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Biomedical subjects

L Harrison

Publications and source records attributed to L Harrison.

At least 37 records · Page 2Linked to original sources
PubMed2001

Health gain and outcome predictors during inpatient and related day treatment in child and adolescent psychiatry.

OBJECTIVE: To investigate health gain and its predictors during inpatient and associated day patient treatment. METHOD: Consecutive admissions to two inpatient units for children and young adolescents in northwest England were studied (N = 55). Ascertainments were made from multiple perspectives, including family, teacher, clinician, and an independent researcher. Measures were taken at referral, admission, discharge, and 6-month follow-up; health gain was inferred from change scores on measures. Recruitment lasted from late 1995 to 1997; follow-up was completed during 1998. Independent variables tested as predictors included assessments of presenting symptoms, therapeutic alliance, and family functioning. RESULTS: Significant health gain during hospitalization was found on most measures and sustained to follow-up. There was no symptom change during the waiting-list control condition. Health gain was predicted independently by child and parental therapeutic alliance with the unit early in hospitalization and by preadmission family functioning. Externalizing problems did well if accompanied by good alliance. CONCLUSIONS: Assessment of health gain from multiple perspectives is possible and valuable. Inpatient treatment has significant therapeutic effect. Predictors for health gain lie in process variables of therapeutic alliance and family functioning rather than presenting symptoms. The results are discussed in relation to clinical practice and future research.

Adolescent↗
PubMed2001

Human immunodeficiency virus type 1 env sequences from Calcutta in eastern India: identification of features that distinguish subtype C sequences in India from other subtype C sequences.

India is experiencing a rapid spread of human immunodeficiency virus type 1 (HIV-1), primarily through heterosexual transmission of subtype C viruses. To delineate the molecular features of HIV-1 circulating in India, we sequenced the V3-V4 region of viral env from 21 individuals attending an HIV clinic in Calcutta, the most populous city in the eastern part of the country, and analyzed these and the other Indian sequences in the HIV database. Twenty individuals were infected with viruses having a subtype C env, and one had viruses with a subtype A env. Analyses of 192 subtype C sequences that included one sequence for each subject from this study and from the HIV database revealed that almost all sequences from India, along with a small number from other countries, form a phylogenetically distinct lineage within subtype C, which we designate C(IN). Overall, C(IN) lineage sequences were more closely related to each other (level of diversity, 10.2%) than to subtype C sequences from Botswana, Burundi, South Africa, Tanzania, and Zimbabwe (range, 15.3 to 20.7%). Of the three positions identified as signature amino acid substitution sites for C(IN) sequences (K340E, K350A, and G429E), 56% of the C(IN) sequences contained all three amino acids while 87% of the sequences contained at least two of these substitutions. Among the non-C(IN) sequences, all three amino acids were present in 2%, while 22% contained two or more of these amino acids. These results suggest that much of the current Indian epidemic is descended from a single introduction into the country. Identification of conserved signature amino acid positions could assist epidemiologic tracking and has implications for the development of a vaccine against subtype C HIV-1 in India.

Adult↗
PubMed2001

An unusual presentation of thyroglossal duct cyst.

Thyroglossal duct cyst usually presents as a painless swelling in the mid-line of the neck. This is the first documented case of an acute presentation of hoarseness and multi-loculated swelling. It also contrasts the limitations of ultrasonography with the accuracy of magnetic resonance imaging in such atypical swellings.

Adult↗
PubMed2001

Use of individualized versus standard criteria to identify abnormal levels of heart rate or oxygen saturation in preterm infants.

Preterm infants' physiological indicators, such as heart rate, respiratory rate, and oxygen saturation levels, are routinely monitored by devices that can alert nurses to threatening changes in condition. Most Neonatal Intensive Care Units use standard criteria as alerting algorithms to determine when an alert should be issued, and these standard criteria have been adopted uncritically in studies of preterm infants. This article presents results from a study examining preterm infants' physiological responses to a gentle human touch (GHT) intervention in which we compared the use of standard and individualized criteria to define the percentages of abnormally low and high heart rates (HRs) and abnormally low oxygen saturation (O2 sat) levels before, during, and after periods of GHT. Results indicated that there were no differences in the percentages of abnormal HRs or O2 sat values between periods using standard criteria. However, using individualized criteria, there were significantly greater percentages of abnormally low heart rates and O2 sat levels during and after GHT periods as compared to baseline periods. The findings suggest that standard criteria may not be sensitive enough to detect subtle physiological responses to environmental stimuli such as touch. Moreover, consistent with the recognition of the value of individualized developmental care, these results suggest that the clinical effectiveness of individualized criteria for setting monitor alert limits merits further investigation.

