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Biomedical subjects

K Porter

Publications and source records attributed to K Porter.

At least 19 recordsLinked to original sources
PubMed2000

Boranophosphate backbone: a mimic of phosphodiesters, phosphorothioates, and methyl phosphonates.

Nucleoside boranophosphates are distinctive in that one of the non-bridging oxygens in the phosphate diester 1 is replaced by a borane moiety (BH3). Although they retain the same net charge, BH3(-)-ODN have unique chemical and biochemical characteristics relative to other analogs. The change in polarity, lipophilicity, nuclease resistance, and the activation of RNase H cleavage of RNA in RNA: boranophosphate hybrids make boranophosphates very attractive for applications in enzymology and molecular biology and as potential antisense agents.

Antisense Elements (Genetics)↗
PubMed1999

The practical significance of potential biases in estimates of the AIDS incubation period distribution in the UK register of HIV seroconverters.

OBJECTIVES: To assess the practical significance of the following sources of bias for estimates of the AIDS incubation period in a large seroconverter cohort: estimation of the time of seroconversion; presentation with an HIV-related illness; preferential inclusion of survivors; loss to follow-up and analysis cut-off date; the inclusion of Kaposi's sarcoma as an AIDS event; death without an AIDS diagnosis; and representativeness of the HIV population. METHODS: Standard non-parametric survival methods were used to estimate the AIDS incubation period distribution. The practical importance of each type of bias was assessed using various sensitivity analyses. RESULTS: The potential sources of bias of most practical importance in this study were the right-censoring strategy and that due to lack of documentation of a negative HIV antibody test. Five different right-censoring strategies gave estimates of the median time to AIDS ranging from 8.1 to 10.8 years for the 1202 individuals enrolled in the UK Register of HIV Seroconverters. HIV-infected persons with a history of a previous antibody negative test which could not be verified appeared to progress to AIDS more rapidly than persons with such verification (Relative risk = 1.8, 95% confidence intervals = 1.3-2.3). CONCLUSIONS: As a number of possible causes of bias can impact on results, care must be taken to document them and control for them wherever possible. In our study, this was particularly relevant in relation to the documentation of a previous HIV antibody negative test and the choice of analysis cut-off dates. As methods may differ between cohorts, comparison of the published results from one cohort with those of another may be misleading.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Evaluating the effect of year of seroconversion on HIV progression in cohort studies. Italian Seroconversion Study.

OBJECTIVES: To show how a spurious association between the calendar year of seroconversion and HIV progression arises as a result of censoring the follow-up of individuals at their last visit, when the individuals' visits are intermittent. DESIGN: A notional cohort of 1140 seroconverters and a cohort study of 1270 HIV-infected individuals seroconverted between 1985 and 1994, and followed up to December 1995 (the Italian Seroconversion Study cohort). METHODS: Failure times and rate of the patients attending the clinic over the study period were simulated for the notional cohort. Three separate scenarios with different probabilities of making a visit were considered. Standard survival analysis techniques were used to assess the effect of the year of seroconversion on HIV progression. The progression to a CD4 cell count of 200 x 10(6)/l according to the calendar year of seroconversion in the Italian Seroconversion Study was assessed using different censoring strategies. RESULTS: A spurious effect of the year of seroconversion consistently appeared in 100 repeated simulations. When ignoring the visits occurring after the first year of follow-up in the Italian Seroconversion Study cohort, results supported the hypothesis of no effect of the year from seroconversion. CONCLUSIONS: The choice of the censoring strategy is crucial when assessing the effect of year of seroconversion using survival analysis in cohort studies with intermittent visit structure. Different censoring strategies should be considered before firmly concluding that more virulent strains or the use of treatment are modifying the natural history of HIV disease from cohort studies of this nature.

Cohort Studies↗
PubMed1998

Bacterial decontamination of blood stem cell apheresis products.

High-dose chemotherapy using autologous bone marrow or mobilized blood as the source of stem cells for haematologic rescue, is being widely used for a variety of haematological malignancies and solid tumours. To collect sufficient numbers of haematopoietic stem cells for successful engraftment, standard apheresis procedures are performed. Newer techniques and refinements of the procedure allow using only 1 to 2 apheresis products (AP) for autografting. Bacterial contamination of the AP, although very rare, sometimes occurs and may lead to generalized infection in the recipient. The apheresis must be repeated, sometimes even including time-consuming and costly mobilization. At our institution, the patients' blood stem cells are usually mobilized with chemotherapy followed by daily s.c. haematopoietic growth factor injections or with growth factor alone. An apheresis machine is used for collection through a central venous line and the AP is routinely checked for bacterial contamination. Results are only available after the product has been processed and cryopreserved. In the last 5 years, we observed bacterial contamination in four of our AP. Therefore, we investigated the possibility of in vitro antibiotic decontamination. Using standard antibiograms, we determined the sensitivities of the contaminating bacteria. By incubating the products with the specific antibiotics at bactericidal concentrations, we were able to sterilize the probes from the contaminating bacteria. In the concurrently performed controls without the active substance, bacteria were still detectable. We conclude that in selected cases, in vitro decontamination using pretested antibiotics, may be a feasible, cost-effective, and easy alternative to performing additional apheresis procedures.

