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Biomedical subjects

P Ammann

Publications and source records attributed to P Ammann.

At least 19 recordsLinked to original sources

Pregnancy-associated spontaneous coronary artery dissection: impact of medical treatment. Case report and systematic review.

We report on a 22- year-old woman with postpartum dissection of the left anterior descending artery and the intermediate branch. The patient was treated with acetylsalicylic acid (ASA), clopidogrel, and betablocker only. Coronary angiography performed 20 months later revealed complete resolution of the dissection sites. The patient's cardiovascular risk factors included mild smoking and high total cholesterol and low-density-lipoprotein-cholesterol levels, which showed a marked fall after pregnancy without pharmacological cholesterol-modifying therapy raising the question whether pregnancy-related hypercholesterolemia contributed to the pathogenesis of pregnancy-associated spontaneous coronary artery dissection (P-SCAD). In a systematic review of the literature, 16 women [median age 34 (31-36.5) years] with P-SCAD and angiographic follow-up were identified. The majority (69%) of P-SCAD cases occurred postpartum [median time after delivery: 13 (7-21) days]. In 10/16 (63%) patients medical treatment including betablocker and antiplatelet therapy was given leading to complete resolution of the dissection in 5 of them (31% of all patients) at follow-up, whereas in the other 5 patients the dissections were persisting or even progressive. Of the medically treated patients, 80% were free of symptoms suggestive for ischemia at follow-up. In 5/16 patients percutaneous coronary intervention (PCI) was performed as first-line therapy. Three patients underwent coronary artery bypass grafting, which was performed primarily in one patient, and secondarily in two patients with persisting dissections and ongoing ischemic symptoms after previous medical treatment or PCI without stenting, respectively. In conclusion, medical treatment including ASA, clopidogrel and betablocker therapy results in an excellent clinical and angiographic result in approximately one third of patients with P-SCAD.

Adult↗

Toltrazuril treatment to control diaplacental Neospora caninum transmission in experimentally infected pregnant mice.

We addressed the question whether diaplacental transmission of Neospora caninum can be controlled by metaphylactic chemotherapy using toltrazuril or enrofloxacin. Female C57/BL6 mice, infected on day 10 of pregnancy, were medicated for 6 consecutive days p.i. with 52.5 mg toltrazuril or - as an out-group control medication--16.7 mg enrofloxacin per kg body weight per day. Other control groups received either infection but no medication or vice versa. Toltrazuril treatment significantly reduced pre- and perinatal losses (10 deliveries of healthy newborns, versus 1 abortion and 4 failures) when compared to control-enrofloxacin (2 deliveries, versus 1 abortion, 7 failures and 2 pre-parturient deaths of dams) and non-treated animals (3 deliveries, versus 6 abortions, 8 failures and 4 pre-parturient deaths). Simultaneously, PCR-based parasite detection in the brain of mothers, histopathological findings as well as clinical fatality were significantly less frequent in toltrazuril-treated dams. The overall toltrazuril treatment efficacy was determined as 87 %, that of enrofloxacin-treatment as 17 %. The progenies of toltrazuril-treated dams also exhibited a very low rate of PCR-positivity in their brain (3 out of 39), whereas untreated dams delivered litters with mostly PCR-positive brains (12 out of 14) and a relatively high death rate post-partum (5 out of 19 newborns died). Mice subjected to a second mating delivered newborns all negative by N. caninum-PCR, indicating that diaplacental tachyzoite passage does not occur in a later, repeated pregnancy. Overall, our experiments showed that toltrazuril-treatment of an acute N. caninum-infection--induced during pregnancy--results in a clear reduction of fetal losses and a marked reduction of diaplacental passage of the parasite to the fetal brain, whereas enrofloxacin, as an out-group control substance, failed to show the same effect.

Animals↗

Effect of different masticatory functional and mechanical demands on the structural adaptation of the mandibular alveolar bone in young growing rats.

