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Biomedical subjects

M Cirillo

Publications and source records attributed to M Cirillo.

At least 19 recordsLinked to original sources
PubMed2002

Relation of urinary urea to blood pressure: interaction with urinary sodium.

A previous study reported that urinary markers of protein intake are inversely related to blood pressure via unknown mechanisms. In man and rats, protein intake affects renal function and increases renal sodium excretion. The present study investigates the relation between markers of protein intake and blood pressure and the possible role of sodium in this relation. Blood pressure status, overnight urinary urea as index of protein intake, urinary and plasma sodium, and other variables were measured in a population sample of 3705 men and women, aged 25-74 years, without high plasma creatinine. Urinary urea was inversely related to blood pressure and hypertension: in multivariate analyses, 6.5 mmol/h higher urinary urea (about one s.d. in men and women) was related to 4.25 mm Hg lower systolic blood pressure (95% confidence interval = 1.34-8.49), and to 0.65 lower risk of hypertension (95% CI 0.34-0.87). An interaction was found between overnight urinary sodium and the relation of urinary urea to blood pressure: the relation was significant only in persons with overnight urinary sodium above the median. Urinary urea was significantly and inversely also related to plasma sodium. Data confirm an inverse relation to blood pressure of protein intake as measured by urinary urea. The possibility of sodium-related mechanisms is supported by the interaction of urinary sodium with the relation and by the inverse association of urinary urea with plasma sodium. The hypothesis is made that high protein intake could counteract sodium-dependent blood pressure rise via stimulation of renal sodium excretion.

Adult↗
PubMed2001

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer.

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.

Adult↗
PubMed2001

Level of hydration and renal function in healthy humans.

BACKGROUND: High hydration is commonly used in renal studies to improve the completeness of urine collection. The renal effects of hydration are not well defined. METHODS: Renal function was studied under fasting conditions (baseline) and after a meat meal (2 g of protein/kg body weight) in 12 healthy adults on a low and high hydration regimen of 0.5 and 4 mL of oral water per kg body weight/30 min, respectively. RESULTS: Urine flow, urinary and plasma Na, K, urea, and osmolality were stably different on low and high hydration regimens. At baseline, there were significant or borderline significant correlations of plasma and urine osmolality with glomerular filtration rate (GFR; inulin clearance) only in the low hydration regimen. GFR was higher in the low than the high hydration regimen at all time points. The difference was significant at baseline (19.2%) and at 90 to 180 minutes after the meal (14.4%). After the meal, GFR increased significantly over baseline values only in the high hydration regimen (30.0% at peak time). Urinary excretion of Na, urea, and osmoles was lower in the low than the high hydration regimen at all time points: The difference was significant for Na (at baseline) and osmoles (all time points). Urinary K excretion was not different in the two regimens. After the meal, there were significant increases in urinary excretion of Na (in the low hydration regimen) and urea (90 to 180 min after the meal). CONCLUSIONS: In fasting adults, high hydration lowered GFR and increased natriuresis. After a meat meal, GFR increased only in the high hydration regimen and natriuresis only in the low hydration regimen. Hydration affects GFR and natriuresis under fasting conditions and after a meat meal.

Adult↗
PubMed2001

The heart in uremia: role of hypertension, hypotension, and sleep apnea.

Cardiovascular disease is the leading cause of morbidity and mortality in end-stage renal disease. Causes include those usually found in the general population, those related to the uremic status, and those related to dialytic treatment. Hypertension, hypotension, anemia, hypoalbuminemia, malnutrition, dyslipidemia, reactive C protein, calcium-phosphate product, dialysis modalities, and hyperhomocysteinemia are discussed extensively. Special emphasis is put on hyperparathyroidism as a traditional toxin. The emergent role of sleep apnea has been confirmed in animal models as well as in humans studied using polysomnography. There are difficulties in diagnosing coronary disease, because angiography is not risk-free, is expensive, and should be reserved for patients having symptoms of heart failure and/or patients having diabetes mellitus, and/or patients entering a transplantation list. This allows patients with coronary disease to undergo coronary artery bypass (preferably) or percutaneous transluminal angioplasty. Patients for whom surgery is not appropriate should be treated using more traditional medical procedures.

