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Biomedical subjects

A Jahn

Publications and source records attributed to A Jahn.

At least 19 recordsLinked to original sources
PubMed2026

Beyond in silico prediction: multi-omics to identify a pathogenic deep intronic HNRNPK variant in Au-Kline syndrome.

Pathogenic variants in HNRNPK are associated with autosomal dominant Au-Kline syndrome (AKS, Au-Kline-Okamoto syndrome, OMIM #616580). This syndrome is characterized by developmental delay and intellectual disability, hypotonia, and distinctive facial features. Despite the use of whole-genome sequencing (WGS) as a powerful diagnostic tool, we nearly dismissed a novel intronic variant (NM_031263.4(HNRNPK):c.214-55 T > A) affecting HNRNPK splicing and function. Although commonly used bioinformatic splice prediction tools, including SpliceAI and PDIVAS, yielded inconclusive results, Face2Gene analysis indicated a high phenotypic similarity to AKS. Characteristic facial features described by Choufani et al. [1] supported the clinical diagnosis of AKS. Subsequent functional studies demonstrated aberrant splicing with intron retention, and DNA methylation profiling revealed a positive HNRNPK-specific episignature. These insights and the de novo status support an evaluation as likely pathogenic. This case report supports the relevance of facial analysis and comprehensive variant validation strategies, particularly for deep intronic variants with ambiguous in silico splicing predictions.

Journal Article↗
PubMed2007

HIV epidemic trend and antiretroviral treatment need in Karonga District, Malawi.

We describe the development of the HIV epidemic in Karonga District, Malawi over 22 years using data from population surveys and community samples. These data are used to estimate the trend in HIV prevalence, incidence and need for antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early 1990s at 2.2% among males and 3.1% among females, and then levelled off at 1.3% among males and 1.1% among females by the late 1990s. Assuming a 2-year eligibility period, both our model and the UNAIDS models predicted 2.1% of adults were in need of ART in 2005. This prediction was sensitive to the assumed eligibility period, ranging from 1.6% to 2.6% if the eligibility period was instead assumed to be 1.5 or 2.5 years, respectively.

Adolescent↗
PubMed2007

Assessing health worker performance in malaria case management of underfives at health facilities in a rural Tanzanian district.

OBJECTIVE: To study the quality of malaria case management of underfives at health facilities in a rural district, 2 years after the Tanzanian malaria treatment policy change in 2001. METHODS: Consultations of 117 sick underfives by 12 health workers at 8 health facilities in Mkuranga District, Tanzania were observed using checklists for history taking, counselling and prescription. Diagnoses and treatment were recorded. Exit interviews were performed with all mothers/guardians and blood samples taken from the underfives for the detection of malaria parasites and antimalarial drugs. Quality of care was measured using indicators adopted from the integrated management of childhood illnesses multi-country evaluation. RESULTS: Quality of care measured by indicator scores averaged 31% of what was considered optimal. The poorest results were for history taking. Nevertheless, 89% of febrile children were treated with antimalarials, in line with national guidelines for fever treatment. Of these, 61% had a parasitaemia > or =2000/microl. There was no difference in treatment given to those with parasitological malaria compared with those without parasites. Pre-treatment levels of chloroquine and sulphadoxine/pyrimethamine were low and detected in 2% and 13%, respectively. CONCLUSION: Although most febrile children were given antimalarial treatment, quality of care in terms of history taking and counselling was sub-optimal. Despite this, the study community had changed behaviour from self-treatment to seeking care at health facilities. This is encouraging for introduction of artemisinin-based combination therapies policies as one could focus resources into improving care at health facilities and still reach out with treatment to most febrile children.

Antimalarials↗
PubMed2001

Comparison of methods for determination of microbial biomass in wastewater.

Microbial biomass in wastewater was determined by methods used in environmental microbiology and by a method used in wastewater engineering based on a conceptual model simulating fundamental microbial processes in wastewater from measured oxygen uptake rates. The methods originating from environmental microbiology are based on staining and counting of cells for the determination of total cell biomass (acridine orange and DAPI), physiological state of cells (LIVE/DEAD BacLight) and activity of cells (reduction of the redox dye CTC and microautoradiography). Depending on the staining method applied, cell biomasses yielded 15-86% of the biomass defined by the model, and good correlations between cell biomass and model biomass were found. Cell biomass, oxygen uptake and acetate uptake were measured in wastewater, where acetate was added. Substrate uptake rates were found not to be proportional to the increases in cell biomass, suggesting that only a small fraction of the cell biomass was responsible for the main part of the substrate uptake. Despite the differences found between cell biomass and model biomass, it was recommended to use the conceptual model as an engineering tool for simulation of microbial processes and wastewater quality changes. However, there should be a clear distinction between the terms 'model biomass', 'cell biomass' and different activity measurements of cells.

