Intravenous pamidronate as treatment for osteoporosis after heart transplantation: a prospective study.

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46+/-4 years (mean +/- SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (- 6.6%) as well as at the femoral neck (-7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46+/-4 years (mean +/- SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below -2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by -3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation.

Disc degeneration: current surgical options.

Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

Postnatal expression pattern of calcium-binding proteins in organotypic thalamic cultures and in the dorsal thalamus in vivo.

The present study describes the postnatal expression of calbindin, calretinin and parvalbumin and glutamic acid decarboxylase (GAD) and microtubule-associated protein 2 (MAP2) in organotypic monocultures of rat dorsal thalamus compared to the thalamus in vivo. Cultures were maintained for up to 7 weeks. Cortex-conditioned medium improved the survival of thalamic cultures. MAP2-immunoreactive material was present in somata and dendrites of small and large-sized neurons throughout the cultures. Parvalbumin immunoreactivity was present in larger multipolar or bitufted neurons along the edge of a culture. These neurons also displayed strong parvalbumin mRNA and GAD mRNA expression, and GABA immunoreactivity. They likely corresponded to cells of the nucleus reticularis thalami. Parvalbumin mRNA, but neither parvalbumin protein nor GAD mRNA, was expressed in neurons with large somata within the explant. They likely represented relay cells. GAD mRNA, but not parvalbumin mRNA, was expressed in small neurons within the explants. Small neurons also displayed calbindin- and calretinin-immunoreactivity. The small neurons likely represented local circuit neurons. The time course of expression of the calcium-binding proteins revealed that all were present at birth with the predicted molecular weights. A low, but constant parvalbumin expression was observed in vitro without the developmental increase seen in vivo, which most likely represented parvalbumin from afferent sources. In contrast, the explantation transiently downregulated the calretinin and calbindin expression, but the neurons recovered the expression after 14 and 21 days, respectively. In conclusion, thalamic monocultures older than three weeks represent a stable neuronal network containing well differentiated neurons of the nucleus reticularis thalami, relay cells and local circuit neurons.

Déficits dans les apports nutritionnels chez les candidats a la chirurgie bariatrique [Nutritional deficiencies in candidates for bariatric surgery]

98% of patients who have undergone a gastric bypass for treating severe obesity develop multiple micronutrient deficits. However, prior to surgery, it isn't rare to find nutrient deficiencies. Indeed, the dietary intakes of surgery candidates are often unbalanced, lacking in variety especially in high vitamin and mineral nutrients. We present the preliminary results concerning the qualitative and quantitative analysis in a group of patients waiting for a gastric bypass. The recommended daily amounts in vitamin B9, vitamin D and iron are insufficient in the majority of the patients. The correction of nutritional intakes is advisable, even before the surgery, in order to reduce the risks of developing biological deficiencies.

Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol. EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months. RESULTS: Eight dose levels (40-8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days. CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.

Trends in dietary intake in Switzerland, 1999 to 2009.

OBJECTIVE: To assess nutrition trends of the Geneva population for the period 1999-2009. DESIGN: Bus Santé Geneva study, which conducts annual health surveys in random samples of the Geneva population. Dietary intake was assessed using a validated FFQ and trends were assessed by linear regression. SETTING: Population-based survey. SUBJECTS: Data from 9283 participants (50% women, mean age 51·5 (sd 10·8) years) were analysed. RESULTS: In both genders total energy intake decreased from 1999 to 2009, by 2·9% in men and by 6·3% in women (both trends P < 0·005). Vegetable protein and total carbohydrate intakes, expressed as a percentage of total energy intake, increased in women. MUFA intake increased while SFA, PUFA and alcohol intakes decreased in both genders. Intakes of Ca, Fe and carotene decreased in both genders. No changes in fibre, vitamin D and vitamin A intakes were found. Similar findings were obtained after excluding participants with extreme dietary intakes, except that the decreases in SFA, vegetable protein and carbohydrate were no longer significant in women. CONCLUSIONS: Between 1999 and 2009, a small decrease in total energy intake was noted in the Geneva population. Although the decrease in alcohol and SFA intakes is of interest, the decrease in Ca and Fe intakes may have adverse health effects in the future.

