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PubMed1997

Influence of the method of intracavernous injection on penile rigidity: a possible pharmacokinetic explanation.

OBJECTIVES: To study whether the method of intracavernous injection of vasodilators has an effect on the clinical outcome and to explain the mechanism of possible influence. METHODS: In an open clinical study, penile rigidity after bolus injection was compared with rigidity after slow injection in 52 self-injecting, impotent patients. In 35 volunteers, venous plasma levels of intracavernosally injected drugs were followed under different injection conditions: slow injection of undiluted drug, slow injection of diluted drug, bolus injection, use of a tourniquet, or slow injection followed by squeeze of the corpora. RESULTS: Of the 52 patients, 28 reported better penile rigidity after a bolus injection than after slow injection of vasodilators. The other 24 reported no difference in rigidity. Systemic side effects did not occur, but 4 patients reported local pain after bolus injection. In the 35 volunteers, the lowest plasma levels were observed when a tourniquet was used or when a bolus injection was performed; the quickest transfer was observed after a slow injection of a low volume of the drug. CONCLUSIONS: Better rigidity was observed after bolus injection in a majority of the patients using the same dose of vasodilators. This could be due to the pharmacokinetic phenomenon of a slower drug transfer to the systemic circulatory system after a bolus than after a slow injection.

Aged↗
PubMed2002

Role of nitric oxide and beta-adrenoceptors of the central nervous system on the salivary flow induced by pilocarpine injection into the lateral ventricle.

Our studies have focused on the effect of L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS), and L-arginine, the substrate of NOS, on salivary secretion induced by the administration of pilocarpine into the lateral cerebral ventricle (LV) of rats. The present study has also investigated the role of the beta-adrenergic agonists and antagonist injected into LV on the salivary secretion elicited by the injection of pilocarpine into LV. Male Holtzman rats with a stainless-steel cannula implanted into the LV were used. The amount of salivary secretion was studied over a 7-min period after injection of pilocarpine, isoproterenol, propranolol, salbutamol, salmeterol, L-NAME and L-arginine. The injection of pilocarpine (10, 20, 40, 80 and 160 microg/microl) into LV produced a dose-dependent increase in salivary secretion. The injection of L-NAME (40 microg/microl) into LV alone produced an increase in salivary secretion. The injection of L-NAME into LV previous to the injection of pilocarpine produced an increase in salivary secretion. L-Arginine (30 microg/microl) injected alone into LV produced no change in salivary secretion. L-Arginine injected into LV attenuated pilocarpine-induced salivary secretion. The isoproterenol (40 nmol/microl) injected into LV increased the salivary secretion. When injected previous to pilocarpine at a dose of 20 and 40 microg/microl, isoproterenol produced an additive effect on pilocarpine-induced salivary secretion. The 40-nmol/microl dose of propranolol injected alone or previous to pilocarpine into LV attenuated the pilocarpine-induced salivary secretion. The injection of salbutamol (40 nmol/microl), a specific beta-2 agonist, injected alone into LV produced no change in salivary secretion and when injected previous to pilocarpine produced an increase in salivary secretion. The 40-nmol/microl dose of salmeterol, a long-acting beta-2 agonist, injected into LV alone or previous to pilocarpine produced no change in salivary secretion. The results have shown that central injections of L-NAME and L-arginine interfere with the salivary secretion, which implies that might participate in pilocarpine-induced salivary secretion. The interaction between cholinergic and beta-adrenergic receptors of the central nervous system (CNS) for the control of salivary secretion can also be postulated.

Animals↗
PubMed2004

Drug injection practices among high-risk youths: the first shot of ketamine.

Ketamine, a "club drug" commonly administered intranasally among youths for its disassociative properties, has emerged as a drug increasingly common among a new hidden population of injection drug users. Because of a scarcity of epidemiological data, little is known about ketamine injection practices, associated risk behaviors, or the demographic characteristics of ketamine injectors. Using an ethno-epidemiological methodology, we interviewed 40 young (<25 years old) ketamine injectors in New York during 2000-2002 and asked detailed questions about ketamine injection initiation as well as histories of other injection drug use and involvement in the street economy. Our analysis, utilizing descriptive statistics and narrative accounts, compared two groups: ketamine initiates (youths who initiated injection drug use with ketamine) and other initiates (youths who initiated injection drug use with another drug, such as heroin, and later transitioned into ketamine injection). Results indicated that intramuscular injections were more common among ketamine initiates, whereas intravenous injections were more common among other initiates. Drug form and local knowledge within injection groups were important factors underpinning this relationship: liquid ketamine was injected primarily intramuscularly; powder ketamine was injected primarily intravenously virtually irrespective of injection drug use history. In addition, the comparison between ketamine initiates and other initiates revealed differences regarding knowledge about injecting drugs; risk behaviors at initiation; involvement in the street economy, including homelessness and experience dealing drugs; and city or location of ketamine injection initiation. These findings suggest that ketamine injection is an emerging practice among a new hidden population of injection drug users in cities throughout North America.

