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For improvements in exercise tolerance and cognitive function in geriatric patients Multimodal training programs (MTP) are used as combination of physiotherapy, occupational therapy and cardiovascular training. Intermittent Hypoxic-Hyperoxic Training (IHHT), a modified type of intermittent hypoxic training (IHT) is proposed to be included in MTP to elicit more pronounced beneficial effects in exercise tolerance and cognitive functions of geriatric patients likely by an additional pathway than a single MTP. Thirty four patients of the Geriatric Day Clinic aged between 64 and 92 years participated in the placebo controlled clinical trial. They were randomly assigned to receive MTP plus IHHT (experimental group - EG) or MTP plus placebo-breathing through a machine face mask (control group - CG) in a double blind fashion. Before and after the interventions course cognitive performance was assessed by the Dementia-Detection-Test (DemTect) and the Clock-Drawing-Test (CDT), and functional exercise capacity - by the total distance of 6-Minute-Walk-Test (6MWT). After IHHT combined with MTP cognitive performance (DemTect) increased significantly when compared to NG (+16,7 % vs. +0,39 %, p<0,001). The CDT indicated similar results with a significant increase in the EG while the score of the CG even decreased (+10,7 % vs. -8%, p=0,031). Concerning the functional exercise capacity, both groups improved the total distance in the 6MWT but with a significantly larger increase in the EG compared to the CG (+24,1 % vs. +10,8 %, p=0,021). In addition, there was a significant relationship between the changes of the 6MWT and the DemTect Scores and the CDT. IHHT contributed significantly to improvements in cognitive performance and exercise capacity in elderly performing MTP. IHHT sessions are considered to be easily applicable to and well tolerated by geriatric patients up to 92 years.

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BACKGROUND: Nursing homes are confronted more and more with palliative care patients, which present a challenge for nursing and medical personnel. Deficits in the palliative care of geriatric patients have been repeatedly demonstrated and many nursing home residents, especially those suffering from dementia, are undersupplied regarding pain management. OBJECTIVES: The present study was carried out to measure the knowledge and self-efficacy of nursing staff in the province of Carinthia (Austria) regarding palliative care of nursing home residents. MATERIAL AND METHODS: A total of 330 nursing personnel were surveyed using the Bonn test for knowledge in palliative care (BPW), which measures knowledge and self-efficacy in nursing home personnel. In addition to descriptive analyses, the effects of the professional group (registered nurses vs. nursing assistants) and working experience were tested. RESULTS: On average a little more than half of the knowledge items were answered correctly. Nurses' self-efficacy was high. Registered nurses exhibited more knowledge and higher self-efficacy compared to nursing assistants. Effects of working experience could only be demonstrated regarding self-efficacy. CONCLUSION: The results are to a large extent in line with results from Germany and indicate the necessity of interventions for improving nurses' knowledge as a major basis for adequate palliative care in nursing home residents.

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In this study, we tested the hypotheses that, relative to the maximum capacities, ballroom dancing is more intensive for females than males, and that the hold technique (female vs. male) regulates dancing intensity. Ten dance couples were tested in a maximal treadmill test, competition simulation, and stationary dance hold position. Peak heart rate and relative oxygen consumption were measured during the tests, except that oxygen consumption was not measured during competition simulation. Regardless of gender, heart rate increased similarly in the treadmill test and in the competition simulation. In the treadmill test, females achieved an oxygen consumption of 78% of the males (p < 0.05). Compared with males, females achieved 14% higher heart rate (p < 0.05) and similar oxygen consumption during the hold position. Heart rate during competition simulation relative to maximum was greater for females than males. Both heart rate and oxygen consumption measured during the hold, relative to maximum, were greater for females than males. It is concluded that lower class ballroom dancers perform at their vita maxima during competition simulation. Using heart rate as an intensity indicator, ballroom dancing is more intensive for females because of their unique hold technique.

