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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 181 records · Page 10Linked to original sources
PubMed1995

Induction of base damage in DNA solutions by ultrasonic cavitation.

Ultrasound can damage macromolecules by the mechanical (shearing) and sonochemical (free radical generating) action of ultrasonic cavitation. Attributing macromolecular damage to either direct mechanical stress or to indirect mechanisms involving free radicals or other sonochemicals is a challenging problem. DNA damage induced by ultrasound was evaluated by measuring the formation of purine and pyrimidine products using combined gas chromatography-mass spectrometry with selected ion monitoring. Samples of DNA were prepared in 10 mmol dm-3 phosphate buffered saline (pH 7.4) and saturated with a mixture of argon:oxygen (3:1). Continuous 2.17 MHz ultrasound exposures at 0.82 mPa spatial peak negative pressure amplitude were performed in a 60 rpm rotating tube exposure system. Hydrogen peroxide yields were measured after each exposure to quantify the cavitation activity and ranged up to 350 mumol dm-3 for 1-h exposures. Purine and pyrimidine products identified were those typically observed following exposure of DNA to hydroxyl radical-generating systems, such as ionizing radiation, hypoxanthine/xanthine oxidase, or hydrogen peroxide in the presence of transition metal ions. The yields of these products were directly correlated with cavitation activity as measured by residual hydrogen peroxide concentrations. The yields of DNA products increased in the following order: thymine glycol approximately cytosine glycol > 8-oxoAde > FAPyAde approximately 5-HMU approximately 5,6-diOHCyt > FAPyGua. Unexpectedly, 8-oxoguanine did not exhibit a dose-dependent increase above background levels, and this observation is inconsistent with processes involving metal ion-dependent formation of hydroxyl radicals from hydrogen peroxide. In addition, the product yields were far too large to result from the residual hydrogen peroxide. Thus, ultrasonic cavitation appears to have a mode of action distinct from either ionizing radiation or formation of hydroxyl radicals via Fenton-like reaction with transition metals.

Adenine↗
PubMed1995

Thresholds for hemorrhages in mouse skin and intestine induced by lithotripter shock waves.

In vivo biological effects of ultrasound should be characterized as thermal or cavitational to understand their etiology and significance. A spark-gap shock-wave lithotripter was built and used to compare cavitation-induced hemorrhages to the heat-induced petechial hemorrhages caused by continuous-wave ultrasound in mouse intestine. Intestinal hemorrhages induced in anesthetized hairless mice by the lithotripter pulses involved tissue destruction with bleeding into the lumen of the intestine, and were associated with intestinal gas bubbles. Skin hemorrhages were also observed, which appeared to be contusions, with no actual breakage of the skin. Administration of 100 shock waves with peak positive amplitude of 18.5 MPa produced an average of 7.6 (standard error [SE] 3.1, n = 6) intestinal hemorrhages and 45 (SE 11) skin hemorrhages. The counts and severity of hemorrhages increased with increasing numbers (3 to 300) of shock waves. Absorbers of varying thickness were used to reduce the pressure amplitude of the shock waves, which were thereby modified into low frequency ultrasound pulses. For 100 pulse exposures, apparent thresholds for effects occurred between 1.6 and 4.0 MPa for the intestinal hemorrhages and between 0.6 and 1.6 MPa for the skin hemorrhages. The low 1-Hz pulse repetition frequency precluded significant heating, and so these effects were the result of cavitation, which probably occurred inside the intestines or in the surrounding water. Compared to the previously observed thermal petechia, the cavitation-induced hemorrhages could be distinguished on the basis of their appearance upon histological examination, and also by the relative values of the thermal and mechanical exposure indices associated with the two different exposure modes.

Animals↗
PubMed1995

Reoperation for aortic valve periprosthetic leakage: identification of patients at risk and results of operation.

