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Timing of sperm and oocyte nuclear progression after intracytoplasmic sperm injection.

We investigated the time course of human oocyte activation after intracytoplasmic sperm injection (ICSI) by observing the oocyte chromosome configuration at different times after injection. One day old human oocytes were injected with spermatozoa and subjected to cytogenetic analysis at 2, 3, 4 and 5 h after injection. We found that anaphase is initiated in the vast majority of the oocytes between 2 and 3 h after injection, and that by 4-5 h after injection most of the oocytes have reached the chromatin mass stage. Two distinguishable stages of sperm nucleus transformation were observed. The first phase-swelling-was reached within 2 h after the injection and was independent of oocyte activation. The second phase-the "brush'-like stage or decondensed chromatin stage-was found only in activated oocytes. Moreover, this stage was not reached before the chromatin mass stage (late telophase) of the oocyte. The same proportion of metaphase II oocyte chromosome configurations and unchanged sperm nuclei was found at any given time after injection. We conclude that: (i) ICSI allows users to obtain an almost synchronized population of activated oocytes; (ii) anaphase II is initiated in the majority of oocytes not later than 2-3 h after injection and telophase II is reached approximately 5 h after injection; and (iii) there are two distinguishable phases of sperm nucleus transformation after ICSI: oocyte activation-independent swelling of the sperm head and oocyte activation-dependent chromatin decondensation which is coupled to the beginning of oocyte chromosome decondensation.

Cell Nucleus↗

Changes in egg production rate induced by progesterone injection in broiler breeder hens.

A polycystic ovarian follicle (PCOF) syndrome associated with high baseline concentrations of progesterone (P4) without preovulatory luteinizing hormone (LH) surges has been reported in turkey hens. The PCOF syndrome could be induced in turkey hens by injecting P4 (0.33 mg/kg per d) daily early in the reproductive period for 10 to 12 d and then waiting 3 wk for the syndrome to develop. It was hypothesized that an arrest in laying associated with the PCOF syndrome could be induced by daily injection of P4 in restricted-fed broiler breeder hens. Hens were divided into 5 treatment groups and were injected subcutaneously daily with P4 in canola oil at dosages of 0, 0.17, 0.33, 0.5, and 1.5 mg/kg per d for 13 d, at 14 wk of egg production when they were 41 wk of age. Blood samples were collected on d 7 and 13 immediately before P4 injection. Oviductal and ovarian morphologies were measured at necropsy 1 d after the last P4 injection. Egg production rate was reduced by injection of P4 at dosages < 0.17 mg/kg per d. At dosages of 0.5 and 1.5 mg/kg per d, ovarian hierarchical follicles had regressed. None of the broiler breeder hens had the PCOF syndrome at necropsy, but a high incidence of hens holding hard-shelled uterine eggs for several days was observed. Concentrations of LH decreased with P4 injection at > 0.17 mg/kg per d, and P4 concentrations were increased with P4 injection at > 0.5 mg/kg per d. Estradiol-17beta (E2) concentrations were decreased at all P4 dosages. It was concluded that egg production rate was reduced by daily injection of P4 at dosages > 0.17 mg/kg per d, and egg production ceased and ovarian follicles and the oviduct regressed at dosages > 0.50 mg/kg per d. The PCOF syndrome, however, was not induced in restricted-fed broiler breeder hens by P4 injection.

Animals↗

Injecting drug use and HIV infection in southwest China.

