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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 217 records · Page 12Linked to original sources

Factors influencing the delivery of pharmacy services.

This study of 590 community pharmacies examined relationships between prescription payment methods and the number of pharmacy services provided at community pharmacies. Also studied were pharmacists' perceptions regarding: (1) the importance of 24 different pharmacy services, (2) the importance of three motivating factors in providing pharmacy services, (3) satisfaction with three methods of payment for pharmacy services, and (4) agreement with factors cited in the literature as barriers to pharmaceutical care. Results revealed a significant positive relationship (p < 0.05) between the number of pharmacy services provided and the percentage of private-pay prescriptions processed. A significant (p < 0.05) inverse relationship was identified between the number of pharmacy services provided and both the percentage of prescriptions processed for third parties other than Medicaid and the percentage of all third party prescriptions processed. Financial incentives were identified as the most important motivator in providing pharmacy services. Private-pay reimbursement was significantly more satisfactory to respondents than Medicaid reimbursement, and both were more satisfactory than reimbursement by a third party other than Medicaid. The greatest perceived barriers to the provision of pharmacy services involved financial and administrative considerations. Results suggest that financial incentives play a critical role in stimulating the provision of pharmacy services.

Adult↗

Viral taxonomy.

Explore the source record for details and available documents.

Terminology as Topic↗

Lateral thigh free flap in head and neck reconstruction.

To understand the role of the lateral thigh flap in head and neck reconstruction, we performed injection studies and anatomic dissections in 2 fresh and 61 preserved cadaver extremities followed by 10 clinical cases involving defects after tumor ablation. The flap, based on the third perforator of the profunda femoris artery, is designed on the posterolateral aspect of the distal thigh. The pedicle courses through the biceps short head, allowing optional transfer of this muscle. Defects of the oral cavity, pharynx, cervical esophagus, and external skin were successfully restored. One flap was unsuccessful because of intraoperative injury to the vascular pedicle. Compared with the radial forearm flap, the lateral thigh flap provides more tissue and the donor scar is more easily hidden, but the vascular pedicle is shorter, of smaller caliber, and more variable. The lateral thigh flap provides thin, pliable, and reliable tissue for a variety of needs in properly selected patients.

Adult↗

Abdominal wall strength, bulging, and hernia after TRAM flap breast reconstruction.

The incidence of postoperative abdominal bulge, hernia, and the ability to do sit-ups was reviewed in a series of 268 patients who had undergone free TRAM (FTRAM) or conventional TRAM (CTRAM) flap breast reconstruction. Minimum follow-up was 6 months. Patients were divided into four groups: unilateral FTRAM (FT1P; n = 123), double-pedicle bilateral FTRAM (FT2P; n = 45), single-pedicle CTRAM (CT1P; n = 40), and double-pedicle or bilateral CTRAM (CT2P; n = 60). The incidence of abdominal bulges (3.8 percent) and hernia (2.6 percent) was similar in the four groups. Synthetic mesh, however, was required for reinforcement of donor site closure twice as often in the CTRAM patients. The ability to perform sit-ups was greatest in the FT1P group (63.0 percent), slightly lower in the CT1P group (57.1 percent), still lower in the FT2P group (46.2 percent), and lowest in the CT2P group (27.1 percent; p = 0.0005). Patients reconstructed with an FTRAM flap were more likely to be able to do sit-ups (58.3 percent) than were those reconstructed with a CTRAM flap (38.2 percent; p = 0.0074). Patients who had only one muscle pedicle used were more likely to be able to do sit-ups (61.7 percent) than were those who had two muscle pedicles used (35.6 percent; p = 0.0003). We conclude that the incidence of abdominal bulge or hernia is relatively independent of the type of TRAM flap used and the number of muscle pedicles harvested. On the other hand, postoperative abdominal strength, as measured by the ability do sit-ups, is influenced significantly by both of these factors.

Abdominal Muscles↗

Anticoagulants and hematomas in free flap surgery.

A review of systemic anticoagulant use in 517 free flap procedures was performed to determine the associated risk of hematoma formation. Patients were divided retrospectively (not randomly) into five groups: no anticoagulation (227 flaps, 5.3 percent hematomas), low-dose heparin bolus of 2000 to 3000 units and postoperative infusion at a rate of 100 to 400 units/hr for 5 to 7 days (192 flaps, 6.7 percent hematomas), intraoperative bolus of 5000 units of heparin without postoperative anticoagulation (46 flaps, 6.5 percent hematomas), high-dose heparin infusion at a rate of 500 to 1200 units/hr (30 flaps, 20 percent hematomas), and dextran 40 infusion at a rate of 25 ml/hr (22 flaps, 9.1 percent hematomas). Intraoperative blood loss was similar for all groups. The flap loss rate was lower in the bolus (1.0 percent) and low-dose (1.0 percent) heparin groups than in the no-anticoagulation group (4.4 percent), but this difference was not statistically significant. The pedicle thrombosis rate also was lower in the bolus (2.2 percent) and low-dose (2.1 percent) heparin groups than in the no-anticoagulation group (6.2 percent). A cause-and-effect relationship between the use of anticoagulants and flap loss or prevention of thrombosis could not be established. We can conclude, however, that the use of low-dose heparin does not increase significantly the risk of hematoma or intraoperative bleeding.

