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Biomedical subjects

C Ludwig

Publications and source records attributed to C Ludwig.

At least 19 recordsLinked to original sources

Fourier transform Raman and infrared spectra and normal coordinate analysis of organo-arsenic(III), -antimony(III) and -bismuth(III) thiolates.

The FT-Raman and infrared spectra of (PhS)BiPh2, (PhS)2BiPh, (PhS)3Sb, (PhS)3Sb, (PhS)3As and (PhSe)BiPh2 were measured in the range 3600-100 cm(-1). A normal coordinate analysis was performed for all substances in terms of the calculation and discussion of the force constants which are dependent on the element-sulphur and element-selenium group using a modified valence force field. Furthermore, for all compounds 1H-NMR, 13C-NMR and MS data were also given. The investigation of the microbiological activity of some substances against Escherichia coli was an additional aspect because of their strong bactericidal and fungicidal effects.

Carbon↗

NMRLAB-Advanced NMR data processing in matlab

NMRLAB is a toolbox for NMR data processing in MATLAB (The Mathworks). MATLAB is a matrix-oriented high-level programming environment which gives access to fast algorithms for a large number of numerical tasks on many common computer platforms. To take advantage of fast matrix operations in MATLAB most processing commands in NMRLAB have been vectorized. Data processing can be achieved either by scripts or by a user-friendly command structure. An interface to WaveLab enables spectral denoising employing wavelet transforms. The use of wavelet denoising is demonstrated for one- and two-dimensional data. Copyright 2000 Academic Press.

Journal Article↗

Relative hypoleptinemia in patients with type 1 and type 2 diabetes mellitus.

OBJECTIVE: To determine the relation between plasma leptin concentrations and metabolic control in human diabetes mellitus. DESIGN AND SUBJECTS: Cross sectional study consisting of 156 patients with diabetes mellitus type 1 (n=42), type 2 (n=114), and non-diabetic subjects (n=74). RESULTS: Plasma leptin concentrations were lower (P<0.05) in type 1 (8.3+/-1.7 ng/ml) and type 2 diabetic (14.9+/-1.8 ng/ml) than in non-diabetic humans (18.3+/-1.9 ng/ml). Only female type 1 and type 2 diabetic subjects also had decreased leptin/BMI ratios (P<0.05 vs non-diabetic females). The log rank test identified age-adjusted correlation of plasma leptin concentration with sex (P<0.0004) and body mass index (P<0.0218), but not with glycosylated haemoglobin A1c (P>0.5) in all groups. Plasma leptin was correlated with age (P<0.0058) and serum triglycerides (P<0.0199) in type 1 diabetic patients, and with serum cholesterol (P<0.0059) and LDL (P<0.0013) in type 2 diabetic patients. CONCLUSIONS: Defective leptin production and/or secretion might be present independently of metabolic control in female patients with type 1 or type 2 diabetes mellitus.

Adult↗

TP53 mutation and p53 overexpression for prediction of response to neoadjuvant treatment in breast cancer patients.

The value of p53 to predict the cytotoxic effect of two commonly used chemotherapy regimens was assessed in patients with advanced breast cancer. Response to a DNA-damaging combination therapy [fluorouracil, epirubicin, cyclophosphamide (FEC] considered to induce p53-dependent apoptosis was compared with a microtubule stabilizing therapy (paclitaxel) expected to be independent of p53 function. The p53 status of the patients' breast tumors was assessed using both immunohistochemistry (IHC) and direct sequencing of the entire p53 gene. p53 findings were correlated with treatment response, and linkage between p53 function and cellular response was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. In a series of 67 breast tumors, 19% had TP53 gene mutations, 40% had a positive p53 IHC, and 12% had both. In the FEC group, treatment failure was related to both the presence of TP53 gene mutations (P = 0.0029) and a positive IHC (P < 0.0001). Apoptosis was almost exclusively found in tumors having normal p53 in both parameters (P < 0.0001). In the paclitaxel group, treatment response was neither related to apoptosis nor to normal p53. Combination of sequencing and IHC results revealed a significant association between abnormal p53 and response to paclitaxel (P = 0.011). We found TP53 mutations, as well as p53 protein overexpression, to be associated with response to chemotherapy. Whereas clinical response to FEC was found to be dependent on normal p53, the cytotoxicity of paclitaxel was related to defective p53. The efficiency of paclitaxel during mitosis might be supported by lack of G1 arrest due to p53 deficiency. Therefore, patients with p53-deficient tumors may benefit from paclitaxel.

