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Biomedical subjects

R Lehmann

Publications and source records attributed to R Lehmann.

At least 37 records · Page 2Linked to original sources

A plasma glucose concentration below 2.5 mmol L-1 is not an appropriate criterion to end the 72-h fast.

CONTEXT: The classical end-point to terminate the 72-h fast in a patient evaluated for a hypoglycaemic disorder is the occurrence of hypoglycaemic symptoms in association with a low plasma glucose level. However, neither the symptoms nor the plasma glucose level have been exactly defined. OBJECTIVE: To determine whether a useful cut-off plasma glucose concentration as criterion to end the prolonged fast in the absence of neuroglycopenic symptoms can be defined. DESIGN: Single centre case-control study. SETTING: Tertiary referral hospital in Switzerland. SUBJECTS: The 72-h fast was prospectively performed in 23 consecutive patients (17 women and six men) following a standardized protocol between July 1999 and January 2002. All patients were referred to our clinic for evaluation of suspected hypoglycaemia. The criterion to end the fast before 72 h was defined by the occurrence of symptoms or signs typical for neuroglycopenia irrespective of plasma glucose levels. MAIN OUTCOME MEASURE: Insulin levels and insulin to plasma glucose ratios in insulinoma patients and in individuals without insulin-secreting tumours at termination of the fast and at plasma glucose levels </=2.5 mmol L-1, prior to the occurrence of neuroglycopenic symptoms. RESULTS: In seven patients, the fast was terminated before 72 h because they developed neuroglyco-penic symptoms. Insulin-secreting tumours were found and successfully removed in these seven patients. Sixteen individuals developed no neuroglycopenic symptoms throughout the 72-h fast and an insulin-secreting tumour could be excluded in these 16 patients. Five of these 16 individuals had plasma glucose levels </=2.5 mmol L-1 during the 72-h fast. Insulin levels and insulin to glucose ratios in insulinoma patients and healthy individuals overlapped during as well as at termination of the fast. Prior to the occurrence of neuroglycopenic symptoms and at venous plasma glucose </=2.5 mmol L-1, insulin to plasma glucose ratios dropped in insulinoma patients to values within the normal range on several occasions. CONCLUSIONS: Terminating the fast at plasma glucose levels </=2.5 mmol L-1 does not allow confirmation or exclusion of an insulin-secreting tumour. Thus, the occurrence of symptoms or signs typical for neuroglycopenia is the prerequisite criterion to end the fast before 72 h.

Adolescent↗

Large cerebral vessel occlusive disease in Lyme neuroborreliosis.

We report on a 12-year-old, previously healthy girl with an acute hemiparesis as the predominant clinical manifestation of Lyme neuroborreliosis (LNB). The diagnosis of LNB was based on cerebrospinal fluid (CSF) studies, laboratory findings and the clinical course whereas the patient's history and the lack of characteristic skin lesions obscured the diagnosis in the beginning. After four weeks of antibiotic and physiotherapeutic treatment, the hemiparetic symptoms had completely resolved. Although evidence of vasculitic and perivascular inflammation in LNB has been described in the literature, large cerebral vessel occlusive disease represents a rare finding. Appropriate treatment strategies can lead to good clinical rehabilitation, as shown in this case, making the timely diagnosis a crucial issue. We conclude that LNB should be considered in every stroke-like episode of unknown origin in children, even in the absence of a history of a tick bite or typical skin lesions.

Arterial Occlusive Diseases↗

Three-dimensional MR visualization of the intracisternal course of the cranial nerves V-VIII by virtual cisternoscopy.

PURPOSE: A post-processing protocol for 3D visualization of the cranial nerves V-VIII along their intracisternal course is presented. MATERIAL AND METHODS: Six healthy volunteers underwent MR imaging (1.5 T) to obtain high-resolution heavily T2-weighted data sets (3DFT CISS) with isotropic voxels (0.5 mm3). The data sets were post-processed by using volume rendering software in order to visualize the intracisternal courses of the cranial nerves V-VIII as well as their root entry zones. The data acquisition and post-processing protocol was then applied in 14 patients with a suspected neural compression syndrome according to the clinical findings as well as cross-sectional images and evaluated with respect to image quality and diagnostic value by two neuroradiologists, using a five-point scale. RESULTS: Virtual cisternoscopy allowed a comprehensive intracisternal 3D visualization of the affected cranial nerves in 12/14 patients. The mean post-processing time amounted to 13.1/5.6/13.7 min for the cranial nerves V/VI/VII and VIII. The mean score for image quality was 4.2, that for diagnostic value 4.1. 2D and/or 3D reference images were indispensable for appreciating the spatial information provided by virtual cisternoscopy. CONCLUSION: The data acquisition and post-processing protocol presented here allows comprehensive and standardized intracisternal 3D visualization of the cranial nerves V-VIII in a routine setting as a complementary imaging procedure.

