Simultaneous genotyping for factor V Leiden and prothrombin G20210A variant by a multiplex PCR-SSCP assay on whole blood.
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DNA Primers↗
Biomedical subjects
M Meyer
Publications and source records attributed to M Meyer.
Palliative care and AIDS: 2--Gastrointestinal symptoms.
With the use of more intensive antiretroviral therapies (highly-active antiretroviral therapy, HAART) particularly in first world countries, reductions in the mortality and morbidity of HIV infection are being seen. However, though the prevalence of symptoms may change, symptom control does continue to be a problem for many people with HIV, particularly as their disease progresses. This is the second of 2 CME articles about palliative care and HIV infection. The first gave a background to palliative care, and covered symptom control of pain. This article gives suggestions for the treatment of common gastrointestinal symptoms in HIV infection; nausea and vomiting, cachexia and anorexia and chronic diarrhoea.
Acquired Immunodeficiency Syndrome↗
Oh no, here we go again. Health-care costs are soaring--and companies are passing the increases along to their workers.
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Choice Behavior↗
Rat fetal ventral mesencephalon grown as solid tissue cultures: influence of culture time and BDNF treatment on dopamine neuron survival and function.
Free-floating roller tube (FFRT) cultures of fetal rat and human nigral tissue are a means for tissue storage prior to grafting in experimental Parkinson's disease. In the present study, FFRT cultures prepared from embryonic-day-14 rat ventral mesencephalon were maintained for 4, 8, 12, or 16 days in vitro (DIV) in the presence or absence (controls) of BDNF [100 ng/ml]. The dopamine content in the culture medium, analyzed by HPLC, was significantly higher (4-5 fold) in the BDNF group at DIV 8 and DIV 12 compared to the corresponding control levels (40 pg/ml). The number of tyrosine hydroxylase immunoreactive neurons was significantly higher for BDNF treated cultures (2729+/-300) at DIV 8, as compared to controls (1679+/-217). At DIV 12, the culture volume was significantly increased by BDNF (1.05+/-0.12 vs. 0.71+/-0.04 mm3). Similar results were obtained for total protein. Western blot analysis demonstrated increasing signals for GFAP with increasing time in culture, but levels for control and BDNF treated cultures did not differ at any time-point investigated. In conclusion, it is suggested that the time window for effective storage of dopaminergic tissue prior to grafting can be extended by using the FFRT culture technique and that the in vitro storage may be further prolonged by treatment with BDNF.
Animals↗
The targeted deletion of the LAMC1 gene.
Laminin is required for the production of a basement membrane in both the early embryo and in the embryoid body. The absence of the gamma 1 chain leads to different processing of the other subunits in the trimer and prevents the production of a polymerizing laminin molecule. Collagen IV and perlecan are not able to compensate for the loss of the laminin molecule, and nidogen, which would normally bind to the gamma 1 chain, is almost completely lost from the embryoid body. In the embryo the failure of the basement membrane results in embryonic lethality at embryonic day 5.5, a time when the primitive endoderm is differentiating to visceral and parietal endoderm, and the latter is migrating out of the inner cell mass over the trophectoderm. It is likely that failure in one or both of these events leads to the death of the embryo. The absence of the trophectodermal basement membrane normally present in the blastocyst appears not to be necessary for the formation of the blastocystic cavity, which depends on the formation of a polarized epithelium. Hence the first epithelium produced in the developing embryo does so independently of a basement membrane.
Animals↗
Postrest potentiation of active force in mouse papillary muscles is greatly accelerated by increased stimulus frequency.
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Animals↗
Effect of cysteine replacements on the properties of the turgor sensor KdpD of Escherichia coli.
