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Biomedical subjects

A K Sullivan

Publications and source records attributed to A K Sullivan.

At least 19 recordsLinked to original sources

Texting decreases the time to treatment for genital Chlamydia trachomatis infection.

OBJECTIVE: To assess the effectiveness of a text message result service within an inner London sexual health clinic. METHOD: Demographic data, diagnoses, and time to diagnosis and treatment were collected over a 6 month period for patients receiving text messages and a matched standard recall group. Data on messages sent, staff time, and cost in relation to result provision were collected. RESULTS: Over a 6 month period 952 text messages were sent. In the final month of analysis, 33.9% of all clinic results were provided by text, resulting in a saving of 46 hours of staff time per month. 49 messages requested that the patient return for treatment, 28 of these patients had untreated genital Chlamydia trachomatis (CT) infection. The mean number of days (SD) to diagnosis was significantly shorter in the text message group (TG) v the standard recall group (SG) (7.9 (3.6) v 11.2 (4.7), p <0.001). The median time to treatment was 8.5 days (range 4-27 days) for the TG group v 15.0 (range 7-35) for SG, p = 0.005. CONCLUSION: Patients with genital CT infection are diagnosed and receive treatment sooner since the introduction of a text message result service. The introduction of this service has resulted in a significant saving in staff time.

Adult↗

Association of FMR1 repeat size with ovarian dysfunction.

BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (<80 repeats) contributes to the variation in age at menopause; thus, FMR1 could be considered a quantitative trait locus. More importantly, when repeat size exceeds this threshold, the increase in risk for ovarian dysfunction is clinically significant. Intriguingly, this risk appears to plateau, or perhaps decrease, among women with very high repeats (> or =100 repeats).

Adolescent↗

Reconstitution of CD4+ T cell responses in HIV-1 infected individuals initiating highly active antiretroviral therapy (HAART) is associated with renewed interleukin-2 production and responsiveness.

Reconstitution of functional CD4(+) T cell responsiveness to in vitro stimuli is associated with continuous highly active antiretroviral therapy (HAART). Thirty-six antiretroviral naive patients received HAART over 16 weeks. Antigen-specific, mitogen and interleukin (IL)-2 induced lymphocyte proliferative responses and specific IL-2 and IL-4 production were assessed at each time-point, together with quantification of HIV-1 RNA load and lymphocyte populations. Reconstitution of recall responses was limited largely to persistent antigens such as Herpes simplex virus and Candida, rather than to HIV-1 or neo-antigens. Recall antigens, mitogens and IL-2-induced renewed responses were associated with in-vitro production of IL-2, but not IL-4. Differential responsiveness to low versus high concentration IL-2 stimulus increases in a stepwise manner, suggesting normalization of IL-2 receptor expression and improved functionality. These increases in in-vitro proliferative responses thus probably reflect short lived effector clones, driven by ongoing antigenic stimulus associated with persisting long-term organisms. In this context non-responsiveness to HIV-1 antigens suggests ongoing HIV-1 specific clonal T cell anergy.

Anti-HIV Agents↗

Restoration of human immunodeficiency virus-1-specific responses in patients changing from protease to non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

The effect of altering antiretroviral therapy (ART) on responses to viral, recall and human immunodeficiency virus (HIV)-1-specific recombinant antigens and interleukin-2 (IL-2) in HIV-1-infected patients was assessed. A longitudinal cohort study in eight HIV-1 infected individuals following a clinically indicated therapy change (seven for drug intolerance and one for virological failure) from protease inhibitor (PI) to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral regimens was performed. CD4 T-cell counts, viral loads, lymphoproliferative responses, cytokine production and latent proviral deoxyribonucleic acid (DNA) were measured at baseline and at weeks 12 and 24 after therapy substitution. Following therapy-switch there was a 33% proportional increase in mitogen response (95% confidence interval (CI), 3-33%) and a 31% increase (95% CI, 15-48%) in viral and recall-antigen responses. Six patients developed proliferative responses to low concentration IL-2 stimulation. All patients demonstrated an increase in median HIV-1-specific responses, as three had detectable virus at baseline (two being viral rebound); this may reflect an autovaccination effect. Proviral DNA changes largely reflected plasma HIV-1 ribonucleic acid (RNA). In conclusion, NNRTI substitution for a PI may favour immune reconstitution with an improvement in HIV-1-specific responses, which may reflect differential effects on antigen processing and presentation, an autovaccination effect or alternatively a potential suppressive effect of the PI.