Adolescent↗
PubMed1998

The influence of the bolus injection rate of propofol on its cardiovascular effects and peak blood concentrations in sheep.

UNLABELLED: The influence of the bolus injection rate of propofol on its cardiovascular effects has not been extensively studied. We therefore examined the influence of the injection rate of i.v. bolus doses of propofol on its acute cardiovascular effects and peak blood concentrations in seven chronically instrumented sheep. Each received i.v. propofol (200 mg) over 2 min (slow injection) and 0.5 min (rapid injection) on separate occasions in random order. The rapid injection was associated with more profound decreases in mean arterial blood pressure than slow injection (35.7% vs 23.7% maximal reductions from baseline, respectively; P = 0.02). There were no significant differences between the injection rates for peak reductions in myocardial contractility, increases in heart rate, or degree of respiratory depression. Concurrently, the rapid injections were associated with significantly higher arterial (26.9 vs 11.9 mg/L) propofol concentrations in a manner consistent with indicator dilution principles. There were no differences in the peak coronary sinus concentrations between the injection rates. We conclude that the rapid injection of propofol in the context of the induction of anesthesia produced significantly higher peak arterial propofol concentrations and suggest that it is these higher concentrations that produced relatively greater reductions in arterial blood pressure from rapid injections. IMPLICATIONS: Propofol is injected into a vein to initiate anesthesia. It can cause a rapid decrease in blood pressure, which may be dangerous to the patient. We examined the effect of rapid and slow injection rates of propofol in sheep and found that rapid injection caused a greater decrease in blood pressure. This was because rapid injection caused higher concentrations of propofol in the blood immediately after the injection. We believe that if the same processes occur in humans, there may be little advantage in injecting propofol rapidly.

Anesthetics, Intravenous↗
PubMed2006

Poly-L-lactic acid: consultation on the injection techniques.

OBJECTIVES: When poly-L-lactic acid (PLLA) was first introduced (marketed as New-Fill), incorrect injection technique was largely responsible for the manifestation of device-related adverse events in the form of subcutaneous papules and areas of induration. Now marketed as Sculptra, widespread clinical experience with injectable PLLA has resulted in a wealth of information on product reconstitution and correct injection technique. The injection techniques for the optimal use of injectable PLLA are detailed here. RESULTS: When injecting PLLA it is important to adhere to the product guidelines in terms of injection volume, depth and placement. As the material provides a gradual restoration of volume, PLLA should be injected conservatively, avoiding the possibility of overcorrection. Injections should be sufficiently deep to avoid areas of induration in the superficial layers of the dermis. Areas above hypermobile muscles should also be avoided to prevent localized coalescence of injected material. While utilization of a specific injection technique depends on the position and severity of the volume deficiency, all injections use a 26-gauge needle and are separated by 0.5-1.0 cm. In the lower face a 'criss-cross' and 'tunnelling' technique should be employed, depositing the material into the deep dermis at the junction with the hypodermis, followed by massage every 3-4 injections. Massage should be continued by the patient for at least a week following the treatment session. The 'criss-cross' and 'tunnelling' procedures involve the deposition of 0.1-0.2 mL of PLLA per injection. Material injected into the temple area should be deposited deep next to the bone with a 'depot' technique. Injections around the orbits or perioral region are possible, but should not be attempted without sufficient training. CONCLUSION: Adhering to the correct injection technique enables the physician to provide durable, natural-looking volume restoration with a very low incidence of device-related adverse events.

Adult↗
PubMed2004

Computer-controlled delivery versus syringe delivery of local anesthetic injections for therapeutic scaling and root planing.

