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Biomedical subjects

G Schwartz

Publications and source records attributed to G Schwartz.

At least 55 records · Page 3Linked to original sources
PubMed1997

Replacement of Fhit in cancer cells suppresses tumorigenicity.

The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5',5"'-P1,P3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase "dead" Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5',5"'-P1, P3-triphosphate hydrolysis is not required for tumor suppression.

Acid Anhydride Hydrolases↗
PubMed1997

The dexamethasone suppression test and treatment outcome in elderly depressed patients participating in a placebo-controlled multicenter trial involving moclobemide and nortriptyline.

The dexamethasone suppression test (DST) was conducted in 95 elderly DSM-III-R depressed patients randomized for treatment with moclobemide (MOC; 400 mg daily), nortriptyline (NT; 75 mg daily), or placebo (PBO) in a 7-week double-blind multicenter study. Patients were assessed weekly using various clinical scales, including the 17-item Hamilton Depression Rating Scale. The DST was administered at baseline and at the end of treatment. At baseline, no relationship was found between DST status and the various clinical scales used. At the end of treatment, suppressors (DST-) had significantly improved clinical ratings compared to nonsuppressors (DST+), and were mostly found among those treated with NT (71%) as compared to MOC (41%) or PBO (33%) (p < .03). On the other hand, baseline DST measures influenced treatment outcome; DST+ patients had a greater number of treatment responders to NT (48%) than MOC (19%) or PBO (20%) (p < .07). For DST- patients, the situation was reversed: NT, 7%; MOC, 31%. Postdexamethasone cortisol levels were lower in MOC responders (p < .07). An interaction was found between DST and drug-specific response. The DST may be a useful adjunct for predicting and evaluating the outcome of antidepressant therapy.

Aged↗
PubMed1997

Effects of chemical stimulation of masseter muscle nociceptors on trigeminal motoneuron and interneuron activities during fictive mastication in the rabbit.

An electrophysiological study was carried out in sixteen decerebrate and paralyzed New Zealand rabbits to determine how a bolus injection of a nociceptor stimulant (hypertonic saline, 5%) into the masseter muscle influences the activity of the trigeminal motor circuitry during fictive jaw movements. Hypodermic needles connected to a syringe held in a computer-controlled infusion pump were inserted into the anterior deep layer of either the right or the left masseter. Twenty-three infusions of 50, 70 or 80 microl saline were made in fourteen animals at constant rates over 1 min. Eight control infusions of normal saline (0.9%) were made in a subpopulation of five animals in an identical manner. Fictive jaw movements were evoked before and after the infusions by repetitive electrical stimulation of the corticobulbar tract. Effects were assessed by extracellular microelectrode recordings made from the digastric motoneuron pool and from putative last-order interneurons in the oral subnucleus of the spinal trigeminal tract and adjacent structures. In comparison with pre-infusion control cycles, nociceptor stimulation caused significant slowing of the rhythm and a reduction of the area of the digastric motoneuron bursts in the majority of the animals (12/14). The decrease in cycle frequency was due almost entirely to a lengthening of the time between the digastric bursts. Changes usually began 1-2 min after the infusion and returned to pre-infusion values within 10-15 min. No significant effects were seen when isotonic saline was applied. Recordings were obtained from nine interneurons, eight of which had low threshold mechanosensitive receptive fields. One neuron was, in addition, excited by pinch. Eight were not active in the absence of motor activity and this did not change when hypertonic saline was applied. However, once fictive movements began, all started to fire rhythmic bursts of spikes. In five cases, there was a significant post-infusion increase in spike frequency, and three showed decreases. Seven showed significant post-infusion changes in mean phase and/or concentration of their firing within the movement cycle. Changes in the preferred phase of interneuronal firing were significantly correlated to changes in the phase of offset of the digastric burst. The present results provide evidence that the stimulation of nociceptors in a muscle slows the frequency of rhythmical movements in the absence of sensory feedback. They confirm that infusions into one muscle affect the output of its antagonist. The results also suggest that neurons in the oral subnucleus of the spinal trigeminal tract and adjacent reticular formation appear to participate in programming these changes in motor output.

