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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 55 records · Page 3Linked to original sources

Pneumonectomy for malignant disease: factors affecting early morbidity and mortality.

OBJECTIVE: The purpose of this report is to analyze factors affecting morbidity and mortality after pneumonectomy for malignant disease. METHODS: We retrospectively reviewed the cases of all patients who underwent pneumonectomy for malignancy at the Mayo Clinic. Between January 1, 1985, and September 30, 1998, 639 patients (469 men and 170 women) were identified. Median age was 64 years (range 20 to 86 years). Indication for pneumonectomy was primary lung cancer in 607 (95.0%) patients and metastatic disease in 32 (5.0%). Factors affecting morbidity and mortality were analyzed by univariate and multivariate analysis. RESULTS: Cardiopulmonary complications occurred in 245 patients (38.3%; 95% confidence interval 34.6%-42.2%). Factors adversely affecting morbidity with univariate analysis included age (P <.0001), male sex (P =.04), associated respiratory (P =.02) or cardiovascular disease (P <.0001), cigarette smoking (P =.02), decreased vital capacity (P =.01), forced expiratory volume in 1 second (P <.0001), forced vital capacity (P =.002), diffusion capacity of the lung to carbon monoxide (P =.005), oxygen saturation (P <.05), arterial PO (2) (P =.007), preoperative radiation (P =.02), bronchial stump reinforcement (P =.007), crystalloid infusion (P =.01), and blood transfusion (P =.02). Factors adversely affecting morbidity with multivariate analysis included age (P =.0001), associated cardiovascular disease (P =.001), and bronchial stump reinforcement (P =.0005). There were 45 deaths (7.0%; 95% confidence intervals 5.2%-9.3%). Factors adversely affecting mortality with univariate analysis included associated cardiovascular (P <.0001) or hematologic disease (P <.005), lower preoperative serum hemoglobin level (P =.004), preoperative chemotherapy (P =.01), decreased diffusion capacity of lung to carbon monoxide (P =.002), right pneumonectomy (P =.0006), extended resection (P =.04), bronchial stump reinforcement (P =.007), and crystalloid infusion (P =.01). Factors affecting mortality with multivariate analysis included hematologic disease (P =.01), lower preoperative serum hemoglobin (P =.003), and completion pneumonectomy (P =.01). CONCLUSION: Multiple factors adversely affected morbidity and mortality after pneumonectomy for malignant disease. Appropriate selection and meticulous perioperative care are paramount to minimize risks in those patients who require pneumonectomy.

Adult↗

Surgical treatment of primary lung cancer with synchronous brain metastases.

OBJECTIVES: The role of surgical resection for brain metastases from non-small cell lung cancer is evolving. Although resection of primary lung cancer and metachronous brain metastases is superior to other treatment modalities in prolonging survival and disease-free interval, resection of the primary non-small cell lung cancer and synchronous brain metastases is controversial. METHODS: From January 1975 to December 1997, 220 patients underwent surgical treatment for brain metastases from non-small cell lung cancer at our institution. Twenty-eight (12.7%) of these patients underwent surgical resection of synchronous brain metastases and the primary non-small cell lung cancer. RESULTS: The group comprised 18 men and 10 women. Median age was 57 years (range 35-71 years). Twenty-two (78.6%) patients had neurologic symptoms. Craniotomy was performed first in all 28 patients. Median time between craniotomy and thoracotomy was 14 days (range 4-840 days). Pneumonectomy was performed in 4 patients, bilobectomy in 4, lobectomy in 18, and wedge excision in 2. Postoperative complications developed in 6 (21.4%) patients. Cell type was adenocarcinoma in 11 patients, squamous cell carcinoma in 9, and large cell carcinoma in 8. After pulmonary resection, 17 patients had no evidence of lymph node metastases (N0), 5 had hilar metastases (N1), and 6 had mediastinal metastases (N2). Twenty-four (85.7%) patients received postoperative adjuvant therapy. Follow-up was complete in all patients for a median of 24 months (range 2-104 months). Median survival was 24 months (range 2-104). Survival at 1, 2, and 5 years was 64.3%, 54.0%, and 21.4%, respectively. The presence of thoracic lymph node metastases (N1 or N2) significantly affected 5-year survival (P =.001). CONCLUSION: Although the overall survival for patients who have brain metastases from non-small cell lung cancer is poor, surgical resection may prove beneficial in a select group of patients with synchronous brain metastases and lung cancer without lymph node metastases.

