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Biomedical subjects

J Jost

Publications and source records attributed to J Jost.

At least 19 recordsLinked to original sources

Individual variation in the erythropoietic response to altitude training in elite junior swimmers.

OBJECTIVES: Inter-individual variations in sea level performance after altitude training have been attributed, at least in part, to an inter-individual variability in hypoxia induced erythropoiesis. The aim of the present study was to examine whether the variability in the increase in total haemoglobin mass after training at moderate altitude could be predicted by the erythropoietin response after 4 h exposure to normobaric hypoxia at an ambient Po(2) corresponding to the training altitude. METHODS: Erythropoietin levels were measured in 16 elite junior swimmers before and after 4 h exposure to normobaric hypoxia (Fio(2) 0.15, approximately 2500 m) as well as repeatedly during 3 week altitude training (2100-2300 m). Before and after the altitude training, total haemoglobin mass (CO rebreathing) and performance in a stepwise increasing swimming test were determined. RESULTS: The erythropoietin increase (10-185%) after 4 h exposure to normobaric hypoxia showed considerable inter-individual variation and was significantly (p<0.001) correlated with the acute erythropoietin increase during altitude training but not with the change in total haemoglobin mass (significant increase of approximately 6% on average). The change in sea level performance after altitude training was not related to the change in total haemoglobin mass. CONCLUSIONS: The results of the present prospective study confirmed the wide inter-individual variability in erythropoietic response to altitude training in elite athletes. However, their erythropoietin response to acute altitude exposure might not identify those athletes who respond to altitude training with an increase in total haemoglobin mass.

Adolescent↗

Evolving networks with distance preferences.

We study evolving networks where new nodes when attached to the network form links with other nodes of preferred distances. A particular case is where always the shortest distances are selected ("make friends with the friends of your present friends"). We present simulation results for network parameters like the first eigenvalue of the graph Laplacian (synchronizability), clustering coefficients, average distances, and degree distributions for different distance preferences and compare them with the parameter values for random and scale-free networks. We find that for the shortest distance rule we obtain a power-law degree distribution as in scale-free networks, while the other parameters are significantly different, especially the clustering coefficient.

Journal Article↗

[Prospective multi-center study colon/rectum carcinoma (primary tumors)--Results of the year 2000].

INTRODUCTION: Surgical quality control in the form of multicentre studies make it possible to analyse the treatment status of a given surgical illness under quality assurance aspects. MATERIAL/METHODS: On 1. 1. 2000, under the patronage of the Convent of Hospital Chief Surgeons a project (ongoing) - organised and conducted by the Institute for Quality Management in Operative Medicine at the Otto-von-Guericke University of Magdeburg - was initiated to document and collect the data of patients with colorectal cancer throughout the whole of Germany. This work is supported by the German Society of Surgery, and the Surgical Working Group, Quality Assurance within the German Society of Surgery. Currently, some 282 hospitals throughout the country are involved in establishing a prospective documentation of colorectal carcinoma. Participation in this study is on a voluntary basis. The anonymity of both patients and hospitals is guaranteed, and no hospitals wishing to participate are excluded. Both operatively and conservatively treated patients are being documented, and no randomization takes place. RESULTS: In the year 2000, the participating hospitals documented a total of 9 477 patients with a colorectal carcinoma, including 6 975 patients with a carcinoma of the colon, and 3 402 with a rectal carcinoma. The average age of the patients was 68.5 years, and there were 5 010 men and 4 467 women. The operation rate was 99.2 %, the resection rate 95.6 %. The abdominoperineal resection rate was 27.4 %. The indicators for diagnostic quality as set out by Hermanek were largely complied with, but some deviations were noted. DISCUSSION: On the basis of the data collected, structures were established for a uniform Germany-wide quality management for a clinical condition with a major health policy impact. This information make it possible for the hospitals to identify and eliminate deficits in the structural and process quality in the diagnosis and treatment of colorectal cancer, and in this way to improve outcome quality. This means that the results of medical care research have an immediate impact on the individual treatment received by a given patient.

