bluuebunny/crossref_metadata_2025 huggingface dataset:
Benzodiazepine maintenance in opiate substitution treatment: Good or bad? A retrospective primary care case-note review
Authors: Bakker Adam , Streel Emmanuel
Published: January 2017

Background:

Co-prescribing benzodiazepines to patients in opiate substitution treatment is controversial and often alleged to increase mortality. In an inner-London general practice, patients with problematic benzodiazepine co-dependence were allowed benzodiazepine maintenance treatment (BMT) since 1994, providing an opportunity for analysis.

Method:

1) Case-note review of all 278 opiate substitution treatment patients, accruing 1289 patient treatment years; 46% had concurrent BMT. 2) National Health Service database search for patients who died after leaving accrued a further 883 years of information; only patients who left the UK were unaccounted for (4%). Three groups were studied: 1) never obtained benzodiazepine prescription (NOB): n=80); 2) briefly/occasionally prescribed benzodiazepines (BOP): n=71; 3) BMT: n=127.

Outcomes measured:

Treatment retention (months); deaths/100 patient treatment years; deaths after leaving the service/100 years of information.

Results:

Treatment retention: NOB: 34 months; BOP: 51 months; BMT: 72 months. In-treatment mortality: NOB: 1.79/100 patient treatment years; BOP: 0.33/100 patient treatment years; BMT: 1.31/100 patient treatment years. Deaths after leaving service: NOB: 2.24/100 years of information, BOP: 0.63/100 years of information. However, mortality for previously BMT-patients increased by 450% to 5.90/100 years of information.

Discussion:

BMT patients had longer treatment retention than NOB or BOP and lower mortality than NOB patients. It is unlikely that patients had access to prescribed benzodiazepines on leaving the service because of restrictions in the national guidelines but co-dependent patients are a high-risk group who may stand to gain most benefit from opiate substitution treatment if combined with benzodiazepine-maintenance.
Long-Term Tolerability Study of Voltaren
Authors: Miura T
Published: January 2017

Clinical and laboratory examinations were conducted in order to assess the long-term tolerability of Voltaren, a new anti-inflammatory and analgesic agent. Pre-treatment, repeated on-treatment and after-treatment investigations of haemoglobin, erythrocyte count, total and differential leucocyte count, platelet count, SGOT, SGPT, alkaline phosphatase, total serum proteins and urinary protein and sugar were conducted in 13 patients. The period of treatment with Voltaren was 110 to 559 days. In all these tests, there were no unwanted effects attributable to long-term treatment with Voltaren.

Our study would indicate that Voltaren is a safe drug which has no effect on the organs of haemopoiesis, nor on hepatic or renal function, even in long-term therapy. Therefore, Voltaren can be used as an anti-inflammatory and analgesic agent not only in short-term therapy but also in the long-term treatment of chronic diseases.
A Placebo Controlled Trial of Viloxazine with and without Tranquillizers in Depressive Illness
Authors: Magnus R V
Published: January 2017

Two double-blind four-way crossover studies are reported, comparing the antidepressant effect of 14-day courses of: viloxazine, viloxazine with a tranquillizer either perphenazine or diazepam or tranquillizer alone, against a placebo.

In one study the antidepressant effect of viloxazine at a dose of 150 mg daily was statistically greater than that of placebo, whilst in the second study viloxazine was statistically superior to diazepam (15 mg daily). In depressed patients with a clear anxiety component, viloxazine alone seemed preferable to a combination with a tranquillizer as such a combination did not produce an enhanced clinical effect and the incidence of side-effects was possibly increased. Viloxazine was generally well tolerated and side-effects, when they occurred, were generally a mild upper gastro-intestinal disturbance.
Percutaneous Absorption of Betamethasone-17, 21-Dipropionate and Salicylic Acid during the Treatment of Psoriasis and Eczema
Authors: Gip L , Hamfelt A
Published: January 2017

The percutaneous absorption of betamethasone-17, 21- dipropionate and salicylic acid was studied after one and two weeks' treatment of psoriasis and eczema. The treated areas varied between 8 and 41 dm2. No change in the plasma Cortisol levels was detectable by the routinely used laboratory method. The treatment gave no detectable salicylate concentrations in plasma.
Nefopam Hydrochloride*: New Analgesic Agent
Authors: Cohen Albert , Hernandez Carlos M
Published: January 2017

Two dose-levels of nefopam hydrochloride ( i.e. 30 mg and 60 mg) were compared with two dose-levels of aspirin ( i.e. 300 mg and 600 mg) and placebo in 125 male patients having pain associated with muscle disorders. Drugs were given as a single dose and pain intensity and side-effects monitored at thirty minutes and then hourly for four hours. Time-course action of the drugs revealed that aspirin 300 mg failed to achieve statistically significant analgesia at any post-treatment observation, whereas nefopam 60 mg was significantly better than placebo ( p < 0·05) at one and three hours in terms of pain intensity and at one hour in terms of pain intensity difference scores. Aspirin 600 mg was significantly different from placebo ( p < 0·05) at all hourly observations for both efficacy parameters, as was nefopam 30 mg ( p < 0·01). Summation of pain intensity difference scores showed aspirin 600 mg and nefopam 30 mg to be significantly different from placebo at the 0·025 and 0·005 levels respectively.
Amikacin in Gram-Negative Paediatric Infections
Authors: Trujillo Hugo , Manotas Rafael , Ramirez Jose Ivan , Uribe Alvaro , Agudelo Nancy , Zapata Carmen Tulia , Zuluaga Ana Isabel , de Vidal Esther Luisa
Published: January 2017