Blood Gas Analysis↗
PubMed2000

Optimal dosing of subcutaneous unfractionated heparin for the treatment of deep vein thrombosis.

Twice-daily, inpatient, subcutaneous unfractionated heparin is at least as effective and safe as continuous intravenous unfractionated heparin for the treatment of acute deep vein thrombosis. Subcutaneous unfractionated heparin therefore may be suitable for outpatient treatment of deep vein thrombosis. The purpose of this study was to develop a dosing nomogram for a dose each 12 hours (2 doses per day) 12-hourly subcutaneous unfractionated heparin that is suitable for outpatient treatment of acute deep vein thrombosis. A cohort study was performed in patients with acute deep vein thrombosis in two phases. In both phases, the first subcutaneous loading dose of unfractionated heparin was 317 U/kg, and the second dose was 231 U/kg. The activated partial thromboplastin time was measured daily, 6 hours after the morning injection, and subsequent doses of unfractionated heparin were adjusted according to a nomogram, which was modified for phase II. Warfarin was started with unfractionated heparin. In phase I (14 outpatients), activated partial thromboplastin time results were frequently subtherapeutic (9:14) the day after starting unfractionated heparin (day 1), and were frequently supratherapeutic (27:40) after the first 2 days of unfractionated heparin therapy. In phase II (21 patients), to explain the frequently subtherapeutic activated partial thromboplastin time results that were obtained on day 1, the activated partial thromboplastin time results were measured after the initial loading dose. Mean activated partial thromboplastin time results of 86 and 61 seconds were obtained 6 and 12 hours after this dose, suggesting that 317 U/kg is a suitable subcutaneous loading dose. In contrast to phase I, in phase II, unfractionated heparin dose was not increased on day 1 in response to a low activated partial thromboplastin time result. This reduced the frequency of supratherapeutic activated partial thromboplastin time results during the early days of therapy without increasing the frequency of subtherapeutic results. Warfarin therapy had a substantal effect on the activated partial thromboplastin time that appeared to account for a high frequency of supratherapeutic results during the later days of unfractionated heparin therapy; the activated partial thromboplastin time increased by 20 seconds (95% CI, 14-27 seconds) with each increase in the International Normalized Ratio of 1.0. We had limited success at developing a dosing nomogram for subcutaneous unfractionated heparin that reliably achieved activated partial thromboplastin time results within the therapeutic range. However, as oral anticoagulants directly increased activated partial thromboplastin time results, we suggest that adjusting unfractionated heparin dose to achieve prespecified activated partial thromboplastin time results may not be appropriate in patients who are receiving concomitant warfarin therapy.

Acute Disease↗
PubMed2000

Cysticercosis: towards the design of a diagnostic kit based on synthetic peptides.

Cysticercosis caused by Taenia solium is a very common disease in developing countries that seriously affects human health. Diagnosis can only be confirmed with the aid of computerized tomography or nuclear magnetic resonance (NMR) creating obvious difficulties for epidemiological studies. Reliable immunoassays employing cerebrospinal fluid (CSF) have been developed, based on the use of cysticercal antigens. However, the reliance on parasite material is restrictive. Herein, we report the advances in the design of a diagnostic kit based on immunodominant synthetic peptides, targeting four candidate epitopes KETc1, KETc12, 410 and 413 which were identified from three different clones (KETc1, 12 and 4) selected from a cDNA library of Taenia crassiceps. CSF antibodies against T. solium cysticercal antigens (TCA) as well as the four peptides were determined by enzyme-linked immunoabsorbent assays (ELISA) using two panels of CSF from patients with confirmed neurocysticercosis and other neurological diseases. In the first CSF panel which included patients with high level of antibodies against TCA, KETc12 exhibited almost the same sensitivity (87.5%) as TCA (93.7%) and 100% specificity. In the second panel of 110 CSF collected at random, two peptides (KETc1 and KETc12) exhibited sensitivities of 40 and 36% respectively, and were 100% specific.

