The ideal location of the male nipple-areolar complex: A pinpointing algorithm.

Background: In the treatment of gender dysphoria, appropriate nipple-areola complex (NAC) positioning is essential for achieving a natural appearing male chest after subcutaneous mastectomy. An accurate predictive model for the ideal personalized position of the NAC is still lacking. The aim of this study is to determine the anthropometry of the male chest to create individualized guidelines for appropriate NAC positioning in the preoperative setting. Materials and methods: Cisgender male participants were recruited. Multiple chest measurements were manually recorded. Best subset regression using linear models was used to select predictors for the horizontal coordinate (nipple-nipple distance; NN) and vertical coordinate (sternal notch-nipple distance; SNN) of the NAC. Internal validation was assessed using bootstrapping. Furthermore, a cohort of transgender men who had received a mastectomy with replantation of nipples according to current practice was identified. Comparison testing between the algorithm and standard practice was performed to test the limitations of standard practice. Results: One hundred and fifty cis male participants were included (median age: 26, IQR: 22-34 years). Four predictors were found to predict NN (age, weight, chest circumference (CC), anterior-axillar fold to anterior-axillar fold (AUX-AUX)) and reads as follows: NN = 4.11 + 0.035*age + 0.041*weight + 0.093*CC + 0.140*AUX-AUX Two predictors were found to predict SNN (NN and weight), and reads as follows: SNN = 7.248 + 0.303*NN + 0.072*weight. Both models performed well (Bootstrapped R2: 0.63 (NN), 0.50 (SNN)) and outperformed previous models predicting NAC position. Ninety-six transgender men were eligible for evaluation of current practice and showed an average placement error of -0.9 cm for NN and +2.2 cm for SNN. Conclusion: The non-standardized approach of NAC repositioning results in a significant error of nipple placement. We suggest that the two predictive models for NN and SNN can be used to optimize NAC positioning on the masculinized chest wall.Supplemental data for this article is available online at https://doi.org/10.1080/26895269.2021.1884926.

The negative effect of unloading exceeds the bone-sparing effect of alkaline supplementation: a bed rest study.

Potassium bicarbonate was administrated to an already alkaline diet in seven male subjects during a 21-day bed rest study and was able to decrease bed rest induced increased calcium excretion but failed to prevent bed rest-induced bone resorption. INTRODUCTION: Supplementation with alkali salts appears to positively influence calcium and bone metabolism and, thus, could be a countermeasure for population groups with an increased risk for bone loss. However, the extent to which alkalization counteracts acid-induced bone resorption or whether it merely has a calcium and bone maintenance effect is still not completely understood. In the present study, we hypothesized that additional alkalization to an already alkaline diet can further counteract bed rest-induced bone loss. METHODS: Seven healthy male subjects completed two parts of a crossover designed 21-day bed rest study: bed rest only (control) and bed rest supplemented with 90 mmol potassium bicarbonate (KHCO3) daily. RESULTS: KHCO3supplementation during bed rest resulted in a more alkaline status compared to the control intervention, demonstrated by the increase in pH and buffer capacity level (pH p = 0.023, HCO3p = 0.02, ABE p = 0.03). Urinary calcium excretion was decreased during KHCO3 supplementation (control 6.05 ± 2.74 mmol/24 h; KHCO3 4.87 ± 2.21 mmol/24 h, p = 0.03); whereas, bone formation was not affected by additional alkalization (bAP p = 0.58; PINP p = 0.60). Bone resorption marker UCTX tended to be lower during alkaline supplementation (UCTX p = 0.16). CONCLUSIONS: The more alkaline acid-base status, achieved by KHCO3 supplementation, reduced renal calcium excretion during bed rest, but was not able to prevent immobilization-induced bone resorption. However, advantages of alkaline salts on bone metabolism may occur under acidic metabolic conditions or with respect to the positive effect of reduced calcium excretion within a longer time frame. TRIAL REGISTRATION: Trial number: NCT01509456.

Whey protein plus bicarbonate supplement has little effects on structural atrophy and proteolysis marker immunopatterns in skeletal muscle disuse during 21 days of bed rest.