Amikacin was used in the treatment of various Gram-negative infections in sixty-six children ranging in age from two days to thirteen years. Over 72% of the infections treated were classified as severe and the remainder were moderate. Among infections in which the site of origin was the urinary or gastro-intestinal tract, amikacin achieved thirty-eight (95%) complete or partial cures in forty patients. In respiratory tract infections, amikacin completely or partially cured six (75%) out of eight patients. The remaining eighteen infections involved skin, soft tissue and other miscellaneous categories in which amikacin therapy resulted in seventeen (94%) complete or partial cures. Overall, amikacin achieved fifty-four complete cures and seven clinical or bacteriological cures in sixty-six patients, which represents an 82% complete cure rate and 10% partial cure rate for all the patients in the study.
Management of Constipation in Terminally Ill Patients
Authors: Crowther A G O
Published: January 2017

This small study was carried out to assess the effectiveness of lactulose syrup (Duphalac®) in the management of constipation in forty-six patients with terminal illnesses. The daily dose of lactulose was titrated to meet the individual patients requirements and was found to be in the region of 20 to 30 mls twice daily, despite the almost universal administration of opiates as analgesics.

The study lasted 21 days in each patient capable of completing the assessment.

Constipation was relieved within an average of 3 to 4 days, and of the 512 days observed, there were 203 days in which a bowel movement occurred. Of these motions 71% were recorded as easy to move, rather than hard (21%) or loose (8%). Faecal incontinence and nausea attributable to lactulose treatment were extremely rare. Therefore, lactulose appeared to be a useful treatment for constipation in the terminally ill patient.
Cimetidine in the Treatment of Duodenal Ulcer: Double-Blind Study
Authors: Villalobos J J , Elizondo J , Guevara L , Centeno F
Published: January 2017

To determine the efficacy and safety of cimetidine in the treatment of duodenal ulcer, forty-five patients with this diagnosis were selected for a double-blind study. Diagnosis was confirmed by endoscopy and photography of the lesion. Cimetidine in the form of 200 mg tablets was administered to twenty-four patients at the rate of 1 tablet t.i.d.p.c. and 2 tablets h.s. The same dosage of an identically appearing placebo tablet was given to twenty-one patients. The only other medication permitted was an aluminum + magnesium gel antacid p.r.n. Patients and medication were randomized, the same patients being seen by the same physician throughout the six-week observation period.

Laboratory monitoring of patients (complete blood counts, blood chemistry, urinalysis, gastric acidity) took place at one, two, four and six weeks as did clinical observation.

Three placebo patients withdrew from the study.

The patients on cimetidine showed a statistically significant greater number of healed ulcers, early and late in the treatment; earlier and more persistent pain relief in a greater number; and considerably fewer requiring antacid than those patients on placebo.

No side-effects were noted.
A Comparison of the Hypnotic Activity of Loprazolam, Temazepam and Placebo in General Practice
Authors: Gringras M , Beaumont G , Ankier S I
Published: January 2017

One hundred and ninety-seven patients exhibiting a disturbed sleep pattern were recruited by thirty-five general practitioners into this single-blind randomized parallel group multicentre study. There were twelve patient withdrawals or drop-outs leaving sixty-one, sixty-three and sixty-one patients who, following 2 nights on placebo as baseline, completed 5 consecutive nights of treatment on loprazolam (1 mg), temazepam (20 mg) and placebo, respectively.

Loprazolam and temazepam were found to have similar hypnotic activity with both treatments being superior to placebo. There was no statistical difference in the side-effect profile of the three treatment groups.
The Comparative Efficacy of Naproxen Sodium and Pirprofen in the Treatment of Post-Operative Pain
Authors: Baumgartner H. , Kuttelwascher M. , McCaskey D. , Winters L.
Published: January 2017

A randomized, single-blind, parallel study involving 100 adults was performed to compare the efficacy and safety of naproxen sodium with that of pirprofen in the treatment of moderate to severe pain after orthopaedic surgery. Fifty patients received 550 mg of naproxen sodium initially and 275 mg every 6 h thereafter, and 50 received 400 mg of pirprofen every 8 h until either their pain was completely relieved or the 3-day trial ended. Patients who required additional analgesia were given 500 mg of paracetamol 2 h after administration of the test medication. Both medications significantly relieved post-operative pain, and there were no statistically significant differences in efficacy between the groups. Six patients receiving naproxen sodium and two patients receiving pirprofen withdrew from the study because of lack of efficacy. Thirteen patients receiving naproxen sodium recorded 17 adverse events and 13 patients receiving pirprofen recorded 20 adverse events, again with no statistically significant differences between groups. Six patients in each group withdrew from the study because of these adverse events. Naproxen sodium and pirprofen were equally safe and effective in relieving post-operative pain following musculoskeletal surgery.
Adjuvant PSK Immunotherapy in Patients with Carcinoma of the Nasopharynx
Authors: Go P. , Chung C.-H.
Published: January 2017

