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Is intralesional injection of OK-432 effective in the treatment of lymphangioma in children?

BACKGROUND: Intralesional injection of OK-432 has been proposed as an effective treatment of lymphangioma. The aim of this study was to review our experience with OK-432 injection of lymphangioma and to identify factors associated with successful outcome. METHODS: We made a case note review of 19 children who received OK-432 injection. Median duration of follow-up was 17 months. RESULTS: Lesions were diagnosed antenatally in 4 children, at birth in 4 children, and between 1 month and 11 years in the remainder. Anatomic locations were head/neck in 14, axilla in 1, and multiple locations in 4. Median number of injections per child was 2 (range, 1 to 5). Disappearance of the lesion was achieved after OK-432 injection in 2 patients (11%) and a marked reduction in 5 (26%); all these lesions were in the head and neck. Lesions larger than 5 cm and those outside the head and neck region did not respond well to OK-432 injection. Fourteen children (74%) required surgical excision after injection. Complications of OK-432 injection included partial tracheal obstruction, fever, local inflammatory response, and abscess formation. CONCLUSIONS: OK-432 injection was effective in approximately one third of children with lymphangioma. Lesions outside the head and neck and those larger than 5 cm are unlikely to respond to this therapy. Injection of lymphangioma surrounding the airways may be hazardous.

Antineoplastic Agents↗

Incorporation of the acrosome into the oocyte during intracytoplasmic sperm injection could be potentially hazardous to embryo development.

In mice and humans, a normal offspring can be obtained by injecting a single spermatozoon into an oocyte, the process called intracytoplasmic sperm injection (ICSI). When three or more mouse spermatozoa with intact acrosomes were injected into individual mouse oocytes, an increasing proportion of oocytes became deformed and lysed. Oocytes did not deform and lyse when acrosome-less spermatozoa were injected, regardless of the number of spermatozoa injected. Injection of more than four human spermatozoa into a mouse oocyte produced vacuole-like structures in each oocyte. This vacuolation did not happen when spermatozoa were freed from acrosomes before injection. Hamsters, cattle, and pigs have much larger acrosomes than the mouse or human. Injection of a single acrosome-intact hamster, bovine, and porcine spermatozoon deformed and lysed many or all mouse oocytes. This deformation did not happen when these spermatozoa were freed from acrosomes before ICSI, regardless of the number of spermatozoa injected. Because trypsin and hyaluronidase mimicked the action of acrosome-intact spermatozoa, it is likely that the acrosomal enzymes deform and lyse the oocytes. Injection of small amounts of trypsin and hyaluronidase into normally fertilized mouse eggs disturbed their pre- and postimplantation development. In view of potentially harmful effects of acrosomal enzymes on embryo development, the removal of acrosomes before ICSI is recommended for animals with large sperm acrosomes. The removal of acrosomes may increase the efficiency of ICSI in these animals. Although human and mouse spermatozoa do not need to be freed from acrosomes, the removal of acrosomes before ICSI is theoretically preferable.

Acrosome↗

Long-term expression of erythropoietin in the systemic circulation of mice after intramuscular injection of a plasmid DNA vector.

Erythropoietin (Epo)-responsive anemia is a common and debilitating complication of chronic renal failure and human immunodeficiency virus infection. Current therapy for this condition involves repeated intravenous or subcutaneous injections of recombinant Epo. In this report, we describe the development of a novel muscle-based gene transfer approach that produces long-term expression of physiologically significant levels of Epo in the systemic circulation of mice. We have constructed a plasmid expression vector, pVRmEpo, that contains the murine Epo cDNA under the transcriptional control of the cytomegalovirus immediate early (CMV-IE) promoter, the CMV-IE 5' untranslated region, and intron A. A single intramuscular (i.m.) injection of as little as 10 micrograms of this plasmid into immunocompetent adult mice produced physiologically significant elevations in serum Epo levels and increased hematocrits from preinjection levels of 48 +/- 0.4% to levels of 64 +/- 3.3% 45 days after injection. Hematocrits in these animals remained elevated at greater than 60% for at least 90 days after a single i.m. injection of 10 micrograms of pVRmEpo. We observed a dose-response relationship between the amount of plasmid DNA injected and subsequent elevations in hematocrits. Mice injected once with 300 micrograms of pVRmEpo displayed 5-fold increased serum Epo levels and elevated hematocrits of 79 +/- 3.3% at 45 days after injection. The i.m. injected plasmid DNA remained localized to the site of injection as assayed by the PCR. We conclude that i.m. injection of plasmid DNA represents a viable nonviral gene transfer method for the treatment of acquired and inherited serum protein deficiencies.

