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PubMed2002

Effects of gabexate mesilate, a protease inhibitor, on human sphincter of Oddi motility.

Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results.

Acute Disease↗
PubMed2003

Fetal plasma concentrations after intraamniotic sufentanil in chronically instrumented pregnant sheep.

BACKGROUND: Rapid progress is being made in fetal surgery. Because the fetus is capable of pain perception after the 26th week of gestation, adequate postoperative fetal pain management is essential. The preferred approach would provide fetal analgesia without affecting the mother. Intraamniotically administered sufentanil may be an interesting option if it achieves therapeutic plasma concentrations (PCs) in the fetus but not the mother. METHODS: After approval of the study, 25 or 50 microg sufentanil was administered intraamniotically in 10 chronically instrumented pregnant ewes. Maternal and fetal vital signs, arterial blood gases, and uterine blood flow were recorded over 120 min. Sufentanil PCs were determined before and 1, 3, 5, 10, 15, 30, 45, 60, 90, and 120 min after injection. Statistical analysis was performed using one- or two-way analysis of variance followed by Dunnett or Tukey test, as appropriate (P < 0.05; data presented as median [95% confidence interval]). RESULTS: After 25 microg sufentanil, fetal PC stabilized at 134 +/- 89 pg/ml (after 10 min), and maternal PCs stabilized at 44 +/- 11 pg/ml (after 15 min). After 50 microg sufentanil, fetal PCs stabilized at 134 +/- 35 pg/ml (after 15 min), and maternal PCs reached 80 +/- 25 pg/ml (at 30 min). Injection of 25 microg sufentanil intraamniotically did not affect maternal or fetal hemodynamics, uterine blood flow, or arterial blood gases. Fetal heart rate increased after administration of 50 microg sufentanil (maximum change at 10 min: +16 +/- 12%). CONCLUSION: The sheep fetus absorbs sufentanil after intraamniotic instillation. Significantly greater PCs were obtained in the fetal lamb as compared with the ewe. This suggests that investigation of intraamniotic opioids for fetal analgesia might be worthwhile.

Amnion↗
PubMed1995

Production of Brucella allergens and evaluation of their biological activity in a guinea-pig bio-assay.

A study was conducted to evaluate the biological activity of Brucella allergens extracted with hydrochloride or trichloroacetic acid. Smooth and mucoid Brucella abortus cells and the medium in which brucellae were propagated were used to prepare the allergens. The biological activity of the allergens was estimated in guinea-pigs sensitized with Brucella abortus strain 544. The guinea-pigs were intradermally injected with several allergen dilutions. The dilutions were coded and randomized for site of injection so that none of the dilution was injected twice on the same site. Variance analysis using incomplete Latin square was used for the statistical calculation of the results. The calculated biological activity of the allergens was compared with the biological activity of a 'standard' allergen that has proved effective in detecting cattle brucellosis. The skin erythema diameter was best when recorded 32 h after allergen injection. Statistical analysis of the skin erythema diameters showed a great variation in biological activity (12-105%) between the allergens. Only the allergen extracted from the medium in which a mucoid Brucella strain was propagated was as potent as the standard. The use of the incomplete Latin square for variance analysis resulted in the estimation of the biological activity of nine batches of allergen in only 27 guinea-pigs.

Allergens↗
PubMedDate not supplied

Hemodynamic effects of epidural ketamine in isoflurane-anesthetized dogs.

