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Biomedical subjects

R Steen

Publications and source records attributed to R Steen.

At least 19 recordsLinked to original sources
PubMed2001

Eradicating chancroid.

Genital ulcers are important cofactors of HIV transmission in the countries most severely affected by HIV/AIDS. Chancroid is a common cause of genital ulcer in all 18 countries where adult HIV prevalence surpasses 8% and is rare in countries with low-level HIV epidemics. Haemophilus ducreyi, the causative organism of chancroid, is biologically vulnerable and occupies a precarious epidemiological niche. Both simple, topical hygiene and male circumcision greatly reduce risk of infection and several classes of antibiotics--some of which can be administered in single-dose treatment regimens--provide rapid cure. H. ducreyi depends on sexual networks with high rates of partner change for its survival, thriving in environments characterized by male mobility and intensive commercial sex activity. Elimination of H. ducreyi infection from vulnerable groups results in disappearance of chancroid from the larger community. Once endemic in Europe and North America, chancroid began a steady decline early in the twentieth century, well before the discovery of antibiotics. Social changes--resulting in changing patterns of commercial sex--probably disrupted the conditions needed to sustain chancroid as an endemic disease. Sporadic outbreaks are now easily controlled when effective curative and preventive services are made available to sex workers and their clients. More recently, chancroid prevalence has declined markedly in countries such as the Philippines. Senegal, and Thailand, a development that may contribute to stabilization of the HIV epidemics in these countries. Eradication of chancroid is a feasible public health objective. Protecting sex workers and their clients from exposure to sexually transmitted diseases (STDs) and improving curative services for STDs are among the proven strategies that could be employed.

Africa South of the Sahara↗
PubMed2000

Characteristics of haemopoietic progenitor cells related to CD34 epitope class expression.

Haemopoietic progenitor cells (HPCs) express the CD34 molecule, a heavily glycosylated transmembrane protein displaying three main classes of epitopes. The CD34 epitope class expression may vary between different subsets of HPCs. The aim of this study was to characterise the subsets of HPCs expressing CD34 class II and III epitopes. The cells were studied for coexpression of activation-, lineage- and adhesion-associated molecules, and their clonogenic ability and morphological features were examined. CD34+ HPCs expressing class III epitopes outnumbered those expressing class II. Class III expressing HPCs were enriched for CFU-GM and BFU-E and cells coexpressing CD13, CD33, c-kit and CD71 compared to class II expressing HPCs. CD34+ cells exclusively expressing class III epitopes uniformly displayed CD13 and CD33; they had a high clonogenic capacity and morphological characteristics of promyelocytes and myelocytes. The data show that class III epitopes are distributed more broadly on CD34+ HPCs than are class II epitopes, and that lack of class II epitopes is confined to CD34+ HPCs at a late stage of myeloid differentiation. The higher number of class III expressing HPCs coexpressing c-kit and CD71 suggests that these cells exhibit a higher proliferative or differential potential than do HPCs expressing class II epitopes.

Antigens, CD34↗
PubMed2000

A randomised study of allogeneic transplantation with stem cells from blood or bone marrow.

Sixty-one consecutive adult patients with leukaemia, primary myelofibrosis or myelodysplastic syndrome with an HLA-identical or one antigen mismatched family donor were randomised to allogeneic transplantation with PBPC or BM. Progenitor cells were mobilised into the blood by giving the donors 10 microg/kg/day G-CSF subcutaneously for 5-7 days. G-CSF was not given to patients after transplantation. The time to neutrophil counts >0.5 x 109/l was 17 days (95% CI 15.2-18.8 days) in the PBPC group compared to 23 (95% CI 20.3-25.7 days) in the BM group (P = 0.0005). The time to platelet counts >20 x 109/l was 13 days (95% CI 11.7-14.3 days) in the PBPC group and 21 days (95% CI 18.7-23.3 days) in the BM group (P = 0.0005). Acute GVHD of grades II-IV developed in six patients transplanted with PBPC and three patients transplanted with BM. The numbers of patients with chronic GVHD were 15 and 8, respectively. Transplant-related mortality and leukaemia-free survival showed no significant differences. Transplantation with PBPC appears preferable for the recipient due to faster neutrophil and platelet recovery. However, the final conclusion can not be drawn before long-term results on chronic GVHD and relapse incidence in longer randomised trials are available.