Anti-HIV Agents↗

Impact of NNRTI compared to PI-based highly active antiretroviral therapy on CCR5 receptor expression, beta-chemokines and IL-16 secretion in HIV-1 infection.

Interleukin-16 (IL-16) and the beta-chemokines (RANTES, monocyte chemotactic protein-1 (MCP-1), macrophage inhibitory protein (MIP)-1alpha and (MIP)-1beta) are soluble in vitro suppressors of macrophage tropic HIV-1 strains. The reduction of HIV-1 RNA plasma levels in late-stage patients receiving protease inhibitors has been associated with increased concentrations of MIP-1alpha, MIP-1beta, RANTES and IL-16 and a decrease in levels of MCP-1. We determined plasma levels of MCP-1, MIP-1alpha, MIP-1beta, RANTES and IL-16 during the first 16 weeks of highly active antiretroviral therapy (HAART) in chronic HIV-1-infected patients. Patients were administered one of two therapeutic regimens based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). No differences were seen in the levels of RANTES and IL-16 over the first 16 weeks of HAART in either treatment group. MCP-1 decreased significantly in the PI-treated group over the first 16 weeks of HAART (P = 0.0003). A significant increase was observed in the levels of MIP-1alpha and MIP-1beta in the NNRTI cohort (P = 0.0010 and P = 0.0012, respectively). A significant decrease in levels of MIP-1alpha and MIP-1beta (P = 0.0015 and P = 0.0299, respectively) was observed over the 16 weeks in the PI cohort. A significant difference was seen when the levels of MIP-1alpha and MIP-1beta were compared between the NNRTI and the PI cohorts at week 16 (P = 0.04 and P = 0.05, respectively). Evaluation of CCR5 expression ex vivo revealed no difference between the two treatment groups. Patients were genotyped for CCR5 Delta32 and the incidence of heterozygosity was lower than in the HIV-1 seronegative controls (3% compared to 19%).

Adult↗

Bone marrow as a potential source of hepatic oval cells.

Bone marrow stem cells develop into hematopoietic and mesenchymal lineages but have not been known to participate in production of hepatocytes, biliary cells, or oval cells during liver regeneration. Cross-sex or cross-strain bone marrow and whole liver transplantation were used to trace the origin of the repopulating liver cells. Transplanted rats were treated with 2-acetylaminofluorene, to block hepatocyte proliferation, and then hepatic injury, to induce oval cell proliferation. Markers for Y chromosome, dipeptidyl peptidase IV enzyme, and L21-6 antigen were used to identify liver cells of bone marrow origin. From these cells, a proportion of the regenerated hepatic cells were shown to be donor-derived. Thus, a stem cell associated with the bone marrow has epithelial cell lineage capability.

2-Acetylaminofluorene↗

Psychological risk factors and early complications after bone marrow transplantation in adults.

Complications of bone marrow transplantation can compromise its effectiveness, and often it is not possible to predict who is at greatest risk. In a previous study we reported that certain psychological factors correlated with a high incidence of post-transplant mortality, and here we analyze the associated complications and causes of death. Prior to receiving high-dose chemotherapy and bone marrow transplantation, 112 patients underwent a psychodynamically oriented psychiatric assessment (the 'FIT' assessment). Mortality and associated complications were ascertained by a retrospective chart review. The results of the 'FIT' assessment correlated with the incidence of complications and death, whether or not the transplant was performed for hematologic or solid organ cancers, or was from an allogeneic or autologous source. Most individuals with a high risk profile died of progressive major organ dysfunction or recurrent/refractory neoplastic disease in the first year after transplant. We propose that such a psychiatric assessment might identify a subgroup of individuals in whom pre-emptive therapeutic interventions could be most effective.

