Biomedical subjects
Publications and source records attributed to G F Johnson.
Following the curative resection of a pancreatic gastrinoma in a cat, gastrin peptides were purified from the tissue and sequenced. The sequence of cat gastrinoma G17 (18-34) confirms the previously published sequence. The sequence of cat G34 (1-34) is reported for the first time. The NH2-terminal portion of cat G34 differs from that of dog by having a Q (Gln) for L (Leu) at position 10 from the NH2-terminus.
The aim of this study was to examine cortisol dynamics over a range of plasma dexamethasone (DEX) levels using a two-dose dexamethasone suppression test (DST). Two doses of DEX (0.5 and 1.5 mg) were administered in a randomized crossover design to 29 inpatients with major depression and 26 controls to identify the upper range of plasma DEX levels that would allow reliable interpretation of DST results. It was hypothesized that due to inappropriately high plasma DEX levels following 1.5 mg, several depressed patients would switch from suppressors after the 1.5 mg dose to nonsuppressors after 0.5 mg. In contrast, the nondepressed controls with high DEX levels following 1.5 mg would remain suppressors after the lower dose. Fourteen patients were identified as having high 4 p.m. DEX levels (greater than 4 nmol/l) after the 1.5 mg DST. Cortisol was suppressed in all of the subjects with high DEX levels. After 0.5 mg, five of the eight depressed patients with high DEX levels switched to nonsuppressors. In contrast, all six controls with high DEX levels remained suppressors. These results indicate that patients with high DEX levels after a 1 mg DST should be retested with a lower dose. This strategy enhances the sensitivity of the DST without loss of specificity.
We describe a kinetic enzymic method for serum bicarbonate analysis, using wheat germ phosphoenolpyruvate carboxylase (EC 4.1.1.31) coupled through oxaloacetate reduction with NADH in the presence of malate dehydrogenase (EC 1.1.1.37). Inhibition with potassium thiocyanate yielded first-order kinetics with respect to bicarbonate over the concentration range of 0-45 mmol/L. The inhibitor was chosen by evaluating reaction data in the presence of different anions, with use of a monoexponential model. Criteria for first-order kinetics included a constant reaction half-life over the concentration range and SDest for the model comparable with the magnitude of spectrophotometric noise. We compared our kinetic method (y) with an automated ion-selective electrode method (x), obtaining the regression relationship y = 0.97x + 1.2 mmol/L (r = 0.991; n = 77; mean = 25.5 mmol/L; y = 25.3 mmol/L). Within-run precision from duplicates was 3.1% (mean = 25.2 mmol/L; n = 72). Total analytical precision (n = 12) was 9.4% (mean = 15 mmol/L) for the low control and 4.3% (mean = 32 mmol/L) for the high control. We conclude that the kinetic assay allows use of large serum-to-reagent ratios (1:100) and smaller amounts of NADH than an equilibrium assay. The assay is suitable for automated kinetic analysis.
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Two doses of dexamethasone (DEX) (0.5 and 1.0 mg) were administered in a randomized crossover design to 31 patients with major depression, 9 healthy controls, and 14 nondepressed psychiatric patients. Using this modified Dexamethasone Suppression Test (DST), minimum DEX levels of 6 nmol/liter at 8:00 AM and 2.0 nmol/liter at 4:00 PM were required to achieve reliable suppression of cortisol in healthy controls and nondepressed psychiatric patients. Failure to achieve these minimum plasma DEX levels was associated with similar rates of nonsuppression in both depressed and nondepressed patients, thereby reducing the specificity of the DST. Conversely, high DEX levels greater than 13 nmol/liter at 8:00 AM or 4.0 nmol/liter at 4:00 PM were associated with abnormal "suppressibility" in depressed patients, thereby reducing the sensitivity of the test. Controlling for plasma DEX concentrations by selecting a test result that fell within a plasma DEX window at 8:00 AM and 4:00 PM increased the sensitivity and specificity of the DST. Significant differences in plasma DEX between suppressors and nonsuppressors were no longer evident when comparing patients with adequate DEX levels, thus ensuring that cortisol escape reflected HPA axis changes associated with depression and not peripheral mechanisms responsible for the availability of DEX. These results suggest that the clinical utility of the DST would be significantly enhanced by extending the standard 1.0-mg DST and retesting those patients with levels outside the DEX window with a higher or lower dose. The data also indicate that the measurement of plasma DEX is essential to validly interpret DST status and highlight the need to standardize DEX assays to compare DST results between research centers.
The elimination of total digoxin after digoxin-specific Fab fragment therapy in a patient in end-stage renal disease is described. Two-component, nonlinear exponential regression of the patient's total digoxin concentration data revealed biphasic elimination: a fast phase with a half-life of 43 h and a slow phase with a half-life of 330 h. Serum total digoxin concentration decreased 20% 12 h after the initiation of Fab fragment therapy. The mean serum concentrations of total digoxin and apparent total digoxin as measured by fluorescence polarization immunoassay during a 520-h period after the initiation of therapy were 18.42 and 14.77 ng/ml, respectively (n = 15). The correlation between the two measurements was good (r = 0.987). The time course of free digoxin concentration obtained after ultrafiltration at 2, 20, or 37 degrees C is also described. The free digoxin concentrations (n = 10) at these temperatures averaged over a 282-h period were 0.35, 0.53, and 0.82 ng/ml, respectively (p less than 0.001, 2 degrees C vs. 37 degrees C).