Antineoplastic Agents, Phytogenic↗

Construction of a highly bioluminescent Nitrosomonas as a probe for nitrification conditions.

Cloned luciferase-encoding operons were transferred by conjugation to a natural isolate of the ammonia-oxidizing bacterial strain Nitrosomonas sp. RST41-3, thereby establishing conjugation as a tool for gene transfer into Nitrosomonas strains. Luminescence was dependent on the pH of the medium and the concentration of the substrate ammonium chloride. Moreover, the luminescence of the transconjugants was reduced immediately by micromolar concentrations of nitrapyrin and allylthiourea, which are specific inhibitors of nitrification. Our results indicate that luminescent Nitrosomonas strains may be useful as a probe to detect nitrification conditions in the natural environment as well as in sewage plants.

Ammonium Chloride↗

The TP53 genotype but not immunohistochemical result is predictive of response to cisplatin-based neoadjuvant therapy in stage III non-small cell lung cancer.

BACKGROUND: The cytotoxic effects of cisplatin and anthracyclins have been attributed to apoptosis induction, which has been recognized as a major function of the TP53 gene. The TP53 gene appears to be mutated in about 50% of cases of non-small cell lung cancer. A possible dependence of chemotherapy response on TP53 genotype was evaluated retrospectively in a group of patients with advanced non-small cell lung cancer and induction treatment. METHODS: Patients with complete or partial remission were compared with those with stable or progressive disease with respect to TP53 genotype and overall survival. Mutations in the TP53 gene were detected by complete direct sequencing (exons 2-11). RESULTS: A normal TP53 genotype proved to be significantly associated with major response to chemotherapy (P <.001). Overall, no association was found between p53 protein expression and TP53 genotype. A normal TP53 genotype was found to be highly sensitive in predicting response to treatment, whereas a mutant genotype was revealed to be specific in predicting lack of response. The difference in overall length of survival was significant between patients exhibiting a normal TP53 genotype (corresponding to those whose disease responded to chemotherapy) and patients showing mutant TP53 genotype (corresponding to those who had disease resistant to chemotherapy, P =.027). CONCLUSIONS: In a small cohort of patients with advanced non-small cell lung cancer we found a direct link between normal TP53 genotype and response to cisplatin-based induction treatment and also between mutant genotype and resistance to treatment, whereas p53 immunohistochemical result was predictive of neither.

Antineoplastic Combined Chemotherapy Protocols↗

Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

Adult↗

Are airbags dangerous?

Several articles have shown that airbags are not without danger. A brief overview of the literature shows their impact on motor vehicle collisions. Several criteria of severity are listed to avoid underestimating airbag-crash patients with a "no crash" look.

Air Bags↗

Elevation of plasma leptin concentrations in obese hyperinsulinaemic hypothyroidism before and after treatment.

BACKGROUND: Plasma leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to decrease leptin expression. This study was therefore designed to test the hypothesis that hyperthyroidism results in lower leptin concentrations, whereas hypothyroidism leads to higher plasma leptin concentrations. In addition, the effects of normalization of thyroid function on plasma leptin were investigated. MATERIALS AND METHODS: Fasting plasma leptin concentrations and body fat mass (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were monitored during an oral glucose tolerance test (OGTT 75 g). RESULTS: Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL-1, hypothyroid 10.2 +/- ng mL-1, euthyroid 12.7 +/- 3 ng mL-1). In obese hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) than in lean hypothyroid patients, twofold higher (P < 0.005) than in obese hyperthyroid patients matched for fat mass and 30% increased (P < 0.01) compared with obese euthyroid subjects. There were no differences between fasting and post-prandial (OGTT) leptin concentrations in any group. Normalization of thyroid function did not affect plasma leptin, which remained elevated (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mass index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma leptin correlated with plasma insulin concentration only in hyperthyroid patients (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects. CONCLUSION: The results indicate that (a) the correlation of leptin with body fat mass is preserved in thyroid dysfunction, (b) plasma leptin is markedly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.