Animals↗
PubMed1997

Interleukin-2 fusion protein: an investigational therapy for interleukin-2 receptor expressing malignancies.

DAB389IL-2 is an interleukin-2 receptor (IL-2R) specific fusion protein with a molecular weight of 58 kD containing the enzymatic and translocation domains of diphtheria toxin (DT) and human IL-2. This fusion protein is able to direct the cytocidal action of the DT enzymatic region only to cells which bear the IL-2R. The human IL-2R exists in three forms: low, intermediate and high affinity. The high-affinity form is believed to be the biologically relevant form on mature, activated T-lymphocytes, B-lymphocytes and monocytes. DAB389IL-2 is able to bind selectively to the high-affinity IL-2R in a concentration-dependent manner, and once bound is internalised via receptor-mediated endocytosis. Upon acidification of the formed vesicle, the enzymatic portion of the fusion protein is believed to pass into the cytosol where it ultimately inhibits protein synthesis by inactivation of elongation factor-2, resulting in cell death. The constitutive expression of the IL-2R on certain leukaemic and lymphomatous cells of T and B cell origin has been reported to occur in patients with chronic lymphocytic leukaemia, cutaneous T cell lymphoma (CTCL), Hodgkin's disease and non-Hodgkin's lymphomas (NHLs). A multicentre DAB389IL-2 dose-escalation study of patients with IL-2R expressing lymphomas has been conducted. A 10-fold range of doses were evaluated on a five-daily dose schedule. Patients received up to six courses, with an additional two courses permitted for patients with partial responses that appeared to be still improving after six courses. Most adverse experiences were transient and mild. Preliminary assessment of response indicated five complete responses (CR, duration ongoing at 20, 11, 7, 5 and 4 months) and seven partial responses (PR, duration 3-20 months) in the 35 patients with CTCL. One CR (duration > 20 months) in a patient with NHL (Lennett's lymphoma) and two PR (duration 9 and 2 months) in 17 patients with B-cell NHL have been observed. Based on the mode of action of DAB389IL-2, its safety profile, and the patient responses associated with the phase I/II clinical trials, a phase III programme in CTCL patients has been initiated and plans for additional trials in NHL patients are targeted for 1996.

Antineoplastic Agents↗
PubMed1997

Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer.

PURPOSE: We performed a phase I study to determine the appropriate dose of PN401, a uridine (URD) prodrug, to use as a rescue agent for fluorouracil (FU) and than to determine the maximum-tolerated dose (MTD) of FU when given with PN401. PATIENTS AND METHODS: Patients with advanced cancer received oral PN401 as either a suspension or a tablet in escalating doses. A pharmacokinetic analysis was performed to determine which dose best achieved a target value of sustained levels of URD > or = 50 mumol/L. In the first phase of the study, all patients received a fixed dose of FU 600 mg/m2 as a rapid intravenous bolus followed by 10 doses of PN401 given at 6-hour intervals. PN401 therapy commenced 24 hours after FU. After determination of the appropriate dose of PN401, a second group of patients received escalating doses of FU with a fixed dose of PN401. RESULTS: Thirty-eight patients with advanced cancer received PN401 and FU. Pharmacokinetic analysis indicated that either 6.6 g of PN401 as an oral suspension or 6 g given in tablet form resulted in high bioavailability of URD, with sustained plasma concentrations greater than 50 mumol/L. In the second phase of the study, FU doses were escalated from 600 to 1,000 mg/m2. FU was given as a rapid intravenous bolus weekly for 6 weeks with a 2-week rest. The MTD of FU given in this fashion with PN401 rescue was 1,000 mg/m2, at which level two of six patients had neutropenic fever. FU at doses of 800 mg/m2 for 6 weeks was well tolerated without significant toxicity when given with PN401 rescue. CONCLUSION: Oral PN401 is well tolerated and total doses of 6 g every 6 hours yield sustained levels of URD in the target range of 50 mumol/L. The MTD of FU with PN401 rescue is 1,000 mg/m2 and the recommended dose for phase II trials is 800 mg/m2 given weekly for 6 weeks with dose escalation. Further studies to define better the appropriate interval for PN401 rescue and the appropriate dose of FU when given with biochemical modulation, such as with leucovorin, are indicated.

