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1.
J R Soc Interface ; 16(157): 20190218, 2019 08 30.
Article in English | MEDLINE | ID: mdl-31387487

ABSTRACT

Correlative imaging combines information from multiple modalities (physical-chemical-mechanical properties) at various length scales (centimetre to nanometre) to understand the complex biological materials across dimensions (2D-3D). Here, we have used numerous coupled systems: X-ray microscopy (XRM), scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), optical light microscopy (LM) and focused ion beam (FIB-SEM) microscopy to ascertain the microstructural and crystallographic properties of the wall-plate joints in the barnacle Semibalanus balanoides. The exoskeleton is composed of six interlocking wall plates, and the interlocks between neighbouring plates (alae) allow barnacles to expand and grow while remaining sealed and structurally strong. Our results indicate that the ala contain functionally graded orientations and microstructures in their crystallography, which has implications for naturally functioning microstructures, potential natural strengthening and preferred oriented biomineralization. Elongated grains at the outer edge of the ala are oriented perpendicularly to the contact surface, and the c-axis rotates with the radius of the ala. Additionally, we identify for the first time three-dimensional nanoscale ala pore networks revealing that the pores are only visible at the tip of the ala and that pore thickening occurs on the inside (soft bodied) edge of the plates. The pore networks appear to have the same orientation as the oriented crystallography, and we deduce that the pore networks are probably organic channels and pockets, which are involved with the biomineralization process. Understanding these multiscale features contributes towards an understanding of the structural architecture in barnacles, but also their consideration for bioinspiration of human-made materials. The work demonstrates that correlative methods spanning different length scales, dimensions and modes enable the extension of the structure-property relationships in materials to form and function of organisms.


Subject(s)
Animal Shells/anatomy & histology , Thoracica/physiology , Animal Shells/physiology , Animals , Biomechanical Phenomena , Microscopy , Microscopy, Electron, Scanning
2.
Med Eng Phys ; 47: 190-197, 2017 09.
Article in English | MEDLINE | ID: mdl-28716304

ABSTRACT

Cardiopulmonary bypass procedures are one of the most common operations and blood oxygenators are the centre piece for the heart-lung machines. Blood oxygenators have been tested as entire devices but intricate details on the flow field inside the oxygenators remain unknown. In this study, a novel method is presented to analyse the flow field inside oxygenators based on micro Computed Tomography (µCT) scans. Two Hollow Fibre Membrane (HFM) oxygenator prototypes were scanned and three-dimensional full scale models that capture the device-specific fibre distributions are set up for computational fluid dynamics analysis. The blood flow through the oxygenator is modelled as a non-Newtonian fluid. The results were compared against the flow solution through an ideal fibre distribution and show the importance of a uniform distribution of fibres and that the oxygenators analysed are not susceptible to flow directionality as mass flow versus area remain the same. However the pressure drop across the oxygenator is dependent on flow rate and direction. By comparing residence time of blood against the time frame to fully saturate blood with oxygen we highlight the potential of this method as design optimisation tool. In conclusion, image-based reconstruction is found to be a feasible route to assess oxygenator performance through flow modelling. It offers the possibility to review a product as manufactured rather than as designed, which is a valuable insight as a precursor to the approval processes. Finally, the flow analysis presented may be extended, at computational cost, to include species transport in further studies.


Subject(s)
Blood/diagnostic imaging , Blood/metabolism , Extracorporeal Membrane Oxygenation/instrumentation , Extracorporeal Membrane Oxygenation/methods , Models, Cardiovascular , Oxygen/blood , Tomography, X-Ray Computed/methods , Blood Physiological Phenomena , Computer Simulation , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Humans , Imaging, Three-Dimensional/methods
4.
Cancer ; 92(8): 2023-9, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11596015

