Subcutaneous apomorphine injections as a treatment for intractable pain in Parkinson's disease.
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Aged↗
Biomedical subjects
D L Brown
Publications and source records attributed to D L Brown.
Effect of glycoprotein IIb/IIIa inhibitors on the individual components of composite endpoints used in clinical trials of unstable angina and non-Q-wave myocardial infarction.
Inhibitors of the platelet glycoprotein (GP) IIb/IIIa receptor complex have recently been approved for the treatment of patients with unstable angina and non-Q-wave myocardial infarction (MI). We performed a meta-analysis to ascertain the effect of these agents on the individual endpoints of death, myocardial infarction, refractory ischemia, and major bleeding after 30 days of follow-up. Five randomized, placebo-controlled trials involving 17,255 patients were identified. The odds ratios for each of the endpoints in each trial were calculated and combined using a fixed-effects model. There was no significant reduction in death (OR, 0.87; 95% CI, 0.73-1.03; P = 0.1), myocardial infarction (OR, 0.91; 95% CI, 0.82-1.004; P = 0.06), or refractory ischemia (OR, 0.92; 95% CI, 0.78-1.1; P = 0.36) in patients treated with GP IIb/IIIa inhibitors. There was a significant increase in major bleeding following treatment with GP IIb/IIIa inhibitors (OR, 1.2; 95% CI, 1.06-1.4; P = 0.005). When used to treat unstable angina and non-Q-wave MI, this new class of agents appears to be associated with minimal clinical benefit and an increase in major bleeding complications.
Angina, Unstable↗
Staging of advanced ovarian cancer: comparison of imaging modalities--report from the Radiological Diagnostic Oncology Group.
PURPOSE: To compare ultrasonography (US), magnetic resonance (MR) imaging, and computed tomography (CT) for diagnosing and staging advanced ovarian cancer. MATERIALS AND METHODS: US, CT, and MR imaging were performed in 280 patients. Images were read by three radiologists from each of the five hospitals. Image analysis included determination of malignancy within the peritoneum (11 sites), lymph nodes (10 sites), and hepatic parenchyma. The standard of reference was based on surgical and histopathologic findings. Statistical methods used were receiver operating characteristic (ROC) curve analysis, pairwise comparison of areas under the ROC curves (A(z)), analysis of sensitivity and specificity pairs, and assessment of agreement between the degree of suspicion and standard of reference. RESULTS: There were 118 patients with malignant tumors; 73 (62%) had stage III or IV disease. Metastases were found in the peritoneum in 70 (59%), nodes in 20 (17%), and liver in seven (6%) cases. In the peritoneum, MR imaging and CT (A(z) = 0.96 for both) were more accurate than US (A(z) = 0.86), especially in the subdiaphragmatic spaces and hepatic surfaces. MR imaging and CT were more sensitive than US (95%, 92%, and 69%, respectively) for peritoneal metastases. MR imaging was more accurate than CT for detection of lymph node metastases (A(z) = 0.76 vs 0.57, P =.04). In the liver, the A(z) values for the three modalities were 0.77-0.94. CONCLUSION: CT and MR imaging are equally accurate, and either modality can be used to stage advanced ovarian cancer.
Adult↗
Post-roll effects on attitude perception: "the Gillingham Illusion".
BACKGROUND: Several aircraft each year are lost because of an unexplained collision with the ground. The attitude of most of these aircraft prior to impact was nose-low and with excessive bank, i.e., greater than 90 degrees . Prior to these accidents, each aircraft was noted as either changing heading or making an abrupt roll. HYPOTHESIS: Could there be some underlying tendency for the pilot to make unnoticed stick inputs after completing a roll from one bank angle to another? METHODS: Since ground-based flight simulators cannot create the true sensation of rolling an aircraft from one side to the other, the instrumented CALSPAN NT-33 aircraft was used for this study. Six pilots were given a series of three roll rates and two head positions while the aircraft automatically changed bank from 45 degrees of bank in one direction to 45 degrees of bank in the opposite direction. The subject's view of the external visual scene was restricted with a blue-amber vision restricting transparency combination. All attitude-indicating instruments were blanked, requiring the subjects to make stick inputs based on their vestibular (somatosensory) feedback. RESULTS: Subjects experienced a consistent tendency to increase bank angle after given control of the aircraft immediately following the roll maneuver, while thinking they were maintaining a constant bank angle. In some cases, the pilots rolled the aircraft completely inverted. CONCLUSION: When pilots rely on their perception of bank, following a roll, they will inadvertently increase their bank in the direction of the previous roll.
Accidents, Aviation↗
Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery: results of a phase I randomized, double-blind, placebo-controlled trial.