The influence of masticatory functional and mechanical demands on the structural adaptation of the alveolar bone has not been investigated in both animals and humans. The effect of two experimental factors, the insertion of a bite-opening appliance and the alteration of food consistency, was investigated in young growing rats, with a particular emphasis on three-dimensional (3D) bone microstructure. Thirty-six male albino rats were divided into two equal groups, fed with either the standard hard diet or soft diet, at the age of 4 weeks. After 2 weeks, half of the animals in both groups had their upper molars fitted with an upper posterior bite block, an appliance similar to those used in clinical orthodontics. The remaining animals served as a control. After another 4 weeks, the animals were sacrificed, and their left hemimandibles were excised. Bone mineral density (BMD) and bone microstructure parameters of the alveolar process were subsequently measured, using dual-energy X-ray absorptiometry (DXA) and micro-computed tomography (micro-CT). The alveolar process width was also measured. Both experimental factors led to significant shape and structure modification of the mandibular alveolar bone in the growing rat. The bite block applied a continuous light force, which was associated with an inhibition of alveolar process vertical growth and a significant increase of cortical thickness. Soft diet and the consequent reduction of the intermittent forces applied to the alveolar bone during mastication resulted in a reduction of bone mineral density, accompanied by decreased trabecular bone volume and thickness. This rat model could prove to be a useful tool for the in vivo investigation of the role of muscular forces on the shape and structure adaptation of bone.

Absorptiometry, Photon↗

A new selective estrogen receptor modulator HMR-3339 fully corrects bone alterations induced by ovariectomy in adult rats.

The selective estrogen receptor modulator (SERM) raloxifene has been shown to reduce the risk of vertebral fracture, but without significant effect on nonvertebral fractures. However, there is a need for SERMs capable of improving mechanical competence and reducing the risk of fractures at multiple skeletal sites, with minimal side effects. We investigated the effects of a new steroidal SERM, HMR-3339, compared to raloxifene, on bone strength and its determinants (BMD, microarchitecture, dimensions) at various skeletal sites (lumbar spine, tibia, and femur) of adult ovariectomized rats in both prevention and intervention protocols. In a prevention study, HMR-3339 and raloxifene treatments fully prevented alterations of bone strength. In an intervention protocol, where treatment was started 8 weeks after ovariectomy, HMR-3339 fully restored mechanical properties by influencing both areal BMD and outer diameter. This effect was observed at skeletal sites formed of cancellous and cortical bone or of cortical bone only. In contrast, raloxifene positively influenced structures containing mainly cancellous bone. In HMR-3339-treated rats, IGF-I plasma levels were higher than in ovariectomized controls; this was not observed with raloxifene. In conclusion, these results indicate that HMR-3339 increased not only bone mineral mass, but also restored bone mechanical strength at multiple sites in adult osteoporotic rats. In contrast to raloxifene, HMR-3339 also influenced skeletal sites predominantly formed of cortical bone.

Animals↗

Time course of serial cystatin C levels in comparison with serum creatinine after application of radiocontrast media.

BACKGROUND: The delayed increase of creatinine after radiocontrast application is a potential reason for overlooking radiocontrast nephrotoxicity. Cystatin C may be more useful to rapidly assess a decrease in glomerular filtration rate (GFR). We compared cystatin C and creatinine to examine their kinetics after application of radiocontrast media. PATIENTS AND METHODS: Forty-one patients (60.8 +/- 8.8 years, 68% males) with normal to subnormal GFR scheduled for coronary angiography (27% with angioplasty), were studied for serum cystatin C and creatinine levels before, 5 h, 24 h and 48 h after angiography. Furthermore, alpha1-microglobulin was checked for evidence of tubular damage. RESULTS: At 5 hours after angiography, there was no significant change compared to baseline in either serum creatinine nor cystatin C. In comparison with the value immediately before coronary angiography, the increase of cystatin C achieved a maximum at 24 h after the application of the contrast agent (+7.2%). Within 48 h, cystatin C decreased to the level before angiography. Serum creatinine increased at 24 h (+7.7%) and continued to increase at 48 h (+11.3%). CONCLUSION: Cystatin C increases earlier after radiocontrast application compared with creatinine. Therefore, cystatin C needs to be investigated as a potential early marker for nephrotoxicity, especially in the upcoming setting of short-time hospitalizations for coronary angiographies and interventions. Thus, further studies in patients with renal failure undergoing radiocontrast application are warranted to assess the usefulness of cystatin C in respect of an earlier detection of radiocontrast nephrotoxicity.

Aged↗

Bone strength and its determinants.

