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A comparison of two double-injection techniques for peribulbar block analgesia: infero-temporal plus supero-medial vs. infero-temporal plus medial-percaruncular.

BACKGROUND: Combinations of infero-temporal and either supero-nasal ('inferior-superior') or medial percaruncular ('inferior-medial') injections are popular double-injection techniques for establishing peribulbar block analgesia. This study compared the efficacy of these two techniques in achieving ocular and lid akinesia. METHODS: One hundred patients were randomized to receive inferior-superior or inferior-medial injections in a study in which injectate, injectate volumes, 5-min ocular akinesia scoring (0-8), lid scoring (0-2) and supplemental injection protocols were standardized. The numbers of supplemental injections required at each observation period and the total volume of injectate required to produce ocular and lid akinesia were compared. RESULTS: The two test groups were demographically similar. The inferior-medial combination achieved greater ocular akinesia than the inferior-superior combination 5 min after the initial injections (mean score +/- standard deviation of 1.74 +/- 1.86 vs. 2.66 +/- 2.39; P < 0.05), with a reduced requirement for supplementary injections (3 vs. 23 supplementary injections; P < 0.025). The inferior-superior technique achieved greater lid akinesia at 5 min than the inferior-medial technique (mean score +/- standard deviation of 0.7 +/- 0.9 vs. 0.3 +/- 0.58; P < 0.005). A medial subconjunctival hemorrhage occurred in one patient in the inferior-medial group. CONCLUSION: Compared with the inferior-superior technique, the inferior-medial combination achieved more rapid ocular akinesia with less need for supplementation, but induced less efficient lid akinesia and had a propensity to cause iatrogenic subconjunctival hemorrhage. The latter complication is considered by our surgeons to be a contraindication to the inferior-medial technique in patients undergoing trabeculectomy.

Aged↗

Long-term histological response to subcutaneously injected Polytef and Bioplastique in a rat model.

OBJECTIVE: To compare the long-term carcinogenic effect of Polytef and Bioplastique in the subcutaneous space of the rat. MATERIALS AND METHODS: One hundred Sprague Dawley rats received a subcutaneous injection of one of two particulate plastics; subsequently 48 of those injected with Polytef paste containing polytetrafluoroethylene, 48 injected with silicone containing Bioplastique, and 48 control animals were available for assessment. Animals were killed when they became unwell, developed a tumour, or were 2 years of age. The injection site and all major organs and tumours were examined histologically. RESULTS: One or more tumours were found in 30 Polytef-injected rats, 34 Bioplastique-injected animals and 36 of the controls. The majority of the tumours were breast and pituitary adenomas with a similar incidence in each group. No tumours were found at the injection site of the Polytef-injected animals. Four poorly differentiated sarcomas were found on the back of Bioplastique-injected rats; three were intimately associated with silicone particles, whereas the fourth was separate from the injection site. CONCLUSION: This study would suggest that the carcinogenic risk from injectable plastics is low, but further work should be conducted with the larger particles, to ensure that their use in humans is safe.

Animals↗

The effect of location of the ureteric orifice on the efficacy of endoscopic injection to correct vesico-ureteric reflux.

OBJECTIVE: To review our 11-year experience and identify the mechanisms responsible for the failure of endoscopic injection for vesico-ureteric reflux (VUR) with three different injectable agents, based on the location of the ureteric orifice on endoscopy. PATIENTS AND METHODS: We retrospectively reviewed the charts and endoscopic video-photographs of 46 patients (26 girls, 20 boys, median age 6 years, range 2-16) with VUR treated once or twice by subureteric injection with PTFE, or polydimethylsiloxane or dextranomer/hyaluronic acid copolymer, from 1992 to 2003. Five patients were lost to follow-up and six ectopic and/or duplicated ureters were excluded from the analysis; in all, 52 ureters were analysed. According to the international classification, the VUR was grades I to V in four (8%), 12 (23%), 16 (31%), 13 (25%) and seven (13%) ureters, respectively. RESULTS: After 3 months, voiding cysto-urethrography showed that VUR continued in six of 19, seven of 12 and eight of 21 ureters (38%), respectively, after subureteric PTFE, polydimethylsiloxane and dextranomer/hyaluronic acid copolymer injection; after the second injection, reflux continued in two of six, four of seven and three of eight ureters, respectively. Mound displacement and/or volume loss was the most common failure with all three bulking agents after both the first (62%) and second injections (44%) (P < 0.05). The first injection failed in 32% (11 of 35) normally located ureters and 10 of 17 lateral ureters (P < 0.05). The second injection failed in 11% (four of 35) normal and five of 17 lateral ureters (P < 0.05). CONCLUSIONS: A lateral ureteric orifice may decrease the efficacy of endoscopic injection, as the likelihood of a faulty injection is greater. However, a more careful second injection decreases the failure rate, particularly in those with low- to medium-grade refluxing ureters.