ABSTRACT

BACKGROUND: Primary hepatic non-Hodgkin lymphoma (PHL) is a rare and difficult to diagnose lymphoproliferative disorder of unknown etiology. It is believed that the prognosis in affected patients is dismal, consisting of early recurrence and short survival. METHODS: A retrospective cohort review of patients with PHL diagnosed between 1974 and 1995 at a university cancer center was performed. RESULTS: Twenty-four patients with PHL were identified. Typically, the disease occurred in middle-aged men (median age, 50 years). The primary presenting complaint was right upper quadrant abdominal pain, with hepatomegaly found at physical examination. Serum liver enzymes, lactate dehydrogenase, and beta-2-microglobulin levels all were elevated, but alpha-fetoprotein and carcinoembryonic antigen levels were within normal range. Hypercalcemia was found in 6 of 15 patients who were tested. Six of 10 patients who were tested were positive for the hepatitis C virus (HCV). Liver scans demonstrated either a solitary lesion or multiple lesions. Pathologic examination revealed diffuse large cell lymphoma in 23 patients (96%). Combination chemotherapy was the mainstay of treatment; surgery consisted of diagnostic biopsy. The complete remission rate was 83.3%, and the 5-year cause specific and failure free survival rates were 87.1% and 70.1%, respectively. HCV infection did not appear to influence the outcome of therapy. CONCLUSIONS: The outcome of patients with PHL who are treated with combination chemotherapy may be more favorable than that reported elsewhere. The frequent association of PHL with HCV infection observed in this series warrants further investigation.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Liver Neoplasms/drug therapy , Lymphoma, Non-Hodgkin/drug therapy , Adult , Aged , Doxorubicin/administration & dosage , Female , Hepatitis C/complications , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/virology , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/virology , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/virology , Male , Middle Aged , Remission Induction , Retrospective Studies , Survival Analysis
5.
ANZ J Surg ; 71(7): 394-7, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11450912

ABSTRACT

BACKGROUND: Mirizzi Syndrome (MS) is an important but uncommon complication of gallstones characterized by narrowing of the common hepatic duct (CHD) due to mechanical compression or inflammation. This study aimed to assess the impact of preoperative and intraoperative diagnosis of MS on the performance, safety and efficacy of laparoscopic cholecystectomy. METHODS: From a consecutive series of 1,281 patients having surgery for gall bladder disease between 1990 and 1998, nine patients with MS were identified from a prospective database and their clinical progress examined. RESULTS: Five out of the nine patients with MS presented with pain (2/5 were also jaundiced), and four presented with acute cholecystitis. Liver function tests were abnormal in all patients. Preoperative diagnosis of MS based on ultrasound was made in only two patients, and in a third on findings of a nasobiliary cholangiogram. In six patients, the diagnosis was intraoperative. In seven patients cholecystectomy was completed by laparoscopy. Two patients needed conversion to open cholecystectomy. In two patients the common bile duct was mistaken for the cystic duct and the error was recognized on relaxation of traction on the gall bladder in one, but in the other a duct injury occurred that was not recognized until the postoperative period. CONCLUSIONS: Preoperative diagnosis of MS is difficult, and a high index of suspicion is necessary to avoid serious complications. Once the diagnosis is known, successful laparoscopic management is possible but care should be taken to avoid duct injury.


Subject(s)
Cholecystectomy, Laparoscopic , Cholelithiasis/complications , Cholelithiasis/surgery , Hepatic Duct, Common/pathology , Adult , Cholecystectomy , Constriction, Pathologic/etiology , Constriction, Pathologic/pathology , Female , Humans , Intraoperative Care , Male , Preoperative Care , Prospective Studies , Syndrome
6.
Surg Laparosc Endosc Percutan Tech ; 10(3): 158-62, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10872978

