Search PubMed⌕ Search

Biomedical subjects

A May

Publications and source records attributed to A May.

At least 145 records · Page 8Linked to original sources
PubMed1998

Photodynamic ablation of early cancers of the stomach by means of mTHPC and laser irradiation: preliminary clinical experience.

BACKGROUND: Radical surgical treatment has been the first choice for early gastric cancer, but high resolution endosonography allows in situ diagnosis with a high sensitivity and specificity and in consequence the option of local endoscopic treatment. AIMS: To evaluate photodynamic therapy (PDT) using meso-tetrahydroxyphenyl-chlorin (mTHPC) as the photosensitiser in superficial gastric cancer. METHODS: Twenty two patients with superficial early gastric cancer received mTHPC (0.075 mg/kg intravenously) and were treated 96 hours later with red light at 652 nm (20 J/cm2). Tumour response was assessed by endoscopy and extensive biopsy. RESULTS: Endoscopies performed two to three days after PDT showed a haemorrhagic fibrinoid necrosis of the mucosal layer. Complete remission was achieved in 16/22 (73%) patients: 13/16 (80%) with intestinal type cancer and 3/6 (50%) with a diffuse Lauren's carcinoma. The mean follow up period was 12 months and 20 months, respectively. An average of 1.8 treatment sessions was required. Severe side effects were not observed. Seven patients had mild to moderate skin photo-sensivity reactions; 12 had local pain after PDT for 1-10 days. CONCLUSION: PDT using mTHPC as the photosensitiser represents a safe and efficient method for topical treatment of early gastric cancer, especially of Lauren's intestinal carcinoma. If the preliminary results can be verified in larger patient series and during long term follow up, local treatment of early cancers of the stomach by PDT could be considered as a therapeutic option for selected patients.

Adult↗
PubMed1998

Laser lithotripsy of difficult bile duct stones: results in 60 patients using a rhodamine 6G dye laser with optical stone tissue detection system.

INTRODUCTION: Laser lithotripsy of bile duct stones has become a widely accepted endoscopic treatment modality for giant, impacted, or very hard stones. The procedure is usually carried out under direct endoscopic control in view of the potential risk of bile duct injuries in "blind" laser application. AIMS: To investigate the use of a rhodamine 6G laser lithotriptor with an integrated optical stone tissue detection system (oSTDS). METHODS: From 1 September 1991 to 7 March 1997, 60 patients with giant or impacted common bile duct stones refractory to endoscopic papillotomy stone extraction, and mechanical lithotripsy were treated via the endoscopic retrograde route using a rhodamine 6G dye laser (595 nm, 2.5 micros, 80-150 mJ pp, Lithognost Telemit/Baasel Corp., Germany) with integrated oSTDS. In case of tissue contact oSTDS cuts off the laser pulse after 190 ns (transmission of 5-8% of the total pulse energy). 47 patients (78.3%) were subjected to x ray targeting (oSTDS) alone, five (8.3%) to choledochoscope targeting alone, and eight (13.3%) to both techniques. RESULTS: At the end of treatment 52 (87%) patients were completely stone-free. The only major complications included transient haemobilia, cholangitis, and pancreatitis in five patients. All five were successfully treated by conservative methods. CONCLUSIONS: Laser lithotripsy using the described rhodamine 6G dye laser with oSTDS seems to be safe and effective and allows "blind" fragmentation of difficult common bile duct stones under radiological control only.

Adult↗
PubMed1998

[Photodynamic therapy of early squamous epithelial carcinomas and severe squamous epithelial dysplasias of the esophagus with 5-aminolevulinic acid].

