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Biomedical subjects

M Hennig

Publications and source records attributed to M Hennig.

At least 19 recordsLinked to original sources
PubMed2007

Cardiac index monitoring by pulse contour analysis and thermodilution after pediatric cardiac surgery.

OBJECTIVES: To validate a new device (PiCCO system; Pulsion Medical Systems, Munich, Germany), we compared cardiac index derived from transpulmonary thermodilution and from pulse contour analysis in pediatric patients after surgery for congenital heart disease. We performed a prospective clinical study in a pediatric cardiac intensive care unit of a university hospital. METHODS: Twenty-four patients who had had cardiac surgery for congenital heart disease (median age 4.2 years, range 1.4-15.2 years) were investigated in the first 24 hours after admission to the intensive care unit. A 3F thermodilution catheter was inserted in the femoral artery. Intracardiac shunts were excluded by echocardiography intraoperatively or postoperatively. Cardiac index derived from pulse contour analysis was documented in each patient 1, 4, 8, 12, 16, 20, and 24 hours after admission to the intensive care unit. Subsequently, a set of three measurements of thermodilution cardiac indices derived by injections into a central venous line was performed and calculated by the PiCCO system. RESULTS: The mean bias between cardiac indices derived by thermodilution and those derived by pulse contour analysis over all data points was 0.05 (SD 0.4) L x min x m(-2) (95% confidence interval 0.01-0.10). A strong correlation between thermodilution and contour analysis cardiac indices was calculated (Pearson correlation coefficient r = 0.93; coefficient of determination r2 = 0.86). CONCLUSIONS: Pulse contour analysis is a suitable method to monitor cardiac index over a wide range of indices after surgery for congenital heart disease in pediatric patients. Pulse contour analysis allows online monitoring of cardiac index. The PiCCO device can be recalibrated with the integrated transpulmonary thermodilution within a short time frame.

Adolescent↗
PubMed2005

Phase II study of weekly oxaliplatin plus infusional fluorouracil and folinic acid (FUFOX regimen) as first-line treatment in metastatic gastric cancer.

Oxaliplatin plus fluorouracil/folinic acid (5-FU/FA) every 2 weeks has shown promising activity in advanced gastric cancer. This study assessed the efficacy and safety of weekly oxaliplatin plus 5-FU/FA (FUFOX regimen) in the metastatic setting. Patients with previously untreated metastatic gastric cancer received oxaliplatin (50 mg m(-2)) plus FA (500 mg m(-2), 2-h infusion) followed by 5-FU (2000 mg m(-2), 24-h infusion) given on days 1, 8, 15 and 22 of a 5-week cycle. The primary end point of this multicentre phase II study was the response rate according to RECIST criteria. A total of 48 patients were enrolled. Median age was 62 years and all patients had metastatic disease, with a median number of three involved organs. The most common treatment-related grade 3/4 adverse events were diarrhoea (17%), deep vein thrombosis (15%), neutropenia (8%), nausea (6%), febrile neutropenia (4%), fatigue (4%), anaemia (4%), tumour bleeding (4%), emesis (2%), cardiac ischaemia (2%) and pneumonia (2%). Grade 1/2 sensory neuropathy occurred in 67% of patients but there were no episodes of grade 3 neuropathy. Intent-to-treat analysis showed a response rate of 54% (95% CI, 39-69%), including two complete responses. At a median follow-up of 18.1 months (range 11.2-26.2 months), median survival is 11.4 months (95% CI, 8.0-14.9 months) and the median time to progression is 6.5 months (95% CI, 3.9-9.2 months). The weekly FUFOX regimen is well tolerated and shows notable activity as first-line treatment in metastatic gastric cancer.

Adult↗
PubMed2005

Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial.

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m(-2) twice daily on days 1-14) plus intravenous docetaxel (75 mg m(-2) on day 1) every 3 weeks as first- (n = 16) or second-line (n = 8) therapy. Patients received a median of four cycles of treatment (range, 0-6). The median follow-up is 16.5 months (range, 7.9-21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5-7.7 months). The median survival was 15.8 months (95% CI, 7.8-23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.

Adenocarcinoma↗
PubMed2005

Randomized clinical trial of vertical or transverse laparotomy for abdominal aortic aneurysm repair.

BACKGROUND: The objective of this randomized trial was to evaluate the incidence of incisional hernia after transverse or vertical incisions for open aortic aneurysm repair. METHODS: The study group comprised 69 patients who underwent elective aneurysm repair between November 1998 and November 2000 (60 men, nine women; mean age 72.8 (range 56-95) years). Patients were randomized to a transverse (n = 32) or vertical (n = 37) incision for the procedure. Of the 42 patients who were still alive in February 2004, 37 (15 transverse, 22 vertical incisions) attended for review. Laparotomy scars were assessed both clinically and ultrasonographically by the same examiner, to look for incisional hernia. RESULTS: Mean follow-up was 4.4 years. A multivariable logistic regression analysis revealed that the type of incision was the only parameter that significantly influenced the rate of incisional hernia: six of 15 patients with a transverse laparotomy versus 20 of 22 with a vertical laparotomy (P = 0.010). CONCLUSION: The incidence of incisional hernia was high after aortic aneurysm repair, but was lower in patients who had a transverse incision.