Adult↗

Optimization of the kinetics of cooling of kidneys: a pig model.

We determined the kinetics of cooling in multiple organ procurement for the kidney in a pig model. A biometric analysis by regression enables us to define the factors which influence the rate of temperature decrease: weight of the donor, average rate of perfusion and difference of temperature between the rectal temperature and the temperature of the perfusion solution at initiation of cooling. The description of the temperature as a function of time follows an exponential model of the type T(t) = T0. e(dt) where d is the rate of decrease. The rate of decrease varies according to the above factors. The cellular viability ratio (CVR), was correlated to the rate of cooling. The mean CVR was 91% (SD 4.95) when the rate of cooling was more than 1 degrees C/min. This was compared to 75% (SD 11.17) when the rate was less than 1 degrees C/min (p = 0.023). Our experience leads us to believe that the average cooling rate is frequently too low (<1 degrees C/min). This model can be used to predict and control the kinetics of cooling and may help to define the best way of cooling for future xenotransplantation.

Animals↗

A comparative study of the backbone dynamics of two closely related lipid binding proteins: bovine heart fatty acid binding protein and porcine ileal lipid binding protein.

The backbone dynamics of bovine heart fatty acid binding protein (H-FABP) and porcine ileal lipid binding protein (ILBP) were studied by 15N NMR relaxation (T1 and T2) and steady state heteronuclear 15N[1H] NOE measurements. The microdynamic parameters characterizing the backbone mobility were determined using the 'model-free' approach. For H-FABP, the non-terminal backbone amide groups display a rather compact protein structure of low flexibility. In contrast, for ILBP an increased number of backbone amide groups display unusually high internal mobility. Furthermore, the data indicate a higher degree of conformational exchange processes in the microsec-msec time range for ILBP compared to H-FABP. These results suggest significant differences in the conformational stability for these two structurally highly homologous members of the fatty acid binding protein family.

Animals↗

N-cadherin/catenin-mediated morphoregulation of somite formation.

Somitogenesis during early stages in the chick and mouse embryo was examined in relation to N-cadherin-mediated adhesion. Previous studies indicated that N-cadherin localizes to the somite regions during their formation. Those observations were extended to include a spatiotemporal immunohistochemical analyses of beta-catenin and alpha-catenin, as well as a more detailed study of N-cadherin, during segmentation, compaction, and compartmentalization of the somite. N-cadherin and the catenins appear early within the segmental plate and are expressed as small patch-like foci throughout this tissue. The small foci of immunostaining coalesce into larger clusters of N-cadherin/catenin-expressing regions. The clusters subsequently coalesce into a region of centrally localized cells that express N-cadherin/catenins at their apical surfaces. The multiple clusters are spaced wide apart in the anterior segmental plates that form the first 6 somite pairs, as contrasted to segmental plates that form somites 7 and beyond. To examine the functional significance of N-cadherin, segmental plates were exposed to antibodies that perturb N-cadherin-mediated adhesion in the chick embryo. The multiple, anomalous somites that result in these experiments indicate that each N-cadherin/catenin-expressing cluster can give rise to a somitic structure. beta-Catenin involvement in somitogenesis suggests a role for Wnt-mediated signaling. Embryos treated with LiCl also show induction of similar anomalous somites indicating further the possibility that Wnt-mediated signaling may be involved in the clustering event. It is suggested that beta-catenin serves to initiate the adhesion process which is spread then by N-cadherin. Later during compartmentalization, N-cadherin/catenins remain expressed by the myotome compartment. Taken together, these results suggest that the Ca2+-dependent cell adhesion molecule N-cadherin and the intracellular catenins are important in segmentation and formation of the somite and myotome compartment. It is proposed that the N-cadherin-mediated adhesion process may serve as a common, evolutionarily conserved, link in the differentiation pathways of skeletal and cardiac muscle.