INTRODUCTION: Photodynamic therapy (PDT) is a new local, endoscopically controlled therapeutic concept based on the selective sensitization of malignant and precancerous lesions prior to light-induced tissue destruction. 5-aminolaevulinic acid (5-ALA) appears to be a promising alternative photosensitizer with a high mucosa specificity without phototoxic side effects on the skin. We report on our experience with this new form of PDT in 24 patients. PATIENTS AND METHODS: Five females and 19 males (aged 50 to 79 years) with histologically proven high-grade dysplasia (n = 9) and early cancer (normal EUS or uTlNOMO, n = 15) of the esophagus were included in this study. Four to six hours after oral ingestion of 5-ALA (dosage of 60 mg/kg b.w.) laser light irradiation was conducted with a dye laser system (XP 800 KTP/YAG, Laserscope, San José, USA) at a wavelength of 635 nm. With a light dose of 150 J/cm2. RESULTS: The length of the segment with severe dysplasia or mucosal cancer varied between 0.5 and 9 cm (mean length: 3.6 cm). High-grade dysplasia was eradicated in all patients (9/9). In addition, 16 mucosal carcinomas in 15 patients were successfully treated in 8/16 cases with an average of 1.8 treatment sessions and a mean follow-up of 14.5 months (range: 3-31 months). A method-related mortality and morbidity was not observed. CONCLUSIONS: Severe dysplasia and superficial (< or = 2 mm) mucosal cancer of the esophagus can be completely ablated by 5-ALA-PDT. Patients with early carcinoma thicker than 2 mm are not suitable for 5-ALA-PDT. PDT with 5-ALA has few side effects and might offer an alternative to esophagectomy or radio-chemotherapy.

Administration, Oral↗
PubMed1998

The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia.

Pyridoxine-responsive, X-linked sideroblastic anaemia (XLSA) has been shown to be caused by missense mutations in the erythroid-specific ALA synthase gene, ALAS2. These are scattered widely across the part of the gene encoding the catalytic domain and in half the cases affect residues conserved throughout evolution. Only a loose correlation has been found between the in vitro kinetics and stability of the catalytic activity of the recombinant variant enzymes and the in vivo severity and pyridoxine-responsiveness of the anaemia. Enhanced instability in the absence of pyridoxal phosphate (PLP) or decreased PLP and substrate binding have been noted. A detailed explanation of the anaemia and its response to pyridoxine, however, requires greater insight into the structure-function relationships of this protein than we have at present. Knowledge of its tertiary structure and further knowledge of intracellular factors which impinge on the ability of normal and variant ALAS2 to contribute to haemoglobin production are also required. Mutations in the same gene which affect mitochondrial processing, terminate translation prematurely, or are thought to abolish function altogether cause an XLSA that is refractory to treatment with pyridoxine. A major complication of this disorder is its accompanying increased iron absorption and iron overload which occurs in patients and female heterozygotes. Mutation detection enables the early diagnosis of those affected, targeted education of families, early treatment with pyridoxine and prevention of iron overload. It also allows for a distinction to be made between late-onset variants of this condition and the more insidious refractory anaemia with ring sideroblasts. The next few years of investigation should be illuminating as tools now exist to study all aspects of this protein from the gene to the mitochondrial matrix.

5-Aminolevulinate Synthetase↗
PubMed1998

DNA repair and transcription in human premature aging disorders.

The human progeroid disorders Cockayne syndrome and Werner syndrome present with several clinical features that are associated with normal aging. These include distinct changes in the skin. The genes responsible for these conditions have recently been cloned and characterized. They both contain a characteristic helicase sequence, and helicase activity has been demonstrated using the purified Werner protein. Helicases are involved in a number of DNA metabolic transactions, including transcription, replication, and DNA repair. Cockayne cells are deficient in a special type of DNA repair, transcription coupled DNA repair, but they also appear to be defective in basal transcription. The diverse functions of the Cockayne protein are under intense study. Werner cells may have subtle defects in DNA repair, and possibly also in transcription. The biochemical clarification of the precise role of these gene products is likely to provide very significant clues into the mechanism of aging.

Aging↗
PubMed1997

Reflections for action.

This is the second of three articles based on a major report launched by the Foundation of Nursing Studies last year-Reflection for Action-which looked at the dissemination and implementation of research in nursing. This article discusses two of the studies that made up the report.

Clinical Competence↗
PubMed1997

Novel isoforms of the beta and gamma subunits of the Xenopus epithelial Na channel provide information about the amiloride binding site and extracellular sodium sensing.

