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Biomedical subjects

L Strong

Publications and source records attributed to L Strong.

At least 19 recordsLinked to original sources

Obstacles to needle exchange participation in Rhode Island.

OBJECTIVE: This study explores obstacles to participation in needle exchange programs (NEPs) among injection drug users (IDUs) in the state of Rhode Island, U.S.A. METHODS: A written questionnaire was administered at two Rhode Island drug detoxification sites in 1998. RESULTS: 488 self-administered surveys were completed, 226 (46.3%) respondents had injected drugs in the past 6 months. 62.1% reported sharing syringes in the past 6 months, and each syringe was used a mean of 10.7 times. Major obstacles to NEP participation were a lack of awareness of the program (25.6%), inconvenient location or hours (15.9%), and fear of identification and/or police harassment (12.2%). Non-white race was a significant predictor of being unaware of the NEP (p = .01) and not participating in the NEP (p = .03). 13.1% of IDUs who used the NEP were referred to the detoxification program by the NEP. Among all IDUs surveyed, 51.0% had participated in a NEP. CONCLUSIONS: NEPs are important in reducing the spread of bloodborne pathogens among IDUs and are effective referral sources for drug treatment. Surveys of IDUs at sites other than NEPs, such as detoxification facilities, can identify obstacles to the use of NEPs.

Acquired Immunodeficiency Syndrome

TP53 mutation and haplotype analysis of two large African American families.

Two large apparently unrelated African American families with a high incidence of breast cancer and other tumors characteristic of Li-Fraumeni breast sarcoma cancer family syndrome were studied. Mutation screening revealed that in both families the affected members carried a germline mutation of the TP53 gene at codon 133 (ATG--> ACG, M133T). In order to determine whether an ancestral haplotype was shared by these two families, polymorphic markers within and flanking the TP53 gene were studied. Haplotype analysis using five markers revealed an identical haplotype shared by the two families. Loss of heterozygosity at the TP53 locus in the probands' tumor tissues from each family was observed; in each case, the retained allele carried the common haplotype. The frequency of this haplotype in the general African American population is <0.003. This unique haplotype, combined with the rare TP53 mutation, suggests that these African American families share a common ancestry. This finding suggests that other African Americans may be carriers of this mutation and thus may be at risk of early-onset breast cancer or other cancers characteristic of the Li-Fraumeni breast sarcoma cancer family syndrome. The finding of recurring mutations in African Americans may facilitate carrier screening and identification in this population.

Alleles

Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.

A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.

Chromosomes, Human, Pair 17

The effect of faecally excreted ivermectin and fenbendazole on the insect colonisation of cattle dung following the oral administration of sustained-release boluses.

The effects of faecal drug residues following the administration of anthelmintics in the form of sustained-release boluses, on dung-colonising Coleoptera and Diptera are reported. In blind field trials, pats of standard weight and size were prepared from the dung of cattle treated with an ivermectin (Ivomec SR Bolus, MSD Agvet) or a fenbendazole (Panacur Bolus, Hoechst) sustained-release bolus, and from a third control group of cattle that received no treatment. Pats were recovered after 7, 14, 21 and 42 days in the field and searched for invertebrates. There were no differences in the numbers of adult beetles found in the pats from the three treatment groups. Pats made from the dung of ivermectin-treated animals contained no larval Diptera Cyclorrhapha and significantly fewer larval Scarabaeidae than pats made from the dung of the other two groups. Furthermore, larval Scarabaeidae in the ivermectin pats were inhibited in their development. The pats from fenbendazole-treated animals contained similar numbers of larval Scarabaeidae and Diptera to the pats from untreated animals throughout the trial. At 42 days, the solid matter of the control and fenbendazole-containing cow pats were reduced to a crumbling, granular texture, while the pats from the ivermectin-treated animals were solid and compacted. Pitfall trapping, using traps baited with dung from the three groups, showed no significant difference between the numbers of adult Scarabaeidae attracted, though a trend towards higher numbers attracted to the dung of both anthelmintic-treated groups was evident. The results provide evidence of the toxic effects of excreted ivermectin on key dung-colonising families of insects, and show that fenbendazole lacks such toxic effects.

