Search PubMed⌕ Search

Biomedical subjects

T R Miller

Publications and source records attributed to T R Miller.

At least 91 records · Page 5Linked to original sources

Lacrimal gland lymphoma: a cytomorphologic and immunophenotypic study.

The cytomorphology of lacrimal gland lymphoma has not been specifically described. Herein we present six cases of histologically proven lacrimal gland lymphoma which we analyzed using fine-needle aspiration cytology, cell suspension immunophenotype analysis, and immunoglobulin gene rearrangement studies. Fine-needle aspiration cytology revealed atypical populations of cells comprised of either monomorphic small round lymphocytes with or without plasmacytoid features (4 cases), a mixed population of small and large irregular lymphocytes (1 case), or a population of large irregular lymphocytes (1 case). The initial cytologic diagnosis was malignant lymphoma in all six cases. Cell suspension immunophenotype analysis demonstrated that the lesions were composed predominantly of B-cells that expressed monotypic surface immunoglobulin. Three cases demonstrated an immunoglobulin heavy chain gene rearrangement. The atypical cytologic features and the abnormal immunophenotype were consistently predictive of malignant lymphoma. Given that these lesions are small and biopsy material is often limited, fine-needle aspiration offers the advantage of providing tissue that is ideal for cytologic and cell suspension immunophenotype evaluation, obviating the need to provide surgical biopsy material for this purpose. We conclude that fine-needle aspiration can identify malignant lymphoid lesions of the lacrimal gland and may serve as a valuable adjunct in the assessment of these lesions. Additional study is warranted to determine whether fine-needle aspiration can reliably distinguish between benign and malignant lymphoid proliferations of the lacrimal gland.

Aged↗

Estimating the costs of occupational injury in the United States.

This article estimates workplace injury costs in the U.S. These costs have been studied in less detail than most injury costs. Our methods, which mostly use regularly published data, produce order-of-magnitude estimates. Overall, workplace injuries cost the U.S. an estimated $140 billion annually. This estimate includes $17 billion in medical and emergency services, $60 billion in lost productivity, $5 billion in insurance costs, and $62 billion in lost quality of life. One sixth of the societal costs result from the 3% of workplace injuries in motor vehicle crashes. Motor vehicle costs per injury are almost 6 times the workplace injury average.

Absenteeism↗

Desmoplastic small cell tumor of the ovary: a unique polyphenotypic tumor with an unfavorable prognosis.

Desmoplastic small cell tumor (DSCT) is a recently described intraabdominal neoplasm of uncertain histogenesis that occurs predominantly in boys and young men. We report a case in a young woman that presented clinically as bilateral ovarian tumors with extensive pelvic and abdominal dissemination. The patient had cytoreductive surgery followed by combination chemotherapy. She had a complete clinical remission, but tumor recurrence was detected 1 year after diagnosis and the patient died of her disease 18 months after presentation. DSCT has a distinctive histologic appearance and a unique immunophenotype. It can present as an ovarian neoplasm and must be considered in the differential diagnosis of small cell tumors of the ovary.

Adult↗

Corneal stromal abscesses in the horse: a review of 24 cases.

The medical records of 24 horses with corneal stromal abscesses were reviewed. Twenty of the horses initially presented with a corneal ulcer, corneal opacity, or evidence of ocular pain. All of the horses were treated with topical antibiotics prior to referral. Most had also been treated with topical atropine sulphate and systemic flunixin meglumine. Ophthalmic examinations revealed focal, yellow-white corneal opacities, corneal vascularisation and evidence of iridocyclitis. Nine of the horses were treated primarily medically as the initial response to topical and systemic medication was rapid. Fifteen horses were treated both medically and surgically. Surgical treatment was undertaken when corneal rupture was imminent, the iridocyclitis was intractable or when there was minimal response to intensive medical therapy. The surgical procedure performed in most cases was a deep keratectomy with a conjunctival pedicle flap. Intraoperative specimens for cytology, culture, and/or histopathology contributed to the aetiological diagnosis in 5 of 8 cases in which preoperative cytology and cultures were nondiagnostic. All horses, excluding one that was enucleated at presentation for iris prolapse, had vision at discharge.

Abscess↗

A cost-benefit analysis of enforcement efforts to reduce serving intoxicated patrons.

