In-flight ultrasound identification of pneumothorax.

Ultrasound is a standard adjunct to the initial evaluation of injured patients in the emergency department. We sought to evaluate the ability of prehospital, in-flight thoracic ultrasound to identify pneumothorax. Non-physician aeromedical providers were trained to perform and interpret thoracic ultrasound. All adult trauma patients and adult medical patients requiring endotracheal intubation underwent both in-flight and emergency department ultrasound evaluations. Findings were documented independently and reviewed to ensure quality and accuracy. Results were compared to chest X-ray and computed tomography (CT). One hundred forty-nine patients (136 trauma/13 medical) met inclusion criteria. Mean age was 44.4 (18-94) years; 69 % were male. Mean injury severity score was 17.68 (1-75), and mean chest injury score was 2.93 (0-6) in the injured group. Twenty pneumothoraces and one mainstem intubation were identified. Sixteen pneumothoraces were correctly identified in the field. A mainstem intubation was misinterpreted. When compared to chest CT (n = 116), prehospital ultrasound had a sensitivity of 68 % (95 % confidence interval (CI) 46-85 %), a specificity of 96 % (95 % CI 90-98 %), and an overall accuracy of 91 % (95 % CI 85-95 %). In comparison, emergency department (ED) ultrasound had a sensitivity of 84 % (95 % CI 62-94 %), specificity of 98 % (95 % CI 93-99 %), and an accuracy of 96 % (95 % CI 90-98 %). The unique characteristics of the aeromedical environment render the auditory element of a reliable physical exam impractical. Thoracic ultrasonography should be utilized to augment the diagnostic capabilities of prehospital aeromedical providers.

Temporal Dysregulation of the Angiopoietin-2/-1 Ratio After Trauma and Associations With Injury Characteristics and Outcomes.

Traumatic injury and hemorrhagic shock result in endothelial cell activation and vascular dysfunction that, if not corrected, can propagate multiorgan failure. Angiopoietin-1 and angiopoietin-2 are important regulators of endothelial cell function, and the ratio of plasma angiopoietin-2-to-1 is a useful indicator of overall vascular health. We therefore characterized plasma angiopoietin-2/-1 ratios over time after trauma in adults in an effort to gain insight into the pathophysiology that may drive post-traumatic vasculopathy and organ injury. We performed a single-center prospective observational study to measure plasma angiopoietin-1 and -2 levels and determine angiopoietin-2/-1 ratios in adult trauma patients upon hospital arrival and after 12, 24, and 48 h. Compared with levels in healthy adults, angiopoietin-1 levels were significantly elevated at hospital arrival, and angiopoietin-2 levels were significantly elevated at 12, 24, and 48 h. These kinetics translated in angiopoietin-2/-1 ratios that were significantly greater than controls at 24 and 48 h. After regression analysis, elevated angiopoietin-2 levels were independently associated with blunt injuries at admission, with coagulopathy at admission and 12 h, and with hemorrhagic shock at 24 and 48 h. Significant correlations were observed between both angiopoietins and 24-h transfusion requirements. Angiopoietin-2/-1 ratios correlated with mechanical ventilation duration and intensive care unit and hospital lengths of stay. In this study, we demonstrate novel temporal associations between angiopoietin dysregulation and blunt injuries, acute coagulopathy, and hemorrhagic shock. Moreover, our findings highlight the presence of endothelial activation following traumatic insults in adults that may contribute to worse clinical outcomes.

Plasma Angiopoietin-2/-1 Ratio is Elevated and Angiopoietin-2 Levels Correlate With Plasma Syndecan-1 Following Pediatric Trauma.

