Pharmacogenomics as a tool to prevent drug-related hospitalization of elderly cardiology-oncology patients receiving chemotherapeutic agents and multiple symptomatic treatments: a pilot study planned for the Italian health system.

OBJECTIVE: Current precision medicine approaches offer powerful tools to optimize medication regimens; however, the potential impact of these tools in cancer patients with multiple drug treatments has not fully appreciated yet. Here we describe a planning project scheduled to start in the next six months. PATIENTS AND METHODS: The overall endpoint of this project is to explore the potential association between the presence of individual genetic profile and severe toxicity rates in so-called "frail" cancer patients, using a nested case-control study design. The pilot study includes the detection of the individual pharmacogenetic profile of 150 (cases), prospect enrolled cancer "frail" patients, and 150 (control) retrospectively paired enrolled individuals. Methods for addressing the primary endpoint include: (a) Evaluation of cost-effectiveness analysis by recording QALY criteria; (b) Data recording by a brief self-administered questionnaire used to evaluate the adherence of a patient's tests and the impact of this genotyping on the patient's adverse drug reactions (ADR); (c) A sample size of paired (for age, gender, education, social status, geriatric syndromes, number of medications and comorbidities) 150 (cases) and 150 (controls); (d) Genotyping method choice by current widely diffuse platforms. RESULTS: The investigators believe that genotype screening and the management of the overall cost of health care personalized therapy has the potential to reduce the health care costs of the Italian national health system (SSN). CONCLUSIONS: Finally, the innovative issue of this project is to advocate the creation of a new model of the co-operative team (Physicians, pharmacist, geneticist and lab manager) that join for planning the most appropriated personalized therapy for their patient.

Spectral analysis of the voice in Down Syndrome.

The voice quality of individuals with Down Syndrome (DS) is generally described as husky, monotonous and raucous. On the other hand, the voice of DS children is characterized by breathiness, roughness, and nasality and is typically low pitched. However, research on phonation and intonation in these participants is limited. The present study was designed to provide data from the spectral analysis of the human voice in DS people. A cross-sectional, observational design was applied. Thirty DS adults and 48 DS children were enrolled after clinical evaluation. Thirty men, 30 women and 46 children constituted the control group. The participants had to repeat a set of Italian words twice. The Real Time Pitch software manufactured by KayPENTAX recorded the voice. The following spectral descriptors were obtained for each word: Mean Frequency and standard deviation, Energy, Duration, Jitter and Shimmer. Test-retest performance was also checked. The voice of DS adults was characterized by a significantly higher Mean Frequency, particularly in males (p<0.0001), by a smaller variation (p=0.0044 in males and p=0.0046 in females) and by a significantly lower level of Energy (p=0.0037 in males and p=0.0025 females). Furthermore, limited to male adults, a shorter Duration (p=0.0156) and a smaller value of Shimmer (p=0.0014) was observed. The difference between DS children and age-matched controls was limited, reaching significance only for the Coefficient of Variation (CV) (p=0.031). The difference in Mean Frequency between adults and children was more evident in the control males than in all other groups. The lack of marked difference between voice characteristics of children with and without DS is outlined by findings. Pearson's correlation coefficients on repeated productions ranged from 0.23 (Jitter) to 0.86 (Mean Frequency) in children, and from 0.07 (Shimmer) to 0.86 (Mean Frequency) in adults. In the control group, all the coefficients ranged between 0.85 and 0.98. As expected, women had a higher Mean Frequency than men, but the CV was around 0.1 for both. By contrast, children had a significantly higher Mean Frequency and a lower CV. In conclusion, spectral analysis of the human voice is recommended in each laboratory of speech and language rehabilitation to exploit the accuracy of voice descriptors.

Spectral analysis of the human voice: a potentially useful tool in rehabilitation.