Periprosthetic leakage occurs in 1 to 3.5% of patients after aortic valve replacement. Antecedent or active infection increases the risk of perivalvular leakage. Other factors predisposing to perivalvular leakage have not been clearly identified. To determine whether clinical and/or early transthoracic echocardiographic features can identify patients who require reoperation for periprosthetic leakage, we reviewed 1,743 consecutive patients who underwent aortic valve replacement from 1983 through 1991. Thirty patients (1.7%) subsequently required repeat operation for correction of periprosthetic leakage, at a median of 18.0 months (range 0.5-81.0) after aortic valve replacement. Comparison of these 30 patients with periprosthetic leakage to those undergoing primary aortic valve replacement showed no differences in patient age, gender, native valve disease type or etiology, prosthetic valve type, or prosthetic valve size (all p = NS). Of the 30 patients with periprosthetic leaks, 20 had early postoperative transthoracic echocardiography, at a median 5.3 months (range 0.3 - 40.0) after aortic valve replacement. In this early postoperative study, 14 patients (70.0%) had no periprosthetic leak detectable by echocardiography; two patients had trivial leaks, and only four patients had significant periprosthetic leakage by echocardiography. During subsequent operation, aortic valve re-replacement was performed in 26 patients (86.7%), and the periprosthetic leak was repaired in the remaining four patients. Thirty-day and 5-year survival probabilities were 0.90 (70% CI, 0.84-0.96) and 0.73 (70% CI, 0.65-0.82), respectively. It is concluded that in this study, there were no clinical features that distinguished patients undergoing aortic valve replacement who later developed severe perivalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Ribozyme mediated degradation of beta-amyloid peptide precursor mRNA in COS-7 cells.

Two sets of eucaryotic expression vectors encoding trans-acting hammerhead ribozymes and trans-acting hairpin ribozymes were constructed. In one set of vectors ribozyme RNA transcription was placed under the control of a mouse mammary tumor virus long terminal repeat (MMTV-LTR). In the other set ribozyme expression was controlled by a metallothionein IIA (Mt-IIA) promoter. Each ribozyme was directed to the first target sequence in the Alzheimer amyloid peptide precursor mRNA (beta APP mRNA), 5' decreases GUC decreases 3'. Ribozyme RNA transcribed from these vectors, which should cleave all six alternatively spliced forms of beta APP mRNA as well as beta APP pre-mRNA, was shown to cleave a beta APP RNA substrate analog in vitro. Stably transfected COS-7 cell lines bearing both vector types were prepared. Steady-state levels of beta APP mRNA were reduced 25-30% in cells containing either active or mutant hammerhead ribozyme vectors driven by the MMTV-LTR promoter grown in the presence of glucocorticoids. In cell lines bearing Mt-IIA driven ribozymes steady-state levels of beta APP mRNA were reduced 67-80% in both hammerhead and hairpin ribozyme containing cell lines following promoter induction by glucocorticoids. These levels correlate with the appearance of low levels of induced ribozyme RNA. In contrast, steady-state alpha-actin mRNA and G3PDH mRNA levels in these cells remained constant. Western blotting of cell extracts revealed that all forms of beta APP were correspondingly reduced. Neither the RNA nor protein decreases observed in ribozyme transfected cell lines were observed in stably transfected control cells bearing the vector alone. These results suggest that ribozyme-mediated degradation of beta APP mRNA in COS-7 cells does not depend on ribozyme cleavage.

Amyloid beta-Protein Precursor↗
PubMed1994

Biodistribution of boron in dogs with spontaneous intracranial tumors following borocaptate sodium administration.

