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Biomedical subjects

M J Miller

Publications and source records attributed to M J Miller.

At least 253 records · Page 14Linked to original sources

The free transverse rectus abdominis musculocutaneous flap for breast reconstruction: one center's experience with 211 consecutive cases.

All patients undergoing breast reconstruction with free transverse rectus abdominis musculocutaneous (TRAM) flaps from February 1989 to November 1992 were registered into a computerized database and followed prospectively. There were 211 free TRAM flap breast reconstructions in 163 patients; 48 reconstructions were bilateral. A muscle split technique was used in 108 of 211 reconstructions (51%). Total flap loss occurred in 3 of 211 reconstructions for a success rate of 99%. Complications occurred in 81 of 211 reconstructions (38%). Fat necrosis or partial flap loss occurred in 15 of 211 (7%). Hernia or bulge occurred in 11 patients (5%). The bulge/hernia rate tended to be lower in the muscle split group (4 of 108 [4%]) than in those who did not have muscle split procedures (7 of 103 [7%]), whereas the fat necrosis rate was slightly higher in the former group (9 of 108 [8%]) than in the latter (6 of 103 [6%]). Neither difference was statistically significant. However, patients who currently or previously smoked cigarettes did have a significantly higher incidence of fat necrosis: 12 of 99 smokers (12%) had fat necrosis compared with 3 of 112 nonsmokers (3%; p = 0.02).

Adult↗

Implantable venous Doppler microvascular monitoring: laboratory investigation and clinical results.

The purpose of this study was to compare the sensitivity of a 20-mHz ultrasonic Doppler device to detect microvascular thrombosis placed on the vein with that placed on the artery. A feasibility study in animals preceded a comparative clinical study in patients. Six rabbits were used to develop a bilateral hind limb perfusion model. The femoral artery and vein were isolated, and Doppler probes were affixed to each. Clamping of the artery and vein separately was followed by simultaneous measurements in both vascular probes using audio signals and strip-chart recordings. A total of 48 measurements were obtained. Probes placed on the artery immediately detected an arterial occlusion but continued to record pulsation for 220 +/- 40 minutes following venous occlusion. Mean arterial waveform amplitudes diminished by 50 percent of initial values 1 hour following venous occlusion but showed little change thereafter when followed for 6 hours. By contrast, probes placed on the vein detected venous occlusion immediately and arterial occlusion at 6 +/- 2.4 minutes (p < 0.001). Over a 4-year period, 133 patients had free-tissue transfers monitored by implantable 20-mHz ultrasonic Doppler devices: 30 arterial and 103 venous. The arterial monitors detected vascular thromboses in 4 of 6 patients, with 3 flaps salvaged. Venous Doppler monitors detected 16 of 16 thromboses, with 12 flaps salvaged. Six patients had probe/machine malfunctions during their postoperative course and were monitored by clinical means thereafter without thrombosis. There were two late extrusions of the probe cuffs implanted in subcutaneous locations. No adverse effects on the flap vessels were noted in the study. The 20-mHz ultrasonic Doppler device is an effective monitor of blood flow in microvascular anastomoses. When it is placed on the vein, a greater degree of sensitivity is demonstrated, particularly to venous obstruction, compared with probes monitoring arterial flow. The device has been reliable in a variety of institutions and nursing units without need for intensive care monitoring and has resulted in an increased salvage rate for flaps experiencing vascular thrombosis.

Adolescent↗

Health policies and procedures for medical students at US medical schools: a progress report.

This paper presents the current status of school health policy at US medical schools and discusses implications for medical students with respect to physical health and occupational risks. The authors discuss the responsibility of schools to ensure that students are healthy and fit, both for their own benefit and to provide models of good health maintenance for their future patients. Schools have an obligation to monitor public safety issues, particularly in cases of chemical impairment, student mistreatment and infection control procedures.

Education, Medical, Undergraduate↗

Application of PCR to multiple specimen types for diagnosis of cytomegalovirus infection: comparison with cell culture and shell vial assay.

