Intravenous Drip Infusion Research Articles

Prostate Cancer: Detection of Lymph Node Metastases Outside the Routine Surgical Area with Ferumoxtran-10–enhanced MR Imaging

To prospectively evaluate the feasibility of magnetic resonance (MR) imaging with ferumoxtran-10 in patients with prostate cancer to depict lymph node metastases outside the routine pelvic lymph node dissection (PLND) area. The study was approved by the institutional review boards at all four hospitals; patients provided written informed consent. Two hundred ninety-six consecutive men (mean age, 67 years; range, 47-83 years) with prostate cancer and an intermediate-to-high risk for nodal metastases (prostate-specific antigen level >10 ng/mL, Gleason score >6, or stage T3 disease) were enrolled. MR lymphography of the pelvis was performed 24 hours after intravenous drip infusion of ferumoxtran-10. Positive nodes at MR lymphography were indicated to be inside or outside the routine dissection area (RDA). On the basis of MR lymphography computed tomographic (CT)-guided biopsy, routine PLND, or MR imaging-guided minimal extended PLND was performed. MR lymphography findings were positive in 58 patients. Of these, 44 had histopathologic confirmation of lymph node metastases. In 18 of 44 patients (41%), MR lymphography findings showed nodes exclusively outside the RDA, which were confirmed with MR lymphography-guided extended PLND (n = 13) and CT-guided biopsy (n = 5). In another 18 patients (41%), positive nodes were located both inside and outside the RDA at MR lymphography. In these 18 patients, routine PLND was used to confirm the nodes inside the RDA (n = 11); CT-guided biopsy was used to confirm nodes outside the RDA (n = 7). In the remaining eight patients, MR lymphography findings showed only nodes inside the RDA, which was confirmed with PLND (n = 5) and CT-guided biopsy (n = 3). In 14 of the 58 patients (24%), there was no histologic confirmation. In 41% of patients with prostate cancer, nodal metastases outside the area of routine PLND were detected by using MR imaging with ferumoxtran-10.

Non-preventive use of antibiotics in patients with severe acute pancreatitis treated with integrated traditional Chinese and Western medicine therapy: a randomized controlled trial

To investigate the prognostic effects of integrated traditional Chinese and Western medicine therapy without antibiotics in treatment of patients with severe acute pancreatitis (SAP). SAP patients were randomly divided into treatment group (26 cases included) and control group (28 cases included). In addition to the same protocol of integrated traditional Chinese and Western medicine treatment for both groups, intravenous drip infusion of 0.5 g imipenem-cilastatin was administered to the patients in the control group every eight hours for ten days. The 48-hour Ranson score, 24-hour acute physiology and chronic heath evaluation II score, and incidence rates of complications were observed. The concentrations of serum C-reactive protein (CRP) on days 1, 3, 7 and 10 were measured, and strains of infection were detected with smear and culture examination for bacteria and fungi. There were no statistical differences in demographic information, baseline data and incidence rates of complications between the two groups (P>0.05), but fungal infection rate in the control group was higher than that in the treatment group (P<0.05). There were no statistical differences in infection rates of G- and G+ germs between the two groups; blood and some organs including lung, pancreas, intestine, and urethra were infected with bacteria and fungi. There were also no significant differences in the serum CRP concentrations on days 1, 3, 7 and 10 between the two groups (P>0.05), but the serum CRP concentrations on days 1, 3, 7 and 10 in infected patients were higher than those in non-infected patients (P<0.05, P<0.01). The study cannot confirm that the incidence rates of secondary infection and mortality in SAP patients treated with integrated traditional Chinese and Western medicine are reduced by prophylaxis with imipenem-cilastatin.