Bacteria↗
PubMed2001

Meningitis propagation in southern Tanzania: the role of a village video show.

An outbreak of meningitis with 85 secondary cases and an unusually high attack rate of 16% occurred in a rural village in southern Tanzania. We investigated risk factors for clinical illness in a community-based case-control study. Attending a commercial mobile video show carried an age- and sex-adjusted odds ratio of 8.0 (95% confidence interval: 3.8-16.8). The videos had been shown in a windowless and overcrowded storeroom and had been attended by the primary case, a visitor from neighbouring Mozambique who died from meningitis on the following day. We conclude that mobile video shows, which have become popular in many developing countries, constitute a potential health hazard in areas prone to meningitis epidemics.

Adolescent↗
PubMed2000

In vivo measurements of the internal pH of Hediste (Nereis) diversicolor (Annelida, Polychaeta) exposed to ambient sulphidic conditions using pH microelectrodes.

The effect of different ambient sulphide concentrations on the internal pH regime of Hediste (Nereis) diversicolor was studied under in vivo conditions using liquid membrane pH microelectrodes, a method which is new to marine sciences. As a case study, the hypothesis was tested whether organisms exposed to ambient sulphidic conditions are able to lower their internal pH which, in effect, would reduce sulphide influx into the animals and thus could represent an effective detoxification mechanism. It was shown that a significant lowering of the internal pH occurred within only 20 min after adding sulphide. This pH lowering appeared to be dependent on the external sulphide concentration of the ambient medium and showed a saturation beyond a threshold level of about 130 microM. It is discussed whether this sulphide-induced pH drop is an active regulatory mechanism and acts as an effective protection mechanism against sulphide during short-term exposures.

Animals↗
PubMed2000

Between fear and relief: how rural pregnant women experience foetal ultrasound in a Botswana district hospital.

Ultrasound technology has achieved almost universal coverage in industrialised countries with particular importance in antenatal surveillance. Its routine use has, however, been viewed critically from medical as well as from sociological perspectives. Studies on women's perception of ultrasound underline the crucial role of client provider communication supporting the technical procedure. Ultrasound is now increasingly available in developing countries. Little is known about how clients in these settings perceive the technology. This study was concerned with women's experience of ultrasound scanning in an African district hospital setting and how their experience concurs with the health professionals' views about the new technology. The study was qualitative and used semi-structured in-depth interviews with 41 clients and structured non-participant observation of the examination process, as well as semistructured interviews with health staff. Most women viewed ultrasound as being beneficial. Some expressed considerable fear. The quality of client-provider interaction played a decisive role in how the procedure was perceived. Many statements, however, reflect women's overestimation of the diagnostic power of ultrasound and prenatal therapeutic possibilities. Technology and its often expatriate providers tend to be mystified and at the same time non-technological procedures provided by local staff in the context of normal history taking and antenatal care undervalued. Health staff expressed very positive views of ultrasound. They admitted, however, that since the availability of ultrasound they were tempted to take histories and physical examinations less thoroughly than before. Irrational expectations from the clients' side and unindicated overuse of ultrasound by health professionals may in the long run interact in a way that possibly undermines the quality and rational utilisation of antenatal care and respective referral guidelines. Indications for the use of ultrasound must be clearly specified within specific societal contexts and mechanism of ensuring adherence to these criteria be established. Communication with patients and appropriate information about the benefits and limitations of ultrasound are essential to alleviate fear, and to discourage irrational expectations and demand.

Botswana↗
PubMed2000

Maternity care in rural Nepal: a health service analysis.