Osteoporosis is a disease defined by decreased bone mass and alteration of microarchitecture which results in increased bone fragility and increased risk of fracture. The major complication of osteoporosis, i.e., fracture, is due to a lower bone strength. Thus, any treatment of osteoporosis implies an improvement in bone strength. Bone strength is determined by bone geometry, cortical thickness and porosity, trabecular bone morphology, and intrinsic properties of bony tissue. Bone strength is indirectly estimated by bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA). Since DXA-measured BMD accounts for 60-70% of the variation in bone strength, some important factors are not captured by DXA in the progression of osteoporosis and the effects of antiosteoporotic treatment. Geometry and trabecular microarchitecture have also to be taken into account. Thus, the assessment of intrinsic mechanical quality of bony tissue should provide a better understanding of the role of tissue quality in determining bone strength. The careful investigation of all the determinants of bone strength (bone tissue included) should be considered in the pathophysiology of osteoporosis and in the mechanisms of action of antiosteoporotic drugs.

Biomechanical Phenomena↗

[A case of coronary vasospasm treated with stent placement].

We report about a 49 year old woman with repeated chest pain at rest. During hyperventilation significant ST-segment elevation in leads V1-V5 appeared. Bicycle stress test did not provoke any ECG changes. Coronary angiography showed a significant stenosis of the left anterior descending coronary artery. Successful balloon angioplasty followed by stent implantation was performed. After an uneventful course of twelve months, hyperventilation could provoke neither chest pain nor ECG changes again without any antispastic medical treatment. Impact of fixed atherosclerotic lesions for the occurrence of coronary vasospasm, usefulness of hyperventilation as a non-invasive provocation test and therapy are discussed.

Angina Pectoris, Variant↗

Differential use of cardiac troponin T versus I in hemodialysis patients.

BACKGROUND: Cardiac troponin T (cTnT) is frequently elevated in asymptomatic hemodialysis (HD) patients and predicts increased cardiovascular morbidity and mortality. Compared to cTnT, cardiac troponin I (cTnI) has a shorter half-life. How this influences its diagnostic reliability in chronic HD patients is only partially known. PATIENTS AND METHODS: First, in a cross-sectional study cardiac troponins were measured in 31 asymptomatic HD patients. A third-generation cTnT assay was used. The rate of false positive tests and the intraindividual variability were determined. Second, in a retrospective analysis over 12 months all acute events with clinical suspicion for acute coronary syndrome (ACS) were analysed in the same patients to determine the diagnostic power of cTnT by receiver-operating curve (ROC) plot. RESULTS: Cross-sectional study: 9 of 52 (17%) cTnT and 0/52 cTnI (0%) tests were positive in asymptomatic HD patients with a low intraindividual variability. Retrospective analysis: 16 acute clinical events with determination of cTnT were recorded, and in 4/16 an ACS was diagnosed. Using a cut-off level of 0.1 microg/l, the cTnT test reached a sensitivity of 100%, a specificity of 42%, a positive predicitive value of 36% and a negative predictive value of 100%, using a cut-off level of 0.2 microg/l the corresponding values were 75%, 58%, 38% and 88%. CONCLUSIONS: Cardiac TnT, but only rarely cTnI, is elevated in a significant number of asymptomatic HD patients. For diagnosis of ACS in HD patients, a combination of cTnT and cTnI may be used, since the former has higher sensitivity and the latter higher specificity. A higher threshold value for cTnT in HD patients could further increase its diagnostic accuracy.

Adult↗

[Spontaneous coronary artery dissection as a rare cause of an acute coronary syndrome].

Spontaneous coronary artery dissection is a rare cause of an acute coronary syndrome. This report describes a previously healthy woman without cardiovascular risk factors who presented with an acute anterior non-ST elevation myocardial infarction. Coronary angiography revealed an isolated longitudinal dissection in the middle part of the left anterior descending coronary artery (LAD) with normal flow of the contrast media. The patient was treated conservatively with heparin, aspirin, clopidogrel, and beta-receptor blocker. Stress exercise test was normal at discharge. After an event-free follow-up of three and a half months coronary angiography showed a completely normal LAD. Literature about epidemiology, pathogenesis, diagnosis and treatment of spontaneous coronary artery dissection is reviewed.

Adrenergic beta-Antagonists↗

Recovery of proximal tibia bone mineral density and strength, but not cancellous bone architecture, after long-term bisphosphonate or selective estrogen receptor modulator therapy in aged rats.