OBJECTIVES: To determine the prevalence of drug injection among drug users, the seroprevalence of HIV and risk factors for HIV infection among injecting drug users (IDU), and to determine heterosexual transmission of HIV among IDU and their spouses in southwest China. METHODS: Using a cross-sectional design, we conducted an HIV seroprevalence and behavioral survey in three rural counties of Yunnan province, Ruili, Longchuan and Luxi in southwest China, bordering Myanmar (Burma). A total of 860 drug users were recruited in randomly selected communities at the three study sites (response rate, 97%). In addition, a random sample of 62 wives of HIV-infected IDU were assembled from 460 known HIV-positive IDU in Ruili and Longchuan (response rate, 81%). RESULTS: In the sample of 860 drug users, 33% reported injecting drugs. Among the 282 subjects who injected drugs, 82% began intravenous drug use after 1988; 64% injected drugs at least once every day. All subjects shared needles but none cleaned the injection equipment with alcohol or bleach. Overall, 49% tested HIV-positive. HIV seropositivity was independently correlated with a longer history of drug injecting, daily injecting, frequent needle-sharing, being younger, and living in Ruili county. Among the 62 wives of HIV-positive IDU, none used condoms during sex and 10% tested HIV-positive. CONCLUSIONS: We conclude that the introduction of HIV into drug-using communities and the rapid increase in heroin injecting in this population appear to have triggered an explosive HIV epidemic among IDU in southwest China. We recommend that AIDS prevention efforts should begin immediately and focus on discouraging the shift from opium smoking to heroin injecting, needle-sharing, and unprotected sex among drug users and their partners.

Adult↗

Maximum impact of HIV prevention measures targeted at injecting drug users.

OBJECTIVE: To examine whether the decrease in HIV incidence and injecting risk behaviours is ongoing in Amsterdam, and to study the determinants of injecting risk behaviours. DESIGN: Prospective open cohort study (1986-1997) amongst injecting drug users (IDU). METHODS: HIV incidence was studied using Poisson regression analysis. Trends in injecting risk behaviours were determined using 6645 visits of 879 participants, stratified by HIV serostatus and number of the follow-up visit. Generalized estimating equations were used to account for repeated measurements, and additive model structures were used. RESULTS: A large initial risk reduction (1986-1991) occurred concerning borrowing and lending of used needles, multiple needle use and frequent injecting. However, except for frequent injecting, the rate of behaviour change significantly decreased, and from 1991-1993 onwards there was no substantial further risk reduction. HIV incidence followed a similar pattern. Injecting risk was much lower at follow-up visits. The following determinants of borrowing and lending among both HIV-positive and negative IDU were largely comparable: young age, non-injecting heroin and cocaine use, frequent tranquillizer use, multiple needle use, injecting with others, and irregular use of needle-exchange programmes. CONCLUSIONS: The observed residual risk, given the extensive HIV prevention measures in Amsterdam, indicates that further prevention is difficult. Because this risk was associated with an HIV incidence of 3-4% per year, HIV prevalence is likely to be high for many years. Therefore, prevention measures should be maintained because of the possibility of behavioural relapse associated with recent availability of potent HIV treatments. To prevent an HIV epidemic amongst a new generation of drug users, prevention of injecting itself is warranted.

Adult↗

Thermodilution right ventricular ejection fraction measurements: room temperature versus cold temperature injectate.

