Pietro Cugini

Primary adrenocortical nodular dysplasia, a distinct subtype of cushing's syndrome

: Twenty-nine adult patients with cystic fibrosis who had chronic bronchopulmonary infection were randomly assigned to receive 750 or 1,000 mg of oral ciprofloxacin every 12 hours for two weeks. Assessments for efficacy and safety were made on treatment Days 7 and 14 and one week following completion of therapy, and pharmacokinetic data were collected on Days 1, 7, and 14. Fifteen of 28 evaluable patients showed clinical improvement, and none had clinical deterioration. The higher dosage of ciprofloxacin did not enhance the clinical response. Statistically significant, stepwise changes in clinical scores, pulmonary function, and sputum concentrations of Pseudomonas aeruginosa and Staphylococcus aureus were noted, but regression toward initial values occurred by one week after treatment. Although all P. aeruginosa isolates were initially inhibited by 2 mg/liter of ciprofloxacin or less, 45 and 35 percent of isolates were resistant after 14 days of therapy and one week later, respectively. Outpatient oral ciprofloxacin therapy was commonly associated with clinical improvement in adult patients with cystic fibrosis who have chronic bronchopulmonary infection, regardless of the emergence of resistant P. aeruginosa, and adverse reactions were infrequent. Further studies must delineate the long-term consequences of the frequent emergence of bacterial resistance.

Iodine deficiency in pregnant women residing in an area with adequate iodine intake

OBJECTIVE To prevent iodine deficiency disorders, the World Health Organization, United Nations Childrens Fund, and International Council for the Control of Iodine Deficiency Disorders established that for a given population median urinary iodine concentrations (UIC) must be 100-199 microg/L in clinically healthy subjects and 150-249 microg/L in clinically healthy pregnant women. We evaluated whether in the urban area of Rome, Italy, where a salt iodination program (30 mg/kg) was introduced since 2005, an increased demand of iodine during pregnancy is guaranteed. METHODS During 2006, 51 pregnant women at first trimester of a physiologic gestation were consecutively enrolled on presentation to evaluate UIC in morning spot urine samples. As controls, 100 age-matched clinically healthy non-pregnant women were evaluated. RESULTS The median UICs were 182 microg/L (range 85-340 microg/L) and 74 microg/L (range 17-243 microg/L), respectively, in the control and pregnant groups. This difference was highly significant (P < 0.001). In particular, the UIC was found to be lower than adequate in 4% of control women compared with 92% of pregnant women. This difference of occurrences was highly significant (P < 0.001). CONCLUSION This observational study demonstrated that, despite the adequate supplementation of iodine intake, most pregnant women appear not to be protected against iodine deficiency. If confirmed in larger case studies, this finding claims the attention of relevant professionals to monitor iodine nutrition during gestation, assuming that ordinary supplementation of iodine intake seems to be sufficient only in non-gestational conditions.

Describing and interpreting 24-hour blood pressure patterns in physiologic pregnancy

The time course of blood pressure in clinically healthy (pregnant and nonpregnant) women was followed by automatic ambulatory monitoring. Chronobiologic methods revealed the time course of dynamic rhythm characteristics as a function of gestational age. Differences were found between nonpregnant and pregnant women with an overall lowering during pregnancy of the rhythm-adjusted midline estimating statistic of rhythm (mesor).

Circadian rhythms of plasma renin, aldosterone and cortisol on habitual and low dietary sodium intake.

To examine the effects of reducing sodium intake upon the renin-angiotensin-aldosterone system (RAAS), 5 healthy men and 5 healthy women, 17-37 years old, living under standardized conditions, were sampled around the clock, once on habitual and once on restricted sodium intake. Plasma renin activity (PRA), aldosterone (PA) and cortisol (PC) were determined by radioimmunoassay. All three variables were found to exhibit a statistically significant circadian rhythm, both on habitual and restricted salt intake. After salt restriction, an increase in midline-estimating statistic of rhythm (mesor) of PRA and PA, but not of PC, was observed. The acrophase (an estimate of the time of high values) for PC lagged behind that for PRA and PA. This difference in acrophase was of specially high statistical significance when subjects were on a sodium-restricted diet. These results demonstrate the importance of inferential statistical so-called rhythmometric methods: parameters such as the acrophase can also be used for the assessment of novel effects and for a quantification in time. The derivation of confidence intervals for each rhythm parameter allows one to verify that a given variable exhibits values bracketing an average not only between a higher and a lower, but also between an earlier and a later limit. Changes that may involve only the acrophase, such as a lead or lag, as here noted, are then detected and are of factual as well as methodological interest.

Rhythm characteristics of plasma renin, aldosterone and Cortisol in five subtypes of mesor-hypertension

The possible role of the renin-angiotensin system and ACTH in controlling the tem-poral organization of circadian rhythm of aldosterone was studied in patients with mesor-hypertension (MH) by simultaneous radioimmunological determinations of within-day changes in plasma renin, aldosterone and Cortisol. Thirty-nine uncomplicated, untreated mesor-hyperten-sive patients, divided in subtypes, were examined. The interrelationship between the rhythm components revealed that the circadian cyclicity of aldosterone in both mesor-normotensive and mesor-hypertensive subjects, with either normal or high renin patterns, has a similar timing in ac-rophase with renin periodicity, which leads the circadian Cortisol rhythm. In low-renin mesor-hypertensive subjects a circadian rhythm of aldosterone and Cortisol, but not of renin, remains demonstrable. The confidence limits of the estimated acrophase for circadian Cortisol rhythm do not, however, overlap the confidence arcs of the aldosterone phase. These findings suggest that in normal or high renin MH subjects the aldosterone rhythmicity is mainly controlled by the renin-angiotensin system. Conversely in low-renin MH subjects the temporal organization of the aldosterone circadian sequences seems to be completely independent of renin-angiotensin control.

