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Incubation periods and survival times for mice injected stereotaxically with three scrapie strains in different brain regions.

Incubation period and survival time were determined in C57BL mice which had been injected stereotaxically with either the 139A, ME7 or 22L strain of scrapie in one of five different brain regions (cerebral cortex, caudate nucleus, thalamus, substantia nigra, cerebellum). The injection of 139A in the caudate nucleus, thalamus, substantia nigra or cerebellum resulted in significantly shorter incubation periods than following cerebral cortex injection. For ME7, mice injected in the thalamus and cerebellum had incubation periods approximately 2 weeks shorter than the cerebral cortex group. For 22L, the incubation periods after substantia nigra or cerebellum injection were significantly shorter than after cortex injection. The cerebellum injection group had a significantly shorter incubation period than the substantia nigra injection group. The survival times for mice injected with a particular scrapie strain were directly related to the incubation periods. The groups with the shortest incubation also had the shortest survival time (e.g. 22L in the cerebellum). On histological examination, 139A and ME7 produced brain lesions in all brain areas regardless of injection site. For the 22L strain, after cerebellum injection vacuolation was limited to the cerebellum, while injection into the cerebral cortex and other forebrain regions resulted in vacuolation in all brain regions examined. Despite the difference in the distribution of vacuolation seen in cerebellum- compared to cortex-injected (22L) mice, infectivity titres were similar in the cortex, cerebellum, cerebellar cortex and medulla plus pons.

Animals↗

The influence of injected cyclic AMP protein kinase catalytic subunit on the sodium efflux in barnacle muscle fibres.

1. A study has been made of the response of the Na efflux in single barnacle muscle fibres to the injection of cyclic AMP protein kinase catalytic subunit (CSU).2. (i) Injected CSU stimulates the Na efflux in unpoisoned and ouabain-poisoned fibres. (ii) Stimulation in both situations is always sustained, and (iii) stimulation of the ouabain-insensitive Na efflux is observed with as low a concentration as 10(-7) M-CSU.3. (i) The response to injected CSU depends on [Ca](o) but is unaffected by prior external application of verapamil. (ii) An effect fails to occur in fibres cooled to 0 degrees C.4. (i) Injection of 5'-guanylylimidodiphosphate (Gpp(NH)p) following peak stimulation by CSU causes a further sustained stimulatory response. (ii) Injection of CSU following peak stimulation by Gpp(NH)p causes a further sustained stimulatory response. (iii) Injection of undialysed cholera toxin following CSU causes little or no effect, whereas injection of dialysed cholera toxin causes a stimulatory effect. Injection of CSU following undialysed cholera toxin causes little or no effect, whereas its injection after dialysed cholera toxin causes a fairly appreciable effect.5. (i) The response to CSU is reduced by prior injection of protein kinase type 2 regulatory subunit (R(II)) but not when R(II) is injected following peak response to CSU. (ii) Injection of protein kinase inhibitor partially reverses the response to CSU.6. (i) Injection of Mg(2+) fully reverses the response to CSU. (ii) Fe and Zn cause only partial reversal.7. (i) External imipramine but not trifluoperazine reduces the response to CSU. (ii) Diphenylhydantoin is ineffective.8. These results support the view that CSU behaves as a modulator of the ouabain-insensitive Na efflux and that Mg(2+), Fe and Zn are inhibitors of the catalytic reaction.

Animals↗

Drug injection and HIV prevalence in inmates of Glenochil prison.

OBJECTIVE: To determine prevalence of HIV infection and drug injecting behaviour among inmates of Glenochil Prison on a specified date a year after an outbreak of hepatitis B and HIV infection. DESIGN: Cross sectional: voluntary, anonymous HIV salivary antibody surveillance and linked self completion questionnaire on risk factors. SETTING: Glenochil prison, Scotland, a year after an outbreak of hepatitis B and HIV transmission related to drug injection. SUBJECTS: 352 prisoners, of whom 295 (84%) took part; 284 questionnaires (96%) passed logical checks. MAIN OUTCOME MEASURES: HIV prevalence; proportion of all inmates who had ever injected drugs, had ever injected inside prison, had started injecting drugs while inside prison. RESULTS: More than half (150/284) the current inmates were also in Glenochil Prison during the critical period of January to June 1993, when hepatitis B and HIV were transmitted. Similar proportions of current inmates and men who were also in Glenochil during the critical period were drug users (27% (75/278) v 30% (44/149)). A quarter of injecting drug users (18/72) had first injected inside prison, irrespective of whether they were in Glenochil in January to June 1993 and regardless of the calendar period when they first injected. Significantly more inmates from Glasgow (41%; 56/138) than from Edinburgh (21%; 7/34) or elsewhere (11%; 12/106) were injecting drug users. On testing for HIV, seven saliva samples out of 293 gave positive results--four were presumed to be from inmates known to be infected with HIV, and the others from injecting drug users from Glasgow, all of whom had been in Glenochil during January to June 1993, when two of the three had injected drugs and had been tested for HIV, with negative results. The ratio of overall (2.4%) to disclosed (1.4%) HIV prevalence was 1.7. For men who had injected drugs in Glenochil during January to June 1993, HIV prevalence was estimated at 29%. CONCLUSION: Between a quarter and a third of prisoners who injected drugs in Glenochil in January to June 1993 were infected with HIV. There is widespread ongoing risk of bloodborne virus infection within prisons, which is probably long standing but demands urgent attention.