Animals↗

Gene therapy by intramuscular injection of plasmid DNA: studies on firefly luciferase gene expression in mice.

Direct injection of nonviral, covalently closed circular plasmid DNA into muscle results in expression of the DNA in myofiber cells. We have examined the expression of firefly luciferase DNA constructs injected into adult murine skeletal muscle. Considerable variation in luciferase enzyme expression was noted among constructs with different regulatory elements, among different batches of the same DNA construct, and among similar transfection experiments performed at different times. This variation was minimized by using single batches of plasmid DNA and by performing comparable sets of experiments concurrently. A quantitative experimental protocol was defined for comparing various aspects of the transfection process. We report that a luciferase construct containing the human cytomegalovirus immediate-early gene promoter plus intron A (a construct termed "p-CMVint-lux") showed the highest expression among several constructs tested. Dose-response and time course analyses of p-CMVint-lux DNA injections showed that maximal luciferase expression was achieved with 25 micrograms of DNA at 7-14 days post-injection. Selected manipulations of the transfection process were examined for their influence on luciferase expression. Variations in the rate of DNA injection, needle size, injection volume, and vehicle temperature had no significant effect on luciferase expression. The presence of endotoxin, cationic peptide, muscle stimulants or relaxants, vasoconstrictors, metal chelators, or lysosomal lytic reagents had no significant effect on expression. However, linearization of the DNA, injection of the DNA in water rather than saline, or inclusion of a DNA intercalating agent nearly abolished luciferase expression. And finally, increasing the injection dose by giving multiple injections over a 10-day period increased expression proportionally to the number of injections.

Amino Acid Sequence↗

Uptake, biodistribution, and time course of naked plasmid DNA trafficking after intratumoral in vivo jet injection.

Nonviral jet injection is an applicable technology for in vivo gene transfer of naked DNA. However, little is known about the biodistribution and clearance of jet-injected DNA, or about its localization within tissue and cells. Therefore, in this study we analyzed the intratumoral and systemic biodistribution of jet-injected naked DNA in human colon carcinoma-bearing NCr-nu/nu mice, which were jet-injected with the pCMVbeta plasmid DNA. Intratumoral and systemic plasmid DNA biodistribution was analyzed 5, 10, 20, and 40 min and 3, 6, 24, 48, and 72 hr after jet injection, using quantitative real-time polymerase chain reaction. In the tumors, a rapid drop in naked DNA load within 24 hr of jet injection was shown. Detailed analysis of intratumoral distribution of rhodamine-labeled DNA revealed the presence of plasmid DNA within tumor cells 5 min after jet injection and further accumulation of significant DNA amounts in the cell nuclei 30 to 60 min after jet injection. In the blood, DNA amounts rapidly dropped within 10 to 40 min of jet injection to less than 0.001 pg of plasmid per 250 ng of tissue DNA and only minimal plasmid DNA dissemination was detected in liver, lung, spleen, kidney, and ovaries, which was cleared 3 to 6 hr after jet injection. By contrast, in heart, bone marrow, and brain almost no plasmid DNA was detectable.

Animals↗

Retinal function and histologic changes following intravitreal injection of indocyanine green in a rabbit model.

