Heme Oxygenase-1/High Mobility Group Box 1 Pathway May Have a Possible Role in COVID-19 ARDS (Acute Respiratory Distress Syndrome): A Pilot Histological Study.

COVID-19 is a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The persistent and excessive inflammatory response can build up a clinical picture that is difficult to manage and potentially fatal. Potent activators of inflammatory phenomena are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). HMGB1 is an intranuclear protein that is either passively released during hypoxia-related necrosis or actively released by macrophages. Heme oxygenase (HO-1) has an anti-inflammatory effect by inhibiting HMGB1, which could be a therapeutic target to reduce COVID-19 inflammation. In our study, we evaluated CD3, CD4, CD8, HMGB1 and HO-1 in the COVID-19 lung and correlated it to clinical data.

Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study.

BACKGROUND: Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. OBJECTIVE: The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. METHODS: A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. RESULTS: A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. CONCLUSIONS: Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.

The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects.

OBJECTIVE: To investigate the changes in the aggregation index (AI) and the elongation index (EI), in severe obese subjects (MbObS) undergoing laparoscopic adjustable gastric banding (LAGB). AI and EI are measured by Laser assisted Optical Rotational Red Cell Analyzer (LORCA) and are markers of erythrocyte aggregation and deformability, respectively. DESIGN AND SUBJECTS: Before, 3 and 6 months after LAGB plus lifestyle changes (Mediterranean diet plus daily moderate exercise), we evaluated AI, EI, body mass index (BMI), total (ToT) cholesterol (Chol), high-density lipoprotein (HDL)-Chol, low-density lipoprotein (LDL)-Chol, triglycerides and fasting glucose and insulin levels in 20 MbObS. The Student's t-test was used for comparisons between independent groups and the analysis of variance to assess differences in AI and EI at the 3 time points. Pearson's correlation coefficient was used to assess correlation among continuous variables and multiple linear regression analysis to assess predictive factors for AI and EI changes. RESULTS: BMI and all blood parameters showed a statistically significant decline 3 and 6 months after LAGB as compared with basal, except for EI and HDL-Chol that significantly increased. Stepwise selection of predictors shows that at 3 and 6 months, EI values depended on HDL-Chol values at the same time point. In the EI model, blood glucose was also statistically significant at 6 months. CONCLUSION: Our data show a significant improvement in EI after LAGB-induced weight loss, which correlates with an improved lipid pattern and support the idea that the rapid weight loss induced by LAGB plus lifestyle changes might reduce the thromboembolic risk and the high mortality risk found in MbObS.

[Hemorheology and microcirculation in some pathologies of internal medicine]. / Alterazioni emoreologiche e microcircolatorie in alcune patologie di interesse internistico.

