PubMed HealthSearch

Biomedical subjects

M Porta

Publications and source records attributed to M Porta.

At least 37 records · Page 2Linked to original sources

Do we believe what patients say about their neoplastic symptoms? An analysis of factors that influence the interviewer's judgement.

In order to analyze factors that influence an interviewer's judgement of the validity of responses given by patients on the duration of their neoplastic signs and symptoms, 183 consecutive symptomatic patients hospitalized for a digestive tract neoplasm were personally interviewed. The validity of the answers was judged by the interviewers to be high in 156 cases (85%), and low in 27 (15%). The subjective validity of the interview (SVI) was inversely related to the time elapsed from first medical symptom to interview (TFMSI), even after adjusting for the duration of the interview (p < 0.05). SVI was not influenced by whether patient and interviewer agreed on the first symptom. SVI was inversely related to educational level (p < 0.01) and to occupational class (p = 0.04). Patients whose Karnofsky's Index (KI) was > or = 80 were over twice as likely to yield valid responses (TFMSI-adjusted odds ratio [OR] = 2.82, p = 0.037). Multivariate analyses selected education, TFMSI and KI as independent predictors of the interviewer assessment. The SVI of patients admitted to the hospital through the Emergency Department was lower than that of subjects whose admission was planned (OR = 6.49, p = 0.005). In this study SVI related in a logical manner to the characteristics of the interview, of the subjects and of their clinical course. It hence appeared to reasonably estimate the validity of data collected. Identifying factors that affect the reliability of patients' responses would help increase the validity of studies on the duration of cancer symptoms.

Aged

Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions.

This study aimed at verifying whether thiamine, a co-enzyme which decreases intracellular glycolysis metabolites by allowing pyruvate and glyceraldheyde 3-phosphate to enter the Krebs cycle and the pentose-phosphate shunt, respectively, corrects delayed replication caused by high glucose concentrations in cultured human umbilical vein (HUVEC) and bovine retinal endothelial cells (BREC). After incubation in physiological (5.6 mmol/l) or high (28.0 mmol/l) glucose with or without 150 mumol/l thiamine, cells were counted and proliferation assessed by mitochondrial dehydrogenase activity. Lactate was measured in both cell types as an index of glycolytic activity and fluorescent advanced glycosylation end-products (AGE) concentration was determined in the HUVEC lysate. Both cell counts and proliferation assays in either of the cell types confirmed the impairment to cell replication induced by high glucose. When thiamine was added to cells kept under high glucose conditions, the number of surviving cells was significantly increased and the reduced cell proliferation appeared to be corrected. Lactate assays confirmed the increased production of this metabolite by BREC and HUVEC in high glucose, which was reduced by thiamine. Fluorescent AGE determination showed that thiamine may prevent non-enzymatic glycation in HUVEC. Thiamine restores cell replication, decreases the glycolytic flux and prevents fluorescent AGE formation in endothelial cells cultured in high glucose, suggesting that abnormal levels of glycolytic metabolite(s) may damage cells.

Animals

Causal thinking, biomarkers, and mechanisms of carcinogenesis.

The use of biomarkers is increasing both in acute and chronic disease epidemiology, but the rationale for their introduction is not always firmly established (e.g., when and how their use is scientifically justifiable and cost effective). The use of biomarkers should be considered within the context of causal models in epidemiology, and of the intertwining of causation and pathogenesis. Unlike infectious diseases, for cancer and cardiovascular disease external "necessary" causes have not been identified. Thus, the classification of cancer and other chronic diseases cannot be based on unequivocal criteria such as the "etiologic" classification of infectious diseases. As far as morphology is concerned, "neoplasia" and "anaplasia" are attributes of cancer that cannot be defined in a straightforward way. Tissue pathologies are minimal and difficult to differentiate from normal tissue in some cancers but are obvious in others. From a mechanistic point of view, unless molecular biology discovers specific mechanistic steps in carcinogenesis, which indicate the existence of "necessary" events in carcinogenesis, we cannot adopt an unequivocal definition of cancer. The potential contribution of biomarkers to the elucidation of the pathogenetic process should be considered in the light of such uncertainties. There is a range of indications for biomarkers, from the use of very specific measurements aimed at single molecules, to measurements indicating cumulative exposure to agents with the same mechanism of action. The potential uses of markers in chronic disease epidemiology include (1) exposure assessment in cases in which traditional epidemiologic tools are insufficient (particularly for low doses and low risks); (2) multiple exposures or mixtures, in which the aim is to disentangle the etiologic role of single agents; (3) estimation of the total burden of exposure to chemicals having the same mechanistic target; (4) investigation of pathogenetic mechanisms, and (5) study of individual susceptibility (e.g., metabolic polymorphism, DNA repair).