The aim of this animal study was to investigate the effects of intravitreal injection of indocyanine green (ICG) applied in macular hole surgery on retinal functional, morphology, and histologic changes. Eighteen (18) New Zealand albino rabbits were divided equally into three groups (6 rabbits in each). In Group A, both eyes of each rabbit were vitrectomized by perflouropropane gas compression. One (1) month later, 0.1 cc of different doses of ICG was injected into the vitreous in the left eyes. In the right eyes, 0.1 cc of balanced salt solution was injected intravitreally, allowing them to serve as control eyes. In Group B, the same doses of ICG were injected intravitreally. ICG was washed out by fluid-fluid exchange 3 minutes after injection. In Group C, the same doses of ICG were injected intravitreally in nonvitectomized eyes. Scotopic and photopic electroretinogram (ERG) recordings and indirect ophthalmoscopy examinations were performed to detect any functional and morphologic changes. Rabbit eyes were enucleated 4 months after ICG injections to observe histologic changes. Significant decreased of scotopic and photopic ERG amplitude and marked histologic changes were noted in eyes injected with 0.5 mg/cc and 0.1 mg/cc of ICG in nonvitrectomized eyes (Group C). In vitrectomized eyes (Group A), decreased scotopic and photopic ERGs and mild histologic changes were noted in eyes injected with 0.5 mg/cc, but no histologic changes were noted in eyes injected with 0.1 mg/cc. There was a transient, mild decrease in scotopic and photopic ERGs and no morphologic changes were noted in the eyes with fluid-fluid exchange (Group B). The toxicity of intravitreous ICG is dose- and time-dependent. ICG at 0.5 mg/cc, with short exposure time, is recommended in macular hole surgery.

Animals↗

Intramuscular atropine sulfate in children: comparison of injection sites.

In children undergoing inhaled induction of anesthesia with halothane who suffer bradycardia, submental glossal injection of atropine may result in more rapid onset of vagolysis than traditional intramuscular sites. We compared the intervals between injection and onset of heart rate acceleration (tHR increases) after intramuscular injection of atropine into the deltoid, vastus lateralis, and glossa in children between 1 mo and 10 yr of age scheduled for elective surgery. The tHR increases was determined by measuring the interval between atropine injection and the time point at which the slope of the heart rate curve initially became positive. To ensure that the drug had taken effect before surgical stimulation, heart rate observation was continued until it increased at least 5% above baseline with evidence of continuing acceleration. Anesthesia was induced in all subjects by mask with nitrous oxide and halothane. After tracheal intubation, constant inspired concentrations of the anesthetics were administered for 3 min. While heart rate was monitored, atropine (0.02 mg/kg) was injected into one of the three sites. Each patient's end-tidal anesthetic concentrations were recorded, and minimum alveolar anesthetic concentrations (MAC) were subsequently calculated and adjusted for age. The tHR increases was recorded and averaged for each group. The study groups did not differ by age, weight, end-tidal anesthetic concentrations, age-adjusted MAC, or heart rate at the time atropine was administered. After submental glossal injection (n = 11), tHR increases increase was fastest (3.0 +/- 1.1 min) and was significantly faster than that found with deltoid injection (n = 16; 4.4 +/- 1.1 min) or vastus lateralis injection (n = 8; 6.4 +/- 2.4 min) (P < 0.05 compared with both). The tHR increases also differed significantly between the deltoid and the vastus lateralis (P < 0.05). We conclude that submental glossal injection of atropine results in a more rapid onset of vagolysis than injection at traditional intramuscular sites.

Anesthesia, Inhalation↗

Medial canthus single-injection episcleral (sub-tenon anesthesia): computed tomography imaging.

UNLABELLED: Single-injection medial canthus periocular anesthesia is a promising regional anesthesia technique for ophthalmic surgery. The purpose of this computed tomography (CT) study was to confirm that this technique is an episcleral injection and to explain why it provides a good akinesia of the globe. Four fresh nonpreserved cadavers (eight eyes) were injected with fractioned various volumes of a contrast media using a previously described technique. For each injection and each eye, CT scans were performed in three planes of the space, and the site and spread of the injection was observed. We confirm that single-injection medial canthus periocular anesthesia is, in fact, an episcleral anesthesia, which explains the good sensory block of the globe. When larger volumes are injected, the contrast media spreads to the lids and extraocular muscle sheaths. We believe that this may explain why this technique provides good sensory and motor block of the globe and eyelids. This technique is a promising alternative to both retro- and peribulbar anesthesia. IMPLICATIONS: We describe medial canthus single-injection periocular anesthesia by a computed tomography injection study in eight human cadaver eyes. It was confirmed to be an episcleral injection. Akinesia of the eyeball is provided by spreading of the local anesthetic solution from the episcleral space to the rectus muscle sheaths.