AIM: It is very interesting in physiopathology to evaluate the blood flow in the microvasculature of patients affected by diabetes, arterial hypertension, lipoproteinosis, peripheral occlusive arterial disease (POAD) and liver failure. METHODS: We studied 4 groups. Group 1: controls formed by 25 healthy subjects (15 males and 10 females aged 36+/-3 years); group 2: diabetes, including 32 patients (group 2A, 20 subjects with diabetes type 1: 12 males and 8 females aged 43+/-4 years and group 2B, 12 subjects with diabetes type 2: 6 males and 6 females aged 45+/-3 years); group 3: liver failure, formed by 6 subjects (3 males and 3 females aged 44+/-5 years); group 4: hypertensives, 50 subjects (group 4A, 28 smokers 12 males and 16 females aged 40+/-4 years and group 4B, 22 non-smokers: 12 males and 10 females aged 38+/-3 years). We evaluated the capillary morphology using computerized videocapillaroscopy, the hemorheology (red blood cell RBC deformability and aggregability) using LORCA (Laser assisted Optical Rotational Red Cell Analyzer) and tissue oxygenation using transcutaneous oxymeter (Periflux 5000 Perimed). Statistical analysis were performed using the Student t-test. RESULTS: The capillary loops in patients with diabetic microangiopathy had in 50% of the patients studied an image such as ''deer horns'', as ''elephant nose'' in 72% and as ''cork screw'' in 44%. In diabetics we found also a capillary rarefaction in 28% of them. An improvement in perfusion was observed in patients with liver failure one week after liver transplantation from cadaver in 83% of them. Morphological alterations were present in hypertensives (27% in non-smokers, 46% in smokers). The RBC deformability evaluated as elongation index (EI) and RBC aggregability (t1/2 expressed in seconds) were detected using LORCA. Group 1: EI 0.59+/-0.02, t1/2 3+/-1 s; group 2A: EI 0.55+/-0.01; t1/2 2+/-0.5 s p<0.05 vs controls; group 2B: EI 0.56+/-0.01; t1/2 2+/-0.2 s p<0.04 vs controls; group 3: EI 0.56+/-0.02, t1/2 2+/-0.4 s p<0.04; group 4A: EI 0.56+/-0.02, t1/2 2+/-0.6 s p<0.03; group 4B: 0.57+/-0.02, t1/2 2+/-0.6 s p<0.04. We evaluated also the TcpO2 at the dorsum of the right foot expressed in mmHg: group 1, 96+/-11 mmHg; group 2A, 74+/-9 p<0.05 vs controls; group 2B, 76+/-8 mmHg p<0.05; group 3, 69+/-6 mmHg p<0.05; group 4A, 70+/-5 mmHg p<0.05; group 4B, 77+/-9 mmHg p<0.05. CONCLUSION: This study indicates an interesting and complete methodology in order to evaluate the microcirculation condition in different pathologies inducing microvasculature alterations.

MELD predictive value of alterations of brain perfusion during liver transplantation.

INTRODUCTION: The systemic circulation of patients with liver failure is characterized by low vascular resistance and a compensatorily increased cardiac output. In addition, some patients show functional loss of the autoregulation system for cerebral blood flow, creating enhanced risk during orthotopic liver transplantation (OLT), a possible cause of the high incidence of central nervous system complications after OLT. PATIENTS AND METHODS: Sixteen consecutive patients undergoing OLT were enrolled and characterized by the Child-Pugh (CTP), the MELD, and the HCC-adjusted-MELD score before surgery. OLT was performed with the "piggyback" technique. Brain perfusion and oxygenation was monitored by NIRO300 by Hamamatsu. This instrument detects concentration changes in oxygenated hemoglobin (DeltaHbO(2)), deoxygenated hemoglobin (DeltaHHb), and total volume of hemoglobin (DeltaHbT). It also calculates the tissue oxygenation index (TOI), namely HbO(2)/HbT expressed as a percentage, and the tissue hemoglobin index (THI). RESULTS: The lowest levels of brain perfusion were recorded at the washout, DeltaHbO(2) = -13.95 (-20/-5.3) micromol L(-1) and TOI = 51.5 (35.2/70.7)%, while immediately after, at reperfusion, the highest peaks were observed: DeltaHbO(2) was 0.16 (16.9/13) micromol L(-1); DeltaHbT was 1.1 (22.3/11.8) mumol L(-1); and TOI was 73.6 (78.1/65.3)%. CONCLUSIONS: Patients with more severe liver deficiency scores showed higher levels of brain perfusion and oxygenation during surgery. Both the MELD and the CTP score predict alterations in brain perfusion.

Solutions for organ perfusion and storage: haemorheologic aspects.