Anti-Bacterial Agents↗
PubMed1998

Indirect methods for estimating prevalent HIV infections: adults in England and Wales at the end of 1993.

Two indirect methods were used to estimate the point prevalence of HIV infection in England and Wales at the end of 1993 using data on diagnosed HIV infections, AIDS cases, HIV-related deaths and HIV testing behaviour from unlinked anonymous surveys. The methods estimated the proportion of all prevalent HIV infections that diagnosed infections represented. Most of those exposed to HIV infection through injecting drug use or sexual intercourse between men had had their infections diagnosed compared to less than half of those exposed through heterosexual intercourse. The total estimated number of prevalent infections was 22,350 for the diagnosis interval method and 20,540 for the test history method, and about 56-57% of these were in homo/bisexual men. These indirect methods are cheap and simple applications of surveillance data which provide estimates that compare favourably with those produced by more complex methods.

England↗
PubMed1998

The prenatal diagnosis of cloacal exstrophy.

PURPOSE: We assess and clarify diagnostic features for making the prenatal diagnosis of cloacal exstrophy. MATERIALS AND METHODS: We evaluated 9 patients born with cloacal exstrophy at our institutions (2 prospectively and 7 retrospectively) for diagnostic features on prenatal ultrasound studies. We also thoroughly reviewed the literature on 13 previous prenatally diagnosed cloacal exstrophy cases. Diagnostic criteria were assessed by combining the findings in our patients and those in previous reports. RESULTS: Of the 22 patients with prenatal ultrasound studies and cloacal exstrophy whom we analyzed 1 of our 9 and 2 in the literature had a cloacal membrane that persisted at 22 weeks of gestation. Major ultrasound criteria for diagnosing cloacal exstrophy prenatally are nonvisualization of the bladder, a large midline infraumbilical anterior wall defect or cystic anterior wall structure (persistent cloacal membrane), omphalocele and lumbosacral anomalies. Seven less frequent or minor criteria include lower extremity defects, renal anomalies, ascites, widened pubic arches, a narrow thorax, hydrocephalus and 1 umbilical artery. CONCLUSIONS: We propose major and minor criteria to assist in the prenatal diagnosis of cloacal exstrophy. Despite these major and minor criteria the certainty of establishing a prenatal diagnosis remains challenging. Persistence of the cloacal membrane beyond the first trimester in 1 patient was an exception to the classic concept of cloacal exstrophy embryogenesis. An accurate prenatal diagnosis requires validation of these criteria by further correlation of prenatal and postnatal observations.

Cloaca↗
PubMed1998

Improvements in poverty and income in 1995 tempered by troubling long-term trends.

Census data on poverty and income show short-term improvements in 1995, but the trends were not as positive over the longer term. Poverty rates remained higher than they were at comparable points in previous economic cycles. The incomes of lower- and middle-income households grew in 1995, but only the wealthiest fifth of the population completely recovered from the recession of the early 1990s. Although poverty rates fell and incomes rose for most groups in 1995, Hispanic households did not share in the overall economic gains. In addition, economic improvements were not shared by all geographic areas--the reduction in poverty was concentrated in suburban areas. The current poverty measure does not show the full impact of government benefit programs on poverty, as it does not take into account the effect of non-cash benefits or taxes. An alternative poverty measure gives a much better picture of the effectiveness of government benefit programs in reducing poverty.

Censuses↗
PubMed1997

Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21.