We have previously identified three homologous subunits alpha, beta, and gamma of the highly selective amiloride-sensitive Na channel from the Xenopus laevis kidney A6 cell line, which forms a tight epithelium in culture. We report here two novel genes, termed beta2 and gamma2, which share 90 and 92% sequence identity with the previously characterized beta and gamma XENaC, respectively. beta2 and gamma2 transcripts were detected in lung, kidney, and A6 cells grown on porous substrate. The physiological and pharmacological profile of the Na channel expressed after alphabeta2gamma XENaC cRNA injection in Xenopus oocyte did not differ from alphabetagamma XENaC. By contrast, the channel expressed after alphabetagamma2 injection showed: (i) a lower maximal amiloride-sensitive sodium current, (ii) a higher apparent affinity for external sodium and inactivation of the sodium current by high sodium concentrations, and (iii) a lower apparent affinity for amiloride (KI alphabetagamma2; 1.34 microM versus alphabetagamma 0.35 microM). These data indicate that the gamma (and/or gamma2) subunit participates in amiloride binding and the sensing of the extracellular sodium concentration. The close homology between gamma and gamma2 will help to define the domains involved in sensing external sodium and in the structure of this important drug receptor.

Amiloride↗
PubMed1997

Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets.

BACKGROUND: Activated platelets tether and activate myeloid leukocytes. To investigate the potential relevance of this mechanism in acute myocardial infarction (AMI), we examined cytokine induction by leukocyte-platelet adhesion and the occurrence of leukocyte-platelet conjugates in patients with AMI. METHODS AND RESULTS: We obtained peripheral venous blood samples in 20 patients with AMI before and daily for 5 days after direct percutaneous transluminal coronary angioplasty (PTCA) and in 20 patients undergoing elective PTCA. Throughout the study period, CD41 immunofluorescence of leukocytes (flow cytometry) revealed increased leukocyte-platelet adhesion in patients with AMI compared with control patients (mean +/- SE of fluorescence [channels] before PTCA: 77 +/- 16 versus 35 +/- 9; P = .003). In vitro, thrombin-stimulated fixed platelets bound to neutrophils and monocytes. Within 2 hours, this resulted in increased mRNA for interleukin (IL),1 beta, IL-8, and monocyte chemoattractant protein (MCP)-1 in unfractionated leukocytes. After 4 hours, IL-1 beta and IL-8 concentration of the cell-free supernatant had increased by 268 +/- 36% and 210 +/- 7%, respectively, and cellular MCP-1 content had increased by 170 +/- 8%. Addition of activated platelets to adherent monocytes had a similar effect and was associated with nuclear factor-kappa B activation. Inhibition of binding by anti-P selectin antibodies reduced the effect of activated platelets on cytokine production. CONCLUSIONS: In patients with AMI, leukocyte-platelet adhesion is increased. Binding of activated platelets induces IL-1 beta, IL-8, and MCP-1 in leukocytes. Our findings suggest that leukocyte-platelet adhesion contributes to the regulation of inflammatory responses in AMI.

Adult↗
PubMed1997

Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells.

Cockayne syndrome (CS) is characterized by increased photosensitivity, growth retardation, and neurological and skeletal abnormalities. The recovery of RNA synthesis is abnormally delayed in CS cells after exposure to UV radiation. Gene-specific repair studies have shown a defect in the transcription-coupled repair (TCR) of active genes in CS cells from genetic complementation groups A and B (CS-A and CS-B). We have analyzed transcription in vivo in intact and permeabilized CS-B cells. Uridine pulse labeling in intact CS-B fibroblasts and lymphoblasts shows a reduction of approximately 50% compared with various normal cells and with cells from a patient with xeroderma pigmentosum (XP) group A. In permeabilized CS-B cells transcription in chromatin isolated under physiological conditions is reduced to about 50% of that in normal chromatin and there is a marked reduction in fluorescence intensity in transcription sites in interphase nuclei. Transcription in CS-B cells is sensitive to alpha-amanitin, suggesting that it is RNA polymerase II-dependent. The reduced transcription in CS-B cells is complemented in chromatin by the addition of normal cell extract, and in intact cells by transfection with the CSB gene. CS-B may be a primary transcription deficiency.

