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At least 397 records · Page 22Linked to original sources

PubMed2000

Decreased plasma levels of nitric oxide derivatives in obstructive sleep apnoea: response to CPAP therapy.

BACKGROUND: Reduced endothelium dependent vasodilation has been reported in patients with obstructive sleep apnoea (OSA) but direct measurements of the most potent naturally occurring vasodilator, nitric oxide (NO) or its derivatives (nitrate and nitrite, NO(x)), have not yet been performed in these patients. METHODS: In 21 patients with OSA of mean (SE) age 54 (2) years, body mass index (BMI) 30.9 (1.1) kg/m(2), and apnoea-hypopnoea index (AHI) 37 (4)/h, NO(x) levels were measured in peripheral venous blood samples by chemiluminescence. Blood samples were obtained before and after two nights of continuous positive airway pressure (CPAP) and after 5.5 (1.5) months of follow up. Thirteen age matched, healthy volunteers and 18 patients without OSA but with a similar spectrum of comorbidity served as controls (control groups 1 and 2). RESULTS: Before CPAP NO(x) levels were 21.7 (1.5) microM in patients with OSA compared with 42.6 (2.2) microM and 36.7 (1.7) microM in control groups 1 and 2, respectively (p<0.01 for each comparison). NO(x) concentrations increased to 32.1 (2.7) microM after two nights of CPAP and remained constant at 32.9 (2.3) microM at follow up (p<0.01 compared with levels before CPAP). CONCLUSIONS: Plasma NO(x) levels are reduced in OSA and can be increased by short and long term CPAP therapy. Although the precise mechanism underlying this observation remains to be clarified, it may have important implications for the development of cardiovascular disease in patients with OSA and for the life saving effect of CPAP.

Case-Control Studies↗

PubMed1975

Anticipation of dental anomalies induced by radiation therapy.

Therapeutic irradiation of the head and neck of children up to the age of 16 years can cause malformation and developmental arrest of the permanent teeth. Dental anomalies occurring after irradiation of the palatal tumor in an 8-year-old are described and compared with a normal 8-year-old's developmental sequence to demonstrate that the immature, noncalcified dental structures are most susceptible to radiation injury. The stage of dental development at the time of therapy may be precisely determined by a routine oral radiographic survey, which provides a reliable estimate of the deformation that may be anticipated following radiotherapy.

Child↗

PubMed2004

Sensitization of tumor-associated endothelial cell apoptosis by the novel vascular-targeting agent ZD6126 in combination with cisplatin.

PURPOSE: ZD6126 is a novel vascular-targeting agent that selectively disrupts the tubulin cytoskeleton of endothelial cells. In the immature vessels characteristic of tumor vasculature, this leads to endothelial cell contraction, blood vessel congestion, and, consequently, tumor cell death. ZD6126 has been shown to delay tumor growth in a range of xenograft models. The antitumor effect of ZD6126 can be increased in combination with cisplatin or radiation therapy, although the precise mechanism of this enhancement has not been demonstrated. ZD6126 treatment has also been shown to inhibit lung metastasis, and the present study has explored the potential to increase the antimetastatic effect of ZD6126 by combining with cisplatin, and the underlining mechanism has been investigated. EXPERIMENTAL DESIGN: Human lung adenocarcinoma PC14PE6 cells were injected into the tail vein of nude mice. Five weeks after injection animals were treated with ZD6126 (200 mg/kg i.p.), cisplatin (6 mg/kg i.v.), or a combination of the two agents. The animals were sacrificed 24 hours later, and the extent of lung metastases and the presence of apoptotic cells were assessed. RESULTS: Histologic analysis revealed that the ZD6126/cisplatin combination resulted in a 2 to 4-fold increase in the total number of tumor-associated apoptotic cells compared with either treatment alone. ZD6126 alone induced apoptosis of tumor-associated endothelial cells in tumors, and the extent of apoptosis was increased 2-fold in combination with cisplatin. The lung weight was significantly reduced, and the number of metastatic nodules significantly was lower in the combined treatment group than in the control group. CONCLUSIONS: These data suggest that the antimetastatic effect of the vascular-targeting agent ZD6126 can be increased by use in combination with cisplatin, which increases the incidence of endothelial cell apoptosis.

Animals↗

PubMed1993

Growth hormone and diabetes mellitus. A review of sixty-three years of medical research and a glimpse into the future?