Whole-mount confocal immunofluorescence of mammalian CNS.

Bright-field wholemount labeling techniques applied to the mammalian central nervous system (CNS) offer advantages over conventional methods based on sections since an immediate and three-dimensional view of the stained components is provided. It thereby becomes possible to survey and count large number of cells and fibers in their natural relationships. The ability of confocal laser scanning microscopy to visualize in one focal plane the fluorescence associated with multiple markers could be most valuable by the availability of reliable wholemount fluorescent techniques. Accordingly, based in our previously published bright-field wholemount protocols [Brain Res. Prot. 2 (1998) 165-173], we have devised an effective immmunofluorescence wholemount procedure. We show that reliable wholemount fluorescent staining can be obtained using isolated complete CNS aged up to rat embryonic day 17, with antibodies penetration in the millimeter range. Examples are shown of preparations in which colocalization can be observed in nerve cells of cytoskeletal and calcium-binding proteins.

Gériatrie [Geriatry]

This review discuss several studies published in 2007 that will modify current therapeutic attitudes. New evidence confirm that antipsychotics increase mortality in demented elderly persons with behavioral symptoms. Unfortunately, donepezil was no more effective than placebo to treat agitation in these patients. Aspirine, nonsteroidal anti-inflammatories, as well as supplementation with folate, vitamines B6 and B12 did not prove beneficial to prevent cognitive decline. Hormonal substitution with DHEA, testosterone, and growth hormone is ineffective as anti-aging medicine, while calcium and vitamin d'effectiveness was confirmed in fracture prevention. Finally, several studies report prognostic information that will prove important to improve preparation plan for future heat wave.

Dietary intake according to gender and education : a twenty-year trend in a Swiss adult population

We assessed trends in dietary intake according to gender and education using repeated cross-sectional, population-based surveys conducted between 1993 and 2012 in Geneva, Switzerland (17,263 participants, 52.0 ± 10.6 years, 48% male). In 1993-1999, higher educated men had higher monounsaturated fatty acids (MUFA), carotene and vitamin D intakes than lower educated men, and the differences decreased in 2006-2012. In 1993-1999, higher educated women had higher fiber, iron, carotene, vitamin D and alcohol intakes than lower educated women, and the differences decreased in 2006-2012. Total energy, polyunsaturated fatty acids, retinol and alcohol intakes decreased, while mono/disaccharides, MUFA and carotene intake increased in both genders. Lower educated men had stronger decreases in saturated fatty acid (SFA) and calcium intakes than higher educated men: multivariate-adjusted slope and 95% confidence interval -0.11 (-0.15; -0.06) vs. -0.03 (-0.08; 0.02) g/day/year for SFA and -5.2 (-7.8; -2.7) vs. -1.03 (-3.8; 1.8) mg/day/year for calcium, p for interaction <0.05. Higher educated women had a greater decrease in iron intake than lower educated women: -0.03 (-0.04; -0.02) vs. -0.01 (-0.02; 0.00) mg/day/year, p for interaction = 0.002. We conclude that, in Switzerland, dietary intake evolved similarly between 1993 and 2012 in both educational groups. Educational differences present in 1993 persisted in 2012.

Predictors of trabecular bone score in school children.