OBJECTIVES: To investigate the effect of whey protein plus potassium bicarbonate supplement on disused skeletal muscle structure and proteolysis after bed rest (BR). METHODS: Soleus (SOL) and vastus lateralis (VL) biopsies were sampled from ten (n=10) healthy male subjects (aged 31±6 years) who did BR once with and once without protein supplement as a dietary countermeasure (cross-over study design). The structural changes (myofibre size and type distribution) were analysed by histological sections, and muscle protein breakdown indirectly via the proteolysis markers, calpain 1 and 3, calpastatin, MuRF1 and 2, both in muscle homogenates and by immunohistochemistry. RESULTS: BR caused size-changes in myofiber cross-sectional area (FCSA, SOL, p=0,004; VL, p=0.03), and myofiber slow-to-fast type transition with increased hybrids (SOL, p=0.043; VL, p=0.037) however with campaign differences in SOL (p<0.033). No significant effect of BR and supplement was found by any of the key proteolysis markers. CONCLUSIONS: Campaign differences in structural muscle adaptation may be an issue in cross-over design BR studies. The whey protein plus potassium bicarbonate supplement did not attenuate atrophy and fibre type transition during medium term bed rest. Alkaline whey protein supplements may however be beneficial as adjuncts to exercise countermeasures in disuse.

Fifty years of human space travel: implications for bone and calcium research.

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth.

Calcium kinetics during bed rest with artificial gravity and exercise countermeasures.

UNLABELLED: We assessed the potential for countermeasures to lessen the loss of bone calcium during bed rest. Subjects ingested less calcium during bed rest, and with artificial gravity, they also absorbed less calcium. With exercise, they excreted less calcium. To retain bone during bed rest, calcium intake needs to be maintained. INTRODUCTION: This study aims to assess the potential for artificial gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space flight. METHODS: We performed two studies: (1) a 21-day bed rest (BR) study with subjects receiving 1 h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study with 1 h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10 days of BR, and blood, urine, and feces were sampled for up to 14 days post dosing. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. RESULTS: Less Ca was absorbed during BR, resulting in lower Ca balance in BR+AG (-6.04 ± 3.38 mmol/day, P = 0.023). However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased, and there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide excretion increased in controls during BR, but not in the EX group. Markers of bone formation were not different between treatment groups for either study. Ca intake decreased during BR (by 5.4 mmol/day in the AG study and 2.8 mmol/day in the EX study), resulting in lower absorbed Ca. CONCLUSIONS: During BR (or space flight), Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca.

Sclerostin and DKK1 levels during 14 and 21 days of bed rest in healthy young men.

OBJECTIVES: Wnt signaling pathway may be crucial in the pathogenesis of disuse-induced bone loss. Sclerostin and DKK1, antagonists of the Wnt signaling pathway, were assessed during immobilization by bed rest in young, healthy people. METHODS: Two bed rest studies were conducted at the German Aerospace Center in Cologne. 14 days of 6° head-down-tilt bed rest were applied to eight healthy young male test subjects in study 1 and 21 days of head-down-tilt bed rest to seven healthy male subjects in study 2. RESULTS: Sclerostin levels increased in both studies during bed rest (study 1, 0.64±0.05 ng/ml to 0.69±0.04 ng/ml, P=0.014; study 2, 0.42±0.04 ng/ml to 0.47±0.04 ng/ml, P=0.008) and they declined at the end of the 14- and 21-day bed rest periods. DKK1 decreased during the bed rest period in study 1 (P<0.001) but increased during bed rest in study 2 (P=0.006). As expected, bone formation marker PINP decreased (study 1, P=0.013; study 2, P<0.001) and bone resorption marker NTX increased during bed rest (P<0.001). CONCLUSION: Data suggest that the Wnt signaling pathway is involved in disuse-induced bone loss in young, healthy humans.

The 2nd Berlin BedRest Study: protocol and implementation.

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p < .0001), though similarly in all groups (p > or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed.

Vibration training intervention to maintain cartilage thickness and serum concentrations of cartilage oligometric matrix protein (COMP) during immobilization.

