Prevalence, risk factors and evolution of diabetes mellitus after treatment in primary aldosteronism. Results from the SPAIN-ALDO registry.

PURPOSE: To evaluate the prevalence, risk factors and evolution of diabetes mellitus (DM) after targeted treatment in patients with primary aldosteronism (PA). METHODS: A retrospective multicenter study of PA patients in follow-up at 27 Spanish tertiary hospitals (SPAIN-ALDO Register). RESULTS: Overall, 646 patients with PA were included. At diagnosis, 21.2% (n = 137) had DM and 67% of them had HbA1c levels < 7%. In multivariate analysis, family history of DM (OR 4.00 [1.68-9.53]), the coexistence of dyslipidemia (OR 3.57 [1.51-8.43]) and advanced age (OR 1.04 per year of increase [1.00-1.09]) were identified as independent predictive factors of DM. Diabetic patients were on beta blockers (46.7% (n = 64) vs. 27.5% (n = 140), P < 0.001) and diuretics (51.1% (n = 70) vs. 33.2% (n = 169), p < 0.001) more frequently than non-diabetics. After a median follow-up of 22 months [IQR 7.5-63.0], 6.9% of patients developed DM, with no difference between those undergoing adrenalectomy and those treated medically (HR 1.07 [0.49-2.36], p = 0.866). There was also no significant difference in the evolution of glycemic control between DM patients who underwent surgery and those medically treated (p > 0.05). CONCLUSION: DM affects about one quarter of patients with PA and the risk factors for its development are common to those of the general population. Medical and surgical treatment provides similar benefit in glycemic control in patients with PA and DM.

Ganglio centinela en la metástasis ganglionar por cáncer papilar de tiroides: validez diagnóstica y aplicación en la práctica clínica / Sentinel lymph node biopsy in papillary thyroid cancer: Accuracy and application in clinical practice

Introducción La biopsia selectiva del ganglio centinela (BSGC) puede completar el estudio preoperatorio detectando adenopatías no visibles ecográficamente. De este modo, se puede estadificar a los pacientes y estratificar el riesgo de recidiva de forma más precisa y, por tanto, ayudar a definir el tipo de tratamiento tanto quirúrgico como con 131I que debemos realizar. El objetivo fue validar la BSGC para su utilización en el diagnóstico de la metástasis ganglionar por cáncer papilar de tiroides. Métodos Estudio observacional prospectivo de cohortes que incluye a 55 pacientes intervenidos por cáncer papilar de tiroides sin sospecha de afectación ganglionar clínica o radiológica, desde febrero de 2012 hasta febrero de 2015, con un seguimiento de entre 6 y 8 años. Se utilizó 99Tc con nanocoloide intratumoral y una sonda portátil de la gammacámara para la detección de los ganglios centinelas. Variables: edad, género, histológicas, analíticas y estadificación preoperatoria y postoperatoria. Se calculó la sensibilidad, la especificidad y los valores predictivos de la técnica. La validación se determinó calculando la detectabilidad y los falsos negativos de la prueba. Resultados En 53 de los 55 (96,36%) pacientes hubo detección del ganglio centinela. Los falsos negativos fueron 4 (7,5%) pacientes. Del resto, tras aplicar la BSGC, 24 (48,9%) se mantuvieron como N0, 14 (28,5%) pasaron a ser N1a y 11 (22,4%) se clasificaron como N1b. Las diferencias observadas en el estudio fueron significativas (p<0,05). La sensibilidad fue del 86,21%, la especificidad del 100%, el VPP del 100% y el VPN del 85,71%. La precisión diagnóstica fue del 92,45%. Conclusiones La BSGC es una técnica válida para su utilización en los pacientes afectos de cáncer papilar de tiroides, con una alta precisión diagnóstica (AU)

Introduction The presence of lymph nodes metastasis in papillary thyroid cancer modifies the type of surgical resection as well as the indication of the treatment with 131I in the postoperative period. This therapeutic approach is based on the results of the diagnostic tests, like the cervical ultrasonography. Currently other methods of diagnostic are tested as selective sentinel lymph node biopsy (SLNB). It can complement to the ultrasound results. The aim was to validate the SLNB for use in the diagnosis of lymph node metastasis by papillary thyroid cancer. Methods Observational prospective cohort study of 55 patients who underwent papillary thyroid cancer without suspicion of lymph node involvement clinical or radiological, since February 2012 through February 2015, with a follow-up between 6 and 8 years. It was used 99Tc with intratumoral nanocoloid and a portable tube of the gamma camera for the detection of the sentinel node. Variables: age, gender, histological, analytical and preoperative and postoperative staging. The sensitivity, specificity and predictive values of technique was calculated. The validation was determined by calculating the detectability and the false negative results of the test. Results In 53 of the 55 patients (96.36%) there was the sentinel node detection. The false negative were 4 patients (7.5%). Of the rest, after applying the SLNB, 24 (48.9%) were kept as N0, 14 (28.5%) became N1a and 11 (22.4%) were classified as N1b. The differences observed in the study were significant (P<.05). The sensitivity was 86.21%, the specificity of 100%, the PPV was 100% and the NPV of 85.71%. The diagnostic accuracy was 92.45%. Conclusions The SLNB is a valid technique for use in patients suffering from papillary thyroid cancer with a high diagnostic accuracy (AU)