OBJECTIVE: To compare thermodilution right ventricular ejection fraction measurements using 10 mL room temperature injectate vs. 10 mL cold temperature injectate. DESIGN: Prospective, clinical study. SETTING: Adult surgical intensive care unit (ICU) in a university hospital. PATIENTS: Sixty adult surgical ICU patients requiring hemodynamic monitoring by a pulmonary artery catheter. INTERVENTIONS: Patients were in a supine position with the bed flat during thermodilution measurements. Four 10 mL room temperature injections were alternated with four 10 mL cold temperature injections. MEASUREMENTS AND MAIN RESULTS: One hundred eleven paired thermodilution right ventricular ejection fraction measurements were made in patients during a "steady state." There were no restrictions regarding body temperature, cardiac index, heart rate or rhythm. Injectate temperature was measured by an in-line temperature probe. Injections were synchronized with end-expiration of mechanical ventilator breaths. The first injection was deleted from each temperature group. Reproducibility of individual right ventricular ejection fraction measurements was assessed by calculating the mean variation of triplicate measurements in each temperature group. Mean values of room temperature measurements were compared with cold temperature measurements by Student's t-test. Linear regression analysis, bias, and precision were also calculated. There was no significant difference (p = .752) between mean right ventricular ejection fraction measurements determined with room temperature (23.9 +/- 1 degrees C) vs. cold temperature (8.0 +/- 1.1 degrees C) injectate. There was a high degree of correlation between measurements (r2 = .876, p < .001). The bias of room temperature measurements compared with cold temperature was -0.39% and the precision was +/- 3.3%. The mean variation between individual measurements in all room temperature and cold temperature right ventricular ejection fraction measurements was 9.7% and 8.0%, respectively. There was no significant difference and there was a high degree of correlation in mean right ventricular ejection fraction measurements when data were grouped according to body temperature, heart rate, cardiac index, right ventricular ejection fraction, central venous pressure, pulmonary vascular resistance index, right ventricular end-diastolic volume index, or right ventricular stroke work index. CONCLUSIONS: The results suggest that room temperature injectate may be used for right ventricular ejection fraction measurements in critically ill adult surgical patients. Utilizing room temperature injectate for right ventricular ejection fraction measurements may save time and costs in the critical care unit.

Adult↗

Iced temperature injectate for thermodilution cardiac output determination causes minimal effects on cardiodynamics.

OBJECTIVES: Controversy exists regarding the ideal injectate temperature for measuring cardiac output. Iced temperature injectate gives a higher signal/noise ratio and less variability in the measured cardiac output. Thus, less volume and fewer measurements are required. Advocates of room temperature injectate have suggested that iced temperature injectate may perturb cardiodynamics. This concern has remained largely untested. To help resolve this controversy, we examined the effects of 5 mL iced injectate (0 degrees to 4 degrees) infusions on cardiodynamics. DESIGN: Prospective, randomized, controlled study. SETTING: A critical care research laboratory. SUBJECTS: Five domestic pigs, weighing between 20 to 25 kg. INTERVENTIONS: Under barbiturate anesthesia, pigs underwent placement of a) a thermodilution catheter in the right internal jugular vein; b) a right carotid artery catheter for mean arterial pressure; and c) sonomicrometry crystals for dynamic measurements of left ventricular dimensions. Calculations were made of end-systolic and end-diastolic left ventricular volume and ejection fraction. Six cardiac output measurements were performed in each pig. Data were obtained at baseline (just before iced temperature injectate infusion) and every 3 sec for 9 secs. MEASUREMENTS AND MAIN RESULTS: The only significant effect seen with iced temperature injectate infusion was a small, transient decrease in heart rate (-5.9 +/- 1.1 beats/min from a baseline heart rate of 144.8 +/- 20.6 beats/min). Indices of preload, contractile function, and dynamic cardiac geometry were unaffected. CONCLUSIONS: Iced temperature injectate used in clinically relevant volumes causes transient negative chronotropic effects, but reservations regarding other perturbations of cardiodynamics are unfounded. Thus, the use of iced temperature injectate for cardiac output determination is still a viable alternative to room temperature injectate use, especially when a larger signal/noise ratio is required.

Analysis of Variance↗

Viscoelasticity of rabbit vocal folds after injection augmentation.