OBJECTIVE: We conducted a cost-benefit analysis of a pilot program of increased enforcement of laws forbidding service to intoxicated patrons. This study provides an example of the issues that typically arise in cost-benefit analysis applied to a program directed at alcohol abuse. We provide a methodology for translating reported DWIs into cost savings. We also present benefit measures that distinguish pain and suffering from productive loss, that distinguish social costs from losses internalized by the individual and that allow for substitution of other unsafe activity. METHOD: The analysis is based on a case study conducted in Washtenaw, Michigan. We used data from police files on sources of DWIs before and after implementation of a program aimed at enforcement of alcohol server laws. To estimate the dollar value of benefits from reducing DWIs, we use incidence data and a number of different recently developed measures of alcohol-involved crash costs. Our study, however, provides the component costs of alcohol-involved crashes and distinguishes external costs from other costs. RESULTS: Our estimates indicate that the Washtenaw SIP program provides benefits that greatly exceed its costs. This result holds under a variety of different assumptions about the appropriate measurement of social benefits. CONCLUSIONS: Although the benefits are in all cases large relative to the costs, they are highly sensitive to whether the savings include personal losses and losses borne directly by intoxicated drivers, and whether harmful activity is diverted to other costly activities. Thus, our study highlights the importance of underlying assumptions that are commonly made in conducting cost-benefit analyses of programs aimed at substance abuse.

Alcohol Drinking↗

Injury prevention counseling by pediatricians: a benefit-cost comparison.

OBJECTIVES: The American Academy of Pediatrics believes that health education, through office-based counseling, can contribute to childhood injury prevention. This report extends previously published work on the effectiveness of primary care-based counseling and compares the costs and estimated monetary value of the benefits of safety counseling targeting children ages 0 to 4 years. METHODS: We estimate the savings achievable with comprehensive childhood injury prevention counseling organized around the three Framingham Safety Surveys used in The Injury Prevention Program (TIPP) developed by the American Academy of Pediatrics. We verify the estimated savings by comparing them with the effects of pediatrician counseling from separate analyses of the most fully evaluated interventions--in child motor vehicle occupant injuries, burns, and falls. RESULTS: TIPP pediatrician injury counseling sessions between the ages of 0 and 4 years can achieve estimated savings of $880 per child or $80 per visit. If all 19.2 million children ages 0 to 4 years completed TIPP, we estimate that $230 million would be saved annually in medical spending, and injury costs would decline $3.4 billion. each dollar spent on TIPP childhood injury prevention targeting children ages 0 to 4 years returns nearly $13. CONCLUSION: TIPP pediatrician injury counseling is a cost-effective method of preventing childhood injuries and should be more widely adopted.

Accident Prevention↗

An Internet-based nuclear medicine teaching file.

UNLABELLED: Teaching file cases play an important role in the training of nuclear medicine residents; however, film-based teaching files have limitations, such as difficulty in accessing cases in a department with several remote clinical sites. The goal of this project was to develop a digital teaching file with the capability for local and remote (Internet) network access, with the additional requirements that viewing existing cases and addition of new cases be easy and simple. METHODS: The teaching file software (TF-Web) utilizes applications developed for the World-Wide-Web in combination with locally developed programs for importing images, entering case information, indexing, searching, case selection and case editing. The time required to add cases to the TF-Web and to access existing cases from local and remote network sites as well as computer storage requirements were assessed. RESULTS: Cases entered in TF-Web may be viewed either with or without diagnoses and may be accessed with acceptable speed (2-14 sec) from both local and remote network sites. A relatively complex case required 1.2 megabytes of storage, with lesser storage requirements for simpler cases. CONCLUSION: A digital teaching file has been developed that allows easy access from computers located both locally and elsewhere on the Internet. Digital storage requirements are reasonable, and, because of the unique nature of TF-Web, case storage may be distributed among multiple institutions.

Computer Communication Networks↗

Characterization of cloned human dopamine D1 receptor-mediated calcium release in 293 cells.

