Linear energy transfer characterization of five gel dosimeter formulations for electron and proton therapeutic beams.

Gel dosimeters, including radiochromic types like Fricke, as well as polymer formulations, are considered to be the only reliable option for accurate 3D dosimetry. Nevertheless, their implementation in daily clinical quality assurance still remains strongly limited for a few high specialized radiotherapy centres. Although gel dosimeters present very good water-equivalence due to their inherent chemical and isotopic compositions, addressing the corresponding dosimetry outputs is highly challenging, needing careful assessment in terms of the different radiation qualities involved in the mixed field. Accurate estimations of the linear energy transfer for each gel dosimeter formulation stands as a baseline for further accurate dose deconvolution in mixed radiation fields. The present study reports on the linear energy transfer characterization of five different gel dosimeter formulations, Fricke, Itabis, Magic, Nipam, and Pagat, for electron and proton therapeutic beams as obtained by Monte Carlo approaches, along with experimental results for validation purposes. The linear energy transfer, as a function of beam quality and penetration depth, is obtained for electron and proton therapeutic beams remarking the presence of non-negligible variations, which need to be accounted for a further accurate implementation of gel dosimetry as well as for precise dose deconvolution in mixed radiation fields.

The burden of hospitalization related to diabetes mellitus: a population-based study.

BACKGROUND AND AIMS: To estimate the impact of diabetes and its complications, overall and in different age classes, on the likelihood of hospital admission for specific causes. METHODS AND RESULTS: We carried out a record-linkage analysis of administrative registers including data on 8,940,420 citizens in 21 Local Health Authorities in Italy. Individuals with pharmacologically treated diabetes (≥2 prescriptions of antidiabetic agents during the year 2008) were paired in a 1:1 proportion with those who did not receive such drugs (controls) based on propensity-score matching. Odds Ratios (ORs) of hospitalization for macro and microvascular conditions in individuals with diabetes as compared to controls were estimated. The system identified 498,825 individuals with diabetes pharmacologically treated (prevalence of 5.6%). Prevalence of diabetes in people aged <14 years, 14-39 years, 40-65 years, and ≥65 years was 0.1%, 0.6%, 6.4%, and 18.2%, respectively. Overall, 23.9% of subjects with diabetes and 11.5% of controls had had at least a hospital admission during 12 months for the causes considered. Diabetes increased the likelihood of hospitalization by two to six times for the different causes examined. In absolute terms, diabetes was responsible for an excess of over 12,000 hospital admissions per 100,000 individuals/year. CONCLUSION: Despite the availability of effective treatments to prevent or delay major complications, diabetes still places an enormous burden on both patients and the health care system. Given the continuous rise in diabetes prevalence both in middle-aged and elderly individuals, we can expect an additional, hardly sustainable increase in the demand for health care in the near future.

Post-thyroidectomy dysphonia in patients with bilateral resection of the superior laryngeal nerve: a comparative spectrographic study.

The most serious complications of total thyroidectomy, in cases of widespread and invasive diseases, are mainly hypoparathyroidism and laryngeal inferior nerve palsy. Lesions of the external branch of superior laryngeal nerve instead, although less obvious than the those caused by the recurrent laryngeal nerve lesions, have been taken less into consideration. The frequency of this lesion varies from 14% to 20% of cases, although in reality it is underestimated; in fact, on the one hand it is difficult to assess this, and on the other, post-thyroidectomy dysphonia is often considered inevitable. In the present retrospective research, 15 thyroidectomized patients (4 male, 11 female), have been subjected to qualitative and quantitative evaluation of the voice. Of these, 7 had a nerve lesion, while 8 did not. All the patients received a self-evaluation voice questionnaire (VHI). In all cases, a videolaryngostroboscopy has been carried out and the voice acoustic features examined through a spectrographic analysis. The results showed that removal of the thyroid, at the end of a 12-month post-surgery period, still causes an impact on the qualitative and quantitative aspects of the vocal function, whether the superior larynx nerve was injured or not. The majority of the patients, in both groups, reported that their voice had worsened in quality and durability. Hence, we have shown that the patients with upper larynx nerve lesion have an alteration of F0, show a lower energy level and a modified spectrographic quality compared to patients without injury. This low voice is often considered by patients as a normal consequence of thyroid surgery. The present research confirms that the attempt to identify and protect the superior laryngeal nerve is essential to prevent post-thyroidectomy dysphonia, but this is not sufficient to obtain the best results because of the existence of muscular and psychogenic factors that reduce the still voice capacity of the patient.

