Doctor to warrior.
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History, 20th Century↗
Biomedical subjects
D C Smith
Publications and source records attributed to D C Smith.
A hospital review of advanced gynecologic endoscopic procedures.
OBJECTIVE: Our purpose was to review the findings of a Gynecologic Endoscopic Review Committee established to monitor and review operative endoscopic procedures performed by the staff at a large private hospital, Swedish Hospital Medical Center, in Seattle. STUDY DESIGN: Hospital charts of patients undergoing the endoscopic procedures under review are pulled monthly, and the data are extracted, particularly as related to performance of the procedures, length of surgery and hospitalization, and occurrence of complications. This study is a compilation of the committee's review of a 15-month interval, Jan. 1, 1992, to March 31, 1993. RESULTS: Forty-two surgeons performed 227 endoscopic procedures on 218 patients, 100 hysteroscopically and 127 laparoscopically. Significant complication rates were associated with the transhysteroscopic operative procedures and with many of the translaparoscopic procedures, including oophorectomy, ovarian cystectomy, myomectomy, pelviscopic lysis of adhesions, and laparoscopic-assisted vaginal hysterectomy. CONCLUSIONS: A significant complication rate was found for many of the advanced endoscopic procedures performed at Swedish Hospital Medical Center. This is likely related to operator inexperience in performing relatively difficult endoscopic procedures involving new and ever-expanding arrays of techniques and instruments.
Female↗
A phase I trial of high-dose continuous-infusion hydroxyurea.
Hydroxyurea inhibits ribonucleotide reductase, resulting in depletion of intracellular deoxynucleotide pools and inhibition of DNA repair. It has been used in a variety of malignancies and is usually given orally. Deoxynucleotide depletion is directly related to the concentration of and duration of exposure to hydroxyurea; thus, prolonged continuous infusion may result in increased therapeutic efficacy. A total of 30 patients were treated on this trial, designed to determine the maximum tolerated doses (MTD) of intravenous hydroxyurea given as a 24- or 48-h continuous infusion. The MTD for the 24-h infusion was 13,520 mg/m2 following a bolus of 1,690 mg/m2, and the mean (+/- SD) plasma steady-state concentration was 1.93 +/- 0.52 mM. For the 48-h infusion, the MTD was 17,576 mg/m2 following a bolus of 2,197 mg/m2 and the mean steady-state level was 1.43 +/- 0.31 mM. The dose-limiting toxicity on both schedules was marrow suppression manifesting as neutropenia and thrombocytopenia. Pharmacokinetic analysis revealed decreasing clearance with increasing dose, implying that drug elimination is saturable. Pharmacodynamic analysis showed a slight correlation between steady-state plasma levels and the degree of marrow suppression.
Adult↗
Phase II trial and pharmacokinetic assessment of intravenous melphalan in patients with advanced prostate cancer.
Alkylating agents have been reported to yield response rates of up to 20% in hormone-refractory prostate cancer. Melphalan was studied in four small trials in which the drug was given orally. In this phase II trial, melphalan (30 mg/m2) was given intravenously every 28 days to 27 patients with hormone-refractory prostate cancer. Pharmacokinetic sampling was performed so as to describe the clearance of melphalan in this population and in an attempt to carry out pharmacodynamic modeling for toxicity and response. Prostate-specific antigen (PSA) was also assessed prospectively. No objective responses to this regimen were documented. The median survival for patients on this trial was 11.5 months. There was no correlation between drug clearance and measured creatinine clearance and no relationship between systemic exposure and toxicity. A decrease of > 50% in serum PSA that was sustained for > 6 weeks was documented in two patients, most notably in one patient who has survived for more than 29 months. Intravenous melphalan is not an active agent in hormone-refractory prostate cancer.
Aged↗
The effect of preoperative beta-blocker therapy on cardiovascular responses to weaning from mechanical ventilation and extubation after coronary artery bypass grafting.
The hemodynamic and electrocardiographic changes during weaning from mechanical ventilation and tracheal extubation were studied in 75 patients after elective coronary artery bypass surgery. Transfer from synchronized intermittent mandatory ventilation to spontaneous respiration through a T-piece was associated with an increase greater than 20% over baseline in systolic (SBP) and diastolic (DBP) blood pressure in 27% of patients, and in heart rate (HR) in 5% of patients. Although baseline SBP, DBP, and HR differed significantly between the patients taking chronic beta-blocker therapy and those not on beta-blockers (P values all < 0.003), there were no differences between these groups in their response to transfer to the T-piece. (P values: SBP = 0.98; DBP = 0.46; HR = 0.20). Tracheal extubation was associated with an increase greater than 20% of baseline in SBP in 18.9%, DBP in 16.2%, and HR in 5% of patients. However, there were significant differences between the chronically beta-blocked and non-beta-blocked groups, both in baseline values for SBP, DBP, and HR (P values all < 0.001), and also in the SBP response (P = 0.007) and HR response (P = 0.02) to extubation. Extubation was associated with a greater than 20% increase in SBP in 8.2% and DBP in 12.2% of chronically beta-blocked patients, compared to 40% and 23% of non-beta-blocked patients, although the DBP response was not statistically different (P = 0.14) between the groups. Similar proportions of patients in both groups increased their HR more than 20% above baseline, but the increase was much greater in the non-beta-blocked group (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic beta-Antagonists↗
Achieving a healthy death: the dying person's attitudinal contributions.