Anterior Spinal Artery as a Collateral Channel in Patients With Acute Bilateral Vertebral Artery Occlusions -Two Case Reports-

Retrograde flow through the anterior spinal artery (ASA) from the cervical vertebral artery (VA) to the intracranial distal VA due to disrupted perfusion caused by bilateral VA occlusion is rare. We report two cases of hemodynamic vertebrobasilar circulatory insufficiency caused by bilateral VA occlusion. In these patients, the ASA filled in the retrograde direction, and provided collateral support to the ipsilateral posterior inferior cerebellar artery. The patients were treated with drip intravenous infusion of edaravone and/or argatroban. One patient had a good collateral supply from the posterior communicating artery and recovered almost completely within one month, but the other did not and lapsed into a coma, with generalized hyperreflexia, pin-point pupils, and ataxic respiration. Severe calcified lesions on three-dimensional computed tomography angiography at the occlusion site in the second patient indicated direct surgery including right superficial temporal artery to superior cerebellar artery anastomosis, rather than the endovascular approach. Retrograde flow through the ASA may be observed in this type of critical situation, and may be an important source of collateral supply to the posterior fossa territory.

A study of the mechanism of Qingre Huatan therapy in treatment of acute exacerbation of chronic obstructive pulmonary disease by improving airway inflammation and mucus hypersecretion

To explore the effects of Tanreqing injection, a traditional Chinese herbal preparation for clearing heat and resolving phlegm, in treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) by improving airway inflammation and airway mucus hypersecretion. A randomized controlled trial (RCT) was designed. Ninety AECOPD patients were randomly divided into Tanreqing group, ambroxol hydrochloride group and control group. The patients in the three groups were all treated with conventional therapy. Furthermore, intravenous drip infusion of 20 ml Tanreqing injection (once daily) and 15 mg ambroxol hydrochloride injection (twice daily) were administered respectively to the patients in the Tanreqing group and ambroxol hydrochloride group. They were all treated for 10 days. Symptom score of traditional Chinese medicine (TCM), plasma concentrations of interleukin-8 (IL-8), IL-10 and neutrophil elastase (NE) were detected before and after treatment. Cough, sputum amount, expectoration, dyspnea, fever, coated tongue and pulse tracings were improved obviously in Tanreqing group (P<0.05), and the effects of Tanreqing on improving cough, sputum amount and expectoration were better than the conventional therapy (P<0.05), while there was no significant difference between Tanreqing group and ambroxol hydrochloride group (P>0.05). Compared with ambroxol hydrochloride group and the control group, the coated tongue was improved obviously in Tanreqing group (P>0.05). After treatment, plasma concentrations of IL-8, IL-10 and NE were decreased in Tanreqing group and ambroxol hydrochloride group (P<0.05), and the levels of IL-8 and IL-10 in the control group were decreased (P<0.05). The change of IL-8 level before and after treatment in Tanreqing group was greater than that in ambroxol hydrochloride group and the control group. The changes of IL-10 and NE levels in ambroxol hydrochloride group were greater than those in Tanreqing group and the control group, while there was no significant difference in the changes of serum levels of IL-8, IL-10 and NE among the three groups (P>0.05). Total response rates in Tanreqing group and ambroxol hydrochloride group were higher than that in the control group (P<0.05), while there was no significant difference in total response rate between Tanreqing group and ambroxol hydrochloride group (P>0.05). There was no significant difference in total response rate among the three groups (P>0.05). Tanreqing injection can improve TCM signs and symptoms in AECOPD patients, and the mechanism maybe due to the decrease of serum levels of IL-8 and NE and improvement of IL-10 level.

Effects of gastrodin injection on blood pressure and vasoactive substances in treatment of old patients with refractory hypertension: a randomized controlled trial

To examine and determine the contents of endothelin (ET) and nitric oxide (NO) in plasma, and to observe the effects of gastrodin injection on blood pressure, ET and NO levels in old patients with refractory hypertension. A total of 63 old patients with refractory hypertension, 30 patients with common hypertension and 30 healthy people were included. The contents of ET and NO in plasma of patients in different groups and healthy people were examined and analyzed. The old patients with refractory hypertension were randomly divided into two groups: gastrodin-treated and routine treatment groups. Besides conventional hypotensive drugs, intravenous drip infusion of 1 000 mg gastrodin was administered to the patients in gastrodin-treated group for two courses (4 weeks), while the patients in routine treatment group were treated only with conventional hypotensive drugs. The changes of blood pressure, ET and NO levels before and after treatment in different groups were measured. The plasma level of ET in refractory hypertension group was higher than that in common hypertension group (t=3.27, P=0.008), while the level of NO was lower (t=-3.81, P=0.002). The systolic pressure and pulse pressure difference in gastrodin-treated group were decreased significantly after one course of treatment (t=1.85, P=0.03; t=1.74, P=0.04). The level of ET in gastrodin-treated group decreased gradually after treatment, but there were no significant difference between before treatment and two courses of treatment, while the level of NO in gastrodin-treated group was increased after treatment (t=-2.70; P=0.04). Gastrodin injection is beneficial to old patients with refractory hypertension, and can improve the balance of ET and NO levels in plasma.

