino acid induced orotic aciduria is dependent upon the physiological state of the animal, varying with the state of digestion and the supply of arginine.


Effect of energy concentration of milk on voluntary intake of lean and obese piglets. Voluntary intake responses of neonatal lean and obese pigs, fed high and low energy diets, were measured. Piglets were maintained in individual cages from 4 to 22 days of age. The 18-day trial was divided into six 3-day ad libitum feeding periods. All piglets received a purified high energy diet (1.12 kcal/ml) in periods 1, 3, 5, and low energy diet (0.57 kcal/ml) in periods 2, 4, and 6. Average daily volume intakes for periods 1 to 6 were 36.8, 55.2, 41.4, 56.2, 38.4, and 47.8 ml/100 g body weight (BW), respectively. Average daily energy intakes were 40.5, 28.7, 45.5, 29.2, 42.2, and 24.9 kcal/100 g BW. Even though piglets consumed greater volumes of low energy diet, energy intake was not maintained during periods 2, 4, and 6. It is possible that gastrointestinal capacity limited intake before energy demand was met. Compared to lean piglets, obese piglets were hyperphagic and consumed more volume (52.0 versus 39.8 ml/100 g BW/day) and more energy (40.0 versus 30.4 kcal/100 g BW/day). It is conclused that neonatal lean and obese piglets possess a sensitive mechanism (s) to control food intake in response to changes in energy content of the diet. The control mechanism in the obese piglets appears to function at a higher level of energy demand than in the lean piglets.


Regulation by dietary fats of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase in rat liver. The effects of various dietary fats on the activity of 3-hydroxy-3-methylglutaryl-Coenzyme A (HMG-CoA) reductase in rat liver microsomes, the rate-limiting enzyme in cholesterogenesis, were examined. A series of experiments demonstrated the dependency of the HMG-CoA reductase activity on the nature of dietary fats. When saturated fats with chain length of 12 to 18 were the dietary sources and were fed at the 10% level for 19 days, feeding fats with shorter chain fatty acids caused a lower enzyme activity compared to those with longer chain fatty acids. The activity was also regulated by the degree of unsaturation of dietary fats; when safflower oil, camellia oil or tristearin were fed at the 10% level for 18 days, the higher the unsaturation, the lower the activity. When trimyristin or tripalmitin were fed at the 10% level for 14 days, addition of essential fatty acid, at the level of minimum daily requirement (1% was replaced by safflower oil), did not affect the enzyme activity. Through the rate of incorporation of mevalonate into cholesterol in the 12,500 x g supernatant fraction of the liver was also found to be influenced by the types of dietary fats, the extent of the response appeared much smaller than that of HMG-CoA reductase. No consistent correlation between the HMG-CoA reductase activity and the content of microsomal cholesterol or cholesteryl ester and the fatty acid composition of microsomal lipids was observed.


Effect of pectin, gum arabic and agar on cholesterol absorption, synthesis, and turnover in rats. A series of five experiments was conducted to determine the effect of pectin, gum arabic and agar (5%) on cholesterol absorption, biosynthesis and turnover in rats. In the study of cholesterol absorption, a tracer dose of labeled cholesterol was included in the last meal. The rats were killed 12 hours later. The proportion of the labeled cholesterol recovered in the whole body was used as an estimation of the efficiency of absorption of dietary cholesterol. Cholesterol biosynthesis was estimated by determining the activity of labeled digitonin-precipitable sterols biosynthesized from labeled glucose which was included in a test meal. In turnover studies, rats were injected intravenously with labeled cholesterol using serum as a vehicle, and the activity of labeled cholesterol in tissues was determined after various time intervals. All three complex carbohydrates decreased cholesterol absorption and pectin had the greatest effect. Pectin and gum arabic increased cholesterol biosynthesis in rats fed a cholesterol-containing diet, but had no effect in a cholesterol-free diet. Pectin slightly increased the turnover of cholesterol, but gum arabic and agar had no effect. This work supports the hypothesis that pectin lowers cholesterol levels by interfering with cholesterol absorption and by increasing cholesterol turnover. The study also suggests that complex carbohydrates differ in their effects on cholesterol metabolism. The reason for these differences remains to be determined.


The effects of fasting on body composition, glucose turnover, enzymes and metabolites in the chicken. Chickens (1,200 g) were fasted 1, 4, or 8 days. Significant decreases occurred in total body protein and fat with fasting, with the greatest energy loss from fat. Glucose production determined with either [2-3H] or [6-3H] glucose injected simultaneously with [U-14C] glucose remained constant with fasting at 10 to 13 mg/minute/kg body weight which is much higher than reported for mammals. Blood lactate and glycerol were unchanged with fasting, while pyruvate increased and plateaued. Plasma alanine, serine and glycine levels were extremely high compared to values in fasted mammals. Blood beta-hydroxybutyrate increased dramatically with fasting (350 to 3,500 nm/ml), while acetoacetate remained constant. The hepatic lactate: pyruvate ratio was unchanged with fasting, while the beta-hydroxybutyrate:acetoacetate ratio increased. These ratios have been reported to influence phosphoenolpyruvate (PEP) and glucose production in mammals. Hepatic and renal phospyoenolpyruvate carboxykinase (PEPCK) levels remained constant, while hepatic lactate dehydrogenase increased with fasting. Beta-Hydroxybutyrate dehydrogenase levels were very low at all times. The results indicate little glucose sparing adaptation per kg in the fasting chicken.


