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Biomedical subjects

K Kirchner

Publications and source records attributed to K Kirchner.

At least 19 recordsLinked to original sources
PubMed2001

Reactivity of a metallacyclopentatriene intermediate: metal-to-ligand-to-metal re-migration of a phosphine ligand versus a 1,2 hydrogen shift.

The reaction of nona-2,7-diyne, deca-2,8-diyne and hex-1-yne with [RuCp(PR3)(MeCN)2]PF6 (R = Cy, Ph, Me) affords, depending on the structure of the alkyne and the substituent of the phosphine ligand, ruthenium metallacyclopentatriene, allyl carbene and/or butadienyl carbene complexes involving either metal-to-ligand-to-metal migration of the phosphine ligand with concomitant C-H activation or a facile 1,2 hydrogen shift.

Journal Article↗
PubMed2000

Maximum urine concentrating ability in children with Hb SC disease: effects of hydroxyurea.

Studies in adults with Hb SC disease suggested that hydroxyurea reduced hemolysis and increased red cell hydration. Because increased hydration should diminish the polymerization tendency of Hb S we hypothesized that hydroxyurea might repair the urine concentration defect of HbSC disease. Eight Hb SC disease patients, aged 10 to 17 years, were given hydroxyurea daily. Maximal urine concentrating ability following overnight fasting and after subcutaneous arginine vasopressin (dDAVP), blood counts, and cell volumes were observed for 12-15 months. All patients had impaired urine concentrating ability prior to hydroxyurea treatment and failed to increase their ability to concentrate urine following treatment (maximum urine concentration after an overnight fast and dDAVP, 520-530 mOsm). Mean corpuscular volume (MCV) and reticulocyte MCV increased after administration of hydroxyurea, and the reticulocyte count and ratio of red cell hemoglobin to reticulocyte hemoglobin fell but there was little change in PCV. Hb F increased substantially in 2 patients but showed little change in the remaining patients. There was no evidence that hydroxyurea was associated with increased urine concentrating ability in children with Hb SC disease. These results may reflect irreversible renal medullary damage prior to beginning treatment or insufficient intensity or duration of treatment.

Adolescent↗
PubMed1997

Role of endothelin in mediating the attenuated renal hemodynamics in Dahl salt-sensitive hypertension.

The aim of this study was to evaluate the role of endothelin (ET) in the hypertension associated with giving a high sodium diet in Dahl salt-sensitive (DS) rats. To achieve this goal, we examined the effects of intravenous infusion of the nonspecific ET(A)-ET(B) antagonist on arterial pressure and renal function in conscious, chronically instrumented DS and Dahl salt-resistant (DR) rats. After 3 weeks on a high sodium (8%) diet, mean arterial pressure (MAP) in DS rats (166+/-3 mm Hg) was significantly higher than in DR rats (124+/-3 mm Hg). Baseline glomerular filtration rate (GFR) and renal plasma flow (RPF) in DS rats (1.92+/-0.25 mL/min and 7.07+/-0.80 mL/min) were lower than in DR rats (2.52+/-0.21 mL/min and 7.98+/-0.85 mL/min), respectively. Renal vascular resistance was significantly higher in DS rats (32.78+/-5.88 mm Hg x mL(-1) x min(-1)) than in DR rats (24.60+/-5.04 mm Hg x mL(-1) x min(-1)). Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg). In contrast, the effect of the ET antagonism on MAP in DR rats was not significant. ET-antagonist infusion tended to improve GFR and RPF in DS but not in DR rats. To determine the renal effects of ET antagonism independent of the systemic hemodynamic responses, we examined the effects of the same ET antagonist in rats chronically implanted with a renal interstitial catheter. Arterial pressure in DS rats (181+/-5 mm Hg) was significantly higher than in DR rats (135+/-3 mm Hg). Renal interstitial infusion of SB 209670 at a dose of 200 ng x kg(-1) x min(-1) for 60 minutes caused no change in MAP in DS or DR rats. Intrarenal ET antagonism significantly increased GFR (25%), RPF (30%), urine flow (32%), and urinary sodium excretion (25%) in DS rats, while it had no significant effect in DR rats. Fractional excretion of sodium was not significantly changed by renal interstitial infusion of the ET antagonist in DS rats, indicating that improved renal excretory function in DS rats is most likely due to the associated improvement in renal hemodynamics. We conclude that ET may play a role in the attenuated renal hemodynamics and possibly the development of Dahl salt-sensitive hypertension.