Surgical management of lip cancer.

Lip cancer is the most frequent malignant neoplasm of the oral cavity. The study reported herewith refers to the clinico-pathological features and surgical treatment of lip cancer. The most frequent tumour related to the lips is squamous cell carcinoma, with the lower lip more commonly involved than the upper lip. Typically, squamous cell carcinoma originates in the red lip, whereas basal cell carcinoma involves the white lip. The management of lip cancer involves the control not only of the primary tumours with oncologically appropriate margins and subsequent reconstruction to allow oral competence during the oral phase of swallowing, but also the possible metastatic spread to the neck. Reconstruction is a surgical challenge especially for advanced and extended lesions. A successful reconstruction depends on careful pre-operative planning, knowledge of the anatomy and use of the various surgical techniques. Lymph node neck metastases significantly reduce long-term survival. Although the management of the neck is controversial in lip cancer, particularly with respect to the neck, elective or curative supra-omohyoid neck dissection is the best choice for occult or evident loco-regional metastases. Early stage tumours have good prognostic, aesthetic and functional results after surgery compared to the treatment of advanced lesions, which alter the appearance and functionality of the lip. The Authors report their experience in the treatment of lip tumours at the primary site, considering reconstructive problems, together with management of neck metastases.

Transparotid approach for mandibular condylar neck and subcondylar fractures.

Mandibular condylar neck fractures and subcondylar fractures represent, respectively, 19-29% and 62-70% of all mandibular fractures; treatment involves some problems, common to both, concerning the choice of an adequate approach. Herewith, personal experience is reported related to the surgical treatment of some cases of mandibular condylar neck and subcondylar fractures by transparotid approaches with partial parotidectomy, removing the salivary tissue overlying the condylar neck and/or the subcondylar region. Over the last 5 years, we observed 22 fractures of the condylar neck and 10 fractures of the subcondylar region. In 13 patients (11 male, 2 female, age range 10-68 years, mean 33 years), 10 of whom had other mandibular and/or other maxillo-facial and skeleton fractures - 50% of these with dislocated condylar heads - and the other 3 for their free choice, regarding the different treatments, 18 transparotid approaches with partial parotidectomy (bilateral in 5 cases), were performed reducing and fixing 12 condylar neck fractures and 5 subcondylar region fractures with appropriate plates (2.0 mm) and screws. After surgery, no intermaxillary fixation was performed. Complications included 4 salivary fistulae (bilateral in 1 patient), which closed spontaneously after 4 or 5 weeks with a dressing, 1 case of Frey's syndrome, which healed after 2 treatments with botulin and 6 cases of transient facial palsy lasting 4-8 weeks (1 case bilateral) affecting zygomatic, buccal and marginal mandibular nerves. During follow-up, functional parameters considered were: restoration of original pre-injury occlusion; vertical, lateral and protrusion mandibular movements. All patients re-acquired the original pre-injury occlusion; the maximal post-operative intrinsical distance was at least 40 mm after a variable period of rehabilitation and lateral and protrusion movements also led to satisfactory final results. All patients were free of pain and had no deflection or clicking upon opening or chewing. None suffered from haematoma, miniplate fractures, bone resorption or condylar necrosis. In our experience, the Transparotid approaches with partial parotidectomy permits very good anatomical repositioning of the displaced condylar or subcondylar osseous segments in all cases, since isolation of the facial nerve branches and removal of a limited part of the parotid gland tissue overlying the lesion allow perfect exposure of the fracture site. The wide operation field allows the facial nerve to be preserved and permits easy internal rigid fixation with plates, as the drill, screws and screwdriver can be positioned exactly perpendicular to the bone surface instead of obliquely, as occurs with many different approaches.

[Epidemiology of hospital loads in patients with multiple hospitalizations due to diabetes]. / Epidemiologia dei carichi assistenziali ospedalieri in pazienti con ricoveri ripetuti per diabete.