Adult↗

Spectral properties and synchronization in coupled map lattices.

Spectral properties of coupled map lattices are described. Conditions for the stability of spatially homogeneous chaotic solutions are derived using linear stability analysis. Global stability analysis results are also presented. The analytical results are supplemented with numerical examples. The quadratic map is used for the site dynamics with different coupling schemes such as global coupling, nearest neighbor coupling, intermediate range coupling, random coupling, small world coupling and scale free coupling.

Journal Article↗

Antiretroviral prophylaxis for community exposure to the human immunodeficiency virus in Switzerland, 1997-2000.

OBJECTIVE: To analyse the data from Swiss nationwide voluntary reporting on non-occupational HIV-postexposure prophylaxis (HIV-PEP) by prescribing physicians. METHODS: One hundred and seventy-six persons, who received antiretroviral prophylaxis for community exposure to HIV between December 1997 and March 2000, were included in this prospective cohort study with standardised data collection. Information on the source, the exposed person, type of exposure, treatment, and outcome was reported by physicians on a voluntary basis to three co-ordinating centers. RESULTS: HIV-PEP was prescribed predominantly following sexual exposure (69%). Needle injury was the second most common type of exposure (19% of all exposures), mostly occurring in a non-healthcare related "professional" setting (i.e., housekeepers, concierges [caretakers], and policemen). Needle sharing accounted for only 4% of all cases of exposure. The HIV status of the source often remained unknown (56%). Most patients received a combination of three antiretroviral drugs (zidovudine/lamivudine/nelfinavir in 34.1%; zidovudine/lamivudine/indinavir in 22.8%; zidovudine/lamivudine/nevirapine in 18.6%; various triple combinations in 13.8%). Follow-up information was available for 86 patients. In this group 78 (91%) completed at least one week of prophylaxis. Side-effects were common (70.9%), particularly diarrhoea (29.6%) and nausea (20.9%). Two patients experienced severe side effects, nephrolithiasis with sepsis, and toxic hepatitis, respectively. CONCLUSIONS: In most of the cases where HIV-PEP was prescribed the indication was questionable, with the HIV status of the source unknown. The role of HIV-PEP as part of HIV prevention programs should be well defined in view of the cost and potential for causing severe side-effects.

Adolescent↗

Intensification of stable background therapy with abacavir in antiretroviral therapy experienced patients: 48-week data from a randomized, double-blind trial.

OBJECTIVES: To evaluate antiretroviral efficacy of abacavir (ABC) in antiretroviral-experienced patients, by intensifying current antiretroviral therapy (CART) in patients with stable, detectable plasma HIV-1 RNA. METHODS: Thirty-two European centres recruited HIV-1 positive patients with < or = 36 months of CART experience. Patients were randomized to receive either ABC (300 mg twice daily) plus CART (ABC + CART) or ABC placebo plus CART (CART). We assessed efficacy as measured by plasma HIV-1 RNA and CD4+ cell counts and safety at baseline, weeks 2, 4 and every 4 weeks thereafter until week 48. Protocol-defined criteria enabled patients to switch to open-label ABC from week 8 onwards. RESULTS: Ninety-two patients with a median plasma of 3.66 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 408 cells/microL were randomized to ABC + CART and 93 patients with a median plasma of 3.52 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 411 cells/microL were randomized to CART. From weeks 8-48, 11 (12%) patients in the ABC + CART group and 34 (37%) patients in the CART group switched to open-label ABC. At week 48, significantly more patients on ABC + CART (23/92, 25%) than on CART (5/93, 5%) had plasma < or =400 HIV-1 RNA copies/mL (P < 0.001, intent-to-treat switch = failure population). Neither duration of previous nucleoside reverse transcriptase inhibitor treatment (up to 18 months) nor prior lamivudine therapy affected ABC efficacy. In the ABC + CART group, 16/25 (64%) patients with the M184V mutation at baseline had < or = 400 copies/mL or a decrease > or = 1 log10 copies/mL at week 16. More patients (19/46, 41%) with baseline viral load < or = 5000 copies/mL had plasma < 400 HIV-1 RNA copies/mL at 48 weeks than those > 5000 copies/mL (4/44, 9%). CD4+ cell counts increased by 102 cells/microL and 57 cells/microL at week 48 for the ABC + CART and CART groups, respectively (intent-to-treat, switch included). ABC addition had minimal impact on the CART safety profile. CONCLUSIONS: ABC intensification, in CART-experienced patients with low viral loads and limited reverse transcriptase mutations, most of whom had previously been on double-therapy, resulted in a significant and durable plasma HIV-1 reduction and concomitant increase in CD4+ cell count. The presence of M184V at baseline had minimal impact on the efficacy of ABC.