This study addressed the question of whether there are attitudes that may be psychologically beneficial to the dying, their families, and their caregivers. The Omega Attitudes Inventory was distributed to 467 systematically selected hospice coordinators nationwide. The responses of 327 (70%) indicated high concordance with patient attitudes contributing to a "healthy" death. The identified attitudes were qualitatively enhanced through anecdote and the literature. The study concluded with implications for clinical practice and further research.
Adaptation, Psychological↗
Metabolic effects of dobutamine.
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Dobutamine↗
Fresh frozen plasma and edrophonium in a patient with a plasma cholinesterase deficiency.
A 35-year-old woman undergoing laparoscopic sterilisation developed prolonged apnoea after suxamethonium. Fresh frozen plasma was given to replenish plasma cholinesterase, but recovery of neuromuscular transmission was not accelerated. Routine use of quantitative neuromuscular monitoring simplified her postoperative management.
Adult↗
Blood sampling from paediatric arterial cannulae.
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Adult↗
Arteriovenous fistula: a complication of cardiac pacemaker lead placement and its management with percutaneous embolization.
A right internal mammary artery to right brachiocephalic vein fistula was discovered following implantation of a permanent cardiac pacemaker. The fistula was closed via percutaneous embolization.
Aged↗
Changes in recording electrode impedance during anaesthesia have no effect on evoked electromyographic responses.
Changes in electrical impedance at the recording electrodes have been blamed for the failure of evoked electromyographic responses to return to baseline during the offset of neuromuscular block, but a relationship between electrode impedance and electromyographic responses has never been shown. In 50 fit adults, the resistive and capacitive (reactive) components of the impedance of the recording electrodes were measured during electromyographic monitoring of neuromuscular transmission under enflurane anaesthesia. In 25 patients six 1 mm-deep punctures were made in the skin under both active recording electrodes, and in the other 25 no puncture was made. Electrode impedance was measured using an impedance bridge at a current density less than 60 microA cm-2. Skin puncture made no difference either to the electrode impedance, or to the decrement from the baseline of the first electromyographic response to the train-of-four stimuli after offset of neuromuscular blockade. The electrode impedance decreased in 48 of the patients, and increased slightly in the other two patients. There was no relationship between the decrease in the T1 response from baseline and the change in electrode impedance during electromyographic monitoring.
Adult↗
Gingival and other oral manifestations in tuberous sclerosis: a case report.
Tuberous sclerosis is a rare congenital disorder characterized by cutaneous angiofibromas, mental retardation, seizure disorders, and a variety of other, less common systemic anomalies. The present report details the features and periodontal management of a patient with gingival fibromata secondary to tuberous sclerosis.
Adult↗
High-dose oral tamoxifen, a potential multidrug-resistance-reversal agent: phase I trial in combination with vinblastine.
