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PubMed2006

Can home-made injectable opiates contribute to the HIV epidemic among injection drug users in the countries of the former Soviet Union?

AIMS: Home-made preparation of heroin is common in countries of the former Soviet Union (FSU), and the addition of blood during its preparation and the use of contaminated syringes to distribute it may play a role in the rapid spread of HIV-1 among injecting drug users (IDUs). This study was designed to determine the viability of HIV-1 during these procedures. SETTING: Field observations of home-made opiate manufacture in four FSU countries were used to develop a consensus protocol to replicate manufacture in the laboratory that included the addition of human blood contaminated with HIV-1. DESIGN AND MEASUREMENT: Following the addition of HIV-1-contaminated blood during manufacture or storage, we attempted to recover viable HIV-1. The recovery was measured by propagation of the virus in stimulated white blood cells from uninfected donors. FINDINGS: In experiments in which HIV-1 contaminated blood was added during manufacture, no viable HIV-1 was recovered. In experiments in which chornaya was introduced into HIV-contaminated syringes, the percentage of syringes containing viable HIV-1 was reduced. The reduction appeared to be related to the interaction of HIV-1 contaminated blood with a component of the poppies. While HIV-contaminated syringes used to dispense or inject home-made opiates might transmit HIV, the ability of chornaya to reduce HIV viability seems to make this route of transmission less efficient. CONCLUSIONS: The epidemic of HIV-1 among IDUs in the FSU resulted more probably from recognized injection risk behaviors-including sharing syringes and drug solutions--than from opiate solutions harboring viable HIV-1.

Disease Outbreaks↗
PubMed1985

A multiple injection regimen using an insulin injection pen and pre-filled cartridged soluble human insulin in adolescents with diabetes.

A multiple insulin injection regimen using a self-contained injection device Novopen (Novo Industries, Bagsvaerd, Copenhagen, Denmark) was assessed in 11 adolescents (age range 12.1-16.9 years) with diabetes. Ten patients completed the 3-month study period and eight expressed a wish to continue with the regimen, finding that the advantages it offered out-weighed the inconvenience of multiple injections. Mean glycosylated haemoglobin fell over the 3 months of the study period from 13.7 +/- 2.7% to 11.7 +/- 3.4% (NS) and there was a trend towards lower mean blood values which reached significance at the pre-lunch measurement (p less than 0.02).

Adolescent↗
PubMed1991

Endoscopic treatment for bleeding peptic ulcers: randomised comparison of adrenaline injection and adrenaline injection + Nd:YAG laser photocoagulation.

Forty two patients with haemorrhage from peptic ulcers with visible vessels were enrolled in a randomised study comparing endoscopic haemostasis with adrenaline (1:10,000) injections (adrenaline group) and adrenaline injection + neodymium yttrium-aluminium-garnet (Nd:YAG) laser photocoagulation (adrenaline + laser group). The two groups (21 patients each) were well matched for factors affecting outcome. Surgery was performed for continued haemorrhage uncontrolled by endoscopic treatment or rebleeding after two endoscopic treatments. Haemostasis after one treatment was similar in the two groups: adrenaline 16/21 (76%), adrenaline + laser 18/21 (86%). Haemostasis after two treatments was numerically (0.05 less than p less than 0.10) greater in the adrenaline + laser group: 21/21 (100%) v 18/21 (86%). Three patients (14%) in the adrenaline group underwent uneventful emergency surgery. There were no deaths or procedure related complications in either group. Most bleeds from peptic ulcers with visible vessels can be controlled endoscopically without the need for surgery. Both treatments in this study proved highly efficacious in securing haemostasis. Adrenaline injection treatment seems to be the treatment of choice in view of its simplicity, low cost, and availability. Additional Nd:YAG laser treatment may provide a marginal improvement in efficacy, although a much larger trial would be required to prove this.

Aged↗
PubMed2003

Criminal outcomes and costs of treatment services for injecting and non-injecting heroin users: evidence from a national prospective cohort survey.

