Search PubMed⌕ Search

Biomedical subjects

P Kern

Publications and source records attributed to P Kern.

At least 37 records · Page 2Linked to original sources

Reorganization of perinatal care in Greenland.

INTRODUCTION: September 2000 the planning of a major reform of health services was launched aimed at improving perinatal care and decreasing perinatal mortality and morbidity. The activities became effective from January 2002. METHODS: A new organization plan was developed, a special medical record was designed for perinatal care and training programs for health workers in perinatal care were instituted, including basic ultrasound scan for gestational age. Professional guidelines for perinatal care were distributed countrywide, stipulating that at risk pregnancies should be referred for delivery to Queen Ingrid's Hospital, as well as offering treatment suggestions for various complications. RESULTS: There was a marked improvement in the referral rate for at risk pregnancies and consequently a sharp rise in the share of at risk patients in Queen Ingrid's Hospital, calling for extra resources to be allocated. However, the rate for instrumental deliveries remained low at the special unit at the same time as the rural health care centres were relieved of the burden of high-risk deliveries. DISCUSSION: Transferring women for delivery, in many cases leaving their families for a substantial amount of time, undoubtedly has psychosocial implications. Will the impact of the programme on perinatal mortality and morbidity make up for these costs? Will we be able to reduce the rate of instrumental deliveries in the rural health care centres as well as the number of acute--and very costly--evacuations of patients by chartered aircraft? The questions are many--we hope to provide some answers.

Female↗

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Age Factors↗

Polymorphisms of the TAP1 and TAP2 genes in human alveolar echinococcosis.

We postulated that TAP genes may influence the susceptibility of some individuals to Echinococcus multilocularis infection. Six coding region variants (codons 333 and 637 in TAP1, and 379, 565, 651 and 665 in TAP2) were typed in 94 patients and 100 controls. Thr/Thr homozygosity at TAP2/665 was more prevalent in patients than in controls [64% vs. 45%, respectively; odds ratio (OR) = 2.1 (95% confidence interval (CI) 1.1; 2.7)] and Thr/Ala heterozygozity was less prevalent (32% vs. 50%, respectively) (P = 0.014). Of the 38 patients with progressive lesions, 76% were Thr/Thr, as compared with 55% of patients without progressive lesions and 45% of controls (P = 0.058 and 0.02, respectively), independent of HLA status. To determine whether this association is functionally relevant, functional analyses and/or confirmation in distinct populations of patients with alveolar echinococcosis would be required.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Pro-inflammatory (IL-1beta, IL-18) cytokines and IL-8 chemokine release by PBMC in response to Echinococcus multilocularis metacestode vesicles.

In humans infected with Echinococcus multilocularis, larval metacestodes will develop, proliferate and progressively infiltrate the surrounding host tissues by exogenous budding of parasitic microvesicles or cell lines which detach from the original tumour and thus become transported through blood or lymph vessels into other organs. Cellular effector mechanisms constitute the most effective means to restrict parasite persistence and proliferation, and here we demonstrate that E. multilocularis vesicle antigens will induce pro-inflammatory, regulatory and chemokine release by PBMC from patients. The pro-inflammatory cytokines IL-1beta and IL-18 were reduced in echinococcosis patients, regulatory IL-10 was similar, but parasite vesicle-induced IL-8 was dominant and clearly elevated in patients. Such selective and opposite dynamics of inflammatory cytokines and chemokine release may prevent overwhelming and pathogenic inflammation, and constitute an appropriate response for attraction of effector cells into the periparasitic tissues with the capacity to limit E. multilocularis metacestode proliferation and dissemination.

Animals↗

Imported Falciparum malaria in Europe: sentinel surveillance data from the European network on surveillance of imported infectious diseases.

Malaria continues to have a high morbidity rate associated among European travelers. Thorough recording of epidemiological and clinical aspects of imported malaria has been helpful in the detection of new outbreaks and areas of developing drug resistance. Sentinel surveillance of data collected prospectively since 1999 has begun within TropNetEurop, a European network focusing on imported infectious diseases. TropNetEurop appears to cover approximately 10% of all patients with malaria seen in Europe. Reports of 1659 immigrants and European patients with Plasmodium falciparum malaria were analyzed for epidemiological information and data on clinical features. Regional data were quite diverse, reflecting local patterns of immigration and international travel. By far, the most infections were imported from West Africa. Europeans had more clinical complications; consequently, all deaths occurred in this group. Compared with European standards, the mortality rate was low (0.6% in Europeans). Data from TropNetEurop member sites can contribute to our understanding of the epidemiological and clinical findings regarding imported falciparum malaria.

Adolescent↗

A new accelerated vaccination schedule for rapid protection against hepatitis A and B.