This study describes the results of a retrospective study carried out to evaluate the hospitalizations of patients with type 2 diabetes admitted from January to June 2001 in the teaching hospital "SS. Annunziata" of Chieti. This research evaluates the generic appropriateness using the PRUO manual and the specific appropriateness using the guidelines approved by Italian Diabetes Association, Italian Diabetes Society and Italian College of General Practitioners. A sample of 196 medical charts was examined. The percentage of inappropriate admission was 21.9%. The "critical" clinical conditions of patients were responsible for only 23.7% of inappropriate admissions. The first reason of the inappropriateness of the admission was the execution of diagnostic examinations (60.5%), followed by the execution of medical therapy (23.2%) and waiting for surgical intervention (16.3%). 46.5% of inappropriate hospitalization was prescribed by specialists. Concerning specific appropriateness, 42.3% of hospitalization was inappropriate. These findings suggest that a system for the assessment of disease management of diabetes should be started up in the Abruzzo region. Moreover, guidelines utilization should be implemented in order to get a more correct utilization of acute hospital by specialists and GPs.

[Regional epidemiology of chronic nephropathies: referral to nephrologist and initiation of dialysis]. / Epidemiologia regionale/locale delle nefropatie croniche: profili di "referral" ambulatoriale e inizio dialisi.

BACKGROUND: The epidemiology of pre-dialysis chronic nephropathies (CN) in well-defined contexts is essential to prevent delays in delivering appropriate care. METHODS: The registration of consecutive patients in seven out-patient and four in-patient dialysis centers of Basilicata (2001) formed a retrospective study on clinical charts and dialysis registers integrated with ad hoc data. RESULTS: Newly observed outpatients (I) numbered 328; prevalent patients (P) numbered 343. The age and gender of both I and P patients was similar (males: 60%, age media: 67 yr). In 316 I patients with creatinine (mean Cr: 2.3 mg/dL), the mean filtration rate (GFR) was 40.9 mL/min/1.73 m2: 13.6% were in advanced stage (S5) of GFR (<15 mL/min), 23.4% in S4/severe (15-29), 45.6% in S3/moderate (30-59), 10.8% in S2/mild (60-89), and 6.6% in S1 (>90). When compared to I patients, P patients had a mean GFR of 35.0 mL/min; S4+S5 was 48% (vs. 37%); hypertension 68% (vs. 58%); vasculopathies 15% (vs. 10%); coronary disease 10% (vs. 4%); erythropoietin 13% (vs. 7%); and low-protein diet 34% (vs. 20%) (p<0.01). Of 316 I patients, 117 in S5+S4 ('late referral' 37%) had a (mean) GFR of 18.4 mL/min, Cr 3.7 mg/dL, and were aged 70 yrs (vs. 64 yrs for 'early referral'). Of 53 new patients on dialysis, 26 (49%) were seen for the first time <6 months prior to starting (mean age: 71 yr vs. 62; female 58% vs. 26%; complications 50% vs. 17%). CONCLUSIONS: In this population, age-related factors are associated with late referral. Although sociodemographic variables depend on local contexts, these results are consistent with similar international studies. Social and cultural factors may influence physicians to postpone referring patients to a nephrologist, independently of clinical conditions.

[Using Dialysis and Transplantation Registries for regional and small-area epidemiology]. / L'uso dei Registri Dialisi e Trapianto per l'epidemiologia regionale/locale.

BACKGROUND: Aim of this review on Italian Dialysis and Transplantation Registries (RDTR), mostly of recent implementation, is to assess the use of epidemiological data for planning purposes, in order to promote local developments of regional registries. METHODS; Medline and reports on the website of the Italian Society of Nephrology. RESULTS: We selected two publications with data from the Italian Registry (RIDT) and 56 articles on RDTR. Most papers refer to RDTR for the Italian regions of Piedmont, Lombardy and Lazio. RIDT reports containing 1998-1999 data for all the regions are published on web. Consistent with international figures, epidemiological data show an increasing incidence and prevalence of end-stage renal disease patients on renal replacement therapy (RRT), particularly older patients with diabetes and vascular diseases. Important regional variations are observed (RIDT data): 1995-97 dialysis provision (3-25 centres pmp; private: 2%-83%) - 1999 frequency figures: RRT incidence (75-200 pmp); dialysis prevalence (437-842 pmp), transplant prevalence (21-344 pmp) - 1995 mortality (8%-15%). Data on referral modalities and access to RRT seem scarce. Some studies assess hospital use among dialysis patients, while no papers have been found on the decision-making processes in local planning and policy. CONCLUSIONS: RDTR are still under-utilised for developing local data, both for further investigating epidemiological and clinical differences, and for guiding decisions in regions with different resources and cultural background. We believe that linking RDTR data with other regional databases represents an effective strategy.

