Effect of weekly hiking on cardiovascular risk factors in the elderly.

BACKGROUND: Hiking is one of the most popular activities among the elderly in Alpine regions. Due to the long-lasting, moderately intensive nature of this form of physical activity, hiking is generally considered to be beneficial to health. However, it is currently unclear whether once-weekly hiking--as commonly practiced at weekends--really does yield such positive effects in elderly persons aged 60 years and over. OBJECTIVES: This study investigated the effect of a single weekly mountain hiking session on cardiovascular risk factors. MATERIALS AND METHODS: A 9-month mountain hiking program was completed by 14 male (age 65.6 ± 2.7 years) and 10 female (age 66.2 ± 4.4 years) elderly participants. The program consisted of a single weekly hiking session with the goal of achieving a 500-m altitude increase within 3 h. Before and after the 9-month program, an electrocardiogram (ECG) was performed and blood pressure, glycated hemoglobin (HbA1c), high-density (HDL) and low-density lipoprotein (LDL) measurements were made. RESULTS: The elderly participants showed a normal cardiovascular risk profile at the start of the investigation. The estimated net energy expenditure for one hiking session was approximately 521 ± 91 kcal. Over the 9-month period, no changes were found in any of the investigated parameters for the entire group. However, participants with untreated hypertension showed a reduced systolic blood pressure. CONCLUSION: The present investigation showed that moderate-intensity activity only at weekends does not improve cardiovascular risk factors in elderly persons with a relatively normal cardiovascular risk profile. Conversely, elderly persons suffering from hypertension might profit from such a practice.

[Osteochondrosis dissecans and osteochondral lesions of the talus: clinical and biochemical aspects]. / Die Osteochondrosis dissecans und osteochondrale Läsionen des Talus: klinische und biomechanische Aspekte.

BACKGROUND: The natural course of osteochondral lesions of the talus are varied and the disease pattern is not clearly defined. There is an ongoing discussion among clinicians concerning the aethiopathology and the correct treatment. METHODS: In this article all relevant studies are analysed with regard to aetiology, long-term outcome and the different established treatment options. Against the background of the current biomechanical understanding, an approach is made to this controversially discussed disease pattern utilising our own biomechanical laboratory results. RESULTS: The available literature deals with longitudinal analyses regarding the natural history of the disease, conservative treatment, surgical options like debridement and anterograde drilling, retrograde drilling, osteochondral transplantation and autologous chondrocyte transplantation (ACT). Biomechanical trials describe high loads in the anterolateral parts of the joint. In most of the published studies the average age of the patients is around 28 years, younger patients have more favourable outcomes compared to older ones. In children the highest rate of spontaneous and advantageous course of the disease can be expected. Around 75% of the published outcomes relating to surgical therapy are satisfactory while 10% of the patients will suffer from osteoarthritis in the long term. CONCLUSION: While the aetiopathology of the disease remains unclear, histopathological studies reveal subcortical bone necrosis. In 90% of the cases there is an ankle sprain in the past medical history although a direct correlation with trauma as exclusive trigger is not obvious. A possible approach is an osteochondral fracture in combination with an already existing osteonecrosis. A staged treatment regime is advised. In asymptomatic cases conservative treatment is advocated independent of the stage. Symptomatic patients with Hepple stages I, II and V and intact cartilage surface should undergo retrograde drilling in combination with a subchondral filling with cancelleous bone. If a cartilage defect is present (Hepple stages III, IV, V), an osteochondral transplantation is reasonable. Only if the defect zone is >2.5 cm2 should a debridement combined with a transplantation of cancellous bone and an ACT be considered. The sole anterograde drilling in our opinion should only be performed as an exception.

In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.

The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of [¹4C]taranabant, the majority of the radioactivity was excreted within 72 h. In both rats and rhesus monkeys, taranabant was eliminated primarily via oxidative metabolism, followed by excretion of metabolites into bile. Major pathways of metabolism that were common to rats and rhesus monkeys included hydroxylation at the benzylic carbon adjacent to the cyanophenyl ring to form a biologically active circulating metabolite M1, and oxidation of one of the two geminal methyl groups of taranabant or M1 to the corresponding diastereomeric carboxylic acids. Oxidation of the cyanophenyl ring, followed by conjugation with glutathione or glucuronic acid, was a major pathway of metabolism only in the rat and was not detected in the rhesus monkey. Metabolism profiles of taranabant in liver microsomes in vitro were qualitatively similar in rats, rhesus monkeys and humans and included formation of M1 and oxidation of taranabant or M1 to the corresponding carboxylic acids via oxidation of a geminal methyl group. In human liver microsomes, metabolism of taranabant was mediated primarily by CYP3A4.

