Doing more with less: new supply program cuts total delivered costs.
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Cost Savings↗
Biomedical subjects
R Adams
Publications and source records attributed to R Adams.
Neonatal septicemia in calves: 25 cases (1985-1990).
Historical, physical, and clinicopathologic findings in 25 septicemic calves were examined to further characterize the clinical features of naturally induced bovine neonatal septicemia. Owners often reported single organ disease, but physical examination revealed multiple organ disease in more than half the calves. A third of the calves were admitted as representative of a herd problem. Laboratory findings were variable, but commonly included changes in the differential WBC count and plasma fibrinogen concentration. Low serum immunoglobulin concentrations were found in approximately half the calves. Escherichia coli was the most frequently isolated organism, but gram-positive infections were found in 10%, and polymicrobial infections in 28%, of the calves. Previous antimicrobial administration did not appear to affect culture yield. At necropsy, lesions were seen in multiple organs in most calves. The respiratory and gastrointestinal systems were most commonly affected. Few of the calves had umbilical infections. The survival rate was poor (< 12%).
Animals↗
6-[18F]fluoro-L-dihydroxyphenylalanine metabolism and positron emission tomography after catechol-O-methyltransferase inhibition in normal and hemiparkinsonian monkeys.
Increased and sustained central delivery of L-dihydroxyphenylalanine (L-DOPA) is a desirable therapeutic strategy in Parkinson's disease. We investigated the effects of peripheral catechol-O-methyltransferase (COMT) inhibition, by the non-toxic drug nitecapone on the metabolism of 6-[18F]fluoro-L-dihydroxyphenylalanine (6FD) and on its positron emission tomography (PET) imaging in non-human primates. Nitecapone produced a dose-dependent inhibition in the formation of 3-O-methyl-6-[18F]fluorodihydroxyphenylalanine (OMFD). This inhibition of OMFD formation was attended by increased production of other metabolites, in particular 6-[18F]fluorodopamine (6FDA), 6-[18F]fluorodihydroxyphenylacetic acid (FDOPAC), 6-[18F]fluorohomovanillic acid (FHVA) and [18F]-sulfated conjugates (FSC). Although nitecapone had no effect on plasma 6FD pharmacokinetics, high-dose nitecapone increased contrast of cerebral 18F uptake and retention between regions with high (striatum) versus sparse (parieto-occipital lobes) dopaminergic innervation. 18F uptake contrast was also improved between structures known to possess an intermediate dopaminergic innervation, including the upper brainstem, frontal and temporal lobes, versus sparsely innervated regions. This increased contrast was secondary to decreased activity in sparsely innervated structures and not to increased activity in highly innervated structures. Contrast was correlated inversely with the plasma OMFD/6FD concentration ratio, OMFD being the main 6FD metabolite which can cross the blood brain barrier. We conclude that nitecapone is an effective inhibitor of COMT in non-human primates. This inhibition results in increased 6FD flux through other catabolic pathways. Because of decreased OMFD formation, however, COMT inhibition improves the specificity of 6FD-PET and facilitates in-vivo detection of a wide range of dopaminergic innervation densities in cerebral structures.
Animals↗
Cloning and mapping of the Bacillus subtilis locus homologous to Escherichia coli ent genes.
Here, we report the cloning of a 3.5-kb HindIII fragment of chromosomal Bacillus subtilis DNA carrying at least two open reading frames exhibiting significant homology with entA and entE of Escherichia coli. This B. subtilis ent locus was mapped at about 41 degrees. Its inactivation did not cause any detectable phenotype.
Bacillus subtilis↗
Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans.