The diabetogenic action of pituitary extracts containing growth hormone has been recognised for more than 60 years and the importance of growth hormone in the development and progression of diabetic retinopathy for more than 30 years. Hypophysectomy was the first effective treatment for retinopathy but was discontinued because of the risk of severe hypoglycaemia that it produced and the development of an alternative, less dangerous therapy--photocoagulation. The precise role and significance of growth hormone in diabetes care, however, remains to this day a mystery. The fact that modern, highly purified biosynthetic preparations of growth hormone still retain full diabetogenic potency and the fact that diabetes develops in up to 25% of patients with acromegaly indicate growth hormone's potential for involvement in the aetiology of diabetes mellitus, although most will agree that this is not likely to be an important factor in the large majority of 'idiopathic' cases. There is strong evidence to indicate a substantial hypersecretion of growth hormone in 'idiopathic' diabetes mellitus (particularly insulin-dependent cases and those with retinopathy), which appears to be more related to residual pancreatic insulin secretion than to metabolic control. Since the advent of biosynthetic growth hormone in sufficient quantity to perform trials in adults, we are more aware of growth hormone's considerable potency in the regulation of body composition, growth factor production and intermediary metabolism. In this article, we review the literature and, from this and our own work, propose a new hypothesis which links the hypersecretion of growth hormone to reduced hepatic secretion of insulin-like growth-factor I (IGF-I) as a direct result of reduced portal insulin levels in diabetes mellitus. The hypersecretion of growth hormone exposes peripheral organs such as the retina and kidney to conditions favouring the expression of growth-hormone-dependent growth factors such as IGF-I which may contribute to the development of diabetic microvascular disease by autocrine and/or paracrine effects. If this hypothesis proves to be true, it offers new opportunities for the prevention of diabetic microvascular complications through suppression of growth hormone secretion which in turn will increase insulin sensitivity and facilitate good glycaemic control.

Diabetes Complications↗

PubMed1991

Renal cyst formation as a complication of primary distal renal tubular acidosis.

Morphologic studies using renal sonography and CT scanning were performed in 6 patients with primary distal renal tubular acidosis who were followed for 6 to 18 years. Nephrocalcinosis and renal cysts were identified in all patients. Multiple bilateral renal cysts were detected in 3 patients, and unilateral single or several renal cysts were detected in 3 patients. Size and number of the renal cysts in 1 patient did not change over 5 years of alkali therapy. Although the precise mechanism for renal cyst formation has not yet been established, renal cysts may be a common complication of primary distal renal tubular acidosis.

Acidosis, Renal Tubular↗

PubMed2006

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects.

BACKGROUND: Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties. RESULTS: Bioconjugates were prepared from different combinations of the approved drug, saquinavir, the antiviral agent, R.I.CK-Tat9, the polymeric carrier, poly(ethylene) glycol and the cell uptake enhancer, biotin. Anti-HIV activities were measured in MT-2 cells, an HTLV-1-transformed human lymphoid cell line, infected with HIV-1 strain Vbu 3, while parallel studies were performed in uninfected cells to determine cellular toxicity. For example, R.I.CK-Tat9 was 60 times more potent than L-Tat9 while the addition of biotin resulted in a prodrug that was 2850 times more potent than L-Tat9. Flow cytometry and confocal microscopy studies suggest that variations in intracellular uptake and intracellular localization, as well as synergistic inhibitory effects of SQV and Tat peptides, contributed to the unexpected and substantial differences in antiviral activity. CONCLUSION: Our results demonstrate that highly potent nanoscale multi-drug conjugates with low non-specific toxicity can be produced by combining moieties with anti-HIV agents for different targets onto macromolecules having improved delivery properties.

Journal Article↗

PubMedDate not supplied

The spectrum of congenital myasthenic syndromes.

The past decade saw remarkable advances in defining the molecular and genetic basis of the congenital myasthenic syndromes. These advances would not have been possible without antecedent clinical observations, electrophysiologic analysis, and careful morphologic studies that pointed to candidate genes or proteins. For example, a kinetic abnormality of the acetylcholine receptor (AChR) detected at the single channel level pointed to a kinetic mutation in an AChR subunit; endplate AChR deficiency suggested mutations residing in an AChR subunit or in rapsyn; absence of acetylcholinesterase (AChE) from the endplate predicted mutations in the catalytic or collagen-tailed subunit of this enzyme; and a history of abrupt episodes of apnea associated with a stimulation dependent decrease of endplate potentials and currents implicated proteins concerned with ACh resynthesis or vesicular filling. Discovery of mutations in endplate-specific proteins also prompted expression studies that afforded proof of pathogenicity, provided clues for rational therapy, lead to precise structure function correlations, and highlighted functionally significant residues or molecular domains that previous systematic mutagenesis studies had failed to detect. An overview of the spectrum of the congenital myasthenic syndromes suggests that most are caused by mutations in AChR subunits, and particularly in the epsilon subunit. Future studies will likely uncover new types of CMS that reside in molecules governing quantal release, organization of the synaptic basal lamina, and expression and aggregation of AChR on the postsynaptic junctional folds.