BACKGROUND: The hydroxyethyl starch (HES) contained in University of Wisconsin (UW) solution causes erythrocyte aggregation. The effect of UW on red blood cell (RBC) deformability is still unclear. HES-free preservation solutions, Celsior (CS) and Custodiol (CU) are available. In this study we evaluated whether they really showed a reduced aggregating and stiffening effect on RBCs when compared with UW. We was also evaluated the effect of these solutions on cellular membranes by measuring acetylcholinesterase (AChE), which is a marker of RBC membrane integrity. METHODS: The determination of RBC aggregation and deformability was performed by a laser-assisted optical rotation cell analyzer (LORCA). AChE measurement was performed with a spectrophotometric technique. RESULTS: The mean RBC aggregation index (AI) measured in pure blood control samples was 28.00 +/- 0.73%. The AI measured samples containing UW was 38.82 +/- 1.58%. In samples with CS, it was 13.307 +/- 0.64% and in samples with CU the mean AI was 12.47 +/- 0.42%. Also the RBC aggregating time was quicker in presence of UW compared with controls. AChE concentration in blood was 3.043 +/- 0.4 nmol. CS and UW did not produce any significant change; a significant reduction was found when CU was added to blood, namely 1.975 +/- 0.1 nmol (P < .05). The use of UW or CS or CU did not result in any significant change in RBC deformability. DISCUSSION: CS and CU solutions do not aggregate erythrocytes, whereas Wisconsin does massively. CU causes an alteration of RBC cellular membrane as demonstrated by depletion of AChE.

Stress response and antihypertensive treatment.

Results from many studies suggest that the central nervous system may play an important role in enhancing and maintaining sympathetic, metabolic and haemodynamic effects in patients with hypertension. Likewise, emotional and mental stresses may provoke phasic and sustained adrenergic responses in normotensive and untreated hypertensive patients. Because the various antihypertensive medications have different mechanisms of action, and elicit different neurovegetative responses, it is useful to distinguish between the effects of different treatments on sympathetic activity. To identify the effect of stress on sympathetic reactivity, we evaluated the extracardiovascular and haemodynamic responses to various stressor agents using noninvasive techniques. This psychophysiological approach allowed us to standardise stress, to identify individual cardioneurovegetative responses both before and during treatment, and to establish the effects of various treatments on the cardioneurovegetative response. The extracardiovascular psychophysiological response of patients with a family history of hypertension and of normotensive patients who later became hypertensive was characterised by an inability to recover after mental challenge. Therefore, prolonged sympathetic activity resulting from mental stimulation may contribute to the development of hypertension. Antihypertensive medications affected sympathetic reactivity differently. For example, nifedipine worsened sympathetic reactivity, while verapamil was able to correct abnormal neuroadrenergic responses. Furthermore, verapamil was successfully combined with enalapril in patients whose hypertension was resistant to monotherapy with the angiotensin converting enzyme (ACE) inhibitor. Therefore, the functional and structural consequences of sympathetic stimulation resulting from daily activation and pharmacological blood pressure adjustments are important in hypertensive patients, because they may have abnormal sympathetic reactivity to various stimuli.

Lipids and cardiovascular reactivity changes in hypertensive cigarette smokers: enalapril versus nifedipine treatment effects.

Cigarette smoking has many effects on the cardiovascular system, psyche, and serum lipids, which can create a vicious circle that is pejorative to the well-being of hypertensive patients, even if they are under pharmacologic treatment. To investigate the effect of two different antihypertensive agents, nifedipine and enalapril, on cardiovascular reactivity and lipoprotein patterns in cigarette smokers with hypertension, 92 essential hypertensive (175 +/- 11/103 +/- 8 mm Hg) subjects were studied, who had no sign of lipidosis, and subdivided into four groups in order of smoking habit and therapy. Over a 30-month follow-up period, the percentage changes in blood pressure (BP), heart rate (HR), triglycerides, total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol were evaluated while the patients underwent a session of psychophysiologic tests to assess sympathetic reactivity. The response was calculated through the difference in cumulative percentage changes (DC%) in systolic blood pressure (SBP), diastolic blood pressure (DBP), HR, muscular contraction (EMG), skin conductance (SCL), and peripheral temperature (TP). The office BP was reduced significantly in all groups. In the nonsmokers, enalapril reduced (p < 0.05) the SCL-, TP-, SBP-, and DBP-DC% reactivity, lowered (p < 0.05) TR, C-tot, and LDL, and increased (p < 0.05) the HDL. However, nifedipine magnified the sympathetic responses and the atherosclerotic lipoproteins and decreased (p < 0.05) the HDL.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes modifies cardiovascular reactivity during hypertension.