Adolescent↗

The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team.

OBJECTIVE: To compare the antiviral activity of abacavir (ABC) with stable background therapy (SBG) and SBG alone in antiretroviral therapy-experienced subjects as demonstrated by the proportion of subjects with plasma HIV-1 RNA < or = 400 copies/ml, plasma HIV-1 RNA and CD4 cell count profiles, and safety and tolerance of the two regimens over 16 weeks. DESIGN: One-hundred and eighty-five HIV-1 infected adults, with CD4 cell counts > or = 100 x 10(6)/l and plasma HIV-1 RNA of 400-50,000 copies/ml and who had received SBG therapy for at least 12 weeks, were randomized to receive ABC (300 mg twice daily) or placebo in a double blind, multi-centre study. METHODS: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 cell counts. Genotypic and phenotypic resistance was determined at baseline and week 16. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. RESULTS: At week 16 significantly more subjects receiving ABC + SBG had plasma HIV-1 RNA < or = 400 copies/ml (36/92, 39%) than subjects receiving SBG alone (7/93, 8%; P < 0.001). A similar response was observed in both the lamivudine naive and lamivudine-experienced subjects. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a > or = 1.0 log10 copies/ml reduction in plasma HIV-1 RNA or had a value of < or = 400 copies/ml by week 16. CONCLUSIONS: ABC was generally well tolerated and exerted significant antiviral effect when added to combination antiretroviral therapy over 16 weeks.

Adolescent↗

[Water births and the exposure to HIV].

The risk of a work related HIV-exposure or infection to midwives, or other HCW, in attending waterbirths of (possible unrecognized) HIV-positive women is unknown. Our goal was the quantification of the loss of blood of the childbearing woman after a waterbirth into the waterpool, in taking pool-water-samples of 14 different waterbirths and measuring the hemoglobin in the plasma, and then correlating the mean found loss of blood and the mean quantity of poolwater with a hypothetical HIV-RNA viral load of 10(3)-10(6) copies per milliliters (ml) blood. All attended waterbirths were evaluated with a questionnaire regarding: parity of the child-bearing woman; serostatus for HIV/Hepatitis-B (HBV) and Hepatitis-C (HCV); length of the birth-process; perineum-rupture or not, etc. Questions concerning the HCW in implementing universal precautions like: type of gloves and garment used, if at all; duration of water contact with the hands; existing skin lesions; HBV-vaccination-status; years of professional experiences as a midwife; how many waterbirths attended etc. were also evaluated. The mean calculated loss of blood into the pool was 300 ml, the mean pool-water content 633 liters. With a hypothetical (maximal) HIV-RNA viral load of 10(6) copies per ml blood, we calculated a mean HIV-RNA viral load of 476 copies per ml pool-water. We also found 37% of the interviewed midwives (n = 14) to have skin lesions on hands or fingers; 1 received splashes into her (unprotected) face and 1 was not immunized against HBV. The mean loss of blood of 300 ml into the pool is a relevant amount. The skin-contact of the HCW with the potentially contaminated water is the norm, because of the failure of the type of used gloves. Because of the diluting effect of the poolwater, we estimate the potential risk for a HIV-exposure to intact skin as minimal and, therefore a potential HIV-infection as "low level" and to be unlikely. However, a risk for nosocomial HBV-infection is significantly higher. We recommend wearing long-sleeved gloves, waterproofed garment, and HBV-vaccination to all HCW.