Escherichia coli responds rapidly to K+-limitation or high osmolarity by induction of the kdpFABC operon coding for the high affinity K+-translocating Kdp-ATPase. This process is controlled by the membrane-bound histidine kinase KdpD and the response regulator KdpE. Here, it is demonstrated that replacements of the native Cys residues at positions 409, 852, and 874 influence distinct activities of KdpD, whereas replacements of Cys residues at positions 32, 256, and 402 have no effect. Replacements of Cys409 in KdpD reveal that transmembrane domain I is important for perception and/or propagation of the stimulus. When Cys409 is replaced with Ala, kdpFABC expression becomes constitutive regardless of the external stimuli. In contrast, when Cys409 is replaced with Val or Tyr, induction of kdpFABC expression in response to different stimuli is drastically reduced. KdpD with Ser at position 409 supports levels of kdpFABC expression comparable to those seen in wild-type. Since neither the kinase nor phosphatase activity of these proteins is affected, it is proposed that different amino acid side-chains at position 409 alter the switch between the inactive and active forms of the kinase. When Cys852 or Cys874 is replaced with Ala or Ser, kinase activity is reduced to 10% of the wild-type level. However, kinetic studies reveal that the apparent ATP binding affinity is not affected. Surprisingly, introduction of Cys852 and Cys874 into a KdpD protein devoid of Cys residues leads to full recovery of the kinase activity. Labeling studies support the idea that a disulfide bridge forms between these two residues.
Bacterial Proteins↗
[Validation of the "Digest Questionnaire" for consistency and reproducibility with reference to upper abdominal symptoms].
"Digest" is a international effort to record the prevalence of digestive symptoms in the general population. The international questionnaire was tested in German translation for reliability and reproducibility. The questionnaire consists of 14 symptoms, which were investigated by standardized questions. Each symptom was described in 3 dimensions: frequency, severity and impact on daily activities. 127 successive patients referred for upper gastrointestinal endoscopy were interviewed twice by a young assistant and by an experienced gastroenterologist before the diagnostic work-up. A further 72 volunteers served as a control group. In these volunteers no upper gastrointestinal endoscopy was performed. Reliability and reproducibility were calculated by the Spearman rank test. The most frequent diagnoses were: organic diseases (oesophagitis [28], gastric ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases (dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was satisfactory by accepted standards (p > 0.7). Reliability was very good, with r-values for each symptom between p 0.96-0.99. The impact on daily activities was highest in the case of heart-burn or localized upper gastrointestinal pain, and lowest in the case of belching and fullness. The questionnaire can be easily administered by the non-specialist and the results discriminate well between functional/organic diseases and healthy people, thanks to excellent reproducibility and reliability.
Activities of Daily Living↗
Spectroscopic Techniques using Synchrotron Radiation and Free-Electron and Conventional Lasers.
Considerable progress in the investigation of the electronic and vibrational properties of atoms, molecules, materials, surfaces and interfaces has been achieved by combining different photon sources of complementary characteristics. In this paper some experimental results obtained recently at LURE by using two synchronized sources, such as the IR free-electron laser (FEL) CLIO, the VUV storage ring FEL, synchrotron radiation and table lasers, are presented. Using CLIO synchronized with a YAG laser allows the investigation of the vibrational properties of adsorbed species by the non-linear optical technique of visible-IR sum (difference) frequency generation, as shown for the adsorption of hydrogen on platinum in the electrochemical environment. The second result reported here relates to the study of the intersubband stimulated emission in GaAs/GaAlAs quantum wells by pump-probe experiments using the two-colour configuration of CLIO. The combination of a mode-locked Ar(+) laser and synchrotron radiation has been used for investigations in a pump-probe arrangement of the ionization of Xe atoms via the resonant state Xe* 5p(5)5d [3/2](1). The final example is a time-resolved core-level spectroscopy study of photoexcited Si(111) 2 x 1 surfaces by using a combination of the naturally synchronized UV storage ring laser and synchrotron radiation.
Journal Article↗
[Immobilizing muscle weakness accentuated in leg and proximal muscles].
A 54 year old waiter was referred to the hospital because of proximal muscle weakness, most pronounced in his legs, which progressed to an inability to stand or walk within weeks. Myopathy was diagnosed based on the muscle biopsy findings and myositis was ruled out by laboratory and biopsy results. Further investigations led us to exclude an endocrine cause, hypovitaminosis D, infectious myopathy or a paraneoplastic syndrome. Heteroanamnesis revealed severe alcoholism, lasting for more than 30 years. The presumed alcohol induced hepatopathy was confirmed by liver biopsy. There were no signs of an acute alcoholic myopathy, as the weakness had developed rather insidiously, there was no elevation of the CK serum level nor myoglobinuria and a type 2 fibre atrophy was found by muscle biopsy. As expected the weakness improved under abstention. Thus the final diagnosis of a chronic alcohol induced myopathy was established.
