Distinct roles of age and abdominal visceral fat in reducing androgen receptor-dependent negative feedback on LH secretion in healthy men.

Testosterone (T) impacts luteinizing hormone (LH) secretion through negative feedback via the androgen receptor (AR) in the hypothalamo-pituitary system. An untested postulate is that increasing body mass index (BMI), abdominal visceral fat (AVF) or total abdominal fat (TAF) with ageing decreases LH secretion by heightening T negative feedback via AR. This hypothesis was tested in a prospective, randomized double-blind cross-over study of 19 healthy men comparing the effects of flutamide, a selective non-steroidal AR antagonist and placebo administration on basal and pulsatile LH secretion as a function of age and obesity measures. To this end, serum levels of 2-hydroxyflutamide (2-OHF), a major active flutamide metabolite, were measured by mass spectrometry, and AVF/TAF quantified by abdominal computerized tomography. Statistical analysis showed that antiandrogen administration elevated 6-h mean LH concentrations to 5.4 ± 1.3 IU/L compared with 3.3 ± 1.2 IU/L for placebo (p < 10(-3) ), and total T by 35% (p < 10(-4) ). The LH-T concentration product doubled (p < 10(-8) ). According to deconvolution analysis, flutamide exposure increased total LH secretion (p < 10(-3) ) and pulsatile LH secretion (p = 0.0077), along with LH pulse frequency (p = 0.019). Despite feedback inhibition, the LH-T product declined as a linear function of AVF (p = 0.021) and TAF (p = 0.017). This was explained by the fact that higher BMI was associated with lower 2-OHF concentrations (R = -0.562, p = 0.012). In contrast, age was associated with less pulsatile LH secretion (R = -0.567, p = 0.011) even when LH responses were normalized to antiantrogen levels. In conclusion, increased AVF, TAF and BMI predict decreased LH and flutamide blood levels, whereas older age is marked by impaired stimulation of pulsatile LH secretion even when normalized for antiandrogen levels, suggesting different mechanisms of regulation by adiposity and age.

Biobanks and personalized medicine.

We provide a mini-review of how biobanks can support clinical genetics in the era of personalized medicine. We discuss types of biobanks, including disease specific and general biobanks not focused on one disease. We present considerations in setting up a biobank, including consenting and governance, biospecimens, risk factor and related data, informatics, and linkage to electronic health records for phenotyping. We also discuss the uses of biobanks and ongoing considerations, including genotype-driven recruitment, investigations of gene-environment associations, and the re-use of data generated from studies. Finally, we present a brief discussion of some of the unresolved issues, such as return of research results and sustaining biobanks over time. In summary, carefully designed biobanks can provide critical research and infrastructure support for clinical genetics in the era of personalized medicine.

Transcriptome meta-analysis of peripheral lymphomononuclear cells indicates that gestational diabetes is closer to type 1 diabetes than to type 2 diabetes mellitus.

We performed a meta-analysis of the transcription profiles of type 1, type 2 and gestational diabetes to evaluate similarities and dissimilarities among these diabetes types. cRNA samples obtained from peripheral blood lymphomononuclear cells (PBMC) of 56 diabetes mellitus patients (type 1 = 19; type 2 = 20; gestational = 17) were hybridized to the same whole human genome oligomicroarray platform, encompassing 44,000 transcripts. The GeneSpring software was used to perform analysis and hierarchical clustering, and the DAVID database was used for gene ontology. The gene expression profiles showed more similarity between gestational and type 1 diabetes rather than between type 2 and gestational diabetes, a finding that was not influenced by patient gender and age. The meta-analysis of the three types of diabetes disclosed 3,747 differentially and significantly expressed genes. A total of 486 genes were characteristic of gestational diabetes, 202 genes of type 1, and 651 genes of type 2 diabetes. 19 known genes were shared by type 1, type 2 and gestational diabetes, highlighting EGF, FAM46C, HBEGF, ID1, SH3BGRL2, VEPH1, and TMEM158 genes. The meta-analysis of PBMC transcription profiles characterized each type of diabetes revealing that gestational and type 1 diabetes were transcriptionally related.

Evaluation of negative outcomes associated with medication (NOM) by pharmacists at a home assistance programme in a Brazilian teaching hospital

Background The concept of pharmaceutical care (PC) specifically refers to the pharmacist being able to identify, prevent and resolve negative outcomes associated with medication (NOM). According to the Third Consensus of Granada, these are patient health-related outcomes not consistent with pharmacotherapy objectives, and are associated with the proper or erroneous use of medicines. In this way, pharmacists might provide the pharmacist to provide the correct use of medicines to patients who are attended at home. Objective This study aimed to detect, classify and quantify NOM, according to the Third Consensus of Granada, in patients treated at home, who were assisted by the Home Assistance Programme of the University Hospital of University of Paulo, Brazil. Method A descriptive, observational and cross-sectional study was conducted. The pharmacotherapy plan was filled during the interview with the patient or caregiver. Results The study included 87 patients with a mean age of 66 years old, adults (89%), children (11%), female (58%) and retired (62%). A total of 62% patients presented NOM, with an average of 1.13 NOM per patient. The NOM included untreated health problems (20.6%), effects from unnecessary medicines (9.1%), non-quantitative ineffectiveness (34.5%), quantitative ineffectiveness (3.4%), non-quantitative safety problems (11.4%) and quantitative safety problems (3.4%). Patients with the following characteristics were more prevalent than expected in the NOM effectiveness group: those aged between 65 and 74 years (p=0.0199), those with a low education level (p=0.0266), those with increased comorbidity (p=0.0461), those using medicine for the digestive tract and (..) (AU)

