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Biomedical subjects

C Lehmann

Publications and source records attributed to C Lehmann.

At least 19 recordsLinked to original sources

Rapid improvement of liver function in a patient with HIV and hepatitis B coinfection treated with lamivudine and tenofovir.

Since the introduction of HAART, the clinical importance of hepatitis virus infection and its complications in human immunodeficiency virus (HIV)-infected persons have continuously grown. Coinfection with hepatitis B virus (HBV) and HIV is one of the leading causes of morbidity and mortality. To date, neither the optimal time point for initiation of anti-HBV therapy nor the best therapeutic approach has been clearly defined. We report the case of a 22-year-old African woman infected with HBV- and HIV-1 coinfection and severe impairment of liver function. HAART including lamivudine and tenofovir was started. Three weeks later, the patient achieved not only a restoration of her clinical situation and liver function, but she also demonstrated a complete suppression of both viruses. This impressive clinical course might be explained by the application of antiviral combination therapy including lamivudine and tenofovir. Tenofovir has shown a higher activity against HBV than other drugs. In addition, combination therapy for chronic hepatitis B might be more effective than monotherapy. Future studies need to clarify the value of combination treatment for patients with chronic hepatitis B.

Adenine↗

[Solitary fibrous tumor of the liver].

Solitary fibrous tumor (SFT) is commonly found on serosal surfaces, and is rarely localized in the liver. There are benign and malignant variants of hepatic SFT. We report a new case of benign SFT. Our patient, a 63-year old woman, who has been followed for 5 years for an asymptomatic liver mass, was admitted for abdominal pain. Ultrasonography (US), CT, MR Imaging and angiography showed the liver mass with typical imaging features, situated in the right hepatic lobe with blood supply from the hepatic artery. Histopathological examination demonstrated a highly vascularized tumor, composed of short spindle cells alternating with hypocellular collagenous regions, with a hemangiopericytoma-like vascular pattern. The immunohistochemical staining was positive for CD 34. Tumor resection was performed. Follow-up 8 years after the resection showed no tumor recurrence or metastasis, thus confirming the initial diagnosis of benign SFT.

Female↗

Serum osmolality and outcome in intensive care unit patients.

BACKGROUND: The aim of the present study was to compare 16 routine clinical and laboratory parameters, acute physiologic and chronic health evaluation (APACHE) and sequential organ failure assessment (SOFA) score for their value in predicting mortality during hospital stay in patients admitted to a general intensive care unit (ICU). METHODS: A retrospective observational clinical study was carried out in a 15-bed ICU in a university hospital. Nine hundred and thirty-three consecutive patients with ICU stay > 24 h (36.2% surgical, 29.1% medical and 34.7% trauma) were observed. Blood sampling, patient surveillance and data collection were performed. The primary outcome was mortality in the hospital. We used receiver operating characteristic (ROC) analyses and logistic regression to compare the 16 relevant parameters, APACHE II and SOFA scores. RESULTS: Two hundred and thirty-three out of the 933 patients died (mortality 25.0%). One laboratory parameter, serum osmolality [area under the curve (AUC) 0.732] had a predictive value for mortality which lay between that of APACHE II (AUC 0.784) and SOFA (AUC 0.720) scores. When outcome prediction was restricted to long-term patients (ICU stay > 5 days), serum osmolality (AUC 0.711) performed better than either of the standard scores (APACHE AUC 0.655, SOFA AUC 0.636). Using logistic regression analysis, the association of clinical parameters, age and diagnosis group with mortality was determined. CONCLUSION: Elevated serum osmolality at ICU admission is associated with an increased mortality risk in critically ill patients. Serum osmolality is cheaper and more rapid to determine than the scoring systems. However, further studies are needed to evaluate the predictive value of serum osmolality in different patient populations.