Requirement and utilization of egg protein by Japanese young men with marginal intakes of energy. The effect of marginal intakes of energy on the requirement and utilization of egg protein was evaluated in 46 Japanese young men. The subjects were given a standard diet for 1 week and then low protein diets for 2 weeks. These diets contained about 32, 64, and 80 mgN/kg with whole eggs as the protein source. In the first experiment with excess energy, the energy intakes of 31 subjects were kept constant during the 3 week experiment, the mean intakes being 48.2 +/- 1.5 kcal/kg. The body weight was affected by changing protein intakes while maintaining energy intakes at 48 kcal/kg. From regression analysis, the N requirement for apparent N equilibrium was estimated to be 82.0 +/- 8.0 mgN/kg, where NPU was calculated as 56. In the second experiment with submaintenance energy, 15 subjects received 40 kcal/kg. The N requirement was 124 +/- 21 mgN/kg, where NPU was calculated as 37. From these results and those of previous studies, it was concluded as follows: 1) N balance and NPU were remarkably affected by energy intake changed around maintenance level; and 2) the NPU for egg protein in young men for maintenance intakes of energy and N is about 50 to 55. For estimation of the protein requirement for Japanese adults, a correction factor of 100/55 (about 1.8) was used instead of 1.3 adopted by the 1973 FAO/WHO.


The behavior of muscle phosphorylase as a reservoir for vitamin B6 in the rat. Current belief that vitamin B6 deficiency causes depletion of muscle phosphorylase in animals appears to be erroneous. We present evidence that vitamin B6 deficiency is ineffective in reducing total phosphorylase in gasttocnemius muscle of young rats over a period of at least 8 weeks. Rats that had accumulated high levels of muscle phosphorylase while ingesting diets containing normal or excess amounts of the vitamin retained their phosphorylase after transfer to a vitamin B6 deficient diet. Prolonged deficiency did ultimately lead to enzyme depletion but this was after anorexia had developed and weight loss had occurred. When rats were partially starved for 1 to 4 days (fed 10% of normal energy intake) they lost muscle phosphorylase while retaining alanine and aspartate aminotransferases. When totally starved, the rats lost more phosphorylase than during partial starvation, but completely retained alanine aminotransferase, and lost some aspartate aminotrasferase. We conclude that the behavior of muscle phosphorylase is consistent with the Krebs-Fischer proposal that it acts as a reservoir for vitamin B6 and that starvation, but not vitamin B6 deficiency per se, causes depletion of muscle phosphorylase. It appears that phosphorylase may function as an adjunct ot adipose tissue necessary for the animal to efficiently meet the exigencies of starvation.


The antihypercholesterolemic activity of candicdin as a function of dietary cholesterol in cockerels. In the first of two experiments using White Leghorn cockerels, a multifactorial analysis of variance was employed to characterize the antihypercholesterolemic responses (AHC) to candicidin (a heptaene macrolide antifungal antibiotic)-containing diets and the manner in which hypercholesterolemic challenges of different magnitudes modify these responses. In hypercholesterolemic diets, oral candicidin reduced plasma cholesterol concentration in a dose-dependent manner. The relative AHC effects of the diet were dependent on and varied directly with the presence and magnitude of the hypercholesterolemic challenge. The AHC effects of oral candicidin appeared to be additive to the homeostatic mechanisms limiting the rise in plasma cholesterol concentration induced by hypercholesterolemic diets. In the second experiment the absorption of oral 14C-candicidin was studied. Radioactivity above background levels was not found in any of the sampled tissues 4 days after administration of the 14C-candicidin pulse. The total cumulative recovery of radioactivity in the excreta was approximately 95% of the administered dose after 4 days. Within the limits of detection, oral candicidin did not appear to be absorbed from the intestine and appeared to be rapidly and quantitatively eliminated from the body in the feces. Chronic provision of candicidin appeared to increase transit time through the gastrointestinal tract.


Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. The clinical and immunologic features of 11 patients with transient hypogammaglobulinemia of infancy are reported and compared with those of the 16 patients previously reported. Seven were re-evaluated three to ten years after infancy. Two groups were identified: six who were found by screening relatives of patients with other types of immunodeficiency and five whose sera were sent because the patients were having frequent or unusual infections. Those in the first group had no significant health problems during early infancy or childhood. In the second group recurrent infection was a problem during early infancy but not in later years; the latter patients also frequently had other health problems. Serum immunoglobulin concentrations were entirely normal at the last evaluation in five of the six THI patients with immunodeficient relatives. In the second group, the concentrations of one or more immunoglobulin classes, although greatly increased, were still below the normal range. All 11 patients were found to be capable of synthesizing antibodies to human type A and B erythrocytes and to diphtheria and tetanus toxoids, usually by 6 to 11 months of age, and well before immunoglobulin concentrations became normal. Lymphocyte studies in vitro showed no abnormalities in the percentages of cells in the different subpopulations or in their responses to the mitogens. None of the patients was given immune serum globulin replacement therapy and none experienced serious infections during their period of follow-up. The finding of only 11 cases of THI among over 10,000 patients whose sera were sent for immunoglobulin studies over a 12-year period suggests that this is not a common entity.


Intelligence, behavior, and dysmorphogenesis in the fetal alcohol syndrome: a report on 20 patients. In a sample of 20 patients with the fetal alcohol syndrome, ages 9 months to 21 years, the average IQ was 65, with a range of 16 to 105; 60% of the patients had IQ's more than two standard deviations below the mean. The sample included patients who ranged in severity of dysmorphogenesis from mild to severe. The severity of the dysmorphic features was related to degree of mental deficiency; children with the most severe manifestations of FAS had an average IQ of 55, whereas children with lesser manifestations had an average IQ of 82. All children were growth deficient for height and/or head circumference, but in this study only height was significantly correlated with IQ. Environmental and behavioral characteristics of the sample are discussed, and two adults with the fetal alcohol syndrome are presented.