Acetylcholinesterase↗

PubMed1998

Efficacy of long-term sulfamethoxazole-trimethoprim therapy in a boy with hyperimmunoglobulin E syndrome.

A boy with hyperimmunoglobulin E syndrome (HIE syndrome), who was successfully treated with long-term sulfamethoxazole-trimethoprim (SMX-TMP) is reported. He had been suffering from recurrent pruritic dermatitis soon after birth and had a significant high level of serum immunoglobulin E. Although an initiation of SMX-TMP therapy resulted in resolution of his clinical manifestations, cessation of the treatment exacerbated the symptoms. Chemoprophylaxis of other oral antibiotics, which were suitable for Staphylococcus aureus isolated from lesions of the patient were unsuccessful. Another trial of low-dose SMX-TMP therapy resulted in gradual subsidence of the clinical manifestations. From these observations, efficacy of SMX-TMP therapy to prevent bacterial infection in the patient is clinically apparent. Although precise mechanism of the therapy remains speculative, long-term SMX-TMP therapy might be of benefit and low clinical toxicity in HIE syndrome.

Anti-Bacterial Agents↗

PubMed1986

Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.

Administration, Cutaneous↗

PubMed2004

Mitotic cell death in BEL-7402 cells induced by enediyne antibiotic lidamycin is associated with centrosome overduplication.

AIM: Mitotic cell death has been focused on in tumor therapy. However, the precise mechanisms underlying it remain unclear. We have reported previously that enediyne antibiotic lidamycin induces mitotic cell death at low concentrations in human epithelial tumor cells. The aim of this study was to investigate the possible link between centrosome dynamics and lidamycin-induced mitotic cell death in human hepatoma BEL-7402 cells. METHODS: Growth curve was established by MTT assay. Cell multinucleation was detected by staining with Hoechst 33342. Flow cytometry was used to analyze cell cycle. Aberrant centrosomes were detected by indirect immunofluorescence. Western blot and senescence-associated beta-galactosidase (SA-beta-gal) staining were used to analyze protein expression and senescence-like phenotype, respectively. RESULTS: Exposure of BEL-7402 cells to a low concentration of lidamycin resulted in an increase in cells containing multiple centrosomes in association with the appearance of mitotic cell death and activation of SA-beta-gal in some cells, accompanied by the changes of protein expression for the regulation of proliferation and apoptosis. The mitochondrial signaling pathway, one of the major apoptotic pathways, was not activated during mitotic cell death. The aberrant centrosomes contributed to the multipolar mitotic spindles formation, which might lead to an unbalanced division of chromosomes and mitotic cell death characterized by the manifestation of multi- or micronucleated giant cells. Cell cycle analysis revealed that the lidamycin treatment provoked the retardation at G2/M phase, which might be involved in the centrosome overduplication. CONCLUSION: Mitotic cell death and senescence can be induced by treatment of BEL-7402 cells with a low concentration of lidamycin. Centrosome dysregulation may play a critical role in mitotic failure and ultimate cell death following exposure to intermediate dose of lidamycin.

Aminoglycosides↗

PubMed2003

Chromosomal translocations involved in non-Hodgkin lymphomas.