OBJECTIVES: This study evaluated the safety, efficacy and validity of 6-[18F]fluorodopamine positron emission tomographic scanning of cardiac sympathetic innervation and function in humans. METHODS: Positron emission tomography (PET) scans, arterial blood and urine were obtained after a 3-min intravenous infusion of 6-[18F]fluorodopamine (1 to 4 mCi, 188 to 809 mCi/mmol) in healthy volunteers, with or without pretreatment with oral desipramine to inhibit neuronal uptake of catecholamines. RESULTS: 6-[18F]Fluorodopamine PET scanning visualized the left ventricular myocardium. Blood pressure increased slightly and transiently. The estimated absorbed radiation dose to the main target organ, the wall of the urinary bladder, was 0.8 to 1.0 rad/mCi of injected 6-[18F]fluorodopamine. By 24 h after the injection, the main 6F-compound in urine was 6F-vanillymandelic acid, a metabolite of 6F-norepinephrine. Desipramine attenuated accumulation of myocardial 6-[18F]fluorodopamine-derived radioactivity and plasma 6F-dihydroxyphenylacetic acid. CONCLUSIONS: 6-[18F]Fluorodopamine produces negligible hemodynamic effects and acceptable radiation exposure at doses that visualize the left ventricular myocardium. Sympathetic nerves take up 6-[18F]fluorodopamine, which is translocated from the axoplasm into storage vesicles, where is it beta-hydroxylated to the fluorinated analogue of the sympathetic neurotransmitter norepinephrine. Therefore, the basis for visualization of myocardium after 6-[18F]fluorodopamine injection in humans is radiolabeling by 6-[18F]fluorodopamine and 6-[18F]fluoronorepinephrine of vesicles in sympathetic terminals. 6-[18F]Fluorodopamine PET scanning provides a novel means for assessing sympathetic innervation and function noninvasively in the human heart.
Adult↗
Single photon emission computerised tomography in elderly patients with Alzheimer's disease and multi-infarct dementia. Regional uptake of technetium-labelled HMPAO related to clinical measurements.
Single photon emission computerised tomography (SPECT) was used to measure regional brain uptake of technetium-99m hexamethylpropyleneamine oxine (Tc99m-HMPAO) in elderly patients with Alzheimer's disease (AD), multi-infarct dementia (MID) and normals (n = 20 in each group). Different patterns of uptake were found between groups when cortical uptake was normalised to cerebellar uptake. Reductions occurred in all regions in AD, being most marked in temporal and posterior parietal areas. Significant correlations were found in AD between memory impairment and decreased temporal uptake bilaterally, and between duration of illness and reduced uptake in most brain regions. MID patients showed higher uptake in the anterior parietal region than did the other groups. A variable comparing anterior to posterior uptake significantly discriminated the two patient groups.
Aged↗
The effect of manipulation on range of movement at the ankle joint.
Manipulation is commonly used by physiotherapists in the treatment of musculoskeletal disorders; however, there have been few studies evaluating its use in peripheral joints. The purpose of this study was to investigate the effect of manipulation on dorsiflexion range of movement at the ankle joint. Twenty asymptomatic subjects participated, one ankle acting as the experimental ankle and receiving the manipulation intervention, while the other ankle acted as the control. The manipulation studied was a longitudinal talocrural manipulation. Dorsiflexion range of movement was measured at 5 consecutive torque levels pre and post manipulation intervention in the experimental ankle and pre and post no intervention in the control ankle. These values were compared using analysis of trend within an analysis of variance framework. There was no statistically significant change in dorsiflexion range of movement following manipulation. It was concluded that in the case of asymptomatic subjects these results did not provide support for the experimental hypothesis that a single talocrural manipulation alters dorsiflexion range of movement. It was suggested that future research investigate the effects of manipulation in a symptomatic population.
Adult↗
3-Deazaadenosine: a therapeutic strategy for myasthenia gravis by decreasing the endocytosis of acetylcholine receptors.