Baths↗

Delavirdine in combination with zidovudine in treatment of human immunodeficiency virus type 1-infected patients: evaluation of efficacy and emergence of viral resistance in a randomized, comparative phase III trial. The M/3331/0013B Study Group.

We compared the activity of delavirdine (DLV) plus zidovudine (AZT) (n = 300) with that of AZT (n = 297) against human immunodeficiency virus type 1 in a randomized, double-blind, placebo-controlled trial. DLV exerted a transient antiviral effect, and mutations for resistance to DLV were found in more than 90% of subjects at week 12. The K103N mutation, which confers nonnucleoside reverse transcriptase inhibitor cross-resistance, was found in 85% of the patients.

Anti-HIV Agents↗

Incidence and predictors of virologic failure of antiretroviral triple-drug therapy in a community-based cohort.

Highly active antiretroviral therapy fails to reach its recommended goal of sustained suppression of viral replication in a substantial proportion of patients. We analyzed incidence and predictors of virologic failure of the first regimen of a triple-drug combination therapy, including a protease inhibitor and two nucleoside analog reverse transcriptase inhibitors (NRTIs), in 274 HIV-infected patients. Long-term virologic response to combination therapy including salvage regimens was assessed 2.5 years after treatment initiation. During an initial observation period of up to 1.8 years (median, 0.8 years) 152 patients (55%) experienced sustained suppression of HIV-1 RNA to <500 copies/ml. Failure to reduce viral load to <500 copies/ml within 6 months (initial failure) was observed in 51 patients (19%). Independent risk factors for initial failure included higher baseline viral load; addition of a protease inhibitor to an unchanged NRTI regimen; use of saquinavir hard-gel capsules; and longer duration of prior NRTI treatment. Within a median of 7 months viral load rebound above 500 copies/ml occurred in 71 of 223 patients (32%) whose viral load had initially decreased below this threshold. In proportional hazard analysis none of the potential risk factors was significantly associated with viral load rebound. However, in 40 patients (56%) with viral load rebound, incomplete adherence to therapy or treatment interruptions preceded the rebound. Virologic outcome after 2.5 years correlated with initial response to the first regimen: viral load was <500 copies/ml in 88, 55, and 21% of patients with sustained suppression, viral load rebound, and initial failure, respectively.

Adult↗

Efficacy and safety of combination therapy with delavirdine and zidovudine: a European/Australian phase II trial.

The objective of the study was to investigate the safety and antiviral effect of three delavirdine dose regimens or placebo in combination with zidovudine in patients who were already taking zidovudine. Eighty-nine symptomatic HIV-1 seropositive individuals with CD4 cell counts between 50 and 350 cells/microl were included in this trial The influence of combination therapy on viral susceptibility to both zidovudine and delavirdine was investigated. Death or the occurrence, or re-occurrence of an AIDS-defining illness was considered as a clinical endpoint. The addition of delavirdine to the antiretroviral treatment regimen resulted in a significant, but transient, reduction in virus load, as determined by quantitative RNA measurements. CD4+ cell count did not change significantly. Susceptibility to zidovudine remained unchanged after 12 weeks of combination therapy, while 70% of the patients demonstrated a substantial decrease (> 10-fold) in sensitivity to delavirdine. Two patients suffered from an AIDS-defining disease during the study. No deaths occurred. Generally, the drug appeared to be safe. Skin rash was the most frequently observed adverse event (52%). In most patients the rash either resolved spontaneously or was treated successfully with a short course of antihistamines. The definite place of the compound in the management of HIV disease, in particular when given in combination with other antiretroviral agents, remains to be further explored.