Hypertension and diabetes often occur in the same patient, and this observation inspired the search for a new common pathogenetic hypothesis. The onset of diabetes during hypertension also could modify cardiovascular autonomic arousal. To identify a peculiar hemodynamic and psychophysiologic reactivity, a male population of mild essential hypertensive (166 +/- 6/102 +/- 8 mm Hg) patients (EH) and non-insulin-dependent hypertensive (169 +/- 10/101 +/- 7 mm Hg) diabetic subjects (HD) underwent a session of stress tests. Four tests, Mental Arithmetic, Incomplete Phrases, Cold Pressor, and Handgrip, were preceded and followed by a 10-minute recovery period. Functional tests were performed to identify any possible cardiac autonomic neuropathy. During the entire session, by means of a beat-to-beat noninvasive computerized device, hemodynamic and extracardiovascular functions were measured. The findings suggested the presence of a sympathetic hyperactivity in both HD and EH. In particular, HD showed a peculiar "tropism" for the peripheral vasculature. In these patients, in fact, total vascular resistance and peripheral temperature responses were 89.2% and -64.2%, respectively, versus 33.7% and -50.6%, which were found in EH. On the other hand, the ejection ventricular index was more depressed in HD (-27.9%) than in EH (-23.8%), although they did not seem to be affected by cardiac autonomic damage. The different profiles appear to confirm the increase of functional vascular damage in diabetic hypertensive patients, probably because of the insulin resistance or obsolete muscular cardiac damage.

A non invasive optical oximetry in humans: preliminary data.

In order to evaluate the oxygen saturation of hemoglobin in living tissues we use a new experimental instrument: the optical oximeter (LOX). The LOX uses 2 LEDs, like the pulse oximeter (PO). One LED operates at 670 nm (Hb absorption), the other one operates at 830 nm, i.e., near the isosbestic point for which Hb and HbO2 show the same extinction. The oxygen saturation of Hb can be expressed as a linear function of the ratio of the absorption coefficients at the wavelengths of the 2 LEDs. Indeed the LOX is based on diffused reflectance measurements and not on light transmission such as the POs. We studied in standard conditions 10 healthy volunteer subjects (6 M, 4 F aged 40 +/- 4 years) non smokers. We used TO (Combi Sensor) at the subclavicular standard area and at the right ankle, PO with the probe always at 2nd finger of the right hand and LOX at right wrist and at right ankle. We obtained a significant relationship between values of TO, PO and LOX (p < 0.01). Our preliminary data suggest that this could be a new methodology to evaluate tissular oxygenation, also exploring living tissues several centimeters deep.

Red blood cell (RBC) deformability, RBC aggregability and tissue oxygenation in hypertension.

