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Initiation to heroin injecting among heroin users in Sydney, Australia: cross sectional survey.

BACKGROUND: Heroin injection is associated with health and social problems including hepatitis C virus (HCV) transmission. Few studies have examined the circumstances surrounding initiation to heroin injecting, especially current users initiating others. The current study aimed to examine the age of first heroin use and injection; administration route of first heroin use; relationship to initiator; the initiation of others among a group of heroin users; and to examine these factors in relation to HCV status and risk. METHOD: Heroin users in Sydney were recruited through needle and syringe programs, a methadone clinic and snowballing. Participants were interviewed about their own initiation to heroin use, blood-borne virus risk and knowledge, and whether they had initiated others to heroin injecting. Information on HCV status was collected via self-report. Data was analysed using univariate and multivariate statistical techniques for Normally distributed continuous and categorical data. RESULTS: The study recruited 399 heroin users, with a mean age of 31 years, 63% were male, 77% reported heroin as their primary drug and 59% were HCV positive (self-report). Mean age at first heroin use and injection was 19 and 21 years, respectively. The majority of heroin users commenced heroin use via injecting (65%), younger users (<25 years, 25-30 years) were less likely than older users (>30 years) to commence heroin use parenterally. Participants were initiated to injection mainly by friends (63%). Thirty-seven percent reported initiating others to heroin injection, but few factors were related to this behaviour. Those with longer heroin using careers were more likely to report initiating others to heroin injection, but were no more likely to have done so in the preceding 12 months. Participants who had initiated others were more likely to have shared injecting equipment (12 vs 23%), but were no more likely to be HCV positive (self-report) than those who did not. CONCLUSION: Interventions to prevent heroin users initiating others to injecting are necessary. Peer groups may be well positioned to implement such interventions.

Journal Article↗

Risk factors associated with injection initiation among drug users in Northern Thailand.

BACKGROUND: Circumstances surrounding injection initiation have not been well addressed in many developing country contexts. This study aimed to identify demographic factors, sexual behaviors and drug use characteristics related to injection initiation among drug users in northern Thailand. METHODS: A cross-sectional survey was conducted among 2,231 drug users admitted to the Northern Drug Treatment Center in Mae Rim, Chiang Mai, Thailand, between February 1, 1999 and December 31, 2000. A multiple logistic regression was employed to identify the independent effects from potential risk factors of transition into injection. RESULTS: After controlling for other covariates, being 20 years of age or older, single, ever receiving education, urban residence, and having a history of smoking or incarceration were significantly associated with higher likelihood of injection initiation. Multiple sex partners and an experience of sex abuse were associated with an increased risk of injection initiation. Comparing to those whose first drug was opium, individuals using heroin as their initiation drug had greater risk of injection initiation; conversely, those taking amphetamine as their first drug had less risk of injection initiation. Age of drug initiation was negatively associated with the risk of injection initiation: the older the age of drug initiation, the less the risk of injection initiation. CONCLUSION: Injection initiation was related to several demographic factors, sexual behaviors and drug use characteristics. Understanding these factors will benefit the design of approaches to successfully prevent or delay transition into injection.

Journal Article↗

Incomplete suppression of thyrotropin secretion after single injection of large L-triiodothyronine doses into hypothyroid rats.

In order to examine the mechanism underlying incomplete suppression of TSH secretion by thyroid hormones, we measured serum TSH and T3 levels (radioimmunoassay) in 3,5,3'-triiodothyromine (T3)-injected groups of euthyroid and hypothyroid rats. In 2 experiments, euthyroid rats received a single injection of 10 mug T3 and 25 mug T3/100 g body weight (BW). After T3 injection, the TSH levels fell rapidly to the undetectable range of the assay (1-5 ng/ml) within 3 h. TSH concentration returned to control levels following reduction of plasma T3 to pre-injection values as a result of hormone metabolism. Hypothyroid rats were used in the remaining experiments. They were injected with T3, 25 mug/100 g BW in 2 studies and 1000 mug/100 g BW in one. TSH levels in vehicle-injected groups were relatively constant for 9 days. In T3-injected groups, TSH decreased rapidly to about 10% of pre-injection concentrations within 5 hours. In the 3 studies, TSH remained at 100 ng/ml, 40 ng/ml and 30 ng/ml for 3-6 days despite markedly elevated T3 values. TSH then increased toward pre-injection values when T3 concentrations decreased to the euthyroid range. In an additional study, the daily injection of T3, 1 mug/100 g BW, resulted in a further decrease in plasma TSH to undetectable values only after 15-25 days. These studies show 2 components of TSH suppression in hypothyroid rats. Ninety per cent suppression occurs rapidly (hours) after a large dose of T3 Suppression of the residual TSH to the undetectable assay range occurs slowly, requiring prolonged (15-25 days) T3 administration. Further studies showed that TSH isolated from plasma of hypothyroid rats after T3 injection had an apparent molecular weight of 29,000 Daltons and exhibited an immunoassay curve parallel to rat TSH RP-1. Persistent secretion of TSH in the face of very high plasma T3 concentrations may reflect partial autonomy of thyrotrophs in TSH secretion or a nonspecific leak of TSH which is related in amount to the number of thyrotrophs present and/or their secretory activity in different thyroid states.