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KEY POINTS: Loss-of-function mutations of the skeletal muscle ClC-1 channel cause myotonia congenita with variable phenotypes. Using patch clamp we show that F484L, located in the conducting pore, probably induces mild dominant myotonia by right-shifting the slow gating of ClC-1 channel, without exerting a dominant-negative effect on the wild-type (WT) subunit. Molecular dynamics simulations suggest that F484L affects the slow gate by increasing the frequency and the stability of H-bond formation between E232 in helix F and Y578 in helix R. Three other myotonic ClC-1 mutations are shown to produce distinct effects on channel function: L198P shifts the slow gate to positive potentials, V640G reduces channel activity, while L628P displays a WT-like behaviour (electrophysiology data only). Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function. ABSTRACT: Myotonia congenita is an inherited disease caused by loss-of-function mutations of the skeletal muscle ClC-1 chloride channel, characterized by impaired muscle relaxation after contraction and stiffness. In the present study, we provided an in-depth characterization of F484L, a mutation previously identified in dominant myotonia, in order to define the genotype-phenotype correlation, and to elucidate the contribution of this pore residue to the mechanisms of ClC-1 gating. Patch-clamp recordings showed that F484L reduced chloride currents at every tested potential and dramatically right-shifted the voltage dependence of slow gating, thus contributing to the mild clinical phenotype of affected heterozygote carriers. Unlike dominant mutations located at the dimer interface, no dominant-negative effect was observed when F484L mutant subunits were co-expressed with wild type. Molecular dynamics simulations further revealed that F484L affected the slow gate by increasing the frequency and stability of the H-bond formation between the pore residue E232 and the R helix residue Y578. In addition, using patch-clamp electrophysiology, we characterized three other myotonic ClC-1 mutations. We proved that the dominant L198P mutation in the channel pore also right-shifted the voltage dependence of slow gating, recapitulating mild myotonia. The recessive V640G mutant drastically reduced channel function, which probably accounts for myotonia. In contrast, the recessive L628P mutant produced currents very similar to wild type, suggesting that the occurrence of the compound truncating mutation (Q812X) or other muscle-specific mechanisms accounted for the severe symptoms observed in this family. Our results provide novel insight into the molecular mechanisms underlying normal and altered ClC-1 function.

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BACKGROUND: Until recently the measurement of pain in cognitively impaired patients represented a neglected field in the diagnostics and treatment of pain. Investigations indicate a prevalence of pain in nursing home residents of between 45 % and 80 %. MATERIAL AND METHODS: This study investigated the reliability of the German translation of the Doloshort scale and compared it with the visual analog scale (VS). The aim of this study was to determine the practical applicability of this scale in the clinical routine and to calculate the intrarater reliability (retest) and interrater reliability. RESULTS: The interrater and intrarater reliability of the Doloshort scale was between 0.949 and 0.970. There was a highly significant correlation between the values of the Doloshort scale and the VAS. CONCLUSION: The Doloshort scale is a well suited measurement instrument for the evaluation of pain in cognitively impaired patients. Because of the short form only simple instructions are necessary and it has a high acceptance with users.

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We propose a mechanism of an inner medullary concentrating process in which water extraction is accomplished by a colloid osmotic mechanism and hydrostatic pressure. There are 3 essential features of the proposal: 1. the fluid compartmental structure of the inner medullary interstitium: owing to molecular exclusion, negatively charged macromolecules, i.e. hyaluronan and extravasated plasma albumin form separate compartments (the HA and the EPA compartments); the resulting Gibbs-Donnan effect governs the movements of both ions and water. 2. NaCl, in high concentration in the inner medulla conditioned by the outer medullary countercurrent processes, significantly reduces the equilibrium colloid osmotic pressure between these compartments. 3. Urea, also accumulated here by special transport mechanisms, increases the mobility of water molecules and the flexibility of the HA fibrils by loosening hydrogen bonds. These features suggest that rhythmic, small pressure increases of the pelvic/calyceal muscles squeeze dilute fluid out of the HA compartment and, at the same time, accelerate the outflow of fluid and albumin into the ascending vasa recta from the EPA compartment. Further, they suggest a mechanism for the phenomenon that living organisms utilize hydrostatic pressure generated by muscle contractions in water economy namely, concentrating and diluting body fluids.