Alcoholism↗
Effects of combined BDNF and GDNF treatment on cultured dopaminergic midbrain neurons.
Neural transplantation is an experimental therapy for Parkinson's disease. Pretreatment of fetal donor tissue with neurotrophic factors may improve survival of grafted dopaminergic neurons. Free-floating roller tube cultures of fetal rat ventral mesencephalon were treated with brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), or a combination of both. Dopamine content of the culture medium, the number of tyrosine hydroxylase-immunoreactive neurons, and culture volumes were moderately increased in the BDNF- and GDNF-treated cultures but significantly increased by 6.8-, 3.2- and 2.4-fold, respectively after treatment with the combination of both factors. We conclude that pretreatment of dopaminergic tissue in culture with a combination of BDNF and GDNF may be an effective means to improve the quality of tissue prior to grafting.
Analysis of Variance↗
Urodilatin, a natriuretic peptide with clinical implications.
Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also profit from URO treatment, as it increases stroke volume and PCWP. Moreover, preliminary results from recent studies indicate that URO may also be effective in patients suffering from hepato-renal syndrome.
Acute Kidney Injury↗
Structure-activity relation of NH2-terminal human parathyroid hormone fragments.
Human parathyroid hormone (hPTH) is involved in the regulation of the calcium level in blood. This hormone function is located in the NH2-terminal 34 amino acids of the 84-amino acid peptide hormone and is transduced via the adenylate cyclase and the phosphatidylinositol signaling pathways. It is well known that truncation of the two NH2-terminal amino acids of the hormone leads to complete loss of in vivo normocalcemic function. To correlate loss of calcium level regulatory activity after stepwise NH2-terminal truncation and solution structure, we studied the conformations of fragments hPTH-(2-37), hPTH-(3-37), and hPTH-(4-37) in comparison to hPTH-(1-37) in aqueous buffer solution under near physiological conditions by circular dichroism spectroscopy, two-dimensional nuclear magnetic resonance spectroscopy, and restrained molecular dynamics calculations. All peptides show helical structures and hydrophobic interactions between Leu-15 and Trp-23 that lead to a defined loop region from His-14 to Ser-17. A COOH-terminal helix from Met-18 to at least Leu-28 was found for all peptides. The helical structure in the NH2-terminal part of the peptides was lost in parallel with the NH2-terminal truncation and can be correlated with the loss of calcium regulatory activity.
Amino Acid Sequence↗
Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70.
Brief ischemic periods lead to myocardial dysfunction without myocardial infarction. It has been shown that expression of inducible HSP70 in hearts of transgenic mice leads to decreased infarct size, but it remains unclear if HSP70 can also protect against myocardial dysfunction after brief ischemia. To investigate this question, we developed a mouse model in which regional myocardial function can be measured before and after a temporary ischemic event in vivo. In addition, myocardial function was determined after brief episodes of global ischemia in an isolated Langendorff heart. HSP70-positive mice and transgene negative littermates underwent 8 min of regional myocardial ischemia created by occlusion of the left descending coronary artery, followed by 60 min of reperfusion. This procedure did not result in a myocardial infarction. Regional epicardial strain was used as a sensitive indicator for changes in myocardial function after cardiac ischemia. Maximum principal strain was significantly greater in HSP70-positive mice with 88+/-6% of preischemic values vs. 58+/-6% in transgene-negative mice (P < 0.05). Similarly, in isolated Langendorff perfused hearts of HSP70-positive and transgene-negative littermates exposed to 10 min of global ischemia and 90 min of reperfusion, HSP70 transgenic hearts showed a better-preserved ventricular peak systolic pressure. Thus, we conclude that expression of HSP70 protects against postischemic myocardial dysfunction as shown by better preserved myocardial function.
Animals↗
[Infection registration underestimates the frequency of surgical wound infection].
Two consecutive bedside prevalence studies of 455 surgical patients were made by the same infection control nurse in 15 surgical and gynaecological departments in eight Danish hospitals. Four point six percent had a deep and another 4.6% a superficial surgical wound infection (SWI). Two months after the second survey only one third of the infections were correctly recorded by the hospital routine surveillance of surgical wound infections (SWI). Registration systems that are simpler and more valid than the existing ones need to be developed. A follow-up was carried out with self-administered questionnaires in 2976 patients, of whom 1447 (48.6%) responded. A patient-diagnosed SWI was defined as an antibiotic treatment of a wound and/or a wound reopening by a health care professional. A total of 311 patients were treated for a SWI, 42% with antibiotics, 27% with wound reopening and 31% received both these treatments. Post-discharge surveillance cannot be recommended as a routine.
