Phenylketonuric diet negatively impacts on butyrate production.

BACKGROUND AND AIMS: Phenylalanine (Phe) restricted diet, combined with Phe-free l-amino acid supplementation, is the mainstay of treatment for phenylketonuria (PKU). Being the diet a key factor modulating gut microbiota composition, the aim of the present paper was to compare dietary intakes, gut microbiota biodiversity and short chain fatty acids (SCFAs) production in children with PKU, on low-Phe diet, and in children with mild hyperphenylalaninemia (MHP), on unrestricted diet. METHODS AND RESULTS: We enrolled 21 PKU and 21 MHP children matched for gender, age and body mass index z-score. Dietary intakes, including glycemic index (GI) and glycemic load (GL), and fecal microbiota analyses, by means of denaturing gradient gel electrophoresis (DGGE) and Real-time PCR were assessed. Fecal SCFAs were quantified by gas chromatographic analysis. RESULTS: We observed an increased carbohydrate (% of total energy), fiber and vegetables intakes (g/day) in PKU compared with MHP children (p = 0.047), as well a higher daily GI and GL (maximum p < 0.001). Compared with MHP, PKU showed a lower degree of microbial diversity and a decrease in fecal butyrate content (p = 0.02). Accordingly, two of the most abundant butyrate-producing genera, Faecalibacterium spp. and Roseburia spp., were found significantly depleted in PKU children (p = 0.02 and p = 0.03, respectively). CONCLUSION: The low-Phe diet, characterized by a higher carbohydrate intake, increases GI and GL, resulting in a different quality of substrates for microbial fermentation. Further analyses, thoroughly evaluating microbial species altered by PKU diet are needed to better investigate gut microbiota in PKU children and to eventually pave the way for pre/probiotic supplementations.

Efficacy of non-invasive mechanical ventilation in the general ward in patients with chronic obstructive pulmonary disease admitted for hypercapnic acute respiratory failure and pH < 7.35: a feasibility pilot study.

AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.

Reliability and validity of the Italian version of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V).

OBJECTIVES: To evaluate the reliability and validity of the Italian version of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V). PATIENTS AND METHODS: Eighty dysphonic patients and 120 asymptomatic subjects were enrolled. The voice signal of each participant was recorded, listened to and rated by 3 licensed speech-language pathologists using the GRBAS scale and the Italian version of the CAPE-V. The intra- and interrater reliability of the CAPE-V was assessed as well as the degree of association between the CAPE-V and GRBAS judgments. The CAPE-V values were also compared between the patients with dysphonia and the asymptomatic subjects. RESULTS: The intra- and interrater reliability appeared to be good for all the parameters except for the strain parameter. The attributes 'consistent' and 'intermittent' demonstrated optimal intra- and interrater reliability. The difference between pathological and control groups was significant for six perceptual parameters. The highest average correlation between GRBAS and CAPE-V judgments was found between overall severity and grade while the lowest was found between the two strain scales. CAPE-V profiles differed significantly between different pathological groups. CONCLUSION: The Italian version of CAPE-V appears to be a reliable and valid tool for the perceptual analysis of the voice signal.

Tinea corporis due to Trichophyton rubrum in a woman and Tinea capitis in her 15-day-old baby: molecular evidence of vertical transmission.

We report a case of a 40-year-old Caucasian woman who came under our observation with a 7-year history of a chronic erythematous scaly dermatitis, diagnosed as psoriasis, involving gluteal area and thighs, and treated with topical steroids without benefit. During pregnancy, a progressive worsening of her condition and an extension of cutaneous lesions were observed. Her newborn, a 15-day-old girl, presented a similar scaly and squamous lesion on her scalp. Mycological examination was positive for Trichophyton rubrum in both cases, and random amplified polymorphic DNA analysis confirmed the isogenicity of the two isolates. We performed a diagnosis of T. rubrum tinea corporis and tinea capitis. The case we describe illustrates an unusual clinical presentation of tinea corporis with remarkable extension of cutaneous lesions due to the diagnostic delay and the continuous use of local steroids, together with a rare tinea capitis in the newborn. Our experience highlights the possibility of mother-child transmission and the importance of an early diagnosis.

Characterization of Candida parapsilosis complex strains isolated from invasive fungal infections.