A method for quantifying the unstable and highly polar drug nafamostat mesilate in human plasma with optimized solid-phase extraction and ESI-MS detection: more accurate evaluation for pharmacokinetic study

An advanced quantification method was developed with solid-phase extraction (SPE) and mass spectrometry (MS) determination for nafamostat, an unstable and highly polar drug, in human plasma. For unstable drugs with an ester group, the main analytical challenge is how to avoid the ester hydrolysis, and strong acid or alkaline conditions should be excluded during sample preparation. Considering that, we developed a relatively mild method with SPE for sample preparation without strong acid and alkaline treatment, which was optimized with different pHs and salt concentrations in phosphate-buffered saline treatment. The results indicated that pH 5 gave the most efficient extraction and 0.1 M salt concentration enhanced the extraction the most, with a minor effect on MS monitoring. The extraction method effectively avoided drug hydrolysis and achieved good drug enrichment over 82.2%. The linear range of quantification was 1.25-160 ng mL(-1). The stability of the drug in sample treatment was fully validated according to the sample processing procedure, including the stability in fresh blood, mobile phase, plasma and acidic methanol, and the results indicated that the drug remained stable during the whole sample preparation. Compared with a previous isotope-labeling method, more accurate and specific quantification of plasma concentration was achieved with liquid chromatography-electrospray ionization MS determination. With use of our method, nafamostat mesilate pharmacokinetics in 30 Chinese healthy volunteers was investigated with three doses via intravenous-drip infusion. The pharmacokinetic parameters were also estimated and compared with those of Japanese volunteers (slightly lower plasma concentration and longer terminal elimination half-life for Chinese volunteers). The difference in the pharmacokinetics may be ascribed to the quantification method, because previous isotope labeling may have overestimated the parent drug.

Graves' Disease with Intractable Diarrhea, Chylous Ascites, and Chylothorax: A Case Report

A 50-year-old woman was admitted to our hospital because of severe diarrhea, irritableness, and severe pitting edema of the legs. The patient had been well until 5 years before admission, when a tremor and tachycardia developed and a diagnosis of Graves' disease was made. Treatment with methimazole was effective in reducing her tremor and tachycardia; however, she was often nonadherent with her antithyroid medication because of improvement of her symptoms. On admission, a thyroid swelling, exophthalmos, a pleural effusion, and ascites were observed. The results of thyroid function tests (free triiodothyronine: 21.5 pg/mL; free thyroxine: 7.17 ng/dL; thyroid-stimulating hormone (TSH): <0.01 microIU/mL; TSH receptor antibodies: 95.9%) were consistent with Graves' disease. Biochemical analysis of pleural and ascitic fluid was consistent with chylothorax and chylous ascites, respectively. Serum calcium, total protein, and albumin were very low. Her symptoms and signs except severe diarrhea, edema, pleural effusion, and ascites disappeared after receiving intravenous drip infusion of fluid replacement, and methimazole and iodine. Because of malnutrition, she was given a high-calorie intravenous infusion. Three months after admission, her pleural effusion and ascites began to improve, as did her diarrhea and hypoalbuminemia. An appropriate treatment of Graves' disease is crucial to avoid serious sequelae of longstanding, poorly controlled hyperthyroidism.