Comparison of lipases for in vitro models of gastric digestion: lipolysis using two infant formulas as model substrates.

The aim of this study was to find a lipase suitable as a surrogate for Human Gastric Lipase (HGL), since the development of predictive gastrointestinal lipolysis models are hampered by the lack of a lipase with similar digestive properties as HGL. Three potential surrogates for HGL; Rhizopus Oryzae Lipase (ROL), Rabbit Gastric Lipase (RGL) and recombinant HGL (rHGL), were used to catalyze the in vitro digestion of two infant formulas (a medium-chain triacylglyceride enriched formula (MC-IF) and a predominantly long-chain triacylglyceride formula (LC-IF)). Digesta were withdrawn after 0, 5, 15, 30, 60 min of gastric digestion and after 90 or 180 min of intestinal digestion with or without the presence of pancreatic enzymes, respectively. The digesta were analyzed by scanning electron microscopy and gas chromatography to quantify the release of fatty acids (FAs). Digestions of both formulas, catalyzed by ROL, showed that the extent of gastric digestion was higher than expected from previously published in vivo data. ROL was furthermore insensitive to FA chain length and all FAs were released at the same pace. RGL and rHGL favoured the release of MC-FAs in both formulas, but rHGL did also release some LC-FAs during digestion of MC-IF, whereas RGL only released MC-FAs. Digestion of a MC-IF by HGL in vivo showed that MC-FAs are preferentially released, but some LC-FAs are also released. Thus of the tested lipase rHGL replicated the digestive properties of HGL the best and is a suitable surrogate for HGL for use in in vitro gastrointestinal lipolysis models.

Aldosteronismo primario senil asociado a carcinoma suprarrenal funcionante / Senile primary aldosteronism associated with adrenal carcinoma

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[5 days Cefaclor vs. 10 days amoxicillin/clavulanate in the treatment of childhood streptococcal pharyngitis. Data from a randomized clinical trial]. / Efficacia di Cefaclor 5 giorni vs. amoxicillina-acido clavulanico 10 giorni, nella terapia della faringotonsillite streptococcia del bambino. Risultati di uno studio clinico randomizzato.

AIM: The duration of therapy represents a fundamental aspect in the compliance to the therapy of child pathologies, such as pharyngotonsillitis, treated with oral therapy. Although penicillin and amoxicillin are the first choice antibiotics in the case of a child suffering from pharyngotonsillitis with the proven presence of Group A ß-hemolytic Streptococcus (GAS), the number of orally administered doses and 10 days of therapy, considerably lower the compliance. METHODS: An open phase IV randomized multicenter clinical trial was conducted in parallel groups, involving 49 family pediatrician (FP), distributed over the entire national territory, enrolling 435 children suffering from GAS-FT. 210 children received Cefaclor, 50 mg/kg/day, administered twice daily for five days, whilst 213 children received amoxicillin/clavulanate 40 mg/kg/day administered twice daily for 10 days. RESULTS: The results showed percentages of eradication of 88.4% for the Cefaclor group and 94.3% for the amoxicillin/clavulanate group, and a positive clinical judgement of 92.3% for the Cefaclor group and 96.6% for the amoxicillin/clavulanate group. The two arms of the study did not have any significant statistical differences, neither for the eradication, nor for the clinical judgement nor for the reduction of the Milano Score between the beginning and the end of treatment, with a P=0.042 for amoxicillin/clavulanate for eradication. CONCLUSION: This study confirms that the administration of Cefaclor for five days during GAS-FT has the same efficacy as a 10-day therapy with amoxicillin/clavulanate, with a clearly different compliance.

Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease.

