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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 199 records · Page 11Linked to original sources
PubMed1996

Tc-99m sestamibi cardiac SPECT imaging during coronary artery occlusion in humans: comparison with dipyridamole stress studies.

PURPOSE: To compare the magnitude of change in regional myocardial perfusion during dipyridamole stress with that during coronary occlusion. MATERIALS AND METHODS: The authors prospectively studied 14 men with more than 50% diameter stenosis in at least one major coronary artery. Same-day rest and dipyridamole technetium-99m sestamibi single photon emission computed tomography (SPECT) was performed 24 hours before coronary angioplasty. During angioplasty, while the vessel was occluded, 15 mCi(555 MBq) of tracer was injected, and SPECT studies were obtained 60 minutes later. Extent of regional perfusion abnormalities was estimated. RESULTS: Regional perfusion defect was greater during stress and occlusion than during rest (20%, P = .001 and 14%, P = .009, respectively). SPECT defect during coronary occlusion was similar to that obtained during pharmacologic stress with dipyridamole (53% vs 47%, P = .02). CONCLUSION: Tc-99m sestamibi SPECT with dipyridamole stress is a good predictor of the extent of perfusion abnormalities that occur during coronary occlusion and may facilitate estimation of the total myocardium in jeopardy from a stenotic lesion.

Adult↗
PubMed1996

Effects of theophylline on pharyngeal dilator and diaphragm muscle contractile properties.

Theophylline alleviates central and obstructive apneas of prematurity, and may improve adult obstructive sleep apnea. One mechanism of action appears to be a stimulatory effect on the motor output to upper airway dilator muscles. The purpose of the present study was to determine whether theophylline might have a second mechanism of action, namely that of improving the force and/or endurance of the pharyngeal dilator musculature. Rat sternohyoid muscle strips were studied in vitro and compared to diaphragm strips. The isometric twitch force and twitch kinetics of neither muscle were altered by theophylline (100 mg/l). Theophylline significantly slowed the rate at which the diaphragm fatigued during intermittent 40-Hz stimulation (p < 0.001). In contrast, theophylline produced no improvement in the fatigue resistance of the sternohyoid muscle. The degree of force potentiation during the early portion of the fatigue protocol was not altered by theophylline for either muscle. These results suggest that the mechanism by which theophylline improves obstructive apnea is unlikely to be due to a beneficial effect on pharyngeal dilator muscle force or endurance.

Animals↗
PubMed1996

Prospects for cooperative management of international migration in the 21st century.

"This essay attempts, first, to identify patterns and trends from an overview of the modern history of international migration. It examines, then, aspects of human agency and macro-systematic factors to sift for clues as to the future role of international migration and prospects for cooperation management of it. Finally, specific features of the regional migration system in Asia are identified, which will contribute to shape the future course of international migration."

Asia↗
PubMed1996

Regulation of insulin secretion and blood glucose metabolism by adrenomedullin.

Adrenomedullin (AM), a recently discovered hypotensive peptide, is expressed in the endocrine pancreas of different species, as demonstrated by immunocytochemistry. Electron microscopic studies with double immunogold showed colocalization of AM and pancreatic polypeptide. A homogeneous expression of AM receptor was found throughout the islet using in situ hybridization. Six different insulin- producing cell lines have been analyzed by reverse transcription-PCR and showed expression of both AM and its receptor. Two experimental models have been used to study the effects of AM in pancreatic physiology. 1) Analysis of isolated rat islets shows that AM inhibits insulin secretion in a dose-dependent manner. The monoclonal antibody MoAb-G6, which neutralizes AM bioactivity, was able to increase insulin release 5-fold; this effect was reversed by the addition of synthetic AM. 2) Oral glucose tolerance tests showed that iv injection of AM reduces the levels of insulin in the bloodstream with a concomitant increase in circulating glucose. These studies implicate AM as a newly defined factor of the insulin regulatory system that could be involved in disorders such as diabetes and obesity.

Adrenomedullin↗
PubMed1996

A retrospective analysis of the costs and consequences of a tobacco-cessation program for active duty service members.

