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Biomedical subjects

J Carr

Publications and source records attributed to J Carr.

At least 55 records · Page 3Linked to original sources
PubMed1999

Development of calibrated viral load standards for group M subtypes of human immunodeficiency virus type 1 and performance of an improved AMPLICOR HIV-1 MONITOR test with isolates of diverse subtypes.

Accurate determination of plasma human immunodeficiency virus type 1 (HIV-1) RNA levels is critical for the effective management of HIV-1 disease. The AMPLICOR HIV-1 MONITOR Test, a reverse transcription-PCR-based test for quantification of HIV-1 RNA in plasma, was developed when little sequence information on HIV-1 isolates from outside North America was available. It has since become apparent that many non-subtype B isolates, particularly subtypes A and E, are detected inefficiently by the test. We describe here the AMPLICOR HIV-1 MONITOR Test, version 1.5, an upgraded test developed to minimize subtype-related variation. We also developed a panel of HIV-1 standards containing 30 HIV-1 isolates of subtypes A through G. The virus particle concentration of each cultured viral stock was standardized by electron microscopic virus particle counting. We used this panel to determine the performance of the original AMPLICOR HIV-1 MONITOR Test and version 1.5 of the test with HIV-1 subtypes A through G. The original test underestimated the concentration of HIV-1 subtype A, E, F, and G RNA by 10-fold or more, whereas version of the 1.5 test yielded equivalent quantification of HIV-1 RNA regardless of the subtype. In light of the increasing intermixing of HIV-1 subtypes worldwide, standardization of PCR-based tests against well-characterized viral isolates representing the full range of HIV-1 diversity will be essential for the continued utility of these important clinical management tools.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Overview of the role of molecular methods in the diagnosis of malignant lymphomas.

OBJECTIVE: To review the role of molecular genetics in the diagnosis of malignant lymphomas. DATA SOURCES AND STUDY SELECTION: Primary research studies and reviews published in the English literature that focus on molecular genetics and malignant lymphoma, in particular, clonality, chromosomal translocations, tumor suppressor genes, and Hodgkin disease. DATA EXTRACTION AND SYNTHESIS: Molecular genetics has an important role in the assessment of malignant lymphomas. Clonality, detected by Southern blot analysis or the polymerase chain reaction, is helpful for establishing the diagnosis of lymphoma in lesions with ambiguous morphologic and immunophenotypic findings. Southern blot analysis is the "gold standard" for clonality assessment, but the process is labor-intensive and time-consuming. Polymerase chain reaction analysis is more convenient, but a potentially significant false-negative rate exists in the analysis of some antigen receptor genes as a result of using consensus primers and the process of somatic hypermutation. Chromosomal translocations, which result in oncogene activation, occur in many types of B- and T-cell lymphomas, and their detection is helpful in classification as well as in establishing a diagnosis of malignancy. Gene rearrangements and chromosomal translocations also can be used to monitor minimal residual disease. Tumor suppressor genes, although their analysis is relatively less useful for diagnosis, are involved in both pathogenesis and tumor progression and will be more important diagnostically as this field continues to expand. Molecular genetic analysis has played a major role in improving our understanding of Hodgkin disease. CONCLUSIONS: Molecular genetic tests are currently important ancillary tools for the diagnosis and classification of malignant lymphomas, and their role is likely to increase in the future.

Chromosomes↗
PubMed1998

Genome size, complexity, and ploidy of the pathogenic fungus Histoplasma capsulatum.

The genome size, complexity, and ploidy of the dimorphic pathogenic fungus Histoplasma capsulatum was determined by using DNA renaturation kinetics, genomic reconstruction, and flow cytometry. Nuclear DNA was isolated from two strains, G186AS and Downs, and analyzed by renaturation kinetics and genomic reconstruction with three putative single-copy genes (calmodulin, alpha-tubulin, and beta-tubulin). G186AS was found to have a genome of approximately 2.3 x 10(7) bp with less than 0.5% repetitive sequences. The Downs strain, however, was found to have a genome approximately 40% larger with more than 16 times more repetitive DNA. The Downs genome was determined to be 3.2 x 10(7) bp with approximately 8% repetitive DNA. To determine ploidy, the DNA mass per cell measured by flow cytometry was compared with the 1n genome estimate to yield a DNA index (DNA per cell/1n genome size). Strain G186AS was found to have a DNA index of 0.96, and Downs had a DNA index of 0.94, indicating that both strains are haploid. Genomic reconstruction and Southern blot data obtained with alpha- and beta-tubulin probes indicated that some genetic duplication has occurred in the Downs strain, which may be aneuploid or partially diploid.