Aged↗
PubMed2005

[MS registry in Germany--design and first results of the pilot phase].

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS </=4.0. The great effect of this disorder was underscored by the fact that one third of the patients had prematurely retired due to MS. After successful completion of the pilot phase, the MS register will provide reliable data and thus serve as an important tool to improve the overall situation of MS patients in Germany.

Adult↗
PubMed2003

Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory oesophageal cancer.

This phase II trial assessed the toxicity and efficacy of irinotecan plus docetaxel in cisplatin-pretreated oesophageal cancer. Irinotecan 160 mg m(-2) plus docetaxel 65 mg m(-2) once every 3 weeks led to severe myelosuppression in four patients, all of whom experienced neutropenic fever. After amendment of this regimen, 24 patients (male/female=18/6; median age=58.5 years; ECOG performance status 0/1/2=9/11/4) with advanced oesophageal cancer (adenocarcinoma/epidermoid carcinoma=13/11) received irinotecan 55 mg m(-2) plus docetaxel 25 mg m(-2) on days 1, 8 and 15 of a 28-day cycle. Serious adverse events occurred in five patients, one with lethal outcome (pneumonia). Haematological toxicity >or=3 degrees was rare, whereas nonhaematological toxicity >or=3 degrees was noted in nine out of 24 patients (asthenia in five patients, diarrhoea in three patients, nausea/emesis in two patients, constipation in one patient). Median survival time was 26 (range 2-70) weeks. Response rate, assessed according to the WHO criteria, was 12.5% (95% CI 2.7-32.4%); rate of disease stabilisation (partial remission and stable disease) was 33.3% (95% CI 15.6-55.3%) with a median duration of 18.5 (range 16-51) weeks. Although the nonhaematological toxicity proved to be considerable, weekly irinotecan plus docetaxel is feasible and shows some activity in extensively pretreated patients with oesophageal cancer.

Adenocarcinoma↗
PubMed2003

Male factors determining the outcome of intracytoplasmic sperm injection with epididymal and testicular spermatozoa.

During a period of 8 years, 1,079 intracytoplasmic sperm injection (ICSI) procedures with aspirated epididymal or testicular spermatozoa were performed. Epididymal spermatozoa were used in 172 cycles and testicular spermatozoa or spermatids in 907 cycles. Multiple biopsies were obtained from at least two different locations in the testes. Retrieved spermatozoa were used after cryopreservation (frozen) or immediately after aspiration (fresh). Three hundred patients had obstructive azoospermia (OA) or ejaculation failure. In 414 cases, azoospermia was caused by impaired spermatogenesis resulting from maldescended testes, chemotherapy/radiotherapy, or by Sertoli-cell-only syndrome, genetic disorders or unknown aetiology. Transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal spermatozoa in men with OA (28% average birth rates in both cases). However, birth rates differed significantly with regard to the status of spermatogenesis. Treatment of men with nonobstructive azoospermia (NOA) resulted in a birth rate of 19% per cycle. In all patient groups, there was no difference in the birth rates achieved with fresh and cryopreserved spermatozoa. While testicular volume, follicle-stimulating hormone level and age of the male patient are no statistically significant prognostic factors, the underlying cause of azoospermia is the most important factor determining the outcome of ICSI with epididymal and testicular spermatozoa. The pregnancy rate is lower in NOA patients than in those with OA.

Epididymis↗
PubMed2002

Cardiac output determination in children: equivalence of the transpulmonary thermodilution method to the direct Fick principle.