Adolescent↗
PubMed2000

Evidence of declining STD prevalence in a South African mining community following a core-group intervention.

OBJECTIVES: To reduce the prevalence of curable sexually transmitted diseases (STDs) in a South African mining community through provision of STD treatment services, including periodic presumptive treatment and prevention education to a core group of high-risk women living in areas around the mines. METHODS: Women at high risk for STDs attended a mobile clinic monthly for examination and counseling, and were treated presumptively for bacterial STDs with a directly observed 1-g dose of azithromycin. Gonococcal and chlamydial infection rates were measured by urine ligase chain reaction, and genital ulcers were assessed by clinical examination. Changes in STD prevalence among local miners were assessed through comparison of prevalence in two cross-sectional samples of miners taken 9 months apart, and through routine disease surveillance at mine health facilities. RESULTS: During the first 9 months of the intervention, 407 women used the services. Baseline prevalence of Neisseria gonorrhoeae and/or Chlamydia trachomatis in women was 24.9%; 9.7% of these women had clinical evidence of genital ulcer disease (GUD). The proportion of women with incident gonococcal or chlamydial infections at the first monthly return visit (69% follow-up rate) was 12.3%, and genital ulcers were found in 4.4% of these women. In the miner population, the prevalence of N gonorrhoeae and/or C trachomatis was 10.9% at baseline and 6.2% at the 9-month follow-up examination (P<0.001). The prevalence of GUD by clinical examination was 5.8% at baseline and 1.3% at follow-up examination (P< 0.001). Rates of symptomatic STDs seen at mine health facilities decreased among miners in the intervention area compared with miners living farther from the site and with less exposure to the project. DISCUSSION: Provision of STD treatment services to a core group of high-risk women may significantly reduce their burden of disease, and may contribute to a reduction in community STD prevalence. In the absence of sensitive and affordable screening tests for STDs in women, periodic presumptive treatment coupled with prevention education is a feasible approach to providing STD services in this population.

Adult↗
PubMed1999

Thrombopoietin combined with early-acting growth factors effectively expands human hematopoietic progenitor cells in vitro.

Thrombopoietin (TPO) is established as a powerful stimulant of megakaryocyte differentiation and platelet production both in vivo and in vitro. In preparation for future transplantation of ex vivo expanded CD34+ hematopoietic progenitor cells (HPCs), we have examined the in vitro effect of TPO on cultures of HPC when combined with other early-acting hematopoietic growth factors (GFs) in an attempt to decrease post-transplant thrombocytopenia and accelerate engraftment. By adding TPO to all possible combinations of GM-CSF, IL-3, and c-kit ligand (CKL) in a suspension culture system, we found a significant increase in both relative and absolute numbers of cells in cultures containing TPO of the megakaryocytic lineage and CD34+ cells after 14 days of culture. The most efficient GF combinations for expansion of cell populations of the megakaryocytic lineage and HPCs were TPO, GM-CSF, and CKL, which increased the number of cells of the megakaryocytic lineage 78 fold and the number of CD34+ cells 1.8 fold. The number of CD34+ cells decreased in the cultures containing GM-CSF and CKL with no TPO present, and the number of cells of the megakaryocytic lineage was increased merely 27 fold. Based on our findings, we suggest adding cells from HPCs expanded in cultures containing TPO, GM-CSF, and CKL to unexpanded stem cells for stem cell transplantation.

Antigens, CD↗
PubMed1999

The use of epidemiologic mass treatment and syndrome management for sexually transmitted disease control.