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Approximately four decades ago, the countercurrent theory became influential in studies on the concentrating process in the mammalian kidney. The theory successfully represented the concentrating process in the outer medulla, but the problem of the concentrating mechanism in the inner medulla, as defined by Homer Smith has remained essentially intractable. In a recent comprehensive review by Knepper and coworkers of various theories and models, attention was refocused on the possible role of hyaluronate (HA) in the inner medullary concentrating process. The authors proposed a hypothesis that HA can convert hydrostatic pressure to concentrating work.Here, we briefly survey the earlier ideas on the role imputed to HA and present a new hypothesis which is different from that of Knepper and coworkers. We estimate that the hydrostatic pressures available in the inner medulla can account only for a very small fraction of the concentrating work. We hypothesize that the role of HA is tied up with extravasated plasma albumin and suggest that owing to the property of HA solutions to exclude other macromolecules, extravasated plasma albumin and HA constitute two fluid compartments in the interstitium in the inner medulla. In this proposed two-compartment model, the Gibbs-Donnan distribution influences the movement of ions and water between the HA and the extravasated albumin compartment. To relate the hypothetical role of HA to the concentrating process, we briefly describe new results obtained by other investigators on the accumulation of urea in the inner medulla. This subject has been critically reviewed recently by Yang & Bankir.Many processes have been identified as contributing to the concentrating process in the mammalian inner medulla. We speculate that among these many processes, the primary responsibility for the final concentration of the excreted urine may be portioned out differently in different mammalian species.

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The Shouldice operation has been increasingly applied in our department since 1996. Between 1998-2000 its proportion has achieved 58% (Lichtenstein: 30%, laparoscopy: 2%, TEPP: 3%, other: 7%). A total of 343 patients have been operated on according to Shouldice. These patients were followed for 3-5 years in the mean. So far we observed 3 recurrences corresponding to a recurrence rate of 0.9%. The recurrence rate decreased compared to a historical control group from 10 to 0.9% using the Shouldice technique instead of Bassini. We conclude from this study that the surgeon must know several surgical techniques and choose the most applicable one during operation. The overwhelming majority of cases can be resolved by the Shouldice operation. For elderly patients, the Lichtenstein operation is an appropriate alternative. For cases with large defects of the posterior wall we can choose between Lichtenstein operation, the laparoscopic procedures and transinguinal preperitoneal mesh plasty.

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The authors discuss some aspects of radical gastrectomy. They analyse whether there is any progress in their results in the treatment of stomach cancer in the past 5 years. They describe some aspects of total gastrectomy with regards to the need for splenectomy. During 36 years (01.07.1952-30.06.1962 and 1974-1999) 1614 patients were treated for stomach cancer. In the last two 5 year long periods (1990-1994 and 1995-1999) the number of radical operations was 106 and 114. In the second period we used laparoscopic exploration in some patients. We carried out total gastrectomies with modern suturing devices (AutoSuture Premium Plus CEEA, Proximate ILS Straight Intraluminal Stapler Endo Surgery, TA Premium) without compromising the principles of radicality using Rochard-Aesculap retractor in most patients. We tried to avoid splenectomy when possible. In the past 5 years we carried out lymphadenectomy according to the Japanese classification, excising group I and II lymph nodes. The resectability rate rose in the last 6 years compared to the previous ten year period (55.3%, 36.1%, 48.4%, 64.3%). The ratio of total gastrectomies increased from 8.6% (10 out of 106 resections) to 42.9% (49 out of 114 resections) in the two 5 year periods. Mortality for partial and total gastrectomy were 4.6% (65/3) and 6.1% (49/3). They could preserve the spleen in 32.6% of the cases. We found that laparoscopic exploration rarely influenced the operation. Partial resection in intestinal type stomach cancer should be performed, if a margin of 6 cm can be achieved. If the patient is in good general health, total gastrectomy should be performed unless the size, type and lymph node involvement of the cancer indicated otherwise. We think that increased resectability is related to both increased capabilities and better diagnostic tools. It is important to preserve the spleen where oncology principals allow.

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INTRODUCTION: Many causes are given as the main reason for inadequate pain therapy. The objective of our study was to demonstrate the current position of doctors in general practice all over Austria who prescribe prescriptions. METHODS: A total of 5,359 questionnaires were sent out to general practitioners in all federal states of Austria. These questionnaires contained 21 main questions on subjects relevant to pain therapy. RESULTS: On average, 16% of all general practitioners returned the questionnaires; 89.3% of these are acquainted with the WHO graduated scale, 87% have prescribed strong opioids. Old prejudices such as concerns about the side effects are hardly to be found now. Modern therapy strategies are used. CONCLUSION: Based on the data at hand, pain therapy for patients should be excellent. The reality, however, is somewhat different. The large number of doctors who did not reply makes it enormously difficult to make a statement about the position of pain therapy in Austria.