Health system records of 126 active-duty (AD) service members who were participants in the Davis-Monthan AFB "Quitters are Winners" tobacco cessation program (QAWP) between June 1993 and May 1994 were reviewed retrospectively during the fall of 1994. Participants received an average of 2.84 (+/- 1.46) prescriptions for transdermal nicotine replacement therapy representing 6 weeks duration. Tobacco abstinence, determined by 6-month point prevalence abstinence (PPA), was 19.05 and 15.08% for 6-month continuous abstinence (CA). PPA and CA rates were significantly higher than expected (z = 3.94, p < 0.002; z = 2.38, p < 0.02). Average operational cost per successful outcome at 6 months after entry into the QAWP were $778.93 using PPA and $983.92 using CA. Additional analyses revealed corresponding increases between average cost per successful outcome and duration of TNRT. This research provides an initial analysis of the efficiency of the QAWP for AD participants and a model for subsequent evaluations within military medical treatment facilities.

Adult↗
PubMed1996

MR appearance of the internal architecture of Ammon's horn.

PURPOSE: To determine whether the four subdivisions of Ammon's horn and six layers of CA1 seen histologically can be demonstrated with MR imaging. METHODS: Specimens of cadaver brains were imaged in a 3.0-T MR imager with a 3.0-cm solenoid coil. The specimens were sectioned, stained, and examined histologically. On anatomic sections, the four subdivisions of Ammon's horn and six layers of CA1 were identified. The MR images were then compared with the anatomic sections. RESULTS: Using geographic characteristics, we identified the four subdivisions of Ammon's horn. In CA1, the six layers could be identified by variations in signal intensity, width, and location. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, the internal architecture of Ammon's horn may be identified.

Brain Mapping↗
PubMed1995

Outcome and complications of extended cranial-base resection requiring microvascular free-tissue transfer.

OBJECTIVES: To determine the complications of extensive cranial-base resection requiring free-tissue transfer (FTT) and the effect of these resections on local control and survival among patients with malignant neoplasms of the skull base. BACKGROUND: Before the advent of FTT, cranial-base surgery was often limited by our inability to adequately repair defects comprising communication between the central nervous system and upper aerodigestive tract. The use of FTT in cranial-base resections was therefore assessed to determine whether the improved procedure (ie, extensive resections) would improve local control and prolong survival. DESIGN: A retrospective review of 39 consecutive craniofacial resections with FTT reconstruction in patients with malignant neoplasms involving the cranial base. PATIENTS: All 39 patients had malignant neoplasms, including 20 squamous cell carcinomas, eight basal cell carcinomas, two melanomas, two neuroendocrine carcinomas, two adenoid cystic carcinomas, and various other malignant neoplasms. Resections involved the anterior, middle, or posterior cranial fossa in 19 patients (49%), 10 patients (26%), and three patients (8%) of cases, respectively. The remaining seven surgeries (18%) involved resection of more than one of these cranial base sites. RESULTS: Early (< 14 days after surgery) complications occurred in 14 (36%) of 39 patients. Major complications included failure of microvascular anastomosis (n = 1), pneumonitis (n = 3), perioperative myocardial infarction (n = 1), and cerebrovascular accident (n = 1). The microvascular anastomosis failure was promptly treated with surgical intervention. Two patients (5%) experienced late postoperative complications; one had cellulitis at the donor site, and the other had pneumonitis. No perioperative deaths or complications such as meningitis, epidural abscess, or tension pneumocephalus occurred. The 2-year disease-specific survival rate was 55%, and the 2-year local control rate, 49%; both were determined by the Kaplan-Meier method. The nine patients who died of their disease had a median survival of 9 months. Log-rank testing showed that pathologically positive margins and transdural pathology were the most significant predictors of local recurrence and death of disease. CONCLUSIONS: Contemporary surgical approaches provide an opportunity for wide surgical excision of dura and skull-base structures that normally separate the intracranial and extracranial cavities. These major skull-base resections can be reconstructed safely and effectively with FTT. Patients with malignant neoplasms of the dura and skull base should be approached with the understanding that transdural disease portends an increased risk of local recurrence and death of disease.

Adolescent↗
PubMed1995

Tenidap in rheumatoid arthritis. A 24-week double-blind comparison with hydroxychloroquine-plus-piroxicam, and piroxicam alone.

