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Biomedical subjects

N Keller

Publications and source records attributed to N Keller.

At least 91 records · Page 5Linked to original sources
PubMed1993

Residual cornea and the degenerate eye of the cryptophthalmic Typhlotriton spelaeus.

The cave-dwelling Typhlotriton spelaeus larvas live in daylight. The larvas undergo a metamorphosis when the thyroxin level (T3 and T4) increases. They leave aquatic life for terrestrial and subterranean aphotic life. The larval eyes are normal and show good vision response to tests. On the contrary, in the oldest larva and the adult, the eyes are small with poor vision or no vision at all. The lens can disappear but in any case the eyelids grow over the eye. The retinal degeneration takes place during and after metamorphosis. The admitted statement that "after metamorphosis . . . the developing lids close over the eye and invade the cornea" is not confirmed concerning the invasion, because it is now evident that the eyelids separate spatially from the residual cornea. Consequently, the fibroblasts of the eyelids are not able to invade the corneal stroma. In fact, the periocular tissues do not invade the cornea but invade the eyelids' tissues. We are able to confirm that the development of the larval eyes is complete and apparently normal. After metamorphosis, the eyes decrease in size. The cornea "sinks" with the eye into orbit tissues. The eyelids cover the eye and are themselves replaced by a supraocular skin. This fits the description of the human cryptophthalmia. We also demonstrate that even in the degenerate eye the residual cornea retains the main structure of a normal salamander cornea. The preservation of the endothelium and of the Descemet membrane is exceptional in blind cave-dwelling vertebrates because in the other degenerate corneas the edema of the stroma depends on the spatial disjunction of the underepithelial stroma and the supraendothelial stroma. Perhaps, the very advanced development of the eye and the late start of the degenerative processes could explain the relative preservation of the cornea. Thus, the arguments put forward tend to prove that the thyroxinic metamorphosis sets off the growth and fusion of the eyelids but that the eye degeneration is related to hereditary processes.

Animals↗
PubMed1993

Tumor necrosis factor alpha (TNF-alpha) production in mice immunized with Escherichia coli: correlation with mortality after lethal challenge and production of a native inhibitor of TNF-alpha activity.

The kinetics of tumor necrosis factor alpha (TNF-alpha) production, the correlation between cytokine levels and mortality rates after lethal challenge, and the production of a native inhibitor of TNF-alpha activity was investigated in mice immunized with formalin-killed Escherichia coli. Groups of mice were injected for 8 weeks with either untreated bacteria or bacteria treated with 0.5 MIC of aztreonam and subsequently challenged with 100 50% lethal doses of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with aztreonam-treated E. coli was significantly lower than that of mice immunized with untreated E. coli. There were no measurable levels of TNF-alpha in sera obtained from control mice during the entire period of immunization. TNF-alpha levels ranging from 90 to 306 U/ml were measured 90 min after each vaccination in sera obtained from mice immunized with untreated E. coli. Sera from mice immunized with antibiotic-treated E. coli showed lower TNF-alpha levels, ranging from 40 to 128 U/ml. TNF-alpha levels measured 90 min after lethal challenge correlated with the mortality rate observed in each group (r = 0.95). The cytotoxic activity of recombinant murine TNF-alpha was inhibited by the sera from immunized mice but not by the sera from controls. The inhibition was drastically reduced by preincubation of the sera with staphylococcal protein A. In immunoblot experiments, class G immunoglobulins reacting with recombinant murine TNF-alpha were observed in the sera of immunized mice. These data confirm the correlation existing between TNF-alpha levels and mortality and suggest that native inhibitors may play a role in the regulation of the biological function of the cytokine.

Animals↗
PubMed1992

A double-blind, parallel-group comparison of flosequinan and enalapril in the treatment of chronic heart failure.