BACKGROUND: Epidemiologic mass treatment and syndrome management are two sexually transmitted disease (STD) control strategies that are receiving increased attention internationally. The former is a population-based intervention, whereas the latter attempts to improve the quality and efficiency of clinic-based STD case management. METHODS: The published literature on these subjects was reviewed. RESULTS: Epidemiologic mass treatment refers to treatment of whole communities (mass treatment) or high-risk subgroups within communities (targeted presumptive treatment) based on high STD prevalence rates. Syndrome management overcomes many obstacles to provision of quality STD case management by basing treatment decisions on recognition of easily identifiable syndromes. Experience with application of these strategies is summarized, and their possible use as STD control measures in communities with similar conditions is discussed. CONCLUSIONS: Epidemiologic mass treatment may be an effective approach to rapidly reduce STD transmission in high prevalence communities, especially when high-risk core groups are effectively reached. Once high prevalence rates are brought down, however, longer term strategies, including improved STD case management, are essential to maintain reduced rates.

Adolescent↗
PubMed1998

CD34 molecule epitope distribution on cells of haematopoietic origin.

The CD34 molecule belongs to the mucin membrane molecule family and is expressed on virtually all normal haematopoietic progenitor cells (HPC). Due to its heavy glycosylation, several different epitopes exist on the molecule. Based on the sensitivity of the glycosylated molecule to degradation with a glycoprotease from Pasteurella haemolytica and neuraminidase, three classes of epitopes have been identified. The class I and II epitopes are probably related to the glycosylated part of the molecule while class III epitopes are core protein related. It has been known for some time that CD34 class I epitopes are absent on CD34 molecules expressed on high endothelial venules. Here we review recent observations that expression of both class I and II epitopes, but not class III epitopes, is impaired on mature myeloid CD34-pos. HPC while no diverse class epitope expression was observed on immature HPC. In addition, cells from patients with CD34-pos. acute myeloid leukaemia of FAB classification M4-M5, i.e., leukaemic blast cells of relatively mature morphologic phenotype, also express less class I and II epitopes than class III epitopes. It therefore seems that HPC maturation and class I and II epitope deprivation are concomitant events and that CD34 class I and II epitopes are lost prior to downregulation of the CD34 molecule per se. The biological significance of this observation is discussed as well as the need to carefully select CD34-specific monoclonal antibodies for research and clinical purposes.

Antigens, CD34↗
PubMed1998

Notes from the field: practical issues in upgrading STD services based on experience from primary healthcare facilities in two Rwandan towns.

OBJECTIVE: In order to assess the feasibility of upgrading STD management at the primary healthcare level in Rwanda, a project was piloted in a health centre and a hospital dispensary in two up country towns. METHODS: Nurses trained in syndrome based management treated all patients with genitourinary complaints at first visit without laboratory results. They provided condom demonstration and risk reduction advice, and gave coupons for partner referral. Principal findings and decisions were recorded on individual patient records. Partners presenting referral coupons were treated presumptively and their records linked to the index case. RESULTS: Three quarters of symptomatic patients seen at the two primary healthcare facilities were women. With training and supervision, nurses applied the syndromic STD management guidelines correctly in over 90% of cases. Symptomatic treatment failure at first follow up visit varied from 0% for male urethritis to 27% for genital ulcer, the one condition that was not treated syndromically. Four fifths of women presenting with vaginal discharge had clinical signs of cervicitis, and the presence of cervical signs was 86% sensitive for presence of leucocytes on cervical Gram stain. CONCLUSIONS: With adequate post-training supervision, nurses were able to apply the syndromic STD management guidelines and a high degree of clinical improvement was achieved. Syndromic algorithms that recommend treatment for all common pathogens at the first visit had higher rates of symptomatic cure at follow up than the algorithm employing a sequential treatment approach. Clinical and laboratory evidence suggests a high prevalence of cervicitis in this population of women seeking care.

Algorithms↗
PubMed1998

Indicators and the measurement of STD case management in developing countries. STD PI6&7 Working Group.