The basic abnormality in myasthenia gravis is the depletion of acetylcholine receptors (AChRs) at neuromuscular junctions, which is due in part to excessive endocytosis brought about by the action of pathogenic antibodies. We asked whether 3-deazaadenosine (3DZA), an inhibitor of phospholipid methylation, could decrease the rate of endocytosis of muscle AChRs and thereby interfere with this pathological process. The rationale for the use of 3DZA is that methylation of phospholipids alters membrane properties, and inhibition of methyltransferase reactions is known to slow the process of endocytosis. In this study, we have tested the effects of 3DZA and other methylation inhibitors on the degradation and synthesis of AChRs in an in vitro model of myasthenia gravis, using primary rat skeletal muscle cultures and serum from human myasthenic patients. In normal cultures (without myasthenic serum), 3DZA inhibited AChR degradation with a broad dose-response relationship, beginning as low as 2 microM (P < .0001). There was no acute effect on synthesis of AChRs or on other measures of muscle cell integrity. When human myasthenic serum was added to the cultures to accelerate the endocytosis and degradation of AChRs, 3DZA still potently inhibited the degradation rate. Because the drug allows accumulation of AChRs in the surface membrane of the muscle cell by reducing endocytotic degradation, it provides a potential strategy for therapy in human myasthenia gravis.
Animals↗
Physiologic differences between twin and single born beef calves in the first two days of life.
Behavioral observations and hematological, serum biochemical and blood gas measurements were made on 8 naturally occurring twin calves during the first 48 hours of life. These values were compared to similar measurements collected from 30 single born calves, born under the same calving conditions. All calves survived to at least 3 weeks of age without physically detectable disease. Although the gestational age of the twins and singles were not different, the twins had a lower mean birth weight. Calving difficulty score, time interval to standing and time interval to nursing were not different between the 2 groups. Twin calves had significantly lower rectal temperatures, arterial oxygen tensions and blood glucose concentrations than the single calves through the first 12 hours of life. Hct, Hgb concentration, and RBC were lower in twin calves throughout the 48 hour period. The N:L ratio was lower in the twins at birth. Mean serum IgG1 concentrations were lower in twins only at 24 hours whereas IgM concentrations were lower at both 24 and 48 hours in twins. Serum chemistry value differences between twin and single calves were most numerous at 24 hours of age when serum proteins, urea nitrogen, total bilirubin, sodium, chloride, and total calcium concentrations were higher in the twins and serum phosphorus concentration was lower in the twins.
Animals↗
Gram-negative bacterial infection in neonatal New World camelids: six cases (1985-1991).
Gram-negative bacterial infections were documented in 6 neonatal New World camelids (5 Ilamas and 1 alpaca). The organisms isolated from blood before death or from multiple organs after death were Escherichia coli (n = 3), Actinobacillus sp (n = 1), and Klebsiella pneumoniae (n = 1). Only 2 crias survived, and 1 became blind secondary to retinal detachment and ocular inflammation, which developed after treatment for bacterial infection. Abnormal events during the perinatal period (prematurity, dystocia, cesarean section, weak at birth) were reported in all 6 crias. Signs of depression, convulsions, and/or coma were observed in all animals. Diarrhea and respiratory distress were also noticed in the 3 crias that died shortly after admission. Serum immunoglobulins were assessed, but without the benefit of a stall-side test specific for Ilama immunoglobulins. All crias were suspected to have poor transfer of maternal immunoglobulins. Hemograms and serum biochemical values prior to the initiation of treatment were obtained on 5 of the 6 crias. Total nucleated cells ranged from 1,400 to 23,100 cells/microliter. Four of the 5 crias has a left shift, and 2 crias had toxic neutrophils. Serum glucose concentrations, measured in 5 of 6 crias, ranged from 83 to 293 mg/dl. Serum creatinine values were high in 2 of 5 crias, 1 of which had acute tubular necrosis. Three crias with high serum electrolyte (sodium, chloride, or potassium) values subsequently died. Arterial blood gas values were assessed in 3 crias, 1 of which had respiratory alkalosis and mild hypoxemia.
Animals↗
The use of transcranial ultrasonography to predict stroke in sickle cell disease.