Animals↗
PubMed1995

Baseline characteristics of participants in phase II of the Trials of Hypertension Prevention (TOHP II). Trials of Hypertension Prevention (TOHP) Collaborative Research Group.

Phase II of the Trials of Hypertension Prevention (TOHP II) is a multicenter, controlled clinical trial designed to test whether weight loss, a reduced sodium intake, or a combination of weight loss and a reduced sodium intake will lower blood pressure (BP) and prevent the occurrence of hypertension. The study population consists of middle-aged, moderately overweight individuals with a diastolic BP between 83 and 89 mm Hg. Of the 2382 randomized participants, 816 (34%) are female and 494 (21%) are from a racial or ethnic minority background. At baseline, mean dietary intakes of sodium, based on measurements of 24-hour urinary excretion, were 199 mmol/d in men and 154 mmol/d in women. The average body mass index was 30.9 kg/m2. Across the four randomized groups, there was no substantial imbalance in the distribution of baseline variables; however, the mean age in the four groups was slightly but significantly different (range: 43.2 to 44.2 years, P = 0.02). A comparison of baseline characteristics of TOHP II participants with those of participants in three other primary prevention trials reveals a high level of mean dietary sodium intake in each study. Data reported in this article indicate that any subsequent differences in BP among the randomized groups are unlikely to result from maldistribution of known confounding variables at baseline. Finally, because of the high prevalence of overweight and excessive sodium intake in the United States, results from TOHP II should be broadly applicable to the general population.

Adult↗
PubMed1994

Lack of effectiveness of a low-sodium/high-potassium diet in reducing antihypertensive medication requirements in overweight persons with mild hypertension. TAIM Research Group. Trial of Antihypertensive Interventions and Management.

The Trial of Antihypertensive Interventions and Management (TAIM) was a multicenter randomized drug (double-blind, placebo-controlled)-diet trial. One objective of TAIM was to assess the long-term ability of a low-sodium/high-potassium (Na+ decreases/K+ increases) diet to maintain blood pressure control in persons at 110% to 160% ideal weight with diastolic blood pressure from 90 to 100 mm Hg who were on no drugs or on low-dose monotherapy. Participants, 56% men and 33% black, were randomized to usual diet (n = 296) or to Na+ decreases/K+ increases diet (n = 291) and within each diet group to placebo, 25 mg/day chlorthalidone, or 50 mg/day atenolol. Treatment failure was defined as lack of blood pressure control requiring additional drugs according to specified criteria. At baseline, the mean value for age was 48 years; blood pressure, 143/93 mm Hg; weight, 88 kg; and 24-h urinary sodium and potassium excretion rates, 133 and 57 mmol/day, respectively. At 3 years, the net difference in 24-h urinary sodium/potassium excretion rates between the Na+ decreases/K+ increases and the usual diet groups was -30 and +11 mmol/L/day. The relative risk of treatment failure for Na+ decreases/K+ increases compared to usual diet by proportional hazards regression was 0.95 (P = .71). This study provides no support for the sole use of a low-sodium/high-potassium diet as a practical therapeutic strategy in maintaining blood pressure control in the moderately obese.

Adult↗
PubMed1993

Reduction in long-term antihypertensive medication requirements. Effects of weight reduction by dietary intervention in overweight persons with mild hypertension.

BACKGROUND: Increasing concern over long-term drug treatment of mild hypertension has stimulated several studies of weight reduction. Phase I of the Trial of Antihypertensive Interventions and Management demonstrated a short-term effect of weight loss on blood pressure control in overweight persons with mild hypertension, who were either taking placebo or taking low-dose monotherapy. Phase II investigates the long-term benefit of weight loss on the ability to maintain blood pressure control. METHODS: From 10148 community-based screenees, 587 persons (5.8%), aged 21 to 65 years, entered a multicenter, randomized drug (double-blind, placebo-controlled) and diet trial. Participants had a diastolic blood pressure between 90 and 100 mm Hg and were at 110% to 160% of their ideal weight. They were randomized to a usual diet (n = 296) or to a weight loss diet (n = 291) and within each diet group to placebo, chlorthalidone, 25 mg/d, or atenolol, 50 mg/d. Treatment failure was defined as using additional antihypertensive medications if diastolic blood pressure rose above 90 mm Hg according to protocol-specified criteria. RESULTS: At baseline, mean diastolic blood pressure was 93 mm Hg; systolic blood pressure, 143 mm Hg; weight, 88 kg; percent ideal weight, 137%; age, 48 years; 56% were men; and 33% were black. Mean follow-up was 4.5 years. There was a net loss of 2 to 3 kg with weight loss diet compared with usual diet over most of the follow-up period. The 5-year incidence of treatment failure was 56.7 per 100 participants with usual diet and 49.8 per 100 with weight loss. Long-term weight loss decreased failure of blood pressure control for those receiving placebo or low-dose diuretic or beta-blocker by 23%. The results were similar in direction in each drug group. CONCLUSIONS: The Trial of Antihypertensive Interventions and Management demonstrated that weight reduction is an effective long-term therapy for maintaining blood pressure in the normal range when used as monotherapy or in combination with either thiazide diuretics or beta-blockers. Consequently, weight loss should be recommended for the management of obese individuals with mild hypertension.