Adult↗
PubMed2001

Renal hemodynamics in space.

Renal excretory function and hemodynamics are determined by the effective circulating plasma volume as well as by the interplay of systemic and local vasoconstrictors and vasodilators. Microgravity results in a headward shift of body fluid. Because the control conditions of astronauts were poorly defined in many studies, controversial results have been obtained regarding diuresis and natriuresis as well as renal hemodynamic changes in response to increased central blood volume, especially during the initial phase of space flight. Renal excretory function and renal hemodynamics in microgravity are affected in a complex fashion, because during the initial phase of space flight, variable mechanisms become operative to modulate the effects of increased central blood volume. They include interactions between vasodilators (dopamine, atrial natriuretic peptide, and prostaglandins) and vasoconstrictors (sympathetic nervous system and the renin-angiotensin system). The available data suggest a moderate rise in glomerular filtration rate during the first 2 days after launch without a significant increase in effective renal plasma flow. In contrast, too few data regarding the effects of space flight on renal function during the first 12 hours after launch are available and are, in addition, partly contradictory. Thus, detailed and well-controlled studies are required to shed more light on the role of the various factors besides microgravity that determine systemic and renal hemodynamics and renal excretory function during the different stages of space flight.

Diuresis↗
PubMed2001

Body mass changes, energy, and protein metabolism in space.

Most astronauts lose body mass during their stay in microgravity. The early hypothesis, which attributed this phenomenon to an increase in diuresis and natriuresis after entering microgravity, is now untenable. Although a fluid shift from the lower to the upper body occurs, it does not lead to a marked fluid loss in the first 2 days of space flight. The continuous day-by-day body mass measurement during the Euromir 94 mission showed that there was a gradual reduction over the entire mission instead of a rapid loss of 2 to 3 kg at the beginning of a mission. The daily energy intake during this mission and the negative energy balances found in the Skylab and LMS-Mission show that lowered body mass is very likely caused by an insufficient energy consumption and its accompanying effects. These include the metabolization of endogenous energy stores, ie, glycogen, protein, and fat. Mobilization of glycogen and protein buffers will also cause the water that is bound to both to be lost. Thus, a gradual decrease in body mass and a concomitant reduction in total body fluid occurs without a significant increase in urine flow or natriuresis. In conclusion, the body mass loss in microgravity is likely a result of undernutrition instead of diuresis and natriuresis caused by the fluid shift.

Animals↗
PubMed2001

Revised hypothesis and future perspectives.

Results from space have been unexpected and not predictable from the results of ground-based simulations. Therefore, the concept of how weightlessness and gravity modulates the regulation of body fluids must be revised and a new simulation model developed. The main questions to ask in the future are the following: Does weightlessness induce a diuresis and natriuresis during the initial hours of space flight leading to an extracellular and intravascular fluid volume deficit? Can sodium in excess be stored in a hitherto unknown way, particularly during space flight? Why are fluid and sodium retaining systems activated by spaceflight? Why are the renal responses to saline and water stimuli in space attenuated compared with those of ground simulations? How can the effects of weightlessness on fluid and electrolyte regulation be correctly simulated on the ground? The information obtained from space may be of relevance to fluid and electrolyte balance in edematous patients.

Blood Volume↗
PubMed2001

Nephrotic edema.

This article starts with a concise synopsis of the history of edema. The role of underfilling, overflow, antidiuretic hormone, and acquaporins is subsequently discussed. Emphasis is given to the use of diuretics in edematous patients. The role and risks of albumin infusion are illustrated. The new hypothesis of pulse reverse osmosis is discussed. The final section deals with the measurement of colloid osmotic pressure in the clinical setting.

