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[A study of the drug distribution on intra-hepatic arterial infusion chemotherapy; how much difference between continuous infusion and rapid infusion?].

The subjects were 41 cases with implantable reservoir systems for unresectable hepatic tumors. We evaluated the difference in drug distribution between intra-hepatic arterial continuous infusion and rapid infusion using hepatic perfusion scintigraphy by 99mTc-macroaggregated albumin via reservoirs. The 41 cases were divided into 2 groups (A and B) according to the imaging of the perfusion scintigraphy. There were 17 cases in group A with equal distribution and 24 cases in group B with a different distribution between the continuous infusion and the rapid infusion. The 24 cases in group B were subdivided into groups according to the distribution of 99mTc-MAA in and around liver. In some cases the distribution pattern after rapid infusion improved more than with continuous infusion. These results suggested that the infusion method must be selected for every case.

Antineoplastic Agents↗

[Ultra-slow infusion dynamic MRI using an infusion pump: a new method for the evaluation of drug distribution in arterial infusion chemotherapy].

Ultra slow infusion dynamic MR imaging using an infusion pump(IP-MRI) was performed in six patients with metastatic liver tumor or unresectable gastric cancer to evaluate ant-cancer drug distribution. We used un implanted port for the infusion of Gd-DTPA by infusion pump. On IP-MRI, the speed of Gd-DTPA infusion was very slow (0.01 ml/sec) , the same as drug infusion at chemotherapy. The contrast enhancement of tumors was extremely clear. Therefore, IP-MRI was considered feasible for the evaluation of drug distribution.

Adult↗

Labor induction in women with an unfavorable Bishop score: randomized controlled trial of intrauterine Foley catheter with concurrent oxytocin infusion versus Foley catheter with extra-amniotic saline infusion with concurrent oxytocin infusion.

OBJECTIVES: This study was undertaken to determine whether the addition of extra-amniotic saline infusion improves the efficacy of the Foley catheter in women undergoing cervical ripening and induction of labor with an unfavorable cervical examination. STUDY DESIGN: One hundred consenting women with a Bishop score less than 5 with singleton gestation, intact membranes, vertex presentation, who required induction of labor were randomly assigned to 2 groups: Foley alone (Foley, n=49) or to the Foley catheter with extra-amniotic saline infusion (EASI, 30 mL of NS per hour infused through the distal port of the Foley, n=51). All women received concurrent dilute oxytocin infusion per protocol. The primary analysis was intent to treat. Nonparametric tests were used as indicated. RESULTS: At randomization, the groups were well balanced for potential confounders including: parity, gestational age, prior cesarean delivery, preeclampsia, mean dilation, effacement, and Bishop score. There were no differences between the groups for time to delivery (Foley 17.7 +/- 10.5 hours vs EASI 17.4 +/- 11.7 hours, P=.9), the proportion of women delivered before 24 hours (Foley 41/49 [84%] vs EASI 39/51 [77%], P=.37) or cesarean rates (Foley 9/49 [17.7%] vs EASI 9/51 [18.4%], P=.92). There were also no differences in complications, including chorioamnionitis, endometritis, and neonatal morbidity. CONCLUSION: EASI does not increase the efficacy of cervical ripening and induction of labor with a Foley catheter and concurrent oxytocin infusion.

Administration, Intravaginal↗

[Continuous infusion of remifentanil and target-controlled infusion of propofol for coronary surgery in elderly patients: comparison with continuous infusion of remifentanil and propofol].

OBJECTIVES: Comparison of the length of mechanical ventilation and postoperative complications after coronary surgery in elderly patients anaesthetised with propofol associated with either alfentanil or remifentanil. STUDY DESIGN: Retrospective study with an historic control group. PATIENTS: Three hundred thirty-eight consecutive patients (75-year-old or more) undergoing isolated coronary surgery. One hundred and fifty seven patients operated between January 1998 and June 2000 received alfentanil (1 microg/kg/minute) with a manually control infusion of propofol, 181 operated between July 2000 and 2002, remifentanil 0.25 microg/kg/minute with target controlled infusion of propofol (target blood concentration: 1.5 to 2 microg/ml). METHODS: The two groups were compared for preoperative and surgical data. The length of mechanical ventilation, stay in ICU and the main postoperative complications were compared between the two groups. RESULTS: Length of mechanical ventilation was significantly reduced in the remifentanil group (6 +/- 9 h vs. 13 +/- 63 h ; p <0.0001), 70% of the patients were extubated before the 6th postoperative hours against 53% in the alfentanil group (p =0.0023). This was not associated with a reduction of stay in ICU or postoperative complications. During surgery, an increased used of vasopressor was observed in the remifentanil group (40.2% vs 2.4% ; p <0.0001) with a postoperative elevation of blood concentration of CKMb (35.7 +/- 38.2 microg/l, vs. 27.7 +/- 31.9 microg/l, p =0.02). CONCLUSION: Elderly patients undergoing coronary surgery were extubated earlier with remifentanil. However, this had no effect on duration of ICU stay but was associated with an increased used of vasopressor.