Amanitins↗
PubMed1997

Bone replacement by ionomer cement in osteoplastic frontal sinus operations.

Ionomer-based cement is a new bone replacement material. After promising results in middle ear and skull base surgery, we started to use Ionocap as an alternative to metal osteosynthesis material. Between 1992 and 1995, 20 men and 9 women were treated with an osteoplastic approach for complicated frontal sinus diseases at Johann Wolfgang Goethe University. Ionocap as bonding material for bone was used in 22 of the patients. The indications for osteoplastic surgery were recurrent frontal rhinosinusitis, mucoceles, skull base fractures, osteomas and meningocele. The surgical procedure using bone cement was found to be much easier and shorter, the functional stability achieved was at least equal and the cosmetic outcome was clearly superior when compared to cases done with metal osteosynthesis. No rejection of the material or osteonecrosis was observed. In no case was the cement placed in direct contact to dura mater. Our findings show that ionomer-based cement can be recommened in osteoplastic frontal sinus surgery, but Ionocap should only be used strictly according to the guidelines of the supplier.

Adolescent↗
PubMed1997

[Chloride conduction of nasal fibroblasts in polyposis patients with cystic fibrosis and in patients without cystic fibrosis. Relevance for the ENT physician].

Cystic fibrosis (CF) is a complex systemic disease that has pathological alterations in the upper airways, including the recurrent formation of nasal polyps. Although the fibroblast is the predominant cell type in nasal stroma and nasal polyps, little is known about the electrophysiological properties of nasal fibroblasts. We investigated whether fibroblasts possess a cAMP-regulated chloride conductance which is impaired in patients with CF. Thus far the few studies concerning conductance in fibroblasts have been performed on skin fibroblasts using indirect methods and have yielded conflicting results. Therefore we studied chloride conductance in fused nasal fibroblasts by employing conventional microelectrodes. We have demonstrated that a cAMP-regulated chloride conductance is present in fibroblasts. However, this chloride conductance cannot be activated in fibroblasts from CF-patients. Thus, we present direct evidence that the impairment of the cAMP-regulated chloride conductance in CF is not confined to epithelial cells but also affects the fibroblast. We discuss how this conductance might modulate fibroblast proliferation to produce polyp formation.

Child↗
PubMed1997

The serotonin syndrome and psychosis-like side-effects of fluvoxamine clinical use--an estimation of incidence.

OBJECTIVE: The incidence of the serotonin syndrome or serotonin-syndrome-like side effects during treatment with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine should be evaluated. METHOD: 200 inpatients treated for the first time with fluvoxamine were prospectively evaluated for the occurrence of a serotonin syndrome over a period of 8200 treatment days. Retrospective follow-up data of outpatient treatment covered 8891 days. RESULTS: No full-blown serotonin syndrome occurred, but 3 patients developed a reversible change of mental status with insomnia, agitation, confusion and incoherent thoughts without other symptoms of the serotonin syndrome. CONCLUSIONS: It is concluded that the occurrence of a potentially lethal serotonin syndrome is rare in fluvoxamine treatment psychosis-like syndromes as a side effect of serotonergic stimulation might occur. In the investigated sample the rate was 0.006-0.04 per 100 treatment days.

Adolescent↗
PubMed1997

Early effect of aldosterone on the rate of synthesis of the epithelial sodium channel alpha subunit in A6 renal cells.