OBJECTIVE: To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquine-plus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients. METHODS: A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mg/day and piroxicam 20 mg/day, or piroxicam alone 20 mg/day, for 24 weeks. RESULTS: At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicam-treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated patients (6.4%) manifested mild, nonprogressive, reversible proteinuria of presumed renal proximal tubular origin, and 3-4% of patients had elevated transaminase levels. CONCLUSION: In the treatment of patients with RA, tenidap is as effective as the combination of hydroxychloroquine-plus-piroxicam, and is more effective than piroxicam alone; moreover, tenidap's safety profile is comparable to that observed with piroxicam alone, and with hydroxychloroquine-plus-piroxicam. The clinical response observed in this study, as well as the prompt decreases in acute-phase protein levels of CRP and SAA, and in plasma IL-6 levels, suggest that tenidap represents a new type of antiarthritic medication, with properties similar to, but not identical to, a therapeutic combination of a nonsteroidal antiinflammatory drug with disease-modifying antirheumatic drugs.

Adult↗
PubMed1995

Microvascular craniofacial reconstruction in cancer patients.

BACKGROUND: Resections of large malignancies involving the middle and upper thirds of the face and cranium result in complex defects, posing a difficult challenge for the reconstructive surgeon. Free tissue transfer may be the best means of reconstruction. METHODS: We reviewed 54 consecutive microvascular craniofacial reconstructions after tumor ablation performed at the University of Texas M.D. Anderson Cancer Center from May 1988 to September 1992. Information regarding patient characteristics, tumor stage and histology, history of prior therapy, the defect after tumor ablation, and the details of the reconstruction were entered in a microcomputer database at the time of the initial surgery. Free flap outcome, the number and type of complications, control of malignant disease, and the use of adjuvant therapy were recorded prospectively. RESULTS: Patients had defects of the scalp and cranium (15 of 50) or of the maxilla/orbit/cranial base (35 of 50) after resections for a variety of tumors. Immediate reconstruction was completed in 40 patients and delayed in 10. Prior therapy included surgery (39 of 50) and/or radiotherapy (35 of 50). The free flap success rate was 96% (52 of 54). In patients with successful flaps, significant wound complications occurred in 13.5% of patients (seven of 52) and donor site problems in 11.1% (six of 54) for an overall complication rate of 24.1% (13 of 54). There were no operative deaths or neurologic complications. The timing of surgery or a history of prior surgical therapy or radiotherapy did not significantly influence the complication rates. CONCLUSION: Free tissue transfers provide optimal restoration of large craniofacial defects resulting from cancer resection.

Combined Modality Therapy↗
PubMed1995

Perineal wound closure with the rectus abdominis musculocutaneous flap after tumor ablation.

BACKGROUND: We describe the transpelvic rectus abdominis musculocutaneous flap for closing large, often irradiated, perineal defects in patients with cancer. METHODS: We studied 9 men and 17 women who underwent wide excision of advanced T3 and T4 tumors and who had preoperative chemotherapy, radiotherapy, or both. After tumor ablation, we used a transpelvic rectus abdominis musculocutaneous flap to fill pelvic dead space and primarily close the perineal wounds. Twelve simultaneous vaginal reconstructions were performed. RESULTS: Wounds healed promptly in 14 patients. Healing was delayed in the remaining 12 patients due to poor flap adherence to irradiated tissue beds (9), complete flap loss (2), or partial flap loss (1). Delayed healing was associated with the combination of obesity and prior irradiation. Other perioperative complications included localized abdominal wound infection (2), enterocutaneous fistula (1), and abdominal herniation (1). Local disease was controlled in 20 of 26 patients. Mean follow-up was 22 months. CONCLUSION: Transpelvic rotation of the rectus abdominis musculocutaneous flap facilitates healing large, difficult, perineal wounds, resulting from cancer ablation.

Adult↗
PubMed1995

Role of inducible nitric oxide synthase expression and peroxynitrite formation in guinea pig ileitis.

BACKGROUND & AIMS: Inflammatory bowel disease is characterized by increased synthesis of nitric oxide. The aim of this study was to determine if inducible NO synthase (iNOS) was responsible for tissue injury, potentially via peroxynitrite formation, in the guinea pig model of gut inflammation. METHODS: Inflammation was induced in guinea pig ileum by intraluminal administration of the hapten trinitrobenzene sulfonic acid in 50% ethanol. iNOS gene expression was assessed by reverse-transcriptase polymerase chain reaction and Western blotting, immunohistochemistry was determined by its localization, and activity was inhibited with the specific inhibitor aminoguanidine administered via the drinking water for 7 days. Nitration of tyrosines was assessed by immunohistochemistry. RESULTS: In control animals, iNOS gene expression was minimal to absent, whereas, in hapten, inflammation-marked iNOS gene expression was evident from day 1 to 7. Nitrotyrosine and iNOS immunohistochemistry were colocalized, and positive staining was most intense in epithelia and neurons. Inhibition of NO formation prevented nitrotyrosine formation. Aminoguanidine inhibited the inflammatory response and restored morphology. CONCLUSIONS: The colocalization of tyrosine nitration with iNOS immunoreactivity suggests that iNOS may be responsible for tissue injury and the formation of NO-dependent nitrating species, potentially peroxynitrite. Inhibition of iNOS may afford a new therapeutic approach to the treatment of inflammatory bowel disease.