Curative effect of alpha-lipoic acid on peripheral neuropathy in type 2 diabetes: a clinical study

To evaluate the effect of alpha-lipoic acid (ALA) on diabetic peripheral neuropathy (DPN). 95 type 2 diabetic patients complicated with DPN were randomly divided into 2 groups: treatment group (n = 52), receiving ALA 600 mg/d in normal saline 250 ml given by intravenous drip infusion once a day for 14 days; and control group (n = 43), administered with radix salviae 20 ml by intravenous drip infusion once a day for 14 days. Before and 7 and 14 days after the management fasting glucose (FPG), fasting insulin (FINS), supersensitive C reactive protein (sCRP), and HbA1c were measured, and total symptom score (TSS) and Michigan neuropathy screening instrument (MNSI) were used to evaluate the nervous symptoms. 50 cases of the treatment group and 43 control cases completed the study. Compared with the control group, the TSS of the treatment group reduced significantly after 1 week, but the MNSI score did not change significantly. The TSS 7d after ALA administration of the treatment group was significantly lower than that before the ALA treatment in the same group and that of the control group 7 days after the radix salviae infusion as well (both P < 0.05). The TSS and MNSI score 14 days after the management of the treatment group were significantly lower than those of the control group (both P < 0.01). The symptom scores of numbness, sting sensation, and burning sensation reduced significantly 2-weeks after ALA treatment, but there were no significant differences in these symptoms after the management in the control group. The total gratification rate of the treatment group was 90% (45/50), significantly higher than hat of the control group (13.95%, 6/43, P < 0.01). One patient of the 50 patients receiving ALA treatment felt chest distress 2 days after ALA administration, but the symptom was improved in the same day after the velocity of intravenous drip was slowed down, and no other adverse effects were found in these two groups. ALA effectively improves the sensitive symptoms of DPN patients and is safe for most of the patients.

Effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic model

To investigate the effect of GrlA mutation on the development of quinolone resistance in Staphylococcus aureus in an in vitro pharmacokinetic (PK) model and to examine the relationship between the emergence of resistance and PK/pharmacodynamic parameters. A wild-type and a GrlA mutant of S. aureus were exposed to the Japanese clinical dose of ciprofloxacin in an in vitro PK model, and the development of resistance was measured by population analysis. In addition, several doses of four quinolones (pazufloxacin, ciprofloxacin, levofloxacin and tosufloxacin) were tested against the GrlA mutant. All model simulations were single-dose design and were conducted over 24 h. Four quinolones were tested against the GrlA mutant, and a resistant population emerged after treatment with 250 mg pazufloxacin intravenous drip infusion, 600 mg ciprofloxacin intravenous drip infusion, 200 mg levofloxacin oral dosing and 150 mg tosufloxacin oral dosing. The emergence of a resistant population was not induced by treatment with 500 mg pazufloxacin intravenous drip infusion, 2,400 mg ciprofloxacin intravenous drip infusion, 400 mg levofloxacin oral dosing and 600 mg tosufloxacin oral dosing. Treatment with the clinical dose of ciprofloxacin induced the development of resistance in the GrlA mutant, but not in the wild-type strain. These data suggest that the frequency of acquisition of additional mutations differs between the wild-type and the GrlA mutant of S. aureus. Also, GrlA mutation predisposes S. aureus to develop high-level quinolone resistance.