The effects of flosequinan and enalapril on exercise capacity (bicycle exercise duration), quality-of-life symptomatology (visual analogue scales) and New York Heart Association (NYHA) grading, were compared in 61 patients with chronic heart failure (NYHA, grade III). Bicycle exercise duration improved similarly with flosequinan (+27%) and enalapril (+18%); in patients completing the study, flosequinan produced a significantly greater increase in exercise time at week 12, compared with enalapril (P = 0.02). Improvements in visual analogue scores relating to general health, energy and vitality, ability to perform physical activities and breathing performance, were equivalent for both drugs. Changes in NYHA classification showed that 27 (55%) of 49 patients completing the study had improved by at least one NYHA grade (15 (68%) patients on flosequinan; 12 (44%) on enalapril). The overall safety and tolerability of the two treatments was similar; 18 patients reported adverse effects while on flosequinan, compared with 19 patients on enalapril. Neither treatment was associated with any clinically important changes in haematological or biochemical variables, although some treatment-related effects were observed. This study confirms that flosequinan achieved similar efficacy to enalapril in the symptomatic relief of chronic heart failure. The effect of flosequinan on survival in chronic heart failure has not been tested; pending such studies, our data suggest that it may prove a useful alternative therapy in patients where ACE inhibitors are contraindicated or poorly tolerated.

Adult↗
PubMed1992

Mucosal peptic activity during Helicobacter pylori infection in pediatric patients.

Intramucosal peptic activity may participate in the genesis of acute and chronic superficial gastritis. The proteolytic activity of homogenates of gastric mucosa (antrum and body) and duodenum were measured at pH 2.0 (total peptic activity) after exposure to pH 8.0 (pepsinogen) and the activated pepsinogen (pepsin) was calculated in pediatric patients investigated for the presence of Helicobacter pylori (H pylori), 122 antral, 77 stomach body, and 74 duodenal biopsies were examined in 43 H pylori positive patients, 51 controls, and 28 H pylori negative gastritis patients. Activated pepsinogen was significantly reduced in the stomach of H pylori positive patients only. Pepsinogen values were similar in all the anatomical areas tested in all patients. In 13 H pylori positive patients reinvestigated three months after antibiotic therapy, antral mucosal activated pepsinogen activity increased significantly (mean pretreatment 1.56 (1.0) U/mg protein versus mean post-treatment 2.72 (1.7) U/mg protein) and reached values comparable with controls. The decreased activated pepsinogen activity in association with normal pepsinogen content observed in the antrum of H pylori positive gastritis patients indicate local pepsin inactivation or alternately enhanced removal into the gastric lumen or backflow into the circulation.

Adolescent↗
PubMed1991

Effect of sub-minimal inhibitory concentrations of ciprofloxacin and fleroxacin on the bacterial capsular antigen and opsonophagocytosis by human polymorphonuclear leukocytes.

We have studied the effect of sub-minimal inhibitory concentrations (sub-MIC) of ciprofloxacin and fleroxacin on capsulated (K+) and non-capsulated (K-) Gram-negative bacilli (Escherichia coli O1:K1, O7:K1, O1:K-, O7:K-, and Klebsiella oxytoca) as well as on Staphylococcus aureus and we investigated the interaction of antibiotic pretreated bacteria with human serum and polymorphonuclear leukocytes (PMN). Following overnight growth in the presence of 1/2 MIC of the antibiotics, bacteria were opsonized in human serum and incubated with PMN. Opsonophagocytosis was quantified as the ratio of uptake by PMN of radioactively labeled bacteria. Ciprofloxacin and fleroxacin enhanced the phagocytosis rate of E. coli K+ strains (control 5-10%; 1/2 MIC of ciprofloxacin and fleroxacin 70-80%) of K. oxytoca (control O-2%; 1/2 MIC of ciprofloxacin and fleroxacin 35-40%) as well as of Staph. aureus (control 5-10%; 1/2 MIC of the antibiotics 35-40%). Opsonophagocytosis of K- strains was not altered. The enhancement of opsonophagocytosis was a complement dependent process. Exposure of capsulated E. coli to ciprofloxacin as well as to fleroxacin resulted in decreased amounts of the capsular antigen.

Agglutination Tests↗
PubMed1991

Immunization of mice with antibiotic-treated Escherichia coli results in enhanced protection against challenge with homologous and heterologous bacteria.