OBJECTIVES: To assess the incremental cost-effectiveness of drug addiction treatment programmes provided in the UK by the National Health Service and not-for-profit agencies in terms of crime-related outcomes. All costs and crime-related outcomes were implicitly evaluated relative to a 'no treatment' alternative. METHODS: Longitudinal observational data on a national sample of heroin addicts referred to addiction treatment services throughout England were re-analysed. Predictions from a Poisson random-effects model were used to estimate the incremental effectiveness and cost-effectiveness of treatment programmes. Interaction variables were used to assess whether the injecting of heroin on entry to treatment had an impact on cost-effectiveness. RESULTS: The findings rejected the null hypothesis that increasing time in treatment (and therefore treatment cost) has no mean crime prevention effect on clients referred for community-based methadone treatment, treatment delivered within specialist drug dependency units and residential rehabilitation programmes (P < 0.05). However, the size of the cost per unit of effect based on model predictions was sensitive to the exclusion of a small group of outlying observations. The interaction between client injecting status and time in treatment was found to be statistically significant (P < 0.05), with an estimated reduction in treatment cost-effectiveness across all treatment programmes for clients who reported injecting drugs at treatment intake. CONCLUSIONS: Whilst the analyses did not include an evaluation of the effect of treatment programmes on client health and quality of life and stopped short of providing a social weighting for the predicted reduction in crimes, they do offer a useful starting point for establishing the cost-effectiveness of treating heroin addiction. The onus is on public decision-makers to decide whether the predicted reductions in crime are worth the opportunity costs of investing extra resources in a major expansion of treatment services.

Cost-Benefit Analysis↗
PubMed2006

Service uptake and characteristics of injection drug users utilizing North America's first medically supervised safer injecting facility.

In 2003, the city of Vancouver, British Columbia, opened North America's first government-sanctioned safer injecting facility, where injection drug users (IDUs) can inject preobtained illicit drugs under the supervision of nurses. Use of the service by IDUs was followed by measurable reductions in public drug use and syringe sharing. IDUs who are frequently using the program tend to be high-intensity cocaine and heroin injectors and homeless individuals. The facility has provided high-risk IDUs a hygienic space where syringe sharing can be eliminated and the risk of fatal overdose reduced. Ongoing evaluation will be required to assess its impact on overdose rates and HIV infection levels, as well as its ability to improve IDU contact with medical care and addiction treatment.

Ambulatory Care Facilities↗
PubMed1993

HIV risk-related sex behaviors among injection drug users, crack smokers, and injection drug users who smoke crack.

OBJECTIVES: This study was designed to assess and compare sex risk behaviors for human immunodeficiency virus (HIV) transmission of three drug user groups: injectors who do not smoke crack, crack smokers who do not inject, and injectors who also smoke crack. METHODS: Sexual risk behaviors for HIV were assessed among 246 drug users from Denver, Miami, and San Francisco. Respondents were classified into the three drug groups based on self-report and verified through urinalysis and physical inspection. RESULTS: An increased risk for HIV through sexual transmission was associated with crack cocaine use, particularly among those who also injected. Crack smoking injectors were more likely to report sex with an injector, exchanging sex for drugs and/or money, drug use before or during sex, and unprotected sexual intercourse. They also injected more than injectors only, smoked crack as often as smokers only, and reported higher overall frequencies of drug use. CONCLUSIONS: These findings, together with the higher rates of gonorrhea and syphilis reported by smokers and injectors/smokers, are indicators of the risk crack poses for the heterosexual transmission of HIV.

Adult↗
PubMed1996

The protective effect of AIDS-related behavioral change among injection drug users: a cross-national study. WHO Multi-Centre Study of AIDS and Injecting Drug Use.

