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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 325 records · Page 18Linked to original sources

Cushing syndrome due to primary pigmented nodular adrenocortical disease: findings at CT and MR imaging.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of Cushing syndrome in infants, children, and young adults. It is characterized by non-adrenocorticotropic hormone-dependent hypersecretion of cortisol by multiple, pigmented nodules of hyperplastic adrenocortical cells. With a single exception, adrenal glands have been described as normal with computed tomography (CT) in all previous series. Eight patients had Cushing syndrome due to surgically proved PPNAD. Four of the eight patients had stigmas of Carney complex (lentigines, calcified Sertoli cell tumors of the testes, and cardiac and soft-tissue myxomas). CT and/or magnetic resonance (MR) imaging demonstrated unilateral or bilateral nodularity in five of six patients examined. Macronodules (greater than 10 mm) were seen in the two oldest patients. As the clinical presentation of Cushing syndrome in this group of patients may be atypical (severe osteoporosis or short stature), the detection of multiple, small adrenocortical nodules with CT or MR imaging supports, or may even suggest, the diagnosis of PPNAD.

Adolescent↗

Relationships among the cerebral amyloid peptides and their precursors.

Alzheimer's disease is characterized by deposits of amyloid in cerebral blood vessels and neuropil. Qualitative analyses of partially purified preparations of these amyloid deposits revealed the presence of a unique polypeptide now often called "beta peptide". This peptide is 40 residues long and it exhibits some amino terminal heterogeneity, which may result from the isolation procedure. The major amyloid peptide comprises at least 30% of the dry mass and 70% of the protein of washed neuritic plaque cores. These results indicate that the major peptide is the predominant proteinaceous component of cores; furthermore, they demonstrate that although cores may contain other substances such as aluminum silicate, polysaccharides, and lipids, amyloid peptide is a major component. More careful analysis reveals that the core amyloid peptide differs significantly from cerebrovascular amyloid peptide. Although the core amyloid peptide is constructed of the same backbone as the cerebrovascular amyloid peptide, it contains modifications that render the amino terminal region uncleavable by Edman degradation or by trypsin. It is unknown whether the lower solubility of core amyloid is related to these modifications. The original impetus for characterizing the differences between the core and cerebrovascular amyloid peptides arose from the question of whether both amyloid peptides were formed by a sequential pathway. Our results showing that core amyloid peptide is more extensively modified than vascular amyloid leads us to conclude that if a sequential pathway exists, vascular amyloid peptide must precede core amyloid peptide. Nevertheless, the discovery that amyloid precursor mRNA is widely and abundantly distributed throughout most tissues tends to discourage such a simple account of the relationship between these forms of amyloid.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

Prospective evaluation of hepatic imaging studies in the detection of colorectal metastases: correlation with surgical findings.

Nineteen patients with isolated colorectal liver metastases were preoperatively evaluated with five hepatic imaging studies. The results of these studies were correlated with operative findings. One study involved the use of EOE-13, an intravenously administered lipid contrast agent that enhances liver parenchyma on computed tomography (CT) scans (EOE-CT). Another study, arterial portography (AP-CT), was performed with injection of a water-soluble contrast agent into the superior mesenteric artery during CT scanning. Delayed CT scanning (DS-CT) was completed 4 hours after AP-CT. In addition, T1- and T2-weighted magnetic resonance imaging (MRI) (T1-MRI, T2-MRI) scans were done. All patients subsequently underwent laparotomy with identification of 78 lesions. A lesion-by-lesion analysis revealed that the sensitivity of EOE-CT (83%), AP-CT (78%), DS-CT (82%), and T1-MRI (84%) was comparable. T2-MRI had a significantly lower sensitivity (64%) compared with EOE-CT, DS-CT, and T1-MRI. The false-positive rate for AP-CT was 31%, which was significantly higher than that of all other studies. The T1-MRI examination had the lowest false-positive rate and proved to be the best hepatic imaging study in the detection of colorectal metastases. EOE-CT and DS-CT were comparable, whereas AP-CT and T2-MRI proved to be inferior tests.