BACKGROUND: Stroke, especially cerebral infarction, is a major cause of morbidity and mortality in children with sickle cell disease. Primary prevention of stroke by transfusion therapy may be feasible if there is a way to identify the patients at greatest risk. Transcranial Doppler ultrasonography can measure flow velocity in the large intracranial arteries. The narrowing of these arteries, which leads to cerebral infarction, is characterized by an increased velocity of flow. METHODS: Using transcranial Doppler ultrasonography, we prospectively measured the velocity of cerebral blood flow in children and young adults being followed because of sickle cell disease. The results were classified as either normal or abnormal on the basis of the highest velocity of flow in the middle cerebral artery. Abnormal velocity was defined as a flow greater than or equal to 170 cm per second, a definition determined by post hoc analysis to maximize the predictive success of the test. The end point was a clinically apparent first cerebral infarction. RESULTS: Two hundred eighty-three transcranial ultrasound examinations were performed in 190 patients with sickle cell disease (age at entry, 3 to 18 years). After an average follow-up of 29 months, cerebral infarction was diagnosed in seven patients. In 23 patients the results of the ultrasound examinations were abnormal, and in 167 patients they were normal. The clinical and hematologic characteristics of the two groups were similar, but six of the seven strokes occurred among the 23 patients with abnormal ultrasound results (P less than 0.00001 by Fisher's exact test). In this group, the relative risk of stroke was 44 (95 percent confidence interval, 5.5 to 346). CONCLUSIONS: Transcranial ultrasonography can identify the children with sickle cell disease who are at highest risk for cerebral infarction. Periodic ultrasound examinations and the selective use of transfusion therapy could make the primary prevention of stroke an achievable goal.
Adolescent↗
Follow-up studies in a case of unusual congenital myopathy, suggestive of nemaline type.
A 20-month-old boy--offspring of consanguinous parents, whose mother presumably had subclinical myopathy--presented with clinical signs of congenital non-progressive myopathy, neurogenic-myogenic electromyographic findings and normal motor conduction velocity. Biopsy of quadriceps muscle showed fiber-type disproportion with hypotrophic type 1, hypertrophic 2A and absent 2B fibers. Subsarcolemmal segmental foci of abnormally, in part regularly arranged bundles of mostly thin myofilaments were found in 13% of hypotrophic type 1 fibers. Rods were seen in only 1 fiber out of 20 tissue blocks. Reexamination 6 years later revealed slightly increased muscle force, myopathic EMG pattern and borderline motor and sensory nerve conduction velocities. Biopsy specimen from deltoid muscle consisted of untypable fibers of varying diameters with jagged Z-lines and increased variability of myofibrillar diameters. Multiple rods were present in 1% of the fibers, the formerly seen segmental foci in 0.1% only. Several intramuscular nerves were normal. The case contributes some new features to the spectrum of congenital myopathies of the nemaline type and suggests different stages of arrested maturation of type 1 fibers at least in this particular case.
Biopsy↗
Reliability of speech naturalness ratings of stuttered speech during treatment.
This study evaluated the reliability with which relatively sophisticated and unsophisticated judges used a 9-point scale to rate the speech naturalness of speech samples from 10 clients in a treatment program for stuttering that employed prolonged speech. Judges rated repeated speech samples from different speakers during various phases of the program. Different groups of sophisticated and unsophisticated judges made ratings at either 15 sec, 30 sec, or 60 sec intervals while listening to the samples. Of the reliability indices, intraclass correlations were significantly higher for sophisticated judges although the consistency and agreement of unsophisticated judges were generally equivalent to that of sophisticated judges. Both agreement scores and intraclass correlations were higher when ratings were made at 60 sec rather than 30 sec intervals. The predominant variable that influenced judgement reliability appeared to be differences among the subjects. The methodology partially replicated Martin, Haroldson, and Triden's (1984) initial investigation on the use of this scale. However, the levels of intra- or interjudge reliability in this study were lower than the levels achieved by Martin et al.'s judges. There were important differences between the Martin et al. study and this one that may account for the findings, and these are discussed.
Adult↗
Differences in neutralization of simian lentivirus (SIVMAC) in lymphocyte and macrophage cultures.