Acetates↗
PubMed1997

The genetic and bacteriological aspects of Peyronie's disease.

PURPOSE: Peyronie's disease has been associated with HLA tissue types, including HLA-A1, DR3, DQw2 and HLA-B7 cross-reactive group antigens which include HLA-B27. This association was tested as was the process of molecular mimicry where the host HLA surface antigen cross-reacts with a microorganism. MATERIALS AND METHODS: HLA tissue typing was performed on 51 white patients with Peyronie's disease, of whom 15 also had Dupuytren's contracture of the hand. Fecal, urine and urethral samples were taken from patients with Peyronie's disease who had proved penile inflammation on biopsy. The samples were cultured for species of Campylobacter, Shigella, Salmonella, Yersinia, Chlamydia and gonococcus, all known to cross-react with the HLA-B27 surface antigen. Antibodies to Klebsiella species, Proteus species and Escherichia coli were also assessed in the sera of 65 patients with Peyronie's disease. RESULTS: A significant association between Peyronie's disease and HLA-B27 was found (p = 0.02). The remaining antigens of the HLA-B7 group were not significantly associated with the disease individually (HLA-B7 p > 0.2, HLA-B22 p > 0.6, HLA-B40 p > 0.7) or as a group (p = 0.69). The previously found associations did not reach significance in this study (HLA-A1 p > 0.5, HLA-B8 p > 0.2, HLA-Cw7 p = 0.1, HLA-DR3 p > 0.4, HLA-DQ2 p > 0.4). Cultures for all enteric and urethral organisms were negative, and patients with Peyronie's disease did not have elevated serum titers of anti Klebsiella, anti Proteus or anti E. coli antibodies. CONCLUSIONS: Although there is an association between Peyronie's disease and HLA-B27, molecular mimicry does not occur with the organisms tested, and an infectious agent has not been found in this study.

Bacterial Infections↗
PubMed1997

High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes.

PURPOSE: To identify clinical factors predictive of treatment outcome after high-dose chemotherapy (HDC) for Hodgkin's disease and to develop a prognostic model for progression-free and overall survival. PATIENTS AND METHODS: 102 patients with relapsed or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, carmustine, and etoposide and autologous marrow and/or peripheral blood progenitor cell support. Median follow-up of survivors is 4.1 years (1.8-7.5 years). Factors potentially important for treatment outcome were examined in univariate analysis, and Cox regression with forward selection was performed. A prognostic model was developed. RESULTS: Poorer progression-free and overall survival were associated with nodular sclerosis histology, abnormal performance status, progressive disease at HDC, more than one extranodal site of disease, and shorter time from initial diagnosis to HDC. These factors and the presence of B symptoms at relapse also predicted for decreased overall survival. Progressive disease immediately prior to HDC, more than one extranodal disease site, and abnormal performance status retained significance for both progression-free and overall survival in multivariate analysis. Progression-free and overall survival are 42% (95% confidence interval, CI, 34 to 53) and 65% (95% CI 54 to 73) at three years. A model based on number of risk factors present divides patients into low, intermediate, and high risk groups with three-year actuarial survival of 82%, 56%, and 19% respectively. Treatment outcome for patients treated with HDC at first chemotherapy relapse was not significantly different from that of the group overall (p > 0.3). CONCLUSIONS: Asymptomatic patients with Hodgkin's disease involving at most one extranodal site whose disease is controlled by conventional dose chemotherapy or radiation therapy at the time of HDC have good outcomes after this therapy. Presence of increasing numbers of risk factors are associated with poorer outcomes. Results of HDC compare favorably to those of standard dose salvage therapy. These data can be used to estimate likely outcomes in patients undergoing HDC for Hodgkin's disease, to identify potential candidates for innovative therapies, and to evaluate strategies for the optimal use of HDC in Hodgkin's disease.