Animals↗

Occurrence of coring in insulin vials and possibility of rubber piece contamination by self-injection.

Coring is reported to occur because rubber pieces are shaved off from a rubber stopper when a needle is inserted into the rubber stopper of transfusion liquid formulation. We verified whether coring really occurs in insulin vials of self-injecting patients. We collected insulin cartridges from 30 hospitalized patients and used the primary injection (trial injection), the secondary injection and the cartridge remaining preparation as samples. We observed the rubber pieces using a microscope and measured the shape, number of pieces. The occurrence rate of coring was 73% for the primary injection, 47% for the secondary injection and 97% for the cartridge remaining preparation. The rubber pieces in the primary injection and the secondary injection which went through the needle are mostly in aggregate shape and the rubber pieces in the cartridge remaining preparation which did not go through the needle are mostly in needle-like shape. A number of small rubber pieces are found in both the primary injection and the secondary injection, indicating a high possibility that rubber pieces may be injected under subcutaneous tissue. The coring is considered to occur because needles are repeatedly inserted and rotated at the same spot. It is required to improve the structure to mount a needle to the pen-type injector in future. Coring is a very serious problem from the medical and pharmaceutical points of view. Further study should be made on the implication to latex allergy and lipodystrophy.

Adult↗

Effect of injectate temperature and thermistor position on reproducibility of thermodilution cardiac output determinations.

STUDY OBJECTIVE: The purpose of this study was to evaluate the effect of thermistor position with varying injectate temperatures on the reproducibility of thermodilution cardiac output determination. The key hypothesis to be tested was that the positioning of the proximal thermistor at the right atrial port would improve the reproducibility of thermodilution cardiac output determination, independent of injectate temperature. DESIGN: Prospective randomized trial. SETTING: The study was performed in the cardiac catheterization laboratory of the West Haven Veterans Affairs Medical Center. PARTICIPANTS: Twenty consecutive patients undergoing right and left heart catheterizations were enrolled in the study. INTERVENTIONS: Each patient underwent triplicate determination of thermodilution cardiac output measurements under four experimental conditions: (1) ambient or room temperature injectate using an external thermistor in the injectate reservoir; (2) iced injectate using an external thermistor; (3) room temperature injectate using an internal right atrium (RA) thermistor; and (4) iced injectate using an RA thermistor. Reproducibility was assessed by the coefficient of variation (CV) and standard error of the mean percent (SEM%), of the triplicate measurements. MEASUREMENTS AND RESULTS: Using an internal RA thermistor improved the reproducibility of cardiac output determinations independent of injectate temperature. Using room temperature injectate, the CV was 12.8 percent using an external thermistor and 7.9 percent using an internal RA thermistor (p < 0.05). Using iced injectate, the CV was 10.2 percent using an external thermistor and 5.5 percent using an internal RA thermistor (p < 0.05). CONCLUSIONS: Reproducibility of thermodilution cardiac output determinations is improved when injectate temperature is measured internally, at the RA, as opposed to externally in the reservoir. This has clinical implications for determining significant changes in serial cardiac output determinations.

Analysis of Variance↗

Initial injection pressure for dental local anesthesia: effects on pain and anxiety.