A controlled study using adjuvant PSK immunotherapy in patients with nasopharyngeal carcinoma was initiated with the aim of improving survival by enhancing the host immune system against tumour cells. A total of 38 patients were randomly selected, all of whom had previously received radiotherapy with or without chemotherapy. Eight patients in the PSK immunotherapy group ( n=21) developed local recurrence, three of whom later died due to distant metastasis. In the control group ( n=17) three patients developed local recurrence while six patients developed distant metastasis. All of these six patients later died due to disease progression. It seems that PSK exerts its antitumour effect systemically; the risk of distant metastasis occurring is decreased, but it is apparently ineffective in improving local disease control. The estimated median survival time of the PSK-treated group compared with the control was significantly increased (35 months versus 25 months, P=0.043). The 5-year survival rate was also significantly better in the PSK immunotherapy group (28% versus 15%, P=0.043). It is concluded that PSK deserves careful consideration as an important immunotherapeutic agent in the management of nasopharyngeal carcinoma.
A 1-Year Follow-Up Study on the Effect of Atenolol on Serum β2-Microglobulin Level in Hypertensive Diabetic Patients
Authors: Koh H. , Waki M. , Nambu S.
Published: January 2017

Hypertensive diabetic patients are particularly prone to renal function impairment. A total of nine out-patients with diabetes and hypertension were, therefore, entered into this single-blind uncontrolled study on the effects of 50 mg/day atenolol on reducing blood pressure and preserving normal kidney functioning. Treatment and evaluations were continued for 12 months. Serum β2-microglobulin concentration was used as the index for measuring renal impairment. Atenolol significantly reduced heart rate, systolic and diastolic blood pressure, and serum β2-microglobulin concentrations compared with baseline. Plasma glucose and glycosylated haemoglobin levels were unchanged, and blood urea nitrogen levels were increased slightly (non-significant). Serum creatinine showed a tendency (non-significant) to reflect the changes in β2-microglobulin concentration. Ways in which atenolol may act to improve kidney functioning are suggested. It is concluded that atenolol is a favourable choice for the treatment of hypertension in diabetic patients with normally functioning kidneys since, even in long-term use, normal renal functioning is preserved.
The Use of a Hand-Held Computer to Record Clinical Trial Data in General Practice: A Pilot Study
Authors: Tattersall A. B. , Ellis R.
Published: January 2017

A system has been developed to collect and process clinical trial data in general practice using a hand-held computer in the patient's presence. It was based on a Psion Organiser II (model XP) computer using software produced for the trial. The major advantages are: (a) avoidance of protocol violations and other incorrect data entries; and (b) saving of time for investigators and company personnel. The present coding of symptoms was found to be the only major drawback, but this problem could be remedied for future studies.
A Comparison of Itraconazole and Griseofulvin in the Treatment of Tinea Corporis and Tinea Cruris: A Double-Blindb Study
Authors: Panagiotidou D , Kousidou T , Chaidemenos G , Karakatsanis G , Kalogeropoulou A , Teknetzis A , Chatzopoulou E , Michailidis D
Published: January 2017

A total of 40 patients with clinically and mycologically documented tinea corporis or tinea cruris were treated with 100 mg/day itraconazole ( n = 19) or 500 mg/day griseofulvin ( n = 21) for 15 days. Of the itraconazole-treated patients, 83.3% were healed or markedly improved, i.e. ‘responders', after 15 days compared with 85.7% of griseofulvin-treated patients. At 15 days after the end of treatment, 88.2% of itraconazole- and 80.9% of griseofulvin-treated patients were classed as ‘responders'. The mycological cure rate (both microscopy and culture negative) was generally lower than the clinical response rate. Both treatments were equally effective at the end of 15 days' treatment with 66.7% of patients cured, but itraconazole was superior to griseofulvin at the 15-day follow-up visit (77.8% of itraconazole-treated patients compared with 66.7% of griseofulvin-treated patients were cured). Both therapies were well tolerated; only one patient treated with itraconazole reported minor side-effects (dizziness, headache and gastro-intestinal disturbances). The results confirm those of earlier comparative trials and suggest that griseofulvin-treated patients are more at risk of relapse than are itraconazole-treated patients.
Effects of Bifemelane Hydrochloride on Atherosclerosis in Aged Rats Fed Low-Calcium Diets
Authors: Yasui M , Ota K , Oshima A
Published: January 2017

The preventative effects of bifemelane (4-( o-benzylphenoxy)- N-methylbutylamine hydrochloride) on atherosclerosis in aged rats fed low-calcium diets were investigated. Male 18-month-old Wistar rats were maintained for 90 days on the following: (A) standard diet ( n = 7), (B) low calcium, low magnesium, high aluminium diet ( n = 8), (C) standard diet plus oral intubation with 10 mg bifemelane/kg daily ( n = 6), (D) low calcium and magnesium, high aluminium diet plus oral intubation with 10 mg bifemelane/kg daily ( n = 6). All groups were give these diets and water ad lib for 90 days, after which blood samples were taken from the abdominal aorta and samples of aorta were examined for atherosclerotic changes. The serum concentrations of the following were determined: calcium, magnesium, zinc, aluminium, inorganic phosphorus, cholesterol, glutamate–oxaloacetate transaminase, glutamate–pyruvate transaminase, lactate dehydrogenase, cholinesterase, creatine phosphokinase, blood urea nitrogen and N-terminal parathyroid hormone. The only significant differences between the groups in serum chemistry were reduced concentrations of cholinesterase and magnesium in groups B and D, increased aluminium in group B, and increased N-terminal parathyroid hormone in groups B and D. In groups C and D the atherosclerosis was much improved compared with that in groups A and B. It appears that bifemelane largely prevents atherosclerosis caused by calcium deposition in the arteries of rats fed low-calcium diets, due to its effect in maintaining magnesium and calcium in bones.
Chondroid Syringoma of the Scrotum
Authors: Poku J W , Sant G R , Ucci A A
Published: January 2017