Anti-HIV Agents↗

Effects of iron supplementation on total body hemoglobin during endurance training at moderate altitude.

The aim of the study was to test the hypothesis that iron supplementation in well-trained non-iron-depleted athletes leads to an enhanced increase of total body hemoglobin (TBH) during training at moderate altitude. Therefore, the members of the national German boxing team were randomly assigned to treatment with ferrous-glycine-sulfate (1335 mg equivalent to 200mg elementary iron daily) or with placebo during 18 days of endurance training at moderate altitude (1800 m). Before and after altitude training TBH was determined by CO-rebreathing, measures of exercise performance were determined with an incremental treadmill test. Before, during and after the stay at moderate altitude erythropoietin (Epo), reticulocytes (Retics) and parameters of iron metabolism were measured in venous blood. The results show that TBH did not change significantly in the placebo-group and even slightly, but significantly decreased in the iron-treated group. However, there was a significant increase of Epo and Retics in both groups during training at moderate altitude whereas parameters of iron metabolism remained unchanged. VO2max did not change either. To test whether a training-induced hemolysis, an increased urinary iron excretion or gastrointestinal blood loss could explain the unexpected drop of TBH we tested most of the boxers again during a similar training camp at low altitude (400-1000 m) to obtain measures of hemolysis, urinary iron excretion and occult hemoglobin loss with the stools. Although there were signs of an increased erythrocyte turnover no iron loss could be observed. We conclude that 18 days of endurance training at an altitude of 1800 m does not lead to an increase of TBH in non-iron-depleted athletes with and without iron supplementation.

Adult↗

The occurrence of percutaneous injuries to health care workers: a cross sectional survey in seven Swiss hospitals.

OBJECTIVES: In 1995, a cross sectional survey was conducted in 7 Swiss hospitals to estimate the incidence of percutaneous injuries among nurses, surgeons, anesthetists and domestic personnel, and to describe the circumstances of these injuries and the reporting process within the hospital. METHODS: An anonymous questionnaire was distributed and filled out on-site in the case of nursing staff and domestic personnel, and was sent by post to physicians (anesthetists and surgeons). Participants were asked to report in detail on percutaneous injuries of the last workday and the last working month (nurses and physicians), and of the last month and the last year for domestic personnel. The overall response rate was 72%, representing a total of 3116 health care workers. RESULTS: The annual incidence rates of percutaneous injury with material contaminated with blood or other biological fluids were calculated by type of worker for the two available units of time. For nurses, the incidence was 0.49 and 2.23, for surgeons 4.28 and 11.05, for anesthetists 2.11 and 3.14, and for domestic personnel 0.11 and 0.17 respectively. Most of the injuries occurred in a "normal" situation (no emergency, no stress, no fatigue) and were described as avoidable. Compliance with universal precautions was not optimal and declaration rates within the hospital rather low (nurses 39.7%, physicians 3.4%, domestic personnel 87.9%). CONCLUSION: Percutaneous injuries with blood-contaminated material are frequent in health care workers, and are not always adequately assessed because of under-reporting of accidents within the hospital. This may result in underestimation of current occupational exposure of health care workers to HIV and other blood-borne viruses.

Accidents, Occupational↗

Coagulation and thrombomodulin in response to exercise of different type and duration.