[The need for integrated care of patients with chronic nephropathies: the epidemiology of 'late referral']. / Epidemiologia dei bisogni di gestione integrata: il "late referral" in Nefrologia.

BACKGROUND: The recent need for information has prompted this collaboration between health system epidemiologists (Basilicata) and clinicians to compare models of 'local' epidemiology in the management of diseases. The referral of patients to a nephrologist represents a working hypothesis of research- intervention. METHODS: Analysis of renal registry (RR) and administrative databases (hospital discharge abstracts/HDA, ambulatory);ad hoc surveys. RESULTS: Patients on dialysis between 1994 and 1998 are 594, cumulative deaths are 190 (32%). Males and the elderly (age = 65 years) are associated with more than 50% and threefold increase in relative risk of death, and with a diabetic nephropathy of 60% vs other renal diseases. Of 570 patients alive in 1996, 442 are linked with 2,628 HAD. Comorbid conditions are underreported in the RR (the Charlson index has been computed using HDA). Of 66 new dialysis cases, 31 are referred to a nephrologist only 6 months before the start of dialysis (47%) (22% diabetics). Patients discharged with chronic nephropathies (CN) and diabetes are 21% of CN patients (5% of diabetics). Of 100 patients with pre-end stage renal disease and diabetes, only 11-14 are discharged from the nephrology ward. At the local level, 3 out of 4 patients with serum creatinine higher than 1.5 mg/dl are not referred to a nephrologist. The prevalence of CN may vary from 0.4% to more than 1%. CONCLUSIONS: While an improvement in health databases in the regions is underway, collaboration studies are essential for planning specific interventions for prevention and management of diabetic nephropathy to improve the use of resources in nephrology.

[Experimentation with a socioeconomic deprivation index in Basilicata]. / Sperimentazione di un indice di svantaggio socioeconomico in Basilicata.

Deprivation measures have become important tools, in microarea and small area studies, both for examining variations in health and health care, and for planning services and allocating resources. To value the level of municipal deprivation in Basilicata (Southern Italy), 1991 Census data were used. As a first analytic step, variables selected as deprivation measures were calculated. "Elderly" variable was included at the first step since it was considered as an indicator of social burden and need. As a second analytic step, factorial analysis was performed in order to help in selecting the most valuable ones. The final choice led to five variables (elderly, low education, unemployment, no indoor bathroom, lone parent with children) which were combined in an Index of Deprived Area (IAS). The IAS showed a variation between -5.4 and 7.4. To validate the IAS, the municipal level of income was used: the index increased with decreasing income (r = -0.5). Municipalities were then ranked according to their IAS (decreasing) and divided into five deprivation categories, with about equal population number in each group. After excluding the "elderly" indicator, the ranking order showed irrelevant changes (modified IAS). Overall, the IAS seemed to well describe the difference among Municipalities, particularly between the first quintile (54 small towns with high prevalence of old people) and the last group (the urban area of the region). The developed tool and the obtained results may be used by administrators and health/social workers and professionals in charge of the Regional Epidemiological Observatory to improve the selection of health and social indicators for Local Health Authorities and Municipalities.

[Hospital management of the acute cerebrovascular patient. Results of a study carried out in the region of Abruzzo]. / La gestione ospedaliera del paziente cerebrovascolare acuto. Risultati di uno studio condotto nella Regione Abruzzo.