A 65-year-old man presented with a 3.5 cm scrotal mass. Ultrasound showed a solid mass of indeterminate aetiology within the skin. Excisional biopsy revealed a benign chondroid syringoma. This is the first report of chondroid syringoma involving the scrotum.
Lack of a platform
Authors: Williams Nigel
Published: January 2017

It is the lack of a space where people can speak for themselves that constitutes ‘censorship’ in British society.
Raw Meat
Authors: Pomerantsev Igor
Published: January 2017

Poets should be poets, not prophets
‘Guiding’ the Press
Authors: Mal
Published: January 2017

South Korean authorities tell editors what to publish, how to present it, and what to suppress
Happy Easter
Authors: Vaculík Ludvík
Published: January 2017

‘Although there are no guarantees, the atmosphere has, nevertheless, improved. The jazzmen got less than we expected … I write what I please, and, with the exception of Radio Free Europe, nobody censors what I write. It's more than half a year now since I was last invited to a threat session …’
The Uses of Glasnost
Authors: Kustarev Aleksandr
Published: January 2017

What social factors lie behind the drive for a more open Soviet society?
Reflections on an invalid fatwa
Authors: Taheri Amir
Published: January 2017

Last year, when Ayatollah Khomeini issued his death fatwa against Salman Rushdie, Taheri was one of the many Muslim students of international politics who tried to predict the future course of the drama unleashed and to imagine a possible denouement. Now he looks back on the year
Emblems of failure
Authors: Rieff David
Published: January 2017

Its failure in former Yugoslavia illustrates only too clearly that the UN is out of tune with the world it inhabits. Chances that the rulers will change to fit the reality are, however, slim
Time to do business
Authors: Pope Nicole
Published: January 2017

A controversial new report on Turkey's Kurds has forced the debate on the Kurdish situation into the open
Notes from prison
Authors: Maryniak Irena
Published: January 2017

When they visited me in prison they would always emphasise that the case was in their hands, that the judges, the prosecution, the whole system was subordinate to them. Nobody can live on a salary, they said. This is the free market. Everyone has to find other means to survive: bribes, business interests, protection rackets… They were pretty convincing about their unlimited power. When I asked them about the practicalities of controlling the judiciary, the two FSS men rocked with laughter. First you have to ‘work’ on them, they volunteered cheerfully, catch them out when they're not on the level. Then you take them aside and paint their future in the darkest possible terms — if they're exposed. By then they'll be sweating and ready to do anything to ensure that the FSS preserve their reputation. Then you sweeten them up. After that they'll be only too keen to show their gratitude. They'll be under threat of compromise for life.

It had taken me a long time to understand why the two FSS men had kept so ‘sweetly’ persuading me to give them information about drug-taking among children of politicians, financiers, and the artistic elite. They laughed, as ever. ‘It's dynamite,’ they said. ‘You can get anyone by the throat if you threaten to compromise their children. After all,’ they said, amazed at my inability to understand these elementary things, ‘the elections are coming.’
Keeping rights relevant
Authors: Galang Rosalinda
Published: January 2017

Human rights workers in the Philippines have been forced to adapt their methods to a changing world
The murderers in our midst
Authors: Maja-Pearce Adewale
Published: January 2017

‘I have devoted all my intellectual and material resources — my very life — to a cause in which I have total belief, and from which I cannot be blackmailed or intimidated.’

Ken Saro-Wiwa, 1941-1995
Minsk, Pinsk and other places
Authors: Feldman Anna
Published: January 2017

‘The Jews who live here, in their new homeland, have taken over more from the Belarusians than the Belarusians have taken from them. The mighty force of the Belarusian land has given a special spiritual and physical appearance to the Belarusian Jews. Now they differ from all other Jews, and throughout the whole world they are called “Litvaks”.’ The Jews of Belarusia Zmitrok Biadula (Minsk 1918)
Freedom of oppression
Authors: Bely Alexander
Published: January 2017

With its papers banned and no access to state-owned TV and radio, the opposition has no way of getting its message across
VAST HELL
Authors: Martínez Guillermo
Published: January 2017

Guillermo Martínez was born in Bahía Blanca, in the province of Buenos Aires, Argentina, in 1962, four years before General Onganía came into power. In 1982 he was awarded the first prize in the National Short Story Competition ‘Roberto Arlt’ for his book La jungla sin bestias (The Beastless Jungle); six years later he received the first prize from the Fondo Nacional de las Artes for his second collection of short stories, Infierno Grande (Vast Hell). His first novel, Acerca de Rodorer (Concerning Rodorer) was published in 1992.

