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Biomedical subjects

J M Pascual

Publications and source records attributed to J M Pascual.

At least 55 records · Page 3Linked to original sources

Microalbuminuria, left ventricular mass and ambulatory blood pressure in essential hypertension.

The objective of the present study was to assess the relationship between microalbuminuria (Malb) and left ventricular hypertrophy (LVH), when levels of ambulatory BP was token in to account as a confounder factor. Patients with essential hypertension, aged 25 to 50 years old, never treated with antihypertensive drugs, were included in the study. The inclusion criteria were: (a) absence of diabetes, renal disease or urinary tract infection; (b) urinary albumin excretion (UAE) estimated in urine of 24 hours in two separate days; (c) echocardiography suitable for measurement of left ventricular mass (LVM); and (d) good quality ambulatory blood pressure monitoring during 24 hours. UAE was measured using a immunonephelometric assay (Behring Institute) and Malb was considered when UAE 30 to 300 mg/24 hours during the two days. LVM was calculated by the Devereaux formula and referred to height (LVMI g/m). AMBP was performed using an oscilometric device (Spacelabs 90202 or 90207) during a regular working day. Readings were programmed every 20 minutes between 6 a.m. to midnight and thereafter every 30 minutes. The average BP during a 24 hour period was calculated. One hundred and fifty one patients (96 male, mean age 37 +/- 8 years, body mass index 27.7 +/- 3.7 g/m2) were included. The average values of office BP was 148 +/- 15/96 +/- 8 mm Hg, and the average BP during 24 hours was 137 +/- 13/88 +/- 12 mm Hg. UAE was 30.1 +/- 52.3 mg/24 hr and the LVMI 140.6 +/- 44.1 g/m. The percentage of Malb patients was 28% and those with LVH 34%. A significant relationship between UAE and office and ambulatory SBP and DBP was observed. LVMI was also significantly related to ambulatory SBP and DBP, a relationship that was not found for office BP. In a multiple regression model, significant relationship between UAE and LVMI emerged, independent of diastolic ambulatory BP, age and sex (P < 0.04). In conclusion; we observed a significant relationship between UAE and LVMI, in part, independent of blood pressure. The fact that Malb is associated with the presence of LVH, supports the idea that Malb is a risk marker in essential hypertensive patients.

Adult↗

CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance.

Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expression. Immunohistochemical analysis of formalin-fixed paraffin-embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone.

8,11,14-Eicosatrienoic Acid↗

[Urinary albumin excretion during the night in essential arterial hypertension].

BACKGROUND: The value of nocturnal minute-by-minute urine was analyzed for the detection of microalbuminuria in high blood pressure. METHODS: Urinary albumin excretion (UAE) was measured by immunonephelometry in 70 patients with essential arterial hypertension (34 males, mean age 44 +/- 5 years, body mass index [BMI] 28 +/- 4, clinical blood pressure [BP] 157 +/- 12/97 +/- 7 mmHg) and 12 healthy normotensive controls (5 males, mean age 38 +/- 4 years, BMI 27 +/- 3; clinical BP 126 +/- 12/79 +/- 5 mmHg). Both 24 hours urine as well as nocturnal urine were collected over 2 days. The intraindividual variability was evaluated by calculation of the intraclass correlation coefficient and by the Bland and Altman method. RESULTS: Mean 24-hour UAE was 24.7 +/- 41.9 micrograms/min, greater than nocturnal urine (17.7 +/- 32.8 micrograms/min) (p < 0.05). The UAE rate was significantly greater in the hypertensive patients than in the controls (p < 0.01) for both the 24-hour and nocturnal urine. The intraindividual variability estimated as the percentage of repeatability was 35% for 24-hour UAE and 43% for nocturnal UAE, being slightly higher values than those observed in the controls. Microalbuminuria was detected in 17 (24%) of the patients in 24-hour samples while in the nocturnal urine 12.12 or 10 patients were found according to whether the threshold considered was 14 micrograms/min, 14.9 micrograms/min or 20 micrograms/min, respectively. While the specificity in nocturnal minute-by-minute urine was 98% and the positive predictive value was 0.91 for any of the thresholds considered, sensitivity ranged from 59% for the higher threshold (20 micrograms/min) to 70% for the lower threshold (14 micrograms/min). CONCLUSIONS: The determination of microalbuminuria in minuted nocturnal urine in patients with essential arterial hypertension is less sensitive than that determined in 24-hour urine.