Adult↗

Depression severity and drug injection HIV risk behaviors.

OBJECTIVE: This study examined the association of depression severity and drug injection HIV risk behavior among injection drug users. METHOD: Injection drug users who met the DSM-IV criteria for major depressive disorder, dysthymia, or substance-induced mood disorder lasting at least 3 months were asked how often they used "needles or syringes that someone else had used" (injection risk behavior) in the past 90 days. Depression severity was measured by using the Modified Hamilton Rating Scale for Depression. RESULTS: Of the 109 subjects, 63% were male, 82% were Caucasian, and 10% were HIV positive. The subjects' mean modified Hamilton depression scale score was 21.0 (SD=3.9). The mean number of reported instances of injection risk behavior (needle sharing) in the past 90 days was 57.5 (SD=134.7). In a logistic regression analysis in which the effects of age, race, gender, number of days on which injection drugs were used (injection days), and average number of injections per injection day were controlled, depression severity was associated with injection risk (odds ratio=1.5; 95% confidence interval=1.1-2.3). CONCLUSIONS: Greater severity of depression is associated with greater frequency of injection risk behavior among depressed injection drug users. Risk reduction programs that target depressed injection drug users need to be designed.

Adult↗

Profiles of risk: a qualitative study of injecting drug users in Tehran, Iran.

BACKGROUND: In Iran, there are an estimated 200,000 injecting drug users (IDUs). Injecting drug use is a relatively new phenomenon for this country, where opium smoking was the predominant form of drug use for hundreds of years. As in many countries experiencing a rise in injecting drug use, HIV/AIDS in Iran is associated with the injection of drugs, accounting for transmission of more than two-thirds of HIV infections. This study aimed to: describe the range of characteristics of IDUs in Tehran, Iran's capital city; 2) examine the injecting-related HIV risk behaviors of IDUs, and 3) suggest necessary interventions to prevent HIV transmission among IDUs and their families and sex partners. METHODS: Using rapid assessment and response methods with a qualitative focus, six districts of Tehran were selected for study. A total of 81 key informants from different sectors and 154 IDUs were selected by purposeful, opportunistic and snowball sampling, then interviewed. Ethnographic observations were done for mapping and studying injecting-related HIV risk settings and behaviors. Modified content analysis methods were used to analyze the data and extract typologies of injecting drug users in Tehran. RESULTS: Evidence of injecting drug use and drug-related harm was found in 5 of 6 study districts. Several profiles of IDUs were identified: depending on their socioeconomic status and degree of stability, IDUs employed different injecting behaviors and syringe hygiene practices. The prevalence of sharing injection instruments ranged from 30-100%. Varied magnitudes of risk were evident among the identified IDU typologies in terms of syringe disinfection methods, level of HIV awareness, and personal hygiene exhibited. At the time of research, there were no active HIV prevention programs in existence in Tehran. CONCLUSION: The recent rise of heroin injection in Iran is strongly associated with HIV risk. Sharing injection instruments is a common and complex behavior among Iranian IDUs. For each profile of IDU we identified, diverse and targeted interventions for decreasing sharing behavior and/or its harms are suggested. Some notable efforts to reduce the harm of injecting drug use in Iran have recently been accomplished, but further policies and action-oriented research for identification of effective preventive interventions are urgently needed.

Journal Article↗

Detection of retinyl palmitate and retinol in the liver of mice injected with excessive amounts of retinyl acetate.