Abducens Nerve↗

[Psychological reaction in private accident insurance. Differences in legal apprehension].

According to the provisions of private accident insurance, mental or psychological reactions are in contrast to basically not covered by insurance. The body is the object of insurance, not like third party insurance, which covers health. Since 1993 private accident insurance companies have been able to offer better coverage for mental or psychological reactions. But these possibilities for modifications of the AUB (terms and conditions of private accident insurance) introduced in 1993 constitute a departure from the traditional terms and conditions of the AUB.

Accidents↗

Poly(A)-independent regulation of maternal hunchback translation in the Drosophila embryo.

Development of the Drosophila abdomen requires repression of maternal hunchback (hb) mRNA translation in the posterior of the embryo. This regulation involves at least four components: nanos response elements within the hb 3' untranslated region and the activities of Pumilio (PUM), Nanos (NOS), and Brain tumor. To study this regulation, we have developed an RNA injection assay that faithfully recapitulates the regulation of the endogenous hb message. Previous studies have suggested that NOS and PUM can regulate translation by directing poly(A) removal. We have found that RNAs that lack a poly(A) tail and cannot be polyadenylated and RNAs that contain translational activating sequences in place of the poly(A) tail are still repressed in the posterior. These data demonstrate that the poly(A) tail is not required for regulation and suggest that NOS and PUM can regulate hb translation by two mechanisms: removal of the poly(A) tail and a poly(A)-independent pathway that directly affects translation.

3' Untranslated Regions↗

[Therapy of osteoporosis from the viewpoint of evidence-based medicine].

DEFINITION AND SOCIOECONOMIC ASPECTS: Osteoporosis is a disease characterized by low bone mass and an increased susceptibility to fractures. It represents an enormous burden for the social security systems in developed countries. In Germany, approximately two million women and 800,000 men suffer from vertebral fractures and estimates for hip fracture incidence are in the range of 70,000-130,000 per year. The resulting costs for hip fractures alone could be calculated to 3-5 billion German marks. THERAPY ACCORDING TO EVIDENCE-BASED MEDICINE (EBM): According to Sackett et al. 1996, evidence-based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence-based medicine means integrating individual clinical expertise with the best available external evidence from systematic research. OSTEOPOROSIS THERAPY: The goal of osteoporosis therapy is to prevent fractures and several therapeutic options are available for this disease. With respect to proven fracture benefit, however, the quality of evidence from randomized clinical trials varies substantially among therapies. From systematic research the best external evidence is available for a supplementation with calcium and vitamin D and a therapy with the bisphosphonates alendronate or risedronate, as well as the SERM raloxifene. For other therapeutic agents like fluorides, vitamin D metabolites, calcitonin, and etidronate the quality of evidence is much lower. So far, there is no evidence for other pharmaceutical therapies. Hip protectors are effective for the prevention of hip fractures.

Clinical Trials as Topic↗

Complex arrangement of genes within a 220-kb region of double-duplicated DNA on human 2q37.1.

Gene duplication events are followed by divergence of initially identical gene copies, due to the subsequent accumulation of mutations. These mutations tend to be degenerative and may lead to either nonfunctionalization or subfunctionalization of the gene copies. Here we report the molecular characterization of a 220-kb genomic DNA fragment from human 2q37.1, in which a double duplication and a partial triplication event has taken place. As a result, this region contains four copies of alkaline phosphatase (P), four copies of the ECEL1 gene (X), two copies of a newly identified gene (N), and two copies of a cholinergic receptor subunit (R), in the order N-P-X-P-X-P-X-N-P-X-R-R. While three of the four ECEL1 copies, one copy of the phosphatase gene and one copy of the newly identified gene have lost their function, three phosphatase gene copies and the two receptor subunits are still functionally active and thus may provide an example for subfunctionalization of duplicated genes.