APACHE↗

AIDS-related progressive multifocal leukoencephalopathy in the era of HAART: report of two cases and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system. It is caused by the JC virus (JCV), a human polyomavirus replicating in human glial cells. PML is the result of the reactivation of latent JCV infection that usually occurs in the setting of cellular immunodeficiencies such as HIV-1 infection. Epidemiologic data suggest that the impact of highly active antiretroviral therapy (HAART) on the incidence of PML is less profound than seen with other opportunistic infections. Given the lack of an effective and specific therapy for PML, HAART remains the only therapeutic option in patients with PML. However, a significant number of cases appear unresponsive to antiretroviral therapy. Moreover, there is growing data on unexpected inflammatory cases of PML after initiation of HAART. Thus, PML will remain a relevant cause of morbidity and mortality in HIV- 1-infected patients. Here we report two cases of PML, along with a concise review of the literature on this important disease.

AIDS-Related Opportunistic Infections↗

Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphoma.

Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

[The Bremen mortality index].

The Bremen Mortality Index (BreMI) is an electronic data file providing all information found on death certificates of former Bremen citizens who have died after December 31, 1997. BreMI follows the example of the National Death Index (NDI) in the USA, which has provided information on the vital status of US citizens and cause of death since 1979. The Bremen Mortality Index has been linked successfully to the Bremen Cancer Registry and has improved the efficiency of following up cancer patients. A substantial number of death certificates may be checked automatically for the presence of a cancer diagnosis or any other diagnosis. The Bremen Mortality Index may be used as a primary source for data on particular causes of death. It will be used for developing a German thesaurus for automated coding of medical entities and for determining causes of death.

Cause of Death↗

Measurement of spin-correlation parameters ANN, ASS, and ASL at 2.1 GeV in proton-proton elastic scattering.

At the Cooler Synchrotron COSY/Jülich spin-correlation parameters in elastic proton-proton (pp) scattering have been measured with a 2.11 GeV polarized proton beam and a polarized hydrogen atomic beam target. We report results for A(NN), A(SS), and A(SL) for c.m. scattering angles between 30 degrees and 90 degrees. Our data on A(SS)--the first measurement of this observable above 800 MeV--clearly disagrees with predictions of available pp scattering phase-shift solutions while A(NN) and A(SL) are reproduced reasonably well. We show that in the direct reconstruction of the scattering amplitudes from the body of available pp elastic scattering data at 2.1 GeV the number of possible solutions is considerably reduced.

Journal Article↗

Fatal outcome of lung transplantation in cystic fibrosis patients due to small-colony variants of the Burkholderia cepacia complex.

The aim of this study was to investigate the possible role of small-colony variant morphotypes of Burkholderia cepacia-like organisms in infectious complications in cystic fibrosis patients following lung transplantation. Respiratory tract specimens from 470 cystic fibrosis patients were screened over a 22-month period for Burkholderia cepacia-like organisms. Nineteen patients were positive for these organisms, eight of whom harboured small-colony-variant morphotypes. Three patients underwent bilateral lung transplantation during the study, two of whom harboured small-colony variants in addition to clonally identical wildtypes of Burkholderia multivorans and Burkholderia cepacia genomovar III prior to lung transplantation. Both patients developed fatal systemic infections post transplantation due to small-colony variants. In vitro testing revealed that small-colony variants exhibited increased serum resistance in comparison to wildtypes. The results of this study indicate that diagnostic efforts should be undertaken to carefully identify small-colony variants of Burkholderia cepacia complex, since they might be an indicator of poor post-transplantation outcome in patients with cystic fibrosis.

Adolescent↗

[The effect of dopexamine and iloprost on plasma disappearance rate of indocyanine green in patients in septic shock].