OBJECTIVES/HYPOTHESIS: Vocal fold function is related to the viscoelasticity of the vocal fold tissue. Augmentation substances used for injection treatment of voice insufficiency may alter the viscoelastic properties of vocal folds and their vibratory capacity. The objective was to compare the mechanical properties (viscoelasticity) of various injectable substances and the viscoelasticity of rabbit vocal folds, 6 months after injection with one of these substances. STUDY DESIGN: Animal model. METHODS: Cross-linked collagen (Zyplast), double cross-linked hyaluronan (hylan B gel), dextranomers in hyaluronan (DHIA), and polytetrafluoroethylene (Teflon) were injected into rabbit vocal folds. Six months after the injection, the animals were killed and the right- and left-side vocal folds were removed. Dynamic viscosity of the injected substances and the vocal folds was measured with a Bohlin parallel-plate rheometer during small-amplitude oscillation. RESULTS: All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Hylan B gel and DiHA showed the lowest dynamic viscosity values, and vocal folds injected with these substances also showed the lowest dynamic viscosity (similar to noninjected control samples). Teflon (and vocal folds injected with Teflon) showed the highest dynamic viscosity values, followed by the collagen samples. CONCLUSION: Substances with low viscoelasticity alter the mechanical properties of the vocal fold to a lesser degree than substances with a high viscoelasticity. The data indicated that hylan B gel and DiHA render the most natural viscoelastic properties to the vocal folds. These substances seem to be appropriate for preserving or restoring the vibratory capacity of the vocal folds when glottal insufficiency is treated with augmentative injections.

Animals↗

Injection laryngoplasty for management of unilateral vocal fold paralysis.

PURPOSE OF REVIEW: The purpose of this review is to provide an up-to-date review of injection laryngoplasty technique and currently available injectable materials in the management of unilateral vocal fold paralysis (UVP). RECENT FINDINGS: Many new materials are currently available as substances for injection laryngoplasty. These materials have been developed along distinct of lines reasoning that address the inherent shortcomings of the previously available injectable substances, namely, poor tissue biocompatibility and poor persistence within the larynx. Accordingly, the past decade has seen heightened efforts toward developing implants with improved biocompatibility and longevity. The past year has witnessed publications reporting animal studies and, on occasion, human clinical trials involving the intralaryngeal injection of calcium hydroxyl-appetite, autologous fascia, particulate silicone and hyaluronic acid derivatives, and others, for managing glottic insufficiency. SUMMARY: In recent years, the application of injection laryngoplasty to unilateral vocal fold paralysis (UVP) has regained popularity. The technique of injection laryngoplasty has several appealing qualities including relative technical ease, low cost, and wide availability in many clinical settings. A growing number of injectable substances have been developed and tested in the clinical setting of glottic insufficiency. When used to manage unilateral vocal fold paralysis, however, injection laryngoplasty has one irrefutable shortcoming: an inability to address posterior glottic insufficiency. Therefore, while injection laryngoplasty technique becomes increasingly popular for vocal fold augmentation in cases vocal fold paresis, atrophy, and scarring, its role in the treatment of UVP should be limited to cases with an appropriate glottal defect. These techniques should be considered as part of a complimentary armamentarium with framework surgery.

Adjuvants, Immunologic↗

AIDS and the transition to illicit drug injection--results of a randomized trial prevention program.

Illicit drug injection is a major component of the AIDS epidemic in the United States, Europe and some developing countries. Prevention of illicit drug injection would not only reduce HIV transmission but would also reduce the other health, psychological and social problems associated with illicit drug injection. One hundred and four subjects who were using heroin intranasally ('sniffing') were recruited for a study of the transition to drug injection. Eligibility criteria included sniffing as the most frequent route of administration and no more than 60 injections in the past 2 years. All subjects received thorough basic information about AIDS, including HIV antibody test counseling. Subjects were then randomly assigned to a four-session social learning based AIDS/drug injection prevention program or a control condition. Eighty-three subjects were successfully followed at a mean time of 8.9 months. Twenty (24%) of the followed subjects reported injecting illicit drugs during the follow-up period. Drug injection during follow-up was associated with being in the control group, intensity of non-injected drug use, prior injection, and having close personal relationships with current intravenous (IV) drug users.

Acquired Immunodeficiency Syndrome↗

Thymocytes induced by antigen injection into the anterior chamber activate splenic CD8+ suppressor cells and enhance the antigen-induced production of immunoglobulin G1 antibodies.