Alkaline Phosphatase↗

Oogenesis: Setting one sister above the rest.

Recent studies have revealed that the Par-1 protein, in addition to its established role in anterior-posterior patterning of the Drosophila oocyte, has both microtubule-dependent and microtubule-independent roles very early in oogenesis.

Animals↗

[The significance of postprandial glycemia].

Both acute and chronic hyperglycemia cause tissue lesions which ultimately lead to micro- and macrovascular diabetic complications. The newly developed insulin secretagogues and quick-acting insulin analogues are pharmacological options to reduce the amplitude of glucose fluctuations, thereby reducing acute glucose toxicity. There is hope that new pathophysiologically based therapeutic options will improve glucose control of type 2 diabetes and that physicians can be convinced to change their frequently expressed opinion that rising glucose levels represent the natural course of the disease. The Diabetes Control and Complications Trial has clearly shown that intensive insulin therapy is effective in treating complete insulin deficiency in type 1 diabetes over many years, achieving a stable HbA1c and thereby preventing diabetic complications [1].

Blood Glucose↗

Adsorption and Bioactivity of Protein A on Silicon Surfaces Studied by AFM and XPS.

The adsorption of protein A on silicon surfaces was studied by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy. The deposition was made statically from various concentrations of protein A in water solution. The biological activity was checked by the immobilization of rabbit immunoglobulin G. The protein adsorption occurs in least two different phases and leads to a multilayer film. The first monolayer of proteins is rapidly adsorbed on the surface. The adsorption of the second layer of proteins occurs much more slowly (a thousand times slower) and also involves the third monolayer. The protein A of the first monolayer is denaturated and biologically inactive. On the contrary, the proteins of the second monolayer keep their natural diameter and remain biologically active. AFM artifacts such as the convolution with small objects and the resulting estimation of the coverage ratio are discussed. Copyright 2001 Academic Press.

Journal Article↗

Overexpression of glutamine:fructose-6-phosphate-amidotransferase induces transforming growth factor-beta1 synthesis in NIH-3T3 fibroblasts.

Increased flux through the hexosamine biosynthetic pathway with glutamine:fructose-6-phosphate-amidotransferase (GFAT) as rate-limiting enzyme has been linked to the enhanced bioactivity of the prosclerotic cytokine transforming growth factor beta1 (TGF-beta1) in fibrotic complications, particularly in diabetic kidney disease. Here, we investigate in a stable transfection system the effect of overexpression of GFAT on TGF-beta1 synthesis in NIH-3T3 fibroblasts. We demonstrate a 1.8-fold stimulation of TGF-beta1 mRNA and a 1.9-fold increased protein expression, whereas TGF-beta2 production was not upregulated. The 1.5-fold enhanced TGF-beta1 promoter activity suggests a transcriptional regulation. The elevated TGF-beta1 protein is biologically active since GFAT-overexpressing cells exhibit a 2-fold fibronectin production. The results indicate a GFAT-dependent induction of TGF-beta1 synthesis.

3T3 Cells↗

Alkaline liquid chromatography/electrospray ionization skimmer collision-induced dissociation mass spectrometry for phosphopeptide screening.

A rapid on-line method for the identification of phosphorylated peptides in enzymatic protein digests by specific marker ion signals is described. In our study we investigated the use of alkaline conditions together with a previously described method for selective and sensitive detection of phosphopeptide ions combining high-performance capillary liquid chromatography (LC) and electrospray ionization mass spectrometry (ESI-MS). Phosphorylation-specific marker ions (m/z 79, PO(3)(-), and m/z 97, H(2)PO(4)(-)) were generated by skimmer collision-induced dissociation (sCID) in the negative-ion mode. The method was evaluated and validated for mono-phosphorylated synthetic peptides using different alkaline pH values and CID offsets. Alkaline conditions (pH 10.5) enhance the generation of phosphopeptide-specific fragment ions from serine- and tyrosine-phosphorylated peptides, and enable the use of m/z 79 (PO(3)(-)) and m/z 97 (H(2)PO(4)(-)) as phosphorylation-specific marker traces. Note that HPLC separation in trifluoroacetic acid containing solvents impairs the use of m/z 97 (C(2)F(3)O(-) fragment ion at m/z 97) as a phosphorylation-specific marker. The optimized method was applied for the detection of phosphorylated peptides in a tryptic beta-casein digest. The expected mono- and tetra-phosphorylated peptides were detected and rapidly identified by (mu)LC/ESI-sCID-MS and (mu)LC/ESI-MS analysis.