Adult↗

K+ pore structure revealed by reporter cysteines at inner and outer surfaces.

The structure of the carboxyl half of the pore-forming region of Kv2.1 was studied by replacing each of 15 consecutive residues between positions 383 and 369 with a reporter cysteine residue. Extracellular application of charged, membrane-impermeant methanethiosulfonates irreversibly modified currents at four cysteine-substituted positions, K382, Y380, I379, and D378. Intracellular exposure to methanethiosulfonate ethyltrimethylammonium revealed another set of reactive mutants (V374, T373, T372, and T370). Our results indicate that positions 378 and 374 are exposed at outer and inner mouths of the channel, respectively, and immersed in the aqueous phase. In contrast to present topological models, the 383-369 region appears to span the pore mainly as a nonperiodic structure.

Amino Acid Sequence↗

Multiple residues specify external tetraethylammonium blockade in voltage-gated potassium channels.

We have mapped residues in the carboxyl half of the P region of a voltage-gated K+ channel that influence external tetraethylammonium (TEA) block. Fifteen amino acids were substituted with cysteine and expressed in oocytes from monomeric or heterodimeric cRNAs. From a total of six mutant channels with altered TEA sensitivity, three were susceptible to modification by extracellularly applied charged methanethiosulfonates (MTSX). Another residue did not affect TEA block but was protected from MTSX by TEA. MTSX modification of position Y380C, thought to form the TEA binding site, affected TEA affinity only moderately, and this effect could be reversed by additional charge transfer from an oppositely charged MTSX analog. The results show that TEA block is modulated from multiple sites, including residues located deep in the pore and that several side chains besides that of Y380 are exposed at the TEA receptor.

Amino Acid Sequence↗

Functional role of a conserved aspartate in the external mouth of voltage-gated potassium channels.

Mutation of the glycines in a conserved Gly-Tyr-Gly-Asp sequence in the P-region of voltage-gated K channels has identified determinants of Na/K selectivity. But the function of the negatively charged Asp is not known because mutations at this position are not tolerated, owing to the fourfold replication of mutations in a tetrameric channel. We have successfully mutated Asp378-->Thr in a tandem dimer Kv2.1 construct to yield a twofold neutralization of charge at this site. When expressed in Xenopus oocytes, the mutated channels showed markedly altered ion conduction and blockade. Potassium conduction in the inward direction was selectively reduced, so that the instantaneous current-voltage relationship obtained in isotonic KCl became strongly outwardly rectifying. The relative permeability to Na+, PNa/PK, increased from 0.02 to 0.10 without changing the ion selectivity sequence K > Rb >> Cs >> Na. The IC50 for block by external tetraethylammonium (TEA) increased more than 100-fold without affecting block by internal TEA. We conclude that Asp378 is an essential part of a potassium ion binding site associated with the Na/K selectivity filter at the external mouth of the pore.

Amino Acid Sequence↗

[The prognostic value of plasma triglycerides in human immunodeficiency virus infection].

