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Biomedical subjects

J Ittner

Publications and source records attributed to J Ittner.

12 recordsLinked to original sources
PubMed2001

Improved innate immunity of endotoxin-tolerant mice increases resistance to Salmonella enterica serovar typhimurium infection despite attenuated cytokine response.

During infection with gram-negative bacteria, exposure of immune cells to lipopolysaccharide (LPS) from the bacterial cell membrane induces a rapid cytokine response which is essential for the activation of host defenses against the invading pathogens. Administration of LPS to mice induces a state of hyporesponsiveness, or tolerance, characterized by reduced cytokine production upon subsequent LPS challenge. In the model of experimental Salmonella enterica serovar Typhimurium infection of mice, we assessed the question of whether complete LPS tolerance induced by repetitive doses of LPS interfered with cytokine production and host defense against gram-negative bacteria. Although production of various cytokines in response to serovar Typhimurium was attenuated by LPS pretreatment, LPS-tolerant mice showed improved antibacterial activity, evidenced by a prolongation of survival and a continuously lower bacterial load. We attribute this protective effect to three independent mechanisms. (i) Peritoneal accumulation of leukocytes in the course of LPS pretreatment accounted for enhanced defense against serovar Typhimurium during the first 6 h of infection but not for decreased bacterial load in late-stage infection. (ii) LPS-tolerant mice had an increased capacity to recruit neutrophilic granulocytes during infection. (iii) LPS-tolerant mice showed threefold-increased Kupffer cell numbers, enhanced phagocytic activity of the liver, and strongly improved clearance of blood-borne serovar Typhimurium. These results demonstrate that despite attenuated cytokine response, acquired LPS tolerance is associated with enhanced resistance to infections by gram-negative bacteria and that this effect is mainly mediated by improved effector functions of the innate immune system.

Animals↗
PubMed1998

Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss. Ciblos Study Group.

Osteoporosis is a well-recognized adverse effect of corticosteroid therapy. This study aimed to investigate the effect of etidronate, intermittent cyclical therapy, in the prevention of corticosteroid-induced bone loss. Patients with various medical conditions starting high-dose corticosteroid therapy were enrolled in the study. The treatment had to be expected to continue for at least 12 months with the initial 90 days at a mean daily dose of at least 7.5 mg of prednisone, with subsequent treatment of at least 2.5 mg/day. One hundred seventeen patients were randomly assigned oral etidronate 400 mg/day, or placebo, for 14 days, followed by 76 days of oral calcium carbonate (500 mg elemental calcium), cycled over 12 months. The primary outcome measure was the difference in percent change from baseline in bone mineral density of the lumbar spine between the groups at the end of year 1. Secondary measures included changes in femur bone density and in biochemical markers of bone remodeling. The mean (+/- SEM) lumbar spine bone density changed 0.30 +/- 0.61% and -2.79 +/- 0.63% in the etidronate and placebo groups, respectively. The mean difference between groups after 1 yr was 3.0 +/- 0.84% (P = 0.004). The changes in the femoral neck and great trochanter were not different between the groups. There was a decrease in pyridinium crosslinks, significant from baseline at both 6 and 12 months, in the etidronate group. Osteocalcin increased in the placebo group, and difference between groups was -25.07 +/- 14.89% (P = 0.032) and -34.68 +/- 19.77% (P = 0.051), at 6 and 12 months respectively. There was no significant difference between the groups in number of adverse experiences, including gastrointestinal disorders. Etidronate intermittent cyclical therapy prevents lumbar vertebral bone loss in patients starting high-dose corticosteroid therapy.

Adrenal Cortex Hormones↗
PubMed1993

Serum concentrations of procollagen I C-terminal propeptide, osteocalcin and insulin-like growth factor-I in patients with non-lethal osteogenesis imperfecta.

