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Biomedical subjects

K Valnes

Publications and source records attributed to K Valnes.

At least 19 recordsLinked to original sources
PubMed2000

Efficacy and tolerability of a combination tablet of candesartan cilexetil and hydrochlorothiazide in insufficiently controlled primary hypertension--comparison with a combination of losartan and hydrochlorothiazide.

This randomized, double-blind study compared the antihypertensive effect, safety and tolerability of a candesartan cilexetil/hydrochlorothiazide (candesartan/HCT; 16/12.5 mg) combination tablet with that of a losartan/HCT (50/12.5 mg) combination tablet in patients with mild-to-moderate primary hypertension insufficiently controlled on previous monotherapy. Men and women, aged 20-80 years, with a sitting diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg and sitting systolic blood pressure (SBP) < or = 200 mmHg during treatment with any kind of antihypertensive monotherapy for at least 4 weeks were randomized to candesartan/HCT or losartan/HCT once daily for 12 weeks. All BP measurements were performed 24 h after previous dose. Mean values and standard deviations (SD) or confidence intervals (CI) are given. A total of 340 patients were enrolled, of whom 299 (144 women and 155 men, mean age 59.5 [10.5] years) were randomized to candesartan/HCT (n = 151) or losartan/HCT (n = 148). BPs at randomization were 159.5 (15.4)/98.4 (5.8)mmHg and 160.5 (16.1)/98.5 (5.4)mmHg, respectively. There was a greater reduction in BP with candesartan/HCT than with losartan/HCT: DBP -10.4 (-11.8; -8.9) vs -7.8 (-9.3; -6.3) mmHg, difference between treatments -2.6 (-4.7; -0.5) mmHg (p = 0.016); SBP -19.4 (-22.1; -16.7) vs - 13.7 (-16.5; - 10.9) mmHg, difference between treatments -5.7 (-9.6; -1.8) mmHg (p = 0.004). The proportion of patients achieving a DBP < or = 90 mmHg was greater in the candesartan/HCT group: 60.9 (53.1; 68.7) vs 49.3 (41.3; 57.4)% (p = 0.044). There were 12 withdrawals in the candesartan/HCT group, of which 8 were due to adverse events, and 17 and 12, respectively in the losartan/HCT group. We conclude that the combination of candesartan and HCT reduces BP effectively and is well tolerated. BP was normalized in 61% of these patients who had insufficient response to previous monotherapy. The reduction in BP and the proportion of patients with normalized BP were greater with the candesartan/HCT 16/12.5 mg combination than with the losartan/ HCT 50/12.5 mg combination.

Adult↗
PubMed1990

Relation between T cell number and epithelial HLA class II expression quantified by image analysis in normal and inflamed human gastric mucosa.

Epithelial expression of HLA class II determinants and the number of lamina propria and intraepithelial T cells were quantified in gastric body mucosa by means of paired immunofluorescence staining which was subjected to computerised image analysis. In normal mucosa, epithelial HLA-DR expression was virtually absent. A significantly increased expression was seen in simple chronic gastritis, most extensively in the isthmus zone, where a positive reaction was seen in 34% of the epithelial area when the gastritis was of low degree and in 85% when it was of moderate severity. The most extensive HLA-DR expression was found in moderate 'stump gastritis' 28 to 32 years after Billroth II resections. In these patients the epithelial area in the foveolar and isthmus zones showed 83% and 92% positive responses, respectively. The HLA subregion products were expressed in a differential manner (DR greater than DP greater than DQ). The number of both intraepithelial and lamina propria T cells increased significantly with increasing severity of gastritis, and the fraction of putative memory T cells was also raised. Correlation analyses showed a positive relation between the epithelial expression of HLA-DR and the intraepithelial as well as the lamina propria density of T cell. These results suggest a biological link between T cells, aberrant HLA-DR expression, and gastritis, although the pathogenic importance of this relation is unknown. Enhanced epithelial presentation of autoantigens or luminal antigens, or both leading to increased activation of T cells is one possible explanation.