In the present work, we studied the distribution of Candida parapsilosis complex species and the antifungal susceptibility of clinical isolates collected during an Italian surveillance study of yeast invasive fungal infections (IFIs) in intensive care units (ICUs). Minimum inhibitory concentrations (MICs) were determined using the Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution method. BanI digestion patterns of the secondary alcohol dehydrogenase polymerase chain reaction (PCR) products were used to identify C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis. A total of 138 C. parapsilosis isolates were stored (January 2007-December 2008). The overall frequency of C. parapsilosis complex in IFIs was 22%. Of the 138 tested isolates, 95% were C. parapsilosis sensu stricto, 3.6% were C. orthopsilosis, and 1.4% were C. metapsilosis. The MIC(50) values (expressed as µg/ml) for anidulafungin, caspofungin, and micafungin for C. parapsilosis complex were 2, 1, and 2, respectively, and the MIC(90) values were 4, 2, and 4, respectively. The MIC(50) and MIC(90) values for itraconazole and posaconazole were 0.12 and 0.25, respectively, and for fluconazole, they were 1 and 4, respectively. This study, the most comprehensive study conducted to date to evaluate the frequency and antifungal susceptibility profiles of C. parapsilosis complex isolates from critically ill patients in Italy, highlights the low prevalence of C. orthopsilosis and C. metapsilosis in IFIs.

Developing a cell-bound detection system for the screening of oxidase activity using the fluorescent peroxide sensor roGFP2-Orp1.

Accurate yet efficient high-throughput screenings have emerged as essential technology for enzyme engineering via directed evolution. Modern high-throughput screening platforms for oxidoreductases are commonly assisted by technologies such as surface display and rely on emulsification techniques to facilitate single-cell analysis via fluorescence-activated cell sorting. Empowered by the dramatically increased throughput, the screening of significantly larger sequence spaces in acceptable time frames is achieved but usually comes at the cost of restricted applicability. In this work, we tackle this problem by utilizing roGFP2-Orp1 as a fluorescent one-component detection system for enzymatic H2O2 formation. We determined the kinetic parameters of the roGFP2-Orp1 reaction with H2O2 and established an efficient immobilization technique for the sensor on Saccharomyces cerevisiae cells employing the lectin Concanavalin A. This allowed to realize a peroxide-sensing shell on enzyme-displaying cells, a system that was successfully employed to screen for H2O2 formation of enzyme variants in a whole-cell setting.

Adaptation and validation of the Italian MD Anderson Dysphagia Inventory (MDADI).

INTRODUCTION: Oropharyngeal dysphagia is a common symptom in patients with head and neck tumours. The MD Anderson Dysphagia Inventory (MDADI) is a questionnaire currently used in North America for the assessment of dysphagia-related disability in patients with head and neck cancer. The aim of the study is to analyze reliability and clinical validity of the Italian MDADI. MATERIAL AND METHOD: 48 persons with no history of dysphagia and 50 head and neck cancer patients with a chronic and stable dysphagia have been included in the study. Each subject completed alone the Italian MDADI twice with a week interval between the two questionnaire completion. Intra-subject reliability was analyzed through Pearson test in both groups of subjects. Clinical validity was calculated through the non parametric Mann Whitney test of the first MDADI assessment in both groups. RESULTS: Internal consistency and test-retest reliability were high for each MDADI subscale in subjects without dysphagia as well as in those with dysphagia. The difference between MDADI values in subjects with and without dysphagia was significant for each subscale. DISCUSSION: The Italian MDADI is reliable and clinically valid. The application of the MDADI is recommended in clinical practice as well as in descriptive, outcome and efficacy research.

Microbiologic and clinical characteristics of biofilm-forming Candida parapsilosis isolates associated with fungaemia and their impact on mortality.