Animals↗

[Value and limits of conventional mediastinoscopy in preoperative evaluation of primary bronchial cancer].

PURPOSE OF THE STUDY: Retrospective evaluation of conventional mediastinoscopy in the preoperative staging of primary lung cancer. METHODS: Between 1978 and March 1997, 117 consecutive patients underwent conventional mediastinoscopy in the preoperative staging of primary lung cancer, after imaging had shown mediastinal lymph nodes larger than 1.5 cm. RESULTS: In 8 instances no material was found at mediastinoscopy, in 38 the lymph nodes showed no tumorous infiltration, and in 71 the lymph nodes were metastatic. 48 patients underwent thoracotomy in the same stage, with resection achieved in 41. Contraindications for thoracotomy (in 69) were N2 (45) or N3 (11) disease adn/or small cell lung cancer (18). Mediastinal lymphadenectomy was performed in 26 of the 41 patients who underwent lung resection; half of those with negative nodes at mediastinoscopy had in fact N2 disease, with involvement of 2 areas of more in half. There were no deaths due to mediastinoscopy but 4 complications. CONCLUSIONS: A favorable mediastinoscopy is not synonymous with resectable disease, nor does it exclude N2 disease; it does however serve to avoid unnecessary thoracotomies in more than half of cases.

Adult↗

[Infectious spondylodiscitis--an important differential diagnosis in backache].

All cases of spondylodiscitis diagnosed in our hospital between January 93 and April 96 have been analysed retrospectively. With regard to potentially severe complications, spondylodiscitis is an important differential diagnosis of back pain. In our results 50% of the patients had a positive bacterial culture either from blood or tissue. No complication has been observed. The most relevant diagnostic procedures are: determination of CRP, magnetic resonance imaging and eventually computed tomography in combination with biopsy and blood cultures. Magnetic resonance imaging is a very sensitive method for early stage osteomyelitis. Antimicrobial therapy should be based on the result of culture and sensitivity tests. An antibiotic with good penetration into bone is preferred.

Aged↗

Rubber band ligation of hemorrhoids: relapse as a function of time.

Rubber band ligation is a well established treatment of internal second-degree hemorrhoids. Up to now, the long-term results (> 5 years) of this method have not been assessed. The aim of this study was to determine the long-term success rate of rubber band ligation in patients with a first episode of second-degree hemorrhoids not responding to medical treatment (local cream with laxative). A total of 92 patients who were treated between 1979 and 1997 for second-degree hemorrhoids responded to a questionnaire. The need for complementary conservative (sclerotherapy, cryotherapy or rubber band ligation) or surgical treatment was considered indicative of relapse. The collected data were analyzed according to the Kaplan-Meier method. The average follow-up time was 5.6 years. There were 21 patients who suffered a relapse. The probability of successful treatment was 0.77 (range: 0.67-0.88) after 5 years and 0.68 (range: 0.5-0.86) after 10.6 years. We conclude that rubber band ligation represent an efficient long-term treatment for second-degree hemorrhoids. Approximately two thirds of the patients are cured after 5 years and more than a half after 10 years.

Female↗

Chronic gastritis in tigers associated with Helicobacter acinonyx.

Helicobacter pylori-like organisms (HPLOs) were isolated from the gastric mucosa of two Sumatran tigers and identified by polymerase chain reaction analysis as Helicobacter acinonyx. At histological examination, both tigers revealed a chronic gastritis associated with HPLOs as demonstrated by immunolabelling and electron microscopy. This is the first isolation of H. acinonyx from tigers, in which, as previously reported in cheetahs, it may be a cause of gastritis.

Animals↗