Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. METHODS: This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. FINDINGS: Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. INTERPRETATION: To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).

Field Campaign Evaluation of Sensors Lufft GMX500 and MaxiMet WS100 in Peruvian Central Andes.

The research presents the inter-comparison of atmospheric variables measured by 9 automatic weather stations. This set of data was compared with the measurements of other weather stations in order to standardize the values that must be adjusted when taken to different areas. The data of a set of a total of 9 GMX500, which measures conventional meteorological variables, and 10 WS100 sensors, which measures precipitation parameters. The automatic stations were set up at the Huancayo Observatory (Geophysical Institute of Peru) for a period of 5 months. The data set of GMX500 were evaluated comparing with the average of the 9 sensors and the WS100 was compared with an optical disdrometer Parsivel2. The temperature, pressure, relative humidity, wind speed, rainfall rate, and drop size distribution were evaluated. A pair of GMX500 sensors presented high data dispersion; it was found found that the errors came from a bad configuration; once this problem was solved, good agreement was archived, with low RMSE and high correlation. It was found that the WS100 sensors overestimate the precipitation with a percentage bias close to 100% and the differences increase with the greater intensity of rain. The drop size distribution retrieved by WS100 have unrealistic behavior with higher concentrations in diameters of 1 mm and 5 mm, in addition to a flattened curve.

Risk factors for recurrence and prognosis of low-grade endometrial adenocarcinoma; vaginal versus other sites.

Endometrial adenocarcinoma is the most common gynecologic cancer in the United States. The prognosis is generally favorable, however, a significant number of patients do develop local or distant recurrence. The most common site of recurrence is vaginal. Our aim was to better characterize patients with vaginal recurrence of low-grade endometrioid adenocarcinoma with respect to associated tumor parameters and clinical outcome. We compiled 255 cases of low-grade (FIGO Grade I or II) endometrioid adenocarcinoma on hysterectomy specimens with lymph node dissection. A total of 113 cases with positive lymph nodes or recurrent disease were included in our study group. Seventy-three cases (13 Grade 1, 60 Grade 2) developed extravaginal recurrence and 40 cases (7 Grade 1, 33 Grade 2) developed vaginal recurrence. We evaluated numerous tumor parameters including: percentage myoinvasion, presence of microcystic, elongated, and fragmented pattern of myoinvasion, lymphovascular space invasion, and cervical involvement. Clinical follow-up showed that 30% (34/113) of all patients with recurrent disease died as a result of their disease during our follow-up period, including 31 (42.5%) with extravaginal recurrence and 3 (7.5%) with primary vaginal recurrence (P=0.001). The 3 patients with vaginal recurrence developed subsequent extravaginal recurrence before death. Vaginal recurrence patients show increased cervical involvement by tumor, but lack other risk factors associated with recurrent disease at other sites. There were no deaths among patients with isolated vaginal recurrence, suggesting that vaginal recurrence is not a marker of aggressive tumor biology.

Use of probiotics for prevention of radiation-induced diarrhea.

AIM: To investigate the efficacy of a high-potency probiotic preparation on prevention of radiation-induced diarrhea in cancer patients. METHODS: This was a double-blind, placebo-controlled trial. Four hundred and ninety patients who underwent adjuvant postoperative radiation therapy after surgery for sigmoid, rectal, or cervical cancer were assigned to either the high-potency probiotic preparation VSL#3 (one sachet t.i.d.,) or placebo starting from the first day of radiation therapy. Efficacy endpoints were incidence and severity of radiation-induced diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication. RESULTS: More placebo patients had radiation-induced diarrhea than VSL#3 patients (124 of 239 patients, 51.8%, and 77 of 243 patients, 31.6%; P<0.001) and more patients given placebo suffered grade 3 or 4 diarrhea compared with VSL#3 recipients (55.4% and 1.4%, P<0.001). Daily bowel movements were 14.7 +/- 6 and 5.1 +/- 3 among placebo and VSL#3 recipients (P<0.05), and the mean time to the use of loperamide was 86 +/- 6 h for placebo patients and 122 +/- 8 h for VSL#3 patients (P<0.001). CONCLUSION: Probiotic lactic acid-producing bacteria are an easy, safe, and feasible approach to protect cancer patients against the risk of radiation-induced diarrhea.

Prophylaxis of diarrhoea in patients submitted to radiotherapeutic treatment on pelvic district: personal experience.

