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Biomedical subjects

J Marty

Publications and source records attributed to J Marty.

At least 73 records · Page 4Linked to original sources
PubMed1999

Water soluble 20(S)-glycinate esters of 10,11-methylenedioxycamptothecins are highly active against human breast cancer xenografts.

Water-soluble 20(S)-glycinate esters of two highly potent 10,11-methylenedioxy analogues of camptothecin (CPT) have been synthesized and evaluated for their ability to eradicate human breast cancer tumor xenografts. The glycinate ester moiety increases the water solubility of the 10,11-methylenedioxy analogues 4-16-fold. However, in contrast to CPT-11, a water-soluble CPT analogue that was recently approved for second line treatment of colorectal cancer, the 20(S)-glycinate esters do not require carboxylesterase for conversion to their active forms. The glycinate esters are hydrolyzed to their parent, free 20(S)-hydroxyl active analogues in phosphate buffer (pH 7.5) and in mouse and human plasma. The glycinate esters are also 20-40-fold less potent than CPT-11 in inhibiting human acetylcholinesterase. In vivo, we examined 20(S)-glycinate-10,11-methylenedioxycamptothecin, 20(S)-glycinate-7-chloromethyl-10,11-methylenedioxycamptothecin, and CPT-11. We found that the two 10,11-methylenedioxy analogues had antitumor activity against breast cancer xenografts that was comparable to that of CPT-11. Our results indicate that water-soluble 20(S)-glycinate esters of highly potent CPT analogues provide compounds that maintain biological activity, do not require interactions with carboxylesterases, and do not inhibit human acetylcholinesterase.

Animals↗
PubMed1999

Enhanced antitumor activity of 6-hydroxymethylacylfulvene in combination with irinotecan and 5-fluorouracil in the HT29 human colon tumor xenograft model.

6-Hydroxymethylacylfulvene (MGI-114) is a semisynthetic analogue of the toxin illudin S, a product of the Omphalotus mushroom. MGI-114 induces cytotoxicity in a variety of solid tumors in vivo, including the refractory HT29 human colon cancer xenograft. In this study, the potential application of MGI-114 in the treatment of colon cancer was further explored by evaluating the activity of MGI-114 in combination with irinotecan (CPT-11) and 5-fluorouracil (5FU). Groups of 9 nude mice bearing HT29 xenografts were treated with either single agent MGI-114, CPT-11, or 5FU, or MGI-114 in combination with CPT-11 or 5FU. MGI-114 was administered at doses of 3.5 and 7 mg/kg i.p. daily on days 1 through 5, and CPT-11 and 5FU were administered at doses of 50 and 100 mg/kg i.p. on days 1, 12, and 19. In the single agent studies, MGI-114, CPT-11, and 5FU all resulted in decreased final tumor weights compared with vehicle-treated controls (P<0.05), but only MGI-114 at 7 mg/kg produced partial responses. When MGI-114 at 3.5 mg/kg was combined with CPT-11, significant decrements in final tumor weights occurred compared with monotherapy with the same doses of MGI-114 and CPT-11 (P< or =0.001). Also, administration of the low-dose combination (MGI-114 at 35 mg/kg and CPT-11 at 50 mg/kg) resulted in final tumor weights similar to those achieved after administration of high-dose MGI-114 as a single agent. Moreover, the combination of MGI-114 and CPT-11 produced partial responses in nearly all of the animals, with some animals achieving complete responses. The outcome with the combination of MGI-114 and 5FU was less striking, with fewer partial responses and no complete responses. These results suggest enhanced activity when MGI-114 is combined with CPT-11, and clinical trials to further evaluate this combination regimen are planned.

Animals↗
PubMed1999

Fluid therapy directly interferes with immunoassay for cardiac troponin I.