OBJECTIVES: To evaluate the effect of dopexamine and iloprost on the plasma disappearance rate (PDR) of indocyanine green (ICG) in patients in septic shock in a prospective clinical trial. METHODS: In 40 consecutive patients in septic shock, a femoral arterial fiberoptic catheter (COLD system) and a gastrotonometric probe were placed. Patients received either dopexamine infusion (0.5 microgram/kg body weight/min) or iloprost (1 ng/kg body weight/min) for 24 h i.v. PDR, intramucosal pH of stomach wall (pHi), cardiac index (HI) and intrathoracic blood volume (ITBV) were determined before, 1, 6, and 24 h after dopexamine or iloprost infusion and 1 h after end of infusion. RESULTS: PDR was significantly increased 24 h after starting dopexamine infusion from 12.2 +/- 1.8%/min to 17.8 +/- 2.2%/min (+45.9%) and 1 h after the end of infusion PDR decreased to baseline values. PDR increased to 16.4 +/- 2.1%/min, 1 h after starting iloprost infusion and increased to a maximum value of 18.6 +/- 2.2%/min (+33.8%, p < 0.05) 24 h after start of infusion compared to the baseline (13.9 +/- 1.7%/min). After the end of infusion PDR decreased to baseline values. Baseline values of pHi were in normal ranges in all groups and there was no change during the observation period. Cardiac index and ITBV were stable during the study. Dosage of norepinephrine could be reduced by dopexamine infusion. CONCLUSIONS: Dopexamine and iloprost have a positive effect on the plasma disappearance rate of ICG and therefore have a protective effect on splanchnic perfusion and liver function, respectively.

Adult↗

[Clinical results with the "open lung concept"].

Elements of the "open lung concept" are being increasingly included in clinical ventilatory strategies. Despite encouraging experimental investigations to date, relatively few studies exist that examine the clinical application of the complete concept. The aim of this study was to prove that with effective recruitment maneuvers and titrated PEEP levels this concept is applicable in clinical settings. We sought to determine if it was possible to achieve a significant improvement in oxygenation and also to examine what side-effects resulted. Twenty consecutive patients who had had an acute lung injury (ALI) for less than 72 hours, with an oxygenation index (P/F-Ratio = quotient from arterial partial pressure of oxygen [PaO2] and the inspiratory fraction of oxygen [FiO2]) of less than 200 torr, and with a PEEP > or = 10 cmH2O were treated using a recruitment manoeuvre (RM). A PEEP was titrated to keep the lung open, and the patients were kept under pressure-controlled ventilation. The P/F-Ratio increased while using a recruitment pressure of 66 +/- 13 cmH2O from 137 +/- 41 to 381 +/- 150 torr (p < 0.001). The titrated PEEP which kept the lung open after recruitment was 17 +/- 3 cmH2O. One patient developed a pneumothorax. The dose of norepinephrine was increased in ten patients from 0.24 +/- 0.12 to 0.31 +/- 0.1 microgram/kg/min. Due to elevated liver enzymes within the first 48 hours, titrated PEEP had to be decreased in three patients. The clinical application of the "open lung concept" demonstrated a quick and effective improvement in oxygenation in many patients. Side-effects in some patients limited the use of high PEEP levels.

Adult↗

Retrieval of long and short lists from long term memory: a functional magnetic resonance imaging study with human subjects.

Previous studies have shown that reaction time in an item-recognition task with both short and long lists is a quadratic function of list length. This suggests that either different memory retrieval processes are implied for short and long lists or an adaptive process is involved. An event-related functional magnetic resonance imaging study with nine subjects and list lengths varying between 3 and 18 words was conducted to identify the underlying neuronal structures of retrieval from long and short lists. For the retrieval and processing of word-lists a single fronto-parietal network, including premotor, left prefrontal, left precuneal and left parietal regions, was activated. With increasing list length, no additional regions became involved in retrieving information from long-term memory, suggesting that not necessarily different, but highly adaptive retrieval processes are involved.

Adult↗

Lymphocytes in the bronchoalveolar space reenter the lung tissue by means of the alveolar epithelium, migrate to regional lymph nodes, and subsequently rejoin the systemic immune system.