The paper reviews methodologies for measuring quality of sexually transmitted disease (STD) case management through facility based assessments. These include observations and interviews of providers, as promoted by the World Health Organization's Global Programme on AIDS, and some of the viable alternatives including patient exit interviews, mystery patients, record review and patient encounter forms with supervisory visits. The paper concludes that the alternative approaches are feasible in resource poor settings and that they provide crucial data for evaluation and continued program development.

Case Management↗
PubMed1997

Efflux of CD34+ cells from bone marrow to peripheral blood is selective in steady-state hematopoiesis and during G-CSF administration.

Comparative studies of the CD34+ cell population in peripheral blood (PB) and bone marrow (BM) may contribute to understanding the mechanisms involved in mobilization of hematopoietic progenitor cells (HPCs) from BM to PB. PB-CD34+ and BM-CD34+ cells in steady-state hematopoiesis and during granulocyte colony-stimulating factor (G-CSF) administration were studied for the expression of activation-associated, lineage-associated and adhesion-associated molecules and for their cloning capacity [granulocyte-macrophage colony-forming cells (CFU-GM) and burst-forming unit-erythrocytes (BFU-E)]. G-CSF increased significantly the number of CD34+ cells in PB as well as in BM and resulted in a reduction of CD34+ cells coexpressing the adhesion-related molecule CD49d. Further, G-CSF reduced the relative number of lymphoid progenitors (CD34+ cells coexpressing CD10, CD19, CD20, CD2, or CD7) in both compartments. However, G-CSF had no major impact on the observed differences between PB-CD34+ and BM-CD34+ cells seen during steady-state hematopoiesis despite a relative decrease in PB and increase in BM of certain immature progenitors (CD34+DR- cells). Circulating CD34+ cells, even in steady-state, were enriched for colony-forming cells, and individual colonies appeared larger compared with their BM counterparts. PB-CD34+ cells contained relatively more myeloid progenitors (CD34+CD13+ cells) and fewer B lymphoid progenitors (CD10, CD19, and CD20 cells) than BM-CD34+ cells. CD34+DR-cells were present in a higher proportion of the CD34+ cells in PB than in BM. There were lower numbers of CD34+ cells expressing CD49d and c-kit in PB than in BM. To summarize, the differences between PB-CD34+ and BM-CD34+ cells observed during steady-state hematopoiesis were largely conserved during G-CSF administration. G-CSF, therefore, mainly has an effect on the quantity not the composition of the circulating CD34+ cell pool. Our data also suggest that the egress of HPCs from BM during steady-state hematopoiesis, as well as during G-CSF administration, is a selective process; that is, certain subsets are more prone to enter into circulation than others, and this release may be mediated via common pathway possibly involving downregulation of c-kit and VLA-4 (CD49d).

Antigens, CD34↗
PubMed1997

STD services for women at truck stop in Tanzania: evaluation of acceptable approaches.

AIDS continues to be the commonest cause of death in Tanzania among those aged between 15 and 45 years. Both ulcerative and non-ulcerative sexually transmitted diseases have been identified as major co-factors in HIV transmission. Certain groups including long distance truck drivers and their sexual partners have been reported as having a disporportionate effect on the transmission dynamics of STD including HIV, in a population. In 1993 African Medical and Research Foundation decided to add an STD component to their HIV/AIDS prevention programme along the Tanzania-Zambia highway which had been targeting truck drivers and their sexual partners through peer education and condom distribution since 1989. A study to evaluate the acceptability and feasibility of four different approaches of delivering STD services, was conducted over a period of one year. The approaches for delivering STD services were: special STD services offered twice a week at a site and at hours of the women's choice, special outreach services once every three months, or STD services integrated into the nearest Primary Health Clinic. Drugs were provided at three of the four interventions. 1,330 women at seven truckstops, participated in the evaluation study. The women were generally satisfied with all approaches that included the provision of drugs. The most expensive and ineffective way of treating STD was by not providing drugs. These findings confirm the fact that it is feasible to provide STD services to women at high risk in HIV high transmission areas. These women would utilise STD services provided in a manner that suits them if mobilised and encouraged by their peer educators.