Isolated Adrenocorticotropic Hormone Deficiency Presenting With Delirium

Back to table of contents Previous article Next article Letters to the EditorFull AccessIsolated Adrenocorticotropic Hormone Deficiency Presenting With DeliriumKIYOTAKA NEMOTO M.D.YOICHI KAWANISHI M.D., Ph.D.HIROAKI SUZUKI M.D., Ph.D.KATSUYOSHI MIZUKAMI M.D., Ph.D.TAKASHI ASADA M.D., Ph.D.,KIYOTAKA NEMOTO M.D.Search for more papers by this authorYOICHI KAWANISHI M.D., Ph.D.Search for more papers by this authorHIROAKI SUZUKI M.D., Ph.D.Search for more papers by this authorKATSUYOSHI MIZUKAMI M.D., Ph.D.Search for more papers by this authorTAKASHI ASADA M.D., Ph.D.Search for more papers by this author,Published Online:1 Sep 2007https://doi.org/10.1176/appi.ajp.2007.07010193AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: Adrenocortical insufficiency causes various physical symptoms, including weakness, fatigue, and loss of appetite due to cortisol deficiency. It is also known to cause psychiatric symptoms such as depression or apathy. However, there are only a few reports of delirium associated with this insufficiency (1) . We present a case of delirium, which was caused by secondary adrenocortical insufficiency because of isolated adrenocorticotropic hormone deficiency. “Mr. A,” a 74-year-old man without a history of neuropsychiatric disease, complained of diarrhea followed by fatigue and a loss of appetite. A general practitioner found hyponatremia, and an intravenous drip infusion of normal saline solution was performed for 1 week. However, the patient’s fatigue and loss of appetite remained. Two weeks later, he went into a delirious state and was admitted to our psychiatric unit.On admission, a physical examination revealed weakness of the patient’s extremities. He did not have a history of receiving glucocorticoids or skin and mucosal pigmentation. Blood examinations showed hyponatremia (121 mEq/l), neutropenia, and eosinophilia (white blood cell: 4600/ml [20.3% neutrophils and 8.3% eosinocytes]). Potassium and plasma glucose were within normal limits. These findings led us to consider the possibility of adrenocortical insufficiency, and we consulted an endocrinologist for further evaluation. Additional tests revealed low levels of cortisol (1 mg/dl) and adrenocorticotropic hormone (5.9 pg/ml). The growth hormone, luteinizing hormone, follicle-stimulating hormone, all of the thyroid hormones, and prolactin levels were within normal limits. A quad pituitary stimulation with the corticotropin releasing hormone, growth hormone releasing hormone, thyrotropin releasing hormone, and gonadotropin releasing hormone caused a normal elevation of growth hormone, thyroid-stimulating hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone levels. However, the adrenocorticotropic hormone level remained low. A magnetic resonance imaging study showed no tumor or atrophy of the pituitary. These results excluded panhypopituitarism and led us to diagnose the patient with secondary adrenocortical insufficiency because of isolated adrenocorticotropic hormone deficiency. A daily dose of hydrocortisone (20 mg by mouth) was administered, which resulted in a dramatic improvement of the patient’s consciousness level and hyponatremia, followed by recovery from the delirium in 3 days.To our knowledge, our case is the second report of delirium associated with adrenocortical insufficiency because of isolated adrenocorticotropic hormone deficiency. Isolated adrenocorticotropic hormone deficiency is a rare cause of secondary adrenocortical insufficiency generally observed in the elderly. Clinical features overlap greatly in isolated adrenocorticotropic hormone deficiency and Addison"s disease. Since symptoms are nonspecific, diagnosis is often delayed, particularly in the identification of isolated adrenocorticotropic hormone deficiency (2) . In our case, noticing neutropenia and eosinophilia, along with hyponatremia, was the key to the right diagnosis (2) . Delirium can be found in adrenocortical insufficiency as well as cortisol excess. Therefore, in patients with delirium, recognizing the potential role of cortisol as a cause is important. If adrenocortical insufficiency lies behind the delirium, cortisol replacement will be the only effective treatment, and dramatic recovery from the delirious state can be expected. Tsukuba, Ibaraki, JapanThe authors report no competing interests.This letter (doi: 10.1176/appi.ajp.2007.07010193) was accepted for publication in April 2007.

Effect of intravenous drip infusion of cyclophosphamide with high-dose Astragalus injection in treating lupus nephritis

To observe the effect of high-dose Astragalus injection and cyclophosphamide (CTX) on infection, urine protein and immune function of the patients with lupus nephritis. Forty-three patients diagnosed as systemic lupus erythematosus (SLE) complicated by kidney damage and qi-deficiency syndrome were randomly divided into trial group (n=23) and control group (n=20). Patients in both groups were treated for 3 months. Intravenous drip infusion of 0.8 g CTX was administered to all patients once a month, while intravenous drip infusion of 20 ml Astragalus injection was only administered to patients in the trial group every day for 12 days in each month. The decrease of active clinical symptom score after the treatment in the trial group was greater than that in the control group (P<0.05). The infection rates of the trial group and the control group were 4.35% and 25% respectively. The decrease of 24-hour urine protein and CD8, and the increase of red blood cell count and serum albumin in the trial group were greater than those in the control group, and there were significant differences between the two groups (P<0.05). White blood cell count in the trial group was decreased less than that in the control group after the treatment (P<0.05). High-dose Astragalus injection used together with CTX is more effective than CTX alone in decreasing infection rate and urine protein and improving immune function for patients with lupus nephritis.