Epithelium↗
PubMed1990

Measurements of serum IgA and IgG activities to dietary antigens. A prospective study of the diagnostic usefulness in adult coeliac disease.

Serum samples from 458 consecutive adult patients with intestinal symptoms and/or suspected food intolerance were examined for IgG and IgA antibody activities to gluten, egg, and cow's milk antigens by an enzyme-linked immunosorbent assay (ELISA). Increased IgA and/or IgG activities to gluten were seen in 61 patients: 35 had coeliac disease (CD) as suggested by jejunal villous atrophy and subsequent histologic and/or clinical improvement on a gluten-free diet; 4 were previously diagnosed CD patients with clinically suspected dietary failure; 2 had dermatitis herpetiformis with a CD-like intestinal morphology; and 3 had possible gluten intolerance without villous atrophy. The rest had other disorders that might have affected the permeability of the gastrointestinal mucosa or the hepatic IgA catabolism. When the IgA activity to gluten was increased, neither the IgA/IgG activities to nongluten antigens nor the ratio of nongluten to gluten antibodies could discriminate between CD patients and those without CD. However, the median IgA activity to gluten was significantly higher in the CD group. The probability for CD thus increased from 33% in patients with IgA activity to gluten between 0.4 and 0.8 OD units to 90% in those with such activity above 2.4 OD units. Nevertheless, seven untreated CD patients had IgG and IgA activities to gluten within the normal range. ELISA determinations of serum antibodies to gluten antigens are a valuable adjunct in the diagnosis of adult CD, but a negative test does not exclude this disorder.

Adolescent↗
PubMed1989

Subclass distribution of mucosal IgG-producing cells in gastritis.

IgG-mediated immune reactions are probably involved in the maintenance of gastritis and glandular atrophy; the mucosal IgG-subclass pattern may therefore influence the effect of local hypersensitivity mechanisms. In this study the proportions of IgG1-, IgG2-, IgG3-, and IgG4-producing immunocytes were determined by paired immunofluorescence staining in specimens from simple gastritis, gastritis after Billroth II (BII) resection, and gastritis associated with dermatitis herpetiformis (DH). The results were related to histopathological degree of inflammation and atrophy. Generally, IgG1 immunocytes predominated (48-60%) in all types of gastritis. With increasing severity of inflammation, the IgG2-cell proportion was significantly increased from 4-6% to 26-34% in simple and BII gastritis, whereas the ratio of IgG1 immunocytes was correspondingly decreased from 58-69% to 38-43%. In the same types of gastritis the proportion of IgG3 cells was increased in association with severe (35-38%) compared with mild (15-23%) atrophy, whereas the proportion of IgG1 cells was correspondingly decreased. In severe gastritis associated with DH, the proportion of IgG1 cells was relatively high (60%) and that of IgG2 cells relatively low (13%), and severe atrophy did not seem to influence significantly the subclass proportions.

Antibody-Producing Cells↗
PubMed1988

Local immune defence in relation to gastritis in Billroth-II-resected stomachs.

Biopsy specimens from Billroth-II-resected stomachs obtained endoscopically 28-32 years after the operation were subjected to an immunohistochemical study by two-colour immunofluorescence staining. The epithelial distribution of immunoglobulin A (IgA), secretory component (SC), lysozyme (Ly), and lactoferrin (Lf) was evaluated, and IgA-, IgM-, and IgG-producing cells were quantified in the lamina propria. Gastric body mucosa excised from resected stomachs obtained from patients with duodenal ulcer was used as control and showed considerably less extensive gastritis than the stump mucosa. Both specimen categories showed enhanced expression of epithelial IgA, SC, Ly, and Lf associated with severe gastritis, except for areas with intestinal metaplasia, which lacked Ly and Lf. The number of IgA-, IgM-, and IgG-producing cells was significantly increased with increasing degree of gastritis, particularly so for IgG cells on a relative basis. After partial gastrectomy, therefore, the stump mucosa generally responds with activation of local immune mechanisms; this response is principally similar to that seen in simple gastritis of comparable severity.