Borocaptate sodium (Na2B12H11SH) is a potentially useful compound for boron neutron capture therapy of intracranial tumors. Tumor and normal tissue boron concentrations were evaluated in 30 dogs with naturally occurring intracranial tumors after i.v. borocaptate sodium infusion (55 mg boron/kg). Postmortem tissue boron concentrations were measured for three postinfusion time periods (2, 6, and 12 h) by inductively coupled plasma atomic emission spectroscopy. Mean boron concentrations for extracerebral tumors were 40.6 +/- 16.9 (2 h; n = 8), 25.9 +/- 11.7 (6 h; n = 5), and 8.6 +/- 4.5 micrograms boron/g (12 h; n = 6). Mean boron concentrations for intracerebral tumors were 30.6 +/- 17.5 (2 h; n = 7) and 2.9 +/- 1.8 micrograms boron/g (6 h; n = 4). Mean tumor boron concentrations were lower at longer postinfusion times. The tumor:normal brain boron concentration ranged from 0.8 to 19.8. Tumor:blood boron concentrations were less than one for all but three dogs and ranged from 0.04 to 1.4. Mean peritumor boron concentrations were highly variable but exceeded that of normal brain in 10 of 20 dogs. In some dogs, the mean peritumor boron concentration was similar to or exceeded the tumor boron concentration. Distant or contralateral normal brain had consistently low boron concentrations. Some cranial and systemic tissues had high boron concentrations, indicating substantial extravascular boron. The spontaneous animal tumors provided a realistic spectrum of data and enabled extensive sampling of diseased and normal tissues. The biodistribution of boron from borocaptate sodium administration was partially favorable because of high tumor boron concentrations. Empirical radiation dose tolerance studies should be used to determine the impact of the unfavorably high boron concentration of blood and some cranial tissues.

Adenoma↗
PubMed1994

Editing of the mitochondrial small subunit rRNA in Physarum polycephalum.

Post-transcriptional insertion, substitution or deletion of nucleotides in RNA (RNA editing) has been observed in RNAs from a number of organisms but always in messenger RNA or transfer RNA. We report here that the 17S rRNA of the mitochondrial ribosome of Physarum polycephalum is edited at 40 sites with single cytidine insertions. The locations of the editing sites are fairly evenly distributed throughout the RNA and do not correspond to any obvious feature of the primary sequence or secondary structure. In addition to these cytidine editing sites are editing sites in which a nucleotide other than cytidine is inserted. At two sites a uridine is inserted and at two sites adenosine residues are inserted. This is the first report of mixed nucleotide insertional editing. These results imply that the editing mechanism in Physarum may be different from those proposed for the kinetoplastid protozoa.

Animals↗
PubMed1994

Conductivity differences distort probe measurements of magnetically induced electric fields.

Measuring internal induced electric fields in animals with a miniaturized probe involves a potential error related to the difference between the hole conductivity (sigma h) and the surrounding tissue conductivity (sigma t). Theory was developed to describe this phenomenon and checked by probe measurements in agar-filled petri dishes. The value measured in the hole is 2 sigma t/(sigma h + sigma t) times the actual field in the tissue. For example, a probe hole in muscle, which is filled with blood, could yield a measurement only about 22% of the true value in the muscle. This potential source of error can be mitigated to some extent by not actually cutting a hole, by using a low-conductivity (e.g., 0.2 S/m) coupling medium in the hole, or by ensuring contact between the probe's electrodes and the tissue.

Agar↗
PubMed1994

Combined operation for lung cancer and cardiac disease.

From 1965 through 1992, 30 patients (23 men and 7 women) underwent pulmonary resection for primary lung cancer and a concomitant open heart operation (combined group). Median age was 68 years (range, 50 to 79 years). Coronary artery bypass was performed in 23 patients, mitral valve repair in 2, mitral valve replacement in 2, and other procedures in 3. Pulmonary resections included pneumonectomy in 1 patient, bilobectomy in 1, lobectomy in 21, and wedge excision in 7. Twenty-three patients were in postsurgical stage I. There were two operative deaths (6.7%), one from myocardial ischemia and one from pulmonary insufficiency. Overall 5-year survival was 34.9% and was not affected by the stage of the disease. During the same period, 15 other patients underwent an open heart operation (coronary artery bypass in 11, aortic valve replacement in 2, and other in 2) followed by pulmonary resection (pneumonectomy in 5, lobectomy in 9, and wedge excision in 1) for lung cancer 1 to 11 months later (median, 2 months) (staged group). There were no operative deaths. Six patients were in postoperative stage I. Overall 5-year survival was 53.0% (p = not significant), but it was significantly affected by the stage of lung cancer. Most important, a significant difference was observed in stage I survival between the two groups. Five-year survival for stage I patients in the staged group was 100.0%, compared with only 36.5% for the combined stage I patients (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Results of surgical resection in patients with N2 non-small cell lung cancer.