BACKGROUND: Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 microg versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in patients undergoing CABG. Twenty-four patients were randomized to 10 microg of bFGF (n=8), 100 microg of bFGF (n=8), or placebo (n=8), in addition to undergoing CABG. There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0+/-6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-microg bFGF group had angina, whereas all patients in the 100-microg bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7+/-3.7% to 23.8+/-5.7%, P=0.06), no significant change in the 10-microg bFGF group, and significant improvement in the 100-microg bFGF group (19.2+/-5.0% to 9.1+/-5.9%, P=0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic area in the 100-microg bFGF group (10.7+/-3.9% to 3. 7+/-6.3%, P=0.06). CONCLUSIONS: This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that cannot be adequately revascularized.
Alginates↗
Practice of coronary angioplasty in California in 1995 : comparison to 1989 and impact of coronary stenting.
BACKGROUND: This study seeks to analyze changes in the practice of PTCA in California between 1989 and 1995 by use of the Office of Statewide Health Planning and Development (OSHPD) data set. METHODS AND RESULTS: All hospital discharges in 1995 with a procedure code for PTCA or stent were identified. The 1995 PTCA data were compared with previously published data from 1989 obtained from the same database. The number of PTCAs performed increased by 49% between 1989 and 1995, from 24 883 to 37 118. The percentage of female patients increased from 29.8% to 32.7% (P=0.0001). The percentage of diabetics increased from 14.4% to 21.6% (P=0.0001) between 1989 and 1995. Procedures on patients with a principal diagnosis of acute myocardial infarction increased from 19.3% of all PTCAs in 1989 to 27.5% of PTCAs in 1995 (P=0.0001). In-hospital mortality increased from 1.4% in 1989 to 1.9% in 1995 (P=0.0001). There were 3087 admissions with stent placement in 1995. In-hospital mortality after stent placement was 0.9% (P=0.0001 versus PTCA). Patients undergoing PTCA in hospitals performing >400 PTCAs in 1995 had a 4% incidence of death or emergency bypass surgery compared with a 6% incidence when PTCAs were performed in hospitals performing </=400 PTCA in 1995 (P<0.0001). Patients undergoing stent implantation in hospitals performing >75 stent procedures in 1995 had a 1.3% incidence of death or emergency bypass compared with an incidence of 4% when the procedure was performed in a hospital performing </=75 stent placements in 1995 (P<0.0001). CONCLUSIONS: The 1995 OSHPD data continue to suggest an inverse relationship between hospital PTCA and stent volume and adverse patient outcomes.
Aged↗
Differences in TIMI frame count following successful reperfusion with stenting or percutaneous transluminal coronary angioplasty for acute myocardial infarction.
The Thrombolysis In Myocardial Infarction (TIMI) flow grade achieved in the infarct-related artery (IRA) during reperfusion therapy for acute myocardial infarction (AMI) is directly related to myocardial salvage. Recently, several series have demonstrated the safety of stenting in AMI and documented a larger postprocedure luminal diameter than that found at angioplasty, although no study has compared the effect of PTCA and stenting in AMI on flow characteristics of the IRA. The residual stenosis and the number of frames required to opacify standardized angiographic landmarks normalized for vessel length (corrected TIMI frame count) or compared with flow in a corresponding normal coronary artery (TIMI frame count index) were determined for the IRA of 39 patients who underwent angioplasty or stenting for AMI. Baseline characteristics were similar for the 20 patients who underwent stenting and the 19 patients who underwent percutaneous transluminal coronary angioplasty. After intervention, the luminal diameter was greater (3.24 vs 2.09 mm, p <0.0001) and the residual stenosis was less (-9.4% vs. 26.7%, p <0.0001) after stenting than after percutaneous transluminal coronary angioplasty. These changes in vessel geometry were associated with a lower corrected TIMI frame count (16.1 vs 30.7, p <0.002) and a lower TIMI frame count index (0.68 vs 1.3, p <0.002). Thus, stenting in AMI is associated with a greater postprocedure luminal diameter and improvement in coronary blood flow as measured by the TIMI frame count method.
Aged↗
Cisplatin-modification of DNA repair and ionizing radiation lethality in yeast, Saccharomyces cerevisiae.