Adenocarcinoma↗

Lobar torsion after pulmonary resection: presentation and outcome.

OBJECTIVE: We reviewed our experience on postoperative lobar torsion. METHODS: Between January 1972 and January 1998, 7887 patients underwent pulmonary resection at our institution. Seven (0.089%; 4 women and 3 men; median age, 68 years) patients required surgical reintervention for lobar torsion. RESULTS: The indications for pulmonary resection were non-small cell carcinoma in 5 patients, lymphoma in 1 patient, and metastatic prostate carcinoma in 1 patient. The right upper lobe was resected in 3 patients, the left lower lobe in 2 patients, and the right middle and right lower lobe in 1 patient each. Postoperative radiographs demonstrated pulmonary infiltrates and volume loss in 5 patients and complete opacification in 2 patients. The median white blood cell count was 10.6 x 10(9) cells/L (range, 9.3-14.9 x 10(9) cells/L), and the median peak temperature was 38.4 degrees C (range, 37.8 degrees C-40.2 degrees C) during the first 48 hours postoperatively. The diagnosis of lobar torsion was made a median of 10 days (range, 2-14 days) after the initial operation; 4 patients underwent completion pneumonectomy, and 3 had lobectomy. Median hospitalization was 24 days and ranged from 10 to 56 days. There were no postoperative deaths. Complications after reoperation included respiratory failure in 2 patients, atrial arrhythmia in 2 patients, and empyema, urinary tract infection, and a transient ischemic attack in 1 patient each. CONCLUSIONS: Lobar torsion represents a difficult diagnostic dilemma in the early postoperative period after pulmonary resection. A high index of suspicion is necessary to avoid a delay in treatment. Late diagnosis results in further pulmonary resection and prolonged hospitalization in the majority of cases.

Aged↗

Photodisruptive laser nucleation of ultrasonic cavitation for biomedical applications.

Pulses of high intensity laser light, when focused into transparent materials, may produce localized electron-ion plasmas through optical breakdown. By simultaneously incorporating the resulting volume of vaporized material within the focal volume of a high intensity ultrasound source, the photodisruption (1.05 microm wavelength) void served as a nucleation site for ultrasonic cavitation. Dilute suspensions of canine erythrocytes in phosphate buffered saline were exposed in a flow-through exposure chamber and the percentage of lysed cells was used as a measure of the biologically effective cavitation activity produced in the chamber. Brief (about 30 micros) acoustic emissions were detected from the photodisruption alone (indicating laser nucleation of bubbles), but the cell lysis produced was undetectable against the background. However, combined exposure greatly increased both the duration of the acoustic emissions (up to 1.5 ms) and the amount of cell lysis above an ultrasonic pressure amplitude threshold of about 4.3 MPa at 2.5 MHz. The amount of cell lysis (sometimes approaching 100%) increased with increasing ultrasonic intensity, laser pulse energy and laser PRF. Addition of 5% serum albumin enhanced the effect, apparently by stabilizing bubbles and nuclei. Photodisruptive laser nucleation of ultrasonic cavitation can provide controlled and synergistic enhancement of bioeffects.

Animals↗

Hyperactivation of MAPK induces loss of ERalpha expression in breast cancer cells.

