[Endoscopic techniques in bronchogenic carcinoma. Changes in recent decades]. / Técnicas endoscópicas en carcinoma broncogénico. Cambios en las últimas décadas.

A 57-year old woman with arterial hypertension under treatment. She has smoked since she was 18 years old with an accumulated index of 70 years/pack. She was studied in our Respiratory Department due to constitutional syndrome, the X-ray showing an image of focal pulmonary lesion in the right upper lobe of more than 3cm of peripheral location. The computed tomography (CT) scan confirmed the existence of a 3.3cm mass in the upper right lobe and detected paratracheal and subcarinal mediastinal abnormal lymph nodes. A subsequent Positron Emission Tomography (PET) confirmed pathological uptake of the mass and both lymph node locations. Which additional studies do you consider to be indicated for a correct diagnosis and mediastinal staging? Do bronchoscopy techniques alone establish the final diagnosis and staging of this patient?

Prophylaxis against postcontrast acute kidney injury (PC-AKI): updates in the ESUR guidelines 10.0 and critical review. / Profilaxis de la lesión renal aguda poscontraste (LRA-PC). Actualización según la guía clínica ESUR 10.0 y revisión crítica.

The European Society of Urogenital Radiology (ESUR) updated its guidelines for prophylaxis against postcontrast acute kidney injury (PC-AKI) in 2018 (ESUR 10.0). These guidelines drastically reduce the indications for prophylaxis against PC-AKI after iodine-based contrast administration, lowering the cutoff for administering prophylaxis to glomerular filtration rates <30ml/min/1.73m2 and eliminating most of the prior risk factors. Moreover, in cases where prophylaxis is considered necessary, the periods of hydration are shorter than in the previous version. These guidelines have been approved by most radiological societies, although they have also been criticized for excessive relaxation regarding risk factors, especially by the nephrological community. In this article, we critically review the changes to the guidelines.

An update on tolvaptan for autosomal dominant polycystic kidney disease.

Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This has been the rationale for the use of tolvaptan to halt the progression of ADPKD, mainly through slowing kidney growth and decline in renal function. Two major randomized clinical trials have demonstrated the benefits of tolvaptan in slowing the progression of ADPKD in terms of kidney growth and decline in renal function at 1 and 3 years (REPRISE and TEMPO). However, the long-term effectiveness of treatment with tolvaptan remains to be determined.

Acute tubulointerstitial nephritis associated with atezolizumab, an anti-programmed death-ligand 1 (pd-l1) antibody therapy.

Direct stimulation of the antitumor activity of immune system through checkpoint inhibitors (ICIs) has demonstrated efficacy in the treatment of different cancer types. The activity of these antibodies takes place in the immunological synapse blocking the binding of the negative immunoregulatory proteins, thus leading to the finalization of the immune response. Despite having a favorable toxicity profile, its mechanism of action impedes the negative regulation of the immune activity which can potentially favor autoimmune attacks to normal tissues. Renal toxicity has been described in several ICI but not with atezolizumab, an IgG1 monoclonal antibody targeting PD-L1 (programmed death ligand 1), approved by FDA as a second-line therapy for advanced urothelial carcinoma. Here we present a patient with a single kidney and metastatic renal cell carcinoma treated with atezolizumab and bevacizumab combination, with biopsy-proven acute interstitial nephritis, who had a complete resolution of renal dysfunction after steroid therapy.

[Hypertension in hemodialysis: prevalence and associated factors in Catalonia. The PRESDIAL study]. / Prevalencia y factores asociados a hipertensión arterial en hemodiálisis en Cataluña. Estudio PRESIDIAL.