OBJECTIVE: To show the equivalence of the transpulmonary thermodilution method to the direct Fick principle in children. DESIGN: Prospective single-centre study. SETTING: A 16-bed paediatric cardiac ICU and a cardiac catheterisation laboratory at an university affiliated centre for paediatric cardiology and congenital heart disease. PATIENTS: We consecutively investigated 18 patients (mean age 12.1 +/- 6.4 years) during cardiac catheterisation and after corrective cardiac operation. METHODS AND RESULTS: We prospectively defined limits of equivalence for cardiac index (CI) for both methods of +/- 0.25 l/min x m(2). We measured oxygen consumption for determination of CI by Fick as the clinical "gold standard" and performed a set of three transpulmonary thermodilution measurements. The mean CI(Fick) was 2.88 +/- 1.07 l/min x m(2) (range 1.10-4.62 l/min x m(2)) and CI(TPID)was 2.85 +/- 1.03 l/min x m(2)(range 1.02-4.49 l/min x m(2)). The mean difference between CI(Fick) and CI(TPID)was 0.030 +/- 0.168 l/min x m(2), and limits of agreement -0.306 to 0.366 l/min x m(2)(90% confidence interval -0.040 to 0.099 l/min x m(2)). The regression equation was : CI(Fick)=1.0244 x CI(TPID)-0.040, r(2) = 0.976, P < 0.0001. The intraclass coefficient of reliability for three repeated measurements of CI(TPID) was 0.97, the corresponding lower limit of the 95% confidence interval was 0.94. CONCLUSION: We demonstrated the equivalence of CI measurement by transpulmonary thermodilution and the Fick principle in children. This new method may improve hemodynamic monitoring and management in seriously ill children.

Adolescent↗
PubMed2001

X-ray structure of junctional adhesion molecule: structural basis for homophilic adhesion via a novel dimerization motif.

Junctional adhesion molecules (JAMs) are a family of immunoglobulin-like single-span transmembrane molecules that are expressed in endothelial cells, epithelial cells, leukocytes and myocardia. JAM has been suggested to contribute to the adhesive function of tight junctions and to regulate leukocyte trans migration. We describe the crystal structure of the recombinant extracellular part of mouse JAM (rsJAM) at 2.5 A resolution. rsJAM consists of two immunoglobulin-like domains that are connected by a conformationally restrained short linker. Two rsJAM molecules form a U-shaped dimer with highly complementary interactions between the N-terminal domains. Two salt bridges are formed in a complementary manner by a novel dimerization motif, R(V,I,L)E, which is essential for the formation of rsJAM dimers in solution and common to the known members of the JAM family. Based on the crystal packing and studies with mutant rsJAM, we propose a model for homophilic adhesion of JAM. In this model, U-shaped JAM dimers are oriented in cis on the cell surface and form a two-dimensional network by trans-interactions of their N-terminal domains with JAM dimers from an opposite cell surface.

Animals↗
PubMed2001

Internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of Bavarian chimney sweeps.

This study was carried out to evaluate the internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of chimney sweeps in Bavaria compared to a control group without occupational exposure. The PCDD/PCDF concentrations in the blood fat of 227 chimney sweeps were compared with the concentrations in samples from 60 controls. Using an internal standard containing 17 (13)C(12)-labeled PCDD/F congeners, the samples were cleaned up after fat elution using standard methods. The statistical analysis was adjusted to account for demographic differences, dietary habits, smoking status, and both occupational and nonoccupational contact with chlorinated hydrocarbons. Detailed information on the type of heating in the households swept, the length of time the chimney sweeps had carried out the profession (min 34, med 195, max 466 months) and the protective measures employed, were used to examine the influence of the working conditions specific to chimney sweeps on the internal PCDD/PCDF exposure. The correlation between blood-fat PCB concentrations as well as urinary chlorophenol concentrations and the exposure to PCDDs/PCDFs was evaluated. The sum of PCDD/PCDF components in chimney sweeps, expressed by International Toxic Equivalents (I-TEQ), was significantly increased compared to the control group (median: 26.36 versus 20.75 pg I-TEQ/g blood fat). For 37 chimney sweeps (16.3%) the sum of PCDDs/PCDFs exceeded the 95th percentile of the control group, i.e., 38.23 pg I-TEQ/g blood fat. Multiple regression analysis revealed that in addition to occupation, the variables age, district, and proximity to a waste incineration plant seem to have an effect on the internal PCDD/PCDF exposure. An additional influence on the internal exposure could not be determined for any of the special aspects of the work. We identified no high correlations between the concentrations of PCBs and chlorophenols and PCDDs/PCDFs. This study revealed significantly higher internal exposure to PCDDs/PCDFs in chimney sweeps than in the control group. The differences are small and within the range of the internal exposure to PCDDs/PCDFs in blood found in the general population in Germany since 1989. Further investigations in to PCDD/PCDF-related diseases in these study groups were not carried out.

Adult↗
PubMed2001

The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial.

The effect of an adjuvant mistletoe extract treatment was tested in a prospective, randomised controlled clinical trial involving 477 patients with head and neck squamous cell carcinoma. The patients were stratified into two treatment groups that underwent surgery or surgery followed by radiotherapy and both groups were randomised for additional treatment with mistletoe extract. Patients treated with a mistletoe lectin-1 (ML-1) standardised mistletoe preparation had no lower risk of local/locoregional recurrences, distant metastases or second primaries. In the main analysis based on 202 patients treated with surgery and 275 patients treated with surgery and radiotherapy the adjusted hazard ratio for the disease-free survival (DFS) was 0.959 (95% confidence interval (CI) 0.725-1.268). The 5-year survival rates of patients from the mistletoe group were no better than the survival rates of patients from the control group. Furthermore, no significant changes in the cellular immune reaction or in quality of life could be detected. We conclude that the used mistletoe preparation has no indication in the adjuvant treatment of patients with head and neck cancer.