Acute cerebrovascular disease is a major cause of morbility, disability and mortality. Despite its enormous importance in term of public health, considerable uncertainty still exists regarding the efficacy and cost-effectiveness of many routine clinical practices currently used in the management of stroke. A multicenter study was conducted on 204 patients (100 males and 104 females; mean age 71.5 years; range 21-94) consecutively admitted in 12 hospitals in Abruzzo (Southern Italy) from September 1, 1990 to December 31, 1990, because of sudden onset of neurological deficit which was presumed to be of a vascular origin. One hundred and ninety-six patients were hospitalized less than 24 hours after stroke onset. Cerebral computerized tomography was performed in 135 patients, but only 43 had the examination within 24 hours of symptoms onset. Other instrumental investigations (carotid doppler, transcranial doppler, echocardiography, etc.) were rarely performed. Ischemic stroke was diagnosed in 69 patients, intraparenchimal hemorrhagic stroke in 33, sub-arachnoid hemorrhage in 10, undefined stroke in 40 and transient ischemic attack in 49. Antioedema were largely used in the first 48 hours after admission, and osmotic diuretics (glycerol and mannitol) were preferred to steroid treatment. Antiplatelet drugs (25.8%), calcium antagonists (20.1%) and barbiturates (19.1%) were also frequently prescribed. In conclusion, our study had shown an absolute lackness of standard criteria for management of patients with acute cerebrovascular disease.

Family history and socioeconomic factors as predictors of myocardial infarction, unstable angina and stroke in an Italian population. PROGETTO 3A Investigators.

A comprehensive case-control study was conducted in an Italian region in order to compare the influence of family history of cardiovascular events, socioeconomic factors, social networks, and their joint associations with major risk factors, on the risk, of myocardial infarction (MI), unstable angina (UA) and ischemic stroke (IS). A total of 513 patients with MI, 178 with UA, 237 with IS, and 928 hospitalised controls were recruited. The odds ratio (OR) of MI for two or more relatives with a positive history of MI was 3.6 (95% CI: 1.8-7.3). Family history of MI was predictive for UA (OR = 5.8; 95% CI: 1.2-28.7), but not for IS. A family history of stroke was more associated with the risk of MI than of IS. After adjustment for known risk factors, the OR of MI for more educated people was 2.1 (1.3-3.6) compared with less-educated people. Large family size seemed to be protective for MI. The effect of major risk factors on MI ranged from additive (diabetes) to multiplicative jointly with high education and family history of MI. A family history of stroke increased IS risk threefold jointly with smoking and hyperlipidemia, and eightfold with diabetes. Besides a family history of MI and IS, in this community a higher educational status seems to better identify groups at increased risk of MI. The joint associations have important preventive implications since by identifying high-risk individuals (for MI and IS) a more careful assessment and control of risk factors amenable to intervention may be performed.

A positive relation between high hemoglobin values and the risk of ischemic stroke. Progetto 3A Investigators.

We examined the relationship between the hemoglobin concentration and the risk of ischemic stroke using data from a hospital-based case-control study. A total of 143 patients (age 30-69 years) with a diagnosis of cerebral infarction confirmed by computerized tomography scan and 143 age- and sex-matched controls entered the study. Hemoglobin was higher in the patients with stroke (14.2 +/- 1.6 g/l, mean +/- SD) than in controls (13.7 +/- 1.6 g/l; p < 0.05). Compared with subjects with hemoglobin levels of less than 13 g/l (reference category), the relative risk of ischemic stroke, after allowance for potential risk factors, was 2.0 (95% CI 0.8-4.9) for the 13-13.9 g/l quartile, 2.8 (95% CI 1.2-6.5) for the 14-14.9 g/l quartile, and 3.2 (95% CI 1.4-7.4) for the 14 + g/l quartile (chi 2 for linear trend 7.27, p < 0.01). We conclude that the hemoglobin concentration may be an indicator of risk for ischemic stroke.

Serum cholesterol and risk of ischemic stroke: results of a case-control study. On behalf of PROGETTO 3A Investigators.

BACKGROUND: While a positive relation between serum cholesterol and the risk of myocardial infarction has been consistently reported, the association between serum cholesterol and the risk of ischemic stroke lacks consistency. To further investigate the strength of cholesterol as a risk factor for myocardial infarction and stroke we conducted a comparative study. METHODS: A case-control study was conducted from 1990 to 1992. A network of 21 hospitals in Abruzzo, southern Italy, was created. First, computerized tomography scans confirmed ischemic stroke patients (230 with median age: 64; range: 31-69 years) and 230 sex- and age-matched controls with acute disorders unrelated to known cardiovascular risk factors. Acute myocardial infarction patients (513) and 513 matched controls were simultaneously recruited for a parallel study comparison. Total serum cholesterol concentration was measured within the first 48 hr following admission and the response to a structured questionnaire was evaluated. RESULTS: The mean (standard deviation) serum cholesterol level was 220.7 mg/dl (50.9) among stroke patients and 201.5 mg/dl (41.6) among controls (P < 0.0001). Compared with the lowest quintile (< 160 mg/dl), the odds ratio of ischemic stroke for patients in the highest quintile (> 240 mg/dl), after simultaneous adjustment for other potentially confounding covariates, was 2.6 (95% confidence interval: 1.4-4.8). A significant linear trend in risk was found (chi 2 1 df = 7.27, P < 0.01). Within each total serum cholesterol quintile, adjusted odds ratios for myocardial infarction were higher than that for ischemic stroke, and a stronger linear trend in risk was found (chi 2 1 df = 21.3, P < 0.0001). CONCLUSIONS: Our data confirm the strong linear relationship between total serum cholesterol and the risk of myocardial infarction and suggest that, at least in our population, cholesterol seems to be an indicator of ischemic stroke risk.