Martínez belongs to the generation of writers who grew up in the midst of the Argentina of the ‘dirty war’ between the military dictatorship and the guerrilla, a war that left the country shattered and from which Argentina has not recovered in spite of the present government's attempts to erase all memory of those past atrocities. The war did violence to everyone and everything, including the Argentine language. The writers of Martínez's generation were forced to reconstruct a tongue destroyed by the abuse of power, by irrational violence, by forced stupidity which infected words like a virus infects the blood. Their task was not only to bear witness and to build imaginary landscapes for their chronicles which are not, it must be said, mere documentaries. First they had to rescue the words themselves from debasement, using a pared-down, clear-cut language, free from the rhetoric, far-fetched metaphor and bombast so dear to the military heart.
Remade in Hong Kong
Authors: Siu Helen
Published: January 2017

When China tells Hong Kong to ‘Keep on dancing, keep on horse racing’, locals ask to what extent ‘the people of Hong Kong’ can choose to dance to their own tunes?
Talking about race quietly
Authors: Lacey Nicola , Williams Patricia
Published: January 2017

Patricia J Williams, American law professor and this year's BBC Reith lecturer, returns race to the centre of everyday discourse — and meets the media en route
On the line
Authors: Harsono Andreas
Published: January 2017

Government control over the media is absolute and unyielding — and woe betide those who overstep the mark
Whatever happened to Soviet childhood?
Authors: Maryniak Irena
Published: January 2017

The state of Russia's children provides a metaphor for the collapse of the Communist dream
Eros and innocence
Authors: Lucie-Smith Edward
Published: January 2017

Images of childhood in western art reflect society's changing attitudes to children. While the erotic force of past masters is beyond reproach or banishment, the intrusion of the camera provokes outrage and censoriousness
Covert
Authors: le Carré John
Published: January 2017

I went to Marseille… I prowled the streets all day, feeling very strung up and ready to pounce, determined to ‘trap’ life - to preserve life in the act of living. Above all, I craved to seize the whole essence, in the confines of one single photograph, of some situation that was in the process of unrolling itself before my eyes.
Death of the photographer
Authors: Griffiths Philip Jones
Published: January 2017

Men still kill one another, they have not yet understood how they live, why they live: politicians fail to observe that the earth is an entity, yet television has been invented. Tomorrow we shall be able to look into the heart of our fellow-man, be everywhere and yet be alone… The unambiguousness of the real, the truth in the everyday situation is there for all classes.
Using participatory and mixed-methods approaches in GIS to develop a Place-Based Food Insecurity and Vulnerability Index
Authors: Meenar Mahbubur R
Published: January 2017

This paper discusses the development of a Place-Based Food Insecurity and Vulnerability Index (PFIVI), which incorporates six indicators and 30 variables. It also presents an application of this Index within the context of Philadelphia, a postindustrial U.S. city. The paper argues that in order to thoroughly measure a multidimensional socioeconomic problem that is tied to the built environment (e.g., food insecurity and vulnerability), the use of participatory and mixed-methods approaches in GIS (e.g., participatory GIS or PGIS) may produce more comprehensive results compared to other commonly used methods. This paper makes an intervention in the food environment literature, which tends to analyze food access in a narrow way, by applying a methodology conceptually grounded in community food security and operationalized through a PGIS project. It also contributes to still-evolving PGIS methodologies by directly engaging stakeholders in a complicated GIS-based analytical process.
Redeeming the Chinese modernity? Zen Buddhism, culture-led development and local governance in Xinxing County, China
Authors: Qian Junxi
Published: January 2017

This article explores culture-led urban development in Xinxing County, Guangdong Province. Arguing for the relevance of cultural governance to the study of culture-led development in China, it heeds to the specific cultural knowledge and discourses that frame policy, and thinks critically on the creation of a unitary, all-encompassing idea of culture, which many culture-led development projects fall prey to. Empirically, this article presents a study of the Ecological Tourism Industrial Park of the Sixth Patriarch’s Hometown, a high-end leisure and recreation complex. It first sketches the ways in which Zen is re-packaged as a redeeming force that cures the alienating effects of modernisation. It moves to an analysis of the production of culturally encoded consumption spaces envisioned by the Plan of the Ecological Tourism Industrial Park of the Sixth Patriarch’s Hometown. Finally, this article reflects on how the Ecological Tourism Industrial Park of the Sixth Patriarch’s Hometown imposes a dominant, unitary conception of local culture, excluding pre-established practices and routines that connect local people and Zen in lived and habitual ways, yet are devalued by the notion of Zen as high-end symbolic goods.
Usefulness of 13C-Urea Breath Test in the Diagnosis of Gastric Helicobacter Pylori Infection
Authors: D'Elios M.M. , Amedei A. , Benagiano M. , Azzurri A. , Del Prete G.
Published: January 2017

Helicobacter pylori chronically infects half of the human population and is associated with gastritis, peptic ulcer and gastric cancer. 13C-urea breath test (UBT) is the main in vivo tool for the diagnosis of H. pylori infection. In this study, the safety and the accuracy of UBT were evaluated.

A group of 492 dyspeptic patients was studied by UBT, the results were expressed as the difference over baseline at 30 min (DOB30). All patients were evaluated for systemic, gastrointestinal or allergic-type adverse reactions after ingestion of 75 mg 13C-urea and citric acid in aqueous solution. The first 256 patients enrolled also underwent endoscopy and gastric biopsy. Patients positive on histology were considered infected.

UBT was well tolerated and none of the 492 patients had any systemic or allergic-type adverse reaction. Among the 256 patients studied with histology, 116 were H. pylori positive on biopsies. Using 4% o as cut-off value for DOB30, 115 out of the 256 patients were positive on UBT, with only 2 false positive and 3 false negative. With this threshold, the sensitivity, specificity, and accuracy of the UBT were 97.4%, 98.5%, and 98.0%, respectively.