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This is a multipoint kinetic method for simultaneously determining acetoacetate (AcAc) plus beta-hydroxybutyrate and lactate plus pyruvate in a single cuvette of the Multistat III centrifugal analyzer. In the first step, AcAc and pyruvate are completely reduced, using 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) and lactate dehydrogenase (EC 1.1.1.27) in the presence of excess NADH at pH 7.5, to beta-hydroxybutyrate and lactate, respectively. After dilution, the endogenous beta-hydroxybutyrate and lactate and that resulting from reduction are simultaneously oxidized by their respective dehydrogenases in the presence of excess NAD+ at pH 9.0. Adjustment of the relative enzyme concentrations allows simultaneous estimation of AcAc plus beta-hydroxybutyrate and lactate plus pyruvate by analyzing multipoint absorbance data, collected during the oxidation reaction, with use of a two-component linear-regression model. Total run-to-run CVs were 6.4% and 6.1% at 5 mmol/L beta-hydroxybutyrate and 5 mmol/L lactate, respectively. The method was designed to be useful for identifying the cause of an increased anion gap in serum.
The Weismann-Netter syndrome is a rare, heritable dysplasia of anterior bowing of tibiae and fibulae, often with lateral bowing of femora, short stature, and mild mental retardation. The condition is probably due to a primary metabolic abnormality of bone. The disease process is inactive in the adult. The pathogenesis is unknown. The patient reported here is the only child described in the Anglo-American literature.
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This is an automated method for the kinetic measurement of the combined concentrations of acetoacetate and beta-hydroxybutyrate in a single channel of the "Multistat III" centrifugal analyzer. Acetoacetate is first reduced with high concentrations of NADH by catalysis with 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30). This reaction mixture is diluted with excess NAD+. The endogenous beta-hydroxybutyrate and that resulting from acetoacetate are then measured kinetically. Comparing the combined concentration of acetoacetate and beta-hydroxybutyrate (y) with the sum of acetoacetate and beta-hydroxybutyrate measured as described by Hansen and Freier (Clin Chem 1978;24:475) (x) yielded the relationship: y = 0.99x - 0.57 (r = 0.93, n = 25). The run-to-run CVs for low (5 mmol/L) and high (15 mmol/L) acetoacetate controls were 12% and 6%, respectively. The method is useful for determining the concentration of ketone bodies in 2-microL samples of serum of patients with diabetic ketoacidosis. The sensitivity can be increased to determine ketone body concentration in nonketotic individuals by increasing sample volume to 10 microL.
This study elucidates a craniofacial profile pattern similarity among four family members with the Robinow syndrome. Using eight angular measurements, these profiles (created from standard scores and correlation coefficients (rz) among siblings) exceed 0.80. Dental examination of these same children demonstrates an unusual incisal edge morphology that could comprise one additional identifying feature in this disorder. The accumulation of findings in this study, along with those previously reported, emphasizes midline craniofacial involvement in the Robinow syndrome.
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The effect of the addition of sorbitol to an oral regimen of multiple doses of activated charcoal on serum theophylline concentrations was studied after the ingestion of slow-release theophylline in nine healthy male volunteers. At 6, 7, 8, 10, and 12 hours after Theo-24 (1200 mg/70 kg) ingestion, each subject received, in a randomized crossover design, either 300 ml water, 20 gm activated charcoal in water, or 20 gm activated charcoal in water plus 75 ml 70% sorbitol at 6 and 8 hours only. The serum AUCs from 6 to 30 hours after Theo-24 ingestion during the water, charcoal, and charcoal plus sorbitol phases were 305 +/- 16, 113 +/- 6, and 85 +/- 10 mg-hr/L (mean +/- SE), respectively. We conclude that the addition of sorbitol to an oral regimen of multiple doses of activated charcoal decreased the serum theophylline concentrations after therapeutic doses of slow-release theophylline to a significantly greater extent than did the activated charcoal regimen alone.
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The therapeutic effects of lithium in depression are reviewed. The acute antidepressant effect of lithium alone is neither as impressive nor as predictable as its antimanic action, nor is it equivalent to that of tricyclic antidepressants. In patients who are 'refractory' to tricyclics or monoamine oxidase inhibitors, combined treatment with lithium may augment antidepressant response. Lithium is an effective prophylactic treatment in both unipolar and bipolar disorder and in the latter is the drug of choice. Aspects of monitoring, such as range of therapeutic plasma levels, dosage regimen and adverse effects, are discussed. Current evidence suggests that, in patients who fail to respond to lithium or are unable to tolerate side-effects, carbamazepine should be considered.
A combination of the Robin sequence with pre- and postaxial oligodactyly was observed in a mother and her son. This familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome.