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Biomedical subjects

K Bond

Publications and source records attributed to K Bond.

At least 19 recordsLinked to original sources

Post-exposure HIV prophylaxis following sexual exposure: a retrospective audit against recent draft BASHH guidance.

OBJECTIVES: To retrospectively audit the management of post-exposure HIV prophylaxis following sexual exposure (PEPSE) against the British Association for Sexual Health and HIV 2004 draft guidance. METHODS: A retrospective review of case notes from January 2000 to November 2004. The draft guidelines were not adopted into clinical practice during the study period. RESULTS: 76 patients received PEPSE. 79% (95% CI 68.08 to 87.46) of PEPSE prescriptions were given for exposures that were in accordance with the guidelines' recommended indications (target 90%). 87% (95% CI 77.13 to 93.51) of PEPSE was prescribed within 72 hours of risk exposure (target 90%). 91% (95% CI 81.94 to 96.22) of recipients received a recommended antiretroviral combination. 53% (95% CI 40.84 to 64.21) of recipients completed the PEPSE course (target 75%). 45% of patients attended for the 3 month follow up HIV test but only 12% (95% CI 5.56 to 21.29) attended for both the 3 month and 6 month HIV test (target 75%). CONCLUSION: PEPSE is predominantly being prescribed for recommended indications and is dispensed within 72 hours of risk exposure. PEPSE completion rates and attendance for 3 months and 6 months post-exposure HIV testing need improving, perhaps by introducing a PEPSE clinic.

Adult↗

Identification of a circulating soluble form of CD80: levels in patients with hematological malignancies.

The release of soluble forms of CD80 provides a potentially powerful mechanism for the modulation of anti-tumor responses. In this report we investigated whether a soluble form of CD80 (sCD80) circulates in vivo and whether levels are altered in patients with hematological malignancies. Circulating sCD80 was detected by ELISA in all normal donor (0.024-0.318 ng/ml) and patient (0.02-3.75 ng/ml) blood analyzed. The majority of acute myeloid leukemia (13/17) and multiple myeloma (11/12) patients had normal sCD80 levels. Significantly elevated levels were detected in chronic lymphocytic leukemia (CLL, P = 0.0001) and mantle cell lymphoma (MCL, P = 0.0002) patients. MCL patients had the highest levels with 8/9 having levels > 0.318 ng/ml. Increased sCD80 levels in CLL were significantly associated with poor prognosis markers such as low platelet (P = 0.01) and hemoglobin (P = 0.002) levels, elevated WBC counts (P = 0.03) and expression of CD38 (P = 0.048). The immunoreactivity of the sCD80 in both normal and patient plasma was inhibited by the presence of CTLA-4-Ig, suggesting sCD80 is functional. Comparison of sCD80 and soluble CD86 levels demonstrated that these molecules were independently elevated in 39% of patients. The finding that a proportion of CLL and the majority of MCL patients contain elevated levels of sCD80 and the demonstration that sCD80 can interact with CTLA-4-Ig suggests a potential role for sCD80 in modulating anti-tumor responses during the malignant process.

Abatacept↗

HOVIS -- The Hertfordshire/Oxfordshire Violent Incident Study.

Violence in psychiatric inpatient units is a major and growing problem. Research interest has primarily focussed on patient characteristics. The role of staff factors and the antecedents of violent incidents has been neglected, despite the fact that staff factors and behaviour may be more readily amenable to change than patient characteristics. The HOVIS study sought to obtain the views of a sample of mental health nurses in current clinical practice about staff-related factors, which they perceive to contribute to, or protect against, the occurrence of violent incidents. A total of 108 nurses working in psychiatric acute admission, intensive care and low secure units, in two NHS Trusts were interviewed using a specially designed semistructured interview schedule. These nurses identified a variety of behaviours, clinical skills, personal characteristics and interpersonal skills that they believe impact on the occurrence of violent incidents. These findings are discussed in relation to their possible training and managerial implications.

Adult↗

HIV-specific cytotoxic T lymphocytes, HLA-A11, and chemokine-related factors may act synergistically to determine HIV resistance in CCR5 delta32-negative female sex workers in Chiang Rai, northern Thailand.

Understanding how highly HIV-exposed individuals remain HIV uninfected may be useful for HIV vaccine design and development of new HIV prevention strategies. To elucidate mechanisms associated with resistance to HIV infection, immunologic and genetic factors were examined in 14 HIV-exposed but persistently seronegative (HEPS) female sex workers from Chiang Rai, northern Thailand and in ethnically matched, HIV-positive (n = 9) and HIV-negative women (n = 9). The HEPS women were identified in a study of commercial sex workers who had an HIV-1 incidence of 20.3 per 100 person-years. A high frequency of HLA-A11 was observed in HEPS women (86%) compared with northern Thai controls (56%). HIV-specific cytotoxic T lymphocyte (CTL) lytic responses were detected in cryopreserved peripheral blood mononuclear cells (PBMCs), using HLA-A-matched subtype E HIV-1 peptides in four of seven (57%) HEPS women, eight of eight HIV-positive women, and zero of nine HIV-negative unexposed controls (p = 0.019 HEPS women vs. HIV-negative controls). CTL lysis levels were low, but responses were detected to peptides from Nef, Pol, Gag, and Env. Nef responses predominated in HEPS women. Compared with controls, HEPS women tended to have higher frequencies of CCR5 promotor 59402GG and SDF-1 3'UTR 801A genotypes known to influence HIV transmission or course of disease. HEPS women also had higher levels of spontaneous RANTES production by PBMCs than other groups. Each of these factors could potentially contribute to HIV resistance. As most HEPS women had one or more of these factors, they may prevent HIV infection synergistically by blocking HIV cell entry, delaying its dissemination, or killing HIV-infected cells.

Adult↗

A new member of the spalt like zinc finger protein family, Msal-3, is expressed in the CNS and sites of epithelial/mesenchymal interaction.

We have identified a new member of the spalt-like gene family in mice, msal-3. We compared the expression patterns of msal-3 and msal-1 during development and show that they exhibit overlapping yet exclusive patterns of expression in the developing forebrain, diencephalon, midbrain/hindbrain boundary and spinal cord. Both genes are expressed from E7 in opposite gradients in primitive streak mesoderm. Subsequently their transcripts are localized to regions of mesenchyme/epithelial interaction in the palate, heart, limbs, anal and urogenital region.

Animals↗

Results of steroid-based therapy for the hepatitis C-autoimmune hepatitis overlap syndrome.

OBJECTIVE: Overlap syndromes in which persons manifest clinical, histological, or immunological features of both hepatitis C infection and autoimmune hepatitis are well described. The discordant forms of treatment for hepatitis C and autoimmune hepatitis have made medical management of these patients difficult. We report our experience in using corticosteroids as first line therapy for the hepatitis C-autoimmune hepatitis overlap syndrome. METHODS: Seven patients with this overlap syndrome (diagnosis based on the presence of serum hepatitis C antibody by RIBA and serum hepatitis C RNA by polymerase chain reaction, and serum hypergammaglobulinemia, elevated ANA or ASMA titers, or histological findings consistent with autoimmune hepatitis) were treated with prednisone with or without azathioprine or cyclosporine, and followed for a median duration of 44.5 months. RESULTS: Five patients (71%) showed improvement of median serum ALT level from 162 U/L to 38 U/L (p = 0.04) and median serum gamma-globulin from 2.1 g/dl to 1.4 g/dl (p = 0.04) by 6 months of therapy. The mean modified histological activity index score also decreased from 11.4 +/- 2.5 to 6.6 +/- 2.6 (p = 0.04) by at least 1 yr of therapy. One patient discontinued prednisone while taking azathioprine and experienced a rebound elevation of serum ALT that did not respond to retreatment with prednisone. Antiviral therapy was subsequently administered and resulted in biochemical and virologic response. Hepatitis C virus RNA remained detectable in all other patients. CONCLUSION: Corticosteroids are beneficial as a first line therapy for some patients with the hepatitis C-autoimmune overlap syndrome, resulting in appreciable biochemical and histological response but without viral eradication.

Adult↗

Direct inhibition of in vitro PLD activity by 4-(2-aminoethyl)-benzenesulfonyl fluoride.

While conducting a purification protocol of phospholipase D (PLD) from human granulocytes, we observed that PLD activity was inhibited by a commonly-used protease inhibitor cocktail. Of the six inhibitors present in the cocktail, the serine protease inhibitor, 4-(2-aminoethyl)-benezensulfonyl fluoride (AEBSF), was found to be the sole inhibitor of PLD. AEBSF caused a loss of neutrophil and purified plant PLD activities in vitro, but not in intact cells at the concentrations used, nor did it affect the related phospholipases A(2) and C, that were utilized as specificity controls. The compound AEBSNH(2), which has the fluoride replaced by an -NH(2) group, failed to affect PLD activity as did other compounds structurally related to AEBSF with known protease inhibitory capabilities. Finally, basal- and agonist-stimulated PLD activity was inhibited in phosphatidylcholine-specific anti-PLD immunoprecipitates (IC(50) = 75 microM). These results suggest that AEBSF, in an effect probably unrelated to its anti-proteolytic ability, directly interferes with PLD enzymatic activity, making it a significant compound to begin analyzing the role of PLD in mammalian cell signaling.