OBJECTIVES: Biofilm formation (BF) by fungal isolates may dramatically complicate infection. We determined the ability of Candida parapsilosis isolates from single fungaemia episodes to form biofilms and we analysed biofilm subgroups for antifungal susceptibility and pathogenic potential. We then correlated BF with clinical characteristics and outcomes of the episodes. METHODS: BF was measured using the crystal violet biomass assay. Antifungal susceptibility of preformed biofilms was assessed, and virulence was studied using the Galleria mellonella model. A retrospective analysis of patients' clinical records was performed. RESULTS: Of 190 patient-unique isolates, 84, 38 and 68 were identified as having high BF (HBF), moderate BF (MBF) or low BF (LBF), respectively. Among 30 randomly selected isolates, nine (eight HBF and one MBF), six (all HBF) and one (HBF) isolates had elevated sessile minimum inhibitory concentrations to fluconazole, anidulafungin or amphotericin B; all HBF and MBF isolates had elevated voriconazole sessile minimum inhibitory concentrations. G. mellonella killing rates of HBF isolates were significantly greater than MBF (or LBF) isolates (50% vs. 20%, 2 days from infection). By comparing HBF/MBF (106 patients) and LBF (84 patients) groups, we found that HBF/MBF patients had more central venous catheter-related fungaemias (62/106 (58.5%) vs. 29/84 (34.5%), p 0.001) and were more likely to die at 30 days from fungaemia onset (61/106 (57.5%) vs. 28/84 (33.3%), p 0.01). In the HBF/MBF group, azole antifungal therapy and central venous catheter removal were significantly associated with a higher and lower 30-day mortality rate, respectively. CONCLUSIONS: C. parapsilosis BF influences the clinical outcome in patients with fungaemia.

Does peripheral arterial occlusive disease influence muscle strength and exercise capacity in COPD patients?

BACKGROUND: The pathophysiology of chronic obstructive pulmonary disease (COPD) is complex and understanding of it has been changing in recent years, with regard to its multisystemic manifestations, especially peripheral dysfunction and its influence on intolerance to exercise. OBJECTIVES: To evaluate the relationship between peripheral arterial occlusive disease (PAOD) and peripheral muscle strength and exercise capacity in COPD patients. METHODS: We conducted a cross-sectional study of 35 patients with COPD who were evaluated with the Ankle-Brachial Index, handgrip strength test, 1 repetition maximum (1RM) of knee extensors and flexors, and distance covered in the incremental shuttle walking test (dISWT). RESULTS: COPD patients with coexisting PAOD had lower dominant handgrip strength test results (33.00 vs. 26.66 kgf, p = 0.02) and worse performance in the dISWT (297.32 vs. 219.41 m, p = 0.02) when compared to the COPD patients without PAOD. Strong correlations were found between the result of the handgrip strength test and both the dISWT (r = 0.78; p < 0.001) and the 1RM/knee extension (r = 0.71; p = 0.03); and also between the dISWT and both the 1RM/knee extension (r = 0.72; p = 0.02) and the 1RM/knee flexion (r = 0.92; p < 0.001). The linear regression model showed that the dISWT variable alone explains 15.3% of the Ankle-Brachial Index result (p = 0.01). CONCLUSION: COPD patients with PAOD exhibit reduced muscle strength and lower exercise capacity than COPD patients without PAOD.

CONTEXTO: A doença pulmonar obstrutiva crônica (DPOC) apresenta uma complexa fisiopatologia e sua compreensão vem se modificando nos últimos anos, com atenção para as manifestações multissistêmicas, em especial a disfunção periférica e sua influência na intolerância ao exercício físico. OBJETIVO: Avaliar o impacto da doença arterial periférica obstrutiva (DAOP) na força muscular periférica e na capacidade de exercício dos portadores de DPOC. MÉTODOS: Estudo transversal realizado com 35 portadores de DPOC, que foram avaliados pelo índice tornozelo-braquial, teste de força de preensão palmar (FPP), uma repetição máxima (1RM) de extensores e flexores de joelho, e a distância no incremental shuttle walking test (dISWT). RESULTADOS: Portadores de DPOC com DAP coexistente apresentaram menor FPP da mão dominante (33,00 versus 26,66 kgf, p = 0,02) e pior desempenho no dISWT (297,32 versus 219,41 m, p = 0,02) quando comparados aos portadores de DPOC sem DAP. Fortes correlações foram encontradas entre a medida da FPP e a dISWT (r = 0,78; p < 0,001) e a 1RM/extensão de joelho (r = 0,71; p = 0,03); entre a dISWT e a 1RM/extensão de joelho (r = 0,72; p = 0,02) e a 1RM/flexão de joelho (r = 0,92; p < 0,001). O modelo de regressão linear identificou que a variável dISWT explica isoladamente 15,3% do resultado do índice tornozelo braquial (p = 0,01). CONCLUSÃO: Portadores de DPOC com DAOP coexistente apresentam maior perda da força muscular periférica e pior desempenho da capacidade de exercício quando comparados aos portadores de DPOC sem DAOP.