PURPOSE: The present study was conducted to evaluate the role of the duration of exercise and the impact of the exercise type for exercise-induced activation of coagulation. METHODS: Eleven male triathletes were subjected to stepwise maximal (17 min) and 1-h maximal exercise in swimming, cycling, and running. Changes of hemostatic variable sand of plasma thrombomodulin, a marker of endothelial cell activation, were monitored. RESULTS: Irrespective of the type of exercise, alterations in markers of thrombin (prothrombin fragment 1 + 2, thrombin-antithrombin III complexes) and fibrin formation (fibrinopeptide A) were more pronounced after 1-h exercise than after stepwise maximal exercise. Hemostatic parameters rose to the highest levels after running resulting in substantial fibrin formation as indicated by fibrinopeptide A increasing from 1.33 ng.mL-1 to 2.25 ng.mL (P < 0.05) after 1-h exercise testing. Significant changes of plasma thrombomodulin were detected exclusively after running with increases from 38.2 ng.mL-1 to 44.2 ng.mL-1 (1 h, P < 0.01). CONCLUSIONS: The data demonstrated that prolonged exercise is necessary for exercise-induced activation of coagulation resulting in thrombin and fibrin formation and suggested that endothelial cell activation possibly due to mechanical factors associated with running might play a role.

Adult↗

[Post-exposure HIV prevention within and outside the hospital].

There is a low risk of infection with the human immunodeficiency virus (HIV) for HCW through exposure in the work place. The mean risk of infection with HIV after a percutaneous exposure is 0.3%. This risk can be considerably higher depending on various factors: for example, a deep percutaneous injury or the source patient being in an end stage of HIV infection. Despite compliance with adequate precautions, it is not always possible for HCW to avoid injuries. This fact has made intervention desirable after such exposure. Zidovudine (AZT) was available as the first effective drug for treatment of HIV infection. Also, animal experiments have shown efficacy in prophylactic use of zidovudine. Therefore, since the beginning of the 90's, there has been an increased use of postexposure prophylaxis with zidovudine for exposed HCW, and during this period of use more evidence has come up to show the efficacy of PEP. In fact, a large retrospective case-control study showed a 81% reduction of HIV transmission to exposed HCW in the zidovudine treated group after percutaneous exposure. Based upon this impressive evidence and other data which indicate the efficacy of PEP, postexposure prophylaxis has become a standard procedure in the health care setting after a significant exposure to HIV. A combination of three antiretroviral drugs, usually including a protease inhibitor, is used today. Based on our current pathogenetic understanding, PEP should be started as soon as possible after exposure to HIV. There are effective tools for preventing HIV transmission in the general population. However, these tools do not provide universal protection: rupture of condoms, needle sharing and unprotected intercourse with a HIV infected person are situations at risk of HIV transmission. In spite of a different mode of exposure when compared to the health care setting, PEP in timely application is believed to be efficacious. To date there is no controlled data to support PEP in such situations; however, PEP with a combination of antiretroviral drugs after anal, oral (with ejaculation) or vaginal intercourse and needle sharing with a HIV-positive partner is recommended for a minimum of two weeks. There are reservations in recommending PEP after unprotected sexual intercourse with a partner of unknown serostatus.

Anti-HIV Agents↗

Homelessness, severe mental illness, and the institutional circuit.

OBJECTIVE: Research on homelessness among persons with severe mental illness tends to focus on aspects of demand, such as risk factors or structural and economic forces. The authors address the complementary role of supply factors, arguing that "solutions" to residential instability-typically, a series of institutional placements alternating with shelter stays-effectively perpetuate homelessness among some persons with severe mental illness. METHODS: Thirty-six consecutive applicants for shelter in Westchester County, New York, in the first half of 1995 who were judged to be severely mentally ill by intake workers were interviewed using a modified life chart format. Detailed narrative histories were constructed and reviewed with the subjects. RESULTS: Twenty of the 36 subjects had spent a mean of 59 percent of the last five years in institutions and shelters. Analysis of the residential histories of the 36 subjects revealed that shelters functioned in four distinctive ways in their lives: as part of a more extended institutional circuit, as a temporary source of transitional housing, as a surrogate for exhausted support from kin, and as a haphazard resource in essentially nomadic lives. The first pattern dominated in this group. CONCLUSIONS: Shelters and other custodial institutions have acquired hybrid functions that effectively substitute for more stable and appropriate housing for some persons with severe mental illness.

Adolescent↗