Adult↗
PubMed1990

[Quantifying aortic valve insufficiency using color Doppler echocardiography].

UNLABELLED: 51 consecutive patients with the clinical signs of aortic valve incompetence (AI) were evaluated by color-coded Doppler flow mapping (CDF) before angiography (AG). Quantitation of the severity of AI was performed by measurement of length and width of the extension of regurgitant jet (grade I-IV). After AG results both -AG and CDF- were compared. In 36 patients the results of both methods concurred exactly by use length in CDF. With CDF, the regurgitation was overestimated in 7 cases by one grade and underestimated in 8 patients also by one grade. Width of regurgitant jet relative to size of outflow space is a useful parameter to distinguish between mild and severe A1 (limit 0.50). CONCLUSION: CDF is a suitable method for semiquantitative assessment of AI. In presence of unequivocal CDF signs and in consideration of clinical and other patients findings AG will be dispensable before aortic valve replacement.

Adolescent↗
PubMed1990

[Echocardiographic evaluation of mechanical and biological heart valve prostheses].

The complex echocardiography is the method of choice for the non-invasive assessment of patients with prostheses of the cardiac valve. The particular advantages of the method lie in the non-invasiveness, the common ability of repetition, the complete risklessness, the lacking radiation exposure and, what is particularly of importance for the early postoperative phase, the bedside applicability also on the intensive care unit. With regard to potential complications (thrombo-embolism, prosthetic endocarditis) the echocardiography is superior to the invasive examination methods with suspicion to malfunction or leak. The most important prerequisite for an exact interpretation of the findings is the possibility of the comparison with the basis documentation. Moreover, the judgement of prostheses of the cardiac valve demands particular echocardiographic experience, as it in general can be acquired only in a centre. Disturbing echos by valve ring and valve body must be regarded as disadvantage. Disturbances of the cardiac rhythm may simulate defective functions particularly in replacement of the mitral valve with mechanical prostheses.

Bioprosthesis↗
PubMed1990

Effect of insulin on renal sodium handling in hypertensive rats.

Spontaneously hypertensive rats have reduced peripheral insulin sensitivity. To determine whether hypertensive rats demonstrate reduced response to the antinatriuretic effect of insulin, urinary sodium excretion was determined in hypertensive and normotensive rats (n = 7 per group) before and during euglycemic insulin administration at two infusion rates (21 milliunits/kg load and 4 milliunits/kg/min or 85 milliunits/kg load and 8 milliunits/kg/min). Hypertensive and normotensive time controls received the vehicle for insulin administration. Mean arterial pressure was greater (p less than 0.05) and inulin clearance was less (p less than 0.05) in hypertensive than normotensive rats before insulin infusion. Baseline fractional sodium excretion was not different between groups. Low dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.81 +/- 0.43% to 0.31 +/- 0.07% in hypertensive rats and from 1.05 +/- 0.37% to 0.47 +/- 0.18% in normotensive rats. High dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.67 +/- 0.22% to 0.21 +/- 0.08% in hypertensive rats and from 0.81 +/- 0.15% to 0.30 +/- 0.09% in normotensive rats. Sodium excretion was unchanged in time controls. The reduction in sodium excretion was similar in both rat groups during low dose and high dose insulin infusions. Mean arterial pressure and inulin clearance were unchanged from baseline values during insulin infusion in all rat groups. Glucose requirement to maintain euglycemia was greater (p less than 0.05) in normotensive than hypertensive rats at both insulin infusion rates. Thus, while hypertensive rats have reduced sensitivity to the hypoglycemic effects of insulin, the antinatriuretic response to insulin is not different from that of normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Differential sensitivity to cocaine in spontaneously hypertensive and Wistar-Kyoto rats.