Transepithelial Na+ reabsorption across tight epithelia is regulated by aldosterone. The amiloride-sensitive epithelial sodium channel (ENaC) is a major target for the natriferic action of aldosterone. In this study, the effect of aldosterone on ENaC mRNA abundance and the rate of protein synthesis for each of the three ENaC subunits (alpha, beta and gamma) in the A6 kidney cell line were examined. In cells grown on plastic, aldosterone induced a large and rapid increase in epithelial sodium channel (ENaC) beta and gamma subunit mRNA abundance, but this effect is not translated into the synthesis of the corresponding proteins. In cells grown on a porous substrate, amiloride-sensitive electrogenic sodium transport was expressed and was upregulated by aldosterone (300 nM) as early as 1 h after the addition of the hormone. The alpha, beta, and gamma mRNA abundance was not changed by aldosterone during the first 3 h of stimulation, whereas a fourfold increase over control was observed after 24 h. The rate of synthesis of alpha subunit was significantly increased above control already 60 min after aldosterone addition, whereas beta subunit synthesis increased only 6 h after hormone addition, with no significant change for the gamma subunit. The half-lives of each subunit as assessed by 35S methionine pulse-chase experiments were short (between 40 and 50 min) and were not modified by aldosterone. Taking into account the short half-life of ENaC protein and assuming that the synthesis of the alpha subunit is a limiting factor in the assembly and expression of new channels at the cell surface, it is proposed that the aldosterone regulation of sodium transport might be, in part, mediated by de novo synthesis of the channel protein.

Aldosterone↗
PubMed1996

Gene-specific repair in human CD4+ lymphocytes reflects transcription and proliferation.

We have measured the gene-specific repair of ultraviolet irradiation (UV)-induced cyclobutane pyrimidine dimers (CPD) in freshly isolated human peripheral blood CD4+ T-lymphocytes. Two populations of CD4+ lymphocytes were assayed: resting and proliferating cells. DNA repair was assessed in the essential gene dihydrofolate reductase (DHFR) as well as in each of its strands, in the proliferation inducible c-myc gene and in the inactive delta-globin gene. Transcription rates in these genes were determined by nuclear run-on assay in the two cell populations. The rate of DHFR transcription increased 10-fold from resting to proliferating lymphocytes. Transcripts from c-myc were present only in proliferating cells, and we detected no delta-globin transcripts in either cell population. During the 24-h period after UV irradiation, there was little or no repair in any of the genes in the resting cells; there was some repair in the transcribed strand of the DHFR gene, but no repair in its nontranscribed strand. In the proliferating cells where the transcription of DHFR was much increased, the repair was efficient. The delta-globin gene was not expressed in either cell population, but it was more efficiently repaired in the proliferating than in the resting cells. We suggest that the gene-specific repair activity in CD4+ lymphocytes can reflect the proliferative state of the cells as well as the transcriptional state of the gene.

Autoradiography↗
PubMed1996

Platelet activation and coronary stent implantation. Effect of antithrombotic therapy.

BACKGROUND: Platelet activation and surface expression of adhesive glycoproteins play a key role in ischemic thrombotic complications after coronary intervention. The purpose of this case-control study was to evaluate the effects of two different antithrombotic regimens on platelet function after coronary Palmaz-Schatz stent implantation. METHODS AND RESULTS: The study group consisted of 46 "low-risk" patients who were treated with ticlopidine (250 mg BID) and aspirin (100 mg BID) after stenting. The control group was derived from a cohort of 151 patients receiving conventional anticoagulation therapy, including phenprocoumon (target international normalized ratio, 3.5), heparin (activated partial thromboplastin time, 80 to 120 seconds), and aspirin (100 mg BID) after stenting. Criteria for matching were indication for stenting, target vessel, balloon size, inflation pressure, and number of inserted stents. Matches were obtained for 38 patients. Platelet function was evaluated before and daily for 12 days after stenting in venous blood samples with immunologic activation markers. Patients receiving anticoagulation therapy showed a significantly increased surface exposure of LIBS1 (activated fibrinogen receptor; P < .05) and CD62P (P-selectin; P < .001) above prestent values, peaking days 3 to 6 after stenting. In contrast, in patients receiving ticlopidine, expression of LIBS1 decreased (P < .01) and expression of CD62P remained basically unchanged after stenting. Platelet count significantly decreased after stenting in patients treated by anticoagulation (day 3; P < .01), whereas no significant changes were found in the ticlopidine group. CONCLUSIONS: Significant platelet activation occurs in patients receiving anticoagulation therapy after stenting, while platelet deactivation is found in patients treated with combined antiplatelet therapy. This may contribute to a lowering of the incidence of subacute stent thrombosis.

Adult↗