BACKGROUND: Increasing travel stresses the requirement for rapid protection against infections such as hepatitis A and B. METHODS: This randomised, multicentre study investigated an accelerated vaccination schedule using a combined hepatitis A and B vaccine (Twinrix, Smithkline Beecham Biologicals) compared with simultaneous administration of the two corresponding monovalent vaccines. The combined vaccine was administered on days 0, 7 and 21, whereas the comparison group received hepatitis A vaccine on day 0 and hepatitis B vaccine on days 0, 7 and 21. All subjects received booster vaccination at month 12. RESULTS: At month 1, 100% of subjects in the combined group and 99% of the controls were seropositive for anti-HAV antibodies. The corresponding seroprotection rates for anti-HBs antibodies were 82.0 and 83.9%, respectively. Examination of the 95% confidence intervals (CIs) for the treatment differences showed the two vaccines to be equivalent in terms of immunogenicity 1 week after the initial vaccination course. Just prior to the booster, the seropositivity rate for anti-HAV was 96.2% in the combined group and 95% in the control group. For anti-HBs, this was 94 and 91.6%, respectively. All subjects were seropositive for anti-HAV and seroprotected against hepatitis B at month 13. The anti-HAV GMCs were 9571mIU/ml with the combined vaccine and 5206mIU/ml in control subjects. The anti-HBs titre was 26002 and 29,196mIU/ml, respectively. Both groups had a similar reactogenicity profile. CONCLUSIONS: The accelerated schedule of the combined vaccine provides a good immune response against hepatitis A and B antigens and is suitable for last minute immunisation.

Adolescent↗

Glycopeptide use at four university hospitals in southern Germany.

BACKGROUND: Excessive use of glycopeptide antibiotics may enhance the risk of glycopeptide resistance among enterococci and staphylococi, but there is little data on the use of these antibiotics in German hospitals. METHODS: Hospital pharmacy records for the years 1992 to 1994 were evaluated. The number of defined daily doses (DDD) per 100 patient days was calculated to compare glycopeptide use between four state university hospitals. At one of the hospitals with comparatively low glycopeptide usage but an active antimicrobial management program, data were prospectively evaluated for 1995 to 2000 to assess the variation of glycopeptide use over time. RESULTS: The 3-year averages in glycopeptide use for the four hospitals ranged between 1.03 and 3.14 DDD/100 patient days. In all four hospitals, glycopeptide use was higher in the medical service (range, 1.59-7.26) than in the surgical service (range, 0.66-4.39). Active antimicrobial management in one of the hospitals was associated with containment of glycopeptide consumption in the medical and surgical service at < 1.5 DDD/100 patient days in the last 3 years. CONCLUSION: Glycopeptide use differs considerably at tertiary care hospitals in southern Germany, but use of < 1.5 DDD/100 patient days in both surgical as well as medical tertiary care hospital departments appears achievable.

Anti-Bacterial Agents↗

Digital arterial occlusive disease and parvovirus B19 infection.

We report a case of a 37-year-old white woman, who presented with digital arterial occlusions associated with parvovirus B19 infection. Two other member of the family presented acute febrile illness, polyarthralgia (husband), and erythema infectiosum (son) during the same month. This new report gives weight to the concept that acute human parvovirus infection could become part of the differential diagnosis of acute digital occlusive arteriopathy.

Adult↗

Anti-inflammatory effect of low-dose X-irradiation and the involvement of a TGF-beta1-induced down-regulation of leukocyte/endothelial cell adhesion.

PURPOSE: Low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect, but the underlying radiobiological and immunological mechanisms remain elusive. In recent studies, we observed a reduced adhesion of peripheral blood mononuclear cells (PBMC) to endothelial cells (EC) after LD-RT (0.3-0.7 Gy). This shows that this treatment affects the initial steps of the inflammatory response. To explore the role of inflammatory mediators in this process, we investigated the expression of Transforming growth factor beta(1) (TGF-beta(1)) and Interleukin 6 (IL-6) after LD-RT. MATERIALS AND METHODS: EC were grown to subconfluence and irradiated with single-dose LD-RT. Twenty-hours after irradiation, EC were treated with IL-1beta for 4 h and then incubated with peripheral blood mononuclear cells (PBMC). Adherent PBMC were counted when using light microscopy. Expression of the cytokines TGF-beta(1) and IL-6 was measured by ELISA, and mRNA levels were analysed by the RNAse-protection assay (RPA). Surface expression of E-selectin was quantified by flow cytometry. RESULTS: A relative minimum of adhesion was observed after LD-RT between 0.3 and 0.7 Gy. This was paralleled by an expression maximum of TGF-beta(1) and IL-6, as shown by protein and mRNA levels, respectively. Neutralization of TGF-beta(1) by monoclonal antibodies, but not of IL-6, increased PBMC adhesion to EC nearly to control levels. In addition, fluorescence activated cell sorter (FACS) analysis of irradiated EC demonstrated a down-regulation of E-selectin in the same dose range. CONCLUSION: Low-dose X-irradiation between 0.3 and 0.7 Gy induced a relative maximum of TGF-beta(1) production by stimulated EC. This results in a down-regulation of leukocyte/PBMC adhesion and may contribute to the anti-inflammatory effect of LD-RT.

