The multiplication of an influenza C virus in an established line of canine kidney (MDCK) cells. JJ/50 and four other strains of influenza C virus grew in an established line of canine kidney (MDCK) cells. Multicycle virus growth was markedly enhanced by the addition of trypsin to the culture medium and these viruses could be passaged serially in this system. The addition of appropriate concentrations of trypsin to the agar overlay medium enabled plaquing of influenza C/JJ/50 virus. Titration by plaque assay on MDCK cells was more sensitive than that by intra-amniotic inoculation of fertile hens' eggs.


Presence of genomic polyadenylate and absence of detectable virion transcriptase in human coronavirus OC-43. Human coronavirus RNA, prepared by extraction of purified virions with phenol-chloroform, consists of a major 15 to 55S class and a minor 4S class of RNA fragments. Polyadenylic acid [poly (A)] sequences are present in 15 to 55S but not in 4S RNA, suggesting different functions for each class. A stretch of poly (A) of approximately 19 adenosine monophosphate residues was obtained in sizing experiments after digesting OC-43 RNA with pancreatic and T1 ribonucleases. An OC-43 virion RNA transcriptase could not be detected with systems optimal for detecting the transcriptases of influenza and Newcastle disease virus.


New type B retrovirus isolates associated with kinetochores and centrioles of the host cell. Two new virus isolates, M432 and M832, obtained from the Southeast Asian mouse have been characterized morphologically with respect to their composition and intracellular assembly. The mature virions resemble in certain respects the type B murine retroviruses. The new isolates, however, have an intracellular precursor, a type A particle, closely associated with the mitotic apparatus. The intracellular transport of the type A particles to the cell surface, where they are released by budding, is closely associated with the microtubule system of the cell.


The development of Colorado tick fever virus within cells of the haemopoietic system. Electron microscopic examination of haemopoietic liver tissue from mice infected in utero or when newborn showed inclusions of Colorado tick fever virus within erythroblasts, reticulocytes and erythrocytes. Inclusions were also seen within erythroblastoid cells undergoing mitosis. Other evidence of virus replication within erythropoietic cells was the presence of intracytoplasmic and intranuclear fibres, which have been shown to be associated with Colorado tick fever virus replication. The findings reported here support the hypothesis that virus replication within infected erythropoietic cells occurs concurrently with differentiation of the infected cell, resulting in the presence of virions within erythrocytes.


Justifying inpatient admissions at a community mental health center. A model for screening and reviewing inpatient psychiatric admissions at a community mental health center is presented in which the process, including the use of both a diagnostic criteria set and a functional criteria scale, is described. Results of a time-limited experimental program indicated that the diagnostic criteria set could be applied in approximately three fourths of the admissions, while the scale of function could be utilized in all cases. Also, a statistically high rate of concordance was found both when the two methods were used by the same evaluator, and when two independent evaluators were employing the same method. At the conclusion of the final review, 6 of 273 admissions or 2.2 per cent were unjustified. The pilot program demonstrated that 90 per cent of the admissions could be screened adequately by nonphysicians. The average time expended by in-house staff including screeners, reviewers, and supportive staff was estimated to be 58.4 minutes per admission with an average direct cost per case of $6.68. Had the review been performed by physicians in local practice, the average cost per case was estimated to be $8.93. The six unjustified admissions represented an average reviewing cost of about $240 per case.


Family history as a diagnostic aid in two samples of adolescents. Psychiatric diagnostic patterns were examined in two different samples of adolescents, one a group of psychiatric inpatients and the second youth apprehended by the law for alcohol-related difficulties. Affective disorder in parents was most closely correlated with a similar patient diagnosis or constellation of depressive-type symptoms in both samples of youth. Parental antisocial personalities, alcohol abuse, or drug problems correlated most closely with high levels of similar difficulties in individuals in the two studied groups. However, antisocial, alcohol, or drug problems of a mild degree were present in all subgroups of the two samples, perhaps representing a nonspecific reaction to parental illness or the occurrence of a broken home. A follow-up of future problems in both samples will be carried out to determine the importance of the family history and clinical picture in predicting the future course of problems.


Psychological correlates of monoamine oxidase activity in normals. This study replicates and extends earlier work by finding that low levels of platelet monoamine oxidase (MAO) activity correlate with sensation seeking, high ego strength, positive affect, and high leisure time activity levels, somewhat similar psychological correlates also being found for plasma amine oxidase activity. Although there are several ways in which a schizophrenia/MAO relationship may exist and still be congruent with the present data, these results pose difficulties for theories which link low MAO activity levels specifically to schizophrenia. Nothing in the present findings, however, is incongruent with the possibility of an association between low platelet MAO activity and bipolar affective disorder.


Implications for concepts of psychopathology of studies of economic principles in behavior therapy programs. In several studies of token economies, it has been observed repeatedly that chronic psychiatric patients conform to the same economic principles as explain the activities of presumably normal participants in the national consumer economy. Such observations are consistent with behavior therapy's assumptions that those labeled mentally ill follow the same psychological and social lows as those considered normal and that behavior is responsive to specific situational determinants. Although they disprove nothing, these observations may pose problems for more traditional approaches which view psychopathology as the result of central disorders or deficits with diffuse effects across a wide range of ordinary life situations.


A comparison of four scales that assess premorbid competence. Premorbid competence has come to be considered an important dimension in predicting outcome in schizophrenia. From the growing number of social adjustment scales, this study focused on the four instruments that are currently used to assess premorbid competence specifically. The usefulness of these instruments was compared using the degree of inter-rater reliability and scale intercorrelation. Although the concept of premorbid adjustment appears increasingly complex, consisting of stages of adjustment and different levels for a single patient, at present the Phillips Scale has the best relative accuracy and clinical applicability.


Single case study. A novel psychiatric adjunct to cancer therapy. Confronted with the hazards of a patient unable to cooperate predictably with a 3-day radium implantation procedure as a part of cancer therapy, the authors describe in a case report their solution to an unusual clinical dilemma. The patient displayed adverse responses to psychotropics and nursing care was markedly restricted by radiation exposure limits. Behavioral management of the patient through the interval of radium therapy was successfully effected by the use of closed-circuit television monitoring combined with brief nursing interventions. This novel psychiatric adjunct to cancer therapy averted the threat posed by displacement of the radium implants.


Single case study. Possible organophosphate-induced parkinsonism. A case of possible organophosphate-induced parkinsonism is presented. The patient was a crop duster with numerous episodes of acute organophosphate intoxication and chronic organophosphate exposure. The etiology of parkinsonism is discussed in terms of a balance hypothesis between cholinergic and dopaminergic neurotransmission in the striatum. A possible relationship between chronic organophosphate exposure and alterations in central cholinergic or dopaminergic activity is suggested. The course of this patient raises the possibility that agricultural workers may be at risk for the late development of parkinsonism.


Effect of lergotrile on 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain. Lergotrile, a dopamine agonist, lowered whole brain DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rats. At low doses down to 0.5 mg/kg of lergotrile mesylate, this effect occurred within 30 min, whereas at higher doses (20 mg/kg) the decline in DOPAC was delayed. The decrease in DOPAC persisted for several hours and presumably resulted from a compensatory decrease in brain dopamine turnover secondary to receptor stimulation by lergotrile. Other indications of decreased brain dopamine turnover after lergotrile included (a) a slower decline in dopamine concentration after synthesis inhibition by alpha-methyltyrosine, (b) a slower decline in alpha-methyl-m-tyramine, a false transmitter that is stored and released by dopamine neurons, and (c) a decreased accumulation of dopamine in response to gamma-butyrolactone, an agent that blocks firing and dopamine release by dopamine neurons. Lergotrile mesylate (20 mg/kg) also increased brain levels of 5-hydroxyindoleacetic acid and of 3-methoxy-4-hydroxyphenylethylene glycol sulfate, metabolites of serotonin and norepinephrine, respectively, and these increases were not antagonized by spiperone, a dopamine receptor antagonist.


Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. Each of six kynurenines tested (DL-kynurenine, quinolinic, 3-hydroxy-anthranilic, xanthurenic, picolinic, and nicotinic acids) injected into brain ventricles in mice in doses of 25--60 mcg produced motor excitement and/or clonic convulsions. Anthranilic acid did not produce these effects. The strongest metabolite was quinolinic acid, which was active in a dose of 1 mcg. It was also the only compound which produced motor excitement and convulsions after intraperitoneal injection (in doses of 400--600 mg/kg, i.e. 10,000--15,000 mcg per mouse). The hypothermic effect of intraventricularly-injected kynurenines was roughly similar to that of intraperitoneally-injected material at 100--1000 times higher doses. These data suggest poor penetration of kynurenines formed in the liver into the brain, and the possible involvement of these metabolites of tryptophan (particularly if they are formed inside the brain) in the mechanism of seizures.


Adrenocorticoids control 5-hydroxytryptamine metabolism in rat brain. The influence of surgical adrenalectomy was examined on the biosynthetic capacity for 5-hydroxytryptamine of rat brain. The results demonstrate that adrenalectomy decreased tryptophan hydroxylase activity and its substrate tryptophan in the brain stem. A parallel change in the concentration of 5-hydroxytryptamine was seen in brain stem and striatal region of adrenalectomized rats. In contrast, the level of 5-hydroxyindoleacetic acid was significantly elevated in both of these brain regions. Replacement therapy with corticosterone (10 mg/kg i.p.) produced time-dependent increases in tryptophan, tryptophan hydroxylase and 5-hydroxytryptamine and decreases in 5-hydroxyindoleacetic acid levels. Alterations in these neurochemical parameters were more conspicuous in adrenalectomized rats receiving corticosterone for 7 days as compared to those given only for 3 days. Our data demonstrate that adrenocortical hormones regulate brain 5-hydroxytryptamine synthesis probably by enhancing both the levels of tryptophan and the activity of rate-limiting enzyme tryptophan hydroxylase. It is postulated that emotional instability seen during altered adrenocortical function might partly be associated with abnormal metabolism of central 5-hydroxytryptamine.


The synaptic significance of metoclopramide induced dyskinetic-dystonic head and neck movements in pregnancy. Two young, pregnant women presenting dyskinetic-dystonic crises limited to head and neck (HNDD) due to metoclopramide (MP) were observed. Evidence has been brought for the specific extrapyramidal effect of dyskinetic-dystonic head and neck movements induced by MP in young females. The synaptic action of MP differs from that of the generally accepted dopamine receptor blocking neuroleptics such as the phenothiazines. Concomittant quasi opposing neuroleptic and nonneuroleptic like effects of this drug can not support the mechanism of dopamine receptor blockade as the explanation of the synaptic effect. The concept of "dopamine receptor imbalance" may explain the synaptic action of the metoclopramide.


