Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers.

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 microg of SCT orally, a placebo, and a 10-microg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5-1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 microg exceeding those of 10 microg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.     

严重肢体缺血的干细胞治疗研究进展

大量动物实验和临床试验揭示干细胞移植可望成为一种非常有前途的治疗严重肢体缺血的手段.笔者对干细胞移植治疗严重肢体缺血的适应证、干细胞来源及分离方法、移植途径、安全性及有效性等方面研究进展进行综述.     

Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis)

Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus precluding the use of this route of administration for clinical purposes. Based on these results, in Hispaniolan Amazon parrots, butorphanol tartrate dosed at 5 mg/kg IV or IM would have to be administered every 2 and 3 hours, respectively, to maintain plasma concentrations consistent with published therapeutic levels. To our knowledge, this is the first published study presenting the pharmacokinetic analysis of butorphanol tartrate in a psittacine species as well as the first study presenting pharmacokinetic analysis of butorphanol after oral administration in any avian species.     

An assessment of the value of intraperitoneal meperidine for analgesia postlaparoscopic tubal ligation

Patients undergoing laparoscopic procedures may experience postoperative pain. The intraperitoneal (IP) administration of drugs is controversial but has proven effective in some studies for the relief of postoperative pain. However, some investigators have not been able to confirm the analgesic efficacy of IP local anesthetics. The administration of IP opioids for the relief of postoperative pain has received little attention. At the end of laparoscopic tubal ligation, 100 patients received 80 mL of 0.125% bupivacaine with 1:200,000 epinephrine IP and 50 mg of meperidine either IP or IM. Postoperative pain scores were measured at rest and with movement. Pain scores were significantly lower in the group receiving the IP meperidine both at rest (P: < 0.01) and with movement (P: < 0.05). We conclude that the combination of intraperitoneal bupivacaine and intraperitoneal meperidine was better than the combination of IP bupivacaine and IM meperidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation. IMPLICATIONS: The combination of bupivacaine and meperidine delivered to the intraperitoneal cavity proved superior to equivalent doses of intraperitoneal bupivacaine and IM meperidine for postoperative pain relief in patients undergoing laparoscopic tubal ligation. Intraperitoneal delivery of analgesia proved effective in this study and merits further study and more widespread use.     

A comparison of photosensitizer administration routes for interstitial photodynamic therapy of the liver

Accurate localization of laser light within a tumour lessens the need for selective tumour retention of the photosensitizer. The aim of this study was to investigate different routes of photosensitizer administration for interstitial photodynamic therapy (IPDT) of the liver. Sprague-Dawley rats were photosensitized with HPD 5 mg kg⁻¹ intravascularly at 48 h or by regional administration 60 min prior to light delivery or by interstitial injection (0.04 mg, 0.15 ml) directly into the hepatic parenchyma at 10 and 60 min prior to light delivery. Thirty-two joules of light from a helium-neon (HeNe) laser were delivered interstitially into the median lobe of the liver via a 200-μm optical fibre. Four days after light delivery the liver was harvested, sectioned and stained with haematoxylin and eosin (HE). The maximum cross-sectional area of photodamage was estimated for each photosensitizer administration route in six livers. Both conventional PDT and interstitial routes of administration of the photosensitizer showed comparable areas (±s.e.m.) of bioactivity (8.32±2.03 mm² and 9.5±1.44 mm²) that were greater than those for control livers treated with light only (1.89±0.39 mm²,p<0.01). The maximum area of biological effect was noticed in livers regionally photosensitized by the portal vein or hepatic artery 60 min prior to light delivery (intraportal vein 13.32±1.52 mm² and intrahepatic artery 14.21±4.19 mm²,p<0.01). These results suggest that for IPDT, regional administration of a photosensitizer may achieve the greatest biological effect. This route may be the most appropriate route for interstitial PDT using a selective light delivery system within the liver.     