Influence of noninvasive ventilation by BiPAP on exercise tolerance and respiratory muscle strength in chronic obstructive pulmonary disease patients (COPD).

This study aimed to assess the effect of BiPAP, by nasal mask, on exercise tolerance and respiratory muscle strength in patients with a clinical and spirometric diagnosis of moderate/severe COPD (FEV1 < 60% of predicted). Ten patients of 59.4+/-8.9 years old, with FEV1/FVC <70% of predicted level, were treated with 30 minutes of BiPAP (IPAP:10 and 15 cmH2O; EPAP:4 cmH2O), three days per week, during two months. Before and after the treatment, spirometry, inspiratory (MIP) and expiratory (MEP) muscle strength and the distance walked in six minutes (6MWT) were measured. We observed a significant increase (Wilcoxon, p<0.05) in the mean values of MIP (from -55+/-17 to -77+/-19, respectively), MEP (from 75+/-20 to 109+/-36, respectively) and walking distance (from 349+/-67 to 448+/-75). Based on these results, we concluded that BiPAP improves respiratory muscle strength and exercise tolerance in these COPD patients.

Absence of familial association between dementia of Alzheimer type and Down syndrome.

The aim of this study was to test whether there is an excess of dementia of Alzheimer type (DAT) cases in Down syndrome (DS) relatives. We conducted a case-control study in families of DS children with classical trisomy 21. A control group was constituted of families of children referred to the same hospital for benign diseases. Families of 188 DS children and 185 controls were recruited. We obtained vital statistics on 1,850 (response rate 82%) grandparents and great-grandparents in the DS group and 1,525 (69%) in the control group. Rates of possible severe dementia were calculated on ancestors over age 60 years with available data on mental function, 1,336 in the DS group and 1,113 in the control group. Rates of possible severe dementia were similar in the two groups: 5.6% (78 cases) in DS and 6.2% (66 cases) in control. Dementia with insidious onset suggestive of DAT was observed in 2% (28 cases) of DS ancestors and 2.6% (28 cases) of control ancestors. Our results argue against an excess of dementia cases with insidious onset suggestive of DAT in families of children with classical trisomy 21.

Investigation of the system copper(II) carbonic anhydrase and HCO3-/CO2.

Copper(II) substituted human and bovine carbonic anhydrases B in the presence of bicarbonate have been investigated in solution through water-solvent proton nuclear magnetic resonance (nmr) at variable magnetic fields. HCO3-, contrary to all the other monoanionic inhibitors, partially reduces the water proton relaxation rates. This has been accounted for on the basis of the availability within the active cavity of two coordination positions partially overlapping. 13C-nmr measurements on both CO2 and HCO3- confirm that HCO3- binds the metal, whereas CO2 interacts with the paramagnetic center at nonbonding distance. The upper limit for the CO2 in equilibrium HCO3- interconversion has been estimated to be 10 sec-1.

Investigation of the system cobalt(II) bovine carbonic anhydrase B-trichloroacetaldehyde.

The interactions between hydrated trichloroacetaldehyde and cobalt(II)bovine carbonic anhydrase B have been investigated as a function of pH by means of electronic spectroscopy of FT nmr spectroscopy. The hydrated aldehyde is bound to the metal ion and its apparent affinity constant is pH dependent with a bell-shaped profile. The kinetic parameters of the dissociation process have also been determined.

Structural quantitative information on the active sites of hemocyanins and related model compounds by the XAS approach: the role of multiple-scattering calculations.

In this contribution, we will present an overview of the role of the multiple scattering (MS) calculations in the X-ray absorption spectroscopy (XAS) approach in order to extract from experimental data quantitative structural information on the active sites of the hemocyanin derivatives and of the related model compounds considered.

Per-urethral transvesical first-trimester amniocentesis.

