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Biomedical subjects

A Lang

Publications and source records attributed to A Lang.

At least 73 records · Page 4Linked to original sources

Net mass transfer of plasma cholesteryl esters and lipid transfer proteins in normolipidemic patients with peripheral vascular disease.

The role of plasma cholesteryl ester transfer and lipid transfer proteins in atherosclerosis is unclear. Recent data suggest both antiatherogenic and atherogenic properties for cholesteryl ester transfer protein (CETP). The overall effect of CETP on atherosclerosis may thus vary depending on individual lipid metabolism. To test whether lipid transfer parameters are of importance even in patients without major lipid risk factors for atherosclerosis, CETP mass and activity, net mass transfer of cholesteryl esters between endogenous lipoproteins (CET), and phospholipid transfer protein (PLTP) activity were determined in plasma from 18 normolipidemic male patients with peripheral vascular disease and 21 controls. Furthermore, lecithin: cholesterol acyltransferase (LCAT) activity was tested. The results show that CETP mass, CETP activity, and LCAT activity are not different between patients and controls. However, specific CETP activity (CETP activity/CETP mass) is lower in the patients (P < .02). On the contrary, higher CET is observed in patients' plasma (P < .001). Increased plasma PLTP activity (P = .052) is demonstrable in the patients. If the data of all subjects are combined, CET correlates positively with triglycerides ([TG], r = .45, P < .001) and with PLTP activity (r = .32, P < .05) but negatively with specific CETP activity (r = -.37 P < .05). CET and specific CETP activity remain significantly different in TG-matched patients and controls and are more strongly interrelated (r = -.71, P < .001), suggesting a higher and selective influence of lipid transfer inhibitor(s) on CET and CETP activity in the patients. CET allows the best discrimination between patients and controls in univariate and multivariate analysis. Eighty-eight percent of the subjects are correctly classified by CET as a single parameter. The results suggest that increased CET in the patients may reflect atherogenic alterations in TG metabolism and/or in lipid transfer protein activities despite normal fasting lipoprotein levels.

Aged↗

Analysis of edge glare phenomena in intraocular lens edge designs.

PURPOSE: To determine the image and relative intensity of reflected glare images from 4 commonly used intraocular lens (IOL) edge designs to assess the potential for noticeable postoperative edge glare. SETTING: University of Texas Medical School, Houston, Texas, USA. METHODS: The interaction of light rays from 4 common IOL edge designs were examined in an eye model using the OptiCAD 3-D radiometric ray-tracing program (Opticad Corp.). Comparison of the potential of the 4 edge designs to produce visual sensations was derived from plots of the spatial location and energy distribution of rays forming the retinal image. RESULTS: Edge designs with no anterior and posterior dioptric powers at the lens periphery (lenticular) and rounded corners distributed the edge glare rays over a large retinal area. Edge designs with sharp edges formed by "cropping" the anterior and posterior optic zones focused edge glare rays into distinct arc-shaped images. The peak intensity of the arc-shaped image was 8 to 10 times stronger than the peak intensity of the diffuse image formed by lenses with rounded edges. CONCLUSIONS: Rounded IOL edges distribute reflected glare image over a significantly greater area than sharp edges. Rounded edges reduce the potential for edge glare phenomena that appear to the patient as a thin crescent or partial ring.

Glare↗

Management of Parkinson's disease a review of current and new therapies.

The management of Parkinson's disease has undergone recent changes with the advent of new therapies, both pharmacotherapy and surgery. Available interventions are discussed. Levodopa remains the mainstay of therapy. New drugs include the dopamine agonists and COMT inhibitors. New dopamine agonists which may have a levodopa "sparing effect;" it has been suggested that some of the drugs should be considered as first line treatments for newly diagnosed Parkinson's disease patients. We review roles of these drugs. The concept of neuroprotection in neurodegenerative disorders such as Parkinson's disease became popular in the mid 1980s and it is hoped that eventually therapy will be directed at slowing progression of the disease. A great deal more work needs to be done before a suitable agent is identified as being neuroprotective. Potential neuroprotective agents are reviewed. Surgical therapies for Parkinson's disease consisting of various forms of lesion surgery as well as stimulation procedures are reviewed. Complications of drug therapy include motor problems such as motor response fluctuations, as well as psychiatric complications including levodopa-induced psychosis. Atypical neuroleptic agents and ECT for psychiatric syndromes associated with Parkinson's disease are discussed. Algorithms for the management of early disease as well as the management of psychosis in Parkinson's disease are included. Treatment options for advanced disease are tabulated.