ERalpha-negative breast tumors tend to overexpress growth factor receptors such as epidermal growth factor receptor or c-erbB-2. Raf-1 is a key intermediate in the signal transduction pathways of these receptors. High levels of constitutive Raf kinase (Deltaraf) activity imparts ERalpha- positive MCF-7 breast cancer cells with the ability to grow in the absence of estrogen. Deltaraf transfectants maintained in estrogen-depleted media showed greatly diminished responses to 17beta-estradiol or the pure antiestrogen ICI 182,780. Western blotting, ligand binding, and immunohistochemistry assays revealed a loss of ERalpha protein expression, and ribonuclease protection assays indicated that this correlated with loss of ERalpha message. In examining the basal expression of estrogen-induced genes in the stable transfectants or in transient cotransfection assays with an estrogen-response element- reporter construct and Deltaraf or constitutively active MAPK kinase (DeltaMEK), no ligand- independent activation of ERalpha was observed. Transient expression of Deltaraf and double-label immunostaining showed ERalpha was lost in those cells that transiently expressed Deltaraf. Abrogation of Raf signaling via treatment with the MEK inhibitors PD 098059 or U0126 resulted in reexpression of ERalpha. Similar studies performed with MCF-7 cells overexpressing epidermal growth factor receptor or c-erbB-2 confirmed that hyperactivation of MAPK resulted in down-regulation of ERalpha that was reversible by MEK inhibition or transfection with dominant negative ERK1 and ERK2 constructs. These data suggest that the hyperactivation of MAPK in epidermal growth factor receptor- or c-erbB-2-overexpressing breast cancer cells is directly responsible for generation of an ERalpha-negative phenotype and, more importantly, that this process may be abrogated by inhibiting these pathways, thus restoring ERalpha expression.

Blotting, Northern↗

Diagnostic ultrasound activation of contrast agent gas bodies induces capillary rupture in mice.

Interaction of diagnostic ultrasound with gas bodies produces a useful contrast effect in medical images, but the same interaction also represents a mechanism for bioeffects. Anesthetized hairless mice were scanned by using a 2.5-MHz transducer (610-ns pulses with 3.6-kHz repetition frequency and 61-Hz frame rate) after injection of Optison and Evans blue dye. Petechial hemorrhages (PHs) in intestine and abdominal muscle were counted 15 min after exposure to characterize capillary rupture, and Evans blue extravasation was evaluated in samples of muscle tissue. For 5 ml small middle dotkg(-1) contrast agent and exposure to 10 alternating 10-s on and off periods, PH counts in muscle were approximately proportional to the square of peak negative pressure amplitude and were statistically significant above 0.64 MPa. PH counts in intestine and Evans blue extravasation into muscle tissue were significant above 1. 0 MPa. The PH effect in muscle was proportional to contrast dose and was statistically significant for the lowest dose of 0.05 ml small middle dotkg(-1). The effects decreased nearly to sham levels if the exposure was delayed 5 min. The PH effect in abdominal muscle was significant and statistically indistinguishable for uninterrupted 100-s exposure, 10-s exposure, 100 scans repeated at 1 Hz, and even for a single scan. The results confirms a previous report of PH induction by diagnostic ultrasound with contrast agent in mammalian skeletal muscle [Skyba, D. M., Price, R. J., Linka, A. Z., Skalak, T. C. & Kaul, S. (1998) Circulation 98, 290-293].

Abdominal Muscles↗

Enhanced toxicity of Bacillus thuringiensis Cry3A delta-endotoxin in coleopterans by mutagenesis in a receptor binding loop.

We used site-directed mutagenesis to modify the Bacillus thuringiensis cry3A gene in amino acid residues 350-354. Two mutant toxins, A1 (R(345)A,Y(350)F,Y(351)F) and A2 (R(345)A,DeltaY(350), DeltaY(351)), showed significantly improved toxicity against Tenebrio molitor (yellow mealworm). The mutant toxin A1 was also more potent against both Leptinotarsa decemlineata (Colorado potato beetle) and Chrysomela scripta (cottonwood leaf beetle), while A2 displayed enhanced toxicity only in L. decemlineata. Competitive binding assays of L. decemlineata brush border membrane vesicles (BBMV) revealed that binding affinities for the A1 and A2 mutant toxins were ca. 2.5-fold higher than for the wild-type Cry3 toxin. Similar binding assays with C. scripta BBMV revealed a ca. 5-fold lower dissociation rate for the A1 mutant as compared to that of Cry3A.

Animals↗

Early adopters of olestra-containing foods: who are they?