Arterial hypertension could be considered a progressive ischaemic syndrome interesting the macro and the microcirculation. In order to improve the clinical and therapeutic approach to the treatment of arterial hypertension, research has centered on blood flow to evaluate the different components and their very intricate relationships influencing the micro- and the macrocirculation. Of course the main problem is to study the link between the blood flow and the peripheral tissue oxygenation. During hypertension very important alterations in rheological, mechanical and biochemical characteristics of erythrocytes and of blood flow have been shown. It is very relevant the increase in blood viscosity, the decrease in red blood cell (RBC) deformability, the formation of RBC "rouleaux" and RBC aggregates. These hemorheological determinants can favour an increase of peripheral resistances and of arterial blood pressure, causing or worsening hypertension, a decrease in oxygen transport to tissue and peripheral perfusion, a decrease of the active exchange surface area in the microvasculature, especially in complicated hypertension. We have studied 320 patients: 123 with Essential Hypertension (EH) (M 59, F 64 aged 50 +/- 25 years); 81 with Secondary Hypertension (SH) without associated other pathologies influencing hemorheology (M 42, F 39 aged 48 +/- 20 years); 116 SH with other pathologies or conditions associated influencing hemorheology such as: diabetes, lipoidoproteinosis, obesity, smoking, HD, elderly, etc. (M 48, F 68 aged 46 +/- 20 years). Using a Laser-assisted Optical Rotational Red Cell Analyzer (LORCA) acc. to Hardeman (1994) we studied Elongation Index (EI) and aggregation kinetics of red blood cells in these patients. We also evaluated TcpO2 and TcpCO2 using a transcutaneous oxymeter (Microgas 7650, Kontron Instruments). In hypertensives we found a decrease in erythrocyte deformability (evaluated with EI), in erythrocyte aggregation time, a fibrinogenaemia increase, an increase of shear rate to disaggregate erythrocytes, a decrease in cellular oxygen delivery and tissue oxygenation, an impairment of microcirculation. These changes may be involved in the development of arterial hypertension and in its pathogenesis. These patterns also are more impaired in hypertensives with diabetes, lipoidoproteinosis, etc. These patterns are not related with the age of the patients but they are significantly and directly related (p < 0.01) with the patient hypertension-age. This could be a new way to realize a better treatment in hypertensives and a prevention of cardiovascular complications (i.e.: myocardial infarction, TIA, etc.).

Hemorheology in complicated hypertension.

During essential and secondary arterial hypertension it is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as an increase in blood viscosity or the formation of the red blood cell "rouleaux" which favour an increase in peripheral resistance and can cause or worsen arterial hypertension. We studied 21 healthy subjects (11 male and 10 female aged 42 +/- 4) and 26 hypertensive subjects (14 male and 12 female aged 49 +/- 3). The patients were non smokers and non suffering from respiratory or haemathological pathologies. They were not undergoing antihypertensive or vasodilatory pharmaceutical treatment. The patients suffered from mild hypertension (II WHO) with Peripheral Occlusive Arterial Disease (POAD II "a" acc. to Leriche-Fontaine class.). The patients showed an increase in cholesterolaemia (6.42 +/- 0.81 mmol/l) and trygliceridaemia (2.73 +/- 0.09 mmol/l) at an average level. The patients were studied in standard conditions with a constant temperature of 22 degrees C. We measured SBP, DBP, MBP, and the HR. We also measured the elongation index (EI) (with shear stress range 0.30 to 30 pascals) using LORCA, acc. to Hardeman method (1994), in order to study the erythrocyte deformability and aggregation kinetics in dynamic condition. To evaluate deformability in static conditions we calculated the Erythrocyte Morphologic Index (EMI), acc. to Forconi method, via the bowl/discocyte ratio (for 100 red blood cells fixed in glutaraldehyde at 0.3% and observed with an optical microscope under immersion in glycerol). Peripheral oxygenation was taken transcutaneously (TcpO2). To establish the level of vascular disease we used the Regional Perfusion Index (RPI = TcpO2 foot/TcpO2 subclavean) and doppler guided Winsor Index (WI). The Student "t" test and linear regression were used for the statistical analysis. Our data confirm a reduction in peripheral tissue oxygenation in hypertensives especially if suffering from vascular disease which correlates significantly (p < 0.01) with a reduction in red blood cell deformability. This itself can increase peripheral resistances and favour the onset of hemorheological complications, at a cerebral-vascular level, which are frequent in hypertensives.

Cytosolic calcium and hemorheological patterns during arterial hypertension.