DNA, Fungal↗
PubMed1997

Resistance of experientially-induced changes in murine plus-maze behaviour to altered retest conditions.

Prior exposure to the elevated plus-maze results in profound behavioural alterations in rats and mice, with 24 h retest profiles indicative of fear sensitization. The present study was designed to examine the influence of retest cues on this phenomenon in male DBA/2 mice. Results confirmed the potent influence of prior maze experience on subsequent behavioural patterns, and showed that this was not affected by manipulations of extra-maze cues (90 degrees re-orientation of the maze or use of a different laboratory) on Trial 2. Data are discussed in relation to experientially-induced shifts in behavioural strategy and the apparent involvement of simple proximal cues (probably thigmotactic) in this enduring and adaptive form of spatial learning.

Animals↗
PubMed1997

Implementing a hospital-wide pain management strategy.

The purpose of this article is to describe the process of undertaking a large scale nursing pain management initiative, that we entitled "Pain Month." Several educational resources and strategies were employed in an effort to increase nurse's knowledge on the subject of pain management. Pre and post patient satisfaction surveys were conducted to test the effect of the education on actual pain management. The results showed improvements in actual pain scores and in satisfaction with pain management; however, several more improvements were shown to be necessary to achieve excellent pain management for patients. Follow-up initiatives such as a pain resource nurse program, an interdisciplinary pain committee and continued, patient surveys have been implemented to address some of these existing issues.

Analgesics↗
PubMed1997

The significance of the IgG anti-B-cell crossmatch on renal transplant outcome.

Transplantation in the presence of anti-class I antibodies usually results in allograft hyperacute rejection. Because of the perception of its uncertain clinical significance, B-cell crossmatch which identifies presence of anti-class II antibodies is not universally performed. In a retrospective study, the clinical course of renal transplant recipients with IgG anti-B-cell antibodies was analyzed and compared with case control patients transplanted contemporaneously, matched demographically and immunologically. The incidence of hyperacute, acute, and chronic rejection as well as graft loss were significantly higher in the group with anti-IgG B-cell antibodies compared to the control. We conclude that anti-B-cell IgG antibodies are harmful to allografts with a spectrum of events that include hyperacute, acute, vascular and chronic rejection. While allografts were successful in some patients, our experience suggests caution whenever anti-donor B-cell IgG is present. If transplants are performed, then more potent immunosuppression should be used.

Acute Disease↗
PubMed1996

Sufficient conditions for effective treatment of substance abusing homeless persons.

Treatment efficacy for homeless substance abusers (primarily crack cocaine) was studied in a randomized control design with subjects (n = 176) assigned to usual care (UC) or an enhanced day treatment program plus abstinent contingent work therapy and housing (EC). Subjects met DSM-III-R criteria for Substance Use Disorder and McKinny Act criteria for homelessness. UC involved weekly individual and group counseling. EC involved a day treatment program consisting of daily attendance, transportation, lunch, manualized psychoeducational groups, and individual counseling. A total of 131 (74.4%) subjects (62 UC and 69 EC) were treated and followed. UC subjects attended 28.5% and EC attended 48.4% of expected treatment during the first 2 months. After 2 months, EC subjects experienced up to 4 months of abstinent contingent work therapy (44.9% of EC subjects) and housing (37.7% of EC subjects), with day treatment available two afternoons per week. Longitudinal Wei-Lachin analyses of medians (reported alcohol use, days homeless and employed) and proportions (cocaine toxicologies) were conducted across 2-, 6-, and 12-month follow-up points. EC had 36% fewer positive cocaine toxicologies at 2-months and 18% fewer at 6-months than UC with regression toward baseline at 12-months. EC had 8 days fewer days of reported alcohol use in the past 30 days, 52 fewer days homeless in the past 60 days, and 10 more days employed in the past 30 days from baseline to the 12-months. UC showed no changes except a temporary increase in employment at 6-months. This is one of the first demonstrations that homeless cocaine abusers can be retained and effectively treated.