ABSTRACT

The lower-limb venous return, assessed by the peak systolic venous velocities (PSVV) of the left common femoral vein, was recorded at different stages of operation for five patients undergoing major gynecologic operative laparoscopy. The average baseline PSVV was 23.1 cm/s. After positioning the patient in the Trendelenburg position, the PSVV increased to an average of 31.5 cm/s; this was a statistically significant increase. Creation of the pneumoperitoneum changed the waveform from a normal phasic pattern to a dampened, continuous, monophasic waveform. The average PSVV was reduced to 15.9 cm/s; this dampening was statistically significant. Further dampening was evident 1 hour intraoperatively, and the flow became intermittent, with cycles of dampened flow followed by periods of absent flow; these changes in PSVV were not statistically significant. Calf compressors did not increase the femoral PSVV at the beginning of operation, nor at I hour intraoperatively; the decrease was not statistically significant. After release of the pneumoperitoneum, the baseline waveform pattern and velocity returned. The Trendelenburg position used for gynecologic operative laparoscopy was associated with a statistically significant increase in the lower-limb PSVV. This increase did not fully counteract the dampening effect of a pneumoperitoneum on lower-limb PSVV. The authors' study did not support the benefit previously reported on the use of pneumatic calf compressors. The authors therefore recommend continuing the practice of antithrombotic measures for patients undergoing gynecologic operative laparoscopy.


Subject(s)
Femoral Vein/physiology , Head-Down Tilt/physiology , Hysterectomy , Adult , Blood Flow Velocity , Female , Humans , Hysterectomy/methods , Laparoscopy , Middle Aged , Pneumoperitoneum, Artificial , Regional Blood Flow
7.
Int J Radiat Oncol Biol Phys ; 41(3): 647-50, 1998 Jun 01.
Article in English | MEDLINE | ID: mdl-9635715

ABSTRACT

PURPOSE: To review the long-term clinical effects of unilateral kidney irradiation on overall renal function and blood pressure in patients with gastric lymphoma. METHODS AND MATERIALS: In the study were 27 patients with Stage I or II gastric lymphoma who had undergone irradiation of at least 24 Gy to > or = 1/3 of the left kidney. They include 16 women and 11 men, aged 31 to 77, with a mean age of 57.6 years (median 56). Fifteen patients had Stage I and 12 had Stage II disease. In 13 patients the whole kidney had been irradiated, and 14 had had partial kidney irradiation, at doses ranging between 24 and 40.5 Gy. All patients received combined chemotherapy with various drugs: all patients received corticosteroids, and five received cis-platinum. Their follow-up ranged between 0.7 and 7.8 years (mean 3.4 years). Data on possible effects of the treatment on blood pressure, renal function as assessed by blood urea and creatinine, and kidney shrinkage as seen by serial computed tomography scanning were collected on all patients. RESULTS: Three patients had persistent, mild elevations of urea and creatinine levels, which did not require special treatment. All three also received cis-platinum. Ipsilateral kidney shrinkage was evident in most patients. In 19 patients the craniocaudal measurement of the kidney shrank by > or = 1.6 cm. Shrinkage in other dimensions was also evident. The degree of atrophy was related to the volume of kidney irradiated. Only two patients developed hypertension, both at a low level of 150/90; one patient had had 40 Gy to the whole kidney, the other 40 Gy to half the kidney. Neither patient had elevated urea or creatinine. CONCLUSIONS: Notwithstanding the shrinkage to the irradiated part of the kidney, the treatment did not lead to clinically significant hypertension or renal dysfunction. The administration of cis-platinum to patients with gastric lymphoma that requires kidney irradiation should be further evaluated.


Subject(s)
Kidney/radiation effects , Leukemia, Lymphocytic, Chronic, B-Cell/radiotherapy , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Lymphoma, Large B-Cell, Diffuse/radiotherapy , Stomach Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Kidney/physiopathology , Male , Middle Aged
8.
Int J Radiat Oncol Biol Phys ; 40(2): 377-86, 1998 Jan 15.
Article in English | MEDLINE | ID: mdl-9457824

ABSTRACT

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.


Subject(s)
Hodgkin Disease/diagnostic imaging , Hodgkin Disease/pathology , Lymphography , Abdomen , Adult , Cohort Studies , Female , Humans , Laparotomy , Male , Neoplasm Staging/methods , Probability , Sex Factors , Spleen/pathology
11.
Leuk Lymphoma ; 26(1-2): 77-82, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9250790