Adolescent↗

The effect of injection speed on the pain of lidocaine infiltration.

OBJECTIVE: To determine whether reducing the speed of injection is effective in reducing injection pain for buffered and unbuffered lidocaine solutions. METHODS: A prospective, single-blind, randomized, crossover, laboratory study was performed. Adult volunteers were recruited from ED staff at an urban teaching hospital to serve as subjects. Twenty-nine subjects each received 4 1-mL injections into the dorsum of the hands. Each subject received fast and slow injections of buffered and unbuffered lidocaine. Subjects rated the pain of each injection on a 100-mm visual analog scale (VAS). Mean pain scores for each intervention were compared using analysis of variance. RESULTS: The mean pain VAS score for fast injection of buffered lidocaine was 14.1 mm. For slow buffered injection, the mean pain score was 11.4 mm (p = 0.98). For unbuffered lidocaine, the means were 28.7 mm for fast injection and 22.2 mm for slow injection (p = 0.40). CONCLUSIONS: Reducing injection speed did not produce a statistically significant change in injection pain for either buffered or unbuffered solutions.

Adult↗

Local toxicity of different drugs after intramuscular or intralipomatous injection in pigs: serum concentrations after three different formulations of cis(Z)-clopenthixol.

Findings made by computerized tomography scanning of pelvis of patients suggested that the majority of injections intended to be intramuscular in fact are delivered in the fat tissue. This finding has raised the question what difference it makes when drugs are injected intramuscularly or intralipomatously. We have studied local toxicity after intramuscular or intralipomatous injection of different drugs in pigs, which have a subcutaneous layer of fat comparable to that of man. The pigs were killed 1, 3, 7 or 14 days after injection of antibiotics, vitamins, neuroleptics, diazepam, digoxin, pentazocine, sulphadimidine and vehicles. The tissues at the injection site were examined macro- and microscopically. In another series of experiments an aqueous or two different oily preparations of the neuroleptic drug cis(Z)-clopenthixol were given intramuscularly or intralipomatously to pigs and a series of blood samples were taken for drug level determination. The tissue examinations showed that all drugs causing local muscle damage after intramuscular injection caused considerably less extensive damage with a faster regeneration after intralipomatous injection. The pharmacokinetic study showed that there was virtually no difference between plasma-concentration-time curves after intramuscular or intralipomatous injection. Our findings indicate that intralipomatous injection of irritating drugs is better tolerated than intramuscular injection since intralipomatous injection causes less local toxicity. Our findings also suggest that the pharmacokinetics are not different. However, further studies are required to substantiate whether the findings are of general relevance.

Absorption↗

Effect of palatal injections on pulpal blood flow in premolars.

The effect of palatal infiltration injections using 2% lignocaine hydrochloride with 1:80,000 adrenaline was evaluated for sound maxillary first premolar teeth. The influence of the injections on pulpal blood flow and local anaesthesia was investigated. Ten human volunteers were given the following injections on different days: 1 ml palatal infiltration; 1 ml buccal infiltration; 1 ml palatal and 1 ml buccal infiltration; and 2 ml buccal infiltration. The blood flow was observed with a laser Doppler flowmeter with the probes held against the buccal surfaces of the teeth by a splint. Blood flow was recorded digitally on a computer in machine units. Pulpal anaesthesia was assessed using a monopolar electric pulp tester. All injections significantly reduced blood flow from baseline levels (p<0.05). The 1-ml palatal injection produced a significantly longer period of reduced blood flow (mean 40 min) compared with the other injections (p<0.05). The duration of blood flow reduction was shorter than the duration of pulpal anaesthesia for every injection. Only seven out of 10 palatal injections achieved pulpal anaesthesia. The 2-ml buccal injection and the combined buccal and palatal injections produced significantly longer anaesthesia than the 1-ml buccal injection (p<0.05).