Cis-diamminedichloroplatinum II (cisplatin) is a DNA inter- and intrastrand crosslinking agent which can sensitize prokaryotic and eukaryotic cells to killing by ionizing radiation. The mechanism of radiosensitization is unknown but may involve cisplatin inhibition of repair of DNA damage caused by radiation. Repair proficient wild type and repair deficient (rad52, recombinational repair or rad3, excision repair) strains of the yeast Saccharomyces cerevisiae were used to determine whether defects in DNA repair mechanisms would modify the radiosensitizing effect of cisplatin. We report that cisplatin exposure could sensitize yeast cells with a competent recombinational repair mechanism (wild type or rad3), but could not sensitize cells defective in recombinational repair (rad52), indicating that the radiosensitizing effect of cisplatin was due to inhibition of DNA repair processes involving error free RAD52-dependent recombinational repair. The presence or absence of oxygen during irradiation did not alter this radiosensitization. Consistent with this result, cisplatin did not sensitize cells to mutation that results from lesion processing by an error prone DNA repair system. However, under certain circumstances, cisplatin exposure did not cause radiosensitization to killing by radiation in repair competent wild type cells. Within 2 h after a sublethal cisplatin treatment, wild type yeast cells became both thermally tolerant and radiation resistant. Cisplatin pretreatment also suppressed mutations caused by exposure to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a response previously shown in wild type yeast cells following radiation pretreatment. Like radiation, the cisplatin-induced stress response did not confer radiation resistance or suppress MNNG mutations in a recombinational repair deficient mutant (rad52), although thermal tolerance was still induced. These results support the idea that cisplatin adducts in DNA interfere with RAD52-dependent recombinational repair and thereby sensitize cells to killing by radiation. However, the lesions can subsequently induce a general stress response, part of which is induction of RAD52-dependent error free recombinational repair. This stress response confers radiation resistance, thermal tolerance, and mutation resistance in yeast.
Cisplatin↗
Absence of thrombotic thrombocytopenic purpura following coronary stenting in the ticlopidine era.
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Humans↗
Re: Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.
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BRCA2 Protein↗
Circumferential abdominal skin defect possibly due to umbilical cord encirclement.
We report on a newborn black male twin with a distinctive circumferential abdominal skin defect who was identified through the Active Malformation Surveillance Program at the Brigham and Women's Hospital. There were no other malformations, and amniotic disruption was not present. Although it cannot be proven, we believe that this skin defect may have been caused by in utero encirclement of the abdomen by an umbilical cord.
Abdomen↗
4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2).
A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2.
Animals↗
Effect of stent design on reduction of elastic recoil: a comparison via quantitative intravascular ultrasound.
The increase in minimum lumen diameter achieved by coronary stent placement can be further enhanced by reducing the immediate recoil that occurs after stent deployment. The effect of various stent designs-flexible coils, slotted tubes, and a locking stent-on minimization of postdilation stent recoil was evaluated using an in vitro model of circumferential compression. The stents were expanded to 7 atm (3.82 +/- 0.02 mm); as pressure was reduced, lumen diameter and cross-sectional area (CSA) were determined by on-line intravascular ultrasound imaging (30 MHz) positioned inside the dilating balloon (n = 10-15 inflation-deflation cycles). Stent recoil was assessed by calculation of percent change in CSA from 7 atm to negative balloon pressure: -33.1 +/- 5.6% (GR-II) and -22.4 +/- 3.8% (Wiktor) in the coil stents; -20.0 +/- 4.2% (JJIS coronary), -8.4 +/- 2.6% (JJIS biliary), and -6.9 +/- 1.5% (Multilink) in the slotted tube stents; and -1.9 +/- 3.2% in the Navius ZR1 locking stent (P < 0.05 vs. Multilink, P < 0.0001 vs. others). A range of resistances to recoil is demonstrated by this model, with coil stent designs undergoing greater elastic recoil than slotted tube stent designs. The locking stent design demonstrated the greatest radial strength and the most reduction in elastic recoil.
Angioplasty, Balloon, Coronary↗
Complications of regional blocks: what do we really know?
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Anesthesia, Conduction↗
A prospective comparison of laparoscopic ultrasound vs intraoperative cholangiogram during laparoscopic cholecystectomy.
BACKGROUND: The laparoscopic ultrasound (US) probe provides a new modality for evaluating biliary anatomy during laparoscopic cholecystectomy (LC). METHODS: We performed a laparoscopic US examination in 65 patients without suspected common bile duct (CBD) stones prior to the performance of a laparoscopic cholangiogram (IOC). We then compared the cost, time required, surgeon's assessment of difficulty, and interpretations of findings. RESULTS: There was a significant difference in the cost of US versus the cost of IOC ($362 +/- 12 versus $665 +/- 12; p < 0.05). Surgeons who had performed >10 US (EXP) were compared with those who had performed </=10 (NOV). There were significant differences between the EXP and NOV groups in ease of examination, visualization of biliary anatomy, and accuracy of measurement of the CBD. CONCLUSIONS: The use of laparoscopic US for the accurate evaluation of the CBD and biliary anatomy requires that the surgeon has surpassed the learning curve, which we have defined as having performed >10 US exams.