Aged↗

Short versus long duration infusions of paclitaxel for any adenocarcinoma.

BACKGROUND: Paclitaxel has become a standard drug used in a number of common cancers. At first long infusions were used to reduce the rate of inflow of the drug and as a result reduce the occurrence of hypersensitivity types of allergic reactions. Trials with shorter durations of infusion, and using a cocktail of anti-allergic drugs to prevent hypersensitivity reactions, some randomised, were begun. These were interpreted as showing that effectiveness of treatment was not lessened by a short infusion time. These studies also appeared to show that some important toxicities were less common with short infusions and that they were more convenient for the patient and the hospital. OBJECTIVES: To assess the effect of varying the duration of infusion of paclitaxel on its anti-cancer effectiveness and side-effects. SEARCH STRATEGY: Electronic searches of the Cochrane Gynaecological Cancer CRG, the Cochrane Register of Controlled Trials, MEDLINE, EmBase, CANCERLIT, PDQ, Meta-register (mRCT) and the M.D. Anderson Cancer Centre, GOG were carried out. Information from the manufacturer and authors of reports of studies was also acquired. SELECTION CRITERIA: The review was restricted to randomised controlled trials of single agent paclitaxel or paclitaxel with other drugs, where the only variable was the duration of paclitaxel infusion. The review only included patients with advanced adenocarcinoma. DATA COLLECTION AND ANALYSIS: Data was extracted by two independent reviewers and where there was disagreement this was resolved by discussion. Where possible the data was synthesised in a meta-analysis. MAIN RESULTS: Three hour paclitaxel infusions appear to result in a smaller fall in white blood cell count, less fever, infection and sore mouth than 24 hour infusions. In contrast, 24 hour infusions cause less nerve toxicity. Other side-effects are not dependent on the duration of infusion. Evidence from individual trials suggesting efficacy may be slightly greater with 24 hour infusions is inconclusive. Combination of data from trials of different cancer sites in a meta-analysis must be considered speculative, but the combined data also suggest that 24 hour infusions of paclitaxel may be slightly more effective. REVIEWER'S CONCLUSIONS: This review confirms that, apart from neurological effects, three hour infusion of paclitaxel causes significantly less side effects than 24 hour infusion. Insufficient data exists to state whether varying the duration of infusion has a significant effect on its anti-cancer effectiveness. Further study would be required to establish whether there genuinely is a significant difference in efficacy according to the duration of infusion of paclitaxel.

Adenocarcinoma↗

Amphotericin B infusion-related toxicity: comparison of two- and four-hour infusions.