UNLABELLED: Trabecular bone score (TBS) is a DXA-based tool that assesses bone texture and reflects microarchitecture. It has been shown to independently predict the risk of osteoporotic fracture in the elderly. In this study, we investigated the determinants of TBS in adolescents. INTRODUCTION: TBS is a gray-level textural measurement derived from lumbar spine DXA images. It appears to be an index of bone microarchitecture that provides skeletal information additional to the standard BMD measurement and clinical risk factors. Our objectives were to characterize the relationship between TBS and both age and pubertal stages and identify other predictors in adolescents. METHODS: We assessed TBS by reanalyzing spine DXA scan images obtained from 170 boys and 168 girls, age range 10-17 years, gathered at study entry and at 1 year, using TBS software. The results are from post hoc analyses obtained using data gathered from a prospective randomized vitamin D trial. Predictors of TBS were assessed using t test or Pearson's correlation and adjusted using regression analyses, as applicable. RESULTS: The mean age of the study population was 13.2 ± 2.1 years, similar between boys and girls. Age, height, weight, sun exposure, spine BMC and BMD, body BMC and BMD, and lean and fat mass are all significantly correlated with TBS at baseline (r = 0.20-0.75, p < 0.035). Correlations mostly noted in late-pubertal stages. However, after adjustment for BMC, age remained an independent predictor only in girls. CONCLUSIONS: In univariate exploratory analyses, age and pubertal stages were determinants of TBS in adolescents. Studies to investigate predictors of TBS and to investigate its value as a prognostic tool of bone fragility in the pediatric population are needed.

Inappropriate prescribing to the oldest old patients admitted to hospital: prevalence, most frequently used medicines, and associated factors

Background: Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited, as is available information on inappropriate prescription (IP) and its associated factors. The study aimed to describe medicine prescription, potentially inappropriate medicines (PIM) and potentially prescribing omissions (PPO) and their associated factors on this population. Methods: In the context of an observational, prospective and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year, a sub-analysis of those aged 85 years and over was performed. To assess PIMs, the Beers and STOPP criteria were used, and to assess PPOs, the START and the ACOVE-3 criteria were used. To assess factors associated with IP, a multivariate logistic regression analysis was performed. Patients were selected randomly every week on consecutive days from the hospitalization lists. Results: A total of 336 patients were included in the sub-analysis with a median (Q1-Q3) age of 88 (8690) years. The median medicines taken during the month prior to admission was 10 (713). Forty-seven point two per cent of patients had at least one Beers-listed PIM, 63.3% at least one STOPP-listed PIM, 53.6% at least one START-listed PPO, and 59.4% at least one ACOVE-3-listed PPO. Use of benzodiazepines in patients who are prone to falls (18.3%) and omission of calcium and vitamin D supplements in patients with osteoporosis (13.3%) were the most common PIM and PPO, respectively. The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines (OR = 5.7, 95% CI 1.8-17.9 and OR = 13.4, 95% CI 4.0-44.0, respectively). The main factors associated with the START-listed PPO was a non-community dwelling origin (OR 2.3, 95% CI 1.0-5.0), and multimorbidity (OR1.8, 95% CI 1.0-3.1). Conclusions: Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over. Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO, respectively. Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM.

Uusintamurtumien ehkäisy kaatumisen aiheuttaman yläraajamurtuman kokeneilla yli 50-vuotiailla henkilöillä