Various bisphosphonates and the selective estrogen receptor modulator (SERM) raloxifene are approved treatments of postmenopausal osteoporosis. They increase bone mineral density (BMD), decrease bone turnover, and reduce vertebral fracture incidence through different cellular mechanisms. We investigated the bone cellular activities, architecture, mineral content/density, and strength of ovariectomized (ovx) rats on a long-term bisphosphonate or SERM treatment, at doses of either agent correcting bone strength. Eleven weeks postovariectomy, 6-month-old rats were treated with the SERM MDL 103,323 or with the bisphosphonate pamidronate for 5 months. Doses of pamidronate and MDL 103,323 were selected from previous studies showing correction of the ovx-induced decrease of ultimate strength of proximal tibia. Ultimate and yield strengths, BMD, and histomorphometric parameters were all quantified at the same site, i.e., the proximal tibia metaphysis. Long-term pamidronate decreases bone turnover and bone formation activity, leading to trabecular thinning. MDL 103,323 decreases bone turnover to a lesser extent, and slightly protects trabecular architecture by uncoupling bone resorption and formation activities. The yield strength is corrected by pamidronate, but not by MDL 103,323 treatment. However, neither compound restores the ovariectomy-induced cancellous bone loss. Total tissue area and cortical thickness are unchanged with pamidronate or MDL 103,323 treatment, indicating that cortical bone mass, thickness, and cross-sectional area are not modified. The discrepancy between proximal tibia BMD and mechanical resistance to fracture modifications, on the one hand, and cancellous bone volume, on the other hand, could be due to changes in the degree of mineralization of bone matrix and/or of the intrinsic properties of the bone matrix.

Aging↗

Dietary essential amino acid supplements increase bone strength by influencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet.

This study was designed to investigate whether the administration of dietary essential amino acid supplements in adult rats made osteoporotic by estrogen deficiency and reduced protein intake could reverse the deleterious effects caused by these maneuvers. This animal model was selected to mimic the situation observed in elderly women in whom estrogen deficiency and/or low-protein intake (but also calcium and vitamin D deficiency) are known to contribute to the pathogenesis of osteoporosis. Six-month-old rats were ovariectomized (OVX) and fed an isocaloric 2.5% casein diet for 10 weeks or sham-operated (SHAM) and fed an isocaloric 15% casein diet. The animals fed the 2.5% casein diet were given isocaloric supplements of essential amino acids in similar relative proportion to that of casein at doses of 2.5% or 5% of total diet for an additional 16 weeks. Vertebrae, femur, and tibia bone mineral density (BMD); ultimate strength; and microtomographic histomorphometry were evaluated before and after dietary essential amino acid supplements. Essential amino acid supplements increased vertebrae, femur, and tibia bone strength in OVX rats fed a low-protein diet. The mechanical changes induced by this dietary isocaloric supplement were associated with the prevention of a further BMD decrease or even with some increases and changes in microarchitecture such as from a rod to a plate trabecular spacial configuration and increased cortical thickness. Higher insulin-like growth factor (IGF) I levels, as well as greater bone formation and reduced bone resorption as assessed by biochemical markers of bone remodeling, were found in rats receiving essential amino acid supplements. In conclusion, dietary essential amino acid supplements increased bone strength through modifications of BMD, trabecular architecture, and cortical thickness possibly by an IGF-I-mediated process.

Amino Acids, Essential↗

Gain in bone mineral mass in prepubertal girls 3.5 years after discontinuation of calcium supplementation: a follow-up study.

BACKGROUND: Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS: Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS: We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION: Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

Absorptiometry, Photon↗

Elevation of troponin I in sepsis and septic shock.

OBJECTIVE: To detect myocardial damage in severe systemic inflammation by cTnI measurements in patients without acute coronary syndromes. DESIGN: Prospective case control study. SETTING: Tertiary referral center. PARTICIPANTS: Twenty patients with sepsis, septic shock, and systemic inflammatory response syndrome (SIRS) were examined and compared to controls without coronary artery disease or myocarditis. MEASUREMENTS AND RESULTS: cTnI levels were assessed in patients with SIRS, sepsis, and septic shock. Eight patients (two female/six male) suffered from septic shock, nine (three female/six male) from sepsis without shock, and three (three male) from SIRS. Seventeen patients (85%) showed elevated cTnI (median 0.57 microg/l; 0.17-15.4), whereas no patient in the control group showed elevated cTnI (P < 0.0001). Six patients (30%),--three with septic shock and three with sepsis--died during hospitalization, five of them with elevated cTnI. Four out of five autopsies showed normal coronary arteries. Coronary angiography, autopsy, and stress echocardiography ruled out significant coronary artery disease in ten cTnI-positive patients (59%). In 41 % of cTnI-positive patients, Streptococcus pneumoniae could be cultured, whereas no cTnI-negative or control patient showed signs of infection due to S. pneumoniae. CONCLUSION: Cardiac troponin I was elevated in 85% of patients with sepsis, septic shock or SIRS in our study. A high percentage showed infection caused by S. pneumoniae. In what way microorganisms cause cTnI elevations is not yet understood.