Respiratory obstruction and apnea in infants with bilateral abductor vocal cord paralysis, meningomyelocele, hydrocephalus, and Arnold-Chiari malformation. This report describes 21 infants and children with bilateral abductor vocal cord paralysis and associated meningomyelocele, Arnold-Chiari malformation, and hydrocephalus. Two life-threatening forms of respiratory distress are distinguished: (1) upper airway obstruction due to bilateral abductor cord paralysis and (2) apnea. Clinically significant episodes of apnea were documented in 13 infants. Ten infants had evidence of aspiration and dysphagia. Vocal cord paralysis, apnea, aspiration, and dysphagia were frequently temporally related to increased intracranial pressure.


A distinct human variant of hypoxanthine-guanine phosphoribosyl transferase. A variant form of hypoxanthine-guanine phosphoribosyl transferase has been found in a neurologically normal pediatric patient who presented with hematuria an episodes of oliguria and azotemia. The level of erythrocyte enzyme activity was 3% of normal. Electrophoretic mobility was more rapid than normal. The Km for hypoxanthine was approximately ten times normal. Immunochemical analysis indicated that the variant enzyme cross reacted with antibody to normal HPRT. A system is described for the systematic characterization of a variant HPRT.


Galactose-1-phosphate uridyl transferase deficiency due to Duarte/galactosemia combined variation: clinical and biochemical studies. The most common abnormality detected by the screening of newborn infants for galactosemia is a deficiency of galactose-1-phosphate uridyl transferase due to the presence in one individual of allelic genes for the Duarte variant and for galactosemia. Clinical studies of ten untreated individuals with this genetic compound, including three adults, failed to reveal evidence of cataracts, liver disease, or mental subnormality, the major clinical complications associated with galactosemia. Galactose-1-phosphate was not detectable in umbilical cord blood from one infant. Galactose was not detectable in random blood specimens from any of the individuals and was present in only small amounts following ingestion of milk in one infant and a child. It would appear that this common gentic variation is usually, if not always, benign.


Urinary citrate excretion in the diagnosis of distal renal tubular acidosis. Since hypocitraturia in distal renal tubular acidosis, we screened the asymptomatic children in three families with familial dRTA, by comparing their 24-hour urine citrate excretion to values obtained in 45 normal children. Subsequent acid loading uncovered four new cases of dRTA suspected because of the finding of hypocitraturia. Because hypocitraturia probably contributes to nephrolithiasis/nephrocalcinosis and subsequent renal damage in dRTA, affected family members were treated with alkali (4 mEq/kg/day), which normalized urine citrate in three children; in a fourth child citrate excretion rose but was not normal. Measurement of urine citrate excretion was superior to other currently proposed screening tests for dRTA (first morning urine pH and sediment, urine concentration).


A father and son with cholestasis and peripheral pulmonic stenosis: a distinct form of intrahepatic cholestasis. We report a father and son with the syndrome of cholestasis and peripheral pulmonic stenosis. These cases demonstrate the clinical and biochemical features noted in previous reports of this entity and allows us to differentiate clearly this syndrome, with its benign course, from other more progressive forms of intrahepatic cholestasis. The vertical transmission supports a genetic etiology for this disease. Although serum bile acid levels are elevated in these patients, the individual bile acids do not display a distinctive pattern and no abnormal bile acids are identified.


Developmental changes in red blood cell counts and indices of infants after exclusion of iron deficiency by laboratory criteria and continuous iron supplementation. The developmental changes in red blood cell counts and indices were determined in infants after mild iron deficiency was excluded. The normal values were obtained from a selected group of healthy, term infants who were receiving continuous iron supplementation during a period of one year while normal values for transferrin saturation and serum ferritin were being maintained. The data indicated marked developmental changes in red blood cell counts and indices during the first year of life that are independent of iron intake. Serial analysis of individual infant's values indicated that the red cell measurement at 4 months of age are, to some extent, predictive of the level of subsequent values within the normal range.


The effects of moderate alcohol consumption during pregnancy on fetal growth and morphogenesis. Information on fetal hazards arising from moderate or low levels of maternal alcohol consumption is unavailable in man. In order to study this question an unselected group of pregnant women was interviewed during pregnancy regarding their alcohol intake. At the time of delivery pairs of high-risk and control infants were examined without knowledge of maternal drinking history. Of 163 infants examined, 11 were judged clinically to show signs compatible with a prenatal effect of alcohol on growth and morphogenesis. Nine of these 11 came from the high-risk drinking group. Only two of these infants were classified as having the fetal alcohol syndrome, and each of the mothers was a very heavy drinker. The other seven infants, who showed lesser alterations of growth and morphogenesis suggestive of fetal alcohol syndrome, were born to women who reported drinking an average of one ounce or more of absolute alcohol per day in the month prior to recognition of pregnancy. These results indicate that both moderate and high levels of alcohol intake during early pregnancy may result in alterations of growth and morphogenesis in the fetus.


