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Biomedical subjects

K Carter

Publications and source records attributed to K Carter.

At least 19 recordsLinked to original sources

Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort.

OBJECTIVE: To explore the association between specific nucleoside reverse transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying roles of hepatitis C (HCV), vitamin B12 deficiency, and impaired glucose tolerance. METHODS: The authors conducted a prospective cohort study of 147 HIV-infected adults at two sites chosen to emphasize demographic differences. Standardized assessments included detailed antiretroviral histories, neurologic examinations, skin biopsies for epidermal nerve quantitation, and quantitative sensory testing. RESULTS: There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%. CONCLUSIONS: Exposure to stavudine and didanosine was significantly associated with a heightened risk for symptomatic sensory neuropathy. Reduced vibration thresholds and epidermal nerve fiber densities had the highest diagnostic efficiency of the laboratory indicators of neuropathy examined, but were relatively insensitive in isolation.

Adult↗

Upper limits on a stochastic background of gravitational waves.

The Laser Interferometer Gravitational-Wave Observatory has performed a third science run with much improved sensitivities of all three interferometers. We present an analysis of approximately 200 hours of data acquired during this run, used to search for a stochastic background of gravitational radiation. We place upper bounds on the energy density stored as gravitational radiation for three different spectral power laws. For the flat spectrum, our limit of omega0 < 8.4 x 10(-4) in the 69-156 Hz band is approximately 10(5) times lower than the previous result in this frequency range.

Journal Article↗

Iron loading and morbidity among relatives of HFE C282Y homozygotes identified either by population genetic testing or presenting as patients.

BACKGROUND AND AIMS: Although most cases of hereditary haemochromatosis are associated with homozygosity for the C282Y mutation of the HFE gene, clinical penetrance varies and other genes may modify disease expression. If so, relatives from clinically affected families, by inheriting such genes, may accumulate more iron. To seek evidence for this, we compared iron status and morbidity in unselected first degree relatives of two groups of index cases from South Wales, namely asymptomatic C282Y homozygotes identified by genetic screening of blood donors (n = 56) and C282Y homozygous haemochromatosis patients presenting clinically (n = 60). METHODS: All participating relatives had a structured interview, clinical assessment, and laboratory investigations. Health related quality of life was measured (SF-36 version 2). RESULTS: In total, 92% of 180 eligible first degree relatives were interviewed in the "screened" family group and 85% of 143 eligible relatives in the "patient" group. Of 59 relatives homozygous for C282Y, 76% of men and 32% of women had the "iron phenotype" (raised transferrin saturation and serum ferritin). Logistic regression modelling of the iron phenotype risk showed that 42% of the initial model deviance could be explained by homozygosity for C282Y, another 6% by lifestyle factors, and 6% by being male. Family group membership was not a significant risk factor. Morbidity and SF-36 scores did not differ significantly either between C282Y homozygotes and relatives lacking C282Y, or between C282Y homozygotes from the "screened" and "patient" groups. Serious morbidity (including cirrhosis) was low in both groups of relatives. CONCLUSIONS: HFE C282Y homozygosity has a high penetrance for iron accumulation but a low clinical penetrance. Lack of excess morbidity among C282Y homozygous relatives of index cases who presented clinically suggests that residual unknown genetic or environmental factors do not greatly influence clinical outcome among C282Y homozygotes.

Adolescent↗

Limits on gravitational-wave emission from selected pulsars using LIGO data.

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10(-5) for the four closest pulsars.

Journal Article↗

Use of a hydrocapillary dressing in the management of highly exuding ulcers: a comparative study.

OBJECTIVE: To evaluate the safety and performance of Alione Hydrocapillary dressing (Coloplast A/S) in the management of highly exuding chronic venous leg ulcers and compare it with two hydropolymer dressings,Tielle and Tielle Plus (Johnson & Johnson). METHOD: A comparative clinical trial was conducted on 97 patients with an ankle brachial pressure index > or = 0.8 and a highly exuding leg ulcer. Ulcer duration was at least four weeks. Treatment continued until healing or for a maximum of 12 months. RESULTS: There was no statistically significant difference in healing time or wound area reduction between the two treatment protocols. The test dressing (Alione Hydrocapillary) had better absorption capacity and was more comfortable for the patients than the comparator dressings (Tielle/Tielle Plus) and adhered less to the wound bed.Also, more patients preferred the test dressing to their previous treatment. Although severe leakage and maceration were observed more frequently in the comparator group compared with the test group, this was not statistically significant. CONCLUSION: Both treatment protocols were safe and effective in treating highly exuding chronic venous leg ulcers. The test dressing performed as well as or better than the comparator dressings for all study parameters and more patients preferred the test dressing to their previous dressing compared with the comparator dressings.