Brassica↗

The treated prevalence of bipolar disorder in a large staff-model HMO.

OBJECTIVE: The treated prevalence of bipolar disorder was examined in a large staff-model health maintenance organization (HMO) in western Washington state. METHODS: Automated data for all 294,284 adults enrolled in the HMO or treated by HMO providers were used to determine the number of patients treated for bipolar disorder between July 1, 1995, and June 30, 1996. Patients with bipolar disorder were identified using computerized records of inpatient diagnoses, outpatient visit diagnoses, and outpatient prescriptions of mood stabilizers. Validity of the identification procedure was confirmed by review of a random sample of outpatient records. RESULTS: The treated prevalence of bipolar disorder in the HMO was .42 percent. Somewhat higher treated-prevalence rates were found for women, younger enrollees, family members of HMO subscribers, enrollees in some of the individual plans within the HMO, and enrollees in the state's Basic Health Plan program for low-income residents. Of the 1,236 adults treated for bipolar disorder, 93 percent made at least one visit to specialty mental health services, and 86 percent received mood-stabilizing medications. Only a small percentage of the 1,236 patients received treatment with an antidepressant, an antipsychotic, or a benzodiazepine without having a mood stabilizer prescribed. CONCLUSIONS: The treated-prevalence rate found in this HMO population is higher than rates previously reported for prepaid health plans and lower than estimates from large population surveys. The majority of treated patients received specialty mental health services and treatment with mood-stabilizing medications.

Adult↗

Two-centre evaluation of the Abbott CD3500 blood counter.

The CD3500 blood counter (Abbott Laboratories) is a 33 parameter fully automated blood counter that produces a five part differential count with flagging of leucocyte abnormalities. In this evaluation excellent correlation between CD3500 and Coulter STKR blood counter was found for all red cell and platelet parameters on the 221 samples tested. Studies of carryover, mixing efficiency and precision also gave excellent results. There was a good correlation with manual 400 cell differential counts for neutrophils, lymphocytes, monocytes and eosinophils for the 468 samples compared. Correlation of CD3500 and manual basophil counts was poor. Normal samples stored at 4 degrees C and analysed while cold showed satisfactory stability for WBC, RBC, Hb, MCV and platelets for 48 h and a stable differential for 24 h. Correlation with the differential count produced by the Coulter STKS showed good correlation for neutrophils, lymphocytes, monocytes and eosinophils; correlation with STKS basophils was poor. False positive flagging rate varied between 8.9% (Band and/or IG) and 0.9% (NRBC) depending on the nature of the flag; 5.8% of samples exhibited two or more false positive flags. No significant breakdowns were encountered during the period of the evaluation. The scatterplot displays of laser light scatter produced by the instrument provide an interesting adjunct to conventional morphology.

Blood Cell Count↗

Continuous monitoring of fetal temperature by noninvasive probe and its relationship to maternal temperature, fetal heart rate, and cord arterial oxygen and pH.

The human fetus is normally warmer than its mother. The principal route of fetal heat dissipation is through the placental circulation. We developed a technique that is noninvasive to the fetus to record the fetal skin and maternal uterine wall temperatures, from which we derived the temperature difference. We have established a range of normal values (mean temperature difference 0.24C) and present some preliminary data. The results show a correlation between changing temperature and baseline fetal heart rate (r = 0.628, P less than .001) and the influence of contractions and epidural analgesia on these measurements. Measurement of the fetal-maternal temperature difference during labor may help detect abnormal umbilical-placental blood flow, resulting in fetal distress, and may help distinguish sinister from iatrogenic fetal tachycardias. Our technique provides the first simple means of recording this basic fetal variable.

Body Temperature↗

Epidural analgesia in labor and fetal hyperthermia.