Adult↗
PubMed1987

Local immunoglobulin production is different in gastritis associated with dermatitis herpetiformis and simple gastritis.

The degree of inflammation and atrophy in gastric body mucosal specimens (n = 38) from 28 patients with dermatitis herpetiformis (DH) was graded histologically. Immunoglobulin (Ig) producing cells were enumerated by paired immunofluorescence staining in a 500 microns wide section area from the muscularis mucosae to the lumen (mucosal 'tissue unit'). The number of immunocytes of the three main classes (IgA, IgM, and IgG) was significantly raised with increasing degree of gastritis. All three classes were increased in specimens showing atrophy compared with those without atrophy. IgA cells predominated as in simple gastritis, but a striking difference was a marked increase of IgM cells in specimens with the most pronounced DH-associated gastritis. Relative class distribution of immunocytes within different mucosal zones showed that the percentage of IgA cells was significantly higher in the luminal than in the basal zone, whereas the contrary was true for IgG cells. IgM cells did not show any zonal preference. No relation was seen between small bowel and gastric lesions. The disproportionate increase of gastric IgM producing cells in DH might nevertheless reflect seeding of precursor cells of the secretory immune system generated in the proximal small intestine where the local IgM response is relatively pronounced.

Adolescent↗
PubMed1987

Production and secretion of immunoglobulins in the gastrointestinal tract.

Two decades ago it was shown that the major immunoglobulin (Ig) present in human secretions is a dimeric IgA covalently bound to an epithelial glycoprotein of about 80 kD, now called the secretory component (SC). Pentameric IgM is likewise actively enriched in most exocrine fluids and is associated with SC, although not in a covalently stabilized complex. Three findings explain the selective translocation of polymeric Ig (pIg) into exocrine fluids: (1) preferential local production; (2) J-chain-expressing capacity of pIg-producing immunocytes; and (3) SC-mediated epithelial transport. Human hepatocytes lack SC and the human liver, therefore, cannot act as an efficient "IgA pump". This is in contrast to the rat liver which shows a remarkable capacity for transport of dimeric IgA from blood into the bile. The J chain of pIg and the epithelial SC represent the "lock and key" in the glandular transport of secretory IgA (SIgA) and SIgM. It has recently been shown that SC is synthesized as a transmembrane protein of about 95 kD and constitutes the actual pIg surface receptor. Complexing between ligand and receptor in the plasma membrane is followed by endocytosis. The completed SIgA and SIgM molecules are then translocated in cytoplasmic vesicles through the epithelial cell to the gland lumen along with an excess of free SC. The main function of SIgA is to exert immune exclusion; that is, by intimate cooperation with innate nonspecific defense factors it decreases penetration of soluble antigens and inhibits epithelial colonization of bacteria and viruses. Especially in selective IgA deficiency, SIgM may exert a similar protective function since its synthesis is markedly increased in the intestinal mucosa. Leakage of IgG into exocrine fluids is enhanced by mucosal irritation. Although IgG should not be considered as a SIg, it may contribute to immune exclusion. This is seen especially in the respiratory tract where IgG is less easily subjected to proteolytic degradation than in the intestinal juice. In contrast, by activating complement, IgG antibodies may at the same time be phlogistic and accelerate mucosal penetration of antigens. IgG may thus contribute to persistent immunopathology in mucosal disease. The same is true for IgE antibodies which may be carried into mucous membranes and secretions by mast cells and cause their degranulation with local histamine release. Traces of IgD may likewise be found in the secretions but without obvious biologic significance. Regulation of secretory immunity takes place both in organized lymphoepithelial structures, such as the Peyer's patches, and adjacent to the glands in the lamina propria.(ABSTRACT TRUNCATED AT 400 WORDS)

Celiac Disease↗
PubMed1986

Enzyme level changes in the cerebrospinal fluid of patients with acute stroke.

