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Leptin values are higher in obesity. Physical exercise reduces fat mass (FM) and decreases leptin levels. Intensity of physical training seems to play a role in reducing circulating leptin. In 16 obese subjects (8 men and 8 women, age 38.6±3.9 years, BMI 35.9±1.8 kg/m(2)), leptin was sampled before and after 4 weeks of controlled training. Eight subjects (4 men and 4 women) performed an aerobic training schedule (Group A), the remainders an aerobic training program with a bout of work beyond the anaerobic threshold (AT) (Group B). Training determined a reduction in leptin levels in both groups, which was significant in Group A (12.2 vs. 27.8 µg/l, p<0.05), even when related to the change in FM (0.372 vs. 0.762 µg/l/kg, p<0.05). FM decreased significantly in Group B when compared to Group A (-7.4 vs. -2.6 kg, respectively, p<0.001). While in Group A the slight loss of FM was aggregated to a significant decrease in leptin levels, the opposite occurred in Group B. In Group A, leptin lowering was proportional to the amount of total work performed (p<0.001, R(2)=0.89). In obesity, a reduction is observed in leptin levels after short-term training, which is seemingly dissociated from concomitant decrease of FM. Aerobic training alone appears to be linked to a greater leptin reduction, which is well correlated with the amount of work performed.

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OBJECTIVES: To assess the diagnostic value of bronchoalveolar lavage fluid (BALF) ferritin as a lung tumor marker by comparing serum and BALF ferritin concentrations in patients with peripheral lung cancer versus control subjects with benign lung disease, and to examine the theory of ferritin compartmentalization around the tumor area by comparing ferritin concentrations in serum and bilateral (affected and unaffected side) BALF in cancer patients. METHODS: Four groups of patients were investigated: 10 control nonsmokers, 10 control smokers, 10 smokers with chronic obstructive pulmonary disease (COPD), and 22 patients with primary bronchogenic carcinoma. A bronchoalveolar lavage (BAL) was performed in all subjects (both sides in 13 oncological patients, one side in the others) and samples of BALF and blood were submitted to biochemical analysis. RESULTS: As a lung tumor marker, BALF ferritin showed 54% sensitivity and 93% specificity and serum ferritin 22% sensitivity and 93% specificity. A significant difference was observed between the two sides in the cancer patients (p = 0.033), and between BALF ferritin from the affected side and COPD patients (p = 0.025). Greater differences were obtained when BALF ferritin in the affected side of cancer patients was compared with values in both control nonsmokers (p < 0.0001) and control smokers (p < 0.001). CONCLUSIONS: These findings seem to confirm the relative diagnostic value of BALF ferritin as a lung tumor marker and the theory of ferritin compartmentalization. However, further studies are required to clarify the relations between iron and ferritin on the one hand and inflammation, tumorigenesis and host response on the other.

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Work capacity and cardiopulmonary performance were studied in a group of 11 young obese subjects (BMI 39.9 kg/m2) and a group of 10 young normal subjects (BMI 22 kg/m2). First of all they underwent an incremental cycle ergometer test up to exhaustion. Subsequently, every subject of the two groups performed a constant work rate test at different work loads to estimate cardiac output (Q) below anaerobic threshold (AT) by a 20-second CO2 rebreathing method. Obese subjects had a significantly lower AT (79 vs. 109 W). The ratio between oxygen uptake and heart rate (VO2/HR) (O2 pulse) was higher in the obese group; nevertheless, this variable became significantly lower if we took into consideration the ratio between O2 pulse and kilogram fat-free body mass or kilogram body weight. Both these observations suggest that their reduced work tolerance is linked with a reduced oxygen supply to the muscles in activity. Q increased in similar ways in obese and normal subjects at the preset work rates. The ratio Q/body surface (cardiac index; CI) that we considered in order to try to minimize the differences in body sizes between the two groups, increased less in response to increasing work rates in our obese subjects than in normal subjects. As a whole, these data appear to be in line with a relatively less efficient cardiac performance during progressive work rates in obese subjects.