This study assesses the performance of maternity care and its specific service components (preventive interventions in antenatal care, antenatal screening, referral, obstetric care) in Banke District, Nepal, using a set of structure, process, and output/outcome indicators. Data sources included health service documents in 14 first level health units and two hospitals, covering 1378 pregnancies and 1323 deliveries, structured observations, antenatal exit interviews (n = 136) and interviews with maternity users (n = 146). Coverage of antenatal care (28%) and skilled delivery care (16%) was low. In antenatal care, preventive interventions were only partially implemented (effective iron supplementation in 17% of users). On average one minute was spent on individual counselling per consultation. 41% of pregnancies were identified as high risk and 15% received referral advice, which was followed in only 32%. Hospital deliveries accounted for 9.8% of all deliveries. Hospital-based maternal mortality was 6.8/1000 births and the stillbirth rate 70/1000. High rates of stillbirth were observed in breech delivery (258/1000 births), caesarean section (143/1000) and twin delivery (133/1000). The risk of stillbirth was higher for rural women (RR 2.3; 95% CI 1.51-3.50) and appeared to be related to low socio-economic status. Emergency admissions were rare and accounted for 3.4% of hospital deliveries or only 0.4% of all expected deliveries. There was hardly any accumulation of high-risk pregnancies at hospital. The population-based rate of caesarean section was 1.1% (urban 2.3%, rural 0.2%). The estimated unmet obstetric need was high (82 cases or 61% of expected live-threatening maternal conditions did not receive appropriate intervention). The limited effectiveness of maternity care is the result of deficiencies of all service components. We propose a two-pronged approach by starting quality improvement of maternity care from both ends of maternity services: preventive interventions for all women and hospital-based obstetric care. Antenatal screening needs to be rationalized by reducing inflated risk catalogues that result in stereotypical and often rejected referral advice.

Cesarean Section↗
PubMed2000

Why do at-risk mothers fail to reach referral level? Barriers beyond distance and cost.

In southern Tanzania, few high-risk pregnancies are channeled through antenatal care to the referral level. We studied the influences that make pregnant women heed or reject referral advice. Semi-structured interviews with sixty mothers-to-be, twenty-six health workers and six key-informants to identify barriers to use of referral level were conducted. Expert-defined risk-status was found to have little influence on a woman's decision to seek hospital care. Besides well known geographical and financial barriers, we found that pregnant women have different perceptions and interpretations of danger signs. Furthermore, rural women avoid the hospital because they fear discrimination. We conclude that a more individualised antenatal consultation could be provided by taking into account women's perception of risk and their explanatory models. Hospital services should be reorganised to address rural women's feelings of fear and insecurity.

Attitude of Health Personnel↗
PubMed1999

Trends in maternal mortality ratio among women of German and non-German nationality in West Germany, 1980-1996.

BACKGROUND: Maternal mortality is a sensitive indicator for inequity in health. We describe recent trends in overall and cause-specific maternal mortality ratio among women of German and non-German nationality residing in West Germany. METHODS: Using birth and death register data for 1980-1996 we related 1067 cases of maternal death (ICD 9: 630-676) to 11.2 million live births. We assessed the effects of nationality and of marital status, a proxy for socioeconomic status, controlling for year of death and age of the mother in a Poisson regression model. RESULTS: Maternal mortality ratio in West Germany decreased from 13 per 100000 live births in 1980-1988 to 6.1 in 1989-1996. The crude relative risk for non-German nationality decreased from 1.9 (95% CI: 1.6-2.3) to 1.3 (1.0-1.7); after adjusting for age, year of death and marital status it was 1.7 (95% CI: 1.4-2.1) and 1.6 (95% CI: 1.2-2.1). Unmarried women incurred an adjusted relative risk of 1.8 (95% CI: 1.5-2.3). Non-German women experienced an excess mortality from abortions which largely disappeared in 1989-1996; concurrently, being unmarried no longer conveyed an additional risk to them. The risk status of German mothers developed unfavourably: increasing proportions are unmarried, which continues to be a marker of elevated relative risk in this group. CONCLUSIONS: Our findings suggest continuously improving accessibility and quality of obstetric services, in particular for women of non-German nationality. Still, inequity in maternal risk continues to exist. Maternal risk, however, is not determined by the simple distinction 'German' versus 'non-German'; its association with socioeconomic status extends beyond nationality.

Abortion, Induced↗
PubMed1998

Routine screening for intrauterine growth retardation in Germany: low sensitivity and questionable benefit for diagnosed cases.