Prediction of pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in humans using animal data

The pharmacokinetics of CS-023 (RO4908463, formerly R-115685), a novel parenteral carbapenem antibiotic, in humans was successfully predicted using the data collected from mice, rats, rabbits, and dogs; while inclusion of the monkey data led to a significant underestimation of the total plasma clearance (CL). Double logarithmic plots of CL and distribution volume at the steady-state (Vss) vs. body weight in four animal species were linear with high correlation coefficients; and the predicted CL and Vss values in humans agreed well with the observed values after administration of CS-023 by an intravenous drip infusion for 30 min. The plasma concentration–time profile in humans, which was predicted using a bi-exponential equation fitted to a complex Dedrick plot of the animal data, approximated the observed profile. An underestimation of CL caused by including the monkey data in a prediction is quite likely due to the net tubular reabsorption in monkeys, but not at least in rabbits, dogs, and humans.

Prediction of pharmacokinetics of CS-023 (RO4908463), a novel parenteral carbapenem antibiotic, in humans using animal data

The pharmacokinetics of CS-023 (RO4908463, formerly R-115685), a novel parenteral carbapenem antibiotic, in humans was successfully predicted using the data collected from mice, rats, rabbits, and dogs; while inclusion of the monkey data led to a significant underestimation of the total plasma clearance (CL). Double logarithmic plots of CL and distribution volume at the steady-state (Vss) vs. body weight in four animal species were linear with high correlation coefficients; and the predicted CL and Vss values in humans agreed well with the observed values after administration of CS-023 by an intravenous drip infusion for 30 min. The plasma concentration-time profile in humans, which was predicted using a bi-exponential equation fitted to a complex Dedrick plot of the animal data, approximated the observed profile. An underestimation of CL caused by including the monkey data in a prediction is quite likely due to the net tubular reabsorption in monkeys, but not at least in rabbits, dogs, and humans.

Analysis of Human Error in Administration of Intravenous Drip Infusion and Injection, and Medicine in a Cardiovascular Center

Analysis of Human Error in Administration of Intravenous Drip Infusion and Injection, and Medicine in a Cardiovascular Center

CHAPTER 14: Indications for whether oral or injection drugs should be used

Indications for whether oral or injection drugs should be used: Oral drugs are easy to use, which is the greatest benefit. However, high concentrations cannot generally be obtained after oral administration, with a great difference in bioavailability after oral and intravenous administration. Also, some patients cannot take drugs orally. Meanwhile, definite concentrations can be achieved at an early stage after administration of injection drugs (generally, via intravenous drip infusion), although the use of injection drugs involves cumbersome procedures. The indications for whether oral or injection drugs should be used are presented below. It goes without saying that, the best option is determined based on patient’s demographic information, and finally left to the judgment of the physician giving treatment. Indications for the use of oral drugs: Mild or moderate pneumonia with meal consumption possible Indications for the use of injection drugs: Severe or extremely severe pneumonia, or moderate pneumonia with meal consumption impossible An intradermal reaction test was a previous requirement before the use of antimicrobial agents for injection; however, this has now been abolished. Instead, physicians are required to interview patients sufficiently regarding their medical history before drug administration and record this information in their medical chart. Therefore, when an antimicrobial agent is administered, comprehensive drug use and allergy histories should be taken. The special committee on intradermal reactions of the Japanese Society of Chemotherapy released “Measures for anaphylactic shock occurring with administration of antimicrobial agents.” The contents consist of 1. Important precautions when antimicrobial agents are administered intravenously, 2. Measures to be taken to prevent the occurrence of anaphylactic shock, 3. Monitoring during administration, 4. Examples of drug required in the event of anaphylactic shock occurring, 5. Symptoms and level of shock, and 6. Specific measures for first-aid treatment. These guidelines provide the details of the above number 3. Monitoring during administration below. Carefully monitor the patient after the start of administration (particularly, immediately after the start of administration). If any of the following symptoms appear, administration should be discontinued immediately, and appropriate action taken. Symptoms associated with suspected immediate allergic reaction

