Prediction of normal tissue response and individualization of doses in radiotherapy

In this work we estimate the therapeutic gain that could be obtained using a radiotherapy programme in which doses were based on a radiosensitivity test that was able to predict the final response of normal tissues to radiation for each particular patient. To date, no good radiosensitivity assay has been demonstrated and by way of example we use an assay based on initial DNA damage. The individualized programme we propose is based on an increase in the dose delivered to patients showing a resistant behaviour to radiation and on the adoption of alternative programmes or a careful monitoring of those patients in whom an excessive reaction is expected. To quantify the results produced by the individualization programme, both analytical and Monte Carlo simulation methods are used. The increase in tumour control probability obtained by means of this individualization strongly depends on the dose-response curve for the particular tumour. In certain cases, this enhancement can be marked, and 40% of the patients considered in this work could attain more than 10% increase in tumour control probability. The quantitative estimations in this study indicate the need to seek a predictive assay of radiosensitivity, for both normal and tumour tissue response, in order to develop individualized treatment protocols.     

Assessing the use of p16(INK4a) promoter gene methylation in serum for detection of bladder cancer

OBJECTIVE: This study was undertaken to investigate whether hypermethylation in p16(INK4a) gene promoter could serve as plasma biomarker of bladder cancer. METHODS AND PATIENTS: We examined the p16(INK4a) status using methylation-specific PCR in 86 cancer patients and 49 controls (31 healthy people and 18 patients with benign urological diseases). RESULTS: The p16(INK4a) methylation was found in 22% of the serum samples and in 26% of the bladder cancer biopsies; one of them with carcinoma in situ. The presence of hypermethylated p16(INK4a) in serum seems to be a product from tumour cells because a strong statistical association was found between both matched DNA signals (p<0.0001). Using the control group, the presence of methylated p16(INK4a) in the serum of individuals with suspicion of bladder cancer was found to be associated with the tumour presence (p=0.0009). Aberrant p16(INK4a) methylation was also observed in one non-cancer patient, which is undergoing further assessment. CONCLUSIONS: According with our results, methylation of p16(INK4a) promoter may be involved in the bladder cancer genesis and the presence of p16(INK4a) methylated in serum of these patients could be useful in the cancer diagnosis with values of sensitivity, specificity and positive predictive value of 0.226, 0.950 and 0.98, respectively. These figures support the use of methylated p16(INK4a) as a new class of tumour marker in bladder cancer.     

Penile carcinoma. Retrospective study in the XIII area of the community of Valencia

We have analyzed a set of 27 patients diagnosed of penile cancer who have been treated in our Hospital during the last 17 years (since january 1984 to december 2000). The annual incidence was set in 1.7 patients/100,000 men/year. The average age has been 64 years (range 42-85). Patients delayed medical consulting of their lesions for 15 months (2-120). Histologic analysis found an epidermoid carcinoma in 19 patients, and verrucous carcinoma in 8. The average follow-up has been 48 months (range 2-120). As a conclusion we don't belive necessary prophylactic inguinal lymphadenectomy. Correct followup, for early detection of lymph nodes does not worsen survival and it avoids unnecessary operations with a high rate of morbidity. The prognostic factors in our patients have been the presence of lymph nodes and the degree of local extension. We lack of experience with radiotherapy and chemotherapy.     

Satisfaction with primary medical care: population determinants

OBJECTIVES: To study the level of satisfaction with the family physician in the general population, and to evaluate the influence of characteristics of the individual and the available health care services. METHODS: Cross-sectional survey with a representative sample of 1,505 beneficiaries of the Social Security, older than one year, from the city of Matar?o (Barcelona). A questionnaire, administered by home interview, examined the socio-demographic situation, health status, health care organizations and services used and the preferences and knowledge in relation to them. Satisfaction was measured on the scale of Hulka BS et al. developed at Andalusian primary care centres. RESULTS: Satisfaction with the family physician had, on a scale from 0 to 100, a mean score of 61.3 (standard deviation, 13.5) points. The main determinant of satisfaction was the model of primary care, users of non-reformed centres being less satisfied. It was followed by better knowledge of ambulatory services, age and better attitudes towards primary care, which were positively related to satisfaction. Indicators of health care accessibility and continuity, as well as the number of medical visits fulfilled, the subject's main activity and their level of health were also independent determinants of satisfaction. The explained satisfaction's variation was 38.98%. CONCLUSIONS: Satisfaction with family physician is a complex and multifactorial behaviour which is under constant change due to the interrelation of the individual with his social and health care environment.     