OBJECTIVE: To investigate interference in cardiac troponin I (cTNI) immunoassay induced by some widely used loading fluids. SETTING: A biochemistry unit of a university hospital. MEASUREMENTS AND RESULTS: Human serum with a cTNI concentration of 0.32 microg/l was diluted at 10, 20, 40, and 80% with saline serum (SS), Plasmion (P) (a modified fluid gelatin), hydroxyethyl starch (HES), and 20% human albumin (Alb). Serum with a cTNI concentration of 1.29 microg/l was diluted at 20, 40, 60, and 80%. Four samples with increasing cTNI concentrations (from 0 to 8.14 microg/l) were diluted at 80% with the four fluids. Differences (delta-C) between expected concentrations resulting from the dilutional effect and those measured with the Access cTNI immunoassay were expressed in microg/l. Statistical analysis was performed using a nonparametric test. No false positivity was observed. At a low cTNI concentration (0.32 microg/l), interference was observed with SS and HES at 40 and 80% dilution and with P and Alb at 80%. When cTNI was 1.29 microg/l, interference was observed with each fluid at a dilution of 20% and increased with the increase in dilution. The highest interference was observed with HES, the lowest with P. When the dilution was at 80% for increasing concentrations of cTNI, the higher the initial cTNI was the higher the interference appeared, mostly with SS and HES. CONCLUSIONS: SS, P, Alb, and HES interfere in this cTNI immunoassay. This interference is higher with SS and HES and is higher when the percentage of hemodilution or real cTNI concentration increases.

Fluid Therapy↗
PubMed1999

Evidence of enhanced in vivo activity using tirapazamine with paclitaxel and paraplatin regimens against the MV-522 human lung cancer xenograft.

PURPOSE: Tirapazamine (3-amino-1,2,4-benzotriazine 1,4-dioxide; SR 4233) is a bioreductive agent that exhibits relatively selective cytotoxicity towards cells under hypoxic conditions and can enhance the antitumor activity of many standard oncolytics. In the present study we examined the interaction between tirapazamine in vivo with paclitaxel and paraplatin in two- and three-way combination studies using the MV-522 human lung carcinoma xenograft model. METHODS: Agents were administered as a single i.p. bolus, with tirapazamine being given 3 h prior to paclitaxel, paraplatin, or their combination. Tumor growth inhibition (TGI), final tumor weights, partial and complete responses, and time to tumor doubling were determined after drug administration. RESULTS: Tirapazamine as a single agent was ineffective against this human lung tumor model. A substantial increase in TGI was seen in animals treated with the triple-agent regimen (tirapazamine-paclitaxel-paraplatin) compared to animals treated with double-agent regimens that did not include tirapazamine. The addition of tirapazamine to paclitaxel-paraplatin therapy resulted in a 50% complete response rate; there were no complete responses seen when only the paclitaxel-paraplatin combination was administered. Time to tumor doubling was also significantly improved with the addition of tirapazamine to the paclitaxel and paraplatin combinations. Tirapazamine did not increase the toxicity of paclitaxel, paraplatin, or their combinations as judged by its minimal impact on body weight and the fact that no toxic deaths were observed with tirapazamine-containing regimens. CONCLUSIONS: These results are important since recent studies have suggested that the combination of paclitaxel and paraplatin may be particularly active in patients with advanced stage non-small-cell lung cancer. Since tirapazamine can significantly improve efficacy, but does not appear to enhance the toxicity of paclitaxel and paraplatin, its evaluation in future clinical trials in combination with paclitaxel-paraplatin-based therapy appears warranted.

Animals↗
PubMed1999

A quality control program for acute pain management in out-of-hospital critical care medicine.

STUDY OBJECTIVE: This study was conducted to evaluate a quality control program for improving pain treatment in the out-of-hospital setting. METHODS: Pain was evaluated for all patients at the beginning (T(0)) and the end (T(end)) of out-of-hospital management. During the first part of the study (part 1, n=108), the administration and choice of analgesics was left to the physician's discretion. Pain protocols were then modified to encourage the use of opioids. The effectiveness of this new pain management was analyzed (part 2, n=105) using pain scales and quality of relief. RESULTS: Seventy percent of patients who expressed meaningful pain did not request analgesia, and 36% did not receive any analgesia in part 1 in contrast to 7% in part 2 of the study. The verbal rating scale and visual analog scale scores were substantially improved at T(end) versus T(0) in both periods, but the improvement was greater in part 2 (mean visual analog scale score at T(end) was 29.3+/-23 mm [+/-SD]) than in part 1 (38.6+/-25 mm). The percentage of patients who expressed satisfactory relief increased in part 2 (67% versus 49% in part 1). The mean dose of intravenous morphine was 7.2+/-6 mg. Adverse effects were rare and minor. CONCLUSION: This program focusing on pain treatment plus implementation of pain protocols (with intravenous morphine) improved pain management in the field.