Edema↗
PubMed2001

Bioelectrical impedance analysis in heart transplantation: early and late changes.

The objectives of this study were to perform bioelectrical impedance analysis before and after heart transplantation with comparison to healthy subjects. Eight patients (7 men, 1 woman) before (day 0) and after transplantation (day 3, 7, 12, 15, and 180) and 24 healthy controls, matched for sex, age, and body mass were studied. Data collection included bioelectrical impedance analysis (resistance, reactance, and estimates of body water), clinical, and laboratory measurements. Compared with controls, patients had at baseline significantly higher reactance, not significantly different resistance, body weight, total body water, and intra- to extracellular water ratio. After surgery, for reactance, there was an acute decrease followed by a slow, progressive increase up to normal level by day 15. Resistance and body weight did not significantly change; the intra- to extracellular water ratio significantly decreased with stable total body water. Changes in reactance are the main effects induced on bioelectrical impedance by heart transplantation. Acutely, there is a large decrease which likely reflects changes both in water distribution and in cell membrane function. The late changes more likely reflect the shift of body water from the extra- to the intracellular space with stable total body water.

Adult↗
PubMed2001

Impact of the Gubbio population study on community control of blood pressure and hypertension. Gubbio Study Research Group.

BACKGROUND: Awareness and treatment of hypertension have markedly increased in the last 30 years in most parts of the world, but a satisfactory control of blood pressure is still infrequent OBJECTIVES: To describe trends in community control of hypertension and blood pressure levels in the small town of Gubbio, Italy. METHODS: Large samples of the populations (aged 30-79 years) were examined 6 years apart for measurement of blood pressure, other cardiovascular risk factors and knowledge, attitude and practice towards control of hypertension. Data were available from a total of 1125 men and 1445 women with two examinations and 1566 men and 1658 women with at least one examination. Two different definitions of hypertension were used (old definition: systolic blood pressure (SBP) > or = 160 mmHg or diastolic blood pressure (DBP) > or = 95 mmHg or use of antihypertensive drugs; recent definition: SBP > or = 140 mmHg or DBP > or =90 mmHg or use of anti-hypertensive drugs). RESULTS: Awareness, treatment and control of hypertension increased from one survey to the other, whatever definition of hypertension was used. Control rose from 41 to 63% (old definition) and from 12 to 24% (recent definition). In a 6-year period, the average population SBP declined 2-8 mmHg and DBP declined 2-3 mmHg depending on type of analysis, against an expected rise of 9 mmHg for SBP and 2 mmHg for DBP. These trends are partly explained by a marked decline in alcohol consumption and by more common and intensive anti-hypertensive treatment, while change in body mass index, which showed a slight but systematic increase, cannot be considered as a contributor to this trend. CONCLUSIONS: An epidemiological study has motivated a population group and its medical profession towards a better control of hypertension.

Adult↗
PubMed2001

Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population Study.

OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases. This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events. METHODS: A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events. RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5) and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory. CONCLUSIONS: Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.

Adult↗
PubMed2000

Pulse pressure and isolated systolic hypertension: association with microalbuminuria. The GUBBIO Study Collaborative Research Group.