Ultrastructural changes in the anterior horn synapses of rat spinal cord under different locomotor conditions. Ultrastructural changes in axodendritic synapses of the spinal cord ventral horn are studied in rats subjected to different locomotor conditions: immobilization, control and physical loading. Enhanced motor activity results in a reduction of the number of synaptic vesicles in the axon terminal, as well as flattening and diminution of their size. Other changes correlated with the different motor regimes are likewise established in the number of terminal ending's mitochondria, in "active zones", in subjunctional dense bodies, and in the bouton area. Data are treated by means of variation analysis. The significance of differences is established by "T"-criterion.


Outcome following severe head injuries in children. The outcome in 53 children following severe head injury is presented. All children were graded using the Glasgow Coma Scale; 90% made a good recovery or were moderately disabled, and 8% died or were left vegetative. All patients were treated with controlled ventilation and steroids; mannitol, and, if necessary, Nembutal (pentobarbital) were used to maintain the intracranial pressure below 20 torr. With this regimen, only one death occurred due to uncontrollable intracranial hypertension. All patients with a coma scale of 5 or greater recovered well. The worst prognostic sign was the presence of flaccidity: 33% of these patients died or were vegetative. Five of seven patients who were decerebrate or flaccid with bilateral fixed pupils and absent caloric responses made a good recovery or were moderately disabled. The relatively low incidence of mass lesions (23%) and high incidence of diffuse cerebral swelling (34%) suggest a different pathophysiological response of the child's brain to injury, which may play a role in the improved survival of children following severe head injury when compared to adults.


Autoregulation and CO2 responses of cerebral blood flow in patients with acute severe head injury. Regional cerebral blood flow (rCBF), cerebral intraventricular pressure (IVP), systemic arterial blood pressure, and cerebral ventricular fluid (CSF) lactate and pH were studied repeatedly in 23 patients during the acute phase of severe brain injury lasting from 3 to 21 days after the trauma. Cerebrovascular autoregulation was tested repeatedly by means of angiotensin infusion in 21 of the patients, and CO2 response in 14 by means of passive hyperventilation. The pressure in the brain ventricles was measured continuously in all patients and kept below 45 mm Hg during the study. If the IVP increased more than 10 mm Hg during the angiotensin infusion (as in one case), the autoregulation test was considered contraindicated and the angiotensin infusion was discontinued. Dissociation between cerebrovascular autoregulation and CO2 response was a common phenomenon. Typically, autoregulation appeared preserved in the most severely injured areas of the cerebral cortex when the patient was deeply comatose, but deteriorated concomitantly with recovery; by the time the patient became alert, the autoregulation was always impaired. The CO2 response was impaired only in patients who were deeply comatose and had attacks of decerebrate rigidity; during recovery the CO2 response became normal. Thus, preserved autoregulation associated with imparied CO2 response indicated very severe brain damage, whereas impaired autoregulation associated with preserved CO2 response suggested moderate or severe brain damage in recovery. These paradoxical observations raise the question whether the preserved autoregulation seen in severely injured brain tissue is a true autoregulation caused by an active vasoconstrictor response to an increase in blood pressure.


The value of repeat pan-angiography in cases of unexplained subarachnoid hemorrhage. Four-vessel angiography was repeated in 56 patients with confirmed subarachnoid hemorrhage in whom the initial investigation was negative. Only one aneurysm was demonstrated. The results suggested that, with good technique, careful observation, and a complete four-vessel cerebral angiography, a false negative rate of less than 2% can be achieved. It is suggested that to repeat pan-angiography is seldom justified unless further bleeding episodes occur.


Detachable balloon catheter. Its application in experimental arteriovenous fistulae. Recent Russian reports have described the use of balloon occlusion in both the diagnosis and treatment of various pathological processes affecting intracranial vessels. This intraluminal approach has demonstrated successful results in vascular problems such as carotid-cavernous fistulae, arteriovenous malformations, and large inoperable aneurysms. Despite widespread interest in the neurosurgical community, the application of a similar technique in the Western hemisphere has been hindered by lack of an adequate, functional, inflatable apparatus. The authors describe their experience with the prototype of a safe, reliable, detachable balloon. Because of a unique development, the apparatus may be filled with liquid and detached from its parent catheter without subsequent leakage. In order to satisfy variable requirements, balloons are available in several sizes ranging from 0.5 to 4.0 mm in diameter. When fully inflated these devices will hold from 1 to 3 cc of fluid. The authors' study involved 18 dogs with artificially created carotid-jugular fistulae that were visualized by angiography. Under fluoroscopic control, detachment of inflated balloons on the venous side of the defect not only successfully occluded the fistulae but also preserved the arterial vasculature. X-ray films taken several weeks later failed to show any change either in size or position of the inflated devices.


Effects of ethanol- and saline-base PGE1 on the canine cerebral circulation. The effects of ethanol- and saline-base prostaglandin E1 (PGE1) on systemic arterial blood pressure ((ABP), cerebral blood flow (CBF), cerebral vascular resistance (CVR), and cerebrospinal fluid (CSF) pressure were determined in anesthetized dogs. Progressively greater carotid intra-arterial infusions of ethanol-base PGE1 moderately decreased systemic ABP and CVR while perfusion of the CSF system with PGE1 moderately increased ABP and CVR; CBF was unaffected by either route of administration and CSF pressure was constant except for a slight decrease at the lowest intraventricular perfusion rate. Similar infusions of PGE1 were administered in saline base solutions in another group of dogs. Carotid intra-arterial infusion decreased ABP and CBF moderately at the highest infusion rate and caused a transient increase in CSF pressure. Cerebrospinal fluid system perfusion increased ABP moderately but did not affect the other parameters. These data indicate that PGE1 does not have a significant effect on cerebral hemodynamics when infused via the CSF system, but may produce slight cerebral vasodilation when infused into the carotid arteries in an ethanol base. This vasodilation may be due to autoregulation.


Primitive neuroectodermal tumors of the central nervous system in children. A series of 18 primitive neuroectodermal tumors in children (15 cerebral and three spinal) is reported. These are highly malignant neoplasms, both histologically and clinically. They are rapidly growing tumors, with a brief duration of symptoms and a rapidly progressive course. Forty percent of the patients were alive at 6 months, only 10% at 1 year, and all patients had died within 2 years following diagnosis.


Value of cerebrospinal fluid cytology for the diagnosis of malignancies in the central nervous system. The authors present a retrospective analysis of the results of the cytological examinations of cerebrospinal fluid (CSF) samples and tumor-cyst aspirates deriving from 262 patients treated for malignant intracranial primary and secondary tumors, and vertebral and peridural metastastic processes. Positive preoperative CSF samples were found in 15.3% of all cases of primary cerebral malignancies (13.9% of all gliomas) and positive postoperative CSF samples were found in 40% (91% of the medulloblastoma cases). In all cases of single or multiple secondary cerebral tumors, positive preoperative CSF samples were found in 20%.


A surgical approach through the pedicle to protruded thoracic discs. Three cases of thoracic disc herniation presenting with signs of spinal cord compression are reported. The patients were operated on by an approach through a midline incision in which a pedicle is removed. Two patients were cured and one has improved.


Clearance of edema fluid into cerebrospinal fluid. A mechanism for resolution of vasogenic brain edema. The authors present the results of an investigation studying the resolution of vasogenic brain edema using cold injury in cats. The appearance of RISA-I131 and sucrose-C14 lebeled edema fluid in the ventricular cerebrospinal fluid (CSF) was assessed by means of ventriculocisternal perfusion. The effect of low- or high-pressure perfusion on edema spread was determined by measuring the water, sodium, RISA-I131, and sucrose-C14 content of serial tissue blocks taken from the injured cortex through the white matter to the ventricular ependyma. The findings indicate that increasing the hydrostatic pressure gradient between edematous brain and CSF enhances the clearance of edema fluid into the ventricular CSF. This was conclusively demonstrated with low-pressure ventricular perfusion which markedly diminished the amount of edema close to the ventricles compared to the controls. The concentration of albumin, sodium, and potassium to the fluid removed from the tissue during low-pressure perfusion indicates that bulk flow was the primary method of edema movement through the extracellular space. With high-pressure perfusion the concentration profiles suggested alternative mechanisms of edema resolution, such as diffusion and reabsorption into capillaries.


Aneurysm of azygous anterior cerebral artery. A case report. This report describes a patient with a fusiform aneurysm of an azygous anterior cerebral artery (ACA) associated with a ruptured saccular aneurysm at its distal end. Gross, microscopic, and radiological documentation of this anomaly is presented. It is suggested that in cases where the question of an unpaired ACA arises, a projection paralleling the radiological baseline be employed during angiographic studies thus affording better visualization of these vessels. Clinically, in patients with pericallosal aneurysms, their frequent association with azygous ACA's should be borne in mind, as injury to this common arterial trunk will affect both hemispheres and the corpus callosum with tragic results.


Meningeal melanocytoma with invasion of the thoracic spinal cord. Case report. A case is presented of meningeal melanocytoma that invaded the thoracic spinal cord of a 71-year-old woman. The light and electron microscopic features of the lesion indicate that it derives from melanocytes normally found in the leptomeninges. This tumor closely resembles the dermal cellular blue nevus and does not have the ultrastructure of a meningioma. "Melanotic meningioma" is consequently a misnomer and the name "meningeal melanocytoma" is more appropriate. These tumors may appear to be benign histologically, but they are locally aggressive. Total surgical excision offers the best chance for cure.


Asymptomatic subdural chondrosarcoma. Case report. This report describes a large, asymptomatic, subdural skeletal-type condrosarcoma originating from the meninges. Distinction between the mesenchymal and skeletal types of intracranial chondrosarcoma is important since they have different prognoses.


Dural mesenchymal chondrosarcoma. Case report. A dural mesenchymal chondrosarcoma is reported in a 19-year-old man. This tumor had features of angioblastic meningioma (meningeal hemangiopericytoma), by light microscopy. However, ultrastructurally this tumor could be distinguished from angioblastic meningioma, and its similarity to extracranial mesenchymal chondrosarcoma was confirmed.


