[Diagnostic value of the reactivity of E.E.G. foci to diazepam injection. (Statistical study of 327 cases)].
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Adolescent↗
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Results for “Injectables--statistics”
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Luteinizing hormone-releasing hormone agonist triptorelin in combination with cytotoxic chemotherapy in patients with advanced ovarian carcinoma. A prospective double blind randomized trial. Decapeptyl Ovarian Cancer Study Group.
BACKGROUND: Several lines of evidence suggest that the proliferation of ovarian carcinoma might be stimulated by gonadotrophins. A number of Phase I/Phase II clinical trials have reported that the suppression of endogenous luteinizing hormone and follicle-stimulating hormone secretion by luteinizing hormone-releasing hormone (LHRH) analogs induced objective remissions and/or disease stabilization in 10-30% of patients with advanced refractory ovarian carcinoma. The current study was performed to evaluate whether the addition of LHRH agonist treatment to standard platinum-based chemotherapy could prolong survival of patients with surgically treated Stage III or IV epithelial ovarian carcinoma. METHODS: One hundred and thirty-five patients with Stage III or IV epithelial ovarian carcinoma participated in this prospective randomized double blind trial. After cytoreductive surgery, 69 patients received monthly injections of a depot preparation of the LHRH agonist [D-Trp6] LHRH (triptorelin, 3.75 mg) and 66 patients received placebo until their deaths or termination of trial, respectively. All patients were treated with a standard platinum-based chemotherapy, and, if necessary, with second- or third-line cytotoxic regimens. RESULTS: Endogenous gonadotrophins were reliably suppressed in patients treated with triptorelin. However, their progression free and overall survival were not significantly different from that of patients receiving placebo injections (statistical power > 80% for a difference between both groups of > or = 20%). CONCLUSIONS: The results of this trial suggest that the suppression of endogenous gonadotrophins by conventional doses of an LHRH agonist produces no relevant beneficial effects in patients with advanced ovarian carcinoma who receive standard surgical cytoreduction and cytotoxic chemotherapy.
Adult↗
Prophylactic diazepam in prevention of contrast media-associated seizures in glioma patients undergoing cerebral computed tomography.
Five milligrams of intravenous diazepam given prior to contrast media injection statistically significantly reduced the incidence of contrast media-associated seizures from 16% to 2% in a prospective, randomized series of glioma patients. Factors related to increased risk of contrast media-associated seizures are (1) prior seizure history due to glioma and/or prior contrast media and (2) prior or concurrent brain antineoplastic therapy. Factors not related to an increased risk of contrast media-associated seizures are (1) contrast media dosage, (2) type or grade of glioma, and (3) computerized tomographic appearance of the glioma. Theories regarding the etiology of contrast media-associated seizures are discussed.
Adolescent↗
Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP-2) in the nude mouse by prostacyclin, forskolin, and ketoconazole.
Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell-platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP-2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 micrograms), forskolin (150 micrograms), and ketoconazole (180 micrograms) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P less than 0.001), percentage of liver surface area occupied by tumor (P less than 0.001), and number of tumor colonies (P less than 0.004 for prostacyclin, P less than 0.005 for forskolin, and P less than 0.001 for ketoconazole). These agents also strongly inhibited RWP-2-induced platelet aggregation in human platelet-rich plasma.
Adenocarcinoma↗
A prospective, randomised double-blind crossover study to examine the efficacy of strontium-89 in pain palliation in patients with advanced prostate cancer metastatic to bone.
The palliative efficacy of strontium-89 chloride has been evaluated in a prospective double-blind crossover study comparing it with stable strontium as placebo in 32 patients with prostate cancer metastatic to bone. Response was assessed 5 weeks after each treatment. 26 patients were evaluable. Complete pain relief was only reported following strontium-89 injection. Statistical comparison between placebo and strontium-89 showed clear evidence of a therapeutic response to strontium-89 compared with only a limited placebo effect (P less than 0.01).
Aged↗
Effect of nickel(II)acetate on distribution of calmodulin in the rat kidney.