Diarrhoea is a severe side-effect of radiotherapy on the pelvic area. It is due to acute enteric damage. We aimed at determining the ability of a highly concentrated freeze-dried living bacteria compound (VSL/3) to reduce these side-effects in 190 patients receiving radio therapy on the pelvic area. A total of 95 patients received radiotherapy alone and 95 were also administered VSL/3 bags, at doses of one bag three times a day beginning on the first day of the radiotherapy treatment. The same diet was indicated for both groups. All patients were irradiated for 6 to 7 weeks, with Linac X-6 MV or 15 MV through a box multiportal technique with the lower limit of the fields below the obturator foramina, upper limit at L5-S1, lateral limit 1.5 cm beyond the innominate hip. The total radiated dose ranged from 60 to70 Gy for a daily dose of 180 cGy. Gastroenteric toxicity was rated in WHO degrees. Two patients receiving radiotherapy alone had to discontinue the treatment due to acute enteritis. Toxicity was found in 52 (50.6%) patients with radiotherapy alone vs 36 (30.5%) patients receiving VSL/3. None of them had to discontinue radiotherapy. Toxicity of degrees 3 or 4 was found in 28 patients receiving radiotherapy alone vs 7 with VSL/3. These preliminary data suggest the effectiveness of VSL/3 in preventing the occurrence of diarrhoea in patients submitted to radiotherapy with a direct and indirect improvement of their quality of life and a good tolerance.

Concurrent carboplatin and radiotherapy in the treatment of squamous cell carcinoma of the head and neck, stage IV. Preliminary data of a phase II study.

About two-thirds of the patients with squamous cell carcinoma of the head and neck (SCCHN) are diagnosed when the disease is in a locoregionally advanced stage. If surgery is not advisable, radiotherapy is the only treatment presently available to obtain radicality. In order to improve the therapeutic efficacy of radiotherapy (RT), chemotherapy has been associated with it with the aim of eradicating possible micrometastatic foci outside the radiotherapic fields and to enhance the cytotoxic effects of radiation. Results with concomitant chemoradiotherapy have been encouraging. We carried out a phase II study with the combination of carboplatin 300 mg/m2 every 21 days and RT at conventional doses in SCCHN stage IV (non M1). We obtained an overall response of 85.7% with an 18-month survival of 70%. The toxicity was moderate. These results encourage us to continue the accural of patients.

Palliative-radiotherapy in lumbosacral carcinomatous neuropathy.

The authors report their own experience in obtaining pain relief in 13 recurrent or disseminated cancer patients affected by lumbosacral carcinomatous neuropathy (LCN). The site, where the disease involved the lumbosacral plexus or its branches, was palliatively irradiated with a few large fractions. The average duration of response was 196 days. Median survival (uncensored) was 185 days (range 47-636 days).

[Contribution of computerized tomography to the diagnosis of patients with non-calcified solitary pulmonary nodule, without known neoplasm]. / Contributo della tomografia computerizzata alla diagnostica dei pazienti con nodulo solitario polmonare non calcifico, in assenza di neoplasia nota.

We define a solitary pulmonary noncalcified nodule (NPS) as a single focal rounded or ovoid lesion in the lung parenchyma, less than 4 cm in diameter, without associated adenopathy, atelectasis or pneumonia. An NPS, in the absence of a known primary malignancy, can be lung cancer (NPSM), a metastasis of unknown origin (NPSMT), or a benign lesion (NPSB). The best approach to the management of NPS and the value of CT are still controversial and uncertain. The finding on cross-section CT of a bronchus leading directly to, or contained within, the nodule is called "positive CT bronchus sign" (CT-BS). Our study was aimed at investigating the usefulness of CT bronchus sign, as studied on thin-slice (2 mm thick) CT sections, in order to establish the most appropriate diagnostic sequence in patients with solitary noncalcified pulmonary nodules (NPS). We evaluated 47 NPS (9 NPSB, 34 NPSM and 4 NPSMT) with thin-slice CT to detect the presence of CT bronchus sign. Seventeen cases had CT-BS (15 NPSM; 1 NPSB; 1 NPSMT); of them, 13 were diagnosed by means of transbronchial biopsy and brushing (TBB). Only one case (NPSM) of the 30 (19 NPSM; 3 NPSMT; 8 NPSB) without CT-BS, was diagnosed by TBB. TBB was negative in the 9 NPSB. The CT-BS is not pathognomonic of malignancy; in fact, the sign was observed in NPSB (one tuberculoma) too. Our results suggest that the CT bronchus sign is valuable in predicting the success of TBB in malignant solitary pulmonary nodules. On the other hand, it seems to be useless for NPSB. Therefore, to establish the most appropriate diagnostic sequence, thin-section CT should be performed in each patient with peripheral noncalcified lung lesions to plan whether TBB or transthoracic needle aspiration should come next. If biopsy results are poor, either surgery or the "wait and watch for growth" approaches can be suggested. The choice can be guided by the presence of predisposing factors for cancer or infection.