The murine immune response to Escherichia coli exposed to subminimal inhibitory concentrations of four antibiotics was investigated. Groups of mice were injected for 8 weeks with formalin-killed bacteria and subsequently challenged with 10 x LD50 of viable E. coli. Mice receiving saline only (controls) died within 24 h. The mortality of mice immunized with ciprofloxacin-treated E. coli was significantly lower than that of mice immunized with E. coli untreated or treated with other antibiotics. Sera from mice immunized with ciprofloxacin-treated bacteria showed better bacteriostatic capacity and enhanced production of antibodies that bound to homologous and heterologous lipopolysaccharide isolated from several smooth and rough gram-negative strains. The better protection observed in mice immunized with ciprofloxacin-treated E. coli was probably due to an enhanced production of antibodies to epitopes on lipopolysaccharide that became better exposed and so more accessible after treatment with ciprofloxacin.

Animals↗
PubMed1991

Microcomputer software applied to corneal stromal biometry.

Here we report a new method for image analysis of the corneal stroma. To obtain the biometric characteristics of a given area, we perform three different treatments of the same image. These automated predictions closely match each parameter (length, surface area, etc.), as measured manually by a "blind investigator." Furthermore, to obtain quantifiable, average values, we have increased the number of successive image measurements, which has led to the development of a series of programs designed to optimize automated data handling. Finally, the acquired, calculated parameters are summarized in the form of intermediate tables for each series of images, and as a final summary table incorporating t-test values and permitting comparison between two stromas (e.g., normal and pathological). Multivariate analysis and an ascending hierarchical classification demonstrate the main trends in differences of pathological vs. normal stroma.

Algorithms↗
PubMed1991

Effects of dobutamine and salbutamol on haemodynamics and atrial natriuretic factor in patients with severe congestive heart failure.

The influence of two cardiac inotropic drugs, dobutamine and salbutamol, on plasma atrial natriuretic factor (ANF) was investigated in 20 patients with congestive heart failure. All were in New York Heart Association class-III or IV. The patients underwent right heart catheterization with determination of central pressures, cardiac output, and pulmonary arterial plasma ANF during incremental infusions with dobutamine or salbutamol. Fourteen patients completed the study. Both drugs induced comparable increases in cardiac index and decreases in total systemic vascular resistance (P less than 0.01) without significant changes in central pressures. Heart rate rose after salbutamol (P less than 0.05), but not after dobutamine. No changes in plasma ANF were observed after either of the drug infusions. ANF secretion rate was calculated from simultaneous measurements of ANF in right atrial and pulmonary arterial plasma before and after salbutamol infusion, and median values rose more than seven-fold (P less than 0.05). The results demonstrate that ANF secretion rate is augmented after beta-adrenergic agents, possibly by a direct beta 2-adrenergic stimulation, in patients with severe congestive heart failure, and that changes in plasma ANF are an insufficient measure of ANF release when patient samples are small.

Adult↗
PubMed1991

Significance of adrenoceptor-mediated atrial natriuretic factor release in normal humans.

To assess the potential role of adrenoceptor-stimulated atrial natriuretic factor (ANF) release in healthy humans, 18 volunteers, divided into groups of six, underwent experiments with infusion of incremental doses of salbutamol with and without beta-blockade with propranolol, propranolol alone, and bolus injections of clonidine before and after alpha-blockade with phentolamine, and phentolamine alone. Since changes in right atrial pressure have been shown to influence ANF release, central venous pressure (CVP) was continuously measured 30 min before, during the 120 min duration of drug infusions, and for 30 min after the bolus injections of the drugs. ANF was serially determined in central venous plasma during all drug infusions, and plasma catecholamines were measured to determine any possible influence of endogenous sympathetic activation on ANF levels. Plasma ANF was unaffected by all individual drugs and drug combinations, despite significant reductions in CVP in the salbutamol, phentolamine and phentolamine + clonidine groups, and a doubling of heart rate during salbutamol administration (p less than 0.01 for all). The results do not suggest a major role for adrenoceptor-mediated ANF release in normal humans, and do not indicate that plasma ANF levels are determined by tonic inhibition or facilitation of the sympathetic nervous system.

Adult↗