The transport of subcutaneously injected retinyl acetate (RA, 100,000 IU/mouse, 105,470 nM) was investigated in male ICR mice (10-week-old) at 0, 3, 6, 12, 18, 24 and 72 hr after a single injection. The retinol and retinyl palmitate levels of liver homogenates, bile in the gallbladder and serum from peripheral blood were measured by high performance liquid chromatography (HPLC) method. Retinyl palmitate in the lipid droplets of hepatocytes and Ito cells was localized by a modified gold chloride staining method. Accumulation of retinyl palmitate peaked at 12 hr post-injection and decreased thereafter until 24 hr post-injection. Fluorescence microscopy revealed many fluorescent vitamin A-containing lipid droplets in hepatocytes around central veins at 12 hr post-injection, but such droplets were not observed in the vehicle control mice or at in the RA-injected mice after 18 hr of injection. Electron microscopic observation also indicated that many retinyl esters-containing lipid droplets were observed in hepatocytes around the central veins at 12 hr post-injection, but no droplets were seen in the controls or 18 hr post-injection. The retinyl palmitate levels in liver homogenates assessed by HPLC decreased from 12 to 24 hr post-injection and increased significantly in bile, while retinol in liver homogenates and serum markedly increased. One of the morphological alterations was intense vacuolization in hepatocyte cell cords from the portal toward the central vein observed at 24 hr post-injection. Transitional lipid droplets between vacuoles and lipid droplets were identified in those hepatocytes. These results of HPLC analysis of retinol and retinyl palmitate in liver homogenates, serum, and bile, together with the results of gold chloride staining suggested that subcutaneously injected RA was first incorporated in hepatocytes at 12 hr and then partially metabolized through vacuoles, transferred into the blood and secreted into the bile over a 24 hr period. Many retinyl esters-containing lipid droplets were visualized in Ito cells at 72 hr post-injection. Most of vitamin A in the liver homogenates measured by HPLC was retinyl palmitate. Therefore, the contents in those lipid droplets might be retinyl palmitate.

Animals↗

Luteinizing hormone release after two injections of synthetic luteinizing hormone releasing hormone in the ewe.

Anoestrous ewes were given two injections of 30 mug synthetic luteinizing hormone releasing hormone (LH-RH) separated by one of the following intervals: 1-5, 3, 6, 12 or 24 h. The first injection caused an increase in the plasma LH concentration in each animal. The response to the second injection was dependent on the interval between the injections. When the second injection was administered 1-5 h after the first it caused a further increase in the LH concentration to maximal levels which were significantly greater than those induced in the other anoestrous groups. When the second injection was administered 3 h after the first, there was no significant difference between the responses to the two injections although the time to reach the maximal LH concentration was shorter and the height of the LH peak was greater in each animal following the second injection. When the second injection was administered 6, 12 or 24 h after the first, the LH response was significantly less, in terms of height and area of the induced peak, than following the first injection. The LH response to the second injection was particularly low in the 12 and 24 h groups. Two injections of 30 mug synthetic LH-RH were also administered at 1-5 h intervals to ewes on either day 10 of the oestrous cycle or at onset of oestrus. The pattern of LH responses in all these animals was similar to that observed in anoestrous ewes injected at 1-5 h intervals. The total LH release, as assessed in terms of the induced peaks, was significantly greater in the onset of oestrus group than in the day 10 group or any of the anoestrous groups. Presumably the sensitization-desensitization sequence of the pituitary gland to LH-RH which has been demonstrated, together with the effects of sex steroid hormones, must play an important part in the development and decay of the natural preovulatory LH peak.

Anestrus↗

Anamnestic response of neonatal chickens to sheep red blood cells as influenced by the number of weeks between the first and second injections.

In two experiments primary and secondary hemagglutination titers of chickens were determined in response to intravenous injections of 1 mL of a 5% suspension of sheep red blood cells (SRBC). All birds received the primary injection at 4 wk of age. In the first experiment, equal numbers of male and female birds were randomly selected to receive the secondary injection at 2, 4, 6, and 8 wk following the initial injection. Based on the level of IgG antibody to SRBC, all postprimary injections affected an anamnestic response. Furthermore, the anamnestic response obtained following the 6 and 8-wk postprimary injection was significantly higher than those obtained with injections 2 or 4 wk after the primary injection. In the second experiment, secondary injections were administered either 3 or 6 wk after the primary injections. The anamnestic response of birds receiving the 6-wk postprimary injection was higher than those injected 3-wk after the primary injections.

