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Biomedical subjects
Publications and source records attributed to K C Johnson.
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The dissolution rates of two lots of hydrocortisone (fine and coarse) were simulated using a computer program based on a Noyes-Whitney-type equation. Derivations of the equation were made to compare the accuracy of simulations using spherical and cylindrical particle geometry, with and without a time-dependent diffusion layer thickness. To approximate better the shape of the hydrocortisone particles, a shape factor was used to relate cylindrical length to radius. The most accurate simulations were obtained by assuming cylindrical geometry with and without a time-dependent diffusion layer thickness for the fine and coarse hydrocortisone, respectively. The program was also modified to simulate initial particle size distributions based on the log normal probability density function.
To determine resident physician recognition and treatment of hypercholesterolemia, a retrospective chart audit was performed on 300 systematically selected patients seen in an internal medicine resident's continuity care clinic during the spring of 1992. A self-administered resident survey was given after completion of chart selection. Of the 300 patients, 64 (21%) did not have a cholesterol reading on the chart. The frequency of screening was unaffected by cardiac risk factors, patient race or sex, or resident level of training or specialty. Of the 96 patients who had a total cholesterol greater than 240 mg/dL documented in the chart, 48% received diet therapy, 46% received other nonpharmacologic therapy, 24% received drug therapy, 4% were referred to a lipidologist, and 30% received no treatment. Fasting lipid profiles were ordered for 57% of these patients. The frequency of therapy was unaffected by patient race or sex, resident level of training or specialty, or presence of two or more cardiac risk factors, although patients with a diagnosis of hypercholesterolemia and patients younger than age 65 were treated significantly more often. Resident action primarily involved evaluation rather than therapy. Efforts to improve the aggressiveness of treatment for hypercholesterolemia by resident physicians are necessary.
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The authors believe that the computerized medical record may enhance physician-delivered preventive services by providing timely individual feedback. Additionally, we note that interest in health promotion and disease prevention in the medical community as well as the general population has been increasing during the last decade. In response to this increased interest, we believe that health promotion and disease prevention activities should be conducted by every clinician and should include basic measures such as immunizations, appropriate screening tests, and advice and counseling about lifestyle. Additional investigation into the use of computers and computer-generated reminders to enhance the delivery of preventive services is needed.
The Ah receptor regulates induction of cytochrome P450IA1 and mediates certain toxicities of polyhalogenated aromatics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been characterized previously in continuous cell lines, notably the mouse hepatoma line Hepa 1, the human squamous cell carcinoma line A431, and the human liver cell line Hep G2. The present work extends our knowledge of the Ah receptor in continuous human liver cell lines. Ah receptor can be detected in Mz-Hep-1, a hepatitis B virus-negative cell line derived from a Thorotrast-induced hepatocellular carcinoma. The mean concentration of Ah receptor in Mz-Hep-1 cells was 341 +/- 22 fmol/mg cytosol protein (mean +/- SEM, nine separate determinations). This is equivalent to approximately 30,000 sites per cell. The concentration of Ah receptor in Mz-Hep-1 cells is similar to that in Hepa 1 cells and approximately three times higher than that in Hep G2 cells. The Mz-Hep-1 Ah receptor sedimented in continuous sucrose gradients at approximately 9 S. Specificity of binding by [3H]TCDD was demonstrated by competitive binding of non-radiolabeled 2,3,7,8-tetrachlorodibenzofuran, 3-methylcholanthrene (MC), and dibenz[a,h]anthracene in 50-fold molar excess. Phenobarbital, which is not a substrate for P450IA1, did not compete with [3H]TCDD for binding to Mz-Hep-1 Ah receptor. Dexamethasone and estradiol also did not compete with [3H]TCDD for binding, suggesting non-identity of Ah receptor with glucocorticoid or estrogen receptor. In separate experiments, glucocorticoid receptor was identified in Mz-Hep-1 cells. By Scatchard plot analysis, the apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Mz-Hep-1 Ah receptor was estimated to be 4.4 nM, compared to 0.8 nM in Hepa 1 cells. By Woolf plot analysis the Kd was 5.4 nM, compared to 1.2 nM in Hepa 1 cells. The [3H]TCDD.Ah receptor complex extracted from nuclei of Mz-Hep-1 cells incubated with [3H]TCDD in culture at 37 degrees sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was detectable in Mz-Hep-1 cells after pretreatment with inducing chemicals. Mz-Hep-1 cells have the highest concentrations of Ah receptor in any continuous human liver cell line thus far investigated. The Mz-Hep-1 Ah receptor is similar physicochemically to that described in murine systems. AHH activity is inducible in Mz-Hep-1 cells.
Niacin (nicotinic acid) is available in several forms, including crystalline preparations and various types of sustained-release preparations. Evidence exists that sustained-release niacin, with respect to both dosage and severity, is more hepatotoxic than crystalline niacin. Three patients who developed hepatitis during treatment with sustained-release niacin were rechallenged with equivalent or higher doses of crystalline niacin, with no evidence of recurring hepatocellular damage. Although the mechanism for niacin-induced hepatitis is unknown, these cases support previous observations that crystalline niacin may be less hepatotoxic than sustained-release preparations in certain patients.