OBJECTIVE: To evaluate the prevalence of hypertension (HT) in prevalent hemodialysis (HD) patients in our region, and to analyze the associated clinical and biochemical variables. METHODS: Observational, cross-sectional and multicentric study including a representative sample of prevalent and stable (> 6 months) HD patients from all the HD centers (in and out of Hospitals) in Catalonia, Spain. Clinical and biochemical variables were recorded and predialysis blood pressure (BP) was determined (x3) in each dialysis session during 1 month, as well as the pre/post weight weekly. HT was defined as having at least one of these criteria: a mean (12 determinations) systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or antihypertensive treatment for at least 3 months. RESULTS: The sample comprised 387 patients from 32 of the 40 centers included, 231 of whom where men, with mean age of 63 +/- 14 years. The prevalence of HT in this sample was 67.4%, varying according to the etiology of End-Stage Renal Disease: diabetic 81%, vascular 81%, glomerulonephritis 61%, PKD 52%, unknown and others 64%. The prevalence of additional CV risk factors was 83%. One of each hypertensive 4 patients were treated, of whom 58% had systolic BP > or = 140 or dyastolic > or = 90, in contrast to 28% of untreated patients. The proportion of individuals according to the number of antihypertensive agents was 21% (no agents), 48% (1 agent), 20% (2 agents), 11% (3 agents). Blood pressure was higher among patients receiving higher number of antihypertensive agents. No differences according HT were found in age (64 +/- 13 in hypertensive patients versus 60 +/- 15 in normotensives), time on dialysis (4 +/- 4 vs 4 +/- 4 years), interdialysis weight gain (2.1 +/- 0.8 vs 2.1 +/- 0.8 kg), proportion of weight gain (3.3 +/- 1.4 vs 3.1 +/- 1.4%) or proportion of patients with > 5% weight gain with respect to dry weight (32.5 vs 27.3%). While 84% of hypertensive patients had an additional CV risk factor, this value was 67% in the patients without HT (p < 0.001). CONCLUSION: In HD patients HT has a high prevalence in our region and is poorly controlled. The causes of this poor control may be multiple, and weight gain parameters seem not to be a main factor in these stable patients. Due to the aggregation of risk factors in these patients, strategies in order to improve BP control in HD are mandatory.

[Baclofen-associated encephalopathy in a hemodialysis patient with hiccups]. / Encefalopatía asociada a baclofeno como tratamiento del hipo refractario en un paciente en hemodiálisis.

Baclofen is a centrally acting gamma-ammino butyric acid agonist that is used like muscular relaxant in disorders with spasticity and intractable hiccups. Although encouraging and safe results were provided 5 mg/day in hemodialysis patients, his pharmacokinetic and pharmacodinamic properties are not well known in end stage renal disease. We present here the case of a hemodialysis patient with intractable hiccups who developed baclofen-associated encephalopathy with this recommended dose.

Cambios en las indicaciones en la Unidad de Endoscopia Respiratoria del Hospital Universitario 12 de Octubre en los últimos años / Changes in the type of bronchoscopies in last years in the endoscopy respiratory unit of university hospital 12 octubre

Los objetivos de este trabajo son estudiar y valorar si han existido cambios en las indicaciones de broncoscopia en la Unidad de Endoscopia Respiratoria (UER) del Hospital Universitario (H.U.) 12 de Octubre en los últimos años, puesto que se han observado cambios epidemiológicos en distintas patologías respiratorias y se han incorporado nuevas técnicas endoscópicas. Por otra parte y dado que el trasplante pulmonar se introdujo en este hospital en el año 2008, también hemos valorado las diferencias en cuanto a las indicaciones de broncoscopia entre los pacientes sometidos a trasplante frente al resto en un segundo periodo de tiempo. Para realizar el estudio se ha utilizado la base de datos de la Unidad de Endoscopia Respiratoria del H.U. 12 de Octubre. Se han comparado pacientes de dos periodos de tiempo similares de 5 años: 2003-2008 vs. 2013-2018. En este último grupo se han valorado las diferencias entre los pacientes con trasplante pulmonar frente al resto. En los últimos cinco años se ha observado un mayor requerimiento de técnicas diagnósticas más complejas, una utilización mayoritaria de la sedación y un mayor número de pacientes en régimen hospitalario. Los pacientes con trasplante pulmonar tienen mayor necesidad de exploraciones urgentes y en régimen hospitalario, con mayor requerimiento de técnicas como la biopsia transbronquial y el lavado broncoalveolar. Por tanto como conclusión podemos decir que se han producido cambios en las indicaciones con una mayor complejidad en los últimos cinco años (AU)

