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Biomedical subjects

R R Miller

Publications and source records attributed to R R Miller.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of relative stimulus validity: learning or performance deficit?

This research examined whether the effect of relative stimulus validity (A.R. Wagner, F.A. Logan, K. Haberlandt, & T. Price, 1968) is a deficit of acquisition or performance. Experiment 1 demonstrated the relative validity effect using rats in a conditioned lick suppression. task. A target cue trained in the presence of another cue that was a more valid predictor of reinforcement exhibited less behavioral control than a target cue that had been trained in the presence of an equally valid predictor of reinforcement. In Experiment 2, the more valid predictor was extinguished after training. This manipulation increased responding to the target cue, thereby attenuating the effect of low relative validity. This outcome suggests that the relative validity effect is a performance deficit. In addition, recovery from the relative validity deficit was specific to the particular target stimulus that was trained in the presence of the subsequently extinguished cue.

Animals↗
PubMed1995

Assessment of the Rescorla-Wagner model.

The Rescorla-Wagner model has been the most influential theory of associative learning to emerge from the study of animal behavior over the last 25 years. Recently, equivalence to this model has become a benchmark in assessing connectionist models, with such equivalence often achieved by incorporating the Widrow-Hoff delta rule. This article presents the Rescorla-Wagner model's basic assumptions, reviews some of the model's predictive successes and failures, relates the failures to the model's assumptions, and discusses the model's heuristic value. It is concluded that the model has had a positive influence on the study of simple associative learning by stimulating research and contributing to new model development. However, this benefit should neither lead to the model being regarded as inherently "correct" nor imply that its predictions can be profitably used to assess other models.

Association Learning↗
PubMed1995

Neuroendocrine cell hyperplasia and obliterative bronchiolitis in patients with peripheral carcinoid tumors.

Specimens from 25 consecutive patients undergoing lung resection for peripheral carcinoid tumor were examined for evidence of neuroendocrine cell hyperplasia and associated obliterative bronchiolitis. Where available, the CT scans (n = 11) were reviewed for evidence of multiple tumors, and pulmonary function data (n = 16) were reviewed for evidence of airflow obstruction. Nineteen of the 25 patients (76%) had neuroendocrine cell hyperplasia in addition to the dominant carcinoid tumor. Eight patients (32%) had lesions of obliterative bronchiolitis associated with foci of neuroendocrine cell hyperplasia, and two of these patients had asymptomatic airflow obstruction that could not be related to smoking or other lung disease. We conclude that multicentric neuroendocrine cell proliferation is common in patients with peripheral carcinoid tumor of the lung. Associated bronchiolar fibrosis occurs in a high proportion of such patients, but it is usually asymptomatic.

Adult↗
PubMed1995

Bronchiectasis: comparison of preoperative thin-section CT and pathologic findings in resected specimens.

PURPOSE: To compare thin-section computed tomographic (CT) and pathologic findings in patients who have undergone resection for bronchiectasis. MATERIALS AND METHODS: Twenty-two consecutive patients underwent thin-section CT (1.0-1.5-mm collimation) and resection for bronchiectasis. CT scans were reviewed by two observers without knowledge of the pathologic findings. The presence and extent of bronchiectasis and associated findings were assessed. All pathologic specimens were reviewed by a pathologist. RESULTS: Forty-seven lobes had pathologically proved bronchiectasis. CT allowed detection of bronchiectasis in 41 lobes (87%). CT findings included lack of tapering of bronchial lumina (n = 37), internal diameter of bronchi greater than that of the adjacent pulmonary artery (n = 28), visualized bronchi within 1 cm of pleura (n = 21), and mucus-filled dilated bronchi (n = 3). Forty lobes had bronchiolitis. CT scans depicted bronchiolitis in 30 lobes (75%). CT findings of bronchiolitis included mosaic perfusion (n = 21), bronchiolectasis (n = 17), and centrilobular nodules or branching areas of soft-tissue attenuation (n = 10). CONCLUSION: Thin-section CT depicted bronchiectasis in most of the resected bronchiectatic lobes.

Adolescent↗
PubMed1995

Acute lung disease in the immunocompromised host. Diagnostic accuracy of the chest radiograph.