Aged↗

Mechanisms of action and therapeutic potential of strontium in bone.

The processes of bone resorption and formation are tightly governed by a variety of systemic and local regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium (Sr), have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, strontium was found to have anabolic activity in bone, and this may have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium has been thought to have potential interest in the treatment of osteoporosis. This review summarizes the mechanisms of action of strontium on bone cells, the evidence for its beneficial effects on bone mass in vivo, and its potential therapeutic effects in osteopenic disorders.

Animals↗

Protein intake and bone disorders in the elderly.

Malnutrition, most notably protein deficiency, contributes to the occurrence of osteoporotic fractures not only by decreasing bone mass but also by altering muscle function. Furthermore, malnutrition is associated with increased morbidity in patients with osteoporotic fractures. The somatomedin system (IGF-1) may be directly involved in the pathogenesis of osteoporotic hip fractures and their complications in elderly patients. A low IGF-1 level is a risk factor for hip fracture. In subjects with appropriate intakes of vitamin D and calcium, giving protein supplements to correct an inadequate spontaneous protein intake increases circulating IGF-1 levels, improves clinical outcomes after hip fracture, and prevents bone mineral density loss at the proximal femur. Supplemental protein also significantly reduces the length of inpatient rehabilitation care. These data emphasize the importance of adequate nutrient intake in the prevention and treatment of osteoporotic fractures.

Age Distribution↗

Incorporation and distribution of strontium in bone.

The distribution and incorporation of strontium into bone has been examined in rats, monkeys, and humans after oral administration of strontium (either strontium chloride or strontium ranelate). After repeated administration for a sufficient period of time (at least 4 weeks in rats), strontium incorporation into bone reaches a plateau level. This plateau appears to be lower in females than in males due to a difference in the absorption process. Steady-state plasma strontium levels are reached more rapidly than in bones, and within 10 days in the rat. The strontium levels in bone vary according to the anatomical site. However, strontium levels at different skeletal sites are strongly correlated, and the strontium content of the lumbar vertebra may be estimated from iliac crest bone biopsies in monkeys. The strontium levels in bone also vary according to the bone structure and higher amounts of strontium are found in cancellous bone than in cortical bone. Furthermore, at the crystal level, higher concentrations of strontium are observed in newly formed bone than in old bone. After withdrawal of treatment, the bone strontium content rapidly decreases in monkeys. The relatively high clearance rate of strontium from bone can be explained by the mechanisms of its incorporation. Strontium is mainly incorporated by exchange onto the crystal surface. In new bone, only a few strontium atoms may be incorporated into the crystal by ionic substitution of calcium. After treatment withdrawal, strontium exchanged onto the crystal is rapidly eliminated, which leads to a rapid decrease in total bone strontium levels. In summary, incorporation of strontium into bone, mainly by exchange onto the crystal surface, is dependent on the duration of treatment, dose, gender, and skeletal site. Nevertheless, bone strontium content is highly correlated with plasma strontium levels and, in bone, between the different skeletal sites.

Administration, Oral↗

Protein intake and bone growth.

Among osteotrophic nutrients, proteins play an important role in bone development, thereby influencing peak bone mass. Consequently, protein malnutrition during development can increase the risk of osteoporosis and of fragility fracture later in life. Both animal and human studies indicate that low protein intake can be detrimental for both the acquisition of bone mass during growth and its conservation during adulthood. Low protein intake impairs both the production and action of IGF-I (Insulin-like growth factor-I). IGF-I is an essential factor for bone longitudinal growth, as it stimulates proliferation and differentiation of chondrocytes in the epiphyseal plate, and also for bone formation. It can be considered as a key factor in the adjustments of calcium-phosphate metabolism required for normal skeletal development and bone mineralization during growth. In healthy children and adolescents, a positive association between the amount of ingested proteins and bone mass gain was observed in both sexes at the level of the lumbar spine, the proximal femur and the midfemoral shaft. This association appears to be particularly significant in prepubertal children. This suggests that, like for the bone response to either the intake of calcium or weight-bearing exercise, the skeleton would be particularly responsive to the protein intake during the years preceding the onset of pubertal maturation.

Animals↗