Administration, Oral

Pleuropulmonary blastoma: a marker for familial disease.

OBJECTIVE: To catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB). METHODS: Data have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible. RESULTS: In 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations. CONCLUSIONS: The occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases.

Adult

False aneurysm--a complication following an inversion ankle sprain: a case report.

Sprains of the lateral ligamentous structures of the ankle joint as a result of inversion are common and frequently result in pain. In most cases, the pain is related to soft-tissue injury and the associated hemorrhage and swelling. This case report describes the complication of posttraumatic false aneurysm of the peroneal artery following an inversion ankle sprain in a 22-year-old athlete, a complication which should be added to the differential diagnosis as a rare, but important possibility. Emphasis of the case report is placed on the rehabilitation of the patient following medical intervention.

Adult

Met proto-oncogene product is overexpressed in tumors of p53-deficient mice and tumors of Li-Fraumeni patients.

Inappropriate expression of Met, the receptor for hepatocyte growth factor/scatter factor, has been implicated in sarcomagenesis via an autocrine mechanism. Sarcomas occur at high frequency in individuals with Li-Fraumeni syndrome as well as in p53-deficient mice. Here we show that these tumors express high levels of Met. Moreover, late passage fibroblast cell lines established from p53-deficient animals overexpress Met and can be tumorigenic in athymic nude mice, suggesting that progression occurs in vitro. The tumor explants display increased hepatocyte growth factor/scatter factor expression and Met turnover, indicating that autocrine Met activation contributes to tumor progression. Thus, the loss of wild-type p53 appears to greatly enhance the opportunity for inappropriate Met expression. Loss of p53 function does not by itself cause transformation, but inappropriate Met expression may be an important factor in sarcomagenesis.

3T3 Cells

Structural analysis of the human nov proto-oncogene and expression in Wilms tumor.

We have cloned and sequenced the nov gene (novH) which is the homolog of the chicken nov proto-oncogene overexpressed in avian nephroblastomas. The novH gene is highly conserved and encodes a putative IGF-binding protein similar to that of chicken. We report that relative to autologous normal kidney expression of novH is elevated in Wilms tumors containing predominantly stromal elements and is inversely correlated in these tumors to the expression of WT1. Our results suggest that the regulation of IGFII expression by WT1 and increase of novH in Wilms tumors might be interrelated and represent a key element in tumor development in human.

Amino Acid Sequence

Concordance between parental origin of chromosome 13q loss and chromosome 6p duplication in sporadic retinoblastoma.

Two hypotheses are capable of explaining nonrandom loss of one parent's alleles at tumor suppressor loci in sporadic cases of several pediatric cancers, including retinoblastoma--namely, preferential germ-line mutation or chromosome imprinting. We have examined 74 cases of sporadic retinoblastoma for tumors in which at least two genetic events--loss of heterozygosity for chromosome 13q markers and formation of an isochromosome 6p--have occurred. Sixteen cases were found to contain both events. In 13 of 16 such tumors, the chromosomes 13q that were lost and chromosomes 6p that were duplicated are derived from the same parent. These data may be explained within the framework of the genome imprinting model but are not predicted by preferential germ-line mutation.

Chromosome Deletion

Overview: the impact of avermectins on pastureland ecology.

Avermectins, a relatively new class of broad spectrum pesticides, are used widely to control livestock parasites. Following treatment, avermectins are eliminated in the livestock faeces where they also have a wide range of harmful affects upon certain characteristic insects that breed in dung, few of which are pests, and many of which are beneficial. The effects range from acute toxicity in larvae and adults, through disruption of metamorphosis, to interference with reproduction. Different methods of drug administration lead to different concentrations of drug residues in the faeces, which in turn influence the responses of non-target organisms. Higher Diptera are particularly sensitive to drug residues and show a wide range of responses from death of larvae to developmental abnormalities in the adults. Larvae and immature adults of Coleoptera show some mortality in the dung of recently treated animals, while delayed effects upon reproduction and physiology have been observed in adults feeding on dung at longer post-treatment times. Although the impact of lethal doses has been described in some species, the effects of sub-lethal doses have hardly been recognised at the present time. Correlated with the deleterious effect upon dung-breeding insects, a retardation in the rate of loss of biomass of dung pats from avermectin-treated cattle has been observed following the various forms of drug administration. Differences in methodology, inappropriate statistics, and/or extremes of climatic conditions prevailing at the time of testing, explain the results of those studies where such delays have not been observed. It is short-sighted to consider only dung dispersal in relation to avermectin usage, a practice that overlooks the impact on the insects themselves and their diverse roles in pastureland ecology.