CONTEXT: The discovery that recurrent chromosomal translocations are involved in the pathogenesis of non-Hodgkin lymphomas has greatly improved our understanding of these diseases and revolutionized their diagnosis. OBJECTIVE: To review the mechanisms by which chromosomal translocations occur and contribute to the pathogenesis of various types of non-Hodgkin lymphomas and to review the utility of molecular genetic methods for the assessment of these translocations. DATA SOURCES AND STUDY SELECTION: Primary research studies and reviews published in the English language that focus on chromosomal translocation and non-Hodgkin lymphomas. DATA EXTRACTION AND SYNTHESIS: Chromosomal translocations, which usually result in oncogene activation, occur in many types of B- and T-cell lymphoma, and their detection is helpful for establishing an accurate diagnosis and monitoring disease following therapy. However, the precise mechanisms that explain how translocations occur remain unknown, although for some types of translocations a clear relationship has been established with immunoglobulin gene rearrangement mechanisms. In recent years, a number of genes deregulated by chromosomal translocations have been identified, and the detailed molecular mechanisms by which chromosomal translocations contribute to the pathogenesis of non-Hodgkin lymphoma are beginning to be elucidated. CONCLUSIONS: Molecular genetic analysis has played a major role in improving our understanding of B- and T-cell non-Hodgkin lymphomas and has allowed more precise definition of lymphoma types. Molecular genetic tests to detect these translocations are important ancillary tools for the diagnosis and classification of malignant lymphomas.

Chromosome Breakage↗

PubMed1999

[New epileptic syndromes].

The recent and increasing interest for previously undescribed forms of epilepsy has been due to the description of families in which several affected members presented specific forms of epilepsy. Most epilepsies representing the description of new epilepsy phenotypes are partial epilepsies, although a new form of generalized epilepsy (generalized epilepsy with febrile seizures plus or GEFS+) has also been described. Our understanding of the clinical and genetic characteristics of the new familial epilepsy syndromes and the identification of informative families should accelerate the discovery of the basic mechanisms implicated in the production of partial seizures. The recent description of the syndrome of autosomal dominant nocturnal frontal lobe epilepsy, its localization to chromosome 20, the identification of the responsible gene (the alpha 4 subunit of the nicotinic cholinergic receptor) and the characterization of a mutation in two families are a good example. The recognition of the new epilepsy syndromes is of great interest for clinical neurologists and should lead to the establishment of more precise prognoses and therapies. In those families with several affected members, genetic knowledge may be important for genetic counseling purposes.

Epilepsy↗

PubMed1976

Arterial vasoconstrictor therapy for bleeding oesophageal varices.

Upper gastrointestinal bleeding in patients with hepatic cirrhosis carries considerable mortality. Difficulties are encountered both in determining the source of bleeding and in controlling blood loss. The techniques of selective visceral angiography not only supply diagnostic information, but can be used to administer selective intra-arterial vasoconstrictor therapy to control blood loss. We report our experience with 28 patients in whom angiography was performed with particular reference to six patients treated with selective vasoconstrictor therapy. Although the precise role of the technique is not yet established, early experience is most promising. We believe it will play an important role in a difficult group of patients in the future and may well supplant present methods of controlling bleeding.

Adult↗

PubMed2001

Problems and possibilities in understanding the natural history of asthma.

In early life, asthma symptoms can occur intermittently or may not be severe enough to limit normal activities, which makes it difficult for the clinician to make reliable predictions and administer therapy with some precision. In the case of pediatric asthma, the identification of children who will experience the development of a clinically important illness that will impair their quality of life can be a complex process. The usual methods for describing this information include the prognostic statistics of sensitivity, specificity, likelihood ratio, and positive predictive value. The sensitivity, specificity, and likelihood ratio of various early markers of asthma have been calculated from several cohort studies. (J Allergy Clin Immunol 2000;106:S144-52.)

Asthma↗

PubMed2001

[Comparison between arteriography and magnetic resonance angiography in patients with leg peripheral arterial disease ].

PURPOSE: The anatomic information before surgical therapy must be precise. Contrast angiography fails to opacify distal vessels in a large number of cases. We have evaluated the capability of magnetic resonance angiography to depict peripheral arteries. Materials and methods. We examined fourty-eight patients. CA was performed from a femoral or humeral approach, with or without subtraction. MRA were obtained using a 1.5 T magnet. Ankles and feet were placed in a head coil; three sequences were performed: Reconstructions and axial source images were reviewed. RESULTS: MRA is superior to CA to demonstrate patent arterial segments in a majority of cases. CONCLUSION: MRA is an effective method to identify distal lower extremity arteries.

Aged↗

PubMed2001

[Opto-electronic techniques and 3D body surface reconstruction for the control of patient positioning in the radiotherapy of breast cancer].

