Perry Syndrome

Disease characteristics. Perry syndrome is characterized by parkinsonism, hypoventilation, depression, and weight loss. The mean age at onset is 48 years; the mean disease duration is five years. Parkinsonism and psychiatric changes (depression, apathy, character changes, and withdrawal) tend to occur early; severe weight loss and hypoventilation manifest later. Diagnosis/testing. The diagnosis is based on clinical findings and molecular genetic testing of DCTN1, the only gene known to be associated with Perry syndrome. Management. Treatment of manifestations: Dopaminergic therapy (particularly levodopa/carbidopa) should be considered in all individuals with significant parkinsonism. Although response to levodopa is often poor, some individuals may have long-term benefit. Noninvasive or invasive ventilation support may improve quality of life and prolong life expectancy. Those patients with psychiatric manifestations may benefit from antidepressants and psychiatric care. Weight loss is managed with appropriate dietary changes. Surveillance: routine evaluation of weight and calorie intake, respiratory function (particularly at night or during sleep), strength; and mood. Agents/circumstances to avoid: Central respiratory depressants (e.g., benzodiazepines, alcohol). Genetic counseling. Perry syndrome is inherited in an autosomal dominant manner. The proportion of cases attributed to de novo mutations is unknown. Each child of an individual with Perry syndrome has a 50% chance of inheriting the mutation. No laboratories offering molecular genetic testing for prenatal diagnosis are listed in the GeneTests Laboratory Directory; however, prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified.

Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy?

The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.

GEPM: gestió d'equipaments públics municipals

Aquest projecte presenta una solució integral e integrada per a la gestió d’equipaments públics municipals. És integral ja que contempla tots els aspectes de la gestió, mitjançant diferents canals en funció del perfil d’usuari que l’utilitza ; és integrada ja que proporciona una solució integrada amb l’ERP corporatiu existent actualment a l’Ajuntament per al qual s’ha desenvolupat. El projecte presenta els següents canals de gestió: Aplicació Windows desenvolupada en .NET, Extranet de gestió amb gestió de continguts, Aplicació web per dispositius mòbils i Web informativa de recollida selectiva i neteja viària. El projecte també disposa de connexió al gestor documental Documentum de EMC2.

When to Quit Under Uncertainty? A real options approach to smoking cessation

This paper models the decision to quit smoking like an investment decision where the quitter incurs a sunk withdrawal cost today and forgoes their consumer surplus from cigarettes (invests) and hopes to reap an uncertain reward of better health and therefore higher utility in the future (return). We show that a risk-averse mature smoker who expects to benefit from quitting may still rationally choose to delay quitting until they are more confident that quitting is the right decision for them. Such a decision by the smoker is due to the value associated with keeping their option of whether or not to quit open as they learn more about the damage that smoking will have on their future utility. Policies which reduce a smoker’s uncertainty about the damage that smoking with have on their future utility is likely to make them quit earlier.

Social isolation causers mortality by disrupting energy homeostrasis in ants

Social deprivation can have negative effects on the lives of social animals, including humans, yet little is known about the mechanisms by which social withdrawal affects animal health. Here we show that in the carpenter ant Camponotus fellah, socially isolated workers have a greatly reduced life span relative to ants kept in groups of ten individuals. By using a new tracking system, we found that social isolation resulted in important behavioral changes and greatly increased locomotor activity. The higher activity of single ants and their increased propensity to leave the nest to move along the walls suggested that the increased mortality of isolated ants might stem from an imbalance of energy income and expenditure. This view was supported by the finding that while isolated ants ingested the same amount of food as grouped ants, they retained food in the crop, hence preventing its use as an energy source. Moreover, the difference in life span between single and grouped individuals vanished when ants were not fed. This study thus underlines the role of social interactions as key regulators of energy balance, which ultimately affects aging and health in a highly social organism.

Measuring the diffusion of palliative care in long-term care facilities - a death census

ABSTRACT: BACKGROUND: The dissemination of palliative care for patients presenting complex chronic diseases at various stages has become an important matter of public health. A death census in Swiss long-term care facilities (LTC) was set up with the aim of monitoring the frequency of selected indicators of palliative care. METHODS: The survey covered 150 LTC facilities (105 nursing homes and 45 home health services), each of which was asked to complete a questionnaire for every non-accidental death over a period of six months. The frequency of 4 selected indicators of palliative care (resort to a specialized palliative care service, the administration of opiates, use of any pain measurement scale or other symptom measurement scale) was monitored in respect of the stages of care and analysed based on gender, age, medical condition and place of residence. RESULTS: Overall, 1200 deaths were reported, 29.1% of which were related to cancer. The frequencies of each indicator varied according to the type of LTC, mostly regarding the administration of opiate. It appeared that the access to palliative care remained associated with cancer, terminal care and partly with age, whereas gender and the presence of mental disorders had no effect on the indicators. In addition, the use of drugs was much more frequent than the other indicators. CONCLUSION: The profile of patients with access to palliative care must become more diversified. Among other recommendations, equal access to opiates in nursing homes and in home health services, palliative care at an earlier stage and the systematic use of symptom management scales when resorting to opiates have to become of prime concern.