Colorectal Neoplasms↗

Localization of islet cell tumors.

In summary, although similar imaging techniques are used for the localization of insulin and gastrin secreting islet cell tumors, the success rates are very different. Fortunately, the best results are obtained in the tumor for which effective medical treatment is less available, namely insulinomas, which can be found and successfully resected in over 90 per cent of patients. Both portal venous sampling and experienced intraoperative ultrasound are critical for successful surgery of small insulin-secreting tumors. Facilities without these resources should not explore patients when the conventional imaging studies are negative. Gastrinomas, on the other hand, will elude detection by even the most experienced surgeons in over 20 per cent of patients with sporadic Zollinger-Ellison syndrome in spite of positive portal venous sampling and intra-arterial secretin studies. The very small size of these tumors and their occurrence in more difficult to explore extrapancreatic sites provides the basis for this difference. However, patients with negative imaging studies and negative surgical explorations have an excellent prognosis on long-term follow-up when gastric acid hypersecretion is controlled. An annual computed tomographic scan is recommended since the appearance of a tumor would mandate surgical resection because of the significant incidence of malignancy in larger tumors. However, progression to imageable tumors has been unusual in our experience with this group of patients. There remains a small group of patients with highly malignant, rapidly metastasizing, gastrin-secreting islet cell carcinomas for whom localization is simple but of little relevance. However, locally invasive gastrinomas may often be resectable and provide prolonged remission and even cure. Aggressive surgery, supported by detailed cross-sectional and angiographic localization, has a role in this small group of patients.

Adenoma, Islet Cell↗

Mixing studies during hepatic artery infusion in an in vitro model.

A glass model of the hepatic artery network was used to study the effect of infusion rate on the degree of mixing from an end hole catheter placed in the gastroduodenal artery. Red dye solutions were infused at rates ranging from 1 ml/hour to 20 ml/minute. Effluent samples from each of 16 branch arteries were collected and dye concentrations were analyzed by means of a spectrophotometer. Low infusion rates, e.g., up to 5 ml/minute, showed streaming of the dye solutions and a nonhomogeneous dye distribution in the distal branches. At 20 ml/minute, dye distribution was much more uniform. These experiments are designed to simulate intrahepatic infusion of chemotherapeutic drug solutions. Theoretical considerations suggesting a pharmacokinetic advantage of intraarterial delivery implicitly assume uniform distribution of drug solutions to all perfused tissue. The in vitro data in this study suggests that this assumption may not be operative under certain infusion conditions. Slow infusion can lead to streaming and nonuniform distribution of infused drug solutions, which may in part explain the variability in tumor response in different tissue regions and also some observed toxicities, such as bile duct stricturing and fibrosis after intrahepatic infusions.

Antineoplastic Agents↗

Extrahepatic tumor deposits misdiagnosed as intrahepatic metastases.

Focal hepatic lesions seen on roentgenologic evaluation of the liver in patients with cancer are usually assumed to be caused by parenchymal metastases. In this report, liver imaging tests showed six patients with filling defects caused by peritoneal carcinoma indenting the liver parenchyma. Extrahepatic tumor deposits were misdiagnosed in all but one of these cases. The roentgenographic characteristics that can assist in the differentiation of intrahepatic and extrahepatic metastases are a lens-shaped defect, a defect adjacent to the hemidiaphragm, and a halo around the liver suggesting peritoneal carcinomatosis. A high index of suspicion for extra-hepatic tumor masses causing intrahepatic filling defects may help prevent unnecessary exploratory surgery for treatment of hepatic metastases. Angiography may occasionally be helpful in distinguishing intrahepatic from extrahepatic disease.