Adult↗
PubMed1999

Placebo-controlled study of inhaled nitric oxide to treat hypoxaemia during one-lung ventilation.

The aim of this prospective, placebo-controlled study was to assess if unilaterally inhaled nitric oxide 20 ppm could treat hypoxaemia during one-lung ventilation. Sixty patients undergoing pulmonary resection using a lateral thoracotomy were allocated randomly to a control or nitric oxide group (NO group). During one-lung ventilation in the lateral decubitus position, the lungs were ventilated mechanically with 90% oxygen--10% nitrogen. After randomization, if PaO2 decreased to less than 9.3 kPa during one-lung ventilation, nitric oxide 20 ppm or nitrogen was added to the inspired gas. The criterion for treatment efficacy was an increase in PaO2 to greater than 9.3 kPa after gas administration. Eight patients in the control group and eight in group NO experienced hypoxaemia during one-lung ventilation. PaO2 was not significantly different in the two groups at the time of gas administration (control group mean 8.0 (SD 0.6) kPa; NO group 8.5 (0.5) kPa). The efficacy criterion was reached in two of eight patients in the control and NO groups. The results of this study showed that inhaled nitric oxide 20 ppm, administered in the dependent lung, was not superior to nitrogen in the treatment of hypoxaemia during one-lung ventilation. Nitric oxide should not be recommended as an alternative to conventional management of hypoxaemia in this condition.

Adult↗
PubMed1999

Effect of mild hypothermia on the vascular actions of phenylephrine in rat aortic rings.

Intraoperative mild hypothermia is common. We have investigated the effects of mild hypothermia (34 vs 38 degrees C) on phenylephrine--(10(-8) to 10(-5) mol litre-1) induced contractions of rat aortic rings mounted for isometric tension recordings. A marked decrease in Emax (maximal tension) (P < 0.05) and significant increase in EC50 (phenylephrine concentration producing 50% of maximal tension) were observed at the lower temperature in endothelium intact rings, but there was no effect of temperature when the endothelium had been removed. The decreased contraction with hypothermia in the endothelium intact vessels was restored to 84% by administration of the nitric oxide synthase inhibitor L-NNA and a small additional amount of tone was restored in the presence of the cyclooxygenase inhibitor, indomethacin. We conclude that mild hypothermia markedly decreased phenylephrine-induced rat aortic contraction in vitro by endothelium dependent mechanisms, largely related to increased nitric oxide production or action.

Animals↗
PubMed1999

Continuous versus intermittent portal triad clamping for liver resection: a controlled study.

OBJECTIVE: The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping (CPC) or intermittent pedicular clamping (IPC). SUMMARY BACKGROUND DATA: Reduced blood loss during liver resection is achieved by pedicular clamping. There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma. METHODS: Eighty-six patients undergoing liver resections were included in a prospective randomized study comparing the intra- and postoperative course under CPC (n = 42) or IPC (n = 44) with periods of 15 minutes of clamping and 5 minutes of unclamping. The data were further analyzed according to the presence (steatosis >20% and chronic liver disease) or absence of abnormal liver parenchyma. RESULTS: The two groups of patients were similar in terms of age, sex, nature of the liver tumors, results of preoperative assessment, proportion of patients undergoing major or minor hepatectomy, and nature of nontumorous liver parenchyma. Intraoperative blood loss during liver transsection was significantly higher in the IPC group. In the CPC group, postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma. Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma, with two postoperative deaths. All of them were in the CPC group. CONCLUSIONS: This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC, especially in patients with abnormal liver parenchyma.