Cord blood fatty acid composition in infants and in their mothers during the third trimester. Since essential fatty acids are required for normal brain development, we studied plasma lipids and EFA levels in 16 postpartum mothers (28 to 44 weeks) and in the umbilical vein and artery of 32 newborn infants. Groups of eight 24 to 33-, 34 to 37-, 38 to 42-, and 43 to 44-week-old infants were studied. Plasma fatty acid composition was studied in PL, CE, TG, and FFA by thin-layer and gas-liquid chromatography. Increased values for PL, CE, and TG (P less than 0.001) were noted in maternal plasma compared to cord plasma; linoleic acid was lower (P less than 0.001) in cord plasma PL, CE, and FA. EFA derivatives dihomo-gamma-linolenic, arachidonic, and docosahexaenoic acids were higher in cord plasma (P less than 0.001). Total polyenoic EFA increased with advanced gestation, and at term, was close to maternal levels. delta-5,8,11-eicosatrienoic acid (elevated in EFA deficiency) was elevated in cord plasma as compared with maternal values (P less than 0.001); other criteria of EFA deficiency were absent. These data indicate that fetal EFAs are elongated and desaturated during the third trimester. These higher polyenoic acids may incorporate into lipids in the developing CNS. The lower linoleic acid levels in the fetus may be important to the transplacental transport of EFA.


Medical management of small preterm infants with symptomatic patent ductus arteriosus. During 1975, 38 of 44 infants with a birth weight of less than or equal to 1,500 gm who developed pulmonary edema and congestive heart failure due to a patent ductus arteriosus were managed medically until the ductus closed spontaneously days or weeks later. Overall survival was 71%, and there were no deaths among 11 infants weighing more than 1,250 gm. Pulmonary complications were prevalent and were attributed to the extensive use of mechanical ventilation required to control pulmonary edema. The results of this study document the results to be expected when small preterm infants with a symptomatic patent ductus arteriosus are managed without surgical or pharmacologic intervention and provide a basis for the rational design of clinical trials evaluating other management approaches.


Echocardiographic diagnosis: pitfalls in the premature infant with a large patent ductus arteriosus. Thirty-one infants with clinical and radiographic evidence of a large left-to-right shunt across a patent ductus arteriosus underwent echocardiographic study to determine the magnitude of shunting. Seven patients were found to have a normal-left atrial dimensions and a normal left atrial/aortic root dimension at the time when physical and roentgenographic findings of a large PDA were most pronounced. In contrast, left ventricular end diastolic dimensions were excessive in these infants. After ductal closure (four, surgery; two, indomethacin, one, spontaneous) the left ventricular end diastolic dimension fell to the normal range. Optimal echocardiographic accuracy in infants with PDA should combine analysis of both atrial and ventricular dimensions; the former, used alone, may be misleading.


Oral antibiotic therapy for skeletal infections of children. II. Therapy of osteomyelitis and suppurative arthritis. Antimicrobial regimens consisting of a brief initial period of parenteral therapy followed by oral therapy were investigated in infants and children with suppurative bone and joint disease. There were 30 patients with acute hematogenous disease (19 osteomyelitis; three osteoarthritis; eight arthritis) and five with subacute or chronic osteomyelitis. Disease was due to Staphylococcus aureus in 26, Hemophilus influenzae in five, streptococci in three, and S. aureus plus Streptococcus pyogenes in one patient. Pus was removed by surgical drainage or needle aspiration. Oral therapy was monitored by assay of antibiotic concentration and bactericidal activity in serum. Adjustments in dosage were made when necessary to assure a peak serum bactericidal titer of at least 1:8. One patient progressed to chronic osteomyelitis but all other patients with acute disease responded well. Oral therapy provides increased patient comfort and decreases the risk of nosocomial infection associated with prolonged intravenous therapy. It should be carried out only under carefully monitored conditions in hospital to assure compliance and adequacy of serum bactericidal activity.


The effect of cyproheptadine and human growth hormone on adrenocortical function in children with hypopituitarism. The cortisol response to insulin hypoglycemia was determined in ten hypopituitary children treated for four months with both growth hormone and cyproheptadine, and in six other children with hypopituitarism treated for four months with hGH alone. All patients had previously normal responses to orally administered metyrapone. There was no demonstrable difference in the F responses to insulin hypoglycemia before and four months following its discontinuation in the patients receiving hGH alone. In the ten patients on combined therapy the F response to insulin hypoglycemia was normal in five and subnormal in five patients. These ten patients were retested at least two months after cessation of CPH therapy. The F response reverted to normal in four of the five patients in whom it had been subnormal. There was no significant change in the five patients with initial normal response. No patients had signs or symptoms of glucocorticoid insufficiency. In some cases, long-term administration of CPH to children with hypopituitarism is associated with decreased F response to insulin hypoglycemia; this may represent decreased adrenocortical reserve in these patients. The previously reported enhancement of growth of hypopituitary children treated with hGH and CPH may in part be a result of decreased F production.


Pediatric home care: an ambulatory "special care unit". A pediatric home care program is described which has operated as an ambulatory special care unit in an urban hospital center since 1970. The program provides care for seriously or chronically ill children, who would not be adequately served through traditional ambulatory services because of either the severity and complexity of their medical problems or the inability of their families to use such services. An interdisciplinary PHC team provides comprehensive pediatric care and integrates medical and psychosocial services for the child and family. This form of special ambulatory care appears to offer advantages to patients who are at risk in existing ambulatory schemes and is an alternative to inpatient care.


Sickle cell syndromes. II. The sickle cell anemia-alpha-thalassemia syndrome. Five American black patients, ages 1 to 16 years, with the sickle cell anemia-alpha-thalassemia syndrome are described. Each patient had persistent microcytosis not explained by iron deficiency, and in each family the presence of alpha-thalassemia in combination with sickle cell trait was demonstrated in one of the parents. In one patient, in whom the diagnosis of sickle cell anemia was established at birth, an elevated level of Barts (gamma4) hemoglobin was also found. In these patients levels of alkali-resistant hemoglobin and reticulocyte counts were similar to those of sickle cell anemia patients of comparable age; however, stained smears of their peripheral blood rarely showed the presence of irreversibly sickled cells. No major ameliorative effect of the alpha-thalassemia on the clinical expression of the sickle cell disease of these patients was evident.