OBJECTIVE: The purpose of this study was to determine the hemodynamic effects of epidural ketamine administered during isoflurane anesthesia in dogs. STUDY DESIGN: Prospective, single-dose trial. ANIMALS: Six healthy dogs (five males, one female) weighing 25.3 +/- 3.88 kg. METHODS: Once anesthesia was induced, dogs were maintained at 1.5 times the predetermined, individual minimum alveolar concentration (MAC) of isoflurane. Dogs were instrumented and allowed to stabilize for 30 minutes before baseline measurements were recorded. Injection of 2 mg/kg of ketamine in 1 mL saline/4.5 kg body weight was then performed at the lumbosacral epidural space. Hemodynamic data were recorded at 5, 10, 15, 20, 30, 45, 60, and 75 minutes after epidural ketamine injection. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. All data were compared with baseline values. A P < .05 was considered significant. RESULTS: Baseline values +/- standard error of the mean (X +/- SEM) for heart rate, mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke index, systemic vascular resistance, pulmonary vascular resistance, and rate-pressure product were 108 +/- 6 beats/min, 85 +/- 10 mm Hg, 10 +/- 2 mm Hg, 3 +/- 1 mm Hg, 5 +/- 2 mm Hg, 2.3 +/- 0.3 L/min/m2, 21.4 +/- 1.9 mL/beat/m2, 3386 +/- 350 dynes/sec/cm5, 240 +/- 37 dynes/sec/cm5, and 12376 +/- 1988 beats/min x mm Hg. No significant differences were detected from baseline values at any time after ketamine injection. CONCLUSIONS: The epidural injection of 2 mg/kg of ketamine is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE: These results suggest that if epidural ketamine is used for analgesia in dogs, it will induce minimal changes in cardiovascular function.

Anesthesia, Epidural↗
PubMed1993

Gene injection into canine myocardium as a useful model for studying gene expression in the heart of large mammals.

We have investigated the regulated expression of genes injected into the heart of large mammals in situ. Reporter constructs using the chloramphenicol acetyltransferase gene under the control of muscle-specific beta-myosin heavy chain (beta-MHC) or promiscuous (mouse sarcoma virus) promoters were injected into the canine myocardium. There was a linear dose-response relation between the level of gene expression and the quantity of plasmid DNA injected between 10 and 200 micrograms per injection site. The level of reporter gene expression did not correlate with the amount of injury imposed on the cardiac tissue. There was no regional variation in expression of injected reporter genes throughout the left ventricular wall. By use of both the mouse sarcoma virus and a muscle-specific beta-MHC promoter, reporter gene expression was one to two orders of magnitude greater in the heart than in skeletal muscle. Expression in the left ventricle was threefold higher than in the right ventricle. Chloramphenicol acetyltransferase activity was detected at 3, 7, 14, and 21 days after injection, with maximal expression at 7 days after injection. Statistical analysis of coinjection experiments revealed that coinjection of a second gene construct (Rous sarcoma virus-luciferase) is useful in the control of transfection efficiency in vivo. Furthermore, using reporter constructs containing serial deletions of the 5' flanking region of the beta-MHC gene, we performed a series of experiments that demonstrate the utility of this model in mapping promoter regions and identifying important regulatory gene sequences in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

beta-Endorphin and naloxone in psychiatric patients: clinical and biological effects.

The authors conducted single- and double-blind studies of the responses of 7 chronic male schizophrenic patients to 10 mg of naloxone. BPRS ratings were made before and 6 hours after the injection; ACTH blood levels were determined before and 1 1/2 and 6 hours after injection. Statistically significant improvement of psychotic behavior occurred after 6 hours. The greatest improvement occurred in the patient who showed the most pronounced diurnal variation of ACTH levels, and there was no improvement in the patient who had no diurnal changes. Prolactin plasma levels following endorphin injections were apparently dose-dependent and peaked at approximately 30 minutes. The mean half-life of elimination of exogenous beta-endorphin was between 12 and 35 minutes. The authors theorize that positive and negative behavioral responses to naloxone depend--as possibly do many placebo responses in general--on the relative stress produced by experimental or therapeutic interventions.

Adrenocorticotropic Hormone↗
PubMed1998

Unilateral versus bilateral botulinum toxin injections in adductor spasmodic dysphonia.