Lacertus fibrousus compression of the median nerve. Case report. A 47-year-old guitar player presented with inability to use his right hand because of progressive weakness and numbness. Examination suggested compression neuropathy of the median nerve at the elbow. Exploration of the median nerve revealed compression by a tight aponeurosis of the biceps tendon. Release resulted in prompt recovery of function.


Hepato-biliary scintigraphy and hepatography with Tc-99m diethyl-acetanilido-iminodiacetate in obstructive jaundice. Tc-99m diethyl-IDA was used for combined serial hepato-biliary scintigraphy and processing of hepatographic curves, using a scintillation camera and an image-processing system. Patients with obstruction of the common bile duct, proven by operation, were investigated. Hepatograms from an area of interest corresponding to the periphery of the right liver lobe varied predictably with changes in the serum levels of alkaline phosphatase and bilirubin. Both anatomical and functional information was obtained. The investigation could be carried out even under reduced liver function. Hepatic uptake of the agent was noted at serum alkaline phosphatase levels up to 1000 U/l and serum bilirubin levels up to 170 mumol/l.


Visualization of nonfunctioning adrenal adenomas with iodocholesterol: possible relationship to subcellular distribution of tracer. [131I] 19-iodocholesterol (I-131 C) correctly located adrenocortical adenomas in four patients who had no clinical or biochemical evidence of excessive steroid production. Three of the four "nonfunctioning" adenomas showed significant quantities of lipid histologically. To clarify the discordance between uptake and adrenal-steroid excretion, the subcellular location of I-131 C was studied. Normal rats and rats treated with ACTH or aminogluthimide (AG) were injected intravenously with I-131 C or [3H] cholesterol (H-3 C) and killed after three days. The homogenized adrenals were subjected to subcellular fractionation. Treatment with AG increased both the amount and the percentage of both I-131 C and H-3 C contained in the lipid fraction. ACTH treatment decreased H-3 C content but did not change I-131 C content in the lipid layer, suggesting an impairment of I-131 C mobilization from lipid droplets. The data demonstrate that excess steroid production is not necessary for I-131 C uptake and provide an explanation why certain biochemically nonfunctioning adrenocortical adenomas are visualized with I-131 C.


Simultaneous emission and fluorescent scanning of the thyroid. A comparison study of lithium-drifted silicon [Si(Li)] and high purity germanium (HpGe) was performed to explore the feasibility of replacing the current Si(Li) detector with the higher-efficiency HpGe detector. The improved efficiency of HpGe permits the use of collimators with higher resolution, which results in improved image quality over that achieved by the current Si(Li) system in use at Vanderbilt with an overall reduction in sensitivity of 29%. Since a 10 mm thick HpGe detector is about 75% efficient at 140 keV, the added advantage exists of simultaneously (a) imaging the stable-iodine distribution within the thyroid by x-ray fluorescence, and (b) the distribution of administered radiotracers such as [99mTc] pertechnetate. This comparison study shows that HpGe can compete with Si(Li) in overall detector efficiency, with the added benefits of better collimation to improve spatial resolution plus the simultaneous imaging of Tc-99m, all at the same equipment cost.


Computerized transaxial tomography and cerebral serial scintigraphy in intracranial tumors--rates of detection and tumor-type identification: concise communication. In 215 cases of intracranial tumors with subsequent histological identification, computerized transaxial tomography (CTT), and cerebral serial scintigraphy (CSS) with [99mTc] pertechnetate were carried out to compare the efficiency of each method in detecting and classifying such tumors. With a tumor detection rate of 99%, CTT turned out to be superior to CSS (91%). On the other hand, CSS findings enhanced the CTT rate of correctly identified tumor types in meningiomas from 85 to 92% and in high-grade gliomas from 82 to 89%. In metastases, low-grade gliomas, and various other tumors, CSS supported CTT by confirming a number of these tumor types. Therefore, the most important use of CSS in intracranial tumors today is its role as a supplement to CTT in order to establish and confirm type-specific diagnoses.


Steroid-induced suppression of gallium uptake in tumors of the central nervous system: concise communication. The effect of steroids given in greater than replacement doses on the gallium and technetium glucoheptonate brain scan is evaluated by comparing the relative sensitivity of both radiopharmaceuticals in patients both on and off steroids. The study shows a significant steroid effect on the sensitivity of 95% to 64% following steroids. Steroids did not significantly alter the sensitivity of the technetium glucoheptonate study. The superiority of the TcGH brain scan over the gallium citrate brain scan in the steroid population suggests a difference in the uptake mechanism for the two radiopharmaceuticals.


Studies on gallium accumulation in inflammatory lesions: III. roles of polymorphonuclear leukocytes and bacterial. The role of polymorphonuclear leukocytes (PMN) and bacteria in the accumulation of gallium-67 in inflammatory lesions was studied using an animal model. A plastic practice golf ball was implanted in the subcutaneous tissue of the abdominal wall of rabbits, and sterile or bacterial inflammation was induced inside the ball. Gallium accumulated in the inflammatory exudates induced by either sterile casein or Staphylococcus aureus. Two rabbits were made agranulocytic by prior treatment with myleran before the injection of S. aureus and gallium. These also accumulated gallium, although in one agranulocytic rabbit there were no PMN in the inflammatory exudate. Analysis of the inflammatory exudates showed that most of the gallium was in the noncellular fraction (2,500-g supernatant) in both sterile and bacteria-induced inflammation. The results indicate that gallium accumulates in the inflammatory lesions, even in the absence of either PMN or bacteria.


Indium and iron as tracers for erythroid precursors. External visualization and delineation of functional bone marrow is important for diagnostic, prognostic and therapeutic purposes. Because of difficulties in using the isotopes of iron for bone-marrow imaging, indium-111 chloride has been used extensively for this purpose. In this investigation we attempted to solve the problem of cellular localization of indium chloride by employing a rat model with erythropoietic precursors selectively damaged by lethal intracellular radiation from the Auger electrons of Fe-55. In the rat, we have shown that the absolute marrow uptakes of indium and iron are different, whereas the absolute uptakes of indium and sulfur colloid are the same. However, in animals whose erythroid activity was partially destroyed with Fe-55, the fractional depressions of iron and indium uptakes were the same and corresponded to the extent of the remaining erythroid activity. In addition, following an in vitro separation of the cellular elements of marrow with iron carbonyl, both iron and indium were found in the erythroid-rich supernatant, whereas sulfur colloid was in the precipitate. These results indicate that, in the rat, In-111 chloride is an effective in vivo marker for the early phases of iron uptake by the bone marrow.


Abnormal cisternogram associated with Diamox therapy. A cisternogram characteristic of normal-pressure hydrocephalus was obtained from a patient on Diamox who was being evaluated for rapid mental deterioration. A repeat cisternogram after Diamox was discontinued was nearly normal. We hypothesize that the initial abnormality resulted from reduced cerebrospinal fluid production caused by carbonic anhydrase inhibition; this defect (reduced flow) led to a net reflux of tracer into the ventricles. The reflux is believed to be due to the reduction of bulk cerebrospinal fluid from the ventricles.


Tantalum-178--a short-lived nuclide for nuclear medicine: production of the parent W-178. The physical decay characteristics of the short-lived radionuclide Ta-178 (half-life 9.3 min) appear to be suitable for use in conjunction with low-energy detection systems such as the multiwire proportional camera. This camera is inefficient for emissions with energies greater than 100 keV. The gamma-ray spectrum of Ta-178 is dominated by the characteristic hafnium x-rays (55--65 keV), emitted as a result of electron-capture decay. The parent nuclide, W-178 (half-life 21.7 d), was produced in the Michigan State University cyclotron by proton bombardment of stacked natural tantalum-foil targets. Optimum production was found to occur with an incident proton energy of 34 MeV at an effective activity of 1.1 mCi/muA-hr per MeV of target thickness. Tungsten-178 was chemically separated from the Ta foils with a yield of 98%.


Tantalum-178--a short-lived nuclide for nuclear medicine: development of a potential generator system. We describe a chemical separation that may form the basis of a generator system for the short-lived radionuclide Ta-178 (T 1/2 = 9 min). The parent nuclide W-178 (T 1/2 = 21.7 days) is loaded on an anion-exchange column and the daughter eluted with a mixture of dilute hydrochloric acid and hydrogen peroxide. The yields of tantalum and the breakthrough of the tungsten parent as a function of the eluting conditions are discussed, and preliminary animal distribution data are presented for various treatments of the eluant solution.


Electrolytic complexing of glucoheptonate and technetium-99m. Solutions of glucoheptonate and sodium pertechnetate (Tc-99m) were subjected to electrolysis at various ampere-time products until a charge was found that consistently promoted tagging of greater than 90% efficiency. It was found that 9 coulombs (100 mA, 90 sec) consistently yielded a final product that contained less than 10% total radiochemical impurities (unbound pertechnetate and reduced, hydrolyzed technetium). Radiochemical purity of the final product was established using a two-solvent thin-layer chromatographic system with methyl-ethyl ketone and normal saline as the solvents. The tagging efficiency and stability of the tagged complex were determined with similar chromatographic analysis. It was shown that use of a 15% solution of calcium glucoheptonate resulted in a more stable product than that prepared from commercially available stannous glucoheptonate. The rapid, accurate chromatographic method for determination or radiochemical purity of the product is described. The final product is considered equal or superior to commercial Tc-99m (Sn) glucoheptonate and was produced at considerably less cost.


Rapid radioiodination of rose bengal at room temperature. Published methods for radioiodination of rose bengal require reaction times of 1 hr or more at temperature from 50 to 120 degrees C. Through the use of an acidified ethanol solvent and potassium iodate oxidant, purified rose bengal is radioiodinated at room temperature within 15 min with chemical yields ranging between 93 and 97%. Radiochemical impurities are sufficiently minimized to permit preparation in a single 10-ml serum vial, requiring no additional purification steps. The method reported here is readily adaptable to cold-kit preparation.