Animals↗
PubMed2000

Functional and quality-of-life outcomes in patients with rectal cancer after combined modality therapy, intraoperative radiation therapy, and sphincter preservation.

PURPOSE: Locally advanced primary and recurrent rectal cancers treated with external beam radiation therapy, intraoperative radiation therapy, and chemotherapy represent a complex group of patients in the setting of extensive pelvic surgery and sphincter preservation. We sought to define functional outcome and quality of life in this subset of patients. METHODS: We retrospectively reviewed our experience with locally advanced primary and recurrent rectal cancer patients who underwent intraoperative radiation therapy with either low anterior resection (n = 12) or coloanal anastomosis (n = 6) between 1991 and 1998. Current functional outcome and quality of life were evaluated by a detailed questionnaire. RESULTS: Median time from operation to assessment was 24 (range, 6-93) months. Using a standardized Sphincter Function Scale, incorporating the number of bowel movements per day and degree of incontinence, patients were graded as poor, fair, good, or excellent function. Of all patients, 56 percent reported unfavorable (poor or fair) function. Of the subset of patients with coloanal anastomosis or very low low anterior resection, 88 percent had unfavorable function as compared with 30 percent with standard low anterior resection. (P = 0.02; Fisher's exact probability test). A quality-of-life satisfaction score based on social, professional, and recreational restrictions demonstrated 56 percent of patients to be dissatisfied with their bowel function. CONCLUSIONS: The majority of patients with advanced rectal cancers who require external beam radiation therapy, extensive pelvic surgery, and intraoperative radiation therapy report unfavorable functional and quality-of-life outcomes after sphincter preservation. In this setting patients being considered for coloanal anastomosis or very low anterior resection may be better served by permanent diversion.

Adult↗
PubMed2000

Tumor necrosis factor alpha and interleukin 1beta up-regulate gastric mucosal Fas antigen expression in Helicobacter pylori infection.

Fas-mediated gastric mucosal apoptosis is gaining attention as a cause of tissue damage due to Helicobacter pylori infection. We explored the effects of H. pylori directly, and the effects of the inflammatory environment established subsequent to H. pylori infection, on Fas-mediated apoptosis in a nontransformed gastric mucosal cell line (RGM-1). Exposure to H. pylori-activated peripheral blood mononuclear cells (PBMCs), but not H. pylori itself, induced Fas antigen (Fas Ag) expression, indicating a Fas-regulatory role for inflammatory cytokines in this system. Of various inflammatory cytokines tested, only interleukin 1beta and tumor necrosis factor alpha induced Fas Ag expression, and removal of either of these from the conditioned medium abrogated the response. When exposed to Fas ligand, RGM-1 cells treated with PBMC-conditioned medium underwent massive and rapid cell death, interestingly, with a minimal effect on total cell numbers early on. Cell cycle analysis revealed a substantial increase in S phase cells among cells exposed to Fas ligand, suggesting an increase in their proliferative response. Taken together, these data indicate that the immune environment secondary to H. pylori infection plays a critical role in priming gastric mucosal cells to undergo apoptosis or to proliferate based upon their Fas Ag status.

Animals↗
PubMed2000

Comparison of service member and military spouse satisfaction with installation fitness facilities and exercise programs.

Satisfaction with fitness facilities has long been accepted as a positive contributing factor to physical activity, readiness, and overall quality of life for military families. Our findings are based on a random sample of military families surveyed at 38 installations worldwide and at remote locations. A total of 8,572 service member and 3,493 spouse (55% and 32% response rate, respectively) questionnaires were completed and returned. Overall, members were satisfied with fitness facilities and programs, but spouses were less satisfied and more unfamiliar with these facilities. Most valued programs were fitness centers and swimming pools. Members reported that elimination of fitness facilities would greatly decrease the quality of life on installations, particularly at sites outside the continental United States, whereas spouses reported that this would not have a dramatic effect. The results of this study could be used to direct funding allocations, improve the health and fitness of military families, and suggest areas for further research.

Adult↗
PubMed1999

In vitro repair of synthetic ionizing radiation-induced multiply damaged DNA sites.