Creatine kinase (CK), brain CK (CKBB), lactate dehydrogenase (LD), and aspartate aminotransferase (ASAT) levels were determined in cerebrospinal fluid (CSF) obtained from 35 patients with acute stroke. In patients with transient, minor neurological disturbances, only LD levels increased; in those who remained comatose and died, the levels of all the enzymes, except ASAT, increased. Patients who remained with focal motor defects had increased CK and LD levels, while CKBB and ASAT levels were variable. In most of the CSF samples, muscle CK activity was also detectable, suggestive of a leakage from blood to CSF. The pattern of the enzyme increase could be related to the causative mechanisms for the strokes. The study suggests that CSF enzyme determinations may provide supplementary information as to the extent and severity of brain damage and the recovery potentials of selected patient groups with strokes.

Acute Disease↗
PubMed1986

Quantitative distribution of immunoglobulin-producing cells in gastric mucosa: relation to chronic gastritis and glandular atrophy.

Immunoglobulin (Ig)-producing immunocytes were quantified by paired immunofluorescence staining in specimens of gastric antral (n = 52) and body (n = 117) mucosa obtained from 45 patients with various gastrointestinal disorders. Enumerations were carried out in a 500 micron wide zone from the muscularis mucosae to the lumen ('tissue unit'). The specimens were divided into three categories according to the degree of inflammation, and each specimen received a grade for atrophy (0-2). The total number of IgA-, IgM- and IgG-producing cells per tissue unit increased strikingly with increasing degree of inflammation, both in antral and body mucosa. IgA immunocytes predominated (61-91%) in all specimens, but the IgG isotype showed the largest relative increase (four to 17-fold), particularly in the basal part of the mucosa. In this layer of the gastric body the proportion of IgG cells was also significantly raised in association with atrophy, irrespective of degree of inflammation. Locally produced IgG may be of protective significance in terms of internal (or 'second line') defence but may at the same time maintain immunopathological mechanisms contributing to the chronicity of gastritis.

Adolescent↗
PubMed1985

Retardation of immunofluorescence fading during microscopy.

Polyvinyl alcohol (PVA) mounting medium containing paraphenylenediamine (PPD), n-propyl gallate (NPG), or 1,4-diazobicyclo(2,2,2)-octane (DABCO) was compared with PVA alone or buffered glycerol with regard to capacity for preservation of immunofluorescence preparations. The results were based on staining of an artificial substrate with homogeneous antigen distribution followed by microphotometric determination of the initial light emission from bound fluorescein isothiocyanate (FITC)-labeled antibody and the subsequent fluorescence fading during 3-min exposure to blue excitation light. At a concentration of 0.2-2.0 g/liter and 6 g/liter, respectively, PPD and NPG were shown to effectively retard fluorescence fading without notably decreasing the initial emission intensity; two requisites were that the modified PVA used must be rather fresh and that the mounted preparations be examined within a few days. Although addition of DABCO (6 g/liter) afforded a mounting medium that tolerated storage before use better, but both PPD and NPG were more advantageous in practice. The retarding effect of PPD on fading of FITC emission was confirmed by performance testing on human tissue sections. Remounting in PVA alone is recommended for prolonged storage of sections that have been mounted in PVA modified with one of the above-mentioned compounds.

Fluorescein-5-isothiocyanate↗
PubMed1985

The antisecretory effects of RP 40 749 in patients with previous duodenal ulcer.

Thirteen male patients with a history of duodenal ulcer were given 150 mg RP 40 749 or placebo tablets at bedtime in a double-blind crossover study. The medication was given for two periods of 10 days with an 11-day wash-out period between. pH and pepsin concentrations were determined each hour in aspirates of gastric juice for 24 h on day 1, 10, 22, 31, and a 2-h collection of gastric juice was examined in the middle of the treatment and wash-out periods. At defined hours blood samples were examined for gastrin, somatostatin, and pancreatic polypeptide (PP) by radioimmunological methods, and concentrations of RP 40 749 were determined in blood and gastric juice. Meals were served at fixed hours on days 1, 10, 22, and 31. After treatment with RP 40 749 a highly significant elevation of pH was found after the 1st day compared with placebo, most pronounced during night hours. The pepsin activity was slightly elevated. The serum concentrations of gastrin were increased and those of somatostatin and PP decreased during the first 3-4 h after medication, with a subsequent normalization. No side effects were observed.