Animals↗

Sclerotherapy of varicose leg veins. Technique, indications and complications.

The aim of treatment by sclerotherapy is the fibrous occlusion of varicose veins and the absence of recanalization of an intravascular thrombus. Modern sclerotherapy started at the beginning of the 20(th) century in Europe. Tournay in France, Sigg in Switzerland and Fegan in Ireland developed different schools of practice. Recently ultrasound-guided sclerotherapy has appeared, mainly for the treatment of saphenous trunks and incompetent perforating veins. The precise diagnosis of varicose vein disease and the recognition of the most proximal point of reflux dictates the choice of optimal treatment and reduces the risk of recurrence and complications such as pigmentation or matting. The risk of complications depends on the agent used, its concentration and the quantity injected. Sclerotherapy is the treatment of choice for spider veins and is indicated in the treatment of reticular and short saphenous varicose veins. There is currently no consensus on the place of sclerotherapy in the treatment of the long saphenous vein and incompetent perforating veins. Neither is there a consensus on the type and duration of the compression to be applied after sclerotherapy. Sclerotherapy is safe and in the hands of experts the risk and secondary side effects of the treatment are minimal.

Humans↗

5,6-carboxyfluorescein diacetate succinimidyl ester-labeled apoptotic and necrotic as well as detergent-treated cells can be traced in composite cell samples.

Detection of dividing cells by staining with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) has been widely used in flow-cytometric protocols. We analyzed the fate of CFSE in cells undergoing apoptotic or necrotic cell death, respectively. Peripheral blood mononuclear cells (PBMC) were stained with CFSE. Apoptosis was induced by UVB irradiation and necrosis by incubation at 56 degrees C for 30 min. In some experiments, labeled cells were permeabilized with detergent and CFSE association with nuclei was assessed. We observed that (i) CFSE remains stably detectable in apoptotic and necrotic cells; (ii) CFSE remains stably associated with the nuclei of cells even after their lysis by detergent; (iii) CFSE labeling does not interfere with the induction of cell death; and (iv) CFSE is not transferred from stained dying cells to unstained neighboring counterparts. We conclude that, in addition to tracking viable cells, CFSE can be used to trace dying cells in composite samples. We demonstrated that CFSE labeling does not influence the induction and the execution of apoptosis or necrosis.

Apoptosis↗

A new ImmunoCAP assay for detection of Echinococcus multilocularis-specific IgE.

In alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E.m.), increased levels of total and parasite-specific IgE are frequently found. These may not only have diagnostic but are also supposed to have prognostic value in the follow-up of AE patients. However, there is no commercial test available for quantification of E. m.-specific IgE (sIgE). The only commercial test available is based on E. granulosus (g.) hydatid antigen, which is not optimal for detection of E. m.-specific IgE. Therefore, a new ImmunoCAP with covalently bound crude antigen of E. m. was developed in cooperation with Pharmacia Research Forum for the analysis of E. m. sIgE. The E. m. ImmunoCAP was evaluated in 53 AE patients with different clinical disease progression and 20 healthy controls. Our data showed a higher sensitivity for sIgE determination with E. m. ImmunoCAP compared to the E. g. ImmunoCAP (73.6% vs 61.5%) and a positive correlation between total IgE and sIgE. Furthermore, there was a significant correlation between sIgE in both tests. In conclusion, the new E. m.-specific ImmunoCAP test proved to be a valuable tool for determination of sIgE. It may provide the basis for the development of further E. multilocularis-specific IgE immunotests which are essential for evaluation of sIgE during clinical course of AE.

Adult↗

[Surgical therapy of alveolar echinococcosis and long-term outcome].

INTRODUCTION: The incidence of alveolar echinococcosis (AE) is low, and studies and progress reports with regard to surgical procedures are rare. METHODS: Retrospective analysis of surgical therapy of AE and its long-term results between 1983 and 2000 by evaluating medical records and questionnaires. SETTING: German university hospital within the endemic area. RESULTS: Twenty-five surgical procedures were performed in 19 patients with AE (12x partial resection of the liver, 3 of them with additional extrahepatic resection; 3x just extrahepatic resection, 4x bilidigestive anastomosis, 5x exploratory laparotomy, 1x bypass procedure). Fifteen patients were operated on the first time with that diagnosis, four due to a relapse. Seven surgical procedures were estimated to be curative, whereas 18 were palliative, because the parasitic mass could not be resected in toto. One patient died from persistent systemic sepsis as a consequence of microbial superinvasion of a splenic parasitic mass. Morbidity was 28%. All patients had additional medical treatment and periodic follow-up. Three of seven patients estimated for curative surgery developed a relapse. One of the patients discharged following palliative surgery died 13 years after diagnosis with liver insufficiency. Advances in conservative and interventional treatments have greatly improved the prognosis of the disease. CONCLUSION: Curative surgery for AE is feasible only in a minority of patients, because frequently the disease has already spread widely when diagnosed. The minimum distance between the lesion and the cut surface should be 2 cm. Taking the advances in conservative treatment into consideration, the benefit of palliative surgery is uncertain and today there is no evidence for prolonged survival by palliative surgical procedures. Palliative surgery should therefore be reserved for cases with complications that could not be managed by conservative and interventional treatment.