Introducción Para utilizar el concepto de de Atención Farmacéutica (AF) en su más amplio significado, el farmacéutico debe haber podido identificar, prevenir y resolver los resultados negativos asociados a la medicación (RNM). Según el Tercer Consenso de Granada, estos RNM están relacionados con los resultados en la salud del paciente no adecuados al objetivo de la farmacoterapia y asociados al uso o fallo en el uso de medicamentos. Así pues, el farmacéutico puede facilitar el uso correcto de los medicamentos a los pacientes en régimen domiciliario. Objetivo El objetivo de este estudio es detectar, clasificar y cuantificar los RNM, según el Tercer Consenso de Granada, en pacientes tratados en régimen domiciliario que fueron atendidos a través del Programa de Asistencia Domiciliaria del Hospital Universitario de São Paulo en Brasil. Método Estudio descriptivo y observacional de corte transversal. La planificación del tratamiento farmacológico se completó durante la entrevista con el paciente o el cuidador. Resultados El estudio contó con 87 pacientes con una edad media de 66 años, del cual el 89% eran adultos, el 11% niños, el 58% mujeres y el 62% jubilados. El sesenta y dos por ciento de los pacientes presentó RNM, con una media de 1,13 RNM por paciente. La prevalencia de RNM fue: problemas de salud no tratados (20,62%), efecto de medicamentos innecesarios (9,1%), ineficacia no cuantitativa (34,5%), ineficacia cuantitativa (3,4%), problemas de salud no cuantitativos (11,4%) y problemas de salud cuantitativos (3,4%). La probabilidad de ocurrencia de RNM de eficacia aumentaba en pacientes con: edades de entre 65 y 74 años (p = 0,0199), nivel de educación bajo (p = 0,0266), más comorbilidades (p = 0,0461), uso de medicamentos para el (..) (AU)

Evaluation of negative outcomes associated with medication (NOM) by pharmacists at a home assistance programme in a Brazilian teaching hospital.

BACKGROUND: The concept of pharmaceutical care (PC) specifically refers to the pharmacist being able to identify, prevent and resolve negative outcomes associated with medication (NOM). According to the Third Consensus of Granada, these are patient health-related outcomes not consistent with pharmacotherapy objectives, and are associated with the proper or erroneous use of medicines. In this way, pharmacists might provide the pharmacist to provide the correct use of medicines to patients who are attended at home. OBJECTIVE: This study aimed to detect, classify and quantify NOM, according to the Third Consensus of Granada, in patients treated at home, who were assisted by the Home Assistance Programme of the University Hospital of University of Paulo, Brazil. METHOD: A descriptive, observational and cross-sectional study was conducted. The pharmacotherapy plan was filled during the interview with the patient or caregiver. RESULTS: The study included 87 patients with a mean age of 66 years old, adults (89%), children (11%), female (58%) and retired (62%). A total of 62% patients presented NOM, with an average of 1.13 NOM per patient. The NOM included untreated health problems (20.6%), effects from unnecessary medicines (9.1%), non-quantitative ineffectiveness (34.5%), quantitative ineffectiveness (3.4%), non-quantitative safety problems (11.4%) and quantitative safety problems (3.4%). Patients with the following characteristics were more prevalent than expected in the NOM effectiveness group: those aged between 65 and 74 years (p=0.0199), those with a low education level (p=0.0266), those with increased comorbidity (p=0.0461), those using medicine for the digestive tract and metabolism (p=0.0475) and those using medicine for blood and blood-forming organs (p=0.0466). For the NOM necessity group, patients with endocrine, nutritional and metabolic diseases (p=0.0587) were in greater numbers than expected; and for the NOM safety group, only patients aged over 74 years (p=0.01809) were in greater numbers. CONCLUSION: For this population, it was concluded that there were several factors related to the occurrence of NOM: age, education, number of comorbidities, use of medicines for the digestive tract and the metabolism and medicines for blood and blood-forming organs. The use of the Third Consensus of Granada classification was very important for the recognition and measurement of NOM.

Elder mistreatment.

Elder mistreatment is a widespread problem in our society that is often under-recognized by physicians. As a result of growing public outcry over the past 20 years, all states now have abuse laws that are specific to older adults; most states have mandated reporting by all health care professionals. The term "mistreatment" includes physical abuse and neglect, psychologic abuse, financial exploitation and violation of rights. Poor health, physical or cognitive impairment, alcohol abuse and a history of domestic violence are some of the risk factors for elder mistreatment. Diagnosis of elder mistreatment depends on acquiring a detailed history from the patient and the caregiver. It also involves performing a comprehensive physical examination. Only through awareness, a healthy suspicion and the performing of certain procedures are physicians able to detect elder mistreatment. Once it is suspected, elder mistreatment should be reported to adult protective services.