Adult↗
PubMed1996

A comprehensive genetic map of the mouse genome.

The availability of dense genetic linkage maps of mammalian genomes makes feasible a wide range of studies, including positional cloning of monogenic traits, genetic dissection of polygenic traits, construction of genome-wide physical maps, rapid marker-assisted construction of congenic strains, and evolutionary comparisons. We have been engaged for the past five years in a concerted effort to produce a dense genetic map of the laboratory mouse. Here we present the final report of this project. The map contains 7,377 genetic markers, consisting of 6,580 highly informative simple sequence length polymorphisms integrated with 797 restriction fragment length polymorphisms in mouse genes. The average spacing between markers is about 0.2 centimorgans or 400 kilobases.

Animals↗
PubMed1996

Differences in the distribution of CD34 epitopes on normal haemopoietic progenitor cells and leukaemic blast cells.

The CD34 molecule expressed on haemopoietic progenitor cells contains a large number of epitopes whose expression may be related to the maturation or function of the cells. Monoclonal antibodies specific for different epitopes have been reported to detect different numbers of CD34+ leukaemic blast cells. We wanted to confirm this observation and study whether parallel findings could be observed for normal haemopoietic progenitor cells. The cells were immunophenotyped by flow cytometry with a series of monoclonal antibodies reactive with different CD34 epitopes. Class III epitopes (resistant to enzymatic cleavage with neuraminidase, chymopapain and a glycoprotease from Pasteurella haemolytica) showed a broader distribution on normal haemopoietic progenitor cells and leukaemic blast cells than class I epitopes (sensitive to cleavage with all three enzymes) and class II epitopes (sensitive to degradation with glycoprotease and chymopapain, and resistant to neuraminidase). The subpopulation of normal progenitor cells which exclusively expressed class III epitopes had flow cytometric characteristics compatible with mature myeloid progenitor cells whereas class I, II and III epitopes were equally expressed on cells enriched for immature subsets. No discordant epitope expression could be observed for the more immature leukaemias (AML-M0/1) and a higher percentage of the more mature leukaemic blast cells (AML-M3 and AML-M4/5) expressed class III epitopes compared to the percentage expressing class I and II epitopes. These data indicate that CD34 class III epitopes are more broadly distributed on normal haemopoietic progenitor cells and leukaemic blast cells than class I and II epitopes, and that class I and II epitopes may be down-regulated prior to class III epitopes during normal haemopoietic progenitor cell differentiation. These findings should be considered when selecting CD34 mabs for quantification and positive selection of haemopoietic progenitor cells for research and clinical purposes.

Acute Disease↗
PubMed1996

Partner referral as a component of integrated sexually transmitted disease services in two Rwandan towns.

OBJECTIVE: To document partner referral rates at health centres with improved STD services, and to determine factors contributing to successful referral. METHODS: Partner referral was initiated as part of the upgrading of STD services in primary care health facilities in two semi-urban Rwanda towns. After syndromic management of the presenting complaint, index patients received prevention education and condom demonstration, and were urged to refer sexual partners to the health centre for a free examination. Partner referral coupons linked by code number to the symptomatic index patient were given to facilitate referral; no identifying information was collected on partners from the index patients. RESULTS: Three quarters of the symptomatic patients seen at the two primary health care facilities were women. Overall, the ratio of referred partners to index patients was 26%. Only 58% of index patients accepted partner referral coupons. The referral rate for those who did accept coupons was 45%. Partner referral worked best for regular partners. Most index patients and partners were married and only four index patients referred more than one partner. Women index patients, especially when pregnant, were more successful in referring partners than men. Index patients who referred partners tended to be older than those who did not. Awareness of STD symptoms in the partner, and diagnosis of cervicitis were associated with a higher rate of STD symptoms in the partner, and diagnosis of cervicitis were associated with a higher rate of partner referral. CONCLUSIONS: Efforts to improve rates of partner referral should begin at the clinic level with improved counselling to convince more index patients of the importance of partner referral. Partner symptom recognition may be useful for increasing rates of partner referral. Supplementary strategies are needed to reach non-regular partners. When syndromic management is used, counselling should take into account the lower predictive values of identifying STD in women in order to avoid partner accusation. Despite limitations, patient referral of sexual partners can be an effective strategy for reaching a population at high risk for STD with minimal additional investment in health worker staff time.