OBJECTIVE: To investigate the influence of infusion duration on infusion-related adverse effects (IRAEs) associated with prophylactic or treatment regimens of amphotericin B in patients with leukemia/bone marrow transplant (BMT). DESIGN: Randomized, double-blind, 2-arm, complete crossover, prospective clinical trial. SETTING: A university-affiliated tertiary care teaching hospital. PARTICIPANTS: The study population consisted of 25 consecutive patients with leukemia/BMT who received 162 prophylactic regimen infusions and 169 treatment regimen infusions of amphotericin B via a central line. Prior to each infusion all patients received a parenteral IRAE prophylaxis regimen of diphenhydramine 25 mg and hydrocortisone 25 mg. No test doses or incremental amphotericin B doses were administered. Patients were monitored closely for IRAEs, which were documented by using a standardized data collection form. MAIN OUTCOME MEASURES: The incidence and nature of IRAEs during a 6-hour monitoring period following the initiation of each infusion was measured. Patients served as their own controls. IRAEs were compared according to infusion duration and therapeutic indication. RESULTS: Three hundred and thirty-one 2- and 4-hour amphotericin B infusions were administered. We found no difference between 2- and 4-hour infusions in the incidence and severity of IRAEs, including overall events (29% of 166 2-hour infusions vs. 25% of 165 4-hour infusions), chill scores (8% of 166 2-hour infusions vs. 7% of 165 4-hour infusions; highest score 7 vs. 6), nausea and vomiting (7% vs. 12%; highest score 4 in both groups), fever (3% vs. 2%), highest temperature increase (2.4 vs. 1.6 degrees C), systolic hypotension (6% vs. 2%), greatest decrease from baseline (40 vs. 62 mm Hg), diastolic hypotension (5% vs. 3%), and greatest decrease (30 vs. 28 mm Hg) (p > 0.05). Overall, IRAEs were less common in prophylactic treatment regimens (35 events [22%] in 162 infusions) than in treatment regimens (55 events [32%] in 169 infusions) (p < 0.05). CONCLUSIONS: This study demonstrates that patients with leukemia/BMT without myocardial or renal dysfunction who receive hydrocortisone and diphenhydramine as premedications can tolerate 2-hour central line infusions of prophylactic or treatment regimens of amphotericin B as well as 4-hour infusions.

Adult↗

Infusion-related reactions to infliximab in patients with rheumatoid arthritis in a clinical practice setting: relationship to dose, antihistamine pretreatment, and infusion number.

OBJECTIVE: We describe infusion-related reactions to infliximab (during infusion or within 1 hour postinfusion) in patients with active rheumatoid arthritis (RA) treated in a quaternary care center. METHODS: We followed 113 patients for a mean of 60.6 +/- 28.9 weeks, obtaining 10.5 +/- 4.9 infusions per patient. RESULTS: We observed 1183 infusions resulting in 104 infusion reactions (8.8%). All reactions resolved within several hours following cessation of the infusion and none was serious enough to warrant hospitalization. Reactions included allergic reactions (pruritus, urticaria) in 4.2% of infusions, cardiopulmonary (hypotension, hypertension, tachycardia) in 3.0%, and miscellaneous reactions (headache, nausea, vomiting) in 2.0%. Reactions occurred in 8.0% of 3 mg/kg infusions and in 10.3% of 5 mg/kg infusions. Reactions occurred in 13.2% of infusions that involved antihistamine pretreatment compared to only 7.5% of infusions that involved no pretreatment. At both infliximab doses, there was a similar frequency of infusion reactions in patients pretreated due to a previous infusion (12.6%) compared to those pretreated strictly based on infusion number (14.7%). A number of the reactions involving antihistamine pretreatment may be explained by known side effects of diphenhydramine, including headache, dizziness, nausea, and palpitations. CONCLUSION: Infusion-related reactions to infliximab were infrequent, rarely severe, and easily manageable. The frequency of reactions was equivalent in patients treated with 3 mg/kg compared to 5 mg/kg. Reactions were significantly more frequent in infusions where patients were pretreated with the antihistamine diphenhydramine, compared to those not involving pretreatment.

Adolescent↗

Effects of continuous nicotine infusion on nicotine self-administration in rats: relationship between continuously infused and self-administered nicotine doses and serum concentrations.

RATIONALE: The efficacy of nicotine replacement therapy (NRT) for smoking cessation is limited. One reason for this limited efficacy may be that typical serum nicotine concentrations provided by NRT do not match the peak arterial nicotine concentrations achieved from smoking. OBJECTIVE: The purpose of the present study was to determine whether continuous nicotine infusion at a rate producing serum nicotine concentrations that match the estimated peak arterial nicotine concentrations associated with nicotine self-administration (NSA) in rats produces greater suppression of NSA than lower infusion rates. METHODS: The effects of continuous nicotine infusion were studied by intravenously administering nicotine at various rates (1.0, 3.0, and 8.0 mg/kg per day) to rats concurrently self-administering nicotine (0.03 mg/kg per infusion) during 23-h sessions or cocaine (0.17 mg/kg per infusion) during 2-h sessions. RESULTS: Continuous nicotine infusion suppressed NSA in a rate-related fashion. NSA was suppressed by 17, 50, and 73% at infusion rates of 1.0, 3.0 and 8.0 mg/kg per day, respectively. The 8.0-mg/kg per day infusion rate, which provided venous serum nicotine concentrations equaling the peak arterial concentrations associated with NSA, suppressed NSA to a greater extent than lower infusion rates. The 8.0-mg/kg per day nicotine infusion rate had no effect on cocaine-maintained responding, demonstrating that its effects were specific for suppression of NSA. This infusion rate provided a mean percentage replacement of nicotine from NSA of more than 700%. Reacquisition of NSA after suppression by the two highest infusion rates was delayed compared with reacquisition after saline extinction. CONCLUSIONS: Continuous nicotine infusion produced an infusion rate-related suppression of NSA that was greatest when the infusion provided nicotine doses and venous serum concentrations substantially higher than those typically associated with NRT in humans.