Thyroarytenoid injection of botulinum toxin is the therapy of choice in spasmodic dysphonia. However, there is no convincing evidence as to whether unilateral or bilateral injections are to be preferred. For this reason, a prospective study was designed in which voice quality, duration of effect, and side effects were assessed. Twenty-seven patients with adductor spasmodic dysphonia were treated with percutaneous injections of botulinum toxin. The first treatment consisted of injection of 5 units in the left thyroarytenoid muscle. The second treatment, 2.5 units in both sides, took place when the effect of the first procedure had completely ceased. All patients underwent both procedures. By means of self-rating scales, effects and side effects were assessed over at least 3 months. There was no difference between the procedures in duration of voice improvement, nor in the occurrence of breathy dysphonia. After a bilateral injection, statistically more patients reported swallowing problems. However, most patients preferred the bilateral injection, in spite of more and longer-lasting side effects.

Adult↗
PubMed1975

Acute effects of thyroxine, triiodothyronine, and iodide on thyrotropin secretion.

Rats fed a Purina or low-iodine diet (LID) for varying periods were serially sampled before and after a single iv injection of T4, T3, iodide or saline. Suboptimal replacement doses of T4 and T3 were given to rats fed LID for 2 months or 1 year (basal TSH, approximately 1000 and 2000 muU/ml, respectively). Both 1 mug T4 and 0.25 mug T3/100 g BW dropped plasma TSH to 70% of the initial level at 15 min and to 10--20% at 4 h. By 12 h TSH had begun to rise in 2-month LID rats, followed by a secondary decline 3--5 days after injection. Statistical comparison of the slopes of the initial TSH decline indicated there was no significant difference between the effect of T4 and T3. There effect of graded doses of T3 (0.01--0.3 mug/100 g) was also examined. There was a highly significant correlation of the magnitude of TSH suppression with the dose of T3 administered. Saline had no effect but 0.65 mug iodide/100 g BW (equal to that in 1 mug T4) had a delayed effect, depressing TSH to a minimum of 25% of the initial value at 48 h in 2-month LID rats. There was no difference in the effect of these doses of T4, T3, or saline in purina-fed rats (basal TSH, 170 muU/ml). T4 or T3 in physiologically equivalent doses thus produces an identical prompt rate of decrease in plasma TSH, indicating that both hormones possess intrinsic hormonal activity. The delayed effect of iodide is presumably because it must first be incorporated into T4 and T3 and secreted by the thyroid gland. The similarity of depression of plasma TSH by thyroid hormones or saline injection in Purina-fed rats is believed due to a nonspecific stress effect in these animals with a low basal rate of TSH secretion. The non-specific inhibition of TSH secretion is minimal in the iodine-deficient rats with a much higher basal rate of TSH secretion, presumably because of relative vectorial influences.

Animals↗
PubMed1999

Comparison of vestibular and cochlear ototoxicity from transtympanic streptomycin administration.

HYPOTHESIS: The relative dose-related cochlear and vestibular ototoxicity produced by transtympanically injected streptomycin (SM) compared to that of gentamicin (GM) was assessed. BACKGROUND: Although SM, the first aminoglycoside used transtympanically, is thought to be selectively vestibulotoxic, it has been replaced by GM in current clinical use. Little experimental data exist that directly demonstrate the relative cochlear and vestibular ototoxicity resulting from transtympanic administration of SM compared to GM. METHODS: Histologic evaluation was performed on inner ears from Mongolian gerbils to study vestibular and cochlear damage. Comparisons were made between animals receiving single (1 x SM) and five daily (5 x SM) injections of SM/Gelfoam-slurry and similarly injected and noninjected controls. These data were compared to results obtained using GM (1 x GM and 5 x GM) reported previously. RESULTS: Two weeks after injection, parallel qualitative and quantitative changes were seen in posterior cristae and cochlear sensory epithelia in the 1 x and 5 x SM injected groups, similar to those resulting from GM injections. Statistically significant decreases in number of hair cells were seen when 5 x SM injected ears were compared to 1 x SM injected ears and control ears. Increased damage was seen with increased dosage of each drug. Whenever damage was observed to the posterior crista sensory cells, damage was also seen in cochlear hair cells. CONCLUSIONS: In this model, SM and GM produced significant cochlear damage when vestibular damage occurred. These results suggest that, in the gerbil, SM and GM are ototoxic but not selectively vestibulotoxic. Increasing the number of transtympanic injections generally increases the damage to sensory hair cells in the posterior crista and the cochlea. A variation in interanimal susceptibility to ototoxic effects exists, but the amount of damage is consistent in cochlear and vestibular hair cells from the same animal. No evidence for selective vestibular ototoxicity from transtympanic SM was found.