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A modified Casson equation was established, verified satisficatorily for real conditions and suggested for use in clinical hemorheology. It provides 5 Casson parameters, i.e., Casson yield stress, Casson viscosity, the first critical point of shear rate to cause rouleaux to be broken down into smaller units, the second critical point of shear rate to completely disaggregate into individual erythrocytes, the difference between the two critical points, and also gives two series of the 5 above-mentioned Casson parameters, respectively, under original hematocrit and the standardized hematocrit of 45%. This equation not only reveals the apparent abnormalities of hypertensive patients and normalities of the healthy persons, but also reveals hidden abnormalities for patients with either low or high hematocrit. For 20 cases of hypertensive patients with low hematocrit, the 5 Casson parameters have lower values than control, but the modified equation reveals their hidden higher values than control when their hematocrit is standardized to 45%. For 7 cases of polycythemia complicated with hypertension, the 5 Casson parameters are higher at their original hematocrit, and the modified equation reveals the higher parameters than control also when the hematocrit is standardized to 45%. For 8 cases of polycythemia without complications, the 5 Casson parameters are higher at their original hematocrit than control, while the modified equation still reveals their normalities when standardizing their hematocrit to 45%.

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The aim of this study was to evaluate the selection criteria and characteristics of the patients who have access to rehabilitation facilities after having experienced an acute stroke. Between January 1993 and February 1994, 383 patients were recruited in 13 hospitals in Lombardy, and telephonically followed up four months after study entry. The data were collected by members of the Associazione Volontari Ospedalieri (Hospital Volunteers' Association). The 4-month mortality rate was 23%. The primary selection criterion for gaining access to rehabilitation facilities was the degree of disability; the secondary factor was age. Rehabilitation facilities were not available to very severely afflicted or self-sufficient patients, but were preferentially made available to young, partially-dependent patients. A rehabilitative intervention within the first month was made available to fewer than 50% of the patients for whom it was indicated. The absence of care for elderly patients and the delay in its availability for those who actually receive it underline the need for new organisational methods. The data presented here also show that voluntary associations can work as observers of the health service. A more complete study is required in order to understand the real dimensions of the problem and the clinical and social characteristics of the population involved.

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The study aimed at evaluating selection criteria and basic characteristics of acute stroke patients admitted to rehabilitation programs. From January 1993 to February 1994, 373 patients from 13 hospitals of the Lombardy region were admitted to the study. The 4 months telephone follow-up was performed by the AVO (Hospital Volunteers Association) volunteers. The 4 months fatality rate was 23%. The patients with a higher disability level were prescribed a rehabilitation program. Rehabilitation resources were not available for very severe or dependent patients being mostly the younger and partially dependent patients more often referred to the services. Only 50% of eligible patients received a rehabilitation intervention within 1 month from the index episode of stroke. The lack of caring resources and the long waiting times stress the need for a reorganization of the rehabilitation services. This study also shows that volunteers can play a role of stricter collaboration with doctors and are ready to collaborate in data collection. A larger and more detailed study is warranted in order to gain a better knowledge on the problem and on the clinical and social characteristics of the stroke victims.

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Some controversial issues exist whether regional cerebral blood flow (rCBF) changes are present both in migraine with and without aura during the interictal period. For this reason we have studied rCBF characteristics in migraine patients when headache-free. rCBF examinations were performed by the 133Xe inhalation method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10 migraine patients with (A+) and on 10 without (A-) aura. The values of each patient were compared with the age-matched control population mean by a computer-assisted mapping system that allows statistical analysis in real time. To compare inter-individual variability 10 subjects, out of 39 normals, constituted an age-, sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant alterations of CBF in comparison with the age-matched control population. The analysis between the age-, sex- and CO2 matched groups showed significant differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period a derangement of the cerebral perfusion is present in both migraine with and without aura, suggesting they are due to the same disease process. Furthermore they show the usefulness of a computer-assisted mapping system, suitable for clinical use, in discovering small alterations in cerebral perfusion.