Anesthesia, Conduction↗

The effects of morphine, MK-801, an NMDA antagonist, and CP-96,345, an NK1 antagonist, on the hyperesthesia evoked by carageenan injection in the rat paw.

BACKGROUND: The spinal mechanisms underlying the hyperesthetic state during inflammation are little understood. To gain a better understanding of these mechanisms, this study evaluated the effects of intrathecal morphine; MK-801, an N-methyl-D aspartic (NMDA) antagonist; and CP-96,345, an NK1 antagonist, on the hyperesthesia observed after carageenan injection of the rat paw. METHODS: In rats injected with 2 mg carageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carageenan injection. Drugs were administered 2 h after the carageenan injection. The magnitude of hyperesthesia was evaluated with the difference score (DS), which was calculated by subtracting the PWL of the untreated paw from the PWL of the injected paw. RESULTS: Intrathecal morphine increased PWLs of both the injected and the untreated paws equally in a dose-dependent manner, but intrathecal morphine did not affect the level of DS. Intrathecal MK-801 increased PWLs of the injected paw to the level of the untreated paw in a dose-dependent manner and increased the DS levels. Intrathecal CP-96,345 had no effect on PWLs of either the injected or the untreated paw. Coadministration of MK-801 with morphine reduced the DS for each dose of morphine. CONCLUSIONS: These data indicate that (1) an NMDA receptor, but not an NK1 receptor, plays an important role in maintaining the hyperesthesia after carageenan injection; and (2) NMDA antagonism has a simple additive interaction with morphine in the carageenan model of inflammatory hyperesthesia.

Animals↗

Effect of injection site on circulation times during cardiac arrest.

Cardiopulmonary resuscitation requires effective, prompt drug administration. In order to analyze Advanced Cardiac Life Support (ACLS) recommendations for site of drug administration, we studied dye circulation times after central, femoral, and peripheral venous injection during both closed and open chest CPR using a canine arrest model. Measurements of circulation times were made after injection of indocyanine green dye at femoral, central, and peripheral venous sites. Circulation times during closed chest CPR were 62.7 +/- 19.6 sec after central injection, 86.6 +/- 23.5 sec after femoral injection, and 93.6 +/- 17.9 sec after peripheral injection (p less than .001). During closed chest CPR, peak dye concentration after central injection was significantly higher than that after peripheral injection (4.0 +/- 1.3 vs. 3.1 +/- 0.8 mg/L, p less than .01). Circulation times were significantly shorter during open chest CPR with times again shortest after central injection. This animal model suggests that prompt drug delivery during CPR is enhanced by central venous injection of medication. There appears to be no advantage in femoral over peripheral injection.

Animals↗

Exacerbation of ischemic brain damage by localized striatal injection of interleukin-1beta in the rat.