Early amniocentesis (before 13 weeks' gestation) using a per-urethral transvesical route is studied. Eight samples were obtained in eight patients scheduled for elective termination of pregnancy. The volume of amniotic fluid averaged 12.5 +/- 7.8 ml. Culture was successful in all samples. In one case, culture was achieved with only 2 ml of amniotic fluid. The amniotic fluid can be easily obtained via the per-urethral transvesical route. We conclude that early per-urethral amniocentesis before 13 weeks amenorrhea may be an alternative to the transabdominal route. A clinical trial should be carried out in order to evaluate both techniques.

[Prolonged use of intravenous nitro derivatives in acute myocardial infarction (AMI)]. / Uso prolungato di nitroderivati per via endovenosa in corso di I.M.A.

A retrospective survey is made on 166 cases of acute myocardial infarction, treated with intravenous nitro-derivatives for eight days of continuous therapy. This therapeutic modality appears to gain four goals: a reduction in mortality of patients, a faster return of ST tract on isoelectric guideline, fewer ventricular pump failures. In the authors' point of view, a delay in the downward return of ST tract towards the isoelectric guideline is an important but ominous prognostic sign in this group of patients. Therefore, this modality of treatment is suggested for all patients with AMI, wherever the myocardial coronary lesion is localized.

[Prolongation of the Q-T interval and hyperkinetic ventricular arrhythmias probably induced by terfenadine use in liver cirrhosis patients]. / Allungamento dell'intervallo Q-T ed aritmie ventricolari ipercinetiche probabilmente indotte dall'uso di terfenadina in paziente con cirrosi epatica.

The authors describe the prolongation of Q-T interval and secondary appearance of ventricular sustained ectopic beats in a 57 years old cirrhotic female treated for 4 days with antihistaminic drug (terfenadine) 240 mg/die/os. The pro-arrhythmic properties of terfenadine may be due to the quinidine-like mechanism of the drug and is strictly linked to the direct effect of the drug on H1 histaminergic receptors, which cause the prolongation of the myocardial cells action potential.

[Alcoholic hepatopathy, deficiency pathology and serum transaminases. Presentation of 2 clinical cases]. / Epatopatia alcolica, patologia carenziale e transaminasi sieriche. Presentazione di due casi clinici.

The authors describe two cases of Vit B1 and B6 deficiency in alcoholics with malnutrition. In the first case serum levels of AST and ALT, initially below norm became higher after Vit B1 and Vit B6 intake; the second, with AST and ALT above norm in previous months, had AST and ALT with normal activity during the disease. The authors suggest that normal activity of AST and ALT during alcoholic hepatopathy could be related to a depletion of Vit B1 and Vit B6.

[Increase of liver enzymes during treatment of myocardial infarct using intravenous nitro-derivatives]. / Aumento di enzimi di pertinenza epatica in corso di trattamento dell'infarto miocardico con nitroderivati per via endovenosa.

A transitory serum elevation of hepatocellular enzyme alanine-aminotransferase (ALT) and gamma GT is reported during i.v. treatment with nitroderivatives of acute myocardial infarction. authors have reviewed 144 case (105 males and 39 females) admitted to the emergency ward for acute myocardial infarction: of the 144 cases reviewed, 54 males and 16 females (48.6% of the total) presented a significative increase of ALT and gamma GT, up to the maximum value of 220 U/l, during the first week of continuous i.v. therapy with nitroderivatives. This elevation was transient, with return to normal values during the first month. The AA postulate that this increase is dose-dependent, linked to individual susceptibility and possibly due to the production of free oxygen radicals.

[A case of wet beriberi]. / Su di un caso di beri-beri umido.

The AA. report a case of thymine acute deficiency in a 35 year old chronic alcoholic and malnourished male, who was admitted to the hospital because of high-output heart failure, peripheral polyneuropathy, cortico-cerebellar atrophy (associated with RMN), ataxia and peripheral edema. The diagnosis of wet Beri-beri combined with Wernicke-Korsakoff syndrome was made and appropriate therapy with pulse daily dose of parenteral thymine instituted. At the fifth day of therapy the cardio-circulatory hyperkinetic syndrome was markedly improved and after three weeks neurological damage was also alleviated. The AA. outline the importance of early diagnosis and treatment for this form of high-output heart failure, which has a poor prognosis and, if left untreated, can determine the death of the patient in a few days.