Adult↗
Disparate effects of the 1989 Loma Prieta and 1994 Northridge earthquakes on hospital admissions for acute myocardial infarction: importance of superimposition of triggers.
BACKGROUND: Most occurrences of presumed triggers of acute myocardial infarction (AMI) do not actually trigger an AMI. The relation between vulnerability to development of AMI and timing of triggers of AMI is poorly understood. The 1989 Loma Prieta earthquake struck the San Francisco Bay Area at 5:04 PM during a period of relatively reduced circadian vulnerability to AMI. The 1994 Northridge earthquake awakened citizens of Los Angeles at 4:31 AM, also during a period of otherwise reduced vulnerability to AMI, but superimposed the stress of the earthquake upon the known stress of awakening. Study of times of onset of natural disasters and their effect on precipitation of AMI may provide insight into the physiology of triggering. This study was designed to compare the triggering ability of 2 similarly intense earthquakes that occurred singly or superimposed upon another trigger. METHODS AND RESULTS: California discharge records were analyzed from the week before, the day of, and the 6 days after the Loma Prieta and Northridge earthquakes and the same dates of control years for total admissions, AMI admissions, and congestive heart failure admissions. There was no statistically significant increase in AMI admissions in the San Francisco Bay Area on the day of the Loma Prieta earthquake compared with the days before or after the earthquake or compared with the same day in 1990. In contrast, there was a 110% increase in admission rate for AMI in Los Angeles County on the day of the Northridge earthquake compared with the average of the 7 days before the earthquake (z = 4.349, P <.001). Similarly, there was a >80% increased risk of admission for AMI on the day of the Northridge earthquake in 1994 compared with the same date in 1995 (relative risk 1.828, 95% confidence intervals 1.289 to 2.592). CONCLUSIONS: Extreme emotional stress superimposed on the stress of awakening results in enhanced triggering of AMI. When emotional stress occurs at less vulnerable periods, there is no significant increase in incidence of AMI.
California↗
Two pathways for the induction of apoptosis in human lymphocytes.
PURPOSE: To assess the roles of cell membranes and DNA as targets in radiation-induced apoptosis. MATERIALS AND METHODS: Peripheral blood lymphocytes from normal human donors were exposed to different types of apoptosis-inducing agents. Several measures of apoptosis were used to compare the kinetics of the processes induced, as well as to correlate the processes with DNA damage and membrane oxidation. RESULTS: Two kinetically distinct processes were observed. DNA-damaging agents, such as ionizing radiation, bleomycin, cisplatin and the topoisomerase inhibitor m-amsacrine, induced apoptosis by a kinetically slow process initiated by DNA damage and dependent on protein synthesis, but which did not correlate with membrane oxidation. Conversely, the agents t-butyl hydroperoxide and cumene hydroperoxide induced apoptosis by a kinetically fast process independent of protein synthesis and which did correlate with membrane oxidation. CONCLUSIONS: Slowly repaired or unrepairable DNA lesions, such as some of those produced by ionizing radiation exposure, trigger apoptosis by a kinetically slow process. This slow apoptotic pathway is distinct from a fast process not induced by radiation but which is induced by membrane-oxidizing agents.
Apoptosis↗
Apoptosis and the adaptive response in human lymphocytes.
PURPOSE: To determine whether the sensitivity of human lymphocytes for apoptosis induced by either a membrane oxidizing agent or a DNA damaging agent is modified by an adaptive response. MATERIALS AND METHODS: Peripheral blood lymphocytes from normal human donors were exposed to low doses of the DNA damaging agent gamma-radiation, or the membrane oxidizing agent t-butyl hydroperoxide (t-BuOOH), incubated for various times and then tested for their sensitivity to induction of apoptosis by a subsequent exposure to a high dose of either agent. Apoptosis was measured using a fluorescent assay of DNA unwinding or a terminal deoxynucleotide transferase assay. RESULTS: The results show that Go lymphocytes pre-exposed to an adapting dose of radiation or DNA strand breaking agent are not protected but can become sensitized to subsequent apoptosis induced by radiation (a kinetically slow process). Inter- and intraindividual variations were observed. However, neither pre-exposure to radiation nor to a membrane oxidizing agent sensitized lymphocytes from any donor to apoptosis induced by a membrane oxidizing agent (a kinetically fast process). CONCLUSIONS: Since an increase in the elimination of genetically damaged cells by apoptosis could reduce the risk of cancer from exposure to radiation or other DNA damaging agents, this cellular sensitization for apoptosis may represent a novel adaptive response mechanism.
Adaptation, Physiological↗