The effect of subcutaneous injection of a single dose of nickel(II)acetate (95 mumol/kg body wt.) on the distribution of calmodulin in the membrane and cytosolic fractions of kidneys of F344/NCr rats was studied with the use of radioimmunoassay. Over the first 8 h post-injection, the membrane-bound calmodulin concentration increased by 20% versus the control value of 3.84 +/- 0.54 SE micrograms/g wet tissue. That increase was then followed by a gradual decrease to the control value in 7 d. At the same time intervals, the cytosolic calmodulin concentration first decreased by 13% from the control value of 8.81 +/- 2.1 SE micrograms/g wet tissue and then slowly increased, reaching a level of 12% above the control at day 7 post-injection. Statistical analysis of the results after 8 h revealed a downward trend in the membrane-bound (P less than 0.0014) and upward trend in the cytosolic (P less than 0.0207) calmodulin concentrations until day 7. However, the total renal calmodulin calculated from the membrane/cytosolic distribution data did not show any statistically significant treatment-related differences among the mean values (13.39 micrograms/g for the nickel(II)acetate-treated rats vs. 12.56 micrograms/g wet tissue for the controls between days 1 and 7). Therefore, the observed effect of nickel(II)acetate must be attributed only to temporary transfer of calmodulin from the soluble cytosolic form into an insoluble, membrane-bound form, without any detectable influence on its degradation or synthesis rate.
Acetates↗
Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases.
Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.
Bone Neoplasms↗
Mechanistic imbalance of pulmonary vasomotor control in progressive lung injury.
BACKGROUND: Pulmonary hypertension is the major hemodynamic feature of progressive lung injury. We hypothesized that the mechanisms of pulmonary vasorelaxation become progressively impaired in progressive lung injury. The purpose of this study was to examine the following mechanisms of pulmonary vasorelaxation in a rat model of monocrotaline-induced progressive lung injury: endothelial-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), endothelial-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol), and hypoxic pulmonary vasoconstriction. METHODS: Rats were studied 2, 7, and 14 days after monocrotaline injection (100 mg/kg intraperitoneally). Pulmonary vasomotor control mechanisms were studied in isolated pulmonary artery rings. Controls were studied 14 days after saline injection. Statistical analysis was by ANOVA; p < 0.05 was considered significant. RESULTS: A progressive impairment of pulmonary vasorelaxation was observed. By 14 days after monocrotaline injection acetylcholine produced only 25% +/- 5% relaxation versus 95% +/- 5% in controls (p < 0.05), nitroprusside produced 46% +/- 5% relaxation versus 100% in controls (p < 0.05), and isoproterenol produced only 18% +/- 5% relaxation versus 94% +/- 4% in controls (p < 0.05). At the same time hypoxic pulmonary vasoconstriction became progressively exaggerated. CONCLUSIONS: Progressive dysfunction of pulmonary vasomotor control may contribute to the pulmonary hypertension seen in progressive lung injury.
Animals↗
Biochemical and histopathological alterations induced in rats by Tityus serrulatus scorpion venom and its major neurotoxin tityustoxin-I.
Intravenous injection into the rat of sublethal doses of Tityus serrulatus scorpion venom (100 micrograms protein/kg) or its major neurotoxin tityustoxin-I (TsTX-I, 20 micrograms/kg) caused, 30-180 min after injection, statistically significant increases in the serum levels of aspartate aminotransferase, amylase, creatine kinase and lactate dehydrogenase, as well as hyperglycemia, a high level of plasma free fatty acids and a low level of liver glycogen. The in vitro serum levels of the above enzymes did not change. For alanine aminotransferase, gamma-glutamyl transferase and alkaline phosphatase, neither in vitro nor in vivo alterations were observed. The whole venom and TsTX-I caused hepatic congestion with hemolysis and hydropic degeneration. Other histological lesions included edema and congestion with subpleural hemorrhage in the lungs, hypertrophy of fibers with degeneration areas in the heart, and congestion and hemorrhage in the kidneys. In the salivary glands, alterations to the acini and ductules were visible. In the adrenal glands no morphological alterations could be detected at the studied doses. The results suggest that the in vivo enzymatic and histopathological alterations are due to tissue lesions evoked by the whole venom and TsTX-I. An indirect effect, however, induced by stimulation of acetylcholine and catecholamine release in the postganglionic nerve terminals, cannot be excluded.
