Song recordings suggest feeding ground sharing in Southern Hemisphere humpback whales.

The Atlantic sector of the Southern Ocean (ASSO) has one of the highest densities of Antarctic krill (Euphausia superba) compared to other polar and subpolar regions, which attracts migratory baleen whale species to aggregate in this area for feeding. Humpback whales (Megaptera novaeangliae) also sing extensively while on the Southern Ocean feeding grounds which allows for the exploration of song similarity between feeding grounds and breeding populations which helps to understand population mixing. The results of comparative song analyses between the ASSO and the Ecuadorian and Brazilian breeding populations and recordings from the Chilean, South African and Namibian migration routes/mid-latitude feeding grounds revealed that individuals from at least three humpback whale breeding populations most likely migrate to shared feeding grounds in the ASSO. Humpback whales from different populations potentially mix at different times (i.e., years) at feeding hotspots in variable locations. The ASSO seems to provide sufficient prey resources and seems to present an important area for both cultural and maybe even genetic exchange between populations supporting the maintenance of large gene pools. Assuming that multi-population feeding hotspots are also suitable habitat for krill and other krill-dependent predators, these areas in the ASSO should be carefully managed integrating population, ecosystem and fisheries management.

Central Nervous System Vasculopathy in HIV-Infected Children Enrolled in the Pediatric AIDS Clinical Trials Group 219/219C Study.

BACKGROUND: Central nervous system (CNS) vasculopathy has been reported in human immunodeficiency virus-infected (HIV+) adults and children. In children, it often presents with HIV encephalopathy, stroke, or intracerebral aneurysms. The etiology, incidence, and risk factors of HIV-associated CNS vasculopathy in children are unknown. METHODS: We identified HIV+ children with a diagnosis of vasculopathy or other cerebrovascular events among children enrolled between 1993 and 2004 in 2 prospective, multicenter cohort studies. Demographic and laboratory data, history of antiretroviral use, and signs, symptoms, and diagnostic studies pertaining to the CNS event were reviewed. RESULTS: Among the 3338 HIV+ children, 51 had diagnoses that suggested CNS vasculopathy. Of these, 12 (24%) were included in this analysis, after excluding those with alternative diagnoses and those from closed sites. Among these 12, 4 (33%) were female, 4 (33%) were white, and 10 (83%) had perinatal HIV. Their average age at the event was 10.8 years with a median CD4 count of 22 cells/mm(3) and median HIV-1 viral load of 94 304 copies/mL. Fifty-eight percent of subjects had a history of opportunistic infections before the CNS event. Fifty percent had cerebral aneurysms on imaging. The overall incidence among HIV+ subjects was 3.4 cases per 10 000 person-years (95% confidence interval, 1.8-6.0). CONCLUSIONS: CNS vasculopathy in HIV+ children is uncommon but more common than in the general pediatric population. Cerebral aneurysms are the most common manifestation. Although the pathogenesis remains unclear, older children and those with low CD4 counts and high HIV viral loads are at the highest risk.

90Y-labeled tin fluoride colloid as a promising therapeutic agent: preparation, characterization, and biological study in rats.

In this study, tin fluoride colloid (SnF-c) was prepared, labeled with yttrium-90 ((90)Y), and characterized with respect to its physicochemical properties and biological behavior in an animal model. Particle size of SnF-c, at constant concentration of SnF(2), was dependent on pH, concentration of sodium fluoride (NaF), temperature, and time. The particle size of SnF-c decreased with an increase in NaF concentration and a decrease in reaction mixture pH. Radiolabeling yield of (90)Y-SnF-c at higher temperature increased and it was greater than 98% for the preparation at 95 °C. The (90)Y-SnF-c demonstrated high in vitro stability both in human serum and human synovial fluid at 37 °C up to 7 days. In vivo distribution studies in healthy male Wistar rats of (90)Y-SnF-c (particles <1 µm), following intravenous administration, revealed that the localization takes place preferably in the liver. The (90)Y-SnF-c (particles >1 µm) was well retained in the synovial space for 96 h after intra-articular injection, whereas leakage of (90)Y from the joint was 1.96% over this period. Because of high labeling yield and stability, (90)Y-SnF-c might be a promising agent for radiosynovectomy or therapy of liver malignancies.

Clinical investigations of 99mTc-p-aminohippuric acid as a new renal agent.