This study quantitatively assessed injection pressure, pain, and anxiety at the start of injection of a local anesthetic into the oral mucosa, and confirmed the relationship between injection pressure and pain, as well as between injection pressure and anxiety. Twenty-eight healthy men were selected as subjects and a 0.5-inch (12 mm) 30-gauge disposable needle attached to a computer-controlled local anesthetic delivery system (the Wand) was used. A 0.5 mL volume of local anesthetic solution was injected submucosally at a speed of either 30 or 160 s/mL. Three seconds after the start of local anesthetic injection, injection pressure was measured and pain and anxiety were assessed. Injection pressure was measured continuously in real time by using an invasive sphygmomanometer and analytical software, and pain was assessed on the Visual Analogue Scale and anxiety on the Faces Anxiety Scale. A significant correlation was evident between injection pressure and pain (rs = .579, P = .00124) and between intensity of injection pressure and state anxiety (rs = .479, P = .00979). It is therefore recommended that local anesthetic be injected under low pressure (less than 306 mm Hg) to minimize pain and anxiety among dental patients.

Administration, Buccal↗

Excretion of tetramethyllead, trimethyllead, dimethyllead and inorganic lead after injection of tetramethyllead to rabbits.

Rabbits were divided to groups of 3, and injected either 9.9 mg of tetramethyllead (Me4Pb)/kg of body weight (7.7 mg Pb/kg) or 39.7 mg/kg (30.8 mg Pb/kg) into the ear vein once only, respectively, and urinary and fecal excretions of lead were studied for chemical species and total lead during the following 7 days. In the group injected 9.9 mg/kg, the urinary total lead excretion was composed of about 73% dimethyllead (Me2Pb2+), about 19% trimethyllead (Me3Pb+), about 6% inorganic lead (Pb2+), and about 2% Me4Pb on the day following the injection, and 100% Me3Pb+ 7 days after the injection. In the group injected 39.7 mg/kg, the urinary total lead excretion was composed of about 67% Me2Pb2+, about 14% Me3Pb+, about 17% Pb2+, and about 2% Me4Pb on the day following the injection, and about 8% Me2Pb2+, about 74% Me3Pb+, about 17% Pb2+, and about 1% Me4Pb 7 days after the injection. In both groups, the fecal total lead excretion during 7 days after the injection was entirely composed of Pb2+. During the 7 days, 1-3% of either administered dose was excreted in the urine, and 7-19% in the feces. The urinary total lead excretion in the rabbits injected Me4Pb was similar to that in the rabbits injected tetraethyllead, but the fecal total lead excretion in the former was extremely smaller. This extremely small fecal excretion of total lead appeared to have resulted from the less elimination of lead into the bile of Me4Pb-injected rabbits.

Animals↗

Effect of temperature of CO2 injection on the pH and freezing point of milks and creams.

The objectives of this study were to measure the impact of CO2 injection temperature (0 degree C and 40 degrees C) on the pH and freezing point (FP) of (a) milks with different fat contents (i.e., 0, 15, 30%) and (b) creams with 15% fat but different fat characteristics. Skim milk and unhomogenized creams containing 15 and 30% fat were prepared from the same batch of whole milk and were carbonated at 0 and 40 degrees C in a continuous flow CO2 injection unit (230 ml/min). At 0 degree C, milk fat was mostly solid; at 40 degrees C, milk fat was liquid. At the same total CO2 concentration with CO2 injection at 0 degree C, milk with a higher fat content had a lower pH and FP, while with CO2 injection at 40 degrees C, milks with 0%, 15%, and 30% fat had the same pH. This indicated that less CO2 was dissolved in the fat portion of the milk when the CO2 was injected at 0 degree C than when it was injected at 40 degrees C. Three creams, 15% unhomogenized cream, 15% butter oil emulsion in skim milk, and 15% vegetable oil emulsion in skim milk were also carbonated and analyzed as described above. Vegetable oil was liquid at both 0 and 40 degrees C. At a CO2 injection temperature of 0 degree C, the 15% vegetable oil emulsion had a slightly higher pH than the 15% butter oil emulsion and the 15% unhomogenized cream, indicating that the liquid vegetable oil dissolved more CO2 than the mostly solid milk fat and butter oil. No difference in the pH or FP of the 15% unhomogenized cream and 15% butter oil emulsion was observed when CO2 was injected at 0 degree C, suggesting that homogenization or physical dispersion of milk fat globules did not influence the amount of CO2 dissolved in milk fat at a CO2 injection temperature of 0 degree C. At a CO2 injection temperature of 40 degrees C and at the same total CO2 concentration, the 15% unhomogenized cream, 15% vegetable oil emulsion, and 15% butter oil emulsion had similar pH. At the same total concentration of CO2 in cream, injection of CO2 at low temperature (i.e., < 4 degrees C) may produce a better antimicrobial effect during refrigerated shelf life due to the higher concentration of CO2 in the skim portion of the cream.