Animals

Sex as a prognostic factor in gastric cancer.

The aim of this study was to assess whether survival of gastric cancer patients differed between males and females. Although it is well known that the incidence of gastric cancer is higher for men than for women, the existence of a sex-specific prognosis has seldom been addressed. Studies based on population registries have not assessed the role of stage and histology. Cases of histologically confirmed gastric carcinoma were obtained from three Spanish hospitals in Soria (n = 405), Barcelona (n = 249) and Mataró (n = 197). Differences in possible confounders were tested between men and women and survival analyses were performed separately by hospital. Cox's proportional hazards models were used to account for age, tumour stage, histology and tumour sub-location. Only in Mataró was a significant difference in the stage distribution observed between women and men, with a lower proportion of local stage tumours among women (P = 0.047). No statistically significant differences of histological type between men and women were observed in any of the centres. After adjusting for tumour stage and age, women were observed to have significantly better survival in Barcelona (female to male hazard ratio (HR) = 0.578, P < 0.001); this effect was marginal in Soria (HR = 0.788, P = 0.092) and non-significant in Matar-o (HR = 0.895, P = 0.54). Age-adjusted hazard ratios were calculated within each tumour stage. For Barcelona, the effect of better prognosis among women was most marked at local stage (HR = 0.320, P = 0.013), and in Soria at the regional stage (HR = 0.426, P = 0.002). Although in Mataró all HRs were below unity, none were statistically significant. Little effect was observed at the disseminated stage. The other covariables exerted no influence. Women appear to have a better prognosis than men, and the difference could be tumour stage dependent. Confirmation of these findings would give a valuable insight into gastric cancer growth and ultimately be of use in planning treatment.

Aged

Improvement in survival after myocardial infarction between 1978-85 and 1986-88 in the REGICOR study. (Registre GIroní del COR) registry.

Aspirin, intravenous nitrates and fibrinolysis were being used by 1986 in Girona, Spain. These combined factors should be reflected in myocardial infarction patients' outcome. We assessed changes in 28-day and 3-year survival after a first myocardial infarction between 1978-85 and 1986-88 in the REGICOR (Registre GIroní del COR) registry. This included 1216 consecutive patients with a first transmural myocardial infarction (834 in 1978-85 and 372 in 1986-88). Their 28-day and 3-year mortality rates were 14.6% and 8.8% respectively. Although patients admitted in the second period were more frequently hypertensive and diabetic, a history of angina was less common in patients admitted between 1978 and 1985. After adjusting for diabetes, hypertension, age, and sex, the relative risk of 28-day mortality of those admitted in the second period was 0.65 (95% confidence interval 0.42-0.99). The lower severity, as measured by Killip class of patients in the second period, was the main (confounding) variable responsible for this protective effect. Three-year mortality of those surviving 28 days in 1978-85 (8.3%) did not differ from 1986-88 (8.3%). In the second study period hospitalized patients with myocardial infarction in Girona, Spain showed a better 28-day survival. It is possible that therapeutic and diagnostic refinements, together with other factors not controlled in the present study, have resulted in such an improvement. However, 3-year mortality remained unmodified among those surviving 28 days.

Adult

Pancreatitis and the risk of pancreatic cancer.

To offer quantitative evidence on the association between pancreatitis and pancreatic cancer, we analyzed data from a hospital-based case-control study conducted in northern Italy between 1983 and 1992, including a total of 362 incident cases of histologically confirmed pancreatic cancer and 1,408 controls admitted to hospital for acute, nonneoplastic, nondigestive tract disorders. Information was obtained using a structured questionnaire on sociodemographic characteristics and lifestyle habits (including tobacco and alcohol consumption) and a problem-oriented medical history, which included history of pancreatitis and age at its first diagnosis. Pancreatitis was reported by 24 (6.6%) cases and 18 (1.3%) controls, yielding an age- and sex-adjusted relative risk (RR) of 5.7 (95% confidence interval, 2.9-11.4). The risk of pancreatic cancer was appreciably higher 5 or more years after diagnosis of pancreatitis (RR = 6.9) than in the first 4 years (RR = 2.1), and in subjects below age 60 (RR = 8.3) than in elderly ones (RR = 2.6), but similar in males and females. The time-risk relationship is strongly indicative of a real relationship between pancreatitis and pancreatic cancer. After allowing for tobacco and alcohol, besides area of residence and education, the association between pancreatitis and pancreatic cancer appeared to be partly explained by such covariates (RR = 3.9); however, this may represent some degree of overadjustment if, for instance, alcohol is causally linked to pancreatitis, which, in turn, is causally related to pancreatic cancer. In terms of population attributable risk, pancreatitis would explain approximately 5% of pancreatic cancer cases.