Serum concentrations of procollagen I C-terminal propeptide (PICP) were studied in 74 patients with various forms of non-lethal osteogenesis imperfecta and 27 unaffected family members. Using the standard deviation (SD) score, PICP concentrations were found to be > or = -1 SD in 16%, between -1 and -2 SD in 26% and < or = -2 SD in 58% of the patients with osteogenesis imperfecta compared to healthy controls. PICP values were lowest in osteogenesis imperfecta type I (-2.4 +/- 0.4 SD, n = 37) followed by type III (-1.9 +/- 0.5 SD, n = 13) and type IV (-1.3 +/- 0.7 SD, n = 20). Four patients with osteogenesis imperfecta with an atypical clinical course had normal or even elevated levels which may indicate heterogeneity in the underlying primary defects. In osteogenesis imperfecta type I, PICP concentrations proved to be a helpful serum marker for pedigree screening. Osteocalcin was high in 25 of 28 patients with osteogenesis imperfecta in the first decade but only in 1 of 18 older patients. Insulin-like growth factor-I was within the normal range in 53 cases of osteogenesis imperfecta, decreased in 2 and elevated in 3 patients. We conclude that PICP concentration is a useful parameter in the clinical management of osteogenesis imperfecta, including the assessment of future therapeutic interventions.

Adolescent↗
PubMed1989

Beta-adrenergic blood pressure regulation in Shy-Drager syndrome and pheochromocytoma.

Both Shy-Drager syndrome and pheochromocytoma are characterized by an abnormal catecholamine secretion, e.g. a reduced secretion in Shy-Drager syndrome, and an excessive stimulation in pheochromocytoma resulting in adrenergic dysfunction and in adrenergic hyperactivity, respectively. The relationship between extreme variations in circulating catecholamines and beta-adrenergic receptor activity was studied in two patients with severe orthostatic hypotension (Shy-Drager syndrome) and in a patient with pheochromocytoma with excessive spontaneous catecholamine increases using the lymphocyte beta 2-adrenoceptor assay. In both patients with Shy-Drager syndrome, basal plasma concentrations of epinephrine and dopamine were low under resting conditions and could not be stimulated in the upright position. Norepinephrine was low in the first patient, and could not be stimulated; whereas the second patient had a normal basal concentration of norepinephrine, which could be moderately stimulated. There was no beta-adrenoceptor abnormality in the first patient: however, in the second patient, there were no measurable beta-adrenoceptors on membrane fractions, whereas a population of receptors only in the low affinity state could be identified on intact cells. Alpha-adrenoceptor density on thrombocyte membranes was slightly increased in both patients with Shy-Drager syndrome and showed no substantial change during upright posture. Catecholamine increases in the pheochromocytoma patient were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of beta-adrenoceptors. Plasma concentrations of cAMP paralleled the increase in receptor density and blood pressure. The findings in pheochromocytoma add support to the theory that an acute catecholamine stimulation gives rise to an acute beta-adrenergic sensitization leading to blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1988

[Bone loss in female patients with anorexia nervosa].

Osteoporosis is occasionally seen in young women with episodes of anorexia nervosa. To study anorectic osteopenia we have examined 10 patients aged 18 to 37 years before, during and after treatment. Treatment consisted of hospitalization for correction of underweight by tube feeding and subsequent psychotherapy. Bone-density measurements performed with high-precision, low-dose, quantitative computed tomography of the distal radius and the distal tibia before treatment showed an age-dependent pattern. Linear regression suggests a trabecular bone loss of approximately 3% per year. This loss might be caused by low estrogens, because all patients were amenorrheic. After tube-feeding periods of 27 to 89 days (5 patients), trabecular bone density of the tibia was further reduced by 10.3% (range 6-13%) below pretreatment values. One year later average trabecular bone diminution was 17.3% (range 8-28%). Such rapid bone loss may cause osteoporosis within a few years, and treatment is therefore required for prevention of this skeletal deterioration.

Adolescent↗
PubMed1986

Long-term fluoride therapy of postmenopausal osteoporosis.

The benefit of sodium fluoride (NaF) in the therapy of osteoporosis is still controversial. For 3 years we monitored patients with postmenopausal osteoporosis subjected to a continuous treatment with 80 mg NaF/day and patients without fluoride treatment. Every 3 months peripheral total and trabecular bone densities were evaluated with high-precision low-dose quantitative computed tomography, every 6 months biochemical parameters were measured, and every year new crush fractures were determined. The untreated osteoporotics as a group lost bone at a rate of 2.5%/year. In the fluoride-treated group trabecular bone density of the distal tibia remained unchanged in 5 of 15 treated patients; 2 patients experienced a bone loss, 8 patients showed at least a temporary bone gain. After 3 years trabecular bone density of the treated patients was 8% higher than that of the untreated patients. Total bone density was not increased. The fracture rates in a group of untreated and a group of NaF-treated patients matched with regard to age, height, weight, initial fracture rate, and initial trabecular bone density were significantly different in the first year, with 0.3 new fractures in the untreated group and 2.9 new fractures in the treated group. During the second and third year the mean number of new fractures was approximately equal in both groups. In 47% of the treated patients, osteoarticular side effects were observed. In 27%, scintigraphy of the ankle was positive, alkaline phosphatase was increased, and radiologic signs of healing stress fractures were present.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Reduced parathyroid hormone response to peroral phosphate in osteoporotic patients.