AIM: The study was aimed at providing normal data from the spectral analysis of the human voice. This step of the research has a bearing in the field of speech and language retraining. The possibility of providing quantitative data would hasten monitoring of possible improvements along a rehabilitation program. METHODS: A cross-sectional, observational design was applied. Thirty-two men, 30 women and 34 children were the healthy volunteers participating to the study. The adult participants had to repeat the 12 words of the ENPA instrument for Italian language. The children repeated words from the Fanzago test. Real Time Pitch Model 5121 manufactured by Kay PENTAX recorded the voice. The following spectral descriptors were obtained for each word: mean frequency, standard deviation, loudness, duration, jitter and shimmer. Test-retest performance was also checked. RESULTS: As expected, women had a higher mean frequency than men (119+/-3 v. 193+/-5 Hz), but the variation coefficient (CV: SD/mean) was the same, namely 0.1. By contrast, children had a significantly higher mean frequency (245+/-35 Hz) and a lower CV. Under this respect, groups could be statistically divided. Loudness was practically the same among the groups, whereas the children had short time duration in word uttering. Children had also the highest jitter values, whereas shimmer values were higher in men. CONCLUSIONS: Spectral analysis of the human voice is recommended in each laboratory of speech and language rehabilitation. The usual testing is not replaced but can exploit the accurate definition of voice descriptors.

Kinetic changes of alpha B crystallin expression in neoplastic cells and syngeneic rat fibroblasts at various subculture stages.

Alpha B crystallin, a structural at variable levels, in many extraocular tissues where it plays a protective role in stress conditions. In fact, heat or toxic shocks, as well as pathological states, increase alpha B crystallin levels in many cell types. Here we show that alpha B crystallin expression is also modulated in subcultures of rat fibroblasts and Galliera sarcoma cells. Western blots analysis with anti alpha B crystallin antibodies reveals the presence of the protein in both cell populations, although the kinetic pattern of expression is different. Galliera fibroblasts constitutively express the protein up to the 70th subculture and afterwards the synthesis ceases. On the other hand, Galliera sarcoma cells do not contain alpha B crystallin in the early stages of the culture, but there is a progressive increases between the 20th and 40th cell subculture. Differences also exist concerning the intracellular distribution: alpha B crystallin is diffusely localized in the cytoplasm of fibroblasts while in sarcoma cells it localizes mainly to the perinuclear region. Alpha B crystallin is totally recovered as soluble protein in the supernatants obtained after low speed centrifugation of fibroblast homogenates, while in sarcoma cells a portion of the protein is also recovered in the insoluble pellet. Intracellular pH measurements show an alkaline cytosol in sarcoma cells compared to fibroblasts. Heat shock treatment of fibroblast subcultures constitutively expressing alpha B crystallin induces an over-expression of the protein, while in fibroblasts whose biosynthetic capacity is lost, heat shock is unable to activate the crystallin gene. Correlation between alpha B crystallin expression and proliferative rate shows that highly proliferating fibroblasts do not express alpha B crystallin, while neoplastic cells do.

Phonetic rehabilitation after laryngectomy.

This work deals with the phonetic rehabilitation of patients after laryngectomy, describing the various types of alaryngeal voice. The rehabilitation was monitored with a computer by means of a specific voice programme which permits the registration, visualization and reproduction of each sound emitted in conjunction with the classification of the principal parameters, thus allowing the patient to check his acoustic feedback.

Hydrogen peroxide-induced cytotoxicity in cultured epithelial cells (WISH): A functional and morphological study.

The effect of hydrogen peroxide on cultured epithelial cells (WISH) was investigated with particular emphasis on cell functions: cell morphology and cytoskeletal components were also studied. The presence of low concentrations of H(2)O(2) (0.1-0.4 mM) in the culture medium markedly inhibited cell growth, although WISH contained catalase and glutathione-peroxidase activities. After 1 hr of incubation with H(2)O(2) up to 5 mM, the majority of the cells were still alive, but reincubation in normal medium for 24 hr clearly reduced cell viability. Cell adhesion was dose-dependently reduced by H(2)O(2) treatment (0.1-0.5 mM) for 4 hr. Incubation with 1.5 mM-H(2)O(2) gave rise to a bleb appearance on the cell surface and to mitochondrial swelling, as shown, respectively, by scanning and transmission electron microscopy. Immunofluorescence studies revealed changes in microtubules and microfilaments, which are two of the main cytoskeletal components. The modification of microtubules was also confirmed by Western blot analysis of WISH protein homogenates submitted to SDS-PAGE. WISH treated with 1.5 mM-H(2)O(2) showed decreased levels of GSH compared with control cells: glutathione transferase activity was reduced, whereas other enzymes of the glutathione cycle were unchanged.