Bardet-Biedl syndrome (BBS) is a clinically and genetically heterogeneous autosomal recessive disorder characterized by retinitis pigmentosa, polydactyly, obesity, hypogenitalism, mental retardation, and renal anomalies. To detect linkage to BBS loci, 29 BBS families, of mixed but predominantly European ethnic origin, were typed with 37 microsatellite markers on chromosomes 2, 3, 11, 15, 16, and 17. The results show that an estimated 36-56% of the families are linked to the 11q13 chromosomal site (BBS1) previously described by M. Leppert et al. (1994, Nature Genet. 7, 108-112), with the gene order cen-D11S480-5 cM-BBS1-3 cM-D11S913/D11S987-qter. A further 32-35% of the families are linked to the BBS4 locus, reported by R. Carmi et al. (1995, Hum. Mol. Genet. 4, 9-13) in chromosomal region 15q22.3-q23, with the gene order cen-D15S125-5 cM-BBS4-2 cM-D15S131/D15S204-qter. Three consanguineous BBS families are homozygous for three adjacent chromosome 15 markers, consistent with identity by descent for this region. In one of these families haplotype analysis supports a localization for BBS4 between D15S131 and D15S114, a distance of about 2 cM. Weak evidence of linkage to the 16q21 (BBS2) region reported by A. E. Kwitek-Black et al. (1993, Nature Genet. 5, 392-396) was observed in 24-27% of families with the gene order cen-D16S408-2 cM-BBS2-5 cM-D16S400. A fourth group of families, estimated at 8%, are unlinked to all three of the above loci, showing that at least one other BBS locus remains to be found. No evidence of linkage was found to markers on chromosome 3, corresponding to the BBS3 locus, reported by V. C. Sheffield et al. (1994, Hum. Mol. Genet. 3, 1331-1335), or on chromosome 2 or 17, arguing against the involvement of a BBS locus in a patient with a t(2;17) translocation.

Abnormalities, Multiple↗
PubMed1997

Inoculation of plasmids expressing the dengue-2 envelope gene elicit neutralizing antibodies in mice.

To develop a nucleic acid vaccine against dengue type-2 virus, the PreM and 92% of the envelope (E) genes were cloned into different eukaryotic plasmid expression vectors (pkCMVint Polyli and pVR1012). The resultant plasmid constructs (pD2ME and P1012D2ME) properly expressed the truncated E protein in vitro as evidenced by the expected protein size on SDS-PAGE and the ability of the protein to be recognized by monoclonal antibodies directed against conformational epitopes. Three-week-old BALB/c mice were given intradermal inoculations of each construct. Plasmid expression vectors without dengue genes were used as controls. One hundred percent of the mice that received the pD2ME and p1012D2ME constructs developed anti-dengue antibodies. These antibodies were shown to neutralize dengue type-2 virus in vitro. This is the first demonstration of the use of nucleic acid inoculation in the development of potential dengue virus. vaccines.

Animals↗
PubMed1997

Critical pathways and cost-effective practice.

With increasing pressure by third-party payers and federal reimbursement systems to reduce health care expenditures, cost-effective means to care for the resource intensive vascular surgical population must be explored. The challenge of meeting these cost-saving priorities while maintaining or improving quality of care can result in conflicting demands on surgeons, particularly in academic practices. The adaptation of an industrial management tool-the critical pathway method-to health care delivery is an attempt to reduce length of stay and improve efficiency. Utilization of vascular nurse practitioners, concentration of vascular patients into a dedicated unit, reduction in angiography through more aggressive use of the vascular laboratory, and optimal use of rehabilitation units and skilled nursing facilities are important adjuncts to reduce length of stay without sacrificing quality of care. This report describes the critical pathway method as implemented in a university teaching hospital, and the integration of other modalities in the care of vascular patients that has reduced length of stay by as much as 40% for some vascular surgical procedures.

Cardiology Service, Hospital↗
PubMed1997

Decrease in tumor cell contamination and progenitor cell yield in leukapheresis products after consecutive cycles of chemotherapy for breast cancer treatment.

In this retrospective study, we assessed the impact of each of three consecutive cycles of conventional-dose chemotherapy on CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and contaminating breast cancer cells collected in the leukapheresis products of patients with metastatic breast cancer. The patients subsequently underwent high-dose chemotherapy followed by autologous blood progenitor cell transplantation. We analyzed 172 leukapheresis products from 17 patients and have correlated the long-term clinical outcome with tumor cell contamination. The induction chemotherapy regimen consisted of three cycles of cyclophosphamide 750 mg/m2 i.v., epirubicin 100 mg/m2, and 5-fluorouracil (5-FU) 750 mg/m2 i.v., followed by 5 microg/kg body weight of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) daily until leukapheresis was completed. An average of 10 leukapheresis products (three to four collections after each cycle of chemotherapy) were obtained from each patient. Numbers of CD34+ cells, CFU-GM, and mononuclear cells (MNCs) in the leukapheresis products were determined at the time of collection. Aliquots from the same products were frozen and breast cancer cells were detected by immunocytochemistry with a cocktail of anti-cytokeratin antibodies (AE-1, AE-3, CAM 5.2, Keratin 8+18+19) using a standardized immunoalkaline phosphatase method. A minimum of 10(6) cells were examined by light microscopy and by at least two blinded observers. Cells were considered positive when immunostaining was detected in the cytoplasm and on the cell membrane, and cellular morphology was consistent with a malignant phenotype. Of the 172 samples analyzed, 13 of 57 (23%) leukapheresis products collected after cycle I were positive for tumor cells; 3 of 60 (5%) after cycle II; and 4 of 55 (7%) after cycle III. The likelihood of contamination by breast cancer cells after cycle I was significantly higher than after subsequent cycles of chemotherapy (p = 0.0052). Simultaneously, there was a significant decrease in quantity of CD34+ cells and CFU-GM (p < 0.0001 for both comparisons). Our study indicated that leukapheresis products collected after the second or third cycles of induction chemotherapy carry a significantly lower likelihood of tumor cell contamination, albeit the quantity of CD34+ cells or CFU-GM collected was also significantly reduced.