Interleukin-1beta (IL-1beta) has been implicated in ischemic brain damage. The site of action of IL-1beta in such damage is not known, but we have demonstrated previously that injection of the interleukin-1 receptor antagonist (IL-1ra) in the striatum but not the cortex of rats inhibits damage caused by permanent middle cerebral artery occlusion. The present study investigated the site of action of IL-1beta on ischemic damage by examining the effects of intracerebroventricular, striatal, or cortical injection of recombinant IL-1beta at the onset of permanent middle cerebral artery occlusion in the rat. Intracerebroventricular injection of IL-1beta (2.5 ng) significantly increased infarct volume in the striatum (35%, P < 0.0001) and in the cortex (44%, P < 0.0001) compared with vehicle treatment. Direct injection of IL-1beta into the striatum also increased infarct volume in both the striatum (36%, P < 0.0001) and the cortex (38%, P < 0.0001), whereas injection of IL-1beta into the cortex failed to affect infarct volume in either the striatum or the cortex. Cortical injection of a higher dose of IL-1beta (20 ng) also failed to affect ischemic damage in either the striatum or the cortex. Injection of IL-1beta into the striatum contralateral to the infarction had no effect on striatal damage in the ischemic hemisphere, but did increase cortical damage by 18% (P < 0.0001). In separate groups of animals, IL-1beta (2.5 ng) was injected into either the striatum or the cortex, and body temperature was recorded continuously in conscious free-moving animals by remote telemetry. Injection of IL-1beta at either site failed to influence body temperature, suggesting that exacerbation of brain damage by striatal injection of IL-1beta is not caused by effects on body temperature. These results imply that IL-1beta exacerbates ischemic damage by specific actions in the striatum where it can influence damage at distant sites in the cortex.

Animals↗

A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania.

There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder. In this study, 201 agitated patients with bipolar mania were randomly assigned to receive one to three injections of the atypical antipsychotic olanzapine (10 mg, first two injections; 5 mg, third injection), the benzodiazepine lorazepam (2 mg, first two injections; 1 mg, third injection), or placebo (placebo, first two injections; olanzapine, 10 mg, third injection) within a 24-hour period. Agitation was measured at baseline, every 30 minutes for the first 2 hours, and at 24 hours after the first injection using the Positive and Negative Syndrome Scale-Excited Component subscale and two additional agitation scales. At 2 hours after the first injection, patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam. At 24 hours after the first injection, olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania, whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine. Furthermore, no significant differences among the three treatment groups were observed in safety measures, including treatment-emergent extrapyramidal symptoms, the incidence of acute dystonia, or QTc interval changes. These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania.

Adult↗

Factors influencing vascular and hepatic enhancement at CT: experimental study on injection protocol using a canine model.

PURPOSE: The purpose of this work was to evaluate the effects of contrast medium injection parameters on aortic, portal vein, and hepatic enhancement at spiral CT and to assess optimal injection protocol for hepatic CT. METHOD: Ten 15 kg dogs underwent single level dynamic CT through the hepatic hilum at 5 s intervals just after the injection of contrast medium for 3 min. With use of different volumes (1, 2, and 3 ml/kg), injection rates (0.5, 1, and 2 ml/s), and concentrations (150, 200, and 300 mg/ml), a total of 270 spiral CT scans were performed. In each scan, time-attenuation curves of aorta, portal vein, and liver were obtained. The degree of maximum contrast enhancement (Imax), time to maximum enhancement (Tmax), and time to equilibrium phase (Teq) for to each injection protocol were analyzed. RESULTS: Alterations in contrast material volume, injection rate, and concentration had significant impact on contrast enhancement of the liver. With increasing volume of contrast medium, Imax, Tmax, and Teq of aorta, portal vein, and liver increased (p < 0.005). With increasing rate of injection, on the other hand, Imax of aorta and liver increased (p < 0.05), but Tmax and Teq decreased (p < 0.005). Change of concentration of contrast medium had a significant effect on Imax of vessels (p < 0.05). CONCLUSION: Maximum contrast enhancement of liver and vessels was influenced mainly by injection volume of contrast medium and the time to peak enhancement by injection rate of contrast medium. Under given amounts of contrast medium, therefore, the strategy of increasing volume by dilution and faster injection might give better Imax values without penalty for the duration of an optimal temporal window (Tmax and Teq).

Animals↗

Minimal injection site pain and high patient satisfaction during treatment with long-acting risperidone.