Blood Loss, Surgical↗

Morbidity and functional outcome of free jejunal transfer reconstruction for circumferential defects of the pharynx and cervical esophagus.

Free jejunal transfer has been criticized by some surgeons as unreliable, poorly tolerant of radiation therapy, and associated with significant morbidity and dysphagia. To determine the validity of these criticisms, we reviewed 93 patients who underwent 96 free jejunal transfers for repair of circumferential pharyngoesophageal defects over a 5-year period. The free jejunal transfer success rate was 97 percent; all 3 failures were repaired with repeated free jejunal transfer. The complication rate was 57 percent (55 of 96); fistula (19 percent) and stricture (15 percent) were the most common complications. An oral diet was tolerated by 80 percent of patients; 85 percent of these resumed their diet within 2 weeks of surgery. Causes of dysphagia were multifactorial. Postoperative radiation therapy did not increase morbidity or dysphagia. The perioperative mortality rate was 2 percent. We conclude that free jejunal transfer is a reliable method of pharyngoesophageal reconstruction that has an acceptable morbidity rate and a low mortality rate. Postoperative radiation therapy is well tolerated by the free jejunal transfer.

Adolescent↗

Pure paraflagellar rod protein protects mice against Trypanosoma cruzi infection.

The paraflagellar rod proteins (PAR) purified from Trypanosoma cruzi epimastigotes were shown to protect mice against an otherwise lethal challenge inoculum of 10(3) bloodstream-form trypomastigotes. The injection route used for immunization was shown to have a marked impact on the development of protective immunity. Mice receiving subcutaneous (s.c.) injections of PAR proteins had reduced bloodstream parasitemias and showed 100% survival following challenge. In contrast, mice immunized via the intraperitoneal (i.p.) route developed parasitemia levels equivalent to those of unimmunized controls and did not survive infection. Western blotting (immunoblotting) demonstrated that sera from both i.p. and s.c. immunized mice reacted specifically with PAR proteins; however, the antibody titer of the i.p. immunized mice was approximately 64-fold greater than that of the s.c. immunized mice, suggesting that the protective response in the s.c. immunized mice is cell mediated rather than humoral.

Animals↗

Central effects of endothelin on respiratory output during development.

Both endothelin-1 protein and endothelin-1 specific binding sites have been identified in areas of the medulla oblongata involved in respiratory control. We examined whether endothelin acting centrally affects respiratory output during early postnatal life. We initially examined the effect of intracisternally administrated endothelin on respiratory output in 10 2- to 18-day-old piglets. Endothelin-1 administration at 50 nmol to 1 mumol caused respiratory inhibition. We subsequently examined whether this response is mediated through chemosensitive areas of the ventral medulla. Endothelin-1 was microinjected into specific ventral or dorsal medullary regions in 31 14- to 22-day-old piglets. Microinjection of endothelin-1 (10 fmol to 0.1 pmol) just above the hypoglossal roots, lateral to the pyramids, and within 1 mm from the surface (n = 24) attenuated respiratory output, and complete apnea occurred with 1 pmol in all animals. However, microinjection of endothelin-1 3 mm below the ventral surface (n = 5) and into the dorsal medulla (n = 3) had no inhibitory effect. Comparable doses of angiotensin II (n = 5) and norepinephrine (n = 5) microinjected into the endothelin-1 sensitive area also did not influence respiratory output. These effects of endothelin-1 were not altered by prior endothelin-B receptor blockade (IRL-1038) but could be reversed by endothelin-A receptor blockade (BQ-610). These results suggest that endothelin-1 release may cause ventilatory depression mediated through endothelin-A receptors located in the chemosensitive areas of the ventrolateral medulla.

Animals↗

Neurochemical control of tissue resistance in piglets.