Animals↗

Continuous infusion of ceftazidime with an elastomeric infusion device.

The serum disposition, antimicrobial activity, and stability of ceftazidime continuously infused with an elastomeric infusion device (Homepump, Block Medical) were studied. Twelve healthy adult volunteers were given a 500-mg bolus dose of ceftazidime infused i.v. over two minutes, followed by a continuous i.v. infusion of 3 g over 24 hours. Blood samples were drawn five minutes before and at intervals up to 24 hours after the start of the bolus infusion. Samples were collected from the infusers immediately before and at the end of the 24-hour infusion. Infusers were insulated with ice packs. Ceftazidime concentrations were determined by high-performance liquid chromatography. Minimum inhibitory concentrations (MICs), serum inhibitory titers (SITs), and serum bactericidal titers (SBTs) were determined by the microdilution technique. Mean +/- S.D. serum ceftazidime concentrations ranged from 39.50 +/- 6.92 micrograms/ml at peak (30 minutes after the start of the bolus infusion) to 15.30 +/- 2.83 micrograms/mL at trough (24 hours after the start). The ceftazidime MIC for Pseudomonas aeruginosa was 1 microgram/mL; this MIC was exceeded 100% of the time. Serum ceftazidime concentrations achieved a median SIT and SBT of 1:32 and 1:16, respectively, at 30 minutes and 1:8 and 1:8, respectively, at 24 hours. Six infusers met or exceeded the 24-hour infusion time; ceftazidime was stable in these infusers. A 500-mg i.v. bolus of ceftazidime followed by a continuous infusion (3 g over 24 hours) delivered by an elastomeric infusion device produced serum drug concentrations that were constantly above the MIC for P. aeruginosa and maintained serum bactericidal activity against that organism. Adequate stability of ceftazidime was ensured by placing an ice pack next to the infuser.

Adult↗

Using slow-infusion MR arteriography and an implantable port system to assess drug distribution at hepatic arterial infusion chemotherapy.

OBJECTIVE: The purpose of this study was to assess perfusion patterns seen on slow-infusion MR arteriography using the hepatic arterial infusion system compared with those seen on CT arteriography. SUBJECTS AND METHODS: In 37 patients with liver metastases who had implantable port systems for hepatic arterial infusion chemotherapy, slow-infusion MR arteriography using an infusion rate of 10 mL/hr through an implantable port and CT arteriography using an injection rate of 0.7 mL/sec were performed. In 15 of 37 patients, we evaluated enhancement patterns of tumors of the liver and visceral organs using slow-infusion MR arteriography. In all 37 patients, we compared slow-infusion MR arteriography with CT arteriography concerning intra- and extrahepatic perfusion patterns. RESULTS: On slow-infusion MR arteriography performed 10-20 min after initiation of infusion, tumors of the liver revealed significant enhancement with only a slight effect of systemic enhancement. In seven (19%) of 37 patients, intrahepatic distributions on slow-infusion MR arteriography differed from those on CT arteriography. In eight patients, the patterns of extrahepatic perfusion into the duodenum and the pancreas head differed on slow-infusion MR arteriography from those seen on CT arteriography. In addition, strong artifact caused by platinum coils in the gastroduodenal artery interfered with the evaluation of perfusion in the area around the coils on CT arteriography, whereas no imaging artifact was seen on slow-infusion MR arteriography. CONCLUSION: We believe that slow-infusion MR arteriography reflects the actual distribution of infused drugs more accurately than CT arteriography. When clinical complications occur during treatment, slow-infusion MR arteriography should be used to assess perfusion abnormalities.

Adult↗

Elimination rate constant describing clearance of infused fluid from plasma is independent of large infusion volumes of 0.9% saline in sheep.