OBJECTIVE: To test the hypotheses that 1) 14-days of immobilization of young healthy subjects using a 6 degrees -"head-down-tilt-bed-rest"-model (6 degrees -HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric matrix protein (COMP) concentration and 2) isolated whole body vibration training would counteract the bed rest effects. METHOD: The study was performed and designed in compliance with the Declaration of Helsinki and is registered as trial DRKS00000140 in the German Clinical Trial Register (register.germanctr.de). Eight male healthy subjects (78.0+/-9.5kg; 179+/-0.96cm, 26+/-5 years) performed 14 days of 6 degrees -HDT. The study was designed as a cross-over-design with two study phases: a training and a control intervention. During the training intervention, subjects underwent 2x5-min whole body vibration training/day (Frequency: 20Hz; amplitude: 2-4mm). Magnetic resonance (MR) images (slice thickness: 2mm; in-plane resolution: 0.35x0.35mm; pixels: 448x512) were taken before and after the 6 degrees -HDT periods. Average cartilage thicknesses were calculated for the load bearing regions on the medial and lateral articulating surfaces in the femur and tibia. RESULTS: While the control intervention resulted in an overall loss in average cartilage thickness of -8% (pre: 3.08mm+/-0.6mm post: 2.82mm+/-0.6mm) in the weight-bearing regions of the tibia, average cartilage thickness increased by 21.9% (pre: 2.66mm+/-0.45mm post: 3.24mm+/-0.63mm) with the vibration intervention. No significant differences were found in the weight-bearing regions of the femur. During both interventions, reduced serum COMP concentrations were observed (control intervention: -13.6+/-8.4%; vibration intervention: -9.9+/-3.3%). CONCLUSION: The results of this study suggest that articular cartilage thickness is sensitive to unloading and that vibration training may be a potent countermeasure against these effects. The sensitivity of cartilage to physical training is of high relevance for training methods in space flight, elite and sport and rehabilitation after illness or injury.

Effects of 21 days of bed rest, with or without artificial gravity, on nutritional status of humans.

Spaceflight and bed rest models of microgravity have profound effects on physiological systems, including the cardiovascular, musculoskeletal, and immune systems. These effects can be exacerbated by suboptimal nutrient status, and therefore it is critical to monitor nutritional status when evaluating countermeasures to mitigate negative effects of spaceflight. As part of a larger study to investigate the usefulness of artificial gravity as a countermeasure for musculoskeletal and cardiovascular deficits during bed rest, we tested the hypothesis that artificial gravity would have an effect on some aspects of nutritional status. Dietary intake was recorded daily before, during, and after 21 days of bed rest with artificial gravity (n = 8) or bed rest alone (n = 7). We examined body composition, hematology, general blood chemistry, markers of oxidative damage, and blood levels of selected vitamins and minerals before, during, and after the bed rest period. Several indicators of vitamin status changed in response to diet changes: serum alpha- and gamma-tocopherol and urinary 4-pyridoxic acid decreased (P < 0.001) and plasma beta-carotene increased (P < 0.001) in both groups during bed rest compared with before bed rest. A decrease in hematocrit (P < 0.001) after bed rest was accompanied by a decrease in transferrin (P < 0.001), but transferrin receptors were not changed. These data provide evidence that artificial gravity itself does not negatively affect nutritional status during bed rest. Likewise, artificial gravity has no protective effect on nutritional status during bed rest.

Effects of artificial gravity during bed rest on bone metabolism in humans.

We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6 degrees head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 G(z) at the heart, 2.5 G(z) at the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group (P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant (P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest.

A 2-year prospective study of bone metabolism and bone mineral density in adolescents with anorexia nervosa.

Osteopenia and osteoporosis are complications of adolescent anorexia nervosa (AN) and may result in a permanent deficit of bone mass in adulthood. It is still unclear if a complete catch-up in bone mineral density (BMD) is possible after weight rehabilitation in AN. METHODS. We investigated bone formation (bAP, PICP), bone resorption (CTX) and BMD (lumbar spine, femoral neck) along with endocrinological parameters in 19 girls with AN (14.4 +/- 1.6 years) and in 19 healthy controls for 2 years after inpatient re-feeding. RESULTS. Re-feeding normalised bone formation activity in patients. The pattern of bone turnover in patients after 2 years was similar to the pattern healthy controls had shown 2 years before. BMD of patients was significantly lower than in controls and did not change throughout the entire study. CONCLUSIONS. Weight rehabilitation leads to prolonged normalization of bone turnover in adolescent AN. Since we could not observe a "catch up" effect in BMD of girls with AN in a 2-year follow-up, BMD of these patients needs to be carefully monitored until adulthood to detect early osteoporosis.

