What is your diagnosis? Inflammatory epithelium and ceruminous gland adenocarcinoma.
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Adenocarcinoma↗
Biomedical subjects
Jonathan M Miller
Publications and source records attributed to Jonathan M Miller.
Estimation of intramolecular cyclization activation energies via isothermal gravimetric analysis: a technical note.
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Antihypertensive Agents↗
Behavioral therapy for treatment of stereotypic movements in nonautistic children.
Although typically described in autistic, mentally retarded, and sensory-deprived individuals, motor stereotypies also occur in normal children. In this preliminary report, the behavior modification techniques of habit reversal and differential reinforcement of other behavior were evaluated as a therapeutic modality for the suppression of stereotypic movements in nonautistic subjects. Twelve children, ages 6 to 14 years, with physiologic stereotypies were treated using a standardized treatment protocol. Clinical outcomes were based on differences between assessments obtained at baseline and on telephone follow-up. Evaluation scales included measures of the frequency, intensity, interference, and number of stereotypies (Stereotypy Severity Scale motor portion and Stereotypy Linear Analog Scale) and assessment of global function (Child Global Assessment Scale and Stereotypy Severity Scale global portion). The results were correlated with the child's level of motivation and the number of treatment sessions. After a mean follow-up of 12.1 months, motor stereotypies showed significant improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale total score, P = .009 and P = .046, respectively. Both scales showed a relationship between the number of treatment sessions attended and a reduction in movements. The Child Global Assessment Scale also improved with therapy, but there was no correlation with the number of treatment sessions. Highly motivated patients had greater improvement on the Stereotypy Linear Analog Scale and Stereotypy Severity Scale scales compared with less motivated patients, but motivation had no impact on the Child Global Assessment Scale. The combined use of habit reversal and differential reinforcement of other behavior is beneficial in reducing motor stereotypies in nonautistic children.
Adolescent↗
Rapid, small-scale determination of organic solvent solubility using a thermogravimetric analyzer.
A rapid gravimetric method for determining drug candidate solubility in organic solvents has been developed. The scale, speed, precision, and accuracy of the method make it ideal for solubility screening of pharmaceutical compounds during early development. The method utilizes a thermogravimetric analyzer to automate drying and weighing. Results for model compounds compare favorably with literature values.
Organic Chemicals↗
Identifying the stable polymorph early in the drug discovery-development process.
The thermodynamically most stable polymorph under ambient conditions is almost without exception the most desirable crystalline form for development by a pharmaceutical company. It is, therefore, beneficial to discover and to characterize this polymorph at the earliest possible stage of development. A screen for discovering the stable polymorph of a pharmaceutical compound early in the drug discovery-development process is developed and described. In this screen, a small amount of compound is suspended in a diverse group of solvents for two weeks in an effort to crystallize the most stable polymorph. The solubility of the compound in each solvent utilized in the stable polymorph screen is also simultaneously determined using a simple gravimetric method. Ritonavir and an early development candidate (Pfizer compound A) are used as model compounds to demonstrate the utility of the screen for finding the stable polymorph early in the drug discovery-development process.
Anti-HIV Agents↗
Primary splenic mesenchymal chondrosarcoma in a dog.
A large splenic mass was found during exploratory celiotomy in a 12-year-old Labrador retriever. Histologic examination of the mass revealed a mesenchymal chondrosarcoma. The dog was euthanatized 7 wk postoperatively, due to suspected tumor recurrence. Extraskeletal mesenchymal chondrosarcomas are rare in dogs and are associated with a guarded prognosis.
Animals↗
Rapid estimation of kinetic parameters for thermal decomposition of penicillins by modulated thermogravimetric analysis.