OBJECTIVE: This study assessed the relationship between self-reported acquired immunodeficiency syndrome (AIDS) behavioral change and human immunodeficiency virus (HIV) serostatus among injection drug users. METHODS: The study sample involved 4419 injection drug users recruited from drug abuse treatment and nontreatment settings in 11 cities in North America, South America, Europe, Asia, and Australia. The World Health Organization multisite risk behavior questionnaire was used, and either blood or saliva samples for HIV testing were obtained. Subjects were asked, "Since you first heard about AIDS, have you done anything to avoid getting AIDS?" RESULTS: The protective odds ratio for behavioral change against being infected with HIV was 0.50 (95% confidence interval = 0.42, 0.59). While there was important variation across sites, the relationship remained consistent across both demographic and drug use history subgroups. CONCLUSIONS: Injection drug users are capable of modifying their HIV risk behaviors and reporting accurately on behavioral changes. These behavioral changes are associated with their avoidance of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2000

HIV-1 subtypes in injecting drug users & their non-injecting wives in Manipur, India.

The presence of HIV-1 antibodies was determined among the injecting drug users (IDUs) and their non-injecting wives. A total of 233 (72%) were found to be HIV-1 seropositive among the 322 subjects recruited in this study between August, 1996 and September, 1997. The distribution of HIV-1 subtypes among the injecting drug users (IDUs) and their wives was determined using peptide enzyme immunoassay (EIA). Sexual transmission of HIV-1 occurred frequently (45%) from HIV-1 infected IDUs to their spouses. The majority of the subjects (167/233) were infected with subtype C followed by subtype Thai B (29/233). Subtype C was the most common among both IDUs (78%) and their wives (57%), followed by subtype Thai B (12% and 13% respectively). The distribution of subtypes was significantly different between IDUs and their wives with a lower percentage of subtype C and higher percentage of subtype D in the infected wives (P < 0.03). Discordance for subtypes transmitted from IDUs to their wives suggests the occurrence of dual and/or recombinant infection in the IDUs.

Female↗
PubMed2001

Projecting severe sequelae of injection-related hepatitis C virus epidemic in the UK. Part 2: Preliminary UK estimates of prevalent injection-related hepatitis C carriers, and derivation of progression rates to liver cirrhosis by gender and age at hepatitis C virus infection.

BACKGROUND: In Part 2, we illustrate how available data can be used to obtain preliminary estimates for Scotland of prevalent injection-related hepatitis C carriers and of maternally hepatitis C virus (HCV)-infected infants. Novel approaches to reducing uncertainty about the number of Scotland's HCV infected children of injector parents are discussed in brief. Three approaches, one direct and two indirect, to estimating the number of current and ever-injectors are presented for England and Wales. METHODS: Diagnosed HCV infections in injectors and HCV test uptake by current injectors are combined with survey estimates for the ratio of ever-injectors to current injectors to estimate prevalent injection-related hepatitis C carriers. Household surveys give direct but potentially biased estimates of the number of current and ever-injectors. Indirect estimates make use of hepatitis C diagnoses in injectors, HCV prevalence and test-uptake by injectors, or exploit international comparisons. We comment on key reporting problems that inhibit synthesis of HCV progression studies; and suggest how to derive preliminary gender-and-age specific progression rates to liver cirrhosis for use in projections. RESULTS: Preliminary estimates for Scotland of prevalent injection-related hepatitis C carriers are: central estimate 39,000, inner uncertainty 16,000-59,000; of maternally hepatitis C virus (HCV)-infected infants central estimate 260, uncertainty 110-1100; and for England and Wales estimates of the number of prevalent ever-injectors are central estimate 360,000, uncertainty 240,000-835,000. Both hepatitis C prevalence in injectors and estimated numbers of current injectors are similar in Australia, and England and Wales (but not so for Scotland), Australian work on projections of severe HCV sequelae from hepatitis C infections may therefore be a suitable starting point for projections for England and Wales. Australia anticipates a doubling in the number of persons living with hepatitis C cirrhosis from 8500 in 1997 to over 17,000 in 2010. DISCUSSION: Australian projections of severe HCV sequelae used progression rates that, for simplicity, were independent of gender and of age at HCV infection. Faster HCV progression for males, and their higher injector prevalence, means that the impact of HCV infection on, for example, liver cancer may be evident to a greater extent and earlier in males.