Since epidemiologic changes regarding bronchogenic carcinoma had been related and new endoscopic techniques are available, one of the objectives of this study is evaluate the changes in bronchoscopy indications in the Unity of Respiratory Endoscopy of the H.U. 12 de Octubre. On the other hand, since lung transplantation has been introduced in H.U. 12 de Octubre in 2008, another objective is evaluate the differences related to bronchoscopy indication between patients with lung transplantation and not. We have used the database from the Unity of Respiratory Endoscopy of the H.U. 12 de Octubre. We have compared patients from two different periods: 2003-2008 (Period 1) and 2013-2018 (Period 2). We have also evaluated the differences between lung transplantation and not during period 2. Along the last five years we have related the following changes: a larger requirement of diagnostic techniques (TBP, BAL), a main use of sedation and a larger number of patients under hospital admission. As a conclusion, the bronchoscopy has become more complex. Patients with lung transplantation have more necessity of urgent examination under hospital admission and a larger request of specific techniques such as transbronchial biopsy and bronchoalveolar lavage. Therefore, this patients had entailed changes in the complexity if the bronchoscopy techniques in the last five years (AU)

Role of Sp1 in the induction of p27 gene expression in vascular smooth muscle cells in vitro and after balloon angioplasty.

-The abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis and restenosis. Although several studies have implicated the growth inhibitory protein p27(Kip1) (p27) in the control of myocyte growth and hypertrophy, little is known about the molecular mechanisms that regulate p27 expression in the cardiovascular system. In the present study, we demonstrate the interaction of the transcription factor Sp1 with 2 GC-rich sequences within the p27 promoter in cultured VSMCs. Importantly, point mutations that disrupted Sp1 binding markedly reduced p27 promoter activity, demonstrating that Sp1 is required for efficient p27 gene transcription in cultured VSMCs. Because p27 expression is upregulated after balloon angioplasty, we investigated Sp1 expression and activity in control and balloon-injured rat carotid arteries to assess the role of Sp1 as a physiological regulator of p27 expression. Although immunohistochemical analysis disclosed Sp1 protein expression in both control and balloon-injured arteries, a high level of Sp1 DNA-binding activity was found only in response to balloon angioplasty. Collectively, these results demonstrate that Sp1 is essential for maximum p27 promoter activity in VSMCs and suggest that posttranslational induction of Sp1 DNA-binding activity contributes to the induction of p27 expression and VSMC growth arrest at late time points after balloon angioplasty.

Rotura traqueal iatrogénica en paciente con COVID-19 resuelta con manejo conservador / Iatrogenic tracheal rupture in COVID 19 patient solved with conservative management

El síndrome de distrés respiratorio del adulto por SARS-CoV-2 ha sido una de las causas de requerimiento de intubación orotraqueal (IOT) en pacientes con insuficiencia respiratoria grave. En los pacientes ingresados en la Unidad de Cuidados Intensivos (UCI) con dificultad para la desconexión de ventilación mecánica invasiva, se considera la traqueostomía como una opción terapéutica para la progresión respiratoria. La traqueostomía percutánea es una técnica que ofrece varias ventajas en comparación con la quirúrgica, es más rápida, más barata y tiene menos complicaciones de forma global, si bien es cierto que presenta mayor riesgo de laceración o rotura traqueal. Presentamos un caso de rotura traqueal en paciente con neumonía grave SARS-CoV-2 tras traqueostomía percutánea resuelta con manejo conservador y una revisión de la literatura

SDRA secondary due to SARS-Cov 2 infection is one of the causes of tracheal intubation. In patients with acute respiratory failure. In ICU patientes with difficcult weaning of mechanical ventilation tracheostomy is one of the therapeutic approach. Percutaneous tracheostomy have so many advantages instead of surgical tracheostomy wiht less complications rate, cheaper and quicker. One of the complications of this technique is the risk of tracheal rupture. We present a case of tracheal rupture in a patient with severe SARS- Cov-2 pneumonia secondary a percutaneous tracheostomy solved with conservative management and a literatura review

¿Es necesaria la realización de ecocardiograma en la valoración de hipertensión pulmonar previa a una criobiopsia transbronquial? / Transbronchial cryobiopsy, is essential to rule out pulmonary hypertension?