Adult↗
PubMed1996

Comparison of fluvoxamine, imipramine, and placebo in the treatment of outpatients with panic disorder.

Fluvoxamine and imipramine were compared to placebo in an 8-week doubleblind randomized multicentre trial comprising of 148 outpatients between 19 and 57 years of age (mean: 35) with a DSM-III-R diagnosis of Panic Disorder. mean daily dose at endpoint was: fluvoxamine, 171.4 mg; imipramine 164.7 mg. The mean number of panic attacks per week at baseline were 10.9, 14.4 and 6.5 for fluvoxamine, imipramine and placebo, respectively. The intent-to-treat analysis of the change from baseline (difference score) of the number of panic attacks at endpoint revealed: a difference of 3.3 attacks (95% CI: -0.3, 6.8) between fluvoxamine and placebo and a difference of 6.0 attacks (95% CI: 1.5, 10.5) between imipramine and placebo. Treatment was stopped prematurely in 31 (62%) on fluvoxamine, 16 (33%) on imipramine and 29 (58%) on placebo. The number of patients withdrawing due to intolerance was 13 (26%) for fluvoxamine, 10 (21%) for imipramine and 4 (8%) for placebo. The number of patients withdrawing due to lack of efficacy was 10 (20%) for fluvoxamine, 4 (8%) for imipramine and 12 (24%) for placebo. Overall, this study demonstrated that fluvoxamine was not effective in the treatment of panic disorder but did show a strong effect for imipramine. A chance occurrence of significantly fewer number of panic attacks in the placebo group at baseline may limit the conclusions of this study.

Adult↗
PubMed1996

Picomole scale stereochemical analysis of sphingosines and dihydrosphingosines.

We have developed a simple picomole (low nanogram) scale HPLC scheme which can separate all eight isomers of sphingosine and dihydrosphingosine thus leading to the identification of their relative and absolute configurations. The amino group of the sample is derivatized to its fluorescent N-naphthimide which is analyzed by normal and chiral phase HPLC, coupled with fluorescence peak detection. If necessary, the results of this HPLC method can be further corroborated by measurements of circular dichroic (CD) spectra of the N-naphthimido-derivatives and/or N,O-chromophoric derivatives.

Chromatography, High Pressure Liquid↗
PubMed1996

Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.

PURPOSE: Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS: Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION: Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.

Adolescent↗
PubMed1996

Neoadjuvant therapy of high-risk gastric cancer: a phase II trial of preoperative FAMTX and postoperative intraperitoneal fluorouracil-cisplatin plus intravenous fluorouracil.

PURPOSE AND METHODS: We identified patients with gastric cancer at high risk for recurrence before therapy using endoscopic ultrasonography (EUS). Neoadjuvant therapy using the fluorouracil, doxorubicin, and metrotrexate (FAMTX) regimen was given for three courses before planned laparotomy with the intention to perform curative resection. Postoperatively, intraperitoneal (IP) cisplatin and fluorouracil (FU) and intravenous (i.v.) FU were administered to patients undergoing resection. RESULTS: Fifty-six assessable patients were treated. Preoperative FAMTX therapy was tolerable, with the major toxicity being neutropenic fever. One treatment-related death was seen. Eighty-nine percent of patients underwent surgical exploration and 61% had potentially curative resections. There were two postoperative deaths. Comparison of pathologic tumor (pT) stage with EUS-predicted tumor stage showed apparent downstaging in 51% of patients. Postoperative IP chemotherapy was delivered to 75% of eligible patients. Toxicity was acceptable. There was no increase in operative morbidity or mortality compared with concurrent nonstudy patients undergoing a similar operative procedure and not receiving preoperative therapy. With a median follow-up time of 29 months, the median survival duration was 15.3 months. For patients who underwent potentially curative resections, the median survival duration was 31 months. Peritoneal failure was seen in 16% of patients. CONCLUSION: Chemotherapy with the FAMTX regimen is tolerable in patients with locally advanced gastric cancer, without an increase in operative morbidity or mortality. IP therapy can be successfully delivered to most resected patients. The intraabdominal failure pattern appears to be decreased compared with expected. This approach is an appropriate investigational arm to pursue in future studies.

