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48 records · Page 3Linked to original sources

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Although SM, the first aminoglycoside used transtympanically, is thought to be selectively vestibulotoxic, it has been replaced by GM in current clinical use.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↗

PubMed2005

Multicenter study of hyaluronic acid obtained by biotechnology to evaluate clinical efficacy and safety in knee osteoarthritis.

Viscosuppplementation with intra-articular hyaluronic acid (hyaluronan [HA]) is a relatively new option for improving pain and articular function in patients with symptomatic knee osteoarthritis. An open multi-center study was performed in 365 patients with definite and symptomatic knee osteoarthritis from seven Latin American countries. Five doses of HA were administered once a week. The parameters studied were pain (six items), stiffness (two items) and functional capacity (17 items). The parameters were evaluated 1 week after the corresponding injection. Statistical differences were found when basal determinations of the three parameters were compared with the results of the first and fourth administration (p < 0.05). Intra-articular HA administration was well tolerated. Treatment-related nonserious adverse events were registered in 2.5% of administrations. Based on the results obtained, HA is a useful and well-tolerated symptomatic treatment for knee osteoarthritis with a rapid onset of action.

Biotechnology↗

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↗

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