Animals↗
Osteogenic response of rabbit tibia to hydroxyapatite particle-Plaster of Paris mixture.
A mixture of hydroxyapatite (HA) particles and plaster of Paris (POP) with saline solution was injected into the bone marrow of 30 unilateral tibiae of 30 rabbits. As a control, POP with saline solution was similarly injected into the bone marrow of 30 unilateral tibiae of 30 additional rabbits. Five rabbits in each group were killed 2, 4, 8, 12, 24 and 40 weeks after injection. Histological examination was performed on three tibiae of five killed animals, and X-ray diffraction analysis of the bone marrow was performed on the remaining two tibiae. In two of three tibiae, bridges of new bone were formed between the hydroxyapatite particles and the cortical bone, 4 weeks after the injection of the HA particle-POP mixture. New bone formation was seen in all three tibiae at 8 weeks and thereafter. No new bone formation was observed in the tibiae of the control group. The affinity index, a parameter of osteogenesis, was 0% at 2 weeks, 52.2+/-14.0% at 4 weeks, 74.8+/-5.3% at 8 weeks, 86.1+/-6.1% at 12 weeks, 90.1+/-8.3% at 24 weeks and 92.8+/-4.1% at 40 weeks after injection. Statistically significant increases were found between the affinity indexes of 2 weeks and 4 weeks and between those of 4 weeks and 8 weeks, p < 0.03 and p < 0.05, respectively. Between 12, 24 and 40 weeks, the indexes showed tendencies toward increases. X-ray diffraction of bone marrow of two tibiae into which HA particle-POP mixture or POP alone was injected showed that POP had disappeared 8 weeks after injection.
Animals↗
Hemodynamic effects of microbubble echo contrast.
The dose-related hemodynamic effects of an active (bubble-rich) echo contrast agent were compared with those of a bubble-free contrast agent and saline solution to determine whether the microbubbles contained in the echo contrast agent are truly passive indicators in the circulation or whether they actively alter the hemodynamic state independent of the volume and osmotic loading associated with such injections. The study population consisted of 13 fully instrumented open-chest mongrel dogs. Four hundred ninety-two bolus injections were made of three different types: active contrast agent (Levovist, Schering AG, Berlin) (n = 333), saline solution (n = 112), and bubble-free contrast agent (n = 47). Levovist was administered in five dose ranges spanning 0.013 to 0.341 gm/kg and, like the saline solution, was administered in bolus volumes of 0.053 to 1.136 ml/kg. For each injection type, the percent change in hemodynamic parameters after administration of the bolus were calculated on the basis of the dose or volume of the injectate. Audio Doppler signal intensity was used to document the presence of bubbles in the injectate. Statistical significance was defined at the p = 0.05 level; clinical significance was defined as a greater than 15% change in a hemodynamic parameter. Statistically, but not clinically, significant changes were noted in almost all hemodynamic parameters regardless of injection type, and at all dose and volume ranges. Although statistically significant, injection of an active contrast agent in the human dose range resulted in a < 5% change in hemodynamic parameters. High doses of a contrast agent (active or bubble-free) increased the left atrial pressure and had associated changes in peripheral vascular hemodynamics because of the osmotic load. Clinically significant increases (> 15%) in pulmonary artery pressure and pulmonary vascular resistance were unique to the active contrast agent at high dose ranges. Standard doses of the active contrast agent changed the hemodynamics by less than 5% in healthy dogs. Transient clinically significant increases in pulmonary artery pressure and pulmonary vascular resistance are a unique side effect to high dose bolus injections of microbubble echo contrast agent.
Animals↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