Tarkoitus: Tarkoituksena oli selvittää murtumien tehostetun ehkäisyohjelman vaikutuksia yläraajamurtuman saaneiden yli 50-vuotiaiden henkilöiden elämäntapoihin, murtumien riskitekijöihin, kaatumisiin, kaatumisvammoihin ja elämänlaatuun. Aineisto: 219 yli 50-vuotiasta kotona asuvaa, kaatumisen seurauksena yläraajamurtuman saanutta henkilöä satunnaistettiin koe- (n = 105) ja kontrolliryhmiin (n = 114). Menetelmä: Koeohjelma sisälsi yksilöllisen, yhdessä lääkärin, terveydenhoitajan ja tutkittavan kanssa laaditun hoito- ja kuntoutussuunnitelman sekä kutsun murtumien ehkäisyn koulutusohjelmaan. Kontrolliryhmän tutkittavat saivat kehotuksen hakeutua murtumahoitajan ohjaukseen. Seuranta-aika oli 14 kuukautta. Tulokset analysoitiin ryhmissä tapahtuneina muutoksina alkuja loppumittausten välillä sekä ryhmien välisenä erona muutoksissa. Tulokset: Keskimääräinen luun tiheys lannerangassa lisääntyi koeryhmässä (p<0,001) ja kontrolliryhmässä (p = 0,038), ryhmien välinen ero ei ollut tilastollisesti merkitsevä (p = 0,134). Reisiluun kaulassa luun tiheys ei muuttunut kummassakaan ryhmässä. Päivittäinen kalsiumin saanti lisääntyi koeryhmässä keskimäärin 167 mg (p<0,001) ja kontrolliryhmässä 30 mg (p = 0,475), ryhmien välinen ero oli tilastollisesti merkitsevä (p = 0,031). Kala-ateriat ja päivittäinen D-vitamiinilisä sekä kenkien liukuesteiden säännöllinen käyttö liukkaalla lisääntyivät molemmissa ryhmissä, mutta ryhmien välillä ei ollut eroa. Viiteen tuolilta nousukertaan käytetty aika vähentyi koeryhmässä keskimäärin 0,49 sekuntia (p = 0,185) ja lisääntyi kontrolliryhmässä 0,39 (p = 0,475), ero ryhmien välillä oli tilastollisesti merkitsevä (p = 0,02). Kymmenen metrin kävelyssä ei tapahtunut tulosten keskiarvossa muutoksia kummassakaan ryhmässä. Ortostatismi vähentyi kontrolliryhmässä (p = 0,049), ja masentuneisuus vähentyi koeryhmässä (p = 0,041), mutta ryhmien välillä ei näissä ollut merkitsevää eroa. Osteoporoosilääkkeiden käyttö lisääntyi molemmissa ryhmissä, ryhmien välillä ei ollut eroa. Alkoholin käytössä oli vähäisiä mutta ei merkittäviä muutoksia. Muissa testatuissa muuttujissa, kuten liikunnan viikoittainen määrä, tupakointi, näkökyky, tasapaino ja elämänlaatu, ei ollut merkitseviä muutoksia ryhmissä tai ryhmien välillä. Kaatumisten (koeryhmä 33, kontrolliryhmä 35) ja murtumien (koeryhmä 5 ja kontrolliryhmä 3) määrissä ei myöskään ollut merkitseviä eroja ryhmien välillä. Johtopäätökset: Noin neljällä viidestä kaatumisen seurauksena yläraajamurtuman saaneista, yli 50 vuotta täyttäneistä henkilöistä oli alentunut luun tiheys, ja noin joka toisella oli lisääntynyt kaatumisriski. Kaatumisen riskitekijöiden kliiniset mittaukset olivat nopeita toteuttaa ja auttoivat ehkäisytoimenpiteiden suunnittelussa. Murtuman saaneet olivat motivoituneita murtumien riskitekijöiden selvittämiseen ja myös toteuttamaan annettua lääkehoitoa. Elämäntavoissa helpoimmin toteutuivat muutokset ruokailutottumuksissa. Liikuntatottumuksien muuttaminen sen sijaan onnistui melko huonosti. Ryhmien välillä oli merkitsevä ero ainoastaan kalsiumin päivittäisessä käytössä ja tuolilta nousutestissä. Murtumariskien tunnistaminen, niiden syiden selvittäminen ja toimenpiteiden käynnistäminen riskien vähentämiseksi tulisi kuulua jokaisen pienienergisen murtuman saaneen potilaan kokonaisvaltaiseen hyvään hoitoon.

Using data mining to identify factors that influence the degree of leg injuries in broilers

Locomotor problems prevent the bird to move freely, jeopardizing the welfare and productivity, besides generating injuries on the legs of chickens. The objective of this study was to evaluate the influence of age, use of vitamin D, the asymmetry of limbs and gait score, the degree of leg injuries in broilers, using data mining. The analysis was performed on a data set obtained from a field experiment in which it was used two groups of birds with 30 birds each, a control group and one treated with vitamin D. It was evaluated the gait score, the asymmetry between the right and left toes, and the degree of leg injuries. The Weka ® software was used in data mining. In particular, C4.5 algorithm (also known as J48 in Weka environment) was used for the generation of a decision tree. The results showed that age is the factor that most influences the degree of leg injuries and that the data from assessments of gait score were not reliable to estimate leg weakness in broilers.