INTRODUCCIÓN: El objetivo de nuestro estudio fue valorar la posibilidad de diagnosticar la Hipertensión Pulmonar (HP) mediante signos en la tomografía computarizada (TC), en pacientes con EPID que van a ser sometidos a criobiopsia transbronquial (CBxTb) sin necesidad de realizar ecocardiograma transtoracico (EcoC) sistemático y si la existencia de HP en TC influye de manera relevante en el riesgo de complicaciones de sangrado y en las demoras de realización de la técnica. MATERIAL Y MÉTODOS: Estudio prospectivo de casos controles de todos los pacientes en los que se realizó CBxTb en un período de 20 meses. Los controles fueron los pacientes en los que se realizó CBxTb con EcoC previa protocolizada y los casos los pacientes en los que se realizó EcoC pre CBxTb sólo sin había signos de HP en la TC. Analizamos la correlación entre los datos de HP de la TC y EcoC, las complicaciones por sangrado y la demora al procedimiento entre los grupos. RESULTADOS: Se han realizado 40 CBxTb. Se incluyeron 16 controles; 12 (75%) sin signos de HP en la TC con una especificidad de ésta en relación al EcoC del 85%, sensibilidad 71% y VPN 82%. Se incluyeron 24 casos y, tras los hallazgos de la TC, sólo se solicitó EcoC preCBxTb a 4 pacientes, de los que 3 resultaron falsos positivos. No hubo diferencias entre grupo de controles y casos en cuanto al sangrado (18,7% vs. 16,7%; p= 0,54) pero si en la demora diagnóstica (62 vs. 37; p= 0,03). CONCLUSIÓN: En nuestra serie de pacientes con EPID y CBxTb consideramos indicada la realización de EcoC sólo en casos con signos de HP en la TC, permitiendo acortar la demora diagnóstica sin aumento de sangrados

INTRODUCTION: Our objective was to assess whether the performance of EcoC only in those patients in which the caliper measurement of the PA on CT suggested the existence ofPAH, relevant influence on the risk of bleeding complications and delays CbxTb conducting. MATERIAL AND METHODS: It has been conducted prospective, case-control, of all patients who underwent CbxTb in our unit over a period of 20 months. Defining control group those patients who EcoC was done protocolised, before CbxTb, and cases all patients who EcoC was made only in cases where there were signs of PAH in CT. We analized the correlation in HP diagnosis signs between CT and EcoC data, risk of bleeding and delays in the procedure. RESULTS: We were performed 40 patients. In the control group include 16 patients, CTdetected no signs of HP in 12 (75%) cases, with a specificity of 85%, sensitivity of 71% and negative predictive value of 82%. In our cases group, we include 24 patients, and EcoC was only made before the procedure in 4 cases, 3 of them false positives. No differences in bleeding was found between control and cases groups (18.7% vs. 16.7%; p= 0.54) but for the delays in the procedure was lower in the cases group (62 days vs. 37; p= 0.03) .Conclusion. In our study with interstitial lung disease and CbxTb we conclude that EcoC was indicated only in the cases with PH findings on CT reducing the delays in the procedure without bleeding rate increase

Oral calcium supplementation reduces intraplatelet free calcium concentration and insulin resistance in essential hypertensive patients.

We evaluated the effect of oral calcium supplementation on blood pressure, calcium metabolism, and insulin resistance in essential hypertension. After receiving a standard diet with 500 mg of calcium per day during a 4-week period, 20 nondiabetic, essential hypertensive patients were randomized in a double-blind fashion to receive oral calcium supplementation (1500 mg of calcium per day) or placebo for 8 weeks. At the end of the 4-week period of low-calcium diet and after the 8-week period of intervention, we measured blood pressure (by both office and 24-hour ambulatory blood pressure monitoring), calcium-regulating hormones [urinary hydroxyproline and serum osteocalcin, parathormone, and 1,25(OH)2-vitamin D3], intraplatelet free calcium concentration, fasting plasma glucose and insulin levels, and the insulin-sensitivity index (euglycemic-hyperinsulinemic clamp). Compared with patients maintained at low calcium intake, essential hypertensive patients under oral calcium supplementation significantly reduced serum osteocalcin (from 22.2 +/- 1.9 to 17.9 +/- 2.0 micrograms/L; P = .0015), parathormone (from 4.20 +/- 0.38 to 3.30 +/- 0.36 pmol/L; P = .0003), and 1,25(OH)2-vitamin D3 (from 98.0 +/- 11.0 to 61.6 +/- 5.7 pmol/L; P = .0062). Likewise, we found a significant reduction in intraplatelet free calcium concentration (from 35.9 +/- 1.2 to 26.5 +/- 0.8 nmol/L; P = .0005) and fasting plasma insulin levels (from 71.8 +/- 5.9 to 64.6 +/- 6.2 pmol/L; P = .05) and a significant increase in the insulin-sensitivity index (from 2.89 +/- 0.77 to 4.00 +/- 0.95 mg.kg-1.min-1; P = .0007). None of these parameters were significantly modified in patients maintained at low calcium intake. Office and 24-hour mean values of systolic and diastolic blood pressure did not change after 8 weeks of oral calcium supplementation or placebo.