BACKGROUND: The long-term risk of end-stage renal disease is high in persons with isolated systolic hypertension, that is, those with an elevation of pulse pressure and not of diastolic pressure. Other data suggest that pulse pressure is a predictor of the hypertension-induced organ damage. Microalbuminuria is considered an early sign of glomerular damage caused by hypertension. The study shows the relationship of pulse pressure and isolated systolic hypertension to microalbuminuria in nondiabetic subjects. METHODS: This is a cross sectional analysis for a population sample of 677 men and 890 women, aged 45 to 64 years, who were without diabetes mellitus and macroalbuminuria. Data collection included: overnight urinary albumin and creatinine excretion; fasting plasma glucose, cholesterol, and creatinine; creatinine clearance; and blood pressure, weight, height, medical history, and smoking habit. Pulse pressure was calculated as systolic minus diastolic pressure. Isolated systolic hypertension was defined as systolic pressure > or =140 mm Hg in persons not on antihypertensive drugs and with diastolic pressure <90 mm Hg. Microalbuminuria was defined as urinary albumin excretion > or =20 microg/min. RESULTS: Pulse pressure and isolated systolic hypertension were significantly related to urinary albumin excretion and the prevalence of microalbuminuria in univariate and multivariate analyses. Controlling for gender and other variables, the risk of microalbuminuria was 1.71 with a 15 mm Hg higher pulse pressure (95% CI, 1.31 to 2.22) and 4.95 in the presence of isolated systolic hypertension (95% CI, 3.15 to 7.76). CONCLUSIONS: In nondiabetic, middle-aged adults, pulse pressure and isolated systolic hypertension are directly related to microalbuminuria, independent of diastolic pressure and other correlates.

Age Distribution↗
PubMed2000

First risk functions for prediction of coronary and cardiovascular disease incidence in the Gubbio Population Study.

BACKGROUND: The Gubbio study is an Italian population study which measures the risk factors and incidence of major cardiovascular diseases. This analysis produces multivariate models for the prediction of cardiovascular end-points. METHODS: A population sample of 2,963 men and women aged 35-74, free from major cardiovascular diseases, was examined in 1983 with risk factor measurement, and a 6-year incidence was computed for coronary heart disease and all cardiovascular (atherosclerotic) events. Proportional hazards models were solved for the prediction of these events. RESULTS: Over a 6-year period, 74 hard criteria, and 126 any criterion coronary heart disease and 174 cardiovascular events were recorded. Multivariate models showed the predictive power of sex (relative risk ranging 1.63 to 2.60), age (relative risk for 5-year difference ranging 1.38 to 1.48), systolic blood pressure (relative risk for 20 mmHg difference ranging 1.17 to 1.27), HDL cholesterol (relative risk for a difference of 10 mg/dl ranging 0.73 to 0.81), non-HDL cholesterol (relative risk for 40 mg/dl difference ranging 1.15 to 1.27), cigarette smoking (relative risk for 10 cigarette difference ranging 1.21 to 1.28), and body mass index (relative risk for 3 units ranging 0.99 to 1.02). All coefficients were statistically significant except that for body mass index, they were larger for hard criteria coronary heart disease, and their magnitude was similar to that found in previous Italian population studies. CONCLUSIONS: Traditional cardiovascular risk factors predict coronary and cardiovascular events in another Italian population study confirming previous findings and similar predictive models.

Adult↗
PubMed1999

Headache and cardiovascular risk factors: positive association with hypertension.

The study analyzes the prevalence of cardiovascular risk factors in 1343 patients with severe headache (399 men and 944 women), aged 15 to 64 years; analyses were controlled for sex, age, and type and frequency of headache. Prevalence of various forms of headache was different between men and women. Age and days per year with headache were significantly different among various forms of headache. For men and women with headache, age directly related to prevalence of hypertension, hypercholesterolemia, and obesity. Due to low prevalence, analyses by age were not done for diabetes mellitus. For cigarette smoking, prevalence was not related to age in men, but was inversely related to age in women. With control for age, prevalence of cardiovascular risk factors was not significantly different among patients with different forms of headache, except for cluster headache. Among men with cluster headache, prevalence was high for cigarette smoking, but low for hypercholesterolemia. With control for age, days per year with headache did not relate to prevalence of cardiovascular risk factors except for cigarette smoking in men. Compared to data for a population sample used as control, patients with headache had higher prevalence of hypertension in both sexes, independent of age (odds ratio 1.51, 95% confidence interval 1.28 to 1.80); the difference between patients with headache and the control population was lower with increasing age. The high prevalence of hypertension among patients with headache was not due to overweight. The data indicate that headache is significantly associated with hypertension, but not with other cardiovascular risk factors.

Adolescent↗