BACKGROUND: The efficacy of nebulized corticosteroids in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD) has been poorly studied. OBJECTIVE: To evaluate the efficacy and tolerability of nebulized flunisolide (1 mg) + salbutamol/ipratropium bromide (1,875/375 microg) b.i.d. in comparison with placebo + salbutamol/ipratropium bromide. METHODS: This was a randomized, parallel-group, double-blind study on 114 patients with COPD of moderate-to-severe degree. The main outcome was the frequency of severe exacerbations over a 6-month period. Before and after treatment, respiratory symptoms, forced expiratory volume in 1 s (FEV(1)), shuttle walking test distance and St. George's Respiratory Questionnaire scores were evaluated. RESULTS: The total number of exacerbations was slightly lower in the flunisolide group compared to the placebo group (19 vs. 34, p = 0.054); the number of patients experiencing at least one exacerbation during the study was also decreased (16 vs. 26, p = 0.059). In particular, type 3 Anthonisens's exacerbations were significantly reduced by flunisolide (p = 0.044). In the placebo group, scores were higher than in the flunisolide group but nonsignificant for dyspnea, cough, sputum amount and purulence. FEV(1) was significantly increased compared to baseline in both groups, and the area under the FEV(1)-time curve during the 6-month period was significantly greater in the flunisolide group (5.2 +/- 10.6 vs. 2.1 +/- 5.0, flunisolide vs. placebo, respectively; p = 0.047). For shuttle walking test distance and scores of the St. George's Respiratory Questionnaire, no significant difference between the baseline evaluation and the end of the study was observed in both groups. CONCLUSIONS: Nebulized flunisolide is a good alternative to other inhaled corticosteroids when added to nebulized salbutamol/ipratropium bromide in the long-term treatment of moderate-to-severe COPD patients.

Ginecomastia e hipertiroidismo: estudio hormonal a propósito de un caso / Gynecomastia and hyperthyroidism : hormonal study of one case

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Coma prolongado con daño neurológico por un insulinoma oculto / Prolonged coma with severe neurological damage due to an unsuspected benign insulinoma

Una mujer de 30 años ingresó en el hospital en coma profundo sin causa aparente ni duración conocida. Los estudios posteriores revelaron un hiperinsulinismo endógeno con hipoglucemia como origen del cuadro. La cateterización selectiva arterial de las ramas del tronco celíaco con inyección de calcio y recogida de muestras en vena hepática permitió localizar un insulinoma en la cabeza pancreática, no evidente en ninguna de las otras exploraciones practicadas. La cirugía subsiguiente fue curativa, pero quedaron secuelas neurológicas con lesiones groseras evidentes en la RMN. Aunque infrecuente, la posibilidad de una hipoglucemia debida a un insulinoma debe tenerse presente en el diagnóstico diferencial de un paciente en coma sin etiología evidente. El debut de un insulinoma con un único episodio de coma puede tener un efecto devastador a nivel cerebral, con importantes secuelas neurológicas (AU)

Desmopressin and imipramine in the management of nocturnal enuresis: a multicentre study.

The efficacy and safety of desmopressin (Minirin/DDAVP) treatment compared with imipramine were investigated in a multicentre, open, cross-over design in 57 patients, aged 6-15 years, affected by nocturnal enuresis to establish the best therapeutic approach to this condition. After a two-weeks observation and control period, patients were randomised to one of two groups: intranasal administration of desmopressin, 30 micrograms/day for three weeks, followed by imipramine, 0.9 mg/kg for a further three weeks, or imipramine 0.9 mg/kg for three weeks, followed by desmopressin, 30 micrograms/day for a further three weeks. Following treatment, all patients were observed for a further two weeks. Administration of either treatment protocol resulted in a statistically significant decline in the number of enuretic episodes per week compared to the control. The greater antidiuretic effect observed in the group receiving imipramine followed by desmopressin suggests the two compounds have different profiles. Also, when the treatment period was compared with the follow-up, the antidiuretic effect had a longer duration in the group initially given imipramine. No further improvement was seen when desmopressin was administered first, with a mild worsening of the effect sometimes occurring, suggesting a different carry-over effect between the two treatments. This suggests that desmopressin offers a better approach to the management of nocturnal enuresis.

Nocturnal enuresis and daytime wetting: a multicentric trial with oxybutynin and desmopressin.

OBJECTIVE: Different etiopathological mechanisms of enuresis are today under study, and different therapies and drugs have been proposed. The Italian Multicentric Trial was undertaken in twelve pediatric and urological centers in order to assess the efficacy of two of the most popular drugs, desmopressin (DDAVP) and oxybutynin. METHODS: 114 enuretic patients were enrolled in the study. After a 2-week observation period, 66 patients with primary monosymptomatic enuresis were treated with DDAVP, 30 micrograms/day intranasally, for 6 weeks, 48 patients with enuresis and voiding dysfunction were randomly assigned to a protocol with oxybutynin alone or oxybutynin plus DDAVP. The efficacy of the two drugs was measured in terms of reduction of wet nights per week during the 6-week treatment period and a 2-week follow-up period. Children with 0-3 dry nights/week were considered as nonresponders. RESULTS: Patients with monosymptomatic enuresis treated with DDAVP reported a significantly lower number of wet night during treatment than during the baseline period, with 79% showing a 'good' (6-7 dry nights/week) or 'intermediate' response (4-5 dry nights/week). Of the patients with diurnal voiding disturbances and enuresis, those treated with oxybutynin alone had a 54% success rate. The patients treated with both oxybutynin and DDAVP showed a better response, with a 71% rate of success. CONCLUSIONS: The efficacy of the two drugs is confirmed in patients carefully selected on the clinical basis of voiding disturbances. In patients with enuresis and voiding dysfunction, the reduced urinary output and the lower bladder filling rate due to DDAVP can reduce uninhibited bladder contractions, thus enhancing the oxybutynin action.