BACKGROUND: The authors conducted a study to compare administration of local anesthetic using a computer-controlled delivery device with an aspirating syringe for therapeutic scaling and root planing. The anterior middle superior alveolar, or AMSA, injection was compared with other maxillary injections. METHODS: Twenty healthy adults with moderate periodontal disease participated in this single-blind crossover study. Subjects were evaluated by a trained examiner and were treated by experienced dental hygienists. Subjects provided written and verbal pain ratings via a visual analog scale, or VAS, and a verbal rating scale, or VRS. AMSA injections were compared with syringe-delivered injections--greater palatine, or GP, and nasopalatine, or NP, blocks, and anterior superior alveolar and middle superior alveolar injections--in maxillary quadrants. Bleeding and changes in attachment were evaluated after one month. RESULTS: VAS and VRS scores for AMSA were significantly lower for computer-controlled delivery when compared with NP injections and combined maxillary injections (VAS scores) and with GP and combined maxillary injections (VRS scores). Mean injection times were similar for both groups. Mean gains in attachment were equal, 0.19 millimeters for quadrants anesthetized using computer-controlled injections and 0.22 mm for syringe injections. CONCLUSIONS: Subjects reported having less pain with GP and NP injections delivered using the computer-controlled device, and total injection time was similar to that required for syringe injections. Both techniques provided adequate anesthesia for therapeutic scaling and root planing. Clinical Implications. The two anesthetic delivery techniques were therapeutically equivalent for mandibular injections, and the AMSA injection has clinically significant advantages for maxillary injections.

Adult↗
PubMed2005

Injection Safety Practice among Health Workers in Static Immunisation Centres in an Urban Community of Nigeria.

BACKGROUND: Immunisation injection accounts for less than one-tenth of the global total injections, and it is believed to be safer than therapeutic injections. However, reports have it that about one-third of immunisation injections are unsafe in many countries of the world including Africa. OBJECTIVES: This study was conducted to determine the practice of sage immunisation injection among health workers in static immunisation centres in a urban community in Nigeria with a view to assessing the safety of immunisation injection services in the area. STUDY DESIGN/METHODS: Pre-tested semi-structured questionnaires were administered to 102 consenting staff and observation checklist was completed for each of the 13 fixed immunisation centres in the study area. RESULTS: Most of the subjects 82(80.4%) had poor knowledge of safe immunisation injection and about the same number were not aware of any policy on injection safety. Injection abscess was the main health hazard of unsafe injection reported by majority 71(69.9) of the subjects while as few as 10(9.8%) mentioned needle prick as a health hazard. The common infections associated with unsafe injection listed by the subjects were abscess, HIV and Hepatitis in that order of frequency. Also, most of them 69(67.5%) felt that open burning is the ideal method of disposal of injection waste, while the actual method of disposal practised in most health facilities were mainly open burning (48%) and open dumping into an insecure pit (24%). Up to 83% of the subjects preferred the use of standard disposable syringes and needles for vaccination, but most of them (75(73.5%) confirmed that they use both sterilisable and disposable syringes and needles for vaccination in their health centres. BCG vaccine was exclusively administered using sterilised needles and syringes, while tetanus toxoid was given using disposable syringes and needles in virtually all the centres. Re-use of syringe for vaccine withdrawal and re-capping of used needles before discard were common practices observed while accidental needle stick injury was reported by about half (49%) of the subjects. CONCLUSION: Staff re-training, adequate supplies of injection equipment and provision of appropriate facilities for disposal of injection waste would go a long way to enhance safe immunisation injection practice in the area. Key words: immunisation, injection practice, injection safety.

Disposable Equipment↗
PubMed1996

Healing of muscle trauma after intramuscular injection of antibiotics in sheep: correlations between clinical, macroscopic and microscopic scores.