Splanchnic tissue oxygenation, but not brain tissue oxygenation, increases after feeds in stable preterm neonates tolerating full bolus orogastric feeding.

OBJECTIVE: The objective of this prospective, observational study was to test the hypothesis that tissue oxygenation in the splanchnic bed compared with tissue oxygenation in the cerebral circulation changes after feeding in preterm neonates who are tolerating full bolus orogastric feeds. STUDY DESIGN: Clinically stable premature neonates with postmenstrual age between 32 and 35(6/7) weeks who were tolerating full bolus feedings were studied before feeding and 1 h after feeding using near-infrared spectroscopy. The ratio of oxygenated to reduced hemoglobin (tissue oxygenation index, TOI) in the splanchnic circulation bed was divided by the TOI in the cerebral circulation, thereby yielding the cerebro-splanchnic oxygenation ratio (CSOR). We compared TOI and CSOR before and after feeding. As the changes in TOI and CSOR had non-Gaussian distribution, nonparametric statistics were used. RESULT: Among 32 infants, CSOR increased significantly after feeding (median difference 0.08; range -0.48, +0.58; P=0.011), whereas pulse oximetry did not change significantly (P=0.600). The change in CSOR with feeding was associated with a significant increase in splanchnic TOI (preprandial median 43.8, range 25.2-68.4 vs postprandial 47.5, range 25.8-70.8; P=0.013), without any significant change in brain TOI (preprandial median 64.9, range 44.5-75.4 vs postprandial 58.9, range 42.2-72.3; P=0.153). CONCLUSION: This study indicates that CSOR and splanchnic TOI, but not brain TOI, increase significantly after feeding in stable preterm infants who are tolerating full orogastric feeds.

[From endoscopic mucosa ressection to gastrectomy. How radical must surgery be for stomach cancer?]. / Von der endoskopischen Mukosaresektion bis zur Gastrektomie. Wie radikal muss die Magenkrebs-OP sein?

The aim of surgical treatment is complete resection (Ro-resection) of the tumor in all dimensions of its growth, i.e. resection of the tumor infiltrated stomach including the locoregional lymph nodes. This can be achieved by stage- or histology adapted surgery resulting in subtotal distal and total gastrectomy as complementary procedures. Local excision of gastric carcinoma in curative intent is indicated only in mucosal carcinoma of the intestinal type. The extent of lymph node dissection is still under discussion; the results depend on the experiences of the surgeon. Several studies have shown a prognostic improvement after systematic (D2) lymphadenectomy in stage II/IIIA-disease or in patients with a low incidence of lymph node metastases. Pancreas preserving splenectomy is suggested in tumors of the proximal stomach or after direct infiltration of these organs. The Roux-en-Y procedure represents the most commonly used method of reconstruction after subtotal distal or total gastrectomy. The importance of the duodenal passage as well as of the pouch construction must be investigated in prospective studies in the future. This is true for the value of perioperative multimodal treatment options.

Successful perinatal management of hydrops fetalis due to hemolytic disease associated with D-- maternal phenotype.

We report the successful management of a case of hemolytic disease and hydrops fetalis secondary to anti Rh 17 antibodies in a woman with the rare D-- phenotype. We discuss the efficacy of intravenous immunoglobulins in treating hemolytic disease of the newborn infant.

Light interference from single atoms and their mirror images.

A single atom emitting single photons is a fundamental source of light. But the characteristics of this light depend strongly on the environment of the atom. For example, if an atom is placed between two mirrors, both the total rate and the spectral composition of the spontaneous emission can be modified. Such effects have been observed using various systems: molecules deposited on mirrors, dye molecules in an optical cavity, an atom beam traversing a two-mirror optical resonator, single atoms traversing a microwave cavity and a single trapped electron. A related and equally fundamental phenomenon is the optical interaction between two atoms of the same kind when their separation is comparable to their emission wavelength. In this situation, light emitted by one atom may be reabsorbed by the other, leading to cooperative processes in the emission. Here we observe these phenomena with high visibility by using one or two single atom(s), a collimating lens and a mirror, and by recording the individual photons scattered by the atom(s). Our experiments highlight the intimate connection between one-atom and two-atom effects, and allow their continuous observation using the same apparatus.

