Biomedical subjects

R W Nelson

Publications and source records attributed to R W Nelson.

At least 145 records · Page 8Linked to original sources

PubMed1981

Intrathecal methotrexate-induced neurotoxicities.

The pharmacokinetics, therapeutic index, neurotoxicities, methods of administration, and dosages of intrathecal methotrexate are reviewed. The intrathecal administration of methotrexate can provide therapeutic concentrations in the cerebrospinal fluid (CSF) without the use of high-dose intravenous methotrexate. Major neurologic complications have been reported to occur in 3--40% of patients following intrathecal methotrexate. The development of neurotoxicity is related to dose, concentration of methotrexate in the CSF, age of the patient, anatomical and physiological abnormalities in the CNS, type of dilutional vehicle, intracranial radiation, and intravenous methotrexate. Substantial evidence is lacking that chemical preservatives and methotrexate breakdown products are risk factors. The use of intrathecal methotrexate is a reasonably safe and effective chemotherapeutic modality when proper administrative techniques are observed.

Humans↗

PubMed1979

Neuropsychological test performances of paranoid schizophrenic and brain-damaged patients.

Predicted that simple tests that require attention and motor speed would be able to differentiate paranoid schizophrenics from brain-damaged patients better than more complex, problem-solving neuropsychological tests. The strategy was to improve discrimination between schizophrenic and brain-damaged patients by selecting a schizophrenic subgroup with a recognized cognitive strong point. Fourteen organic, 14 paranoid schizophrenic, and 14 nonpsychotic psychiatric patients matched for sex, education, and IQ were tested. As predicted, the attention and speed measures differentiated the brain-damaged and paranoid groups, while the four more complex measures from the Halstead-Reitan Battery did not separate the groups. There were no significant differences between the two psychiatric groups.

Adult↗

PubMed1978

Multilayer film elements for clinical analysis: applications to representative chemical determinations.

Using the general concept of a dry multilayer analytical element, we can change chemical procedures and configurations to assay several blood components. In the assay of serum urea nitrogen, urease in the reagent layer catalyzes the hydrolysis of urea. A semipermeable membrane excludes aqueous base, but allows ammonia to diffuse to an underlying indicator layer. For the amylase determination, the enzyme hydrolyzes a dyed-starch substrate coated on top of the spreading layer; this produces small fragments, which diffuse to a registration layer. The increase of absorbance at 540 nm is correlated with amylase activity. Bilirubin complexes with a cationic polymer at the interface between the spreading and reagent layers. The direct reading at 460 nm allows determination of total bilirubin in the range 1 to 500 mg/liter. Tirglycerides are hydrolyzed in the spreading layer, and the resulting soluble glycerol readily diffuses into the reagent layer, where it is phosphorylated and subsequently oxidized by glycerophosphate oxidase to yield dihydroxyacetone phosphate and hydrogen peroxide. Peroxidase catalyzes production of a color commensurate with the hydrogen peroxide produced.

Amylases↗

PubMed1977

Determination of plasma and erythrocyte lithium concentrations by atomic absorption spectrophotometry.

We describe a method for determining plasma and erythrocyte lithium concentrations by atomic absorption spectrophotometry. Plasma and hemolyzed whole-blood are diluted and analyzed, with use of a lithium hollow-cathode lamp, at 670.8 nm. Erythrocyte lithium concentrations are calculated indirectly from the hematocrit. The standard deviation for a 0.43 mmol/liter pool of whole blood, run daily over 11 months, was +/-20 mumol/liter (CV=5.1). The lithium concentration of a lyophilized pool assayed periodically over the same period (n=127) was 1.84+/-0.05 mmol/liter (CV=2.7%). The relatively low erythrocyte/plasma lithium ratio and the microhematocrit centrifugation force (9600 to 13 600 X g) make corrections for trapped plasma insignificant. Problems with matrix matching and viscosity are overcome by using a plasma pool standard for calculations. Values for erythrocyte lithium concentrations were unchanged in samples stored at room temperature up to 24 h. Hemolysis appears to be of possible clinical significance. This method is useful as a routine clinical laboratory procedure for monitoring patients with affective disorders, who are undergoing therapy with lithium.

Erythrocytes↗

PubMed1976

Plasma and erythrocyte kinetic considerations in lithium therapy.