Adult↗

The 16189 variant of mitochondrial DNA occurs more frequently in C282Y homozygotes with haemochromatosis than those without iron loading.

BACKGROUND: Patients with hereditary haemochromatosis (HH) are usually homozygous for the C282Y mutation in the HFE gene. They have variable expression of iron overload and present with a variety of complications, including liver disease, diabetes, arthropathy, fatigue, and cardiomyopathy. The mitochondrial 16189 variant is associated with diabetes, dilated cardiomyopathy, and low body fat at birth, and might contribute to genetic predisposition in further multifactorial disorders. The objective of this study was to determine the frequency of the 16189 variant in a range of patients with haemochromatosis, who had mutations in the HFE gene. METHODS: Blood DNA was analysed for the presence of the 16189 variant in British, French, and Australian C282Y homozygotes and controls, with known iron status, and in birth cohorts. RESULTS: The frequency of the mitochondrial 16189 variant was found to be elevated in individuals with haemochromatosis who were homozygous for the C282Y allele, compared with population controls and with C282Y homozygotes who were asymptomatic (42/292 (14.4%); 102/1186 (8.6%) (p = 0.003); and 2/64 (3.1%) (p = 0.023), respectively). CONCLUSIONS: Iron loading in C282Y homozygotes with HH was exacerbated by the presence of the mitochondrial 16189 variant.

Adult↗

Iron absorption from Spatone (a natural mineral water) for prevention of iron deficiency in pregnancy.

The absorption of iron from Spatone Iron-Plus has been investigated in pregnant women with iron deficiency anaemia. A total of 25 mg Fe was taken and absorption determined from the increase in serum iron concentration during a period of 3 h. Mean absorption was 28%, significantly higher than in nonpregnant, nonanaemic women (14%). These studies demonstrate that Spatone provides an alternative to the standard ferrous sulphate tablet for prevention of iron deficiency in pregnancy. As only lower doses of iron are required, the unpleasant side-effects of iron therapy are largely avoided.

Adult↗

Ophthalmology inpatient consultation.

OBJECTIVE: To profile inpatients and eye problems evaluated and managed by the Ophthalmology Consultation Service of a large university teaching hospital. DESIGN: A hospital-based retrospective, cross-sectional study. PARTICIPANTS: One thousand four hundred seventy-two patients admitted to the University of California Los Angeles Medical Center. METHODS: We reviewed the inpatient medical records, discharge summaries, and Ophthalmology Consultation Service notes of every patient evaluated by the Service from July 1990 through January 1997. MAIN OUTCOME MEASURES: We recorded demographic information, hospitalization information, and eye examination information, including reason for consultation, type of consultation (screening examination, new eye problem, or preexisting eye problem), as well as primary and secondary ophthalmologic diagnoses. RESULTS: Internal medicine services requested 39.7% of consultations, surgery services 20.9%, and trauma services 13.5%. There were 92 different reasons why consultations were requested. The most common reason was decreased vision. Eye problems that developed either on the day of admission or some time during hospitalization accounted for 39.6% of consultations, preexisting eye problems accounted for 31.6%, and screening examinations for the remaining 28.7%. We recorded 166 unique primary ophthalmologic diagnoses and 130 unique secondary ophthalmologic diagnoses. The top five common primary ophthalmologic diagnoses were refractive error (88 patients), fungal endophthalmitis ruled out (80 patients), conjunctivitis (56 patients), diabetic retinopathy (52 patients), and corneal abrasion (52 patients). Refractive error was the most common secondary ophthalmologic diagnosis (201 patients). Inpatient diagnostic or surgical procedures were performed 7911 times. There were 947 unique primary and 1391 unique secondary hospital discharge diagnoses. The most common primary discharge diagnosis, human immunodeficiency virus infection, accounted for only 1.6% of all hospitalizations, indicating a considerable diversity of systemic disease in the study population. CONCLUSIONS: This study profiled the typical patients and eye problems an ophthalmologist may expect to encounter when inpatient consultation is requested. The information may be useful for the planning and management of consultation services in residency training programs.

Adolescent↗

Plaque removal characteristics of electric toothbrushes using an in vitro plaque model.