Excretion of iron in response to deferoxamine in sickle cell anemia. Iron chelation with deferoxamine was studied in ten patients with sickle cell anemia who had received 2 to 37 liters of red blood cells. Urinary excretion of iron in response to 1.5 gm of deferoxamine administered intravenously ranged from 5.9 to 28.7 mg/24 hours and was closely related to the amount of iron acquired from transfusions. Administration of ascorbic acid did not improve deferoxamine-induced excretion of iron. Urinary excretion of iron in response to 0.75 gm of DFO intramuscularly was 4.7 to 6.9 mg/24 hours in three patients who had received 15 to 37 liters of red cells. The data  indicate that measurement of DFO-induced excretion of iron is of value in detecting increased iron stores in children with sickle cell anemia who have received repeated transfusions and that chelation therapy will retard the accumulation of iron.


Intestinal surface area in infants with acquired monosaccharide intolerance. Acquired monosaccharide intolerance is characterized by the malabsorption of all carbohydrates, resulting in profuse acidic diarrhea. Five infants with this syndrome, ranging from two to six months of age, were studied by measuring their ability to absorb glucose given by intestinal perfusion. Jejunal biopsies obtained at the time of perfusion were studied by light and electron microscopy, and surface area measurements were obtained. Glucose absorption and surface area were significantly decreased (P less than 0.005) during the acute phase of the disease and improved during convalescence. A linear correlation (r = 0.8757) was observed between the ability to absorb glucose and intestinal surface area. It is concluded that the loss of absorptive surface is a major cause of the reduced carbohydrate absorption and consequent diarrhea.


Intestinal function in infants with severe congenital heart disease. We evaluated digestive tract function in 21 young infants with severe congenital heart disease. One group had congestive heart failure and ventricular septal defect or single ventricle; the other had cyanosis and transposition of the great arteries. Enteric protein loss was excessive in eight patients, and steatorrhea was found in five. These abnormalities were mild and not related to the type or severity of the cardiac lesion. Available evidence points to a need of these babies for calories in excess of normal requirements for weight. The present study suggests that in designing dietary regimens for these very sick patients, their potential for defective gastrointestinal function must be considered. Because no consistent pattern of abnormalities in apparent, each patient who fails to thrive may deserve gastroenterologic evaluation.


Iron burden in sickle cell anemia.

Iron burden in sickle cell anemia. Total body iron burden was estimated by two indirect methods in 23 patients with sickle cell anemia. Concentrations of serum ferritin correlated directly and significantly with age of the patients. Eleven of 15 patients under 20 years of age had normal levels of serum ferritin. Deferoxamine-induced urinary excretion of iron was considerably less than that reported in patients with thalassemia major who were receiving regular blood transfusions. These data imply that patients with sickle cell anemia generally do not acquire excessive iron burdens during the first two decades of life. The risks of transfusional hemosiderosis in patients with sickle cell anemia who are included in hypertransfusion programs are discussed.


Plasma amino acid concentrations in newborn infants breast-fed ad libitum. Plasma amino acid concentrations were measured in peripheral venous blood of 40 newborn infants breast-fed ad libitum. When these data are compared with amino acid concentrations of umbilical cord artery plasma, only lysine and threonine show a striking decrease after birth: the concentrations of hydroxyproline, asparagine, glutamine, proline, cystine, leucine, tyrosine, and ornithine significantly increase during the first days of life. The high-protein concentration of colostrum and transitional milk may explain this observation.


Olfactory reflexes in the newborn infant. Clinical responses to peppermint odor were observed in 100 healthy term and preterm infants during active sleep on two successive days. Thirty-six asphyxiated term infants and three infants with holoprosencephaly also were tested. Olfactory reflexes were regularly elicited in normal infants after 32 weeks' gestation, but some premature infants as young as 28 weeks also responded. Responses included initiation of sucking and arousal-withdrawal. Habituation occurred after two or three trials. A Moro response was seen only in a few asphyxiated infants; loss of olfactory reflexes appeared to parallel suppression of brainstem reflexes. Olfactory reflexes are useful in excluding cerebral malformations associated with agenesis of the olfactory bulbs.


Intermediate phototherapy in the treatment of jaundice in the premature infant. A controlled trial of the use of intermittent phototherapy for the treatment of hyperbilirubinemia in newborn infants is reported. Periods of illumination of (1) 15 minutes light on, 15 minutes light off, (2) 15 minutes on, 30 minutes off, and (3) 15 minutes on, 60 minutes off are as effective as is continuous illumunation. A comparison with previous trials of intermittent phototherapy is made and differences in results are explained using as a model the action of light on bilirubin.


Iron chelation therapy with deferoxamine in Cooley anemia. The iron-chelating agent, deferoxamine, was studied in 16 patients with thalassemia major. Urinary excretion of iron in response to 0.75 gm of deferoxamine, intramuscularly, ranged from 2.2 to 44.8 mg Fe/24 hours. In response to a subcutaneous infusion of 1.5 gm deferoxamine for 18 hours, iron excretion increased by an average of 240%. The intravenous infusion of large doses of deferoxamine for 18 hours resulted in the highest rate of iron excretion, as much as 447.5 mg Fe/24 hours in response to 16 gm of deferoxamine. Administration of vitamin C increased chelation-induced excretion of iron in most patients more than five years of age. Preliminary evidence suggests that further iron accumulation can be prevented and excessive iron stores can be depleted by the intramuscular, subcutaneous, or intravenous administration of deferoxamine.