Animals↗

Safety of immunization injections in Africa: not simply a problem of logistics.

In 1995, the WHO Regional Office for Africa launched a logistics project to address the four main areas of immunization logistics: the cold chain, transport, vaccine supply and quality, and the safety of injections in the countries of the region. The impact of this logistic approach on immunization injection safety was evaluated through surveys of injection procedures and an analysis of the injection materials (e.g. sterilizable or disposable syringes) chosen by the Expanded Programme on Immunization (EPI) and those actually seen to be used. Re-use of injection materials without sterilization, accidental needle-stick injuries among health care workers, and injection-related abscesses in patients were common in countries in the WHO African Region. Few health centres used time-steam saturation-temperature (TST) indicators to check the quality of sterilization and, in many centres, the injection equipment was boiled instead of being steam sterilized. Facilities for the proper disposal of used materials were rarely present. Although the official EPI choice was to use sterilizable equipment, use of a combination of sterilizable and disposable equipment was observed in the field. Unsafe injection practices in these countries were generally due to a failure to integrate nursing practices and public awareness with injection safety issues, and an absence of the influence of EPI managers on health care service delivery. Holistic rather than logistic approaches should be adopted to achieve safe injections in immunization, in the broader context of promoting safe vaccines and safety of all injections.

Africa↗

Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: a phase II study.

This paper reports the result of an open-label, non-randomized clinical trial investigating the efficacy and safety of an injectable preparation of testosterone undecanoate (TU) dissolved in castor oil and given over a 3.2-year period. In a previous study we demonstrated that injections of TU every 6 weeks resulted in satisfactory substitution but a tendency toward testosterone accumulation. Here we investigate prolonged TU treatment at extended injection intervals in 7 hypogonadal men. Injections were given at gradually increasing intervals between the fifth and 10th injection, and from then on every 12 weeks. Steady state kinetics were obtained after the 13th injection. Well-being, sexual activity, clinical chemistry, prostate volume, and prostate-specific antigen (PSA) and serum hormone levels were monitored. Patients were clinically well-adjusted throughout the study. Before the next injection, testosterone, dihydrotestosterone, and estradiol levels were mostly within the normal range and showed a tendency to decrease with increasing injection intervals. Body weight, hemoglobin, serum lipids, PSA, and prostate volume did not change significantly during the 3.2 years of treatment. PSA levels were always within the normal limit. Maximal testosterone levels during steady state kinetics were measured after 1 week with 32.0 +/- 11.7 nmol/L (mean +/- SD). Before the last injection, mean testosterone concentrations were 12.6 +/- 3.7 nmol/L. Compared with conventional testosterone enanthate or cypionate treatment requiring injection intervals of 2-3 weeks and resulting in supraphysiological serum testosterone levels, injections of TU at intervals of up to 3 months offer an excellent alternative for substitution therapy of male hypogonadism.

Adult↗

Fluoroscopic guided lumbar interlaminar epidural injections: a prospective evaluation of epidurography contrast patterns and anatomical review of the epidural space.

OBJECTIVE: To evaluate the pattern and flow of epidural contrast in fluoroscopically guided lumbar interlaminar steroid injections. DESIGN AND METHODS: A prospective case series of 25 (twenty-five) consecutive patients receiving 25 (twenty-five) injections. Patients had either lumbar spinal stenosis (LSS) or herniated nucleus pulposus (HNP). All patients received their injection using a loss of resistance technique. Once the epidural space was felt localized 0.5 mL of Isovue contrast was injected to confirm accurate needle placement. If in the epidural space, another 4.5 mL was injected for a total of 5 mL contrast media. Both AP and lateral radiographs were obtained and reviewed by a physician trained in fluoroscopic injections for review of the contrast pattern. Patterns recorded were Unilateral, Bilateral, Ventral or Dorsal. The dorsal flow was also characterized as being cephalad or caudad and the number of lumbar intervertebral levels of flow were recorded as well. RESULTS: Dorsal contrast flow occurred in all 25 injections. Thirty-six percent (9 out of 25) resulted in ventral spread of contrast. Eighty-four percent (21 out of 25) of the injections had flow of contrast unilaterally and 16% (4 out of 25) was bilateral. The mean number of levels of flow of contrast cephalad from the injection site was 1.28 and caudally 0.88. There was a significant difference in more cephalad than caudal contrast flow (P = 0.004) CONCLUSION: Thirty six percent of the injections observed in the study revealed ventral contrast flow. Bilateral contrast flow occurred in 16% of the injections. Caudad contrast flow is less than cephalad. The observed contrast flows need to be studied clinically to determine if this can affect clinical outcome.