Adult↗

Effects of focal injection of kainic acid into the mouse hippocampus in vitro and ex vivo.

Intra-hippocampal kainate injection induces an epileptiform activity termed status epilepticus. We examined the emergence of this activity with extracellular and intracellular records of responses (1) to focal kainate (KA) application in slices of mouse hippocampus and (2) of slices from mice injected with KA. The effects varied with distance from the injection site of KA. At distances less than approximately 800 microm, KA injection induced a strong increase in extracellular firing which ceased after 2-4 min. Pyramidal cells in this zone fired and depolarized to a potential at which action potentials were no longer evoked. No further activity was detected near the injection site for 3-5 h. In longitudinal slices of the CA3 region, firing induced by KA injection spread at a velocity close to 1 x 10(-)(4) mm ms(-)(1). The velocity increased to approximately 1 x 10(-)(1) mm ms(-)(1) when synaptic inhibition was blocked, suggesting that inhibitory processes normally restrict the spread of firing. At distances of 1.5-2.5 mm, KA injection induced a short-term increase in firing which was maintained, and often increased and rhythmic at gamma frequencies at 2-5 h after injection. We also examined slices prepared from animals injected with KA, at a delay of 2-5 h corresponding to the expression of status epilepticus. Near the injection site, Gallyas silver staining revealed cellular degeneration, and no activity was recorded. Interictal-like activity was generated by ipsilateral slices distant from KA injection. Contralateral slices also generated an interictal-like activity, but no cell death was detected. Hippocampal oscillations generated at distant sites may be associated with status epilepticus.

Action Potentials↗

Dorsal root reflexes and cutaneous neurogenic inflammation after intradermal injection of capsaicin in rats.

The role of dorsal root reflexes (DRRs) in acute cutaneous neurogenic inflammation induced by intradermal injection of capsaicin (CAP) was examined in anesthetized rats. Changes in cutaneous blood flow (flare) on the plantar surface of the foot were measured using a laser Doppler flowmeter, and neurogenic edema was examined by measurements of paw thickness. To implicate DRRs in neurogenic inflammation after CAP injection, the ipsilateral sciatic and femoral nerves were sectioned, dorsal rhizotomies were performed at L(3-)-S(1), and antagonists of GABA or excitatory amino acid receptors were administered intrathecally. Intradermal injection of CAP evoked a flare response that was largest at 15-20 mm from the injection site and that spread >30 mm. Acute transection of the sciatic and femoral nerves or dorsal rhizotomies nearly completely abolished the blood flow changes 15-20 mm from the CAP injection site, although there was only a minimal effect on blood flow near the injection site. These procedures also significantly reduced neurogenic edema. Intrathecal bicuculline, 6-cyano-7-nitroquinoxaline-2,3-dione, (CNQX) or D(-)-2-amino-7-phosphonoheptanoic acid (AP7), but not phaclofen, also reduced dramatically the increases in blood flow 15-20 mm from the CAP injection site, but had only a minimal effect on blood flow near the injection site. Neurogenic edema was reduced by the same agents that reduced blood flow. Multiunit DRRs recorded from the central stumps of cut dorsal rootlets in the lumbar spinal cord were enhanced after CAP injection. This enhanced DRR activity could be reduced significantly by posttreatment of the spinal cord with bicuculline, CNQX or AP7, but not phaclofen. It is concluded that peripheral cutaneous inflammation induced by intradermal injection of CAP involves central nervous mechanisms. DRRs play a major role in the development of neurogenic cutaneous inflammation, although a direct action of CAP on peripheral nerve terminals or the generation of axon reflexes also may contribute to changes in the skin near the injection site.

Animals↗

Intramyocardial injections and protection against myocardial ischemia. An attempt to examine the cardioprotective actions of adenosine.