Ca2+ in the dense tubules: a model of platelet Ca2+ load.

In this work, we explored the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules (DT) and the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in circulating human platelets and examined the relationship between blood pressure (BP) and these platelet parameters. Studying platelets from 32 healthy men, we showed that the maximal reaction velocity (Vmax) of the SERCA significantly correlated with FECa2+ in the DT and with the protein expressions of SERCA 2 and 3. BP positively correlated with both the Vmax of the SERCA (r=.462, P=.010) and the FECa2+ sequestered in the DT (r=.492, P=.005). The relationships between these platelet Ca2+ parameters and BP were in part confounded by increased levels of serum triglycerides and diminished HDL cholesterol with a higher BP. No correlation was observed between the resting cytosolic Ca2+ and BP. Collectively, these findings indicate that (1) an increase in the cellular Ca2+ load in platelets is expressed by a higher activity of the SERCA and an increase in the expressions of SERCA 2 and 3 proteins, coupled with an increase in the FECa2+ in the DT, and (2) a higher BP is associated with an increase in platelet Ca2+ load in human beings, expressed by a rise in the FECa2+ in the DT and the upregulation of SERCA activity.

Renin-angiotensin system genetic polymorphisms and salt sensitivity in essential hypertension.

We evaluated the association between salt-sensitive hypertension and 3 different genetic polymorphisms of the renin-angiotensin system. Fifty patients with essential hypertension were classified as salt sensitive or salt resistant, depending on the presence or absence of a significant increase (P<0.05) in 24-hour ambulatory mean blood pressure (BP) after high salt intake. The insertion/deletion (I/D) angiotensin-converting enzyme (ACE) gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 (AT1) receptor gene polymorphisms were determined with the use of standard polymerase chain reaction methods. Twenty-four (48%) patients with significantly increased (P<0.05) 24-hour mean BP with high salt intake (from 107.3+/-9.4 to 114.8+/-10.6 mm Hg) were classified as salt sensitive. In the remaining 26 patients (52%), high salt intake did not significantly modify 24-hour mean BP (from 107.6+/-10 to 107. 8+/-9 mm Hg), and they were classified as having salt-resistant hypertension. We did not find any significant association between either M235T AGT or A1166C AT1 receptor genotypes and the BP response to high salt intake. However, patients with essential hypertension homozygous for the insertion allele of the ACE gene (II) had a significantly higher BP increase with high salt intake (9. 8+/-8.1 mm Hg for systolic BP and 5.2+/-4.2 mm Hg for diastolic BP) than that observed in patients homozygous for the deletion allele (DD) (1.2+/-5.9 mm Hg for systolic BP; P=0.0118 and -0.2+/-4.2 mm Hg for diastolic BP; P=0.0274). Heterozygous patients (ID) exhibited an intermediate response. The prevalence of salt-sensitive hypertension also was significantly higher (P=0.012) in II (67%) and DI patients (62%) compared with DD hypertensives (19%). We conclude that a significant association exists between the I/D polymorphism of the ACE gene and salt-sensitive hypertension. Patients with II and DI genotypes have significantly higher prevalence of salt sensitivity than DD hypertensives.

G-Protein beta(3) subunit gene variant and left ventricular hypertrophy in essential hypertension.

