Tapentadol prolonged release and the long-term management of chronic musculoskeletal pain in the elderly - focus on anxiety, depression, cognitive status and life quality: the TaPE study.

OBJECTIVE: The use of long-term opioids for the management of chronic musculoskeletal pain is a hot topic in the scientific community, especially when it concerns the elderly. This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining µ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain. The effect of this molecule on anxiety, depression, cognitive status, and overall quality of life were investigated. PATIENTS AND METHODS: This was a spontaneous, observational, open-label, prospective study, in 80 older patients aged ≥80 years, naïve to strong opioids, presenting moderate-to-severe chronic pain from different etiologies. Tapentadol PR was initially prescribed at the dose of 25-50 mg/day and increased gradually in case of insufficient analgesia. Pain intensity was assessed by a 10-point Numeric Rating Scale (NRS). Other endpoints were as follows: DN4 questionnaire for the evaluation of the neuropathic component of pain, SF12, HADS, and MMSE questionnaires to evaluate the quality of life, anxiety, and cognitive impairment, respectively. Safety evaluations were also performed through the assessment of the frequency and severity of adverse events. RESULTS: At T45, NRS score reduction was achieved in 86.0% of patients. On average, pain decreased by 55% from a mean of 8.2 to a mean of 3.6. At T90, tapentadol PR did not affect the psychophysical and cognitive abilities of older patients. CONCLUSIONS: The benefits with tapentadol PR in controlling pain have improved the quality of life of our patients, also showing a favorable effect on their cognitive performance.

Impairment of plasma nitric oxide availability in senescent healthy individuals: apparent involvement of extracellular superoxide dismutase activity.

To verify the potential involvement of the age-dependent modifications of EC-SOD activity in the impairment of plasma NO availability with advancing age, 40 healthy men divided into 4 age groups for the purpose of comparison (young: 27.4 +/- 1.5 years; middle: 50.8 +/- 2.2, years; old: 70.0 +/- 1.8 years; very old: 86.1 +/- 1.1 years) were enrolled in this study. Plasma samples were used for measurements of the stable end-product nitrite/nitrate (NOx), as an expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, low density lipoprotein (LDL) copper-mediated oxidation in vitro and total antioxidant capacity (TEAC). Our results indicated a significant age-related progressive decrease of plasma NOx content and EC-SOD activity and their values were positively correlated (r = 0.713, p < 0.001). Increased TBARS amount together with reduced lag time for in vitro oxidation of LDL and decreased content of TEAC were observed with advancing age. Finally, EC-SOD values were negatively correlated with plasma TBARS values (r = -0.855, p < 0.001). Findings of the present study suggest that the decrease of antioxidant defence strategies play a primary role by compromising NO availability in normally aged individuals, particularly through a progressive decrease of EC-SOD activity.

Possible involvement of oxidative stress in exercise-mediated platelet activation.

In this study, we have attempted to verify whether a single bout of strenuous exercise performed by sedentary healthy individuals may interfere with the mechanisms controlling platelet sensitivity through exercise-related modifications of plasma oxidant/antioxidant equilibrium. Strenuous exercise resulted in an increased ADP- and collagen-evoked platelet aggregation associated with modified membrane fluidity and ion homeostasis. We also observed an enhanced plasma accumulation of secondary products of lipid peroxidation together with an increased susceptibility of low density lipoprotein (LDL) to in vitro oxidation and a decreased total plasma antioxidant potential. Notably, an acute elevation of nitrite/nitrate (NOx) amount was detected in plasma, whilst a decreased NOx content was measured in platelets. Findings of the current study suggest that oxidative stress induced by acute strenuous exertion may interfere with platelet responsiveness by promoting ox-LDL-mediated platelet activation and by decreasing platelet-derived nitric oxide bioactivity.

Possible involvement of plasma antioxidant defences in training-associated decrease of platelet responsiveness in humans.

The aim of this study was to evaluate in sedentary individuals the effects of a 20-week exercise training program on ex vivo platelet responsiveness and the possible involvement of plasma antioxidant defences in relation to the mechanisms controlling platelet sensitivity. A statistically significant decrease in ADP- and collagen-evoked platelet aggregation was observed after physical training together with an increase in plasma total antioxidant capacity (TEAC), superoxide dismutase activity, and high-density lipoprotein cholesterol (HDL-C) concentration. Additionally, a rise in lag time for in vitro low-density lipoprotein (LDL) oxidation as well as a decreased plasma level of secondary products of lipid peroxidation were observed after training, and the values for lag time were significantly correlated with TEAC and HDL-C. Nitrate/nitrite (NOx) content both in plasma and in platelet cytosol was significantly enhanced at the end of the training period and a significant positive correlation was found between plasma and intraplatelet NOx values. Furthermore, intraplatelet NOx content was positively correlated with HDL-C levels. The findings of the current study suggest that the improvement of antioxidant defences induced by moderate regular exercise may be involved in desensitising blood platelets most likely through the inhibition of LDL oxidation and the simultaneous enhancement of plasma and intraplatelet NOx bioavailability and HDL-C level.