Physiological, pharmacological and toxicological responses to two regimens of cocaine administration were compared between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. An initial experiment examined renal excretory and hemodynamic function in response to an acute volume load in anesthetized SHR and WKY following subacute cocaine treatment (20 mg/kg, s.c., twice a day for 9 days). Anticipated renal responses to volume loading were obtained but the responses of cocaine-treated SHR and WKY did not differ from vehicle-treated rats. A second group of experiments compared responses to continuous i.v. infusions of cocaine (1.25 mg/kg.min). In freely moving animals, no differences were noted between SHR and WKY in the increases in mean blood pressure (MBP) and heart rate (HR) produced during cocaine infusion. The elapsed time-to-onset of convulsions (Tc) elicited by cocaine was similar in both strains. However, when rats were subjected to restraint during the infusion period, pressor and tachycardic responses were observed to be significantly less in WKY than in SHR or in freely moving rats of either strain. Restraint also differentially affected rectal temperature (RT) responses to cocaine. Hypothermic responses to cocaine were observed in all WKY. Both hypothermic and hyperthermic responses were observed in SHR. A significant correlation was demonstrated between the Tc and the maximal change in RT produced during cocaine infusion. Division of SHR into two arbitrary groups was made, based on the direction of cocaine-induced change in RT. A significant (p less than 0.01) shortening of the Tc was obvious in SHR (8 of 15) in whom cocaine produced a hyperthermia. These animals were designated SHRH. The mean value for Tc in those SHR which demonstrated a lowering in RT (SHRL; 7 of 15) in response to cocaine was similar to that for WKY. Moreover, the SHRH evidenced significantly greater increases in HR, but not MBP, to cocaine infusion than did SHRL. The results indicate that restraint stress causes expression of a significant heterogeneity in the RT response of SHR to cocaine. The magnitude and direction of the RT responses are negatively correlated with sensitivity to the convulsive effects of cocaine in SHR. Stress may modify toxic responses to cocaine by interactions with body temperature homeostasis.

Animals↗
PubMed1989

Anti-class II antibody production prolongs renal allograft survival.

It is widely accepted that transfusions are beneficial to the outcome of renal allotransplantation. Whereas some investigators suggested that transfusions may induce both specific and nonspecific suppression of the cell-mediated immune response, others disagree. To lend clarity to this discrepancy, we collected 40 serum samples before and after blood transfusion therapy of first-time cadaveric renal allograft recipients and evaluated each for T cell and B cell cytotoxic antibodies using an Amos modified complement-dependent microlymphocytotoxicity assay. When greater than 10% of the panel cells reacted with a grade 4 or better, the panel was considered significant, and when a lymphocyte specificity was lysed by antibody-rich serum greater than 50% of the time, the antibody was considered specific. Control T and B cell PRA assays employed sera from 27 normal nontransfused volunteers of similar age and sex. Survival distributions of differences in the PRA before and after blood transfusions and posttransfusion PRA levels were compared using the Gehan generalized Wilcoxon test. Other factors which influence allograft survival such as HLA-A, -B and -DR matches, number of blood transfusions, immunosuppressive therapy, age, sex, parity, previous positive crossmatch, circulating cytotoxic antibodies matching the graft, prior dialysis, length of time on the waiting list, lapse of time between transfusion and transplantation and the underlying primary diagnosis were also considered using the Gehan generalized Wilcoxon test or the chi 2 approximation. Transfusion-related B cell cytotoxic antibodies, HLA-DR monospecific or multispecific antibodies and HLA-A, -B matching extended graft survival in a significant manner. Sex influenced the production of B and T cell transfusion-related cytotoxic antibodies with females producing greater quantities of antibodies than males. Parity and the production of monospecific or multispecific antibody were associated with an increase in transfusion-related B cell cytotoxic antibody. A difference in sex was not linked to the production of monospecific or multispecific HLA-DR antibodies. The majority of males failed to respond to multiple blood transfusions with the production of B cell cytotoxic antibodies although more than half were successfully grafted. All females and males who responded with the production of B cell cytotoxic antibodies monospecific or multispecific, with the exception of 1 female, demonstrated an allograft survival of greater than 1 year. In conclusion, differences between pre- and post-transfusion B cell PRAs and monospecific or multispecific HLA-DR antibodies identified in patient sera following transfusions were good predictors of renal allograft survival in both males and females.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Transfusion↗
PubMed1988

Strongly enhanced toxicity of the mushroom toxin alpha-amanitin by an amatoxin-specific Fab or monoclonal antibody.