BACKGROUND: Angiopoietin-1 (Agpt-1) and Agpt-2 are cytokine regulators of vascular endothelial integrity. Elevated plasma Agpt-2 levels and ratios of Agpt-2:Agpt-1 are associated with adverse outcomes in adult trauma and pediatric sepsis populations. However, the behavior of the angiopoietins after pediatric trauma has not been characterized, and their relationship to endothelial glycocalyx damage, indicated by plasma syndecan-1 (Syn-1) levels, has not been established. METHODS: We performed a secondary analysis of prospectively collected data from 52 pediatric trauma patients and 12 control patients at a level one pediatric trauma center from 2013 to 2016. We measured Agpt-1, Agpt-2, and Syn-1 levels from plasma taken upon hospital arrival and 24 h after admission. Angiopoietin levels were compared to controls, and the correlation between Agpt-2 and Syn-1 was assessed. RESULTS: Plasma Agpt-1 and Agpt-2 levels are elevated immediately after pediatric trauma compared with controls. At 24 h, trauma patients demonstrated significantly elevated plasma Agpt-2:Agpt-1 ratios relative to controls due to decline of Agpt-1 levels to near that of controls. Higher 24-h Agpt-2 levels are associated with more hypoperfusion, and elevated 24-h Agpt-2:Agpt-1 ratios are associated with adverse clinical outcomes. Significant positive correlations between Agpt-2 and Syn-1 upon admission and at 24 h after injury were identified. CONCLUSION: Our findings suggest dysregulation of circulating angiopoietins after pediatric trauma that may be linked to endothelial glycocalyx injury. Larger prospective studies are needed to validate these findings and determine the relationship of Agpt-2 with other markers of endotheliopathy.

Pulmonary metabolism of mutagens and its relationship with lung cancer and smoking habits.

The S-12 fractions of lung peripheral parenchyma obtained from 80 male individuals, aged 17-71 years, were assayed as blind samples for the ability either to convert promutagens into bacterial mutagens or to decrease the potency of direct-acting mutagens in the Ames reversion test. In this system, lung preparations were completely ineffective in activating an N-nitroso compound (i.e., N-nitrosomorpholine) and polycyclic aromatic hydrocarbons [i.e., 3-methylcholanthrene and benzo(a)pyrene] or their metabolites [i.e., 3-hydroxy-benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol]. They yielded a borderline and sporadic activation of a cigarette smoke condensate, and a weak but frequent activation of an aromatic amine (i.e., 2-aminofluorene), of a heterocyclic amine (i.e., 2-amino-3,4-dimethylimidazo[4,5-f] and of a diamide (i.e., cyclophosphamide). The pulmonary metabolism was more oriented in the sense of detoxification, as shown by the consistent decrease of potency of direct-acting mutagens, including a metal (i.e., sodium dichromate), an acridine and nitrogen mustard derivative (i.e., 2-methoxy-6-chloro-9-[3-(2-chloromethyl)aminopropylamino]acridine or ICR 191), an epoxide (i.e., epichlorohydrin) and an N-oxide (i.e., 4-nitroquinoline-N-oxide). As assessed by means of a numerical score quantifying the variation of mutagenicity, a marked interindividual variability (up to 20-fold) was detected in the ability of lung specimens to affect the mutagenicity of test compounds. Such variability was not significantly related to the protein concentration of S-12 fractions, nor to the age of the patients under scrutiny, who during hospitalization were on normal institutional diets and did not receive any special drug treatment. The only significant difference between 20 noncancer and 60 lung cancer patients, irrespective of the histological type, was a decreased activation of cyclophosphamide in the latter group. Probably due to the high prevalence of smokers among lung cancer patients, a significantly decreased activation of cyclophosphamide was also observed in the group of smokers. Smoking habits were associated with a stimulation of detoxifying mechanisms which, in agreement with the results of a previous study with human alveolar macrophages (F. L. Petrilli et al., J. Clin. Invest., 77:1917-1924, 1986), was significant in the case of sodium dichromate. Such effect was further enhanced by considering only individuals smoking during the last 24 h before collecting lung specimens, and under these conditions it became significant also for ICR 191.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients.

Lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (LC, n = 54) or a nonneoplastic lung disease (n = 20). Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECDE), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities and glutathione and malondialdehyde contents were determined in 12,000 X g supernatant fractions from nontumorous parenchymal tissues. Interindividual differences in enzyme activities ranged from 11- to 440-fold, and glutathione content varied by 17-fold; the values showed unimodal distributions. AHH, ECDE, EH, and UDPGT activities were significantly and positively correlated to each other; a significant negative correlation was found between GST and the other enzymes. A relationship between enzyme activity and number of cigarettes smoked (pack-years) was found only for GST. Ignoring detailed smoking histories in the 6-month period preceding surgery, no difference was found in enzyme activities or glutathione content between LC and nonneoplastic lung disease patients or between smokers and nonsmokers. However, when the number of days since stopping smoking was considered, in smokers a significant increase was found for AHH, EH, and UDPGT activities and a significant decrease was found for GST activity, as compared to nonsmokers. LC patients who had smoked until the day before surgery had higher activities of AHH, ECDE, EH, and UDPGT than nonsmokers, while GST activity was reduced by one-third. The activities of these enzymes returned to the basal level found in nonsmokers within 59 (AHH), 108 (EH), 67 (UDPGT), and 40 (GST) days. LC patients who were recent smokers (within 30 days prior to surgery) had significantly induced AHH and ECDE activities when compared with smoking nonneoplastic lung disease patients. These results show that pulmonary drug metabolism can be altered by tobacco smoking and that these effects can last 40 to 108 days after cessation of smoking. These new findings should be considered in studies on the role of carcinogen-metabolizing enzymes in determining susceptibility to lung cancer.