The present study aimed to predict the resultant healing from early lesions (found days 3 and 10 post injection) caused by the intramuscular injection of veterinary antibiotic formulations. Nineteen marketed drugs were selected in order to screen a wide range of irritation conditions at the injection site. Nineteen ewes were each injected intramuscularly with one of the formulations. Each injection was at a different site, 3 and 10 days prior to slaughter. Fourteen of these ewes also received intramuscular injections at two other sites 21 and 32 days prior to slaughter. The tolerance was monitored by clinical examination of the injection site and by gross and microscopic pathology. Myodegeneration and fibre necrosis were determined histologically. The clinical scores did not correlate with the other findings. Myodegeneration correlated with the size of the lesion on day 3 post-injection and was not found thereafter. Although occasionally found alone, it was generally associated with and surrounded by fibre necrosis. When myodegeneration was the only lesion, regeneration was complete by day 21 and the fibrosis was minimal or absent. Necrosis at day 10 post-injection correlated with necrosis at days 3, 21 and 32 post-injection. Fibrosis became prominent around the necrotic muscles from day 10 post-injection. Healing from necrosis was slow with, in some instances, encapsulated debris still persisting at day 32 post-injection. The tissue irritation index correlated well with myodegeneration and necrose (acute lesions) and fibrose and necrose (older lesions). Thus, after considering a large sample of antibiotic formulations, this study indicated that healing could be predicted from the muscle fibre histopathology at days 3 and 10 post-injection. If myodegeneration was found alone, full recovery within 21 days could be predicted. If fibre necrosis was extensive, the healing involved encapsulating the necrotic tissues and thus resulted in extensive scar formation. The tissue changes explained why the irritation index of the lesions at days 21 and 32 post-injection could be predicted from their irritation index at days 3 and 10 post-injection. Likewise, the size of the lesion at days 21 and 32 post-injection could not be predicted from its size at day 3 post injection.

Animals↗
PubMed1958

Studies on the transfer of lymph node cells. XI. Effect on the anti-Shigella agglutinin titers of recipient rabbits of the prior injection of leucocytes from the donor animals.

The transfer to rabbits of homologous lymph node cells which have been incubated in vitro with Shigella-trypsin filtrate leads to the appearance of agglutinins to Shigella in the sera of the recipients. In the present study it has been found that the prior injection of the prospective recipients with blood leucocytes from the donor animals prevented the appearance of anti-Shigella agglutinins. The following observations have been made in this system: 1. The degree of the pre-injection effect was found to be a function of the number of leucocytes injected and of the interval between such pre-injection and the transfer of the antigen-incubated lymph node cells. 2. The pre-injection of leucocytes at appropriate intervals could also cause the failure of antibody to appear in sera of recipients of lymph node cells when these were obtained from donor rabbits injected with Shigella, 1, 2, or 3 days prior to cell transfer. 3. Agglutinins failed to appear in cell-transfer experiments after the pre-injection not only of blood leucocytes, but also of lymph node cells, peritoneal exudate cells, or thymus cells of rabbits. This effect was not brought about by pre-injection of erythrocytes of rabbits or leucocytes of chicken, cow, or horse. The pre-injection of leucocytes of human blood had an effect of partial suppression. 4. When the leucocytes for pre-injection were pooled from groups of rabbits, either the prospective donors of the lymph node cells or other rabbits, essentially complete suppression of agglutinin titers occurred regularly. When the leucocytes for pre-injection were obtained from an individual rabbit and the lymph node cells from another rabbit the suppression of the recipients' titers occurred sporadically. 5. When the recipient's own leucocytes were pre-injected the subsequent agglutinin titers were somewhat lower than those of the non-pre-injected controls. When the recipient's whole blood was re-injected as the source of leucocytes the subsequent agglutinin titers were as high as those of the non-pre-injected controls. 6. The pre-injection effect was not obtained if the leucocytes had been heated, frozen and thawed, suspended in distilled water, lyophilized, or treated with sodium iodoacetate. However, sonic oscillation or x-irradiation of the leucocytes had no effect on their capacity to bring about the pre-injection effect.

Agglutination↗
PubMed2005

Cessation of injecting drug use among street-based youth.

Young injecting drug users (IDUs) are at high risk for a number of negative health outcomes such as hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infection. However, very little is known about injecting drug-use patterns among this population, particularly with respect to cessation of injection. We sought to identify the factors associated with cessation of injection in a population of young street-based IDUs. A prospective cohort study design was used to assess long-term (> or = 1 year) cessation of drug injection. Data was collected between January 1995 and September 2000 in Montreal, Québec, Canada. Subjects were originally recruited from various street-based outreach programs in Montreal and, for this study, had to have reported injecting drugs within the prior 6 months at baseline or during follow-up and had to have completed at least two semiannual follow-up questionnaires. Cessation incidence rates stratified by duration of injection and adjusted hazard ratios (AdjHRs) were calculated. A Cox proportional hazards regression model was used to identify risk factors independently associated with cessation of drug injection. Of 502 young IDUs, 305 subjects met the inclusion criteria. Cessation of injection for approximately 1 year or more occurred in 119 (39%) of the young IDUs. The incidence of cessation was 32.6/100 person-years but consistently declined as duration of time spent injecting increased. Independent predictors of cessation of injection were currently injecting on a less than monthly or less than weekly basis (HR = 6.4; 95% confidence interval (CI): 3.0-13.6 and HR = 2.4; 95% CI = 1.1-5.3, respectively); currently injecting two or fewer different types of drug (HR = 2.1; 95% CI = 1.1-4.0); currently employed (HR = 1.7; 95% CI = 1.1-2.7); and having at least one parent born outside of Canada (HR = 1.4; 95% CI = 1.1-1.7). Independent predictors of not ceasing injection were currently attending a needle-exchange program (HR = 0.5; 95% CI = 0.3-0.8); and current homelessness (HR = 0.6; 95% CI = 0.4-1.0). The early sharp decline in cessation of drug injection followed by a consistent decrease in this rate suggest difficulties in breaking the habit later on in the drug injecting career. Intensity of drug use and factors which may help to stabilize the social environment of the young IDU may also influence the ability to stop injecting.