Human cytomegalovirus (CMV) is a herpesvirus that is responsible for significant morbidity and mortality in congenitally infected infants and immunocompromised patients. Antiviral therapies are available, thus making timely diagnosis of significant importance to at-risk patients. A PCR system was devised. The newly devised system, unlike previously described systems, can be applied to a wide variety of specimen types in a clinical microbiology laboratory setting. Specimens from all sites routinely accepted for CMV culture were shown to be acceptable for CMV PCR. Sensitivity and specificity were established in comparison with those of both monolayer culture and shell vial assay (SVA). The sensitivity and specificity of PCR for detection of CMV in specimens exclusive of urine and blood were 97.5 (77 of 79 specimens) and 87.2% (41 of 47 specimens), respectively. The sensitivity and specificity of PCR for urine and blood specimens were 100 (10 of 10) and 95.7% (45 of 47) and 66.7 (4 of 6) and 78.8% (41 of 52), respectively. Discrepancies of positive PCR results with negative culture or SVA results occurred for specimens flanked chronologically by other culture- or SVA-positive specimens and were likely culture failures, increasing the specificity (100%) of PCR. Discrepancies of negative PCR results with positive culture or SVA results occurred in specimens with few cells or infectious foci by SVA or culture and may represent sampling variability associated with low virus titers.

Cytomegalovirus↗

Central chemosensitivity affects respiratory muscle responses to laryngeal stimulation in the piglet.

Stimulation of laryngeal afferent fibers triggers reflex apnea, which can be very long in the neonatal period. The purpose of this study was twofold: 1) to determine the effect of superior laryngeal nerve (SLN) stimulation on expiratory as well as inspiratory muscle activity and 2) to compare the respiratory response to SLN stimulation under conditions that would appear to alter the level of central chemosensitivity in anesthetized spontaneously breathing piglets. In protocol 1, we measured electromyogram (EMG) responses from the diaphragm (DIA), triangularis sterni, and transversus abdominis muscles to graded SLN stimulation; in protocol 2, we compared the DIA response to different levels of SLN stimulation during normocapnia, hypercapnia, and cooling of the ventrolateral medullary surface (VMS). SLN stimulation performed during normocapnia caused significantly greater inhibition of both expiratory muscles (triangularis sterni and transversus abdominis) than of the DIA. During hypercapnia, laryngeal stimulation-induced inhibition of all three muscles was significantly diminished, and the degree of inhibition for the three muscles became equivalent. Inhibition of the DIA EMG was significantly greater with SLN stimulation during VMS cooling than with a VMS temperature of 38 degrees C. We conclude that the magnitude of respiratory inhibition induced by laryngeal stimulation during early postnatal life is inversely related to the level of central chemical input and speculate that functional deficiency of structures located in the VMS may contribute to potentially life-threatening apnea in infants.

Animals↗

Responses of lung parenchyma and airways to tachykinin peptides in piglets.

The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral endopeptidase has been shown to modulate this effect. In these studies, we compared the SP and NKA responsiveness of piglet airways and lung parenchymal tissues in anesthetized paralyzed open-chest piglets 2-3 wk old, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti). During tidal breathing, pressure was measured at the trachea and in two alveolar regions by means of alveolar capsules. Intravenous administration of SP caused concentration-dependent increases in Rti and Raw and a decrease in dynamic lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of RL, and at any level of constriction, Rti accounted for > 50% of RL. The responses of Rti and Raw to NKA were negligible and were always significantly weaker than those to SP. These results indicate that both central airways and tissue contractile elements respond vigorously to SP, but not to NKA, in maturing piglets.

Airway Resistance↗

The neu-oncogene: signal transduction pathways, transformation mechanisms and evolving therapies.