From space to Earth: advances in human physiology from 20 years of bed rest studies (1986-2006).

Bed rest studies of the past 20 years are reviewed. Head-down bed rest (HDBR) has proved its usefulness as a reliable simulation model for the most physiological effects of spaceflight. As well as continuing to search for better understanding of the physiological changes induced, these studies focused mostly on identifying effective countermeasures with encouraging but limited success. HDBR is characterised by immobilization, inactivity, confinement and elimination of Gz gravitational stimuli, such as posture change and direction, which affect body sensors and responses. These induce upward fluid shift, unloading the body's upright weight, absence of work against gravity, reduced energy requirements and reduction in overall sensory stimulation. The upward fluid shift by acting on central volume receptors induces a 10-15% reduction in plasma volume which leads to a now well-documented set of cardiovascular changes including changes in cardiac performance and baroreflex sensitivity that are identical to those in space. Calcium excretion is increased from the beginning of bed rest leading to a sustained negative calcium balance. Calcium absorption is reduced. Body weight, muscle mass, muscle strength is reduced, as is the resistance of muscle to insulin. Bone density, stiffness of bones of the lower limbs and spinal cord and bone architecture are altered. Circadian rhythms may shift and are dampened. Ways to improve the process of evaluating countermeasures--exercise (aerobic, resistive, vibration), nutritional and pharmacological--are proposed. Artificial gravity requires systematic evaluation. This review points to clinical applications of BR research revealing the crucial role of gravity to health.

Whole-body vibration can reduce calciuria induced by high protein intakes and may counteract bone resorption: A preliminary study.

Excess protein intake can adversely affect the bone via an increase in calcium excretion, while suitable mechanical loading promotes osteogenesis. We therefore investigated whether vibration exposure could alleviate the bone mineral losses associated with a metabolic acidosis. Ten healthy individuals aged 22 - 29 years (median = 25) underwent three 5-day study periods while monitoring their dietary intake. The study consisted of recording the participants' usual dietary intake for 5 consecutive days. Participants were then randomly divided into two groups, one of which received a protein supplement (2 g x kg(-1) body mass x day(-1); n = 5) and the other whole-body low-magnitude (3.5 g), low-frequency (30 Hz) mechanical vibration (WBV) delivered through a specially designed vibrating plate for 10 min each day (n = 5). Finally, for the third treatment period, all participants consumed the protein supplement added to their normal diet and were exposed to WBV exercise for 10 min per day. Daily urine samples were collected throughout the experimental periods to determine the excretion of calcium, phosphate, titratable acid, urea, and C-telopeptide. As expected, when the participants underwent the high protein intake, there was an increase in urinary excretion rates of calcium (P < 0.001), phosphate (P < 0.003), urea (P < 0.001), titratable acid (P < 0.001), and C-telopeptide (P < 0.05) compared with baseline values. However, high protein intake coupled with vibration stimulation resulted in a significant reduction in urinary calcium (P = 0.006), phosphate excretion (P = 0.021), and C-telopeptide (P < 0.05) compared with protein intake alone, but did not affect titratable acid and urea output. The participants showed no effect of WBV exercise alone on urinary excretion of calcium, phosphate, urea, titratable acid, or C-telopeptide. The results indicate that vibration stimulation can moderate the increase in bone resorption and reduction in bone formation caused by a metabolic acidosis.

Tyramine in the assessment of regional adrenergic function.

Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action. We characterized the response to tyramine, isoproterenol, and dopamine in adipose tissue with microdialysis probes in normal subjects. We measured glycerol concentrations to follow changes in lipolysis and monitored tissue perfusion with ethanol dilution. During perfusion with tyramine, dialysate glycerol concentration increased dose-dependently from 83+/-8 microM at baseline to 181+/-18 microM at 3.5 mM tyramine (p<0.001) followed by a fall down to 121+/-9 microM at 35 mM tyramine (p<0.001). Propranolol almost completely blocked this response. A similar lipolytic response was not observed in isolated human adipocytes. Dopamine <35 microM did not replicate the tyramine-induced lipolysis; however, dopamine >35 microM potently inhibited lipolysis. We conclude that tyramine-induced lipolysis is explained by a pre-synaptic mechanism. Tyramine applied through a microdialysis probe in concentrations up to 3.5 mM can be used to assess pre- and post-synaptic mechanisms regulating lipid mobilization.