Diagnostic Errors↗

Nuclear and mitochondrial revertants of a yeast mitochondrial tRNA mutant.

We isolated revertants capable of respiration from the respiratory deficient yeast mutant, FF1210-6C/170, which displays greatly decreased mitochondrial protein synthesis due to a single base substitution at the penultimate base of the tRNAAsp gene on mitochondrial (mt) DNA. Three classical types of revertant were identified: (1) same-site revertants; (2) intragenic revertants which restore the base pairing in the acceptor stem of the mitochondrial tRNAAsp; and (3) extragenic suppressors located in nuclear DNA. In addition a fourth type of revertant was identified in which the mutant tRNAAsp is amplified due to the maintenance of both the original mutant mtDNA and a modified form of the mutant mtDNA in which only a small region around the tRNAAsp gene is retained and amplified. The latter form resembles the mtDNA in vegetative petite (rho-) strains which normally segregates rapidly from the wild-type mtDNA. Each revertant type was characterized genetically and by both DNA sequence analysis of the mitochondrial tRNAAsp gene and analysis of the quantity and size of RNA containing the tRNAAsp sequence. These results indicate that the mitochondrial tRNAAsp of the mutant retains a low level of activity and that the presence of the terminal base pair in tRNAAsp is a determinant of both tRNAAsp function and the maintenance of wild-type levels of tRNAAsp.

Base Sequence↗

The influence of hematocrit on hemolysis by ultrasonically activated gas-filled micropores.

In vitro studies of ultrasonic bioeffects typically employ cell number densities much lower than those present in vivo, which can lead to difficulties in interpretation and extrapolation. In this study, the influence of cell number density on the hemolytic effect of ultrasonic gas-body activation (a low-level form of cavitation) was investigated. Hydrophobic membranes with 4 micron diameter gas-trapping micropores were immersed in saline suspensions of erythrocytes with hematocrits (HCT) from 0.001 to 0.3, and whole blood, and exposed to 1.7 MHz continuous-wave ultrasound in a 37 degrees C saline-filled exposure bath. Significant hemolysis was observed for spatial peak intensities above about 45-90 mW/cm2 for the 16 min exposures. The percentage of cells hemolyzed tended to decrease with increasing hematocrit such that the number of cells hemolyzed, which is proportional to the product of the hematocrit and the percent hemolysis, remained roughly constant. Readily observable in vitro effects may therefore become quite subtle when diluted, as for in vivo conditions, by large numbers of cells.

Blood Cell Count↗

Mixing problems of low flow hepatic artery infusion. Improvement with small caliber double lumen balloon catheters.

The problem of inhomogeneous mixing encountered during hepatic artery (HA) chemotherapy infusion was assessed and a practical solution examined. A glass model of the human HA distribution was used to determine mixing homogeneity of low flow (1.4 mL/minute) dye infusion into pulsatile flow (280-300 mL/minute) of a fluid isoviscous to blood. Dye concentration in each of 16 HA branches was determined by photospectrometry. Dye infusion was carried out through 2-2.5F double lumen end hole or proximal side hole balloon catheters without balloon inflation, with balloon inflation maintaining full HA flow, and with the balloon inflated so that HA flow was reduced by 50%. The measurements taken without balloon inflation showed gross inhomogeneity of dye concentration in various branches. The inhomogeneity was not improved during balloon inflation as long as full HA flow was maintained. After balloon inflation reduced HA flow by 50%, dye mixing was improved significantly, with infusion through side hole catheters (alpha = .002) but not significantly (alpha = .2) with infusion through end hold catheters. This investigation suggests that the proposed technique might be useful for clinical application and deserves further evaluation in an in vivo system.

Antineoplastic Agents↗

Particle gathering and microstreaming near ultrasonically activated gas-filled micropores.