Animals↗

Stability of an ofloxacin injection in various infusion fluids.

The stability of ofloxacin was evaluated in 10 different infusion fluids under various storage conditions. Solutions of ofloxacin (0.4 mg/mL and 4.0 mg/mL) were prepared in (1) 0.9% sodium chloride injection; (2) 5% dextrose injection; (3) 5% dextrose and 0.9% sodium chloride injection; (4) 5% dextrose and lactated Ringer's injection; (5) 5% sodium bicarbonate injection; (6) Plasma-Lyte 56 and 5% dextrose injection; (7) 5% dextrose, 0.45% sodium chloride, and 0.15% potassium chloride injection; (8) 1/6 M sodium lactate injection; (9) water for injection; and (10) 20% mannitol injection. Each solution was injected into polyvinyl chloride bags and stored at (1) 24 degrees C for 3 days, (2) 5 degrees C for 7 days, (3) 5 degrees C for 14 days, (4) -20 degrees C for 13 weeks and then 5 degrees C for 14 days, or (5) -20 degrees C for 26 weeks and then 5 degrees C, for 14 days. Samples were assayed initially and after storage by high-performance liquid chromatography and examined for visual clarity, pH, turbidity, and particulates. Ofloxacin was stable in all solutions and under all storage conditions. All of the solutions were clear, pH was stable, and particulate-matter counts were acceptable under all storage conditions (except for the 20% mannitol solution, which formed crystals at 5 degrees C and -20 degrees C). An injectable formulation of ofloxacin was stable for at least 3 days at 24 degrees C, 14 days at 5 degrees C, and 26 weeks at -20 degrees C in all tested infusion fluids. Crystals formed in refrigerated or frozen solutions prepared with 20% mannitol injection.

Bicarbonates↗

Tumor accumulation of gadolinium in lipid-nanoparticles intravenously injected for neutron-capture therapy of cancer.

Gadolinium-incorporating lipid-nanoemulsions (Gd-nanoLE) for neutron-capture therapy were prepared. As a more convenient administration route than the intraperitoneal (i.p.) injection previously reported, the intravenous (i.v.) injections in tumor-bearing hamsters were carried out at an administration volume of 1 ml, which was the maximum tolerable injection volume of an i.v. injection and half that of an i.p. injection. When the standard-Gd-nanoLE of 1.5 mgGd/ml was administered, the absolute bioavailability in the i.p. injection was 57%, probably resulting from incomplete absorption from the peritoneal cavity into the blood stream. The biodistribution data revealed that the i.v. injection had three advantages over the i.p. injection, namely, a faster and higher accumulation of Gd-nano LE, and a more extended retention time in the tumor. Two i.v. injections of the standard-Gd-nanoLE with a 24h interval doubled the tumor accumulation of Gd, resulting in 49.7 microg Gd/g wet tumor 12h after administration. By using a twofold Gd-enriched formulation (High-Gd-nanoLE) of 3.0 mgGd/ml in the repeated administration schedule, the accumulation was doubled again, reaching 101 microg Gd/g wet tumor. This level was comparable to the maximum level in the single i.p. injection previously reported. These results demonstrated that i.v. injection could be an alternative to i.p. injection as an administration route.

Animals↗

Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G.

The contribution of benzathine penicillin G to residues in tissues and injection sites of yearling beef steers was assessed by treating seven groups of five to seven steers with either benzathine and procaine penicillin G together or benzathine penicillin G alone. Steers were injected with a commercial combination of benzathine and procaine penicillin G according to the Canadian (intramuscular) or United States (subcutaneous) label dosages of 8600 and 8800 IU penicillin G/kg body weight, respectively. They were killed 14 or 30 days after the intramuscular injections, and 30 days after the subcutaneous injections. At the label withdrawal times, Canadian 14 days and United States 30 days, the levels in the injection sites for all of the treatments were 30-60 times above the Canadian and United States' Maximum Residue Limit of 50 micrograms/kg, while liver, kidney and gluteal muscle levels were below the Maximum Residue Limit. Other steers were injected intramuscularly with 24,000 IU benzathine/procaine penicillin G/kg body weight and slaughtered 8, 14 or 50 days after injection. Fifty-day injection site residues were 24 times the Maximum Residue Limit. Another group of steers was injected intramuscularly with benzathine penicillin G alone at 12,000 IU/kg body weight and slaughtered 14 days later. Penicillin G levels in the injection sites were 156 times the Maximum Residue Limit. The persistence of penicillin G residues at the injection sites in all the treatment groups appears to be attributable primarily to benzathine penicillin G. Visual inspection of muscle surfaces did not reliably reveal all injection site lesions in the underlying musculature.