13C-UBT has proven to be a safe and simple, yet accurate, test for the non-invasive diagnosis and monitoring of H. pylori infection.
Hierarchy of Baby-Linked Immunogenetic Risk Factors in the Vertical Transmission of Hepatitis C Virus
Authors: Martinetti M. , Pacati I. , Cuccia M. , Badulli C. , Pasi A. , Salvaneschi L. , Minola E. , De Silvestri A. , Iannone A.M. , Maccabruni A.
Published: January 2017

Mother-to-infant transmission of Hepatitis C Virus (HCV) represents the major cause of pediatric HCV infection today. Immunogenetic influence has been poorly investigated and mainly confined to HLA-class II serological polymorphisms. Among 290 parities, 135 from Pavia and 155 from Bergamo, of HCV-RNA-infected Italian women, 21 babies (7.24%) were HCV-RNA positive at birth and steadily positive over 20 months of life. All the 21 infected babies and 44 randomly selected uninfected ones, born to HCV-RNA+ mothers but steadily negative for HCV-RNA during a follow-up of 2 years, and their mothers were investigated for HLA-G, -C, -DRB1, -DQA1 and -DQB1 genomic polymorphisms. Among the different covariates, HLA-Cw*07, -G*010401, -DRB1*0701, -DRB1*1401 and homozigosity for HLA-G 14bp deletion can be considered as risk factors for HCV vertical transmission. On the contrary, protection was conferred by the HLA-DQB1*06, -G*0105N, -Cw*0602, DRB1*1104 and -DRB1*1302 alleles. Our initial question was: has the immunogenetic profile any role in the protection of the fetus growing in an infected milieu and, if so, is it independent from the other non-immunogenetic parameters? The answer to both questions should be yes.
Clopidogrel-Associated Acute Migratory Arthritis following Kidney-Pancreas Transplantation
Authors: Muthusamy A.S.R. , Vaidya A. , Friend P.J.
Published: January 2017

Clopidogrel is a potent inhibitor of platelet aggregation and has been used as an alternative, or as an adjunct to aspirin in reducing the risk of thrombosis. A 34-year-old uremic type 1 male diabetic patient who underwent simultaneous kidney-pancreas transplantation was given clopidogrel as he was allergic to aspirin. He developed polyarthralgia one week later, followed in a few days by symmetrical migratory polyarthritis, which resolved completely on withdrawing the drug. The implications to clinical management in a transplant setting are discussed.
Activation of P2X7 Receptors Stimulates the Expression of P2Y2 Receptor mRNA in Astrocytes Cultured from Rat Brain
Authors: D'Alimonte I. , Ciccarelli R. , Diiorio P. , Nargi E. , Buccella S. , Giuliani P. , Rathbone M.P. , Jiang S. , Caciagli F. , Ballerini P.
Published: January 2017

Under pathological conditions brain cells release ATP at concentrations reported to activate P2X7 ionotropic receptor subtypes expressed in both neuronal and glial cells. In the present study we report that the most potent P2X7 receptor agonist BzATP stimulates the expression of the metabotropic ATP receptor P2Y2 in cultured rat brain astrocytes. In other cell types several kinds of stimulation, including stress or injury, induce P2Y2 expression that, in turn, is involved in different cell reactions. Similarly, it has recently been found that in astrocytes and astrocytoma cells P2Y2 sites can trigger neuroprotective pathways through the activation of several mechanisms, including the induction of genes for antiapoptotic factors, neurotrophins, growth factors and neuropeptides. Here we present evidence that P2Y2 mRNA expression in cultured astrocytes peaks 6 h after BzATP exposure and returns to basal levels after 24 h. This effect was mimicked by high ATP concentrations (1 mM) and was abolished by P2X7-antagonists oATP and BBG. The BzATP-evoked P2Y2 receptor up-regulation in cultured astrocytes was coupled to an increased UTP-mediated intracellular calcium response. This effect was inhibited by oATP and BBG and by P2Y2siRNA, thus supporting evidence of increased P2Y2 activity. To further investigate the mechanisms by which P2X7 receptors mediated the P2Y2 mRNA up-regulation, the cells were pre-treated with the chelating agent EGTA, or with inhibitors of mitogen-activated kinase (MAPK) (PD98059) or protein kinase C, (GF109203X). Each inhibitor significantly reduced the extent to which BzATP induced P2Y2 mRNA. Both BzATP and ATP (1 mM) increased ERK1/2 activation. P2X7-induced ERK1/2 phosphorylation was unaffected by pre-treatment of astrocytes with EGTA whereas it was inhibited by GF109203X. Phorbol-12-myristate-13-acetate (PMA), an activator of PKCs, rapidly increased ERK1/2 activation. We conclude that activation of P2X7 receptors in astrocytes enhances P2Y2 mRNA expression by a mechanism involving both calcium influx and PKC/MAPK signalling pathways.
Escherichia Coli Specific Secretory IgA and Cytokines in Human Milk from Mothers of Different Ethnic Groups Resident in Northern Italy
Authors: Ciardelli L. , Garofoli F. , Avanzini M.A. , De Silvestri A. , Gasparoni A. , Sabatino G. , Stronati M.
Published: January 2017