Bone accumulation of the Tc-99m complex of carbamyl phosphate and its analogs. Carbamyl phosphate, an organic molecule containing a single phosphate group, has been used in the therapy of sickle-cell disease. Carbamyl phosphate bound Tc-99m and achieved bone uptake in mice, rabbits, and a human volunteer. By examination of the structural formula, a working hypothesis was developed that predicted that the Tc-99m complexes of the analogous compounds acetyl phosphate, propionyl phosphate, and butyryl phosphate, each carrying single phosphate and carbonyl groups, would also show bone specificity. This was confirmed experimentally. Phosphonoacetic acid is a structural analog of these compounds. The structural analysis also predicted that aminomethylphosphonic acid and phosphoenolpyruvate would not have as avid bone affinity, and this was also confirmed. These compounds represent a new class of bone-seeking agents that have the common properties of a lone phosphate and a carbonyl function. Such agents may permit the synthesis of additional analogs in an effort to obtain optimal affinity in the Tc-99m complexes.


Deadtime measurements in scintillation cameras under scatter conditions simulating quantitative nuclear cardiography. Deadtime performance of scintillation cameras is sensitive to such factors as scatter fraction and analyzer window width. Data from manufacturers and previous investigators do not predict counting-rate losses under clinical conditions. Scintillation cameras used with Tc-99m for quantitative nuclear cardiology should be evaluated for deadtime performance by the two-source method using a scatter phantom designed to simulate the spectrum from Tc-99m in the heart. Under these conditions, scintillation cameras were found to follow the paralyzable model; accurate estimates could be obtained for data losses and maximum useful counting rates in a clinical setting. A survey of 39 contemporary scintillation cameras yielded a range of paralyzing deadtime values of 4.3 to 10 musec, with a 20% window centered on the Tc-99m photopeak. For an average deadtime of 6 musec, counting rates should be maintained below 36,000 cps to avoid undue data losses in excess of 25%.


Comparing the performance of two gamma cameras under high counting rates: principles and practice. The performance of two large Anger cameras at high counting rates was compared, and the principles for measuring the relevant parameters, especially deadtime loss and coincidence artifacts, are discussed. The results demonstrate the importance of the following factors: modern pulse-shaping circuitry with short paralyzable deadtime, and anti-pileup circuit, and uniform energy information within the field of view, which requires separate summing matrices for energy and position. Elaborate testing of the specifications should be carried out before purchase of a gamma camera.


The effect of photon energy on tests of field uniformity in scintillation cameras: concise communication. Although Co-57 is generally used for testing the field uniformity of scintillation cameras, the various photon energies of other radionuclides require uniform response throughout the entire range of energies to which a scintillation camera can respond. The use of Co-57, however, may not adequately demonstrate the field response, which may be uniform at 122 keV but not at other energies. Two scintillation camera systems were investigated in this regard by storing field-flood images, obtained at several photon energies, in a minicomputer. The stored data were analyzed using the Kolmogorov-Smirnov test, revealing that field uniformity may change with photon energy. One of the scintillation cameras showed a variation in field response with photon energy, whereas the other camera did not. These results, however, should not be extrapolated to other cameras of the same type. If a particular scintillation camera is to be used routinely with several energies, its performance should be tested with each one to provide assurance that valid information is being obtained. The effects of dynamic uniformity field correction remain to be evaluated.


Effects of force-feeding and dietary cellulose on liver lipid accumulation and lipid composition of liver and plasma in growing chicks. Changes of content and composition of lipid in liver and plasma affected by force-feeding and dietary cellulose were investigated in 14-day old Single-Comb White Leghorn male chicks. They were given a purified high energy diet (starch-casein diet without fiber) supplemented with or without dietary cellulose. Chicks were fed ad libitum or force-fed the experimental diet. Force-feeding of excess food improved the growth rate of chicks and feed efficiency, but feeding of cellulose did not affect body weight gain and feed efficiency, though a slight improvement in nitrogen retention was observed. Liver weight and lipid content in liver and plasma were markedly elevated by force-feeding, and were markedly depressed by dietary cellulose in the force-fed chicks. It is suggested that changes of liver lipid by force-feeding and dietary cellulose are mainly originated from the changes of triglyceride in the liver lipid. No marked changes were observed in fatty acid composition of abdominal fat and liver lipid in the cellulose-fed chicks. These results suggest that dietary cellulose may affect lipid metabolism in growing chicks.


The influence of dietary fat levels and environmental temperature on digestible energy and absorbability of animal fat in catfish diets. A study was conducted on the effects of three dietary levels of animal fat (5%, 10%, and 15%) and two environmental temperatures (23 and 28 degrees) on the digestible energy (DE) and apparent absorbability (AA) of animal fat in diets of 150 g catfish. Results obtained by the use of the chromic oxide indicator technique demonstrated that at 28 degrees and substitution levels up to 10% of diet, animal fat had a DE value of 7,000 kcal/kg and an AA of 94%. At the 15% level of substitution, both DE and AA were substantially reduced. At each level of substitution, DE and AA values were considerably lower in fish reared at 23 degrees. At supplemental levels up to 10% of diet, the DE and AA values for catfish at 23 degrees were 6,130 kcal/kg and 70%, respectively. Results from this study reconfirmed previous growth data which indicated that animal fat is an excellent dietary energy source for catfish which are reared at optimum temperatures.


The effects of starvation and refeeding on muscle protein synthesis and catabolism in the young rat. We studied the effects of acute starvation and refeeding on muscle protein synthesis and degradation in young rats. As measures of synthesis, we determined muscle RNA concentration and the rate of incorporation of [14C]leucine into skeletal muscle protein (Sm). As an estimate of nitrogen retention we measured urea production (UrP). Starvation reduced these variables significantly. One refeeding period returned Sm to control values, only partially restored RNA concentration, and increased UrP. We determined the urinary excretion rate of 3-methylhistidine (3-MH) as a measure of the rate of myofibrillar protein degradation. Excretion of 3-MH was lowest in control and highest in starved rats. Refeeding decreased 3-MH excretion to a level midway between control and starved animals. Growth was attended by high rates of synthesis and low rates of degradation. Starvation depressed synthesis and increased degradation. With refeeding, synthesis increased and degradation decreased, compared with the starved state.


Effects of dietary folate deficiency on developmental increase of myelin lipids in rat brain. Rats were fed a folic acid deficient purified diet from day 12 of gestation throughout the lactational period. Offsprings were fed the same diet after weaning. Control rats were given 170 microgram of folic acid per day per rat supplemented to the same diet, which was fed ad libitum or by pair-feeding. At 3 and 6 weeks of age, myelin was isolated from rat brains. It was found that in comparison with the controls, myelin yield was significantly decreased as well as the brain weight in the folic acid deficient rats at 6 weeks of age. There were no differences of gross composition of myelin, protein, ratio of cholesterol, glycolipids, phospholipids, and total lipid with or without folate deficiency either at 3 or 6 weeks of age. The hydroxy fatty acid composition of myelin lipids in brain was not changed with folate deficiency at 3 or 6 weeks of age. The developmental increase of the percentages of 22:6, 22:4, and 20:1 in nonhydroxy fatty acids of myelin lipids from the folic acid deficient rats were significantly lower at 6 weeks of age in comparison with the controls. The n-3:n-6 ratio in myelin fatty acids from the folic acid deficient rat brains was abnormally low at 3 weeks of age and was not increased at even 6 weeks of age. The implications of these findings are that folic acid may play an important role in desaturation or chain elongation of polyunsaturated fatty acids in the brain of developing rats.


Taurine: an essential nutrient for the cat. Cats fed a purified diet containing purified casein as the source of protein develop retinal degeneration due to the lack of taurine in the diet. To test whether cats can synthesize this sulfur amino acid from sulfate or cystine, radioisotopes of these substances were injected into taurine-depleted and control cats. Sulfate did not serve as a precursor for taurine synthesis, whereas cystine underwent only a moderate conversion to taurine. This is in keeping with the low level of cysteinesulfinic acid (CSA) decarboxylase activity in cat liver. There was no difference between the activity of CSA decarboxylase in tissues from control cats and that in tissues from taurine-depleted cats. The pattern of tissue accumulation of [35S]taurine and from [35S]cystine also indicated that tissues from taurine-depleted cats do not synthesize [35S]taurine more rapidly than tissues from control cats. The data did not indicate a difference in taurine uptake by tissues of control and deficient cats, but progressive accumulation in deficient cats suggested that the turnover rate of taurine is decreased by the deficiency. Since supplementation of the purified diet with cysteine has been found previously to be inadequate to prevent progressive taurine depletion of the retina and its subsequent degeneration and since conversion of sulfur compounds to taurine in vivo is inadequate, taurine can be considered an essential nutrient for the cat.


Intestinal disappearance and portal blood appearance of amino acids in sheep. The intestinal disappearance and simultaneous arterial inflow and portal appearance of individual amino acids (AA) were studied in sheep fed closed formula, unrefined high (H.P.) and medium (M.P.) protein diets. Gut contents were sampled through four intestinal cannulae and blood was sampled through portal and arterial catheters. The amount of total and amino N that was fed decreased on passage into the duodenum but increased in the jejunum, and then again decreased steadily towards the terminal ileum. The amounts of AA passing into the duodenum were significantly higher when the H.P. rather than the M.P. diet was fed. No dietary differences in AA were noted at the ileo-cecal junction, however, meaning that greater amounts of AA disappeared from the intestine when the H.P. diet was fed. The amounts of AA appearing in portal blood were 30 to 80% of those disappearing from the intestine and were greater in sheep fed the H.P. diet. The amount of AA passing into the duodenum also significantly affected the concentrations of AA in arterial blood. Less [U-14C]glutamic acid than [U-14C]alanine, that was infused into abomasum, was detected in the digesta passing through the pylorus. The same also was true for the unlabeled free form of glutamic acid. The portal appearance of both unlabeled and labeled glutamic acid was negligible, but that of alanine was considerable. Variable amounts of [14C]citrulline, [14C]arginine, and [14C]urea were detected in the blood following the abomasal infusions of labeled glutamic acid or alanine. The portal appearance of these labeled metabolites was always negative, however, implying that they were utilized, and not formed, by gut tissues.


Copper deficiency in the laying hen.

Copper deficiency in the laying hen. Copper deficiency in the laying hen resulted in anemia and the production of eggs which were abnormal in size and shape. Many of the eggs had shells which were wrinkled and rough in texture. There was also an increase in the number of shell-less eggs. Examination of malformed egg shells using the scanning electron microscope revealed ultrastructural changes in the mammillary layer of the shell. The effect of copper deficiency on shell formation was attributed to the shell membranes which were altered in color, appearance, and physical consistency. Amino acid analysis of the membranes indicated that the membranes from copper deficient hens were characterized by an increase in lysine content. This suggests that copper is necessary for the formation of lysine derived cross-links in a manner similar to that which occurs in connective tissue. The exact nature of these cross-links is unknown at this time.