A variety of pathways exist to transmit biological signals. One mechanism used for the regulated control of cell growth and differentiation is through the transduction of signals resulting from the binding of soluble polypeptide growth factors to their cognate receptors. The specificity of growth factor action is mediated by the interaction of ligand with cognate receptors which can lead to exquisite control in a tissue- and developmental-specific manner. In addition, individual receptors on the cell surface can form complex assemblies with other receptor/signal transduction molecules that potentially lead to additional levels of signal transmissions. Biological signaling by peptide ligands can be mediated through the enzymatic activation of the receptor resulting in the triggering of a defined biochemical pathway. Ultimately, a mitogenic or differentiation signal is delivered to the nucleus, completing the biological action of the growth factor. The biochemical mechanisms of signal transduction by the p185 neu/c-erbB-2 growth factor receptor and the subsequent physiological responses are the topics of this review. Study of the p185 growth factor receptor has helped to illustrate the functional role of receptor homo- (and hetero-) dimerization in enzyme activation and, in malignant cells, the detrimental results of structural mutations or aberrant gene expression which may effect this dimerization. The ability of one type of growth factor receptor to affect the activity of another (as illustrated by the p185/epidermal growth factor receptor heterodimeric complex) is likely to be a common regulatory feature of growth factor receptor action. The nomenclature to be used in this review will refer to the oncogenic mutated form of the rat protein as 'p185neu', the proto-oncogenic rat protein as 'p185c-neu' and the human form as 'p185c-erbB-2'. The term 'p185' will be used to refer to any type of protein, regardless of the source.

Animals↗

Minimally invasive techniques of tissue harvest in head and neck reconstruction.

Minimally invasive surgery (MIS) is a revolutionary method of performing complex invasive procedures with minimal direct surgical exposure. This type of surgery requires specially designed instruments and video imaging of the surgical field. A variety of surgical specialties are developing MIS procedures with anticipated decreased morbidity and cost of surgery. At the University of Texas M. D. Anderson Cancer Center, we have explored the use of these techniques to harvest jejunal segments and the rectus abdominis and latissimus dorsi muscles, donor tissues useful in head and neck reconstruction. It is possible to successfully harvest these flaps using MIS, thus making available the potential benefits of MIS to head and neck cancer patients.

Head↗

Breast reconstruction with myocutaneous flaps in previously irradiated patients.

Breast reconstructions performed with latissimus dorsi and transverse rectus abdominis myocutaneous (TRAM) flaps in 82 patients with a history of previous chest-wall irradiation were compared with similar reconstructions in 202 nonirradiated patients to determine whether prior irradiation was associated with more frequent complications and to determine the success rate of breast reconstruction using distant flaps in irradiated patients. The mean dose of radiation administered was 5637 cGy. Complications in the reconstructed breast were more frequent in the irradiated patients (39 percent) than in the nonirradiated patients (25 percent; p = 0.03). In the irradiated group, breast complications were more common in reconstructions performed with the latissimus dorsi flap (63 percent) than in those performed with the TRAM flap (33 percent; p = 0.063). Aesthetic outcomes also were slightly poorer in the irradiated patients. Although complications were more common and aesthetic outcomes not as good in previously irradiated patients, we do not consider such irradiation to be a contraindication to breast reconstruction.

Abdominal Muscles↗

A single center's experience with 308 free flaps for repair of head and neck cancer defects.

Since its inception at our institution in 1988, microvascular reconstructive surgery has become an integral part of the treatment of head and neck cancer patients. This review of 308 free flaps performed over the last 4 years was done to evaluate the complication and flap loss rates and to investigate which factors may contribute to these rates. The overall complication rate was 36.1 percent, the vessel thrombosis rate was 6.8 percent, the flap loss rate was 5.5 percent, and the flap salvage rate was 19.0 percent. Multifactorial analysis of delayed reconstruction, tobacco use, alcohol consumption, previous radiation therapy, previous surgery, and use of vein grafts showed that only previous surgery and the use of vein grafts led to significantly higher rates of flap loss (p < 0.01 for both).

Adolescent↗

Imaging white matter tracts and nuclei of the hypothalamus: an MR-anatomic comparative study.

PURPOSE: To evaluate the MR appearance of the hypothalamus and its associated white matter tracts. METHODS: Coronal and sagittal spin-echo images were obtained in cadaver brains. Gross and histologic sections were made of the cadaver brains. The size, shape, signal intensity, course, and pattern of structures in the hypothalamic region were identified in MR images by comparison with the anatomic sections. RESULTS: The mamillary bodies, paraventricular zone of hypothalamic nuclei, postcommissural fornix, mammillothalamic fasciculus, and anterior commissure were identified on the MR images. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, some of the tracts and nuclei in the hypothalamus may be identified.