BACKGROUND: P-glycoprotein mediates resistance to natural-product anti-neoplastic agents like vinblastine through an active transport process resulting in reduced intracellular concentration of these agents. The triphenylethylene antiestrogen tamoxifen and its major metabolite N-desmethyltamoxifen at concentrations of 4-6 microM enhance the intracellular concentration of natural-product antineoplastics and augment the cytotoxicity of such drugs three-fold to 10-fold in a variety of human and murine cell lines. PURPOSE: On the basis of these preclinical findings, we conducted a phase I clinical trial of high-dose, oral tamoxifen administered in conjunction with a 5-day continuous infusion of vinblastine. METHODS: We studied 53 patients with advanced epithelial tumors. Tamoxifen was given orally as a loading dose on day 1, followed by two doses a day on days 2-13. Vinblastine was given as a 120-hour continuous infusion (1.5 mg/m2 per day) on days 9-13 of each tamoxifen course. The starting dose of tamoxifen was 40 mg/m2 administered twice a day following a loading dose of 150 mg/m2. The maximum dose was 260 mg/m2 twice a day following a loading dose of 680 mg/m2. Treatment cycles were repeated every 28 days. RESULTS: The dose-limiting toxic effects of tamoxifen were neurologic and began within 3-5 days after the start of treatment. They consisted of tremor, hyperreflexia, dysmetria, unsteady gait, and dizziness. One patient experienced a grand mal seizure 24 hours after the last tamoxifen dose. Toxic effects were rapidly reversible. Asymptomatic prolongation of the QT interval on electrocardiogram occurred at doses of tamoxifen of 80 mg/m2 or higher given twice a day. No coagulation or ophthalmologic abnormalities occurred. Tamoxifen did not enhance the toxicity of vinblastine. Mean plasma concentrations of tamoxifen or N-desmethyltamoxifen at 260 mg/m2 tamoxifen given twice a day for 13 days were 6.04 and 6.56 microM, respectively. There was no relationship between plasma antiestrogen content and the development of neurotoxic effects. CONCLUSIONS: Tamoxifen at 150 mg/m2 given twice a day following a loading dose of 400 mg/m2 results in plasma levels of tamoxifen and N-desmethyltamoxifen of 4 and 6 microM, respectively, without dose-limiting toxicity. We recommend this dose for phase II trials of tamoxifen to modulate P-glycoprotein-mediated drug resistance. IMPLICATIONS: Our study demonstrates that high-dose tamoxifen can be safely administered and that plasma concentrations that may inhibit P-glycoprotein function can be achieved.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a phase I trial.
1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance may be mediated by repair of chloroethylated guanine before stable cross-linking occurs. Guanine adducts may be repaired by the enzyme O6-alkylguanine-DNA alkyltransferase (O6-AGAT). Such repair irreversibly inactivates O6-AGAT. Streptozotocin (STZ) forms adducts at the O6 position of guanine; repair of these adducts consumes O6-AGAT. In vivo STZ potentiates BCNU cytotoxicity. The purpose of this trial was to determine the maximum tolerated dose of BCNU that can be administered together with STZ. The STZ dose was 500 mg/m2/day for 4 days and was not escalated. BCNU was given 4 h after the third dose of STZ at a starting dose of 75 mg/m2. A total of 43 patients were entered in the study. There were 4 dose escalations, reaching a maximum tolerated BCNU dose of 175 mg/m2. At this dose, thrombocytopenia was the dose-limiting toxicity (one patient, 25-49 x 10(9)/liter; 2 patients, less than 25 x 10(9)/liter); neutropenia was less severe (2 patients, 2.0-3.9 x 10(9)/liter, 1 patient, 1.0-1.9 x 10(9)/liter). Two other commonly seen toxicities were elevations in the serum alkaline phosphatase and mild elevations in the serum creatinine. Peripheral blood lymphocyte O6-AGAT levels decreased from a mean of 212 fmol/mg protein pretherapy to 8.2 fmol/mg protein on day 3 prior to BCNU (P = 0.03). Three partial responses were seen. There were no therapy-related fatalities, and toxicity was easily managed. This study established that 150 mg of BCNU can be administered safely together with STZ, 500 mg/m2/day for 4 days. Additional studies are required to determine whether O6-AGAT-mediated BCNU resistance is suppressed.
Adult↗
Missing arteries?
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Cardiac Catheterization↗
Nacre initiates biomineralization by human osteoblasts maintained in vitro.
When nacreous shell produced by the marine oyster Pinctada maxima, used as a biomaterial in oral surgery, is implanted in human bone, new bone formation occurs, resulting in a tight welding of the bone to the nacre [16]. These findings are consistent with the possibility that nacre adjacent to bone can locally stimulate osteogenic activity. To test this hypothesis, we have evaluated the effect of the simultaneous presence of bone and nacre on human osteoblasts in vitro. Nacre chips (1 mm3) were placed at approximately 1 mm distance from a similarly sized bone chip on a layer of first passage human osteoblasts. None of the chemical inducers generally required to obtain bone mineralization in vitro (in particular, beta-glycerophosphate) was added to the cultures. Mineralized sections of the cultures were evaluated by light and electron microscopy, contact microradiography, and Laser Raman Spectroscopy. The results demonstrated that nacre has strong osteogenic effects on human osteoblasts when placed in proximity to bone in vitro. New bone formation occurred by both appositional growth on the existing bone and by the formation of mineralized nodules within the matrix adjacent to the bone explant. Electron microscopic evaluation of these sites demonstrated findings typical of those described in the course of bone formation in vivo, and no evidence of toxicity was observed. In addition, under the conditions of culture used, nacre can also promote the formation by osteoblasts of a structure with characteristics similar to nacre (e.g., lamellar organic matrix mineralized with aragonite, as demonstrated by Laser Raman Spectroscopy).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Phase I study of BCNU and intravenous 6-mercaptopurine in patients with anaplastic gliomas.
On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2 x 1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily x 3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.
Adolescent↗