Adult↗
PubMed1985

The human gastrointestinal secretory immune system in health and disease.

The main function of secretory IgA is to exert immune exclusion; that is, by intimate cooperation with innate non-specific defence mechanisms, it dampens down penetration of soluble antigens and inhibits epithelial colonisation of bacteria and viruses. Secretory IgM may exert a similar protective function in the gut as its local synthesis sometimes is markedly increased, especially in selective IgA deficiency. IgG should not be considered a secretory immunoglobulin because its external translocation depends on passive intercellular diffusion. By activating complement, antibodies of this isotype may cause increased mucosal permeability and tissue damage. IgG may thus contribute to persistent immunopathology in mucosal lesions. The same is true for IgE antibodies which, in atopic individuals, may be carried into the gut mucosa by mast cells and cause their degranulation with histamine release. Secretory IgA and secretory IgM are the products of two cell types: plasma cells synthesise IgA dimers and IgM pentamers which, by non-covalent association, become complexed with the secretory component (SC) which is synthesized by serous-type glandular cells. The adsorption of the Ig polymers to the SC-expressing epithelial cells depends on J chain-determined binding sites. This fact gives biological significance to the striking J chain expression shown by mucosal immunocytes regardless of the Ig class they produce. The immunocytes populating the gut mucosa apparently belong to relatively early memory B cell clones. The obvious functional goal of J chain expression at this stage of clonal differentiation is local generation of SC-binding IgA and IgM polymers. In various gut diseases, altered immune regulation results in a disproportionately increased number of J chain-negative IgG-producing cells in the mucosa. Such altered immunological homeostasis may contribute to perpetuation of inflammatory bowel diseases.

Adult↗
PubMed1984

Sensitivity and efficiency of four immunohistochemical methods as defined by staining of artificial sections.

Direct (DIF) and indirect (IIF) immunofluorescence, indirect immunoperoxidase conjugate (IPC) and unlabelled antibody peroxidase antiperoxidase (PAP) staining was performed on sections of artificial substrate containing different concentrations of human immunoglobulin (Ig)A or IgG. Detection sensitivity, in terms of the lowest amount of discernible antigen, was evaluated by direct microscopy and by microphotometry. Staining efficiency (signal-to-noise ratio) was evaluated by microphotometry. Only minor differences in antigen detection sensitivity were found when IPC and PAP were compared with DIF and IIF under appropriate conditions. The sensitivity of DIF was only marginally improved by raised conjugate concentration and prolonged incubation time. Microphotometry of DIF on ethanol-fixed IgA substrate revealed that the staining intensity increased proportionally with the antigen concentration whereas on formaldehyde-fixed substrate a progressive masking of the antigen was indicated which, however, could be overcome by applying raised conjugate concentration and prolonged incubation time. Such antigenic self masking was of relatively little importance to IPC and PAP staining, probably because of the inherent amplification in these methods. An additional masking effect due to extraneous protein was revealed by DIF when ethanol-fixed sections had been soaked in bovine serum albumin and postfixed with formaldehyde; unmasking was achieved by proteolytic treatment of the sections.

Antigens↗
PubMed1984

Paired indirect immunoenzyme staining with primary antibodies from the same species. Application of horseradish peroxidase and alkaline phosphatase as sequential labels.

Paired indirect immunoenzyme staining based on primary antisera from the same species was performed sequentially without intermediate antibody elution. The first antigen was labelled brown by an immunoperoxidase procedure (either the two-stage indirect method, the unlabelled antibody peroxidase-antiperoxidase method, or the avidin-biotin bridge method using diaminobenzidine (DAB) and hydrogen peroxide as the substrates. The second antigen was labelled blue by applying a two-stage indirect immuno-alkaline phosphatase procedure using naphthol AS phosphate and Fast Blue BB salt as the substrate. In this way, polyclonal mucosal immunocytes were revealed in distinctly contrasting colours when stained for kappa and lambda light chains. Glucagon and somatostatin (D) cells in human pancreatic islets, and gastrin and D cells in human gastric antral glands, were likewise clearly differentiated. Conversely, a mixed colour appeared in some immunocytes after staining for alpha and kappa chains. However, unbalanced colour mixing was sometimes difficult to interpret, and additional experiments demonstrated that unwanted interactions could take place between the two sequences of reagents if the density of the DAB deposits was insufficient. These pitfalls were incompatible with unequivocal double staining in the same cell. Nevertheless, paired staining could be conveniently applied with the described procedures when prior knowledge had established that the antigens in question were located in separate cells.