BACKGROUND/AIM: The purpose of the study was to investigate and quantify the efficacy of plaque removal by commercially available electric toothbrushes using an in vitro system based on artificial plaque grown on glass slides. MATERIAL AND METHODS: Artificial plaque based on Streptococcus sanguis and Streptococcus mutans was cultured in a series of phosphate buffer solution, sucrose solution and brain heart infusion on sterile glass slides, for a period of 5 weeks. 7 different electric toothbrushes of current designs were operated in contact with the glass slides under loads of 1 or 2N for 10 s after which image analysis of the brushed slides was undertaken to calculate the absolute and relative areas of removal. RESULTS: The electric toothbrushes showed a larger area of plaque removal as loading force increased from 1 to 2N. The area of biofilm removed also depended on the head design and ranged from 258 mm(2) (1N, Interplak) and 314 mm(2) (2N, Interplak), to 30 mm(2) (1N, Braun 3D), and 148 mm(2) (2N, Blend-a-Dent). The area of biofilm removal was significantly different among all electric toothbrushes at p<0.01 (ANOVA). All electric toothbrushes removed more biofilm than the actual contacting tufted area of the head. CONCLUSION: The artificial plaque model system under different loading conditions showed differences in the absolute area of removal per electric toothbrush and also differences in the relative removal per unit contact bristle area. These differences on operating variables should be considered when evaluating new electric toothbrushes.

Algorithms↗

HFE mutations, iron deficiency and overload in 10,500 blood donors.

People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE genotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were 8.23% and 15.3% respectively. Heterozygosity for C282Y occurred in 1 in 7.9 donors, for H63D in 1 in 4.2 donors, and 1 in 42 were compound heterozygotes. Homozygosity for H63D occurred in 1 in 42 donors and 1 in 147 (72) were homozygous for C282Y. Mean values increased for transferrin saturation (TS) and serum ferritin (sFn), and decreased for unsaturated iron binding capacity (UIBC) in the order: donors lacking the mutations, H63D heterozygotes, C282Y heterozygotes, H63D homozygotes, compound heterozygotes and C282Y homozygotes, but serum ferritin (sFn) concentrations were no higher in H63D heterozygotes and C282Y heterozygous women than in donors lacking mutations. The percentage of donors failing the screening test for anaemia or of those with sFn < 15 microg/l did not differ among the genotype groups. C282Y and H63D heterozygotes and donors homozygous for H63D were at no greater risk of iron accumulation than donors lacking mutations, of whom 1 in 1200 had both a raised TS and sFn. The risk was higher for compound heterozygotes (1 in 80, P = 0.003) and for C282Y homozygotes (1 in 5, P < 0.0001). There was no correlation between sFn and either age or donation frequency in C282Y homozygotes. None of the 63 C282Y homozygous donors interviewed showed physical signs of overload or were aware of relatives with haemochromatosis. The Welsh Blood Service collects blood from about 140 000 people each year including an estimated 950 who are homozygous for HFE C282Y. They are probably healthy and unaware of any family history of iron overload.

Adult↗

Essential competencies for teaching students with hearing loss and additional disabilities.

The purpose of this national study was to establish an initial database of the essential competencies needed for working with students who are deaf or hard of hearing with additional disabilities. Surveys were sent to program supervisors across the United States; each supervisor was asked to give the survey to a professional on his or her staff who worked with students who were deaf or hard of hearing with additional disabilities. Respondents indicated that there were 67 specific competencies needed for working with this diverse population of students. A list of the specific competencies and a rationale for providing more in-depth training for teachers is provided.

Adult↗

Stress ulceration requiring definitive surgery after severe trauma.

Despite antiulcer prophylaxis 19 severely injured patients at our institution developed stress ulceration (SU) between 1989 and 1999 requiring surgery for perforation (n = 4) or bleeding (n = 15). A herald bleed (HB) 10.7 +/- 1.2 days after admission, 7.2 +/- 1.2 days before definitive operative therapy, and requiring 7.1 +/- 0.9 units of blood occurred in 93 per cent of patients operated on for bleeding. Bleeding preceded perforation in one patient. Central nervous system damage was part of the injury pattern in 68 per cent of the patients including spinal cord (42%), severe head injury (16%), or both (10%). Forty-two per cent had acalculous cholecystitis found at surgery. Eight patients had vagotomy and antrectomy (VA), and 11 patients had vagotomy and pyloroplasty (VP). VA required more time than VP (255 +/- 41 vs 158 +/- 13 minutes; P = 0.02). One patient (12.5%) rebled after VA versus two (18%) after VP; one patient in each group required reoperation. There was no difference in mortality, length of stay, or intensive care unit stay. A herald bleed preceded recurrent hemorrhage of SU by one week. Spinal cord or head injury increase the risk of SU. More than 40 per cent of patients with SU had acalculous cholecystitis found at operation. VA provides no benefit on rebleeding or reoperation over VP, so anatomical considerations and not rebleed rates should determine the surgical procedure.

Adolescent↗

Bioinformatics issues for automating the annotation of genomic sequences.