Arsenic dose in patients with cutaneous carcinomata and hepatic haemangio-endothelioma after environmental and occupational exposure

A total of 16 male cases with malignant tumours associated with arsenic-polluted water were observed in Tarapacá and Antofagasta Provinces, northern Chile. Fifteen of them had skin carcinomata and the remaining one a haemangio-endothelioma of liver. The 15 skin cancer cases had latent periods ranging from 12–45 years. Three patients were studied in detail. The first one (skin cancer) had a latent period of 20 years with a weighted mean dose of 1.2 mg/day (total dose for latent period 8.4 g). The second one (skin cancer) had a latent period of 23 years with a weighted mean dose of 1.0 mg/day (total dose for latent period 8.3 g). The third case (liver tumour) exhibited a latent period of 14 years with a weighted mean of 0.6 mg/day (total dose for latent period 3.1 g).Fifteen of the 16 cancer patients were labourers. For normal subjects of different ages and both sexes (n=290) and ingesting arsenic-polluted water (0.60 ppm), the relationship between mean age and mean arsenic dose is expressed by a weighted least square polynomial regression, of second degree: (y) = _o + ₁ ^t + ₂ ^{t 2} where y is mean arsenic dose (mg/person/day) and t is mean age (years). For the general male population and for male labourers, the respective equations are presented.Deceased. National Academy of Medicine, Santiago, Chile     

Handgrip Strength: Associations with Clinical Variables,Body Composition,and Bone Mineral Density in Adults with Cystic Fibrosis

Background: Loss of fat-free mass (FFM) is associated with an increase in morbidity and mortality in cystic fibrosis (CF) patients. Handgrip strength (HGS) measures muscle function and may be associated with clinical parameters with prognostic value. Our objectives were to evaluate muscle strength through HGS in CF patients and to determine if there are any associations with respiratory clinical variables, FFM, and bone mineral density (BMD). Methods: A cross-sectional study conducted in clinically stable patients. We evaluated muscle function through HGS, respiratory function—forced expiratory volume in 1 s (FEV1) (%), forced vital capacity (FVC) (%), bronchorrhea, annual exacerbations, and body composition (FFM and FFM index, FFMI: fat-free mass in kg/height in m²) and Bone Mineral Density (BMD) through densitometry (DXA). Results: The study included 53 CF patients (58.5% females, mean age 28.3 ± 8.1, body mass index (BMI) 21.7 ± 3.4). The mean values for dynamometry were 40.2 ± 8.1 kg in males and 23.1 ± 7.0 kg in women, being 20.8% below the 10th percentile. Patients with lower muscle strength showed significantly more exacerbations and lower FEV1% and FVC%, as well as lower BMI, worse BMD (g/cm²), T-score, and Z-score. A significant and positive correlation was found between the mean and maximum dynamometry values and age, FVC%, BMI, FFMI, FFM (kg), and BMD. Conclusions: For adults with CF, HGS is a practical tool for assessment of health status. Low values reflect poor nutritional status and are associated with poor respiratory function, low fat-free mass and low bone mineral density.     

Riveting hammer vibration damages mechanosensory nerve endings

Hand‐arm vibration syndrome (HAVS) is an irreversible neurodegenerative, vasospastic, and musculoskeletal occupational disease of workers who use powered hand tools. The etiology is poorly understood. Neurological symptoms include numbness, tingling, and pain. This study examines impact hammer vibration‐induced injury and recoverability of hair mechanosensory innervation. Rat tails were vibrated 12 min/d for 5 weeks followed by 5 week recovery with synchronous non‐vibrated controls. Nerve fibers were PGP9.5 immunostained. Lanceolate complex innervation was compared quantitatively in vibrated vs sham. Vibration peak acceleration magnitudes were characterized by frequency power spectral analysis. Average magnitude (2515 m/s², root mean squared) in kHz frequencies was 109 times that (23 m/s²) in low Hz. Percentage of hairs innervated by lanceolate complexes was 69.1% in 5‐week sham and 53.4% in 5‐week vibration generating a denervation difference of 15.7% higher in vibration. Hair innervation was 76.9% in 5‐weeks recovery sham and 62.0% in 5‐week recovery vibration producing a denervation difference 14.9% higher in recovery vibration. Lanceolate number per complex (18.4 ± 0.2) after vibration remained near sham (19.3 ± 0.3), but 44.9% of lanceolate complexes were abnormal in 5 weeks vibrated compared to 18.8% in sham. The largest vibration energies are peak kHz accelerations (approximately 100 000 m/s²) from shock waves. The existing ISO 5349‐1 standard excludes kHz vibrations, seriously underestimating vibration injury risk. The present study validates the rat tail, impact hammer vibration as a model for investigating irreversible nerve damage. Persistence of higher denervation difference after 5‐week recovery suggests repeated vibration injury destroys the capability of lanceolate nerve endings to regenerate.     

Registro Nacional de Síndrome Coronario Agudo en Paraguay (RENASCA-PY)

Objective:

To determine the initial management and in-hospital mortality of patients with acute coronary syndrome who attended referral hospitals in Paraguay.

Method:

Observational, multicenter study, in patients over 18 years with a confirmed diagnosis of acute coronary syndrome.

Results:

780 patients were included from May 2015 to February 2016; the mean age was 64.1 ± 12.3 years, 64.1% male. The clinical presentation was acute coronary syndrome with ST elevation in 40.1% and without elevation in 59.9%. In patients with ST elevation there is a high percentage of late attendance, more than 12 h of evolution in 49.8%; those with less than 12 h of evolution underwent reperfusion in 52.2% of the cases, received fibrinolytics in 36.3% of the cases, and primary percutaneous coronary intervention 15.9%. In-hospital mortality for acute coronary syndrome was 10.3%, with ST-segment elevation was 12.8%, and without ST-segment elevation was 8.6%.

Conclusions:

The management of acute coronary syndrome in Paraguay needs a comprehensive approach, which promotes earlier care, and increases the implementation of reperfusion therapies in the health services network, in order to improve the therapeutic response rates and decrease hospital mortality.