Humans↗

Bilateral breast reconstruction: conventional versus free TRAM.

Free TRAM flap transfer is now routinely offered to patients requiring breast reconstruction. This study compares results of conventional superior-pedicled TRAM flaps and free TRAM flaps in bilateral breast reconstructions. A total of 92 breasts were reconstructed in 46 patients. Eighteen patients had free TRAM flap reconstructions, and 28 patients were reconstructed with conventional TRAM flaps. Comparison of average operative blood loss and average operative time for the two techniques showed blood loss of 575 cc and an operative time of 9.6 hours for the free TRAM reconstructions and a blood loss of 313 cc and an operative time of 6.6 hours for the conventional TRAM reconstructions. For free TRAM flap reconstructions, both blood loss and operative time decreased significantly between the first and second group of nine patients: from 819 to 360 cc of blood loss and from 10.5 to 8.9 hours of operative time. Partial flap loss (skin and fat necrosis) and fat necrosis only occurred in 13 and 7 percent, respectively, of conventional TRAM flaps, but neither occurred in free TRAM flaps. However, early in the series, three free flaps were lost in two patients, requiring implant placement. Bilateral breast reconstruction using the free TRAM flap may offer a lower complication rate than the conventional TRAM flap by virtue of improved blood supply and less abdominal wall disruption. Surgeons, however, are forewarned that this procedure has a steep learning curve, and surgeons lacking microsurgical expertise may be better served by the conventional TRAM flap.

Blood Loss, Surgical↗

Frequency and consequences of intimal hyperplasia in specimens retrieved by directional atherectomy of native primary coronary artery stenoses and subsequent restenoses.

Although intimal hyperplasia is a frequent occurrence after arterial interventional procedures, the overall frequency and significance of intimal hyperplasia in primary coronary lesions has not been previously addressed. The incidence of intimal hyperplasia was therefore examined using standard light microscopy in specimens obtained from native coronary arteries of patients undergoing directional coronary atherectomy. The associated clinical history, angiographic results and clinical outcomes were also tabulated. Intimal hyperplasia was identified in 51 of 55 patients (93%) treated with directional coronary atherectomy for restenosis after a prior intervention. These restenosis lesions had less acute gain in lumen diameter after directional coronary atherectomy, a smaller late lumen diameter, more severe late stenosis (p < 0.04), and tended to have more restenosis defined as late stenosis > or = 50% (restenosis rate 40% for prior restenosis vs 26% for primary lesions). Surprisingly, however, intimal hyperplasia was also identified in 45 of 102 (44%) primary stenoses. Primary lesions (n = 45) with intimal hyperplasia were more likely to occur in younger patients and in the left anterior descending artery than were either primary lesions without intimal hyperplasia (n = 57) or prior restenosis lesions. There were otherwise no differences in the baseline characteristics, angiographic findings or clinical outcome of primary lesions with or without intimal hyperplasia (restenosis rate 28 and 24%, respectively). The event-free survival (72% at 12 months) was similar in all 3 groups. Thus, even though intimal hyperplasia is an almost universal finding in restenosis lesions, intimal hyperplasia is not specific for restenosis since histologically identical hyperplasia may be found in nearly half of primary coronary artery stenoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Phase I trial of dihydrolenperone in lung cancer patients: a novel compound with in vitro activity against lung cancer.