ABSTRACT

We conducted a phase I clinical trial of a new combination of fludarabine and paclitaxel in which 19 patients with histologically confirmed recurrent low-grade non-Hodgkin's lymphoma (NHL) were treated at five dose levels. Fludarabine was administered intravenously by bolus for 5 days and paclitaxel was given by intravenous (I.V.) continuous infusion for 96 or 72 hours starting day 1. Courses were repeated every 4 weeks. Patients whose disease responded received a maximum of six courses. All 19 patients received at least one course and could be evaluated for toxic effects, and 18 patients could be evaluated for response. The maximum tolerated dose (MTD) was 20 mg/m2/day I.V. bolus for 5 days of fludarabine plus 60 mg/m2/day I.V. of paclitaxel given as a continuous infusion over 72 hours. The limiting toxic effect was neutropenic fever, which was observed in five of the seven patients treated at the highest dose level. Grade 3 non-hematologic toxic effects of stomatitis (14%), neuropathy (14%), and hypotension (14%) were also observed at the highest dose level. No grade 4 non-hematologic toxic effects or treatment-related deaths occurred. One patient had herpes zoster infection of the skin 1 year after the completion of therapy. The overall response rate was 50%, with the two patients whose disease completely responded remaining disease free at 22 and 17 months. Patients with no prior exposure to either paclitaxel or fludarabine had 62% response rate. We conclude that the combination of fludarabine and paclitaxel appears to have promising activity for the treatment of recurrent low-grade NHL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Female , Follow-Up Studies , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives
12.
Br J Haematol ; 96(2): 328-32, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9029021

ABSTRACT

In order to determine the activity of paclitaxel in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II clinical trial in which eligible patients received paclitaxel 200 mg/m2 intravenously over 3 h. Treatment was repeated every 3 weeks. Patients achieving complete or partial responses after two courses of paclitaxel continued to receive therapy for a maximum of eight courses, otherwise they were removed from the study. Of 96 evaluable patients, 45 (47%) had primary refractory disease, and 51 (53%) had relapsed lymphoma. The median number of prior treatment regimens was two (range one to 10 regimens). 45 patients had lowgrade, 44 had intermediate-grade, and seven had mantle cell lymphoma. 24/96 patients responded (10 complete and 14 partial remissions) for an overall response rate of 25% (95% CI 17-35%). Patients with relapsed lymphoma had a higher response rate than those with primary refractory disease (19/51 = 37% v 5/45 = 11%; P < 0.01), and patients with relapsed intermediate-grade lymphoma had a higher response than those with relapsed low-grade lymphoma (9/18 = 50% v 10/31 = 32%; P = 0.22). The treatment was very well tolerated with the most common side-effects being alopecia (100%), peripheral neuropathy (35% of > or = grade II), and arthralgia/myalgia (25% of > or = grade II). After the first course of paclitaxel, grade III/IV thrombocytopenia and neutropenia were observed in 21% and 23% of the patients respectively. 23 episodes of neutropenic fever developed after 250 courses of paclitaxel therapy (8%). We conclude that paclitaxel, at this dose and schedule, is an active new drug for the treatment of non-Hodgkin's lymphoma. The activity of paclitaxel combination programmes are currently under investigation.


Subject(s)
Lymphoma, Non-Hodgkin/drug therapy , Paclitaxel/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged , Paclitaxel/adverse effects , Recurrence , Treatment Outcome
13.
Ann Oncol ; 8 Suppl 1: 129-31, 1997.
Article in English | MEDLINE | ID: mdl-9187446

ABSTRACT

Paclitaxel (Taxol) was recently tested in patients with relapsed and refractory lymphoma in two phase II clinical trials using two different infusion schedules. The first, reported from the NCI (USA), used a 96-hour intravenous continuous infusion schedule, and the second, from our group, used a 3-hour infusion. In the NCI trial, 29 evaluable patients were treated with 140 mg/m2 every three weeks, which achieved a 17% response rate (all PRs); while we treated 96 evaluable patients with 200 mg/m/ every three weeks, which achieved a 25% response rate (10 CRs and 14 PRs, 95% CI: 17%-35%). In our trial, patients with relapsed (not primary refractory) intermediate-grade lymphoma had a response rate of 50%, and those with relapsed low-grade lymphoma had a response rate of 31%. In a follow-up trial, 12 patients who failed to respond to 3-hour infusion of paclitaxel were crossed over to receive paclitaxel by 96-hour infusion. None of the 12 evaluable patients achieved a major clinical response. Similarly, of 25 patients treated with cyclosporine A and paclitaxel after failing therapy with single-agent paclitaxel, only one patient (4%) responded. We conclude that paclitaxel has a promising single-agent activity, most prominently in patients with relapsed intermediate-grade lymphoma. Paclitaxel-based combination programs are currently being evaluated in our institution.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Lymphoma/drug therapy , Paclitaxel/administration & dosage , Drug Administration Schedule , Humans , Infusions, Intravenous
14.
Australas Radiol ; 40(3): 273-5, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8826734