Placebo effect and adaptation to noninvasive monitoring of BP.

Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different.

Pulmonary embolism in neurosurgical patients: diagnosis and treatment.

Pulmonary embolism was suspected in 45 neurosurgical patients who were treated between January, 1980, and December, 1981. Hypoxemia with respiratory alkalosis and sudden tachycardia gave rise to this suspicion more often than any other sign or symptom. Perfusion lung scanning confirmed the presence of pulmonary embolism in 23 of these cases. A retrospective analysis of the clinical course of these 23 patients suggested that one or more previous episodes of pulmonary embolism had occurred in 16 cases (69.6%), and had been either overlooked or misdiagnosed. Treatment was started immediately after diagnosis. Twenty-one patients were given heparin; however, two could not be treated because of contraindication to using anticoagulant drugs. Two patients died during treatment. The 21 surviving patients were assessed and 11 of them submitted again to perfusion lung scanning 1 week after diagnosis: 14 had improved, but seven did not show significant changes either clinically or on perfusion lung scanning. Nine treated patients developed hemorrhage, but it was readily controlled. In two of the nine patients, hemorrhage involved the surgical area. It is stressed that pulmonary embolism may be suspected and diagnosed in neurosurgical patients at an early stage. Heparin may be given and the survival rate appears to be better than previously reported figures.

Factors affecting regional pulmonary blood flow in chronic ischemic heart disease.

To assess the effect of left heart disease on pulmonary blood flow distribution, we measured mean pulmonary arterial and wedge pressures, cardiac output, pulmonary vascular resistance, pulmonary blood volume, and arterial oxygen tension before and after treatment in 13 patients with longstanding ischemic heart failure and pulmonary edema. Pulmonary edema was evaluated by a radiographic score, and regional lung perfusion was quantified on a lung scan by the upper to lower third ratio (U:L ratio) of pulmonary blood flow per unit of lung volume. In all cases, redistribution of lung perfusion toward the apical regions was observed; this pattern was not affected by treatment. After treatment, pulmonary vascular pressures, resistance, and edema were reduced, while pulmonary blood volume did not change. At this time, pulmonary vascular resistance showed a positive correlation with the U:L ratio (r = 0.78; P less than 0.01), whereas no correlation was observed between U:L ratio and wedge pressure, pulmonary edema, or arterial oxygen tension. Hence, redistribution of pulmonary blood flow, in these patients, reflects chronic structural vascular changes prevailing in the dependent lung regions.

[Prolonged use of intravenous nitro derivatives in acute myocardial infarction (AMI)]. / Uso prolungato di nitroderivati per via endovenosa in corso di I.M.A.

A retrospective survey is made on 166 cases of acute myocardial infarction, treated with intravenous nitro-derivatives for eight days of continuous therapy. This therapeutic modality appears to gain four goals: a reduction in mortality of patients, a faster return of ST tract on isoelectric guideline, fewer ventricular pump failures. In the authors' point of view, a delay in the downward return of ST tract towards the isoelectric guideline is an important but ominous prognostic sign in this group of patients. Therefore, this modality of treatment is suggested for all patients with AMI, wherever the myocardial coronary lesion is localized.

[A case of wet beriberi]. / Su di un caso di beri-beri umido.