Alkaline Phosphatase↗
PubMed1984

Specific and nonspecific humoral defense factors in the epithelium of normal and inflamed gastric mucosa. Immunohistochemical localization of immunoglobulins, secretory component, lysozyme, and lactoferrin.

Epithelial distributions of immunoglobulin A, secretory component, lysozyme, and lactoferrin were studied by paired immunofluorescence staining in ethanol-fixed biopsy specimens from gastric antral and body mucosa. Fluorescence scores were assigned semiquantitatively for the epithelium in three mucosal zones (foveolar, isthmus, and glandular). In each case, degree of inflammation was graded blindly after conventional histologic staining of serial sections. The results showed that the overall epithelial expression of local defense factors was significantly enhanced in association with gastritis, both with regard to nonspecific antimicrobial substances (lysozyme and lactoferrin) and the external transfer of immunoglobulin A (mediated by secretory component) as a potential carrier of protective antibodies. The antral isthmus and glandular zones were most active in both respects. Despite the expression of relatively large amounts of epithelial immunoglobulin A and secretory component in metaplastic glands, these elements lacked the nonspecific defense factors (except for lysozyme in Paneth cells)--even when they occurred in the antral mucosa--and may, therefore, represent particularly vulnerable areas.

Adult↗
PubMed1983

Quantitation of immunoglobulin- and peptide hormone-producing cells in gastrointestinal mucosa. Comparison of direct immunofluorescence and the unlabelled antibody peroxidase--antiperoxidase method.

Direct immunofluorescence (DIF) and the unlabelled antibody peroxidase--antiperoxidase (PAP) methods were compared on a quantitative basis with regard to visualization of IgA immunocytes and gastrin cells in human gastric mucosa, and secretin cells in canine duodenal mucosa. With both DIF and PAP, two serial sections from 13 biopsy specimens were evaluated for each cell type--thus keeping tissue preparation the same with both staining methods. The three cell types were well visualized regardless of method, and there was no significant difference between cell numbers recorded with the DIF or PAP. When blind duplicate counts were obtained with an interval of three weeks, comparisons of weighted differences and the Kendall's rank correlation test indicated good precision; the reproducibility of duplicate enumerations with each method was comparable to that between the two methods. It was concluded that DIF and PAP are equally applicable for studies of these three cell types under the conditions used in this investigation.

Cell Count↗
PubMed1983

Comparative study of cimetidine and trimipramine in the short-term treatment of duodenal and gastric ulcer.

Sixty-nine outpatients with endoscopically confirmed duodenal and prepyloric (DU) or gastric ulcers (GU) completed a 4-week double-blind trial with either cimetidine, 1 g/day, or trimipramine, 50 mg/day. Ulcer healing was assessed by endoscopy at 4 weeks. At the end of the study 14 of 23 patients with DU treated with cimetidine and 13 of 25 treated with trimipramine had healed ulcers. In the patients with GU 7 of 11 ulcers (cimetidine) and 4 of 10 (trimipramine) healed. The differences in healing rates between the two treatment groups were not statistically significant, either in DU and GU groups separately or in the total material. The number of pain attacks per week decreased and the symptoms improved significantly in both treatment groups in DU, GU, and totally. Both drugs were well tolerated, but two patients in each treatment group developed a slight increase in serum transaminases. No serious side effects occurred. The study suggests trimipramine as an alternative drug to the well-established drug cimetidine in the treatment of duodenal and possibly also of gastric ulcer.

Cimetidine↗