Long-acting injectable antipsychotic formulations of conventional antipsychotics were developed to address the problem of partial adherence among patients with schizophrenia. Injection site pain, other skin reactions and patient satisfaction with treatment were assessed in two large, multicentre studies of long-acting injectable risperidone (Risperdal CONSTA, Janssen Pharmaceutica Products, Titusville, New Jersey, USA), the first available long-acting atypical antipsychotic agent. Patients rated injection site pain using a 100-mm Visual Analogue Scale (VAS), and investigators rated injection site pain, redness, swelling and induration. Patient satisfaction with treatment was assessed with the Drug Attitude Inventory (DAI). VAS pain ratings were low at all visits across all doses in both studies, and decreased from first to final injection. In the 12-week, double-blind study, mean +/- SD VAS scores at the first and final injections were 15.6 +/- 20.7 and 12.5 +/- 18.3 for placebo-treated patients, and 11.8 +/- 14.4 (first) and 10.0 +/- 12.4 (final) for 25 mg; 16.3+/-21.9 (first) and 13.6 +/- 21.7 (final) for 50 mg; and 16.0 +/- 17.9 (first) and 9.6 +/- 16.0 (final, P<0.01) for 75 mg of long-acting risperidone. Mean VAS scores in the 50-week, open-label study at the first and final injection were: 17.9 +/- 22.2 (first) and 9.5 +/- 16.7 (final, P<0.0001) for 25 mg; 18.1 +/- 19.7 (first) and 10.4 +/- 14.8 (final, P<0.0001) for 50 mg; and 18.5 +/- 21.6 (first) and 13.6 +/- 19.9 (final, P = 0.0001) for 75 mg of long-acting risperidone. Overall, there was no or minimal injection site pain and skin reactions were rare. Mean DAI ratings were available for the 50-week study and indicated high patient satisfaction throughout the trial (baseline = 7.30; endpoint = 7.70; P<0.0001 versus baseline). These findings may positively affect patient and clinician attitudes towards long-term therapy with long-acting injectable risperidone.

Adult↗

The swallowing side effects of botulinum toxin type A injection in spasmodic dysphonia.

Botulinum toxin type A (BOTOX) injection of the thyroarytenoid muscle is used to control speech symptoms in patients with adductor spasmodic dysphonia. Transient difficulty in swallowing liquids is a common treatment side effect. Laryngeal movement durations were measured during swallowing in 13 adductor spasmodic dysphonia patients undergoing treatment and in 6 normal control subjects in order to determine the following: 1. whether, prior to the injection, laryngeal movement durations were longer in the spasmodic dysphonia patients than in the control subjects; 2. whether movement durations increased following the injections; 3. whether preinjection swallowing difficulties related to postinjection swallowing measurements and postinjection patient reports of swallowing problems. A piezoelectric movement transducer was shown to be accurate for noninvasive measurement of laryngeal movement duration in relation to muscle onset and offset for hyoid elevation and relaxation. Before botulinum toxin type A injection, no significant differences in swallowing duration were found between the patient and control groups. Four patients with swallowing complaints prior to injection had longer laryngeal movement durations than the other spasmodic dysphonia patients and the control subjects. Following injection, laryngeal movement durations increased in the patients with spasmodic dysphonia, and eight patients reported dysphagia for an average of 2 weeks. Relationships were found between the patients' initial reports of swallowing problems and increased laryngeal movement durations before and after botulinum toxin type A injection. Those patients initially reporting swallowing difficulties had severe dysphagia for 2 weeks after the injection. Patient reports of dysphagia prior to injection may indicate a greater likelihood of significant dysphagia following thyroarytenoid injection with botulinum toxin type A.

Adult↗

Botulinum toxin for essential tremor of the voice with multiple anatomical sites of tremor: a crossover design study of unilateral versus bilateral injection.