Breast milk supplies many bioactive components. Neonates protection from pathogenic bacteria is mainly attributable to secretory IgA antibodies present in human milk in an amount depending on previous antigenic exposure. To bring new details into the field of immunological memory in secretory immunity, we evaluated the production of s-IgA specific for E. coli (E. coli s-IgA), and of proinflammatory (IL-6 and IL-8) or anti-inflammatory (IL-10) cytokines in the milk of mothers of different ethnic groups exposed in the past to poor conditions, but nowadays living in Italy in adequate conditions. Mothers from Italy, Africa, Asia and Eastern European Countries were included in the study. Anti- E. coli s-IgA, IL-6, IL-8 and IL-10 were determined by ELISA. Breast milk of all the foreign mothers presented higher levels of E. coli s-IgA than Italians, and for Asian and African mothers were significative (p=0.031 and p=0.015, respectively). Milk from women of Eastern European Countries revealed the highest IL-8 levels (p=0.026), while milk from Asian women presented the greatest concentration of IL-6 (p=0.04); however, the Africans reported the lowest concentrations of IL-10 (p=0.045). Since all the mothers had been living in Italy for some time, we believe that the presence of high levels of E. coli s-IgA, supported by high levels of pro-inflammatory cytokine, is part of a persisting immunological secretory memory.
N-Acetylcysteine Synergizes with Oseltamivir in Protecting Mice from Lethal Influenza Infection
Authors: Garozzo A. , Tempera G. , Ungheri D. , Timpanaro R. , Castro A.
Published: January 2017

Many studies have shown that oxidative stress is important in the pathogenesis of pulmonary damage during influenza virus infections. Antioxidant molecules are therefore potentially useful against viral infection. Our previous studies show that N-acetylcysteine (NAC) has a protective effect in a model of lethal influenza infection in mice. NAC administration significantly decreased the mortality in infected mice. Further studies have demonstrated that NAC enhanced survival in combination with the antiviral agent ribavirin. In the present study, we report the effect of combined treatment with NAC and Oseltamivir, clinically used in the treatment and prevention of influenza virus infection, in a murine model of lethal influenza infection. NAC was given as a single daily dose of 1000 mg/Kg starting from 4 h before infection and until day 4 after infection; Oseltamivir was given twice daily at dose of 1 mg/Kg/die for 5 days, starting from 4 h before infection. End-point evaluation was 21-days' survival. NAC alone was slightly effective (20%), since a suboptimal treatment was used. Survival increased to 60% with Oseltamivir and to 100% with Oseltamivir and NAC used in combination. Since NAC alone does not show any antiviral action, the present findings suggest that antioxidant therapy increase survival by an improvement in host defense mechanisms, and/or by a direct antioxidant effect against oxidative stress associated with viral infection. Our studies demonstrate the effectiveness of combining agents acting through different mechanisms, such as antiviral drugs oseltamivir and the antioxidant NAC, indicating a possible advantage of combining the two treatments.
A Complete Response with Rituximab in Metastatic Diffuse Large B-Cell Lymphoma of the Testis: Case Report
Authors: Autorino R. , Lamendola M.G. , Sio De M. , Di Trolio R.A. , Ferraraccio F. , Di Lorenzo G.
Published: January 2017

Primary testicular lymphoma is an uncommon testicular tumour. We present a case of a primary non-Hodgkin lymphoma of the testis, describing its clinical and pathological features and discussing our treatment strategy. A 68-year-old man showed a firm erythematous testicular mass within the right emiscrotum. Subsequent ultrasonography demonstrated a right inferior pole testicular mass with disomogenously hypoecogenic. The patient was submitted to inguinal orchidectomy. Light microscopy demonstrated the classic appearance of a diffuse large B-cell lymphoma. The immunohistochemical study showed tumour cells intensively positive for CD45, Ki67 and CD20. No evidence of extra-testicular involvement by lymphoma was found. At 6 months, a TC-PET showed a clinical relapse in lung and abdominal lymphonodes, while clinical examination demonstrated a single, indolent and erythematous nodule in the left foot. The histologic analysis confirmed diagnosis of CD-20 positive B-cell lymphoma. The patient was treated with an anti-CD 20 monoclonal antibody (rituximab) alone every 3 weeks. After 3 months a complete response was observed in all sites of disease. The patient was free from disease at 12 months follow-up.
Pulmonary Exposure to Carbon Black Nanoparticles Increases the Number of Antigen-Presenting Cells in Murine Lung
Authors: Koike E. , Takano H. , Inoue K.-I. , Yanagisawa R. , Sakurai M. , Aoyagi H. , Shinohara R. , Kobayashi T.
Published: January 2017

Particulate matters can enhance antigen-related airway inflammation and immunoglobulin production. The present study was designed to determine the effects of different sizes of nanoparticles on the antigen-presenting cells (APC) in the lung. ICR mice were exposed to vehicle, carbon black (CB) nanoparticles (14 nm or 56 nm), ovalbumin (OVA), or OVA+nanoparticles intratracheally. The expression of major histocompatibility complex (MHC) class II, costimulatory molecules (CD80, CD86, CD11c), and DEC205 (dendritic cell marker), F4/80 (macrophage marker), and CD19 (B-cell marker) in the lung cells was measured by flow cytometry. 14 nm nanoparticles, but not 56 nm nanoparticles, increased the number of the total lung cells. Combination of OVA and 14 nm or 56 nm nanoparticles increased the total lung cells. The expression of MHC class II and/or costimulatory molecules and the number of APC in the lung were increased by 14 nm nanoparticles in the presence or absence of OVA. The increases were more prominent with combination of OVA and 14 nm nanoparticles. 56 nm nanoparticles did not show any significant effects. 14 nm CB nanoparticles can increase the expression of MHC class II and costimulatory molecules and the number of APC in the lung, especially in the presence of antigen, which can result in subsequent antigen-related airway inflammation and immunoglobulin production.
Increase of Skin-Ceramide Levels in Aged Subjects following a Short-Term Topical Application of Bacterial Sphingomyelinase from Streptococcus Thermophilus
Authors: Dimarzio L. , Cinque B. , Cupelli F. , De Simone C. , Cifone M.G. , Giuliani M.
Published: January 2017