Adolescent↗
PubMed2005

Injection drug use, HIV/AIDS and incarceration: evidence from the Vancouver Injection Drug Users Study.

The reliance on law enforcement as the dominant drug policy approach has resulted in record incarceration rates in many countries. Human rights advocates and public health researchers have argued that the risks of HIV transmission resulting from injection drug use within Canadian prisons must be addressed. Despite a decade of advocacy and some progress made, this remains an urgent public health crisis. In light of these concerns, researchers working with the Vancouver Injection Drug Users Study (VIDUS) have undertaken a series of studies specific to injection drug use and HIV/AIDS in prisons. This article summarizes the body of evidence generated via VIDUS, discusses briefly the related human rights implications, and concludes with recommendations for action.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

Prevention of suppression of alloreactive capacity following intravenous injection of neuraminidase-treated allogeneic cells by co-injection of agents competing for asialoglycoprotein receptor.

Intravenous (i.v.) administration of neuraminidase (Nase)-treated allogeneic lymphocytes resulted in the complete abrogation of the capacity to develop delayed-type hypersensitivity (DTH) responses to the relevant alloantigens (tolerance induction). The Nase treatment did not influence the antigenicity of allogeneic lymphocytes, as subcutaneous inoculation of Nase-treated cells was capable of generating comparable anti-allo-DTH responses to those induced by untreated allogeneic cells. However, Nase-treated lymphocytes were revealed to exhibit strikingly enhanced reactivity to the lectin peanut agglutinin (PNA) as well as adhesion to hepatocytes in the primary culture. Such enhanced PNA-reactivity was inhibited by lactose but not by maltose, and enhanced hepatocyte-adhesion was also inhibited by N-acetyl-galactosamine (GalNAc) but not by N-acetyl-glucosamine (GlcNAc), indicating augmented reactivity of Nase-treated cells to Gal/GalNAc-specific receptors on hepatocytes. It was also demonstrated that i.v. infusion of Nase-treated, 51Cr-labeled lymphocytes leads to an increased radioactivity in the liver and that this enhanced retention of radioactivity can be inhibited by the co-injection of Nase-treated, unlabeled syngeneic erythrocytes. Most importantly, the co-injection of Nase-treated allogeneic lymphocytes and Nase-treated erythrocytes resulted in the prevention of the suppression of anti-allo-DTH responses as induced by the injection of Nase-treated allogeneic cells alone. These results indicate that Nase-treated allogeneic cells are entrapped in the liver in a strikingly increased way through their enhanced reactivity to Gal/GAlNAc receptor of the liver and suggest that such enhanced entrapment by the liver has a crucial role in inducing anti-allo-DTH tolerance.

Animals↗
PubMed1993

Progression of HIV infection among injecting drug users: indications for a lower rate of progression among those who have frequently borrowed injecting equipment.

OBJECTIVE: To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). DESIGN: A prospective epidemiologic study. SETTING AND PATIENTS: We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. MAIN OUTCOME MEASURES: Progression was defined as a decline of the CD4 cell count to < 200 x 10(6)/l on two consecutive follow-up visits or AIDS. RESULTS: Using Cox modelling, the following baseline variables were predictive of progression. Enhanced progression was associated with: age > 30 years [relative hazard (RH), 7.7 [95% confidence intervals (CI), 1.7-36.0]], core antibody negativity [RH, 5.3 (95% CI, 1.6-17.6)], CD4 cell count [for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% CI, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% CI, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l]. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or > 99 times had a RH of 0.44 (95% CI, 0.22-0.88) and 0.19 (95% CI, 0.03-0.37), respectively, compared with IDU who had borrowed < 10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% CI, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. CONCLUSIONS: Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.

Adult↗
PubMed1998

Immediate endoscopic injection therapy of bleeding oesophageal varices: a prospective comparative evaluation of injecting materials in Egyptian patients with portal hypertension.