OBJECTIVE: 99mTc-p-aminohippuric acid (PAH) is a new radiopharmaceutical rapidly secreted by the kidneys in a manner consistent with tubular secretion. A comparative study of renal scintigraphy and clearance with 99mTc-PAH, diethylene triamine pentaacetic acid (DTPA) and mercaptoacetyltriglycine (MAG,) was performed. METHODS: 99mTc-PAH was prepared from a lyophilized kit by addition of sodium pertechnetate in the presence of DTPA. Ten healthy individuals were injected with 110 MBq of 99mTc-PAH. A dynamic study was repeated with 99mTc-DTPA and 99mTc-MAG3 several days later, after a 1-day interval. Clearance measurements were performed in five individuals. RESULTS: The mean values of time-to-peak activity (Tmax) and the time from peak to 50% of peak activity (T(1/2)) for 99mTc-PAH (3.6 +/- 0.9 and 6.9 +/- 2.7 min, respectively) and 99mTc-MAG3 (3.5 +/- 0.8 and 6.8 +/- 2.1 min, respectively) were significantly lower in comparison with those of s99mTc-DTPA (4.9 1.7 and 11.7 +/- 1.9 min, respectively). The mean value of 99mTc-PAH clearance (186.9 +/- 12.2 ml/min) was significantly lower in comparison with MAG3 clearance (303.9 +/- 19.5 ml/min) and significantly higher than DTPA clearance (85.0 +/- 24.1 ml/min). CONCLUSION: Our preliminary results indicate the potential usefulness of 99mTc-PAH for routine renal scintigraphy. Owing to its fast kinetics, excretion properties and high-quality images, it could be a suitable substitute for 99mTc-DTPA. 99mTC-PAH clearance values, however, were significantly lower than those of MAG3, and could not be used for the estimation of renal plasma flow.

Preparation and in vivo evaluation of 90Y-meso-dimercaptosuccinic acid (90Y-DMSA) for possible therapeutic use: comparison with 99mTc-DMSA.

INTRODUCTION: The aim of this study was to find out if (90)Y could form a stabile complex with meso-2,3-dimercaptosuccinic acid (DMSA) and if (90)Y-DMSA may have potential for tumor therapy in the palliative treatment of bone metastases. METHODS: The preparing of (90)Y-DMSA was carried out by varying experimental parameters, such as ligand concentration, pH, time, and temperature of the reaction, in order to maximize the labeling yield. Analysis of the complexes enclosed the radiochemical quality control (instant thin-layer chromatography, paper chromatography, and high-performance liquid chromatography), determination of pharmacokinetical parameters as well as biodistribution study in healthy male Wistar rats. In vitro stability of the complexes was tested too. RESULTS: (90)Y-DMSA could be prepared in high yields (>95%) under optimized conditions of reaction. Stability studies in saline and human serum in vitro showed no significant release of activity from the ligand over 24 hours and 10 days, respectively. The preliminary biodistribution results in rat at 2 hours indicated that (90)Y-DMSA, at both pH levels, was significantly retained into bone. The uptake in the kidneys was lower for (90)Y-DMSA at pH 8.0 then at pH 3.0. The retention in other organs was negligible. CONCLUSIONS: (90)Y complexes could be made with ease with DMSA. (90)Y-DMSA was obtained in good yield and was found to be very stable. A promising biodistribution result of this complex pointed at potential in the palliative treatment of bone metastases.

HIV knowledge and attitudes toward HIV testing of South Side Chicago Housing Authority residents.

High HIV infection rates in the United States are increasingly due to heterosexual risk behaviors, with increased rates in blacks and women. A survey of HIV knowledge and attitudes about HIV testing was conducted in an inner-city public housing population that included a convenience sample of residents of South Side Chicago Housing Authority facilities. The questionnaire addressed knowledge about HIV transmission and disease, health care options, condom use, prior HIV testing, and preferred places for HIV testing and education. Five hundred residents, ages 13-50 years completed the survey, during the period from November 2002 until April 2003. Eighty-three percent of the respondents were female and 50% of those surveyed were from 18-30 years of age. Race/ethnicity was not questioned in order to improve response rate. A comparable sample conducted earlier showed that population was 99% black race. Most respondents were knowledgeable about HIV transmission risk factors, although misinformation about transmission, treatment and prevention existed. Knowledge that HIV therapy is available was high (71%), while 25% thought an HIV vaccine was available and 13% thought there was a cure for HIV. Two thirds of sexually active respondents reported condom use in the past year. Three quarters reported previous testing for HIV and 90% of those tested returned for results. Most respondents wanted to learn more about HIV risk factors, testing and treatment but preferred primary care clinics to specialized places for HIV testing. Targeted HIV education interventions in the public housing facilities or primary care clinics are warranted.