A photoactivatable prenylated cysteine designed to study isoprenoid recognition.

Protein prenylation, involving the alkylation of a specific C-terminal cysteine with a C(15) or C(20) isoprenoid unit, is an essential posttranslational modification required by most GTP-binding proteins for normal biological activity. Despite the ubiquitous nature of this modification and numerous efforts aimed at inhibiting prenylating enzymes for therapeutic purposes, the function of prenylation remains unclear. To explore the role the isoprenoid plays in mediating protein-protein recognition, we have synthesized a photoactivatable, isoprenoid-containing cysteine analogue (2) designed to act as a mimic of the C-terminus of prenylated proteins. Photolysis experiments with 2 and RhoGDI (GDI), a protein which interacts with prenylated Rho proteins, suggest that the GDI is in direct contact with the isoprenoid moiety. These results, obtained using purified GDI as well as Escherichia coli (E. coli) crude extract containing GDI, suggest that this analogue will be an effective and versatile tool for the investigation of putative isoprenoid binding sites in a variety of systems. Incorporation of this analogue into peptides or proteins should allow for even more specific interactions between the photoactivatable isoprenoid and any number of isoprenoid binding proteins.

Estimation of large-scale dimension densities.

We propose a technique to calculate large-scale dimension densities in both higher-dimensional spatio-temporal systems and low-dimensional systems from only a few data points, where known methods usually have an unsatisfactory scaling behavior. This is mainly due to boundary and finite-size effects. With our rather simple method, we normalize boundary effects and get a significant correction of the dimension estimate. This straightforward approach is based on rather general assumptions. So even weak coherent structures obtained from small spatial couplings can be detected with this method, which is impossible by using the Lyapunov-dimension density. We demonstrate the efficiency of our technique for coupled logistic maps, coupled tent maps, the Lorenz attractor, and the Roessler attractor.

[Multimodality therapy concepts in stomach carcinoma]. / Multimodale Therapiekonzepte beim Magencarcinom.

The prognosis of gastric cancer is still poor even after curative R0 resection. Therefore, among various multimodality treatments a lot of phase II/III studies have been carried out evaluating preoperative chemotherapy. Although some positive results have been obtained after this procedure, neoadjuvant chemotherapy is still an experimental approach. In the future the prediction and evaluation of response must be defined more exactly. Using intraoperative radio- or intraperitoneal (hyperthermal) chemotherapy reduction of regional relapse or peritoneal carcinomatosis could be obtained without increased survival in general. According to experience in Japan adjuvant (immuno-)chemotherapy can increase the overall survival rates and even in the Western hemisphere some actual studies with adjuvant chemo- +/- radiotherapy could demonstrate a benefit of survival in patients with lymph node metastases. Nevertheless, multimodality treatment strategies must be investigated in further uniform prospective study protocols.

Motional sidebands and direct measurement of the cooling rate in the resonance fluorescence of a single trapped ion.

Resonance fluorescence of a single trapped ion is spectrally analyzed using a heterodyne technique. Motional sidebands due to the oscillation of the ion in the harmonic trap potential are observed in the fluorescence spectrum. From the width of the sidebands the cooling rate is obtained and found to be in agreement with the theoretical prediction.

The knowledge, attitudes, and practices of dietitians licensed in Oregon regarding functional foods, nutrient supplements, and herbs as complementary medicine.

OBJECTIVE: To examine the perceived knowledge and attitudes of dietitians licensed in Oregon (LDs) regarding the effectiveness and safety of functional foods, nutrient supplements, and herbs as complementary medicine as well as their personal use, recommendations for the use of others, and training needs. DESIGN: A mailed survey was used to gather data. The questionnaire was developed and face-validated after a focus group discussion. SUBJECTS/SETTING: A geographically stratified, random sample of 202 Oregon LDs was surveyed; usable data were collected from 162 LDs (80%). STATISTICAL ANALYSES: Descriptive statistics and chi 2 tests were used to analyze data. The data were weighted to take account of the sampling method and yield population estimates. RESULTS: LDs considered themselves to be knowledgeable of functional foods and nutrient supplements. More than 80% were confident of the effectiveness of functional foods and nutrient supplements for prevention of illness and treatment of chronic illness, and at least 89% were confident of their safety for these uses. Fewer than 75% considered herbs to be safe and only about 50% were confident of the effectiveness of herbs. Only 10% or fewer LDs considered themselves to be knowledgeable about herbs for prevention and treatment of illness. Interest in training about each of these less-traditional nutrition therapies was high. APPLICATIONS/CONCLUSIONS: Oregon LDs consider themselves to be actively practicing in the area of complementary medicine and have a strong desire for further training. The dietetics profession can capitalize on this interest by taking the lead in training dietitians about the role of functional foods, nutrient supplements, and herbs in health.