Rearing of gnotobiotic rodents by feeding a commercially-prepared infant formula. A simple, inexpensive method for the rearing of germfree rats was developed. Germfree rats were fed from age 10 days to 40 weeks a diet consisting of commercially prepared Similac infant formula, water, and corn oil. Weight gains and gross appearances were comparable to littermate controls. Antibodies to bacterial teichoic acid were present in all controls while absent in rats fed the Similac diet.


Comparative effects of saturated and unsaturated lipids on hepatic lipogenesis and cholesterogenesis in vivo in the meal-fed rat. The effects of saturated and unsaturated lipids on in vivo rates of hepatic lipogenesis and cholesterogenesis were compared. Lipogenic and cholesterogenic rates were determined in meal-fed rats either after feeding 1%, 5%, 10%, or 20% dietary corn oil or hydrogenated soybean oil for 14 days, or after intrgastric administration of fatty acyl ethyl esters (18:0, 18:1, or 18:2) for 1 and 3 days. Dietary hydrogenated soybean oil was not absorbed, whereas dietary corn oil and the intragastrically administered fatty acyl ethyl esters were well absorbed. Fatty acid synthesis measured from 3H2O and [14C] alanine was inversely correlated with unsaturated dietary fat content, but was unchanged by saturated dietary fat. A single daily administration of 18:0, 18:1, or 18:2 was ineffective in altering lipogenic rates. However, fatty acid synthesis was decreased by three consecutive daily doses of 18:1 or 18:2 (5 g/kg), but not by 18:0. Hepatic rates of cholesterogenesis from 3H2O and [14C] alanine were markedly enhanced by the administration of 10% or 20% saturated dietary fat. Feeding 1%, 5%, or 10% corn oil diets did not have an effect on cholesterogenesis. The 20% corn oil diet reduced the rate of conversion of [14C]anine into cholesterol while the rate of conversion of 3H2O remained unchanged. Neither the 1 day not 3 day oral administration of 18:0 or 18:1 had any effect on cholesterol synthesis; thereas the administration of 18:2 increased the conversion of [14C] alanine into cholesterol by 30% but did not after the rates of cholesterogenesis from 3H2O. These data suggest the following: a) fatty acid synthesis responds selectively to 18:0, 18:1, and 18:2; b) the inhibition of fatty acid synthesis by unsaturated fatty acids is time dependent; c) the rate of fatty acid synthesis is inversely proportional to the concentration of unsaturated dietary fat; d) prolonged feeding with a completely saturated diet will increase fecal fat excretion and hepatic cholesterol synthesis; and e) the regulation of fatty acid synthesis by dietary lipid is independent of the regulation of cholesterol synthesis.


Blood and liver folacin activity, formiminoglutamic acid excretion, growth and hematology in guinea pigs fed a folacin deficient diet with and without sulfonamides. Dietary folacin deficiency in the presence and absence of dietary sulfonamides was studied in the guinea pig for the purpose of relating the growth and hematologic effects of folacin deficiency to tissue and biochemical changes. Six-week old female guinea pigs fed control and folacin deficient diets with and without 0.1% sulfonamides for 6 to 7 weeks. Growth was significantly reduced in both groups fed the folacin deficient diets, and 25% of all deficient animals died. Macrocytic anemia was not present, but reduced leukocyte numbers were observed in folacin deficiency. Plasma and red blood cell folacin activities were reduced by about 50% in deficient guinea pigs in the presence and absence of dietary sulfonamides. Both liver total folacin activity and urinary formiminoglutamic acid excretion were not significantly altered by the degree of folacin deficiency obtained in this study.


The effect of metabolic state on incorportion of [14C] pantothenate into CoA in rat liver and heart. The effect of metabolic or hormonal status on CoA biosynthesis was studied by comparing the rates of incorporation of [14C]-panthothenate into CoA in fasted and glucose-fed rats. Rat hearts and livers were freeze-clamped 1.5 hours after intravenous injection of [14C] pantothenate. CoA, pantothenate, and other pathway intermediates were separated by chromatography of tissue extracts on DEAE cellulose paper. Compared to the fasted rats, rats forced-fed glucose 0.5 hours before pantothenate injection 69% lower incorporation of radioactivity into CoA in liver, a 69% lower specific radioactivity of liver CoA, a 63% lower specific radioactivity of liver mitochondrial CoA, and a 44% lower incorporation of radioactivity in CoA in heart. The accumulation of labeled pathway intermediates was negligible. The cysteine content of liver was equal for the two conditions. There was no difference in level of unacylated CoASH for fasted and glucose-fed rats, suggesting that hormonal effects on degree of CoA acylation are not involved in this regulator mechanism. The specific radioactivities and concentrations of pantothenate in heart or liver were also nearly equal for the two conditions, so the regulatory mechanism does not involve hormonal effects on pantothenate uptake into tissues. Thus, the effect of glucose-feeding (and related changes of metabolite and insulin-glucagon levels) on the incorporation o[14C] pantothenate into CoA is exerted at a locus on the biosynthetic and/or degradative pathway between pantothenate and CoA.


Carcass and liver composition following acute oxytetracycline treatment of ob/ob mice. Fully mature (24-week old) C57BL/6J ob/ob mice and their lean littermates received daily oxytetracycline injections (50 or 100 mg/kg) during a 10 day period. The effects of the drug on the glucose, IRI, corticosterone levels, and on hepatic and body composition of ad libitum fed obese mice were compared with those of food-restricted and ad libitum fed lean and obese control animals. When compared with food-restricted obese mice, drug treatment led to substantial reductions of serum glucose, serum IRI, carcass fat, and hepatic lipid content, while it increased lean body mass and liver glycogen concentration. Similarly, oxytetracycline decreased body weight, and serum glucose in lean mice, but the drug had no substantial effect on circulating IRI levels or on the lipid content of carcass. A significant increase in hepatic lipid was observed in drug-treated lean mice. No effects of the drug on basal corticosterone levels were noted in either phenotype. These data support previous findings showing the effectiveness of oxytetracycline to reverse many of the metabolic abnormalities of ob/ob mice. In addition, the present results suggest that the drug acts by independently altering abnormal metabolism in many target organs, including pancreas, adipose tissue, liver, and muscle, rather than by merely reducing circulating insulin levels or by generally increasing insulin sensitivity.


Diagnosing occupational disease: a new standard of care? Is a physician civilly liable for failure to diagnose an occupational disease in his patient? Under principles of common-law tort, physicians are held to certain standards of care in treatment. When that standard is breached and a patient is injured, a negligence action may lie. Might a court find that a physician has breached that standard of care if he fails to include in his examination of thorough work history and evaluation of job exposures to toxic chemicals? A number of medical malpractice cases involving standards of care are analyzed and parallels are drawn to the occupational disease context. Although it is impossible to predict how courts will rule in a given case, it appears that it would be prudent for a physician to delve more deeply into his patient's work experience when a patient presents with puzzling symptoms. The standard use of a thorough work history might also lead to early discovery of an industry-wide or community-wide health problem.


Mortality follow-up of workers exposed to 1,4-dioxane. As a result of recent interest in the carcinogenic effect of dioxane, a mortality study was conducted on employees exposed to this compound at a major chemical company plant. Standard follow-up techniques were used to ascertain the vital status of a total of 165 employees ever exposed to dioxane since 1954. Observed deaths from overall cancer were not significantly different from the expected number of deaths. The observations were based on small numbers of deaths of employees who were apparently exposed at low levels and for relatively short exposures.


The use of retirees to evaluate occupational hazards. II. Comparison of cause specific mortality by work area. This article compared the results of mortality studies in  three work areas of the steel industry for the total cohort of workers and for the retirees. This was done to determine further the usefulness and the limitations of retiree studies for occupational mortality studies. The major findings are: 1. Retiree studies detect occupational hazards such as respiratory cancers and nonmalignant respiratory diseases, although the estimated average relative risk will tend, for obvious reasons, to be greater than for the total cohort. 2. Some problems associated with the use of retirees for occupational mortality studies were also discussed. These problems included small sample sizes, the retiree study not indicating significant excess deaths from certain diseases because the excess mortality took place in the younger ages, and differences between the estimates of risk for the retiree study and the total cohort study. 3. The estimates of risk for the studies using all men over age 65 did not vary from the estimates of risk for the total cohort as much as the risks from the retirees did. However, other than the variation seen in the estimates of risk, the exclusion of nonretirees from the retiree study did not seem to affect the overall conclusions. Based on the findings of this study, it was concluded that retiree studies may sometimes be useful tools in detecting occupational hazards when cost and time definitely preclude more comprehensive studies, but that one should be aware of the greater possibility of spurious negative findings due to the limited age group being studied and the smaller sample sizes.


The control of acute diarrhea in a large industrial plant. Diarrhea causes considerable absenteeism and loss of working time among employees in the United States. One hundred employees with acute diarrhea at a Ford Motor Company plant were studied for four months to determine if loperamide hydrochloride treatment would control diarrheal symptoms, reduce absenteeism due to the condition, and be well-tolerated. Diarrhea was controlled with a median dosage of three capsules (6 mg total dose) and a range of two to 12 capsules. Ninety-six percent of the subjects were controlled after the first day, 98% by the third day. A statistically significant number were symptom free at their last clinical visits. Side effects were generally minor in nature. Substantially more than 1,000 man-hours of lost time were saved because of the treatment. Known drug dependents did not suffer from CNS effects or "highs". Loperamide acts directly on the intestinal wall to inhibit excessive peristalsis, thereby providing prompt, effective relief, with normal bowel patterns observed in these patients. The simple, individualized dosage is patient-oriented, rather than based on a fixed regimen. Because of its rapid onset of action, effective control of symptoms, low dosage, and being well-tolerated, loperamide meets the criteria for an effective antidiarrheal agent in industry.


Developmental patterns of renal functional maturation compared in the human neonate. Observations on the influence of extrauterine life upon renal functional maturation in the human being were made in 49 newborn infants of 25 to 41 weeks' GA during the first 48 hours of life, and in serial studies of 12 of these infants whose GA at birth was less than or equal to 34 weeks. GFR was found to be uniformly low in infants born prior to 34 weeks' GA, and increased rapidly after 34 weeks' GA. Glucosuria was found to occur commonly in infants less than or equal to 30 weeks' GA. Glomerulotubular balance for glucose was noted in every infant studied, regardless of GA or length of time since birth. Mean values for TRP at every age prior to feeding was greater than or equal to 85%, and decreased concomitantly with the rise in serum phosphate concentrations after feedings were introduced. The urinary excretion of alpha amino nitrogen was greatest in infants less than 34 weeks' GA. These studies suggest that renal functional development in the human infant is closely related to conceptional (GA + postnatal age) age, and that the pattern of renal functional development for the premature infant during extrauterine life is similar to that of the fetus in utero of corresponding conceptional age.