BACKGROUND: Although adenosine has been proposed to be a cardioprotective agent, direct examination of such protection is confounded by its short half-life and hemodynamic effects. We attempted to avoid these problems by injecting adenosine directly into cardiac muscle. METHODS AND RESULTS: We gave four adenosine injections (each 0.15 mL, 5 mg.mL-1 saline) into the left ventricular wall of rat hearts before a 60-minute occlusion. Although infarcts were smaller in adenosine-treated hearts (29 +/- 6%) than in controls (52 +/- 5%; P < .05), injection of saline also reduced infarct size (29 +/- 7%). Infarcts in hearts subjected to needle insertion but no fluid injection differed neither from control nor from fluid-treated hearts (38 +/- 4%). Adenosine reduced ectopic beats and the incidence of ventricular tachycardia during occlusion. In contrast, saline injection prolonged the duration of arrhythmias. To examine the spatial relationship between protection and the injection site, we gave 18 saline injections (each 0.15 mL) into canine myocardium before a 60-minute occlusion. Infarcts were smaller in saline-treated hearts than in controls (P < .01). Because infarcts in four hearts occupied < 3% of the risk region, we concluded that fluid injection did not itself cause appreciable necrosis and speculated that muscle was protected in the vicinity of the injection site. Previous work indicated that muscle can be protected by stretch. We examined this hypothesis by adding gadolinium chloride (a stretch-activated channel blocker) to the saline (0.008 g.mL-1) injection in rat hearts. We again found small infarcts after saline injection (26 +/- 5%); however, gadolinium blocked protection (50 +/- 7%; P < .03). CONCLUSIONS: Although we were only partially successful in documenting adenosine-mediated cardioprotection, we found evidence for myocyte protection via a stretch-activated mechanism.

Adenosine↗

Adrenocorticotropin release induced by intracerebroventricular injection of recombinant human interleukin-1 in rats: possible involvement of prostaglandin.

ACTH release induced by iv and intracerebroventricular (icv) injection of recombinant human interleukin-1 beta (IL-1 beta) or alpha (IL-1 alpha) was studied in conscious, unrestrained rats. A dose as small as 3 ng of IL-1 beta injected icv induced a significant rise in plasma ACTH levels, whereas 100 ng/100 g body wt (approximately 300 ng/rat) was needed for a significant ACTH response when injected iv. Intracerebroventricular administration of 30 ng IL-1 alpha tended to increase plasma ACTH levels, but not significantly. Intravenous injection of 1000 ng/100 g IL-1 beta induced a maximal response with a pronounced elevation of plasma ACTH levels at 10 and 30 min after injection, but plasma ACTH levels fell at 60 min post injection. On the other hand, icv injection of 30 ng IL-1 beta raised plasma ACTH levels at 10 min, reaching peak values between 30 and 60 min post injection, and plasma ACTH levels remained elevated for 2-3 h after injection. Pretreatment with indomethacin completely prevented the ACTH response induced by either iv or icv injection of IL-1 beta. Administration of indomethacin did not alter the elevation of plasma ACTH levels induced by immobilization stress, however. On the other hand, vagotomy did not alter the ACTH response to iv administered IL-1 beta. Neither iv nor icv injection of IL-1 beta in a dose which induced a maximal ACTH response altered plasma PRL levels. These findings strongly suggest that the brain is the primary site of action of IL-1 beta, and that IL-1 beta transmits the message of the immune system to the brain and, possibly, CRF neurons. It is also suggested that prostaglandins may be involved in this central action of IL-1 beta.

Adrenocorticotropic Hormone↗

Mechanisms by which blood levels of interleukin-6 (IL-6) are elevated after intracerebroventricular injection of IL-1beta in the rat: neural versus humoral control.