From January 1982 to December 1986, 167 patients (121 men and 46 women) with non-small cell lung cancer and a clinically negative mediastinum were found to have N2 lymph node metastases at thoracotomy and underwent pulmonary resection. Ages ranged from 31 to 86 years (median, 66 years). Adenocarcinoma was present in 70 patients (41.9%), squamous cell carcinoma in 64 (38.3%), large cell carcinoma in 20 (12.0%), adenosquamous cell carcinoma in 7 (4.2%), and bronchoalveolar cell carcinoma in 6 (3.6%). Forty-seven patients (28.1%) underwent mediastinoscopy; all results were negative. Pneumonectomy was performed in 64 patients, bilobectomy in 4, lobectomy in 76, segmentectomy in 2, and wedge excision in 21. Twenty patients had an incomplete resection. Thirty-five patients (21.0%) had complications, and the operative mortality was 4.8% (8 of 167 patients). Sixty-seven patients (40.1%) received adjuvant radiation therapy. The 5-year survival for the 147 patients who underwent complete resection was 23.7%. In contrast, 19 of the 20 patients (95.0%) who underwent incomplete resection died within 3 years. Other factors that significantly affected the 5-year survival were the number and location of metastatic lymph node stations, age, type of resection, and whether adjuvant radiation therapy was administered. We conclude that, when N2 disease is found at thoracotomy, complete resection is warranted to achieve long-term survival.

Adult↗
PubMed1994

Using microphysiometry to study the pharmacology of exogenously expressed m1 and m3 muscarinic receptors.

The microphysiometer, an instrument that uses a semiconductor-based sensor to monitor cellular metabolic activity, has been shown to detect the activation of a variety of receptors in living cells, largely irrespective of the signal-transduction mechanism. Using the Cytosensor Microphysiometer, we have studied agonist concentration responses for the activation of CHO-K1 cell lines exogenously expressing rat m1 or m3 receptors. Three levels of receptor expression were investigated for each subtype. Carbachol is more potent for m3 than m1 receptors (0.5 to 1.0 log unit lower EC50); for both, potency correlates positively with receptor density. The results agree well with those obtained by measuring phosphoinositide hydrolysis and intracellular [CA++] in the same cells. We also determined that two subtype-selective antagonists, pirenzepine (for m1) and p-fluoro-hexahydrosila-difenidol (for m3) displayed appropriate differential ability to shift carbachol concentration-response curves in the microphysiometer. This study provides additional evidence that pharmacological results obtained by microphysiometry are consistent with those obtained by more conventional functional assays.

Animals↗
PubMed1994

Cavitation dosimetry: estimates for single bubbles in a rotating-tube exposure system.