Adult

Diabetic retinopathy as a cause of blindness in the province of Turin, north-west Italy, in 1967-1991.

Diabetes is known to be a major contributor to blindness in industrialized countries but few data are available on the situation in Italy. As an introductory step to the implementation of permanent screening for diabetic retinopathy, a search was carried out on the causes of visual loss in the provincial territory surrounding Turin, the main city of North-West Italy. The case notes of all 4549 residents in the province who were certified blind between 1967 and 1991 were examined with regard to cause, age at onset, and year of onset of visual acuity < or = 1/20. Diabetic retinopathy was the second commonest cause of bilateral blindness (13.1% of cases), preceded by cataract (26.7%) and followed by myopia (11.1%), optic atrophy (8.9%), glaucoma (8.9%), retinitis pigmentosa (7.2%), and senile macular degeneration (4.1%). Diabetic retinopathy was the commonest eye disease among those who became blind between the ages of 50 and 70 and remained the leading cause of visual loss when the age groups 20 to 70 were pooled together. The incidence of diabetic retinopathy-related blindness did not show any trend to decrease over the 25 years investigated. It is concluded that, in spite of widespread availability of facilities for its assessment and treatment, diabetic retinopathy remains a leading cause of blindness in North-West Italy. This fully justifies the implementation of screening programmes and efficient referral chains for the early detection and prompt treatment of this complication of diabetes.

Adolescent

Ki-ras mutations as a prognostic factor in extrahepatic bile system cancer. PANK-ras I Project Investigators.

PURPOSE: To assess the prevalence and prognostic significance of Ki-ras codon 12 mutations in extrahepatic biliary system cancer (EBSC). PATIENTS AND METHODS: Patients diagnosed with EBSC between 1980 and 1990 (N = 111) were selected from two hospitals. DNA was amplified from paraffin-embedded tissues and mutations in codon 12 of Ki-ras were detected using the artificial restriction fragment-length polymorphism (RFLP) technique. RESULTS: Tissue was available from 68.5% of patients. The prevalence of mutations was 41%. There was no association between mutations and clinical and pathologic characteristics; however, mutations in Ki-ras were associated with survival, with a median survival duration of 7.7 months for patients with wild-type Ki-ras and 1.7 months for patients with mutated tumors (hazards ratio [HR] = 1.67; P = .075). Among patients with stage I to II tumors, the chance of dying of patients with the mutation was 7.8 times higher than that of patients without the mutation (P = .087); the corresponding HR for patients with stage III to IV disease was 2.9 (P = .003). After adjusting for age, tumor site, histology, differentiation, and stage, the HR for Ki-ras mutations was 2.12 (P = .026). CONCLUSION: Ki-ras codon 12 mutations are an independent prognostic indicator in patients with EBSC. Mutation detection may be of help in the management of these patients.

Adenocarcinoma

Pharmacoepidemiology in practice. Current status and future trends.

Pharmacoepidemiology is the application of epidemiological reasoning, methods and knowledge to the study of the uses and effects (beneficial and adverse) of drugs in human populations. As referred to by the term 'pharmacoepidemiology', the discipline now enters into its second decade, although its origins go back to the beginnings of this century. This article reviews the opinions of leading pharmacoepidemiologists on the scope and prospects for pharmacoepidemiology, and summarises the most important challenges that the discipline faces on its way towards the next century. The future of pharmacoepidemiology requires the development of research methods more able to cope with the specific problems posed by the study of drugs, notably the issue of confounding by indication and the ability to adjust accurately for severity of disease. Capacity building should also continue during the next years; training of professionals, the optimisation of computerised databases for research purposes and their joint use with more traditional epidemiological methods are major challenges. From a public health perspective, a critical task is to assess the impact that vaccines and drugs have on the overall patterns of disease in well defined populations.

Cost-Benefit Analysis

Treatment of Cushing's disease by interstitial pituitary irradiation: short- and long-term follow-up.