OBJECTIVE: To identify the characteristics of people consuming olestra-containing foods when first introduced at a test-marketing site. DESIGN: Data are from the Olestra Postmarketing Surveillance Study (OPMSS). After the introduction of olestra into a large test-marketing site, study participants received 3 follow-up telephone calls, at 3-month intervals, in which they were questioned about their diets during the previous month. SUBJECTS/SETTING: 1,007 adults in Indianapolis, Ind, who participated in a baseline clinic visit (before introduction of olestra into the food market) and completed at least 2 of 3 follow-up telephone calls (after the introduction of olestra into the market). STATISTICAL ANALYSES PERFORMED: Logistic regression was used to examine associations between olestra consumption and sociodemographic characteristics, health conditions, attitudes toward health and diet, and health-related behaviors. RESULTS: Olestra consumption on at least 1 of the follow-up telephone calls was reported by 41.5% of the study sample, and consumption on 2 or more telephone calls was reported by 20.0% of the sample. Factors associated with early adoption of olestra-containing foods included white ethnicity, higher education, overweight, absence of diabetes, attitudes indicative of diet and health concerns (e.g.; perceptions that there is a strong relationship between diet and disease), and a lower fat intake. APPLICATIONS/CONCLUSIONS: In spite of the controversy surrounding the introduction of olestra into the food market persons with attitudes indicative of diet and health concerns were likely to be early adopters of olestra-containing foods. Dietitians and other health care providers should inquire about intake levels of foods with fat substitutes and ensure that these foods are not being consumed in excessive amounts or being consumed instead of nutrient-dense foods that are naturally low in fat.

Adolescent↗

Role of surgical resection in broncholithiasis.

BACKGROUND: Broncholithiasis is an uncommon problem with life-threatening complications. The purpose of this study was to update our experience in patients with broncholithiasis managed by surgical intervention. METHODS: From January 1984 to January 1998, 118 patients were diagnosed with broncholithiasis at our institution. We reviewed the medical records of those patients who underwent surgical treatment. RESULTS: There were 47 patients (19 men and 28 women). Median age was 58 years (range, 18 to 90 years). Indications for operation were symptoms in 44 patients and abnormal roentgenograms in 3 patients. Operative procedures included lung resection in 30 patients, broncholithectomy with or without bronchoplasty in 16, and segmental bronchial resection in 1 patient. There were no operative deaths. Postoperative complications occurred in 16 patients (34%). Follow-up was complete in 46 patients (98%) and ranged from 11 to 165 months (median, 74 months). The 15-year actuarial survival did not differ significantly from that of a matched control group (p = 0.774). At follow-up, 28 patients (68.3%) were asymptomatic. Symptoms continued in 12 patients. Recurrent or persistent disease was documented in 6 patients (14.6%). The site of recurrence was in a new location in 3 patients, a previous site in 2, and unknown in 1 patient. Subsequent management included observation in 3 patients, bronchoscopic removal in 2, and bilobectomy in 1 patient. CONCLUSIONS: Surgical resection for broncholithiasis is an effective method of management for this disease and can be done with low mortality and morbidity. Progression of the disease may lead to recurrence and further surgical intervention.

Adolescent↗

Bronchobiliary fistula: principles of management.

Bronchobiliary fistula is an uncommon entity. Recently, we encountered 2 patients with this problem. Both were treated successfully with resection of the involved pulmonary tissue and interposition of viable tissue between the lung and the fistulous tract. This approach, although invasive, provided a rapid resolution of the patients' problem.

Biliary Fistula↗

Esophageal reconstruction for benign disease: self-assessment of functional outcome and quality of life.