BACKGROUND: Infection with the human immunodeficiency virus (HIV) is associated with an increased prevalence of hypertriglyceridemia, which is more common in advanced stages of disease. Nevertheless, the role of hypertriglyceridemia as a predictive marker of progression of disease and/or mortality is not fully elucidated. METHODS: One-hundred nineteen patients with HIV infection attended at our Outpatient Clinic or hospitalized in our Service were retrospectively studied. At the beginning of the study and every six months a complete medical history and physical examination were obtained, with a complete blood count, serum biochemistry, total lymphocytes and CD4 subpopulations, cholesterol, triglycerides and IgA. With comparative purposes cholesterol and triglyceride values were also determined in a control group of healthy subjects with the same age and gender. The relationship between triglyceride levels and the other clinical and analytical parameters was evaluated by means of the Pearson linear correlation. The risk for developing clinical disease and survival were studied by the method proposed by Kaplan and Meier. RESULTS: The mean age of patients was 27 +/- 6 years and the male/female ratio was 86/33. Eighty-three percent (99) of patients consumed drugs parenterally. Compared with the control group, patients with HIV infection had hypertriglyceridemia (159 +/- 80 mg/dl vs 79 +/- 53 mg/dl) and hypocholesterolemia (143 +/- 41 mg/dl vs 174 +/- 36 mg/dl) (p < 0.05). There was a positive correlation between triglycerides and IgA levels (p < 0.01) and a negative correlation with serum albumin (p < 0.05). A higher risk towards progression of disease was not observed among patients with hypertriglyceridemia (TG > 143 mg/dl) in non-AIDS infected patients, nor mortality in the overall group. CONCLUSIONS: HIV infected patients have a higher prevalence of hypertriglyceridemia and hypocholesterolemia. Plasma triglycerides were not useful as a prognostic factor for the development of disease nor as mortality risk.

Adult↗

Ambulatory blood pressure and microalbuminuria in essential hypertension: role of circadian variability.

OBJECTIVE: To assess the relationship of subclinical urinary albumin excretion with ambulatory and circadian variability of blood pressure. DESIGN AND METHODS: Patients with essential hypertension (82 males and 59 females, mean +/- SD age 38.9 +/- 7.3 years) who had never been previously treated for hypertension were included in the study. Patients with nephropathy or diabetes mellitus, hyperglycemia > 120 mg/dl, glomerular filtration rate < 80 ml/min per 1.73 m2, urinary tract infection and positive dipstick for albumin or glucose were excluded. Twenty-four-hour ambulatory blood pressure monitoring on a regular working day using an oscillometric device was performed. Twenty-four-hour urinary albumin excretion was measured on two separate days using an immunonephelometric assay. RESULTS: Microalbuminuric patients (urinary albumin excretion 30-300 mg/24 h, n = 31) had significantly higher mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) than those with normoalbuminuria (urinary albumin excretion < 30 mg/24 h, n = 96) during the 24-h, daytime (0800-2200 h) and night (2400-0600 h) periods, whereas for office blood pressure only DBP was significantly higher. Urinary albumin excretion was positively correlated with the means of SBP and DBP. Multiple regression analysis similarly confirmed that DBP during daytime was positively and day:night ratio of DBP inversely associated with urinary albumin excretion independent of age, sex and other parameters of ambulatory blood pressure. CONCLUSIONS: In conclusion, the present study indicates that, in middle-aged essential hypertensive patients, the presence of microalbuminuria is a marker for the presence of higher values of blood pressure throughout a 24-h period.

Adult↗

Development of pulmonary hypertension after placement of a ventriculoatrial shunt.

The ventriculoatrial shunt (VAS) was developed to control hydrocephalic syndromes effectively. Several complications, however, have been described after the procedure. One of the most serious consequences is the development of severe pulmonary hypertension attributed to multiple and recurrent pulmonary embolization caused by the catheter of the VAS; however, the frequency is exceedingly low. Herein we describe the experience with three patients in whom severe pulmonary hypertension developed after a VAS procedure. In two patients, refractory heart failure developed, an outcome that caused death within a brief period. The third patient underwent atrial thrombectomy and then pulmonary thromboendarterectomy; recovery was complete. Scientific evidence shows that initial embolization predisposes pulmonary vessels to develop further in situ thrombosis; thus, the vascular lung disease progresses despite removal of the embolic source. A review of the literature revealed that in patients with a VAS, pulmonary embolism and pulmonary hypertension were clinically diagnosed in only 0.4% and 0.3% of the cases, respectively, whereas postmortem diagnoses of pulmonary embolism and pulmonary hypertension were established in 59.7% and 6.3%, respectively. These discrepancies point out the difficulty of establishing the diagnosis of these serious pulmonary vascular complications while the patient is alive.