Methods of blood saving in revision surgery of the hip.

The blood saving protocol, which is the product of 15 years of experience, has gradually been improved, until the current form has been achieved, which includes predeposit, acute intentional isovolemic hemodilution, controlled hypotension, intraoperative blood recovery, postoperative monitoring and blood recovery, external compressive elastic dressing. The acceptance of values for hemoglobin which may even be < 8 g/dl during the late postoperative period, as long as this is well-tolerated by patients, has allowed us to drastically reduce the use of homologous transfusions. Over the last 2 years, out of 59 autotransfused patients submitted to revision surgery of the hip, only 9 (equal to 15%) required homologous transfusion. An analysis of the data shows that the use of homologous blood is associated with the presence of ischemic cardiopathy (p < 0.001) and with a predeposit which is less than 4 units of blood (packed red blood cell+fresh frozen plasma) (p = 0.05).

[Can the changes in dietary fat intake reduce the risk of onset and development of atherosclerosis and of ischemic cardiopathy in particular?]. / Può la modificazione dei grassi alimentari ridurre il rischio di insorgenza e sviluppo dell'aterosclerosi ed in particolare della cardiopatia ischemica?

In this review we have collected data from epidemiologic studies and clinical trials published from 1968 to 1989 on the relationship between dietary fat and risk of coronary heart disease. Although the reported observational studies of diet and coronary heart disease provide general support for the classic diet-heart hypothesis, evidence of specific dietary lipids is weak. A positive association with saturated fat intake was seen in two prospective studies. A positive association with cholesterol intake was found in only two cohort studies, and an inverse relationship with polyunsaturated fat intake in only one. Clear evidence from dietary trials in the prevention of coronary heart disease has not been found. The analysis of trends in coronary heart disease and stroke mortality of developed countries has shown a discrepancy between fat intakes, cholesterol levels and mortality. The reduction in intake of certain foods "at high risk" such as meat, eggs, milk and cheese, as a preventive intervention, is based on weak scientific evidence. A strategy program has to emphasize the maintenance of ideal body weight by caloric control, an adequate level of physical activity, and the control of other risk factors such as hypertension, hypercholesterolemia, and diabetes.

Changes in plasma DHEAS circadian rhythm in elderly men.

Several reports focused the attention on aging that appears to exert an influence on the temporal structure in the endocrine system of man. Considering that: a) DHEAS blood levels consistently decrease as men age and b) this hormone might be involved in the early development of atherosclerosis, aim of the present work to detect: 1) the possible existence of a circadian rhythm of DHEAS in young and elderly men, 2) eventual change in parameters of other hormonal rhythms. 11 young healthy males (28 +/- 2 yrs) and 12 elderly males (73 +/- 1 yrs) were studied over a 24-hr span during spring. They were submitted to the circadian protocol for the evaluation of DHEAS, PRL and cortisol plasma levels. A significant circadian rhythm of DHEAS plasma levels was observed in the young men (mesor micrograms/dl 273.13 +/- 38.25, amplitude 41.37 +/- 9.29, acrophase at 1351 hr). In the elderly subjects no circadian rhythm was found, but amplitude and mesor appeared statistically reduced in comparison with young people (p less than 0.005 and p less than 0.001, respectively). Confirming previous results the circadian pattern of PRL and cortisol did not change in the two groups. It is suggested that both loss of rhythmicity and low levels of blood DHEAS in elderly may be involved in aging process and considered an aspect of the endocrine temporal structure of old people.