Comparison of neutralization of SIVmac251 in primary macrophage cultures with neutralization in lymphocytes (CEM174 cells) showed that neutralizing antibodies induced by SIV251 in infected rhesus macaques protected both macrophages and T lymphocytes against infection when the virus was preincubated with the antibodies. In macrophages, the neutralizing antibodies also protected against infection when added 1 hour after the virus. Addition of antisera to macrophages between 24 and 48 hours after virus inoculation resulted in infection with continuous release of small amounts of p24 into the supernatant fluids but these antibody-treated cultures failed to exhibit cytopathic virus replication. In contrast, the same neutralizing antisera did not protect lymphocytes against infection and subsequent cytopathic replication of the virus when added only 1 hour after virus inoculation. This distinction in the effect that neutralizing antibodies had on the development of cytopathic infection in lymphocytes and macrophages when added after virus inoculation, suggests that they could alter the dynamics of virus replication and therefore the pathogenesis of disease.
Animals↗
Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques.
Neurological disease resulting from lentivirus (including human immunodeficiency virus) infections is usually caused by a strain of virus that replicates productively in microglia in vivo and in macrophage cultures in vitro. We undertook this study using the model of simian immunodeficiency virus in macaques (SIVmac) to test the hypothesis that macrophage tropism is a prerequisite for neurotropism of the virus. Using molecularly cloned SIVmac239, a virus which is lymphocyte- but not macrophagetropic, we showed that this virus failed to infect brain after intracerebral (i.c.) inoculation into two macaques. Rather, these inoculations resulted in disseminated infection in lymphoid organs and the bone marrow. Two sequential passages of infected bone marrow cells inoculated i.c. into new macaques resulted in severe neurological disease and classical neuropathological lesions. Virus obtained from affected brain answered the hypothetical question: it was neurotropic and macrophagetropic. New findings in the study were that both lymphocyte- and macrophage-tropic viruses were present in the animals, but the viruses localized in different tissues: the lymphotropic virus in the spleen, lymph nodes, and plasma and the macrophagetropic virus in the brain and lungs. To determine whether the brain virus was preferentially neurotropic and whether it had neuroinvasive properties, infectious brain homogenate was inoculated into one animal i.c. and into two others peripherally. The i.c. inoculated animal developed fatal encephalitis 5 months later, and examination of tissues showed cell-free virus only in brain homogenates. Only microglia were infected despite persistent viremia and infection in bone marrow cells. The two macaques inoculated peripherally remained healthy and were euthanized at 6 months. Virus replication was detected only in the bone marrow cells and peripheral blood mononuclear cells. No infection in any macrophage population in visceral organs was detected, and the virus did not invade the brain. The strictly microglial specificity of this virus suggested that different macrophage populations in the body may select specific phenotypes of lentivirus from the quasispecies of virus in the bone marrow. This could provide the basis for specific disease affecting different organ systems.
Adaptation, Biological↗
Predicting severity of tricyclic antidepressant overdose.
The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward.
Adolescent↗
Lentivirus induced arthritis in animals.
Retroviral arthritis in sheep and goats depends on persistent infection in the animals. Virus is latent in macrophage precursor cells and viral replication is initiated when these cells are induced to differentiate. Antiviral antibodies and cytokines modulate the efficiency of viral gene product expression. Specific cytokines induced during replication of the lentivirus in mononuclear cells are also responsible for directing infected cells from peripheral blood through the vascular endothelium to particular tissues. Cytokines induced by other infectious agents such as bacteria, mycoplasma or protozoa, may also contribute to this chemotactic process. Once in the tissue, macrophages interact with lymphocytes to induce an inflammatory cascade with further production of cytokines which enhances expression of class II major histocompatibility complex antigens and proliferation of B and CD8 lymphocytes. In addition, immune complexes between viral glycoproteins and immunoglobulins are produced locally and probably lead to further enhancement of pathological changes in the tissues.
Animal Diseases↗
The blepharogram in Horner's syndrome.
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Adult↗