Hypertension can be considered as a progressive ischaemic syndrome interesting micro- and macrovasculature. In hypertensives it is possible to observe a link between an increase in peripheral resistance and blood viscosity, and a decrease in red blood cell (RBC) deformability. It is important to underline the link between the increase of blood viscosity, the decrease of RBC deformability and the cytosolic calcium level, which is related to the ischaemic syndrome in hypertension. The aim of this study was to evaluate the level of Ca++ and its possible correlation with hemorheological patterns during arterial hypertension. Two groups were studied: Group 1 consisted of 18 mild hypertensives (11 males and 7 pre-menopausal females, aged 39 +/- 3 years). This group was of medium risk according to WHO and ISH (1999) with no other pathologies apart from peripheral occlusive arterial disease II stage type A. Group 2 was made up of 14 healthy subjects (9 males and 5 females, aged 34 +/- 4 years). The intraerythrocytic cytosolic calcium was evaluated using a fluorescent marker FURA 2/AM (Calbiochem). The following hemorheological parameters were also assessed using the new Laser assisted Optical Rotational Red Cell Analyzer (LORCA) according to the Hardeman method (1994): RBC deformability-Elongation Index (EI), RBC aggregability- aggregation half time (t 1/2). The data obtained showed that compared to the control group the hypertensives had a significantly higher level of intraerythrocytic cytosolic calcium (p < 0.01), plus a significant decrease in EI and t 1/2 evaluated using LORCA. We also observed a significant correlation (p < 0.01) between an increase in Ca++ and a decrease in EI in the hypertensive patients. Moreover our study revealed a significant correlation between the increase in intraerythrocytic Ca++ and the t 1/2 decrease. The evaluation of the hemorheological patterns and cytosolic calcium could explain the impairment in peripheral perfusion and oxygenation in hypertensive patients and could provide a good model for a better evaluation and treatment of microvasculature perfusion in subjects with essential and complicated hypertension.

Hemorheological aspects in hypertensive menopausal smoker women treated with female hormones.

In postmenopausal hypertensive women (PostMHW) the erythrocyte deformability (ED) is reduced if compared with premenopausal hypertensive women (PreMHW). This might partially explain the increased incidence of cardiovascular diseases (CD) in hypertensive women after menopause. Moreover a positive correlation exists between estradiol and rheological patterns in women. If PostMHW smoke cigarettes, there is an important decrease in hemorheological parameters. On the other hand if PostMHW are submitted to an hormonal replacement therapy (HRT) they can show controversial results with an impairment if hemorheological parameters. The aim of this study was to evaluate the influence of smoking and HRT on PostMHW. We studied four groups of subjects: Group 1: PreMHW (10 F aged 35 +/- 3 years) non smokers; Group 2: PostMHW (8 F aged 45 +/- 2 years) non smokers; Group 3: PostMHW (14 F aged 48 +/- 4 years) smokers (20 cigarettes per day); Group 4: PostMHW (16 F aged 50 +/- 2 years) smokers (20 cigarettes per day) submitted to HRT. We evaluated Elongation Index of erythrocytes under torsion force of 30 pascals (EI--30 Pa) using a new computerized instrument Laser assisted Optical rotational Red Cell Analyzer (LORCA) (Mechatronics, Hoorn, NL) acc. to Hardeman (1994) and, also with the same LORCA, Aggregation Index (AI), t(1/2). We measured the transcutaneous oxygen partial pressure (TcpO2) in subclavicular standard area using a Transcutaneous Oximeter (Microgas 7650 Kontron Instruments with Combi Sensor) and total cholesterolaemia. In PostMHW our data showed a significant (p < 0.01) impairment of hemorheological patterns and tissue oxygenation if compared with PreMHW (Group 1). In Group 3 there is a significant (p < 0.01) decrease in EI, a significant (p < 0.01) increase in AI, a significant (p < 0.01) decrease in t(1/2) and TcpO2 if compared with Control Group 1 and Group 2. Finally a further significant (p < 0.01) impairment in hemorheology and tissue oxygenation showed Group 4. In conclusion, it seems necessary, that many studies will be performed to understand really protective action of HRT on cardiovascular diseases in PostMHW and it is necessary to suppress cigarette smoking to prevent cardiovascular complications in these patients.