Administration, Topical↗
PubMed2000

Pharmacokinetics of several subcutaneous doses of erythropoietin: potential implications for blood transfusion.

1. The aim of the present study was to assess the effectiveness of repeated subcutaneous low-dose recombinant human erythropoietin (rHuEPO) on parameters associated with improved procurement of autologous blood; a procedure regularly used to preclude the need for homologous blood transfusion at the time of elective surgery. 2. Three groups of three volunteers each (n = 9) were administered one of three low doses of rHuEPO (30, 60 or 100 IU/kg bodyweight, s.c.) on days 1, 4 and 8. The plasma pharmacokinetic profile of rHuEPO was studied after the first and third injections. Statistical evaluations were intragroup and intraindividual comparisons. 3. There was a linear relationship between maximum plasma concentration (Cmax) and dose. In the overall study group, Cmax and area under the curve (AUC) were significantly decreased, while the mean residence time (MRT) and elimination half-life (t1/2beta) were significantly increased on day 8 relative to day 1. Significant and sustained increases in reticulocytes were observed after rHuEPO administration, which were maintained above the predose values throughout the study period. 4. In conclusion, rHuEPO, by subcutaneous repeat-dose, was eliminated more slowly and remained longer in the circulation, despite lowered plasma concentrations. Repeated low rHuEPO administration at doses > or = 60 IU/kg bodyweight stimulated modest but sustained reticulocyte concentrations, suggesting that cost may be substantially decreased in autologous blood donation or perioperative treatment programmes.

Adult↗
PubMed1990

Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia.

The purpose of this study was to investigate the effects of tumor-localized hyperthermia at 42 degrees C on the tissue distribution of radioiodinated monoclonal antibody F(ab')2 fragments. Paired-label biodistribution measurements were performed in athymic mice bearing D-54 MG human glioma xenografts on one leg. Mice received both the 131I-labeled F(ab')2 fragment of Mel-14, reactive with human gliomas and melanomas, and nonspecific 125I-labeled RPC 5 F(ab')2. Tumor-bearing legs were placed in a 42 degrees C water bath or a 37 degrees C water bath (control) for 2 or 4 h. In mice sacrificed immediately after 2 h of heating, no hyperthermia-induced differences in the distribution of either fragment were observed. In the 4-h groups, tumor uptake of Mel-14 F(ab')2 increased from 7.04 +/- 1.59% injected dose (ID)/g at 37 degrees C to 20.65 +/- 4.53% ID/g at 42 degrees C (P less than 0.0001), and tumor localization of the control fragment rose from 5.23 +/- 1.35% ID/g to 14.51 +/- 1.37% ID/g (P less than 0.0001). In another experiment, F(ab')2 fragments were injected, tumors were heated for 4 h, and groups were sacrificed at 4, 8, and 16 h after injection. Statistically significant 2- to 3-fold higher uptake of both fragments in tumor were observed at all time points. Hyperthermic conditions also resulted in higher tumor:tissue ratios for both fragments. These results suggest that it may be possible to use tumor-localized hyperthermia to increase the therapeutic utility of radiolabeled monoclonal antibodies, particularly when labeled with short lived nuclides such as the 7.2-h alpha-emitter 211At.

Animals↗
PubMed1985

Atrial natriuretic factor and generalized edema in rats.