Phase II study of neoadjuvant chemotherapy (NAC) with S-1 and cisplatin (CDDP) for patients (pts) with metastatic or locally unserectable gastric cancer (MGC)

4078 Background: To improve the poor prognosis of pts with MGC, we conducted a phase II study to evaluate the feasibility and efficacy of intensive NAC to enhance surgical respectability and survival. Methods: Eligible criteria included histologically proven metastatic or locally unserectable gastric adenocarcinoma and measurable or evaluable disease, PS 0–2 and sufficient organ functions. The primary endpoint was overall survival and the secondary endpoints were overall resonse rate (ORR) and toxicities. Since Oct. 2000, chemotherapy-naïve 120 pts with MGC have received S-1 (80 mg/m2 orally intake for 21 consecutive days) and CDDP (50 mg/m2 intravenous drip infusion on day 8) as NAC. Treatment was repeated every 5 weeks. The median administered courses were three (range: 1–7), and median follow up periods were 13.8 months. Results: The proportion of the duration as an outpatient- therapy was 86%. 77.5% of pts (93/120) went to surgical resection; 36 had distal gastrectomy and 57 had total gastrectomy. ORR was 62.5% (CR 1, PR 74), and 61.7%, 75.7%, 28.6% and 23.8% for primary lesion, metastatic lymph nodes, liver metastases and peritoneal metastasis, respectively. Toxicity (grade 3/4): neutropenia 7.5%, thrombocytopenia 6.7%, anemia 6.7%, anorexia 5.8%, nausea 2.5%; no treatment related death. Survival: median 23 months; 1 year 79%; 4 year 31% in all pts, and 42 months; 83%; 38% in pts with gastrectomy, respectively. In univariate analyses, overall survival (OS) was predicted by the responder, limited tumor location, H0, P0, but not by age, sex, histological type, gross type, T-factor, N-factor, or performance status. In multivariate analyses, H0, P0 and responder independently predicted OS. In pts with gastrectomy, H0, curative resection, PS0 and responder predicted OS. Conclusions: NAC with S-1 and CDDP was feasible and useful for pts with MGC and resulted in a promising survival rate. No significant financial relationships to disclose.

Phase II clinical trials of combination S-1 plus low-dose twice weekly cisplatin for advanced or recurrent gastric cancer

14013 Background: We reported the efficacy and safety of combined S-1 + low-dose consecutive cisplatin therapy for advanced or recurrent gastric cancer (Clin Cancer Res. 10:1664–9, 2004). However, this procedure was complicated because the daily dosage of CDDP was necessary. We confirmed that 6 mg/m2 dosage of twice weekly Cisplatin were maintained equal protein binding Pt concentration after daily treatment of 3 mg/m2 dosage of Cisplatin. We examined an effect and safety of a Combination S-1 plus low-dose twice weekly Cisplatin treatment. Methods: All the subjects were admitted to the hospital as inpatients for the first 2 weeks of therapy. S-1 was administered orally daily at the daily dose level of 80 mg/m2 (administered in two divided doses). Cisplatin 6 mg/m2 was administered by intravenous drip infusion over 30 minutes on 2days of the week (Day1 and Day4). Each treatment cycle consisted of 4 weeks of drug administration followed by a 2-week drug-free period (6 weeks in total). Results: 32 patients were enroled in this study. The response was rated as complete response in 1 case, partial response in 24 cases and stable disease in 5 cases. The response rate was 78.1% (25/32). The median survival time was 10.3 months. The response rate did not differ between previously untreated patients and patients who had received prior treatment. The major adverse reactions to the therapy were bone marrow suppression and gastrointestinal symptoms. The total incidence of grade 3 or more severe adverse reactions was 15.6% (5/32). Conclusion: Combination S-1 + low-dose twice weekly Cisplatin therapy thus appears to be highly efficacious and safe, offers promise as a useful treatment strategy even at outpatient clinics. [Table: see text] No significant financial relationships to disclose.