Microvascular changes during laboratory stimuli and structural haemodynamic indices: the role of pulse pressure.

Office and ambulatory pulse pressure have been recognized as independent predictors of cardiovascular mortality and atherosclerosis in hypertensives as well as in normotensives. On the other hand, the vascular reactivity, in subjects with high pulsatile component of blood pressure, has not been studied yet. The purpose of our study was to identify the regional muscular hemodynamics and the cutaneous microvascular changes during laboratory stimuli in young adult very mild hypertensives with high pulse pressure. The cardiovascular (Finapres), the forearm vascular (plethysmography) and the microvascular cutaneous (laser-Doppler flowmetry and transcutaneous oximetry) responses to psychophysiological stimuli were measured. In addition, the hyperemic forearm vascular response to the ischaemic test was measured as haemodynamic index of vascular damage. We studied 15 very mild hypertensives with higher office pulse pressure and 15 patients with similar age, history of hypertension, metabolic parameters and systodiastolic blood pressure but lower pulse pressure values. Patients with high pulse pressure demonstrated reduced hyperemic response and increased residual vascular resistance at the forearm ischaemic test. They did not vary for all the parameters, except pulse pressure, during the baseline period but the total stress response, as residualized area-under-the-curve, was notably different. Patients with higher office pulse pressure demonstrated a significant increased heart rate, systolic and pulsatile blood pressure reactivity. On the contrary, they showed a reduced forearm and cutaneous blood flow response combined to a reduced transcutaneous tissutal oxygenation. The findings suggest that the increased pulsatile component of blood pressure might be associated to structural and functional vascular impairments since the very early stages of hypertension in young adults without metabolic disorders.

Tissular oxygenation and erythrocyte deformability in haemodialyzed patients using different dialytic membranes.

We studied the effect of some dialytic membrane on tissular oxygenation (TO) and erythrocyte deformability (ED). Sixteen patients (10 M and 6 F, aged 59 +/- 12 years) have been submitted to bicarbonate dialysis (BD) and subdivided into four groups (GR) of 4 patients each: GR 1 (hemophan membrane, 35 BD), GR 2 (polyacrylonitrile, PAN AN 69, 42 BD), GR 3 (polysulphone, 38 BD) and GR 4 (polycarbonate, 37 BD). The TO has been detected with the transcutaneous oxygen pressure (Tc pO2) using a transcutaneous oxymeter and the ED has been evaluated with the EMI (Erythrocyte Morphometric Index), which results from the ratio between deformable erythrocytes (bowl shape) and rigid erythrocytes (discocyte shape), for every 100 red cells fixed in vitro with 0.3% glutaraldehyde. The ED was also evaluated using a laser instrument: Laser Optical Rotational Cell Analyser. During BD was observed a significant decrease of Tc pO2 in the 1st hour only in the 1st and 2nd GR and, in contrast with results obtained in the 3rd and 4th GR, in the same GRs the EMI showed a significant reduction of ED at the end of BD. Finally the LORCA results, showing a significant decrease of ED only in the 1st and 2nd GR, confirmed the data obtained with EMI. In conclusion, our study has suggested that hemophan and PAN AN 69 are less biocompatible than polysulphone and polycarbonate membranes according to effects on ED and TO.

Serial overnight recordings of intracarpal canal pressure in carpal tunnel syndrome patients with and without wrist splinting.

In 15 carpal tunnel syndrome patients pressure was measured during the day and at 2-hourly intervals from midnight to 6 a.m., via a catheter introduced into the carpal canal, using the constant infusion technique. Intracarpal tunnel pressure of the patients always exceeded the critical pressure of 30 mmHg and the highest values were found at 6 a.m. Slightly lower pressures were found when the wrist was splinted, but the difference was not significant, nor were critical pressure levels prevented by splinting.