Antitumor activity of the butyrophenone dihydrolenperone in non-small cell lung cancer was initially suggested by in vitro screening against tumor cells derived from fresh surgical samples using the human tumor colony-forming assay. We have completed a directed phase I trial in patients with lung cancer. Thirty-two patients with lung cancer have completed 25 courses of therapy at doses of 10 to 60 mg/square meter orally on a twice daily schedule. Twenty-three men and 9 women with a median age of 55 (range 24-69) were entered. Twenty-four were performance status 0 or 1 and 8 were 2. The maximum tolerated dose was 50 mg/square meter orally twice daily and the dose limiting toxicity was somnolence. Of the 32 patients, 18 developed symptomatic hypotension (grade 1 or 2). There was no significant hematologic, renal, or hepatic toxicity. In vitro drug testing using the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (thiazolyl blue)] assay confirmed 50% inhibition of non-small cell and small cell lung cancer cell line growth at 70-450 micromolar concentrations. Plasma dihydrolenperone levels were at least 75-fold less than levels at which in vitro activity was observed. We conclude: 1) the maximum tolerated dose in our study is 50 mg/square meter orally twice daily, 2) the dose-limiting side effect of dihydrolenperone is somnolence, and 3) the concentrations of dihydrolenperone observed in plasma are significantly lower than those associated with in vitro activity.

Adult↗

Nitric oxide: the Jekyll and Hyde of gut inflammation.

We studied the effects of seven day treatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine (L-NAME), administered in the drinking water (100 micrograms/ml ad lib) of female guinea pigs. The effects of NOS inhibition were evaluated in naive animals and in guinea pigs with ileitis induced by intraluminal trinitrobenzenesulfonic acid (TNBS). After 7 days, animals were anesthetized, a sterile saline lavage injected into an ileal loop and removed after 30 min for analysis. In naive guinea pigs, L-NAME caused a marked increase in ileal myeloperoxidase activity and conversion of the mucosa from an absorptive to a secretory state. TNBS-treated guinea pigs has a similar, marked increase in granulocyte infiltration and a mucosal secretory response. However, in contrast to naive animals, L-NAME treatment was anti-inflammatory, reverting all responses to the basal state. We conclude that intestinal nitric oxide serves an anti-inflammatory role under basal conditions, whereas in the TNBS model of chronic ileitis, nitric oxide is a critical mediator of gut injury.

Administration, Oral↗

Use of the Edmonton Injector for parenteral opioid management of cancer pain: a study of 100 consecutive patients.

In this retrospective study, we reviewed the patterns of use of the Edmonton Injector (EI) in 100 consecutive cancer patients. Seventy-eight patients used the EI for an average of 23 +/- 27 days. The main reasons for starting the EI were nausea (37 patients) and severe pain (31 patients). The median opioid dose equivalent to parenteral morphine (MEDD) was 264 +/- 443 mg/day. The mean duration of the subcutaneous injection site was 6.5 +/- 9.2 days. The most frequent reasons for change were accidental needle pulling (59%) and erythema (12%). Only two patients developed local infection (1% of 196 sites). The average cost of treatment was $1.65 Canadian per patient per day. No mechanical problems or refusals to start or continue treatment were detected. We conclude that the EI is a safe and simple device that allows for cost-effective parenteral administration of opioids for cancer pain.

Aged↗

Local tolerance to subcutaneous infusions of high concentrations of hydromorphone: a prospective study.

In a prospective open study, 24 patients with cancer pain receiving parenteral opioids were administered highly concentrated solutions of hydromorphone in order to assess the local tolerance to the subcutaneous infusion. Patients received a mean concentration of hydromorphone of 30 +/- 15 mg/mL at a mean rate of infusion of 0.3 +/- 0.25 mL/hr. Of 22 evaluable patients, 17 (77%) had a site duration of more than 7 days with their first subcutaneous site (mean concentration of 34 +/- 8 mg/mL of hydromorphone). Four of the five remaining patients (80%) had site duration of more than 7 days with their second subcutaneous site. Only one patient (5%) did not reach a 7-day duration after three consecutive site changes. Out of 7 subcutaneous sites that presented signs of toxicity before 7 days of infusion, the main problem was erythema in three cases, swelling in two cases, and bleeding in two cases. All sites improved spontaneously and did not require any medical treatment. No correlation was found between the concentration or rate of infusion of hydromorphone and the duration of the subcutaneous site. The duration of the site was significantly correlated with weight, tricep skinfold, subscapular skinfold, and age of the patients. Our findings suggest that hydromorphone can be safely administered in concentrations that are much higher than those commercially available. The availability of highly concentrated formulations of different opioids for parenteral use will make home management simpler and cheaper.

Administration, Cutaneous↗