Adolescent↗
PubMed1992

The effect of postmortem time of injection and freezing on the effectiveness of calcium chloride for improving beef tenderness.

Three experiments were conducted to determine the effect of freezing and time postmortem on the effectiveness of injecting CaCl2 to tenderize beef. In Exp. 1, longissimus muscle treatments included 1) control 0 h, 2) CaCl2-injected 0 h, 3) control 24 h, and 4) CaCl2-injected 24 h. Injection consisted of .3 M CaCl2 at 10% by weight. Injecting CaCl2 at 24 h postmortem reduced (P < .05) shear force requirements compared with the 24 h control but did not (P < .05) tenderize meat as much as injecting at 0 h. In Exp. 2, longissimus muscle treatments included the following: 1) aged 2 d; 2) aged 7 d; 3) frozen d 1, thawed, aged 6 d; 4) CaCl2-injected d 1, aged 6 d; 5) frozen d 1, thawed, CaCl2-injected, aged 6 d; and 6) CaCl2-injected d 1, frozen, thawed, aged 6 d. Injection alone at d 1 or freezing, then thawing and injecting resulted in the lowest (P < .05) shear force requirements. In Exp. 3, longissimus muscle treatments included the following: 1) aged 1 d; 2) aged 7 d; 3) CaCl2-injected 0 h, aged 7 d; 4) CaCl2-injected d 1, aged 6 d; 5) frozen d 1, thawed, aged 6 d; and 6) frozen, thawed, CaCl2-injected, aged 6 d. Both d-1 injection alone and freezing, thawing, then injecting resulted in meat with shear force requirements similar to those of 0-h injected meat. The effect of treatments on cooking loss was inconsistent. Treatments that reduced shear force also reduced (P < .05) calpain and calpastatin activity proportionately.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Influence of Route of Injection on Efficacy and Side Effects of Immunisation.

Immunisation experiments are performed on a large scale in laboratory animals e.g. for the production of antibodies. Depending on the immunisation protocol, severe discomfort may be induced. In several countries, guidelines for the immunisation of laboratory animals were drafted to refine immunisation protocols. One of the aspects that effects the immune response as well as the side effects is the route of injection. Careful selection of the route of injection is therefore crucial to refine immunisation protocols. In several papers the influence of the route of injection on the immune response is studied but generally the induced discomfort in the animals is not evaluated.In several comparative experiments we studied the influence of the route of injection on efficacy and side effects. The most widely used routes of injection were compared in rabbits (subcutaneous and intramuscular injection) and in mice (subcutaneous and intraperitoneal injection). After the injection of several adjuvant- (Freund's adjuvant, TiterMax, RIBI, Specol, or Montanide ISA50) and antigen- (synthetic peptide, glycolipid, or particulate antigen) combinations by different routes, we studied antibody production to evaluate efficacy of the injection and clinical-, physiological- and behavioural parameters and pathology (macroscopy/microscopy) to compare the induced side effects. In both rabbits and mice minimal differences in antibody titers were found between the two routes under study. However, differences in the severity of the induced side effects did occur. In rabbits, no significant differences were found in clinical, physiological and behavioural parameters but severe pathological changes were found depending on the route of injection. In mice, the intraperitoneal injection induces significant discomfort as compared to subcutaneous injection as shown by the severity of the pathological changes in the peritoneum and by the decreased activity of the animals. Important disadvantages of intramuscular and intraperitoneal injections are that these injections are difficult to perform properly and that the injection site is hard to monitor. Since minimal differences in antibody production were found between the two routes of injection, we concluded that the subcutaneous route of injection is preferred for the induction of polyclonal antibodies in rabbits and mice when an adjuvant is applied.