The response to exercise in normal and asthmatic children. Twenty-five normal and 105 asthmatic children were exercised on a treadmill. Pulmonary function was assessed before and after exercise. The maximum fall from the resting value in normal subjects depended on the test used: PEFR 12.5%; FEV1 10%; MMEF 26%; V50 30%; V25 33%. Using these criteria, PEFR and FEV1 detected 99% of those asthmatic children who had a positive exercise response. The largest fall from the resting value was seen with the MMEF, but this test detected only 70% of the positive responders. The pre-exercise function did not affect the severity of the response but did have an effect on the incidence of exercise-induced bronchospasm.


Pacemakers in young patients: 1977.

Pacemakers in young patients: 1977. Recent experience with implanted cardiac pacemakers in nine young patients is reported. Advance in technology include improved pacemaker generator design and placement, and improved lead design and placement. No patients died; our only complication, failure to capture, required repositioning of the lead. All pacemaker replacements were elective. This series helps to define the more favorable current prognosis for the young patient needing pacemaker therapy.


Use of the one-hour blood xylose test as an indicator of small bowel mucosal disease. The one-hour blood xylose concentration was evaluated to determine its usefulness as a screening test for small bowel mucosal disease in infants and children. Six of 13 patients with one-hour blood xylose levels of less than 20 mg/dl had normal small bowel biopsies by light microscopy. Five of 20 children with normal one-hour xylose levels had abnormal small bowel villous architecture. Because of the significant false positive (46%) and false negative results (25%), the one-hour blood xylose concentration should not be used as the sole indicator for small bowel biopsy in infants and children with chronic diarrhea.


One-hour blood xylose test: a reliable index of small bowel function. A retrospective analysis of oral D-xylose tolerance tests in 435 pediatric patients was performed. A significant difference was found between 126 normal subjects and 47 untreated children with celiac disease one hour after load. The one-hour value was found to be more reliable than was fecal fat analysis in screening children for celiac disease. Sex, age, weight, and body surface did not influence the results of the one-hour value in the control subjects. Forty-eight children with cystic fibrosis had one-hour xylose levels within the normal range, but the means at 90, 120, and 180 minutes after load exceeded significantly (P less than 0.01) those of the controls. In a nonceliac group of 63 children with abnormally low xylose levels, almost all were found to have clinical conditions compatible with upper small bowel mucosal impairment. This study shows that a single estimation of xylose in blood one hour after load is a reliable index of small bowel mucosal function. It is a good screening test for celiac disease and small bowel disorders producing malabsorption in children.


Differential effects of cranial radiation on growth hormone response to arginine and insulin infusion. The growth hormone responses to arginine infusion and to insulin-induced hypoglycemia were studied in 13 patients with neoplastic disease after treatment with radiation and chemotherapy. Patients who received intensive cranial radiation (greater than 2,400 rads) had no response to either arginine or insulin; those who received moderate cranial radiation (greater than or equal to 2,400 rads) had GH response to arginine but not to insulin; patients receiving no cranial radiation responded to both arginine and insulin. These data support the hypothesis that GH secretion in response to arginine infusion has a different mechanism in contrast to the response to insulin-induced hypoglycemia and that the latter is more vulnerable to cranial radiation.


The syndrome of inappropriate secretion of antidiuretic hormone in children with bacterial meningitis. Plasma concentrations of arginine vasopressin were determined by radioimmunoassay in 13 normal children, 21 patients with febrile illnesses (not bacterial meningitis), and 17 patients with bacterial meningitis. The mean +/- 1 SD concentrations of AVP in the normal children and patients with various febrile illnesses were 0.7 +/- 0.6 and 1.0 +/- 1.2 muU/ml, respectively. The mean +/- 1 SD concentration of AVP in patients with bacterial meningitis was 3.3 +/- 2.3 muU/ml. The concentrations of AVP in the patients with bacterial meningitis were significantly greater (P less than 0.001) than those noted in the normal children or children with other febrile diseases.


Congenital diaphragmatic hernia associated with homolateral upper limb malformation: a study of possible pathogenesis in four cases. Four cases of congenital diaphragmatic hernia associated with homolateral upper limb reduction deformities are presented and are analyzed in terms of their pathogenesis. Diaphragm and upper limb are supplied by adjacent segments of cervical neural crest, and the sensitive period for upper limb formation occurs during early neural crest development. The evidence supports the possibility of cervical neural crest injury as the underlying pathogenesis.


Familial ichthyosis, dwarfism, mental retardation, and renal disease. The nonrandom association of congenital ichthyosis with neurologic impairment, ectodermal dysplasia, dwarfism, hypogonadism, and renal disease has prompted the review of numerous syndromes. The difficulties in characterization of syndromes in the absence of pathognomonic signs is discussed in relation to three siblings presented herein. Despite extensive investigation, underlying metabolic defects remain obscure.


Hazards of calcium gluconate therapy in the newborn infant: intra-arterial injection producing intestinal necrosis in rabbit ileum. Five infants received 10% calcium gluconate via umbilical artery catheters, which resulted in intestinal bleeding and lesions of the buttock, anus, groin, and thigh. The effects of intra-arterial calcium gluconate in two animal models were investigated. Injection of calcium into the aorta in the region of the posterior mesenteric artery resulted in immediate hyperperfusion of the descending colon; this may be an early hemodynamic response to injury in the area of colon supplied by this vessel. Injections into the arterial arcade of the rabbit ileum resulted in intestinal necrosis and villous atrophy. The use of umbilical artery catheters for administration of calcium gluconate is potentially hazardous.


Neonatal pneumonia associated with medium-chain triglyceride feeding supplement. The appearance of a similar pattern of multifocal pulmonary consolidation in four neonates receiving undiluted medium-chain triglyceride oil suggested a cause-and-effect relationship. This was supported by the demonstration in rabbits that the transtracheal injection of MCTO caused severe pneumonia. It is suggested that MCTO be mixed with formula before it is given to neonates.


Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia. The contribution of an abnormal pulmonary vascular bed to right-to-left shunting in patients with congenital left-sided diaphragmatic hernia and alveolar hypoplasia has not been defined. In three infants we analyzed lungs fixed by perfusion. Left lung volumes (ml/kg birth weight) were 1.7, 6.5 and 4.0 respectively (control = 11.7) and right lung volumes 5.7, 11.7 and 9.8 respectively (control = 14.3). Serial sections were prepared and fifth generation (resistance) vessels identified. Compared to control the medial widths were increased in all lungs and the medial width/external diameter ratios were increased in the left lungs of two patients and the right lung of one. The m/d ratio in the left lung was greater than that in the right lung in two of the three patients. There were fewer pulmonary vessels/cm2 lung tissue in the study lungs than in the control lung, and there were significantly fewer pulmonary vessels/cm2 lung tissue in the left than in the right lung in two of the three patients. Although there was increased smooth muscle in resistance vessels, intravenous therapy with tolazoline HCl did not improve systemic oxygenation. We conclude that this was probably due to the decreased total size of the pulmonary vascular bed and the decreased number of pulmonary vessels per unit lung tissue, causing a fixed high pulmonary vascular resistance.


Free erythrocyte porphyrins in cord blood. Red cell free erythrocyte porphyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children ages 1 to 6 years. The mean FEP value for the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 microgram/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth.


Glycine therapy in isovaleric acidemia.

Glycine therapy in isovaleric acidemia. The therapeutic efficacy of oral glycine was tested in a 3-year-old girl with isovaleric acidemia. An oral leucine load (25 mg/kg) caused a rise of the blood levels of isovaleric, lactic, and pyruvic acids as well as an increase of urinary excretion of the ketone bodies. These changes did not occur when oral glycine (250 mg/kg) was given with the leucine. Glycine supplementation favored the formation of isovalerylglycine, a nontoxic conjugate of isovaleric acid which is excreted rapidly. Excretion of isovalerylglycine rose threefold when leucine and glycine were administered simultaneously. Chronic glycine therapy was tolerated well and may have prevented one episode of ketoacidosis.


Emotional reactions of children to isolation in a cancer hospital. Emotional reactions of 123 hospitalized children and their mothers were evaluated during standard isolation with limited visitation and during peninsula isolation with visitation only through glass partitions. Self-report surveys and behavioral observations by nurses indicated that (1) patients and parents in both isolation facilities had overall high levels of hospital-related anxiety and depression which varied with the patient's  chronologic age; and (2) parents of preschool children had more negative opinions toward peninsula isolation than did parents of older children. These results confirm the need for psychologically supportive programs for the families of children being treated for catastrophic diseases.


Hypnotherapy in the management of childhood habit disorders. Hypnotherapy may sometimes be helpful in treating childhood habit disorders, provided that it is used with the same caution as are other treatment modalities. This paper clarifies some common misconceptions about hypnosis with children, notes indications and contraindications, describes a patient in whom hypnotherapy was used to treat hair pulling, and offers information about training in hypnosis and locating qualified hypnotherapists.


Morphological changes of Herpetomonas samuelpessoai. The promastigote form of Herpetomonas samuelpessoai is modified into a paramastigote-like form during incubation at 28 C in high osmolarity complex media obtained through the addition of various concentrations of KCl, NaCl or glycerol. Morphological changes accompanying this modification include an increase in cell volume during exponential growth, a deep invagination of the cell membrane at the bottom of the flagellar pocket into the cytoplasm, and a prominent bulging at the emergence of the flagellum.