Adult↗

Loss of collagen type IV in rheumatoid synovia and cytokine effect on the collagen type-IV gene expression in fibroblast-like synoviocytes from rheumatoid arthritis.

Collagen type IV is a structural matrix protein which contributes to the structural organization of the synovia. In order to characterize the distribution of this protein in synovia with chronic synovitis, collagen type IV was detected by immunochemistry in normal synovia and in synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). A decrease of collagen type IV was observed in synovial layers of rheumatoid synovia, which statistically correlated with the grade of inflammation and with the thickness of the synovial layer. In vitro, we found no differences in the gene expression of collagen type IV in cultures of fibroblast-like synoviocytes (FLS) derived from OA and RA using a reverse-transcriptase polymerase chain reaction. Nevertheless, we observed a downregulating effect of tumor necrosis factor-alpha and interleukin (IL)-1beta on the gene expression of collagen type IV only in FLS isolated from patients with RA. The effect of IL-1beta was dose dependent. In summary, we observed an inflammation-associated decrease of collagen type IV in the synovial layer of rheumatoid synovia. Inflammatory cytokines may play a role in regulating the synthesis of collagen type IV in the rheumatoid process in vivo.

Arthritis, Rheumatoid↗

Long-term seropositivity against Echinococcus multilocularis in an epidemiological follow-up study in southwestern Germany (Römerstein).

BACKGROUND: Out of 2,560 participants in an epidemiological survey of alveolar echinococcosis (AE) performed in 1996 in southwestern Germany, 47 participants had tested seropositive in one of two crude antigen screening ELISAs and were inconspicuous on hepatic ultrasound. PATIENTS AND METHODS: Out of these 47 seroreactors, 36 attended a follow-up examination 30 months after the primary examination, including ultrasound and serology with various Echinococcus multilocularis-specific antigens. RESULTS: No lesion suspicious for AE was detected in any participant. Serology showed only minor changes as compared to the earlier results. CONCLUSION: Persistent seropositivity without detectable hepatic lesions could be interpreted as an early sign of sonographically not yet detectable AE, immunity to E. multilocularis or unspecific serological reactivity. For seropositive and clinically inconspicuous inhabitants of areas endemic for AE follow-up examinations at intervals of 2-3 years seem to be adequate.

Adolescent↗

Specific RGTA increases collagen V expression by cultured aortic smooth muscle cells via activation and protection of transforming growth factor-beta1.

Regenerating agents (RGTA) are defined as heparan sulfate mimics, which in vivo stimulate tissue repair. RGTA are obtained by controlled grafting of carboxymethyl and sulfate groups on dextran polymers. RGTA are selected in vitro, on their ability to protect heparin binding growth factors such as TGF-beta1 for example, as well as to alter extracellular matrix biosynthesis. We had reported that RGTA were able to modulate smooth muscle cell (SMC) collagen biosynthesis. Here, we demonstrated that a specific RGTA (RG-1503), altered differentially collagen type expression by post-confluent SMC and that this action involves TGF-beta1. RG-1503 decreased, by 50%, collagen I and III biosynthesis and stimulated specifically, by twofold, collagen V biosynthesis. TGF-beta1 stimulated collagen I and V by 1.5- and threefold, respectively. A synergic action for RGTA in association with TGF-beta1 was observed specifically for collagen V expression (eightfold increase). The stimulation of collagen V biosynthesis by RGTA was abolished by TGF-beta1 neutralizing antibodies. These modulations occurred at protein and mRNA levels. RG-1503 did not alter TGF-beta1 mRNA steady state level or total TGF-beta1 protein content (latent+active forms). However, RG-1503 significantly induced an elevated proportion of active TGF-beta1 form, which could result from the selective protection from proteolytic degradation of TGF-beta1 by RG-1503. These data open a rationale for understanding the stimulation of tissue repair induced by RGTA, and also, a new insight for developing drugs adapted to inhibit excess collagen deposition in smooth muscle cells associated vascular disorder, and in fibrotic diseases.

Animals↗