[Conservative treatment of early breast carcinoma. Localization of the booster field]. / Trattamento conservativo del carcinoma mammario iniziale. Localizzazione del volume bersaglio da sovradosare.

The definition of the methods for localizing the booster field used in the conservative treatment of early breast cancer is often blurred in several studies in the current literature. This paper is aimed at reporting a surgical-radiological method more objective than the clinico-anamnestic one used, so far, for planning the booster field. To this purpose 33 patients underwent conservative surgery in healthy tissue and radiopaque clips were inserted at the margins of the excision cavity. The booster field as defined with clinico-anamnestic standards was then simulated and later verified by a radiation therapy simulator. The clinical fields thus set up were correct in 15/33 cases. The authors discuss their results and compare them with literature data. The importance of the use of the surgical-radiological method to localize the booster field is stressed.

[Clodronate and radiotherapy for the treatment of osteolysis caused by metastasis of breast carcinoma and non-small cell lung carcinoma. A retrospective study]. / Clodronato più radioterapia nel trattamento delle osteolisi metastatiche da carcinoma mammario e polmonare non microcitoma. Studio retrospettivo.

We have retrospectively examined 94 evaluable patients with metastatic osteolysis from breast cancer (BC) and non-small cell lung (NSCLC) cancer, who received RT from Nov. 88 to Nov. 89.27 (15 BC and 12 NSCLC) were in treatment with Clodronate for at least 3 days from the beginning of RT; of the remaining 67 treated with RT alone, 31 had NSCLC and 36 BC. We have evaluated: increase in pain (IP) occurring on the first days of RT, percentages of complete pain relief (CPR) at the end of RT and 4-6 weeks after. A decreased occurrence of IP was observed more in NSCLC patients receiving RT + Clodronate compared to those treated with RT alone (33.3% vs 41.9%). Both at the end of RT and 4-6 weeks after, we registered a significant difference in the percentages of CPR in the RT + Clodronate group (40.7 vs 20.9 and 70.3% vs 53.7%). We believe the points of interest focused in this paper-greater precision in centering and defining the target volume, decreased occurrence of IP during the first days of RT, increase in percentage of CPR--need a prospective confirmation.

Patogenicidad de cepas de Microsporum fulvum, aisladas de suelos tratados com herbicidas / Pathonenicity of Microsporum fulvum isolated from soil treated with herbicidas

Cepas de Microsporum fulvum, que se aislaron de suelos cultivables, sin tratamiento desmalezante y con la aplicación de los herbicidas, Metribuzín, Atrazina y Alachlor, fueron estudiadas con el fin de conocer, si la acción fitotóxica de tales agroquímicos, modificó la capaqcidad infectante de las mismas. Para ello se inocularon cuatro lotes de cobayos, con un homogeneizado en gel de agar de parte del desarrolo de esas cepas en sabouraud-glucosa. La inoculación se practicó en la zona de los flancos, previo rasurado y escarificación. De acuerdo a la sintomatología de las lesiones provocadas, las cepas de M. fulvum obtenida de suelos con Atranazina, produjo una marcada reacción ulcerante, com prolongada alpecía en la zona de inoculación. A su vez se determinó la capacidad queratinolítica de tal desarrllo, practicado en um medio de caballo, con incubación a 28§C, durante 60 días. En alícutas de 10 ml que se tomaron de esos cultivos, y los correspondientes testigos, fue valorada la activiudad queratinolítica, como así también los compuestos azufrados resultantes de la misma. Para la primera determinación se usó como sustrato cortes de pelos de cobayos blancos, en medio líquido, determinándo-se el contenido de proteínas espectrofotométricamente a 280 nm. En base a la acción reductora de los radicales sulfhidrilos de la cisteina y S-sulfocisteína sobre el ácido fosfotúngico, fueron valorados los compuestos sulfhidrilados, productos de la queratinolisis. Los datos del ensayo enzimático de la cepa aislada de suelos tratados con Atrazina, mostraron valores significativamente superiores a los obtenidos para los controles. Esas determinaciones se corresponden con la más alta concentración de los compuestos sufhidrilados resultantes. Este comportamiento nos lleva a considerar a esos cultivos de M. fulvum como una mutante bioquímica con manifestación de un fenotipo virulento, originado por los cambios ambientales producidos al incorporarse a los suelos un biocida vegetal como Atrazina.