Factors in the movement of hexose across the intestine of Ascaris suum. Trichloroacetic acid extractable carbohydrate of the intestine of Ascaris suum decreases rapidly when ribbons of the tissue are incubated in a basal salt solution. After 10 min incubation endogenous carbohydrate is 32% and after 80 min it is 19% of the "zero" time control value. In contrast, there is approximately a 2-fold increase in the endogenous carbohydrate of tissue that is incubated in saline with glucose. The increase occurs within the first 5 min and is maintained throughout an 80-min incubation period. Sac preparations of the intestine that are preincubated with glucose and incubated without glucose move 3-0-methylglucose from the luminal to the pseudocoelomic fluid at a rate that is comparable initially to the rate of movement measured for sac preparations that are incubated in saline with glucose. After 10 min the rate decreases. The addition of glycogen or trehalose to the saline bathing the pseudocoelomic side of sac preparations does not facilitated the movement of 3-0-methylglucose. Collectively, the results support the suggestion that the limited movement of  3-0-methylglucose across intestinal sac preparations that are incubated without glucose is due to the tissue's limited carbohydrate reserve and its rapid depletion in vitro.


Evidence that sulfisoxazole, an antibacterial sulfonamide, can adversely affect the development of Brugia pahangi in Aedes aegypti mosquitoes. The average number of infective larvae recovered from Brugia pahangi-infected Aedes aegypti was approximately one-half that recovered from the controls after the former group of infected mosquitoes had ingested a 1.0% solution of sulfisoxazole diolamine (SXZ) in 10% sucrose-water for 4 consecutive days, beginning 4 days after infection. Most of the filarial larvae from the SXZ-treated mosquitoes were small and sluggish compared with those from the controls. There was no increased mortality of mosquitoes that ingested 1.0% SXZ in sugar-water for 4 days. Average filarial larval burdens were not decreased in mosquitoes that ingested a solution of 10(-6) M methotrexate (MTX), a potent dihydrofolate reductase inhibitor, in sugar-water for 4 days, beginning 4 days after infection. The distributional pattern of larval burdens in mosquitoes that ingested combined 1.0% SXZ and 10(-6) M MTX in sugar-water for 4 days closely resembled that seen in mosquitoes that had imbibed 1.0% SXZ only. Average filarial larval burdens were not decreased in mosquitoes with 4-day-old B. pahangi infections that fed upon jirds which received intraperitoneal injections of SXZ (2 g/kg) and MTX (1 mh/kh), alone and in combination, 1 hr previously. Survival of the mosquitoes that fed upon the drug-treated hosts was unaffected, as was the hatchability of their eggs and subsequent growth and development of the mosquito larvae.


Dirofilaria macrodemos and D. panamensis spp. n. (Nematoda: Filarioidea) from Central and South Americal sloths. Two new species of Diorfilaria, Dirofilaria macrodemos and Dirofilaria panamensis, are described from the subserosa of Central and South American sloths. Dirofilaria macrodemos, described from the three-toed sloth, Bradypus tridactylus, in Guyana, is characterized and differentiated from other dirofilarias by its length (female 214mm, male 64mm), relatively long tail (female 140 micron, male 110 micron), and the number and distribution of the caudal papillae (7 pairs) in the male. Dirofilaria panamensis, parasite of the two-toed sloth, Cholopeus hoffmanni, in Panama, was previously described as Dirofilaria incrassata by Caballero (1947), but can be distinguished from both D. macrodemos and D. incrassata on the basis of body size (female 66 mm long by 360 micron wide, male 34 mm long by 250 micron wide), tail length (female 80 micron, male  80 micron), and number (6 pairs) of caudal papillae in the male.


Efficacy of mebendazole and albendazole against Trichinella spiralis in mice. Changes in the sensitivity of Trichinella spiralis to anthelmintic treatment during the first 3 days of infection in mice were studied. Oral administration of either mebendazole or albendazole at 6.25 mh/kg 2 hr after exposure to infection eliminated 95-100% of the worms as determined at necropsy on day 7 postinoculation. Beyond the first day of infection the sensitivity of the parasite to benzimidazole therapy was much reduced and an oral dose of 50 mg/kg was only partially but significantly active against the adult worms. Despite decline in drug sensitivity during the enteral phase, gavage administration of either mebendazole or albendazole at 50 mg/kg for 5 consecutive days during the invasive phase of infection significantly reduced (96 and 67%, respectively) the number of larvae subsequently recovered from host musculature on day 45 postinoculation.


A redescription and neotype designation for Parelaphostrongylus odocoilei (Nematoda: Metastronglyoidea). Parelaphostrongylus odocoilei is redescribed from worms collected from the type host (Odocoileus hemionus columbianus) in California, as well as material from experimentally infected mule deer (O. h. heminus) in Alberta. A single male specimen from the California material is designated as the neotype of P. odocoilei, the type species of Parelaphostrongylus. The male copulatory structures of the 3 species of Parelaphostrongylus (P. tenuis, P. anderscni, and P. odocoilei) are reviewed and a key for the identification of males is provided.


Specific antibody levels in the serum of Heligmosomoides polygyrus-infected mice. Sera from ICR/CD mice were assayed by radial immunodiffusion following oral infection and challenge with Heligmosomoides polygyrus larvae. Infection of these mice was found to alter the concentrations and classes of immunoglobulins, as well as the levels of antiparasitic antibody. Challenge of single- or multiple-infected mice with viable larvae resulted in the appearance of anti-H. polygyrus IgA and IgG in the serum. The kinetics of the detection for both of these antibody classes were consistent with an anamnestic response to an antigen isolated from adult nematodes. There also appeared to be an association in resistant mice of serum IgA levels with early and late events in the life cycle of the parasite.


Spirocamallanus cricotus sp. n. and S. halitrophus sp. n. (Nematoda: Camallanidea) from fishes in the northern Gulf of Mexico. Spirocamallanus cricotus sp. n. (= S. pereirai, in part) and S. halitrophus sp. n. are described from marine fishes of the northern Gulf of Mexico. Spirocamallanus cricotus has a ledge anterior to the basal ring in the buccal capsule, similar spicules with a ratio of 1:1.4 to 2.1, 3 pre- and 5 postcloacal papillae, and 8 rectal glands in the female; S. halitrophus lacks the ledge and possesses dissimilar spicules with a ratio of 1:1.3 to 1.8, 3 pre- and 6 postcloacal papillae, and 4 rectal glands in the female.


Studies on intestinal immunity against tetrathyridia of Mesocestoides corti (Cestoda) in mice. In vitro antiparasitic effects were observed in intestinal extracts from NAMRU mice subcutaneously vaccinated with live tetrathyridia of Mesocestoides corti. All of the tetrathyridia incubated in intestinal extracts from subcutaneously vaccinated mice were dead within 8 hr and completely digested within 24 hr. Tetrathyridia incubated in intestinal extracts from mice either previously orally infected with live tetrathyridia or control mice were alive after 24 hr. A considerable number (17/20) of tetrathyridia pretreated with mouse serum from subcutaneously vaccinated mice were killed within 8 hr of incubation in intestinal extracts from untreated donor mice. The majority of the worms pretreated with either normal mouse serum or phosphate buffered saline (pH 7.2) were alive after 8 hr of incubation in intestinal extracts from untreated donor mice.


The occurrence and distribution of 5-hydroxytryptamine in Hymenolepis diminuta and H. nana. The presence of 5-HT in Hymenolepis diminuta and Hymenolepis nana was detected by 2 biochemical methods and as yellow fluorescence in a histochemical method. In H. diminuta, 5-HT was found in a concentration of about 1.2 micron/g; this amount did not vary significantly in worms aged 6 to 18 days or more or in various regions of the worm. In H. nana, 5-HT was found in a concentration of about 1.8 micron/g. It was histochemically localized in H. diminuta and H. nana in a pattern similar to that of acetylcholinesterase previously described in these 2 cestodes, and it may be the opposing neuro-transmitter to acetylcholine. The lack of 5-HT in the vestigial rostellum of H. diminuta may be correlated with loss of function of this organ.


Progamotaenia ruficola sp. n. (Cestoda: Anoplocephalidae) from the red kangaroo, Macropus rufus (Marsupialia). Progamotaenia ruficola sp. n. is described from the red kangaroo (Macropus rufus) from New South Wales, Australia. It is distinguished from other similar species having paired, nondiverticulate uteri in each prolottis: Progamotaenia festiva (Rudolphi 1819), P. diaphana (Zschokke 1907), and P. macropodis Beveridge 1976, by the extremely broad, straight-edged velum, the lack of an external seminal vesicle, the cirrus armature, the number of testes, the lack of vaginal atrophy following insemination, and the morphology of the egg.


Eimeria waiganiensis sp. n. from the green-winged ground dove (Chalcophaps indica Linnaeus) and the magnificent ground pigeon (Otidiphaps nobilis Gould) in Papua New Guinea. Eimeria waiganiensis sp. n. is described from Green-winged ground dove (Chalcophaps indica Linnaeus) and the Magnificent ground pigeon (Otidiphaps nobilis Gould) in Papua New Guinea. Oocysts broadly ovoid, 22-25 by 19-23 micron (24 by 22 micron); L/W ratio 1.08-1.2 (1.1). Oocyst surface smooth, wall light brown, 1.5 micron thick, 1-layered, the inner surface appearing pitted. Micropyle (4-6 micron) and 2 to 4 polar granules present; oocyst residuum absent. Sporocysts ovoid, 9.0-10.5 by 6.0-7.5 micron (10 by 7 micron) with prominent conical Stieda body and small substieda body. Small, finely-granular sporocyst residuum is sanwiched between the sporozoites. The elongate-ovoid sporozoites possess distinct anterior and posterior refractile globules. Two of 4 ground doves and 1 of 3 ground pigeons were infected with E. waiganiensis sp. n.


Gastrointestinal parasitism of Iowa coyotes in relation to age. Taenia sp., Physaloptera sp., Ancylostoma caninum, Toxascaris leonina, and/or Trichuris vulpis were recovered from gastrointestinal tracts of 141 and 144 (97.9%) coyotes ranging from 1/2 to 8 1/2 years of age. Ancylostoma caninum exhibited a significant decline in both prevalence and mean number per coyote with increasing age of the host. Taenia sp. appeared with consistently high prevalence in all age classes. Physaloptera sp. and T. leonina showed general reductions in prevalence in all age classes. Physaloptera sp. and T. leonina showed general reductions in prevalence and mean nubmer with increasing host age, although the data were not statistically significant. Coccidia were found in 15 of 58 (25.9%) fecal flotations.


Plasmodium pessoai sp. n. from two Costa Rican snakes. A unique malaria parasite species was found in 1/1 Spilotes pullatus (Colubridae) and 1/70 Lachesis muta (Crotalidae) from the moist Atlantic lowland forests of eastern Costa Rica. It is distinguished by small, sausage-shaped gametocytes (x 10.4 by 4.6 mu), growing schizonts that often contain a noticeable digestive vacuole with the contents partially visible, and striking spherical or bouquet-shaped segmenters whose precise merozoite numbers are difficult to discern (about 22-32) because of an intensely staining magenta or rose-colored substance in the matrix of the surrounding vacuole.