When ionizing radiation traverses a DNA molecule, a combination of two or more base damages, sites of base loss or single strand breaks can be produced within 1-4 nm on opposite DNA strands, forming a multiply damaged site (MDS). In this study, we reconstituted the base excision repair system to examine the processing of a simple MDS containing the base damage, 8-oxoguanine (8-oxoG), or an abasic (AP) site, situated in close opposition to a single strand break, and asked if a double strand break could be formed. The single strand break, a nucleotide gap containing 3' and 5' phosphate groups, was positioned one, three or six nucleotides 5' or 3' to the damage in the complementary DNA strand. Escherichia coli formamidopyrimidine DNA glycosylase (Fpg), which recognizes both 8-oxoG and AP sites, was able to cleave the 8-oxoG or AP site-containing strand when the strand break was positioned three or six nucleotides away 5' or 3' on the opposing strand. When the strand break was positioned one nucleotide away, the target lesion was a poor substrate for Fpg. Binding studies using a reduced AP (rAP) site in the strand opposite the gap, indicated that Fpg binding was greatly inhibited when the gap was one nucleotide 5' or 3' to the rAP site. To complete the repair of the MDS containing 8-oxoG opposite a single strand break, endonuclease IV DNA polymerase I and Escherichia coli DNA ligase are required to remove 3' phosphate termini, insert the "missing" nucleotide, and ligate the nicks, respectively. In the absence of Fpg, repair of the single strand break by endonuclease IV, DNA polymerase I and DNA ligase occurred and was not greatly affected by the 8-oxoG on the opposite strand. However, the DNA strand containing the single strand break was not ligated if Fpg was present and removed the opposing 8-oxoG. Examination of the complete repair reaction products from this reaction following electrophoresis through a non-denaturing gel, indicated that a double strand break was produced. Repair of the single strand break did occur in the presence of Fpg if the gap was one nucleotide away. Hence, in the in vitro reconstituted system, repair of the MDS did not occur prior to cleavage of the 8-oxoG by Fpg if the opposing single strand break was situated three or six nucleotides away, converting these otherwise repairable lesions into a potentially lethal double strand break.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Invariant or highly conserved TCR alpha are expressed on double-negative (CD3+CD4-CD8-) and CD8+ T cells.

TCR alpha (TCRA) expression was examined in RNA samples from PBMC and isolated populations of CD4+, CD8+, and DN T cells from 15 healthy individuals. The expressed TCR repertoire was surveyed using spectratype analysis, a technique that displays the distribution of complementarity determining region 3 (CDR3) lengths for each TCRAV gene family. The results revealed the presence of unusual populations of double-negative (DN; CD4-CD8-CD3+) T cells that express invariant or conserved TCRAV4A, AV7, AV19, and AV24 chains. Each of the conserved TCRA families was over-represented in >70% of the individuals studied, and all individuals expressed at least one of the over-represented TCRAV families. Over-represented conserved AV4A or AV7 sequences were also present in CD8+ T cells from most donors. The extent of TCRA sequence conservation is unparalleled. TCRAV4A, AV19, and AV24 sequences were invariant, although AV4A and AV19 transcripts contained N region additions. TCRAV24 transcripts derived from the direct juxtaposition of V and J gene segments. TCRAV7 sequences showed some diversity in two amino acids encoded at junctions of V and J gene segments. Although derivation of DN T cells with conserved TCRA chains is puzzling, the wide-spread expression of these unusual cells suggests an important function.

Adult↗
PubMed1999

A randomized trial comparing 5-mg and 10-mg warfarin loading doses.

BACKGROUND: Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio (INR). Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state; they also may not hasten achieving an INR value between 2.0 and 3.0. This study was designed to prospectively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy. METHODS: Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were randomly allocated to receive an initial dose of 5 or 10 mg of warfarin. Subsequent doses were based on dosing algorithms. The INR was measured daily for 5 days. The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3, 4, or 5 of the study and whose INR did not exceed 3.0 at any point during the study. RESULTS: Five (24%) of 21 patients in the 10-mg group and 21 (66%) of 32 patients in the 5-mg group achieved the primary end point (relative risk 2.22, 95% confidence interval 1.30-3.70 [P < .003]). A trend toward less overanticoagulation was seen in the 5-mg warfarin group. CONCLUSION: A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy.