Intracerebroventricular (icv) injection of interleukin-1beta (IL-1beta) in rats induces elevated IL-6 levels in peripheral blood, exceeding those induced by iv or ip injection. Two hypotheses postulated to explain this phenomenon were tested. Mediation by peripheral sympathetic activation was excluded by showing that agents that blocked preganglionic cholinergic synapses (chlorisondamine), beta-adrenergic receptors (propanalol, butoxamine), and alpha-adrenergic receptors (phentolamine) did not prevent the IL-6 response. That the peripheral response was due to passage of the injected IL-1beta into blood from the brain was supported by several observations. Immunoreactive IL-1beta appeared in peripheral blood by 10 min after icv injection and remained constant between 10-100 min after injection; values after icv injection were virtually identical to those after iv injection at 60 and 80 min. Radioiodine-labeled IL-1beta appeared in blood as early as 5 min, and by phamacokinetic analysis was found to be transferred from the brain at a rate greater than 2% of brain content per min(-1). IL-1beta infused iv in a pattern mimicking brain to blood transfer induced IL-6 levels that were more than double the values induced by a single bolus injection and were not significantly different from the values observed after icv injection. Sustained levels of IL-1beta in blood over time contribute to the high peripheral IL-6 response. This was shown by administering the same total dose iv as a single bolus of 100 ng or in two doses of 50 ng 1 h apart. Rats given a divided dose had 6-10 times higher blood IL-6 levels at 2 h than those given a single injection. The high levels of IL-6 in blood after icv injection of IL-1beta are best explained by the reservoir function of the brain IL-1beta pool and the self-priming effect of IL-1beta in peripheral tissues.

Adrenergic alpha-Antagonists↗

Effects of ovine corticotropin-releasing hormone injection and desmopressin coadministration on galanin and adrenocorticotropin plasma levels in normal women.

The neuropeptide galanin (GAL) has been shown to be located in the pituitary gland and to modulate the secretion of several pituitary hormones. In the human pituitary, GAL is almost exclusively located within corticotrophs. We examined whether GAL is secreted from corticotrophs in response to stimuli that induce ACTH release. Plasma levels of GAL and ACTH were evaluated in six healthy female subjects in the follicular phase of the menstrual cycle after the following treatments: 1) ovine CRH (oCRH) injection during saline (SAL) infusion, 2) oCRH injection during infusion of the arginine vasopressin analog desmopressin (DP), 3) SAL injection during DP infusion, and 4) SAL injection during SAL infusion. DP (4.3 ng/min.kg BW) or SAL was infused from 0-60 min. oCRH (1 microgram/kg BW) or SAL was administered by a 2-min injection at 5 min. The expected ACTH response to oCRH was enhanced by the concomitant DP administration (peak level, 10.39 +/- 1.12 vs. 21.37 +/- 3.43 pmol/L in SAL infusion plus oCRH injection vs. DP infusion plus oCRH injection, respectively; P < 0.05). The mean integrated ACTH response, expressed as the area under the curve, to SAL infusion plus oCRH injection vs. that to DP infusion plus oCRH injection was 288.23 +/- 61.94 vs. 699.70 +/- 91.80 pmol/L.60 min, respectively (P < 0.05). A slight, but not significant, increase was observed in ACTH values after DP infusion plus SAL injection compared to that after SAL infusion plus SAL injection challenge. Plasma GAL levels were highly variable. No changes in GAL levels were found concomitant to ACTH values in either experimental group. In fact, GAL levels were not significantly affected by either treatment. These data confirm that DP potentiates the ACTH response to CRH in humans. Furthermore, our results suggest that GAL is probably not cosecreted with ACTH in normal subjects. The possibility exists that GAL produced by corticotrophs exerts its action principally through a locally mediated paracrine or autocrine mechanism without being secreted into the bloodstream.

Adrenocorticotropic Hormone↗

Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.

OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients. METHODS: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack. Other possible etiologies were excluded. Echo contrast medium was injected in an alternating mode via antecubital or femoral veins. Tests were performed with and without the Valsalva maneuver. The criteria for a PFO were that the contrast pass from the right to the left atrium (TEE) and early detection (<10 seconds) of more than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5% via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral injection plus the Valsalva maneuver. The difference between femoral and antecubital injections was significant with and without the Valsalva maneuver (p < 0.01, chi2 test). There were no differences between TEE and TCD after femoral injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1 seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection. CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral injection. This may be caused by different inflow patterns to the right atrium: inferior vena caval flow is directed to the right atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Thus, femoral injection may help to improve the detection of PFO and may explain the differences between TEE and TCD findings in previous studies.

Adolescent↗

Increase of oral methadone dose in methadone injecting patients: a pilot study.