Antiparkinson Agents↗

Gene regulation in hepatic stellate cell.

Hepatic stellate cells are now recognized as the major source of extracellular matrix in hepatic fibrosis. Following liver injury the hepatic stellate cell changes from a quiescent to an activated cell. The activation process includes an increased proliferation rate, a phenotypic change to a myofibroblast-like cell, loss of vitamin A stores, increased extra-cellular matrix protein synthesis and contractility. Furthermore, hepatic stellate cells have been implicated in hepatic inflammation through their ability to secrete cytokines and chemokines. Here, we review the literature on the molecular pathogenesis of hepatic stellate cells activation with emphasis on the most recent findings. The reviewed topics include transcriptional and post-transcriptional regulation of the genes encoding type I collagen in hepatic stellate cells; the role of the transcription factor nuclear factor Kappa B in the hepatic stellate cell activation; focal adhesion kinase and integrin-mediated signal transduction in hepatic stellate cell, and apoptosis in hepatic stellate cells. New insight into hepatic stellate cell activation and death may lead to the development of novel therapies for hepatic fibrosis.

Apoptosis↗

[Consensus on the diagnosis of multi-system atrophy].

We report the results of a consensus conference on the diagnosis of multiple system atrophy. We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible multiple system atrophy requires one criterion plus two features from separate domains. The diagnosis of probable multiple system atrophy requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite multiple system atrophy requires pathological confirmation.

Diagnosis, Differential↗

The ideal free distribution with unequal competitors: the effects of modelling methods.

We examine two methods of allocating animals between sites of different resource input rate in the context of the ideal free distribution. The basic models are of individuals of two classes of competitive weight distributing themselves between two sites. The importance of arrival sequence and the subsequent movements of animals between sites are investigated. When all the good competitors arrive before the poor competitors, the distribution of each class conforms to the input matching rule. When competitors arrive in a random sequence, poor competitors switch between patches. Resulting distributions are compared with predictions from the ideal free distribution with unequal competitors and from statistical mechanics. The comparisons show fewer animals using the site with the highest resource than predicted by the input matching rule, that is, undermatching is found. The effect of each animal having a unique competitive ability is then examined. We discuss the application of ideal free distribution models to areas of behavioural ecology other than foraging, together with alternative rules to the standard instantaneous intake rates rule. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Consensus statement on the diagnosis of multiple system atrophy. American Autonomic Society and American Academy of Neurology.

We report the results of a consensus conference on the diagnosis of multiple system atrophy (MSA). We describe the clinical features of the disease, which include four domains: autonomic failure/urinary dysfunction, parkinsonism and cerebellar ataxia, and corticospinal dysfunction. We set criteria to define the relative importance of these features. The diagnosis of possible MSA requires one criterion plus two features from separate domains. The diagnosis of probable MSA requires the criterion for autonomic failure/urinary dysfunction plus poor levodopa responsive parkinsonism or cerebellar ataxia. The diagnosis of definite MSA requires pathological confirmation.

Antiparkinson Agents↗

Efficacy and toxicity of 2-Chlorodeoxyadenosine (Cladribine)--2 h infusion for 5 days--as first-line treatment for advanced low grade non-Hodgkin's lymphoma.

2-Chlorodeoxyadenosine (Cladribine) is a new purine analogue with high activity in pretreated low grade non-Hodgkin's lymphoma (NHL). To evaluate the efficacy of this drug in untreated patients with advanced NHL, we performed a prospective multicentre trial. Cladribine (0.12 mg/kg) was administered intravenously daily for 5 consecutive days in an out-patient setting. The treatment was repeated every 28 days for four cycles. Included were patients with a histological diagnosis of low grade NHL according to the Kiel classification and stage III or IV disease. Stage II patients were included when radiotherapy had failed. 55 patients were entered into the study. 50 patients were evaluable. The remission rate was 44/50 (88%; 95% confidence interval 82-100%), including complete remissions (CR) in 14 (28%) patients. Only 2 patients showed progression while on Cladribine treatment. The estimated overall survival, and time to treatment failure (TTF) were 85% and 51%, respectively, after a median observation time of 92 weeks. 11 (22%) patients showed grade 3 or 4 toxicity according to the WHO grading. Haematological toxicity was responsible for 86% of the overall toxicity and 100% of grade 3 and 4 toxicity. 7 patients (14%) had an infection, two of which were opportunistic. 12 (24%) patients did not experience any toxicity during the treatment. The results of this study clearly demonstrate the safety and considerable activity of this regimen. Cladribine is very effective even at lower doses than have been used so far.