Adult↗
PubMed1996

Excimer laser phototherapeutic keratectomy. Surgical strategies and clinical outcomes.

PURPOSE: To assess the different strategies and analyze clinical outcomes of excimer laser phototherapeutic keratectomy (PTK) for a variety of superficial corneal disorders. METHODS: Twenty-eight eyes of 26 patients with one of five general categories of corneal disorders were treated with a variety of PTK techniques. Patients were assessed for preoperative and postoperative corneal thickness, uncorrected and best spectacle-corrected visual acuity, refractive changes, corneal topography and astigmatism, and results of a subjective patient questionnaire. Follow-up ranged from 6 to 30 months. RESULTS: The average number of laser pulses was 418, with a mean decrease in corneal thickness of 31 microns. Uncorrected visual acuity improved in 20 eyes and decreased in 5. Best spectacle-corrected visual acuity improved in 20 eyes and decreased in 5; two patients had two Snellen lines of best-corrected vision loss. Nineteen patients (21 eyes) noted symptomatic improvement. Corneal topography improved in 17 eyes and worsened in 1. The average refractive shift was +1.4 diopters; patients undergoing general PTK, PTK combined with mechanical superficial keratectomy, and superficial scar removal had greater degrees of hyperopic shift. Complications were rare. Two patients who did not appreciate adequate improvement in vision after PTK underwent subsequent penetrating keratoplasty. CONCLUSIONS: A number of PTK techniques are available to treat particular corneal disorders. Planning of surgical strategy is guided by careful patient selection which will minimize optical side effects and optimize visual outcome and subjective symptomatology after the PTK procedure.

Adult↗
PubMed1996

Summary of track A: basic science.

AIM: To review Track A, which is organized into five broad areas of emphasis. TOOLS: A variety of new virologic tools are allowing researchers to more effectively evaluate many aspects of HIV, from various therapies and vaccine candidates to the recombination and international spread of genotypes. PATHOGENESIS: The recent understandings of HIV-1 pathogenesis have led to potential new treatment strategies of early aggressive treatment with combination drugs and the potential for biologic or immunologic therapy directed to blocking viral entry through second receptors. TREATMENT: HIV treatment focused on chemical/drug advances and treatment, and immunologic/genetic advances. Some areas of development include optimizing combination therapies using the oncology model; continued work on new preclinical compounds (e.g. integrase and tat/rev inhibitors); evaluation of viral reduction in all compartments; and resistance surveillance and prevention. Biologics, including fusin/CC-CKR5 inhibitors and CD8 HIV-1 suppressor factors, ex vivo expansion of T cells and in vivo expansion of effector CD8 cells continue to be developed as possible future treatments. VACCINES: In order to obtain worldwide control over HIV, we must have a universally effective vaccine. The question remains as to what specifically is required for a protective response. Mechanisms of CD8 suppression, and cellular and antibody correlates of protection were discussed as areas of research that may shed light on the critical protective immune response. GENOTYPES: Discussion of HIV genotypes focused on international subtypes, correlates of diversity, and HIV-1 recombination. Numerous groups have shown an international intermixing of HIV-1 strains. Recombination during transcription was found to lead to extensive genomic shift and increased diversity, which may also increase HIV-1 fitness and enhance transmission. CONCLUSIONS: The spread and adaptation of HIV-1 is occurring independently of borders. Therefore, HIV-1 research must be global; vaccine development must be international in concept and application; collaboration in all areas is essential for success in combating HIV; and finally, the challenge for the future will be to actively involve all basic scientists in the science of the international epidemics.

AIDS Vaccines↗
PubMed1995

Analysis of calcium-lipid complexes in faeces.