Aged↗
PubMed1999

Do the rich really die young? Alcohol-related mortality and social class in Great Britain, 1988-94.

AIMS: To determine whether social class is a major influence on alcohol-related mortality in the general, economically active population of Great Britain. DESIGN AND PARTICIPANTS: Poisson regression of rates of mortality known to be directly caused by alcohol consumption by age, sex and social class in England, Wales and Scotland. MEASUREMENTS: The measure of alcohol-related mortality is total deaths from ICD-9 categories 291; 303; 357.5; 425.5; 535.3; 305; 790.3; and 571.0-571.3 over the 7-year period 1988-94. (It excludes deaths for which alcohol-attributable fractions would need to be calculated.) The measure of social class is the British Registrar General's six-fold occupational classification, used to code census and death certification data. FINDINGS: Alcohol-related mortality rates are higher for men in the manual occupations than in the non-manual occupations, but the relative magnitude depends on age. Men aged 25-39 in the unskilled manual class are 10-20 times more likely to die from alcohol-related causes than those in the professional class, whereas men aged between 55 and 64 in the unskilled manual class are only about 2.5-4 times more likely to die. For women in paid employment there is no consistent class gradient; younger women in the manual classes are more likely to die from alcohol-related causes, but for older women it is those in the professional class who suffer elevated mortality. CONCLUSIONS: Social class is a risk factor for alcohol-related mortality in Britain, although it is mediated by age and sex. Alcohol appears to be similar to other psychoactive substances, therefore, in that problem use is linked to social structural factors such as poverty, disadvantage and social class. This suggests that social interventions aimed at reducing poverty and inequality have the potential to reduce current levels of alcohol-related harm among the poorest groups in the community.

Adolescent↗
PubMed1999

Radiographic grading for knee osteoarthritis. A revised scheme that relates to alignment and deformity.

OBJECTIVE: To develop a radiographic grading scheme for osteoarthritis of the knee that would relate to arthritic progression and deformity. METHODS: The scheme of Scott, et al was revised to include new fields of Tibial Erosion and Subluxation; the fields of Tibial Osteophytes and Sclerosis were removed. The worst affected compartment only was scored on frontal Standardized Knee Images, which were used to define knee alignment variables. RESULTS: The interreader reliability (kappa = 0.92) and correlation for total scores (r = 0.94) were both excellent (p < 0.001). Individual field scores and total knee scores both correlated well with most limb alignment variables, especially the hip-knee-ankle angle (r = 0.77, p < 0.001). CONCLUSION: These findings encourage further evaluations for outcome measurement, diagnostic sensitivity, and sensitivity to define arthritic change over time.

Arthroscopy↗
PubMed1998

Tsetse thrombin inhibitor: bloodmeal-induced expression of an anticoagulant in salivary glands and gut tissue of Glossina morsitans morsitans.

The tsetse thrombin inhibitor, a potent and specific low molecular mass (3,530 Da) anticoagulant peptide, was purified previously from salivary gland extracts of Glossina morsitans morsitans (Diptera: Glossinidae). A 303-bp coding sequence corresponding to the inhibitor has now been isolated from a tsetse salivary gland cDNA library by using degenerate oligonucleotide probes. The full-length cDNA contains a 26-bp untranslated segment at its 5' end, followed by a 63-bp sequence corresponding to a putative secretory signal peptide. A 96-bp segment codes for the mature tsetse thrombin inhibitor, whose predicted molecular weight matches that of the purified native protein. Based on its lack of homology to any previously described family of molecules, the tsetse thrombin inhibitor appears to represent a unique class of naturally occurring protease inhibitors. Recombinant tsetse thrombin inhibitor expressed in Escherichia coli and the chemically synthesized peptide are both substantially less active than the purified native protein, suggesting that posttranslational modification(s) may be necessary for optimal inhibitory activity. The tsetse thrombin inhibitor gene, which is present as a single copy in the tsetse genome, is expressed at high levels in salivary glands and midguts of adult tsetse flies, suggesting a possible role for the anticoagulant in both feeding and processing of the bloodmeal.

Amino Acid Sequence↗