Adult↗
PubMed2001

Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND: Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability. METHODS AND RESULTS: In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values. CONCLUSIONS: This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

Aged↗
PubMed2000

Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study.

The authors assessed the safety and efficacy of creatine monohydrate (Cr) in various types of muscular dystrophies in a double-blind, crossover trial. Thirty-six patients (12 patients with facioscapulohumeral dystrophy, 10 patients with Becker dystrophy, 8 patients with Duchenne dystrophy, and 6 patients with sarcoglycan-deficient limb girdle muscular dystrophy) were randomized to receive Cr or placebo for 8 weeks. There was mild but significant improvement in muscle strength and daily-life activities by Medical Research Council scales and the Neuromuscular Symptom Score. Cr was well tolerated throughout the study period.

Activities of Daily Living↗
PubMed2000

Detection of N-H...N hydrogen bonding in RNA via scalar couplings in the absence of observable imino proton resonances.

Hydrogen bond networks stabilize RNA secondary and tertiary structure and are thus essentially important for protein recognition. During structure refinements using either NMR or X-ray techniques, hydrogen bonds were usually inferred indirectly from the proximity of donor and acceptor functional groups. Recently, quantitative heteronuclear J(N,N)-HNN COSY NMR experiments were introduced that allowed the direct identification of donor and acceptor nitrogen atoms involved in hydrogen bonds. However, protons involved in base pairing interactions in nucleic acids are often not observable due to exchange processes. The application of a modified quantitative J(N,N)-HNN COSY pulse scheme permits observation of(2h)J(N,N) couplings via non-exchangeable protons. This approach allowed the unambiguous identification of the A27.U23 reverse Hoogsteen base pair involved in a U-A.U base triple in the HIV-2 transactivation response element-argininamide complex. Despite a wealth of NOE information, direct evidence for this interaction was lacking due to the rapid exchange of the U23 imino proton. The ability to directly observe hydrogen bonds, even in D(2)O and in the presence of rapid exchange, should facilitate structural studies of RNA.

Base Pairing↗
PubMed2000

Structure and function of mutationally generated monomers of dimeric phosphoribosylanthranilate isomerase from Thermotoga maritima.

BACKGROUND: Oligomeric proteins may have been selected for in hyperthermophiles because subunit association provides extra stabilization. Phosphoribosylanthranilate isomerase (PRAI) is monomeric and labile in most mesophilic microorganisms, but dimeric and stable in the hyperthermophile Thermotoga maritima (tPRAI). The two subunits of tPRAI are associated back-to-back and are locked together by a hydrophobic loop. The hypothesis that dimerization is important for thermostability has been tested by rationally designing monomeric variants of tPRAI. RESULTS: The comparison of tPRAI and PRAI from Escherichia coli (ePRAI) suggested that levelling the nonplanar dimer interface would weaken the association. The deletion of two residues in the loop loosened the dimer. Subsequent filling of the adjacent pocket and the exchange of polar for apolar residues yielded a weakly associating and a nonassociating monomeric variant. Both variants are as active as the parental dimer but far more thermolabile. The thermostability of the weakly associating monomer increased significantly with increasing protein concentration. The X-ray structure of the nonassociating monomer differed from that of the parental subunit only in the restructured interface. The orientation of the original subunits was maintained in a crystal contact between two monomers. CONCLUSIONS: tPRAI is dimeric for reasons of stability. The clearly separated responsibilities of the betaalpha loops, which are involved in activity, and the alphabeta loops, which are involved in protein stability, has permitted the evolution of dimers without compromising their activity. The preserved interaction in the crystal contacts suggests the most likely model for dimer evolution.

Aldose-Ketose Isomerases↗
PubMed2000

Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon.

Neutral endopeptidase is a mammalian type II integral membrane zinc-containing endopeptidase, which degrades and inactivates a number of bioactive peptides. The range of substrates cleaved by neutral endopeptidase in vitro includes the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor. Due to the physiological importance of neutral endopeptidase in the modulation of nociceptive and pressor responses there is considerable interest in inhibitors of this enzyme as novel analgesics and anti-hypertensive agents. Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution. The structure reveals two multiply connected folding domains which embrace a large central cavity containing the active site. The inhibitor is bound to one side of this cavity and its binding mode provides a detailed understanding of the ligand-binding and specificity determinants.

Amino Acid Sequence↗