ABSTRACT

AIM: To ascertain the accuracy of ultrasound-guided fine needle aspiration and parathyroid hormone assay in the identification of parathyroid adenomas. DESIGN: Case study. SETTING: Tertiary referral clinic. PATIENTS: 12 subjects, consisting of 10 female and two male patients, with documented primary hyperaparathyroidism. INTERVENTION: Ultrasonography of the parathyroid glands was performed using an Acuson XP 128 machine with a linear array 7.5 MHz multihertz probe. Following accurate localization of the parathyroid lesion, fine needle aspiration was performed using a 23 gauge needle, and parathyroid hormone assay was performed on the aspirate. Preoperative localization was compared with intra-operative findings. RESULTS: Ultrasound examination detected 10 out of a possible 12 parathyroid adenomas (83% sensitivity), while ultrasound-guided fine needle aspiration only confirmed nine out of the 12 adenomas (75% sensitivity). CONCLUSIONS: While ultrasound-guided fine needle aspiration may be simple and with minimal morbidity, it does not appear to provide any advantage over ultrasound examination alone for the localization of parathyroid adenomas. It has a potential role in defining the nature of ultrasonically localized nodules.


Subject(s)
Adenoma/pathology , Biopsy, Needle/instrumentation , Parathyroid Neoplasms/pathology , Ultrasonography/instrumentation , Adenoma/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Hyperparathyroidism/diagnostic imaging , Hyperparathyroidism/pathology , Male , Middle Aged , Parathyroid Neoplasms/diagnostic imaging , Sensitivity and Specificity
15.
J Clin Oncol ; 14(1): 233-9, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8558203

ABSTRACT

PURPOSE: Cyclosporin A has been shown to reverse paclitaxel resistance in vitro by inhibiting P-gp function. Therefore, we determined whether addition of cyclosporine to paclitaxel reversed clinical paclitaxel resistance in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients with relapsed NHL were eligible if they had no intervening treatment after failure to respond to paclitaxel (200 mg/m2 over 3 hours), and if they had adequate marrow, renal, and hepatic function, no serious cardiac disease, no CNS involvement, and no antibodies to human immunodeficiency virus-1. A cyclosporin A bolus dose (5 mg/kg over 3 hours) was followed by intravenous infusion (15 mg/kg) over 24 hours. Six hours after the beginning of cyclosporin A, the immediately preceding paclitaxel dose was administered over 3 hours. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Response was assessed after two cycles, and those patients who achieved at least a partial response received a maximum of six courses. RESULTS: All 26 patients entered were assessable for toxicity and 25 were assessable for response. One patient whose disease had progressed during paclitaxel treatment had a partial remission after the addition of cyclosporin A (response rate, 4%; 95% confidence interval, 1% to 20%). Disease progressed in 17 patients (71%) and did not respond in seven (25%). Serum cyclosporin A A levels measured at the time of initiation of paclitaxel infusion were greater than 2,000 ng/mL during 81% of cycles. Treatment toxicity included peripheral neuropathy in 57%, myalgia or arthralgia in 30%, neutropenia in 53%, neutropenic fever in 8%, and thrombocytopenia in 42% of patients. One patient with preexisting asthma had an acute bronchospasm during the first cycle and was removed from the study. There were no renal or hepatic toxicity and no infectious or hemorrhagic deaths. CONCLUSION: Cyclosporin A administered on this schedule did not reverse established clinical resistance to paclitaxel, which suggests that P-gp-mediated drug efflux is unlikely to be the only cause of paclitaxel resistance in this patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclosporine/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Paclitaxel/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cimetidine/administration & dosage , Cross-Over Studies , Cyclosporine/blood , Dexamethasone/administration & dosage , Dextropropoxyphene/therapeutic use , Diphenhydramine/administration & dosage , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Infusions, Intravenous , Male , Membrane Glycoproteins/antagonists & inhibitors , Middle Aged , Neoplasm Proteins/antagonists & inhibitors , Premedication , Recurrence , Remission Induction
17.
Am J Obstet Gynecol ; 173(3 Pt 1): 913-7, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7573268