Alanine Transaminase↗
PubMed1999

[How to handle cardiovascular treatments during general anesthesia?].

The risk of interference with anaesthesia and the risk of decompensation of the disease must be considered for each drug. Beta-blockers reduce the body's capacity to react to hypovolaemia, but they are beneficial by limiting the response to nociceptive stimuli and by reducing the incidence of myocardial ischaemia. Treatment should therefore be continued. Interferences with the dihydropyridine class of calcium channel blockers on peripheral vasomotor activity are moderate and additive. These agents are well tolerated and can be continued until the operation. Verapamil and diltiazem have a chronotropic and negative inotropic effect which is additive with that of anaesthetics. Administration of these drugs before the operation does not raise any major problems, nor does their discontinuation. Angiotensin-converting enzyme (ACE) inhibitors, used in hypertension and heart failure, considerably reduce the tolerance of factors modifying the blood pressure equilibrium, especially hypovolaemia or haemorrhage. In practice, ACE inhibitors carry a risk of intraoperative hypotension, requiring the use of vasopressor amines to maintain blood pressure. Continuation of treatment has only minimal advantages, regardless of the indication and there is no risk of rebound effect after stopping treatment. The treatment washout period depends on the duration of action of the product. However, discontinuation of treatment is never imperative, regardless of the context.

Adrenergic beta-Antagonists↗
PubMed1998

Techniques, hemodynamic monitoring, and indications for vascular clamping during liver resections.

Prevention of intraoperative blood loss during liver resection is an essential prognostic factor for reducing postoperative morbidity and mortality. Several procedures are currently available to ensure vascular occlusion, ranging from selective clamping of a segmental pedicle to total hepatic vascular occlusion. The type of vascular occlusion should be selected according to the indication and, in particular, according to the site of the tumor, presence of associated underlying liver disease, the patient's cardiovascular status, and the experience of the operator. The surgical strategy should be defined with the anesthesiologist and the type of hemodynamic monitoring selected should allow the best choice for management and prevention of complications such as bleeding and air embolism. Transesophageal echocardiography seems to be a new and promising method in this setting.

Echocardiography, Transesophageal↗
PubMed1998

[Areactive unilateral mydriasis after diagnostic celioscopy under general anesthesia].

A unilateral areactive mydriasis occurred in a 49-year-old ASA I woman after a coelioscopic procedure while anaesthesia was maintained for an associated procedure. The various causes of brain stem damage were considered. The inability to perform a complete neurologic assessment resulted in the indication of a cerebral computerised tomography (CT) scan. The diagnosis of Adie's tonic pupil was made a posteriori, taking into consideration: 1) complete recovery without neurologic deficit; 2) unremarkable CT scan; 3) previous transient episodes of unilateral areactive mydriasis.

Anesthesia, General↗
PubMed1998

Continuous epidural infusion of ropivacaine for postoperative analgesia after major abdominal surgery: comparative study with i.v. PCA morphine.

We have compared the quality of three regimens of postoperative analgesia (continuous epidural administration of ropivacaine (Ropi. group), epidural ropivacaine and patient-controlled analgesia (PCA) with i.v. morphine (Ropi. + PCA group) and PCA morphine alone (PCA group)) during the first postoperative 24 h in a multicentre, randomized, prospective study. Postoperative analgesia was studied in 130 patients after major abdominal surgery performed under general anaesthesia. The ropivacaine groups received 20 ml of epidural bolus ropivacaine 2 mg ml-1 via the epidural route at the end of surgery, followed by continuous infusion of 10 ml h-1 for 24 h. The Ropi. + PCA group also had access to i.v. PCA morphine 1 mg, with a 5-min lockout. The PCA group received morphine as the sole postoperative pain treatment. The two ropivacaine groups had lower pain scores (P < 0.01) than the PCA group. Morphine consumption was higher in the PCA group (P < 0.05) than in the two ropivacaine groups. The quality of pain relief was rated as good or excellent in 79-85% of patients in the three groups. The percentage of patients without motor block increased between 4 and 24 h from 61% to 89% in the Ropi. group, and from 51% to 71% in the Ropi. + PCA group.