Effects of Gulf Coast ticks on blood composition and weights of pastured Hereford steers. Studies conducted in 1975 and 1976 were made of lightweight Herefored steers, pastured on native grass pasture and infested with Gulf Coast ticks, Amblyomma maculatum Koch. The effects of tick infestations on the blood composition and weights of steers over an 8-week period were measured each year and compared to tick-free animals maintained similarly. By the end of the 8-week study infested animals averaged 8.21 kg less than control animals in 1975 and 12.42 kg less in 1976. Of the blood parameters measured significant decreases in Hb, and a lymphopenia, neutrophilia, and basophilia occurred in infested animals in 1975. In 1975 and 1976 after infestations began significant increases occurred in total serum protein, serum globulin, and plasma fibrinogen, and decreases occurred in the albumin/globulin ration of infested animals. Of the serum globulin fractions, only gamma globulin increased in infested animals in 1975 and alpha globulin in 1976. Also, during both years, decreases occurred over time in the number of ticks attaching.


The topography of the exoskeleton of Cediopsylla simplex (Baker 1895) (Siphonaptera: Pulicidae). I. The head and its appendages. A topography of the exoskeleton of the head of Cediopsylla simplex (Baker 1895) is presented, based on an examination with the scanning electron microscope. Major sensory regions were observed on the fronto-occipital region, on the antennae, and on the maxillary palps. Sensilla basiconica were observed in all 3 regions, chemosensory hairs are absent, and unique pit sensilla were observed in the clubs of the antennae. The mouthparts are described and illustrated in detail. Other cuticular structures are illustrated, such as hairs, bristles, combs, cuticular teeth, and microtrichia. Sexual dimorphism is evident in the distribution of sensilla basiconica in the fronto-occipital regional and the clubs of the antennae. The validity of the generic name Cediopsylla Jordan 1925 is questioned.


Pharmacokinetics of Aryldihydro-s-triazines with antifolate activity II: Blood levels and their relevance to antineoplastic activity in rats. Blood levels of three aryldihydro-s-triazines in rats were followed: 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-phenyl-s-triazine (I), the prototype of the series; 4,6-diamino-1-(3,4-dichlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine (II); and N-(m-tolyl)-p-(4,6-diamino-1,2-dihydro-2,2-dimethyl-s-triazin-1-yl)hydrocinnamide (III). The blood profiles obtained provide substantial evidence that III, but not II, was precipitated in the peritoneal cavity where it was injected. Precipitation after intraperitoneal injection may explain why III and similar triazines with long nonpolar chains have been reported to be more active against intraperitoneal Walker 256 tumor than is II, even though the latter compound is a far more potent inhibitor of Walker 256 dihydrofolate reductase and of tumor cell cultures in vitro. Precipitation in the peritoneal cavity also may be involved in the difficulty of obtaining the toxicity-free antineoplastic activity expected from certain aryldihydrotriazines selectively inhibiting neoplastic dihydrofolate reductase.


Synthesis, toxicity, and cardiovascular properties of N-aralkyl- and N-acyl-5-aminoethylindans. Secondary amines and amides of 5-aminoethyl-6-methoxyindan and 5-aminoethyl-6-methylindan were synthesized, and the blood pressure lowering effects and accompanying changes in heart rate were evaluated in the unanesthetized desoxycorticosterone acetate hypertensive rat. The acute toxicities of the compounds were determined in mice. The amines were significantly more potent than the amides as antihypertensive agents and also were more toxic. 5-(3,4-Dimethoxybenzyl)aminoethyl-6-methylindan produced the greatest depression in systolic blood pressure at the dose level studied. Structure-activity relationships relevant to blood pressure lowering, heart rate, and toxicity are discussed.


Flavin-catalyzed photooxidation of an acridan drug: a reinvestigation. Anaerobic irradiation of flavin derivatives (IIalpha and IIbeta) in the presence of 2-chloro-9-(3-dimethylaminopropyl)acridan phosphate (Ialpha) resulted in the reduction of the flavins to IValpha and IVbeta and oxidation of an equimolar amount of Ialpha to IIIalpha. This photoreduction occurred from the first excited triplet state of IIalpha and IIbeta and proceeded via a covalent intermediate (V) between flavin and the acridan derivative. If the N-10 of the acridan was blocked by a methyl group, e.g., Ic, V could be observed spectrophotometrically at -40 degrees, decomposing homolytically on warming. With N-10 unsubstituted acridan derivatives, e.g., Ialpha and Ibeta, V could not be observed because of fast heterolytic decomposition, yielding IValpha, IVbeta, and the acridine compounds IIIalpha and IIIbeta. All photoreactions showed a kinetic isotope effect between 1.50 and 2.20 when position 9 of the acridan compounds was substituted by deuterium instead of hydrogen.


Structural survey of carbonate-containing antacids. A series of carbonate-containing antacids was examined by IR and X-ray analysis to establish the role of carbonate and to compare the structure of the antacids to naturally occurring carbonate minerals. Based on IR analysis, the relative degree of perturbation of carbonate increases in the order calcium carbonate, carbonate-containing aluminum hydroxide gel, and dihydroxyaluminum sodium carbonate. The crystalline carbonate-containing antacids were poorly organized forms of the minerals calcite, CaCO3; dawsonite, NaAl(OH)2CO3; and hydrotalcite, Mg6Al2CO3(OH)16-4H2O. Amorphous carbonate-containing aluminum hydroxide gel can be classified mineralogically as amorphous aluminum hydroxycarbonate. IR and X-ray evidence indicates that magaldrate has a hydrotalcite-like structure with sulfate as the major interlayer anion and carbonate also present in the interlayer space.


Treatment of neuroblastoma in mice with bromoacetylcholine and bromoacetate. Bromoacetylcholine (30 mg/kg intratumor one to three times per day) and bromoacetate (12 mg/kg intratumor two times per day) inhibited neuroblastoma in A/J mice efficiently and prolonged the lifespan of these animals at least 200%. Since the neuroblastoma-inoculated A/J mice are considered to be comparable to human neuroblastoma, the cytolytic action of bromoacetylcholine and bromoacetate on murine neuroblastoma warrants further studies on patients. The fact that these tumors were cured in adult mice is very important because older children and adults with neuroblastoma have the poorest prognosis.


Comparison of two methods for obtaining size distribution characteristics of particulate matter in large-volume parenterals. The size distributions of the particulate matter present in six types of large-volume parenteral solutions, as determined by an automatic particle counter and a microscopic counting technique, were compared by plotting log N greater than D versus log D. The resulting data were analyzed individually and also as averages. The data showed a linear relationship between log N greater than D and log D over the 1-100-micron particle-size range, indicating that both methods determine a similar particle-size distribution. The data also indicated that the particle-size distributions were largely independent of the type of solution and obeyed a power law of the form N greater than D = N greater than 1DK. These observations suggest that the major source of contamination is air-borne dust particles, which fall into a solution randomly, and that it may be possible to monitor the smaller, more abundant particles with the automatic particle counter to obtain a rapid estimate of parenteral cleanliness. The automatic particle counter thus appears to be a viable alternative to the microscopic counting technique for assessing the particulate matter content of parenterals.


Isolation and characterization of the sesquiterpene lactones costunolide, parthenolide, costunolide diepoxide, santamarine, and reynosin from Magnolia grandiflora L. The germacranolide sesquiterpene lactones costunolide, parthenolide, and costunolide diepoxide were isolated from the leaves of Magnolia grandiflora L. Costunolide diepoxide might be, at least in part, an artifact derived from air oxidation of parthenolide. The root bark yielded only costunolide together with the two eudesmanolides, santamarine and reynosin. In an attempt to synthesize costunolide diepoxide, the action of m-chloroperbenzoic acid on parthenolide and on costunolide was studied. The products were costunolide diepoxide from parthenolide and the two cyclized derivatives, santamarine and reynosin, from costunolide. The elusive 1,10-epoxide was obtained by epoxidizing costunolide using a biphasic system containing sodium bicarbonate. Under these conditions, epoxidation of costunolide took place without cyclization.


Sustained release from inert wax matrixes I: drug-wax combinations. The melting and energy characteristics of several drug-wax combinations were investigated using differential scanning calorimetry. The phase diagrams of binary mixtures of tripelennamine hydrochloride and tolazoline hydrochloride with carnauba wax and castor wax showed no eutectic formation and gave no indication that a significant interaction was involved. However, in tripelennamine mixtures, a slight depression in the drug melting point was observed at around 50% concentration. For ternary systems, i.e., drug, carnauba wax, and stearyl alcohol, thermograms of samples prepared by a fusion method differed slightly from those obtained with mixtures formulated by dissolving all ingredients in chloroform and evaporating the solvent. However, the location of the peak of each component remained essentially the same. A plot of melting point versus concentration of each compound showed insignificant changes in melting point and indicated that no interaction was occurring. The phase diagrams suggested that the combinations are strictly physical and that it is the physical characteristics, such as the hardness and composition of the core and drug particle size, that influence the release or dissolution of drug from the waxy matrix.


Analysis of betamethasone and its organic esters in pharmaceutical products. A rapid, quantitative analysis for betamethasone and its organic esters at room temperature is described. The method is similar to the official blue tetrazolium reaction for corticosteroids, except that methylene chloride is used as the solvent. The reaction is complete in 27-69 min, and the formazans produced are stable for at least 90 min after the addition of tetramethylammonium hydroxide. The results of the analysis of 13 different pharmaceutical formulations by the proposed method are reported. The degradation of betamethasone and its esters caused by strong bases is a pseudo-first-order reaction in methylene chloride. The average half-life of the corticosteroids studied is 56 min under the basic conditions described.


Effects of paper on performance of antibiotic-impregnated disks. Grades of paper used in the manufacture and assay of antibiotic susceptibility disks have significant effects on the diffusion of antibiotics from the paper when compared to a control grade of paper. The papers also evoke different microbiological responses to changing concentrations of some antibiotics. Regulatory implications and the need for further standardization of assays among control laboratories are explored. Grades of paper generally used for assay and control of susceptibility disks, on the other hand, appear to be comparable to each other in both respects.