Trans-sphenoidal intrasellar implantation of radioactive rods was employed to treat Cushing's disease in our Institution between 1958 and 1981. The patients were followed at regular intervals after the procedure. The aim of this work is to assess retrospectively the results, comparing the short- (1 year) and long-term (average 21.8 years) effects of this treatment. Seventy-six patients received pituitary implantation of 90Y- and one of 198Au-labelled rods, delivering a dose of 100-150,000 rad. Complete remission was obtained in a few weeks to months in 57/76 patients (5 of whom required a second implantation); 2 patients died of meningoencephalitis and 3 of cardiovascular complications associated with hypercortisolism 1 to 2 months after surgery. In 12 patients bilateral adrenalectomy or external pituitary irradiation were required to achieve remission; one of them developed Nelson's syndrome 15 years after implantation. Two were lost at follow-up. Long-term follow-up was possible in 41 patients of the initial series. Of these, 40 were cured of the disease, with hypoadrenalism developing in 25, while recurrence was observed only in the patient treated with 198Au. The incidence of hypothyroidism was 50%, and that of hypogonadism 54%. Permanent diabetes insipidus developed in 1 subject. GH deficiency resulting in retarded growth was found in the youngest patient, who had been operated at the age of 14. In conclusion, interstitial irradiation of pituitary adenomas was a safe and effective procedure for the treatment of Cushing's disease.

Adolescent

Disagreement between hospital medical records and a structured patient interview on the type and date of the first symptom in cancers of the digestive tract.

Medical records have often been found to be less reliable than interviews to patients when data on the initial signs and symptoms of cancer, and the out-of-hospital diagnostic process are sought; in spite of this, a large body of research on "diagnostic delay" in cancer is based on clinical records. As part of a study on delay in neoplasms of the digestive tract we analyzed the agreement on the type and date of the initial symptom between hospital records and a structured personal interview. Records were abstracted for a random sample (N = 60) of 183 patients interviewed. Concordance on the date of the first symptom was deemed to exist if the difference was +/- 30 days. The Kappa index (kappa) and the overall proportion of agreement (with its corresponding 95% confidence interval) were used. Medical records and structured personal interviews were concordant on the type of the first neoplastic symptom in only 61% of cases (kappa = 0.50): 67% in esophagus cancer (kappa = 0.49), 60% in stomach cancer (kappa = 0.52), and 61% in colorectal cancer (kappa = 0.50). Records underestimated the occurrence of anorexia as first symptom and overestimated weight loss and dysphagia. Only 56% of cases were date-concordant, the agreement being lower in colorectal cancer (46%) than in esophageal (67%) and stomach cancer (75%). Records indicated the first symptom to have occurred at a later date than interviews in 33% of cases; overall, a study based on hospital records would have underestimated the symptom to diagnosis interval by 2.2 months per patient. Only 40% of cases were totally (symptom and date) concordant. Marked discrepancies may exist between the information contained in medical records and what patients report during a structured interview. The quality of medical records data on the duration and nature of cancer symptoms should be assessed before its use in etiologic and evaluative research.

Aged

Trends in pancreatic cancer mortality in Europe, 1955-1989.

Trends in death certification rates from pancreatic cancer over the period 1955-1989 were analyzed for 25 European countries (excluding the former Soviet Union and a few smaller countries). In 1985-1989, rates for males ranged between 5.3/100,000 (age-standardized world population) in Spain and 10.3/100,000 in Hungary and Czechoslovakia. Other high-mortality areas were located in Northern Europe (Finland, Iceland, Ireland, Denmark) and Central Europe (Austria, Poland, Germany), whilst mortality was lower in Southern Europe (Portugal, Greece). Between 1955 and 1989, mortality rates increased in all the countries considered, the change ranging between 6% in Scotland and 279% in Spain; the rises were higher in the Mediterranean and Eastern European countries than in Northern Europe. Among females, Nordic countries such as Iceland, Sweden and Denmark had the highest mortality rates in 1985-1989 (over 6/100,000) and, as for males, Southern Europe (Spain, Portugal, Greece) appeared as a low-mortality area (around 3/100,000). During the 1955-1989 period, upward trends were observed in all the countries studied, with the highest increase in Greece, Italy, Bulgaria, Poland and Spain. A negative correlation was observed between the percent change in mortality rates between 1955-1959 and 1985-1989 and the rate in 1955-1959 among both males (r = -0.95, p < 0.001) and females (r = -0.81, p < 0.001). Thus, a systematic levelling of rates was observed in most countries, with the exception of the UK and some Nordic countries, whose rates were already high in the late 1950s. Tobacco smoking and dietary factors could account for some of the generalized upward trends. Improved diagnostic and death certification of the disease might also partially explain the observed figures.

Age Factors