Self-measurement and ambulatory monitoring of blood pressure: a subject's chronobiological perspective.

Population studies show the direct benefit from self-measurement for guiding the treatment of patients with severe hypertension; they also separate groups of children with a positive vs. negative family history of high blood pressure, despite the difficulty of obtaining valid readings during the rest/sleep span, which are needed for a reliable estimation of the circadian parameters. From the viewpoint of preventive maintenance, a 67-year-old woman monitored her blood pressure and heart rate around the clock for 7 days, using concomitantly an ambulatory monitor and a manual instrument. Self-measurement profiles were repeated on several occasions. The results are compared with those of a 62-year-old woman who followed the same initial 7-day protocol. The estimation of the circadian blood pressure pattern differed between the profiles obtained with an ambulatory monitor and by self-measurement. The differences, relatively small in one subject, were much larger for the other subject. Provided the results are chronobiologically analyzed and interpreted in the light of reference limits which are specific to self-measurement series as well as for gender, age and times of sampling, systematic self-measurement of blood pressure may yield a reliable assessment of the circadian variation for some, but not for all, individuals. For those who have been validated in at least one 7-day/24-h profile, occasional automatic ambulatory profiles are tentatively recommended as the main approach, with complementary systematic self-measurement when automatic instruments are scarce. For those with discrepant results, automatic monitoring is invariably recommended.

Chronobiology of blood pressure.

The chronobiology of blood pressure is a useful tool for examining serial data to quantify the dynamics of variability. The implications and applications for diagnosis and therapy are discussed, with clinical examples. The chronobiological patterns of hypertension are described. Chronobiology can make a real contribution to the prevention of disease. Chronobiology helps diagnose circadian hyper-amplitude-tension (CHAT), a condition in which excessive circadian BP amplitude precedes chronic established hypertension.

Hypertensive vascular crisis secondary to chronic total renal artery occlusion.

We have reviewed thirty-three cases of accelerated hypertension associated with chronic total renal artery occlusion. During the process of progressive narrowing of the arterial lumen until complete occlusion, an exceptionally elevated blood pressure occurs when a critical reduction of renal blood flow is attained. Then the patient presents one or more of the following clinical manifestations: III-IV grade KWB retinal changes, hypertensive encephalopathy including convulsive attacks, stroke, heart failure, renal insufficiency. We have called this clinical event 'hypertensive vascular crisis'. Mostly in older patients an actual or anamnestic vascular crisis makes a diagnosis of chronic total renal artery occlusion highly probable.

Accelerated (malignant) hypertension: a study of 121 cases between 1974 and 1996.

A series of 121 consecutive cases with accelerated hypertension is presented. Forty-seven patients had essential hypertension. This diagnosis was confirmed during the follow-up, which lasted from 3 to 255 months (mean 63.1 +/- 58.1). The relationship between the effects of pharmacological treatment on high blood pressure (BP) and disease course were analyzed in accelerated essential hypertensive patients only, to avoid the imponderable influence of basic disease in secondary hypertension. In most cases, therapeutical effect on BP was monitored by multiple daily BP self-measurements. Since 1974, when this study was initiated, plasma creatinine concentration at admission showed a clear-cut decrease, especially after the introduction in the eighties of new hypotensive drugs. A sustained BP decrease assured a long-lasting preservation of renal function, if the initial functional loss was limited (plasma creatinine concentration of 2 mg/dl (176.8 mumol/l) or less). Renal function was preserved even if the BP decrease was not optimal and signs of relapsing malignant retinopathy were observed in the course of disease. Although the whole series showed a 12-year survival rate of about 69%, patients enrolled after 1980 had a 100% survival rate.

Simultaneous and sequential same-arm measurements in the validation studies of automated blood pressure measuring devices.

The oscillometric ambulatory blood pressure recorder Daypress 500 was validated according to the British Hypertension Society protocol. Both sequential and simultaneous measurements were used. Multiple regression analysis demonstrated a significant influence of subject pulse pressure and arm circumference on device-observer systolic pressure differences. Differences between observer consecutive readings were inversely related to heart rate. Device and observer blood pressure readings were closer at simultaneous than at sequential measurements. However, both kinds of measurement led to the same final evaluation (A for diastolic and B for systolic blood pressure), provided that the appropriate grading criteria were applied for each method.

Rapid determination of erythrocyte pyruvate kinase activity.