Adult↗

A concept analysis of parent-infant attachment.

A concept analysis, the clarification of a concept, is the first step towards building the foundations of nursing theory, research and practice. As a relevant concept for nurses working with childbearing families, parent-infant attachment is an important part of the body of nursing knowledge. Wilson's method of concept analysis was used to generate antecedents, critical attributes and consequences of parent-infant attachment, highlighting the need to refine measurements of this concept.

Canada↗

Infrequent mutation of the p16/MTS1 gene and overexpression of cyclin-dependent kinase 4 in human primary soft-tissue sarcoma.

The pl6INK4a/MTS1 (p16) gene encodes a specific inhibitor of cyclin-dependent kinase (CDK)4 and CDK6. The p16 gene is frequently mutated or deleted in many types of cancer cell lines as well as in certain types of primary tumors. p16 knockout mice are viable but predisposed to sarcoma and B-cell lymphoma. To investigate the role of p16 in human soft-tissue sarcoma tumor progression, we examined the p16 gene by Southern blot analysis and PCR sequencing in 30 pairs of primary soft-tissue sarcomas and autologous normal tissue. Only one tumor sample showed possible rearrangement of the p16 gene. In contrast, Western blot analysis of the p16 protein in 20 pairs of samples showed decreased p16 expression in only 20% of the tumors but elevated p16 expression in 40% of the tumors when compared with the autologous normal controls. Overexpression of p16 was not concomitant with loss of the RB protein as is found in several other types of cancers, because more than one-half of the tumors with increased p16 expression also had high levels of RB protein. On the other hand, the p16 target protein CDK4 was overexpressed in at least 60% of the tumors. In the majority of cases, CDK4 overexpression accompanied elevated p16 and/or RB levels. Our results suggest that: (a) alteration of the p16 gene is infrequent in primary soft-tissue sarcoma; (b) Cdk4 may act as an oncogene in soft-tissue sarcoma; and (c) elevated p16 and RB levels might be the result of compensatory up-regulation of these proteins to counteract CDK4 overexpression in these tumors. Our results also suggest that it is more informative to examine aberrations in the "p16-CDK4/cyclin D-RB" pathway than to selectively examine individual components in this pathway when investigating genetic changes involved in human malignancy.

Animals↗

Wild-type p53 and a p53 temperature-sensitive mutant suppress human soft tissue sarcoma by enhancing cell cycle control.

Soft-tissue sarcomas are a heterogeneous group of tumors that are putatively mesenchymal in origin. Therapeutic advances in this disease have been limited over the past several decades. Approximately one-half of all patients will ultimately succumb, usually to uncontrollable pulmonary metastases. Although little is known about the underlying molecular determinants driving soft-tissue sarcoma inception, proliferation, and metastasis, mutation of the p53 gene is the most frequently detected molecular alteration in this disease. Accordingly, we were interested in determining whether transduction of wild-type (wt) p53 into soft-tissue sarcomas bearing mutated p53 genes might alter the malignant phenotype. SKLMS-1 is a human-derived leiomyosarcoma cell line with a codon 245 p53 point mutation. Cationic liposome was used to transfect wt p53 or 143Ala temperature-sensitive mutant p53 into this cell line. SKLMS-1 stable transfectants expressing wt p53 had decreased cell proliferation in vitro, decreased in vitro colony formation in soft agar, and decreased tumorigenicity in severe combined immunodeficient mice in vivo. Flow cytometric analysis of cell cycle components demonstrated markedly increased G1 cell cycle arrest and decreased entry into S phase, which corresponded to the induction of p21cip1 protein in the transfectants. Using SKLMS-1 stable transfectants expressing the 143Ala p53 temperature-sensitive mutant, we demonstrated the kinetics of and the causal relationship between wt p53 expression, the wt p53-dependent induction of cell cycle inhibitor p21cip1, and inhibition of cell cycle progression in p53-transfected SKLMS-1 cells. The ability to restore wt p53 growth-regulatory functions in soft-tissue sarcoma may ultimately be useful as a future therapy in patients with soft-tissue sarcomas.

Animals↗

[Pica in Germany--amylophagia as the etiology of iron deficiency anemia].