The present study was conducted to compare usual sclerosants: polidocanol 1%, ethanolamine oleate 5% and the tissue adhesive: cyanoacrylate in the control of oesophageal variceal bleeding in Egyptian patients with portal hypertension in a prospective comparative trial. Sixty patients with portal hypertension due to schistosomal hepatic fibrosis and/or posthepatitic liver cirrhosis who had presented with acute oesophageal variceal bleeding were enrolled. Patients received balloon tamponade prior to injection were excluded. Resuscitation had been done before or during emergency endoscopy. Emergency endoscopy was conducted within 2 hours from the onset of hematemesis. Patients were immediately randomized during emergency endoscopy to receive polidocanol 1%, ethanolamine oleate 5% or tissue adhesive. Variceal rebleeding was managed by reinjection. The three groups were comparable for age, sex, etiology of portal hypertension, Child-Pugh class and findings at emergency endoscopy. No active bleeding was observed at the end of all injection sessions. Rebleeding had been occurred within the first 24 hours in 2 (10%) patients in polidocanol group and 3 (15%) patients in ethanolamine group (P > 0.05). Reinjection did control rebleeding in 2 (10%) patients in ethanolamine group with a total success rate of 95%. Exsanguinating rebleeding occurred in 2 (10%) patients in polidocanol group and one (5%) patient in ethanolamine group (P > 0.05). Postinjection large ulcers were diagnosed either in polidocanol (15%) or ethanolamine (10%) groups (P > 0.05). Other complications were minor and showed no significant differences between the three groups. In coclusion, polidocanol, ethanolamine and cyanoacrylate are equally safe and effective. For immediate endoscopic injection therapy an experienced team must be available.

Cyanoacrylates↗
PubMed1998

Gender differences in injection-related behaviors among injection drug users in Baltimore, Maryland.

Baseline data from 640 injection drug users in the Stop AIDS for Everyone study, an HIV preventive intervention were used to examine gender differences in self-reports of injection behaviors. In both the bivariate and multivariate analyses men reported injecting alone, in semipublic areas, and at their mother's residence more often than women. In the bivariate analyses, women reported denser personal networks, and in the multivariate analyses, women reported significantly greater overlap between their drug and sex networks. These data suggest that this overlap of sex and drug networks may reduce women drug injectors' ability to adopt and maintain HIV protective behaviors. The data also suggest that interventions need to address gender differences in the social context of risk behaviors.

Adult↗
PubMed2000

Intra-cytoplasmic sperm injection versus partial zona dissection, subzonal insemination and conventional techniques for oocyte insemination during in vitro fertilisation.