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Along with other risk factors in coronary heart and cerebrovascular disease, obesity is frequently associated with the development of atherosclerosis, a disease in which the rheological characteristics of blood are important. We studied the influence of weight reduction on haemorheological parameters of 20 obese adolescents (10 female, 10 male; aged 12-17 years) without metabolic and/or cardiovascular diseases. The control group composed 39 health non-obese subjects (19 female, 20 male; aged 13-17 years). At the beginning of the study the mean (+/- s.d.) body mass indices (BMI) of the obese adolescents were 36.0 +/- 5.3 kg/m2 in males and 36.8 +/- 5.0 kg/m2 in females. This was significantly reduced (31.5 +/- 4.9 kg/m2 in males and 32.5 +/- 4.7 kg/m2 in females) after one month following a diet of 1000 kcal/day: 25% proteins, 26% lipids and 49% carbohydrates. Before dieting, plasma fibrinogen level, whole blood viscosity at low shear rates and plasma viscosity were significantly higher in obese patients than in normal subjects, while the microhaematocrit values of the two groups were not significantly different. After dieting, plasma viscosity, the plasma fibrinogen level and the mean erythrocyte aggregation index of the patients decreased significantly compared to basal values, while whole blood viscosity did not change. Our data seem to indicate that short-term diet improves the haemorheological pattern in obese adolescents, probably as a consequence of an important metabolic rearrangement.

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An impaired plasma Epinephrine (E) and Norepinephrine (NE) response has been described in obese patients during physical exercise. Serum potassium level is influenced either by physical exercise or by the adrenergic system. We studied 12 young obese patients and 12 young controls, all without any cardio-respiratory disorders, who underwent a cycloergometric test with steps of 20 watts every four minutes until exhaustion. During the test we recorded serum potassium levels, E and NE, insulin, glucose and RQ to confirm or not the observation of the reduced adrenergic response in obese patients. During exercise, although both groups reached a not significantly different mean peak value of maximal activity, E and NE increased, more in the controls than in the obese subjects (at peak of exercise 221 +/- 44.1 vs 71 +/- 21.5 pg/ml respectively for E; 2035 +/- 164.8 vs 1141 +/- 313.7 pg/ml respectively for NE). RQ was constantly lower in the obese patients than in the normals both during and after the stress. In both groups potassium increased significantly, but the obese patients had a significantly lower increment at peak of activity when compared to the controls (delta K+: 0.52 +/- 0.11 vs 1.007 +/- 0.17 meq/l respectively, p < 0.05). Insulin and glucose had a behaviour in line with literature in both groups. The behaviour of potassium could be an index of a higher effect of beta-adrenergic system in obese patients than in normals despite the different increases of catecholamines in the two groups. This hypothesis may agree with the preferential metabolic use of fatty acids in our obese patients as indicated by RQ values.

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More rapid and more shallow breathing (RSB) than usual, manifested by a lower tidal volume and greater breathing frequency at a given level of ventilation, may be caused by inspiratory muscle fatigue and pulmonary congestion. It has been observed during recovery in young trained adults after very high exercise levels and in middle-aged patients with cardiac disease, after their maximal work load. We studied the breathing pattern during and after exercise testing up to the maximal work capacity in a group of normal untrained, young people and in a group of young obese subjects. RSB was present in normal subjects after a work load which required a maximal O2 consumption near the theoretical value (93% in our cases) and was not present in obese patients probably because neither inspiratory muscle fatigue, nor pulmonary congestion occurs in these subjects. Maximal heart rate at peak of exercise was significantly higher in normal subjects and a direct correlation between delta Vt and maximal heart rate was found in all normal subjects. This is compatible with the hypothesis that RSB is mainly due to an initial interstitial pulmonary edema, as supposed by other authors.