Determination of newborn special care bed requirements by application of queuing theory to 1975-1976 morbidity experience. The movement of newborn infants from the delivery room of a level III perinatal center to nursing units that provided different levels of care was prospectively documented for 1975 and 1976. These data were employed in a computer modeling experiment based on sequential queuing theory to determine the relationships between numbers of available intermediate and maximum care nursery beds, the probability that a given newborn arrival could not be accommodated, and the occupancy rates for each level of care. The nursery bed requirements for the level III center were used to estimate the number of special care beds needed by the regional Health Service Area.


Fasting and postprandial serum gastrin in normal human neonates. Serum gastrin determinations were performed in 32 normal-term infants to determine the level of this hormone in normal infants at birth and its response to normal feeding. Significant differences were noted between newborn cord blood and maternal blood at birth. Further significant elevations in fasting serum gastrins were noted in these infants over the first 72 hr of life. Pre- and postprandial determinations with normal feeding failed to demonstrate a significant elevation in serum gastrin levels following ingestion of protein-containing formulas. These data suggest a relative insensitivity of the release of gastrin from the gastric antrum in response to protein, a powerful mediator of gastrin release in the adult.


Electron microscopic observations in infantile hypertrophic pyloric stenosis (IHPS). Electron microscopic observations of the pyloric parasympathetic ganglia in IHPS have demonstrated, contrary to previous reports, that no abnormalities exist in the neurons and interstitial cells of the plexuses or the cells of the pyloric smooth muscles. The significance of finding a small number of altered large axons is unclear. In view of finding essentially normal morphology, a "functional" etiology of this disease is suggested.


Massive adrenal hemorrhage in neonatal neuroblastoma. In a neonate with exsanguinating intraperitoneal bleeding admitted with a provisional diagnosis of ruptured liver due to birth trauma, laparotomy revealed the source of hemorrhage to be an adrenal neuroblastoma. This case prompted a review of cases of abdominal neuroblastoma admitted to the Neonatal Surgical Unit in Alder Hey Children's Hospital from 1953 to 1976. The features of 10 cases are presented: in three of them there was hemorrhage into the tumor. Of the 10 cases, six survived tumor free from 2 to 12 yr and there is one short-term survivor. The purpose of this presentation is to emphasize the possibility of an underlying neuroblastoma in cases of neonatal adrenal hemorrhage and also the relatively good prognosis in neuroblastoma presenting in the neonatal period.


Functional and metabolic evaluation of colon replacement of the esophagus in children. Thirteen children with esophageal replacement with colon interposition have been followed at the University of Florida Medical Center between 1962 and 1976. Eight of these patients were evaluated with a detailed functional and metabolic protocol, four requiring colon interposition for esophageal atresia and four for esophageal strictures. Growth was noted to be somewhat delayed in the patients with esophageal atresia, especially those with associated congenital anomalies. Otherwise, excellent functional results were obtained. Significant anemia with depressed serum iron concentrations was noted in four patients, and three patients had abnormal vitamin B12 absorption. This abnormality correlated with length of terminal ileum employed with the interposed segment. Serum parameters of intestinal absorption were normal in each patient. Manometric evaluation revealed absence of peristalsis within the colonic segment, but progressive peristalsis within interposed ileal segments. Radiologic evaluation demonstrated delay in passage of thick material from mouth to stomach and wide variability in overall intestinal transit time.


Congenital vas deferens--ureteral connection. Congenital drainage of the vas deferens into a ureter permits retrograde passage of urine through the vas to the epididymis. If this anomaly is accompanied by urinary tract pathology with vesicoureteral reflux, hydroureter, stasis, and infection, the passage of urine into the vas can very well lead to epididymitis of a chronic or recurring nature and secondary scrotal abscesses. Two cases of this rare anomalous connection are presented in which such scrotal infections occurred. The diagnosis should be suspected on clinical grounds and can be confirmed by cystograms in which the dye refluxes up the ureter and passes into the vas. The association of rectal anomalies is of embryologic significance and may be additionally important clinically by further suggesting the possibility of the ureteral-vas anomaly.


Experimental investigations into the etiology of cholangitis following operation for biliary atresia. Experimental operations carried out on young minipigs appear to show that cholangitis does not occur after simple ligation of the bile duct, but develops nearly invariably is the lymphatic drainage from the liver is also interrupted. The so-called "ascending" cholangitis observed after hepato-porto-entero anastomosis is probably not ascending at all, but blood-borne. When a hepatic portoenterostomy is carried out for biliary atresia, trauma to the lymphatics in the porta hepatis should be avoided and an additional omento-hepato-portopexy should be done. Recent clinical experience appears to confirm this hypothesis.


Histologic studies of rectocolic aganglionosis and allied diseases. It is well-known that some patients exhibiting the symptoms of Hirschsprung's disease are shown to have intramural ganglia in the distal myenteric plexus. Some of them have been described as "pseudo-Hirschsprung's disease". It is likely that a variety of conditions have been included in this group. Using a silver impregnation technique we have made a detailed histologic study of the rectum and large bowel in a number of cases with provisional clinical diagnosis of Hirschsprung's disease but in which rectal biopsy showed small ganglia in Meissner's plexus demonstrated by acetylcholinesterase (Ach-E) staining. Three histologic variations were shown that may be called hypoganglionosis, immaturity of ganglia, and hypogenesis. An attempt is made to relate their clinical picture to the histologic findings.