A functional genetic variant consisting of a C825T substitution in the GNB3 gene, encoding for the G-protein beta(3) subunit, has been associated with enhanced G-protein activation and cell growth. The aim of the study was to investigate the association of this polymorphism with left ventricular hypertrophy (LVH) in a sample of patients with essential hypertension. Left ventricular mass was assessed by 2-mode echocardiography in 86 patients with essential hypertension, and GNB3 C825T genotype was determined by polymerase chain reaction and restriction digestion. Thirty-seven (0.43) patients were homozygous for the C allele (CC), 40 (0.47) were heterozygous (CT), and 9 (0.10) were homozygous for the T allele (TT). The genotype distribution among the patients was in Hardy-Weinberg equilibrium. Values of left ventricular end-diastolic diameter (52.0+/-0.7 versus 48.9+/-0.9 mm, P=0.007), posterior wall thickness (11.3+/-0.2 versus 10.6+/-0.2 mm, P=0.042), and left ventricular mass index (152.7+/-4.4 versus 135.2+/-6.4 g/m(2), P=0. 023) were significantly higher in patients with CT and TT genotypes considered together (CT+TT) than in CC patients. The distribution of the genotypes was significantly different when comparing patients with LVH: 20 (0.33) CC and 40 (0.67) CT+TT patients had this complication, and 17 (0.65) CC and 9 (0.35) CT+TT patients did not (P<0.01). The frequency of the T allele was significantly different among patients with (0.40) and without (0.20) LVH (P<0.01). A logistic regression analysis showed that the association between the T allele and LVH was independent of age, mean blood pressure, body mass index, and alcohol consumption. The relative risk of LVH in patients bearing the T allele (CT+TT group) compared with CC hypertensive patients was 3.03 (95% CI 1.14 to 8.05). The findings suggest an association between LVH and the 825T allele in hypertensive patients.

Erythrocyte sodium transport, intraplatelet pH, and calcium concentration in salt-sensitive hypertension.

We evaluated changes in erythrocyte sodium transport systems, platelet pH, and calcium concentration induced by low and high salt intakes in a group of 50 essential hypertensive patients classified on the basis of their salt sensitivity. Patients received a standard diet with 20 mmol NaCl daily for 2 weeks supplemented in a single-blind fashion by placebo tablets the first 7 days and NaCl tablets the following 7 days. Salt sensitivity, defined as a significant rise (P <.05) in 24-hour mean blood pressure obtained by ambulatory blood pressure monitoring, was diagnosed in 22 (44%) patients. The remaining 28 (56%) were considered to have salt-resistant hypertension. In the entire group of hypertensive patients, high salt intake promoted a significant increase (P <.05) in the maximal rate of erythrocyte NA(+)-Li(+) countertransport (from 271 +/- 19 to 327 +/- 18 microM/(L cells/h) and of the Na(+)-dependent HCO3(-)-CL(-) exchanger (from 946 +/- 58 to 1237 +/- 92 microM/L cells/h) as well as in platelet pH (from 7.15+/-0 0.01 to 7.19+/-0.02 and calcium concentration (from 49+/-2 to 57 +/-2 nmol/L). Depending on salt sensitivity, high salt intake promoted opposing changes in some of the sodium transport systems studied. Salt-sensitive patients increased the maximal rate of the erythrocyte Na(+)-K(+) pump (fom 7.0 +/- 0.4 to 8.8 +/- 0.4 mmol/(L cells/h), Na(+)-K(+)-Cl(-) cotransport (from 416 +/- 37 to 612 +/- 41 micromol/(L cells/h), Na(+)-Li(+) countertransport (from 248 +/- 20 to 389 +/- 17 micromol/(L cells/h) at the end of the high salt period. Conversely, salt-resistant patients decreased the Na(+)-K(+) pump (from 8.0 +/- 0.4 to 6.9 +/- 0.3 mmol/(L cells/h) and Na(+)-K(+)-Cl(-) cotransport (from 578 +/- 53 to 481 +/- 43 micromol/(L cells/h). We conclude that modulation of erythrocyte sodium transport systems by high salt intake depends on salt sensitivity. The Na(+)-K(+) pump, Na(+)-K(+)-Cl(-) cotransport, and Na(+)-Li(+) countertransport increase in salt-sensitive patients, whereas the activity of these sodium transport systems tends to decrease in salt-resistant patients. Independent of salt sensitivity, high salt intake promotes a significant increase in the erythrocyte Na(+)-dependent HCO3(-)-Cl(-) exchanger, platelet pH, and calcium concentration in essential hypertensive patients.

Control of vascular smooth muscle cell growth by cyclin-dependent kinase inhibitory proteins and its implication in cardiovascular disease.