BACKGROUND: Little information exists regarding functional outcome and quality of life after esophagectomy and subsequent esophageal reconstruction for benign disease as evaluated by the patients themselves. METHODS: Eighty-one patients completed a combined two-part questionnaire regarding esophageal function and quality of life (MOS SF-36) a median of 9.8 years (range, 10 months to 18.9 years) after esophageal reconstruction for benign disease. There were 43 men (53.1%) and 38 women (46.9%). Median age at time of esophageal reconstruction was 51 years (range, 6 to 78 years). Intestinal continuity was established with stomach in 58 patients (71.6%), colon in 16 patients (19.8%), and small bowel in 7 patients (8.6%). RESULTS: Dysphagia to solids was present in 48 patients (59.3%) and 27 patients (33.3%) required at least one postoperative dilatation. Heartburn was present in 50 patients (61.7%) which required medication for control in 37 patients (45.7%). The number of meals per day was three to four in 58 patients (71.6%), more than four in 15 patients (18.5%), less than three in 6 patients (7.4%), and unknown in 2 patients (2.5%). The size of each meal was smaller than preoperatively in 46 patients (56.8%), larger in 22 patients (27.2%), unchanged in 12 patients (14.8%), and unknown in 1 patient (1.2%). The number of bowel movements per day increased in 37 patients (45.7%), was unchanged in 36 patients (44.4%), and decreased in 8 patients (9.9%). Resection for perforation was associated with smaller postoperative meals compared with resection for stricture (p < 0.05). Age, sex, and type of esophageal reconstruction did not affect late functional outcome. Regarding quality of life, physical functioning, social functioning, and health perception were decreased (p < 0.05). No significant change was observed in role-physical, mental health, bodily pain, energy/fatigue, and role-emotional scores. CONCLUSIONS: Self-assessment of postoperative esophageal symptoms after esophagectomy and reconstruction for benign disease demonstrates that symptoms are frequently present at long-term follow-up and unaffected by the type of reconstruction.

Adolescent↗

Esophageal reconstruction for benign disease: early morbidity, mortality, and functional results.

BACKGROUND: Esophagectomy for benign disease is performed infrequently. We reviewed the Mayo Clinic's experience with patients who required esophageal reconstruction for benign esophageal disease. METHODS: From March 1956 to October 1997, all patients who required resection and reconstruction for a benign condition of the esophagus were reviewed. RESULTS: There were 255 patients (141 male, 114 female). Median age was 55 years (range, 2 to 100). The original diagnosis was an esophageal stricture in 108 patients (42%), primary motility disorder in 84 (33%), perforation in 36 (14%), hiatal hernia in 18 (7%), and other in 9 (4.0%). Reconstruction was with stomach in 168 patients (66%), colon in 70 (27%), and small bowel in 17 (7%). The anastomosis was intrathoracic in 144 patients (57%) and cervical in 111 (43%). There were 13 postoperative deaths (mortality 5%); 142 patients (56%) had at least one complication. Median hospitalization was 14 days (range, 6-95 days). Follow-up was complete in 226 patients (88.6%) for a median of 52 months (range, 1 month to 29 years). A total of 175 patients (77.4%) were improved. Functional results were classified as excellent in 72 patients (31.8%), good in 23 (10.2%), fair in 80 (35.4%), and poor in 51 (22.6%). CONCLUSIONS: Esophageal reconstruction for benign disease resulted in functional improvement in a majority of patients. It can be done with low mortality and acceptable morbidity. Early morbidity is adversely affected by the diagnosis of perforation and the route through which the conduit is placed. Late functional outcome is adversely affected by the diagnosis of paraesophageal hernia and a cervical anastomosis.

Adolescent↗

Acoustic droplet vaporization for therapeutic and diagnostic applications.

A phase shift droplet emulsion is introduced as an aid to unusual ultrasound (US) applications. The transpulmonary droplet emulsion (90% < 6 microm diameter) is made by mixing saline, bovine albumin and dodecafluoropentane. It has been observed that an acoustic pressure threshold exists, above which the droplets vaporize into bubbles approximately 25 times the original diameter. For frequencies between 1.5 and 8 MHz, the threshold decreases from 4.5 to 0.75 MPa peak rarefactional pressure. This paper presents preliminary results for droplet preparation and their evaporation as a function of applied acoustic pressure and frequency, as well as simulations of the lifetime of these gas bubbles based on gas diffusion. In vivo experiments were simulated by the evaporation of droplets in blood flowing under attenuating material. We propose that this agent might be useful for tissue occlusion in cancer treatment, as well as for phase aberration corrections in acoustic imaging.

Albumins↗

The influence of ultrasound frequency and gas-body composition on the contrast agent-mediated enhancement of vascular bioeffects in mouse intestine.