Injection of antigen into the ocular anterior chamber (AC) of a mouse eye (an immunologically privileged site) induces the activation of immunoregulatory NK1.1+, CD4- CD8-, T-cell receptor (TCR) alphabeta+ thymocytes. These thymocytes transfer the suppression of delayed-type hypersensitivity (DTH) when injected into mice sensitized to the same antigen but do not effect the suppression of DTH. On the other hand, the immunized recipients of these transferred thymocytes produce splenic CD8+ T cells that effect the suppression of DTH. However, it is unclear whether the thymocytes transferred from the AC-injected donor differentiate into and/or activate CD8+ T-splenic suppressor cells. We therefore sought to determine the origin of splenic suppressor cells produced in the recipients of immunoregulatory thymocytes transferred from donors that receive an injection of antigen into the AC. CD45.1+ thymocytes from mice that received an AC injection of 2,4,6-trinitrobenzene sulphonic acid (TNP)-bovine serum albumin (BSA) were transferred to congenic CD45.2+ TNP-BSA-immune recipients. Spleen cells from the recipients were then sorted based on anti-CD45.1 or -CD45.2 antibody binding and assayed for suppressor cells. This was done by the injection of separated spleen cells into the footpad of TNP-BSA-immunized mice, concurrent with the induction of footpad swelling (contact sensitivity) of the footpad elicited by an epicutaneous application of picryl chloride. The systemic distribution of antigen after the injection of antigen into the AC was demonstrated by the injection of fluorescein or 125I-labelled TNP-BSA into the AC. The results demonstrate that (i) splenic CD8+ T-suppressor cells produced in the immunized recipients of immunoregulatory thymocytes are derived from the CD45.2 recipient of the CD45.1+ thymocytes; (ii) the induction of recipient splenic suppressor T cells by the transferred immunoregulatory thymocytes requires that the recipient be immunized to the same antigen as that used to induce immunoregulatory thymocytes; (iii) antigen is introduced to the thymus after an injection of antigen into the AC; (iv) although the transfer of the suppression of DTH by regulatory thymocytes was not dependent on interleukin-4 (IL-4), CD4+ NK1.1- regulatory thymocytes from AC-injected donors enhanced the production of immunoglobulin G1 antibodies to TNP-BSA by an IL-4-dependent mechanism. These observations suggest that the adult thymus plays an active role in the induction and maintenance of anterior chamber-associated immune deviation as manifested by the generation of the suppression of cell-mediated immunity to exogenous antigen and the antigen-induced production of IgG1 antibodies.

Adoptive Transfer↗

Stability of cefmetazole-doxycycline mixtures in sodium chloride and dextrose injections.

This study involved the mixing of cefmetazole 1 and 2 Gm with doxycycline 100 and 200 mg, in sodium chloride and dextrose injections. The mixtures were stored either at ambient temperature for 96 h or at 4 degrees C for 168 h followed by 8 h at ambient temperature. HPLC assay of both cefmetazole and doxycycline levels were performed at prescribed sampling times. Cefmetazole 1 Gm in doxycycline 100 and 200 mg mixtures, in sodium chloride injection was not stable up to 4 h, but cefmetazole 2 Gm in doxycycline 100 and 200 mg mixtures, in sodium chloride injection was stable for up to 24 h. The cefmetazole controls were stable for 72 h in sodium chloride injection. Cefmetazole 1 Gm with doxycycline 100 mg, in dextrose injection was stable up to 72 h. The 2 Gm cefmetazole and 100 mg doxycycline mixture in dextrose injection was stable for 96 h. Cefmetazole 1 Gm and doxycycline 200 mg in dextrose injection was stable up to 96 h, but the 2 Gm cefmetazole-200 mg doxycycline mixture was only stable for 72 h. Cefmetazole controls in dextrose injection were stable for 24 h. Doxycycline 100 and 200 mg were stable with cefmetazole 1 and 2 Gm, in both sodium chloride and dextrose injections for 96 h at ambient temperature. Doxycycline control solutions were also stable for 96 h. Cefmetazole 1 and 2 Gm and doxycycline 100 and 200 mg were generally stable in both sodium chloride and dextrose injections at 4 degrees C for 168 h, and at ambient temperature for 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefmetazole↗

Injection of guanosine and adenosine nucleotides into Limulus ventral photoreceptor cells.