PURPOSE: To assess the diagnostic accuracy of the chest radiograph in the evaluation of acute pulmonary complications in immunocompromised patients. METHODS: The study included the chest radiographs in 149 consecutive acute pulmonary complications seen in immunocompromised patients in whom a definitive diagnosis was made. Twenty-four complications were in patients with AIDS and 125 were in non-AIDS patients. The radiographs were separately reviewed in random order by two independent observers. The observers assessed pattern and distribution of radiographic findings and recorded their first-choice diagnosis. RESULTS: The most common complication in patients with AIDS was Pneumocystis carinii pneumonia (n = 21). In the non-AIDS patients, the most common complications included invasive aspergillosis (n = 25), drug reaction (n = 21), and Pneumocystis pneumonia (n = 20). A correct first-choice diagnosis was made in 90% of patients with AIDS and 34% of non-AIDS patients. IN AIDS patients with Pneumocystis pneumonia, the correct first-choice diagnosis was made in 41 of 42 (98%) readings by the two observers. In non-AIDS patients with invasive pulmonary aspergillosis, drug reaction, and Pneumocystis pneumonia, the correct first-choice diagnosis was made in 38%, 26%, and 43% of readings, respectively. CONCLUSION: The chest radiograph is helpful in the differential diagnosis of acute lung disease in the immunocompromised host, particularly in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Diffuse pulmonary hemorrhage: clinical, pathologic, and imaging features.

Diffuse pulmonary hemorrhage (DPH) is a syndrome characterized by the presence of widespread hemorrhage from the pulmonary microvasculature leading to hemoptysis, iron deficiency anemia, and a chest radiography showing bilateral airspace consolidation. Diagnostic imaging consists primarily of chest radiography, but CT and MR imaging may be helpful in selected cases. There are many causes of DPH, and the differential diagnosis and diagnostic approach depend on whether the patient is immunocompetent or immunocompromised. This review summarizes the clinical, pathologic, and imaging features of DPH and the treatment of its more common causes.

Anemia, Iron-Deficiency↗
PubMed1995

Cryptogenic organizing pneumonia in the immunocompromised patient: radiologic findings and follow-up in 12 patients.

OBJECTIVE: To assess the radiographic, computed tomography (CT) and pathologic findings and response to therapy of cryptogenic organizing pneumonia in immunocompromised patients. PATIENTS AND METHODS: The study group consisted of 12 consecutive immunocompromised patients (seven men and five women), examined between July 1988 and July 1993, who had pathologically proven cryptogenic organizing pneumonia and for whom chest radiographs and CT scans had been obtained within 9 days of diagnosis. The 12 patients were treated with corticosteroids and underwent follow-up radiography. RESULTS: The findings of chest radiography included consolidation (in 10 patients), reticulation (in 3) and small nodules (in 2). None of the radiographic abnormalities were localized to particular zones of the lung. The CT findings included ground-glass attenuation (in nine patients), consolidation (in six), small nodules (in five) and reticulation (in two). In 8 of the 12 patients (67%) these abnormalities were most marked in the subpleural and peribronchovascular regions. The follow-up radiographs showed improvement in 11 (92%) of the patients. CONCLUSIONS: The most common radiographic abnormality associated with cryptogenic organizing pneumonia in these immunocompromised patients was consolidation, and the most common CT finding was ground-glass attenuation with or without associated consolidation or nodules. Most of the patients responded to corticosteroid therapy, irrespective of the initial radiologic pattern.

Adult↗
PubMed1995

Solitary tracheal plasmacytoma: computed tomography and pathological findings.

Extramedullary plasmacytomas most frequently occur in the head and the neck, although intrathoracic cases have occasionally been described. Solitary tracheal plasmacytomas are exceedingly rare. The authors describe the computed tomography and pathological appearance of a solitary tracheal plasmacytoma and briefly discuss the treatment and implications of such a lesion.

Humans↗
PubMed1995

Metabolites of L-735,524, a potent HIV-1 protease inhibitor, in human urine.