The effects of interleukin-2 treatment on endothelin and the activation of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: Recent reports suggest that complex interactions exist between the neuroendocrine and immune systems. It has been shown for example that cytokines are able to stimulate the hypothalamo-pituitary-adrenal axis. In addition, some studies present evidence that endothelin is able to modulate the activity of several hypothalamic-pituitary axes, e.g. by inducing the ACTH production. DESIGN: We investigated the effects of interleukin-2 on endothelin levels and the hypothalamo-pituitary-adrenal axis. We determined the interleukin-6, big-endothelin, endothelin-1, ACTH, cortisol and AVP responses to intravenously and subcutaneously administered interleukin-2 in 8 cancer patients in a randomized placebo controlled trial. PATIENTS: 8 Patients (2 female and 6 male), age 44 +/- 4.8 years, were enrolled. All patients had a World Health Organization performance status of 1 or less and a Karnofsky Index of at least 80%. MEASUREMENTS: Blood-samples were taken before and 15, 30, 45, 60, 120, 180, 240, 300 and 360 min after interleukin-2 injection. Cytokine serum levels and the plasma levels of big-endothelin, endothelin, ACTH and AVP were analysed using radioimmuno-assays. Cortisol was assayed by an enzyme-linked immunosorbent assay. RESULTS: Interleukin-2 treatment significantly increased plasma big-endothelin levels (P < 0.01 vs basal) and endothelin-1 levels (P < 0.05 vs basal) within two hours and this was followed by an increase in ACTH (P < 0.01 vs basal) and cortisol (P < 0.05 vs basal) within three hours. Interleukin-6 levels increased two hours after interleukin-2 administration (P < 0.01 vs basal). Interleukin-2 had no detectable effect on AVP, blood pressure or heart rate. CONCLUSIONS: Our data demonstrate that cytokines are able to activate the human hypothalamo-pituitary-adrenal axis in vivo. On the basis of the observed time kinetics and in connection with previous findings from in vitro and animal models, we conclude that endothelin may be a link between cytokines and corticotrophin-releasing hormone, most probably functioning as a cytokine-induced neuromodulator controlling pituitary functions.

Studies on cytochrome P-450-mediated bioactivation of diclofenac in rats and in human hepatocytes: identification of glutathione conjugated metabolites.

The nonsteroidal anti-inflammatory drug diclofenac causes a rare but potentially fatal hepatotoxicity that may be associated with the formation of reactive metabolites. In this study, three glutathione (GSH) adducts, namely 5-hydroxy-4-(glutathion-S-yl)diclofenac (M1), 4'-hydroxy-3'-(glutathion-S-yl)diclofenac (M2), and 5-hydroxy-6-(glutathion-S-yl)diclofenac (M3), were identified by liquid chromatography-tandem mass spectrometry analysis of bile from Sprague-Dawley rats injected i.p. with a single dose of diclofenac (200 mg/kg). These adducts presumably were formed via hepatic cytochrome P-450 (CYP)-catalyzed oxidation of diclofenac to reactive benzoquinone imines that were trapped by GSH conjugation. In support of this hypothesis, M1, M2, and M3 were generated from diclofenac in incubations with rat liver microsomes in the presence of NADPH and GSH. Increases in adduct formation were observed when incubations were performed with liver microsomes from phenobarbital- or dexamethasone-treated rats. Adduct formation was inhibited by polyclonal antibodies against CYP2B, CYP2C, and CYP3A (40-50% inhibition at 5 mg of IgG/nmol of CYP) but not by an antibody against CYP1A. Maximal inhibition was obtained when the three inhibitory antibodies were used in a cocktail fashion (70-80% inhibition at 2.5 mg of each IgG/nmol of CYP). These data suggest that diclofenac undergoes biotransformation to reactive metabolites in rats and that CYP isoforms of the 2B, 2C, and 3A subfamilies are involved in this bioactivation process. With respect to CYP2C isoforms, rat hepatic CYP2C7 and CYP2C11 were implicated as mediators of the bioactivation based on immunoinhibition studies using antibodies specific to CYP2C7 and CYP2C11. Screening for GSH adducts also was carried out in human hepatocyte cultures containing diclofenac, and M1, M2, and M3 again were detected. It is possible, therefore, that reactive benzoquinone imines may be formed in vivo in humans and contribute to diclofenac-mediated hepatic injury.