BACKGROUND: The purpose of this study was to determine the influence of varying large crystalloid infusion volumes, ranging from a volume that has been safely administered to volunteers to a volume that greatly exceeds a practical volume for studies in normovolemic humans, of rapidly infused 0.9% saline on the elimination rate constant in sheep. METHODS: Six sheep underwent three randomly ordered, 20 min, intravenous infusions of 0.9% saline in volumes of 25 ml/kg, 50 ml/kg and 100 ml/kg. Repeated measurements of arterial plasma dilution were analyzed using the volume kinetic approach to determine the apparent volumes of the central (V1) and peripheral (V2) body fluid spaces, the elimination rate constant (kr) describing clearance from the central fluid space and the rate constant (kt) for the diffusion of fluid between the central and the peripheral fluid spaces. The latter constant was split in to two constants, one describing flow out from the central fluid space and one describing flow into the central fluid space. Urinary output was measured in all sheep. RESULTS: kr was comparable at each infused volume (38.3 +/- 4.5, 32.2 +/- 4.2, and 36.7 +/- 7.0 ml/min, respectively, in the 25 ml/kg, 50 ml/kg, and 100 ml/kg protocols). However, for the largest infusion, other kinetic parameters were influenced by the magnitude of the infusion. V2 was significantly increased (P < 0.05) and the area under the dilution-time curve divided by the infused volume was 20% lower for the largest infusion (P < 0.03). Although urinary output increased as the infusion volume increased, only 59% of the administered volume had been excreted at 180 min after the 100 ml/kg infusion as compared with approximately 90% after the other two infusions (P < 0.01). CONCLUSIONS: Elimination from the central fluid space of large, rapidly infused volumes of saline solution is independent of infused volume. Larger volumes are apparently cleared from the central fluid space (V1) by expansion of a peripheral volume (V2) as renal excretion fails to increase in proportion to the volume of infused fluid.

Anesthetics, Inhalation↗

The site of action of epidural fentanyl infusions in the presence of local anesthetics: a minimum local analgesic concentration infusion study in nulliparous labor.

UNLABELLED: We have previously demonstrated that continuous epidural infusions of fentanyl without local anesthetics elicit analgesia by a systemic mechanism. In this study, we examined the hypothesis that, in the presence of epidural bupivacaine, continuous infusions of epidural fentanyl elicit analgesia by a spinal mechanism. Forty-eight nulliparous women in active labor participated in this prospective, randomized, double-blinded study. Women received lumbar epidural analgesia with 20-30 mL bupivacaine 0.125% until pain free. Subjects were then randomized to either IV or epidural (EPI) fentanyl infusion groups. Each infusion delivered fentanyl 30 microg/h. All women received an epidural infusion of bupivacaine at a rate of 20 mL/h, the concentration of which was determined by the response of the previous woman in the same group to the analgesic regimen used. Unlike previous studies that assessed the minimum local analgesic concentration (MLAC) for bolus administration at the initiation of analgesia, this study assessed MLAC(infusion) for the maintenance of analgesia throughout the first stage of labor. MLAC(infusion) was determined using the up-down sequential analysis described by Dixon and Massey. The MLAC(infusion) of epidural bupivacaine was 0.063% (95% confidence interval, 0.058-0.068) and 0.019% (95% confidence interval, 0.000-0.038) in the IV and EPI groups respectively. A continuous infusion of fentanyl was more than three times as potent when administered by the epidural than by the IV route. This marked increase in potency for the epidural route is highly suggestive for a predominantly spinal mechanism of action for infused epidural fentanyl under the conditions of this study. IMPLICATIONS: This study determined the median effective concentration for epidural infusions of bupivacaine during labor analgesia. Coadministered epidural fentanyl infusions were more than three times more potent than IV fentanyl infusions, suggesting a predominantly spinal mechanism of opioid action under these study conditions.

Adolescent↗

Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time.