Analysis of Different Routes of Administration of Heterologous 5-Azacytidine–Treated Mesenchymal Stem Cells in a Porcine Model of Myocardial Infarction

Stem cell therapy constitutes an exciting, powerful therapy to repair the heart. Nevertheless, there are numerous doubts about the best route of stem cell administration to achieve implantation into the injured myocardium. Development of a preclinical, large animal model may be useful to obtain a better approach to clinical situations. The aim of this work was to study the effectiveness of various routes of heterologous bone marrow mesenchymal stem cell (MSCs) administration in a porcine model of myocardial infarction. MSC treated with 5-azacytidine were stained with a fluorescent compound (DiO) before their administration to previously infarcted pigs via 3 routes: intracoronary (IC), intramyocardial (IM), or endocardial (EC; n = 5 each group). Healthy, noninfarcted animals were used as a control group. At 30 days after delivery, hearts were divided into 12 parts: infarcted zone (1–6), right–left atria, interatrial and interventricular septa, and right–left ventricles. In each zone we looked for and quantified, injected fluorescence-stained cells. In the animals in which presence of DiO-stained cells was detected, cells were located preferentially in the infarcted zone and not in the atria, ventricles, or septa. Comparing various administration routes, the mean number of engrafted cells within the infarct zone was significantly greater after IC infusion than either IM or EC injection. Fluorescent cells were not observed in healthy zones of the myocardium or in healthy animals.     

Effect of ipriflavone on bone mineral density and calcium-related factors in elderly females

The effects of ipriflavone (7-isopropoxy-3-phenyl-4H-1-benzopyran-4-one) on bone mineral density (BMD) of the 3rd lumbar vertebra and on calcium (Ca)-related factors, including serum calcitonin (CT) levels before and after rapid calcium infusion (4 mg/kg for 5 minutes), were studied in 11 elderly female subjects (80 ± 2 years of age, mean ± SE). Ipriflavone (IP) administration (600 mg/day, 7 months) resulted in inhibition of BMD loss in 7 patients (responders, mean change of BMD value 2.2 ± 2.3%), whereas 4 patients showed a loss of BMD (nonresponders, mean change of BMD value -13.1 ± 2.6%) compared with pretreatment values. The responder group showed a significant increase in mean pretreatment serum CT levels (from 20 ± 2 pg/ml to 42 ± 7 pg/ml,P < 0.05) after treatment with IP, and a significant decrease in the mean basal serum level of corrected Ca (from 9.6 ± 0.2 mg/dl to 8.7 ± 0.1 mg/dl,P < 0.01) after treatment with IP; nonresponders did not show these changes. For responders, both the percentage of change and the maximal value of serum CT in response to Ca infusion were maintained at rather high levels, both before and after IP treatment; nonresponders showed almost no response to a stimulation test for CT. These findings suggest that IP inhibits bone loss in elderly female subjects possibly through the mechanism of increasing CT secretion.     

Relation of serum elastin peptide concentration to age, FEV1, smoking habits, alcohol consumption, and protease inhibitor phenotype: an epidemiological study in working men.

BACKGROUND: In clinical investigations elastin peptide concentration has been proposed as one potential marker of lung elastin degradation. No epidemiological study has yet confirmed this hypothesis. METHODS: The relation of elastin peptide concentration to some factors closely related to pulmonary emphysema (age, smoking habits, FEV1 alpha protease inhibitor (PI) phenotype) and to alcohol consumption was examined in an epidemiological study of 310 working men. The elastin peptides used for obtaining antibodies and as reference in an ELISA assay were prepared from chemically hydrolysed elastin. RESULTS: The elastin peptide concentration significantly decreased with age from 2.92 (1.54) micrograms/ml among subjects younger than 30 years to 2.18 (1.14) micrograms/ml among subjects older than 50. Elastin peptide concentration did not differ with smoking habits and was clearly unrelated to FEV1. A lower elastin peptide concentration was observed in all groups of subjects with a protease inhibitor phenotype other than PI MM (PI FM, IM, MP, MS, MZ, and S phenotypes). CONCLUSIONS: The results cast doubts on the usefulness of the elastin peptide concentration as a marker of lung destruction in middle aged, predominantly healthy men. Blood elastin peptide concentration may reflect both elastin degradation and resynthesis. The results of this analysis suggest that several factors (age, alcohol consumption, non-PI MM phenotype) may be associated with decreased resynthesis of lung elastin. Further studies, conducted in various age groups and including estimates of the degree of lung destruction, are needed to unravel the mechanisms underlying lysis and resynthesis of lung elastin.     