Labeling, characterization, and in vivo localization of a new 90Y-based phosphonate chelate 2,3-dicarboxypropane-1,1-diphosphonic acid for the treatment of bone metastases: Comparison with 99mTc-DPD complex.

The goal of this investigation was to examine the possibilities for yttrium-90-labeling of the 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), which is currently labeled with technetium-99m and as a (99m)Tc-DPD clinically used as bone imaging agent. Analysis of the complex enclosed the radiochemical quality control methods, biodistribution studies, as well as the determination of pharmacokinetic parameters. The biological behavior of complexes (90)Y-DPD, (99m)Tc-DPD and (90)Y-labeled DPD-kit formulation [(90)Y-(Sn)-DPD] in animal model was compared. The labeling conditions were standardized to give the maximum yield, which ranged between 93% and 98%. The examined (90)Y complex could be easily prepared, with an outstanding yield and was also found to be very stable for at least 10h after (90)Y-labeling. Protein binding value was 4.6+/-0.7% for (90)Y-DPD complex and the complex possess a hydrophilic character. The satisfactory results of (90)Y-DPD biodistribution in healthy test animals were obtained; the uptake in the bone was 11-13%ID/g after 24h depending on the pH value during the preparation. With high skeletal uptake, a minimum uptake in soft tissues and rapid blood clearance the (90)Y-DPD complex proved to be an excellent candidate for targeting tumor therapy.

Alteration of the organ uptake of the (99m)Tc-radiopharmaceuticals, (99m)Tc-DPD, (99m)Tc-DMSA, (99m)Tc-tin colloid and (99m)Tc-MAA, induced by the applied cytotoxic drugs methotrexate sodium and cyclophosphamide.

AIM: To investigate the influence of certain cytotoxic drugs on the organ uptake of the following (99m)Tc-radiopharmaceuticals: (99m)Tc-2,3-dicarboxypropane-1,1-diphosphonic acid ((99m)Tc-DPD), (99m)Tc-meso-2,3-dimercaptosuccinic acid ((99m)Tc-DMSA), (99m)Tc-tin colloid and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). Methotrexate sodium and cyclophosphamide were used as models to evaluate these effects. METHODS: Two groups of healthy male Wistar rats were treated separately by oral application of the drugs for 7 days. On the eighth day, each of the (99m)Tc-radiopharmaceuticals was applied in a separate group of treated animals. They were sacrificed at different time intervals and the radioactivity in the organs of interest was measured. The organ uptake of the (99m)Tc-radiopharmaceuticals in an additional control group of animals was also studied. RESULTS: The results obtained showed an alteration in the organ uptake of (99m)Tc-radiopharmaceuticals in animals treated with cytotoxic drugs. In rats treated with methotrexate sodium, there was a higher uptake of (99m)Tc-DMSA in the bones, stomach and intestine, a higher uptake of (99m)Tc-DPD in the bones, intestine, blood and muscle, a lower uptake of (99m)Tc-tin colloid in the liver and a lower accumulation of (99m)Tc-MAA in the lungs. Cyclophosphamide-treated animals showed enhanced uptake of (99m)Tc-DMSA in the kidneys, a twofold enhanced uptake of (99m)Tc-DPD in all organs except the stomach, a decreased uptake of (99m)Tc-tin colloid in the lungs, spleen and kidneys and a significantly decreased uptake of (99m)Tc-MAA in the lungs. CONCLUSION: These results confirm that both methotrexate sodium and cyclophosphamide may alter the organ uptake of (99m)Tc-radiopharmaceuticals in experimental animals.

Chemical and biological evaluation of technetium (I) tricarbonyl complexes with EHIDA and DPD. 99m (I) complexes of EHIDA and DPD.