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We report creatine kinase (CK) and CK-MB values during a cycloergometric test up to maximal work capacity in 10 normal subjects aged 20 to 39 years (mean body mass index, 22 kg/m2) and 11 obese patients aged 17 to 42 years (mean body mass index, 41 kg/m2), all without any cardiorespiratory diseases. Total CK was significantly higher in obese patients. The CK-MB was not significantly different between the two groups, except at the first recovery when it was increased in obese patients and decreased in normal subjects. These results could be due to more important total stress of the total musculature, especially cardiac, and especially cardiac musculature in obese patients during a physical effort. Considering the mean values of total CK of our obese patients, it may be possible that they have myocardial damage at percentages of CK-MB less than those of lean subjects generally accepted at more than 4 percent. Moreover, in obese heart patients myocardial distress during exercise testing may be present despite heart rate at peak exercise beneath the theoretic maximal.

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The beta adrenergic-modulated Na+/K+ ATPase pump rate of red blood cells was measured in vitro in 18 non diabetic obese patients. After challenge of erythrocytes with beta adrenergic selective agonist Salbutamol, the decrement of the K+ concentration in the suspending medium was assumed to be related to the Na+/K+ ATPase pump rate or to the number of beta 2 receptors. The mean K+ uptake was markedly increased in the erythrocytes of obese patients (1.58 mEq/l SD 0.18) if compared with 38 normal subjects (1.30 mEq/l SD 0.11) and with a population of 30 atopic patients that we have previously reported to have a reduced red cells beta 2 receptor activity (1.09 mEq/L SD 0.11). These results are not consistent with the hypothesis that a reduction in the Na+/K+ ATPase pump rate (at least in red blood cells) may be responsible for decreased metabolic rates leading to obesity. Since the autonomic nervous system is involved in the regulation of the cardiovascular system, it is conceivable that an increased Na+ ATPase pump rate (or supersensitivity) may be responsible of the increased incidence of hypertension, congestive heart failure and unexplained sudden death associated with obesity in some patients.

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To assess the responsiveness of the cerebral vessels to chronic hypercapnia, we measured middle cerebral artery flow velocity by transcranial Doppler ultrasound in 20 normal subjects and in 14 COLD patients before and after stimulation by progressive hypercapnia (rebreathing test) or by intravenous administration of an acetazolamide bolus. The results showed no statistically significant difference in baseline flow velocity between the normal subjects and the COLD patients. The COLD patients showed a reduced cerebral vascular responsiveness to both stimuli. Cerebral blood flow is normal in chronic hypercapnia and the mechanism by which compensation is achieved leads to a decrease in cerebral vascular responsiveness.

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The influence of the rheological properties of the blood on cerebral perfusion is still unresolved. Data on normal subjects are lacking and difficulties arise regarding the effect of blood viscosity owing to its close relationship with hematocrit. For these reasons we have studied the relationship between two rheological hematocrit-independent parameters and CBF in normal subjects of various ages. 36 normal volunteers, aged 20-74, free from risk factors, have been studied. CBF was measured by the Xenon inhalation method. Erythrocyte aggregability was expressed as Mean Erythrocyte Aggregation Index (MEA). Plasma fibrinogen concentration was evaluated by the coagulative method in 26 subjects. No correlation was found between CBF and MEA or fibrinogen in the subjects under the age of 45. A significant negative correlation was found between CBF and MEA (p = 0.015) and between CBF and fibrinogen (p = 0.011) in the subjects over 45. These data show that cerebral perfusion is influenced by the rheological properties of the microcirulation only with aging. We suggest that a "rheological autoregulation" exists and that it works properly in youth, only to be lost with physiological aging. This finding can be of significance in the pathogenesis of cerebrovascular disease processes in humans.

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Twelve obese patients (six male subjects) aged 17 to 42 years with a mean body mass index (BMI) of 40 kg/m2 and 12 normal subjects (six male subjects) aged 19 to 39 years with a mean BMI of 22 kg/m2 underwent a cycloergometric test until exhaustion to assess work capacity and cardiopulmonary adaptations of the two groups. Minute ventilation, expiratory gas concentrations, and heart rate, together with anaerobic threshold (AT) were determined in each subject during the test. The same subjects were then submitted to normocapnic hyperpnea at rest to assess the oxygen cost of breathing. We found that in the obese patients, the maximal sustainable work rate was not different from that of controls (120 vs 136 W) while AT was significantly lower (78 vs 110 W). Nevertheless, there was no difference in maximum VO2 and in VO2 at AT levels (expressed in milliliters per minute) indicating that cardiac, pulmonary, vascular, and muscle performance did not differ from obese to normal subjects. Greater muscular effort was needed by obese patients when moving their heavier legs and less when doing external work with a decreased gross mechanical efficiency and an identical net mechanical efficiency between the two groups.