Quaternary ammonium salt derivatives of allylphenols with peripheral analgesic effect

Ammonium salt derivatives of natural allylphenols were synthesized with the purpose of obtaining potential peripheral analgesics. These drugs, by virtue of their physicochemical properties, would not be able to cross the blood brain barrier. Their inability to enter into the central nervous system (CNS) should prevent several adverse effects observed with classical opiate analgesics (Ferreira et al., 1984). Eugenol (1) O-methyleugenol (5) and safrole (9) were submitted to nitration, reduction and permethylation, leading to the ammonium salts 4, 8 and 12. Another strategy applied to eugenol (1), consisting in its conversion to a glycidic ether (13), opening the epoxide ring with secondary amines and methylation, led to the ammonium salts 16 and 17. All these ammonium salts showed significant peripheral analgesic action, in modified version of the Randall-Sellito test (Ferreira et al. 1978), at non-lethal doses. The ammonium salt 8 showed an activity comparable to that of methylnalorphinium, the prototype of an ideal peripheral analgesic (Ferreira et al., 1984).

Development of natural products as drugs acting on central nervous system

We have recenty studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP posses not only analgesic activity, but also exert sedative-tranquillizing and hypnotic actions. Results of receptor binding assay and their pre-and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval process. Preliminary clinical studies showed that Hup-A improve short-and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chines frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Short-course thymoglobulin induction and steroid-free immunosuppressive regimen in renal transplantation

Purpose: Optimal induction and maintenance immunosuppressive therapies in renal transplantation are still a matter of debate.Chronic corticosteroid usage is a major cause of morbidity but steroid-free immunosuppression (SF) can result in unacceptably high rates of acute rejection and even graft loss. Methods and materials: We have conducted a prospective openlabelled clinical trial in the Geneva-Lausanne Transplant Network from March 2005 to May 2008. 20 low immunological risk (<20% PRA, no DSA) adult recipients of a primary kidney allograft received a 4-day course of thymoglobulin (1.5 mg/kg/d) with methylprednisolone and maintenance based immunosuppression of tacrolimus and entericcoated mycophenolic acid (MPA). The control arm consisted of 16 matched recipients treated with basiliximab induction, tacrolimus, mycophenolate mofetil and corticosteroids. Primary endpoints were the percentage of recipients not taking steroids and the percentage of rejection-free recipients at 12 months.Secondary end points were allograft survival at 12 months and significant thymoglobulin and/or other drugs side effects. Results: In the SF group, 85% of the kidney recipients remained steroid-free at 12 months. The 3 cases of steroids introduction were due to one acute tubulo-interstitial rejection occurring at day 11, one tacrolimus withdrawal due to thrombotic microangiopathy and one MPA withdrawal because of multiple sinusitis and CMV reactivations. No BK viremia was detected nor CMV disease. The 6 CMV negative patients who received a positive CMV allograft had a symptomatic primoinfection after their 6-month course valgancyclovir prophylaxis. In the steroid-based group, 3 acute rejection episodes (acute humoral rejection, acute tubulointerstitial Banff IA and vascular Banff IIA) occurred in 2 recipients, 3 BK virus nephropathies were diagnosed between 45 and 135 days post transplant No side effects were associated with thymoglobulin infusion.In the SF group, 4 recipients presented severe leukopenia or agranulocytosis and one recipient had febrile hepatitis leading to transient MPA withdrawal. Discontinuation of MPA was needed in 2 patients for recurrent sinusitis and CMV reactivations. Patient and graft survival was 100% in both groups at 12 month follow-up. Conclusion: Steroid-free with short-course thymoglobulin induction therapy was a safe protocol in low-risk renal transplant recipients. Lower rates of acute rejection and BK virus infections episodes were seen compared to the steroid-based control group. A longer follow-up will be needed to determine whether this SF immunosuppressive regimen will result in higher graft and patient survival.

Mineralocorticoid receptor is involved in rat and human ocular chorioretinopathy.