Alkalies↗

Reversible central pontine and extrapontine myelinolysis in a 16-year-old girl.

A rare case of an osmotic demyelination syndrome in a 16-year-old girl is presented. MRI in the acute stage revealed a focal abnormal signal within the basis pontis and both caudate nuclei and putamina. Two years later brain lesions had disappeared on T1- and T2-weighted imaging, indicating that central pontine and extrapontine myelinolysis may be completely reversible.

Adolescent↗

Perfusion and diffusion magnetic resonance imaging in human cerebral venous thrombosis.

BACKGROUND: Diagnosis of cerebral venous thrombosis (CVT) is usually achieved by digital subtraction angiography or magnetic resonance angiography, while structural brain tissue damage can be assessed by computed tomography or magnetic resonance imaging (MRI). Using perfusion and diffusion weighted imaging (PWI, DWI) we aimed in this study to identify pathophysiological patterns corresponding to only functional and hence reversible tissue involvement. METHODS: PWI, DWI, and conventional MRI were performed in six CVT patients acutely and after 16-26 days when their clinical condition had improved. All patients were treated with partial thromboplastin time-effective intravenous heparin. After intravenous administration of a paramagnetic contrast agent, bolus track PWI allows pixel based determination of mean transit time (MTT) and cerebral blood volume (CBV). DWI was performed with two different b values (0, 1000 s/mm2) for calculation of apparent diffusion coefficient (ADC) maps. RESULTS: In five of six cases increased MTT values were observed initially, whereas the CBV was normal, indicating a reduction of cerebral blood flow. ADC values were normal. On follow up after clinical recovery MTT prolongations had resolved. Areas with prolonged MTT did not evolve into structural lesions. CONCLUSION: In patients with CVT, prolongations of MTT in the absence of changes in CBV and ADC seem to indicate reversible involvement of brain tissue, a situation corresponding to the ischaemic penumbra.

Adult↗

Clinical and technical evaluation of a new self-monitoring blood glucose meter: assessment of analytical and user error.

Our study aimed to validate (against the standards of the American Diabetes Association and the International Organization for Standardization) the analytical and clinical accuracy of the new MediSense Precision Plus Electrodes on the QID system when compared with a reference method using the Abbott Vision glucose analyzer. Previous studies have shown that the overall accuracy of the device also depends on the proficiency of the operator, so we also assessed the 'ease of use' of the MediSense system, by comparing the results obtained by the patient and health care professional. Accuracy of the self-monitored blood glucose measurements was evaluated over a wide range of glucose readings (2.6-20.0 mmol/l). Between-run CVs (using the manufacturer's quality control material) were found to be 7% at 2.7 mmol/l and 4.8% at 15.5 mmol/l (n=380). We used the error-grid analysis with target range blood glucose, then separated the data into different subsets. We found that 100% of all measurements were in the clinically acceptable zones of A and B. All measured values of the MediSense QID system complied with the requirements for 'blood glucose monitoring meters', as proposed by the International Organization for Standardization. The rating of the patient questionnaire showed a good to very good overall rating and acceptance with a short instruction time. The results indicate that that the MediSense QID/Precision Plus Electrodes is a reliable and easy to use device, which can be recommended for the majority of patients with diabetes mellitus.

Adult↗

Moving towards the next generation.

In most organisms, primordial germ cells are set aside from the cells of the body early in development. To form an embryonic gonad, germ cells often have to migrate along complex routes through and along diverse tissues until they reach the somatic part of the gonad. Recent advances have been made in the genetic analysis of these early stages of germ line development. Here we review findings from Drosophila, zebrafish, and mouse; each organism provides unique insight into the mechanisms that determine germ cell fate and the cues that may guide their migration.

Animals↗