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Focus is an expert system developed to diagnose, by the findings on neurological examination, the anatomic location of an acute neurologic event. The inference engine uses a forward tracking algorithm and a rule based data base that includes associations of neurological signs with specific anatomic areas. Focus is linked to a data base in which all personal cases and final diagnoses confirmed by laboratory studies are stored. This makes it possible to assess the validity of the system's diagnoses and use personal cases as additional example to the revision of the rules. The program is easy to use and runs on MS-DOS microcomputer. Furthermore the diagnostic rules are accessible so Focus may furnish an interactive teaching device.

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Cerebral blood flow (CBF) was studied at rest by 133-Xenon inhalation method in 15 normal subjects, in 10 patients with cerebral infarction and normal angiograms of major cerebral arteries and in 28 patients with unilateral stenosis-occlusion of the internal carotid artery (ICA), with or without cerebral infarction. All the normals and 20 patients with ICA stenosis-occlusion were tested again after cerebral vasodilatation induced by an intravenous bolus of acetazolamide. At rest the patients with cerebral infarction, irrespective of whether ICa stenosis-occlusion was present or not, showed abnormal side-to-side CBF asymmetry. After cerebral vasodilation variations in side-to-side asymmetry were shown to depend on the inefficiency of the collaterals and not on the degree of ICA obstruction or on the presence of cerebral infarction. These data indicate that at rest side-to-side CBF distribution is influenced more by the presence of an ischemic zone than by a ICA stenosis-occlusion and that under these circumstances the hemodynamic effect of the vascular stenosis cannot be assessed. After cerebral vasodilatation a subset of patients--irrespective of the degree of ICA obstruction and of whether or not cerebral infarction is present--with true cerebrovascular insufficiency can be isolated.

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Eleven obese patients, 5 males; age: 17-42; body mass index (BMI): 40; % of ideal weight: 187%, and 10 normal subjects (5 males; age: 19-39; BMI: 22; % of ideal weight: 103%), both groups without heart and respiratory disorders, underwent a cycloergometric test with subsequent 20-watt increases every 4 min until exhaustion. During the test, ventilation/minute, expiratory gas concentration and heart rate were measured, and the anaerobic threshold (AT) was determined in each subject. The obese patients showed a significantly lower AT than normal subjects (p less than 0.01); showing values which decreased with the increase in the grade of obesity expressed in BMI or in percent of their ideal weight. Moreover, in the obese patients, the O2 consumption (VO2) had significantly increased compared to that of normal subjects at no resistance and at all work levels. The negative correlation between the AT value and the BMI in obese patients can attribute their increase in VO2 during stress to (1) the inertial overloading caused by obesity especially considering the adipose tissue of their legs, or (2) to their level of 'fitness' being lower than that of normal subjects.

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In order to determine whether the alterations of immunoregulatory T cells described both in smokers and in patients with lung cancer occur in the deep lung as well as in peripheral blood, we analyzed T lymphocyte subpopulations in bronchoalveolar lavage (BAL) and in the blood of 12 patients with untreated lung cancer and of 8 controls. The immunocompetent cellular population of BAL fluid analyzed by differential cell count of alveolar macrophages, lymphocytes and neutrophils did not show considerable differences in the two groups studied. By contrast, the analysis of BAL T lymphocytes and their subsets showed significant alterations in patients compared with controls: a percentage increase of OKT3+ and OKT8+ lymphocytes and a decrease of the OKT4+/OKT8+ ratio was found in both the involved and uninvolved lung of patients. The immunologic pattern of T lymphocytes in blood did not show significant differences between patients and controls. Our data indicate that alterations in immunoregulatory T cells in lung cancer are more pronounced in BAL fluid obtained from both lungs than in peripheral blood.

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