The effect of rectal and nasal administration of salmon calcitonin in normal subjects

Summary In order to ascertain the blood levels and the biologic responses obtained after administration of two noninjectable forms of salmon calcitonin (SCT) (i.e., a nasal spray and a suppository), two doses of 200 IU each were administered at 3 hour intervals nasally to 8 normal subjects, and rectally to 9 normal subjects. Five untreated subjects served as controls. All were given a standardized diet for 2 days before the test. Plasma salmoncalcitonin, ionized calcium, phosphate, sodium, proteins, creatinine, and alkaline phosphatase were measured repeatedly after the administration of the drug. Modifications in fractionated urinary calcium, phosphate, sodium, and creatinine excretions (and hydroxyproline for the 8 subjects treated by the nasal spray) were compared with the values measured on the previous day. Plasma concentrations of SCT were found to increase sharply with both routes of administration, the peaks being high and short after rectal administration, low but more sustained after nasal application. Despite these differences, almost similar biologic effects could be demonstrated: transient hypocalcemia, increased calciuria, phosphaturia, and natriuria. Urinary hydroxyproline excretion decreased. Plasma sodium did not increase, whereas it did in the controls. In conclusion, nasal sprays and suppositories of SCT appear to exert the known biologic effects of SCT, and might be favored for long-term treatment in diseases representing indications for calcitonin therapy.     

Absorption and elimination of midazolam by submucosal and intramuscular routes

The purpose of this investigation was to compare the rate of absorption and clearance time of midazolam (Versed) when administered by the submucosal (SM) route), and the intramuscular (IM) route in ten healthy adult volunteers, ranging in age from 25 to 35 years. Each subject received midazolam 0.08 mg/kg, to a maximum of 5 mg, by the SM and IM routes at two week intervals. Vital signs and arterial oxygen saturation levels were monitored every five minutes throughout the 180 minute study period. Blood samples (3 ml) were collected via an intravenous line, prior to midazolam administration and at 2, 5, 10, 20, 30, 45, 60, 90, 120, 150 and 180 minutes, centrifuged and analyzed by gas-liquid chromatography. The mean absorption rates and the mean elimination times of the two routes were not significantly different. The mean peak absorption was reached at 10 minutes by the SM route (80.4 ng/ml) and at 20 minutes (92.0 ng/ml) by the IM route, with considerable individual variability. Vital signs were stable throughout the study period in all subjects with both routes. All subjects reported pain at the injection site during SM injection which continued for up to 48 hours. No pain related to the IM injection was reported.     

A phase II trial with new triptorelin sustained release formulations in prostatic carcinoma

Objectives:The objectives were to assess if a single intramuscular (IM) injection of the GnRH agonist triptorelin, as pamoate Sustained Release (RS) 11.25 mg, was able to induce pharmacological castration and to maintain the plasma testosterone levels in the castrate range (< 1.735 nmol/l) up to 3 months in prostatic carcinoma. Methods:Two different formulations of triptorelin pamoate 11.25 mg were assessed in 2 groups of 10 patients suffering from prostatic carcinoma. Each patient received one IM injection of triptorelin pamoate SR 11.25 mg. Triptorelin and testosterone levels were measured over 3 months. Pain, micturition difficulties, performance status, local and general tolerance, and the occurrence of adverse events were evaluated.Results: Both formulations were able to induce castration levels (< 1.735 nmol/l) of testosterone within 3 to 4 weekspost-injection, and to maintain levels below1.735 nmol/l till the end of 3rd month. The bioavailability of one formulation(DLGSD-3-95-21) tended to be greater.This may explain the quickeronset of castration and the slight better maintenance of low testosterone levels during the 3rd month observed with this formulation. In terms of clinical end-points, the local tolerance of both formulations was excellent. No serious adverse events were recorded except transient hot flushes in 2 cases and slight bone pain in one.Conclusion: Triptorelin pamoate 11.25 mg given in microgranules is a 3-month sustained-release administration form which appears to be safe and effective in advanced prostatic carcinoma. Based on the findings of this study, the formulation with greater bioavailability (DLGSD-3-95-21) was selected as formulation of choice to be used for clinical treatments and further clinical investigation.     

Comparative study of analgesia and plasma level following rectal, intramuscular and intravenous administration of ketamine

Ketamine 25 mg/kg was administered to five foxhounds by the intravenous, intramuscular or rectal route. Plasma concentrations were measured by gas-chromatography and analgesia was tested by two techniques. Intravenous application gave reliable analgesia and well reproducible plasma levels in all subjects. Distribution and elimination half lives were found to be 6 min and 55 min, respectively. Intramuscular injection resulted in peak-plasma levels around the twentieth minute, elimination half life was fifty-two minutes, bioavailability 90%. Analgesia proved satisfactory in four out of the five subjects and lasted longer than after intravenous injection. The rectal route produced a wide range of peak-plasma levels, the average peak appearing after 40 min. We found an elimination halflife of 43 min and a bioavailability of 30%. Analgesia was poor in four out of the five subjects. The low plasma levels following rectal application are due to the poor bioavailability and this appears to be the reason for the unsatisfactory results with this route of administration. Bioavailability depends on the site of application (drainage mainly through the vena cava or portal vein) and the pH of the rectum.     