A pilot study was initiated in seven methadone injecting patients to examine whether intravenous methadone use in patients in oral methadone maintenance treatment could be decreased by increased oral methadone dose. During the study, patients had a standardized methadone dose increase for three weeks, followed by a 12-week follow-up period. Mean methadone doses prior to, and at the end of the study, were 99 mg/day and 163 mg/day, respectively. On week 15, the mean frequency of injection and the mean proportion of methadone dose injected were reduced to 46% of the values measured at week 0 (p = 0.043 and p = 0.028, respectively). Two patients did not modify their fre- quency, nor their dose of injected methadone, four patients decreased their use of injectable methadone, while one completely stopped injecting methadone. Since the completion of the pilot study, an augmentation of oral methadone dose has been proposed as a therapeutic option to 18 other methadone injecting patients. Five patients did not change their frequency of injection. They did, however, either completely stop or decrease their illicit opiate consumption. Nine patients decreased their frequency of methadone injection from a mean 95% down to 35%. Finally, four patients completely stopped injecting methadone. Although the present results have to be confirmed by controlled studies including a larger number of patients, when considering the high frequency of methadone injection in some places and the associated problems, the therapeutic option of increasing methadone dose should be considered further.

Administration, Oral↗

Periodontal ligament injection: a clinical evaluation.

Attaining profound local anesthesia is frequently difficult. Standard block or infiltration injections often are not sufficient; a supplementary injection is often necessary. The purpose of this study was to examine the effectiveness of the periodontal ligament injection in patients who did not have adequate pulpal anesthesia. Information was obtained by questionnaire after 120 periodontal ligament injections. The frequency and rapidity of onset of anesthesia was determined as well as the factors that might affect the technique. The following conclusions were obtained from this study. -Mandibular molars required supplementary anesthesia more frequently than other types of teeth. -Injecting under strong backpressure was important; the greatest frequency of success was attained when injecting under pressure. Injecting without strong pressure on both mesial and distal surfaces resulted in the lowest frequency of anesthesia. -Onset of anesthesia was generally very rapid, usually immediate. -The length and gauge of needle were unimportant in attaining anesthesia. -Rejection was frequently successful if the first periodontal ligament injection failed. -The overall frequency of success in attaining anesthesia with this injection was 92%. This rate included situations in which the injection was administered more than once. -The most critical factor was to inject under strong resistance. This necessitates wedging the finger supported needle into the interproximal space between root surface and bone and applying maximum pressure to the syringe handle.

Anesthesia, Dental↗

Injection pain of bupivacaine with epinephrine vs. prilocaine plain.

BACKGROUND: Prilocaine plain has been described in the literature as causing less pain on injection than bupivacaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution. METHODS: In a double-blind study design, 681 consecutive patients in a general dental practice received maxillary buccal infiltration, posterior palatal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately after injection, patients rated the pain from each injection on a six-point scale. The pain response was analyzed according to treating dentist, location of injection, patient's sex and anesthetic administered. RESULTS: The reported pain on injection of bupivacaine with epinephrine was significantly greater than that of prilocaine plain. Patients reported no significant difference in pain at different injection locations, except that palatal injections caused significantly more reported pain than did anterior maxillary infiltration, posterior maxillary infiltration or inferior alveolar block injections. CONCLUSIONS: Under clinical conditions, the injection of bupivacaine with epinephrine causes significantly more perceived pain than does the injection of prilocaine plain. Clinical Implications. Bupivacaine with epinephrine and prilocaine plain have certain advantages and disadvantages that should be considered before choosing an anesthetic for a dental procedure. A disadvantage of bupivacaine with epinephrine is that it produces more perceived pain than does prilocaine plain.

Adolescent↗

Injection pain: comparison of three mandibular block techniques and modulation by nitrous oxide:oxygen.

BACKGROUND: The authors conducted this study to compare the pain on injection of the three mandibular block techniques and to determine the effect that the delivery of nitrous oxide:oxygen, or N2O:O2, had on this pain. METHODS: Based on sample size calculation, the authors randomly assigned 60 subjects to receive either local anesthetic alone or local anesthetic with N2O:O2 titrated to effect. Each subject received two mandibular block injections bilaterally from three possible pairings: Gow-Gates/standard block, standard block/Vazirani-Akinosi or Gow-Gates/ Vazirani-Akinosi. Subjects scored their pain using a 100-millimeter visual analog scale immediately after each injection. The authors analyzed data using analysis of variance, Student t tests and multiple regression analyses. RESULTS: There were no significant differences in pain on injection among the three injection techniques. The subjects in the group that received N2O:O2 and the local anesthetic demonstrated a statistically significant reduction in pain on injection compared with subjects in the group that received the local anesthetic only (P < .05). When N2O:O2 was used, there was a statistically significant decrease in pain with the first injection (P < .0005), an effect not seen with the second injection. CONCLUSIONS: There was no significant difference in pain among the three mandibular block techniques. N2O:O2 can reduce pain on the first injection given, but this effect is not seen subsequently. CLINICAL IMPLICATIONS: The decision to select one of the three mandibular block techniques should be based on factors other than pain on injection. N2O:O2 reduces pain on the first injection only.