IS MELATONIN CIRCADIAN RHYTHM A PHYSIOLOGICAL FEATURE ASSOCIATED WITH HEALTHY LONGEVITY? A STUDY OF LONG-LIVING SUBJECTS AND THEIR PROGENY

The study investigates the circadian rhythm (CR) of urinary 6-sulphatoxy-melatonin (aMT6s) in long-living (longevous) subjects and their progeny. The aim is to detect whether or not the melatonin CR is a physiological feature associated with healthy longevity. The aMT6s CR was investigated in 10 longevous subjects, 8 of their children and 9 of their grandchildren, all in good health. Control data were obtained respectively from 13 adult subjects and 9 young subjects, in good health, but characterized by a negative family history for longevity. All the subjects were born and living in the same city. The study was performed in the summer of 1996. The aMT6s CR was found to persist in longevous subjects, being characterized by a lower mesor and amplitude. The aMT6s CR was found not to show properties consistently different in children and grandchildren as compared respectively to their adult and young controls. Because of its preservation in longevous subjects, it can be argued that the melatonin CR is a physiological feature associated with healthy longevity. Because of the comparability of aMT6s CR in children and grandchildren, with respect to their controls without a positive family history of longevity, it can be argued that the melatonin CR is not a marker that can be used for an earlier identification of the candidates for longevity. (Chronobiology International, 18(1), 99–107, 2001)

Anxiety, depression, hunger and body composition: III. Their relationships in obese patients

The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age=24±2 years; mean body mass index=21±2 kg/m2 and 48 OP (4 M, 44 W; mean age=40±17years; mean body mass index=32±7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.

Circadian Rhythms of Plasma Renin Activity and Aldosterone: Changes Related to Age, Sex, Recumbency and Sodium Restriction. Chronobiologic Specification for Reference Values

Plasma renin activity (PRA) and aldosterone (PA) levels are characterized by a circadian rhythmicity (CR). The present study revealed that this rhythmicity is influenced by several factors including posture, sodium intake and age. Time-qualified PRA and PA reference intervals can reduce the incidence of false positives and false negatives in a diagnostic work-up. The circadian rhythmicity of PRA and PA have been quantified in relation to posture, sodium intake and age. The cosinor procedure has been applied to quantify the properties of the circadian rhythmicity under these conditions. Chronograms and circadian parameters can be used to optimize the use of PRA and PA measurements in clinical practice. The chronobiological specification of reference values for PRA and PA is of valuable importance since the assessment of PRA and PA circadian rhythmicity has a diagnostic interest for a certain type of clinical disorder. It should be noted that several studies have described circannual variations for renin and aldosterone. The next step in the optimation of laboratory time-qualified reference values is the assessment of changes induced by the deterministic factors on a circannual domain.

Ageing and circadian rhythm of plasma renin and aldosterone

Five men and 8 women, 60-69 yr of age, and 4 men and 5 women, 17-37 yr of age, volunteered for this exploration of possible age-related changes in circadian-rhythm (CR) characteristics of radioimmunoassayable plasma renin (PRA) and aldosterone (PA). Blood was drawn at 06.00, 08.00, 12.00, 18.00, 20.00 and 24.00 from recumbent subjects on a habitual sodium intake of 120-140 mEq/24 h. Time-qualified data of PRA and PA, fitted by a 24-h cosine curve, were summarized by a population mean-cosinor method. Circadian characteristics were compared by a multivariate analysis using Hotellings t2 test. Rhythmometry reveals in the elderly women a lower mesor (P less than 0.001) and amplitude (P = 0.036) of the CR in PRA and a higher mesor and amplitude (P = 0.021 and P = 0.020, respectively) of the PA-CR. The PRA acrophase is delayed (P less than 0.001) in the elderly women (04.40 vs. 08.04) while the timing of the PA acrophase is similar in the age groups of women compared (05.52 vs. 05.20). These differences found in women were not observed in the smaller groups of men. The seventh decade of life may be characterized by an internal circadian desynchronization between the major components of the renin-angiotensin-aldosterone system. A sex-dependent amplification of the extent of circadian variation in aldosterone may precede a decrease in the circadian amplitude occurring during the eighth decade of life, as a sign of the adrenopause in women.

Quantification of sub-clinical anxiety and depression in essentially obese patients and normal-weight healthy subjects.

The aim of this study was to quantify the degree of sub-clinical anxiety and depression in essentially obese patients (EOP) and normoponderal healthy subjects (NHS) in order to identify quantitative differences based on mean scores and percentages (the latter in cases showing a tendency towards pathological anxiety and depression indicated by a score of =8). The study involved 69 EOP (age: 13–72 years; BMI: >25.0 and <35.0 kg/m2) and 66 NHS (age: 18–68 years; BMI: >18.5 and =25.0 kg/m2). The scores, expressed in Anxiety Units (AU) and Depression Units (DU), were computed using ad hoc questionnaires (the ASQ and CDQ) validated for the Italian population. The mean scores of sub-clinical anxiety and depression in the EOP were significantly higher (both p=0.001) than those of the NHS (6.33±2.38 vs 5.02±2.22 AU; 6.42±2.42 vs 5.02±2.03 DU), as were the percentages of cases with a tendency towards pathological anxiety and depression (42% vs 18%, and 43% vs 12%) (both p=0.001). The significantly higher mean sub-clinical anxiety and depression score in the EOP indicate that a worse mood status is associated with obesity in a non-random manner. The significantly higher percentages of EOP with a tendency towards pathologic anxiety and depression indicate that obesity is a clinical condition that predisposes to the development of clinically relevant affective disorders.