L-735,524, N-[2(R)-hydroxy-1(S)-indanyl]-5-(2(S)-(1,1- dimethylethylaminocarbonyl)-4-[(pyridin-3-yl)methyl]piperazin++ +-1-yl)-4(S)- hydroxy-2(R)-phenylmethylpentanamide, is a potent and specific inhibitor of the human immunodeficiency virus type 1 protease and is undergoing clinical evaluation. In an initial clinical study, noninfected male volunteers were administered single, 1000 mg oral doses of nonlabeled compound. Urine samples were collected over a period of 48 hr. Metabolic profile of the urine was determined by HPLC-UV comparison with that from a human liver slice incubation of radiolabeled L-735,524. Seven significant metabolites were isolated from pooled human urine, and were characterized by NMR, MS, and/or chromatographic comparisons with authentic standards. The major metabolic pathways were identified as: a) glucuronidation at the pyridine nitrogen to yield a quaternized ammonium conjugate, b) pyridine N-oxidation, c) para-hydroxylation of the phenylmethyl group, d) 3'-hydroxylation of the indan, and e) N-depyridomethylation. A minor product was identified as 2',3'-trans-dihydroxyindan analog. Urinary excretion of L-735,524 and its metabolites represented a minor pathway of elimination. The intact parent compound seemed to be the major component in the urine, whereas the level of each metabolite was relatively low.

Chromatography, High Pressure Liquid↗
PubMed1995

Absorption and glucuronidation of the angiotensin II receptor antagonist losartan by the rat intestine.

The absorption and metabolism by the rat intestine of the tetrazole-containing angiotensin II receptor antagonist losartan were determined using in vitro, in situ and in vivo models of absorption. The permeability coefficient of losartan was similar at mucosal concentrations of 0.5 to 2 mM when assayed using segments of jejunum in the Sweetana/Grass diffusion cell. The compound was conjugated during transport to form a glucuronide at the N2-position of the tetrazole group; the structure was confirmed by LC/MS/MS. Approximately 12% to 20% of losartan transported across the duodenum and jejunum was conjugated to the glucuronide. The glucuronide was not detected when sections of the ileum or colon were used. In the in situ intestinal loop model, 18% to 23% of the losartan injected into the lumen was recovered in the mesenteric vein by 1 hr. As in the in vitro model, 11% to 15% of the compound was conjugated on the tetrazole group during absorption. EXP-3174, the pharmacologically active carboxylic acid metabolite of losartan, was not detected in either the serosal buffer from the in vitro study or the mesenteric plasma from the in situ intestinal loop. In conscious rats, N2-glucuronide was detected in plasma samples from the portal vein soon after oral administration of losartan. It was detected at low concentrations in only a few of the arterial samples assayed. In conclusion, losartan is conjugated with glucuronic acid at the N2-position of the tetrazole group during absorption by the rat upper gastrointestinal tract.

Angiotensin II↗
PubMed1995

Identification of human cytochrome P450 isozymes responsible for the in vitro oxidative metabolism of finasteride.

Finasteride, a prescription drug for the treatment of benign prostatic hypertrophy and alleviation of symptoms associated with benign prostatic hypertrophy and alleviation of symptoms associated with benign prostatic hypertrophy, has been shown to be metabolized in rat hepatic microsomes by hydroxylation at the t-butyl group (omega-OH finasteride), followed by further oxidation to the corresponding acid (omega-oic acid finasteride), with omega-aldehyde finasteride as an intermediate. In this study, we identified specific human cytochrome P450 (CYP) isozyme(s) involved in the in vitro metabolism of [14C]finasteride using CYP isozyme-selective inhibitors and microsomes containing specific recombinant human CYP isozymes (expressed in human AHH-1 TK+/-cells). Each of the three steps of the oxidative pathway was examined separately by using [14C]finasteride and its consecutive metabolites (omega-OH finasteride and omega-aldehyde finasteride) as substrates, and human liver microsomes or expressed recombinant CYP isozymes as the enzyme source. Gestodene, a mechanism-based inhibitor of CYP3A isozymes, showed a concentration-dependent inhibition of the oxidative metabolism of [14C]finasteride. In addition, the respective omega-OH finasteride and omega-oic acid finasteride metabolites were generated only by microsomes containing recombinant CYP3A4, but not the other isozymes (CYP1A1, CYP2B6, CYP2C8, CYP2C9, CYP2D6, and CYP2E1). Similar results were obtained for the oxidation of omega-OH finasteride to omega-aldehyde finasteride, suggesting that human CYP3A isozymes were involved in the oxidation of omega-OH finasteride. When omega-aldehyde finasteride was incubated with human liver microsomes in the presence of an NADPH regenerating system, both the omega-oic acid finasteride and the omega-OH finasteride were detected, suggesting that oxidative and reductive reactions were occurring simultaneously and that they were NADPH- or NADP-dependent. Inhibitors of CYP3A isozymes inhibited the oxidation of omega-aldehyde finasteride in a concentration-dependent manner; an increase in the reduction was also observed, presumably caused by inhibition of the competitive oxidative reaction. Other selective CYP inhibitors for CYP1A1/2 (alpha-naphthoflavone), CYP2C8-10 (sulfaphenazole), CYP2D6 (quinidine), and CYP2E1 (diallylsulfone) showed minor or no effects on both reactions. Consistent with these results, only microsomes containing human recombinant CYP3A4 catalyzed the oxidation of omega-aldehyde finasteride to omega-oic acid finasteride. These results indicate that the oxidation of omega-aldehyde finasteride was NADPH-dependent and was mediated at least in part by CYP3A4. In addition, NAD-dependent enzymes in cytosolic, microsomal, and mitochondrial fractions were capable of oxidizing omega-aldehyde finasteride to omega-oic acid finasteride. Other cellular fractions, particularly mitochondria, were shown to convert finasteride to omega-oic acid finasteride in a similar fashion.