Lymphocytes in the bronchoalveolar space are routinely obtained and examined in lung diseases such as asthma or sarcoidosis. In a pig model, labeled lymphocytes were found in regional lymph nodes after intrabronchial instillation, indicating that reentry of lymphocytes from the bronchoalveolar space into the body is possible. In the present study, the route and kinetics of the reentry of bronchoalveolar lymphocytes were investigated in a congenic rat model using immunohistochemistry on cryostat and semithin sections and confocal laser scanning microscopy. As early as 15 min after intratracheal instillation lymphocytes were found to leave the bronchoalveolar space by transmigration through alveolar but not bronchial epithelium and were observed in interstitial alveolar tissue. At 6 hr after intratracheal instillation, T and B lymphocytes appeared in the draining lymph nodes of the lung with an increase after 24 and 48 hr. The kinetic pattern clearly differed in nondraining lymph nodes and other organs. After 6 hr, only single cells were found in nondraining lymph nodes, spleen, and blood with a slight increase after 24 hr, and only occasionally were single cells seen in the liver, thymus, or Peyer's patches 24 and 48 hr after instillation. In conclusion, T and B lymphocytes can leave the alveolar space by reentry into the lung tissue through alveolar epithelium. They reach regional lymph nodes by means of lymphatic vessels and are then distributed all over the body to rejoin the systemic immune system. Coming into contact with environmental antigens, these lymphocytes could perform an important function in the lung immune system and might be a target for inhalative therapy.

Animals↗

Crystal structure of a synthetic cyclodecapeptide for template-assembled synthetic protein design.

The structural prototype of a new generation of regioselectively addressable functionalized templates (RAFTs) for use in protein de novo design has been synthesized and crystallized. The structure of the aromatically substituted cyclodecapeptide was determined by X-ray diffraction; it consists of an antiparallel beta sheet spanned by heterochirally induced type IIprime prime or minute beta turns, similar to that observed in gramicidin S. The three-dimensional structure of the artificial template was also examined by an NMR spectroscopic analysis in solution and shown to be compatible with a beta-sheet plane suitable for accommodating secondary functional peptide fragments for the synthesis of template-assembled synthetic proteins (TASPs).

Crystallization↗

Intraoperative blood losses and transfusion requirements during adult liver transplantation remain difficult to predict.

PURPOSE: To identify preoperative factors associated with high blood losses during liver transplantation for chronic end-stage liver disease. METHODS: Four hundred and ten consecutive patients were included in this retrospective study. Blood losses were calculated, based on transfusion requirements. The population was divided into two groups: the upper quartile was defined as the high blood loss (HBL) group and the lower three quartiles as the low blood loss group. Fourteen preoperative variables were collected. Qualitative variables consisted of the type of hepatopathy, Child-Pugh's classification, sex, the surgical team's experience, previous abdominal surgery and portal hypertension. Quantitative variables were age, hemoglobin concentration Hb, platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen concentration, fibrin degradation products (FDP) and euglobulin lysis time. Univariate analysis and stepwise multivariate analysis were conducted. RESULTS: Patients in the HBL group required 12 units of red blood cell or more to maintain a Hb >/= 100g*L(-1). HBL was associated with severe liver disease, previous abdominal surgery, use of a venovenous bypass and little surgical experience in orthotopic liver transplantation (OLT). In the HBL group several hemostatic parameters were more disturbed before surgery. The multivariate analysis disclosed three independent variables associated with HBL: Hb and FDP concentrations and previous upper abdominal surgery. When combined, these resulted in a high specificity (98%) but low sensitivity to predict blood loss. CONCLUSION: Despite our efforts we were unable to identify predictive risk factors of bleeding during OLT even in a homogeneous population. Centres should evaluate their practice individually in an attempt to identify patients at high risk of being transfused.