Nonthermal bioeffects of ultrasound can be induced by the physical mechanisms of radiation force and acoustic microstreaming. In this study, microscopical observations of the influence of these mechanisms on small particles near ultrasonically activated gas-filled micropores in thin plastic sheets were compared to approximate theoretical treatments of the particle behavior. The microstreaming flow was localized within a toroidal eddy around an active micropore, as indicated by isopycnic 1-micron polystyrene spheres. The size of the flow pattern seemed to decrease slowly with increasing frequency in the range 0.7-3.5 MHz. Flow was radially inward along the surface, rather than outward as expected from the theory. All the particles tested, which included particles with density less than, equal to, or more than the medium, seemed to accumulate at the micropores. From the theory for the radiation force, the particles less dense than the medium were expected to be repulsed from the micropores. Therefore, the theories for these phenomena, at least to the level of approximation available, may not be completely adequate for the detailed analysis of these phenomena.

Acoustics↗

Macronodular adrenal hyperplasia in Cushing disease.

Computed tomographic (CT) scans of the adrenal glands were obtained in nine patients with Cushing disease as a result of an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma and macronodular hyperplasia of the adrenal glands. The findings were compared retrospectively with those in six patients with Cushing syndrome as a result of an autonomous adrenal adenoma and 16 with Cushing syndrome as a result of ectopic ACTH production. Seven of nine patients with macronodular adrenal hyperplasia had hyperplastic adrenal glands in addition to single or multiple focal adrenal nodules. The six patients with hypercortisolism caused by an autonomous adrenal adenoma showed atrophic (four patients) or normal (two patients) ipsilateral and contralateral adrenal glands. Fourteen of 16 patients with the ectopic ACTH syndrome had hyperplasia of the adrenal glands without nodularity, and only two had focal nodules.

ACTH Syndrome, Ectopic↗

Intravascular contrast media: effect of dose on renal function.

Effect of contrast material dose on clinically evident change in renal function was studied prospectively in 200 examinations requiring intravenous or intraarterial administration of contrast material. All patients were adequately hydrated. Blood urea nitrogen and serum creatinine were measured before and after the procedure. Ionic and nonionic contrast agents were used. Total dose of contrast material ranged from 30 to 530 mL (mean, 237 mL). There was no tendency to give smaller doses to patients with preexisting renal impairment and no relationship between total dose and patient age. No consistent clinical effect on renal function was demonstrated with increasing dose, regardless of whether ionic or nonionic agents were used. In adequately hydrated low-risk patients with predominantly normal initial renal function and within the dose range studied, there does not appear to be any consistent clinical change in renal function with increasing contrast material dose.

Adolescent↗

Whither the Wada?

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Amobarbital↗

Long-term variability in the spectral loci of unique blue and unique yellow.

The spectral loci of both unique blue and unique yellow were measured over a 16-month period. Using the method of constant stimuli, two neutrally adapted observers made forced-choice green or red responses to monochromatic test flashes. Results showed a consistent difference between observers (about 5 nm), considerable within-subject variability (standard deviation 3 nm), and significant long-term drifts (greater than 5 nm) in spectral loci. These results demonstrate the importance of frequently redetermining unique-hue loci when they are used as baselines in chromatic contrast and adaptation studies.

Adult↗

Evaluation of teaching performance in U.S. dental schools.

This study examines how teaching performance is evaluated in U.S. dental schools. Respondents to the mailed survey were dental school deans. Most schools formally evaluate teaching through student evaluation, yet most deans agreed that evaluation should include input from students and peers. Features that were considered most important in an evaluation program included the provision of a feedback mechanism, the inclusion of faculty input, and a standardization of the evaluation system. The majority of schools provide a program to enhance teaching skills; responsibility for the program varied from the department chairperson to the individual faculty member. More than half of the deans indicated that research productivity can "outweigh" teaching skills in promotion and tenure decisions. The results indicate that dental school deans expect excellence in teaching, but leave doubt as to how faculty members are to gain expertise in this realm of their profession.

Educational Measurement↗