The AA. report a case of thymine acute deficiency in a 35 year old chronic alcoholic and malnourished male, who was admitted to the hospital because of high-output heart failure, peripheral polyneuropathy, cortico-cerebellar atrophy (associated with RMN), ataxia and peripheral edema. The diagnosis of wet Beri-beri combined with Wernicke-Korsakoff syndrome was made and appropriate therapy with pulse daily dose of parenteral thymine instituted. At the fifth day of therapy the cardio-circulatory hyperkinetic syndrome was markedly improved and after three weeks neurological damage was also alleviated. The AA. outline the importance of early diagnosis and treatment for this form of high-output heart failure, which has a poor prognosis and, if left untreated, can determine the death of the patient in a few days.

Ambulatory blood pressure monitoring (24 h), basal blood pressure and left ventricular echocardiographic findings in young adults.

Left ventricular (LV) echocardiography and ambulatory monitoring of blood pressure (BP) were performed in 50 normal 20-year-old subjects previously followed longitudinally for 4 years with annual measurements of basal BP (BBP). The relationship of basal, casual and mean 24-h non-invasive ambulatory BP (ABP) with echo findings, blood chemistries and body fatness was evaluated. Subjects with mean BBP on the 4 years above the 85th percentile showed significantly higher blood levels of urea and glucose and of body fat than subjects below this BP level. Left ventricular echo measurements did not differ in the two groups. Left ventricular diameters and volumes were not correlated with basal, casual or ambulatory BP. Interventricular septum (IVS), LV posterior wall (LVPW) and LV mass were correlated with ambulatory systolic but not with basal or casual BP. A significant increase of wall thickness and LV mass was associated with a mean 24-h ambulatory systolic BP (ASBP) above 129 mmHg. It is concluded that random BP and ABP tend to identify hypertensive subjects with different features.

Novel microRNA correlations in the severely injured.

PURPOSE: Severe injury initiates an inflammatory response that can perpetuate immunological dysfunction, uncontrolled inflammation, and subsequent multisystem organ failure. MicroRNAs (miRNAs) have recently been identified as regulators of this inflammatory response. Our study sought to identify the differential expression of unique miRNAs and their correlations with genes of the Toll-like receptor (TLR) pathways, and clinical parameters in the severely injured. METHODS: Fourteen trauma patients requiring transfusion were prospectively enrolled in this institutional review board-approved study. Inclusion criteria consisted of adult patients deemed clinically to be in hemorrhagic shock necessitating transfusion in the acute phase of their injury care. Peripheral blood samples were obtained after admission to the surgical intensive care unit. Expression of circulating mature miRNA from each patient, as well as from 10 healthy, age-matched controls, was determined and compared using the HiSeq 2500 sequencing system and the R software system. Gene expression of TLR signaling pathways for each patient was examined using custom gene expression polymerase chain reaction arrays. Statistical analyses were performed using general linear models and empirical Bayes methods to determine differential expression and Spearman's nonparametric correlation analysis. RESULTS: Subjects were 21-77 years old (mean, 42), 80% male, Injury Severity Score 11-43 (mean, 26), with 11 blunt and 3 penetrating injuries. Three were intubated and 5 received blood products before arrival. Base deficit upon hospital admission was 3 to 20 (mean, 9). All patients required blood transfusion secondary to blood loss sustained during injury. Survival to discharge was 93%. Controls were 27-64 years old (mean, 40) and 60% male. Sequencing analysis revealed 69 differentially expressed miRNAs (P < .05) in the severely injured. Within the differentially expressed miRNAs, there were 12 direct and 6 indirect correlations with multiple genes involved in the TLR3 and TLR4 signaling pathways. The relationships between these same miRNAs and clinical parameters were also analyzed. We discovered 4 direct correlations with base deficit and HCO3, and 7 indirect correlations involving total fresh frozen plasma transfused, base deficit, HCO3, and PaCO2 levels. CONCLUSION: Differential expression and correlations between miRNAs, genes of the TLR pathways, and clinical parameters are unique findings in the severely injured and may lead to a greater understanding of the regulation of sterile inflammation after severe injury.

Fibrinolytic effects of urokinase and heparin in acute pulmonary embolism: a randomized clinical trial.