Cell lysis and hydrogen peroxide production from cavitation in a 60 rpm rotating-tube exposure system were observed for 2.17 MHz ultrasound at 0.8 MPa peak negative pressure amplitude. Synchronized 10 ms burst mode exposure was utilized to emphasize the phenomenon of bubble cycling each half rotation. Low cell numbers and inhibition of H2O2-consuming enzymes allowed measurement of the residual hydrogen peroxide in exposed cell suspensions. Canine red blood cells (RBCs) or Chinese hamster ovary cells (CHO) suspended at 1 x 10(6) mL-1 in phosphate buffered saline were lysed exponentially with the number of bursts. The CHO cells were lysed faster than RBCs. The H2O2 increased approximately in proportion to the number of bursts. Longer bursts (100 ms) or continuous exposure produced similar trends, but were less effective per unit of total on-time. The number of bubbles per 10 ms burst was estimated from a simple model to be about 7100. The faster lysis of the CHO cells could be explained mostly by the larger size of these cells, which makes them more likely to meet a bubble. The H2O2 production gave concentrations of about 93-155 fM per bubble per burst. Similar calculations gave estimates of 178 fM per bubble for 100 ms bursts and 150 fM per bubble for continuous exposure. The rate of H2O2 production was roughly 500 fmole s-1 while a bubble crossed the tube. This sonochemical yield could be biologically significant under favorable circumstances.

Animals↗
PubMed1994

Heating as a mechanism for ultrasonically-induced petechial hemorrhages in mouse intestine.

Anesthetized hairless mice were exposed to 1.035 MHz unfocused ultrasound in a temperature-controlled water bath. Visible petechial hemorrhages and hyperemia were produced in the intestines. Histologically, the petechiae appeared to be localized mostly to the lamina propria of the mucosa. For 2 min exposure, the number of petechiae and length of hyperemic tissue both increased with increasing spatial peak pressure amplitude above a threshold of about 0.4-0.57 MPa. The magnitude of these effects increased, and the threshold decreased, with increasing exposure duration from 1 min to 4 min. The effects also increased for increasing bath temperature from 32 degrees C to 42 degrees C. The effects decreased markedly for 1 ms burst-mode exposure with 2 ms and 4 ms repetition periods with constant pressure amplitude, but were essentially constant for constant temporal-average intensity. Both effects were also produced by heating from radio-frequency diathermy at 10.35 MHz. The effects were associated with abdominal temperatures above about 42-43 degrees C, which were estimated with a thermocouple at the end of the exposure. The hyperemia is a clearly thermal effect, while the petechiae have been previously associated with the cavitation mechanism. However, the ultrasonically-induced petechiae observed in this study do not represent an unequivocal marker for cavitation, but rather appear to be attributable to heating. These findings help to reduce the expectation of ultrasonic cavitation during medical therapy treatments.

Animals↗
PubMed1994

Nonmelanoma skin cancer in the United States: incidence.

Because death from nonmelanoma skin cancer is uncommon, quantification of its morbidity is particularly important. Although its incidence is increasing rapidly, the most recent nationwide estimates are 16 years old. The purpose of this study was to estimate the 1994 nonmelanoma skin cancer incidence in the United States. We updated the 16-year-old incidence estimates to reflect the growth and changing age distribution of the population and the increases in age-adjusted incidence rates documented in two population-based studies. The projected 1994 incidence of nonmelanoma skin cancer in the United States is 900,000 to 1,200,000 cases, similar in magnitude to the overall incidence of noncutaneous cancers. Nonmelanoma skin cancer imposes an enormous public health burden on the U.S. population. Quantification of its morbidity and its prevention are important priorities.

Age Factors↗
PubMed1994

Modifying problematic mealtime interactions of children with cystic fibrosis and their parents via behavioral parent training.

Implemented behavioral parent training targeting maladaptive mealtime behavior with two children with cystic fibrosis (CF) and their parents. Treatment was implemented in multiple baseline fashion across the two families. Primary dependent measure was coding of parent and child behaviors from videotaped dinners. Data were also collected on the children's daily calorie intake and weight. During treatment and at the posttreatment follow-ups, parents' attention to disruptive behavior decreased, attention to appropriate eating increased, and parental control at meals increased. The children showed an increase in appropriate behavior and a decrease in disruptive behavior; caloric intake and weight also improved. Results are discussed in terms of the applicability of behavioral intervention with feeding problems in children with CF.

Behavior Therapy↗
PubMed1994

Changing use of hospital services and costs at a London AIDS referral centre, 1983-1989.