PURPOSE: In radiotherapy clinical practice, the currently existing gap between the high degree of accuracy in treatment planning and, the possibility of conforming the high-energy radiation beams on the one hand, and the uncertain set-up of each irradiation session on the other is a decisive factor for optimizing radiation treatment. Indeed there is wide experimental evidence that the current methods used for patient alignment and immobilization do not guarantee the necessary precision in delivering therapy with respect to the specifications of the treatment plan. The main reason for this is the lack of control systems that may be applied systematically to provide quantitative real-time feedback on the quality of patient repositioning and immobility during radiation emission. MATERIAL AND METHODS: Opto-electronic techniques and body surface registration methods were sygergisically used for the automatic three-dimensional verification and correction of patient position at the therapy unit. The method is based on radiotherapy applications of real-time opto-electronic human motion analysis using passive markers to control patient repositioning and to acquire and describe body surfaces in three dimensions. The quantitative detection of the localization error relies on the real-time detection of the position of an hybrid set of control points, namely physical passive markers and laser light markers, and their immediate comparison with a reference data set. The data set consists of the reference positions of the passive markers and a three-dimensional model of the body surface. The method was experimentally tested at the Radiotherapy Division of the European Institute of Oncology to control the repositioning of a phantom and of a volunteer, with reference to the clinical realignment procedure applied for breast cancer radiotherapy. RESULTS: The results confirm that the technique represents a valuable method to detect and automatically correct localization errors in the irradiation set-up. The use of the information provided by the laser markers allows one to reduce the potential inaccuracies in the manual relocation of the passive markers on the subject's skin and guarantees that position control is based on a redundant set of data describing the three-dimensional localization and configuration of the irradiated body surface portion. The experimental results show that the initial displacements of the controlled body area were systematically reduced to median values below 1 millimeter and 1.2 millimeters for the phantom and the volunteer, respectively. CONCLUSIONS: The synergistic use of opto-electronic technologies and stereophotogrammetric techniques associated to surface registration methods proved to provide an accurate description of the spatial transformation between the reference position and the actual position of the controlled body area. This allowed us to define an effective procedure to correct the patients position and recover the quality of the irradiation set-up, in agreement with the clinical requirements. The reported results confirm that the dynamic sensing of the body surface by opto-electronic technologies is a particularly promising technique that allows to systematically achieve swift and accurate patient alignment, thus ensuring that the treatment plan specifications are reproduced in the reality of each irradiation session.

Algorithms↗

PubMed2002

[Present and future of flat panel detectors in the world].

Present status of development of flat panel detectors and their clinical application in the world have been surveyed, and future trends are also explored especially in the field of material researches and methods of manufacturing. Also the importance of role of medical physicists on user side is described because characteristic physics measurement of a detector assembly is unavoidable and essential in quality assurance in clinical routine and acceptance test in hospitals. Even though physics measurements and clinical evaluations on flat panel detectors have shown remarkable progress and advances in these several years, future problems of cost down in manufacturing and quality assurance to prevent individual differences between detector assemblies must be resolved. Results of evaluation in mammography, chest radiography, fluoroscopy for cardiovascular examination, bone tumor examination and radiotherapy application indicate that flat panel detectors are future promising materials. Their systematic operation is contributing to heighten accuracy of image examinations and preciseness of radiation therapy. Encouragement to medical physicists relevant to flat panel detectors is also raised in this paper.

Fluoroscopy↗

PubMed2004

[Management strategy in neuroblastoma].

Neuroblastoma is one of the most common (7-10%) childhood cancers and the most frequent malignancy in neonates and infants. The disease course depends not only on the child's age and clinical stage but also on other factors, especially cytogenetic and molecular abnormalities. The currently employed treatment modalities should cure at least 60% of all neuroblastoma patients. But, in a very high risk group (age >1 year, stages 2 and 3 with N-MYC amplification, all patients with stage 4), which constitutes more than half of patients, results of very intensive treatment remain still unsatisfactory. Fewer than one-third of children over one year of age with stage 4 neuroblastoma are expected to survive. The success of treatment depends not only on treatment, which intensity is tailored to the risk of individual patients, but also on detailed and precise diagnosis and therapy monitoring. Children with neuroblastoma, regardless of the presenting signs and age, should undergo comprehensive evaluation, including genetics and molecular studies. Majority of infants with neuroblastoma have a good prognosis, but choice of therapy in these patients depends on disease stage, critical organ function (Philadelphia score), surgical treatment possibilities and on the presence of the N-MYC amplification. Further improvement of therapeutic strategy, especially for advanced neuroblastoma, calls for associating individual centers in large groups, which would cooperate in completing research projects, which currently are being implemented in Europe. Novel treatment modalities should improve the treatment results in the high risk group, as well as decrease the late side-effects number in all children treated for neuroblastoma.

Age Factors↗