Oxidative status in stable renal transplantation.

Increased oxidative stress and hyperhomocysteinemia are frequently observed in patients with end-stage renal disease. The effects of kidney transplantation on oxidative state are incompletely understood. With an aim to evaluate the prevalence and severity of oxidative stress in living donor renal transplant recipients, we conducted a cross-sectional study. Thirty-five renal transplant recipients (mean age 34 years; body mass index 21.93 +/- 1.92) with normal renal function (mean serum creatinine 1.41 +/- 0.33 mg%) were enrolled in the study. All patients were on cyclosporine-based immunosuppression. We assessed serum nitric oxide (NO) levels, plasma total homocysteine levels (tHCy), and malonaldehyde (MDA) levels. We evaluated the antioxidant power ferric reducing ability of plasma (FRAP) assay. The mean duration to the first sampling was 9.23 months after transplantation. Fourteen age- and sex-matched normotensive people were used as controls. The mean tHCy was significantly higher among patients (15.29 +/- 0.66 mmol/L compared with controls (9.58 +/- 2.90 mmol/L; P < .05). The MDA levels in patients (6.405 +/- 2.05 nmol/mL) were comparable to controls (6.093 +/- 1.93 nmol/mL; P = .099). The status of antioxidative power as measured by FRAP showed a trend to higher antioxidative status (697.57 +/- 103.07 mmol/L) in patients compared with controls (518 +/- 120.99 mmol/L; P = NS). The mean NO levels in patients (545.01 +/- 281.49 mmol/mL) were significantly higher than controls (183.49 +/- 64.53 nmol/mL; P < .05). Stable renal transplant recipients display a pattern of increased oxidant stress that may be counterbalanced by an enhanced antioxidant mechanisms.

Comparison of enteric-coated mycophenolate sodium with mycophenolate mofetil in living renal allograft transplantation.

OBJECTIVE: Enteric-coated mycophenolate sodium (MPS) has been developed to decrease the GI side effects of mycophenolate mofetil (MMF). We did a retrospective analysis of 112 patients to compare the safety and efficacy of enteric coated MPS vs MMF in living renal transplantation. METHODS: Patients were divided into two groups. Group A who received MPS [Novartis, Basel, Switzerland] [1.08-1.44 g/d] included 53 patients of mean age 33.5 +/- 11.9 yrs, and M:F gender ratio 37:15 with a mean donor age of 43.2 +/- 9.9 years. Group B who received MMF [1.5-2.0 g/d] included 59 subjects of mean age 33.2 +/- 9.9 yrs and M:F gender ratio 57:6, with a mean donor age of 41.4 +/- 10.9 years. All patients received cyclosporine and prednisolone in addition to mycophenolate. Mean follow-up in the two groups was 11.6 +/- 7.0 and 12.6 +/- 8.5 months, respectively. RESULTS: There were 11 (20.7%) rejection episodes in Group A and 12 (20.3%) rejection episodes in Group B (P = NS). Incidence of CMV disease was 9.61% and 10.1%, and of other infections, 88.7% and 74.7% in Groups A and Group B, respectively [P = NS]. The incidence of GI (18.9% & 20.3%) and hematologic toxicities (9.4% & 5.1%) were similar in the groups. Patient and graft survivals in Group A were 91.9% & 86.6%, and in Group B was 91.3% & 91.3%, respectively [P = NS]. CONCLUSION: Mycophenolate sodium is an alternative immunosuppressant to mycophenolate mofetil in kidney transplant recipients with a similar efficacy and safety profile.

Comparison of generic cyclosporine microemulsion versus neoral in de novo renal transplant recipients managed by 2-hour postdose monitoring.