The natriuretic action of the atrial natriuretic factor (ANF) was studied in massively proteinuric, anti-natriuretic and edematous nephrotic rats with moderate impairment of renal function. Animals were distributed among four groups: NA----NR, NV----NR, NeA----NR and NA----NeR, where normal atrial (NA) or normal ventricular (NV) or "nephrotic" atrial (NeA) extracts were injected (----) into normal rats (NR) or nephrotic rats (NeR). Control (C) clearance measurements were made before iv injection of the extracts and at four 15-min intervals thereafter (E). Mean arterial pressure and glomerular filtration rate did not change consistently in all four groups from the C to the E period. However, during the first 15-min period after extract injection, statistically significant fractional natriuretic peaks of 332, 361 and 662% of preinjection control values were demonstrable for the NA----NR, NeA----NR and NA----NeR groups, respectively, but not for NV----NR. Following the natriuretic peak, natriuresis returned to control values for NA----NR, but remained above control levels for the NeA----NR and NA----NeR groups. We conclude that, since both the atrial extract from nephrotic rats injected into normal rats and the atrial extract from normal rats injected into nephrotic rats elicited marked natriuresis, the anti-natriuretic edematous condition observed in nephrotic animals cannot be attributed either to the absence of ANF in their atria or to the unresponsiveness of their kidneys to ANF.

Animals↗
PubMed1995

Cardiovascular effects of epidurally administered morphine and a xylazine-morphine combination in isoflurane-anesthetized dogs.

Cardiovascular effects of epidurally administered morphine, a morphine-xylazine combination, and saline solution (control) during isoflurane-maintained anesthesia were assessed in 6 healthy dogs. Anesthesia was induced with isoflurane in O2 and was maintained at 2.0% end-tidal isoflurane concentration. Ventilation was controlled to maintain PaCO2 at 35 to 45 mm of Hg. The dorsal pedal artery was cannulated for measurement of systolic, mean, and diastolic pressures, and for blood sample collection. Arterial blood pH and gas tensions were determined every 30 minutes. Cardiac output was determined by thermodilution. The ECG, heart rate, body temperature, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, end-tidal isoflurane concentration, and CO2 tension were monitored. Systemic and pulmonary vascular resistance, arterial HCO3- concentration, base excess, and cardiac index were calculated. After baseline measurements were taken, morphine (0.1 mg/kg of body weight) in 5 ml of isotonic saline solution, morphine and xylazine (0.1 mg of morphine and 0.02 mg of xylazine/kg) in 5 ml of isotonic saline solution, or 5 ml of isotonic saline solution was injected into the lumbosacral epidural space. Data were recorded at 5, 15, 30, 45, 60, 75, 90, 105, and 120 minutes after epidural injection. Statistical analysis included ANOVA for repeated measures. Significance was set at P < 0.05. None of the measured variables was significantly different among the 3 treatments at any time. Results of the study indicated that epidural administration of morphine or morphine and xylazine is not associated with significant cardiovascular side effects during isoflurane-maintained anesthesia in dogs.

Anesthesia, General↗
PubMed1993

[Transcutaneous electric stimulation of the brain: a comparative study of the effects of its combination with peridural anesthesia using bupivacaine-fentanyl during obstetrical analgesia].

In order to test the effectiveness of Anesthelec (transcutaneous cranial electrical stimulation with Limoge currents) during labour and delivery, a randomized study was carried out in 120 primiparous women with extradural anaesthesia during active labor. Combination of transcutaneous cranial electrical stimulation with epidural bupivacaine administration has been showed to provide a 20% pain relief prolongation of the first bupivacaine injection. Statistical studies of drug requirement during labor, of cervical dilatation duration, of mode and duration of delivery and of analgesia quality showed no beneficial additive effect of electrical stimulation for obstetrical analgesia when extradural anaesthesia is performed.

Adult↗
PubMed1996

[A study of intraarticular irrigation-injection therapy of temporomandibular joint and its mechanism].

According to the research that there were some immune and inflammatory substances in the synovial fluid of temporomandibular joint disturbance syndrome (TMJDS), we improved the traditional intraarticular injection and developed an intraarticular irrigation-injection therapy to treat 43 cases of TMJDS and got a good result. The controls include two groups, the simple rinsing and the traditional injection. Statistical analysis showed a highly significant difference in the effects between test and control groups. In order to study the mechanism of the therapy, the tumor necrosis factor (TNF) in synovial fluid of 8 cases were assessed. It was found that the concentration of TNF was reduced markedly after treatment. We think that the new therapy is effectable for TMJDS and could be used widely.

Adult↗