The induction by ultrasound (US) of petechiae and hemorrhages in mouse intestine was examined with injection of gas body-based contrast agents. Production of petechiae in the intestinal wall was enhanced by contrast agents for both continuous and pulsed (10 micros pulses repeated at 1 kHz) exposure relative to a gas body-free blank. For pulsed exposure with 10 mL/kg of Albunex, apparent thresholds for peak negative pressure amplitude were 0.42 MPa at 0.4 MHz, 0.85 MPa at 1.09 MHz and 2.3 MPa at 2.4 MHz. Results at these frequencies were the same for 10-11 cycle pulses with fixed duty cycle (0.01). Thresholds for hemorrhage into the intestinal lumen were not appreciably enhanced by added Albunex, and appear to be compatible with previously reported lithotripsy data when duty factor differences are considered. The agents PESDA, Optison and Levovist had lower thresholds (for example, 1.8 MPa for Levovist) than Albunex at 2.3 MHz, and yielded more petechiae. The thresholds for petechiae induction by US with contrast agents encroach upon the exposure range relevant to diagnostic US practice.

Albumins↗

Sonoporation of monolayer cells by diagnostic ultrasound activation of contrast-agent gas bodies.

Human (A431 epidermoid carcinoma) cells were grown as monolayers on 5 microm thick Mylar sheets, which formed the upper window for a 1-mm thick, 23-mm diameter disc-shaped exposure chamber. A 3.5-MHz curved linear-array transducer was aimed upward at the chamber, 7 cm away, in a 37 degrees C water bath. The chamber contained phosphate-buffered saline (PBS) with 10 mg/mL fluorescent dextran and 1% Optison ultrasound (US) contrast agent. Significant fluorescent cell counts, indicative of membrane damage (i.e., sonoporation), up to about 10% of cells within a 1-mm diameter field of view, were noted for spectral Doppler and two-dimensional (2-D) scan mode with or without a tissue-mimicking phantom. The effect was only weakly dependent on pulse-repetition frequency or exposure duration, but was strongly dependent on contrast agent concentration below 2%. Thus, diagnostic US activation of contrast-agent gas bodies can produce cell membrane damage.

Albumins↗

Risk factors for community-acquired pneumonia diagnosed by general practitioners in the community.

The purpose of this study was to identify risk factors for pneumonia diagnosed in the community by general practitioners, using a case control study in 29 general practices in Nottingham, U.K. Patients with radiographically confirmed pneumonia were compared with adults randomly selected from electoral registers corresponding to the catchment areas of the general practices taking part in the study. Sixty-six cases and 489 controls participated. Significant risk factors in univariate analysis included age, chronic obstructive pulmonary disease, congestive heart failure and lifetime consumption of cigarettes. Multiple logistic regression analysis of these four variables showed that age [adjusted odds ratio = 2.69 (for 30 year increment), 95%CI = 1.66-4.35] and chronic obstructive pulmonary disease (adjusted odds ratio= 1.99, 95%CI = 1.15-3.45) were independent risk factors. Only age and chronic obstructive pulmonary disease were independent risk factors for pneumonia in this study. Since cigarette smoking is the major cause of chronic obstructive pulmonary disease, these data suggest that cigarette smoking is the main avoidable risk factor for community-acquired pneumonia in adults.

Adolescent↗

Risk factors for community-acquired pneumonia diagnosed upon hospital admission. British Thoracic Society Pneumonia Study Group.

A case-control study of risk factors for community-acquired pneumonia in adults admitted to hospital is reported. Cases were surviving patients (n = 178) admitted to 14 hospitals in England. Controls were individuals (n = 385) randomly selected from the electoral registers of the areas served by the hospitals. The two groups were compared with regard to risk factors for pneumonia using a standardized postal questionnaire. Independent risk factors associated with cases in log-linear regression analysis were age, heart disease (as indicated by congestive heart failure and/or digitalis treatment), lifetime smoking history, chronic airway disease (chronic bronchitis and/or asthma), occupational dust exposure, pneumonia as a child, single marital status and unemployment. Corticosteroid and bronchodilator therapy were also independent risk factors in the log-linear regression analysis, but may reflect the severity of underlying lung disease for which these drugs were prescribed. These data suggest that cigarette smoking is the major avoidable risk factor for acute pneumonia in adults.

Adolescent↗