5-alpha Reductase Inhibitors↗
PubMed1994

Basic fibroblast growth factor binds to heparan sulfate in the extracellular matrix of rat growth plate chondrocytes.

Recent studies have demonstrated that basic fibroblast growth factor (bFGF) plays a key role in the terminal differentiation of growth plate chondrocytes during endochondral ossification. We therefore examined the binding of [125I]bFGF to an extract of extracellular matrix (ECM) of rat growth plate. Using a solid phase binding assay, binding of [125I]bFGF to ECM was demonstrated to be specific and saturable at 0.5-1 microgram/ml of bFGF. Scatchard analysis demonstrated the presence of a single class of binding sites with an apparent Kd of 14 nM. The binding of [125I]bFGF to rat growth plate ECM was inhibited by the addition of heparin, heparan sulfate, and dermatan sulfate. The binding was reversible as these glycosaminoglycans were also effective at displacement of bound [125I]bFGF from rat growth plate ECM. Chondroitin 4- or 6-sulfate had no effect on either binding or displacement when added at the same concentrations. Preincubation of the rat growth plate ECM with heparinase or heparitinase resulted in a reduction of the binding of [125I]bFGF to the ECM. Furthermore, these enzymes were able to significantly displace bound growth factor. In contrast, chondroitinase ABC or AC failed to displace bound [125I]bFGF from the ECM. Similar results were obtained when matrix derived from rat growth plate tissue was used for the binding studies. The results demonstrate that bFGF binds to a heparan sulfate in matrix produced by rat growth plate chondrocytes and matrix extracted from rat growth plate and suggest that this glycosaminoglycan may serve as a storage depot for this growth factor during endochondral ossification.

Alkaline Phosphatase↗
PubMed1994

Trial spacing and trial distribution effects in Pavlovian conditioning: contributions of a comparator mechanism.

A potential basis for trial spacing and trial distribution effects was investigated in rats. In Experiment 1, a conditioned stimulus (e.g., CS A) was trained with either massed (e.g., A---->A---->A) or spaced (e.g., A-->A-->A) trials. When trials were massed, brief exposure to the training context (a condition typical of massed training) impaired responding, whereas more extensive exposure to the context during or after training reduced this apparent massed trials deficit. In Experiment 2, different CSs were trained in either a massed (e.g., A-->A-->A--> B-->B-->B-->C-->C-->C) or a distributed (e.g., A-->B-->C-->A-->B-->C, etc.) manner. Trials massed in this sense resulted in impaired responding to the CS, and this impairment was attenuated by posttraining extinction of the context cues. Thus, trial distribution and apparent trial spacing effects are at least in part reversible deficits in performance rather than failures of learning.

Animals↗
PubMed1994

Acute lung disease in the immunocompromised host: CT and pathologic examination findings.