Journal Article↗
PubMed2005

Injection therapy for enthesopathies causing axial spine pain and the "failed back syndrome": a single blinded, randomized and cross-over study.

BACKGROUND: Enthesopathies are a common cause of axial pain that is amenable to "minimally invasive" therapy. OBJECTIVE: To evaluate the effectiveness of injection therapy for enthesopathies. DESIGN: Single blinded, randomized, and cross-over study. METHODS: Thirty-five patients diagnosed as having painful enthesopathies as a major pain generator were studied. Of the patients studied, 86% of patients had undergone prior lumbar spine surgery and all were referred for neurosurgical evaluation for possible surgery. Patients were injected either with anesthetics alone or with anesthetics combined with phenol-glycerol proliferant prolotherapy. Outcomes were analyzed both clinically at the time of regular follow-ups, and by a series of multipart questionnaires. RESULTS: Patients received a total of 86 injections, 39 with local anesthetics, and 47 with prolotherapy. By clinical assessment patients obtained excellent to good relief of pain and tenderness after 80% of prolotherapy injections, but only 47% after anesthetics alone. By questionnaire, 66% reported excellent to good relief after prolotherapy vs. 34% after anesthetics alone. Patients reported improvement in work capacity and social functioning following both types of injections, but a greater reduction in focal pain intensity following prolotherapy injections. The mean and median durations of persistent relief were 2.4 and 1.75 months with prolotherapy vs. 1.8 and 0.75 months with anesthetics alone. Roughly 10% obtained greater than six months of relief from either injection. In the crossover portion of the study, patients reported that prolotherapy injections following initial anesthetic-only injections provided much better relief than that achieved after their anesthetic-only injections, and that anesthetic-only injections following initial prolotherapy injections failed to provide relief as good as that achieved after their prolotherapy. Subsequent to this study, only four of 35 patients required additional spine surgery, but 29 of the 35 patients requested additional injections. CONCLUSIONS: Injection therapy of painful enthesopathies can provide significant relief of axial pain and tenderness combined with functional improvement, even in "failed back syndrome" patients. Phenol-glycerol prolotherapy provides better and longer lasting relief than injection with anesthetics alone. Prolotherapy provides over six months of relief for some patients but generally provides relief for only a few months. However, most patients described good to excellent relief, felt that the injections had been beneficial, and requested additional injections for recurrent or residual focal pain.

Journal Article↗
PubMed1996

The biological effects of radium-224 injected into dogs.

A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224Ra chloride. The 224Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224Ra kg-1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed alpha-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. The occurrence of bone tumors was highest in the dogs given the highest dose in 50 injections. The age-specific incidence rate for mammary tumors was increased in all three injection groups. The results of this study revealed two important exposure-rate effects. Hematological dyscrasia was amplified by delivery of relatively high doses at a high exposure rate. In contrast, bone tumors were amplified by delivery of relatively high doses at a lower exposure rate (i.e. dose delivered over 1 year rather than 1-3 months). There was a dose-response relationship for the induction of nasal mucosal tumors and mammary tumors. These findings in dogs are similar to those in humans injected with 224Ra, except for the nasal tumors. The calculated risk of developing a bone tumor was about 40 times higher in dogs than reported for humans.

Animals↗
PubMed2004

Hydrodynamics-based transfection of the liver: entrance into hepatocytes of DNA that causes expression takes place very early after injection.