Adult↗

Altered blood pressure during sleep in normotensive subjects with type I diabetes.

This study was designed to examine the circadian pattern of blood pressure in children and young adults with type I diabetes who were completely normotensive by standard criteria. Forty-five patients and the same number of age- and sex-matched control subjects were studied. In diabetic children of 10-14 years of age, the nocturnal fall in systolic and diastolic blood pressures was intact. In diabetics of 15-20 years of age, the fall in systolic blood pressure was blunted; in diabetics of 21-37 years of age, the fall in both systolic and diastolic blood pressures during sleep was blunted. When data from all diabetic subjects were pooled and analyzed in a multiple linear regression model, mean blood pressure during sleep correlated best with urinary albumin excretion (r = 0.60). On the basis of this finding, we subdivided our patients into two groups: a microalbuminuric group (urinary albumin excretion > 30 mg per 24 hours; mean, 160.3 +/- 29.7; n = 11) and a normoalbuminuric group (urinary albumin excretion < 30 mg per 24 hours; mean, 6.6 +/- 6.5; n = 34). Both systolic and diastolic blood pressures during sleep were higher in microalbuminuric (121.1 +/- 3.3 and 69.3 +/- 2.5 mm Hg, respectively) than in normoalbuminuric diabetics (114.2 +/- 1.8 and 60.1 +/- 1.2 mm Hg, p < 0.05) or control subjects (113.3 +/- 1.2 and 60.1 +/- 1.2 mm Hg, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Resuscitation of hypovolemia in pigs using near saturated sodium chloride solution in dextran.

A 7.5% sodium chloride/6% Dextran solution (HSD) is effective for restoration of cardiovascular function after hemorrhagic shock. In the present experiments, we tested the usefulness and side effects of a 25% NaCl/24% Dextran solution (SSD), compared to HSD and 0.9% NaCl (NS). After 1 hr of baseline observation, 21 anesthetized pigs were submitted to hemorrhagic shock, maintaining a mean arterial pressure of 45 mmHg for 60 min. Continuous intravenous infusion of one of the solutions was then initiated and the infusion rate adjusted to restore and maintain cardiac output at baseline levels for 2 hr. The NS group required 121 +/- 22 ml/kg to achieve full resuscitation, while the HSD and SSD groups required 6.3 +/- 1.3 and 1.7 +/- 0.2 ml/kg, respectively. We conclude that SSD infusions were exceedingly effective at restoring cardiovascular function in volumes equal to only 10% of bled volume, but were associated with transient hemolysis and peripheral vein inflammation.

Animals↗

Resuscitation of intraoperative hypovolemia: a comparison of normal saline and hyperosmotic/hyperoncotic solutions in swine.

BACKGROUND AND METHODS: We compared a hypertonic saline-dextran solution (7.5% NaCl/6% dextran-70) with 0.9% NaCl (normal saline) for treatment of intraoperative hypovolemia. Fourteen anesthetized pigs (mean weight 36.3 +/- 2.1 kg) underwent thoracotomy, followed by hemorrhage for 1 hr to reduce mean arterial pressure to 45 mm Hg. A continuous infusion of either solution was then initiated and the flow rate was adjusted to restore and maintain aortic blood flow at baseline levels for 2 hrs. RESULTS: Full resuscitation to initial values of aortic blood flow was achieved with both regimens, but the normal saline group required substantially larger volumes and sodium loads to maintain stable hemodynamic values. Normal saline resuscitation produced increases in right ventricular preload (central venous pressure) and afterload (pulmonary arterial pressure and pulmonary vascular resistance), resulting in increased right ventricular work. CONCLUSIONS: Hypertonic saline-dextran solution resuscitation of intraoperative hypovolemia is performed effectively with smaller fluid and sodium loads, and is devoid of the deleterious effects associated with fluid accumulation induced by a conventional isotonic solution regimen.