BACKGROUND: Antenatal screening for fetal growth retardation has proven effective in detecting at-risk pregnancies under study conditions. It is also widely believed to improve pregnancy outcomes. We assessed sensitivity of antenatal screening routines for intrauterine growth retardation under routine service conditions in Germany. We then compared pregnancy management and outcome in small for gestational age neonates with antenatally diagnosed growth retardation to neonates whose growth retardation had remained undetected. METHODS: Historical prospective study covering all 2378 singleton pregnancies with antenatal records delivered within a one-year period at a tertiary level maternity hospital in Germany. Antenatal records were linked with pregnancy outcome data. RESULTS: The sensitivity of screening routines based on ultrasound and non-systematic follow-up investigations was 32% as compared to 80-90% reported for ultrasound screening under study conditions. An antenatal diagnosis of intrauterine growth retardation was associated with a 5 times higher rate of preterm delivery (p<0.001), mainly as a consequence of medical interventions to avoid fetal compromise, when compared to new-borns with growth retardation not detected before delivery; admission rates to neonatal care unit were 3 times higher (p<0.001). The proportion of low Apgar scores and low cord pH, indicating fetal distress, was not significantly different in detected and undetected cases. CONCLUSION: Screening routines for intrauterine growth retardation currently used in Germany miss the majority of cases and do not contribute towards improved pregnancy outcome in detected cases. A benefit of elective preterm delivery in the management of suspected intrauterine growth retardation was not evident.

Diagnosis, Differential↗
PubMed1998

Obstetric care in southern Tanzania: does it reach those in need?

OBJECTIVE: To assess whether antenatal care achieves identification and timely referral of high-risk pregnancies in southern Tanzania. METHODS: We compared the risk profiles of pregnant women in general with those attending obstetric care and investigated the reasons for seeking care. The risk profile of inpatients was drawn up through interviews with maternity cases and analysis of their antenatal records at the regional referral hospital (n = 415); population-based data on the prevalence of specific risk factors were obtained from entries in antenatal care registers (n = 1630) and from literature. RESULTS: A significant risk selection towards obstetric referral level care was observed only for previous caesarean section (prevalence hospital 6.7%, all pregnancies 1.5%, P < 0.005) and for nulliparity (hospital 42.8%, all pregnancies 25.0%, P < 0.005). No significant differences were observed for other risk factors such as previous perinatal death, height < 150 cm, multiple gestation and breech presentation. Prevalence of the risk factors age > 34 years and grand multiparity was significantly lower among hospital users. Coverage of obstetric care was below 50% for all risk factors except previous caesarean section (91.5%). CONCLUSION: Despite pursuing the risk approach and very good coverage, antenatal care in Tanzania has only limited effect on extending obstetric care to high-risk mothers. A critical review of the present screening and counselling practices, including a more focused and client-centred application of risk assessment, is warranted.

Adult↗
PubMed1998

Accumulation of amphotericin B in human macrophages enhances activity against Aspergillus fumigatus conidia: quantification of conidial kill at the single-cell level.

A cytofluorometric assay that allowed assessment of damage to phagocytosed Aspergillus fumigatus conidia at the single-cell level was developed. After ingestion by monocyte-derived macrophages (MDMs), conidia were reisolated by treatment of the cells with streptolysin O, a pore-forming toxin with lytic properties on mammalian cells but not on fungi. The counts obtained by staining of damaged conidia with propidium iodide and quantification by cytofluorometry correlated with colony counts. By the use of this method, we demonstrate that MDMs differentiated in vitro by low-dose granulocyte-macrophage colony-stimulating factor and gamma interferon have only a limited capacity to damage Aspergillus conidia in vitro. The killing rate 12 h after phagocytosis was found to be only 10 to 15%. However, intracellular loading of the phagocytes with amphotericin B (AmB) dose dependently enhanced the anticonidial activity. Preincubation of macrophages with only 1 microg of AmB per ml resulted in an uptake of 18 fg of AmB/cell, leading to killing rates of 50 to 60%. The experimental protocol provides a new tool for the rapid quantification of anticonidial activity against A. fumigatus in vitro. Intracellular accumulation of AmB may represent an important factor underlying the efficacy of this antifungal drug in the prophylaxis and treatment of Aspergillus infections.

Amphotericin B↗