OBJECT: Although recent studies have shown that convection can be used to distribute macromolecules within the central nervous system (CNS) in a homogeneous, targeted fashion over clinically significant volumes and that the volume of infusion and target location (gray as opposed to white matter) influence distribution, little is known about other factors that may influence optimum use of convection-enhanced distribution. To understand the variables that affect convective delivery more fully, we examined the rate of infusion, delivery cannula size, concentration of infusate, and preinfusion sealing time. METHODS: The authors used convection to deliver 4 microl of 14C-albumin to the striatum of 40 rats. The effect of the rate of infusion (0.1, 0.5, 1, and 5 microl/minute), cannula size (32, 28, and 22 gauge), concentration of infusate (100%, 50%, and 25%), and preinfusion sealing time (0 and 70 minutes) on convective delivery was examined using quantitative autoradiography, National Institutes of Health image analysis software, scintillation analysis, and histological analysis. Higher rates of infusion (1 and 5 microl/minute) caused significantly (p < 0.05) more leakback of infusate (22.7+/-11.7% and 30.3+/-7.8% [mean+/-standard deviation], respectively) compared with lower rates (0.1 microl/minute [4+/-3.6%] and 0.5 microl/minute [5.2+/-3.6%]). Recovery of infusate was significantly (p < 0.05) higher at the infusion rate of 0.1 microl/minute (95.1+/-2.8%) compared with higher rates (85.2+/-4%). The use of large cannulae (28 and 22 gauge) produced significantly (p < 0.05) more leakback (35.7+/-8.1% and 21.1+/-7.5%, respectively) than the smaller cannula (32 gauge [5.2+/-3.6%]). Varying the concentration of the infusate and the preinfusion sealing time did not alter the volume of distribution, regional distribution, or infusate recovery. CONCLUSIONS: Rate of infusion and cannula size can significantly affect convective distribution of molecules, whereas preinfusion sealing time and variations in infusate concentration have no effect in this small animal model. Understanding the parameters that influence convective delivery within the CNS can be used to enhance delivery of potentially therapeutic agents in an experimental setting and to indicate the variables that will need to be considered for optimum use of this approach for drug delivery in the clinical setting.

Animals↗

Thermodilution cardiac output measurement during simultaneous volume infusion through the venous infusion port of the pulmonary artery catheter.

OBJECTIVE: To determine the effect on thermodilution cardiac output (TDCO) measurements of continuous volume infusion through the right atrial venous infusion port of the pulmonary artery catheter. DESIGN: Prospective, blinded, randomly allocated crossover. SETTING: Surgical intensive care unit in a university hospital. PARTICIPANTS: Forty-nine hemodynamically stable patients between the ages of 43 and 84 in the intensive care unit and with a pulmonary artery catheter in place. INTERVENTIONS: Each patient received two room-temperature infusions (250 or 500 mL/hr) of 5% dextrose. Consecutive TDCO measurements were taken during each infusion and during a control period (no infusion). The sequence of infusion rates and control period was randomly determined. At both infusion rates, most patients exhibited a decrease in TDCO measurement of between 0.1 and 3.0 L/min. Although some patients exhibited an increase in measured TDCO, this increase was primarily between 0.1 and 0.5 L/min. MEASUREMENTS AND MAIN RESULTS: The mean TDCO measurements at infusion rates of 0, 250, and 500 mL/hr were 6.77, 6.49, and 6.47 L/min, respectively. Measured TDCO decreased on volume infusion by 0.3 +/- 0.13 L/min (mean +/- SD, p < 0.02). CONCLUSION: Rapid continuous infusion of fluid through the venous infusion port of the pulmonary artery catheter significantly limits the accuracy of simultaneous TDCO measurements. Optimally, TDCO measurements should be avoided during rapid volume infusion.

Adult↗

Continuous-infusion contrast-enhanced US: in vitro studies of infusion techniques with different contrast agents.

PURPOSE: To evaluate the infusion properties of three ultrasonographic (US) contrast agents and to compare different infusion techniques for achieving constant signals during harmonic power Doppler US. MATERIALS AND METHODS: In vitro studies were performed in a flow phantom. SH U 508A, NC100100, or FS069 was continuously infused at clinically usable doses and infusion rates. To assess agent-specific physical properties, these agents were administered by using a vertically fixed infusion pump and varying infusion start times. The contrast agents were administered by also using a horizontally oriented infusion pump that was either fixed or continuously rotated to homogenize the agent in the syringe. RESULTS: With SH U 508A and NC100100, constant signals were achieved, regardless of the infusion modality used. Compared with conventional infusion, the continuous homogenization of SH U 508A, although not necessary for signal constancy, increased the agent's usefulness (P <.05). With FS069, only continuous homogenization yielded constant signals (P <.001). CONCLUSION: Continuous infusion of SH U 508A or NC100100 provided constant harmonic power Doppler US signals, regardless of the infusion modality used. Because of the special physical properties of FS069, only homogenization produced constant harmonic power Doppler US signals during continuous infusion of this agent.