Effective Treatment of Manganese-Induced Occupational Parkinsonism With p-Aminosalicylic Acid: A Case of 17-Year Follow-Up Study

Chronic manganese (Mn) intoxication induces syndromes resembling Parkinson disease. The clinical intervention has largely been unsuccessful. We report a 17-year follow-up study of effective treatment of occupational Mn parkinsonism with sodium para-aminosalicylic acid (PAS). The patient, female and aged 50 at the time of treatment, was exposed to airborne Mn for 21 years (1963-1984). The patient had palpitations, hand tremor, lower limb myalgia, hypermyotonia, and a distinct festinating gait. She received 6 g PAS per day through an intravenous drip infusion for 4 days and rested for 3 days as one therapeutic course. Fifteen such courses were carried out between March and June 1987. At the end of PAS treatment, her symptoms were significantly alleviated, and handwriting recovered to normal. Recent follow-up examination at age 67 years (in 2004) showed a general normal presentation in clinical, neurologic, brain magnetic resonance imaging, and handwriting examinations with a minor yet passable gait. This case study suggests that PAS appears to be an effective drug for treatment of severe chronic Mn poisoning with a promising prognosis.

A Prophylactic Infusion of Calcium Solution Reduces the Risk of Symptomatic Hypocalcemia in Patients after Total Thyroidectomy

Several risk factors have been associated with post-operative transient hypocalcemia after thyroid surgery. However, there are no studies evaluating preventive measures to avoid symptomatic postoperative hypocalcemia. Although intravenous infusion of calcium improves hypocalcemic symptoms, it is unknown whether prophylactic infusion prevents symptoms of postoperative hypocalcemia. Five hundred and forty-seven patients underwent total thyroidectomy. Two groups were identified: group A (n = 243) received prophylactic intravenous drip infusion of 78-156 mg of calcium solution at 3-8 hours after operation, and group B (n = 304) received no prophylactic treatment. Prophylactic infusion was used only once if the patients did not have symptoms of hypocalcemia. Serum calcium (Ca) levels, intact parathyroid hormone (i-PTH) levels on the first postoperative day (1st POD), and the prevalence of symptoms of hypocalcemia were prospectively analyzed. The serum Ca levels at the 1st POD in group A patients (7.91 +/- 0.49 mg/dl, mean +/- SD) was significantly higher than group B patients (7.65 +/- 0.54, P < 0.0001), while the serum i-PTH levels were not significantly different between the two groups. The prevalence of numbness and/or tetany before noon on the 1st POD was significantly lower in group A patients. Prophylactic infusion of calcium solution reduced the prevalence of tetany from 8.6% to 2.1%. A prophylactic infusion of calcium solution after total thyroidectomy may be useful in reducing the development of symptomatic hypocalcemia and reduces the patients' risk of having discomfort and anxiety due to hypocalcemia.

Efficacy of Edaravone in Cardioembolic Stroke

We investigated the efficacy of edaravone in patients with cardioembolic stroke. Cardioembolic stroke patients were treated with drip intravenous infusion of edaravone (ED group, n=141) for 7 days, and were retrospectively compared with a historical-controlled cohort of similar patients (control group, n=114). Early improvement (between day 0 and day 10), defined as change in National Institutes of Health Stroke Scale (NIHSS), was seen more frequently in mild patients (NIHSS on admission < or = 7) among the ED group than in the control group (change in NIHSS +2 vs. -2, respectively, p=0.013). Similar efficacy was not seen in the moderate to severe (NIHSS >7) patients. Independent patients (modified Rankin Scale < or = 2) 6 months after the onset were likely to be less frequent in the ED than the control group (28% versus 41%; p=0.066). Other clinical outcomes in the ED group were not significantly different from those in the control group. The results suggest that edaravone may only be effective in mild patients with cardioembolic stroke.