INTRODUCTION: The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers. Cyclosporine (CsA) absorption and exposure is known to differ between healthy volunteers and transplant recipients. Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence. We sought to compare the efficacy of generic cyclosporine (ArpimuneME, RPG Life Sciences) versus Sandimmune Neoral in de novo renal transplant recipients. METHODS: A prospective single-center, open-label study enrolled 20 de novo renal transplant patients (group 1: mean age 30.55 +/- 9.81 years, M:F 19:1, mean donor age 43.4 +/- 10.8). All patients received ArpimuneME along with azathioprine and prednisolone. The results were compared with 17 matched controls (group 2: mean age 28.1 +/- 9.5 years, M:F 13:4, mean donor age 47.8 +/- 6.8) who received Neoral and were transplanted during the same period. C(2) levels were monitored by the cloned enzyme donor immunoassay (CEDIA). RESULTS: Patient and graft survivals were 100% and 100% and 100% and 92.8% in groups 1 and 2, respectively (P = NS). Six patients (30%) experienced rejection in group 1 as compared eight patients (47.1%) in group 2. Mean CsA levels (ng/mL) during the first month were 1419.1 +/- 213.6 and 1460.5 +/- 290.7 and at 3 months, 1296.3 +/- 227.8 and 1342.4 +/- 303.4 in the two groups, respectively (P = NS). The mean serum creatinine levels (mg%) in group 1 and group 2 were 1.6 +/- 0.8 and 2.0 +/- 1.4 at discharge and 1.5 +/- 0.4 and 1.5 +/- 0.8 at 6 months, respectively (P = NS). CONCLUSION: Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with Sandimmune Neoral when drug monitoring was performed by C(2) levels.

Regulation of body fluid and salt homeostasis--from observations in space to new concepts on Earth.

The present manuscript summarizes recent discoveries that were made by studying salt and fluid homeostasis in weightlessness. These data indicate that 1. atrial natriuretic peptide appears not to play an important role in natriuresis in physiology, 2. the distribution of body fluids appears to be tightly coupled with hunger and thirst regulation, 3. intrathoracic pressure may be an important co-regulator of body fluid homeostasis, 4. a so far unknown low-affinity, high capacity osmotically inactive sodium storage mechanism appears to be present in humans that is acting through sodium/hydrogen exchange on glycosaminoglycans and might explain the pathophysiology, e.g., of salt sensitive hypertension. The surprising and unexpected data underline that weightlessness is an excellent tool to investigate the physiology of our human body: If we knew it, we should be able to predict changes that occur when gravity is absent. But, as data from space demonstrate, we do not.

Prospective psychosocial evaluation of related kidney donors: Indian perspective.

With increasing acceptance of living organ transplantation and growing numbers of organ donors, it becomes important to look for any adverse outcomes in this population. Prospective psychosocial evaluation of living related donors and assessment of the outcome of donation process was done. We also tried to identify any risk factors associated with any adverse event. Between January 2003 and December 2003, 75 consecutive donors (mean age 42.8 +/- 11.6 years; M:F 54:21) were interviewed preoperatively and at 3 months postoperatively based on a 57-item questionnaire. Objective assessment of anxiety, depression, and social support was done with "modified Beck's depression inventory," "Speilberg's state and trait anxiety," and "social support" questionnaires. The majority (85.3%) of donors had volunteered for donation. There were no major depressive or anxiety disorders following donation. Though 21.3% donors perceived some negative impact on their health, none regretted the decision to donate and most (96%) would encourage organ donation. Prolonged donor hospitalization, persistent pain, poor recipient reciprocation, or recipient death were associated with a poor psychosocial outcome.

Biodiversity trends in Europe: development and testing of a species trend indicator for evaluating progress towards the 2010 target.

This paper presents a trial of a species population trend indicator for evaluating progress towards the 2010 biodiversity target in Europe, using existing data. The indicator integrates trends on different species (groups), and can be aggregated across habitats and countries. Thus, the indicator can deliver both headline messages for high-level decision-making and detailed information for in-depth analysis, using data from different sources, collected with different methods. International non-governmental organizations mobilized data on over 2800 historical trends in national populations of birds, butterflies and mammals, for a total of 273 species. These were combined by habitat and biogeographical region to generate a pilot pan-European scale indicator. The trial indicator suggests a decline of species populations in nearly all habitats, the largest being in farmland, where species populations declined by an average of 23% between 1970 and 2000. The indicator is potentially useful for monitoring progress towards 2010 biodiversity targets, but constraints include: the limited sensitivity of the historical data, which leads to conservative estimates of species decline; a potential danger of ambiguity because increases in opportunistic species can mask the loss of other species; and failure to account for pre-1970 population declines. We recommend mobilizing additional existing data, particularly for plants and fishes, and elaborating further the criteria for compiling representative sets of species. For a frequent, reliable update of the indicator, sound, sensitive and harmonized biodiversity monitoring programmes are needed in all pan-European countries.