Developments in the analysis and pharmacokinetics of lithium, and the role of the pharmacist in the management of lithium therapy in affective disorders, are described. Research showing that lithium levels in the brain may be better predicted from erythrocyte lithium levels than plasma levels is reviewed. Also reviewed is lithium kinetics in affective disorders. The pharmacist (1) determines relevant aspects of the patient's condition, (2) develops an appropriate blood sampling schedule, (3) initiates and maintains a serial lithium erythrocyte and plasma patient profile, (4) evaluates erythrocyte and serum levels in relation to established criteria to provide a basis for differential diagnosis of the patient, and (5) individualizes lithium dosage and schedules. Four cases are used to illustrate this approach. It is suggested that outpatient mental health clinics would be likely settings for the further development of this clinical role.

Adult↗

PubMedDate not supplied

The use of bioreactive probes in protein characterization.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has in the past decade found routine use in the biological sciences. With this use has evolved several mass spectrometric-based methods directed at the intricate investigation of biomolecular structure and function. One such methodology involves the enzymatic modification of a protein prior to the mass spectrometric readout of the resulting products. The enzyme-modification/mass spectrometric approach has a definite use in a number of applications, including: the verification/identification of protein sequence, elucidation of post-translational modifications, the investigation of protein higher-order structure, and even the characterization of the modifying enzyme. To avoid the potentials of sample loss and autolytic interferences in the mass spectrum, mass spectrometer targets can be covalently derivatized with enzymes for use in the characterization procedures. The enzymatically active, or bioreactive, probes are used by application of the analyte to the activated surface, followed by application of a suitable MALDI matrix and mass analysis from the surface of the probe. Limited transfer and handling steps eliminate sample losses, and surface-tethered enzymes (and autolytic fragments) are prohibited from interfering with analytical signals in the mass spectra. In addition, the probes are rapid and easy to use. Reviewed here are issues of concern during the manufacture and use of the bioreactive probes, and application of the probes to investigate protein structure and function.

Amino Acid Sequence↗

PubMedDate not supplied

Advances in surface plasmon resonance biomolecular interaction analysis mass spectrometry (BIA/MS).

Ongoing, worldwide efforts in genomic and protein sequencing, and the ability to readily access corresponding sequence databases, have emphatically driven the development of high-performance bioanalytical instrumentation capable of characterizing proteins and protein-ligand interactions with great accuracy, speed and sensitivity. Two such analytical techniques have arisen over the past decade to play key roles in the characterization of proteins: surface plasmon resonance biomolecular interaction analysis (SPR-BIA) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). SPR-BIA is used in the real-time investigation of biomolecular recognition events, and is thereby capable of providing details on the association and dissociation kinetics involved in the interaction, information ultimately leading to the determination of dissociation constants involved in the event. MALDI-TOF is used in the structural characterization, identification and sensitive detection of biomolecules. Although the two techniques have found many independent uses in bioanalytical chemistry, the combination of the two, to form biomolecular interaction analysis mass spectrometry (BIA/MS), enables a technique of analytical capabilities greater than those of the component parts. Reviewed here are issues of concern critical to maintaining high-levels of performance throughout the multiplexed analysis, as well as examples illustrating the potential analytical capabilities of BIA/MS.

Amino Acid Sequence↗

PubMedDate not supplied

Practical considerations in BIA/MS: optimizing the biosensor-mass spectrometry interface.

Biomolecular interaction analysis mass spectrometry (BIA/MS) is a multiplexed analytical technique that utilizes a unique combination of surface plasmon resonance (SPR) and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the detection and analysis of small amounts of proteins residing in complex biological systems. In order to achieve high sensitivity during BIA/MS, certain experimental parameters and sequences of events need to be optimized and maintained. Immobilized ligand density, flow rate and biosensor control (in SPR-BIA) and matrix choice and application (in MALDI-TOF MS) have significant influence on the final outcome of the BIA/MS analysis and, consequently, need to be optimized and carefully controlled. In addition, chip washing and cutting are essential in converting the SPR-active sensor chips into target surfaces amenable to MALDI-TOF MS. Reviewed here are the prerequisites for successfully interfacing SPR-BIA with MALDI-TOF MS.

Biosensing Techniques↗

PubMedDate not supplied

Evaluation of peptide/metal ion interactions by UV laser desorption time-of-flight mass spectrometry.