BACKGROUND: The mechanism of gene transfer into hepatocytes by the hydrodynamics-based transfection procedure is not clearly understood. It has been shown that, after a hydrodynamic injection, a large proportion of plasmid DNA remains intact in the liver where it is bound to plasma membrane and suggested that this DNA could be responsible for the efficiency of the transfection. METHODS: We have investigated the problem by giving mice a hydrodynamic injection of isotonic NaCl, followed at different time intervals by a conventional injection of DNA, cold or labelled with (35)S, with cDNA of luciferase as a reporter gene. Then, we determined the consequences of that dual injection on luciferase expression and on DNA uptake by the liver and its intracellular fate. By such experiments, it is possible to establish the time dependency of the induction of liver changes caused by a hydrodynamic injection on the one hand and the expression and DNA uptake and fate on the other. Moreover, some experiments have been performed on primary cultures of hepatocytes isolated after a hydrodynamic injection of DNA. RESULTS: When DNA is given to mice by a conventional injection a few seconds after an hydrodynamic injection of isotonic NaCl, luciferase expression in the liver is considerably lower than that observed after a single hydrodynamic injection of the plasmid. On the other hand, as assessed by the rate of DNA degradation and by centrifugation results obtained after injection of (35)S-DNA, the uptake and the intracellular fate of the bulk of DNA are similar whether DNA is administered by a single hydrodynamic injection or by a conventional injection given up to at least 2 h after a hydrodynamic injection of isotonic NaCl. Hepatocytes isolated a few minutes after a hydrodynamic injection exhibit a maximal expression that does not depend on the large amount of DNA that remains bound to the plasma membrane for a relatively long time. CONCLUSIONS: Our results show that the efficiency of hydrodynamics-based transfection depends on a process that takes place very quickly after injection and is not linked to a delay of DNA degradation and the persistence of a large proportion of DNA bound to hepatocytes of the plasma membrane, strongly suggesting that expression after a hydrodynamic injection is caused by a small proportion of DNA molecules that rapidly enter the cytosol probably by plasma membrane pores generated by the hydrodynamic pressure.

Animals↗
PubMed2001

Comparison of intradermal and subcutaneous injections in lymphatic mapping.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma, with its intradermal (ID) injection, has a higher success rate than SNB for breast cancer, which is typically performed with a subcutaneous (SC) or peritumor injection. It is hypothesized that this is in part due to a slower transit time of lymphatic mapping agents through the parenchymal lymphatics of the breast. No study has investigated differences in transit time between different tissues to account for this clinical observation. The goal of the study was to compare transit time between ID and SC injections with common agents used in lymphatic mapping. METHODS: Four injection sites on five domestic pigs were used. Sites were bilateral and included cervical, forelimb, hindlimb, and flank areas. Agents included technetium sulfur colloid (Tc99, filtered and unfiltered), isosulfan blue (IB) dye, and fluorescein (FL) dye. At each site both ID and SC injections were made and the transit time to reach the sentinel node was recorded. The transit time differences were calculated per centimeter distance from the draining lymph node basin. RESULTS: Sentinel nodes were identified draining all sites and found to be hot, blue, or fluorescent (using a Wood's lamp for identification). The cervical and forelimb injection sites drained to the same cervical lymph node basin and both SC and ID injection sites drained to the same sentinel node. Similarly, the hindlimb and flank injection sites both drained to inguinal lymph node basins. The slowest transit time occurred with Tc99 injected SC and the fastest occurred with Tc99 injected ID, whereas both FL dye and IB traveled rapidly to the sentinel node whether injected SC or ID. Large differences were found using unfiltered Tc99 depending on its injection ID (2.7 s/cm +/- 0.5) vs SC (249 s/cm +/- 14.7, P = 0.008). CONCLUSIONS: Tc99 ID injections were significantly faster than SC injection. The slowest and fastest SC injection agents were unfiltered Tc99 and IB, respectively. Dermal injections provide faster transit of lymphatic agents and may improve the identification rate when applied to patients with breast cancer.

Animals↗
PubMed2000

Comparison of intravenous and pulmonary artery injections of hypertonic saline for the assessment of conductance catheter parallel conductance.

OBJECTIVE: The conductance catheter provides a continuous measure of left ventricular volume. Conversion of raw data to calibrated absolute volume requires assessment of parallel conductance. Conventionally, parallel conductance is determined by injecting a small bolus hypertonic saline into the pulmonary artery and analyzing the signal obtained during passage of the bolus through the left ventricle. However, in some cases, a pulmonary artery catheter is not practicable. Therefore, we investigated whether intravenous hypertonic saline injections yield reliable parallel conductance estimates. METHODS: In 13 anesthetized sheep (33+/-5 kg) parallel conductance was obtained by pulmonary artery and by intravenous injections. Measurements (triplicate) were done at baseline, during dobutamine and pacing, and repeated after embolization of the right coronary artery in order to assess the effects of enlarged right ventricular volumes. We used a multiple linear regression model to determine the relation between parallel conductance obtained by the two methods and to quantify the effects of dobutamine, pacing, and embolization. RESULTS: The two methods show an excellent correlation with a systematic overestimation for intravenous injection. The mean parallel conductance obtained by pulmonary artery injection was 0.690+/-0.009 ohm(-1) whereas intravenous injection yielded 0.739+/-0.015 ohm(-1). Interanimal variability was 0.138 ohm(-1). The difference between the two methods was relatively small, but highly significant (+0.049+/-0.012 ohm(-1), P<0.001). Embolization resulted in significantly higher values (+0.141+/-0.017 ohm(-1), P<0.001), but dobutamine and pacing did not significantly affect parallel conductance (+0.021+/-0.016 ohm(-1), NS). There was no interaction between these interventions and the injection method, indicating that the relation between parallel conductances obtained by the two methods was maintained in all conditions. CONCLUSION: Parallel conductance obtained by intravenous injection was significantly higher (+7%) than by pulmonary artery injection. However, the relation between the two methods is highly linear with an excellent correlation and is not affected by large hemodynamic changes. The systematic difference between the two methods is likely due to increased conductivity of blood in the right ventricle which is present with intravenous injection but not with pulmonary artery injection. Determination of parallel conductance by intravenous injection is a good alternative for conventional pulmonary artery injection and may be applied in studies where pulmonary artery injection is problematic. This may include studies in very small animals or studies in patients prone to arrhythmias or with cardiac anomalies such as pulmonary artery stenosis. In addition, intravenous injection could be used in biventricular studies to obtain right and left ventricular parallel conductances from a single saline injection.