Adolescent↗

Acid-alcohol fast bacilli in sputa of HIV-infected patients.

We identified 34 HIV-infected patients with sputum smear positive for acid-alcohol fast bacilli (AAFB) to determine any factors predictive of subsequent species identification. There were 20 cases of Mycobacterium tuberculosis (MTB), 9 cases of Mycobacterium avium-intracellulare (MAI), 3 cases of Mycobacterium kansasii and one each of Mycobacterium malmoense and Mycobacterium fortuitum. Factors associated with isolation of MAI were lower CD4 cell count, a higher incidence of previous AIDS diagnosis, a history of dyspnoea and a normal chest X-ray. The organism was isolated from blood cultures in 58% of patients with MTB and 78% of patients with MAI infection. Disseminated disease was diagnosed in 45% of MTB patients and 33% of MAI patients.

AIDS-Related Opportunistic Infections↗

Psychiatric assessment of candidates for bone marrow transplantation: a psychodynamically-oriented approach.

OBJECTIVE: To seek possible relationships between psychological factors and survival after an intensive medical therapy, using bone marrow transplantation as a model. METHOD: Candidates for bone marrow transplantation underwent two to three psychodynamically-oriented psychiatric interviews that explored family functioning ("F"), individual psychological maturity ("I"), and the capacity to form and communicate a mature psychological construct of the transplant ("T") process. The results were recorded in a semiquantitative manner, assigning a possible score of 1 to 3 for each parameter, for a possible total of 3 to 9 (the "F.I.T." assessment). Survival after the transplant was analyzed retrospectively in relation to the F.I.T. assessment. RESULTS: In a series of 112 candidates interviewed prior to transplant, those with the lowest F.I.T. assessment tended not to survive as long. By one year, 95 percent of individuals assigned the lowest score (F.I.T. = 3) had died, whereas 96 percent of those assigned the highest scores (F.I.T. = 7-9) remained alive. The strongest predictors were the "I" and "T" parameters. CONCLUSION: This approach to assessment of candidates for bone marrow transplantation may identify individuals who require added, supportive measures, both medical and psychological. Furthermore, the results suggest possible leads in the search for how psychological factors might influence the physiologic response to a toxic stress.

Bone Marrow Transplantation↗

A multidisciplinary vulva clinic: the role of genito-urinary medicine.

OBJECTIVES: To characterise the new patient referrals to a combined vulva clinic and to assess the role of genitourinary services within the clinic. METHODS: A case note review of all new patients attending a monthly, multidisciplinary vulva clinic over a 12-month period. RESULTS: The mean age of the 135 women was 43 years (range 18-86 years). The majority of patients, 64 (47%), were referred by their general practitioner (GP). Using nurse and physician triage 85 (63%) patients were seen by a dermatologist, 55 (41%) by a genitourinary medicine physician, 38 (28%) by a gynaecologist and six (4%) by a psychosexual physician. Fifty-one (38%) women required a consultation by at least two specialties. Itch was the most frequent presenting symptom (70%) and 59 (44%) women had experienced symptoms for between 6 months and 2 years. A previous STD screen had been performed in only 57 (42%), which was negative in 45 (79%). The most frequent initial clinical diagnoses were lichen sclerosus (35, 26%), vaginal candidiasis (21, 16%), vulvodynia (16, 12%), lichen simplex chronicus (13, 10%) and Bowenoid papulosis (13, 10%). Thirty-eight (28%) women had microbiological investigations revealing 13/135 (10%) had vaginal candidiasis and two (2%) bacterial vaginosis, all symptomatic. A biopsy was performed in 32 (24%) confirming the initial diagnosis in 20 (63%) cases. Treatment was initiated in 101 (75%) women: 62 (46%) were prescribed steroid cream, 46 (34%) emollient cream and 22 (16%) treatment for candida infection. Fifty-three (39%) women received more than one treatment. 94 (70%) patients were followed-up in the vulval clinic, five (4%) in the genitourinary clinic and 12 (9%) by their GP. CONCLUSIONS: Despite having genitourinary symptoms less than half the patients had been tested for infection prior to attending the clinic. More than a third of the patients, 46 (34%), were diagnosed with a genitourinary infection. There is a significant role for genitourinary services in the diagnosis, management and ongoing care of patients in a vulva clinic.