Amino Acid Sequence↗
PubMed1995

Design, synthesis, and biological evaluation of isocyanurate-based antifungal and macrolide antibiotic conjugates: iron transport-mediated drug delivery.

The syntheses and preliminary biological evaluation of conjugates of a synthetic isocyanurate-based trihydroxamate siderophore with two antifungal agents, 5-FU (conjugate 9) and norneoenactin (conjugate 12), and a macrolide antibiotic, erythromycylamine (conjugate 18), are described. A 19F NMR study was used to determine the hydrolytic stability of conjugate 9 under assay conditions. Preliminary biological studies with ferric complexes of conjugates 9 and 12 indicated that these antifungal agents are recognized by Candida and perhaps are actively transported into the cell by the siderophore-transport mechanisms. While conjugate 18 did not show any significant antibacterial activity, presumably due to size restriction, the 5-FU conjugate 9 appeared to be moderately active against a variety of Gram-positive strains, and was more active than the 5-FC control against some strains of Staphylococcus.

Anti-Bacterial Agents↗
PubMed1995

New EPSP synthase inhibitors: synthesis and evaluation of an aromatic tetrahedral intermediate mimic containing a 3-malonate ether as a 3-phosphate surrogate.

A new analog of the EPSP synthase enzyme reaction intermediate 1, containing a 3-malonate ether moiety in place of the usual 3-phosphate group, was synthesized from 3,5-dihydroxybenzoic acid. This simple, synthetically accessible aromatic compound (5) is an effective competitive inhibitor versus S3P with an apparent Ki of 1.3 +/- 0.22 microM. This result demonstrates that a simple benzene ring can be a suitable achiral substitute for the more complex shikimate ring in the design of EPSP synthase inhibitors. Furthermore, the greater potency of 5 versus the phenol 6, glycolate 7 and the gallic acid analog 8 demonstrates the requirement for multiple anionic charges at the dihydroxybenzoate 5-position in order to attain effective inhibition of this enzyme. However, this 3-malonate ether substituted compound was at least 10-fold less effective as a bisubstrate inhibitor than the corresponding 3-phosphate. This suggests that tetrahedral intermediate mimics possessing a 3-malonate ether moiety are less effective than their corresponding 3-phosphates in accessing the optimal enzyme conformation stabilizing 1.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1995

Vulnerability of respiratory control in healthy preterm infants placed supine.

OBJECTIVE: We tested the hypothesis that healthy preterm infants have attenuated ventilatory responses to hypercapnia, associated with a decreased rib cage contribution to ventilation, in the supine versus prone position. STUDY DESIGN: We elicited hypercapnic ventilatory responses from 19 healthy preterm infants (postconceptional age 35 +/- 1 weeks) who were being prepared for hospital discharge. The O2 saturation was continuously monitored. Before and during CO2 rebreathing, ventilation was measured with a nasal mask pneumotachygraph and was derived from chest wall motion as determined by respiratory inductance plethysmograph. This measuring method allowed us to compare both ventilation and the percentage rib cage contribution to ventilation between supine and prone positions. Statistical analysis employed analysis of variance with repeated measures. RESULTS: The supine position was associated with a higher respiratory rate (p < 0.02) and lower O2 saturation (p < 0.007) than the prone position. The increase in ventilation in response to hypercapnia was lower in the supine than in the prone position. This was statistically significant for the respiratory inductance plethysmograph (p < 0.008) but not the pneumotachygraph (p = 0.077), and was associated with a smaller rib cage contribution to ventilation in the supine than in the prone position (p < 0.0001). CONCLUSION: Respiratory control may be vulnerable when healthy preterm infants are placed supine. Widespread avoidance of the prone position may not be appropriate for such patients.

Carbon Dioxide↗