Animals↗

[Dementia as a presentation symptom of giant cell arteritis].

Giant Cells Arteritis (GCA) can be presented sometimes with atypical manifestations which greatly difficult its diagnosis. We present a case of GCA in a 58-year-old man with dementia as first symptom. In the anamnesis, signs of rheumatic polymyalgia were observed, as well as a recently started dementia with a very disturbed mini-mental test. The analytic study showed anemia (Hb of 7.44 nmol/l, with 3.2 x 10(12) red cells and a GSR of 85 mm). The diagnosis of GCA was supported by a temporal biopsy. In a study of magnetic resonance, there were no evidences of brain infarct areas. After treatment with prednisone, normalization of GSR and a significant improvement of cortical functions were observed. GCA must be considered in the initial diagnosis of a patient with mental disorders, given that it is one of the curable causes of dementia.

Dementia↗

[Microalbuminuria in essential arterial hypertension].

BACKGROUND: The occurrence of microalbuminuria (mAlb) in essential hypertension (HT) was evaluated. METHODS: 100 patients were studied (56 males), with mean age 39 +/- 6 years, body mass index (BMI) 28 +/- 4. 32 had borderline HT, 47 had mild HT and 21 had moderate HT. 74 were in stage I of the WHO and 26 were in stage II. All had normal renal function (creatinine 91 +/- 12 mumol, Clcr 92 +/- 13 ml/m/1.73 m2) and no proteinuria as measured by sulphosalicylic acid. mAlb was immuno-nephelometrically measured in two 24-hour urine samples, and was given as urinary albumin excretion (UAE). In 62 patients, noninvasive ambulatory recording of blood pressure (NIAR) was carried out. In 39, ventricular mass was estimated by echocardiography. RESULTS: UAE was correlated with SPB24h (r = 0.39) and DBP24h, but not with SBP or DBP. UAE was greater in patients with moderate HT than in those with mild or borderline HT (p less than 0.01). UAE was less than 20 mg/24 h in 70 patients (group A) and greater than 20 mg/24 h in 30 (group B). The comparative analysis of the two groups showed different clinical BP values (SBP p less than 0.01; DBP p less than 0.001) and NIAR (SBP 24 h p less than 0.001; DBP 24 h p less than 0.05). In the 47 patients with mild HT the only differential parameter between groups A and B was SBP24h (p less than 0.05). Regarding echocardiographic data, in higher UAE levels a greater left ventricular mass index was found in males (chi-square p less than 0.05). CONCLUSIONS: Increased mAlb is associated with more severe HT. This finding may be helpful for the initial evaluation of hypertensive patients.

Adult↗

[Acute rhabdomyolysis. A study of 44 cases].

Fourty four patients suffering non traumatic rhabdomyolysis (RM) are studied. The most frequently encountered etiologies were neurologic abnormalities in 26 patients, followed by infections in 7 patients and metabolic abnormalities in four cases. Eleven patients (25%) presented several associated factors. The clinical manifestations of RM were not very significant, with only 18% of patients presenting muscle pain, 38.6% proteinuria and 36.4% hematuria. A significant increase in K, CPK, LDH, and ASAT values was observed after the RM episode (p less than 0.05). Those patients with an infectious RM were older (p less than 0.05) and presented higher urea (p less than 0.01) and creatinine (p less than 0.05) values. Only two patients presented renal failure. One patient with septic shock died. RM is a relatively common condition, often secondary to multiple systemic processes, which can go unnoticed due to the underlying disease.

Acute Disease↗