Central serous chorioretinopathy (CSCR) is a vision-threatening eye disease with no validated treatment and unknown pathogeny. In CSCR, dilation and leakage of choroid vessels underneath the retina cause subretinal fluid accumulation and retinal detachment. Because glucocorticoids induce and aggravate CSCR and are known to bind to the mineralocorticoid receptor (MR), CSCR may be related to inappropriate MR activation. Our aim was to assess the effect of MR activation on rat choroidal vasculature and translate the results to CSCR patients. Intravitreous injection of the glucocorticoid corticosterone in rat eyes induced choroidal enlargement. Aldosterone, a specific MR activator, elicited the same effect, producing choroid vessel dilation -and leakage. We identified an underlying mechanism of this effect: aldosterone upregulated the endothelial vasodilatory K channel KCa2.3. Its blockade prevented aldosterone-induced thickening. To translate these findings, we treated 2 patients with chronic nonresolved CSCR with oral eplerenone, a specific MR antagonist, for 5 weeks, and observed impressive and rapid resolution of retinal detachment and choroidal vasodilation as well as improved visual acuity. The benefit was maintained 5 months after eplerenone withdrawal. Our results identify MR signaling as a pathway controlling choroidal vascular bed relaxation and provide a pathogenic link with human CSCR, which suggests that blockade of MR could be used therapeutically to reverse choroid vasculopathy.

Les hépatopathies auto-immunes et leurs traitements [Auto-immune liver diseases and their treatment]

There are three main types of auto-immune liver disease, auto-immune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. In the case of auto-immune hepatitis, prednisone therapy, with or without azathioprine, can improve quality of life and halt progression to cirrhosis. If there is no response or if the therapy is poorly tolerated, mycophenolate mofetil or cyclosporin should be considered. Ursodeoxycholic acid (UDCA), at a dosage of 13 to 15 mg/kg/day slows the progression of fibrosis in patients with primary biliary cirrhosis. Pruritus may be treated with cholestyramine, rifampicin or opiate antagonists. Ursodeoxycholic acid at a dosage of 20 to 30 mg/kg/day will slow the evolution of fibrosis.

Prévenir la prise de poids à l'arrêt du tabac: pas de solution miracle: revue Cochrane pour le praticien. [Preventing weight gain in smoking cessation: there is no miracle solution]

http://resfranco.cochrane.org/sites/resfranco.cochrane.org/files/uploads/Arrettabac2009.pdf

The Role of Skin Opioid Receptor System in Itch

Opioid receptors are key players in induction of chronic itch. This could be confirmed using opiate receptor knockout mice experiments and clinical studies on patients with chronic itch. We have induced a dry skin dermatitis as a model for chronic itching on -(MOR) and -(KOR) opioid receptor knockout (KO) mice. MOR KO mice scratched significantly less than wild type (WT). Additionally the epidermal hypertrophy caused by chronic dermatitis and the amount of epidermal nerve endings in MOR KO mice were significantly decreased than in WT mice. KOR KO mice showed similar scratching behavior as MOR KO mice; however the changes were less significant. In addition, we performed a double blind, placebo controlled, cross over study using topically applied opioid receptor antagonist, Naltrexone, on patients with pruritus in atopic dermatitis. The results revealed significant effects of the topical application of Naltrexone in patients with chronic pruritus (45% improvement of pruritus by VAS compared to placebo, n=24), but not in patients with acute pruritus (7%, n=15). These studies establish the clinical relevance of MOR system and the peripheral, epidermal nerve endings in chronic pruritus and warrant further research and therapeutic potential for such research.

Time and temperature dependant changes in red blood cell analytes used for testing recombinant erythropoietin abuse in sports.

There has been a long debate since the introduction of blood analysis prior to major sports events, to find out whether blood samples should be analysed right away on the site of competition or whether they should be transported and analysed in an anti-doping laboratory. Therefore, it was necessary to measure blood samples and compare the results obtained right after the blood withdrawal with those obtained after a few hours delay. Furthermore, it was interesting to determine the effect of temperature on the possible deterioration of red blood cell analytes used for testing recombinant erythropoietin abuse. Healthy volunteers were asked to give two blood samples and one of these was kept at room temperature whereas the second one was put into a refrigerator. On a regular basis, the samples were rolled for homogenisation and temperature stabilisation and were analysed with the same haematological apparatus. The results confirmed that blood controls prior to competition should be performed as soon as possible with standardised pre-analytical conditions to avoid too many variations notably on the haematocrit and the reticulocyte count. These recommendations should ideally also be applied to the all the blood controls compulsory for the medical follow up, otherwise unexplainable values could be misinterpreted and could for instance lead to a period of incapacity.