Lung resistance may be influenced by chemoreceptor activity and modulated by inspiratory neural output; however, it is unknown whether the contractile elements of lung tissue participate in these changes during early development. In anesthetized paralyzed open-chest piglets, we measured phrenic electroneurogram, lung resistance (RL), and tissue resistance utilizing alveolar capsules to partition the hypercapnic and hypoxic responses of RL into tissue (Rti) and airway resistance (Raw) components. Inhalation of 7% CO2 significantly increased RL (7.4 +/- 0.5 to 11.3 +/- 0.6 cmH2O.l-1.s), Rti (5.2 +/- 0.5 to 6.9 +/- 0.5 cmH2O.l-1.s), and Raw (2.2 +/- 0.2 to 4.4 +/- 0.4 cmH2O.l-1.s). Inhalation of 12% O2 caused more modest increases in RL, Rti, and Raw. Oscillations in tracheal and alveolar pressures appeared in synchrony with phrenic activity in response to both chemoreceptor stimuli. Cholinergic blockade eliminated these oscillations and significantly reduced the hypercapnic and hypoxic responses of RL, Rti, and Raw. These data demonstrate for the first time that hypercapnia and hypoxia elicit a cholinergically mediated increase in Rti which, just like the airway component of RL, is modulated by inspiratory neural output and is present during early development. Such coordination in neural function throughout the respiratory system may serve to optimize gas exchange during early postnatal life.

Airway Resistance↗

Non-radioactive localization of nucleic acids by direct in situ PCR and in situ RT-PCR in paraffin-embedded sections.

Technological developments have made possible extension of polymerase chain reaction (PCR) analysis to individual cells to localize DNA/RNA with non-radioactive labels at the light microscopic level. This approach, in situ PCR, is particularly useful in resolving low-frequency message expression in mixed populations of cells and tissues. We have established a working protocol for direct in situ PCR and have utilized several controls to validate our results. In this report we outline the procedures for detecting either DNA or RNA in a rapid and reproducible manner. We evaluate the sequential steps required for this analysis, such as protease hydrolysis, DNAse digestion, "hot start" capabilities, and detection methods. We have applied these methods in several applications, including detection of the p53 gene in human tumor samples, localization of insulin-like growth factor-IA mRNA in cell lines with low levels of expression, and distribution of transferrin mRNA in lung cancer cell lines and tumors. We demonstrate from this study that the in situ PCR technique is an investigative approach capable of detecting specific DNA/RNA sequences at the cellular level and of identifying cells with low levels of mRNA expression.

Base Sequence↗

A comparison of swallowing during apnea and periodic breathing in premature infants.

Periodic breathing and apnea are two forms of ventilatory instability which are commonly observed in premature infants. This study was undertaken to characterize the pattern of swallowing during apnea and compare this pattern to that present during breathing. We assessed the frequency and distribution of swallows during the respiratory pauses of apnea and periodic breathing in 22 premature infants birth weight 1.2 +/- 0.2 kg, postconceptional age 34 +/- 2 wk. Twelve infants had apnea and 10 exhibited periodic breathing. During sleep the pharyngeal phase of swallowing was detected by a catheter in the pharynx and esophageal peristalsis by an esophageal pressure catheter. Nasal airflow was monitored by a pneumotachometer. During apnea, the frequency of swallows was significantly greater than during the respiratory pauses of periodic breathing (15.9 +/- 8.2 versus 0.72 +/- 0.73 swallows/min, respectively, p < 0.0001) and also much higher than the rate of spontaneous swallows during sleep in either group (0.66 +/- 0.66 and 0.58 +/- 1.08 swallows/min, respectively). We conclude that an increased rate of swallowing is characteristic of apnea in premature infants, and distinguishes apnea from the respiratory pauses of periodic breathing.

Apnea↗

Perinatal nitric oxide synthase inhibition retards neonatal growth by inducing hypertrophic pyloric stenosis in rats.

Administration of the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) during pregnancy has been shown to compromise fetal growth. This study was designed to determine whether aminoguanidine, a predominate inhibitor of inducible NOS, affects fetal outcome. In addition, we extended the prenatal administration of L-NAME into the postnatal period (14 d) to determine whether neonatal growth and maturation were also affected. L-NAME, but not aminoguanidine, compromises fetal and placental growth. When compared with control 14-d-old pups, postnatal L-NAME compromised neonatal growth, whether it was given directly (intraperitoneally) (39.7 +/- 1.1 versus 24.1 +/- 1.0 g) or indirectly (38.6 +/- 0.5 versus 22.2 +/- 1.2 g) via maternal breast milk. Neonatal growth retardation was asymmetric, with brain sparing, suggesting a nutritional origin. L-NAME administration resulted in growth retardation that extended into adulthood, without evidence of catch-up growth. Treated neonates displayed the hallmarks of hypertrophic pyloric stenosis. Significant increases in stomach weight/pup weight (9.9 +/- 0.3 versus 8.2 +/- 0.4 x 10(3)) and stomach volume/pup weight (12.0 +/- 0.6 versus 9.4 +/- 0.6 mL/100 g) with a concomitant decrease in small intestine weight/length (2.10 +/- 0.08 versus 3.18 +/- 0.13 g/100 cm) was noted in treated versus control pups (p < 0.05). Muscularis hypertrophy at the pyloric sphincter in the L-NAME-treated pups was noted by histology. Blood pressure was elevated in the L-NAME-treated pups (93 +/- 6 versus 60 +/- 5 mm Hg in control pups, p < 0.05). These findings are consistent with inhibition of neuronal and endothelial NOS activity. We conclude that NO, formed via the constitutive isoforms of NOS, is a critical determinant of fetal and neonatal growth and maturation.