BACKGROUND: In vitro fertilisation (IVF) and embryo transfer as treatment for male factor infertility is associated with lower fertilisation and pregnancy rates than for other indications. Since the late 1980s several assisted fertilisation techniques have emerged and have been rapidly developed to try to enhance results for couples with male factor infertility, or to help couples with severe male factor for whom conventional IVF was not possible. The technique of partial zona dissection (PZD) was developed to increase the probability that a sperm capable of fertilisation comes in contact with the oocyte. Although this method improved conventional IVF results, the improvement was only marginal and relatively large numbers of sperm are still required. This drawback applied less to the subsequent technique of subzonal microinjection of spermatozoa into the perivitelline space (SUZI). However, for all of these techniques fertilisation rates remained low, rates of polyspermic fertilisation were increased, and cases with a very limited number of spermatozoa in the ejaculate could still not be treated. The advent of intra-cytoplasmatic sperm injection (ICSI) of a single sperm (or sperm head or nucleus) into the oocyte appears to be an important breakthrough. OBJECTIVES: To investigate whether ICSI improves fertilisation and/or pregnancy rates in comparison to other fertilisation techniques. SEARCH STRATEGY: The Menstrual Disorders and Subfertility Group search strategy (see Review Group details) was used to identify trials that had compared ICSI with other infertility techniques, such as PZD, SUZI, conventional IVF and additional IVF. SELECTION CRITERIA: Trials were included if they compared the effects of these techniques on fertilisation and pregnancy outcomes. Only randomised studies were included in this review. DATA COLLECTION AND ANALYSIS: Ten studies met the inclusion criteria for this review. Eight studies compared ICSI with conventional IVF. One study compared ICSI with SUZI and one study compared ICSI with additional IVF. Data was extracted independently by two reviewers. Where relevant data was missing or unclear, the authors had been consulted. Male participants were classified according to their semen parameters, i.e. normal semen (concentration >20 million per ml, motility >50%, morphology >14%), borderline semen (concentration 10-20 million per ml, motility 30-50%, morphology 4-14% normal forms) and very poor semen (concentration <10 million per ml, motility <30%, morphology <4% normal forms). MAIN RESULTS: For couples with normal semen there is no evidence of a difference in fertilisation rates per retrieved oocyte or pregnancy rates between ICSI and conventional IVF. On the other hand, for fertilisation rate per inseminated oocyte, ICSI appears to result in better outcomes than IVF for normal semen. For couples with borderline semen ICSI results in higher fertilisation rates (all) than IVF. Couples with very poor semen will have better fertilisation outcomes with ICSI than with SUZI or additional IVF. REVIEWER'S CONCLUSIONS: There is evidence from this systematic review that fertilisation rates are significantly better with ICSI than IVF in couples with borderline semen. When the semen parameters are normal there is insufficient evidence of a difference in effectiveness between ICSI and IVF when retrieved oocytes were the unit of randomisation. However, there was a small but statistically significant increase in fertilisation rate when inseminated oocytes were the unit of randomisation. Total fertilisation rates were significantly reduced in ICSI cycles than IVF but there were no damaged oocytes in IVF cycles regardless of the semen parameters.

Embryo Implantation↗
PubMed2002

Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long-acting preparation and milk residues following a single subcutaneous injection.

Separate groups of goats were used to determine drug depletion patterns in serum (n=10), tissue (n=20) and milk (n=8) following a single intramuscular (i.m.) dose of 20 mg/kg of a long-acting oxytetracycline (OTC) formulation (Liquamycin LA-200). Milk residues were also determined following a subcutaneous (s.c.) administration of the same product at the same dose. Serum samples were taken for 24 h post-treatment and tissues (fat, liver, kidney, muscle and injection site) collected at 4, 7, 14, 21 and 28 days following injection. Milk from lactating goats was collected every 12 h for 8 days following both the i.m. and s.c. treatments utilizing an intervening 5-week washout period. Residues in serum and tissue were measured using a microbial inhibition assay, while milk residues were measured using both a microbial inhibition assay and a validated HPLC method. The serum pharmacokinetic parameters of OTC in goats were determined, with a mean AUC=67.4 microg h/mL, mean terminal half-life=14.4 h, and apparent clearance=0.33 L/kg h. Tissue half-lives could not be determined with confidence because the collection times provided only two points at which residues could be measured for most tissues. Oxytetracycline residues in all goat tissue samples measured less then cattle tissue tolerance by 96 h postdosing. One-compartment model describing milk depletion data for i.m. and s.c. dosing had terminal slope half-lives of 20.1 and 36.1 h, respectively. By 96 h post-treatment none of the milk samples contained OTC residues in excess of the cattle milk tolerance (0.3 p.p.m.). For both milk and tissue, the upper-bound 99% confidence intervals for the samples taken from goats 96 h postdosing were lower than approved cow milk and tissue tolerances.

Animals↗
PubMed2004

Large infiltrative hepatocellular carcinomas: treatment with percutaneous intraarterial ethanol injection alone or in combination with conventional percutaneous ethanol injection.