The rapid explosion in the amount of biological data being generated worldwide is surpassing efforts to manage analysis of the data. As part of an ongoing project to automate and manage bioinformatics analysis, the authors have designed and implemented a simple automated annotation system, which is described in this paper. The system is applied to existing GenBank/DDBJ/EMBL entries and compared with existing annotations to illustrate not only potential errors but also that they are generally not up-to-date, as a result of new versions of analysis tools and updates of genomic repositories. We highlight the important Bioinformatics issues of storage and management of information to ensure data and results are kept up-to-date in light of new information becoming available. Surprisingly, from just four database entries, a significant number of new features were found. We describe the results as well as identify important issues that need to be addressed in order to automate the re-analysis/re-annotation of genomic sequences within a reasonable timeframe.

Computational Biology↗

PSGR, a novel prostate-specific gene with homology to a G protein-coupled receptor, is overexpressed in prostate cancer.

PSGR, a new prostate tissue-specific gene with homology to the G protein-coupled odorant receptor gene family, has been identified. Here we report the characteristics of the predicted protein sequence of PSGR and its prostate tissue specificity and expression profile in human prostate cancer and matched normal tissues. Using multiple tissue Northern blots from over 50 different tissues, PSGR expression was restricted to human prostate tissues. Paired normal and tumor specimens from 52 primary prostate cancers, obtained by laser capture microdissection or manual microdissection, were analyzed for PSGR expression by semiquantitative and real-time PCR assays. The differential expression of PSGR between normal and tumor tissues was highly significant (P < 0.001), and 32 of 52 (62%) matched prostate specimens exhibited tumor-associated overexpression of PSGR. Of note, there was very little or no expression of PSGR in many normal specimens in comparison with the generally high expression of PSGR seen in matched tumor specimens. In situ hybridization assays showed restricted PSGR expression in the epithelial cells of the normal and tumor tissue sections. Restricted expression of PSGR in prostatic epithelial cells, overexpression of the PSGR in a significant percentage of prostate cancers, and the predicted protein sequence of PSGR with seven transmembrane domains provide a foundation for future studies evaluating the potential of PSGR as a prostate cancer gene expression marker and the utility of PSGR protein as a novel target for developing immunotherapeutic strategies for prostate cancer.

Amino Acid Sequence↗

Population screening for hemochromatosis by PCR using sequence-specific primers.

Over 90% of patients with hemochromatosis in the United Kingdom are homozygous for the C282Y mutation on the HFE gene. The Centers for Disease Control (CDC) in the United States has recommended that adults should be screened for HFE mutations to identify susceptible individuals before onset of disease. The aim of this study was to evaluate the polymerase chain reaction using sequence-specific primers (PCR-SSP) as a method of large-scale population screening for the common HFE gene mutations, H63D and C282Y. A total of 10,583 consenting blood donors were tested using nonautomated procedures. Three alleles, termed HFE-1, -2, and -3, were detected with phenotype frequencies of 94.56%, 28.33%, and 15.79%, respectively, and gene frequencies of 0.76421, 0.15342, and 0.08237, respectively. All donors identified as homozygous for the C282Y mutation or heterozygous for both the H63D and C282Y mutations were confirmed by heterduplex analysis and/or PCR-SSP. The number of technical failures that affected the identification of donors homozygous for the C282Y mutation was 390 giving an overall repeat rate 3.7%, although this fell to 1% over the last quarter of the study. This study demonstrates that PCR-SSP may be used for large-scale population screening for the C282Y genotype associated with hemochromatosis.

Blood Donors↗

GC-MS analysis of methamphetamine impurities: reactivity of (+)- or (-)-chloroephedrine and cis- or trans-1,2-dimethyl-3-phenylaziridine.

S-(+)-Methamphetamine is frequently found as the only isomer in urine specimens from methamphetamine abuseres. Enantiomerically pure S-(+)-methamphetamine can be synthesized from ephedrine or pseudoephedrine via chloroephedrine intermediates. These intermediates are unstable and capable of cyclizing to form cis- and trans-1,2-dimethyl-3-phenyl aziridine. Studies were done to determine if these intermediates could be detected when using a common gas chromatographic-mass spectrometric analytical method (derivatization with heptafluorobutyric anhydride, HFBA) for toxicological screening of methamphetamine. Analysis of (+)- or (-)-chloroephedrine after extraction into hexane and derivatization with HFBA indicated that both pseudoephedrine and ephedrine were the major compounds detected. Direct derivatization of a hexane solution of cis-1,2-dimethyl-3-phenyl aziridine yielded only the derivatives of ephedrine and pseudoephedrine, indicating that the aziridine intermediate is responsible for the formation of the ephedrine or pseudoephedrine. These studies indicate that the aziridine intermediates would not be detected in methamphetamine samples following HFBA derivatization.

Aziridines↗