Modulated thermogravimetic analysis (MTGA) is evaluated for the rapid estimation of thermal stability using several penicillin antibiotics as model compounds. The MTGA technique utilizes an oscillatory temperature program to obtain Arrhenius kinetic parameters through a mass loss during thermal degradation. To evaluate the reliability of this technique, activation energies (E(a)), log pre-exponential factor (logZ), and log first order rate constants (logk) obtained by MTGA for the thermal decomposition of ampicillin anhydrous, ampicillin trihydrate, ampicillin sodium salt, and penicillin G potassium salt are compared to existing literature values. The logk values estimated by MTGA agreed well with literature values when the weight loss observed by MTGA was shown to be due to the first decomposition step of the compound. The E(a) and logZ values determined by MTGA did not consistently agree with literature values as these parameters increased with decreasing heating rate (beta). The increase in E(a) and logZ values with decreasing beta seemed to offset each other to some extent to yield a relatively consistent logk estimate regardless of beta.
Calorimetry, Differential Scanning↗
Evolutionary genomics of inversions in Drosophila pseudoobscura: evidence for epistasis.
Drosophila pseudoobscura harbors a rich polymorphism for paracentric inversions on the third chromosome, and the clines in the inversion frequencies across the southwestern United States indicate that strong natural selection operates on them. Isogenic inversion strains were made from isofemale lines collected from four localities, and eight molecular markers were mapped on the third chromosome. Nucleotide diversity was measured for these loci and formed the basis of an evolutionary genomic analysis. The loci were differentiated among inversions. The inversions did not show significant differences among populations, however, likely the result of extensive gene flow among populations. Some loci had significant reductions in nucleotide diversity within inversions compared with interspecies divergence, suggesting that these loci are near inversion breakpoints or are near targets of directional selection. Linkage disequilibrium (LD) levels tended to decrease with distance between loci, indicating that some genetic exchange occurs among gene arrangements despite the presence of inversions. In some cases, however, adjacent genes had low levels of interlocus LD and loosely linked genes had high levels of interlocus LD, suggesting strong epistatic selection. Our results support the hypothesis that the inversions of D. pseudoobscura have emerged as suppressors of recombination to maintain positive epistatic relationships among loci within gene arrangements that developed as the species adapted to a heterogeneous environment.
Animals↗
Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice.
BACKGROUND: T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. METHODS AND RESULTS: One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. CONCLUSIONS: These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.
Acute Disease↗
Semi-empirical relationships between effective mobility, charge, and molecular weight of pharmaceuticals by pressure-assisted capillary electrophoresis: applications in drug discovery.
Relationships between effective mobility (m(eff)), calculated charge (Z(c)), and molecular weight (MW) are semi-empirically derived for pharmaceuticals using pressure-assisted capillary electrophoresis (PACE). We determined the m(eff) at 12 different pH points (2.0-11.4) of 66 pharmaceutical-like compounds ranging in MW from 79 to 825 g/mol. Plots of the observed m(eff) values versus Z(c)/MW(x ) (where x is a fractional coefficient) gave linear relationships. For anions, it was found that the best correlation (R(2) = 0.9666) exists when the fractional coefficient is equal to 0.4920, resulting in the equation m(eff) = 0.1853 (Z(c)/MW (0.4920)). For cations, the best linear relationship (R(2) = 0.9861) gave the equation m(eff) = 0.3888 (Z(c)/MW (0.6330)). The m(eff), Z(c)/MW(x) relationships were then applied to: (i) developing a technique for selecting an appropriate pH to achieve optimal separation of pharmaceuticals and (ii) determining the maximum charge of a molecule in the pH range of determination of negative log of the dissociation constants (pK(a)) by PACE, thus enabling the correct choice of model equation to be automated without structure analysis.
Drug Evaluation, Preclinical↗
Laparoscopic portosystemic shunt attenuation in two dogs.
Laparoscopic portosystemic shunt attenuation was successfully performed in two dogs. Aberrant vessels were noted on visual examination of the abdominal vasculature. Cellophane bands were placed around the vessel laparoscopically for attenuation. The dogs had minimal postoperative morbidity, and there was biochemical evidence of adequate shunt ligation at follow-up examination.
Animals↗