Additive interactions of calcitonin gene-related peptide and calcitonin on pancreatic exocrine function in conscious dogs

By convention, establishing a physiologic role for a gut peptide requires demonstration of biologic activity that can be reproduced by exogenous administration of the peptide in amounts that yield plasma concentrations that are not higher than those found after a meal. We have tested the hypothesis that the combined action of two inhibitory peptides may lower the effective doses of each. We further hypothesize that combined peptide responses may be responsible for the action of peptide hormones that have been difficult to demonstrate as physiologically relevant mediators, when examined as independently acting substances. In conscious dogs prepared with chronic pancreatic cannulas, stimulated pancreatic exocrine secretions were depressed in a dose-related manner by intravenous infusions of calcitonin (CT) and calcitonin gene-related peptide (CGRP). Doses of 2.0 nmol/kg/hr of both CT and CGRP yielded maximal inhibition of stimulated secretions of both bicarbonate (greater than 85% inhibition) and protein (greater than 55% inhibition). The lowest effective dose for either CT or CGRP, given alone, was 0.75 nmol/kg/hr, but when infused simultaneously, each at the subthreshold dose of 0.50 nmol/kg/hr, significant inhibition of protein and bicarbonate secretion was achieved. Combined infusions of the submaximal dose of 0.75 nmol/kg/hr resulted in an enhanced inhibitory response. To prove that this effect is not simply combined activation of a common receptor, we tested peptide YY (0.1 to 0.5 nmol/kg/hr) combined with CGRP and obtained similar results. Because a meal simultaneously releases a large number of active peptides, we speculate that such potentiated responses do occur physiologically. Cooperative interaction with other agents may be the primary mode of action for certain gut peptides.     

Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanisms for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPD) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 +/- 4.3, 8.2 +/- 7.5, and 2.5 +/- 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 +/- 14.6 pg/mL after PO, 56.4 +/- 17.6 pg/mL after IV, and 53.8 +/- 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 +/- 523 pg.mL-1.h-1, than after PO, 1,442 +/- 467 pg.mL-1.h-1, or IP, 1,562 +/- 477 pg.mL-1.h1, dosages, P less than 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prospective Randomized Clinical Trial Comparing Intradermal, Intraparenchymal, and Subareolar Injection Routes for Sentinel Lymph Node Mapping and Biopsy in Breast Cancer

Background Multiple injection routes, including intradermal (ID), intraparenchymal (IP), and subareolar (SA), are used for ^99mTc-sulfur colloid administration for sentinel lymph node (SLN) mapping and biopsy in breast cancer. The aim of this study was to compare localization by ID, IP, and SA injection routes based on preoperative lymphoscintigraphy and intraoperative identification.Methods Four hundred prospectively randomized breast cancers underwent SLN mapping and biopsy.Results Preoperative lymphoscintigraphy demonstrated localization to the axilla in 126/133 (95%) ID, 82/132 (62%) IP, and 96/133 (72%) SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.081 IP vs. SA), with a mean duration of preoperative lymphoscintigraphy of 139 ± 18 minutes. Mean time to first localization when localization was demonstrated on preoperative lymphoscintigraphy was 8 ± 14 minutes for ID, 53 ± 49 for IP, and 22 ± 29 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.003 IP vs. SA). Intraoperative identification of a SLN at the time of SLN biopsy was successful in 133/133 (100%) ID, 121/134 (90%) IP, and 126/133 (95%) SA (P < 0.001 ID vs IP; P = 0.014 ID vs. SA; P = 0.168 IP vs. SA), with a mean time from injection of ^99mTc-sulfur colloid to start of SLN biopsy of 288 ± 71 minutes. Mean intraoperative time to harvest the first SLN was 9 ± 4 minutes for ID, 13 ± 6 for IP, and 12 ± 6 for SA (P < 0.001 ID vs. IP and ID vs. SA; P = 0.410 IP vs. SA).Conclusions The ID injection route demonstrated a significantly greater frequency of localization, decreased time to first localization on preoperative lymphoscintigraphy, and decreased time to harvest the first SLN. This represents the first prospective randomized clinical trial to confirm superiority of the ID route for administration of ^99mTc-sulfur colloid during SLN mapping and biopsy in breast cancer.     