Several studies have demonstrated that ceramides play an essential role in both the barrier and water-holding functions of healthy stratum corneum, suggesting that the dysfunction of the stratum corneum associated with ageing as well that observed in patients with several skin diseases could result from a ceramide deficiency. In a previous study our group reported a significant increase in skin ceramide levels in healthy subjects after treatment in vivo with a cream containing a preparation of Streptococcus thermophilus. The presence of high levels of neutral sphingomyelinase activity in this organism was responsible for the observed increase of stratum corneum ceramide levels, thus leading to an improvement in barrier function and maintenance of stratum corneum flexibility. The aim of the present work is to investigate the effects of the topical treatment of a Streptococcus thermophilus-containing cream on ceramide levels of stratum corneum of healthy elderly women. The ceramide levels, transepidermal water loss and capacitance were evaluated on stratum corneum sheets from the forearms of 20 healthy female subjects treated with a base cream or the same cream containing a sonicated preparation of the lactic acid bacterium Streptococcus thermophilus. A 2-week topical application of a sonicated Streptococcus thermophilus preparation led to significant and relevant increase of stratum corneum ceramide levels. Moreover, the hydration values of the treated forearm of each subject was significantly higher than control sites. These results suggest that the experimental cream was able to improve the lipid barrier and to increase a resistance against ageing-associated xerosis.
Size Effects of Nanomaterials on Lung Inflammation and Coagulatory Disturbance
Authors: Inoue K. , Takano H. , Ohnuki M. , Yanagisawa R. , Sakurai M. , Shimada A. , Mizushima K. , Yoshikawa T.
Published: January 2017

Effects of nano-sized materials (nanomaterials) on subjects with predisposing inflammatory disorders have not been well elucidated. This study examined the effects of pulmonary exposure to TiO2 nanomaterials on lung inflammation induced by lipopolysaccharide (LPS) and consequent systemic inflammation with coagulatory disturbance in mice, in particular regarding their size-dependency. Also, gene expression pattern in the lung was compared among the experimental groups using cDNA microarray analysis. ICR male mice were divided into 8 experimental groups that intratracheally received vehicle, three sizes (15, 50, 100 nm) of TiO2 nanomaterials (8 mg/kg), LPS (2.5 mg/kg), or LPS plus nanomaterials. Twenty four h after the treatment, these nanomaterials exacerbated the lung inflammation and vascular permeability elicited by LPS, with an overall trend of amplified lung expressions of cytokines such as interleukin (IL)-1β, macrophage chemoattractant protein (MCP)-1, and keratinocyte chemoattractant (KC). LPS plus nanomaterials, especially of a size less than 50 nm, elevated circulatory levels of fibrinogen, IL-1β, MCP-1, and KC, and von Willebrand factor as compared with LPS alone. The enhancement tended overall to be greater with the smaller nanomaterials than with the larger ones. cDNA microarray analyses revealed that there was no difference in gene expression pattern between the LPS group and the LPS + nanomaterial. These results suggest that nanomaterials exacerbate lung inflammation related to LPS with systemic inflammation and coagulatory disturbance, and that the exacerbation is more prominent with smaller nanomaterials than with larger ones.
Differential Modulation of IgE-Dependent Activation of Human Basophils by Ambroxol and Related Secretolytic Analogues
Authors: Gibbs B.F.
Published: January 2017

Ambroxol is a widely used secretolytic agent originally developed from vasicine, a natural alkaloid found in Adhatoda vasica, extracts of which have been used to treat bronchitis, asthma, and rheumatism. We previously reported that ambroxol inhibits IgE-dependent mediator secretion from human mast cells and basophils, key effector cells of allergic inflammation. Here, the mechanisms involved in the inhibitory properties of ambroxol were assessed in comparison to other secretolytic analogues (e.g. vasicine, bromhexine, sputolysin). The results show that, in comparison to ambroxol, which reduced IgE-dependent histamine release from basophils at 10 μM-1 mM, the release of the amine was only moderately reduced by sputolysin and vasicine at 1 mM. In contrast, above 10 μM, bromhexine was found to be toxic to basophils in vitro as evidenced by induction of histamine release and reduced cell viability. In contrast, the inhibitory actions of ambroxol at concentrations below 1 mM were not toxic and entirely reversible. Ambroxol was also more potent than either sputolysin or vasicine in attenuating basophil IL-4 and IL-13 secretions, whereas bromhexine-induced suppression of de novo cytokine synthesis was due to toxic effects. Additionally, ambroxol reduced IgE-dependent p38 MAPK phosphorylation in basophils, unlike bromhexine, sputolysin and vasicine. These results clearly show that ambroxol is both more potent and effective at inhibiting IgE-dependent basophil mediator release and p38 MAPK activity than the other secretolytic analogues employed. The therapeutic potential of ambroxol as an anti-allergic agent is further underlined by these data.