Contrast Media↗

Controlled ruminal infusion of sodium bicarbonate. 1. Influence of postfeeding infusion interval on ruminal milieu.

Four ruminally cannulated, lactating Holstein cows were assigned to a 4 x 4 Latin square to monitor the effects of intraruminal NaHCO3 infusion on changes in the rumen environment. Sodium bicarbonate (110 g), dissolved in 3.8 L of water, was infused twice daily at a constant rate for 2 h starting at 0, 2, or 4 h postfeeding. All cows had access to their diet containing sorghum silage and concentrate in a 35:65 ration (DM basis) for 45 min twice daily. Ruminal fluid was collected at feeding and every 30 min postfeeding for 12 h on the last day of each 7-d period. Dry matter intake was lower for buffer infusion at 2 to 4 h than for water-infused control but was not affected by the other NaHCO3 infusions. Although total milk yield was not affected, milk fat percentage and fat yield tended to be lower for the NaHCO3 treatments. Compared with the water infusion, the NaHCO3 infusion from 2 to 4 h postfeeding most effectively prevented the postfeeding increase in ruminal free proton concentration. Additionally, volume of ruminal liquid was increased for the NaHCO3 infusions from 0 to 2 h and 4 to 6 h; ruminal liquid turnover time was increased for the NaHCO3 infusion at 4 to 6 h, but ruminal kinetics otherwise were not affected by NaHCO3. Although infusion of NaHCO3 from 2 to 4 h prevented severe alterations in ruminal acid-base status, it did not increase total VFA concentration or the acetate:propionate ratio. Although total VFA concentrations were not affected by NaHCO3 infusion, acetate:propionate ratio was higher for the NaHCO3 infusion from 0 to 2 h than for the control. Based upon alterations in ruminal acid-base status, exogenous buffer ideally should be provided to the rumen from 2 to 4 h postfeeding; however, our results indicate that the effectiveness of this regimen might be improved if buffer is combined with a rapidly released or unprotected dietary buffer.

Acid-Base Equilibrium↗

The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.

This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons: i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS. We assessed the nature of the disease by investigating the clinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows: a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes. b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies. c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS. d) CFS was distinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment. e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS. f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS. g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.

Ambulatory Care Facilities↗

Superiority of hepatic arterial infusion in preventing catabolism of 5-FU compared with portal vein infusion revealed by an in vivo 19F NMR study.

PURPOSE: The aim of this study was to identify the route of administration of 5-FU with the greatest pharmacological advantage in a rat model using non-invasive in vivo 19F nuclear magnetic resonance (NMR) spectroscopy. METHODS: 5-FU (50 mg/kg) was administered to anesthetized Wistar rats cannulated into the hepatic artery, portal vein or tail vein and 11 NMR spectra were acquired from the liver region to 60.5 min every 5.5 min. RESULTS: With systemic i.v. (tail vein) infusion, the 19F-NMR signal for 5-FU from the liver region peaked in the first spectrum (0-5.5 min), and then gradually decreased. The signal for the 5-FU catabolite alpha-fluoro-beta-alanine (FBAL) gradually increased to the sixth spectrum (0-33.0 min) and then plateaued. Following portal vein infusion the intensity of the first 5-FU spectrum was twice as high as that following i.v. infusion, but the intensity decreased and the FBAL signal increased gradually in the sixth spectrum as systemic i.v. infusion. In contrast, the intensity of the 5-FU signal following hepatic artery infusion was the same as that following portal vein infusion in the first spectrum, and maintained a strong intensity to the final spectrum (60.5 min). The FBAL signal was detected from the second spectrum following hepatic artery infusion, but its intensity was significantly weaker than that following i.v. or portal vein infusion. CONCLUSIONS: Hepatic arterial infusion resulted in the active form of 5-FU being present for a longer time and its degradation in the liver being suppressed compared with the results following portal vein infusion. This catabolic advantage of hepatic arterial infusion could lead to a more potent anti-tumor activity against liver metastases, but could also lead to significant host toxicity including biliary toxicity. We recommend that the dose/schedule of 5-FU administered via the hepatic artery should be adjusted carefully.

Animals↗