Journal Article↗

[The effect of injection speed and needle gauge on the spread of sensory blockade in spinal anesthesia].

Unanimity has not yet been reached on the influence of injection speed and needle size on the spread of sensory blockade in spinal anesthesia. While McClure et al. [6] proved that a change in injection speed had no effect on the spread of the blockade, Lanz et al. [4] showed in their investigation that increasing injection speed increases the spread of the blockade. The influence of needle size has hardly been investigated so far. Moore et al. [7] report that the needle size alone has no effect on the spread of the blockade. In this study the influence of injection speed and that of needle size on spread of sensory blockade were considered separately. MATERIALS AND METHODS. Spinal puncture was performed via the midline approach at the L3-4 interspace with the patient in a sitting position. Immediately after the induction of anesthesia the patients were placed in the supine position again. As local anesthetic 15 mg (3 ml) bupivacaine 0.5% with epinephrine 1:200000 was administered. The aim of the study was to find out how far injection speed and size of the spinal needle influenced the sensory spread in isobaric spinal anesthesia. The height of sensory blockade was assessed by means of the pin-prick method in the midline, and the onset of analgesia was determined as height of spread. The injection speeds for the local anesthetic solution were 0.25, 0.5 and 1 ml per second. The needle sizes were 22, 25, and 29 gauge. Each group consisted of 15 patients. RESULTS. It turned out that slow (0.25 ml/s) and the fast (1 ml s) injection was associated with a significantly higher level of analgesia than the medium one (0.5 ml/s). Cephalad spread was to T7 in the first two groups, while the medium injection speed only achieved a level of T9. The results are statistically significant (P less than 0.05). The comparison of different needle sizes (22, 25, and 29 gauge) used for spinal anesthesia showed a higher spread of the sensory blockade with increased diameter of the spinal needle given a constant injection speed. With the 22-gauge needles (n = 15) sensory blockade extended on average to T7, with 25-gauge needles (n = 15) to T9, and with 29-gauge needles (n = 15) to T10. It has to be mentioned, however, that with the 29-gauge needle the standard injection speed of 0.5 ml/s could not be achieved because of the small inner diameter. The differences between 22- and 25-gauge needles are statistically significant (P less than 0.05). DISCUSSION. No direct relation could be proved between the different injection speeds and the spread of the blockade. Our results are hardly comparable with those of other investigators, since other groups have used different local anesthetics or performed investigations in vitro. The use of large spinal needles is associated with spread of the spinal block to a significantly higher level than is achieved with thinner needles.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Tachyphylaxis associated with repeated epidural injections of lidocaine is not related to changes in distribution or the rate of elimination from the epidural space.

The relationship between tachyphylaxis (measured as a decrease in the rate of regression of sensory levels of analgesia) during repeated epidural injections of lidocaine and both the distribution of lidocaine within the epidural space (as measured by spread of simultaneous injection of the tracer technetium-99m diethylenetriaminepentaacetate [99mTc-DTPA]) and elimination of lidocaine from the epidural space (as measured by serum concentrations of lidocaine) was investigated in 18 patients undergoing minor surgery during lumbar epidural analgesia. Twelve patients received four injections of 20 mL of 2% lidocaine at 2-hr intervals. Epidural distribution was assessed by injection of 99mTc-DTPA diluted in saline on the preoperative day and diluted in an equal volume of 2% lidocaine on the morning before surgery and again after the fourth injection of lidocaine 6 hr later. The distribution of 99mTc-DTPA in the epidural space was unchanged during the three measurements despite significant tachyphylaxis in both sensory analgesia and motor blockade (11 of 12 patients had sensory analgesia 2 hr after the first injection in contrast to only 3 of 12 patients during the third injection). In another six patients 20 mL of 2% lidocaine were injected three times at 2-hr intervals before surgery, with measurements of serum concentrations of lidocaine after the first and last injections. Despite tachyphylaxis (no patient had sensory analgesia 2 hr after the third injection), there was no difference in the rate of disappearance of lidocaine from the epidural space as assessed by plasma lidocaine concentration curves during the first and third injection (0.5 +/- 0.1 and 0.3 +/- 0.04 microgram.mL-1.min-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Improved gas chromatographic analysis of organophosphorus pesticides with pulsed splitless injection.