OBJECTIVE: To describe the use of hospital-based services and associated costs over time for HIV-infected individuals by disease stage and year of treatment. METHODS: Data on service use were abstracted from inpatient and outpatient case-notes of 459 HIV-infected patients (121 asymptomatic and 338 AIDS patients) treated at St Mary's Hospital, London between 1983 and 1989. Cost estimates were derived from a survey of the 37 departments involved with HIV-related care. The number and type of admissions and outpatient visits, referral and discharge venues, number and type of tests and procedures performed, drugs prescribed and associated costs for the study period were the outcome measures used. RESULTS: Most patients were homosexual men. At the time of first HIV-related visit, 80.7% lived in London. Most day cases and planned admissions were organized through the outpatient clinic; 31% of emergency admissions were initiated by patients themselves. For people with AIDS the number of day case admissions increased while planned admissions decreased. There was a marked reduction in the duration of inpatient stays, especially for AIDS patients. Costs associated with inpatient care decreased concomitantly. The number of outpatient visits for patients with symptomatic disease increased, resulting in increased outpatient expenditure. Asymptomatic patients had fewer inpatient tests, while outpatient tests did not change over time; costs followed similar patterns. Mean inpatient and outpatient drug-days prescribed did not change nor did average inpatient drug-costs although outpatient drug-costs increased. Inpatient tests performed on symptomatic non-AIDS patients decreased, while mean outpatient tests increased; average costs followed similar patterns. Inpatient drug-days prescribed and costs remained the same, while outpatient drug-days and average drug-costs increased during the study period. For AIDS patients, the number of inpatient tests performed and their average costs decreased but outpatient tests performed increased, though their average costs remained the same. Mean inpatient drug-days prescribed and average drug-costs decreased, while number of outpatient drug-days prescribed and average drug-costs increased markedly over time. For each disease category, expenditure on admissions and related tests decreased over time, while expenditure on outpatient visits and drug-costs increased. CONCLUSIONS: The shift from an inpatient- to an outpatient-based service has resulted in fewer patients being investigated and treated in hospital and more as outpatients. This has resulted in a reduction of inpatient-related costs, while outpatient-related costs have increased. The overall contribution of drug-costs to the total cost has increased greatly over time. With the anticipated advent of new antiviral compounds, the importance of ascertaining their effectiveness as well as their efficacy will become crucial.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Changing presentation and survival, service utilization and costs for AIDS patients: insights from a London referral centre.

OBJECTIVE: To describe the use of services and associated costs for HIV-infected patients by stage of infection in the context of changing patterns of presentation and survival. METHODS: A retrospective analysis of inpatient and outpatient case-notes of 335 AIDS patients and a survey of HIV-related care provided by 37 departments at St Mary's Hospital, London. Survival from time of diagnosis of AIDS, time from diagnosis of HIV infection to AIDS, and use and costs of services per patient-year were outcome measures. RESULTS: During the study period 1 January 1982 to 30 September 1989, 152 AIDS patients were diagnosed before 1987 (group 1) and 183 since 1987 (group 2), most of whom were homosexual men. The median interval of first HIV-related visit to diagnosis of AIDS increased from 0 (group 1) to 264 days (group 2; P < 0.0001). Median survival from AIDS diagnosis increased from 14.6 (group 1) to 21.0 months (group 2; P < 0.02). Group 2 patients used fewer inpatient services than group 1 patients irrespective of disease stage. Symptomatic patients in group 2 used more outpatient services than group 1 patients. Total HIV-related expenditure was lower for patients without AIDS in group 2 than in group 1, while expenditure for AIDS patients remained similar. CONCLUSION: Earlier patient presentation, a shift from inpatient- to outpatient-based clinical care and increased survival from time of AIDS diagnosis has occurred. Increased drug expenditure was offset by reduced inpatient expenditure. Total expenditure per patient-year was stable; increased survival and introduction of new drugs will increase future lifetime use of resources.

Acquired Immunodeficiency Syndrome↗