Urinary incontinence in the elderly. Drug treatment options.

Urinary incontinence is commonly seen in the elderly. It has multiple complications and is often the reason an elderly person is forced to abandon independent living and enter a nursing home. There are multiple causes of urinary incontinence: it is not a single entity or a specific diagnosis. In most patients, the incontinence can be placed into 1 of the following 4 categories: detrusor overactivity (urge incontinence), overflow incontinence, stress incontinence (outlet incompetence) or functional incontinence. To understand the pathophysiology of urinary incontinence, some knowledge of the urinary tract anatomy and physiology is required. It is also important to know how the anatomy and physiology changes in response to the aging process. Successful treatment depends on the specific cause of the incontinence. If incorrectly diagnosed, various treatments may actually worsen the incontinence or cause other problems. Since most elderly patients do not volunteer a problem of urinary incontinence, questions regarding the presence of symptoms must be asked. In most patients, the specific type of incontinence can be diagnosed with a thorough medical history and physical examination. Several simple and widely available laboratory tests may also be useful in the evaluation. Occasionally, urological consultation or urodynamic testing should be performed. Once correctly diagnosed, there are a large number of pharmacological as well as nonpharmacological treatments (behavioural, surgical) available. This article concentrates on the pharmacological therapies for patients with various types of urinary incontinence. Since most patients with urinary incontinence are elderly, they are more susceptible to the effects as well as the adverse effects of medications. This must be taken into account before any pharmacological therapy is initiated. Although many elderly patients believe their symptoms of urinary incontinence to be a part of growing old, urinary incontinence is never a normal change of aging. With proper evaluation and treatment, the majority of patients with urinary incontinence can be helped or cured.

Colonic stents in colorectal obstruction.

Obstruction is the presenting symptom of colorectal cancer in up to 40 per cent of patients. Benign strictures and other neoplasms including lymphoma and gynecologic tumors occur as well. Emergent operative therapy is often suboptimal and associated with significant morbidity and mortality. Our objective was to review our experience with stent placement for colonic obstruction. Seven patients underwent stent placement for a total of eight procedures. There were three patients with unresectable colorectal cancer, two patients with metastatic gynecologic cancer, one patient with rectal lymphoma, and one patient with metastatic cancer of unknown primary. All colonic stents were Wallstents placed by the same endoscopist under fluoroscopic and endoscopic guidance. Stents were successfully placed in all patients without complication. One patient underwent placement of two stents in succession for a long stenosis. Six of seven patients (86%) had resolution of the obstruction and return of bowel function. Five of seven were tolerating a diet within 24 hours. One patient's mental status did not allow for oral intake. Four patients were discharged within 48 hours. Two patients died within the same hospitalization as a result of metastatic disease. One patient was found to have multilevel disease requiring stoma placement. There was no morbidity or mortality associated with stent placement, and 86 per cent of patients had palliation of the obstruction. We conclude that colonic stent placement is a safe and effective therapy for colorectal obstruction at this institution.

Efeito da morfina peridural sobre a pressäo nas vias biliares / Effect of eipdural morphine on common bile duct pressure

Em 15 pacientes submetidos a cirurgias eletivas de vias biliares sob anestesia geral, com tiopental, fentanil, óxido nitroso, isoflurano, foi medida a pressäo no ducto biliar comum antes e 10 min após a injeçäo peridural de 50 µg.kg elevado a menos 1 de morfina diluída em 10 ml de soluçäo salina (grupo I, n=10), ou 10 ml de soluçäo salina (grupo II, n=5). No grupo I a média dos valores de pressäo após a injeçäo (17,25 ñ 4,14 cm H2O), significativamente maior (p < 0,05) que a média dos valores iniciais (12,05 ñ 3,12 cm H2O). No grupo II (controle), näo houve diferença entre as médias dos valores de pressäo antes e após a injeçäo peridural da soluçäo salina. Em quatro pacientes do grupo I, a manometria foi repetida 60 minutos após a injeçäo peridural, persistindo o aumento da pressäo nas vias biliares. Säo feitas consideraçöes sobre a farmacocinética da morfina peridural, correlacionando-as com os resultados

Irradiation of Escherichia coli in the visible spectrum with a tunable organic-dye laser energy source.

Pulsed laser energy was shown to be effective in inhibiting the growth of Escherichia coli. The irradiation source was derived from a tunable organic-dye laser utilizing rhodamine 6G (590 plus or minus 5 nm) solutions as lasing media. The organisms, suspended in nutrient broth, were irradiated both with and without an exogenous photosensitizer. One photosensitizer (toluidine blue) did not appreciably alter the inhibitory effect observed. In the presence of acridine orange, however, some additional growth occurred.