Animals↗

Monoclonal antibody imaging of human melanoma. Radioimmunodetection by subcutaneous or systemic injection.

Fab fragments of monoclonal antibodies (MoAb) to melanoma, radiolabeled with 131I, were evaluated as diagnostic reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight antigen (HMW), or 96.5, which identifies a transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled antibodies demonstrated excellent nodal delineation without specific identification of tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed tumor in nodes. Of patients injected with Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma antibodies was observed in some patients in lymph nodes not containing tumor and was possibly related to antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection. Melanoma metastases can be identified with IV or SQ injection or radiolabeled antibodies. These reagents may be useful in the diagnosis or therapy of human melanoma. Further evaluation will be required before they could be considered clinically useful.

Adult↗

Intramuscular versus subcutaneous injection of unmodified insulin: consequences for blood glucose control in patients with type 1 diabetes mellitus.

Using the perpendicular injection technique lean diabetic patients may often inject insulin intramuscularly (IM). Guided by ultrasound measurements of the subcutaneous (SC) thickness of the thigh, the aim of the present study was to re-evaluate the absorption kinetics of unmodified insulin from IM and SC injection sites and to evaluate the consequences of IM injection of unmodified insulin for blood glucose control in Type 1 diabetic patients. T50% values (time until 50% of the injected insulin is absorbed from the injection site) of SC injected, radioactively labelled, human unmodified insulin (125I-Actrapid) were 338 +/- 13 (+/- SE) min, 289 +/- 27 min, and 287 +/- 27 min during rest, light physical activity, and strenuous exercise, respectively. Intramuscularly injected unmodified insulin was absorbed faster, T50% 232 +/- 20 min, 113 +/- 13 min, and 112 +/- 5 min during the same levels of physical activity in the same order. When unmodified insulin (Actrapid) was given IM 30 min before breakfast, lunch, and dinner together with intermediate-acting insulin (Protaphane) SC at 2200 h, a more physiological profile of plasma free insulin and a more stable blood glucose profile was obtained than with SC administration into the thigh. The coefficient of variation of blood glucose concentration during the study (3 days each route) was lower with IM than with SC injection of unmodified insulin (33 +/- 4 vs 43 +/- 3%, p less than 0.01). No difference in frequency of hypoglycaemic attacks was found and patients claimed that IM injection was no more painful than SC injection. These data suggest that IM injection of soluble insulin into the thigh is beneficial.

Adipose Tissue↗

Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site.

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Absorption↗

Lymphoscintigraphy in breast cancer patients--comparison of peritumoural and intradermal injection.

UNLABELLED: AIM of this study was to determine whether the sentinel lymph nodes (SLNs) can be accurately identified in breast cancer patients with intradermal injection of the radiotracer above the primary tumour in comparison to peritumoural injection. METHODS: In 45 women with breast cancer we performed lymphoscintigraphy on two separate days. We injected Tc-99m nanocolloid on the first day peritumourally, and on a separate day intradermally. The results of both investigations using different injection sites were compared in order to determine the number and location of SLNs. RESULTS: The SLN identification rate using peritumoural injection was 71% (32 of 45 patients) and 96% (43 out of 45 patients) using intradermal injection. In 62% (28 of 45 patients) the number and location of the SLNs were identical. In 97% (31 of 32 patients) in whom a SLN was detected using peritumoural injection, the same SLNs reappeared with intradermal injection. There were no false negative findings with the peritumoural administration of tracer whereas the intradermal administration approach resulted in a false negative rate of 13%. CONCLUSION: In women with breast cancer the reproducibility of lymphoscintigraphy using peritumoural and intradermal injection sites was 62%. The intradermal injection modality enables the detection of a SLN in patients where the peritumoural injection failed but it has the disadvantage of a higher false negative rate in comparison to the peritumoural injection technique.

Adult↗

Distribution of radioisotopic beryllium in mice after administration by various routes of injection.