The use of dietary supplements and medication among Finnish elite athletes

Background: Dietary supplements are widely used among elite athletes but the prevalence of dietary supplement use among Finnish elite athletes is largely not known. The use of asthma medication is common among athletes. In 2009, the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) removed the need to document asthma by lung function tests before the use of inhaled β2-agonists. Data about medication use by Paralympic athletes (PA) is limited to a study conducted at the Athens Paralympics. Aims: To investigate the prevalence of the use of self-reported dietary supplements, the use of physician-prescribed medication and the prevalence of physician-diagnosed asthma and allergies among Finnish Olympic athletes (OA). In addition, the differences in the selfreported physician-prescribed medication use were compared between the Finnish Olympic and the Paralympic athletes. Subjects and methods: Two cross-sectional studies were conducted in Finnish Olympic athletes receiving financial support from the Finnish Olympic Committee in 2002 (n=446) and in 2009 (n=372) and in Finnish top-level Paralympic athletes (n= 92) receiving financial support from Finnish Paralympic committee in 2006. The results of the Paralympic study were compared with the results of the Olympic study conducted in 2009. Both Olympic and Paralympic athletes filled in a similar semi-structured questionnaires. Results: Dietary supplements were used by 81% of the athletes in 2002 and by 73% of the athletes in 2009. After adjusting for age-, sex- and type of sport, the odds ratio OR (95% confidence interval, CI) for use of any dietary supplement was significantly less in 2009 as compared with the 2002 situation (OR 0.62; 95% CI 0.43-0.90). Vitamin D was used by 0.7% of the athletes in year 2002 but by 2% in 2009 (ns, p = 0.07). The use of asthma medication increased from 10.4 % in 2002 to 13.7% in 2009 (adjusted OR 1.71; 95% CI 1.08-2.69). For example, fixed combinations of inhaled long-acting β2-agonists (LABA) and inhaled corticosteroids (ICS) were used three times more commonly in 2009 than in 2002 (OR 3.38; 95% CI 1.26-9.12). The use of any physician-prescribed medicines (48.9% vs. 33.3%, adjusted OR 1.99; 95% CI 1.13-3.51), painkilling medicines (adjusted OR 2.61; 95% CI 1.18-5.78), oral antibiotics (adjusted OR 4.10; 95% CI 1.30-12.87) and anti-epileptic medicines (adjusted OR 37.09; 95% CI 5.92-232.31) was more common among the PA than in the OA during the previous seven days. Conclusions: The use of dietary supplements is on the decline among Finnish Olympic athletes. The intake of some essential micronutrients, such as vitamin D, is suprisingly low and this may even cause harm in those well-trained athletes. The use of asthma medication, especially fixed combinations of LABAs and ICS, is clearly increasing among Finnish Olympic athletes. The use of any physician-prescribed medicine, especially those to treat chronic diseases, seems to be more common among the Paralympians than in the Olympic athletes.

Receptor localization of steroid hormones and drugs: discoveries through the use of thaw-mount and dry-mount autoradiography

The history of receptor autoradiography, its development and applications, testify to the utility of this histochemical technique for localizing radiolabeled hormones and drugs at cellular and subcellular sites of action in intact tissues. Localization of diffusible compounds has been a challenge that was met through the introduction of the "thaw-mount" and "dry-mount" autoradiographic techniques thirty years ago. With this cellular receptor autoradiography, used alone or combined with other histochemical techniques, sites of specific binding and deposition in vivo and in vitro have been characterized. Numerous discoveries, some reviewed in this article, provided information that led to new concepts and opened new areas of research. As an example, in recent years more than fifty target tissues for vitamin D have been specified, challenging the conventional view about the main biological role of vitamin D. The functions of most of these vitamin D target tissues are unrelated to the regulation of systemic calcium homeostasis, but pertain to the (seasonal) regulation of endo- and exocrine secretion, cell proliferation, reproduction, neural, immune and cardiovascular responses, and adaptation to stress. Receptor autoradiography with cellular resolution has become an indispensable tool in drug research and development, since information can be obtained that is difficult or impossible to gain otherwise