Adenocarcinoma↗
PubMed1996

A multicenter double-blind study of controlled-release physostigmine for the treatment of symptoms secondary to Alzheimer's disease. Physostigmine Study Group.

OBJECTIVE: A multicenter trial to evaluate the efficacy of controlled-release physostigmine salicylate, a cholinesterase inhibitor, was conducted in 1,111 mild-to-moderate Alzheimer's disease (AD) subjects. DESIGN: During dose titration, subjects received 18, 24, or 30 mg of physostigmine or placebo daily. After a 2-week washout period, 366 subjects with putative improvement were randomized to receive either placebo or their best dose of physostigmine in a 6-week double-blind trial. Nonresponding patients (439) were randomized to receive in a separate double-blind trial either placebo or their highest tolerated dose of physostigmine. The primary efficacy measures included the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS) and a Clinical Global Impression of Change (CGIC). Secondary measures included the Mini-Mental State Examination and two activities-of-daily-living scales. RESULTS: At the end of the 6-week double-blind phase, physostigmine-treated patients scored 1.75 points higher than placebo-treated patients on the ADAS (p = 0.003) and 0.26 points higher on the CGIC (p = 0.012) in the intent-to-treat analysis. There was no significant improvement on the secondary outcome measures. Patients failing to respond to physostigmine during the dose titration phase failed to respond on any of the outcome measures during the double-blind period of re-exposure. Common adverse events included nausea, vomiting, diarrhea, and anorexia. There were no significant changes in liver function tests. CONCLUSION: This study demonstrated statistically significant differences between physostigmine and placebo on both a performance-based cognitive functioning instrument and a clinician's global evaluation. The magnitude of the effect size was small and occurred only in the subset of patients who responded in the initial dose titration study period. Nevertheless, the results suggest that in a subset of patients, physostigmine can induce a degree of cognitive improvement over 6 weeks of treatment.

Aged↗
PubMed1996

The effect of Yohimbine, an alpha2 adrenergic receptor antagonist, on the growth hormone response to apomorphine in normal subjects.

Yohimbine HCl (16 mg po) administered 30 min before clonidine (CLON) (2 ug/kg infused over 10 min) (N = 5) or apomorphine HCl (Apo) (0.5 mg sc) (N = 10) antagonized the growth hormone (GH) response to CLON but had no effect on the GH response to Apo in normal men. This finding suggests that in humans, alpha2 adrenergic mechanisms do not modulate dopaminergic function, at least not in the hypothalamic-pituitary axis, and that the GH response to Apo is not mediated via an alpha2 adrenergic link.

Adrenergic alpha-Antagonists↗
PubMed1996

Effects of salmon calcitonin on patients with atypical (idiopathic) facial pain: a randomized controlled trial.

The analgesic properties of salmon calcitonin for the treatment of atypical facial pain (AFP) were investigated. An initial open-label trial of salmon calcitonin in subjects with refractory AFP was followed with a randomized, double-blind, placebo-controlled crossover trial of salmon calcitonin in the management of AFP. Salmon calcitonin (100 IU in 1 mL saline) was administered in an open-label fashion to 13 subjects with refractory AFP five times per week for 6 weeks. In the subsequent randomized investigation, salmon calcitonin (100 IU in 1 mL saline) or placebo (1 mL saline) was delivered three times per week for 3 weeks, with a 1-week washout prior to crossover. The percentage of subjects dropping out (57%) exceeded that reported in other pain studies using calcitonin. Therefore, it was imperative to halt the study for ethical reasons. There was no difference in outcome measures (P > .05) in subjects administered either active drug or placebo, and a high incidence of side effects led to dropout in subjects taking salmon calcitonin. Although salmon calcitonin may have analgesic properties, it is not efficacious for AFP, largely because of the side effects.