Gas chromatographic (GC) analysis of 6 organophosphorus pesticides (methamidophos, acephate, omethoate, diazinon, dimethoate, and chlorpyrifos) was performed with cool on-column, splitless, and pulsed splitless injections and with nitrogen-phosphorus or mass-selective detection. The pulsed splitless technique uses a high column flow rate during injection to sweep the sample out of the inlet rapidly, reducing analyte loss due to adsorption or thermal decomposition. After injection, the column flow rate is automatically reduced to normal values for chromatographic analysis. Pesticide recoveries for splitless and pulsed splitless injections were determined by comparison of GC peak areas with those obtained with cool on-column injection. With conventional splitless injection at a column flow rate of 5 mL/min, recoveries of acephate, omethoate, and methamidophos were only 57, 63, and 71%, respectively. Pulsed splitless methods with very fast injection flow rates dramatically improved recoveries, with all 6 pesticides falling in the 97-102% range. Because column flow rates are much less for GC with mass spectral detection (GC/MS), recoveries with splitless injection were lower and improvements with pulsed splitless injection were less dramatic for GC/MS. When splitless injection was used, recoveries of the 6 pesticides spiked into a green bean matrix were better than those of pesticides dissolved in pure solvent, presumably because matrix compounds compete with pesticides for active sites in the inlet. By using pulsed splitless injection of solvent standards with very fast initial column flow rates, systematic analyte losses in the inlet were eliminated, making recoveries of pesticides from solvent and green bean matrix very similar.

Chromatography, Gas↗

Mediastinal node and diaphragmatic targeting after intracavitary injection of avidin/99mTc-blue-biotin-liposome system.

A method for delivering drugs to sites of disease extension in mediastinal nodes is described. Mediastinal node and lymphatic distributions were determined after intracavitary injection of the avidin/biotin-liposome system in normal rats. The effect of the injected dose on lymphatic targeting of liposomes after intraperitoneal injection of (99m)Tc-blue-biotin-liposomes and intrapleural injection of avidin, and vice versa, is presented. Scintigraphic imaging was used to follow the movement of (99m)Tc-blue-biotin-liposomes to determine the pharmacokinetics and organ uptake. Tissue biodistribution studies were performed 22 h after injection of the (99m)Tc-blue-biotin-liposomes. Results indicated that independent of the cavity in which each agent was injected, a dose of 5.0 mg of each agent results in higher mediastinal node targeting (8%-10% ID/Organ) as compared with the injection of a 0.5 mg dose (2%-5% ID/Organ, p < 0.05). Targeting of diaphragm and associated lymphatics was observed when (99m)Tc-blue-biotin-liposomes were injected in peritoneum and avidin in pleural space. In contrast, pleural, and pericardial lymphatic targeting was observed when (99m)Tc-blue-biotin-liposomes were injected in pleural space and avidin in peritoneum. Intracavitary injection of the avidin/biotin-liposome system could potentially be used for the delivery of prophylactic drugs that could reduce tumor metastasis and infection spread to mediastinal nodes.

Animals↗

Limited distribution of pertussis toxin in rat brain after injection into the lateral cerebral ventricles.

In vivo administration of pertussis toxin is often used to study the involvement of guanine nucleotide binding proteins in signal transduction. Especially when it is administered in the brain the effect is often poor. This could be due to the fact that pertussis toxin does not reach the area of interest. To evaluate the extent to which pertussis toxin is distributed in rat brain after intraventricular injection, different techniques were used. Immunohistochemical studies with an antibody against pertussis toxin showed that immunoreactivity was limited to periventricular brain structures less than 0.5 mm from the lumen. The highest immunoreactivity was seen 16-24 h after injection. After 96 h the labeling was very weak. The proportion of guanine nucleotide binding proteins that were ADP-ribosylated by in vivo injection of pertussis toxin into the ventricles as assessed by in vitro [32P]-back-ADP-ribosylation was very low 48 h after the injection, in all regions studied. Direct injection of pertussis toxin into the brain caused a marked ADP-ribosylation localized to the region injected that was maximal at 72 h after injection. At 96 h there were also effects after control injections, indicating non-specific effects. Synaptosomal membranes and other membranes were equally affected by pertussis toxin. The results suggest that in studies regarding the effect of pertussis toxin treatment on signal transduction, the toxin must be injected very close to the brain region of interest and, furthermore, that the rats should be killed 48-72 h after injection. In case of lack of effect on the response of interest one should examine whether the ADP-ribosylation of pertussis toxin-sensitive guanine nucleotide binding proteins in the area of concern has been affected.