Animals↗
PubMed1996

Effect of intravenous or intracerebroventricular injections of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on GH release in conscious, freely moving male rats.

The present study was designed to examine the effects of intracerebroventricular injection of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP) on GH secretion in freely moving conscious male rats and to determine whether the central action of GHRP is mediated by increased GHRH and/or somatostatin (SRIF) release. A significant and dose-related suppression of natural fluctuations in plasma GH occurred immediately after intracerebroventricular injection of GHRP at the doses of 1, 3 and 10 mu g/rat and was sustained for more than 1 h. An intracerebroventricular injection of GHRP also suppressed plasma GH rises after an intravenous injection of [D-Ala2, Nle27] human GHRH (1-28)agmatine (hGHRH analog), but the GH suppression by intracerebroventricular GHRP was significantly blunted in rats treated with antirat SRIF gamma-globulin (SRIF-ab). In addition, the suppression by intracerebroventricular GHRP of hGHRH-analog-induced GH release was observed even in rats treated with anti-rat GHRH goat gamma-globulin (GHRH-ab) which does not cross-react with hGHRH analog, and again its suppression was significantly attenuated by simultaneous treatment with SRIF-ab and GHRH-ab. Furthermore, intracerebroventricularly injected GHRP was effective enough to inhibit the central-nervous-system (endogenous GHRH)-driven natural GH-secretory surges in SRIF-ab-treated rats. When 10 mu g/kg GHRP was injected intravenously every 1 h during a 7-hour observation period in control rats without antibody treatment, plasma GH levels were increased with the peak 10 min after each injection during the surge period of the GH-secretory rhythm, but the plasma GH response to GHRP was frequently absent during its trough period. In addition, in SRIF-ab-treated rats, basal GH levels as well as plasma GH peaks after GHRP injections were markedly elevated and the obvious plasma GH rises after GHRP could be observed even during the trough period. In GHRH-ab-treated rats, basal GH levels were lower, and the plasma GH response to GHRP was significantly attenuated as compared with those in control rats. Plasma GH peaks after GHRP injections in rats simultaneously treated with SRIF-ab and GHRH-ab were higher than those in rats given GHRH-ab alone, but its difference in GH response was obviously smaller than that observed between SRIF-ab-treated and control rats, suggesting a crucial role of endogenous GHRH in GHRP-induced GH release. To further clarify the interaction of GHRH and GHRP in GH release, hGHRH analog was injected intravenously alone or simultaneously with GHRP in rats treated with SRIF-ab and GHRH-ab. The peak GH values after simultaneous injection of hGHRH analog and GHRP were significantly higher than the sum of GH peaks after each injection of hGHRH analog and GHRP. In conclusion, an intracerebroventricular injection of GHRP suppresses GH secretion by a central mechanism which is likely to include increased SRIF release, reduced GHRH release or both. We have confirmed that intravenous injection of GHRP can stimulate GH release by itself in an immunologically nullified condition of circulating endogenous GHRH and SRIF in rats, and that endogenous SRIF modestly suppresses the GH-stimulating effect of intravenously injected GHRP while both endogenous and exogenous GHRH markedly enhance GH release by intravenously injected GHRP in a synergistic manner.

Amino Acid Sequence↗