To determine whether PTH secretion can be stimulated in osteoporosis by peroral phosphate (1.5 g phosphorus), we have compared serum PTH and urinary cyclic AMP responses in 8 osteoporotic patients with vertebral compression fractures to those of 7 age-matched control subjects. While there was no statistically significant difference in the rise of serum phosphate and urinary phosphate excretion and in the fall of serumionized calcium concentrations, serum PTH and urinary cyclic AMP were increased in control subjects, but not in osteoporotic patients (osteoporotics vs. control group: PTH, p less than 0.01; cyclic AMP/glomerular filtrate, p less than 0.05). Moreover, plasma levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were the same in the 2 groups of subjects. Serum levels of the carboxyl-terminal flanking peptide (PDN-21) encoded by the calcitonin gene and cosecreted with calcitonin were similar in normal and osteoporotic subjects before and 3 min after 1-min intravenous calcium infusions (2 mg/kg body weight), and of calcitonin after the calcium infusions. We conclude that calcitonin and PDN-21 responses to intravenous calcium are the same in normal and osteoporotic subjects, whereas stimulation of PTH secretion by peroral phosphate is impaired in some osteoporotic patients.

Administration, Oral↗
PubMed1985

Diagnostic evaluation of measurements of carboxyl-terminal flanking peptide (PDN-21) of the human calcitonin gene in human serum.

Calcitonin and its carboxyl-terminal flanking peptide (PDN-21), also encoded by the calcitonin gene, were measured by RIA in unextracted serum of normal subjects and patients with primary hyperparathyroidism and surgically verified and suspected medullary thyroid carcinoma. Serum PDN-21 was detectable (greater than 0.005 ngeq/ml) in the large majority of normal subjects (92%), and the values increased significantly more in men than women (4.8- and 2.0-fold, respectively; P less than 0.01) in response to 1-min iv calcium injections. Calcitonin was detectable (greater than 0.025 ngeq/ml) in only 25% of normal subjects before iv calcium and became measurable after iv calcium in 88% of men and 41% of women. In patients with chronic hypercalcemia due to primary hyperparathyroidism, PDN-21 and calcitonin were within normal limits. In normal subjects, iv pentagastrin (0.5 microgram/kg BW) did not increase PDN-21, and calcitonin remained undetectable. In 41 medullary thyroid carcinoma patients, basal PDN-21 and calcitonin levels were increased similarly, and they were stimulated in response to iv calcium or iv pentagastrin. In 5 siblings of medullary thyroid carcinoma patients, PDN-21 and calcitonin were increased in response to iv pentagastrin, and we suspect C-cell hyperplasia or medullary thyroid carcinoma. In conclusion, a diagnostically useful RIA for the measurement of PDN-21 in unextracted serum which complements calcitonin measurements has been developed.

Adolescent↗
PubMed1985

[Comparative studies of short-term anesthesia with alfentanil/etomidate and alphaxalone/alphadolone in cats].

In a clinical study alfentanil/etomidat-short-active anaesthesia was used in 150 cats. The anaesthesia progress was compared to usual steroid anaesthesia by using clinical parameters as respiratory and pulse frequency as well as reflexes. Surgical tolerance in both anaesthesia was 6 minutes without and 7 minutes with azaperon premedication. In both anaesthesia excitations occur during waking time. They can be prevented by using a calm waking room or by premedication with azaperon (in subclinical dose of 0.25 mg/kg BW) or diazepam (in the usual dose of 0,2-1 mg/kg BW). Premedication with diazepam is preferred because it has no influence on respiration and circulation and does not intensify the anaesthesia. Indications for alfentanil/etomidat short-active anaesthesia are minor surgery, diagnostic measures and teeth treatment. In addition, alfentanil/etomidat was shown to be suitable for introducing inhalation anaesthesia particularly in old and sick animals.

Adjuvants, Anesthesia↗