Natriuretic peptides: physiological, pathophysiological and clinical aspects

A milestone was reached in cardiophysiology when in 1981 DeBold demonstrated that the heart functions as an endocrine gland by injecting an extract of atrial muscle into rats, resulting in an induction of natriuresis and a drop in blood pressure. This observation then led to the discovery of a family of related peptides with slightly different amino acid compositions working in concert to achieve the maintenance of sodium and volume homeostasis. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Urodilatin (URO) with their tissue-specific distribution including the heart (ANP, BNP), brain (ANP, BNP, CNP), endothelial cells (CNP), and kidney (URO). These peptides were thought to be primarily involved in cardiovascular and renal functions but have now proven to play a role in other physiological systems. In view of their known biological effects, therapeutic efficacy from administration of ANP, BNP or URO might be anticipated, for example in acute renal failure or congestive heart failure. A number of clinical trials suggest that application of these peptides may represent a new pharmacological tool in the treatment or prevention of these diseases, but the clinical benefit still needs to be shown in large controlled studies. In addition to therapeutic options it is possible that plasma concentrations of ANP and BNP could play a role as diagnostic and prognostic markers of cardiac dysfunction.     

A comparison of regularly administered sustained release oral morphine with intramuscular morphine for control of postoperative pain

We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia. IMPLICATIONS: Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.     

Preoperative Enteral Immunonutrition Improves Postoperative Outcome in Patients with Gastrointestinal Cancer

Objectives The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics (IMPACT) diet versus standard enteral nutrition (EN) on the nutritional status and immunity of patients with colorectal or gastrointestinal (GI) cancer and to evaluate whether it influences the incidence of postoperative complication. Methods Sixty patients with GI cancer were randomly divided into 2 groups, immunonutrition (IM) and control diet (CT), each of which was fed with IMPACT and conventional diet, respectively, for 7 days before surgical procedures. Variables of nutritional status and immunity, postoperative complications, infections, and the days of postoperative hospitalization were measured. Results There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively. The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group. Serum concentrations of both prealbumin (PALB) and transferrin (TRF) were lower in the IM than in the CT group on postoperative day 3 (P < 0.01). TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7. However, PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 (P < 0.05). Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 (P < 0.05). Postoperative immunoglobulin G (IgG) level in the IM group was higher than that in the CT group (13.35 ± 2.06 g/l vs. 9.59 ± 2.23 g/l, P < 0.05). CD4/CD8 ratio was significantly higher in the IM group (2.10 ± 0.51 vs. 1.62 ± 0.52, P < 0.05). Conclusions Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections.     

The efficacy of intratracheal administration of vecuronium in rats, compared with intravenous and intramuscular administration

To investigate the suitability of the intratracheal (IT) route as an alternative route for the administration of vecuronium, we compared the pharmacodynamic parameters for neuromuscular block in three groups of rats given vecuronium via the IT, IM, and IV routes. We also examined the pharmacokinetics of vecuronium in the three groups. The doses for the IT, IV, and IM groups were set at 1.50, 0.300, and 2.25 mg/kg, respectively. The onset of action in the IT group (127 +/- 17 s) was significantly earlier than that in the IM group (267 +/- 62 s), and significantly later than that in the IV group (18 +/- 7 s) (P < 0.05 by analysis of variance and the Tukey-Kramer analysis). The duration of action in the IT group (794 +/- 162 s) was significantly longer than that in the IV group (93 +/- 30 s) but not significantly different from that in the IM group (743 +/- 131 s). The recovery index in the IT group (134 +/- 30 s) was significantly shorter than that in the IM group (222 +/- 47 s) and significantly longer than that in the IV group (32 +/- 12 s). Although IT administration of vecuronium is still slower than IV administration, it appears to be more advantageous as compared with IM administration, given the more rapid absorption and faster onset of action.     

Successful removal of an intrapulmonary aberrant needle under video-assisted thoracoscopic surgery; report of a case

Intrapulmonary aberrant needles are rare in clinical practice. We report the successful removal of intrapulmonary aberrant needle. A 59-year-old man, though he was asymptomatic, was referred to our department after an abnormal shadow had been detected on a chest X-ray. Chest X-ray and chest computed tomography (CT) showed a foreign body suspected to be a metal artifact in the left upper lobe. It was diagnosed as an intrapulmonary aberrant needle and an operation under video-assisted thoracoscopic surgery was performed. Using perioperative fluoroscopy, we could confirm the location of the needle and remove it successfully. An intrapulmonary aberrant needle should be removed surgically, even if the patient is asymptomatic, due to the development of lung abscess or pyothorax and the risk containing harmful matter to health.