BACKGROUND: 99mTc-phosphate and 99mTc-IDA complexes, made by the addition of 99mTcO4- to the kits, have been applied to bone and gallbladder imaging respectively, for many years. In this paper, an effort to label DPD and EHIDA with [99mTc(CO)3(H2O)3]+ was carried out. MATERIAL AND METHODS: DPD and EHIDA were synthesised and prepared in kit form in INS "Vinca". A carbonyl labelling agent Isolink (Mallinckrodt Medical B.V.) and a carbonyl precursor (NCRS Demokritos) were applied. The samples of each compound were added to a vial containing 99mTc-carbonyl precursor, in which original pH (10/11) was neutralised to a pH of around 5.5 or 7.5, the same one as the pH of the investigated compounds. After heating, the reaction products were analysed by HPLC equipped with UV and g-detector, with TEAP 0.05 M, methanol and water as solvent. The biological evaluation of 99m99mTc(I)-coordinated compounds, as well as 99mTc-DPD and 99mTc-EHIDA complexes, involved a bio distribution examination on Wistar rats. RESULTS: The results have shown that hydrophilic organometallic [99mTc(CO)3(H2O)3]+ precursor facilitates the formation of Tc (I) complexes with these ligands, based on the tricarbonyltechnetium (I) core. The changes in structure of DPD and EHIDA labelled molecules influenced biological behaviour: 99Tc(CO)3 -DPD did not accumulate in bone (< 1% of the complex was found in the femur), while 99Tc(CO)3-EHIDA has shown slower billiary excretion and faster filtration through the kidneys. DISCUSSION: The results of the labelling of DPD and EHIDA with [99mTc(CO)3(H2O)3]+ and their chemical and biological behaviour, in comparison with the same one for 99mTc-DPD and 99mTc-EHIDA, confirmed that different oxidation states of technetium make the formation of a variety of complexes with quite different behaviour possible.

Mutations linked to drug resistance, human immunodeficiency virus type 1 biologic phenotype and their association with disease progression in children receiving nucleoside reverse transcriptase inhibitors.

BACKGROUND: Few data are available concerning the impact of antiretroviral resistance in response to antiviral therapy in children. We evaluated the development of antiretroviral genotypic resistance and clinical outcome in a subgroup of children involved in a prospective antiretroviral therapy trial (Pediatric AIDS Clinical Trials Group Protocol 152). DESIGN: We studied 26 matched case/control pairs. A case was defined as having clinical disease progression during the study period; controls did not have disease progression. Cases and controls were matched by age and CD4+ cell count at baseline. Matched pairs received treatment with zidovudine (9 pairs), didanosine (12 pairs) or combined therapy (5 pairs). Multiple codons of the reverse transcriptase coding region (41, 67, 70, 74, 151, 184, 210, 215 and 219) were analyzed. Patients were evaluated for CD4+ cell count, HIV-1 viral load and HIV-1 biologic phenotype at baseline and clinical endpoint. RESULTS: The presence of mutations associated with resistance after nucleoside antiretroviral therapy (P = 0.039) and syncytium-inducing phenotype (P = 0.031), were significantly associated with increased risk of clinical disease progression. The mean difference in HIV-1 RNA levels between cases and their matched controls after nucleoside antiretroviral therapy was 0.77 log10 copies/ml higher for cases (P = 0.003). The median difference between cases and controls for CD4+ cell count after nucleoside antiretroviral therapy was 349 cells/mm3 lower for cases (P < 0.001). CONCLUSIONS: In this small prospective study of HIV-infected children, mutations in the reverse transcriptase coding region, syncytium-inducing viral phenotype, higher HIV-1 RNA load and lower CD4+ cell count were significantly correlated with increased risk of HIV clinical disease progression.

Immunoreconstitution in children receiving highly active antiretroviral therapy depends on the CD4 cell percentage at baseline.

The effect of highly active antiretroviral therapy (HAART) in 85 children infected with human immunodeficiency virus type 1 (HIV-1) was compared retrospectively among Centers for Disease Control and Prevention (CDC) immunologic groups 1-3. The duration of HAART did not vary significantly among the immunologic groups (median, 39.07 months). The CD4 cell percentage increased in 39.1%, 58.3%, and 90% of patients in CDC groups 1-3, respectively (P <.001). HAART resulted in the suppression of HIV-1 below detectable levels in 34.8%, 25%, and 32% of patients in the 3 CDC groups, respectively, and in a frequent switch from syncytium-inducing to nonsyncytium-inducing virus. Thymic excision circles increased in a subset of patients with increases in CD4 cell percentage independently of HIV RNA level. The results support the option of delaying HAART in early asymptomatic HIV-1 disease in children and the use of other markers of disease progression, in addition to virus load.