Dopamine (DA) D1 receptors are generally known to couple only to Gs and cAMP production. Recently, D1 receptors expressed in mouse Ltk- cells have been shown to induce cAMP production, phosphoinositide (PI) hydrolysis, and calcium mobilization [Mol. Endocrinol. 6: 1815-1824 (1992)]. To further evaluate second messenger systems that could be activated by the D1 receptor, we examined the effects of DA, (R)-(+)-SKF-38393, and DA antagonists on cAMP production and calcium release in human embryonic kidney 293 cells stably expressing three different levels (Bmax = 0.12, 1.4, and 23 pmol/mg of protein) of the human D1 receptor. DA and (R)-(+)-SKF-38393 activated cAMP production and calcium release in all three D1-293 clones, and their potency was proportional to receptor density. The efficacy of SKF-38393 was also increased with receptor density in both cAMP and calcium studies. The effect of DA on calcium release consisted of a transient peak response (< 20 sec) that declined to an ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-sensitive plateau level above the base-line (>5 min). The effect of DA on cAMP and calcium release was selectively inhibited by SCH23390, a selective D1 antagonist, and not by spiperone, a selective D2 antagonist. DA did not induce PI hydrolysis in any of the three receptor-expressing clones. A 24-hr pretreatment with cholera toxin (2 micrograms/ml) greatly attenuated the effect of DA on cAMP formation and calcium release. To address how DA could activate calcium release without enhancing PI hydrolysis, the effects of forskolin, thapsigargin, and isoproterenol (Iso) were studied. Similarly to the effects of DA, forskolin and Iso stimulated cAMP production and calcium release from D1-293 cells. Cells that were stimulated with Iso or forskolin showed a reduced response to subsequent addition of DA. Pretreatment of D1-293 cells with thapsigargin, a selective Ca2+-ATPase inhibitor, elicited calcium release from the inositol-1, 4, 5-trisphosphate-sensitive calcium store and attenuated the response to subsequent addition of DA. Carbachol stimulated PI hydrolysis and calcium release but had little effect on cAMP production. Prestimulation with carbachol abolished the calcium response to DA, Iso, or forskolin. These studies indicate that D1 receptor-mediated calcium mobilization in 293 cells is dependent on cAMP production and the cAMP-dependent calcium store is part of the inositol-1,4,5-trisphosphate-sensitive calcium pool.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Attenuation correction in cardiac SPECT without a transmission measurement.

UNLABELLED: The accuracy of SPECT cardiac perfusion imaging is impaired by artifacts induced by nonuniform gamma-ray attenuation. This study proposes a method to estimate attenuation in the chest of patients without the additional hardware and expense of transmission imaging. METHODS: After the standard 201Tl or 99mTc-sestamibi delayed images were obtained, 99mTc macroaggregated albumin (MAA) was injected and dual-energy SPECT acquisition was performed with windows centered at 140 keV and 94 keV. Lung contours were obtained by thresholding the on-peak (140 keV) reconstructions. Outer body contours were defined from images produced by reconstruction of the lower energy scatter window obtained simultaneously at the time of the lung (MAA) imaging. Following assignment of standard attenuation values to the lung and nonlung (soft tissue) regions attenuation correction was achieved by means of a modified iterative Chang algorithm. The results were quantitatively evaluated by imaging of a cardiac phantom filled with uniform activity placed in a chest phantom. Sensitivity to the choice of lung and soft tissue attenuation values, the choice of the threshold used for lung segmentation, and errors in registration of the attenuation map were assessed. RESULTS: Application of this technique in a chest phantom and in patients imaged with both 201Tl and 99mTc-sestamibi resulted in improvement in artifactually decreased inferior wall activity without adversely affecting the other walls. The results were relatively insensitive to choice of values for lung and soft-tissue attenuation, lung thresholding, and small (< or = 1.3 cm) registration errors. CONCLUSION: This simple method corrects for nonuniform attenuation in males; studies are underway to adapt the method to determine breast contour in females and to determine the value of the method in clinical practice.

Artifacts↗

Genotypic analysis of Epstein-Barr virus isolates associated with nasopharyngeal carcinoma in Chinese immigrants to the United States.