Dissolution of pulmonary emboli with heparin and urokinase is ascribed, respectively, to anticoagulation and fibrinolysis. Since truly independent assessment of these effects in man is lacking, we administered each drug alone. Fibrinogen and plasminogen plasma levels and the resolution of pulmonary emboli were measured in three randomized groups of 10 patients each: groups A and C infused with small repeated doses of urokinase and a large single dose of urokinase, respectively, and group B who received heparin. After 6 h of treatment, fibrinogen fell in all the groups, while, after 12 h, remained equally reduced in groups A and B and declined further in group C. Plasminogen behaved similarly. Up to 60 h, statistical analysis showed that these effects were related to timing and amounts of urokinase and heparin infusion. These observations suggest that heparin may induce a lytic state. As to signs of pulmonary emboli resolution, no differences between groups were found in lung perfusion and gas exchange recovery at any time (from 1 day to 1 year) and in pulmonary artery pressure reduction at 1 week. The greater angiographic and scintigraphic recovery observed with urokinase, versus heparin alone, after 1 day of treatment in the Urokinase Pulmonary Embolism Trial may be ascribed to a synergistic effect with urokinase of heparin administered during the diagnostic work-out. The indications of heparin and urokinase should be evaluated in the light of these results.

[Cases of pulmonary embolism diagnosed in Pisa from 1969 to 1984]. / Casi di embolia polmonare diagnosticati a Pisa dal 1969 al 1984.

Starting from 1969, the yearly number of patients with pulmonary embolism documented in the S. Chiara Hospital of Pisa is increased, in spite of the unchanged diagnostic procedures. Aim of this work is to verify if this trend is accompanied by earlier diagnosis with an improvement in the clinical outcome of pulmonary embolism, and if a relevant diagnostic failure is still present in our hospital. A comparison of pulmonary embolism cases collected from 1969 to 1971 and from 1980 to 1982 showed that the number of diagnoses made within one week from the onset of symptoms is increased (+24.8%), whereas the number of diagnoses made after more than one month is reduced (-18.1%). At the same time we observed that cases with a standard PaO2 less than 40 mmHg are reduced (-23.1%) while cases with a standard PaO2 greater than 50 mmHg are increased (+29.9%). An earlier diagnosis of pulmonary embolism contributed to treat a larger percentage of patients (+29.7%) and to lower the early mortality (-17.4%). This diagnostic trend can be ascribed to an increased readiness in raising the clinical suspicion of pulmonary embolism and to the prompt availability of perfusion lung scan, that is the center of our diagnostic strategy. Data of our 1,010 patients, compared with those of autoptic series and with the number of admissions, surgical operations and deaths in the wards of our hospital, suggest some persistent diagnostic failure in patients with well documented embolic risk; such as injured, burned, patients affected by neoplasm or motor lesion, patients operated for orthopedic or gynaecologic problems.

[Short-term prognosis of pulmonary embolism]. / Prognosi a breve termine dell'embolia polmonare.

Seven hundred fifty four consecutive cases of pulmonary embolism, diagnosed between 1969 and 1982 at S. Chiara Hospital in Pisa, were examined in order to assess the causes and the rate of the early mortality. Full documentation was not obtained in 47 cases (6.2%) and they were excluded from the study; 81 (11.4%) of the remaining 707 died within 30 days of diagnosis, and in 56.8% of them pulmonary embolism was the primary cause of death. The survival rate was 90.6% in patients with apparently primary pulmonary embolism, 89.8% in post surgical cases, 81.5% in cardiac patients and 75% in patients affected by neoplasm. Twenty five per cent of patients were not treated during the acute phase, because the diagnosis was made more than one month after the onset of symptoms or because the fear of bleeding precluded anticoagulant treatment. The incidence of fatal haemorrhage during treatment was 0.5% overall, and 0.4% in surgical patients. Mortality was 9.2% in patients who received treatment, versus 25.2% in untreated patients. Sixteen fatal recurrent embolisms occurred after the end of treatment: 11 were observed in patients not treated with oral anticoagulants. Routine autoptic examinations, performed in 44.4% of the cases, often demonstrated both recent and organized emboli, especially in cardiac patients. Recurrence of pulmonary embolism may account for both the severity of clinical patterns and the high mortality rate in the early phase of treatment.

A controlled clinical trial on the effect of heparin infusion and two regimens of urokinase in acute pulmonary embolism.