Abdomen↗
PubMed1998

Vascular properties of isoflurane: comparison between normal and cirrhotic rats.

Isoflurane is known to dilate blood vessels and to modulate nitric oxide production. Because cirrhosis is characterized by over production of endothelial nitric oxide, isoflurane-induced vasodilatation may be altered in this situation. We have compared the vasodilator effects of isoflurane in normal rats and rats with secondary biliary cirrhosis. Aortic rings (intact or endothelium denuded) from normal and cirrhotic rats were suspended in HEPES solution and preconstricted with KCl 40 mmol litre-1. Isoflurane dose-dependently relaxed vessels in both groups. Maximal relaxation was comparable between normal and cirrhotic rats in intact (mean 80 (SEM 4) vs 81 (6)%; ns) and in denuded (100 (4) vs 95 (5)%; ns) vessels. Intact vessels relaxed more than denuded vessels in both groups (100 (4) vs 80 (4)% (P = 0.0008) in normal rats and 95 (5) vs 80 (6)% (P = 0.0008) in cirrhotic rats). We conclude that cirrhosis did not modify isoflurane-induced vasodilatation and that the modulator effect of endothelium was conserved.

Anesthetics, Inhalation↗
PubMed1998

Rapid hematopoietic recovery after multicycle high-dose chemotherapy: enhancement of filgrastim-induced progenitor-cell mobilization by recombinant human stem-cell factor.

PURPOSE: To assess the mobilization potential and safety of recombinant human stem-cell factor (SCF) when coadministered with filgrastim to untreated women with poor-prognosis breast cancer. PATIENTS AND METHODS: Eligible women had breast cancer with 10 or more positive axillary nodes, or estrogen receptor-negative tumor with 4 positive nodes, or stage III disease. Patients were randomized to receive SCF plus filgrastim or filgrastim alone. Filgrastim 12 microg/kg daily was administered for 6 days by continuous subcutaneous infusion. SCF was administered by daily subcutaneous injection at 5, 10, or 15 microg/kg concurrent with filgrastim for 7 days, or 10 microg/kg daily starting 3 days before filgrastim for a total of 10 days (SCF pretreatment). Apheresis was performed on days 5, 6, and 7 of filgrastim administration. Patients then had three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2 every 28 days, each supported by one third of the apheresis product. RESULTS: Sixty-two women were treated. Greater yields occurred in patients who received SCF 10 microg/kg daily plus filgastim than those who received filgrastim alone (P=.013 for CD34+ cells; P=.07 for granulocyte-macrophage colony-forming cells [GM-CFCs]). The difference was more marked with SCF-pretreatment than concurrent SCF. Fewer aphereses were required to reach the predetermined target of peripheral-blood progenitor/stem cells (PBPCs) in women who received SCF. SCF was generally well tolerated. Hematologic recovery was rapid after each of the three cycles of chemotherapy. There was no difference in recovery between the different treatment groups. CONCLUSION: Mobilization of PBPCs by filgrastim is significantly enhanced by coadministration of SCF, and commencing SCF before filgrastim can optimize this effect. SCF has the potential to reduce the number of aphereses required to collect a target number of PBPCs.

Adult↗
PubMed1998

[Cardiovascular effects of anesthesia. Management of cardiovascular therapy during the perioperative period].

General anesthesia changes circulatory haemodynamics in three ways: a decrease in sympathetic tone, a decrease in VO2, and a change in baroreceptor reflex function. These effects may have important consequences in patients with cardiovascular disease whose stability depends on these different factors. In addition, the anaesthesia should be adapted to the intensity of the surgical stimuli which tend to increase sympathetic activity, produce tachycardia and increase the blood pressure which may cause decompensation of some cardiac diseases (coronary artery disease for example). Drugs used in the treatment of cardiac disease may interfere with anaesthesia but they are usually continued in order to operate patients under stable cardiovascular conditions.

Anesthesia, General↗