EBV genotypes of first- and second-generation Chinese diagnosed with nasopharyngeal carcinoma in the United States were analyzed by PCR techniques. Previous studies showed a geographical distribution of genotypically distinct sub-types of EBV. Viruses detected at a higher frequency among Chinese NPC patients (Cf) were distinguished from those found in the majority of Caucasian NPC patients (DF) in the United States by polymorphisms in the BamHI F and I regions. Exploiting this distinction, we analyzed the biopsies of Chinese immigrants in the United States for their C/D and F/f genotypes to evaluate the importance of retention of the Cf virus among Chinese NPC patients in a geographical area where the DF virus prevails. This study shows that approximately 45.5 to 50% of first- and second-generation Chinese NPC patients in California harbor the Cf virus, which is present in only 8% of Caucasian NPC patients in California. It is interesting that, while only 48% of the viral isolates from immigrant Chinese to California harbor the "f" variant, 96% harbor the type-C viruses.

Base Sequence↗

Novel Asp32-replacement tetrapeptide analogues as potent and selective CCK-A agonists.

A series of novel CCK tetrapeptide analogues of the general formula Boc-Trp-Lys(Tac)-N(R)-(CH2)nCON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK-A receptor affinity and selectivity. The effect of N-methylation pattern on CCK-A receptor affinity showed consistent trends for analogues in which n = 1, 2, or 3, with the di-N-methylated analogues having the highest affinity in each case. However, none of these analogues had full agonist activity, as measured by percent maximal PI hydrolysis. Two conformationally constrained analogues also demonstrated high CCK-A receptor affinity and selectivity, as well as nearly maximal agonist activity. In addition, one of these conformationally-constrained analogues demonstrated anorectic activity in rats.

Amino Acid Sequence↗

CCK-A-selective tetrapeptides containing lys(N epsilon)-amide residues: favorable in vivo and in vitro effects of N-methylation at the aspartyl residue.

Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N epsilon-carbamoyl) substituent with N epsilon-acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp.

Amino Acid Sequence↗

Tetrapeptide CCK-A agonists: effect of backbone N-methylations on in vitro and in vivo CCK activity.

N-Methylation of backbone amide bonds was conducted on a tetrapeptide that had been identified previously (Shiosaki, K.; et al. J. Med. Chem. 1991, 34, 2387-2842) as a potent and selective CCK-A agonist. N alpha-Methylation at the position corresponding to Asp32 (CCK-33 numbering) was consistent with high affinity, efficacy, and selectivity for the CCK-A receptor. Combination of this (N-Me)Asp with the (N-Me)Phe modification also provided a highly active analogue. The observation of parallel structure-binding affinity profiles with respect to sites of N-methylation in the C-terminal regions of tetrapeptide vs heptapeptide CCK analogues suggests that the two series interact similarly with the CCK-A receptor.

Amino Acid Sequence↗

Tetrapeptide CCK agonists: structure-activity studies on modifications at the N-terminus.

We had reported earlier on a novel series of potent and selective tetrapeptide cholecystokinin-A (CCK-A) agonists of the general structure Boc-Trp-Lys[epsilon-Y]-Asp-N(R)PheNH2 [Y = amides, ureas; R = H, Me] that were potent anorectic agents in rats. In an effort to optimize the potency, selectivity, stability, and efficacy of our lead candidate A-71623 [R = Me, Y = o-tolylaminocarbonyl; Tac] toward development of a clinical candidate, we have explored a series of analogues in which the N-terminal Boc functionality was systematically replaced with various amides, ureas, carbamates, and sulfonamides of differing size, hydrophobicity, and stereoelectronic properties. In general, these analogues maintained good potency and selectivity for the CCK-A receptor (guinea pig pancreas), as well as potent anorectic activity in rats. Those analogues exhibiting equal or superior activity compared to A-71623 but differing physicochemical properties may represent superior drug candidates.

Amino Acid Sequence↗

Fine-needle aspiration biopsy of pituitary carcinoma with cervical lymph node metastases: a report of two cases and review of the literature.

Metastases from pituitary carcinomas are rare lesions that can mimic other tumors on fine-needle aspiration biopsies. Two patients with primary pituitary neoplasms developed cervical lymph node metastases, which were sampled and diagnosed correctly using the fine-needle aspiration biopsy technique. These two cases demonstrate the varied cytologic patterns of pituitary neoplasms, ranging from uniform bland cells to cells with striking anaplastic features. The time period between the onset of symptoms and subsequent metastases is unpredictable as well, underscoring the need for an accurate clinical history before a meaningful cytologic interpretation is made.

Adult↗