Adolescent↗

Continuous s.c. infusion rather than twice-daily injections of IGF-I more effectively increases serum IGF binding protein-3 in female monkeys.

OBJECTIVE: In order to better understand how the IGF-I axis is affected by exogenous IGF-I, this study compared the effects of a constant s.c. infusion of IGF-I with that of twice-daily injections of IGF-I in young adult female rhesus monkeys. Clinical studies suggest that circulating concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) are decreased or unaffected by IGF-I administration, whereas acute increases in IGF-I may increase serum IGFBP-1. However, studies in monkeys indicate that acute or continuous infusion of IGF-I effectively increases serum IGFBP-3. DESIGN AND METHODS: Female monkeys were studied for 5 days with no IGF-I supplementation (baseline) and for 5 days of IGF-I treatment by either constant infusion (120 microg/kg per day s.c., n = 5) or twice-daily injections of IGF-I (60 microg/kg per injection s.c., n = 5). Serum samples were collected daily at 0800 h and at 0800, 0900, 1100, 1500, and 2000 h on days 1 and 4 for each condition. Samples were assayed for IGF-I, IGFBPs-1 and -3, insulin, and glucose. RESULTS: Serum IGF-I was consistently increased above baseline within 24 h of the initiation of constant infusion, but was delayed until the second day of treatment in the injection group. Serum IGFBP-3 followed the pattern of IGF-I, with concentrations increased by day 1 during constant infusion and by day 2 during intermittent injections. Although both treatments effectively increased serum IGFBP-3, the increase was greater during constant infusion (31% above baseline) compared with injection (17%). Immunoblotting revealed that the constant infusion of IGF-I resulted in quantitatively more lower-molecular-mass fragments of IGFBP-3 than were observed during baseline or intermittent injections. Size-exclusion chromatography and ultrafiltration indicated that most IGFBP-3 was found in the ternary complex, with a greater percentage found in the ternary complex during baseline (90%) than during constant infusion (86%) or intermittent injections of IGF-I (87%). In contrast, serum concentrations of IGFBP-1 were increased on day 1 of both treatments, but declined towards baseline values as treatment progressed. Serum concentrations of insulin and glucose were unaffected by either mode of IGF-I treatment. Serum concentrations of IGF-I and IGFBP-3 were increased within 3h of the injection, before declining towards the pre-injection level. In contrast, the daily pattern of serum hormone concentrations was similar between the baseline condition and during constant infusion of IGF-I. Although higher during the treatment phase, serum IGF-I and IGFBP-3 concentrations decreased significantly from 0800 h until the afternoon meal, reaching a nadir in the evening before increasing again the next morning. Serum insulin decreased also after the morning meal and increased significantly immediately after the afternoon meal. Although serum IGFBP-1 also decreased initially after the morning meal, concentrations reached a peak before the afternoon meal as serum insulin reached its nadir. CONCLUSION: The results of the present analysis indicate that the constant infusion of IGF-I more effectively sustains serum concentrations of IGF-I and IGFBP-3 than do twice-daily injections. Although the percentage of IGF-I and IGFBP-3 in the ternary complex was similar during both treatments, the constant infusion regimen produced lower-molecular-mass fragments of IGFBP-3. In addition, serum IGF-I and IGFBP-3 appeared to be regulated diurnally, even during IGF-I infusion, whereas IGFBP-1 and insulin were affected by the timing of food intake. Taken together, these data suggest that, in the monkey, IGFBP-3 is regulated by factors in addition to GH, and that IGF-I can affect its own bioavailability by increasing circulating concentrations of IGFBP-3.

Animals↗