Animals

Some effects of ivermectin on the yellow dung fly, Scatophaga stercoraria.

Ivermectin was added to fresh cattle dung at a range of concentrations based on those found in faeces of livestock treated by injection. Newly hatched larvae of Scatophaga stercoraria were then reared in the dung as a bioassay. The EC50 values for 24 h and 48 h larval mortalities were 0.051 ppm and 0.036 ppm (wet wt.) respectively. When the dung concentration was 0.015 ppm, 50% of the insects failed to pupariate and a level of 0.001 ppm prevented adult emergence in 50% of the insects. When batches of larvae were reared in dung containing as little as 0.0005 ppm, the emerging adults showed developmental abnormalities in wing morphology. In addition to the significantly higher level of fluctuating asymmetry, 23% of the treated insects developed new veins and new cells in the wings. The observations are discussed in relation to previous work and attention is drawn to the practice of failing to observe the full impact of sublethal effects, which can be as serious as those of acute toxicity.

Animals

Research recommendations.

Delegates met on the final morning to identify areas where information is lacking and to highlight priority areas for future research. Five principal topics were discussed: veterinary usage, methodology, invertebrate populations, agricultural impact and integrated pest management.

Animals

Forty-year experience with second malignancies after treatment of childhood cancer: analysis of outcome following the development of the second malignancy.

As the cure rate for childhood malignancies increases, the number of patients at risk for development of second malignancies also increases. Due to the potentially long remaining life span, long-term follow-up is difficult and patients are often at risk after presumptive cures. Some authors believe that cure rates for second malignancies are similar to cure rates for primary malignancies. We reviewed the records of 162 patients seen at our institution who had developed a second malignancy after treatment for childhood cancer. Presentation, age at diagnosis, tumor histology, extent of tumor, treatment (including radiotherapy with dosage when available, and chemotherapy) plus outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3 years. The most common primary malignancy was Hodgkin's disease (33) followed by soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average interval between diagnosis of the first and second malignancy was 10.8 years. These second tumors carried a high mortality. Only 56 patients have no evidence of disease. Five patients are known to be alive with disease and 92 patients have expired due to their second malignancy. Disease status in 8 patients is unknown. The most common second malignancy was osteosarcoma (35) followed by soft tissue sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and others (27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Antibody Targeted Photolysis.

The technique of Antibody Targeted Photolysis (ATPL) is reviewed from an historical perspective with a summary of the literature since the first experiments were performed in 1983. Attention is given to both the biological and photophysical properties of the various immunoconjugates that have been developed. References to critical discoveries and competing technologies in the photodynamic literature are given. Topics include: synthesis of immunoconjugates, in vitro vs. in vivo toxicity, in vivo biodistribution, immunoconjugate delivery, photosensitizer selection based on photophysical properties, light delivery for specific applications, oxygen requirements, and other physicochemical phenomena. A mathematical model of the dynamics for cell killing based upon the transport of phototoxins to the cell surface is developed. A generalized set of coupled differential equations is given, which conveniently summarizes the manifold requirements stressed earlier for successful cell killing. Solutions are then presented for an idealized set of conditions appropriate for an isolated tumor cell. Suggestions for further improvements and follow-up experiments are made that could help in the evolution of ATPL into a useful clinical therapy and/or probe for cell biological studies.

Animals

Sn-chlorin e6 antibacterial immunoconjugates. An in vitro and in vivo analysis.

Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site-selective covalent modification of the monoclonal oligosaccharide moiety. By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared. By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10. Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody. The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process. In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity. Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared. In vivo specificity was demonstrated using rats infected with Fisher immunotype I P. aeruginosa at a site in the left posterior thigh muscle. Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate. Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact.

Animals