1. Several nucleotide and nucleotide analogues had striking effects when pressure-injected into Limulus ventral photoreceptor cells. The poorly hydrolysable GTP analogues guanosine 5'-0-(3-thiotriphosphate) (GTPgammaS), guanylyl imidodiphosphate (Gpp[NH]p) and guanylyl (beta, gamma methylene) diphosphonate (Gpp[CH(2)]p) produced large increases in the frequency of ;discrete events' that were recorded from photoreceptors in darkness. This effect was only observed after the injected cell was exposed to light. Injection of the ATP analogue ATPgammaS had effects similar to those of the GTP analogues.2. We conclude that GTPgammaS, Gpp[NH]p, Gpp[CH(2)]p and ATPgammaS act at a common site to cause a light-dependent, long-term activation of the excitation mechanism of the photoreceptor.3. Injection of GTP or GDP at pH 4.8 was followed by a smooth, transient depolarization that was observed neither when GTP at pH 7.5 was injected nor when ATP, 5'GMP or 2-[N-morpholino] ethane sulphonic acid (MES) were injected at pH 4.8. The reversal potential of the current induced by GTP injection was significantly more positive than the reversal potential of the light-induced current.4. We conclude that GTP injection induces changes of membrane conductance either in addition to, or different from, the light-induced change of membrane conductance.5. Injection of the ATP analogue adenylyl imidodiphosphate (App[NH]p), and the pyrophosphate analogue imidodiphosphate (p[NH]p) produced a drastic decrease in the sensitivity of photoreceptors to light. This decrease in sensitivity was partially reversed when the concentration of calcium ions in the bathing medium was reduced.6. We suggest that App[NH]p and p[NH]p injections act by increasing the cytoplasmic concentration of calcium ions.

Adaptation, Ocular↗

Timing of pre-breakfast insulin injection and postprandial metabolic control in diabetic children.

A peak period of hyperglycaemia in insulin-dependent diabetics occurs after breakfast. A randomised crossover study was performed on nine diabetic children at home to study the effect of varying the time of their morning mixed injection of Monotard and Actrapid insulin on this hyperglycaemic peak. Performing the study at home minimised the children's stress.After diabetic control had been improved children injected their insulin 30 minutes (early injection) or five minutes (late injection) before breakfast on two consecutive Saturday mornings. Blood samples were taken at 30-minute intervals over 3(1/2) hours and analysed for concentrations of glucose, insulin, C-peptide, pyruvate, lactate, alanine, and ketones. Diet, insulin dose, and exercise were kept the same on both test days.The mean blood glucose concentration at breakfast (0 minutes) was 11 mmol/l after the early injection and 10 mmol/l after the late injection. Subsequent concentrations were consistently lower with the early injection regimen than the late regimen. The greatest difference between values in the two groups was 3.7 mmol/l at 150 minutes. Mean plasma insulin concentrations were lower in the children on the early regimen than in those on the late regimen at 30 minutes before breakfast but higher at 0 minutes and thereafter. There were no significant differences in mean concentration of intermediary metabolites between the two injection regimens. These were mainly within the normal range for healthy young adults except for the ketone concentrations, which were raised with both injection regimens until 180 minutes after breakfast.These results suggest that the timing of the morning injection of insulin is important in the control of postprandial hyperglycaemia in diabetic children.

Adolescent↗

Harm reduction measures and injecting inside prison versus mandatory drugs testing: results of a cross sectional anonymous questionnaire survey. The European Commission Network on HIV Infection and Hepatitis in Prison.