A comparison of the effects of two regimens of urokinase infusion not associated to heparin and of continuous heparin infusion was made assessing the rate of emboli and arterial hypoxemia resolution in patients with acute pulmonary embolism. Twenty-nine patients with acute pulmonary embolism, each one diagnosed by means of perfusion lung scan and selective pulmonary arteriography, were admitted to the study and randomly allocated to three treatment groups: A, 10 patients, urokinase: 800,000 CTA units/day for three days followed by oral anticoagulants; B, 9 patients, heparin: mean daily dose 30,000 units for seven days followed by oral anticoagulants; C, 10 patients, urokinase: 3,300,000 CTA units in 12 hours followed by oral anticoagulants. Pulmonary lung scan and PaO2st (PaO2 standardized to PaCO2 of 40 mmHg) were repeated at 1, 3, 7, and 30 days in all the groups of treatment. The mean daily rate of improvement, assessed from both the perfused lung segments and the PaO2st increment, in group C was highest in the first 24 hours and lowest from the first to the third day of treatment. However, from the third to the seventh day of treatment and onwards the mean daily rate of improvement was roughly the same in all the groups. After one month, lung perfusion and the PaO2st had considerably improved, but had not attained full recovery in any of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Slow-release metoprolol and nifedipine in essential hypertension: 24 hour noninvasive ambulatory blood pressure monitoring.

To assess the efficacy and tolerability of metoprolol (MET), 200 mg slow release (SR) q.d., and nifedipine (NIF), 20 mg SR b.i.d., 20 mildly to moderately hypertensive outpatients (14 men and 6 women; mean age 41.5 years, range 27-49 years) were studied. After being withdrawn from previous antihypertensive treatments, the patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized sequence, MET and NIF, both for 2 weeks. At the end of each period of the study, blood pressure (BP) was recorded for 24 h using a noninvasive ambulatory BP monitoring device (ICR System) with readings taken every 10 min (from 6 a.m. to 6 p.m.), 15 min (from 6 to 12 p.m.), and 20 min (from 12 p.m. to 6 a.m.). Five patients did not complete the study because of the occurrence of unwanted effects (one patient on MET and four patients on NIF). In the 15 patients who concluded the study both drugs significantly reduced (p less than 0.01), in comparison with placebo, systolic BP (SBP), mean arterial pressure (MAP), and diastolic BP (DBP) throughout the 24 h (MET: -16.9, -11.5, and -8.9 mm Hg; NIF: -12.7, -8.4, and -6.6 mm Hg, respectively). In comparison with NIF, SBP and MAP but not DBP were significantly reduced by MET (p less than 0.01 and p less than 0.05, respectively). We conclude that in our patient population MET was more effective and better tolerated than NIF. A possible explanation could be the relatively young age of the subjects we studied.

Temporal analysis of blood pressure by ambulatory 24 H blood pressure monitoring.

In order to study the circadian rhythm of BP in man, we performed 24-hour non invasive BP on 15 hospitalized patients. Each subject was monitored twice, with an interval of 24-48 h between the two monitorings. In 14 of the 15 subjects MBP showed a statistically significant circadian rhythm. The curve fitted by the single cosinor method to the mean of the first rhythmometric measurements performed on all 15 subjects was characterized by an acrophase at 12.53, an amplitude of 4.68 mmHg and a mesor of 87.49 mmHg. The same parameters for the second rhythmometric measurements were: acrophase at 13.57, amplitude 4.1 mmHg and mesor 88.35 mmHg. In both cases, overall circadian rhythm resulted to be similar in all the subjects (p less than 0.01). Multivariate analysis of variance showed that each subject has his own characteristic circadian rhythm. Our findings support the hypothesis of a identifiable circadian rhythm of BP in man.

Blood pressure levels in adolescents: the Milan Study.

The relationship between pubertal maturation and blood pressure (BP) was investigated in a cohort of 1,252 adolescents followed for 4 years. Males and females were categorized into two groups (pre and post), according to pubic hair growth (males) and menses onset before or after the age of 12. BP tracking was higher for systolic BP (SBP) than for diastolic BP (DBP), without differences between the two groups of each sex. By multiple regression analysis, initial BP was the major predictor of the final value in all subjects. Body mass index (BMI) annual change was positively correlated to SBP change over time. Analysis of variance showed an increased within-person variability of SBP in pre subjects, with a significant reduction of DBP residual variance at higher initial DBP levels. Our results suggest that early pubertal maturation and high DBP at age 14 years characterize subjects differing at least partially from the general adolescent population in BP determinants.