Calcium is purported to prevent colorectal cancer by forming insoluble complexes with bile acids and long-chain fatty acids in the large bowel. Therefore, a method for analysing calcium-lipid complexes in faeces has been developed to investigate this. The calcium soaps of a long-chain fatty acid (calcium palmitate) and bile acids (calcium deoxycholate, chenodeoxycholate, cholate and lithocholate) were obtained by organic synthesis. Studies with the authentic soaps reveal that they exist in an empirical ratio of calcium-to-lipid of 1:2. On addition to lipid-free faeces, approximately 30% of calcium palmitate could be recovered and quantified in the authentic state by extraction with 72% ethanol and overnight precipitation at 0 degree C. In contrast, the calcium soaps of the bile acids could not be recovered in the authentic state but were quantified entirely as the free acids. The method was applied to the analyses of calcium-lipid complexes in the faeces of adenoma patients partaking in a placebo-controlled calcium-intervention study. The results show that human faeces contain appreciable amounts of calcium long-chain fatty acid soaps predominantly in the form of calcium palmitate and stearate. The faecal concentration of long-chain fatty acid soaps was increased significantly (P = 0.005) during calcium intervention but this did not have a statistically significant effect on the excretion of free long-chain fatty acids (P = 0.4). Calcium long-chain fatty acid soap formation was found by multiple regression to be equally dependent on stool long-chain fatty acid and calcium concentration. Calcium soaps of the bile acids were not detected by this method.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Menopause in women with learning disabilities.

A brief questionnaire concerning previous and current menstrual status was sent to 280 women over the age of 35 on the Wandsworth Register for People with Learning Disabilities: 196 questionnaires (70.4%) were returned. One hundred and seventy-one were used in the analyses; 45 were from women with Down's syndrome. The results suggested that, compared with data on normal women, menopause may occur earlier in women with learning disabilities and earlier still in women with Down's syndrome.

Adult↗
PubMed1995

Treatment outcome as a function of treatment attendance with homeless persons abusing cocaine.

This research examines the influence of treatment attendance at two substance abuse outpatient treatment programs of the Birmingham Substance Abuse Homeless Project on substance abuse, homelessness, and unemployment outcomes with homeless persons abusing primarily crack cocaine. Results revealed that significant reductions across a one year period in alcohol use, cocaine use, and homelessness were more likely to occur in clients who attended an average of 4.1 treatment days per week (High attendance or Enhanced Care group) than clients who attended less than one day a week on the average (Low attendance or Usual Care and Medium attendance groups). These results are consistent with the literature suggesting that more intensive contact early in treatment results in better long-term outcome with cocaine abusers, but has now been demonstrated with homeless cocaine abusers who have additional problems associated with housing and employment.

Adult↗
PubMed1994

Clinical efficacy of antimicrobial drugs for acute otitis media: metaanalysis of 5400 children from thirty-three randomized trials.

OBJECTIVE: To reconcile conflicting published reports concerning the absolute and comparative clinical efficacy of antimicrobial drugs for acute otitis media in children. STUDY SELECTION: Articles were identified by MEDLINE search, Current Contents, and references from review articles, textbook chapters, and retrieved reports. Randomized, controlled trials of therapeutic antimicrobial drugs used in the initial empiric therapy for simple acute otitis media were selected by independent, blinded observers, and scored on 11 measures of study validity. Thirty English and three foreign-language articles met all inclusion criteria. DATA EXTRACTION: Data were abstracted for an end point of complete clinical resolution (primary control), exclusive of middle ear effusion, within 7 to 14 days after therapy started. DATA SYNTHESIS: The spontaneous rate of primary control--without antibiotics or tympanocentesis--was 81% (95% confidence interval, 69% to 94%). Compared with placebo or no drug, antimicrobial therapy increased primary control by 13.7% (95% confidence interval, 8.2% to 19.2%). No significant differences were found in the comparative efficacy of various antimicrobial agents. Extending antimicrobial coverage to include beta-lactamase-producing organisms did not significantly increase the rates of primary control or resolution of middle ear effusion. Pretreatment tympanocentesis was positively associated with individual group primary control rates, negatively associated with the ability to detect differences in clinical efficacy and unassociated with resolution of MEE. CONCLUSIONS: Antimicrobial drugs have a modest but significant impact on the primary control of acute otitis media. Treatment with beta-lactamase-stable agents does not increase resolution of acute symptoms or middle ear effusion; initial therapy should be guided by considerations of safety, tolerability, and affordability, and not by the theoretical advantage of an extended antibacterial spectrum.

Acute Disease↗
PubMed1994

Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi.

DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