OBJECTIVES: (a) To determine both the frequency of injecting inside prison and use of sterilising tablets to clean needles in the previous four weeks; (b) to assess the efficiency of random mandatory drugs testing at detecting prisoners who inject heroin inside prison; (c) to determine the percentage of prisoners who had been offered vaccination against hepatitis B. DESIGN: Cross sectional willing anonymous salivary HIV surveillance linked to a self completion risk factor questionnaire. SETTING: Lowmoss prison, Glasgow, and Aberdeen prison on 11 and 30 October 1996. SUBJECTS: 293 (94%) of all 312 inmates at Lowmoss and 146 (93%) of all 157 at Aberdeen, resulting in 286 and 143 valid questionnaires. MAIN OUTCOME MEASURES: Frequency of injecting inside prison in the previous four weeks by injector inmates who had been in prison for at least four weeks. RESULTS: 116 (41%) Lowmoss and 53 (37%) Aberdeen prisoners had a history of injecting drug use but only 4% of inmates (17/395; 95% confidence interval 2% to 6%) had ever been offered vaccination against hepatitis B. 42 Lowmoss prisoners (estimated 207 injections and 258 uses of sterilising tablets) and 31 Aberdeen prisoners (229 injections, 221 uses) had injected inside prison in the previous four weeks. The prisons together held 112 injector inmates who had been in prison for more than four weeks, of whom 57 (51%; 42% to 60%) had injected in prison in the past four weeks; their estimated mean number of injections was 6.0 (SD 5.7). Prisoners injecting heroin six times in four weeks will test positive in random mandatory drugs testing on at most 18 days out of 28. CONCLUSIONS: Sterilising tablets and hepatitis B vaccination should be offered to all prisoners. Random mandatory drugs testing seriously underestimates injector inmates' harm reduction needs.

Cross-Sectional Studies↗

Impact of a medically supervised safer injection facility on community drug use patterns: a before and after study.

PROBLEM: Illicit use of injected drugs is linked with high rates of HIV infection and fatal overdose, as well as community concerns about public drug use. Supervised injecting facilities have been proposed as a potential solution, but fears have been raised that they might encourage drug use. DESIGN: A before and after study. Participants and setting 871 injecting drug users recruited from the community in Vancouver, Canada. KEY MEASURES FOR IMPROVEMENT: Rates of relapse into injected drug use among former users and of stopping drug use among current users. STRATEGIES FOR CHANGE: Local health authorities established the Vancouver supervised injecting facility to provide injecting drug users with sterile injecting equipment, intervention in the event of overdose, primary health care, and referral to external health and social services. EFFECTS OF CHANGE: Analysis of periods before and after the facility's opening showed no substantial increase in the rate of relapse into injected drug use (17% v 20%) and no substantial decrease in the rate of stopping injected drug use (17% v 15%). LESSONS LEARNT: Recently reported benefits of supervised injecting facilities on drug users' high risk behaviours and on public order do not seem to have been offset by negative community impacts.

Adult↗

High prevalence of iliofemoral venous thrombosis with severe groin infection among injecting drug users in North East Scotland: successful use of low molecular weight heparin with antibiotics.