A 7BeCl2 solution containing 0.5 micrograms Be per mouse was injected subcutaneously, intraperitoneally, intramuscularly, intrathoracically, and intravenously, and distribution was observed for periods up to 1 wk. 7Be was excreted more rapidly following intravenous injection than by the other routes of injection. The amount of Be found in the liver or the spleen was substantial at 1 d after intraperitoneal injection. It increased more in the spleen at 7 d after either intraperitoneal or intrathoracic injection. On the other hand, the amounts of Be stayed almost constant in the kidneys, by the various routes of injection. When injected intrathoracically, the amounts of Be in the heart and the lung were greater than when administered by the other routes of injection. The amounts of Be in the femurs of mice administered by these routes of injection, except with intravenous injection, were greater than in the other organs. The percentage of 7Be in the mineralized bone was 90% of that of 7Be in the femurs when injected intraperitoneally or intrathoracically. However, the ratio of Be in the mineralized bone to that in the bone marrow was 3 to 2. Beryllium had thus a closer affinity for the femurs than for the other organs investigated, with the different modes of administration used. The amount of Be in the entire skeleton was estimated to be substantial. Within the limitations of 1 wk of exposure, the skeleton would appear to be a critical organ. This would suggest that osteosarcomas may occur following administration of Be to laboratory animals for a long-term period.

Animals↗

Prolotherapy injections for chronic low-back pain.

BACKGROUND: Prolotherapy is an injection-based treatment for chronic low-back pain. Proponents of prolotherapy suggest that some back pain stems from weakened or damaged ligaments. Repeatedly injecting them with irritant solutions is believed to strengthen the ligaments and reduce pain and disability. Prolotherapy protocols usually include co-interventions to enhance the effectiveness of the injections. OBJECTIVES: To determine the efficacy of prolotherapy injections in adults with chronic low-back pain. SEARCH STRATEGY: We searched CENTRAL (2004, issue 1), MEDLINE, EMBASE, CINAHL and Science Citation Index from their respective beginnings to January 2004, with no restrictions on language. We consulted content experts to ensure we had not missed any references. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing prolotherapy injections to control injections, either alone or in combination with other treatments, were included. Studies had to include measures of pain and disability before and after the intervention. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials and assessed them for methodological quality. Treatment and control group protocols varied from study to study, making meta-analysis impossible. MAIN RESULTS: We included four high quality studies with a total of 344 participants. All trials measured pain and disability levels at six months, three measured the proportion of participants reporting a greater than 50% reduction in pain or disability scores from baseline to six months.Two studies showed significant differences between the treatment and control groups for those reporting over 50% reduction in pain or disability. Their results could not be pooled. In one, co-interventions confounded interpretation of results; in the other, there was no significant difference in mean pain and disability scores between the groups. In the third study, there was little or no difference between groups in the number of individuals who reported over 50% improvement in pain and disability. The fourth study reporting only mean pain and disability scores showed no differences between groups. REVIEWERS' CONCLUSIONS: There is conflicting evidence regarding the efficacy of prolotherapy injections in reducing pain and disability in patients with chronic low-back pain. Conclusions are confounded by clinical heterogeneity amongst studies and by the presence of co-interventions. There was no evidence that prolotherapy injections alone were more effective than control injections alone. However, in the presence of co-interventions, prolotherapy injections were more effective than control injections, more so when both injections and co-interventions were controlled concurrently.

Chronic Disease↗

Brain temperature change and movement activation induced by intravenous cocaine delivered at various injection speeds in rats.

RATIONALE: Speed of intravenous (i.v.) injection presumably affects the rewarding effects of cocaine in humans. Work with animals has shown alterations in the behavioral and neurochemical effects of cocaine based on delivery speed. OBJECTIVES: We studied the effects of cocaine (1 mg/kg) as both a single i.v. injection and a series of five repeated injections (8-min intervals) delivered at different speeds (4, 16, and 64 s) on brain, muscle, and skin temperatures, and locomotion in awake, unrestrained rats. Since cocaine has a distinctive action on temperature, any enhancement of cocaine's properties by injection speed should readily be seen. RESULTS: When given as a single injection, cocaine increased brain temperature and locomotion, but transiently decreased skin and muscle temperatures; these effects were augmented by a high injection speed. Regardless of injection speed, however, changes in brain temperature and locomotion were strongly correlated with basal brain temperatures; higher temperatures were associated with less change after cocaine injection. When given as a series of five injections, cocaine increased brain temperature and locomotion. Although skin temperature initially decreased, it increased after successive cocaine injections. With each successive cocaine injection in the series, measures of temperature and movement parameters increased to a plateau and brain temperature change became biphasic. CONCLUSIONS: While confirming the results of others that rapid injection speed enhances cocaine-induced locomotor activation, our study suggests that delivery rate also affects the basic physiological actions of cocaine.

Animals↗