Adolescent↗

Double esterase staining and other neutrophilic granule abnormalities in 237 patients with the myelodysplastic syndrome studied by the cancer and leukemia group B.

We investigated double (specific and nonspecific) esterase (DE) staining in marrow cells of 237 patients with the myelodysplastic syndromes (MDS). Additional abnormalities of neutrophilic granules were examined cytochemically and immunocytochemically for myeloperoxidase activity and antigen elastase, lactoferrin and CD15 granule-membrane glycoproteins. Abnormal DE staining (>/=3% of all nucleated marrow cells) was present in 27% of patients with no difference among different MDS subtypes. However, the prevalence of high abnormal DE staining (>/=10%) was significantly lower in refractory anemia with excess blasts in transformation (1%) compared to other MDS subtypes (12-15%; p = 0.004). The prevalence of other granule abnormalities was not statistically different in the DE normal and DE abnormal groups. Abnormal DE staining is relatively common among all MDS subtypes. High DE staining may identify a subgroup of patients with a lower grade MDS.

Bone Marrow Cells↗

An audit of emergency contraception: a look at patient characteristics and the effects of a consultation proforma.

The aim of this study was to examine the characteristics of patients requesting emergency postcoital contraception at a genitourinary medicine (GUM) clinic. We also compared the quality of information obtained during the consultation, before and after a proforma was introduced. A retrospective review of all clinical notes of patients who attended for postcoital contraception between January and December 1994 and April to June 1995 was performed. Eighty-three per cent of patients were aged 17-29 years, 68.8% were in relationship, 41.3% were not using regular contraception, 33.8% accepted a sexual health screen and of these, 14.8% had a concurrent sexually transmitted disease (STD). The introduction of a consultation proforma significantly improved certain areas of the consultation. The results suggest that sexual health screens should be encouraged in women attending GUM clinics for postcoital contraception and that the use of a proforma improves the quality of information obtained.

Adolescent↗

Deficiency of neutrophilic granule membrane glycoproteins in the myelodysplastic syndromes: a common deficiency in 216 patients studied by the Cancer and Leukemia Group B.

Previous studies on neutrophils in patients with the myelodysplastic syndromes (MDS) have indicated deficiencies in the contents of primary and secondary granules. However, the granule membrane remains virtually unstudied despite its essential role in the dynamic function of the cytoplasmic granules. In this study, we examined the membrane glycoproteins of primary and secondary granules of peripheral blood and/or bone marrow neutrophils using the monoclonal antibody H36/71 to CD15 glycoproteins. In addition, myeloperoxidase activity and antigen, elastase and lactoferrin were also studied using cytochemical and immunocytochemical stains. A total of 216 patients were included. Deficiencies of granule membrane glycoproteins were the most common, detected in 49%, followed by myeloperoxidase activity (17%), elastase (16%), myeloperoxidase antigen (9%), and lactoferrin (8%). Multiple deficiencies always included granule membrane deficiency. We conclude that granule membrane defects are common in MDS, may provide a common mechanism for multiple granule deficiencies, and may prove to be an additional abnormality associated with granulocyte dysfunction.

Cytoplasmic Granules↗