PURPOSE: To compare findings at computed tomography (CT) and pathologic examination in immuno-compromised patients with acute lung disease. MATERIALS AND METHODS: Findings in 33 chest CT scans were compared with findings in pathologic specimens obtained at open lung biopsy (n = 29) or autopsy (n = 4) in 32 patients, aged 17-64 years. RESULTS: Nodules were the main abnormality at CT in 14 cases. Pathologically, the 14 nodules were due to infection (n = 10), bronchiolitis obliterans organizing pneumonia (BOOP) (n = 3), or lymphoma (n = 1). Areas of ground-glass attenuation were the main finding in 15 patients. These areas were a result of BOOP (n = 4), cytotoxic drug reaction (n = 4), infection (n = 4), lymphoma (n = 2), or nondiagnostic biopsy (n = 1). Consolidation was the main finding in four cases, being seen with BOOP (n = 2), infarction due to fungal infection (n = 1), and diffuse pulmonary hemorrhage (n = 1). CONCLUSION: The pattern at CT accurately reflected the gross morphologic features seen in the pathologic specimens. Nodules were usually inflammatory lesions, often infections, and open lung biopsy usually revealed their specific origin.

Acute Disease↗
PubMed1994

Invasive aspergillosis of the airways: radiographic, CT, and pathologic findings.

PURPOSE: To assess the radiographic, computed tomographic (CT), and pathologic findings in invasive aspergillosis of the airways. MATERIALS AND METHODS: The study included nine consecutive patients (aged 17-65 years [median, 49 years]) with pathologically proved invasive aspergillosis of the airways. All nine underwent chest radiography and seven underwent CT within 3 days of diagnosis. RESULTS: The radiographic findings include normal parenchyma (n = 1), unilateral consolidation (n = 1), bilateral consolidation (n = 5), and ill-defined nodules (n = 2). The main findings at CT included lobar consolidation (n = 1), bilateral predominantly peribronchial consolidation (n = 3), ground-glass attenuation (n = 1), and centrilobular nodules less than 5 mm in diameter (n = 2). At pathologic examination, the peribronchial infiltrates represented bronchopneumonia and the nodules represented Aspergillus bronchiolitis with a variable degree of peribronchiolar organizing pneumonia and hemorrhage. CONCLUSION: Radiographic findings of invasive aspergillosis of the airways consist of consolidation or ill-defined nodules. At CT, the consolidation can be seen to be peribronchial and the nodules centrilobular.

Adolescent↗
PubMed1994

Bronchogenic carcinoma: utility of CT in the evaluation of patients with suspected lesions.

PURPOSE: To assess the utility of computed tomography (CT) in the evaluation of suspected bronchogenic carcinoma. MATERIALS AND METHODS: CT scans were reviewed of 362 patients who had undergone CT for suspected bronchogenic carcinoma. RESULTS: CT findings of 275 patients were consistent with bronchogenic carcinoma. Sixty-five tumors were deemed unresectable on the basis of CT findings, 21 were deemed unresectable on the basis of CT findings and poor surgical risk, 26 proved to be benign, six were metastatic disease from an extrathoracic primary tumor, and 157 were potentially resectable bronchogenic carcinoma. Surgical mediastinal nodal sampling enabled documentation of metastases in 60 of 159 patients. According to nodal station, the sensitivity of CT for metastases was 67% for nodes measured in the long axis and 58% for nodes measured in the short axis; specificity was 56% and 86%, respectively. CONCLUSION: CT can be used to confirm or exclude the presence of bronchogenic carcinoma and to obviate thoracotomy. The specificity of CT is limited, and a histologic diagnosis or follow-up evaluation is necessary. CT has limited value in staging mediastinal lymph nodes.

Carcinoma, Bronchogenic↗
PubMed1994

Primary pulmonary germ cell tumor with blastomatous differentiation.

We describe the clinical and pathologic findings of a patient with mixed blastoma-germ cell malignancy primary in the lung. Serum alpha-fetoprotein levels were elevated at presentation, and normalized with anti-germ cell chemotherapy. The resection specimen contained massively necrotic germ cell tumor with viable mature neural tissue, plus viable biphasic blastoma with stromal bone and skeletal muscle differentiation. It is not clear whether the germ cell component represents unusual differentiation of a somatic cell line or whether the blastoma component represents an unusual pattern of teratomatous differentiation.

Cystadenoma↗