Adult↗
PubMed1995

Both basic fibroblast growth factor and ciliary neurotrophic factor promote the retention of polyneuronal innervation of developing skeletal muscle fibers.

At birth, nearly all rat muscle fibers receive synaptic inputs from more than one motoneuron at a single end-plate site. By the end of the third postnatal week all but one of these inputs has been eliminated. During this loss of polyneuronal innervation, developing neuromuscular synapses compete with one another. Although the nature of this competition is not known, it is commonly assumed that it is mediated through differential activity of the competing inputs. One means by which such differential activity might be translated into a biological signal would be if the synapses compete in an activity-dependent manner for a scarce supply of neurotrophic molecules. A prediction of this hypothesis is that excess quantities of such trophic molecules will reduce competition and thereby slow down or abolish the normal loss of polyneuronal innervation. In newborn rats, the effects of injection of either basic fibroblast growth factor (bFGF) or ciliary neurotrophic factor (CNTF) on the outcome of neuromuscular synapse elimination were investigated. Daily injections of either bFGF or CNTF were made for 1 week into the lateral gastrocnemius muscle beginning at the postnatal age of 2 days. The amount of polyneuronal innervation of fibers in trophic molecule-injected muscles and saline-injected contralateral muscles was assayed using intracellular recording methods. For both bFGF- and CNTF-injected muscles, an increase in the percentage of polyneuronally innervated fibers relative to saline-injected muscles was noted. For bFGF-injected muscles, the amount of polyneuronal innervation remained at nearly 60% as late as the postnatal age of 14 days (P14). This is the amount of polyneuronal innervation found at age 6 days in normal animals. Nearly 40% of the fibers of CNTF-injected muscles remained polyneuronally innervated at age P14, the amount expected at age 9 days. These results indicate that both bFGF and CNTF exert powerful and long-lasting effects on developing neuromuscular synapses.

Animals↗
PubMed1995

High-dose ifosfamide, carboplatin, and etoposide pharmacokinetics: correlation of plasma drug levels with renal toxicity.

An autologous bone marrow transplant regimen of ifosfamide, carboplatin, and etoposide (ICE) has been developed as treatment for certain malignancies. At maximum tolerated doses renal insufficiency precludes dose escalation. The objective was to examine whether measurement of plasma drug levels early during treatment would provide warning of renal failure. Nine patients received a 96-h continuous infusion of ifosfamide 16,000 mg/m2, carboplatin 1600 mg/m2, and etoposide 1200 mg/m2. Pharmacokinetics, including drug levels and plasma concentration-time curves, of ifosfamide, ultrafiltrable platinum (uPt) and etoposide were analyzed and correlated with renal function. One of the nine patients developed anuric renal failure requiring hemodialysis. By 17 h from the start of infusion, this patient showed substantially higher drug levels of ifosfamide (200 vs mean 217 microM) and uPt (19 vs mean 10 microM) than those patients with preserved renal function. The 95% confidence intervals suggested that a 16-22 h ifosfamide level > 153 microM and an uPt level > microM predict the development of significant renal dysfunction. Although drug levels were substantially higher at 56 h, the serum creatinine did not yet reflect kidney injury. This study suggests that high plasma ifosfamide and uPt levels, analyzed early in the course of a 96-h infusion of high-dose ICE, provide warning of severe and potentially fatal renal injury. Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokinetic-guided dosing may reduce treatment-related toxicity.

Acute Kidney Injury↗