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We report the results of a randomized controlled multicentre study on interferon-gamma (IFN-gamma) treatment of systemic sclerosis as determined by skin sclerosis, renal and other organ involvement, global assessment, subjective symptoms and quality of life. Forty-four patients were enrolled into the trial, 27 in the treatment group and 17 in the control group. All patients presented with type I or type II scleroderma. Twenty-nine patients (64%) finished the study. The mean duration of Raynaud's phenomenon and skin sclerosis was 15.3 and 10.8 years, respectively. The skin scores tended to improve in the treatment group (P > 0.05). Mouth aperture increased significantly from 38.5 to 47.7 mm in the treatment group (P < 0.001). Subanalysis of IFN-gamma treated patients with normalized skin sclerosis scores >/=1 showed significant improvement in both skin involvement and subjective symptoms (P < 0.05). Organ involvement improved in eight of 18 treatment patients and in three of 11 control patients. It worsened in three of 18 treatment patients and in four of 11 control patients. One control patient died due to cardiorespiratory failure during the study. No deterioration of renal function occurred during IFN-gamma treatment. There was a significant improvement in quality of life parameters in the control group but not in the treatment group. Plasma levels of neopterin increased significantly during IFN-gamma treatment but not in the control group, whereas N-terminal procollagen III peptide levels did not change in either group. There was a high frequency of mild to moderate influenza-like adverse events during IFN-gamma treatment. Only four of nine drop-out patients, however, experienced symptoms most probably associated with IFN-gamma treatment. We conclude that IFN-gamma therapy has mild beneficial effects on skin sclerosis and disease-associated symptoms in type I and II scleroderma. IFN-gamma treatment was associated with acceptable tolerability and did not induce major renal dysfunction in our patients.

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The best composition of rifampicin eye-drops for extemporaneous preparation in pharmacies was developed by the authors. The stability of the eye-drops has been studied and storage condition and shelf-life were determined. The preparation, may be stored at minus 12 degrees C for one month and may be subsequently used when stored between 2 and 8 degrees C after the first opening for five days. Rifampicin and its degradation products have been separated by TLC using silicagel layer and chloroform-methanol (42 : 58) eluent. After separation of rifampicin and its degradation products their quantity have been determined by densitometry at 475 wavelength (540 nm for rifampicin quinone). This rifampicin eye-drops have been recommended for inclusion into the 7th Edition of the Official Model Prescriptions (Formulae Normales).

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Recent studies have indicated controversial effects of low molecular weight heparin (LMWH) on lipid metabolism in patients on chronic hemodialysis as compared to unfractionated heparin (UFH). We therefore conducted a cross-sectional multicentre study comparing 153 patients treated with LMWH and 153 patients with UFH, matched for sex, age and diabetes mellitus. Both groups have been treated with LMWH or UFH for six months or longer (14.9 vs. 23.4 months). We observed no differences between the UFH and LMWH treatment groups for total cholesterol, LDL cholesterol, triglycerides, apoB, apoA-IV or Lp(a). The only significant differences were seen for HDL cholesterol and the corresponding apolipoprotein apoA-I, which were significantly higher in the UFH group (HDL cholesterol: 0.97 +/- 0.35 mM/l vs. 0.87 +/- 0.37 mM/l, p < 0.05; apoA-I 1.23 +/- 0.27 g/l vs. 1.15 +/- 0.27 g/l, p < 0.05). We conclude that the results of studies investigating the influence of LMWH on lipid metabolism are as heterogeneous as the substances themselves. This challenges the beneficial influence supposedly had by LMWH preparations on lipid metabolism.

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Numerous studies have investigated lipoprotein(a) (Lp(a)) plasma concentrations in patients with ESRD, a patient group with an enormous risk for atherosclerosis. The reported differences in Lp(a) between controls and patients vary from a decrease of 49% to an increase of more than 1,000%. However, data are not consistent, mostly because of problems with statistical analysis, and only limited data are available for patients treated by continuous ambulatory peritoneal dialysis (CAPD). To estimate the significance of Lp(a) in ESRD and to demonstrate the statistical pitfalls concerning Lp(a) in case-control studies, a large multicenter study including 702 patients treated by either hemodialysis (HD) (N = 534) or CAPD (N = 168) was conducted, and results were compared with results from 256 healthy controls. Both patient groups showed significantly elevated Lp(a) levels in comparison with controls: 23.4 +/- 25.0 mg/dL (P < 0.005; HD) and 34.6 +/- 38.4 mg/dL (P < 0.0001; CAPD) versus 18.4 +/- 22.8 mg/dL (controls). CAPD patients showed significantly higher Lp(a) values than did patients treated by HD (P < 0.001). The difference between the two treatment groups possibly reflects an overproduction of Lp(a) to compensate for protein losses in CAPD patients. Both treatment groups included significantly more patients with Lp(a) values greater than the 75th percentile (25.6 mg/dL) of the control group (33.9 and 41.7% for HD and CAPD, respectively; P < 0.005). The higher Lp(a) values in patients were not explained by differences in isoform frequencies and the increase in Lp(a) was apolipoprotein(a) type specific: only patients with high-molecular-weight apolipoprotein(a) isoforms showed a significant elevation in Lp(a) levels. The increased plasma concentrations of Lp(a) may contribute to the high risk for atherosclerosis in ESRD, especially in patients treated by CAPD. Finally, it is believed that small sample sizes are responsible for the diverging results in Lp(a) literature.