[Glyco-lipid changes in hypertensive diabetic patients undergoing treatment with nifedipine and captopril]. / Alterazioni glico-lipidiche in pazienti ipertesi diabetici in trattamento con nifedipina e captopril.

Atherosclerosis in diabetic subjects is improved by the reduced repair capacity of endothelial damage and by the increased platelet aggregation, peculiar to diabetic pathology. The contemporary presence of high blood pressure, diabetes and lipoidoproteinosis, increasing the possibility of cardiovascular damage, also under well-controlled blood pressure values, certainly increases the risk of atherosclerosis. However we have valued the presence of lipoidoproteinosis in 52 of our diabetic-hypertensive patients in a follow-up of 40 months. The patients have been split in to two groups of 26 patients each, one being treated with nifedipine, the other to with captopril. The data obtained have been compared with the data for the two control groups (non diabetic patients). The selection has been carried out according to established criteria. We have investigated: glycaemia, total cholesterol, HDL-C, LDL-C, triglycerides, tot. Chol./HDL-C, LDL-C/HDL-C. During follow-up the blood pressure values were significantly reduced (p < 0.01) (captopril: delta SBP = -13.88, delta DBP = -12.38, nifedipine: delta SBP = -22.03, delta DBP = -21.35). In the nifedipine group lipoidoproteinosis has been more marked: delta% glicaemia = +17.69, delta% cholesterolemia = +20.11; delta% CFR = +18.57; LDL-C = +35.11; delta% VRF = +34.61, while in the patients treated with captopril we have had the following results: delta% glycaemia = +15.43; delta% cholesterolemia = +16.36; delta% LDL-C = +26.68. The control group with nifedipine treatment have shown only increased values of cholesterolemia: delta% = +4.80, moreover in the control group treated with captopril we have observed a reduction of VRF: delta% = -15. A significant relationship between total cholesterolemia and glycaemia in the group with nifedipine treatment (p < 0.01) and captopril (p < 0.01) has been reported. This study could appear to underline the autonomic nervous system activation by nifedipine which does not affect lipoidoproteinosis in diabetic hypertensive subjects. This would seem to confirm on the contrary, the utility of captopril in the treatment of atherosclerotic subjects, as diabetic hypertensive patients.

[Clinical hemorrheology and arterial hypertension]. / Emoreologia clinica ed ipertensione arteriosa.

In order to have a good haemorheological approach to hypertensives, we have put together a review with haemorheological subjects and with the relationships between plasmatic and haematic viscosity and hypertension in relation to pathophysiology, diagnosis, prognosis and treatment. In this review we deal with: (1) Clinical haemorheology. (2) Haematic viscosity. (3) The relationship between haemorheology and hypertension and between antihypertensive drugs and haemorheology. The study of viscosity and erythrocytes deformability, and of erythrocytes and platelets stickiness could pharmacologically correct the haemorheological disorders which can be some of the causes of hypertension.

[Transcutaneous oximetry in smokers with moderate hypertension and peripheral arterial disease treated with amlodipine and defibrotide, also with total smoking cessation]. / Ossimetria transcutanea in soggetti fumatori con ipertensione moderata e vasculopatia periferica in trattamento con amlodipina e con defibrotide e contemporanea abolizione totale del fumo di sigaretta.

To evaluate the hemorheological influence on oxygen release after a period of 4 months of suspension from smoking and of antihypertensive treatment with amlodipine 10 mg o.d. and defibrotide 400 mg o.d. we have studied 14 smokers with II moderate hypertension (according to the World Health Organization) with hypertensive retinopathy II and slight left ventricular hypertrophy and II stage type a peripheral arterial disease according to Leriche-Fontaine classification. The total suspension for a period of 4 months from smoking associated with a Ca-antagonist such as amlodipine and an hemorheological, antithrombotic drug such as defibrotide together could bring about an improvement on the treatment of hypertension and a notable reduction in the risks linked to the complications found in hypertensives with PAOD II type a.