ABSTRACT

OBJECTIVE: Our purpose was to evaluate the pharmacokinetics of atosiban, an oxytocin antagonist, during and after intravenous infusion in pregnant patients having at least six contractions per hour. The relationship between atosiban infusion and uterine activity was also assessed. STUDY DESIGN: Plasma samples from eight pregnant patients treated with intravenous atosiban (300 micrograms/min for 6 to 12 hours) were analyzed for atosiban concentration by a specific radioimmunoassay procedure. Contraction rate data were obtained by external tocodynamometry for 1 hour before the infusion and during the subsequent infusion. RESULTS: The average steady-state plasma concentrations of patients receiving intravenous atosiban were 442 +/- 73 ng/ml (mean +/- SD), with steady state achieved by 1 hour after the start of the infusion. After the completion of the infusion, plasma concentrations declined rapidly in a biexponential manner with initial and terminal half-life estimates of 13 +/- 3 and 102 +/- 18 minutes, respectively. The effective half-life was 18 +/- 3 minutes. The plasma clearance of atosiban was relatively high (42 L/hr) and the volume of distribution (approximately 18 L) was consistent with distribution into extracellular fluid. Of the seven patients evaluated for uterine activity, the mean contraction rate decreased by 75% during the third hour of treatment and remained low until treatment termination. CONCLUSION: On the basis of earlier published reports, the pharmacokinetics of atosiban in pregnant patients are similar to those in nonpregnant women. Although the patient population was small, a consistent reduction in uterine activity was observed during atosiban infusion.


Subject(s)
Hormone Antagonists/pharmacokinetics , Obstetric Labor, Premature/prevention & control , Oxytocin/antagonists & inhibitors , Tocolytic Agents/pharmacokinetics , Uterine Contraction/drug effects , Vasotocin/analogs & derivatives , Female , Half-Life , Humans , Kinetics , Metabolic Clearance Rate , Pregnancy , Vasotocin/blood , Vasotocin/pharmacokinetics , Vasotocin/therapeutic use
18.
J Clin Oncol ; 13(3): 583-7, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7884419

ABSTRACT

PURPOSE: Paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) is a novel antimicrotubule agent with anti-tumor activity against ovarian and breast carcinomas. Its activity when administered as a 3-hour intravenous infusion in patients with relapsed non-Hodgkin's lymphoma (NHL) has not been studied. PATIENTS AND METHODS: Patients with relapsed NHL were treated with a 3-hour infusion of 200 mg/m2 of Taxol every 3 weeks in an outpatient setting. All patients received premedication (dexamethasone, diphenhydramine, and cimetidine) to prevent allergic reactions. Responses were assessed after two courses of therapy, and patients who achieved at least partial remission (PR) continued to receive Taxol for a maximum of eight courses. RESULTS: Of 60 eligible patients, 54 (90%) were assessable for treatment toxicity and 53 (88%) were for treatment response (22 with primary refractory and 31 with relapsed disease). Twelve patients (23%) achieved a PR (n = 6) or complete remission (CR; n = 6) (95% confidence interval, 12% to 36%). Responses were observed in intermediate-grade (31%), low-grade (14%), and mantle-cell (17%) lymphomas. In the intermediate-grade lymphomas, there was a trend for a higher response rate in relapsed versus primary refractory disease (54% v 13%; P = .08). Treatment-related toxicity included alopecia (100%), peripheral neuropathy (37%), myalgia or arthralgia (25%), and neutropenic fever (11%). None of the patients had allergic reactions or cardiac toxicity. CONCLUSION: At this dose and schedule, Taxol is an active agent in patients with relapsed NHL and can be safely administered in an outpatient setting. Combination programs with Taxol should be investigated for treatment of NHL.