We report a new potentiometric method for determining pyruvate kinase (PK). Enzymatic activity is measured by monitoring the change in pH produced in the reaction buffer under International Committee for Standardization in Haematology (ICSH) standardized assay conditions, and the lactate dehydrogenase reaction is automatically subtracted in each measuring cycle. The analysis, performed at 37 degrees C, requires a 10-microL sample (isolated erythrocytes or whole blood) and is completed in 2.5 min. The intra-assay CV is < 4% (PK between 3 and 35 U/g Hb); the interassay CV is 4.0% (PK 15 U/g Hb); results are linear from 3 to 30 U/g Hb. A good correlation with the ICSH reference method (x) was found: y = 1.011x - 0.05; n = 32; r = 0.9939; Sylx = 0.75 (units: U/g Hb). The reference intervals of the PK activity in isolated erythrocytes (RBC-PK) were estimated in 89 normal subjects. We found that women possess a higher RBC-PK than do men (P < 0.0001) and that the biological variability (CVb) of RBC-PK is 13.5%. Applications of the proposed method to the hematological routine are reported.

Echocardiographic evaluation of children with and without family history of essential hypertension.

A family history of hypertension is considered a risk factor for developing hypertension. We studied two groups of normotensive children (aged 14 years): one comprising 14 subjects with family history of hypertension, the other comprising 15 subjects without family history of hypertension. Children were comparable with respect to age, weight, height, body surface area, heart rate, and arterial blood pressure. M-mode echocardiography demonstrated higher interventricular septum/posterior wall ratio in progeny of hypertensive subjects. Interestingly, all the parameters evaluated were within the normal limits. Our data suggest that a certain degree of cardiac changes is present in children with positive family history of hypertension, though further studies are needed before considering these findings predictive of future essential hypertension.

Circadian variability of blood pressure and heart rate in newborns and cardiovascular chronorisk.

At present, neonates are being given screening tests for relatively rare diseases, such as phenylketonuria. The time has come to give emphasis to assessing the risk for major handicapping diseases, such as coronary heart disease, stroke, and certain diseases of the kidney. Modern technology for blood pressure and heart rate monitoring and data analysis provides noninvasive means to determine when preventive measures are indicated.

Autometrically and automatically monitored, iatrogenous, inhalant-decongestant-associated high blood pressure quantified by rhythmometry.

Blood pressure and heart rate were oscillometrically monitored with an automatic Nippon Colin instrument (Komaki, Japan) and were also self-measured by a 20-year-old man treated with an inhalant-decongestant containing an adrenergic and a corticosteroid analog. The subject also collected 24-hr urines for aldosterone determination. An elevation of urinary aldosterone excretion was observed compared to the usual value range of a peer group. After removal of the drug, urinary aldosterone dropped as did urinary potassium, whereas plasma potassium rose. Chronobiologic serial sections, carried out to follow the time course of blood pressure and heart rate, showed decreasing trends in MESOR after discontinuance of treatment. A decrease in the hyperbaric index, a measure of blood pressure excess over 24 hr, was also observed. Another subject treated with the same and a third treated with a similar inhalant-decongestant, who also monitored their blood pressures automatically and/or with self-measurements, showed similar effects: a decrease in blood pressure after removal of treatment and an increase in blood pressure when (for testing only) treatment was briefly resumed.

A modified bladder washout test to improve diagnostic results in chronic urinary tract infections.

Bladder washout (BWO) and antibody-coated bacteria (ACB) tests were performed on 25 patients with radiological and/or clinical evidence of chronic upper urinary tract infection (UTI) and 12 patients with asymptomatic bacteriuria. Using a traditional single-washout procedure, the BWO test gave equivocal results in many cases of chronic pyelonephritis; this seemed mainly due to the lack of complete bladder sterilization. A modified procedure, including double sterilization and irrigation, biochemical typing of isolated bacteria, and evaluation of temporal pattern of bacteriuria recurrence, was then introduced. Although preliminary results of the modified BWO test demonstrated a general improvement in the diagnosis of the infection site, it seemed rather difficult, at least in chronic UTI, to establish localizing criteria based on definite numeric changes in bacterial counts after washout.

The maternal 24-h blood pressure (BP) profile as a predictor of fetal distress.

No mention is made of any aspect of BP bioperiodicity, among current clinical criteria for diagnosing pregnancy-related hypertension. The abnormal BP, based on a single unqualified measurement, is accepted and utilized as a clinical feature to identify pregnancy at risk. Systolic, diastolic and mean arterial blood pressure were measured every 15 min for 24 h in 5 women (2 non pregnant clinically healthy subjects, 1 clinically healthy subject in her third trimester of pregnancy, 1 presenting mild and 1 severe toxiemia, also in their third trimester of pregnancy) by an automated BP recording apparatus (Dynamap). All variables, analyzed by the single cosinor method, exhibited statistically significant circadian rhythms. A high amplitude could nullify the time-unqualified usual range. The change in circadian amplitude precedes an overt mesor hypertension and constitutes a tool for earlier detection of fetal distress.