PURPOSE: To retrospectively evaluate patients' tolerance and the effectiveness of percutaneous intraarterial ethanol injection (PIAEI), alone or combined with conventional percutaneous ethanol injection (PEI), for treatment of advanced hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Neither institutional review board approval nor informed consent was required for this retrospective study; however, all patients had given their consent to be treated with PIAEI. Fourteen men and four women with cirrhosis and HCC who were ineligible for conventional curative treatment (largest tumor diameter, 35-90 mm; mean, 52 mm +/- 16 [standard deviation]) and whose supplying arteries were visible on computed tomographic (CT) and color Doppler ultrasonographic (US) images were treated with US-guided PIAEI-either alone or combined with PEI. Twelve patients had infiltrative tumors, and six had nodular tumors. Four patients had portal venous tumor involvement. Tumor necrosis and recurrence were evaluated with CT, and 1- and 2-year survival rates were evaluated with Kaplan-Meier analysis. RESULTS: In four patients, the main tumor was treated with PIAEI only, and in 14 patients, the main tumor was treated with combined PIAEI and PEI. One patient died of myocardial infarction before CT evaluation. Tumor necrosis was complete in 15 (88%) and incomplete in two (12%) of 17 patients. Results of subsequent surgery performed in three patients confirmed the radiologic findings: complete tumor necrosis in two patients and incomplete necrosis in one patient. Two severe PIAEI-related complications occurred: liver abscess, which resolved, and fatal acute pancreatitis. During the follow-up period (mean, 15 months +/- 6.7), six patients died owing to recurrent HCC, and 10 patients were alive with no detectable tumor after a mean follow-up period of 18 months +/- 11. One- and 2-year survival rates were 76.6% and 44.5%, respectively. CONCLUSION: For patients with advanced HCC who are ineligible for other curative options, PIAEI could be an effective treatment, despite the associated risk of severe complications.

Aged↗
PubMed2002

Pharmacokinetics of fluconazole in loggerhead sea turtles (Caretta caretta) after single intravenous and subcutaneous injections, and multiple subcutaneous injections.

Superficial and systemic mycotic infections are common among clinically ill sea turtles, which places growing importance on the establishment of pharmacokinetic-based dosage regimens for antifungal drugs. The pharmacokinetic properties of the antifungal drug fluconazole, after intravenous (i.v.) and subcutaneous (s.c.) injections, were studied in juvenile loggerhead sea turtles (Caretta caretta) housed at 23.0-26.5 degrees C. Fluconazole pharmacokinetic properties were further assessed in a multiple-dose s.c. regimen derived from the pharmacokinetic parameters determined in the single-dose study. Pharmacokinetic parameters were calculated, using a two-compartment model, from plasma concentration-time data obtained after single i.v. and s.c. administrations of fluconazole at a dosage of 2.5 mg/ kg body weight in six juvenile sea turtles. Blood samples were collected at intervals through 120 hr after each dose, and the concentration of fluconazole in plasma was measured by reverse-phase high-performance liquid chromatography. The i.v. and s.c. elimination half-lives were 139.5 +/- 36.0 and 132.6 +/- 48.7 hr (mean +/- SD), respectively. Systemic clearance of fluconazole was 8.2 +/- 4.3 ml/kg x hr, and the apparent volume of distribution at steady state was 1.38 +/- 0.29 L/kg. A multiple-dose regimen was derived, which consisted of a loading dose of 21 mg/kg body weight and subsequent doses of 10 mg/kg administered through s.c. injection every 120 hr (5 days). This regimen was administered to four juvenile sea turtles for 10 days, and blood samples were taken to determine peak and trough plasma concentrations of fluconazole. The mean concentrations for the two peak concentrations were 16.9 +/- 1.1 and 19.1 +/- 2.8 microg/ml 4 hr after dosing, and the mean concentrations for the three trough concentrations were 7.2 +/- 2.2, 10.4 +/- 2.7, and 10.7 +/- 2.9 microg/ml 120 hr after dosing. The terminal half-life after the last dose was calculated at 143 hr. Throughout the multiple dosing, fluconazole concentrations remained above approximately 8 microg/ml, a concentration targeted when treating mycotic infections in humans. The results of this study suggest that fluconazole can be effectively administered to sea turtles at a dosage of 10 mg/kg every 5 days after a loading dose of 21 mg/kg.

Animals↗