A new treatment of anal incontinence in children: free autogenous muscle transplantation. A new method is presented for the treatment of anal incontinence in children, including free autogenous muscle transplantation. The primary step is denervation of a skeletal muscle, which 2 wk later is transplanted and placed as a U-sling around the rectum, imitating the position and function of the puborectalis muscle. The transplant is placed in close contact with innervated muscles, which act as reinnervation sources. The results in five consecutive patients are highly promising. An early sign of improvement is the occurrence of a sensation of rectal fullness. All the patients reached an acceptable degree of continence, including abandonment of the use of napkins, 4-12 mo after surgery.


Rorschach protocols for three diagnostic categories of adult offenders: normative data. Rorschach norms were developed for an adult offender population. The 172 subjects were divided into four diagnostic categories: nonpsychotic/nonorganic, organic/nonpsychotic, psychotic/nonorganic, and psychotic/organic. Rorschach norms were developed for three of these categories. Major differences among these diagnostic categories and between Beck's adult normative population and the nonpsychotic/nonorganic category are discussed.


Family relations as perceived by emotionally disturbed and normal boys. The perception of feelings within the family of 9-13-year-old boys were studied. The purpose was to determine the sensitivity of the Family Relations Test (FRT) in discriminating between inpatients, outpatients, and normal controls. Both patient groups more frequently identified family members as sources of negative feelings than normal controls. Inpatients expressed more self-flattery and self-criticism and an absence of a reciprocal, positive relationship with their fathers. The FRT is only able to make a few quantitative differentiations between a clinical and a normal sample of boys but certain qualitative aspects of the responses were particularly noteworthy.


Personality differences between intrinsically religious and nonreligious students: a factor analytic study. By means of Allport's Religious Orientation Inventory (ROI) 145 students were classified as intrinsically religious and 133 as nonreligious. Personality differences between the two groups were explored on the basis of their scores on EPPS, the CPI, and 16 PF Questionnaire. Factor analysis of the combined 49 subscales of these three instruments produced eight factors: Achievement Potential, Self-Control, Social Ascendency, Affiliation, Personal and Social Adequacy, Egocentric Sexuality, Restlessness, and Stereotyped Femininity. Analyses of variance of the factor scores of the two groups of subjects showed significant differences on five of the eight factors, accounting for a total of 25% of the total variance. The intrinsically religious scored significantly higher on Self-Control, Personal and Social Adequacy, and Stereotyped Femininity; the nonreligious scored higher on Egocentric Sexuality and Restlessness. These results were discussed in relation to some of Allport's ideas on religion as a dimension of personality.


Intravenous self-administration of drugs in rats. A standardized self-administration procedure in rats was used to determine the intravenous self-administration liability of graded doses of various drugs. Self-administration was reliably established with the tested addictive drugs (morphine, heroin, fentanyl and d-amphetamine), but not with the nonaddictive drugs (chlorpromazine and nalorphine). However, 1 out of 14 animals on nalorphine clearly demonstrated self-administering behavior. Self-administration was observed with delta1-tetrahydrocannabinol, but the percentage of animals (40% on the highest dose) that initiated this behavior and the amount of drug intake were low in comparison with amphetamine and narcotics. Concerning the narcotic drugs, approximate ED50 values for self-administration under the described conditions were calculated (morphine: 0.65; heroin: 0.05; fentanyl: 0.0025 mg/kg/injection). Total daily drug intake was related to the unit dose delivered per injection in that a higher drug dosage led to more drug intake. In experiments with heroin, this relationship was not caused by prior forced injections. The approximate ED50 value for amphetamine appeared to be 0.145 mg/kg/injection. Narcotic drug administration resulted in a disturbance of the patterns of food and water intake. Shortly after drug administration food intake was stimulated, followed by an increased consumption of water. The patterns of food and water intake remained disturbed in animals showing self-injecting behavior. With amphetamine both the quantity of food and the frequency of eating were reduced. These effects were observed only temporarily in animals tested without prior forced injections. The present results indicate that measuring the reinforcing efficacy of drugs under strictly defined experimental conditions provides quantitative criteria for intravenous self-administration of drugs in rats.


Antiarrhythmic, metabolic and hemodynamic effects of Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) after coronary flow reduction in pigs. The antiarrhythmic activity of the aminosteroid Org 6001 was investigated in young pigs (20-28 kg). Ventricular arrhythmias were induced by restriction of the flow in the left anterior descending coronary artery (LAD) to 25% of its control value during a period of 30 minutes. Nine out of 30 control animals died in this period due to ventricular fibrillation. None of the 19 animals treated with Org 6001 (5-10 mg/kg) or the 12 animals treated with lidocaine (2.75-3.50 mg/kg) fibrillated. Moreover, the number of premature ventricular beats was greatly reduced in pretreated groups compared with the untreated group (P less than .001). The first derivative of left ventricular pressure decreased with 25% (P less than 0.001) after administration of Org 6001. However, during 30 minutes of LAD flow reduction to 25% of control, the adverse effects of Org 6001 were less than those of lidocaine. Myocardial lactate production indicated some delay in onset of ischemia. However, there was no indication that this beneficial effect was long-lasting. When after 30 minutes of LAD flow reduction to 25% of control, the LAD was completely occluded between its second and third branch, all untreated animals fibrillated within 120 minutes, whereas 4 of the 19 animals treated with Org 6001 and 3 of the 12 treated with lidocaine survived. It is concluded that Org 6001 has antiarrhythmic properties in the ischemic pig heart which compare favorably with those of lidocaine.