Adult↗
PubMed1996

Vein morphology and bypass graft stenosis.

Vein wall morphology (intimal and medial thickness) was studied in a consecutive series of 100 veins before organ culture. The development of a proliferative neointima after 14 days in culture was quantified by measuring neointimal thickness, and the relationship between this and the original vein wall morphology was investigated. The correlation between the intimal or medial thickness before culture and neointimal thickness following culture was poor (rs intima/neointima = 0.21, rs media/ neointima = 0.09). Long saphenous vein biopsies were obtained from 53 patients at the time of infrainguinal bypass surgery and their morphology was studied as above. Median intimal and medial thickness before grafting was 21 (range 2-208) and 245 (range 108-557) microns respectively. After 12 months in a colour duplex graft surveillance programme, 46 grafts were patent and 17 of these had developed a stenosis. There was no difference in intimal (28 versus 19 microns, P = 0.1) or medial (247 versus 245 microns, P = 0.47) thickness between stenosed and non-stenosed grafts respectively. Both the laboratory and clinical evidence from this study fail to support the hypothesis that pre-existing vein wall thickening is a key factor in the aetiology of vein graft stenosis.

Aged↗
PubMed1996

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).

X-linked retinitis pigmentosa (xlRP) is a severe progressive retinal degeneration which affects about 1 in 25,000 of the population. The most common form of xlRP, RP3, has been localised to the interval between CYBB and OTC in Xp21.1 by linkage analysis and deletion mapping. Identification of microdeletions within this region has now led to the positional cloning of a gene, RPGR, that spans 60 kg of genomic DNA and is ubiquitously expressed. The predicted 90 kD protein contains in its N-terminal half a tandem repeat structure highly similar to RCC1 (regulator of chromosome condensation), suggesting an interaction with a small GTPase. The C-terminal half contains a domain, rich in acidic residues, and ends in a potential isoprenylation anchorage site. The two intragenic deletions, two nonsense and three missense mutations within conserved domains provide evidence that RPGR (retinitis pigmentosa GTPase regulator) is the RP3 gene.

Amino Acid Sequence↗
PubMed1996

AIDS defining diseases in the UK: the impact of PCP prophylaxis and twelve years of change.

We examined all reports of adult AIDS cases made to the 2 national surveillance centres in the UK for changes in AIDS defining conditions between January 1982 and September 1994. Differences and changes among persons diagnosed since January 1988 who had and had not been aware of their HIV infection prior to their AIDS diagnosis were of particular interest. Pneumocystis carinii pneumonia (PCP) is the AIDS defining disease most often reported at the initial AIDS diagnosis. Its proportion of all AIDS cases has increased significantly between January 1982 and December 1987 and decreased markedly thereafter. Since January 1988 a significant decrease in the proportion of cases diagnosed with cryptosporidial infection was also observed while increases were observed in the proportion of cases diagnosed with: HIV wasting (chi(1)(2) = 5.56) PML (chi(1)(2) = 19.47), mycobacterium avium complex (chi(1)(2) = 35.76) and pulmonary tuberculosis (chi(1)(2) = 144.0). For cases diagnosed between January 1988 and September 1994, PCP was more likely to be diagnosed in patients previously unaware of their HIV infection (P < 0.01) as was extrapulmonary TB (P < 0.01). In contrast, the following diseases were more likely to be diagnosed in patients already aware of their HIV infection prior to the diagnosis of AIDS: oesophageal candidiasis (P < 0.001), HIV wasting (P = 0.07), mycobacterium avium complex (P = 0.0001), cytomegalovirus disease (P < 0.001), HIV encephalopathy (P = 0.0009) and cryptosporidial infection (P = 0.02). Prophylaxis and anti-retroviral therapy appear to have had a significant impact on the temporal changes of the most frequently diagnosed AIDS diseases. While PCP prophylaxis has substantially reduced the likelihood of a PCP diagnosis at AIDS, the corresponding increase in other opportunistic infections suggests that there may be a need for improved prophylaxis for these conditions.

AIDS Dementia Complex↗