A relatively recent method developed to determine the molecular weights of intact peptides and proteins, matrix-assisted UV laser desorption time-of-flight mass spectrometry (LDTOF-MS), has been evaluated as a new means to investigate the metal ion-binding properties of model synthetic peptides. A contiguous sequence of 25 residues on the surface of the 74 kDa human plasma metal-binding transport protein histidine-rich glycoprotein (HRG) has been identified as a bioactive metal-binding domain. The peptide, (GHHPH)5G, was synthesized and evaluated by LDTOF-MS before and after the addition of Cu(II) in solution with 2,5-dihydroxybenzoic acid as the matrix. In the absence of added Cu(II), the major protonated molecular ion (M + H)+ was observed to have a mass equal to its calculated mass (2904.0 Da). In the presence of Cu(II), however, five additional peaks were observed at mass increments of approximately 63.9 Da. The maximum Cu(II)-binding capacity observed for the 26-residue peptide (5 g-atoms/mol) suggested that up to 1 Cu(II) may be bound per 5-residue internal repeat unit (GHHPH) within this peptide; several other monovalent and divalent metal cations were not bound under identical conditions of analysis. The Cu(II)-binding stoichiometry was verified by spectrophotometric titration and by frontal analyses of the immobilized peptide with a solution of Cu(II) ions. These results demonstrate the ability to verify directly the solution-phase binding capacity of metal-binding peptides by LDTOF-MS.

Amino Acid Sequence↗

PubMedDate not supplied

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis.

Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.

Animals↗

PubMedDate not supplied

Occipito-cervico-thoracic spine fusion in a patient with occipito-cervical dislocation and survival.

A 16-year-old man with occipito-cervical dislocation and survival was treated at Rancho Los Amigos Medical Center. The patient had ligamentous instability between the occiput and the cervical spine. His neurologic level was complete at the C1 level, and he was dependent on a mechanical respirator. Sternocleidomastoid and other neck musculature were not functional. A fusion of the occiput to cervical spine and cervical spine to thoracic spine was performed to obviate the need for external neck support. The patient went on to fuse and is now independently mobile with a tongue-switch driven wheelchair with a respirator trailer 2 years after injury. The patient has no need for external support as a result of his fusion.

Adolescent↗

PubMedDate not supplied

Effect of thyrotropin storage on thyroid-stimulating hormone response testing in normal dogs.

The stability of reconstituted, refrigerated thyrotropin was evaluated. Thyrotropin (TSH) was reconstituted at the start of the study and stored at 4 degrees C. A TSH stimulation test was performed in eight healthy, euthyroid dogs at weekly intervals for 1 month. In seven of eight dogs, there was no significant difference (P less than 0.05) between the post-TSH T3 concentrations and the post-TSH T4 concentrations for the duration of the study. For one dog, the post-TSH T4 concentration was below the normal post-TSH T4 range following the administration of reconstituted TSH that had been stored 4 weeks. The T3 response to the TSH, however, was normal. This dog responded normally to freshly reconstituted TSH. The results of this study suggest that reconstituted bovine TSH can be stored at 4 degrees C for at least 3 weeks without loss of biologic activity in the dog.

Animals↗

PubMedDate not supplied

Nutritional management of idiopathic chronic colitis in the dog.

Idiopathic chronic colitis was diagnosed in 13 dogs. Owners sought veterinary care because of semiformed to liquid feces, fresh blood and/or mucus in the feces, tenesmus, increased frequency of defecation, vomiting, weight loss, and flatulence in their dogs. A lymphocytic, plasmacytic infiltration in the colonic lamina propria was found on colonic biopsy specimens. Signs resolved in all 13 dogs after they were fed a low residue, easily assimilated, relatively hypoallergenic diet. In 11 dogs, two commercial diets not previously fed to these dogs were successfully substituted for the initial test diet, without causing recurrence of signs. Only two of these 11 dogs subsequently tolerated a switch to diets that had been fed at the time of onset of signs of colitis. All 13 dogs have been successfully managed from 2 months to 28 months following the initiation of dietary therapy. The results of these dietary challenges strongly suggest a dietary role in the pathogenesis of this disorder, and also illustrate the importance of dietary therapy in the management of idiopathic chronic colitis.

Animals↗

PubMedDate not supplied

Acromegaly in 14 cats.

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

Acromegaly↗

PubMedDate not supplied

Hypoglycemia in four dogs with smooth muscle tumors.

Tumor-associated hypoglycemia has been reported in dogs with pancreatic beta-cell tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes 4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma). Presenting clinical signs included grand mal seizures, lethargy, weakness, ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach and jejunum stained diffusely positive for glucagon. Blood glucose concentrations rapidly returned to normal after complete surgical resection of the tumors, and clinical signs associated with hypoglycemia resolved. Long-term follow-up available in 3 of the 4 dogs found no recurrence of clinical signs related to hypoglycemia at 15, 31, and 38 months after surgery, respectively.