Adult↗
Imaging the microvasculature of choroidal melanomas with confocal indocyanine green scanning laser ophthalmoscopy.
OBJECTIVE: To image the microvasculature of choroidal melanoma with a new confocal scanning laser ophthalmoscope. METHODS: Eighteen consecutive patients, each with a unilateral choroidal melanoma, were examined prospectively. Indocyanine green angiography was performed with a new confocal scanning laser ophthalmoscope that enabled serial optical sectioning through the tumor. Two additional patients were studied with indocyanine green angiography and confocal scanning laser ophthalmoscopy just before enucleation for posterior choroidal melanomas. The histologic identification of microvasculature patterns was compared with the angiograms for these patients. RESULTS: In the series of 18 patients, 16 (89%) indocyanine green angiograms with optical sectioning revealed tubular structures within the melanoma that were identified as tumor vessels based on their angiographic appearance. The microvasculature patterns identified by indocyanine green angiography correlated well with the histologic appearance of these microvasculature patterns in both patients for whom histologic verification was available. CONCLUSIONS: This preliminary study suggests that indocyanine green angiography with confocal scanning laser ophthalmoscopy images the microvasculature of choroidal melanomas and may be capable of detecting microvasculature patterns that have been shown to be prognostically significant from histopathological studies.
Adult↗
Bioavailability of morphine after administration of a new bioadhesive buccal tablet.
A new bioadhesive buccal morphine tablet was developed for controlled release delivery of drug and improved bioavailability compared with oral controlled release tablet. In order to characterize the pharmacokinetic properties of this bioadhesive buccal formulation, a bioavailability study was performed in 12 healthy volunteers who received: a 30 mg oral controlled release tablet (A); a 20 mg aqueous solution retained in the mouth for 10 min (B); and the 60 mg bioadhesive buccal tablet placed between the lower gum and lip for 6 h (C). The mean amount of morphine absorbed from the solution was very low, only 2 mg of the 20 mg dose. After administration of forms A and C, plasma levels exhibit typical sustained release concentration-time curves. The mean amount of drug recovered from the residual bioadhesive buccal tablet after 6 h indicated that approximately 50% of the dose was released from the bioadhesive buccal tablet. The relative bioavailability of the buccal tablet (corrected for residual unabsorbed dose) compared with the controlled-release tablet was 98% based on the morphine AUC values. Good correlations between the AUC and the Cmax of the bioadhesive tablet for the drug and metabolite plotted versus the amount of morphine absorbed were found.
Administration, Buccal↗
Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group.
The Multiple Sclerosis Collaborative Research Group trial was a double-blind, randomized, multicenter, phase III, placebo-controlled study of interferon beta-1a (IFNbeta-1a; AVONEX) in relapsing forms of multiple sclerosis. Initial magnetic resonance imaging results have been published; this report provides additional results. Treatment with IFNbeta-1a, 30 microg once weekly by intramuscular injection, resulted in a significant decrease in the number of new, enlarging, and new plus enlarging T2 lesions over 2 years. The median increase in T2 lesion volume in placebo and IFNbeta-1a patients was 455 and 152 mm3, respectively, at 1 year and 1,410 and 628 mm3 at 2 years, although the treatment group differences did not reach statistical significance. For active patients, defined as those with gadolinium enhancement at baseline, the median change in T2 lesion volume in placebo and IFNbeta-1a patients was 1,578 and -12 mm3 and 2,980 and 1,285 mm3 at 1 and 2 years, respectively. Except for a minimal correlation of 0.30 between relapse rate and the number of gadolinium-enhanced lesions, correlations between MR and clinical measures at baseline and throughout the study were in general poor. Once weekly intramuscular IFNbeta-1a appears to impede the development of multiple sclerosis lesions at an early stage and has a favorable impact on the long-term sequelae of these inflammatory events as indicated by the slowed accumulation of T2 lesions.
Brain↗