Pica (pica = magpie) is an eating disorder that is manifested by a craving for oral ingestion of a given substance that is unusual in kind (nonfood items) or quantity (food items). Pica has been described as a world wide phenomenon, but there are more frequent occurrences of selected substances among selected groups--especially young children and black pregnant and nonpregnant women in the southern part of the USA. In Central Europe and Germany this syndrome has not been described in the moderne literature. For this reason, we report a case of pica for starch associated with severe iron deficiency anemia in Germany. Iron deficiency anemia and--less often-potassium and zinc deficiency are the main complications of an excessive starch or clay ingestion, followed by gastrointestinal obstructions due to gastroliths or impaction. Additionally, naphtalene poisoning (in pica for toilet air-freshener blocks), phosphorus poisoning (in matches pica), mercury poisoning (in paper pica), and lead poisoning (in dried paint pica) have been described.

Adult↗

Differential expression of mRNAs for endopeptidases in phenotypically modulated ('dedifferentiated') human articular chondrocytes.

Human articular chondrocytes modulated away from their original phenotype by serial subcultures in monolayer differentially express mRNAs for endopeptidases. The mRNAs for the cathepsins B and L are extremely low in differentiated cells, but are soon expressed in parallel with the loss of the differentiated state. In contrast, the mRNA for collagenase-1 is strongly expressed by differentiated chondrocytes and declines rapidly following phenotypic modulation. The mRNA for stromelysin-1 and the tissue inhibitor of metalloproteinases-2 is high and does not appreciably change after modulation. Chondrocyte activation induced by alteration of its original phenotype leads to the expression of endopeptidases in a way that markedly differs from that induced by cytokines. The results are relevant to cartilage catabolism in osteoarthritis and suggest a prominent role of fibroblastic metaplasia on the part of the chondrocytes as a mechanism of expressing catabolic endopeptidases.

Adult↗

Blood vessels of the sinus tarsi and the sinus tarsi syndrome.

This study describes the arterial and venous blood vessels in the sinus tarsi of a series of nine anatomical specimens and in a traumatically amputated leg, studied by arteriography. The sinus tarsi artery was formed in all cases from anastomoses between various arteries of the lateral region of the foot. These usually included the anterior lateral malleolar, and proximal lateral tarsal arteries; in 70% there was a branch from the distal lateral tarsal artery, and in 30% a branch from the peroneal artery. In all cases, there were anastomoses within the sinus tarsi between the sinus tarsi artery and the canalis tarsi artery, derived from the posterior tibial artery. Whatever its origins, the sinus tarsi artery was the principal supplier of intrasinusal structures and of the talus. There was a large venous plexus in the sinus tarsi, which drained particularly the venous outflow from the talus and the anterior part of the capsule of the posterior talocalcaneal joint to the lateral and medial venous systems of the foot. Posttraumatic fibrotic changes in the wall and surrounding tissue of the veins, causing disturbance of venous outflow and increased intrasinusal pressure, are proposed by the authors as one possible factor in the pathogenesis of the sinus tarsi syndrome.

Arteries↗

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Aged↗

N-acetyl-S-(dichlorophenyl)cysteines as suitable biomarkers for the monitoring of occupational exposure to 1,2-dichlorobenzene.

A method has been developed for the simultaneous analysis of the isomeric N-acetyl-S-(dichlorophenyl)cysteines (also known as dichlorophenylmercapturic acids, DCPMAs) in urine. This procedure allows the determination of 2,3- and 3,4-DCPMAs at the concentrations expected in the urine samples of employees occupationally exposed to 1,2-dichlorobenzene (1,2-DCB). The results of a 1,2-DCB exposure study under standardized conditions show a first-order kinetic for the excretion of DCPMAs, as well as acceptable linear correlations between the urinary concentrations of DCPMAs and the amount of inhaled 1,2-DCB. It therefore seems it would be possible to derive a biological tolerance value for 1,2-DCB based on isomeric DCPMAs as analytical parameters.

Acetylcysteine↗

Reversible dissociation of sensitivity to dynamic stimuli in Parkinson's disease: is magnocellular function essential to reading motion-defined letters?

A group of 20 control subjects carried out the following visual tests: Snellen acuity; contrast detection threshold for a temporally unmodulated grating and for a temporally modulated grating; speed threshold for recognising motion-defined dotted letters. Normal limits were defined as 2.5 standard deviations from the respective control means. A patient with Parkinson's disease carried out the tests 12 hr after medication was withheld at a time when symptoms were evident ("off" stage), and after administration of medication when it had taken full effect ("on" stage). Confirming previous reports, contrast detection threshold for the temporally modulated grating was much higher during the "off" stage than during the "on" stage, but contrast detection threshold for the temporally unmodulated grating showed little difference. Speed threshold for recognising motion-defined letters did not, however, fall during the "on" stage. We suggest that magnocellular function is not essential for the recognition of motion-defined form.

Contrast Sensitivity↗