Effects of some coronary vasodilator drugs on collateral hemodynamics after chronic myocardial ischemia in the anesthetized dog: appropriate or inappropriate redistribution? These effects of dipyridamole, carbochromen, pentaerythritol tetranitrate (PETN), papaverine and ethaverine on collateral hemodynamics were investigated in anesthetized dogs 5 weeks after experimental coronary occlusion. The retrograde pressure, flow and resistance (RP, RF and RR) and the pressure, flow and resistance of the nonoccluded artery (CP, CF and CR) were measured; the pressure, flow and resistance ratios, i.e., the circulatory relationships which appeared between areas localized on both sides of the well-developed collateral channels, were calculated. Dipyridamole and carbochromen provoked an inappropriate and long-lasting redistribution to the detriment of ischemic areas: RF and RP decreased, whereas CF increased; RP/CP and RF/CF decreased; RR/CR increased. PETN provoked a redistribution in favor of ischemic areas: RF increased and RR decreased; RP/CP and RF/CF increased; RR/CR decreased. These main effects of PETN appeared after a first short period during which the changes in normal and ischemic areas were almost identical. Like PETN, papaverine and ethaverine provoked an appropriate redistribution during a second period. These results are discussed in terms of the selectivity of coronary dilator action on large or small vessels. The methodology used appears to be adequate to evaluate the activities of various drugs on a well-developed collateral coronary circulation.


Renal gluconeogenesis in clofibrate-treated rats. Clofibrate was administered in the diet (0.3% w/w) for varying periods of time to normal rats. Rats were killed by decapitation and several biochemical measurements were made. Clofibrate lowered serum levels of cholesterol and triglyceride and produced a kidney hypertrophy; these effects were maximal after 3 days of feeding and persisted for 21 days. Serum clofibric acid levels were highest on the 3rd day and decreased to maintenance levels by the 7th day. Clofibrate markedly increased the activities of glucose 6-phosphatase, pyruvate carboxylase and phosphoenolpyruvate carboxykinase in kidney cortex and the synthesis of glucose from glutamate, lactate, pyruvate, glycerol and malate by kidney cortex slices. Clofibrate treatment did not affect blood pH or bicarbonate levels. It is concluded that clofibrate enhances renal gluconeogenesis in the rat and that the effect is not caused by altering acid-base balance.


Ascorbic acid and cytochrome P-450.

Ascorbic acid and cytochrome P-450. Liver microsomal cytochrome P-450 is significantly reduced in ascorbic acid-deficient guinea pigs and studies are presented on the biochemical basis for this effect. The activities of the key enzymes involved in heme synthesis, delta-aminolevulinic acid (ALA) synthetase. ALA dehydratase and ferrochelatase, were not significantly reduced in livers from ascorbic acid-deficient animals. In addition, there was no significant difference in the amount of "mitochondrial heme" in normal and ascorbic acid-deficient livers. However, ascorbic acid deficiency did affect induction with diethyl-1,4-dihydro-2,4,6-trimethylpyridine-3,5-dicarboxylate; a 6-fold increase in ALA synthetase activity occurred in liver homogenates prepared from normal animals in contrast to no significant increase in homogenates prepared from ascorbic acid-deficient animals. Multiple forms of cytochrome P-450 exist in guinea-pig microsomes as has been demonstrated in microsomes from other species. Separation of 44,000 to 60,000 dalton polypeptides (molecular weight region for the various forms of cytochrome P-450) by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate revealed quantitative differences in the polypeptides from normal and ascorbic acid-deficient microsomes. Ascorbic acid-deficient microsomes consistently demonstrated reductions in three polypeptide bands (molecular weight 44,000, 52,000 and 57,000) and increases in two polypeptide bands (54,000 and 55,000) compared with normal microsomes. Evidence that these polypeptides are cytochrome P-450 was obtained from heme staining with tetramethylbenzidine and from induction studies with phenobarbital and 3-methylcholanthrene. The results indicate that ascorbic acid deficiency does not affect the availability of heme for cytochrome P-450 synthesis and the effect of ascorbic acid may be on the apoprotein moiety of cytochrome P-450.


Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. The mechanism for trichloroethylene hepatotoxicity was investigated in male Sprague-Dawley rats. Phenobarbital pretreatment increased and CoCl2 pretreatment decreased trichloroethylene hepatotoxicity. After administration of 1(14)C]trichloroethylene, a radioactive material became irreversibly bound to hepatic proteins, while negligible amounts were bound to muscle proteins. When 1(14)C]trichloroethylene was incubated under air with hepatic microsomes and a NADPH-generating system, a radioactive material became irreversibly bound to microsomal proteins; binding was negligible when the NADPH-generating system was omitted; binding was inhibited by carbon monoxide and by piperonyl butoxide; the amount of bound material was greater with microsomes from phenobarbital-pretreated rats and lower with microsomes from CoCl2-pretreated rats than with microsomes from nonpretreated rats. Trichloroethylene administration decreased hepatic glutathione in normal rats but not in piperonyl butoxide-pretreated rats; in vitro, glutathione decreased the amount of trichloroethylene material that bound to microsomal proteins. The reported results are consistent with the view that 1) trichloroethylene is metabolized by cytochrome P-450 into a chemically reactive metabolite which reacts with, and binds to, either proteins or glutathione, 2) binding to proteins produces liver lesions and 3) binding to glutathione decreases the amount of reactive metabolite available for binding to proteins.