OBJECTIVES/HYPOTHESIS: To evaluate the relative efficacy of unilateral and bilateral injections of botulinum toxin injection (BOTOX) in the treatment of essential tremor of the voice (ETV). STUDY DESIGN: Prospective open-label crossover study. METHODS: Patients referred to the Neurolaryngology Clinic at Toronto General Hospital with a diagnosis of ETV were eligible for the study. Patients were sequentially assigned to receive BOTOX as either a bilateral 2.5-U or a unilateral 15-U electromyography-guided injection, followed by the alternative injection 16 to 18 weeks later. Acoustic, aerodynamic, and nasopharyngoscopic data were collected approximately 2, 6, 10, and 16 weeks after each injection. Patients were asked to provide a perceptual evaluation of BOTOX effects at the conclusion of the study. RESULTS: Three of 10 patients demonstrated an objective reduction in tremor severity with bilateral injection, and 2 of 9 with unilateral injection. However, 8 of 10 patients wished to be re-injected at the conclusion of the study. A reduction in vocal effort appeared to be coincident with reduction in laryngeal airway resistance after BOTOX injection. CONCLUSIONS: Using objective acoustic measures, only a small proportion of patients achieved benefit from BOTOX injection for ETV. However, a majority of patients in our study benefited from a subjective reduction in vocal effort that may have been attributable to reduced laryngeal airway resistance.

Aged↗

Effects of iontophoretic versus injection administration of dexamethasone.

PURPOSE: Sixty-eight skeletally mature New Zealand white rabbits were used to study the effects of iontophoresis- and injection-delivered sodium phosphate dexamethasone (DX) on the morphologic, histologic, microscopic, and biomechanical properties of uninjured rabbit patellar tendons over an initial 14-d period. METHODS: Three control (untreated, placebo iontophoresis, and placebo injection) groups and two treatment (iontophoresis and injection) groups underwent serum, ELISA tendon, histology, electron microscopy, and biomechanical analysis. RESULTS: Serum DX levels were detectable and quantifiable in both treatment groups at 1 h but were significantly greater (P < 0.05) in the injected group (11.29 ng.mL-1) compared with the iontophoresis group (6.34 ng.mL-1). The most significant histologic finding was a lack of a cellular inflammatory response in the DX-treated groups at 24 h. Ultrastructural analysis produced no significant differences between size or size ratio of collagen fibrils among any groups. Morphologic examination revealed only injection puncture marks seen in appropriate tendons. Biomechanical testing produced disruption at the patellar insertion in 81% of the specimens. No injected tendon failed at the injection site. Normalized biomechanical properties included: 1) Stiffness increased in control and iontophoresis groups from 1 to 24 h, then gradually declined; the DX-injected specimens showed a similar but delayed effect. 2) Peak load at failure for iontophoresis and control groups was greatest at 24 h. The DX-injected group again showed a delayed response. 3) In general, total energy to failure revealed no significant differences between groups at any time period. CONCLUSION: It appears that iontophoresis or injection-delivered DX may produce anti-inflammatory effects without significantly altering ultrastructural or biomechanical characteristics of the rabbit patellar tendon within an initial 14-d period.

Analysis of Variance↗

Effects of intravitreal indocyanine green injection in rabbits.

PURPOSE: To report the clinical, electrophysiologic, and histologic findings of different concentrations of indocyanine green (ICG) injected into the vitreous cavity of rabbit eyes. METHODS: Forty-two rabbits underwent intravitreal injection of 0.1 mL of ICG in three different concentrations: 0.5 mg/mL (250 mOsm), 5 mg/mL (270 mOsm), and 25 mg/mL (170 mOsm). Fellow eyes were injected with 0.1 mL of balanced salt solution. Biomicroscopy, ophthalmoscopy, electroretinography, fluorescein angiography, and histologic evaluation were performed. RESULTS: Eyes injected with 0.5 mg/mL of ICG showed b-wave latency delay on the first day after injection. Eyes injected with 5 mg/mL of ICG showed b-wave latency delay and decreased b-wave amplitude on the first and seventh days after injection; delayed a-wave latency on the first day after injection was also observed. Eyes injected with 25 mg/mL of ICG showed b- and a-wave amplitude and latency abnormalities during the entire follow-up. Direct correlation of increasing retinal edema proportional to the progressively increasing ICG concentrations was shown on histologic evaluation. CONCLUSION: Intravitreal ICG injection in rabbit eyes may impair retinal function and morphology proportional to the progressively increasing ICG dosages.

Animals↗