A monoclonal antibody, with high affinity against the mushroom toxin alpha-amanitin, was prepared. Administration of the Fab fragment of the monoclonal antibody to mice caused a 50-fold increase in alpha-amanitin toxicity. Electron micrographs showed normal appearance of hepatocytes but typical, amanitin-induced lesions in cells of the proximal convoluted tubules of the kidney. The pronounced nephrotoxicity is mainly explained by glomerular filtration and tubular reabsorption of the Fab-amatoxin complex and, to a lesser extent, of the immunoglobulin-amatoxin complex, which is still c. Twice as toxic as free alpha-amanitin. To our knowledge this is the first reported case where immunoglobulins or their fragments enhance rather than decrease the activity of a toxin. Accordingly, immunotherapy of Amanita mushroom poisoning in humans does not appear promising.

Amanitins↗
PubMed1987

Fungal peritonitis during continuous ambulatory peritoneal dialysis: a report of 17 cases.

Seventeen cases of fungal peritonitis and one case of Nocardia asteroides peritonitis were observed in 141 patients during the first 5 years of our continuous ambulatory peritoneal dialysis program (CAPD). Fungal peritonitis accounted for 7% of the episodes of peritonitis observed in this interval. There were eight deaths associated with fungal peritonitis. In only three instances could factors predisposing to fungal peritonitis be identified. We were unable to predict who would develop fungal peritonitis by analysis of nutritional, demographic, or technical factors associated with the dialysis procedure. The diagnosis of fungal peritonitis was easily established using routine blood agar culture techniques. Successful management of these patients included prompt removal of the Tenckhoff catheter and intravenous (IV) administration of amphotericin.

Amphotericin B↗
PubMed1986

Purification of amatoxin-specific antibodies from rabbit sera by affinity chromatography, their characterization and use in toxicological studies.

Rabbits were immunized with fetuin-beta-amanitin. They produced amatoxin-specific immunoglobulins of various classes, predominantly IgG. The crude IgG fraction was isolated by gel filtration on Sephacryl S-300. By polyethylene glycol precipitation in the presence of tritiated amatoxin, as well as by a solid phase radioimmunoassay technique, the portion of amatoxin-specific antibodies in the IgG fraction was determined to be 5-13%. The affinity of the amatoxin-specific IgG for a tritiated amatoxin derivative was measured by equilibrium dialysis and calculated according to the method of Scatchard. The dissociation constant was 2.6 X 10(-9) M. The amatoxin-specific immunoglobulins were extracted by their affinity to alpha-amanitin-Sepharose 4B and eluted with excess alpha-amanitin. The complex was isolated in 95% yield with a ratio immunoglobulin:toxin of c. 2:1. Alternatively, the uncomplexed IgG could be eluted from the alpha-amanitin-Sepharose 4B with 5 M guanidine hydrochloride; this treatment, however, decreased the binding capacity for amatoxin by 30% (ratio 1.4:1). The purified amatoxin-specific IgG was assayed for its therapeutic efficiency in mice poisoned with alpha-amanitin, but was unable to neutralize the toxic effects of the mushroom toxin. On the contrary, equimolar amounts of the amatoxin-specific immunoglobulins enhanced the toxicity of alpha-amanitin in the mouse by a factor 2.

Amanitins↗
PubMed1985

Tubulin domains responsible for assembly of dimers and protofilaments.

The protein domains responsible for the dimerization and polymerization of tubulin have been determined using chemical cross-linking and limited proteolysis. The intra-dimer bond is formed by the N-terminal domain of alpha-tubulin and the C-terminal domain of beta-tubulin. Conversely, the inter-dimer bond along protofilaments is formed by the N-terminal domain of beta-tubulin (carrying the exchangeable GTP) and the C-terminal domain of alpha-tubulin. The domains of proteolytically cleaved tubulin remain tightly associated in solution. Apart from the monomer, tubulin shows three levels of assembly: the dimer, oligomer and polymer. Several oligomeric species can be visualized by electron microscopy of rotary shadowed phosphocellulose-tubulin, h.p.l.c. and non-denaturing gel electrophoresis. Tubulin's capacity to form the higher level aggregates is not destroyed by enzymatic nicking.

Animals↗