While quiescence is a defining characteristic of differentiated vascular smooth muscle cells (VSMCs) residing within the medial layer of elastic arteries in the adult organism, mature VSMCs can undergo phenotypic modulation and reenter the cell cycle in response to several physiological and pathological stimuli. Abnormal VSMC proliferation is thought to contribute to the pathogenesis of vascular occlusive lesions, including atherosclerosis, vessel renarrowing after successful angioplasty (restenosis), and graft atherosclerosis after coronary transplantation. Therefore, elucidating the molecular mechanisms limiting VSMC growth is currently the subject of active research. This review will focus on the role of cyclin-dependent kinase inhibitory proteins in the regulation of VSMC proliferation and its implication in intimal lesion formation during the pathogenesis of vascular proliferative diseases.

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

Inhibition of cellular proliferation by drug targeting of cyclin-dependent kinases.

Abnormal cellular proliferation is associated with the pathology of several diseases, including cancer, atherosclerosis and restenosis post-angioplasty. Therefore, antiproliferative therapies may be a suitable approach to treat these disorders. Candidate targets for such strategies include specific components of the cell cycle machinery. Progression through the cell cycle in mammalian cells requires the activation of several cyclin-dependent protein kinases (CDKs) through their association with regulatory subunits called cyclins. Active CDK/cyclin holoenzymes phosphorylate cellular proteins including the retinoblastoma susceptibility gene product (pRb) and the related pocket proteins p107 and p130. Several compounds have been described that directly or indirectly inhibit the activity of CDKs, which results in a suppression of cell growth. In this review, we will discuss the use of drugs targeting CDKs and their therapeutic application in animal models and clinical trials.

Safety of the transbronchial biopsy in outpatients.

The objective of our study was to determine the safety of transbronchial biopsy (TBB) in nonhospitalized patients. The design was a prospective study of the consecutive cases from July 1987 until September 1988 in the setting of a university hospital of the third level with 1,800 beds. The patients were a consecutive sample of 169 patients who had 184 procedures of fiberoptic bronchoscopy (FOB) with TBB performed. They suffered from different diseases: lung nodules or masses, diffuse interstitial disease, alveolar condensation, etc. An FOB with TBB was performed in immunocompetent outpatients, who were kept under observation for four hours and then had a chest roentgenogram taken afterwards. We contacted them again after 72 hours to rule out delayed complications. In three cases, more than 100 ml of blood were obtained during the FOB, without significant hemoptysis being recorded in those patients during the observation period; chest pain occurred in 15 patients during the TBB; pneumothorax occurred in two patients (1 percent), one of whom required admission to the hospital, without requiring chest tube drainage. Other complications are reported (bronchospasm, parenchymal hemorrhage, and pneumonia). In conclusion, we consider the TBB to be a technique with a low incidence of complications for outpatients, so therefore we do not believe that admission to the hospital is mandatory for this type of patient, although we do recommend a longer observation period.

The relationship between Ca2+-ATPase and freely exchangeable Ca2+ in the dense tubules: a study in platelets from women.

The main aims of this work were to examine in women: the relationship between the freely exchangeable Ca2+ (FECa2+) in the dense tubules and the activity of the sarco(endo)plasmic reticulum (SER) Ca2+-ATPase (SERCA) in platelets, and the relationship of these parameters with blood pressure and serum lipoproteins. Platelets from 14 white and 13 black women in good health were studied. The FECa2+ was measured as the ionomycin-evoked Ca2+ release (in the presence of thapsigargin) in Ca2+-free medium. SERCA activity was measured as the thapsigargin sensitive, Ca2+ dependent and ouabain resistant, ATP hydrolyses in platelet membranes. Relative expressions of SERCA 2 and 3 isoforms and Ras-related protein (Rap) 1 in platelet membranes were determined by Western immunoblots. Highly significant correlations were observed for FECa2+ in the dense tubules with: 1) the maximal reaction velocity (Vmax) of the SERCA (r = 0.592, P = .0014), and 2) Rapl (r = 0.551, P = .0035). In addition, negative correlations were observed between FECa2+ in the dense tubules and age. No correlations were observed for these variables with blood pressure or serum lipoproteins. We conclude the FECa2+ and the Vmax of the SERCA are reliable indicators of Ca2+ load in platelets from women. However, in women, unlike previous observations in men, these platelet parameters are not correlated with blood pressure and serum lipoproteins.