Injecting drug use, mainly of heroin, currently represents a major public health issue in the North East of Scotland. The recent tendency of the committed injecting drug user to inject into the groin has created novel problems for the Infection Unit. Data are presented on 20 consecutive patients admitted between 1994 and 1999 with iliofemoral venous thromboses, often complicated by severe soft tissue infections and bacteraemia as a result of heroin injection into the femoral vein. Nine had coexistent groin abscesses, four had severe streptococcal soft tissue infection of the right thigh, groin and lower abdomen, and two had coincidental soft tissue infections of the upper limb. Nine were bacteraemic on admission. All of the patients were chronic injecting drug users with a median injection duration of 6.5 years. The 18 patients tested for hepatitis C virus were all seropositive. None of the 14 patients tested was positive for HIV. Seventeen patients were treated with subcutaneous low molecular weight heparin (tinzaparin), three having received intravenous unfractionated heparin initially. The tinzaparin was self administered and given for a median duration of seven weeks. One patient declined to have any treatment. Three months after presentation eight patients were asymptomatic, seven had a persistently swollen leg, and five were lost to follow up. None developed clinically apparent pulmonary embolism after institution of anticoagulant therapy. The management of iliofemoral venous thrombosis in injection drug users is problematic because of poor venous access, non-compliance with prescribed treatment, ongoing injecting behaviour, and coexistent sepsis. It is unlikely that a randomised trial of standard treatment with heparin and warfarin versus low molecular weight heparin alone would be practical in this patient group. These retrospective data indicate that the use of tinzaparin in injecting drug users is feasible and appears to result in satisfactory clinical responses. The possibility of concomitant infection in injecting drug users with venous thrombosis should always be addressed, as it appears to be a common phenomenon. Early drainage of abscesses and antimicrobial chemotherapy, often administered intramuscularly or orally because of lack of peripheral venous access, is central to the appropriate care of these patients.

Abscess↗

ACTH and cortisol responses to sequential CRF injections in fetal sheep.

To determine whether an initial ovine corticotropin-releasing factor (oCRF) injection modifies adrenocorticotropic hormone (ACTH) and cortisol responses to a second injection and to establish whether the effect changes throughout gestation, we studied chronically cannulated fetal lambs of 103-113 and 133-137 days gestation. Experimental groups underwent an injection (500 ng/kg iv) of oCRF, arterial blood sampling for 6 h, then a similar oCRF injection followed by sampling. In control studies, vehicle was the initial injection. After the first oCRF injection, plasma cortisol levels went from 1.7 +/- 0.4 to 9.5 +/- 5.2 (SE) ng/ml ("immature") and from 22.3 +/- 4.9 to 52.5 +/- 5.8 ng/ml ("mature"), remaining elevated for 6 h. In immature fetuses, the first oCRF injection did not alter the ACTH response to a second injection. Cortisol increases were reduced. In mature animals, ACTH and cortisol response to oCRF were eliminated by prior oCRF. Thus a large increase in cortisol after oCRF in mature fetuses is associated with inhibition of the ACTH response to a second oCRF injection, whereas in immature animals a small increase in cortisol after the first oCRF injection is not.

Adrenal Cortex↗

Insulin suppression is associated with hypersomatostatinemia and hyperglucagonemia in glucose-injected rainbow trout.

Rainbow trout, Oncorhynchus mykiss, were used to evaluate the effects of carbohydrate loading on plasma levels of pancreatic hormones and associated changes in metabolic indexes in a carnivorous fish. Glucose (3,000 mg/dl, 10 microliters/g body wt) was injected intraperitoneally into fish (mean wt 54 +/- 5 g) that were killed 0.5-24 h after administration. Glucose injection resulted in hyperglycemia with maximum glucose levels of 306 +/- 13 mg/dl observed 60 min after injection. Glucose administration also resulted in hyperlipidemia. Plasma fatty acids increased twofold in glucose-injected animals. Alterations in plasma metabolites reflected changes in energy stores. Although total lipid concentration was unaffected by glucose injection, lipolytic enzyme activity in the liver was enhanced. Biosynthetic capacity, as indicated by NADPH production from glucose-6-phosphate dehydrogenase, was decreased by glucose injection. Liver glycogen content was reduced in glucose-injected animals 1 h after injection. Glucose injection was attended by increases in the plasma levels of gene II somatostatin-25 (predominant form of pancreatic somatostatin in salmonids) and of glucagon. Insulin levels were initially suppressed after glucose injection. These results indicate that metabolic adjustments caused by glucose administration can be related to the regulatory action of pancreatic hormones. Furthermore, these results suggest that the somatostatin-secreting cells of the trout are sensitive to glucose and that somatostatin-suppressed insulin secretion contributes to the glucose intolerance of trout.

Animals↗