Adenosine Diphosphate Ribose↗

Effects of intravitreally and intraperitoneally injected atropine on two types of experimental myopia in chicken.

Atropine, a non-selective muscarinic receptor antagonist, is currently the most potent agent used to prevent myopia in animal models and children. However, the ocular target tissues are not well defined. To learn more about the effect of atropine on experimental myopia, atropine was applied both intravitreally and systemically (intraperitoneally) to chickens wearing either negative lenses or light diffusers. Furthermore, the effect of ipsilateral intravitreal atropine on myopia development in the saline-treated fellow eye was studied. Monocular intravitreal injections of atropine were performed daily for a period of 4 successive days, starting at day 8 post-hatching. Fellow eyes received saline injections. Chicks were fitted with -7D lenses, either over the atropine-injected eyes only (unilateral "lens-induced myopia (LIM)"), or over both eyes (bilateral LIM). Other groups of chicks were fitted with translucent diffusers over the atropine-injected eyes (unilateral "form deprivation myopia (FDM)"). Finally, atropine was intraperitoneally injected for 4 days in chicks that wore monocularly -7D lenses. Refractive errors (RE) were measured with infrared photoretinoscopy and axial length (AL) with A-scan ultrasonography. Atropine prevented development of myopia in both unilateral LIM and FDM in a dose-dependent fashion. Fifty percent inhibition of myopia was observed at a dose of 25 microg (unilateral LIM) or 90 microg atropine (bilateral LIM) and complete inhibition at 750 microg; in unilateral FDM, 50% inhibition occurred at 2.5 microg and almost 100% inhibition at 250 microg. Interestingly, at the highest dose of atropine (2500 microg), the treated eyes became even more hyperopic compared to the saline-injected contralateral eyes with normal visual experience. In the bilateral LIM model, atropine suppressed development of myopia in both the treated and the saline-injected control eye. However, about 8.3 times higher doses were necessary to achieve comparable contralateral suppression. Since this ratio is lower than the vitreous volume to blood volume ratio (about 1:23 in young chicks), it seems unlikely that systemic dilution of the intravitreally injected drug can fully account for the contralateral suppression. Intraperitoneal injection inhibited myopia development only at the highest dose (2500 microg) but, strikingly, this inhibition was still less when the same dose was provided through the vitreous of the fellow eye. Both eyes seem to be coupled by a yet unknown, perhaps neuronal pathway. Estimations of the scleral concentrations of atropine after intravitreal injection are compatible with the assumption that the suppression of myopia by atropine occurs by direct inhibition of scleral chondrocytes.

Animals↗

Self-administration with UniJect of the once-a-month injectable contraceptive Cyclofem.

The objective of this study was to evaluate women's acceptance of and ability to self-administrate the injectable contraceptive Cyclofem using prefilled UniJect devices. A total of 102 women were invited to participate in the study. Fourteen women (13.7%) refused to participate. Of the remaining 88 women, 32 women (31.4%) consented to participate and were trained using oranges but were still afraid of the procedure and ultimately refused to self-administer the injections. Only 56 women (55%) ultimately self-injected Cyclofem with UniJect. They performed a total of 144 injections, all of them on the ventral side of the thigh. When nurses evaluated women's ability to activate the devices, they found that more than 80% were successful in both the group of women that later self-administered the injections and the group that did not. The evaluation of the self-administered injection technique showed that more than 90% of the women correctly self-administered the contraceptive using UniJect. With respect to the opinion of the women about the self-administration of the contraceptive, more than 50% (32 of 56) of women who self-injected preferred to self-administer the injection and said that they wished to continue with the self-administration, one-third (17) reported that they were afraid, and seven women (12.5%) expressed the opinion that the injection in the thigh was more painful than the administration in the buttocks or arm. In conclusion, our study showed that women can be trained to successfully self-administer the monthly injectable contraceptive Cyclofem and generally respond positively to UniJect.

Brazil↗