[Long-term treatment of central diabetes insipidus with oral DDAVP]. / Trattamento a lungo termine del diabete insipido centrale con DDAVP per via orale.

Clinical use of the DDAVP (1-Deamino-8-D-Arginine Vasopressin) is now the first choice in treatment of Central Diabetes Insipidus. It is an analogue of Vasopressin with a higher antidiuretic potency, less vasopressor activity, and a longer duration of action. This drug still presents some problems of administration route. A lot of studies were published about different administration routes of DDAVP: sublingual tablets, parenteral solution, nose spray and suction de-epithelialized skin. Some authors have utilized the oral route (solution or tablets) with good results in short-term treatment. We think the formulation in tablets of DDAVP is an efficacious support of the therapy in this disease also for long-treatment. In our study 3 patients with Central Diabetes Insipidus (aged 22-56; 2 idiopathic and 1 post-surgery) previously treated with DDAVP nasal solution (10 micrograms/day; 36-156 months), have been submitted to a chronic treatment with DDAVP tablets for a period of 24-36 months. The DDAVP tables were administered at the dosage of 400-600 micrograms/day in 2-3 administrations. The patients were studied at intervals of 3-6 months, and on each occasion full blood count, glucose, azotaemia, creatinine, liver function tests, electrolytes, urine volume, density and osmolality were estimated. The long-treatment with oral DDAVP was able to keep a good control of the disease in all patients. In case 1 we had a significant reduction of urine volume (p < 0.01) and a significant increase (p < 0.01) of urine osmolality in comparison with previous treatment with nasal solution; in case 2 and 3 no significant changes were observed. No side effects were noted during this study. The drug has been well tolerated and the compliance of patients was better during oral DDAVP than nasal solution. In our opinion the oral DDAVP is an effective and safe solution for the treatment of Central Diabetes Insipidus, and give to the patients a better quality of life in comparison to the nasal solution.

[Treatment of central diabetes insipidus using oral DDAVP. Comparison with intranasal treatment]. / Trattamento del diabete insipido centrale con DDAVP per via orale. Confronto con il trattamento per via endonasale.

The Authors have done a clinical study on the efficacy of desmopressin (DDAVP) tablets in the treatment of central diabetes insipidus in 13 patients who were previously treated with intranasal DDAVP. A comparison has been made between peroral and intranasal forms of DDAVP measuring the urinary volume and osmolarity daily. The right dosage of DDAVP tablets was between 150 and 600 micrograms/die. The patients showed very good compliance during the 4 weeks of treatment with DDAVP.

Perirenal and renal subcapsular haematoma as presenting symptoms of polyarteritis nodosa.

Two young men, were hospitalized due to acute massive blood loss with left abdominal flank pain. In both cases renal angiography showed signs of a haemorrhagic event in the left kidney, perirenal in one and subcapsular in the other. Microaneurysms indicated a diagnosis of polyarteritis nodosa, supported by renal biopsy in one case. Renal haemorrhage is an infrequent presentation of polyarteritis nodosa. Furthermore, one patient suffered also from familial Mediterranean fever, and is the fifth reported case with this combination of diseases.

Functional and biochemical modifications of lung beta-adrenoreceptors after in vivo desensitization: prevention by indomethacin.

Desensitization of lung beta-adrenoreceptors induced by 4 day in vivo isoprenaline administration to rats has been investigated both from a functional a biochemical viewpoint. Chronic isoprenaline treatment significantly reduced the relaxing activity of the beta-agonist when tested ex vivo in lung parenchymal strips and also impaired the adenylate-cyclase system. Moreover, the desensitization procedure decreased by about 30% beta-adrenoreceptor number. In vivo indomethacin treatment prevented the loss of pharmacological responsiveness of the tissue to isoprenaline and restored basal adenylate-cyclase activity. These data indicate that in vivo isoprenaline administration actually leads to pulmonary beta-adrenoreceptor desensitization. The involvement of arachidonic acid metabolites in this phenomenon is also discussed.