Elevated endothelin-1 levels after cigarette smoking.

The effect of short-term nicotine consumption on endothelin-1 (ET-1) levels was studied in 10 male healthy smokers. Volunteers smoked in random order on 3 separate days a low-tar cigarette or a high-tar cigarette, or were studied without having smoked (no-cigarette experiment). ET-1, corticotropin, and cortisol levels, heart rate, and blood pressure were determined before and 1, 3, 5, 10, 20, and 30 minutes after smoking. In contrast to results obtained after smoking a low-tar cigarette or not smoking, smoking a high-tar cigarette resulted in a significant increase in ET-1 levels within 10 minutes, followed by an increase in corticotropin levels within 20 minutes after smoking. Thirty minutes after smoking, cortisol levels were higher after a high-tar cigarette compared with a low-tar cigarette or no smoking. Increases in heart rate and systolic blood pressure were likewise higher after smoking a high-tar cigarette than after smoking a low-tar cigarette. In conclusion, it is tempting to speculate that ET-1 may indeed act as the long-searched-for link between vasopressin and corticotropin-releasing hormone (CRH) and thus play an essential role in the stimulation of the hypothalamic-pituitary-adrenal axis. In addition, these results suggest that the increase in the level of ET-1, a powerful vasoconstrictor and mitogen, may play an important part in the disease mechanisms of atherosclerosis arising from smoking.

A study of the dietary counseling practices among Oregon dental hygienists.

PURPOSE: The purpose of the study was to identify the dietary counseling practices of Oregon dental hygienists. Factors which affect the extent of dietary counseling were examined, including the dental hygienists' attitude, confidence, personal dietary practices, and perception of practice constraints. METHODS: A 25-item survey was mailed in summer 1989 to a random sample of 300 Oregon licensed dental hygienists. Likert-scaled statements were used to measure the extent of dietary counseling activities and the factors which affect their extent. Multiple-choice questions measured nutrition knowledge and quality of dietary counseling. Descriptive statistics were computed for each variable. Data were analyzed at the p<.05 significance level. Hypotheses testing included Pearson product-moment correlation, one-way analysis of variance (ANOVA), and chi-square. RESULTS: Of the 212 respondents (72% adjusted response rate), 52% reported providing dietary counseling. Ninety-six percent reported that they did not obtain dietary intake records and 82% did not evaluate their patients' diets for nutritional adequacy. A significant positive relationship (r=.19) was found between the hygienists' nutrition knowledge and quality of dietary counseling. Extent of counseling and the dental hygienist's confidence in nutrition knowledge and dietary counseling skills were found to be significantly related (r=-.31). A significant negative relationship (r= -.29) was found between extent of counseling and the dental hygienist's perception of practice constraints, most notably lack of time and cost-effectiveness. CONCLUSIONS: Dietary counseling is provided to a limited extent by dental hygienists in Oregon oral healthcare practices. Dental hygienists should provide this service based on patients' needs and, when necessary, refer patients to nutrition professionals. Further study could assess the nutrition and dietary counseling content and application in dental hygiene curricula.

Characterization of the T, L, I, S, M and P cell surface (immobilization) antigens of Tetrahymena thermophila: molecular weights, isoforms, and cross-reactivity of antisera.

In the ciliate protist Tetrahymena thermophila the L, H, T, I, S, M and P cell surface proteins (immobilization antigens) are expressed under different conditions of temperature (L, H, T), culture media (I, S), and mutant genotype (M, P). Immunoblot and autoradiographic studies using antisera to purified protein show that the molecular weights of these proteins range from 25,000 to 59,000. The H, T, S, M and P antigens are recognized as single polypeptides, whereas L, I, and one allelic form of T each appear to consist of a family of polypeptides. Although antisera are specific in immobilization and immunofluorescence assays of surface protein in living cells, cross-reactivity is seen with denatured protein on immunoblots. It is hypothesized that the surface protein genes are organized into families of evolutionarily related isoloci.