Abdomen↗

Reduction in intestinal leukocyte adherence in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

OBJECTIVES: To investigate leukocyte adherence in intestinal venules in experimental endotoxemia after treatment with the 21-aminosteroid U-74389G. DESIGN AND SETTING: Prospective, randomized, controlled animal study in an experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190 +/- 40 g. INTERVENTIONS: The rats were divided equally into three groups: (a) control group, (b) endotoxemia (5 mg/kg lipopolysacharide from Escherichia coli O55:B5), and (c) endotoxemia and U-74389G administration 30 min before (3 mg/kg) and 60 min after endotoxin challenge (1.5 mg/ kg). MEASUREMENTS AND MAIN RESULTS: The distal small intestine of the animals was examined using intravital fluorescence videomicroscopy 2 h after endotoxin challenge. Leukocytes were stained in vivo by means of rhodamine 6G. In the endotoxemic animals we observed a fourfold increase in the count of firmly adherent leukocytes in submucosal post-capillary and collecting venules. Treatment with the 21-aminosteroid U-74389G significantly attenuated the count of sticking leukocytes in the collecting venules (control, 61 +/- 10 cells/mm2; lipopolysaccharide, 237 +/- 42 cells/mm2; U-74389G 125 +/- 9 cells/mm2; p < 0.05). In these venules leukocyte rolling behavior was comparable to that in the control group without endotoxin challenge. CONCLUSIONS: Administration of U-74389G, which has radical scavenging properties, attenuates leukocyte adherence in selected populations of intestinal venules which is found increased during endotoxemia. Thus, 21-aminosteroids may have an impact in the treatment of endotoxin-induced intestinal injury.

Animals↗

Control of endoreduplication domains in the Drosophila gut by the knirps and knirps-related genes.

Endoreduplication cycles that lead to an increase of DNA ploidy and cell size occur in distinct spatial and temporal patterns during Drosophila development. Only little is known about the regulation of these modified cell cycles. We have investigated fore- and hindgut development and we present evidence that the Drosophila knirps and knirps-related genes are key components to spatially restrict endoreduplication domains. Our lack and gain-of-function experiments show that knirps and knirps-related which encode nuclear orphan receptors transcriptionally repress S-phase genes of the cell cycle required for DNA replication and that this down-regulation is crucial for gut morphogenesis. Furthermore, we demonstrate that both genes are activated in overlapping expression domains in the fore- and hindgut in response to Wingless and Hedgehog activities emanating from epithelial signaling centers that control the regionalization of the gut tube. Our results provide a novel link between morphogen-dependent positional information and the spatio-temporal regulation of cell cycle activity in the gut.

Animals↗

Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells.

Natural killer (NK) cells can lyse a variety of different tumour cells by exocytosis of perforin, subsequent binding of perforin to the target cell membrane and formation of lytic pores. Some tumour cells, however, are resistant to cellular cytotoxicity. Using the NK-resistant tumour cell lines ML-2, MONOMAC-1, RPMI and L540Cy, we demonstrated that activation of NK cells with interleukin 2 (IL-2) and IL-12 resulted in significant lysis of these tumour targets. To investigate the underlying mechanisms, we isolated the cytotoxic granules from non-activated and IL-2-/IL-12-activated NK cells and compared the killing of K562 leukaemia cells (sensitive to NK cell-mediated lysis) and ML-2 leukaemia cells (resistant to NK cell-mediated lysis). In contrast to K562 cells, which were easily killed by NK-cell granules, ML-2 cells were resistant to granules from non-activated NK cells. However, granules from NK cells activated with IL-2 and IL-12 were able to induce significant tumour cell lysis. Cell death of both K562 and ML-2 cells by granules from activated NK cells was completely blocked by anti-perforin antibodies, indicating that perforin mainly accounts for the lysis induced by NK granules. Comparing granules from non-activated and IL-2-/IL-12-activated NK cells, the increased cell death of ML-2 cells was caused by an improved binding of perforin to the target cell membrane. Functional assays, however, indicated that the differences in perforin binding were not as a result of an augmented production of perforin by activated NK cells. We conclude that activation of NK cells results in an increased binding of perforin and subsequent lysis of tumour cells.

Antibodies, Monoclonal↗