Animals↗

Limb reduction defects after prenatal inhibition of nitric oxide synthase in rats.

To determine the influence of nitric oxide (NO) on vascular tone during fetal development, timed pregnant rats received the NO synthase inhibitor NG-nitro-L-arginine methyl ester for consecutive 4, 7, or 14 d before parturition (postorganogenesis). Offspring demonstrated limb reduction defects (incidence, 53%) involving either or both hindlimbs, whereas forelimbs were uniformly spared. Defects were dose-dependent but independent of the duration of administration occurring with equal frequency in 4-, 7-, and 14-d treatment groups. Histologic analysis revealed features characteristic of vascular disruption with hemorrhagic necrosis and loss of structure. The defects were prevented by concurrent maternal administration of L-arginine or the NO donors S-nitroso-N-acetyl-penicillamine and sodium nitroprusside. Defects were not seen after prenatal treatment with aminoguanidine. To study basal and agonist-mediated NO release, newborn femoral and brachial arteries were cannulated with a glass micropipette under constant pressure, and changes in intraluminal diameter (micrometers) were measured in response to acetylcholine and the NO synthase inhibitor N omega-nitro-L-arginine. Newborn femoral and brachial vessels demonstrated a dramatic (59%) decrease in resting diameter compared with adult vessels (16%). These findings suggest that basal NO release is upregulated during fetal development concurrent with the processes that increase maternal NO release. The data also suggest that up-regulation of NO release occurs throughout the fetal systemic circulation and is not restricted to hindlimbs. This is the first study to demonstrate inhibition of NO release in the pathogenesis of limb reduction defects.

Acetylcholine↗

Expression of adrenomedullin in normal human lung and in pulmonary tumors.

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. In this report we present evidence, using reverse transcriptase-polymerase chain reaction, immunocytochemistry, and in situ reverse transcriptase-polymerase chain reaction, that AM is synthesized by several cell populations of the normal lung, tumor cell lines of pulmonary origin, and tumor specimens. Among the normal cell populations of the lung, we found AM expression in the columnar epithelium, some glands, neurons of the pulmonary parasympathetic nervous system, endothelial cells, chondrocytes, alveolar macrophages, and smooth muscle cells. In tumors, AM expression was located in most of the nonsmall cell lung carcinomas and in half of the small cell lung carcinomas studied. These findings suggest that AM may play a broad role in respiratory homeostasis and lung carcinogenesis.

Adenocarcinoma↗

Reconstruction and the radiated breast: is there a role for implants?

The use of breast implants in irradiated patients is controversial. Recently, 39 irradiated implants were compared with 338 nonirradiated implants in 297 patients between January of 1975 and October of 1994 at The University of Texas M. D. Anderson Cancer Center. Tissue expanders and follow-up time of less than 6 months excluded patients from the study. Five groups of patients were identified. Group 1 consisted of 7 patients and 7 implants who received postoperative adjuvant radiotherapy after implant placement. Group 2 consisted of 5 patients and 7 implants who received preoperative adjuvant radiotherapy prior to implant placement. Groups 3 and 4 consisted of 2 and 12 patients (2 and 19 implants) placed beneath latissimus dorsi flaps who had postoperative and preoperative adjuvant radiotherapy, respectively. Group 5 contained 4 patients with 4 implants placed beneath a transverse rectus abdominis myocutaneous (TRAM) flap who had preoperative radiotherapy. All implants were placed submuscularly or beneath autogenous flaps. The average irradiated breast received 50 Gy. For statistical purposes, two categories were identified. Capsular contracture (Baker III or greater), pain, exposure, and implant removal in 6 of 14 implants that received radiotherapy were compared with similar complications in 33 of 266 implants without irradiation (p = 0.001). The second category contained 10 complications in 25 implants placed beneath autogenous reconstructions with radiotherapy compared with 6 of 72 similar complications in implants placed beneath autogenous reconstructions without radiotherapy (p = 0.000). Results showed that irradiation has significant negative effects on the reconstructive outcome with implants. Autogenous reconstruction did not appear to offer a protective role when placed over implants.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Implants↗

Analysis of small cell lung cancer cell growth inhibition by 13-cis-retinoic acid: importance of bioavailability.