Animals↗

PubMedDate not supplied

Basal and glucagon-stimulated plasma C-peptide concentrations in healthy dogs, dogs with diabetes mellitus, and dogs with hyperadrenocorticism.

Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after i.v. glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.

Adrenocortical Hyperfunction↗

PubMedDate not supplied

Effect of weight gain and subsequent weight loss on glucose tolerance and insulin response in healthy cats.

The effects of weight gain and subsequent weight loss on glucose tolerance and insulin response were evaluated in 12 healthy cats. Intravenous glucose tolerance tests (IVGTT) were performed at entry into the study, after a significant gain of body weight induced by feeding palatable commercial cat food ad libitum, after a significant loss of body weight induced by feeding a poorly palatable purified diet to discourage eating and promote fasting, and after recovery from fasting when body weight had returned to pre-study values and cats were eating commercial foods. A complete physical examination with measurement of body weight was performed weekly, a CBC and serum biochemistry panel were evaluated at the time of each IVGTT, and a liver biopsy specimen obtained 2 to 4 days after each IVGTT was evaluated histologically for each cat. Mean serum glucose and insulin concentrations after glucose infusion and total amount of insulin secreted during the second 60 minutes and entire 120 minutes after glucose infusion were significantly (P < .05) increased after weight gain, as compared with baseline. At the end of weight loss, cats had hepatic lipidosis and serum biochemical abnormalities consistent with feline hepatic lipidosis. There was a significant (P < .05) increase in mean serum glucose concentration and t1/2, and a significant (P < .05) decrease in mean serum insulin concentration and the glucose disappearance coefficient (K) after glucose infusion for measurements obtained after weight loss, compared with those obtained after weight gain and at baseline. Insulin peak response, insulinogenic index, and total amount of insulin secreted during the initial 10 minutes, 20 minutes, and 60 minutes after glucose infusion were decreased markedly (P < .05), compared with measurements obtained after weight gain and at baseline. In addition, the total amount of insulin secreted for 120 minutes after glucose infusion was decreased markedly (P < .05) in measurements obtained after weight loss, compared with those obtained after weight gain. At the end of recovery, all cats were voluntarily consuming food, serum biochemical abnormalities identified after weight loss had resolved, the number and size of lipid vacuoles in hepatocytes had decreased, and results of IVGTT were similar to those obtained at baseline. These findings confirmed the reversibility of obesity-induced insulin resistance in cats, and documented initial deterioration in glucose tolerance and insulin response to glucose infusion when weight loss was caused by severe restriction of caloric intake.

Animals↗

PubMedDate not supplied

Glycosylated hemoglobin concentration for assessment of glycemic control in diabetic cats.

Blood glycosylated hemoglobin (GHb) concentration was quantified in 84 healthy cats, 9 cats with stress-induced hyperglycemia, 37 cats with newly diagnosed diabetes mellitus, and 122 diabetic cats treated with insulin or glipizide. Diabetic control was classified as good or poor in insulin-treated or glipizide-treated cats based on review of history, physical examination findings, changes in body weight, and measurement of blood glucose concentrations. Blood GHb concentration was determined using an affinity chromatography assay. Mean blood GHb concentration was similar for healthy normoglycemic cats and cats with transient, stress-induced hyperglycemia, but was significantly (P < .001) higher in untreated diabetic cats when compared with healthy normoglycemic cats. Mean blood GHb concentration was significantly (P < .001) higher in 84 cats with poorly controlled diabetes mellitus when compared with 38 cats in which the disease was well controlled. Mean blood GHb concentration decreased significantly (P < .01) in 6 cats with untreated diabetes mellitus after insulin and dietary treatment. A similar significant (P < .01) decrease in mean blood GHb concentration occurred in 7 cats with poorly controlled diabetes mellitus after diabetic control was improved by an increase in insulin dosage from 1.1 +/- 0.9 to 1.4 +/- 0.6 U/kg/ 24 h and by feeding a diet containing increased fiber content and in 6 cats with transient diabetes mellitus 8.2 +/- 0.6 weeks after discontinuing insulin treatment. There was a significant (P < .01) stress-induced increase in mean fasting blood glucose concentration and mean blood glucose concentration for 12 hours after administration of insulin or glipizide but no change in mean blood GHb concentration in 5 docile diabetic cats 12.2 +/- 0.4 weeks after the cats became fractious as a result of frequent hospitalizations and blood samplings. Results of this study suggest that evaluation of blood GHb concentration may be a clinically useful tool for monitoring glycemic control of diabetes in cats.

Animals↗