[Pelvic carcinomatous neuropathy: clinical, radiologic, therapeutic implications]. / Neuropatia carcinomatosa pelvica: implicazioni cliniche, radiologiche, terapeutiche.

Carcinomatous involvement of the pelvic nerves (Pelvic Carcinomatous Neuropathy-PCN-) causes disabling sensorial and motor disturbances of the lower extremities. Recurrent rectal carcinomas are the most common cause of PCN because surgical obliteration of the perirectal fascia. In 31 cases of PCN Authors describe the types of the neoplasm and the sites of involvement of the pelvic nerves evaluating clinical syndromes and Computed Tomography. The results of radiotherapy (doses between 36-56 Gy) in 14 cases of PCN by recurrent rectal cancer are also reported. Although the survival of such patients is poor, radiotherapy has obtained a good palliative result in 50% of them. Personalization of radiation treatment planning is advisable in order to avoid acute side-effects.

Nicotinic and M1-, M2-muscarinic cholinergic control of ACTH response to insulin-induced hypoglycaemia in man.

The possible mediation of muscarinic and/or nicotinic-cholinergic receptors in the response of ACTH to insulin-induced hypoglycaemia was evaluated in 18 normal men. Subjects were tested with the insulin (0.15 U/kg) tolerance test (ITT) in basal conditions and in the presence of the M1- and M2-muscarinic antagonist atropine (600 micrograms iv just before insulin injection (time 0) plus 600 micrograms 20 min later in 6 subjects) or the M1-muscarinic receptor blocker pirenzepine (40 mg iv 10 min before ITT or 20 mg at time 0 plus 30 mg at time 20 in 6 subjects). The remaining 6 men were treated with the nicotinic receptor antagonist trimethaphan (0.3 mg/min x 30 min before ITT). ACTH rose 4.7 times in response to hypoglycaemia. The ACTH response to hypoglycaemia did not change after pirenzepine administration, whereas it was significantly increased by atropine and decreased by trimethaphan treatment. These data indicate that nicotinic and muscarinic (M2 but not M1) receptors participate in a different manner in the regulation of the hypoglycaemia-induced ACTH release.

Aislamiento e identificación de Madurella mycetomatis de un micetoma podal / Isolation and identification of Madurella mycetomatis from a foot mycetoma

Comunicamos el primer hallazgo en nuestro laboratorio de un micetoma podal producido por Madurella mycetomatis. La identificación de la cepa, se realizó a través de los siguientes caracteres: aspecto de los gránulos, macro y micromorfología en diversos medios de cultivo y capacidad de asimilación de hidratos de carbono. Se probó además la sensibilidad in vitro a distintos antigúngicos. Destacamos el buen resultado terapéutico obtenido con la medicación utilizada

Primer aislamiento de Trichophyton georgiae (Varsavsky et Ajello), a partir de suelos de corrales e aves en Argentina / First isolation of Trichophyton georgiae (Varsavsky et Ajello), from soils of fowl corrals in Argentine

Informamos el primer aislamiento de Trichophyton georgiae y su forma sexuada Arthroderma ciferii en nuestro país. Se realizaron observaciones morfológicas, pruebas bioquimicas e inoculaciones experimentales en cobayos. Destacamos el hallazgo de este hongo en suelos de corrales de aves que presentó una elevada capacidad saprofítica competitiva en sustratos con queratinas provenientes de plumas. Además no produjo las lesiones típicas de los dermatofitos patógenos en cobayos y fue incapaz de crecer a 31-C

O enfermeiro psiquiátrico na assistência ao doente mental / Psychiatric nurse in care of mental patient

Comentários sobre o papel do enfermeiro psiquiátrico especializado dentro da instituiçäo hospitalar e a importância da orientaçäo dinâmica ao pessoal de enfermagem que assiste ao doente mental.