Adult↗
PubMed1996

Lineage commitment of CD34+ human hematopoietic progenitor cells.

Hematopoietic cells occur in a continuum of many different stages of functional differentiation, from totipotential stem cells to terminally differentiated lineage-specific cells. At some point during differentiation, progenitor cells become committed to a particular lineage. Little is known about the surface molecules that distinguish lineage-committed progenitor cells from multipotential progenitor cells; this study was undertaken to address this issue. Exploiting a thymic stromal cell co-culture system, we show that CD34+ bone marrow cells expressing the T lymphocyte-associated CD2 and CD7 molecules, the B lymphocyte-associated CD10 and CD19, or the myeloid-associated CD33, contain progenitor cells that can generate T lymphocytes, granulocytes, and monocytes, indicating that the expression of any of these molecules on progenitor cells does not imply lineage commitment. CD34+CD13bright, CD34+CD14+, and CD34+CD15+ cells generated myeloid progeny, and CD34+CD20+ cells failed to differentiate along the T lymphoid and myeloid lineages. Thus expression of CD13, which precedes that of CD14 and CD15 during early hematopoiesis, appears to coincide with commitment to myeloid development. Our findings also indicate that expression of CD20 is restricted to progenitor cells committed to B lymphocyte development.

Adult↗
PubMed1995

Haemopoietic progenitor cell differentiation: flow cytometric assessment in bone marrow and thymus.

We have recently shown that expression of any of the lineage-associated molecules CD2, CD7, CD10, CD19 or CD33 does not ensure lineage-commitment of CD34+ progenitor cells. Further, normal progenitor cells and leukaemic blast cells have been shown to coexpress molecules associated with more than one haemopoietic lineage. Five-dimensional flow cytometric analysis of normal bone marrow cells was exploited to investigate the hypothesis of a developmental stage in haemopoiesis comprising CD34+ cells coexpressing CD2, CD5, CD7, CD10, CD19 and CD33 or any combination of these molecules. We report on a subpopulation of CD34+ bone marrow cells constituting < 5% of the CD34+ cells and characterized by extensive coexpression of several molecules associated with the B lymphoid, T lymphoid and myeloid lineages. There is every probability that some cells display the CD34+ CD2+ CD5+ CD7+ CD10+ CD19+ CD33+ phenotype. Studies on postnatal thymocytes suggest that this may be the phenotype or one of a few phenotypes of a candidate thymus-seeding progenitor cell population. Finally, our findings that CD34+ as well as CD34+ CD5+ thymocytes can be driven into non-T-lymphoid differentiation by cytokines, support the notion that the thymus is seeded by uncommitted progenitors.

Adult↗
PubMed1995

Thymic stromal cells support differentiation of natural killer cells from CD34+ bone marrow cells in vitro.

Natural killer (NK) cells are CD3-CD56+ lymphocytes characterized by exhibiting non-MHC restricted cytotoxicity. A developmental relationship between NK cells and T lymphocytes has been proposed, and, moreover, the thymus has been shown to contain NK cell precursors. In this study we utilized an in vitro assay, devised to study T-lymphocyte development from bone marrow progenitors, to investigate the ability of thymic stromal cells to support generation of NK cells from CD34+ bone marrow cells. CD34+ cells purified from healthy adults were seeded on adherent thymic stromal cells. The cells emerging after culture were phenotypically characterized by flow cytometry. We show that lymphocytes expressing the phenotypical characteristics of NK cells were generated from CD34+ bone marrow cells, and that these cells represented 1% of the cells recovered from the cultures. Furthermore, this was accomplished without supplement of exogenous interleukin 2 which is required for NK cell differentiation in bone marrow cultures.

Adult↗