The Ah receptor, a soluble cytoplasmic receptor that regulates induction of cytochrome P450IA1 and mediates toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was detected and characterized in the continuous human liver cell line Hep G2. The mean concentration of specific binding sites for TCDD was 112 +/- 26 (SEM) fmol/mg cytosol protein as determined in eight separate cytosol preparations in the presence of sodium molybdate. This is equivalent to 14,000 binding sites per cell, approximately 40% of the sites per cell found in the mouse hepatoma line Hepa-1. The cytosolic Ah receptor from Hep G2 cells sedimented at 9 S and was specific for those halogenated and nonhalogenated aromatic compounds known to be agonists for the Ah receptor in rodent tissues and cells. Specific binding in the 9 S region was detected with both [3H]TCDD and 3-[3H]methylcholanthrene. 3-[3H]Methylcholanthrene did not bind to any component besides that at approximately 9 S. Phenobarbital, dexamethasone, and estradiol did not compete with [3H]TCDD for binding to the Hep G2 Ah receptor. Specific binding of [3H]triamcinolone acetonide to glucocorticoid receptor could also be demonstrated in Hep G2 cytosol. The apparent equilibrium dissociation constant (Kd) for binding of [3H]TCDD to Hep G2 Ah receptor was 9 nM by Woolf plot analysis, about an order of magnitude weaker than the affinity of [3H]TCDD for the mouse Hepa-1 Ah receptor or for the C57BL/6 murine hepatic Ah receptor. [3H]TCDD.Ah receptor complex, which was extracted from nuclei of Hep G2 cells incubated with [3H]TCDD at 37 degrees C in culture, sedimented at approximately 6 S under conditions of high ionic strength. Aryl hydrocarbon hydroxylase (AHH) activity was significantly induced after 24 h of incubation with polycyclic aromatic hydrocarbons: the EC50 for AHH induction was 5.3 microM for benz(a)anthracene and 1.3 microM for 3-methylcholanthrene. Modification of the preparative technique for cell cytosol, especially inclusion of 20 mM sodium molybdate in homogenizing and other buffers, was necessary to detect cytosolic Hep G2 Ah receptor. Hep G2 cells appear to conserve drug-metabolizing activity associated with cytochrome P450IA1 as well as the receptor mechanism which regulates its induction.
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The intestinal absorption of hydrocortisone and prednisolone are compared with three water-soluble derivatives (succinate, phosphate, and lysinate) in experiments at two levels of biological system complexity. Rates of absorption are compared by measuring permeabilities from rat intestinal perfusions of drugs and derivatives in solution. Extents of absorption are compared over a 10-fold dose range of parent steroid and with the steroid derivatives by measuring plasma levels from solid oral dosage in dogs. While the parent steroids are well absorbed over the entire length of the intestinal tract, variability in plasma levels is observed at higher doses. Limited solubility and resultant dissolution rate variability are likely to be playing a role in the early erratic blood level profiles found at higher doses. While the soluble prodrugs have a dissolution rate advantage which results in a greater concentration gradient, their absorption is limited by their aqueous luminal stability, their polarity and resultant passive membrane permeability, and the distribution and activity of enzyme reconversion sites in the intestinal tract. The unstable lysinate ester, targeted for aminopeptidase, has an absorption profile and permeability similar to that of the parent steroid. The absorption of the moderately stable succinate ester is limited by its polarity and the activity of intestinal esterases. The stable phosphate derivative is well absorbed in the upper intestine, where high levels of alkaline phosphatase exist, while the prodrug polarity and drop-off of enzyme activity limit its absorption from the lower gastrointestinal (GI) tract.
PERT is becoming a necessary approach for controlling the many events that contribute to the success or failure of initiating new diagnostic imaging services. This article first describes the development of a PERT program and offers advice on how to optimize the chance for successful results. It then describes the one single event that is the most critical one that impacts on the total results which are obtained.
This study was conducted to evaluate a detailed diet history questionnaire. Diet histories obtained from 16 men were compared with food records kept by their partners for a 30-day period. Mean estimates for all 13 nutrients calculated were higher with the diet history than with food records. Positive correlation coefficients were found between estimates from the two methods for all nutrients as well as food groups and six of the 13 nutrients gave a good fit for the corresponding regression equations. The questionnaire was also evaluated by repeating it after six months on 26 case-control pairs of an ongoing diet and cancer study. High correlation coefficients were obtained for most nutrients for the controls. However, cases showed lower correlations probably due to changes in their diet. The study found that the diet history method as an estimate of dietary patterns among groups shows sufficient validity and reliability to make it a useful instrument for epidemiologic studies.
A case of leiomyomatosis peritonealis disseminata (LPD) is presented with the unique finding of occasional endometrial glands and stroma within smooth muscle nodules. The possible origins of this tissue are discussed in relation to the histogenesis and prognosis of LPD.
1. The cuspid width is most likely to decrease after treatment (9 of 11) although on occasion a slight increase (2 of 11) was maintained. 2. The molar width is apt to decrease from the beginning of treatment through the postretention period. 3. The cephalometric measurements studied in this sample of good stable occlusions coincided with with the norms and ranges as used by R.M. 4. The age changes of the various cephalometric measurements also agreed with the age changes that R.M. utilize. 5. Lower arch crowding may be due to multiple factors of expanded cuspids, protrusive and labially inclined mandibular incisors, and late skeletal growth changes.