OBJECTIVE: To assess the effect of epidural analgesia on fetal temperature in labor, contrasting intrauterine with oral thermometry. METHODS: Fetal skin and maternal uterine wall temperatures were measured with an intrauterine probe in 57 laboring women at term. Maternal oral temperatures were measured in the normal way by birth attendants unaware that their measurements would be examined. Maximum recorded fetal, uterine, and oral temperatures were compared. RESULTS: Epidural analgesia resulted in a significant fetal temperature rise compared with other methods of analgesia. Duration of epidural analgesia correlated with the fetal temperature (R = 0.44, P = .012). Oral thermometry underestimated fetal temperature in 95% of the studies. CONCLUSIONS: We estimate that 5% of fetuses reached a core temperature in excess of 40C in this study, all in association with epidural analgesia. We suggest that antipyretic measures be considered after 5 hours of epidural analgesia in ambient temperatures above 24C.

Analgesia, Epidural↗

Measuring fetal and maternal temperature differentials: a probe for clinical use during labour.

The healthy fetus maintains a higher temperature than that of its mother during gestation and labour. This results from the thermal balance between the heat generated by the fetus and the heat loss to its maternal surroundings. The heat loss can be by heat exchange via blood flowing in the umbilical cord and placenta, and via conduction through the fetal skin and amniotic fluid to the maternal wall. The temperature difference between the fetal and maternal tissue may reflect the metabolic state of the fetus and the magnitude and changing patterns of placental blood flow during labour. Physiological changes, such as those induced by epidural analgesia, and fetal infection have been shown to exhibit an increase in the absolute temperature. An intrauterine probe, previously used for non-invasive ECG detection, has been equipped with temperature sensors that measure fetal and maternal skin temperature in utero. Laboratory tests to characterize the performance of the probe reveal that absolute and differential temperatures can be resolved to around 0.01 degree C with a thermal time constant of approximately 9 s. Ideally the probe body should have infinite thermal insulation or thermal shunting across the probe will occur reducing the measured temperature difference. In this initial probe design, a high thermal isolation between sensors has been achieved but is not perfect, resulting in around 85% of the actual temperature difference across the probe being registered. Average feto-maternal differences of 0.2 degrees C have been measured in a clinical investigation.

Body Temperature↗

Osteoporosis.

Osteoporosis is a serious condition affecting millions of American women after the age of 45 years. Emphasis in women's health care must be directed toward identification of risk factors and preventive measures. Therapeutic intervention for patients with osteoporosis is based on three goals: halting bone loss, remineralizing bone, and minimizing the danger of falling and fractures.

Female↗

Bioavailable copper complexes offer a physiologic approach to treatment of chronic diseases.

Copper (II)2(3,5-Diisopropylsalicylate)4(H2O)2 has been found to have antiinflammatory, antiulcer, anticonvulsant, anticancer, anticarcinogenic, antimutagenic, and radiation recovery activities and it prevents reperfusion injury. To study pharmacokinetic parameters accounting for these pharmacological effects the double labeled 67Cu(II)2(carboxy-14C-3,5-diisopropylsalicylate)4 complex was synthesized and used to obtain these parameters. Treatment of mice with 1 mumol of this complex revealed that 67Cu was distributed to blood, liver, kidney, intestine, lung, thymus, femur, muscle, spleen, brain, urine, and feces within 0.5 hr and patterned changes in 67Cu content of these tissues and excreta were found throughout the 96 hr term of this study.

Animals↗

The use of administrative data to assess quality of care for bipolar disorder in a large staff model HMO.

We examined patterns of care for 1246 adults treated for bipolar disorder in a large health maintenance organization. Computerized pharmacy and visit data were used to identify patients treated for bipolar disorder. Automated medical records for the following year were used to assess continuity and dosing of treatment with mood stabilizers, laboratory monitoring for adverse effects and therapeutic serum levels, and frequency of follow-up visits. Of our 1246 subjects 83% filled a mood stabilizer prescription during the 1-year study period, and doses were within recommended ranges 80% of the time. Over 75% of the patients on mood stabilizers had at least one apparent interruption in medication use. Approximately half of the long-term users of mood stabilizers had at least one 7-month period without a recorded blood level and approximately half had a similar period without monitoring for adverse medication effects. Of the 116 subjects discharged from a psychiatric hospitalization 58% had a visit with a psychiatrist or a psychiatric nurse practitioner within 30 days. Of those discontinuing mood stabilizer treatment 68% made a mental health visit within 90 days. Our findings demonstrate the feasibility of using administrative data systems for population-based quality of care assessment and suggest opportunities for improving the care of bipolar patients.

Adolescent↗