13-cis-Retinoic acid can mediate differentiation of transformed cells and slow the proliferation of malignant cells, suggesting its use as a potential intervention tool. Specific cDNA probes for retinoic acid receptors demonstrated the expression of mRNAs for the different retinoic acid receptor isoforms in small cell lung cancer cell lines. Addition of 13-cis-retinoic acid to small cell lung cancer cells cultured using serum-free, hormonally defined medium resulted in a 5-8-fold increase in the level of the retinoic acid receptor-beta mRNAs; in medium containing serum, the increase in expression of the retinoic acid receptor-beta mRNAs was less pronounced, usually no more than 2-fold. Using an in vitro proliferation assay, addition of 13-cis-retinoic acid resulted in a significant dose-dependent, growth-inhibitory effect on the small cell lung cancer cell lines tested using serum-free conditions. These inhibitory effects decreased when cells were cultured in medium containing serum or serum components. Molecular size exclusion chromatography and native gel electrophoresis showed that the causative serum component eluted and migrated with serum albumin. Preincubating serum with triglycerides restored the inhibitory effects of 13-cis-retinoic acid demonstrated in serum-free systems. These data suggest that 13-cis-retinoic acid preferentially binds to serum albumin, restricting its inhibitory effects on epithelial cell receptors. Blocking retinoic acid-albumin interactions with a fatty acid source may improve the bioavailability of 13-cis-retinoic acid and significantly enhance the inhibitory effect in vivo.

Blotting, Northern↗

Hydroxocobalamin (vitamin B12a) prevents and reverses endotoxin-induced hypotension and mortality in rodents: role of nitric oxide.

The cobalt atom of hydroxocobalamin (OHC) binds cyanide and nitric oxide (NO) and OHC attenuates vascular responses to NO in vitro. NO mediates the hypotension of endotoxemia. Thus, we tested the postulate that OHC may attenuate the acute phase hypotension and toxicity associated with administration of Escherichia coli endotoxin (LPS). Rats were given OHC (20 mg/kg i.v.) or phosphate-buffered saline (PBS, 1 ml/kg i.v.) 30 min before or 15 min after giving LPS (0.8 mg/kg i.v.). Administration of OHC to PBS-treated control rats did not affect mean arterial pressure (MAP), heart rate or the plasma or urine content of the reactive nitrogen intermediates nitrate and nitrite (RNI). LPS decreased MAP by 50 mm Hg in PBS-treated rats and increased the plasma and urinary content of RNI. Administration of OHC to PBS-treated rats did not affect MAP or RNI. However, treatment with OHC before or after giving LPS attenuated LPS-induced hypotension and increases in plasma RNI and enhanced LPS-induced urinary excretion of RNI. OHC (20 mg/kg i.p.) or cyanocobalamin (10 mg/kg i.p.) given to Swiss-Webster mice 30 min before giving LPS (16 mg/kg i.p.) decreased the 24-hr mortality of LPS from 80 to 50% and the 36- and 96-hr mortality from 100 to 60% (OHC) or 70% (cyanocobalamin). Urine obtained from conscious rats given LPS (5 mg/kg i.p.) and OHC (20 mg/kg i.p.) exhibited a UV-visible absorbance spectrum with absorbance peaks characteristic of that formed after coincubation of NO and OHC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endoscopic technique for free flap harvesting.

We have described the current state of development of endoscopic techniques used for harvest of the latissimus dorsi and rectus abdominis muscles, two of the most versatile reconstructive tissue sources available to plastic surgeons. We also have described our clinical experience with harvest of jejunal segments. The potential for the use of these tissues without the conventional pattern of scarring is very exciting. The broader implications for harvesting other donor tissues such as the gracilis, internal oblique, and serratus anterior muscles, and the thoracodorsal and temporalis fascias are on the near horizon. More sophisticated instrumentation is necessary, however, to facilitate the endoscopic approach in the subcutaneous space. This will necessarily include the development of better mechanisms for the creation and maintenance of the optical space. Fortunately, advances in this important technology are occurring month by month as experience and interest heighten, and instrumentation is improved. With increased experience and instrumentation development, it is possible that minimally invasive tissue harvest will become the future standard.

Endoscopy↗