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UNLABELLED: Between 1983 and 1992, 44 patients with early gastric cancer underwent operative treatment. This group comprised 13.3 percent of all patients with gastric cancer operated on during this period. Every patient underwent oesophago-gastro-duodenoscopy before operation. The indication for surgery was histologically confirmed carcinoma in 37 patients, gastric haemorrhage in 2 patients and gastric ulcer unresponsive to medical treatment in 5 patients. The gastric carcinoma was limited to the mucosa in 28 cases and involved the submucosa in 16. Five patients, one with mucosal and four with submucosal early gastric cancer had regional metastatic lymph node involvement. Life-table calculated patient survival rate at 5 years, excluding the perioperative mortality, was 79.4 percent. CONCLUSIONS: 1. The prevalence of early gastric cancer proved to be similar to previously published in West-Europe and United States. 2. If early gastric cancer is limited only to the mucosa, regional metastatic lymph node is relatively rare. 3. Gastrointestinal bleeding can be the first clinical sign of early gastric cancer. 4. Therapy resistant gastric ulcer requires surgery irrespective of the histological examination of the biopsy specimen.

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The authors reviewed the adjuvant chemotherapeutical treatment after operation of the breast cancer. At their department 6 cycles CMF doses were given to the node positive premenopausal patients. In order to analyse the results a control group was set up. They examined the effect of the treatment concerning the tumour-free survival and survival data. For the calculation the log-rank test--Mantel-Haenszel chi 2-probe was used. The effect of the treatment is favourable.

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The authors deal with the problems of adjuvant therapy of breast cancer. They administrated Zitazonium in those postmenopausal women who had had positive axillary lymph nodes. In the course of analyzing the results, they calculated survival and tumor free survival with "life-table" method, while they used log-rank probe and Mantel-Haenzel X2 probe for showing significance between the diagrams. The results were favourable, but no significant variance could be shown in the group treated with Zitazonium. If lymph nodes were proved to be negative the difference between the graphs were minimal. They refer to the question of steroid receptor determination and emphasize to take into account the biological markers when projecting adjuvant therapy.

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The preparation and binding affinity of a series of tetrahydroisoquinoline carboxylic acids at the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is described, together with a molecular modeling analysis of NMDA agonists and antagonists. Using published NMDA ligands, the active analogue mapping approach was employed in the generation of an agonist pharmacophore model. Although known competitive antagonists such as CPP (1) could be superimposed onto the agonist model, to overcome the assumption that they bind to the same receptor site, an independent modeling approach was used to derive a separate pharmacophore model. Development of a competitive antagonist model involved a stepwise approach that included the definition of a preferred geometry for PO3H2-receptor interactions, multiple conformational searches, and the determination of volume and electronic tolerances. This model, which is described in detail, is consistent with observed affinities of potent NMDA antagonists and has provided an explanation for the observed periodicity in affinities for the known antagonists AP5, AP6, and AP7. The features of the agonist and antagonist models are compared, and hypotheses advanced about the nature of the receptor interactions for these two classes of compounds. The pharmacophore models reported herein are consistent with a single recognition site at the NMDA receptor that can accommodate both agonist and antagonist ligands. To assist in first defining and later exploring the predictive power of the competitive antagonist model, a series of conformationally constrained NMDA antagonist (phosphonoalkyl)tetrahydroisoquinoline-1- and 3-carboxylates was prepared. From this work, 1,2,3,4-tetrahydro-5-(2-phosphonoethyl)-3- isoquinolinecarboxylic acid (89) was identified as the most active lead structure, with an IC50 of 270 nM in [3H]CPP binding. The synthesis and structure-activity relationships of these novel antagonists are described.

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