Subject(s)
Lymphoma, Non-Hodgkin/drug therapy , Paclitaxel/administration & dosage , Adult , Aged , Alopecia/chemically induced , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/therapeutic use , Peripheral Nervous System Diseases/chemically induced , Recurrence , Remission Induction
19.
J Lipid Res ; 35(10): 1773-85, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7852854

ABSTRACT

Lipid-derived free radicals were detected by electron paramagnetic resonance (EPR) spectrometry when cultured endothelial cells attached to Cytodex beads were exposed to iron-induced oxidant stress in the presence of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). Radical adduct formation was enhanced greatly when the cells were supplemented during growth with polyunsaturated fatty acids. The largest EPR signal intensity was observed in cells enriched with docosahexaenoic acid (DHA) or eicosapentaenoic acid, but enhanced radical adduct production also occurred after exposure to arachidonic, alpha-linolenic, gamma-linolenic, or linoleic acids. Radical adduct formation increased as the DHA content of the cells increased and approached a maximum after only 6 h of exposure to DHA. Ascorbic acid, acting as a pro-oxidant, enhanced radical adduct formation in cells enriched with DHA. The EPR signal intensity was reduced when the cells were tested 6 h after replacement of the DHA-enriched medium with a medium containing 5-20 microM oleic acid, indicating that the increased endothelial responsiveness to oxidant stress is reversible. Likewise, when U937 monocytes enriched with DHA were exposed subsequently to 20 microM oleic acid, a 35-45% decrease in radical adduct formation also occurred. These findings suggest that the endothelium may become more susceptible to oxidative injury when it is exposed to elevated amounts of polyunsaturated fatty acids. However, the effect appears to be temporary. The protective action of oleic acid against oxidant stress is not confined to the endothelium; it applies to monocytes as well.


Subject(s)
Endothelium, Vascular/drug effects , Fatty Acids, Unsaturated/pharmacology , Lipids/chemistry , Animals , Cells, Cultured , Docosahexaenoic Acids/pharmacology , Electron Spin Resonance Spectroscopy , Endothelium, Vascular/cytology , Free Radicals , Lipid Peroxidation/drug effects , Oxidation-Reduction , Swine
20.
Surg Laparosc Endosc ; 4(2): 128-33, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8180764

ABSTRACT

The objectives of this research were (a) to determine the effect of insufflation at laparoscopic cholecystectomy to 12 mm Hg on femoral venous blood flow; and (b) to assess the function of intermittent pneumatic compressors (IPC) and intermittent electric calf stimulators (IECS) in the presence of a pneumoperitoneum. Measures of baseline venous blood flow velocity, femoral vein diameter, and maximum blood flow velocity achieved by IPC or IECS were made in the presence or absence of a pneumoperitoneum of 12 mm Hg. The ICP and IECS were randomly allocated to either leg. All measures were made by an experienced sonologist. Insufflation to 12 mm Hg caused a statically significant decrease in femoral blood flow velocity and was accompanied by a significant increase in femoral vein diameter. The IPC and IECS were able to achieve pulsatile venous blood flow despite the presence of a pneumoperitoneum, but they had no effect on the depressed baseline blood flow velocity. We concluded that insufflation to 12 mm Hg causes significant venous stasis in the lower limb and that IPC and IECS cannot completely eliminate this stasis. Further research needs to be done to clarify the optimal methods of prophylaxis in view of the implications for deep venous thrombosis.


Subject(s)
Cholecystectomy, Laparoscopic/adverse effects , Venous Insufficiency/etiology , Adult , Blood Flow Velocity/physiology , Female , Femoral Vein/physiology , Humans , Insufflation/adverse effects , Leg/blood supply , Male , Middle Aged , Pneumoperitoneum, Artificial/adverse effects , Pressure , Thrombophlebitis/etiology
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